Recovery Tracker
How We Compiled Our Data. Visit our Eye on the Stimulus blog. Data current as of Sept. 30, 2009 (the latest available data as of Dec. 2009).
New York County
Funding Breakdown
| U.S. | New York | New York | ||
|---|---|---|---|---|
| Population | 304,059,724 | 19,490,297 | 1,634,795 | |
| Total recovery funding | $260,908,876,834 | $19,782,147,945 | $2,545,464,628 | |
| Direct to County | $188,787,799,322 | $12,004,816,573 | $2,545,464,628 | |
| County Funds per Capita | $621 | $616 | $1,557 | |
| Unemployment (10/09) |
10.2 | 9.0 | 9.2 | |
| Median Household Income | $50,007 | $52,944 | $62,268 | |
| Poverty Rate | 13.3% | 14.0% | 18.0% |
Stimulus contracts, grants and loans as of Dec. 7, 2009.
County Projects
Stimulus contracts, grants and loans in New York County, New York. Data last updated on Sept. 30, 2009 (the latest available data as of Dec. 2009).
Note: There still may be overrepresentation of money going to counties where state capitals are because of funding going to state agencies but where the data did not designate that it was to be used statewide.
Amount refers to both the amount of stimulus funding going toward the project and the face value of the loan.
| Recipient | Amount | Type | Description | Agency | Date |
|---|---|---|---|---|---|
| CORNELL UNIVERSITY, INC | $422,291.00 | Grant | Trans-NIH Recovery Act Research Support Infections with RSV are one of the major causes of viral lower respiratory tract illness. Protection against RSV may be achieved with an efficient vaccination strategy that induces neutralizing humoral immunity and a Th1-dominant cellular response and that does not predispose to Th2-dominant vaccine-induced exaggerated RSV disease. Based on the knowledge that adenovirus (Ad) gene transfer vectors can be used to evoke robust systemic and mucosal immunity against an immunogen expressed as a transgene and that Ad functions as a potent adjuvant, this proposal focuses on the development of a vaccine against RSV using modified Ad vectors. The Ad modifications include the addition of an RGD motif to the fiber knob, a modification known to enhance infection of antigen presenting cells and enhance Th1 immunity, as well as the incorporation of RSV epitopes into the Ad capsid. To assess if anti-RSV immunity can be elicited even in the presence of anti-Ad immunity, the vectors will also be based on the non-human primate serotype AdC7, against which humans do not have immunity. These modified vectors will be assessed for the ability to induce immunity and protection against RSV in adult and neonatal mouse models, with particular focus on potential vaccineenhanced RSV lung disease. Three specific aims outline the studies to achieve these goals. Aim 1. To evaluate the hypothesis that an optimized Ad vector, which is engineered to increase activation and infection of antigen presenting cells, and which expresses the RSV F protein, will evoke robust protective immunity against RSV without causing vaccine-induced RSV disease. Aim 2. To evaluate the hypothesis that modified Ad vectors engineered to contain epitopes of the RSV F and G proteins in the capsid hexon protein, a strategy that enables boosting of the immune response with the identical vector, will evoke robust immunity against RSV without predisposing to vaccine-induced RSV lung disease . Aim 3. To assess if, using an non-human primate serotype AdC7-based vector, against which humans do not have immunity, anti-RSV immunity can be elicited even in the presence of anti-Ad immunity. Show more... | National Institutes of Health | 5/21/2009 |
| NEW YORK FOUNDLING HOSPITAL, THE | $616,245.00 | Grant | ARRA - Head Start ARRA Cost of Living Adjustment(COLA), and Quality | Administration for Children and Families | 6/30/2009 |
| GRAHAM WINDHAM CHILDREN SERVICES (INC) | $103,205.00 | Grant | ARRA - Head Start Funding of ARRA 1.84% and QI | Administration for Children and Families | 6/24/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $173,119.00 | Grant | ARRA - Head Start This is a request for permanent COLA and one-time funds, in response to the COLA and Quality Improvement Program Instruction ACF-Pl-HS-09-06. The permanent 3.06% COLA will be added to all staff positions to raise salaries on a permanent basis in order for salaries to be competitive within the community. Total salary and fringe: $75,803. A non-recurring COLA under ARRA of 1.84% will be provided to all staff. Total salary and fringe: $45,581. Quality Improvement funds totaling $127,538 will be expended as described below: $64,696 are directed to improve the educational benefits of child development and family partnership staff. As per Program Instructions 5A (ii), (iii), funds will enable staff to improve required qualifications and/or assist with advancement on a career ladder, further their education and professional development towards certification, and improve the skills of educational personnel to teach and provide services to children with disabilities. • Four staff members will be supported in completing their Child Development Associate training by covering expenses for their test fees, first aid training, text and materials. This will facilitate the completion of their CDA. • Three staff member will receive funding for tuition, fees, and books that will contribute toward their undergraduate degrees at branches of New York City University. • Three staff members will receive support towards graduate credits, including tuition, fees and books at New York City University, and materials and books at Columbia University School of Social Work and Teachers College. • A Developmental Specialist will be hired at 550/0 effort. Provides professional development for staff in the area of infant curriculum and special needs. • A Certified Social Work Supervisor (7.5% Effort) will be hired to provide the required field work supervision for a Family Partnership staff member to pursue her MSW at Columbia School of Social Work (tuition is covered under current benefit package). Tba staff member will complete her field work placement in her current position at the EHS program. In addition to advancing the staff member on her career ladder, this benefits the program by providing increased skilled mental health and counseling services to children and families. $62,842 are directed to overhead costs. Overhead costs for the Early Head Start Program during grant year 9-1-09 to 8-30-10 are $653,103. QI funds in the amount of $62,842 are being applied to help cover these costs. Show more... | Administration for Children and Families | 6/26/2009 |
| GRAND STREET SETTLEMENT INC | $47,183.00 | Grant | ARRA - Head Start The ARRA Cost Of Living Adjustment will be distributed to staff in the following manner: 1) Four teaching staff who earned the Infant/Toddler Child Development Associate credential during the program year will receive 3.68% additional pay. 2) Three teachers who earned their temporary New York State Early Childhood Teaching certification will receive 5.52% additional pay. 3) The Family Service Coordinator who earned a Master’s in Social Work degree will receive 5.52% additional pay. 4) The remaining staff members will receive 1.82% additional pay. The Quality Improvement (QI) funds will be used for two purposes: 1) To improve the quality of communication between families whose first language is Chinese and the Early Head Start program staff. Based on our community assessment, the number of Chinese-speaking families with children under the age of three in the community has increased. The program seeks to employ an identified part-time (17 hours) staff member who will carry a small home visiting caseload and facilitate communication between the EHS and parents. ($19,581.31 salary plus 29% fringe) This will allow the program to provide continuity of service delivery and support to Chinese-speaking families as the program moves through this transition. The total cost of her retention for the duration of the QI funds exceeds the minimum 50% personnel costs required. 2) To provide a safe and appropriate outdoor play area for our infants and toddlers. While the area where Grand Street Settlement is located has many public playgrounds for children over three, there are none within walking distance for infants and toddlers. The EHS stopped using a preschool playground with padding because the equipment was too large for toddlers. However, the nearest secure open space that could be used by the babies has neither equipment nor safety padding. On the program’s most recent federal review (August 2008), the program was cited for the lack of safety surfacing in this space. Currently, the children have indoor gross motor play and go outdoors for planned walks (change of seasons, neighborhood exploration, etc). However, Grand Street Settlement’s landlord, the New York City Housing Authority (NYCHA) has assisted the program by identifying a space across from the agency’s front door that may be converted from a preschool playground to an open space with safety surfacing. NYCHA has offered to replace the existing gates and reconfigure the entranceway so the space is more aesthetically pleasing and easier to access. Because this issue affects a small number of children, private funders have not expressed any interest in working with the EHS to create a play space that would be safe for children under three. Therefore, the program proposes to use the remaining $10,681.69 to remove the existing large pieces of equipment (the cost of this job has been estimated at $4,000), re-grade the surface and apply safety surfacing to the area. Show more... | Department of Health and Human Services | 7/29/2009 |
| NORTHSIDE CENTER FOR CHILD DEVELOPMENT INC | $93,470.00 | Grant | ARRA - Head Start This grant awards a cost of living adjustment (COLA-ARRA) increase for Head Start and Early Head Start. In addition, this award also provided quality improvement funds for Head Start and Early Head Start. These funds are available for obligation over the entire project period of the grant, which ends September 30, 2010. Show more... | Administration for Children and Families | 6/30/2009 |
| MAYI: FILIPINO THEATRE ENSEMBLE, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/21/2009 |
| NEW YORK CITY BALLET, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/08/2009 |
| DANCE/USA | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| THIN MAN DANCE | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/06/2009 |
| DOVA INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| EDUCATIONAL ALLIANCE INC, THE | $195,656.00 | Grant | ARRA - Head Start The Educational Alliance (The Alliance) will use COLA funds to provide a permanent 3.06% salary increase to all full-time Federal Early Head Start and Head Start staff at all four Educational Alliance Head Start/Early Head Start sites in Downtown Manhattan: 197 East Broadway, P.S.142, P.S.15, and P.S.64. This will be accompanied by a one-time salary increase of 1.84%, and proportional increases in fringe benefits – at the agency’s standard rate of 26% of salary – and indirect costs at a rate of 15%. The remaining portion of COLA funds will be devoted to higher operating costs that will enable The Alliance’s Head Start/Early Head Start programs to better meet the educational needs of children from immigrant families, children who are homeless, children in foster care, children from families in crisis, children referred to Head Start and Early Head Start by welfare agencies, and children who are exposed to chronic violence and substance abuse. Our recent Early Childhood Environment Rating Scale evaluation revealed a significant need for an increase in our capacity to serve these children in the areas of math, fostering creativity and imagination through art, further encouragement of literacy in the family, and promoting the acceptance of diversity. In accordance with Section 640(a)(5) of the Head Start Act, half of QI funds will be dedicated to the compensation of educational personnel, family workers, and child counselors. These expenses will: (i) fund higher education courses for Head Start and Early Head Start full-time staff that will improve staff qualifications and support ongoing improvement and expertise; (ii) pay for New York State Certification Examinations and preparation for those exams for full-time teachers; (iii) pay for teaching assistants to pursue the renewal of their Childhood Development Associates (CDA) credentials; (iv) provide substitute teachers so that Head Start teachers may more efficiently pursue their higher degree course work during daytime hours; (v) fund trips to conferences in the area of early childhood development, including National and regional Early Head Start conferences; and (vi) allow us to contract with consultants who will help us monitor existing practices and conduct in-classroom observation of children who are at-risk for mental health issues. The latter are especially important as our recent Community Assessment revealed that 22% of our children are at-risk of developing mental health conditions. With the remaining QI funding, The Alliance will also add a qualified staff member to reduce the child-to-teach ratio and assist with both the Head Start and Early Head Start Programs. The position will be titled Head Start/Early Head Start Home Visitor and this new staff member will provide much-needed help to Head Start and Early Head Start families who require additional case-management services in their homes. Show more... | Department of Health and Human Services | 6/29/2009 |
| LOWER EAST SIDE I ASSOCIATES | $1,179,187.00 | Grant | Section 8 Housing Assistance Payments Program Special Allocations (Recover Rental Assistance Payment | Department of Housing and Urban Development | 3/16/2009 |
| CHILDREN'S AID SOCIETY, THE | $101,766.00 | Grant | ARRA - Head Start ARRA Cost of Living Adjustment (COLA), and Quality | Administration for Children and Families | 6/29/2009 |
| NEW YORK, CITY OF | $10,615,027.00 | Grant | ARRA - Head Start Funds will be use to pay for health insurance cost | Administration for Children and Families | 9/02/2009 |
| PHIPPS COMMUNITY DEVELOPMENT CORPORATION | $44,393.00 | Grant | ARRA - Head Start ARRA Cost of Living Adjustment (COLA), and Quality | Administration for Children and Families | 6/25/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $585,000.00 | Grant | Trans-NSF Recovery Act Research Support TECHNICAL SUMMARY: This CAREER proposal supports an integrated research and education program that centers on solving problems involving colloidal particle self-assembly using theoretical and computational methods. Unlike most of the work done so far in the field that focuses on how order arises from given local interparticle interactions, this research will study the inverse problem of finding what local interactions are required for the building blocks to self-assemble into a given structure. Using this approach, new strategies will be developed to find particle interactions that are capable of generating specific crystal structures through self-assembly. The role of elastic and amphiphatic surfaces in mediating particle self-assembly and the role of particle aggregation in determining the mechanical and elastic properties of soft interfaces will also be studied. The ability to design particle interactions in a systematic fashion to target desired crystals, and the prospect of manipulating the mechanical properties of microscopic elastic sheets, will be results of great practical importance. The results of this research will help open the way to rational design of structures with novel optical, mechanical and functional properties. The educational aspects of this CAREER award are multifaceted. One major goal is to increase participation of underrepresented groups in the sciences and specifically in chemistry by improving K-12 curriculum activities in nearby Harlem high schools. The PI also plans to develop multi-platform interactive educational software, in the particular form of video games, that will be made freely available to middle and high schools nation wide. This approach is based on the premise that active learning and interactivity will be the key to motivate and inspire the next generation of scientists. This outreach program builds on the framework of the Center for Technology, Innovation, and Community Engagement at Columbia University, and complements the ongoing efforts of the Chemistry Department and the University to reach the Harlem community. NONTECHNICAL SUMMARY: This CAREER award supports a combined research and education program to develop theoretical and computational methods that can predict how molecular building blocks will self-assemble into three-dimensional materials structures. This approach could apply to many materials systems, some representative examples include: aggregation of proteins into functional biomachines on the scale of large molecules, formation of protein coats of viruses, packing of large molecules to form biological membranes, and assembly of nanometer scale particles to make photonic crystals, crystals engineered for specific optical properties, such as transmitting particular colors of light and blocking others. The major research objectives include the development of numerical tools to examine how particles need to interact with each other in order to self-assemble into a desired complex crystal structure, the study of how elastic surfaces or membranes can assist particle self-assembly, and the study of how particle clustering on soft interfaces can be used to determine the mechanical and elastic properties of materials used as templates. The results of this research could help open the way to rational design of structures with novel optical, mechanical and functional properties. This program will build on the strong commitment of Columbia University to the field of nanotechnology. The educational aspects of this CAREER award are multifaceted. One major goal is to increase participation of underrepresented groups in the sciences and specifically in chemistry by improving K-12 curriculum activities in nearby Harlem high schools…The complete abstract for this award is available in Research.gov at: www.research.gov. Show more... | National Science Foundation | 6/12/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $130,000.00 | Grant | Trans-NSF Recovery Act Research Support Quantile regression (Koenker and Bassett, 1978) has emerged as an important statistical methodology, and has been used in a wide range of applications including economics, biology, ecology and finance. Very often a data set is not perfectly obtained. Some variables may be measured with error, while others may contain missing observations. Ignoring measurement errors or missing observations could lead to substantial bias in estimation. For this reason, how to handle measurement errors and missing data has generated a large number of literatures. Unfortunately, most of the existing methods rely on a parametric likelihood form, and hence cannot be applied to quantile regression directly. This proposal targets at developing methods and theories for obtaining unbiased quantile estimates even in the presence of measurement errors and/or missing observations. The specific proposed research activities under this project include the following four aspects. (1) Develop estimation methods for linear quantile models allowing the existence of measurement errors, and investigate the asymptotic properties for the resulting estimator. (2) Extend the estimation method for linear quantile model to semiparametric models, which brings more flexibility and hence facilities a wider range of applications. (3) Develop related inference and model adequacy assessment tools. (4) Extend the proposed methods in 1 - 3 to address missing data problems in conditional quantile models, including estimation, inference and model assessment. The statistical methods to be employed for this proposal cover quantile regression, methods and theories for measurement errors and missing data problems, nonparametric and semi-parametric modeling, goodness-of-fit tests, bootstrapping methods and robust statistics. The proposed research will lead to more accurate inference and more comprehensive qualifications in various research applications in epidemiology, HIV research, genetics, cancer research and environmental science, as measurement errors and missing data commonly exist in those applications. The methodologies to be developed by the investigators are of general interest to statistical research. The proposed research will be widely disseminated through publications, presentations in domestic and international conferences, and collaborations with clinical and public health researchers. Show more... | National Science Foundation | 7/04/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $678,000.00 | Grant | Trans-NSF Recovery Act Research Support With this CAREER award from the Organic and Macromolecular Chemistry Program in the Chemistry Division at the National Science Foundation, Professor Scott A. Snyder of the Department of Chemistry at Columbia University will develop new approaches for the asymmetric halogenation of alkenes by exploring novel classes of electrophilic halogen reagents and surrogates. The success of these efforts will provide the first way to achieve asymmetric halogenation of unactivated olefins as well as direct and indirect halonium-induced cation-pi cyclizations. The addition of these reactions to the synthetic chemistry toolbox would finally make possible the synthesis of dozens of unsolved natural product architectures that possess halogen atoms in combination with unique, and largely unexplored, chemical biology profiles. It should also elucidate principles in reagent design and synthetic strategy that may help to solve other significant challenges. In addition, the support of the Organic and Macromolecular Chemistry Program will enable Professor Snyder to utilize the power of natural products synthesis and reaction design to expand the number and diversity of students pursuing STEM-based careers. These efforts will be focused on both the high school and undergraduate levels. First, Professor Snyder will offer students and teachers from local high schools in the New York City area, particularly public schools with high socioeconomic diversity, an opportunity to participate in a specially tailored experiential visit day at Columbia University, followed by a chance to work in Professor Snyder's laboratory for eight weeks. In the laboratory, they will work on a challenging chemical research problem and develop an experiment that can be utilized in the school's laboratory program for years to come. Second, Professor Snyder will create an inquiry-based laboratory program for Columbia's introductory undergraduate organic chemistry program based on a natural product total synthesis. This concept is meant to modernize the teaching curriculum, better marry its objectives across lecture and laboratory settings, and best illustrate to undergraduates the real nature and excitement of synthetic organic chemistry. Show more... | National Science Foundation | 5/21/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $419,833.00 | Grant | Trans-NSF Recovery Act Research Support I. Intellectual Merit. The nature of price setting by firms is central to many important questions in macroeconomics. Over the last few years, research on firm price setting has been transformed by the increased availability of micro price data. For several years, the PI's have been engaged in developing and analyzing the newly available micro price data at the U.S. Bureau of Labor Statistics (BLS). The goal of the current project is to continue this research along four dimensions. First, the PI's intend to work with the BLS to extend the academic research database on consumer prices further back in time. The current start date of this database is 1988. They hope to be able to extend the database back to the 1970's. This is of particular interest because inflation in the U.S. was much more variable in the 1970's and early 1980's than it has been since. They intend to use the expanded database to analyze how the frequency and size of price changes as well as the degree of price dispersion has varied over time. This will allow them to draw sharper conclusions about the success of different models of price setting than are possible using currently available data. Since the dataset will be constructed as a research database, they expect it will eventually be heavily used by future researchers both in academia and at the BLS. Second, they intend to analyze how product replacement affects exchange rate pass-through. In constructing price indices, price adjustments that occur at the time of product replacements tend to be dropped. If price adjustments disproportionately occur at the time of product replacements, then price adjustments are disproportionately unobserved. This will bias measures of exchange rate passthrough. The preliminary estimates suggest that this bias is large, potentially affecting estimates of exchange rate pass-through for the U.S. by as much as a factor of two. Third, they intend to use a large proprietary dataset we have obtained from AC Nielsen to analyze the comovement of retail prices across products, stores and cities in the U.S. The data consist of weekly prices and quantities for several thousand products and several thousand grocery stores over five years. Preliminary results suggest that a large part of retail price variation is due to dynamic pricing strategies as opposed to contemporaneous demand or supply shocks. The PI's are in the process of collecting an additional new dataset on manufacturer contracts that will allow them to extend their findings to answer the question of whether the observed variation in retail prices arises from complex price discrimination strategies by manufacturers or from dynamic pricing strategies by retailers. Fourth, they intend to use a new dataset on Icelandic consumer and import prices to analyze the role of local costs in explaining failures of purchasing power parity. Several existing studies of failures of purchasing power parity distinguish between traded and non-traded goods to try to evaluate the importance of local costs. An important concern regarding such studies is how to define tradable goods, since many goods that are in principle tradable are in practice rarely traded. The PI's aim to address these concerns by using the unique feature of the Icelandic consumer data that it identifies which products are, in fact, imported and which are not, and by matching the consumer price data with at-the-dock import prices to gauge the importance of non-traded distribution margins. II. Broader Impact. The research is potentially highly relevant to policymakers at the Federal Reserve by shedding new light on the costs of inflation, the likely real effects of monetary policy and the effects of movements in the U.S. dollar on prices. The project involves the creation of a new historical dataset in collaboration with the BLS… The complete abstract for this award is available in Research.gov at: www.research.gov. Show more... | National Science Foundation | 8/04/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $400,000.00 | Grant | Trans-NSF Recovery Act Research Support This CAREER award is for research on creating an energy conversion system that converts the now landfilled petrochemical portion (plastics) of municipal solid wastes (MSW) to value added liquid fuel. The research includes carbon dioxide capture and storage. Until now, these technologies have been developed independently of one another, which has resulted in complex and economically challenged large scale designs. The research will combine carbon mineral sequestration with a MSW-to-Liquid process to achieve process intensification and synergistic net reduction in carbon emissions. The overarching concept is the shift of the water-gas shift (WGS) reaction equilibrium via constant removal of carbon dioxide. This approach will be investigated by injecting engineered mesopored Mg-bearing sorbent into the WGS reactor. One of the direct impacts of this study will be technology for carbon mineral sequestration, benefitting various carbon dioxide generating industries, such as the energy, chemical, and petrochemical industries. The PI will participate in developing national-scale outreach programs for K-12, undergraduate, and graduate students as a member of both the Societal Impact Operating Council and the Research and New Technology Committee of the AIChE. Additionally, the PI will continue to expand the participation of high school students in the activities of her laboratory. Show more... | National Science Foundation | 7/22/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $613,000.00 | Grant | Trans-NSF Recovery Act Research Support What determines human health is known only in part. Even where causal pathways have been identified, great uncertainty frequently exists regarding the strength of the relationship. Compelling and precise estimates of these relationships are needed to inform public policies that will improve population health. This project would improve understanding of these relationships, using natural and quasi-experiments. The project highlights projects on the use of Ramadan to study the effects of maternal nutrition, the effects of heating subsidies in China to study the effects of pollution on prenatal development, and the impact of obesity report cards on obesity and health in Arkansas. This CAREER proposal argues that refutable research hypotheses can be evaluated in an observational setting where identifying variation is plausibly exogenous. Ideally, the research hypothesis has strong implications which can be evaluated in available (i.e. pre-existing) data. The most compelling empirical comparisons do not require sophisticated econometric fixes. Instead, good natural experiments can identify treatment effects with minimal statistical adjustment. The cleanest of experiments, where the treatment is randomly assigned, requires only the comparison of means to estimate causal effects. This controlled experiment should be emulated wherever possible. Operationally, the proposed approach seeks to unearth comparisons in an observational setting where unadjusted impact estimates are quite similar to regression-adjusted impact estimates. Broader Impact: The project will have substantial impact through collaborations outside the usual Economics teaching and research communities. For example, the investigator is working with the Arkansas Center for Health to determine how health information might help reduce childhood obesity. International collaboration is also integral, as illustrated by the proposed study of Chinese air pollution near the Huai river with researchers at Tsinghua and Beijing University. Also, because the health questions engaged are vitally important, substantial interest from policymakers (and the popular press) is likely. Show more... | National Science Foundation | 9/29/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $301,677.00 | Grant | Trans-NSF Recovery Act Research Support Intellectual merit: The intellectual merit of this proposal results from the first demonstration of the directed evolution of specific cell penetrating peptides (SCPPs). The directed evolution technique offers tremendous potential for the engineering of new peptides, but the critical challenge in this approach is the development of appropriate selection procedures. The PIs will use a novel bi-functional platform based on phage display technology, and this will be coupled with a physiologically relevant selection protocol. Once optimized, this platform will allow one to rapidly evolve valuable new SCPP sequences. Broader impacts: The broader impacts of this project arise from the new experimental manipulations and therapeutic treatment options that will be made possible by the novel SCPPs. Recent research efforts have produced many exciting mechanism-based therapies. However, the delivery of these therapies to their targets has been a significant limitation. The new SCPPs will enable the expansion of the armamentarium of potential therapies for these devastating diseases. This interdisciplinary research project will also provide a fertile environment for the teaching, training, and mentoring of new engineers both at Columbia University and in the surrounding community. Show more... | National Science Foundation | 6/17/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $548,837.00 | Grant | Trans-NSF Recovery Act Research Support The project will quantify stratosphere-troposphere exchange (STE) using novel transport diagnostics: one-way cross-tropopause flux distributions and path densities with their associated transport rates. This new approach will extend the current knowledge of STE by revealing, with unprecedented detail and precision, a comprehensive picture of transport across the tropopause and through the troposphere and stratosphere. The flux distributions computed with MATCH (Model of Atmospheric Transport and Chemistry), driven by reanalyzed winds, will allow extant disparate estimates of STE fluxes to be validated and reconciled as differently conditioned integrals of the underlying fundamental flux distributions. The path-density diagnostic will quantify the advective-diffusive 'conveyor' circulation in the atmosphere, partitioned according to the origins and destination regions of different paths and the origin-to-destination transit time. This research will make the first substantial use of idealized general circulation models to analyze atmospheric tracers and transport. Analysis of idealized model experiments will determine how different meteorological processes and flow regimes control STE. The computational efficiency of these idealized models will allow the systematic determination of the sensitivities to model parameters so that the robustness of the results can be assessed. The results of this project will be of value to the wider atmospheric-chemistry community, because the flux-distribution and path-density diagnostics isolate the role of transport in determining atmospheric composition. In particular, the rates and pathways with which different photochemical environments are accessed by both boundary-layer and stratospheric species will be quantified. This will have implications for air quality, by constraining the contribution of stratospheric ozone to boundary-layer air and by quantifying the rates and paths with which boundary-layer air and pollutants are removed to the stratosphere. A baseline climatology of detailed STE transport diagnostics will be provided, from which changes in transport and atmospheric composition caused by future green-house-gas warming can be asssessed. Results will be of value to the observational community, because the geographic distribution of cross-tropopause fluxes, the statistics of deep intrusions and their lifetimes, and the meteorological processes that are conducive to STE will be quantified. This will be useful for planning aircraft and other measurement campaigns. The computed Green functions and the idealized model configurations will be made available to the community. These tools can be used for a wide variety of investigations on the STE of air and trace species. Research activities will be integrated into teaching and educational outreach. A team of a high-school student, a high-school teacher, and an undergraduate university student from the New-York-City area will participate in the project through the New York City Research Initiative during its annual six-week summer outreach program. Show more... | National Science Foundation | 6/19/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $200,000.00 | Grant | Trans-NSF Recovery Act Research Support The PIs will study some fundamental problems in algebraic number theory, particularly problems related to the deep links between Galois representations and special values of L-functions (as conjectured in the Birch-Swinnerton-Dyer Conjecture and the Bloch-Kato Conjectures). More specifically, the PIs will study the following themes: (i) Mod-p Galois representations and mod-p modular forms; (ii) Constructing Galois representations and motives associated to automorphic forms; (iii) The Iwasawa Main Conjecture; (iv) p-adic families of automorphic forms and applications; (iv) Algebraic cycles, p-adic L-functions and Euler systems. Thus the main focus will be on p-adic methods in the theory of automorphic forms and Galois representations. The PIs will arrange short-term visits for collaborative research purposes between themselves, affiliated researchers and new comers in the area, be actively involved in graduate training and postdoctoral advising, and organize two workshops and a final conference, with preparation of a proceedings for dissemination of the results. In nontechnical terms, the problems that the PIs will study involve showing the surprising equality of two number-theoretic objects, one defined analytically and the other algebraically. In this way, the problems to be studied are linked by two common philosophical threads: the notion of a reciprocity law, which has a long and deep tradition in number theory, going back to the quadratic reciprocity law of Gauss, and the notion of a class number formula, which goes back to the fundamental ideas of Dirichlet. Further, such equalities of mathematical objects defined in a priori different ways are not just of theoretical interest but tend to have extremely concrete applications, the most striking recent ones being the resolution of Fermat's last theorem and the Sato-Tate conjecture. The workshops, the final conference, and the graduate and post-doctoral advising will have an important impact on the formation of new researchers in the field and on the promotion of new collaborations. Show more... | National Science Foundation | 6/18/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $200,000.00 | Grant | Trans-NSF Recovery Act Research Support Nearly hundred years after the debut of Einstein's theory of general relativity, gravitational waves are viewed as one of the most intriguing but still elusive astrophysical phenomena. They are expected to be emitted by extreme astrophysical sources such as merging black hole binary systems, spinning neutron stars, gamma-ray bursts or supernovae. Superb and finely tuned gravitational-wave telescopes are required for detection and astrophysics investigations. This award will enable members of the Columbia Experimental Gravity group to participate in activities to improve the performance of the LIGO gravitational wave detectors. Group members will focus on mission-critical activities directly affecting the sensitivity of the LIGO Scientific Collaboration's searches for cosmic gravitational waves such as detector diagnostics and calibration. A well characterized and precisely calibrated detector in turn could enable the data analysts to execute searches that see farther, see more, produce fewer false alarms and extract more information from plausible future detections. Students from high school through graduate level will have the opportunity to participate in this research. In addition, the urban setting and existing outreach infrastructure of Columbia University will enable unique educational and outreach activities based on this research that target schools not only in the local community but also in the greater New York City metropolitan area. Show more... | National Science Foundation | 8/17/2009 |
| MALCOLM X II PHASE A ASSOCIATES | $1,111,039.00 | Grant | Section 8 Housing Assistance Payments Program Special Allocations (Recover Rental Assistance Payment | Department of Housing and Urban Development | 4/17/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $330,000.00 | Grant | Trans-NSF Recovery Act Research Support The objective of this research is to develop a process which integrates high performance thin film silicon circuitry with compound semiconductor devices, and to use this process to demonstrate an active matrix light emitting diode capable of projecting a video brightness image. The approach is to start with high quality compound semiconductor wafers, and then deposit and recrystallize the silicon circuitry using low temperature deposition and a laser annealing process known as sequential lateral solidification. This process produces thin film silicon transistors with high mobility and minimal thermal load to the substrate. Compound semiconductor materials are favored for a number of optoelectronic applications including photodetectors for visible, IR, and UV; light emitting diodes; and lasers. The materials used in these applications, however, generally do not form transistors and cannot be used for switching or local ampli?cation. The approach presented in this proposal reverses the usual heteroepitaxy strategy, in which compound semiconductors are grown on a silicon wafer, and instead fabricates silicon devices on a compound semiconductor wafer. This allows integration of high quality compound semiconductor materials with silicon circuitry for switching and amplification, avoiding the limitations of other approaches. The technology developed has a range of applications including energy efficient displays, lithography, hyperspectral detection, communication systems, and miniature biological sensors. In addition to training a graduate student, the program will mentor a high school student and an undergraduate working on the project. Light emitting diode wafer materials will be used for high school demonstrations and a course on display devices. Show more... | National Science Foundation | 8/14/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $419,444.00 | Grant | Trans-NSF Recovery Act Research Support This project is defining the basis for lower-complexity robotic hands that can grasp a wide variety of objects in noisy and unstructured environments. The new generation of mobile and humanoid robots still lacks basic ?hands? that can reliably grasp objects. Robot hands have been traditionally built as anthropomorphic, high degree-of-freedom (DOF) mechanisms that are expensive and difficult to control. The research team is developing technologies based on defining hand mechanisms that capture two key features of human grasping, versatility and low dimensionality of hand postures. Reducing complexity brings major benefits. Determining the minimal number of hand joints, sensors and actuators can reduce costs and speed research as low-complexity hands can be easily fabricated, designs can be quickly iterated, and control can be simplified. These ideas are used to build a low-cost, low DOF grasping device that is based on hard human grasping data. Further, the new hand designs are being tested in simulation so as to build hardware that is functionally proven for robotic grasping tasks. Important research outcomes include: development of a new low-dimensional, low-cost robotic hand; experiments to gain insights from human grasping and adaptive compliance; and machine learning algorithms for grasping. Broader impacts include: collaboration between neuroscience and robotics; hardware design methods and computational tools for hand researchers; providing robust grasping capabilities in real environments such as robots for home care and assistance for the elderly and disabled; establishing links between neural control and prosthetic devices based on dimensionality reduction; and dissemination of modeling and simulation grasping software. Show more... | National Science Foundation | 6/26/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $2,423,847.00 | Grant | Trans-NSF Recovery Act Research Support This project addresses the question of the nature of dark matter in the Universe with an experimental search for Weakly Interactive Massive Particles (WIMPs) using two-phase xenon detectors. This group is currently operating at the 100 kg mass scale with the XENON100 experiment which has replaced the XENON10 prototype in the same shield and location at the Gran Sasso Underground Laboratory. The worldwide race towards direct dark matter detection has been dramatically accelerated by the fast evolution of detectors based on noble liquids. They have shifted the scale of target mass from a few to tens of kilograms, while reducing the overall gamma/beta background to less than 0.001 events/kg/keV/day, much lower than scintillator and cryogenic bolometer detectors. Despite being only a prototype, XENON10 has shown the potential of two-phase Xe detectors for dark matter searches, bringing the XENON program to the forefront of the field. This award will provide funds to continue the XENON program for 2 more years to complete the dark matter search with the current XENON100 detector within 2009, and to realize an upgraded detector by early 2010 in the same shield and location. Additionally, XENON100 has a robust possibility to address questions related to the DAMA/LIBRA annual modulation signature, shedding new light on this controversial result. The broader impact of the XENON science program addresses questions about the fundamental properties of the Universe and has all the ingredients to captivate the interest and imagination of students and the general public alike. Technical-related work can impact society in a number of ways: liquid xenon imaging detectors and related technologies find applications in several fields outside particle astrophysics, including national security and medical imaging research. Show more... | National Science Foundation | 8/24/2009 |
| PHOEBUS OPTOELECTRONICS, LLC | $99,872.00 | Grant |
Trans-NSF Recovery Act Research Support The grant is a Phase I Small Business Innovation Research award focused on the development of specialized infrared sensors called 'polarimetric sensors,' based on a new class of optical materials called 'metamaterials.' The sensors under development have the potential to dramatically improve the sensing capabilities of infrared remote sensors used for satellite-based global mapping, homeland security and military applications, which currently represent a $1 billion market. During the 6-month effort, Phoebus plans to design, model, produce and characterize an initial prototype metamaterial-based polarimetric sensor. We expect that our initial prototype will yield key performance metrics (i.e., polarization extinction ratios) that are 25x better than those of current polarimetric sensors. Achievement of these results would represent a major breakthrough in remote sensing technology, and would open a clear path to commercialization of the technology Show more...
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National Science Foundation | 6/02/2009 |
| ALLIANCE FOR INCLUSION IN THE ARTS | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/08/2009 |
| MABOU MINES DEV FOUNDATION | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/15/2009 |
| MOVING IMAGE, INC. THE | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of artistic programmin | National Endowment for the Arts | 7/07/2009 |
| WOMEN MAKE MOVIES INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| AMERICAN SYMPHONY ORCHESTRA INC | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/13/2009 |
| OPUS 118 HARLEM SCHOOL OF MUSIC | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/21/2009 |
| AMERICAN SYMPHONY ORCHESTRA LEAGUE | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/13/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $110,920.00 | Grant | Trans-NSF Recovery Act Research Support The PI's proposed research is concerned with the study of canonical Kahler metrics on algebraic varieties. There are deep conjectures relating the existence of extremal metrics to stability of the underlying algebraic variety and understanding this relationship has been studied intensively in the last decade. One major aspect of the PI's research is what one can say when no extremal metric exists. This problem will be studied both on the algebraic side to understand how varieties can be destabilized, and also in terms of metrics, which involves extending many of the existing results on extremal metrics to non-compact manifolds with cusp-like singularities along divisors. Another direction in the PI's proposal is the use of geometric flows to attack the existence of canonical metrics. Here too one of the most fascinating aspects is to study what kinds of singularities can form when no extremal metric exists and the PI will build on his earlier work on the Calabi flow on ruled surfaces and toric varieties and on the Kahler-Ricci flow. Geometric partial differential equations govern much of the physical world. For example solutions of Einstein's equations are intimately related to our understanding of the universe. The proposed research studies differential equations related to Einstein's equations and the key question is how the global structure of a space influences the local, analytic properties of the solutions of such equations. Understanding this phenomenon will have applications in physics and the sciences in general. Show more... | National Science Foundation | 9/21/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $368,585.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses the broad Challenge Area: 08: Genomics, and the specific Challenge Grant Topic: 08-AG-105**: Approaches to study the interactions among individual behaviors, social and physical environments, and genetic/epigenetic processes during critical developmental periods. Project Title: Early Life Exposures before Birth and Adult Epigenetics Extensive epidemiologic evidence has linked many early life and environmental factors to adult- onset diseases. One plausible mechanism how the environment could alter disease risk later in life is through epigenetic effects on somatic cells, leading to activation or silencing of key genes in critical pathways. DNA methylation, one type of epigenetic change, may play an important role in disease causation by altering the proteins that are produced by genes. Thus, people with identical genes, like twins, may have different disease outcomes because of differential changes in DNA methylation that affect the ability of specific genes to produce specific proteins. Human studies have supported that DNA methylation patterns change with age and animal studies have supported that exposures during critical periods can alter epigenetic events. However, until now, there have been few opportunities to link these two lines of evidence in humans by examining exposures during critical periods including the prenatal and early life periods and DNA methylation patterns latter in life. We have recently completed the first study in humans showing associations between early life factors such as birth weight and genomic DNA methylation measured in mid-life among women in a multiethnic birth cohort (1) and also the first study to show that there are persistent epigenetic differences in DNA methylation of the IGF2 gene after exposure to a prenatal famine environment (2). Using resources from an adult follow-up already collected from three birth cohorts in the Netherlands with prenatal famine exposure in born in 1944-1945 and from unexposed time controls and sibling controls (n= 971; 437 men and 537 women), we now propose to examine the associations between maternal famine exposure in the periconceptional period and in different stages of pregnancy on the one hand and DNA methylation patterns in adulthood on the other. We will further examine how the DNA methylation patterns in adulthood are related to disease risk factors for cardio-vascular disease and diabetes such as obesity, elevated blood cholesterol or fasting glucose values. Because some studies suggest that the relation between the early environment and long-term health outcomes may be different in men and women, we will compare these patterns by gender. The field of epigenetics holds great promise in helping us understand the basis of human disease and in particular how environmental exposures can get inside the body to cause disease. Epigenetics may also help explain differences in disease across populations and therefore may be important in understanding how environmental exposures may contribute to health disparities. Conducting large epidemiologic studies with robust measures of exposures based on information already collected in the past during critical periods combined with reliable markers of DNA methylation today are a necessary first step. Such studies can only be conducted by multidisciplinary teams with an understanding of biological mechanisms and methodological issues. Our team has extensive expertise in the design and analysis of life course studies in the US and abroad and is very experienced in dealing with the many methodological issues of critical periods, DNA methylation, and multiple disease outcomes. The full abstract for this award is available at http://projectreporter.nih.gov. Show more... | National Institutes of Health | 9/29/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $27,682.00 | Grant | Trans-NIH Recovery Act Research Support The 1918-20 influenza pandemic was the largest, most lethal epidemic in modern: history. It spread over the entire world in about six months and killed between 20 and 100 million people. Yet, despite such a devastating event, there is little detailed information on how and when the influenza epidemic spread throughout cities and countries in the world, especially the U.S. Because the last influenza pandemic was in 1968, the threat of a future pandemic looms large. It is, therefore, important for public health in the U.S. to not only understand the timing and spatial course of the 1918 pandemic, but to also understand how this great event might have affected the timing and spread of Influenza in non-pandemic seasons. This knowledge could inform targeted prevention strategies for a future pandemic. The proposed research seeks to use weekly mortality data from historical sources and lab surveillance data from the National Respiratory and Enteric Viruses Surveillance System (NREVSS) to study the timing and spread of influenza through the U.S. during pandemic and non pandemic seasons. The first aim of this research is to develop models of the temporal and spatial aspects of influenza In the U.S. for four pandemic and non-pandemic periods: the 1918- 20 pandemic, 1914-1917 Influenza seasons, 1920-1923 influenza seasons, and 1997-2007 influenza seasons. For each influenza season, the week of the first report of influenza mortality or lab confirmation will be plotted for each city and spread vectors will be constructed from this sequence of dates. Models will also be constructed by determining the average time to death or lab confirmation for each city for each season and then constructing linear trend surfaces, which will be plotted on a separate map. The direction of the wave progression will be marked by a vector on each map. The second aim of this study is to compare the time and spatial progression of the 1918 pandemic in the U.S. with those of non-pandemic years. The U.S. will be divided into nine regions to allow for easier analysis and bi-proportionate analysis will be used to compare the spatial and temporal aspects of influenza in pandemic years with those in non-pandemic years. This method will allow the analysis of the combined space-time variability in influenza in the U.S. by standardizing the relative intensity of influenza throughout the years. The completion of these aims and these methods has broad application for disaster preparedness, such as pandemic planning and bioterrorism. Knowledge of the timing and spatial course of influenza in the U.S. could severely limit the impact of a future pandemic and allow public health professionals to more effectively utilize interventions. Show more... | National Institutes of Health | 7/17/2009 |
| RFCUNY - CITY COLLEGE | $408,078.00 | Grant | Trans-NIH Recovery Act Research Support NIH Challenge Grants and Partnerships Program: NIH | National Institutes of Health | 9/23/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $385,703.00 | Grant | Trans-NIH Recovery Act Research Support The objective of this grant is to implement a high throughput screen for small molecules that potentiate the activity of FosB, a transcription factor that promotes resilience and antidepressant-like responses in several animal models and is deficient in the brains of depressed humans. FosB, which is induced in certain brain regions by chronic stress, represents a positive, coping mechanism that promotes positive adaptation to stress. 1) FosB induction in brain by chronic stress correlates with an animal's resilience to the deleterious effects of the stress. 2) Using viral-mediated gene transfer or inducible and brain region-specific bitransgenic mouse models, overexpression of FosB in these specific brain areas is sufficient to render animals resistant to subsequent stress and to reverse behavioral abnormalities induced by chronic stress. 3) Conversely, overexpression of a dominant negative antagonist of FosB in these brain regions makes animals more vulnerable to stress. 4) Chronic administration of standard antidepressant medications also induces FosB in these same brain regions, and overexpression of the dominant negative antagonists of FosB block the antidepressant-like behavioral effects of these medications in several behavioral assays. 5) Depressed humans have lower levels of FosB in these brain regions compared to extensively matched control subjects. This is the ideal time to submit this Challenge Grant, since we are poised to initiate the proposed studies immediately and they can be completed within two years. Thus, Drs. Eric Nestler and Gabby Rudenko have developed a novel high throughput screen to identify small molecule potentiators of FosB. An initial screen of ~50,000 compounds has identified ~500 hits that now require substantial validation. A series of validation assays, first in vitro and then in vivo, have also been developed. While targeting a transcription factor for psychiatric drug development is highly novel, several factors suggest that it represents a viable, albeit high risk, approach. For example, FosB is expressed at low levels throughout brain and peripheral tissues under normal conditions, suggesting considerable tissue specificity. Moreover, even if small molecule FosB activators prove unsuitable for the treatment of depression, high affinity, small molecule ligands for FosB would be invaluable tools to help us better understand FosB action in brain. Such molecules also could potentially be used to image FosB in the living human brain by use of PET or related brain imaging technologies, which would be a major boon to clinical investigations in depression and perhaps represent a novel tool to diagnose depression or other stress-related disorders or to track a patient's progress during treatment. We have recently shown that induction of the transcription factor, DeltaFosB, in brain represents a positive adaptation that helps individuals cope with chronic stress. Interestingly, the protein is also induced in brain by standard antidepressnts treatments, and depressed humans show lower levels of DeltaFosB in brain. We now propose to identify small molecule activators of DeltaFosB as novel treatment agents for depression. Show more... | National Institutes of Health | 9/24/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $499,826.00 | Grant | Trans-NIH Recovery Act Research Support Challenge Area: 14 --Stem Cells Challenge Topic: 14-MH-101*, 'Developing iPS cells for mental disorders' The recent description of somatic cell reprogramming to an embryonic stem (ES) cell-like phenotype, termed induced pluripotent stem (iPS) cell technology, presents an exciting venue toward cell-based models of disease mutations. This technology affords for the first time the potential to analyze neuronal cells grown from individuals carrying a given genetic lesion and offers a unique way of direct assessment of pathology. Recent studies have established an important role for rare copy number variants (CNVs, genomic deletions and duplications) in the etiology of schizophrenia and autism. Rare, but recurrent CNVs affecting the CNTNAP2 gene, a member of the neurexin family, have been described in both disorders. Given the high penetrance and clearly delineated genomic structure, which offers clear clues regarding the underlying functional deficit, this CNV is ideal to model at the cellular level, as well as at the level of the organism. We propose to generate iPS cells and iPS cell- derived forebrain neurons from schizophrenic patients carrying variable size CNTNAP2 gene deletions and their unaffected relatives and undertake an initial characterization of their basic morphological and electrophysiological properties. A unique aspect of our proposal is that the proposed comparisons will use as a reference point data acquired both in vitro and in vivo from hippocampal and cortical neurons from an animal model genetically engineered to carry a Cntnap2 gene deletion. Cell lines generated from individuals with schizophrenia carrying specific well-defined structural mutations offer an unprecedented opportunity to recapitulate pathologic human neural tissue formation in vitro and provide a unique platform for studies aimed at both providing valuable insights into the disease mechanisms, and the potential discovery of new compounds to treat this devastating disorder. PUBLIC HEALTH RELEVANCE: There is considerable promise in generating induced pluripotent stem (iPS) cell lines from patients afflicted with central nervous system diseases, including psychiatric disorders. We propose to generate neurons from patients with schizophrenia carrying CNTNAP2 deletions, a genetic risk factor for the disease, study their properties and compare them to brain neurons of a knock/out mouse model of the same gene. This is an unprecedented opportunity for the field to combine data from human neurons carrying a bona fide genetic risk factor for schizophrenia and an established mouse model of the same genetic lesion. Show more... | National Institutes of Health | 9/28/2009 |
| NEW YORK UNIVERSITY (INC) | $785,863.00 | Grant | Trans-NIH Recovery Act Research Support Cardiovascular disease is a leading cause of morbidity and mortality, accounting for upwards of 900,000 deaths annually in our country and many millions more worldwide. NYU School of Medicine has identified improved cardiovascular health as one of its key strategic priorities for the next decade. . Toward that end, the School of Medicine is Investing in faculty, facilities and infrastructure enhancements to support the continued growth of a world-class program in cardiovascular research, education, and patient care. As part of the NIH NHLBI ARRA/P30 mechanism, this application requests support for a start-up package to hire a Newly-Independent Investigator who will join our Division of Cardiology (Core Center) and the Cardiovascular Research Center. Following a national search, we have identified an extraordinarily promising newly-independent investigator poised to make Important contributions to cardiovascular health through fundamental and translational research in an area of great relevance to the NHLBI - vascular biology and disease. The new investigator will receive a tenure-track appointment in the Departments of Medicine and Cell Biology, and join our Sackler Graduate Program in Biological Sciences. He will join a vibrant research environment within the Division of Cardiology and the broader NYU community, with expertise that ranges from fundamental laboratory-based studies to patient-oriented clinical research. He will be provided with a generous start-up package designed to assure his success as a newly-independent investigator and support his evolution into a productive established investigator, including salary, programmatic and pilot project support for a period of no less than four years. Finally, the newly-independent investigator will benefit from a highly interactive and nurturing environment, with formal mentoring provided by senior investigators with a strong track-record of successful career development and collaboration. The recruitment of this new investigator will most certainly 'contribute to the building of a community of multidisciplinary researchers focusing on areas of biomedical research that are relevant' to the mission of the NHLBI. The clinical manifestations of vascular disease, including Ml, stroke and peripheral vascular disease, are responsible for enormous morbidity and mortality in the US. The newly-independent investigator we have identified is establishing a vibrant program exploring vascular disease pathogenesis. Insights from these studies have the potential to improve cardiovascular health, and therefore are of great biomedical relevance. Show more... | National Institutes of Health | 9/30/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $399,999.00 | Grant | Trans-NSF Recovery Act Research Support Intellectual Merit. High throughput sequencing that allows human genetics to access rare variation 'Next Generation' sequencing is transforming human genetics: several disruptive technologies are coming of age and now enable resequencing throughput of megabases per dollar. Specifically, thousands of individuals can now be sequenced for targeted regions of the genome, in pools of individuals. The complete spectrum of common and rare alleles thus revealed is a key resource for understanding origins, genomics, and heritable traits of our species. Nave tests of association of a heritable trait to a common variant are inappropriate for analysis of rare gene variants, since the contribution of each such rare variant to the trait is often statistically undetectable. The hope for finding an associated gene therefore lies in accumulating association signal across multiple functional variants. The problem of multiple-variant association is complicated by background correlations between nearby variants.This proposal tackles two challenges: 1.Initial task: Recovery of individual identity of mutation carriers from pooled sequencing data 2.Main task: Using individual-level mutation data for scoring of association to multiple variants in a locus. Proposed solution: Bayesian scoring, decomposable by individual and by variant. This proposal involves design of overlapping pools for recovering mutation carrier identity. Each individual will be sequenced in a unique combination of pools. Mutations observed in such a set of pools will be inferred to be carried by the corresponding individual, addressing the initial task. This proposal tackles the main task by Bayesian scoring for genomic intervals containing functional variants. Comparative genomics is used to guide a prior distribution for whether a sequenced variant is likely to be functional. The association score is further decomposed to contributions of each sample and each site, with Markovian dependency between such contributions along the genome. A dynamic-program is proposed for optimizing the causal locus boundaries. Broad Impact: The outcomes of the project would facilitate new paradigms in genetic research, alongside the recently launched high throughput experimental technologies. Specifically, projected impacts include: - software tools and tailored interfaces to be disseminated to the reseaerch community. - Education for undergraduates by project courses implementing proposed research tasks and for K-12 students by curriculum development and delivery to high-school diversity students - allowing a generation to have widespread access to their individual DNA. Show more... | National Science Foundation | 6/12/2009 |
| STEPHEN PETRONIO DANCE COMPANY INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/06/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $401,957.00 | Grant | Trans-NSF Recovery Act Research Support The research objective of this award is to develop a methodology for reliability and safety factor assessment of suspension bridge cables over time using real-time measurements from sensors installed inside the cables. Today, small-scale sensors that can measure environmental parameters like temperature, relative humidity, pH, etc. and that can be fit inside thousands of tightly compacted steel wires are becoming available and are being tested for application in suspension bridge cables. Using these measurements either from the initial construction or from the last in-depth inspection, the proposed methodology will provide an estimate of the current cable strength as it evolves with time, as a function of the environmental conditions. By looking at how the strength changes with time, it will be possible to estimate the rate of deterioration of the cable strength and to extrapolate it for future prediction of the strength variation. This evolution in time is expected to be a deteriorating one. The proposed methodology will be based on a Monte Carlo simulation based approach to account for all the uncertainties involved in the problem. This methodology will be integrated and validated with experimental tests on single bridge wires as well as on a full scale model of a suspension bridge cable. If successful, the results of the proposed research will represent a dramatic improvement over the current inspection methods that are unreliable (e.g. visual inspection) and expensive (e.g. unwrapping and wedging the entire cable). These results will be of major interest to every suspension bridge owning agency to assess the safety and to improve the maintenance of such structures. Undergraduate and graduate students as well as high-school students and teachers will be involved at different levels of the research. Show more... | National Science Foundation | 7/27/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $476,020.00 | Grant | Trans-NSF Recovery Act Research Support One emerging alternative to improving the state of inadequate, or decaying, infrastructure in urban environments, which does not involve a perpetuation of large scale, costly systems, is an approach known as low impact development (LID). LID interventions are small-scale interventions that be used at the building, lot or even neighborhood scale to conserve or reuse water, mange storm-water, and/or reduce energy demands. Because LID interventions are a distributed, rather than centralized, form of infrastructure, they also have the potential to build resilience into existing infrastructure systems. Furthermore, as less costly and more ?nimble? infrastructures, LID interventions hold promise as urban adaptation strategies in the face of uncertain of climate change impacts. A current LID intervention that is increasingly being adopted in urban environments to manage storm-water impacts, improve environmental conditions and reduce energy consumption, is green roof technology. A green roof is an environmental system that incorporates layers of specialized waterproofing and root-resistant materials, drainage or water storage layers, and a growing medium to support vegetation on a structure?s roof. Although green roofs have been in use for over thirty years in Germany, they are relatively new to North America. Nonetheless, green roofs are rapidly gaining popular attention in the U.S. and have recently become a high-profile component of sustainable building construction: They are lauded for provision of multiple benefits in the urban environment, including stormwater management, building energy savings, mitigation of the urban heat island effect and urban air pollution, and provision of habitat and aesthetic amenity. Numerous groups in the U.S. have initiated research programs to investigate green roof behaviors. These groups are using instrumented model roofs, green roof platforms and larger-scale green roofs on buildings in rural and peri-urban environments to further understanding of green roof performance under a variety of different conditions. The unique contribution of this project to this body of ongoing effort is the quantification of extensive green roof behavior in a dense urban environment, where the complexities of local eco- and climatic conditions, coupled with building density, are likely to significantly impact green roof performance. Over the course of three years, the project will develop a monitored Urban Green Roof Network to quantify: (i) the impact of different plant species and growing medium thickness on green roof behavior, (ii) the contribution of evapotranspiration to stormwater retention and reduction of urban heat island effects, (iii) the quality of green roof water run-off, and (iv) the ability of green roofs to trap air-borne particulates and take up other contaminants such as CO2. Results from the project will be used to improve scientific understanding of green roof performance in an urban environment and help identify green roof configurations that can maximize desired environmental performance objectives. The project will also determine whether data collected from small, instrumented ?green roof test boxes? located on urban roof-tops are useful indicators of urban green roof behavior, and examine the applicability of available groundwater/ geo-environmental modeling software for predicting green roof water balance. The project will enhance infrastructure for research and education by establishing an Urban Green Roof Network in New York City that can be used as a living laboratory for research and educational activities alike. In order to widely distribute project results to a broad audience, a green roof consortium, termed The Columbia University Green Roof Consortium, will be formed to provide a unique forum for urban stakeholders to interact and expand their knowledge of urban green roof behavior… The complete abstract for this award is available in Research.gov at: www.research.gov Show more... | National Science Foundation | 6/19/2009 |
| PROSPECT THEATER CO | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| GROUP 1 ACTING COMPANY INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $450,001.00 | Grant | Trans-NSF Recovery Act Research Support As both corporate and consumer-oriented applications introduce new functionality and increased levels of customization and delegation, they inevitably give rise to more complex security and privacy policies. Yet, studies have repeatedly shown that both lay and expert users are not good at configuring policies, rendering the human element an important, yet often overlooked source of vulnerability. This project aims to develop and evaluate a new family of user-controllable policy learning techniques capable of leveraging user feedback and presenting them with incremental, user-understandable suggestions on how to improve their security or privacy policies. In contrast to traditional machine learning techniques, which are generally configured as ?black boxes? that take over from the user, user-controllable policy learning aims to ensure that users continue to understand their policies and remain in control of policy changes. As a result, this family of policy learning techniques offers the prospect of empowering lay and expert users to more effectively configure a broad range of security and privacy policies. The techniques to be developed in this project will be evaluated and refined in the context of two strategically important domains, namely privacy policies in social networks and firewall policies. In the process, work to be conducted in this project is also expected to lead to a significantly deeper understanding of (1) the difficulties experienced by users as they try to specify and refine security and privacy policies, and (2) what it takes to overcome these difficulties. The latter includes developing models of the types of policy modifications users can relate to and exploit as well as an understanding of the tradeoffs between usability and the number of policy modifications users are presented with. It also includes understanding how the effectiveness of user-controllable policy learning is impacted by the expressiveness of underlying policy languages, modes of interaction with the user (e.g. graphical versus text-based), and the topologies across which policies are deployed. Show more... | National Science Foundation | 9/22/2009 |
| AMERICAN MUSEUM OF NATURAL HISTORY, THE | $402,615.00 | Grant | Trans-NSF Recovery Act Research Support The project is a three year survey of nearby stars to find faint companions of these stars and to analyze their spectra to study the chemistry and atomspheric structure. Ultimately, we aim to image planets orbiting nearby stars. Deliverables are published research papers over the course of the project, as well as training of a graduate student and a post doctoral scholar. Show more... | National Science Foundation | 7/13/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $470,000.00 | Grant | Trans-NSF Recovery Act Research Support The objective of this research is to develop an automated design environment for enabling the integration of emerging nanoscale silicon photonic optical interconnect device technologies in next-generation multicore computing architectures. The approach includes a comprehensive simulation framework capable of capturing low-level physical details of both optical and electronic components including, layout footprint, optical losses, and the energy consumption, while maintaining a cycle-accurate functional network simulation. Intellectual Merit: The photonic technologies used to create interconnection networks are fundamentally different from electronic counterparts in how they are designed and perform to achieve interconnect and routing functionalities. Therefore, to exploit the potential advantages of photonic interconnection networks in multicore architectures, a novel design methodology and toolset is developed from scratch in a manner that incorporates the physically different behavior of photonics and provides accurate performance modeling for future multicore systems. Unique to this effort, the physical layer parameters are derived from the design, fabrication, and characterization of real passive and active silicon nanophotonic building blocks devices. Broader Impact: The program advances multiple cross-disciplinary areas in networking, multicore computing architecture, interconnect capabilities and nanoscale silicon photonics. Included in the program are diversity outreach and educational training efforts that emphasize the cross-disciplinary nature of the field. The proposed suite of CAD tools will be made publicly available in an effort to improve the speed and realized complexity of nanophotonic enabled interconnection network development that are able to transform an abstract design concept into a physically-accurate, verified, complex photonic on-chip networks for multicore chip multiprocessors. Show more... | National Science Foundation | 8/06/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $140,456.00 | Grant | Trans-NSF Recovery Act Research Support Auroux-Donaldson-Katzarkov discovered a startlingly simple picture of smooth non-negative-definite 4-manifolds, generalizing Donaldson's interpretation of symplectic 4-manifolds as Lefschetz pencils. They view a 4-manifold, after blowing it up, as the total space of a broken Lefschetz fibration (BLF). In the simplest picture available, the blown-up 4-manifold X is the union of two 4-manifolds X_1 and X_2, each bounding a fibered 3-manifold Y, where X_1 is a Lefschetz fibration over a disc, and X_2 is essentially standard. This proposal focuses on computational and qualitative consequences of this escription. It concerns the Seiberg-Witten theory of broken Lefschetz fibrations and, more particularly, their 'Lagrangian matching invariants' - gadgets developed by the P.I. using symplectic geometry associated with BLFs which conjecturally recapture the Seiberg-Witten invariants. The P.I. will use conceptual tools from symplectic topology to compute Floer-theoretic invariants for the two parts of the 4-manifold: X_1 (combinatorially complicated but symplectic) and X_2 (simple but non-symplectic). These computations are directed at making inroads into some major open problems in 4-dimensional topology: existence of symplectic structures, Seiberg-Witten simple type, and algorithmic computation of Seiberg-Witten invariants. They aim to shed light on the algebraic structures of 3- and 4-dimensional gauge theory. Mathematicians regard 4 as the most mysterious dimension - more so than 2, 3, 5 or 1000. It is also the dimension of physical space- time, and equations devised by physicists have led to techniques that probe the topological structure of 4-dimensional spaces and show that they are governed by more complicated rules than anything in higher dimensions. So far, we have a very limited knowledge of what those rules are, and understanding them better is the focus for this project. Recent developments have shown that we can build all 4- dimensional spaces (technically, smooth, compact 4-dimensional manifolds) from simple but highly structured building blocks. This project will study how the known characteristics (invariants) for 4- dimensional manifolds can be understood in terms of those building blocks by invoking methods from another part of geometry that evolved from physics, symplectic topology. One aim is to elucidate what geometric information the invariants capture. Another is to seek genuinely new invariants. One can hope to do so by using the known invariants as a template; but that will require a deep understanding of how those invariants arise from the building blocks. Show more... | National Science Foundation | 7/13/2009 |
| BOND STREET THEATER COALITION LTD | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/13/2009 |
| NEW 42ND STREET, INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| THEATRE COMMUNICATIONS GROUP, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/13/2009 |
| GOTHAM ARTS EXCHANGE, INC. | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/13/2009 |
| BALLET TECH FOUNDATION, INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/06/2009 |
| OPERA AMERICA INC | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| ARCHITECTURAL LEAGUE OF NEW YORK INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| NATIONAL BOOK FOUNDATION, THE INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| LINCOLN CENTER FOR THE PERFORMING ARTS, INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/15/2009 |
| WORLD MUSIC INSTITUTE | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/20/2009 |
| APOLLO THEATRE FOUNDATION INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs which are thre | National Endowment for the Arts | 7/01/2009 |
| COLLEGE ART ASSOCIATION, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/14/2009 |
| ARTSCONNECTION INC, THE | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/23/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $336,532.00 | Grant | Trans-NSF Recovery Act Research Support This project is focused on implementing novel methods for uncertainty quantification in the context of modeling carbon sequestration. Significant advances in both the basic methodology and computational implementation are proposed. Advances in numerical methodology and computational implementation are planned to result in a tool that will be very effective at the petascale. The project will have a significant impact on a problem of great importance to society. The project will also integrate research and education. Show more... | National Science Foundation | 6/26/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $123,120.00 | Grant | Trans-NSF Recovery Act Research Support The principal investigator will probe the connection between Heegaard Floer homology and Khovanov homology, two theories, inspired by ideas in physics, that have transformed the landscape of low-dimensional topology during the past decade. The project will focus on one partially-understood connection--namely, the relationship between Khovanov theories of tangles and Heegaard Floer theories of their double-branched covers, first discovered by Peter Ozsvath and Zoltan Szabo and later reinterpreted, using Andras Juhasz's relative version of Heegaard Floer homology for sutured manifolds, by the principal investigator and Stephan Wehrli. The naturality of the connection under various TQFT-type operations suggests a path for developing Khovanov-type invariants for a wider class of objects in low-dimensional topology which should, in turn, yield new applications. The broad aim of the present project is to improve our understanding of the topology of 3- and 4-dimensional spaces, i.e., the properties of these spaces that remain unchanged under stretching and contracting (but not under tearing and gluing). Topological ideas underpin the development of efficient computer chips and information networks. The shapes of molecules and proteins determine their electrical properties and biological functions. Basing quantum computing algorithms on large-scale features of a quantum system minimizes their susceptibility to random error. Moreover, knot theory, the study of loops imbedded in 3-dimensional space, has become increasingly important in our understanding of how DNA behaves in cells. Show more... | National Science Foundation | 7/02/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $1,998,242.00 | Grant | Trans-NSF Recovery Act Research Support This project supports the acquisition of a plasma-beam-forming instrument to study the first stages of the formation of organic molecules in gas-phase interactions. The instrument will simulate energy levels and densities in interstellar space, and attempt to characterize physical conditions that might lead to the creation of the earliest organic molecules, and the combination of the first atoms and molecules into solid materials. Show more... | National Science Foundation | 9/21/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $100,077.00 | Grant | Trans-NSF Recovery Act Research Support This proposed research deals with methodological and inferential strategies in some non-standard problems that arise in certain non-parametric scenarios. The 'non-standard' problems include situations exhibiting non-standard asymptotics -- where estimators converge at rates different from the usual square-root-n rate and/or have non-normal limit distributions. In this proposal, the investigator studies three core directions of statistical research. These are: (A) (In)-consistency of different resampling methods in 'non-standard' problems, (B) Estimation and inference with shape restricted functions (where knowledge on the shape of the function, like monotonicity/convexity, is incorporated in estimation), and (C) Estimation of an appropriate 'threshold' in the domain of a function where sharp and potentially substantial changes ('regime changes') occur. There is an inherent lack of 'smoothness' in these problems (sometimes called the 'sharp-edge effect') that manifests in the non-standard rates of convergence and the non-normal limit distributions. Statistical inference in these 'non-standard' problems is difficult as the asymptotic distribution theory is complex (and in some cases unknown) with complicated limit distributions, containing nuisance parameters. Bootstrap methods are a natural alternative and are generally reliable in 'regular' square-root-n convergence problems. Although there has been extensive activity in the last two/three decades in understanding the behavior of bootstrap in different 'regular' scenarios, there has not been much work in such 'non-standard' problems, justifying the research projects undertaken in the proposal. The study of the problems has been greatly stimulated by an astronomy collaboration investigating the dark matter content and distribution in dwarf spheroidal (dSph) galaxies. Recent estimates show that the universe consists of about 96% dark matter and dark energy, though very little is known about them as yet. The dSph galaxies occupy a special position in this study -- they are supposed to be the smallest systems containing dark matter, and hence the study of these galaxies is of considerable importance in understanding the structure of the universe. The proposed research will also have diverse other applications, ranging from disciplines in public health like biomedical studies and epidemiology to aspects of the social sciences, especially economics. This is because 'non-standard' problems arise naturally in the analysis of productions of firms/companies (economics), the study of the risk of succumbing to illness or infection with age (biomedical research), in the investigation of 'sensitive' time periods (affecting health) in the early development of infants (epidemiology), and so on. The frontiers of the proposed research can be extended through incorporation in the Ph.D. level curriculum. Such interdisciplinary research will open up avenues of investigation in other realted areas of universal interest. Show more... | National Science Foundation | 6/14/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $659,995.00 | Grant | Trans-NSF Recovery Act Research Support A major issue in understanding how evolution has shaped social communication is determining how the brains and behavior of communication signal sender and receiver are matched so that signals such as vocalizations convey meaningful social information. Songbirds are used to address this issue because they have innate predispositions for producing and hearing the complex vocalizations (songs) of their own species. Yet, they must learn to produce their own songs during development and to recognize the songs of other birds. The aim of this project is to determine how the interplay of nature and nurture builds the brain mechanisms that mediate vocal communication by testing the relationship between species-specific vocal acoustics and neural auditory tuning, and the role of developmental experience in song production and auditory processing. Three related species that produce very different songs will be raised in the laboratory. Some will be cross-fostered so that birds of one species experience and learn the songs of another species. Using the integrated analysis of behavior, neurophysiology and anatomy, the contributions of genetic identity and experience to the matching of sender and receiver in vocal acoustics and auditory processing in the brain will be determined. Clear contributions of both genetic identity and developmental experience are expected to be demonstrated by hybrid songs and differences in auditory processing between birds raised by their own species and cross-fostered birds. This work will provide a demonstration of how perceptual mechanisms that guide learning and social behavior are created in the brain. Understanding how sensory function differs across species and how those differences are related to species-specific social behavior will describe general mechanisms whereby the brain evolves to support speciation and functional matching between sensory and motor systems. These studies are designed specifically to maximize the participation of undergraduate students in research, and the project includes outreach to the local middle school system. Show more... | National Science Foundation | 6/01/2009 |
| JAZZ AT LINCOLN CENTER, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/22/2009 |
| ANTHOLOGY FILM ARCHIVES INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/06/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $250,000.00 | Grant | Trans-NSF Recovery Act Research Support Wireless Mesh Networks have emerged as a solution for providing last-mile Internet access. By exploiting advanced communication technologies, they can achieve very high rates. However, effectively controlling these networks, especially in the context of advanced physical layer technologies, realistic models for channel interference, and distributed operation, remains a major challenge. Hence, the project focuses on developing effective and practical network control algorithms that make efficient use of wireless resources through joint topology adaptation, network layer routing, MAC layer scheduling, and physical layer power, channel, and rate control. The design of the algorithms leverages recent developments in the control of dynamical systems and randomized algorithms, and takes into account realistic channel models. This includes: (i) topology adaptation algorithms that take advantage of channel allocation, power control, and the controlled mobility capabilities of some of the nodes to dynamically decompose the network into sub-networks in which low-complexity distributed scheduling and routing algorithms are guaranteed to achieve high throughput, (ii) randomized distributed algorithms that solve the scheduling and routing problems in a computationally efficient manner using only local topological and queue size information, and (iii) evaluation of the algorithms? performance in terms of throughput, delay, and complexity. The developed algorithms will enable highly efficient operation of wireless networks. The project incorporates training of graduate and undergraduate students, outreach activities to local high-school teachers, and technology transfer to industry and government laboratories. Show more... | National Science Foundation | 7/29/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $302,302.00 | Grant | Trans-NSF Recovery Act Research Support Interactions between the interstellar medium (ISM) of a disk galaxy and the intracluster medium (ICM) of a massive cluster of galaxies will strip gas from infalling galaxies and can lead to color and morphological changes. These interactions can be used as a probe of both ISM and ICM physics. A recent wealth of new data includes observed tails and wakes, and although simulations have shed some light, much remains to be understood, including a mismatch between the predicted and observed width of wakes, the way in which dense, molecular gas is stripped, and the fate of the stripped gas. To answer these questions, this project will increase the realism of stripping simulations, first by adding radiative cooling to idealized galaxies with constant density and velocity winds, using a high-resolution, adaptive-mesh refinement hydrocode. Secondly, those systems will be placed in realistic cosmological simulations of cluster formation and evolution. Finally, the team will add important extra physical processes such as viscosity, heat conduction and magnetic fields into their simulations. Every stage will stress direct observational comparisons. The work will form the core of a PhD thesis, includes a number of projects suitable for undergraduate students, and will involve New York high school teachers and students through the Science Research Training Program. The growing realism of simulations enables high-quality visualizations to convey up-to-date research results to students and the general public, as the PI has done before, in collaboration with the National Center for Supercomputing Applications and the American Museum of Natural History. Show more... | National Science Foundation | 9/01/2009 |
| NEW YORK UNIVERSITY (INC) | $30,426.00 | Grant | ARRA - Nurse Faculty Loan Repayment Nurse Faculty Loan Program (NFLP) | Health Resources and Services Administration | 8/10/2009 |
| NEW YORK UNIVERSITY (INC) | $376,381.00 | Grant | Trans-NIH Recovery Act Research Support Multifunctional Block Copolymer Scaffolds for Bone | National Institutes of Health | 8/28/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $241,497.00 | Grant | Trans-NIH Recovery Act Research Support This proposal uses knowledge gained from extensive research into the activity of the influenza virus NS1 protein, to devise a strategy that will lead to the discovery of new influenza virus drug candidates. It is widely acknowledged that the consequences of an influenza pandemic could be devastating and that we do not have sufficient therapeutic resources available. Widespread resistance to the M2 inhibitors, and most recently to the neuraminidase inhibitors as well, makes it imperative that we develop new and improved antiviral drugs against influenza virus. We propose to use the influenza virus NS1 protein as a novel target for the discovery of the next generation of antiviral drugs. NS1 functions as an inhibitor of the innate immune response and its actions ultimately determine disease severity in the infected host. Specifically, NS1 prevents the production of interferon in response to virus infection. Influenza viruses that lack NS1 do not cause disease as the host immune response (the most powerful natural antiviral) can function normally and eliminate the virus. Thus, we reason that compounds which inhibit the interferon inhibitor, NS1, should work similarly to prevent virus growth and disease progression. We have developed a cell-based reporter assay for monitoring NS1 function which we will use to screen libraries of small molecular weight compounds and identify those that reduce the immune-suppressing actions of NS1. Such compounds represent new influenza virus drug candidates that can be further evaluated and developed to determine their full potential. PUBLIC HEALTH RELEVANCE: Influenza viruses cause a highly contagious, acute respiratory disease that affects 5-20% of the US population each year. There is heightened concern regarding resistance to both of the two classes of FDA-approved influenza antiviral drugs and therefore we are in great need of new antiviral drugs to treat and prevent influenza infections. In this proposal we describe using the influenza NS1 protein as a new target for finding the next generation of influenza antiviral drugs. Show more... | National Institutes of Health | 6/04/2009 |
| NEW YORK STATE COUNCIL ON THE ARTS | $399,900.00 | Grant |
Partnership Agreements To support the preservation of jobs that are threa
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National Endowment for the Arts | 4/29/2009 |
| CORNELL UNIVERSITY, INC | $413,951.00 | Grant | Trans-NIH Recovery Act Research Support The human malaria parasite, Plasmodium falciparum, possesses a broad repertoire of proteins that are proposed to be trafficked to the erythrocyte cytoplasm or surface, based upon the presence within these proteins of a signal peptide followed by a Pexel/HT erythrocyte trafficking motif. This catalog includes two large families of proteins that are the subject of this proposal: the predicted 2 transmembrane (2TM) proteins that likely function within the erythrocyte membrane, including the RIFIN, STEVOR and Pfmc-2TM families, and the PHIST domain family which likely function within the erythrocyte cytoplasm. The human malaria parasite, P. vivax, and the rodent malaria parasites possess large families of proteins which are topologically similar to the 2TM proteins and also harbor Pexel/HT motifs, suggesting that the function of the 2TM proteins is widely conserved in Plasmodium. We have shown using primary and second generation clonal lines of the P. falciparum isolate, NF54 that expression of stevor and Pfmc-2TM families is clonally variant and undergoes switching. Moreover, the STEVOR and Pfmc-2TM families possess a loop between the 2TM domains that is hypervariable both between paralogs and across isolate boundaries, suggesting that it is exposed to host immune pressure at the erythrocyte surface. Thus host immune pressure has likely driven the amplification and antigenic diversification of the 2TM protein families, and a mechanism of gene expression switching insures that immune responses do not eliminate parasite infections. The topological and sequence similarity of the 2TM proteins to subunits of ion channels prompted us to consider that they might encode the new permeability pathways (NPPs) of infected erythrocytes. We propose here to test this hypothesis using genetically manipulated parasite lines that either dominantly express epitope-tagged versions of 2TM proteins or are globally knocked down in 2TM protein expression via conscription of specific transcription factors. These parasite lines will be used phenotypic assays, such as sorbitol lysis and whole-cell patch clamp. We also present evidence that the methodology of gene knockdown via transcription factor conscription can be used to address the function of other sub-telomeric gene families in P. falciparum, and thereby are likely to contribute to our understanding of parasite-encoded modifications of the infected erythrocyte. We present preliminary studies on the gene expression and cellular localization of select PHIST domain proteins and propose to pursue their function via targeted gene disruption as well as determination of predicted protein-protein interactions within the erythrocyte cytoplasm. In this manner we hope to generate hypotheses on the identity of the functional pressures which have driven the amplification of the PHIST domain family to over 6 members in P. falciparum. Show more... | National Institutes of Health | 7/17/2009 |
| MAKING BOOKS SING, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/20/2009 |
| LUBOVITCH DANCE FOUNDATION INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/08/2009 |
| DANSPACE PROJECT, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/08/2009 |
| FOUNDATION FOR INDEPENDENT ARTISTS, THE | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/09/2009 |
| PAUL TAYLOR DANCE FOUNDATION | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| TRISHA BROWN COMPANY, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| AMERICAN PLACE THEATER INC, THE | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/20/2009 |
| SMACK MELLON STUDIOS INC | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| AMERICAN MUSIC CENTER, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/13/2009 |
| YOUNG CONCERT ARTISTS INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/21/2009 |
| CARNEGIE HALL CORPORATION, THE | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| SOCIETY OF THE THIRD STREET MUSIC SCHOOL SETTLEMENT INC | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| VIVIAN BEAUMONT THEATER INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/15/2009 |
| DANCE THEATER WORKSHOP INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/08/2009 |
| BALLET HISPANICO OF NEW YORK | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/06/2009 |
| FOUNDATION FOR DANCE PROMOTION INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/10/2009 |
| JOSE LIMON DANCE FOUNDATION, INC. | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $200,000.00 | Grant | Trans-NSF Recovery Act Research Support The Division of Chemistry supports Alon Gorodetsky of Columbia University as an American Competitiveness in Chemistry Fellow. Dr. Gorodetsky will develop chemically modified carbon nanotubes (with attached DNA) to be used in field effect transistors. The suitability of these molecular electronic devices to detect small quantities of proteins will be assessed. Dr. Gorodetsky will conduct experimental work in collaboration with scientists at Columbia University, and will work with theorists at Brookhaven National Laboratory. For his plan for broadening participation, Dr. Gorodetsky will recruit and mentor women chemists from Stern College, Yeshiva University in research to be conducted in the laboratories of Prof. Colin Nuckolls at Columbia University. Research like that of Dr. Gorodetsky is aimed at developing new sensors for biological molecules. The ultimate goal of research like this is to develop improved methods for the rapid detection of important biological molecules (e.g. cancer biomarkers) to aid researchers and clinicians in making measurements quickly and inexpensively. The efforts at broadening participation being pursued by Dr. Gorodetsky are aimed at increasing the participation of young people from underrepresented groups in the sciences. Show more... | National Science Foundation | 9/06/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $57,005.00 | Grant | Trans-NSF Recovery Act Research Support The objective of this research is to investigate novel architectures for the realization of ultra-low-power, integrated, pulse-based, ultra-wideband radar and imaging sensors. The approach is to exploit compressive sensing for high-speed baseband processing to simultaneously achieve high dynamic range while consuming ultra-low power. Ultra-wideband, pulse-based radar and imaging sensors require high-speed baseband processing. Compressive-sensing-based architectures take advantage of the presence of inherent structure in the received radar signal, specifically its time-domain sparsity, to significantly reduce the required sampling rate (and hence, power consumption) while preserving the information contained in the signal. The intellectual merit of the proposed research is to devise and investigate the feasibility of compressive-sensing-based ultra-wideband radar and imaging architectures through theoretical and simulation-based studies of the robustness of compressive sensing to practical issues such as noise, interference, presence of insufficient sparsity, and circuit imperfections such as clock jitter. These studies will be linked to measurements performed with prototype radars constructed with off-the-shelf components. The broader impact of the proposed research is in its ability to transform the current vision of ambient intelligence. The low-power and low-cost nature of silicon-based ultra-wideband radar and imaging sensors utilizing compressive sensing potentially enables ubiquitous deployment of massive sensor networks, which can have a dramatic impact on the quality of day-to-day life. The proposed research also bridges the disciplines of integrated analog- and digital-circuit design, signal processing and applied mathematics. This proposal will support the education and training of a graduate student researcher, who will develop skills in all these fields. Show more... | National Science Foundation | 8/27/2009 |
| POETRY SOCIETY OF AMERICA, THE | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| CHASHAMA | $50,000.00 | Grant | Awards to Organizations and Individuals To Support the preservation of jobs that are threa | National Endowment for the Arts | 7/14/2009 |
| NATIONAL NETWORK FOR FOLK ARTS AND EDUCATION, THE | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| NONPROFIT FINANCE FUND | $1,900,000.00 | Grant | The $1.9 million award has pirmarily created a loan pool for pre-development purposes for nonprofit organizations. Organizations will use these loans for reasons including (but are not limited to) environmental assessments; architectural, engineering, and legal fees; feasibility and marketing studies; and business plan development. This product is largely unavailable for our typical clients; by offering such capital, we can help these organizations stabilize or expand their operations and enhance their services. 15% of the award will be used to support loan loss reserves for the organization. Show more... | Community Development Financial Institutions | 6/29/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $17,060.00 | Grant | Trans-NSF Recovery Act Research Support The goal of this project is to explore the link between public demand for and elected officials? supply of efficient, responsive government. In particular, it examines three distinct mechanisms for mobilizing grassroots pressure for good government, and tests the explanatory power of each mechanism through a field experiment in Indonesia. The first is a rights mechanism, which claims citizens will hold politicians accountable when they have a clear understanding of their entitlement to government-provided goods and services. In many new democracies, even this basic knowledge is fragile. The second is a taxpayer mechanism, which suggests citizens will only take action when they make fiscal contributions to government. Since many developing country governments collect only informal fees, taxes and bribes, the challenge is to encourage citizens to see themselves more as creditors than debtors to government. The third mechanism centers on capacity and highlights the importance not of strengthening the motivation but rather the ability to scrutinize by enhancing citizens? proficiency in basic budgeting and public finance issues. To test which mechanism has the most explanatory power, the researcher will partner with PATTIRO, an Indonesian advocacy organization, to conduct an information campaign with content that distinctly reflects the rights, taxpayer and capacity mechanisms. Individuals and villages will be selected to receive the information randomly. Similar to a clinical drug trial, random selection creates a 'treatment' group and a 'control' group that are identical in all key characteristics at the outset. Any difference in outcomes across both groups following the campaign can then solely be attributed to the impact of the campaign itself. The impact of each mechanism on individual attitudes and behavior toward accountability will be measured using a before and after survey of 1600 individuals sampled from both treatment and control groups. By identifying the individual level determinants of empowerment, this study will locate the origins of grassroots pressure for public goods and better government in developing countries. This project should be of interest not only to researchers seeking to understand when citizens hold elected officials accountable but also to the numerous development organizations interested in the most effective strategies for empowering the marginalized and politically disadvantaged. Show more... | National Science Foundation | 7/10/2009 |
| EARLY MUSIC FOUNDATION INC | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/14/2009 |
| PEARL THEATER CO INC, THE | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| FIJI THEATRE COMPANY INC, THE | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/16/2009 |
| SECOND STAGE THEATRE | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $136,135.00 | Grant |
Trans-NSF Recovery Act Research Support The Center for Ethnomusicology at Columbia University holds valuable recordings of traditional Iupiat (Native Alaskan) music recorded in Barrow, Alaska by collector Laura Boulton in 1946. Co-PIs Fox and Dr. Sakakibara are working with Iupiat community leaders, elders, and educators in Barrow, Alaska to 'repatriate' these recordings (and an associated set of photographs held by Indiana University's Archive of Traditional Music), and to collect oral historical important information about the recordings (and an associated set of recently-discovered photographs taken during Boulton's expedition and currently belonging to Indiana University's Archive of Traditional Music). By conducting systematic oral historical interviews with elders and community leaders concerning the contents, significance, and proper future management of the recordings and photographs, the research team is working to make these materials useful and accessible for contemporary Iupiat musicians and dancers, for Iupiat language and culture educators, for descendants of the original performers on the recordings, for the broader community, as well as for scholars of Inuit history and culture, under terms acceptable to all parties. Specifically, through this 'community partnered' repatriation work, the research team is working with Iupiat consultants to develop contemporary applications for these recordings through the creation of a secure and publicly accessible digital resource that will embed the original recordings and photographs in a rich explanatory context reflective of Iupiat cultural values? they are helping community-based music and dance performance groups to develop repertoires based on these recordings (and to explore other archival collections); they are consulting with leading Iupiaq educators to develop language-teaching applications for the materials; and they are working with the Iupiat Heritage, Language, and Culture Commission and colleagues to use this project to model the community's longer-term archiving needs for other valuable heritage materials in other archives and personal collections. Importantly, the research team is documenting the project itself through observation of the effects of our reintroduction of this music into the community. This project is a model for a new, experimental, approach to 'repatriation' of Native cultural heritage resources. By explicitly testing what the team proposes are innovative best practices for collaborative repatriation projects that benefit both Native communities and social scientists who work with these communities, they hope to demonstrate ways of handling the thousands of similar scholarly collections of Native cultural resources in archives and museums in the United States, many of which have not been repatriated at all in part due to what often appear to be intractable challenges inherent in the historical status of such archives and the emergent ethical and legal climate in which their repatriation must now occur. In addition to community-developed resources, the research will result in scholarly articles and a book intended to explore the implications of the project for archivists, scholars, and Native communities alike. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Science Foundation | 6/15/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $1,000,000.00 | Grant | Trans-NSF Recovery Act Research Support This award provides $40,500 per student per year in support to 8 graduate students to do research in various STEM (Science, Technology, Engineering and Mathematics) fields as defined in their individual applications to the Graduate Research Fellows Program. The graduate students will receive this annual support for three years. Show more... | National Science Foundation | 8/12/2009 |
| CITY LORE INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/01/2009 |
| CORNELL UNIVERSITY, INC | $500,002.00 | Grant |
Trans-NIH Recovery Act Research Support Dysfunction of GABAergic interneurons of the cerebral cortex has been implicated in a variety of major neuropsychiatric illnesses, including schizophrenia, autism, anxiety, and epilepsy (where depression is a major source of suffering). However, both our general lack of knowledge regarding how human interneurons develop and function, and our specific lack of knowledge of how disease-related genes may influence this process, greatly hinder our ability to understand, prevent or to treat interneuron-related mental illness. Induced pluripotent stem cells (iPSCs) are an important potential source of human interneurons that could be used to address both genetic influences on interneuron development and function, and to study genetic-environmental interactions in this process. The goal of this proposal is to develop methods and protocols for the consistent derivation of function inhibitory interneurons from human iPSCs, to lay critical groundword for future studies on the role of inhibitory interneurons in neurosychiatric disease. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 9/30/2009 |
| UNDER 21 INC | $326,604.00 | Grant |
ARRA-Health Center Integrated Services development Initiative The Capital Improvement Project will allow Covenant House New York's Clinic to enhance the EHR system, eClinical Works (ECW), currently being implemented, and to replace medical equipment used during examination that is either broken or with newer, more effective apparatus. Implementing the EHR system will enable our clinical providers to maximize access to the clients’ electronic medical information and in turn eliminate the repetitive testing that occurs amongst the homeless population. It will also allow our providers to coordinate and facilitate easier access to healthcare records for this population. By so doing, the patients will benefit from a decreased waiting time and more efficient services. Our Clinic is the largest healthcare provider for homeless youth, a population that has expanded due to the severe economic downturn. Over the last four years, the clinic has had 8173, 8429, 9731 and 10,179 encounters respectively. This project will increase our software licenses and provide system training for the clinic’s supportive services providers such as those working with our mental health patients. The equipment purchased with the grant will also increase the overall effectiveness of all clinic staff using the EHR system through the utilization of new computers and hardware such as the scanner. This project will also facilitate the addition of 1 FTE's to the current health clinic staff as well as the retention of 1 FTE within the agency who is the Technical Manager on the project. The Technical Manager is working in conjunction with the eClinical Works Project Manager and the Medical Director during our current implementation to install the software components. He will also be responsible for the software implementation and supporting the staff with technical difficulties and software issues. The new FTE is an Administrative Assistant who will assist the Medical Director so as to free her up from administrative tasks and data gathering so that the Director can focus more of her time on the EHR implementation and the overall efficiency and effectiveness of the clinic. In addition to the implementation, the Medical Director manages the data gathering and reporting on all health clinic grants, supervises all of the clinicians and also provides direct patient care and consultation on other provider exams. Show more...
There were 114 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
Health Resources and Services Administration | 6/25/2009 |
| NATIONAL DEVELOPMENT AND RESEARCH INSTITUTES, INC. | $599,062.00 | Grant |
Trans-NIH Recovery Act Research Support Substance use among youth remains a major public health problem. About half of all 12th graders have tried an illicit drug and over 72% of this same age group have used alcohol. Rates of abuse of prescription opioids among youth are estimated to have increased about 542% in the past decade. Although effective substance abuse treatment programs for youth exist, they are currently of limited reach. Only 1 in 10 adolescents who need substance abuse treatment receive any care. The limited compatibility of research-based interventions with treatment agency realities may present numerous operational barriers to the transfer of evidence-based practice into community-based settings. An interactive, computer-delivered psychosocial intervention has the potential to address these challenges, as it allows for complex interventions to be delivered at a low cost, without increasing demands on staff time or training needs. It may also be highly acceptable to youth and enable widespread dissemination of sciencebased treatment in a manner that ensures fidelity. In this application, we propose to develop and evaluate the efficacy of an evidence-based, computer-delivered, psychosocial intervention for adolescents in treatment for substance use disorders. To our knowledge, the planned program will be the first interactive program to provide comprehensive, psychosocial substance abuse treatment to adolescents via computer-based technology. AIM 1: Develop an interactive, computer-delivered, psychosocial treatment for adolescent substance use disorders, which will be grounded in the Adolescent Community Reinforcement Approach (A-CRA), a behavioral treatment for adolescents of demonstrated effectiveness and cost-effectiveness. AIM 2: Evaluate the efficacy of the computer-delivered intervention with adolescents in outpatient treatment for substance use disorders. Adolescent participants in a controlled trial will be randomized to (1) computer-delivered A-CRA or (2) standard treatment. We will evaluate the relative efficacy of these interventions on the primary outcome of objective substance use and secondary outcomes of treatment retention, self-reported drug use, HIV risk behavior, therapeutic alliance, psychosocial functioning, and the extent to which participants report their treatment needs are adequately met. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
Department of Health and Human Services | 7/16/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $840,777.00 | Grant | Trans-NIH Recovery Act Research Support Childhood aggressivity at age 7 is associated with a fourfold increased risk for illicit drug dependence at age 25. Despite high rates of aggressivity in children with histories of parental neglect, theory-driven and efficacious drug prevention programs to curtail key precursors of youth substance use initiation (SUI) have not been adapted nor experimentally evaluated with neglected children placed in regular foster homes. The proposed project addresses this critical gap by initially testing a multi-component (child, parenting, and co parenting) early drug prevention intervention for children, their biological parent, and foster parent. The psychosocial intervention is based on a transtheoretical approach (psychobiology of neglect, social learning theory, and family systems) to show improvement primarily in early predisposing SUI processes, child aggressivity, and positive parenting, and secondarily in neuroendocrine (cortisol) functioning, supportive co parenting, and foster home stability by: (1) child training; (2) parenting training; and (3) co parenting training. The intervention is delivered via 12-week Parent and Child Groups which utilizes the Incredible Years programs adapted for a foster care population and led by trained hybrid university-foster agency worker teams. Parenting and Co parenting components are integrated in a joint (multiple biological and foster pairs) parent group format. Groups take place in the foster agency where the children are served. Five foster care agencies and NYU Child Study Center have joined in a community-academic partnership to implement the pilot intervention with N = 100 families. The study uses a within agency design to assign families to intervention (N= 50) or a 'usual care' comparison (N = 50) conditions. A plan to reduce contamination risk is in place. Due to their maltreatment histories, all participating children are considered high-risk for child aggressivity. Three assessments will be conducted: pre-intervention (wave1), postintervention (wave2), and 6 month follow-up after intervention (wave3). Data are gathered from the biological parent, foster parent, child, teacher, a trained observer, and CPS records regardless of whether the child remains in foster care, is discharged home, or enters a preadoptive home. We will complete power analyses regarding the magnitude of intervention effects in primary and secondary outcomes in preparation for a large-scale clinical trial; and feasibility studies (attendance and fidelity) involving this multi component intervention. This application has considerable public health relevance because it will provide information of the value of training frontline foster agency workers in evidence-based interventions, and potentially serve as a model for promoting efficacious protection to SUI for underserved high risk children and their families. Show more... | National Institutes of Health | 8/31/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $41,176.00 | Grant | Trans-NIH Recovery Act Research Support Chronic hepatitis C virus (HCV) infection afflicts about 3 million people in the United States and is the leading indication for liver transplantation (CDC, NHANES III). Currently treatments are effective in only about 50% of patients. Improved treatments and improved methods for studying HCV are a research priority of NIDDK. This project addresses a significant research need by introducing novel cell cultures system for HCV and by introducing methods that are needed to define the structure of the HCV replication intermediate. The cells to be used are mononuclear cells derived from both peripheral blood (PBMCs) and from ascitic fluid (AMCs). In Specific Aim I, we will monitor changes in HCV RNA over time and measure the inhibitory effects of interferon-? and 2'-methyl adenosine (Merck), an inhibitor of the HCV RNA-dependent RNA polymerase, using Real time PCR. Using specialized equipment we developed for this purpose, we will heat RNA extracts to temperatures over 100 C and thereby release genomic (+) and antigenomic (-) HCV RNAs from replication intermediates. Strand-specific PCR assays will be used to detect positive (+) and negative (-) strands. In Specific Aim II, we will investigate the changes in HCV RNA replication that are produced by exposure of cells to cytokines and we will identify HCV mutations associated with high-level replication. The experiments in this aim will define culture conditions for optimal HCV RNA replication. HCV sequence analysis will be performed on the HCV RNA derived from PBMCs and AMCs. In Specific Aim III, we will carry out in-depth analysis of the structure of the HCV replication intermediate and determine the ratio of genomic and antigenomic strands. We postulate that the antigenomic strands within the replication intermediate are almost entirely involved in RNA-RNA duplex structure, while the genomic strands contain both single- and double-stranded regions. Strand-specific PCR amplification will be performed on several HCV gene regions to identify domains that are accessible to PCR primers. In Specific Aim IV, we will be used to investigate the infectivity of cell culture supernatants from the system optimized in Aim II by exposing HCV-naive mononuclear cells to supernatant from the optimized HCV-culture system. Public Health Relevance: The hepatitis C virus (HCV) is a major public health treat; chronic infection causes about 10,000 deaths in the U.S. each year and the number is rising. The development of improved treatments is a research priority. The goal of this project is to develop a model system to study HCV. Our project will contribute to the development of more effective interventions Show more... | National Institutes of Health | 7/17/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $47,210.00 | Grant | Trans-NIH Recovery Act Research Support The 1918-19 influenza virus claimed the lives of more than 20 million people worldwide and the determinants of its extreme virulence are currently under investigation. Influenza A virus harbors a segmented, negative-sense RNA genome contained within an envelope that is decorated with 2 surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The HA mediates both attachment to the host cell via sialic acid and subsequent fusion between the viral envelope and host endosomal membrane. Proteolytic cleavage of HA is a requirement for virus fusion and thus for multicycle viral replication. 1918 influenza virus replication occurs independently of trypsin in cell culture, although it does not contain the multibasic cleavage site within HA normally associated with this feature, such as that found in the highly pathogenic H5 and H7 influenza viruses. Previous work suggests that 1918 NA can facilitate the cleavage of HA, pointing to a mechanism of HA cleavage distinct from H5 and H7 viruses. Our hypothesis is that the ability of NA to facilitate HA cleavage plays a role in the extreme virulence of 1918 influenza virus. The rationale for these studies is based on preliminary data and analogous studies performed with an additional H1N1 virus, A/WSN/33, which point to a role of NA-mediated HA cleavage in pathogenesis. This proposal aims to determine the mechanism of 1918 NA facilitation of HA cleavage, to identify the specific residues in 1918 NA providing this ability, and ultimately, to explore the contribution of this NA activity to pathogenesis. Our approach is to use a combination of virion and cell-based fusion assays to establish a mechanistic model of this phenomenon and to generate recombinant viruses bearing mutant 1918 NAs to determine their effects on 1918 replication in vitro and pathogenesis in vivo. These studies will provide insight into the early events of 1918 influenza virus infection and its mechanism of pathogenesis. By examining the role of NA-mediated HA cleavage in 1918 influenza pathogenesis, we hope to achieve a heightened understanding of the factors that contribute to influenza virulence, which can be monitored in emerging avian influenza viruses. Knowledge of these genotypic signatures of virulence will allow the development of improved predictive measures, prevention techniques, and treatment strategies. Show more... | National Institutes of Health | 6/04/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $418,885.00 | Grant | Trans-NIH Recovery Act Research Support Highly specialized professional antigen presenting cells are distributed throughout the skin and include epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs). Our laboratory established some unique properties of cutaneous DCs. We discovered that in contrast to lymphoid organ DCs, LCs fail to develop in mice that lack the receptor for macrophage ny stimulating factor (MCSFR) (Ginhoux et al. Nat Immunol 2006). We established that in contrast to most DC populations, LCs are maintained by radioresistant hematopoietic precursors that have taken residence in the skin in the steady state (Merad et nature immunology 2002; Merad et al. Nature medicine 2004). We also found that a subset of dermal DCs derive from radioresistant precursors, while the majority derives from circulating radiosensitive precursors (Bogunovic et al. Jem 2006). More recently, we identified a novel population of dermal DCs that express the c-type lectin receptor langerin, thought to be a LC hallmark the skin. In contrast to LCs, dermal langerin+ DCs are recruited from the blood and sojourn briefly in the skin before migrating to the lymph node charged with skin antigens (Ginhoux et al. Jem 2007). These results underline the complexity of the cutaneous dc network system, but 'the raison d'etre' and the mechanisms that regulate the development of this complex system is elusive. In this grant application, we propose to dissect the origin of DC populations in the skin, identify the key molecules that control their development and examine the contribution of each dc compartment to skin immunity. Preliminary data suggest that a wave of LC precursors seed the epidermis during embryonic life. Thus in aim 1, we propose to ex the potential of these embryonic precursors to maintain LC homeostasis throughout life. Mice that are deficient for MCSFR or tgfb1 lack epidermal LCs but the exact role of MCSF and tgfb1 in LC ontogeny is unknown. In this aim, we propose to examine how these molecules control LC development. Preliminary data also suggest that distinct precursors and differentiation pathways control the development of dermal langerin+ and dermal langerin- DCs. Thus in aim 2, we propose to identify the dedicated precursor and the mechanisms that control the development of dermal dc subsets. Finally, we believe that such complex dc network has developed to ensure skin integrity and in aim 3, we propose to examine the contribution of each DC compartment to skin immunity.) PUBLIC HEALTH RELEVANCE: We have recently established that three dendritic cells subsets with separate lineages co-exist in the skin. In this grant application, we propose to dissect the origin of DC populations in the skin, identify the key molecules that control their development and examine the contribution of each DC lineage to the initiation of skin anti- microbial immune responses. We believe that these results will contribute to a better understanding of the immunological cues that govern skin immune responses. These results should also contribute to the design of novel vaccine strategies. Show more... | National Institutes of Health | 7/23/2009 |
| CORNELL UNIVERSITY, INC | $338,362.00 | Grant | Trans-NIH Recovery Act Research Support PTEN Deficiency and Tumor Development PTEN is one of the most frequently mutated genes in human cancer. We have previously demonstrated that PTEN plays an essential role in the maintenance of genomic stability and that PTEN controls genome integrity through multiple mechanisms. The mitotic checkpoint is the most important mechanism for ensuring accurate chromosome segregation during cell division. Our preliminary data show that knockdown of PTEN causes severe mitotic misalignment and increases the frequency of monopolar and multipolar spindles, suggesting that PTEN deficiency impairs kinetochore congression and spindle bipolarity. Moreover, disruption of Pten eliminates the mitotic checkpoint response to spindle damage. We also found that the levels of Bub1 and aurora B which are two critical mitotic checkpoint regulators are reduced in Pten null cells. In this grant application, we propose that PTEN plays a critical role in mitotic checkpoint control and spindle assembly. Our first specific aim is to characterize how PTEN deficiency affects kinetochore functions, spindle assembly and mitotic checkpoint activity. To do so, we will identify potential kinetochore or spindle factors physically associated with PTEN during mitosis. We will also determine whether wild-type PTEN can correct mitotic errors and restore the mitotic checkpoint. Our second specific aim is to determine whether the phosphatase activity of PTEN is necessary for its mitotic function and further define the functional domain of PTEN responsible for bipolar spindle assembly and the mitotic checkpoint. A variety of PTEN mutants with and without the N-terminal phosphatase domain will be tested for their ability to establish spindle bipolarity, sustain the expression levels of checkpoint proteins, and maintain a functional mitotic checkpoint. Our third specific aim is to explore the mechanism of how PTEN participates in the regulation of Bub1 and aurora B in synergy with E2F-1. Our preliminary chromatin immunoprecipitation assays identified both PTEN and E2F-1 on the mitotic gene promoter, which suggests there is functional cooperation of PTEN and E2F-1 on chromatin. We will therefore determine how PTEN acts on chromatin to modulate the transcriptional regulation of mitotic genes by E2F-1. Our final specific aim will be to further evaluate the role of PTEN in controlling the mitotic checkpoint and chromosomal stability using a Cowden syndrome model where PTEN is inherently mutated. We will examine the mitotic checkpoint activity in human lymphocytes with mutant PTEN. We will characterize the gain of function of PTEN mutants and determine whether these dominant-negative PTEN mutants disrupt the mitotic checkpoint and induce chromosome instability. Finally, we will use a PTEN189 mutant knock-in mouse model to determine whether the PTEN189 mutation causes genomic instability and results in tumorigenesis. Successful completion of this project will define PTEN as a controller of the spindle checkpoint and a guardian of the genome. New findings from this project may provide insights into the mechanism whereby PTEN deficiency and consequent mitotic dysfunction lead to tumorigenesis. PUBLIC HEALTH RELEVANCE: PTEN Deficiency and Tumor Development Narrative The PTEN tumor suppressor is frequently mutated in a variety of human cancers. Loss of PTEN leads to tumorigenesis in mouse models. The mitotic checkpoint is a major mechanism for ensuring chromosome inheritance and preventing malignancy. This project will explore novel functions of nuclear PTEN in maintaining genomic stability by revealing its critical role in spindle assembly and chromosome segregation. New findings from this study will answer the fundamental question of how PTEN deficiency impairs the mitotic surveillance machinery, leading to tumor development. Identification of the PTEN-mitotic pathway may offer a profound implication for development of therapeutic strategies against tumorigenesis. Show more... | National Institutes of Health | 5/07/2009 |
| CORNELL UNIVERSITY, INC | $1,946,312.00 | Grant |
Trans-NIH Recovery Act Research Support Cocaine addiction is a major problem for which there is currently no solution. This proposal is focused on developing an anti-cocaine vaccine designed to suppress the pharmacokinetics of cocaine after administration, sufficient to prevent cocaine from reaching its receptors in the brain. Our strategy is based on our almost 2 decades of experience with adenovirus (Ad) gene transfer vectors in experimental animals and humans, and the recognition that these vectors act as potent adjuvants that activate the immune system by infecting antigen presenting cells. We hypothesize that linking cocaine analogs to the proteins on the virion capsid (hexon, fiber, penton) will elicit high level, high affinity cocaine-specific antibodies sufficient to treat cocaine addiction. These capsid modifications will allow the vector to function similarly to a protein immunogen with the added benefit of exploiting the natural adjuvant effect of the Ad. The humoral adaptive immunity induced by Ad is directed against the capsid proteins, including 720 hexons and 96 combined penton bases and fibers, abundant targets for conjugating cocaine. The Ad-cocaine vaccine could be used as a single administration, or more likely, by re-administration in a prime-boost fashion to boost the immunity against the drug epitopes. Based on the preliminary data demonstrating the feasibility of evoking high titer anticocaine antibodies in mice with human serotype 5 or non-human primate serotype C7 Ad with a cocaine analog coupled to the Ad capsid, we propose a focused, rapid-development, multi-component national program with the deliverable at the end of yr 2 to be an adenovirus-based cocaine vaccine ready to move into human clinical trials. To accomplish this, we have formulated the following specific aims: Aim 1 - To develop a panel of Ad5- and AdC7-based anti-cocaine vaccines that elicit high titer, high affinity anti-cocaine antibodies and that will modify the pharmacokinetics of cocaine in murine models; Aim 2 - Using rat models to assess the ability of the best candidate vaccines from aim 1 to evoke anti-cocaine antibodies, suppress the pharmacokinetics of cocaine following administration, and to prevent cocaine-induced behavioral phenotypes; and Aim 3 - Choosing the best candidate vaccine with the optimal performance from aim 2, assess the ability of the vaccine to modify the pharmacokinetics of cocaine and prevent cocaine-related behavioral phenotypes in non-human primates addicted to cocaine. In aims 2 and 3, studies with GMP-produced vaccines will permit parallel collection of toxicology data to support a future FDA Investigational New Drug application for initial clinical studies. Show more...
There were 3 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 9/30/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $34,397.00 | Grant | Trans-NIH Recovery Act Research Support Influenza virus is a seasonal pathogen with the potential to cause pandemic infection; it results in respiratory disease ranging from subclinical symptoms to life-threatening primary viral pneumonia. Despite the availability of a yearly vaccine, it is estimated that an average of 360,000 deaths/year can be attributed to influenza virus infection in the US alone, with severe illness occurring in approximately 3-5 million people worldwide annually. Through the use of small regulatory RNAs, we seek to further the current paradigm of influenza virus infection while developing a safe, effective, and cost-efficient vaccine strain. Influenza A virus is not only a seasonal pathogen, causing yearly epidemics, but also a potential pandemic causative agent. The development of reverse genetics technology for influenza virus has led both to the preliminary characterization of its pathogenicity, as well as to the development of novel vaccine strains. By combining reverse genetics with the newly evolving field of microRNA (miRNA) biology, we seek to further understand influenza virus infection while developing a safe, effective, and easily produced vaccine strain. Through the incorporation of miRNA response elements (MREs), corresponding to ubiquitously expressed mammalian miRNAs, into influenza A virus, we can achieve vaccine quality attenuation. Our first objective will be to characterize this phenomenon, by fully understanding the host response to these attenuated viruses, and by elucidating the viral response to these attenuating mutations. We will also improve upon this technology by identifying the most effective influenza viral transcript to target, with the ultimate goal being influenza virus vaccine design. Our second objective will be to use this new technology to investigate influenza virus tropism and cell-type contribution to viral pathogenicity. Through the use of miRNA-mediated attenuation technology, we will elucidate the role of hematopoietic-specific miRNAs in determining influenza virus tropism, and further our understanding of the contribution made by epithelial subtype populations to influenza virus pathogenicity. As such, this proposal has the potential to offer a significant contribution to human health as the strategy described here could be employed to develop effective and safe vaccines to any desired pathogen. Show more... | National Institutes of Health | 8/13/2009 |
| NEW YORK UNIVERSITY (INC) | $1,194,059.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): Poorly controlled hypertension (HTN) remains one of the most significant public health problems in the United States, in terms of morbidity, mortality, and economic burden. Despite compelling evidence supporting the beneficial effects of therapeutic lifestyle changes (TLC) on blood pressure (BP) reduction, their effectiveness remains untested in primary care practices, especially among minority patients who share a greater burden of HTN-related outcomes including chronic kidney disease, stroke and heart failure. This randomized controlled trial offers a unique opportunity to address this gap in the literature. Among 500 hypertensive African-Americans who receive care in community- based primary care practices, we will test the effectiveness of a culturally-tailored comprehensive therapeutic lifestyle intervention, delivered through group-based counseling and motivational interviewing (MINT-TLC) vs. Usual Care (UC). MINT-TLC is designed to help patients make appropriate TLC and develop skills to maintain these changes long-term. Patients in the MINT-TLC group will attend weekly group classes focused on TLC for 10 weeks (intensive phase); followed by individual motivational interviewing (MINT) sessions for 2 months (extended phase); and then bi-monthly booster MINT sessions for 4 months (maintenance phase). Trained research personnel will deliver MINT-TLC with appropriate treatment fidelity procedures. Patients in the UC condition will receive a single individual counseling session on TLC and print versions of the intervention materials. The primary outcome is within-patient change in both systolic and diastolic BP from baseline to 12 months. Secondary outcomes are levels of targeted therapeutic lifestyle behaviors; and proportion of patients with adequate BP control at 12 months (BP The long-term goal is to refine MINT-TLC and integrate it into standard HTN treatment protocol as a result of the data obtained; thus maximizing the likelihood of its translation to clinical practice. Public Health Relevance: Despite compelling evidence supporting the beneficial effects of therapeutic lifestyle changes or blood pressure reduction, the effectiveness of these approaches in primary care practices remains untested. We will test the effectiveness of a practice-based comprehensive therapeutic lifestyle intervention, delivered through group-based counseling and motivational interviewing in a two-arm, randomized controlled trial in 500 poorly- controlled hypertensive African-Americans, who receive care in community-based primary care practices. Show more... | National Institutes of Health | 9/25/2009 |
| NEW YORK UNIVERSITY (INC) | $400,000.00 | Grant | Trans-NIH Recovery Act Research Support Emerging technologies for manufacture and use of nanoparticles (NP) are numerous and the exponential increase in their use drives the need for understanding toxicology of these particles. Most non-carbon NP contain one or more toxicologically-active metals, including cadmium (Cd). As NP-induced reprotoxicity has yet to be addressed in animal studies and because bulk Cd: is an endocrine disruptor; reduces progesterone levels; alters placental steroidogenesis; can concentrate in the placenta; and, exposure to bulk Cd is associated with fetal instability (i.e., low birth weight [LBW], and pre-term delivery [PTD]), a study is proposed to determine how inhalation of Cd-bearing NP (as CdO) might impair fetal stability in utero, and how these effects are related to physicochemical properties of the particles. We hypothesize that: (1) exposure of pregnant mice to atmospheres containing Cd-bearing (Cd) NP will display reductions in gestational duration/birth weight/fetal growth that are related to particle physicochemical properties and, (2) these outcomes are a result of property-dependent effects on the release and actions of select hormones/cytokines important for pregnancy maintenance and parturition. Timed-pregnant mice exposed to relevant levels of either nanosize (i.e., fresh) or agglomerated (i.e., aged) CdO (or size-matched carbon particles) will be sacrificed on gestational day (GD) 18 or allowed to give birth.Biologic samples collected from each dam will be used in three inter-related Aims to examine effects of inhaled manufactured Cd NP on: 1) PTD/LBW/restricted fetal growth as a function of physicochemical properties of the inhaled particles; 2) GD18 hormone levels critical for pregnancy maintenance/preparation of parturition; and, 3) changes in hormone responsiveness (by examining receptor/hormone expression) shown to be altered in Aim 2). Because: reduction in size can potentiate particle toxicity; Cd from inhaled nanosize CdO can reach the placenta of exposed mouse dams (c.f., Preliminary studies); large numbers of pregnant women will potentially be exposed to Cd-associated nanomaterials; bulk Cd, a potent estrogen mimic, concentrates in the placenta and produces placental toxicity leading to LBW and PTD; pregnant women/fetuses are particularly vulnerable to toxic insult; and, there is a disquieting absence of reproductive toxicology studies examining NP, an investigation is proposed whose major goal is to link physiochemical parameters of Cd-bearing NP with potential adverse reproductive outcomes. Results will provide initial hazard characterization of Cd NP (with regards to their potential for reproductive effects that will be useful in setting appropriate standards/guidelines for pregnant women/fetuses. The proposed studies fit well into the NIEHS program that highlights the need for studies of nanoscale materials that explore the development of appropriate novel toxicological methods to assess potential human health effects. The proposed studies are designed to determine the reproductive toxicity of cadmium nanoparticles on pregnancy stability and parturition in a mouse model. The approach is designed to identify such effects as preterm birth induction, low birth weight and/or restricted fetal growth and underlying hormonal/cytokine dysregulation in relation to the physicochemical properties of the cadmium nanoparticles. The findings will have great relevance to the health of women of reproductive age, particularly in the workplace. Show more... | National Institutes of Health | 9/19/2009 |
| RFCUNY - CITY COLLEGE | $247,954.00 | Grant | Trans-NIH Recovery Act Research Support Research Project: To support a discrete, specified | National Institutes of Health | 7/17/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $854,672.00 | Grant |
Trans-NIH Recovery Act Research Support As stated in the abstract, the overall goal of the proposed research is to determine if pregnant teenagers’ life stress and stress related changes in blood pressure (BP), as well as other biological indices of stress (cytokines, HPA–axis activity) are associated with poorbirth outcomes and alterations in perinatal development. For this study, we aim to monitor BP and mood in 269 pregnant teenagers (ages 14–19) over the course of two years. Pregnant teenagers undergo three 24–hour ambulatory BP monitoring periods (at 1st, 2nd,and 3rd trimester) with the simultaneous assessment of emotions and interpersonal interactions collected on a Personalized Digital Assistant Diary (PDA). Multiple assessments of salivary cortisol also are collected during the BP monitoring periods; two blood assays are collected for inflammatory markers. At two points during pregnancy, fetal heart rate and movement are assessed (Fetal Session #1, 30 weeks gestation and Fetal Session #2, 36 weeks gestation). During Fetal Session #2, fetal heart rate and movement are assessed while teenagers undergo a laboratory stressor. Newborn heart rate is assessed during an orthostatic challenge. Since May 2009, we have set up our laboratory to run study sessions and purchased the majority of equipment necessary for data collection. We have purchased 6 ambulatory BP monitors, six PDAs, two new computers, and cortisol collection supplies. In addition, we have hired three research assistants to perform the duties of recruitment and running the research protocols. At present, we are on target with recruitment/enrollment goals. We have screened 68 pregnant adolescents for the study, 55 qualified, and 49 were successfully enrolled. 49 of these participants have completed their first trimester 24- hour ambulatory BP session and 48- hour cortisol sample collection. Fourteen of these 49 partaicipants have successfully completed both their 1st and 2nd trimester ambulatory BP session and cortisol sample collection, and 7 of these 49 have completed all 3 ambulatory BP sessions. Eight of the 49 teens have completed Fetal Session #1 and 7 have completed Fetal Session #2. Two of the pregnant teens have given birth; both have completed the newborn session. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 5/05/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $514,249.00 | Grant | Trans-NIH Recovery Act Research Support :Neural stem cells (NSCs) can be propagated in vitro for extensive periods of time while retaining the ability todifferentiate into neurons, astrocytes and oligodendrocytes. However, NSCs are limited in their potential toyield specific neuron types. Na¿ve NSCs expanded in vitro give rise primarily to GABAergic interneurons and toa lesser extent glutamate neurons. This suggests that NSCs, while multipotent, may not have access to the fullspectrum of neuron types. In contrast human embryonic stem cells (hESCs) differentiated towards early neuralfates can be readily biased towards various region-specific neuron types such as midbrain dopamine neuronsor spinal motoneurons. We have recently reported that hESC derived neural progeny responsive to suchregional patterning cues are organized into columnar neuroepithelial structures termed neural rosettes (R-NSCs) and characterized R-NSCs in considerable detail1. Our study has identified R-NSCs as novel, uniqueNSC stage based on marker expression, clonal stem cell properties, neural differentiation potential, andgenetic identity1, 2. The most intriguing finding of these studies was the broad patterning potential of R-NSCscompared to other currently available NSC types. R-NSCs are capable of comprehensive differentiationtowards CNS1 and PNS3 derivatives and capable of in vivo engraftment.Despite these exciting preliminary data our studies also revealed major gaps in our current understanding ofRNSC biology. Here we would like to address some of these limitations by defining heterogeneity withinRNSCs and develop genetic strategies for the prospective isolation of fully patternable R-NSCs based on BACtransgenesis. BAC transgenic hESC reporter lines have been recently pioneered in the Studer lab and willserve as reliable readout of R-NSC stage, identity and function. BAC transgenic reporters will also be criticalfor probing function of extrinsic and intrinsic factors affecting R-NSC identity. These studies should providefundamental insights into the genetic and epigenetic mechanisms of neural patterning and ultimately result innovel conditions for the continued in vitro expansion of fully patternable R-NSC - a key step towardsestablishing a stable expandable universal NSC population. Show more... | National Institutes of Health | 9/07/2009 |
| NEW YORK UNIVERSITY (INC) | $84,500.00 | Grant | Trans-NIH Recovery Act Research Support Dermal fibrosis is a hallmark of systemic sclerosis. We have previously demonstrated that stimulation of adenosine A2A receptor promotes collagen production in vitro while blockade of the adenosine A2A receptor attenuates development of dermal fibrosis in vivo in a bleomycin-induced murine model of scleroderma. These findings parallel our observations on models of hepatic fibrosis where adenosine A2A receptor antagonists retard chemically-induced murine cirrhosis. We have recently shown that levels of the fibrogenic cytokine, IL-13 are elevated in the skin in a murine model of high tissue adenosine (adenosine deaminase deficiency). Furthermore, an A2A receptor antagonist reverses the IL-13 increase and decreases message for IL-13 receptor 1. To better understand the mechanisms by which adenosine A2A receptor antagonism protects against dermal fibrogenesis in scleroderma, we will study: Specific Aim 1 The effect of adenosine on IL-13 responsiveness in dermal fibroblasts Specific Aim 2 The effect of adenosine and IL-13 on Fli1 function Specific Aim 3 The effect of adenosine on CCN2. Ultimately, we hope that these studies will allow us to consider the use of small molecules such as adenosine receptor antagonists in the therapy of dermal fibrosis in scleroderma. PUBLIC HEALTH RELEVANCE: Uncontrolled and excessive fibrous tissue formation may result in diffuse skin and organ fibrosis such as that seen in scleroderma. The studies proposed herein are designed to further confirm the role of adenosine and its receptors in promoting fibrosis in the skin as well as the mechanisms by which adenosine receptors stimulate tissue matrix production. A better understanding of the role of adenosine and its receptors in dermal fibrosis could facilitate the development of new agents that prevent or ameliorate the skin fibrosis that characterizes scleroderma, for which no effective treatment exists at present. Show more... | National Institutes of Health | 9/09/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $84,055.00 | Grant | Trans-NIH Recovery Act Research Support This is a 2-year grant application in response to PA-06-391: Research on Autism and Autism Spectrum Disorders R03. Clinical, animal, and genetic evidence points to a role for the hormone oxytocin in autism and suggests that oxytocin related abnormalities may be present in relatives of autism probands. Provocative clues raise a similar possibility for cholesterol. In the proposed pilot study, we plan to assess oxytocin and cholesterol levels in blood from a sample of 30 families (although 15 of these families will be financed through other means) each with a child diagnosed with autism or autism spectrum disorder and 20 families without autistic family members. The preliminary data obtained from this small project will help us design a larger one aimed ultimately at finding susceptibility genes for autism through the improved delineation of phenotypic expressions. Participating autism proband families will also have unaffected children. This will enable us to compare not only autism parents with control parents but also autism siblings with control siblings. We will screen all participants for autism and will subsequently use diagnostic assessments for potentially affected children. Furthermore, we will assess potential relationships between both oxytocin and cholesterol with behavioral and neuropsychological traits associated with the three core symptom domains of autism (social deficits, communication, and behavioral abnormalities), as well as executive functions. While many of these assessments have been used successfully in autism family studies; others have not been used in autism family studies before and are thus exploratory. Beyond their relationships with oxytocin and cholesterol, these measures will serve as a tool to evaluate more specific behavioral and neuropsychological traits, so called endophenotypes. Finally, using a new statistical method, multivariate distance matrix regression methodology, not previously employed in studies of autism or their relatives, we will try to identify subgroups within families, that is, families that can be described through a distinct endophenotypic profile. Clarifying endophenotypes and subgroups within autism families are both useful measures in the search for associated genes through molecular genetic studies. Accordingly, our study will contribute to the information necessary to define the causal factors of autism. PUBLIC HEALTH RELEVANCE: Because autism and autism spectrum disorder are genetically complex, the genes involved in this disorder are still largely unknown. We propose to conduct a study designed to isolate distinct behavioral and cognitive traits and their connections to oxytocin and cholesterol, two organic bio-chemicals that can be measured in the blood that are hypothesized to show abnormalities in autistic proband and their families. This will lead to very important new information that can inform and strengthen genetic studies of autism and ASD and thus help reveal the causes of this severe group of developmental disorders. Show more... | National Institutes of Health | 7/17/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $211,875.00 | Grant | Trans-NIH Recovery Act Research Support ): For most infections, the immune system confers long-term and sometimes life-long protection against many microbial pathogens. One encounter with a microbial pathogen is sufficient to allow the immune system to remember this pathogen for decades to come. This fundamental property forms the basis for vaccination with the main purpose of eliciting long-term protective immunity.Our increasing knowledge of the critical elements involved in the initiation of immune responses points us towards two central players, antigen presenting cells (APCs) and pattern recognition receptors (PRRs). APCs capture microbial pathogens and mobilize a sequence of events that forms the basis for mounting an effective immune response against the pathogen. Adjuvants, used in most vaccine preparations, are a mixture of microbial components that trigger PRR activation and signal the transcriptional initiation of immune response genes. Our studies so far provide strong support for differential innate immune recognition of live and dead bacteria. While live bacteria trigger production of inflammatory alert cytokines, dead bacteria fail to do so. Thus, a component differentially present in live and dead bacteria, and which correlates with microbial viability, appears to be uniquely recognized by APCs. Recognition of this component requires the TLR signaling adaptor MyD88. We hypothesize that the innate immune system is capable of discriminating between live and dead pathogens, and accordingly mobilizes distinct signaling pathways and cellular immune responses. The unique responses triggered by live bacteria may hold the key to long-term immunity. Our specific aims are designed to: 1) Determine the ability of live bacteria to activate cytosolic sensors of infection. 2) Characterize the nature of intracellular compartments carrying live versus dead bacteria. Show more... | National Institutes of Health | 6/04/2009 |
| NEW YORK UNIVERSITY (INC) | $253,688.00 | Grant | Trans-NIH Recovery Act Research Support Trichomoniasis is the most common non-viral STD, estimated to cause ~174 million infections world-wide each year. The Trichomonas vaginalis parasite resides in the urogenital tract of both sexes and can cause vaginitis in women and urethritis and prostatitis in men. However, the disease is known more as a female 'nuisance' condition, which has resulted in a lack of scientific and medical attention and scant interest by public health officials in developing trichomoniasis control programs. Acute infections among women are associated with pelvic inflammatory disease and adverse pregnancy outcomes. Most alarming is the recognition that T. vaginalis infection appears to increase women's susceptibility to HIV-1 infection. Because of the association between T. vaginalis and risk for HIV-1 acquisition, interventions to reduce T. vaginalis infection and transmission would likely result in fewer HIV-1 infections. Completion of the T. vaginalis genome sequence in 2007 has significantly increased our knowledge concerning the biology and mechanisms of pathogenesis of the parasite, but significant gaps remain. In particular, the genetic diversity of the parasite is not known, i.e. whether the parasite is maintained as a clonal population, or whether genetic exchange occurs between parasites in the urogenital tract. The extent of genetic diversity has implications for the control of the disease, for example it determines how virulent parasites spread or how they may evade a vaccine. The focus of this R21 proposal is to examine the genetic diversity of T. vaginalis infecting women attending eight New York City Bureau of STD clinics in inner city areas, and to use some of these isolates to develop a standardized and accessible in vitro model system for the study of colonization of the vagina by the parasite. A panel of polymorphic genetic markers - microsatellites and single copy genes - will be developed using the T. vaginalis genome sequence, and used to genotype T. vaginalis isolates identified in vaginal swabs taken from women attending the clinics. Knowledge of the genetic diversity and colonization characteristics of the parasite will provide important data points for subsequent studies, for example determining associations between T. vaginalis genotypes and the commensal microbes that make up the vaginal 'microbiome'. PUBLIC HEALTH RELEVANCE: Trichomoniasis, caused by the eukaryotic parasite Trichomonas vaginalis, is the most common, non-viral, sexually transmitted infection worldwide, but long considered a female 'nuisance' disease. The goal of this project is to determine the genetic diversity of the parasite in women attending STD clinics in New York City, and to use these extant isolates in the development of a model system for the study of colonization of the vagina. Show more... | National Institutes of Health | 6/18/2009 |
| ST LUKE'S-ROOSEVELT HOSPITAL CENTER | $241,521.00 | Grant | Trans-NIH Recovery Act Research Support Exploring Specific Metabolic Rates of Major Cell Categories in Adiposity-Diverse Adults ABSTRACT Obesity is a significant health problem in the USA. Previous studies observed that obese adults have greater resting energy expenditure (REE), the largest fraction of total energy consumption. Major efforts have been made for predicting REE at the whole-body level (i.e., body mass, BM), molecular level (i.e., fat-free mass, FFM) and organ-tissue level (i.e., major organs/tissues). However, the published REE prediction formulae from normal-weight adults were not valid in obese adults, representing a knowledge gap in energy metabolism investigation. The proposed study aims to deeply understand the REE-body composition relationship at the cellular level. As REE is the collective energy required by all body cells to maintain post-absorptive homeostatic function in the resting condition, we will establish a cellular level REE prediction approach. The new mechanistic model is based on the masses of individual cell categories (Ci) and their specific resting metabolic rates (Ji): REE = #(Ji W Ci). Although various cell categories may have quite different levels of energy consumption, the Ji values have never been quantified in vivo. We will address the Ji values by using multiple linear regression analysis with REE as the dependent variable, and Ci as the independent variables. The REE is measured by indirect calorimetry, and the Ci is quantified from organ/tissue mass by magnetic resonance imaging (MRI), with cellularity measured from body cell mass and lean-soft tissues by whole-body counting and DXA, respectively. The major cell categories include skeletal muscle cells, adipocytes, and organ cells (i.e., liver, brain, heart and kidney cells). In order to predict the Ji values of the six cell categories, this secondary analyses study will combine existing data from two centers in the USA and Germany, and assemble the largest-to-date REE-MRI organ/tissue database (n = 434) with men and women varying in adiposity (BMI 14.4-39.1 kg/m2) and age (18-88 yrs). Our hypothesis is that the derived cellular level approach can accurately predict REE in adiposity- and age-diverse adults. Accordingly, the derived cellular level REE model may fully explain the well-known observation that obese adults have a higher absolute REE, but lower REE/BM and REE/FFM ratios than do normal-weight adults. This study thereby will contribute to our understanding of the inherent relations between REE and body composition and will provide new insights into the energy requirement of obese adults. PUBLIC HEALTH RELEVANCE: Resting energy expenditure (REE) is the largest fraction (65-75%) of total energy consumption. It is known that various cell categories may have quite different levels of energy consumption. However, the specific resting metabolic rates of individual cell categories have never been studied quantitatively. The proposed study aims to establish a new REE prediction model at the cellular level. The potential outcome of this study can be expected to improve our understanding of the inherent relations between REE and cellular level body composition and establishing energy requirement of obese adults. Show more... | National Institutes of Health | 7/16/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $319,359.00 | Grant |
Trans-NIH Recovery Act Research Support Preterm birth, small-for-gestational age (SGA) and pregnancy induced hypertension (PIH) are major pregnancy complications that impact the health of the mother and the child, often resulting in admission to the neonatal intensive care unit following delivery. We propose a highly efficient, intensive pathway-based analysis of genetic variation and preterm delivery, SGA, and PIH that addresses the following specific aims: (1) To investigate the relationship between polymorphisms in the cell-cycle and apoptosis pathways with risk of preterm delivery, SGA, term SGA and pregnancy induced hypertension (PIH); (2) To investigate the relationship between polymorphisms in the angiogenesis pathway with risk of SGA and PIH; (3) To investigate the relationship between polymorphisms in the inflammation pathway with risk of preterm delivery, total and term SGA, and PIH. To address these aims we will be drawing on a well- characterized prospective cohort study of preterm delivery, the Pregnancy, Infection and Nutrition study (PIN), which enrolled over five thousand women over the course of approximately 10 years. In a nested case-control subset of preterm (n=379), term SGA (n=281, an additional 90 are preterm), and PIH cases (n=468) and a random group of controls (n = 936), DNA has already be extracted and is available for genetic analyses. We propose to analyze these DNA specimens using a haplotype-based approach for approximately 93 genes of interest on the Illumina 1536 chip. The priority pathways we have identified bear relevance to the period of placentation, which is a period of development at which these outcomes may be etiologically linked. With additional investment, this cohort could provide the most comprehensive evidence to date linking variants in these pathways of interest with these adverse birth outcomes. PUBLIC HEALTH RELEVANCE: This study promises to generate a markedly enhanced understanding of the genetic epidemiology of preterm, SGA and PIH. This information will provide a foundation for studying other adverse pregnancy outcomes with shared biological mechanisms. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 5/11/2009 |
| NEW YORK UNIVERSITY (INC) | $265,353.00 | Grant | Trans-NIH Recovery Act Research Support Given our long-term goal to discover new therapeutic approaches that can improve patient outcomes, we will investigate a nove therapeutic strategy, intranasal drug delivery, aiming to inhibit the invasion of glioma cells. The proposed studies are the first, to our knowledge, to simultaneously taget two clinically relevant hallmarks associated with malignant glioma; angiogenesis and invasion. These data should provide exploratory information leading towards the development of novel therapies for glioma patientes. Show more... | National Institutes of Health | 7/15/2009 |
| CORNELL UNIVERSITY, INC | $253,250.00 | Grant | Trans-NIH Recovery Act Research Support Ample evidence suggests that a dramatic decrease in mitochondrial Ca2+ retention may contribute to cell death associated with stroke, excitotoxicity, ischemia and reperfusion, and neurodegenerative diseases. Mitochondria from all known tissues can accumulate and store Ca2+, but the maximum Ca2+ storage capacity varies widely and exhibits striking tissue specificity. There is currently no explanation to this fact. A precipitation of Ca2+ and phosphate in the mitochondrial matrix has been suggested to be the form of storage of accumulated Ca2+ in mitochondria. How this precipitate is formed is not known. On the basis of earlier observations and our current data we hypothesize that Ca2+ and phosphate precipitation in the mitochondrial matrix is catalyzed by a specific factor, which serves as a nucleation center for the formation of the precipitate. The amount of this factor determines the maximum mitochondrial Ca2+-storage capacity. Accumulation of Ca2+ above a tissue-specific storage threshold activates a proteinaceous channel termed ?permeability transition pore? (PTP) in the inner membrane of mitochondria. Opening of PTP results in energy deprivation, oxidative stress and may cause cell death. There is no consensus model of PTP that would encompass most of its known structural and regulatory properties and explain its activation by Ca2+ and phosphate. Past studies revealed aspects of PTP structure and regulation, but the molecular identity of its key element, the channel-forming protein(s) is not known. We propose a radically novel model of PTP activation by accumulated Ca2+ and phosphate; we also propose most plausible candidate on the role of PTP channel-forming protein. The specific aims of this project are designed to prove the two key elements of our hypothesis by (1) proving the role of the suggested protein in PTP activation and (2) identifying the nucleation factor responsible for the formation of Ca2+ and phosphate precipitate in the mitochondrial matrix. This project will lay the foundation for the molecular etiology of Ca2+-induced mitochondrial dysfunctions and cell death. It could immensely contribute to the development of targeted interventions and drugs combating the neurodegenerative diseases, stroke, excitotoxic and ischemia-reperfusion induced tissue damage Show more... | National Institutes of Health | 5/15/2009 |
| CORNELL UNIVERSITY, INC | $499,329.00 | Grant | Trans-NIH Recovery Act Research Support M. tuberculosis (Mtb) has caused a global health emergency. Yet little new chemotherapy against Mtb has emerged in decades. This application aims to target a pathway in the pathogen that is not essential for the pathogen to survive in vitro but is essential for the pathogen to resist conditions in the host. Mtb faces reactive nitrogen intermediates (RNI), reactive oxygen intermediates (ROI), acid, amino acid deficiency and other metabolic stresses when it infects the mouse and perhaps man, including during latent TB infection (LTBI). We have identified the proteasome as a non-redundant pathway by which Mtb protects itself against oxidative/nitrosative stress and metabolic stringency. In this project we are exploring and exploiting the differences between proteasomes from Mtb and humans so as to develop inhibitors with sufficient species selectivity, mycobacterial uptake and nontoxicity to host cells to serve as leads for novel anti-TB chemotherapeutics. We are focusing on oxathiazol-2-ones, which act as highly selective suicide substrate inhibitors of the Mtb proteasome but simple substrates for the human proteasome. Our goals are to improve inhibitory potency and species selectivity of oxathiazol-2-ones, widen the therapeutic index, confirm mechanism, determine frequency of resistance, test against Mtb in vitro and in mice, and identify alternative targets. Show more... | National Institutes of Health | 7/15/2009 |
| NEW YORK UNIVERSITY (INC) | $406,961.00 | Grant | Trans-NIH Recovery Act Research Support In a region of the world like West-Central Africa where multiple HIV-1 groups and subtypes co-circulate, the rate of dual infection -the concomitant or sequential infection with two or more geneticallly distinct HIV-1 strains- is frequent and recombinant viruses are common. A key characteristic of HIV-1 is its ability to recombine following dual infection, providing the virus with the opportunity for major evolutionary laps and creating major challenges for diagnosis, treatment, vaccine design and vaccine trials. Despite the fact that dual infection is common, information on how dual infection impacts on the host's anti-viral humoral immune responses is limited. Studying the impact of dual infection by discordant HIV-1 strains should increase our knowledge of the humoral immune response to diverse viruses. Therfore, the occurrence of dual infection provides a unique opportunity to investigate immune responses to multiple viral antigens and to study whether the host immune response is broadened when challenged with multiple, diverse antigens representing distinct viral subtypes and recombnant viruses. In the West-Central African country of Cameroon, multiple HIV-1 subtypes co-circulate, dual infection is common, and we have identified several individuals dually infected with diverse viruses that have remained asymptomatic and drug-naïve for over 3-4 years. The occurrence of dual infections in these drug-naïve individuals provides an opportunity to study virus evolution, to examine and compare the effect of infection by single and multiple subtypes on the host immune system in generating neutralizing antibodies, and to study whether such antibodies exhibit differences in their potency and breadth to autologous and/or heterologous viruses. These kinds of studies will shed light on the emergence of new viral subtypes and recombinants and contribute to the design of vaccines that will induce the most potent and broadly neutralizing antibodies to protect against diverse HIV-1 subtypes. We therefore propose studies in: AIM 1: To examine the potency and breadth of neutralization against autologous and heterologous HIV-1 viruses by sequential plasma specimens from either individuals infected with single HIV-1 strains or dually infected with inter- or intra-subtype strains; AIM 2: To study the genetic evolution and emergence of recombinant viruses in the blood of dually (inter-subtype) infected subjects whose serum neutralizing antibodies display different patterns of breadth and potency; and AIM 3: To study the neutralization sensitivity of the recombinant viruses isolated from individuals with inter-subtype dual infections. Show more... | National Institutes of Health | 8/11/2009 |
| CORNELL UNIVERSITY, INC | $473,959.00 | Grant | Trans-NIH Recovery Act Research Support A one-year NIH R56 (Bridge Award) grant to Dr. Henry Murray to support his continued laboratory research in the treatment of leishmaniasis, a parasitic infection. Expected outcome are: (a) the generation of new scientific results in experimentally infected animals directed at improving treatment of this disease in man, and (b) producing new data and research directions to strengthen a future NIH application for continued support of this laboratory project. Show more... | National Institutes of Health | 6/04/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $162,841.00 | Grant | ARRA - Public Health Traineeship Program The Public Health Traineeship provides a financial resource to help us attract and retain applicants from disadvantaged and underrepresented groups. PHT ARRA funds will support students with documented extreme financial need. These students pursue academic programs such as Biostatistics, Environmental Health Sciences, and Epidemiology and other public health disciplines designated as severe shortage occupational areas nationally, and/or in several additional severe shortage areas in metropolitan New York City. We will use the additional $162,841 in PHT ARRA funds to cover tuition for the selected students in the amounts and years below: 09-10: 2 students $14,976, Total $29,952.10-11: 5 students $22,148, 10-11:1 student $22,149, Total $132,889. Show more... | Health Resources and Services Administration | 9/03/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $51,710.00 | Grant | Trans-NIH Recovery Act Research Support Low dose oral tolerance is defined as the active suppression of a systemic immune response to a specific antigen by regulatory T cells (Tregs) generated in response to repeated ingestion of that antigen. Though ex- tensively studied, the specific mechanisms involved in the generation of regulatory cells in response to oral antigen remain poorly understood. Although previous studies have demonstrated that oral antigen can in- duce both CD4+ and CD8+ Tregs, the role of CD8+ T cells remains controversial. Our preliminary data dem- onstrate that feeding C57BL/6 mice with the MHC Class' I immunodominant peptide of OVA (SIINFEKL) generates tolerance to subsequent immunization with the whole OVA protein, and that this response is de- pendent on the presence of CD8+ T cells. Show more... | National Institutes of Health | 6/04/2009 |
| CORNELL UNIVERSITY, INC | $207,958.00 | Grant | Trans-NIH Recovery Act Research Support As the numbers of patients continue to rise after high-dose chemotherapy and/ or irradiation for cancer and other diseases, more attention is focused on improving their quality-of-life, with fertility one of the top priorities for young people. Women have had fewer options for avoiding iatrogenic infertility and menopause compared with men, and prepubertal girls have virtually none. Cryopreservation or vitrification of embryos is a standard of care, and oocyte banking is now emerging for single women, but neither of these assisted reproductive technologies is universally suitable or acceptable, nor can either help children. Low temperature banking of ovarian tissue slices, and perhaps whole ovaries one day, now offers an option for these people and, so far, six full-term pregnancies have been established after transplanting thawed tissue, and several others after fresh tissue, but no grafts were still functioning after three years. This strategy for preserving fertility is still considered ?experimental?, though proof of principle was established many years ago in animal models. Those studies revealed a large and variable fraction of follicles is lost by ischemia during the first 2-5 days until the grafts are revascularized, whereas the impact of cryoinjury was comparatively minor. According to our hypothesis, a reduction in ischemia time will be beneficial for extending graft function and potentiating fertility by reducing the amount of necrotic tissue and the fraction of wasted follicles. In Aim 1, we will characterize the cellular and molecular determinants of angiogenesis in ovarian grafts and their temporal course in relation to follicular survival. This aim will fill a knowledge gap by investigating the role of candidate factors, notably VEGF and PDGF, involved in revascularizing mouse ovaries grafted into skeletal muscle and human ovarian xenografts in NOD-scid mice as a translational model. The studies will include novel methods to monitor reperfusion non-invasively by microultrasound during the first two weeks post-grafting, and molecular and cellular quantification of vascular growth, angiogenic factors, follicular survival and factors in the extracellular matrix. In Aim 2, we will test two experimental strategies for improving vascular perfusion and follicle survival by tissue engineering either at the future graft site or the graft itself. In the first, we will implant alginate hydrogels into muscle for local, phased release of angiogenic factors to stimulate endothelial cells and pericytes with the goal of accelerating the formation of a stable microcirculation in murine grafts. In the second, we will reduce collagen bulk in human ovarian tissue to test whether the higher fiber density is a barrier to vascular invasion and potentially responsible for the higher fraction of follicles wasted. A successful outcome of either of these experiments could lead to clinical implementation for patients who plan to bank their ovarian tissue to preserve fertility. Show more... | National Institutes of Health | 9/22/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $467,558.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): M. tuberculosis infection is an ongoing global health crisis that requires new drugs or vaccines for effective control. Although many individual genes have been shown to be important for M. tuberculosis pathogenesis in the mouse, we still understand relatively little about how M. tuberculosis responds to varied host environments at the molecular level. The Rip1 (Rv2869c) intramembrane protease is a member of the Site two protease (S2P) class of intramembrane metalloproteases which cleave substrate proteins within transmembrane domains. We have previously shown that Rip1 is a critical determinant of M. tuberculosis growth and persistence in mice and controls cell envelope composition through transcriptional regulation of lipid biosynthetic genes. Further preliminary data presented here identifies three anti-sigma factors as Rip1 substrates: anti-SigK (RskA), anti-SigL (RslA), and anti-SigM (RsmA). Accordingly, we show that Rip1 is necessary for the transcriptional activation of SigK, SigL, and SigM target genes. This data indicates that loss of Rip1 inactivates three downstream transcriptional programs. In addition, we show that Rip1 is required for the activation of mycobactin siderophore biosynthesis in response to iron deprivation, a response that also requires SigL and SigM. These findings demonstrate that Rip1 controls multiple downstream pathways important for M. tuberculosis virulence and identify Rip1, SigL, and SigM as components of the machinery that transduce the low iron signal across the cell envelope. Based on this data, we advance the major hypothesis that the severe attenuation of the Rip1 null strain is due to simultaneous inactivation of these four downstream transcriptional programs. In this proposal we test this hypothesis by characterizing the relative contribution of anti-sigma factor processing and low iron signaling to Rip1 dependent attenuation in the mouse. We will determine the mechanism by which SigL and SigM activate the mbtB promoter and their relationship to IdeR. Finally, we will determine the lipid biosynthetic pathways and transcriptional targets downstream of each Rip1 substrate. These studies will provide a molecular understanding of a novel pathway in M. tuberculosis that transforms host signals into gene expression changes. By clarifying the molecular mechanisms by which Rip1 is critical to virulence, these studies will validate Rip1 as target for drug development to combat M. tuberculosis. PUBLIC HEALTH RELEVANCE: This project seeks to understand the function of the Rip1 protease of M. tuberculosis in the pathogenesis of Tuberculosis. Detailed understanding of the Rip1 pathway will validate this protease as a drug target and further our understanding of this important global pathogen. Show more... | National Institutes of Health | 7/17/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $467,645.00 | Grant | Trans-NIH Recovery Act Research Support To establish the utility of atlases for combining data concerning the dose-volume dependence of complications of radiotherapy from different institutions, atlases documenting the dose volume dependence of radiation pneumonitis in patients who received radiotherapy for non-small cell lung cancer in a phase I dose escalation protocol at Memorial Sloan Kettering Cancer Center have been combined with those from a similar protocol conducted at the Netherlands Cancer Institute. Bio-physical models of complication incidence have been fit to the combined atlas data and compared to those fitted to the raw data. Atlases displaying the dose-volume dependence of the incidence of complications occurring in the esophagus and main stem bronchi of patients who received high dope single fraction treatments for paraspinal tumors have been created. Atlases documenting the dose volume dependence of chest-wall pain and rib fracture in patients who received hypo-fractionated radiotherapy for early stage non-small cell lung cancer are in preparation. Show more... | National Institutes of Health | 5/14/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $393,420.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): Apoptosis is a major form of programmed cell death that multicellular organisms utilize to maintain tissue homeostasis and to eliminate unwanted or damaged cells. It plays a critical role in development, immune responses and many other physiological events. Molecularly, apoptosis is executed by proteases known as caspases. In mammals, a crucial caspase activation pathway is the mitochondrial cytochrome c-mediated pathway. In this pathway, caspase activation is initiated by cytochrome c release from mitochondria. Released cytochrome c binds to and activates the essential mediator Apaf-1 to trigger assembly of a multimeric protein complex, the apoptosome, which is the central caspase activation machinery. Deregulation of the cytochrome c apoptotic pathway can lead to diseases such as cancer, immune disorders, and neurodegenerative diseases. Conversely, targeting apoptotic components by both enhancing and inhibiting apoptosis represents important therapeutic approaches to treat various human diseases. For example, many conventional cancer therapies kill cancer cells via activating the cytochrome c apoptotic pathway, and several promising targeted therapies under clinical trial are designed to specifically activate this pathway. On the other hand, inhibition of this pathway should also be effective in treating symptoms with pathologically enhanced apoptosis such as neurodegeneration, stroke, and ischemic diseases. However, previous efforts in developing anti-apoptotic agents that directly target caspases therapeutically are not successful. In this proposed research, we will develop an Apaf-1 activity assay optimized for high throughput screening, and subsequently utilize the assay to screen for compounds that specifically inhibit Apaf-1 activity, the central mediator of the cytochrome c apoptotic pathway. The mechanism of action of the identified Apaf-1 inhibitors will also be determined in this grant. The identified Apaf-1 inhibitory compounds will be promising drug leads for treating diseases such as neurodegeneration and cerebral/myocardial ischemic injuries. They will also be important pharmacological tools for studying mechanisms and the roles of cytochrome c-mediated apoptosis in various physiological and disease processes. PUBLIC HEALTH RELEVANCE:The goal of this research proposal is to identify small molecule inhibitors for Apaf-1 by high throughput chemical screening and to further determine the mechanism of action of the identified inhibitors. The identified Apaf-1 small molecule inhibitors will be promising drug leads for treating diseases such as neurodegeneration and cerebral/myocardial ischemic injuries. They will also be important pharmacological tools for studying mechanisms and the roles of cytochrome c-mediated apoptosis in various physiological and disease processes. Show more... | National Institutes of Health | 6/04/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $2,155,291.00 | Grant | Trans-NIH Recovery Act Research Support Patients with an acute coronary syndrome (ACS) and comorbid depression have a 2-fold higher risk for recurrent ACS and mortality, worse quality of life, and higher costs of care than nondepressed ACS patients. The strength of these findings prompted the American Heart Association to recommend routine depression screening for CHD patients. Unfortunately, less evidence is available to guide the treatment of post-ACS depression. Pharmacological and behavioral depression treatments are available, but it has not yet been established that any of them improve event-free survival after ACS. The absence of evidence-based treatment guidelines, coupled with the high prevalence of comorbid depression in ACS, poses a serious dilemma for clinicians. A comparative effectiveness trial is urgently needed to inform clinical practice. We therefore propose a multicenter feasibility/vanguard project comparing the effectiveness of two interventions for post-ACS depression. The project will culminate in a well-designed, well-organized multicenter Phase III clinical trial. The multidisciplinary investigative team includes cardiologists, psychiatrists, clinical health psychologists, statisticians, and clinical trialists. The feasibility project is based on the COPES randomized controlled trial (RCT). COPES tested the acceptability and efficacy of Enhanced Depression Care, a patient preference-driven, stepped care depression intervention for post-ACS patients, to Standard of Depression Care, in which depression screening was followed by physician notification of depression and encouragement to implement a physician-preferred depression treatment. Treatment acceptability was higher in the Enhanced depression care group (54%) than in the Standard of care group (18%). The differential change in depression between groups yielded an effect size of .59, considerably higher than reported for other depression interventions for CHD patients. Although COPES was underpowered to detect effects on major adverse cardiac events (MACE), the incidence of MACE was lower in the Enhanced (4%) than in the Standard depression care arm (13%). The COPES RCT was a small efficacy trial. We are now requesting funds for a multicenter feasibility/vanguard project, so that we can move vigorously towards a Phase III comparative effectiveness trial. Aim 1) To determine the feasibility and effectiveness of the COPES intervention at other sites by conducting a 5-site RCT comparing the COPES intervention to standard care for depression in post-ACS patients, and to obtain estimates of yield, acceptance, and retention for use in planning a large phase 3 clinical trial. Aim 2) To propose a Phase III single-blind, parallel-group, comparative effectiveness RCT for post-ACS patients, testing whether Enhanced depression care results in fewer major adverse cardiovascular events (MACE - recurrent myocardial infarction, hospitalization for unstable angina with documented CHD) and lower all-cause mortality (ACM) across an average 2 year follow-up, compared to Standard of depression care. PUBLIC HEALTH RELEVANCE: Depression and coronary artery disease are projected to be the #1 and #2 worldwide disease burdens by 2020. Not only do each cause disability and death, but depression and CHD co-morbidity appears to add further cost, clinical outcome risk, and diminished quality of life. Yet, we do not have clear evidence about which existing depression treatment algorithm would effectively alleviate both. This CEC grant will accelerate answering this pressing public health issue. Show more... | National Institutes of Health | 9/28/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $315,378.00 | Grant | Trans-NIH Recovery Act Research Support AMP-activated protein kinase (AMPK) coordinates metabolism with energy availability in eukaryotes by responding to changes in intracellular ATP and AMP levels. The kinase activity of AMPK is stimulated by AMP and inhibited by excess ATP, and it is thought that this unique regulatory behavior enables AMPK to act as a central cellular 'fuel gauge'. AMPK is thus the subject of intense interest as a target for therapeutics to treat metabolic disorders such as diabetes and obesity. AMPK is an abg heterotrimer that includes a subunit with serine/threonine kinase activity and an adenylate-binding regulatory region composed of elements from all three subunits. In preliminary data for this application we present crystal structures for AMP- and ATP-bound forms of the heterotrimeric adenylate sensor from the Schizosacharomyces pombe enzyme. This complex lacks the kinase catalytic domain, but reveals the conserved trimeric core architecture of AMPKs. ATP and AMP bind competitively to a single site within the g subunit, helping to explain their competing effects. Biophysical experiments show that the adenylate sensor complex binds the a subunit kinase domain in the presence of AMP but ATP binding prevents this association. These data help to provide an initial molecular understanding of AMPK regulation. A crystal structure of an AMPK-ADP complex, surprisingly, reveals a second binding site that can uniquely accommodate ADP. The overarching goal of this application is to gain an atomic-level understanding of AMPK regulation through the following specific aims: (1) characterizes the affinities of binding of various adenylate ligands, and use biophysical methods to determine how ligand binding affects interaction between the regulatory and kinase domains. Results from these studies will be correlated with kinase activity in various ligand-bound states. (2) To gain an understanding of the holoenzyme architecture, we will use site-directed mutagenesis to define the molecular regions responsible for nucleotide-dependent association between the kinase domain and regulatory adenylate sensor. Results from the proposed work will be critical for the rational development of AMPK-directed therapeutics. AMPK, a central regulator of cellular metabolism, is among the most attractive molecular targets for new therapeutics to treat diabetes, obesity, and other metabolic disorders. Prior studies have shown that activators of AMPK administered to diabetic animals can substantially ameliorate the physiological effects of diabetes. Despite the great promise of AMPK-directed therapeutics, little is known about the molecular mechanisms of regulation, and the design of appropriate small molecule drugs has been impeded by the lack of atomic-level information on the architecture of the enzyme. Our preliminary results and the further work proposed will provide high-resolution structural information on AMPK, and should directly enable the rational design of AMPK-directed therapeutics. PUBLIC HEALTH RELEVANCE: AMPK, a central regulator of cellular metabolism, is among the most attractive molecular targets for new therapeutics to treat diabetes, obesity, and other metabolic disorders. Prior studies have shown that activators of AMPK administered to diabetic animals can substantially ameliorate the physiological effects of diabetes. Despite the great promise of AMPK-directed therapeutics, little is known about the molecular mechanisms of regulation, and the design of appropriate small molecule drugs has been impeded by the lack of atomic-level information on the architecture of the enzyme. Our preliminary results and the further work proposed will provide high-resolution structural information on AMPK, and should directly enable the rational design of AMPK-directed therapeutics. Show more... | National Institutes of Health | 7/27/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $552,591.00 | Grant | Trans-NIH Recovery Act Research Support The overall goal of this project is to assess whether exposure to metabolites of endocrine disrupting compounds during pregnancy is associated with a) adverse development (cognitive function, height, weight, weight for height, and for females, age at menarche) in the offspring at birth, early childhood, middle childhood, and adolescence, b) mild deficiencies in maternal thyroid function, and c) whether adverse developmental findings, if any, are attributed in part to deficiencies in exposure to maternal thyroid hormone in utero. We also aim to describe the relationships between the metabolites and parent compounds and to examine the associations between the metabolites and thyroid function in the pregnant women. The proposed study draws on data from the Child Health and Development Study, a longitudinal follow up of children born between 1959 and 1966 to mothers enrolled in the Oakland, California membership of the Kaiser Foundation Health Plan and expands upon previous NIH funded research. Prenatal sera has been appropriately frozen and stored, and are available to assess exposure to the metabolites of organochlorine compounds; exposure to organochlorine compounds and maternal thyroid function during pregnancy has already been measured. Serial measures of growth are available in the same children from birth to age 17 years, as are standardized developmental examinations at ages 5, 9-11, and 15-17. The proposed measures of organochlorine exposure and exposure to measures of maternal thyroid function (thyroid stimulating hormone, free thyroxine, and thyroid peroxidase antibodies). Statistical analyses will estimate associations taking advantage of the repeated measures structure of the data. The analyses will employ generalized estimating equations (GEE) methods for repeated measures, taking account of potentially confounding variables. We will distinguish effects of prenatal organochlorine metabolite exposures from infancy through adolescence. We will also investigate a specific mechanism: via maternal thyroid function. Results will fully describe the effects of prenatal exposure and will also further knowledge about the relation between subclinical maternal thyroid hormone deficiency and childhood development. This line of research could lead to prenatal interventions. PUBLIC HEALTH RELEVANCE: We will distinguish effects of prenatal organochlorine metabolite exposures from infancy through adolescence. We will also investigate a specific mechanism: via maternal thyroid function. Results will fully describe the effects of prenatal exposure and will also further knowledge about the relation between subclinical maternal thyroid hormone deficiency and childhood development. This line of research could lead to prenatal interventions. Show more... | National Institutes of Health | 9/14/2009 |
| ROCKEFELLER UNIVERSITY, THE | $422,291.00 | Grant | Trans-NIH Recovery Act Research Support Our long-term aim is to understand how sensory organs form. Sensory structures allow organisms to assess their environment, and sensory organ defects in humans lead to perceptive and psychological deficits. Lumen formation plays key roles in sensory organ development. Often, a tubular channel formed by glia or epithelia is penetrated by neuronal endings exposed to the environment to form the organ. How this coordinated tubulogenesis occurs is not known. Biological tubes allow liquid and gas flow in plants and animals. In humans, tubes are essential components of most organs. Defects in tube formation and maintenance, or ectopic formation of tubes, underlie numerous human disease states, including vascular aneurysms, intestinal herniations (diverticulosis), and congenital defects of the vasculature, intestine, kidney, and lungs. Excessive vascular tubulogenesis can support malignant growth. Little is known about the molecular mechanisms regulating tube lumen formation and size. The C. elegans amphid sensory organ is an excellent structure in which to study sense organ development. It is composed of 12 neurons with well-defined sensory roles, and two tube-forming glial cells that ensheath the neurons. Amphid architecture is remarkably similar to some sensory organ structures in Drosophila and mammals. Cells of the amphid are easily labeled with fluorescent reporter proteins, and their development can be examined in real time. Furthermore, genetics and molecular biology are generally facile in C. elegans, allowing for discovery of conserved molecular players regulating channel formation. We showed that a key regulator of C. elegans lumen formation is encoded by the daf-6 gene. DAF-6 protein is related to vertebrate and Drosophila Patched, and is expressed in all C. elegans tube classes, localizing to luminal surfaces. We have also shown that mutations in the wrt-6 hedgehog-like gene result in amphid defects similar to those of daf-6. The existence of a Hedgehog-Patched module has not been demonstrated in C. elegans and our results suggest that wrt-6 and daf-6 may indeed be such a module. Finally, we showed that LIT-1/Nlk kinase is a target of DAF-6 signaling, and is, thus, the first described target of Patched-related signaling in C. elegans. Here we propose three aims: (1) We will study the role of wrt-6 in lumen formation. (2) We will study lit-1 function in lumen formation. (3) We will clone previously isolated daf-6 suppressor mutations to reveal additional components of the new signaling pathway we discovered. Because Patched and related proteins are important in many aspects of human development and tumor formation, studies of the new signaling pathway we identified will help understand the functions of these key developmental proteins. In addition, our studies will provide insight into tubulogenesis, a process important for the formation of all organs, defective in congenital diseases, and hyperactivated in cancer. Public Health Relevance: Because Patched and related proteins are important in many aspects of human development and tumor formation, studies of the new signaling pathway we identified will help understand the functions of these key developmental proteins. In addition, our studies will provide insight into tubulogenesis, a process important for the formation of all organs, defective in congenital diseases, and hyperactivated in cancer. Show more... | National Institutes of Health | 6/03/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $403,515.00 | Grant | Trans-NIH Recovery Act Research Support The long-term goal of the proposed research is to understand the complex genetic control of determination of left/right (L/R) body axis in the mammalian embryo. Specification of the L/R axis sets up a developmental cascade that coordinates development of the viscera and is essential for the correct placement and alignment of organ systems and vasculature. Defective L/R patterning can lead to congenital cardiac malformations, vascular anomalies and other serious health issues. We will investigate the roles of two T-box transcription factor genes, Brachyury (T) and Tbx6. T has previously been shown to affect laterality in mice although the phenotype has not been fully explored. Tbx6 had not previously been implicated in laterality determination, but our preliminary studies and published work reveals heterotaxia in mutants, indicating an important role for this gene, and shows effects on Notch signaling and cilia within the node. We will investigate these genes to determine the nature and mechanism of the defects. Understanding how these genes impinge on this basic developmental process will add to understanding of the genetic and morphological landscape within w hich the L/R body axis is determined. Specific Aim 1. To determine the nature and mechanisms of the laterality defects associated with Brachyury (T) mutation in the mouse and place T and Tbx6 in the genetic hierarchy of genes affecting L/R determination. Specific Aim 2. To examine the structure and function of the node and nodal cilia in Tbx6 and T mutant embryos at the time of L/R axis determination. Specific Aim 3. To determine the lineage of cells of the node with respect to their prior expression of Tbx6. Show more... | National Institutes of Health | 7/14/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $381,375.00 | Grant | Trans-NIH Recovery Act Research Support Neurodegeneration associated with brain iron accu ulation (N BIA) comprises a heterogeneous group of disorders, such as infantile neuroaxoal dystroph (INAD), in which disruption of cellular mechanisms leads to accumulation of iron in the b sal ganglia. This group includes patients with discovered mutations in the PLA2G6 gene that enc des group VI Ca ' -independent phospholipase A, (iPLA2 or iPLA2P). Recently, more and more patien with INAD were identified containing mutations in the PLA2G6 gene, designated as PLA2G6-asso iated Neurodegeneration (PLAN). Our broad longterm goal is to characterize the molecular and ceHu ar mechanisms by which dysfunction of iPLA2 leads to neurodegeneration associated with brain iron accumulation in PLAN. iPLA2 catalyzes hydrolysis of sn-2 acyl chains from phospholipids a d plays an important role in cell membrane homeostasis and trafficking. Recently it was report d that iPLA2-knockout mice recapitulate the neurodegenerative features of human INAD. Little i known about how alteration of iPLA2 function causes brain iron accumulation. Previously we rep rted that inhibition of iPLA2 results in the increase of cell-membranous phosphatidylcholines containin polyunsaturated fatty acid residues that induces phosphorylation of p53 through activation of ataxia- elangiectasia mutated and Rad3-related (ATR). We have identified that hepcidin, a hormone regula ing iron export, is activated by inhibition of iPL~ in a p53 dependent manner. These findings allow u to hypothesize that dysfunction of iPLA, leads to a p53-mediated induction of hepcidin expression, ich in turn causes degradation of iron exporter ferroportin, ablation of the iron cellular export, and i on accumulation in the brain of NIBA. In this twoyear ARRA award , our objectives are: 1) to determine the expression of hepcidin in the brains of iPLA2-KO mice using in situ hybridization, 2) to det rmine the effects of mutants of iPLA2 on hepcidin expression in primary iPLA2 -I- neural cells, 3) to ch racterize p53-dependent transcriptional expression of hepcidin in the primary iPLA2 -1- neural cells, and 4) to examine the expression of hepcidin, ferroportin , and ferritin in the brain sectio s of iPLApound'-/p53-'- mice. Achieving this proposal's goals will explain why dysfunction of iPLA2 causes i on accumulation in iPLArKO mice and in INAD patients. In addition, the ARRA funding for this proj ct will preseve jobs, which will significantly contribute to the improvement of our local economy. Show more... | National Institutes of Health | 7/20/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $84,750.00 | Grant | Trans-NIH Recovery Act Research Support The maturation of dendritic cells (DCs) in response to a pathogen is essential for effective immune-mediated control of the infection and protection from subsequent re-infections. Pathogenic viruses have developed strategies to evade immune recognition by antagonizing the cellular machinery responsible for effective DC maturation. DCs, on the other hand, utilize multiple complementary systems to ensure complete maturation when encountering pathogens with the ability to bypass DC activation. These complementary mechanisms are primarily represented by type I IFNs which signal for the expression of anti-viral genes and for the complete maturation of DCs. Sendai virus (SeV) strain Cantell (C) efficiently triggers complete DC maturation irrespective of the presence of functional viral antagonists. Our data have demonstrated that SeV-C is detected in DCs by the intracellular helicases RIG-I and MDA5. Differently from other viruses sensed by these helicases, complete DC maturation in response to SeV-C is fast and independent of cytokine feedback. We have identified SeV defective interfering (DI) particles present in the viral stocks as the responsible for the extraordinarily effective induction of DC maturation by SeV-C. The specific signaling pathways responsible for the potent DC response to SeV-C infection, independently of cytokine complementation, are not known. The goal of this proposal is to implement in our laboratory standard methodology to identify the signaling pathways that participate in the direct response to SeV DI particles. We will use these techniques to perform studies to asses the role of the transcription factors IRFs 3 and 7, NF-kB, and AP-1 and their activation pathways in the induction of a fully functional DC maturation program in response to SeV-C independently of type I IFNs. These transcription factors are known to participate in the transcription of relevant DC maturation genes. The results form this investigation will be used as a lead to design future comprehensive studies aimed to characterize the mechanisms responsible for the direct triggering of complete maturation of DCs by SeV DI particles. The characterization of these mechanisms, which likely constitute the main deterrent for non pathogenic viruses, could lead to novel ways of immune stimulation. PUBLIC HEALTH RELEVANCE: Defective interfering (DI) particles provide SeV stocks with a unique stimulus that triggers potent, fast, and complete maturation of dendritic cells (DCs) independently of the cytokine feedback that is needed to complement the response to other viruses. This grant will allow us to implement in our lab the technology necessary to perform initial studies of the cellular machinery responsible for the extraordinary response to SeV DI particles. These studies are crucial for the comprehensive characterization of the DC mechanisms that efficiently respond to virus infection and should provide novel insights for the development of immunostimulatory molecules. Show more... | National Institutes of Health | 6/04/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $445,660.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses broad Challenge Area (09) Health Disparities and specific Challenge Topic 09-MD- 102 Trans-disciplinary Research to Integrate the Biological and Non-biological Determinants of Health to Address Health Disparities. Description 'Bio-behavioral chronic disease management by families of young minority children' seeks to reduce health disparities by investigating methods to close the gap between health information and health behaviors- specifically, the gap between instruction provided by clinicians to families of young children with chronic diseases and the capacity of economically stressed families to act on that instruction. Whether addressing asthma, diabetes, obesity, or tooth decay, needed now is trans-disciplinary translational research that tailors pharmacological and behavioral interventions to care management plans that parents are able to implement successfully. Envisioned is a computer 'Tool' for use in community sites that assists community health workers in collaboration with families to: (1) determine children's level of risk for chronic diseases, (2) match them to clinicians and care plans, (3) characterize a family's capacity to engage in such plans, and (4) modify care plans to meet family's capacities. Target families are those disadvantaged by low-income, low-literacy, cultural barriers and minority status. Specific research aims are to develop, pilot test, and refine two 'Instruments' that are integral to this Tool: (1) a 'disease risk assessment instrument' and (2) a culturally adaptable 'family capacity assessment instrument.' Early childhood caries ('ECC') was selected as the exemplar chronic disease for this research by an existing 12-member multi-disciplinary Project Team comprised of social and behavioral scientists, clinicians, educational and informatics technologists, and health services researchers. ECC was selected because it is highly prevalent in young children, because preventive and therapeutic bio- behavioral therapies are available but underused, and because significant cost savings may accrue to governmental programs, insurers, and families if the need for dental repair can be reduced. The proposed 'disease risk assessment instrument' will experiment with inputting recognized biological (clinical, laboratory, psychological, and pharmacologic), and non biological (knowledge, logistic, socio-cultural, and environmental) risk factors into algorithm-supported 'classification and regression tree analyses' and machine learning 'artificial neural networks' to improve on current professionally-endorsed methods of classifying young children by risk. As the proposed 'family capacity assessment instrument' has been less developed to date by the Project Team, its ultimate form will be determined by this research. Success in developing and implementing the Tool and its two assessment Instruments can result in better oral health outcomes at lower cost through risk-based early intervention, disease suppression, individualized care, family engagement, and elimination of the need for dental surgery in children under the age of six. Findings of this research will support clinical trials of risk-based caries management in vulnerable minority child populations and is adaptable to management of other chronic diseases in young children. 'Bio-behavioral chronic disease management by families of young minority children' seeks to reduce health disparities by investigating methods to close the gap between health information and health behaviors-specifically, the gap between instruction provided by clinicians to families of young children with chronic diseases and the capacity of economically stressed families to act on that instruction. Specific research aims are to develop, pilot test, and refine two 'Tools' that are integral to this Instrument: (1) a 'disease risk assessment tool' and (2) a culturally adaptable 'family capacity assessment tool.' Show more... | National Institutes of Health | 9/24/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $499,960.00 | Grant | Trans-NIH Recovery Act Research Support This grant responds to NIH Challenge 08-MH-103: Understanding the Genomic Risk Architecture of Mental Disorders. This application builds on recent animal and human data on epigenetic mechanisms mediating 'glucocorticoid programming' to address a critical gap in knowledge about how early experience confers increased biological risk for post-traumatic stress disorder (PTSD). The gap in knowledge will be addressed by examining cytosine methylation of the glucocorticoid receptor (GR) gene. The study of epigenetic modifications in relation to PTSD risk represents an important scientific frontier. PTSD occurs in only a proportion of those exposed to trauma, but has a population lifetime prevalence of 10-14%. Maternal PTSD has been identified as a risk factor for PTSD in 2nd generation offspring (F2) allowing examination of biological mechanisms in association with this risk factor. The GR gene is the focus of investigation because alterations reflecting enhanced GR responsiveness have been demonstrated in F2 with maternal PTSD, and in other PTSD samples.The relationships among cytosine methylation, GR gene expression, and neuroendocrine measures associated with PTSD risk (GR sensitivity, negative feedback inhibition, basal cortisol level and metabolism) will be examined in 120 F2 of Holocaust survivors (grouped by presence or absence of maternal and paternal PTSD) and in 30 subjects with no parental Holocaust exposure or PTSD. Since glucocorticoid programming has also been implicated as a mechanism through which [in utero] maternal stress increases risk for the subsequent development of metabolic syndrome (MetS) in their adult offspring, and recent data have linked PTSD to the development of MetS and its consequences, data on MetS will also be obtained. This project can be accomplished in two years because we can recruit from previously studied Holocaust F2 that agreed to be recontacted. Cytosine methylation will be quantified using polymerase chain reaction (PCR) primers developed by Michael Meaney, Ph.D. that selectively amplify variations in the relevant region of the GR gene for DNA methylation and splice variant analysis of mRNA in the human lymphocyte. Dr. Meaney's group has confirmed that the organization of the human GR gene closely resembles the rat GR. Our primary hypothesis is that cytosine methylation will be greater in F2 with maternal than paternal PTSD. A path analysis model will examine the contribution of this epigenetic modification to neuroendocrine and metabolic consequences associated with PTSD risk, incorporating other relevant aspects of early life experience (parental symptoms, childhood abuse and neglect, parental care and overprotection) to assess their contribution. This work is innovative in attempting to use a naturalistic intergenerational 'model system' to examine the role for an epigenetic mechanism in transmitted vulnerability for PTSD and associated health risks, and determine their relationship to other environmental contributors. The results have implications for detecting persons at risk for PTSD, but may also point to novel targets for prophylaxis and early treatment. Adult children of mothers with post traumatic stress disorder (PTSD) are at increased risk for PTSD, and also show changes in their responsiveness to the stress hormone cortisol that appear to reflect early developmental influences, possibly resulting from maternal stress effects. In this grant we investigate whether the biological changes in these offspring reflect an enduring epigenetic modification, induced by early maternal behavior that resulted in 'recalibrating' the cortisol system in a manner that increases risk for subsequent PTSD and possibly other health consequences. If such changes are observed, this research will yield an early (i.e., pretraumatic) biologic marker that can ultimately be used in screening persons at increased risk for PTSD either before or immediately after they are exposed to trauma. Show more... | National Institutes of Health | 9/25/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $499,817.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses Broad Challenge Area 01 Behavior, Behavioral Change, and Prevention. The specific topic is: Capturing Social Network Information for Groups at High Risk for Negative Health Behaviors; OD-09-003. Latinos in the United States are disproportionally affected by the HIV/AIDS epidemic, which has led to AIDS being the fourth leading cause of death for Latinos. Among Latinos, formerly incarcerated Latino men (FILM) are a critical group in the spread of HIV/AIDS. Latino men are overrepresented in U.S. correctional facilities, and incarceration has been identified as a major risk factor for HIV. Despite the high level of vulnerability to HIV-infection, HIV-prevention interventions targeting the unique needs of FILM are scarce. The majority of HIV- prevention interventions have failed to consider the role of social-familial networks in the post-incarceration experiences of FILM. The lack of attention to contextual factors is worrisome, as research supports the importance of understanding cultural, familial and social network factors for reducing HIV-infection among disproportionately affected populations, including Latinos and formerly incarcerated men. The overall goal of the current submission is to study the role of familial and social networks among FILM in order to develop the foundation for a network-based intervention to reduce HIV among FILM. To advance that broad goal, we propose the following specific aims: 1.) To conduct sixty network-based, open-ended interviews in order to elicit: (a) perspectives about FILM'S reentry into community networks, (b) information on network leisure activities with special emphasis on marijuana and alcohol binge use followed by sexual behavior, and (c) collective expectancies regarding: collective risk behaviors and network members' role in supporting FILM's efforts to reduce concurrent HIV-related risk behaviors. 2.) On the basis of the above data collected, develop a linguistically and culturally appropriate measurement of network and individual HIV risk for FILM, and examine the relationships between network and behavioral determinants on FILM HIV risk behavior via the application of a cross-sectional survey with a sample of 200 FILM and 200 nominated network referents. 3.) To examine the collective meanings attached to (and practices related to) alcohol and marijuana binge use and sexual risk behavior, in order to compare differences among the diverse networks of FILM with respect to the level of collective HIV risk as well as network-level protective factors. PUBLIC HEALTH RELEVANCE: The proposed study will be one of the first studies to investigate HIV risks among networks of formerly incarcerated men. 1. This will be one of the first studies to explicitly examine how social network systems influence concurrent sexual risk, alcohol and marijuana binge use among formerly incarcerated Latino men (FILM). 2. While other studies recruit individuals in order to create superficial intervention groups, where individuals do not necessarily know each other (to participate in sessions where very personal issues are discussed), we propose a network approach research that will lead to future network-based interventions within already existing social networks of FILM with the potential impact of enhancing the health of entire social networks. 3. The proposed study will contribute to the emerging research on ethnic minority men's health and foundational research for effective prevention programming for FILM, a consistently overlooked population in public health. Show more... | National Institutes of Health | 9/24/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $1,168,124.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): The 20% rarest cancers account for approximately 35% of the deaths from cancer in the United States. As a result, a better understanding of the nature of these rare tumors is in the public health's best interest. We study sarcomas, rare cancers of connective tissue: bone, muscle, fat, cartilage, and the other tissues that hold us together. These are cancers that occur disproportionately in children, teens, and young adults, although different forms affect different age groups. In all, sarcomas account for less than 1% of all cancer in the United States. However, since they can arise from so many different tissues, there are 70 or more sarcoma subtypes. We are interested in finding new treatments for the people with these rare cancers, who do not benefit from research on more common cancers. We have identified two new combinations of drugs that may be useful for people with sarcoma. The first of these is A12, an 'insulin-like growth factor 1 receptor' inhibitor, and temsirolimus, an mTOR inhibitor. The second is a blocker of Hh (hedgehog) signaling, GDC-0449, which we are combining with a blocker of gamma secretase (RO4929097) [Notch pathway] in a novel study for people with recurrent sarcomas. We are seeking funding to perform this multi-center study, focusing on biopsies from patients on these two studies for biological correlates of blockade of these various pathways. These biopsies will help us determine would or would not benefit from such therapy. We will also use a software tool we have recently developed, called StudyTracker, to collect the data from the multiple participating centers on the GDC-0449/RO4929097 phase I-II study. With this information, we will be able to use tests of tumors to insure that the right person is receiving the right medication, with the best chance of getting a good result from that treatment. Without such testing, clinical trials are reduced to 'throwing darts'-some people could benefit, but we will not understand why. This approach should lead to new and efficient means to treat patients with sarcomas and may also impact patients with more common cancers. PUBLIC HEALTH RELEVANCE: This is a project to support correlative studies for two multicenter clinical trials of new drugs for patients with sarcomas. These novel approaches will improve the treatment options for this underserved group of patients with this rare family of cancers Show more... | National Institutes of Health | 9/29/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $769,023.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): This application, for a Research and Research Infrastructure 'Grand Opportunities' (GO) grant (RFA- OD-09-004) will focus on 'Comparative Oncology Research' and requests funds for a unique state of the art PET insert for an MR animal scanner which will be used by numerous biomedical research laboratories as an open scientific resource, with a major impact on translational oncology research. There are 30 principal investigators and 37 peer reviewed research projects supported by this application including projects from 9 institutions outside MSKCC. Simultaneous acquisition of PET and MR data will be used for studies of novel dual MR-PET contrast agents, concurrent kinetics, biochemical studies of metabolism, and to study the distribution of labeled antibodies and the effects of hypoxia, tumor perfusion heterogeneity on uptake, targeting and efficacy. Many physiological phenomena (such as hypoxia, perfusion, pharmacokinetics) undergo acute changes, vary from animal to animal, and contrast/radiotracer agent uptake and distribution may depend on different time varying physiological parameters so simultaneous acquisition is critical. Our collaboration with Dr. Cherry envisages construction of a PET insert for MSKCC, and we will provide NMR (lactate pulse sequences, quantitation, radiofrequency coils) and chemistry expertise. We will evaluate the effect of the PET insert on MR image and spectral quality at both 4.7T and 7T and the effect of both magnets on PET performance and provide this data to Dr. Cherry. We will improve and develop novel pulse sequences for lactate detection and imaging which will be used frequently with concurrent fluorodeoxyglucose (FDG) PET scanning since both are measuring different aspects of glycolysis and are markers of prognosis. A critical development will be an isolation chamber in order to allow investigators from many institutions to use the imaging equipment and minimize the risk of cross contamination of animals from different institutions. This chamber is designed to isolate the animal from the scanner and will have ports for respiratory, temperature and cardiac monitoring to decrease morbidity and improve image quality, in addition to a port for inhalation anesthesia and other gases. MSKCC is a world leader in development and translation of radiolabeled small molecules, peptides and antibodies for the imaging and therapy of cancer. We have access to a broad gamut of radionuclides for PET studies and the chemistry expertise to dual label them with 19F, Fe or Gd to produce agents that can be visualized by both MR and PET. We will develop the isolation chamber, lactate detection methods, and novel dual modality contrast agents prior to the delivery of the PET insert for immediate use upon delivery. The MR-PET scanner will support 37 different projects that will yield significant benefit form this research. This project will be started immediately if funded and enhance multidisciplinary research and interactions between investigators of broadly different background, thereby leading to new breakthroughs in cancer care. PUBLIC HEALTH RELEVANCE: Relevance This application, for a Research and Research Infrastructure 'Grand Opportunities' (GO) grant (RFAOD- 09-004) will focus on 'Comparative Oncology Research' and requests funds for a unique state of the art Positron Emission Tomography (PET) insert for an MR animal scanner which will be used by numerous biomedical research laboratories as an open scientific resource, with a major impact on translational cancer research. Show more... | National Institutes of Health | 9/29/2009 |
| ROCKEFELLER UNIVERSITY, THE | $2,261,558.00 | Grant | Trans-NIH Recovery Act Research Support Recent studies of addiction have highlighted several regions of the brain that are thought to be involved in goal directed and drug seeking behaviors. The specific neuronal classes involved in the regulation of these behaviors are beginning to be identified, and attempts to profile the molecular changes in these cell types occurring as a consequence of addiction have met with some success. While these studies demonstrate that it is possible to discover changes in cell types that are correlated with, and in some cases contribute to, addiction, our knowledge in this area is fragmentary and incomplete. This is due to technical obstacles that have faced this field for decades, and that have recently been overcome by novel methodologies developed in our laboratories. The objective of this program of research is to identify all of the changes in gene expression and accompanying alterations in epigenetic regulation that contribute to the addictive state in cell types known to be important in the neural circuitry controlling addiction. The approach we will take in this program is to: 1) employ TRAP methodology and bacTRAP transgenic mouse lines to comprehensively profile the translated mRNAs from fifteen mouse CNS cell types that are components of the neural circuitry controlling addiction; 2) to collect translational profiles from each of these cell types in mice exposed to cocaine, methylphenidate, and methamphetamine 3) perform in depth comparative analysis of these resulting microarray datasets to identify changes in gene expression that accompany the addictive state in each cell type; 4) to concurrently isolate nuclei from each cell type and map cell specific sites of mC and hmC modification to the neuronal genomes; 5) to conduct follow up studies on genomic loci identified in the preceding aims to map additional epigenetic regulatory events by ChIP assays using H3K9m2 and H3K27m3 specific antibodies to identify genomic loci associated with suppression of gene expression in euchromatin. This project will provide information and experimental animals that will stimulate addiction research in a broad spectrum of laboratories, and provide materials and a paradigm for comprehensive studies of these same neural circuits under other experimental conditions. As such, this program will have an enormous impact on modern molecular neurobiology, and on the development of novel targets for pharmacological interventions in CNS disorders. Show more... | National Institutes of Health | 9/25/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $2,195,148.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): The PS-OC has organized a leadership structure to provide expertise and fully support all initiatives. The leadership consists of the Principal Investigator, Franziska Michor, PhD, and the Senior Co-investigator, Eric Holland, MD, PhD. Support personnel consists of the Administrator/Education Director, Desert Horse-Grant, Research/Project Manager, Raquel Sanchez, MBA, and Biostatistician, Mithat Gonen, PhD. The PS-OC leadership and support personnel, also known as the Administration, will work collectively to support and accomplish the proposed research projects, core, educational and training unit, outreach and dissemination unit, and pilot and trans-network projects. The PS-OC Steering Committee (PSC) will meet annually and will consist of two investigators from each PS-OC. The Principal Investigator, Dr. Franziska Michor, and the Senior Co-investigator, Dr. Holland, will represent our PS-OC at the PSC. The Center Advisory Committee (CAC) will bring together investigators with expertise in both the physical sciences and the basic sciences to form a group of voting and non-voting members. Specifically, the CAC will be made up of the following voting members: two physical sciences members, Franziska Michor (PD/Principal Investigator), PhD, and Chris Sander, PhD; two biological/clinical members, William Pao, MD/PhD, and Eric Holland, MD/PhD; and an NCI appointed voting member. Non-voting members will include at least two external advisors with a wide spectrum of expertise, One external advisor will have a broad proficiency in signal transduction, cancer biology, program management and a focus on a tumor type unaffiliated with the projects of the PS-OC. At least one other external advisor will have advanced knowledge of one or more of the following: evolutionary theory, non-evolutionary cancer systems, developmental biology, brain cancer, lung cancer, leukemia, applied mathematics or engineering/micro fabrication. Show more... | National Institutes of Health | 9/29/2009 |
| HARLEM UNITED: COMMUNITY AIDS CENTER, INC. | $102,317.00 | Grant | ARRA-Health Center Integrated Services development Initiative Harlem United proposed a project plan consisting of three inter-related components. 1. Expand dental clinic hours at Harlem United's 123-125 West 124th street site; 2. Expansion of staff through the hire of .26 FTE Dentist and .26 FTE Dental Assistant to staff the expanded hours; 3. Conduct marketing and outreach efforts specifically targeted to the homeless population. The Dental program expanded evening hours on Mondays and Tuesdays from 5:00 pm to 8:00 pm formerly the hours were 9:00 am to 5:00 pm. Additionally, the dental clinic opened on Saturdays, from 9:00 to 1:00 pm twice per month. In order to expand hours Harlem United proposed to hire a .26 FTE Dentist and a .26 FTE Dental Assistant. A Dentist .5 FTE was hired and started employment on August 3, 2009. Through our Health Care for the Homeless program, which conducts outreach in the Harlem Community at Single Room Occupancy residences, homeless shelters and soup kitchens referrals to our dental practice have increased. We postponed our plans to lease a van due to the second quarter hire of a dental provider. As an interim measure, another agency department loaned us van to support outreach and patient transport efforts. We will explore van lease options in the next quarter. Show more... | Health Resources and Services Administration | 3/27/2009 |
| NEW YORK UNIVERSITY (INC) | $746,902.00 | Grant | Trans-NIH Recovery Act Research Support P30 Center in Craniofacial Bone Biology | National Institutes of Health | 9/17/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $421,526.00 | Grant | Trans-NIH Recovery Act Research Support Protein secretion is among¿ the most important functions of hepatocytes. Defects in the secretory pathway can have serious consequences~ For instance, patients with congenital disorders of glycosylation in which secreted proteins are not properly glycosylated and trafficked, have serious and multisystemic problems, including hepatic steatosis that a rapidly progresses to fibrosis requiring liver transplant in very young children. Additionally, stress in the secretory pathway, called ER stress, is associated with fatty liver disease resulting from obesity and alcohol abuse and is a new and exciting line of inquiry in this burgeoning field. Importantly, drugs that improve protein folding, which are currently in clinical use, are proposed as therapies for fatty liver disease (FLO). We are using zebrafish to study the mechanism by which defects in the secretory pathway, namely protein glycosylation and the unfolded protein response, contribute to FLO. We have developed 2 new models of COG in zebrafish. One of these is the foie gras (fgr) mutant, that we identified in an effort to identify vertebrate models of liver diseases through a forward genetic screen in zebrafish. fgr mutants develops steatosis. The fgr gene is recessive embryonic lethal and is well conserved in all animals, but has not been studied in any species other than zebrafish. The gene does not encode any sequence motifs that implicate a specific function or family, and thus it represents a potential novel player in FLO. Our recent data demonstrates an essential role for Fgr in protein N-glycosylation, and fgr mutants display features of COG. The first aim of this work is to characterize the fgr allele and to define the defects in organelle function and protein trafficking that occur as a result oUgr mutation. Our second aim is to investigate the link between the unfolded protein response and steatosis in our zebrafish models of COG and alcohol exposure. Using the power of zebrafish genetics, we will determine the role of each unfolded protein response branch in steatosis in fgr mutants and alcohol-treated fish. This will conclusively demonstrate whether this pathway is protective or pathologic in the development of steatosis. Show more... | National Institutes of Health | 9/14/2009 |
| NEW YORK UNIVERSITY (INC) | $380,438.00 | Grant | Trans-NIH Recovery Act Research Support The goal of this project is to develop a passive immunization approach to prevent humans accidentally exposed to prions from developing a universally fatal disease. Prion diseases (prionoses) are transmissible, invariably fatal, neurodegenerative diseases associated with a conformational transformation of cellular prion protein PrPC into a toxic, infectious, and self-replicating PrPSC conformer for which no effective treatment is currently available. Accidental prion infection in humans may occur as a result of blood transfusion or organ transplant, ingestion of prion contaminated food, or use of prion contaminated surgical instruments. Moreover, prions are considered a potential bioterrorism agent. In this grant, we pursue a research hypothesis that passive immunization with selected anti-prion monoclonal antibodies (Mabs) can effectively prevent neurological consequence resulting from extra- CNS prion infection. Following extra-CNS exposure, PrPSc replicates within the lymphoid organs for months to years before CNS invasion causes clinical symptoms. Therefore, prion infection in the pre-CNS stage can be targeted by therapeutics, which like Mabs are not required to have substantial blood-brain-barrier penetration. Specific aims of this grant are as follows: Aim I will identify Mabs with strong therapeutic effect against human PrPSc replication, which can be humanized for clinical testing and application. Anti-PrP Mabs with strong therapeutic effect are unique. We have identified three Mabs: 6D11, 7H6, and 7A12 capable of permanent PrPSc abrogation in a cell culture model of murine prion infectivity with IC50%<1µg/ml. In our preliminary studies, we have confirmed reactivity of these Mabs with human PrP and thereby we are planning to characterize their therapeutic effect using cell culture model of human prion infectivity, which we are developing. Our testing will also include Mab 3F4, which strongly reacts with human PrPSc and has its antigen epitope located in the central portion of PrP sequence, a characteristic of other therapeutic Mabs. Aim II will provide fundamental data on the pharmacokinetic parameters of the therapeutic anti-PrP Mabs in mouse models of prion infection and non-infected control mice. These studies are of critical importance for understanding the metabolism of anti-PrP in vivo and further development of the optimal passive immunization protocol. Aim III will provide a mechanistic insight into therapeutic effect of Mabs. This aim outlines a set of experiments investigating at what stage(s) of acquisition of scrapie form properties therapeutic anti-PrP Mabs interfere with PrPSc formation and whether they also facilitate PrPSc degradation. Furthermore, we will determine the cellular compartment(s) wherein Mabs activity occurs. Show more... | National Institutes of Health | 7/21/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $549,244.00 | Grant | Trans-NIH Recovery Act Research Support Bone is a complex system whose critical function is to be sufficiently stiff and strong to support the physical forces associated with daily activities. Understanding how genetic and environmental variants compromise this function is critical to fully understanding why certain individuals are more susceptible to fracturing. Trabecular and cortical traits both contribute to load bearing of corticocancellous structures, and variation in the relative proportion of these two tissue types is a critical determinant of fracture risk. However, the cause of variation in the relative proportion of cortical and trabecular tissues among individuals is not well understood. Based on our own work examining functional relationships in mouse and human long bone, we postulate that variation in cortical and trabecular traits arises from an interplay between functional adaptation (Wolff's Law) and genetic variants affecting bone size. We propose to determine how genetic variants affecting vertebral size, a critical determinant of fracture risk, are compensated by specific functional interactions among cortical and trabecular traits. We hypothesize that genetic variation in trabecular bone mass and architecture depends on the degree of load sharing arising from genetic variants affecting cortical size and quality. Further, we propose to determine how the functional interactions among cortical and trabecular traits maintain strength with aging. Because phenotypic covariation gives rise to genetically varying sets of adult traits, we also test the hypothesis that certain adult trait sets will be more resistant to bone loss and better able to maintain strength with aging. We will test these hypotheses using a panel of AXB/BXA Recombinant Inbred (RI) Mouse Strains, which is a powerful model to study compensatory relationships among traits within the normal (i.e., non-pathological) range of genetic variability. In Aim I, we use Path Analysis to test whether trabecular and cortical traits show a compensatory relationship, and identify the trait interactions that compensate for genetic variants affecting adult vertebral size. In Aim II, we determine how phenotypic covariation arises during growth. In Aim III, we assess the impact of phenotypic covariation on the ability of bone cells to maintain stiffness and strength with aging. Finally, we test how sex affects phenotypic covariation throughout growth and aging. This systems analysis, which examines the relationship among traits in the context of functionality, will provide new insight into the genetic basis of fracture susceptibility. PUBLIC HEALTH RELEVANCE: We propose to determine how functional interactions among cortical and trabecular traits compensate for genetic variants affecting vertebral size and contribute to fracture susceptibility. We use genetically randomized inbred mouse strains to determine how compensatory trait interactions arising during growth lead to varying sets of adult traits expressing different abilities to maintain strength with aging. This systems analysis, which examines the relationship among traits in the context of functionality, will provide new insight into the genetic basis of fracture susceptibility. Show more... | National Institutes of Health | 8/07/2009 |
| PRESENT THEATRE COMPANY, THE | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/15/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $497,605.00 | Grant | Trans-NIH Recovery Act Research Support This research proposal, entitled 'A Novel Epigenetic Gene Silencing Technology', addresses the broad Challenge Area: (06) Enabling Technologies, and specific Challenge Topic, 01-OD-107: Functional Modulation of Epigenomic Modifications. The ability to modulate gene expression holds great promise for genome biology research and for novel treatments of intractable human diseases caused by the dysfunction of genes. RNA interference (RNAi) that blocks gene translation to protein by small interfering RNA (siRNA)-triggered messenger RNA destruction has had transformative impact in research and also generated enormous excitement and hope for new therapies. However, due to daunting challenges in siRNA delivery and off-target side effects, the RNAi gene silencing technology has yet to produce new therapeutics. On the other hand, recent advances in the field of epigenetics show that site-specific modifications in chromosomal DNA-packing histones dictate gene expression or silencing in response to physiological and environmental stimuli. For instance, histone H3 lysine 4 methylation (H3K4me) directed by the Trithorax group complex signifies for gene activation, whereas H3 lysine 27 methylation (H3K27me) controlled by the Polycomb group complex is an epigenetic marker for gene silencing resulting from chromatin compaction. While effective in mammalian gene transcriptional control, the Trithorax or Polycomb group complex works through multiple proteins in a highly coordinated fashion. Thus, it is not feasible to direct Trithorax or Polycomb proteins for targeted gene activation or silencing for the purpose of research or therapeutic disease treatments. We have recently discovered a novel viral mechanism for host transcriptional repression centered on histone methylation (Nature Cell Biology, 2008). We show that the chlorella virus uses a viral protein (termed vSET) to modify specifically host histone H3 lysine 27 in the infected cells, thereby switching host transcription machinery for viral replication. Given that this epigenetic silencing mechanism is conserved in eukaryotes, we show that vSET can effectively suppress transcriptional expression of Polycomb target genes in human cells such as the HOX genes. Because of its exquisite activity for methylation of histone H3 at lysine 27, vSET can in principle be developed into a selective epigenetic gene silencing technology by fusing itself to a gene sequence-specific recognition domain, which is the goal of our proposed research. We expect that this novel gene silencing technology, which fills an important technological gap of controlling gene silencing at the transcription level, will have broad impact as a powerful tool in genome research of human biology and disease. Show more... | National Institutes of Health | 9/21/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $496,269.00 | Grant | Trans-NIH Recovery Act Research Support DEVELOPING A NORTH AMERICAN MITOCHONDRIAL DISEASE CONSORTIUM This application addresses one broad Challenge Area, (07) Enhancing Clinical Trials (07-OD(ORDR)-102: Rare Disease Genetic Patient Registry. By most epidemiological studies, primary mitochondrial disorders, defined as inherited defects of the mitochondrial respiratory chain (RC), are rare diseases (<200,000 affected individuals in the US) due to primary mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Mitochondrial diseases are among the most clinically heterogeneous conditions because mitochondria are ubiquitous organelles and the expression of disorders due to mtDNA mutations depends on the proportion and tissue distribution of mutated mtDNAs. Thus, mitochondrial diseases are baffling to general practitioners, scary to patients and families, and generally misunderstood despite the organizational and teaching efforts of the patients advocacy group, the United Mitochondrial Disease Foundation (UMDF). Together with their rarity, the clinical and genetic heterogeneity of mitochondrial diseases has hindered natural history studies and rigorous clinical trials. In no other area of medicine is the need for a North American patient registry more critical. This application aims at establishing the infrastructure needed to launch a mitochondrial disease patient registry, biorepository, and a North American Mitochondrial Disease Consortium (NAMDC) with the support of UMDF. The NAMDC will feature advanced data management systems and statistical design capabilities provided by the Statistical Analysis Center (SAC) in the Department of Biostatistics at Columbia University. This structure will be the indispensable basis for future collaborative studies of epidemiology, natural history, therapeutic trials, as well as in-depth research on pathogenesis. As research on the mitochondrial role in human diseases progresses at a very rapid pace, the time is ripe for the establishment of a North American Mitochondrial Disease Consortium and patient registry, which will provide infrastructure for translational research and prepare the ground for rigorous natural history studies and therapeutic trials that are sorely needed for these generally devastating disorders. Show more... | National Institutes of Health | 9/25/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $647,563.00 | Grant | Trans-NIH Recovery Act Research Support For the hundreds of thousands whose lives have been saved by antiretroviral therapy (ART), scale-up has been a success. There is an urgent need, however, to better understand how access to ART shapes risk and protective behaviors. Moreover, growing concern with the possibility of disinhibition, limited participation in voluntary counseling and testing programs, gender and social class differentials in access to ART, and continuing high transmission rates among sero-discordant couples underline the urgency of research on how access to ART affects communities in both the US and abroad. In the proposed project, we will use comparative ethnographic methods to analyze how people integrate ART into their sexual and reproductive lives, using what we learn to improve individual and population-level health. Drawing on our substantial prior work in five field sites (Washington Heights (NYC), Nigeria, Uganda, Vietnam and Papua New Guinea) representing a wide range of levels of development and epidemiological profiles, as well as on our successful collaborative research on married women's HIV risk (R01HD041724), we will explore the tensions and complementarities between people's overall life goals (their life projects), the ways they care for their bodies, and their sexual, reproductive, and disclosure practices. Research Design Parallel data collection in each setting will include: 1) longitudinal in-depth interviews with 60 individuals (3 interviews/person, collected over three years; 300 individuals & 900 interviews across sites), with each site's sample including 36 who are participating in ART, 12 who are HIV+ but not in care, and 12 who are seronegative or have not been tested; 2) mapping of those 60 individuals' therapeutic itineraries; 3) intensive extended case studies with a subset of 20 selected individuals in each site (15 visits/person; 20 individuals/site; 1500 visits total across 5 sites); participant observation in clinic, support group and community settings; 5) key informant interviews (20/site, 100 total); and 6) collection and analysis of archival and popular cultural materials. The translation plan is grounded in policy science 'best practices' about how research can most effectively shape policy. Through a multi-step process which begins in the first project year, we will work with in-country collaborators to develop widely-applicable program strategies to enable appropriate disclosure, more effectively promote health-protective sexual behaviors, improve participation in testing and counseling, realistically address the partnering and reproductive intentions of people receiving ART, and improve adherence to therapy. PUBLIC HEALTH RELEVANCE: The United States continues to confront an HIV epidemic that is increasingly entrenched among urban minorities. The nation is also a leading funder of programs to increase access to life- saving anti-retroviral therapies (ART) for people around the world who have AIDS. In both domestic and international settings, more information is needed about how access to these powerful medications influences risk and protective behaviors. In this project, anthropologists will work in Nigeria, Uganda, Vietnam, Papua New Guinea and New York City to study the relationship between ART, people's overall goals for their lives, and their sexual and reproductive behavior. This information will be used to improve ART services both domestically and internationally. Show more... | National Institutes of Health | 9/22/2009 |
| NEW YORK UNIVERSITY (INC) | $1,179,863.00 | Grant | Trans-NIH Recovery Act Research Support The most significant determinant of educational and clinical impairment in school-age children with autism spectrum disorders (ASD) is the frequent co-occurrence of hyperactivity and inattention symptoms. In response, clinicians treating ASD are increasingly adopting the terminology, rating scales and medication treatments established for the management of Attention-Deficit/Hyperactivity Disorder (ADHD). However, responses to stimulants are less substantial than obtained in ADHD, and with greater risk of adverse effects. This conundrum can be clarified by examining the neuronal substrates of these symptoms with novel resting state fMRI methods employed by our lab for mapping brain functional connectivity. FMRI signals contain large amplitude low frequency spontaneous fluctuations. Such fluctuations are usually ignored, but 'functional connectivity' (FC) analyses reveal strikingly consistent patterns of intrinsic synchronized activity that delineate entire functional circuits and that differ significantly in multiple psychiatric disorders. Analyzing FC during rest is well suited for studies of children with ASD or ADHD, because the absence of a task minimizes potential floor, ceiling, or practice effects. Our preliminary data demonstrate the feasibility of relating inter-individual differences in hyperactivity, inattention, and social reciprocity to indices of FC strength in key neural circuits. To address ASD heterogeneity with regard to ADHD-like symptoms, we propose relating brain FC to Social Responsiveness Scale (SRS) scores, and to parent ratings of hyperactivity/impulsivity and inattention. Building on ongoing funded studies of children with ADHD and typically developing controls (TDC) [which are already supporting half of the TDC and ADHD samples that would be included in this project], we will characterize three groups of right-handed children (n=100/group) ages 8-11 years (ASD, TDC, and ADHD) with respect to parent SRS ratings, and Conners ratings of hyperactivity/ impulsivity and inattention. Each group will be group- matched on age, sex, and socioeconomic status to address the following specific aims: (1) To determine the extent to which symptoms of hyperactivity/impulsivity and inattention in ASD can be attributed to the presence of abnormalities in the same neural circuits as in ADHD; (2) to identify neural circuits uniquely associated with symptoms of hyperactivity/impulsivity and inattention in ASD; and (3) to determine if brain correlates of social reciprocity in ASD are independent of symptoms of hyperactivity/impulsivity and inattention. If successful, we will be able to differentiate individuals with ASD-related hyperactivity and inattention with underlying pathophysiology indistinguishable from that observed in ADHD from those in whom the pathophysiology is ASD-specific. Such stratification is required for pathophysiology-guided treatment-response studies of ASD- related symptomatology, leading to targeted therapeutics in this highly heterogeneous population. Additionally, this proposal will implement an important goal of the ARRA by supporting the creation of five new full-time positions. PUBLIC HEALTH RELEVANCE: Although many school-age children with autism spectrum disorders are also hyperactive and inattentive, which further limits their school and social functioning, we have not been able to determine whether the brain processes responsible for such ADHD-like symptoms are the same as in typical ADHD or whether they reflect distinct brain processes. Using new methods to measure spontaneous brain function, we propose to disentangle these issues in three groups of children with autism spectrum disorders, ADHD, and typically developing controls. If successful, we will be able to better understand the types of brain mechanisms that are involved in hyperactivity and inattention in children with autism and then be able to use that information to guide targeted treatment studies. Show more... | National Institutes of Health | 9/28/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $851,391.00 | Grant | Trans-NIH Recovery Act Research Support Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM-1) is atransmembrane protein found on leukocytes, endothelium, and epithelium. Its activation canattenuate colitis in murine models. Microarray analysis revealed that CEACAM-1 is increased inthe small bowel during intestinal graft-versus-host-disease (GVHD). We studied the role ofCEACAM-1 in mouse models for allogeneic bone marrow transplantation. We found thatCEACAM-1-/- donor T cells caused significantly more GVHD (p<0.05, while CECAM-1-Tg donor T cells caused significantly less GVHD (p<0.01). Administration of a CEACAM-1 agonistic antibody CC1 also significantly attenuated GVHD (p<0.01). Histopathological analysis revealed significantly increased GVHD of the large bowel in recipients of CEACAM-1-/- T cells (p<0.05). while recipients of CEACAM-1-Tg T cells had decreased GVHD in all organs (p<0.01). We perfomed an extensive analysis and found that alloactivated CEACAM-1-/- T cells (a) have increased CD25 and decreased CD62L expression (b) have increased expression of the gut--homing integrin 4-7 (LPAM) and (c) preferentially infiltrate the intestines, while CEACAM-1-Tg T cells (d) have decreased infiltration of all organs. Therefore the major hypothesis is: CEACAM-1 is an important negative regulator of donor T cells during GVHD. We will test the following specific hypotheses: (1) CEACAM-1 regulates tumor growth and the graft-versus-tumor activity; (2) CEACAM-1 regulates alloreactive T cell trafficking and integrin 4-7 expression; (3) CEACAM-1 regulates DC-mediated imprinting of gut-specific homing of alloreactive T cells; (4) CEACAM-1 regulates T cell polarization toward the Th1, Th2, Th17, and regulatory T cells; and (5) the administration of the CEACAM-1 agonist CC1 can ameliorate GVHD. Show more... | National Institutes of Health | 6/01/2009 |
| NEW YORK UNIVERSITY (INC) | $616,818.00 | Grant |
Trans-NIH Recovery Act Research Support Obesity is one of the most pressing public health problems in the United States. Through its negative influence on cardiovascular disease, diabetes, and cancer, obesity is a significant contributor to premature morbidity and mortality, as well as economic costs. Despite the magnitude of the problem, the public health system is faced with an almost complete dearth of population-level solutions to encourage sustained weight loss or halt weight gain. A large contributor to recent rises in obesity is that highly caloric foods are increasingly eaten outside the home, particularly fast foods. As such, one recently proposed population-level solution is a policy dictating mandatory calorie labeling of all menu items in fast-food restaurants. However, these policies are currently playing out across the country with little to no evidence as to their potential effectives in altering food choice. This project proposes to study calorie labeling as it plays out in two cities to provide evidence as to its effectiveness in combating obesity. The introduction of calorie labeling in some cities and not others provides us with a unique opportunity to study a natural experiment. We will utilize a difference-in-difference design to study calorie labeling as it is introduced in two cities but not in two, separate control cities. We will collect data before and after labeling is introduced in each city (intervention and control) via two separate means. To objectively measure the caloric content of food choice and satisfy our primary aim, we collect receipts from randomly sampled fast food restaurants in the intervention and control city. For our secondary aim, to provide greater insight as to the effectiveness of labeling as well as why labeling is effective or not, we will conduct a telephone survey at the same time the receipt collection occurs. We will focus our examination on the decision making of the consumer, utilizing the concepts of behavioral economics. Even though calorie labeling is being considered and implemented across the country, we have little to no knowledge as to its potential effectiveness. This project has the potential to provide significant insight as to whether this policy is indeed effective in combating the obesity epidemic. Moreover, it will shed light on why the policy is effective or not. The long term goal is to build on this knowledge to develop effective public polices to combat obesity. PUBLIC HEALTH RELEVANCE: Obesity has increased dramatically over the past decade, with its associated negative health consequences. However, we currently have few population-health oriented solutions to address the problem. This application examines whether mandatory calorie labeling influences the food choices of individuals as well as how we might learn from consumer reactions to the policies to develop other obesity-related public policies. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 8/14/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $841,672.00 | Grant | Trans-NIH Recovery Act Research Support Maternal depressive symptoms are associated with reduced maternal quality of life, decreased ability to function, increased infant hospitalizations, reduced breastfeeding, less involvement of mothers with important developmental behaviors such as talking and playing, and increased maternal smoking and alcohol use. Recent studies have begun to examine the contextual setting of the early postpartum period and identify potentially modifiable determinants of postpartum depressive symptoms. Situational factors such as distress from physical symptoms, infant colic, and lack of social support are triggers for postpartum depressive symptoms while social support and mother's efficacy in managing situational stress buffer depressive reactions. We developed and pilot tested an intervention to reduce depressive symptoms in postpartum mothers by preparing and educating women about specific situational triggers of depressive symptoms, by bolstering personal and social resources, by enhancing self-management skills to buffer postpartum demands, and by increasing access to existing healthcare and community resources available to postpartum mothers. We obtained funding from NCMHD to conduct a randomized controlled study to test this intervention in Black and Hispanic mothers. The proposed study will add to this trial women from all racial/ethnic backgrounds. This is feasible within a two year time because of the large volume of deliveries at Mt. Sinai. Two staff members will be hired to accommodate this increased patient flow. Show more... | National Institutes of Health | 5/07/2009 |
| CORNELL UNIVERSITY, INC | $84,500.00 | Grant | Trans-NIH Recovery Act Research Support Chronic exposure to opioids can lead to dependence, a phenomenon that is manifest by withdrawal-induced somatic, autonomic, and aversive symptoms that critically involve the central nucleus of the amygdala (CeA). Avoiding physical withdrawal symptoms can contribute to sustained drug use, however, the experience of withdrawal-associated cues may also facilitate drug seeking behavior. Thus, elucidating the neural processes mediating opioid dependence, particularly the development of withdrawal-cue associations, may be essential to our understanding of the neurobiology of addictive disease. It has been shown that postsynaptic NMDA receptor knockout in CeA neurons inhibits opioid withdrawal-induced place aversion, however the neural mechanisms mediating the relationship between CeA NMDA receptor activity and withdrawal-conditioned aversion are unknown. One of the critical links between NMDA receptor activation and neuro-behavioral plasticity involves functional modulation of GluR2 expressing AMPA receptors. AMPA-type glutamate receptors expressing the GluR2 receptor subunit determine calcium permeability, play a critical role in neural and behavioral plasticity, including addictive processes, and are highly expressed in the CeA. However, there is no direct evidence that GluR2 gene expression in the CeA plays a role in conditioned aversive processes. The primary goal of this application is to test the hypothesis that postsynaptic expression of GluR2 in central amygdala neurons is necessary for opioid withdrawal-induced conditioned place aversion (CPA). This hypothesis will be addressed by the use of a multidisciplinary approach combining spatial-temporal gene deletion, light and electron microscopy, in situ hybridization, and behavioral analysis. Aim 1 of this project is to show that microinjection of a neurotropic adenoassociated viral vector expressing Cre recombinase in floxed GluR2 mice will produce reductions of GluR2 mRNA and postsynaptic protein immunolabeling in neurons without producing untoward neural or gross phenotypic effects. Aim 2 of this project is to demonstrate that bilateral deletion of GluR2 in the CeA will attenuate naloxone-precipitated conditioned place aversion in morphine dependent mice. A model of postsynaptic GluR2 deletion in CeA neurons will provide important information about the role of non-calcium permeable glutamate receptors in opioid dependence. This project should augment existing cellular and systems models of opioid dependence, thus offering the possibility of developing AMPA-GluR2 based small molecule or genetic therapeutics for the management of opioid dependence, and perhaps other components of addictive disease. Show more... | National Institutes of Health | 7/14/2009 |
| CORNELL UNIVERSITY, INC | $295,750.00 | Grant | Trans-NIH Recovery Act Research Support Health Relatedness: Over 400,000 Americans are afflicted with multiple sclerosis (MS), with severe disability ultimately affecting ~85% of the total MS population. Disability in MS is primarily due to demyelination and axonal injury. Axonal injury itself is tied to demyelination as significant axonal transection occurs in acute demyelinatng lesions, and gradual axonal loss is linked to chronic demyelination. Preventing demyelination and enhancing remyelination are essential to preserving CNS integrity and promoting recovery in MS. We propose that the TLR2-MyD88-IRAK1/4 pathway is central to both the process of demyelination and failure of remyelination in MS. Our hypothesis is that activation of the TLR2-MyD88-IRAK1/4 pathway in innate immune cells leads to inflammatory destruction of oligodendrocytes, myelin, and axons, whereas, activation of this same pathway in oligodendrocytes blocks their normal maturation thus preventing remyelination. Long-term goals: Our long-term goals are to define molecular pathways in MS, that play essential roles in the injury and repair process, for use as therapeutic targets. In this proposal our goal is to determine the importance of the TLR2-MyD88-IRAK1/4 pathway in causing demyelination and axonal injury, and in inhibiting remyelination, through in vivo and in vitro modeling. Research Approach: In all three aims, the common goal is to determine the function of the TLR2-MyD88-IRAK1/4 pathway in MS model systems using demyelination, oligodendrocyte death, axonal injury, neuronal death, oligodendrocyte maturation and remyelination as end points. Aim 1 and 2 are dedicated to in vivo modeling of demyelination and remyelination respectively. In aim 1 cuprizone mediated demyelination is used to study the impact of the TLR2-MyD88-IRAK1/4 pathway on the process of demyelination and the contribution in innate immunity to this process. Relevant knock-out mice are used to establish functional significance of TLR2, MyD88, and IRAK1/4. Quantitative assessments of demyelination, oligodendrocyte death, axonal injury, neuronal death, and inflammation will be made. In aim 2 we will study the impact of the TLR2-MyD88-IRAK1/4 pathway on remyelination using the cuprizone and lysolecithin models. Quantitative assessments of remyelination, oligodendrocyte maturation, oligodendrocyte survival, neuronal survival, and axonal integrity will be made. In aim 3 we will use an in vitro approach to dissect the specific effect of TLR2-MyD88-IRAK1/4 activation in oligodendrocytes versus microglia. We will study purified oligodendrocytes from wild-type and relevant knock-out animals for the impact of TLR2-MyD88-IRAK1/4 activation on maturation, survival, and proliferation. We will study microglia in combination with oligodendrocytes or neurons with one of the populations being null for TLR2, MyD88, or IRAK1/4 to isolate the effect in a single cell type. We will validate the results using chimeric cultures composed of mixed CNS cultures from wildtype and relevant knock-out animals. Show more... | National Institutes of Health | 9/28/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $417,780.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): Malignant gliomas are the most common and lethal adult primary brain tumors. Despite aggressive therapeutic interventions, these tumors are difficult to eradicate due to their diffusely infiltrative growth pattern and frequent resistance to chemotherapeutic adjuvant therapy. The severity of these malignant properties may differ among various histologic subtypes of gliomas. In addition, pathologic features may be heterogeneously distributed within individual tumors. Therefore, histopathologic analyses derived from biopsied tumor specimens may not adequately represent all tumor components. The integration of functional and metabolic neuroimaging techniques into navigated surgical protocols may improve biopsy targeting efforts. The long-term objectives of this proposal are to determine whether combined PET and MR imaging strategies can identify and localize key histologic and molecular features of high-grade gliomas at sites corresponding to the imaging findings, improve prognostic assessments, and serve as biomarkers for treatment intervention. This proposal aims to: (1) determine the feasibility of quantifying proliferative activity and microvascular permeability within newly-diagnosed, high grade gliomas on a voxel-by-voxel basis using a novel software platform and combined 18F- FLT PET and DCE-MRI; (2) detail relationships between these parameters and histologic markers at a local level using image-guided neuronavigated surgery and contrast-enhanced intraoperative MRI; (3) assess whether parametric images, derived by pharmacokinetic modeling methods, spatially correlate with regional histologic assays of tumor cell proliferation at corresponding locations; and (4) evaluate whether differences in gene expression, seen between areas of increased and decreased proliferative activity or microvascular permeability on parametric maps, define consistent differential transcriptome signatures, and whether these are interpretable in the context of known molecular subclasses of GBM and pathways. Currently, there is no accurate or reliable method for investigating associations between the histologic and molecular properties of gliomas and molecular imaging findings. The success of this study will establish the groundwork for larger prospective studies assessing 18F-FLT proliferative response as a biomarker in trials of targeted therapy, relating estimates of proliferation with prognosis and clinical outcome. PUBLIC HEALTH RELEVANCE: Malignant gliomas are heterogeneous tumors in both appearance and gene expression, and are uniformly fatal. The identification of characteristic imaging findings using a combination of metabolic and functional imaging strategies, which can be linked to distinct molecular phenotypes, may offer prognostic information, facilitate treatment planning, and improve our understanding of the molecular and pathological heterogeneity within individual tumors. Show more... | National Institutes of Health | 6/01/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $220,224.00 | Grant | Trans-NIH Recovery Act Research Support This revised R21 research grant application represents a partnership between the YMCA of Greater New York (YNY) and Columbia University. Over 2 years, the planned study will adapt a parent-involvement program for combined use with a previously tested program for girls called RealTeen. The resulting combined programs will be tested with a sample of adolescent girls enrolled in YNY after-school programs and the mothers of these girls. Besides testing the outcomes of both prevention programs, the planned research will examine intervention effects on mediator variables of girls' coping responses, refusal skills, mood management skills, conflict resolution abilities, problem-solving skills, self-efficacy to avoid substance use, body esteem, normative beliefs about drug abuse, social supports, disciplinary and delinquency behaviors, and conduct problems. Additional study measures will examine the extent to which the intervention programs affected girls' mothers' use of family rituals, rules against substance use, and mother-daughter affect. Other study aims are to relate girls' and mothers' measured mediator variables to girls' drug use, to test dose-response intervention effects, and to determine whether intervention exerted differential effects related to girls' ethnic-racial group profiles. Girls and their mothers will complete all study measurements online at pretest, posttest, and 6-month follow- up. Intervention delivery will occur via the Internet and CD-ROM. YNY staff and administrators are full participants in all aspects of the planned research, including the analysis and interpretation of data, the dissemination of findings, and requests for follow-on support. Through the R01 research grant mechanism, that follow-on support will sponsor a large- scale test of parent-involvement and RealTeen prevention programs with girls enrolled in YNY after- school programs and the mothers of these girls. In the follow-on test, not only will we measure end- point substance use outcomes, but also we will examine program implementation variables of fidelity and participant feedback and parameters relevant to the adoption and maintenance of the prevention programs within the YNY community. YNY administrators are committed to marketing the tested programs through the 22 YNY centers in New York City and nationwide. PUBLIC HEALTH RELEVANCE: In response to growing rates of substance use among American adolescent girls, this revised and resubmitted grant application describes a collaborative study to refine and pilot test gender- specific and parent-involvement approaches to drug abuse prevention. Study participants will be adolescent girls and their mothers recruited from YMCA centers of Greater New York (YNY). After completing pretest measures via the Internet, girls and their mothers will be divided into intervention and control arms. Girls and mothers in the intervention arm will interact online with prevention programming, and all participants will complete posttests and follow-up measurements online. Once the prevention approaches are carefully tested in a large-scale clinical trial, they will be disseminated nationally through YMCA centers. Show more... | National Institutes of Health | 7/16/2009 |
| NATIONAL DEVELOPMENT AND RESEARCH INSTITUTES, INC. | $225,450.00 | Grant | Trans-NIH Recovery Act Research Support Injection drug use continues to be a major risk factor for HIV and HCV infections worldwide. New approaches to reducing such infections are needed. This project will develop a new Staying Safe Intervention based on the strategies and practices of long term IDUs who have managed to remain uninfected not only with HIV but also with Hepatitis C (HCV). This study will test the efficacy of such an intervention. Show more... | Department of Health and Human Services | 7/16/2009 |
| CORNELL UNIVERSITY, INC | $232,260.00 | Grant | Trans-NIH Recovery Act Research Support Parkinson's disease (PD) is a devastating neurodegenerative movement disorder characterized by a loss of dopamine-containing neurons of substantia nigra, which currently affects about 1.5 million people in the United States. While the causes of PD are unknown, a critical role of oxidative damage and inflammation has been implicated in PD pathogenesis, in that impairment of Nrf2/ARE (NF-E2 related factor 2/antioxidant response element) signaling seems to trigger an irreversible pathway causing oxidative damage, mitochondrial dysfunction and neuroinflammation leading to neurodegeneration. An extremely promising pathway for neurotherapeutics in neurodegenerative diseases is the Nrf2/ARE signaling pathway. The leucine-zipper transcription factor Nrf2 has been identified as a key regulatory factor in the coordinated induction of ARE driven battery of cytoprotective genes, including those encoding for a variety of both antioxidant and anti-inflammatory proteins. We have developed synthetic triterpenoids that are structurally modified to achieve increased bioavailability in the brain and are potent activators of Nrf2/ARE pathway which upregulate large number of genes involved in antioxidant defenses and downregulate genes involved in inflammation. Oral administration of these Nrf2/ARE activators attenuate dopaminergic neurodegeneration caused by parkinsonian neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). We hypothesize that these synthetic triterpenoids possess great potential as therapeutic candidates in preventing dopaminergic neurodegeneration in PD. Two specific aims are proposed to test the hypothesis. Aim 1 will examine the relative efficacy of triterpenoid drugs CDDO (2-cyano-3, 12-dioxooleana-1,9-dien-28-oic acid) methylamide, ethylamide, and trifluoroethylamide that activates the Nrf2/ARE pathway, in exerting neuroprotective effects in both acute and chronic MPTP mouse models of PD and will also determine the Nrf2/ARE signaling modulated by these triterpenoid drugs using wild type and Nrf2 knockout mice in an effort to identify their precise mode of neuroprotection. Aim 2 will examine the therapeutic efficacy and Nrf2/ARE signaling as the mode of action of these triterpenoid drugs in blocking mutant human A53T ?-synuclein-induced PD by selectively expressing this transgene in nigral dopaminergic neurons. Testing neuroprotective efficacy of these triterpenoids that upregulate antioxidant genes and downregulate inflammatory genes by activating Nrf2/ARE pathway in the MPTP and ?-synuclein-induced rodent mo Show more... | National Institutes of Health | 6/01/2009 |
| THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK | $219,927.00 | Grant |
Trans-NIH Recovery Act Research Support The multi-gene family of proteins called connexins form intercellular gap junctions that directly mediate signaling between adjacent cells. These cell-cell channels consist of two hemichannels or so-called connexons from adjacent cells. In addition to forming gap junctions, some members of the connexin family can also function as transmembrane ion channels in the undocked state. Thus, connexins can participate in mediating signaling across the plasma membrane as well as between cells. Both cell-cell channels and hemichannels formed by connexins play a wide variety of roles in a number of different cell types and tissues, as highlighted by numerous studies using genetic and molecular approaches. Connexin channels have also been proposed as new and promising pharmacological targets in the treatment of epilepsy, cardiac arrhythmia, cancer, stroke, essential tremor, and in reducing the extent of cell death following ischemia. However, progress in the identification and characterization of specific and high-affinity inhibitors of these channels, which would greatly assist in the investigation of their physiological and pathophysiological roles, has been unfortunately slow. With the goal of identifying new classes of drugs that inhibit connexin channels, we initiated a collaboration with Dr. Heike Wulff at UC Davis in July 2006, whose laboratory specializes in the design of small molecule ion channel modulators. Through screening of a small number of compounds from Dr. Wulff's libraries enriched in ion channel modulators we have already identified four new small molecule chemotypes that inhibit connexin channels In this grant proposal, we propose to extensively probe the SAR of these molecules using a classical medicinal chemistry approach with the ultimate goal of developing a high-affinity, specific inhibitor(s) of connexin channels. PUBLIC HEALTH RELEVANCE: Proteins called connexins play a wide variety of roles in human physiology and disease. However there are no pharmacological tools to evaluate their role in human biology or to determine their therapeutic utility in prevention/cure of certain types of diseases. Proposed studies are aimed at the development of pharmacological agents for this class of channels. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 5/15/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $254,250.00 | Grant | Trans-NIH Recovery Act Research Support During recent years, the vesicles of the endosomal/lysosomal (E/L) system have emerged as key sites for the regulation of many cellular functions. Their biological importance is exemplified by the occurrence of numerous lysosomal storage diseases (LSDs), each resulting from the deficiency of a single protein in the system, that manifest with severe phenotypes, usually leading to neurodegeneration and early death. How these single gene defects can produce such severe phenotypes is not entirely clear; dissection of the metabolic changes that occur within the E/L system should provide insights towards understanding disease pathogenesis and provide new avenues for screening, early diagnosis, and monitoring of therapeutic approaches. That disease pathogenesis of the LSDs originates in the E/L system presents unique challenges for the characterization of metabolic changes in patients, since circulating biological fluids do not offer a comprehensive view of these changes and obtaining tissue samples on a regular basis is not feasible. We will use a novel approach involving exosomes to identify and characterize the metabolic changes that occur in LSDs. Exosomes are uniquely suited for this type of study because they are secreted by many cell types and are found in biological fluids such as plasma, urine, and cerebrospinal fluid and are derived from the membranes of late endosomes. Thus, they contain a subset of proteins normally found there and can serve as useful source material to characterize the changes that occur within the E/L system as a result of disease. We hypothesize that exosomes derived from disease cells will reflect protein and lipid changes that are specific to the disease. In this respect, exosomes will provide a 'fingerprint' or 'barcode' unique to each LSD. Here, we propose to: 1) test the hypothesis that exosomes from human disease cells have unique protein and/or lipid identifiers that will distinguish them from those of normal cells and reveal alterations of specific metabolic pathways. We will map these pathways and validatelevaluate these changes in vitro and in vivo. 2) Test the prediction that changes in glucose metabolism correlate with NPC1 disease severity and can be used to monitor disease progression. In short, this new approach is a new paradigm in metabolic analysis and will facilitate the efficient discovery/characterization of altered LSD metabolic pathways and provide us with the next step in understanding lysosomal storage disease pathogenesis. Show more... | National Institutes of Health | 6/05/2009 |
| NEW YORK, CITY OF | $770,000.00 | Grant | The Perimeter Security Fencing project will be utilized to provide necessary fencing to ensure security integrity is maintained as required under the applicable facility security plans governed by MTSA 33 CFR Parts 101-105 for NYC Department of Transportation's Staten Island Whitehall Ferry Terminal. As the primary access control measure, perimeter security fencing will enhance measures to ensure that the public utilizing the location continue to be safe while limiting/controlling public, non-credentialed access. This type of access control will prevent infiltration of unauthorized individuals into areas deemed restricted and/or of a sensitive security nature within the Whitehall terminal. Based on costs for Perimeter Security Fencing installed at NYCDOT's other ferry terminal, St. George, the cost is approximately $400 per linear foot. The Personal Protective Equipment project will be utilized to provide necessary personnel protective equipment for first responders of emergency response events for all NYCDOT Staten Island Ferry facilities and vessels. NYCDOT Staten Island Ferry has developed drill and exercise scenarios that require testing and execution on a periodic basis as required by 33 and 46 CFRs as well as the Ferry's own Safety Management System. Security Drills and planning with the NYC Fire and Police departments as well s the Office of Emergency Management require that while performing the drills the equipment must be available, particularly as first responders. It is anticipated that eye protection glasses, respirators, gloves, hearing protection, tyvek suits and rubber boots will be purchased with the awarded funds. Show more... | Federal Emergency Management Agency | 9/29/2009 |
| NEW YORK UNIVERSITY (INC) | $295,969.00 | Grant | Trans-NIH Recovery Act Research Support An estimated 36 million people worldwide have Human Immunodeficiency Virus (HIV) infection, while over 300 million have Hepatitis B Virus (HBV) infection. Among those with HBV mono-infection, HBe seroconversion from the state of Hepatitis B e antigen (HBeAg) positive chronic hepatitis to an 'inactive' or 'carrier' state (HBeAg negative) has historically been considered to mark a change in HBV infection phase or stage and results in a better prognosis. Patients who experience spontaneous HBeAg seroconversion can have reduction in hepatic fibrosis and 'inactive carrier status' patients have more favorable outcomes, with lower incidence of cirrhosis and hepatocellular carcinoma (HCC). The association of HBeAg seroconversion with better outcome may be due to its association with reduction in HBV viral load as HBV DNA level has been shown to be independently associated with risk of HCC. When compared with HBV mono-infection, HIV-HBV co-infection increases risk of liver-related mortality. However there is little information on the virologic and serologic outcomes of those with HIV-HBV co-infection. National HIV guidelines recommend the initiation of HIV antiretroviral therapy (ART) that includes 2 active HBV agents in order to prevent development of drug resistance to HBV. Yet some experts argue that there is insufficient data to warrant dual HBV therapy immediately and that it is reasonable to sequence a second HBV agent if monotherapy does not suppress HBV after 48-96 weeks. Furthermore, limited data suggest that persons with HIV-HBV co-infection are less likely to achieve HBV viral suppression and less likely to lose HBeAg and develop anti-HBe. The AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study is a well characterized cohort of 4371 HIV-infected subjects who have been prospectively randomized to receive ART and have stored samples at a central repository. We therefore propose to identify those subjects with active HBV infection among this ideal cohort and as our primary objective compare the time to HBV virologic suppression and change in HBeAg/anti- HBe status among those who receive 2 HBV active agents compared with those who receive one HBV active agent over a 5 year period. We will also evaluate for Hepatitis D co-infection, genotype for markers of prognosis and perform resistance testing on those who never suppress or have rebound HBV viremia on therapy. The prevalence of HDV co-infection in this cohort is unknown. Although HDV co-infection does not appear to have adverse effects on the immunologic or virologic response to therapy, HDV co-infection is associated with more rapid progression of liver disease. Baseline genotyping will be performed for all subjects since HBV genotype has been shown to affect the rate of both spontaneous HBeAg seroconversion and HBeAg seroconversion on antiviral therapy. Genotyping will be performed for those who fail antiviral therapy; the presence of mutations associated with resistance to antiviral agents has been shown to correlate well with phenotypic resistance to these agents. Further characterizing the disease course of HIV-HBV co-infection will assist in development of future pathogenesis studies and treatment interventional trials. PUBLIC HEALTH RELEVANCE: Hepatitis B Virus (HBV) infection is a significant cause of morbidity and mortality among those with Human Immunodeficiency Viral (HIV) infection. There is limited data on the effectiveness of combination therapies used to treat both HIV and HBV compared with HIV therapies that contain only one active drug against HBV. This proposal will examine the effectiveness of HBV treatment by measuring hepatitis markers and the amount of Hepatitis B virus in stored blood samples from HIV-HBV co-infected patients who participated in prospective, longitudinal randomized HIV clinical trials. Show more... | National Institutes of Health | 6/04/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $191,695.00 | Grant | Trans-NIH Recovery Act Research Support Children with unfavorable histology Wilms tumor (WT) and metastatic disease continue to experience high mortality rates. These patients urgently require new therapies. We have recently reported Phase I data indicating excellent tolerance of the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab (BV) in refractory pediatric tumors. Because this therapy has been validated in adult cancers, it may provide an attractive option for patients with aggressive WT; however, methods of assessing tumor response clinically are lacking. This is a particularly critical issue for pediatric cancer patients, in whom long-term tumor control is the goal. In our previous studies, we reported that experimental WT were initially strikingly suppressed by VEGF inhibitors. Yet consistent with clinical observations that adults treated with BV virtually all progress, we found that even highly responsive xenografts resumed growth if treatment was sustained. The mechanism of resistance to VEGF blockade is poorly understood, and clinical endpoints of resistance remain undefined. Emerging data from our lab and others suggests that tumors subjected to VEGF inhibition exhibit features of ischemic injury, including induction of damage response pathways and vessel remodeling. Further, distinct changes in gene expression, vascular assembly, and perfusion occur both acutely and chronically. For example, we have previously reported that VEGF inhibition can cause striking loss of branching vasculature and ischemia by 24 hours, whereas long-term blockade results in vessel remodeling, recovery of flow, and tumor progression. Key molecular markers of the response to vessel injury include members of gene families that are essential to angiogenesis, including integrins (alphaVbeta3), VEGF receptors (VEGFR-1 and -2), and Notch family members (Jagged-1), and mediators of the response to hypoxia (such as COX-2). High frequency ultrasound is an emerging technology that can provide rapid and longitudinal assessment of the anatomic, functional, and physiological response of WT vasculature to VEGF inhibitors. Further, the excellent sensitivity of newly available commercial scanners to sonographic contrast agents (microbubble) echo-signatures facilitates visualization of vessel architecture, quantification of blood flow, and molecular imaging of endothelial biomarkers in solid tumors. Yet this technology is still in its infancy, and further development of long-circulating and targeted microbubbles is critical for realizing its full potential as a means of evaluating dynamic changes in vessel structure and function. In particular, it is essential to develop a platform suitable for clinical point-of-care use. In these studies, we will investigate vascular remodeling during VEGF blockade using high frequency ultrasound, in the specific context of experimental WT, and using novel microbubble tools and ultrasound imaging techniques. Our goal in these studies is to relate acute and chronic molecular changes in WT angiogenesis with highly quantitative and sensitive architectural and flow characteristics and vascular biomarker expression patterns revealed by ultrasound. PUBLIC HEALTH RELEVANCE: Our ultimate goal is to develop an innovative ultrasound technique to monitor and guide anti-angiogenic therapy for children with clinically aggressive Wilms tumors (WT). We will develop this technology while exploring tumor vascular changes during initial and chronic blockade of vascular endothelial growth factor (VEGF). We hypothesize that molecular changes in WT angiogenesis can be correlated with vascular changes revealed by noninvasive ultrasound. Show more... | National Institutes of Health | 5/07/2009 |
| DANCE THEATER OF HARLEM INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/08/2009 |
| HOUSE FOUNDATION FOR THE ARTS, THE, INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/06/2009 |
| ARMITAGE FOUNDATION INC | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/06/2009 |
| CREATIVE TIME INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/13/2009 |
| INTERNATIONAL CENTER OF PHOTOGRAPHY (INC) | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/13/2009 |
| NEW YORK UNIVERSITY (INC) | $180,089.00 | Grant | Trans-NIH Recovery Act Research Support 1R21HL092370-01A2 MUSCULARIZATION OF PULMONARY ARTERIES INDUCED BY AN ADAPTIVE IMMUNE RESPONSE. Muscularization of pulmonary arteries induced by an adaptive immune response Abstract Pulmonary arterial hypertension (PAH) is a devastating condition because of its deleterious impact on quality of life, and life expectancy. Clinical correlation studies have suggested an immune pathogenesis because of the increased incidence of PAH in autoimmune and infectious diseases. Helminth infections can also cause PAH, but direct injury by the migrating parasites to the arteries has been thought to be the major cause of arterial remodeling. Pulmonary arterial remodeling associated with smooth muscle cell hyperplasia is frequently seen in PAH. In preliminary experiments, severe pulmonary arterial muscularization was induced by intermittent antigen challenge for a prolonged period of time via the inhaled route in primed mice. Essential roles for CD4+ T cells, the antigen- specific T helper (Th)2 response, and a pathogenic Th2 cytokine [Interleukin (IL) 13] in inducing severe pulmonary arterial musularization were identified. This indicated that the host's immune response developed to fight helminth infections alone is sufficient to induce severe pulmonary arterial muscularization, even without the presence of parasites. The severity of arterial remodeling was highly significantly correlated with the numbers of cells that bordered pulmonary arteries and expressed resistin-like molecule (RELM)a. RELMa is known as a smooth muscle cell mitogen, induced by Th2 responses and by chronic hypoxia. But the role of RELMa in pulmonary arterial remodeling has not been experimentally tested. The preliminary data show that the majority of proliferation marker positive cells within the remodeled pulmonary arteries had the appearance of endothelial cells and neo-intima cells. Few cells with smooth muscle morphology were proliferation marker positive. These data indicate that the origin of the cells within the remodeled pulmonary arteries might not be smooth muscle cells. The long range goal of this proposal is to understand how the Th2 immune response induces pulmonary arterial muscularization. To accomplish this goal, specific aims are proposed to identify the origin of the cells that populate the remodeled pulmonary arteries and to define the role of RELM1. The experimental approach will be to study mice that carry fluorescent tags driven by cell-type specific promoters for endothelial cells, leukocytes, and monocytes / myeloid cells, and RELM1 KO mice. Studies with mice that express receptors that can be used for cell ablation, and in vitro cell culture will be used for mechanistic analysis. The working hypothesis is that precursor cell proliferation followed by differentiation into smooth muscle cells and RELM1 are essential contributors to Th2-response-induced pulmonary arterial remodeling. PUBLIC HEALTH RELEVANCE: Muscularization of pulmonary arteries induced by an adaptive immune response Relevance: Pulmonary arterial hypertension (PAH) is a devastating condition that can accompany chronic parasite infections and auto-immune diseases. Thickening of the walls of pulmonary arteries by layers of smooth muscle cells is one of the typical morphological alterations seen in PAH and this process is a target for the development of new treatment strategies. The proposed studies are aimed at delineating the cellular origin and mediators that cause the accumulation of these smooth muscle cells in a mouse model of severe pulmonary arterial remodeling induced by the adaptive immune response. Show more... | National Institutes of Health | 5/15/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $213,574.00 | Grant |
Trans-NIH Recovery Act Research Support There is considerable public and professional concern that the two most widely prescribed stimulants for youth with attention-deficit/hyperactivity disorder (ADHD), mixed salts of amphetamine (MAS) and methylphenidate (MPH), may increase the risk of stroke, myocardial infarction, and other vascular events. These safety concerns are based on spontaneous adverse event reports of vascular disease developing in patients receiving MAS and MPH and the known pressor and chronotropic effects of these stimulants. Yet because large population-based studies have not previously compared the rate of vascular events among youth who do and do not receive these stimulants, no one knows whether, to what extent, and under what conditions MAS and MPH increase the risk of vascular events in young people. This study will examine associations between stimulant treatment and risk of myocardial infarction, stroke, transient cerebral ischemia, angina, and arrhythmia in youth, ages 6 to 21 years, treated for ADHD. Our primary aims are to: 1) evaluate whether stimulant treatment of ADHD increases the risk of vascular events; 2) determine whether MAS is associated with a greater risk of vascular events than MPH and whether the risk of vascular events is more strongly related to longer as opposed to shorter duration of stimulant treatment; 3) examine whether patient age, gender, comorbid medical diseases and co-prescribed medications that predispose to vascular disease moderate the effects of MPH and MAS on the risk of vascular events; and 4) assess whether risk of vascular events increases shortly after stimulant initiation or dosage increase. We will use Cox proportional hazards models and case crossover analyses with time dependent measures of stimulant treatment to assess these associations. Eleven years of integrated prescription and claims data from a large privately insured patient population will be used to determine whether and under what clinical circumstances MPH and MAS increase the risk of vascular events in young people. Data will be extracted concerning the pattern of stimulant treatment and incidence of vascular events of over 350,000 youth treated for ADHD. The size and scope of this data provide a rare opportunity to evaluate effects of stimulants on risk of vascular events. The results will directly inform future practice-based research as well as clinical and regulatory efforts to improve the safety of stimulant treatment in the community management of children with ADHD. PUBLIC HEALTH RELEVANCE: Despite concern that the most commonly prescribed stimulants may increase the risk of stroke, heart attacks, and other serious vascular events, no one knows whether, to what extent, and under what conditions stimulants actually increase these risks. This population-based study will determine whether stimulant treatment increases the risk of serious vascular events in youth with attention-deficit/hyperactivity disorder (ADHD) and will identify youth at especially high risk. The results will directly inform efforts to improve the safety of stimulant treatment in the community management of ADHD. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 5/05/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $200,375.00 | Grant | Trans-NIH Recovery Act Research Support This proposal aims to develop an 18F-labeled agonist PET probe for in vivo quantification of the G-protein coupled high affinity serotonin 1A (5-HT1A) receptors in baboon. We have two major motivations for developing an 18F labeled 5-HT1A receptor agonist radiotracer. First, we have previously shown that 5-HT1A receptors are abnormal in major depression and that elevated binding predicts response to antidepressants. One of the major impediments to using this technology in the clinic is the limited number of centers that can produce C-11 labeled radiotracers. The F-18 tracer can be shipped to multiple medical centers that are within a radius of 4 hours from the production site. Second, an agonist ligand binds preferentially to the G-protein coupled high affinity (HA) state of the receptor and thereby offers several advantages to an antagonist ligand. We have recently synthesized several 11C-labeled agonist compounds characterized by an azauracil structural skeleton that demonstrated specific binding to 5-HT1A receptors in baboon and the lead compound from the series is currently in evaluation in humans. Although this compound has many excellent properties, a limitation is that preliminary data suggest that the kinetics in two regions of interest (amygdala and hippocampus) is slow in humans. The 110-minute half-life of 18F would permit synthesis and imaging over longer duration, facilitating kinetic studies. Thus, these two issues necessitate the development of an 18F-labeled version of the agonist radiotracer by retaining the azauracil structural skeleton that survived the highly demanding toxicity and tolerance requirements. Additionally, the 18F positron energy is the lowest of the first row positron emitters and for this reason imaging can be potentially done at the highest resolution. We have designed flexible synthetic schemes for the synthesis of four 18F-labeled 5-HT1A agonists that are azauracil derivatives. MicroPET scans in adult male rats/ conventional animal dissection studies will be used for the preliminary determination of blood brain barrier permeability and biodistribution of the radiolabeled agonists. The suitable candidates will be then evaluated in baboon as potential PET imaging probes for 5-HT1A receptors. After confirming specific brain uptake in baboon by baseline and block studies, and development of metabolite analyses, the optimal modeling method will be selected on the basis of test/retest reproducibility, identifiability and time stability. Based on the results, the optimal candidate for clinical studies will be used for the in vivo quantification of HA 5-HT1A receptors in baboons. The 18F-labeled agonist PET tracer will provide a clinically useful tool to study the role of 5-HT1A receptors in the pathophysiology of neuropsychiatric disorders, for the prediction of treatment effectiveness in depression and for 5-HT1A targeted drug development. PUBLIC HEALTH RELEVANCE: The serotonin 1A receptor is implicated to play a critical role in major neuropsychiatric disorders including depression, schizophrenia, Alzheimer's disease and anxiety. This proposal aims to develop an 18F-labeled agonist PET probe for in vivo quantification of the G-protein coupled high affinity serotonin 1A receptors in baboon. The successful development of an 18F-labeled agonist PET tracer would provide a clinically useful tool to study the role of serotonin 1A receptors in the pathophysiology of neuropsychiatric disorders, for the prediction of treatment effectiveness in major depression and for the serotonin 1A receptor targeted drug development. Show more... | National Institutes of Health | 5/05/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $287,798.00 | Grant | Trans-NIH Recovery Act Research Support Profound impairment in social interaction is a hallmark of autism spectrum disorders (ASD). Although improvement in social functioning is widely considered to be a crucial target for intervention, social skills treatments for school-age children have been the subject of few controlled investigations. The available literature suggests that cognitive behavioral (CBT) techniques are commonly used and may improve targeted social skills in the short term in individuals with ASD. However, drawing firm conclusions about the efficacy of CBT social skills training remains difficult, particularly with respect to maintenance of skills and generalization to natural settings, owing to methodological limitations of extant studies (e.g., lack of random assignment to groups, small sample size, lack of manual-based curricula, minimal assessment of generalization or maintenance). Several neuroimaging studies have found that individuals with ASD underactivate key brain regions involved in social cognition. However, there is also evidence to suggest that activity in normative neural networks can be increased significantly by providing high-functioning children with ASD with explicit instructions to pay attention to important social cues, such as a speaker's facial expression and tone of voice. This suggests that a cognitive behavioral approach to social skills treatment may increase social responsiveness at both the behavioral and neural levels. The purpose of this investigation is to examine the acute and sustained effects of a CBT-based social skills treatment on social cognition and the neural architecture that supports it. High-functioning children with ASD (8-11 years old) will be randomly assigned to a 12-week cognitive behavioral social skills group or a social play comparison group to control for non-specific therapeutic effects. Functional MRI scans as well as behavioral assessments of social cognition, adaptive functioning, and symptom severity will be acquired at baseline, immediately following treatment, and at a 3- month follow-up. We hypothesize that children in the CBT group will show greater improvement in social functioning and increased activation of key brain regions, relative to children in the social play comparison group, both post-treatment and at follow-up. This study aims to address some of the earlier methodological limitations to provide much needed information about the short-term efficacy and durability of a CBT approach to social skills treatment, as well as the neural events that accompany and/or predict response to treatment. Show more... | National Institutes of Health | 9/23/2009 |
| NEOSTEM, INC. | $108,746.00 | Grant | ARRA-Health Center Integrated Services development Initiative This is a study of bone regeneration in a SCID mouse model. A section of the mouse skull (calvaria) will be removed and a preparation of human VSELs on a Gelfoam scaffold will be inserted into the lesion. VSELs, a pluripotent sub-population of CD34 positive cells, are collected from G-CSF mobilized volunteers by apheresis. All collections are performed under an appropriate IRB. The bone regenerative capacity of this VSEL treatment will be measured by a number of techniques including MRI, radiology and histology. Show more... | National Institutes of Health | 9/29/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $498,817.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses broad Challenge Area (15) 'Translational Science' and specific Challenge Topic '15-AR-104 Bone and the Nervous System'. Bone adaptation requires osteocytes to detect mechanical signals in situ and integrate the signals in the osteocytic network into appropriate activities in the bone cell system. It is conjectured that a bone cell network mimics a simple neuronal system and can acquire short-term memory to in vivo biomechanical stimuli through the elementary forms of implicit learning, e.g., habituation and sensitization. However, none of these behaviors have been confirmed experimentally in bone cell networks, and little is known about how bone cells behave as a neuronal network. The osteocytic network, recognized as the major mechanical sensor in the bone remodeling process, is the most capable candidate to accommodate the memory function in bone. In this study, we hypothesize that 'the ability for elementary forms of plastic change in response to mechanical stimulation is an inherent and fundamental property of the osteocytic network, and the short-term memory in osteocytic networks can be achieved by three elementary forms of implicit learning: habituation, sensitization, and classical conditioning'. In the light of our novel in vitro osteocytic network model and experience in calcium signaling research of bone cells, the goals of this study are to: (1) investigate the habituation, sensitization, and classical conditioning behaviors of osteocytic networks to fluid shear stimuli by recording and analyzing the real-time [Ca2+]i wave propagation inside the cell network and to determine the benign and noxious mechanical stimuli in the implicit learning process of osteocytic networks; and (2) investigate the roles of CaMK pathway, gap junction intercellular communication, and P2Y2 receptor in the habituation, sensitization, and classical conditioning of osteocytic networks to mechanical stimuli by using pharmacological inhibitors or siRNA-based knockdown of one of the 3 proteins. If the significant challenges associated with the memory storage in osteocytic network can be overcome, we will have an opportunity to initiate a new paradigm in research of bone mechanotransduction and behavior studies of fundamental physiological systems. The knowledge will profoundly benefit the hunt for strategies and new drugs for the treatment of osteoporosis, which affects millions of people with more than a $10 billion financial burden. This RC1 application proposes to test a novel hypothesis that the implicit memory exists in osteocyte networks under mechanical loading. The real-time intracellular calcium waves in response to various patterns of fluid flow stimulation will be analyzed to study the three elementary forms of implicit learning, i.e., habituation, sensitization, and classical conditioning, in in vitro osteocytic networks. The mechanotransduction mechanisms have a great importance in understanding the etiology of osteoporosis and preventing bone loss in space. Show more... | National Institutes of Health | 9/22/2009 |
| STUDIO IN A SCHOOL ASSOCIATION INC | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/17/2005 |
| EPIC THEATRE CENTER, INC | $25,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/21/2009 |
| COUNCIL OF LITERARY MAGAZINES AND PRESSES | $50,000.00 | Grant | Awards to Organizations and Individuals To support the preservation of jobs that are threa | National Endowment for the Arts | 7/06/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $498,914.00 | Grant | Trans-NIH Recovery Act Research Support The main objective of this project is to develop a protein based therapy to enhance the endothelial barrier properties. Although acute lung injury (ALI) is a major cause of morbidity and mortality, no curative therapies are available. The main pathology in ALI is attributed to pulmonary edema, a direct result of endothelial (EC) barrier deterioration in the lung. In this project we will purify in their biologically active forms the barrier-protective proteins, Rac1, (-actinin and vinculin. Using our newly developed approach, we will attach these barrier-protective proteins to the cell-permeable peptide, TAT. The proteins will be given by mouse tail vein injection to determine their efficacy in protection against ALI. Procedures: We will use the Baculovirus Expression Vector System (BEVS) to develop the recombinant virus expressing the cDNA of the targeted proteins Rac1, vinculin and (-actinin as a His-tagged protein. This amplified virus will be used to infect the Sf9 insect cells to express each of these proteins. The expressed proteins will be purified from the cell lysates using Immobilized Metal Affinity Chromatography (IMAC). We will apply our newly developed approach to non-covalently complex the cell-permeable peptide, TAT, to His-tagged protein. We will expose cultured endothelial cells to the complexes. We will inject the complexes intravenously in mice. To determine uptake, we will image endothelial cells and lung microvessels by real-time fluorescence imaging. Significance: No therapy exists for ALI. Our research will establish for the first time, novel therapeutic modalities for curing this severe disease. Our approach for delivering therapeutic proteins is novel and potentially, superior to existing approaches. This research will determine preclinical feasibility of therapy that is potentially suitable for human application. PUBLIC HEALTH RELEVANCE: Although acute lung injury (ALI) is a major cause of morbidity and mortality, no curative therapies are available. Major pathology in ALI is attributable to pulmonary edema, which results from endothelial barrier deterioration in the lung. Hence, our aim is to develop therapy directed at endothelial barrier enhancement. We propose to introduce barrier-enhancing proteins in endothelial cells of lung microvessels. Feasibility of this approach is supported by our unpublished studies with purified focal adhesion kinase (FAKp). We have developed a new approach for chemically, non-covalently linking FAKp to the cell permeable peptide, TAT. The TAT-FAKp l Intraveously injected TAT-FAKp is taken up in lung microvessels. Intraveously injected FAKp protects against acid-induced ALI as determined by assays of lung endothelial permeability, extravascular lung water (EVLW) content and leukocyte and protein contents of the broncho alveolar lavage (BAL).We will apply our novel TAT linkage approach to develop intracellular delivery of three barrier-protective proteins, namely, vinculin, (-actinin and Rac1. Our approach for delivering therapeutic proteins is novel and potentially, superior to existing approaches. This research will determine preclinical feasibility of therapy that is potentially suitable for human application. Show more... | National Institutes of Health | 9/18/2009 |
| NEW YORK UNIVERSITY (INC) | $1,996,060.00 | Grant | Trans-NIH Recovery Act Research Support Gut microbiota have long been thought to contribute to inflammatory diseases, and multiple reports in animal models and humans suggest that antibiotic treatment alters autoimmune disease manifestations. We have recently demonstrated in rodents that specific microbes induce the differentiation of Th17 cells in the intestinal lamina propria. There is strong genetic and therapy-based evidence that 'pro-inflammatory Th17 and 'antiinflammatory regulatory T cells (Treg) have critical roles in autoimmune diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and Crohn’s disease. We propose to study the role of gut (intestinal and oral) microbiota in RA and other inflammatory arthritides. Our primary hypotheses are that: 1) characterization of Th17-inducing microbes in human intestine will provide insight into disease pathogenesis; and 2) directed manipulation of the gut microbiota will result in alteration of arthritis biomarkers, including Th17/Treg balance. Insights attained may elucidate how the T cell network responds to microbial interactions with host intestinal components and provide a rationale for the development of new therapeutic approaches for RA. Three Specific Aims are proposed: 1) To create a multidisciplinary center to characterize human gut microbiome in patients with RA and related conditions. 2) To employ Th17-dependent mouse models of RA to study the role of microbiota/T cell interactions in development of disease, to directly assess whether specific bacteria in RA patients can be implicated in disease pathogenesis. Both direct bacterial cocktails and bacteria identified in RA patients will be inoculated into the mice. 3) To study the role of human gut microbiota in RA pathogenesis by: a) cross-sectional study to determine whether a specific taxon or bacterial family in the human gut is associated with RA or PsA; b) clinical and blood examinations to assess baseline disease activity, genetic predisposition and immune cellular function of arthritis patients vs controls; c) prospective, interventional proof of concept biomarker study to determine whether alteration of the gut microbiota normalizes cellular immune functions in patients with RA. We will compare 2 antibiotic regimens to assess whether therapy induces i) characteristic changes in the gut microbiome (including changes in abundance of specific target taxons), and ii) alterations in immune biomarkers, particularly Th17 and Treg cell levels and/or function. Carefully selected outcomes should permit us to correlate the presence of a specific microorganism or microbiome pattern with changes in cellular immune response, other specific biomarkers, and clinical activity. Relevance: This project is consistent with the goals of the Human Microbiome Project, a major NIH Roadmap initiative, and has the potential to be truly transformative by filling a fundamental knowledge gap regarding the cause of inflammatory arthritis. The results could transform our understanding of the relationships between microbes and humans, and lead to innovative diagnostic tests and future treatments. Show more... | National Institutes of Health | 9/29/2009 |
| CORNELL UNIVERSITY, INC | $735,348.00 | Grant |
Trans-NIH Recovery Act Research Support Parkinson?s Disease (PD) as well as other neurodegenerative diseases are associated with oxidative damage. In PD, there is an early reduction in reduced glutathione in the substantia nigra, as well as increases in markers of lipid, protein and DNA oxidation. A number of laboratories have reported increases in plasma and cerebrospinal fluid biomarkers of oxidative stress in PD. We recently found reduced uric acid and increased 8-hydroxy-2-deoxyguanosine (8-OHdG) in plasma of PD patients. We are presently carrying out a phase III clinical trial of the antioxidant nutritional supplement coenzyme Q10 (CoQ10) in PD. Six hundred newly diagnosed unmedicated PD subjects are being randomized to placebo, 1200mg of CoQ10 or 2400 mg of CoQ10 daily. Patients are assessed using the Unified Parkinson?s Disease Rating Scale (UPDRS) every 3 months until they require dopaminergic therapy or they complete 16 months. We propose to measure several markers of oxidative damage at baseline, 1, 8 and 16 months of therapy. We will measure plasma levels of 8-OHdG, malondialdehyde, ascorbic acid, uric acid, oxidized and reduced CoQ10, and oxidized and reduced glutathione. All samples will be examined using metabolomic profiling using HPLC with coulometric array detection. These results in detection of up to 2000 small molecules, which are electrochemically active. The measurements of individual peaks will be correlated with those of established markers of oxidative damage such as 8-OHdG, malondialdehyde and the ratio of oxidized/reduced glutathione, to see if more sensitive and specific novel biomarkers of oxidative stress can be identified. The biomarkers will be correlated with clinical improvements in PD patients as assessed using UPDRS scores. These studies will establish the relative utility of existing biomarkers of oxidative damage, and may lead to the development of novel biomarkers, which will be useful in assessing the efficacy of the antioxidant effects of dietary supplements in vivo, and will help in assessing their effectiveness with respect to human health. As such, these studies may be useful in establishing the effectiveness of a large number of dietary interventions, which may impact human health. Show more...
There were 1 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 9/16/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $2,545,749.00 | Grant | Trans-NIH Recovery Act Research Support In this application, we articulate the vision for a center that will integrate recent computational and experimental advances in cancer systems biology toward the genome-wide prioritization of therapeutic targets using high-throughput screening approaches. The objective is the elucidation of individual and synergistic master regulators of tumor progression and drug- resistance and the identification of their chemical modulators. We address these aims in three specific tumor-related phenotypes for which we have developed detailed computational and experimental models, including (a) Progression from Follicular Lymphoma (FL) to Diffuse Large B Cell Lymphoma (DLBCL) (b) Glucocorticoid resistance in T-lineage Acute Lymphoblastic Leukemia (T-ALL), and (c) the mesenchymal phenotype of Glioblastoma (GBM) associated with the worst clinical outcome in patients with HGG. We will use existing, computationally-inferred molecular interaction networks to prioritize candidate master regulators of tumorigenesis, tumor aggressiveness, and resistance to standard therapeutic agents. These will be further prioritized by positive- and negative-selection genome-wide RNAi screens, using a computational evidence-integration approach. High- ranking targets will be validated in vitro using siRNA/shRNA silencing and then profiled to identify specific expression markers for their inhibition. Then, small molecule screens will be performed to identify compounds that are selectively lethal to tumor cells because of direct or indirect inactivation of the selected high-ranking targets. Other classes of compounds are those that may cooperate with partial knockdown of high priority targets either because they are functionally linked to those targets or because they bind these targets directly. Finally, identified compounds will be tested in vivo using both primary GBM-derived stem-like cells injected intra-cranially in immunodeficient mice or established mouse models of human cancer (DLBCL and T-ALL). PUBLIC HEALTH RELEVANCE: Recent advances in the integration of computational and experimental methods for the understanding of cancer biology are creating unique opportunities to improve our ability to identify biomarkers for early diagnosis and prevention, therapeutic targets that are highly specific to a cancer type, and compounds that inhibit these targets. Investigators at the Herbert Irving Comprehensive Cancer Center have pioneered these type of approaches an implemented a completely integrated computational-experimental approach to the study of cancer called Cancer Systems Biology. In this application, we articulate the vision of a center that will use cancer systems biology tools to identify and prioritize candidate therapeutic targets and to design highly specific molecular screening approaches for the identification of small molecules that inhibit these targets. In particular, we have shown that Master Regulators of tumor progression and chemotherapy resistance can be identified both computationally and experimentally and that these genes provide ideal targets for therapy, either individually or in combination, i.e. using more than one drug. We propose to study three tumor progression and chemotherapy resistance problems, including (a) the mesenchymal signature of Glioblastoma (GBM) associated with the worst clinical outcome in patients with High-Grade Gliomas (HGG), (b) the transformation of Follicular Lymphoma (FL) into Diffuse Large B Cell Lymphoma (DLBCL), and (c) Glucocorticoid resistance in T cell Acute Lymphoblastic Leukemia (T-ALL). Show more... | National Institutes of Health | 9/30/2009 |
| SPIRIT CRUISES LLC | $240,064.00 | Grant | American Recovery and Reinvestment Act Port Securi | Federal Emergency Management Agency | 9/29/2009 |
| LOCAL INITIATIVES SUPPORT CORPORATION | $843,169.00 | Grant | AmeriCorps AmeriCorps members play a vital role in enabling our partner organizations to meet the growing demand for services at the grassroots level. Members will serve as housing counselors to assist low-income residents avoid foreclosure/ predatory lending practices allowing residents to remain in their homes. Others will serve as coordinators for weatherization, energy-efficient, and blight reduction programs to address neighborhood stabilization. Members will also serve as financial counselors in community based centers for working families and provide one-on-one assistance to clients seeking employment, skill development, and access to benefits. All of the member placements support building the organizational capacity of our non-profit partner sites where the members are serving. Show more... | Corporation for National and Community Service | 5/22/2009 |
| TEACHERS COLLEGE, COLUMBIA UNIVERSITY | $117,076.00 | Grant | AmeriCorps This funding provides volunteer support in the NYC K-12 public school system, specifically in low-income communities of Harlem, Washington Heights, and other areas of northern Manhattan. The three primary activities funded by this award include: 1) Supplementary academic support in challenging classrooms, assisting the teacher of record with individual or small-group academic assistance during activities such as reading and writing exercises, doing research and conducting presentations, reviewing and correcting homework assignments, and other classroom activities; 2) Faciliation of college readiness program that begins in the summer for rising high school juniors and seniors, and continues through the academic year. This program uses a comprehensive approach to get low-income youth college-bound, incorporating family and community resources; 3) Programmatic support to local community-based organizations or educational entities in the Harlem, with the responsibilities to develop education program activities and/or curriculum enhancement, support program/organization evaluation efforts and out-of-school best practices in the community through professional development in the area of service delivery and subject content. Show more... | Corporation for National and Community Service | 5/29/2009 |
| RYAN, WILLIAM F COMMUNITY HEALTH CENTER INC | $1,722,730.00 | Grant | ARRA-Health Center Integrated Services development Initiative The CIP funds will be used to improve the Center's infrastructure by renovating the main site and upgrading the facility to improve heating, ventilation, air conditioning, lighting, signage, flooring and several safety features, including the fire alarm system. The renovations are also being designed with the intent to increase operational efficiency by enhancing patient flow throughout the facility. The CIP Project will enhance the environment for both patients and staff, and consequently promote and increase the quality of care to the Center's patients. Show more... | Health Resources and Services Administration | 6/25/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $120,670.00 | Grant | Trans-NIH Recovery Act Research Support Currently, the functional neuroimaging research conducted and supported by the Laboratory of Neuroimaging at the Mount Sinai School of Medicine utilizes fMRI as a primary measure. fMRI is the hallmark of spatial resolution amongst functional neuroimaging techniques, capable of resolving clusters of activation millimeters apart. However, its temporal resolution is on the order of several seconds. The temporal resolution of fMRI is determined not only by sampling interval but also by intrinsic biological factors. Therefore it is not possible to resolve events occurring within as much as one second of each other. An ideal complementary imaging technique for fMRI would have the ability to measure changes in activity with a temporal resolution on the order of milliseconds, and electrophysiological measures such as the electroencephalogram (EEG) or event related potentials (ERPs) have proven to fit this role perfectly. The current proposal aims to purchase an MRI-compatible EEG/ERP recording system in order to supplement fMRI data with high-temporal resolution electrophysiological data in order to expand the scope of hypotheses that are testable using the resources available through the Laboratory of Neuroimaging, a core functional neuroimaging resource of the Mount Sinai School of Medicine. Addition of this resource will facilitate development and testing of models of cognitive function that incorporate factors accounting for the temporal dynamics of networks subserving these functions. In addition to purchase of this system, we also propose the establishment of an unbiased local advisory committee who will oversee the administration of this resource to ensure that it continues to attract new users and that NIH funded projects are given rates of access to the resource commensurate with targeted subject enrollment and project timelines. Purchase of this equipment has direct relevance to public health because it will advance our knowledge of the neural underpinnings of various psychiatric disorders. Use of the new instrumentation in NIH funded projects investigating various aspects of autism, bipolar disorder, and attention deficit/hyperactivity disorder is discussed in detail with specific hypotheses that the instrumentation will permit testing of. With active expansion of the research infrastructure at Mount Sinai with a focus on clinically oriented research, it is expected that utilization of this core by NIH funded researchers will continue to grow over the next several years. PUBLIC HEALTH RELEVANCE: The aim of this proposal is to purchase equipment that will allow researchers to investigate the time course of activation of discrete structures in the brain with high temporal resolution, which is not possible using currently available resources. Purchase of this equipment will benefit several NIH-funded researchers conducting studies on various aspects of psychiatric disorders including autism, bipolar disorder, and attention deficit/hyperactivity disorder. Show more... | National Institutes of Health | 4/28/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $499,997.00 | Grant | Trans-NIH Recovery Act Research Support This proposal addresses broad Challenge Area (15) Translational Science, and specific challenge topic 15-MH-109 Prefrontal cortex regulation of higher brain function and complex behaviors. Nearly all psychiatric disorders, from schizophrenia to depression to addiction, disrupt emotional processing. A key aspect of the pathophysiology underlying these psychiatric disorders is thought to lie in the dysfunction of the pre-frontal cortex, especially with respect to the manner by which the pre-frontal cortex regulates emotions. We focus in this proposal on the interactions between the pre-frontal cortex and the amygdala, a key coordinator of emotional behavior. This circuitry has been highlighted as being critical for controlling emotional responses. Our lab has recently shown that neurons in the primate amygdala respond differentially depending upon whether a cue predicts a reward or an aversive stimulus, with different populations of neurons preferring reward and aversive associations, respectively. More recent preliminary data indicates that this flexible representation of reinforcement contingencies can be 'gated' - or updated instantly - depending upon a subject's learning and applying a rule for interpreting cues accurately. In this proposal, we will test the hypothesis that this gating of neural signals in the amygdala depends critically on input from the orbitofrontal cortex (OFC), a component of the pre-frontal cortex with strong connections to the amygdala. Our approach is to adapt methods for genetically and anatomically targeted expression of channelrhodopsin (ChR2) and halorhodopsin (NpHr) (light-activated channels that can be used to photo-activate or photo-inactivate neurons). These optogenetic techniques will be used in combination with neurophysiological and complex behavioral experiments. We will determine if the flexible physiological properties in the amygdala require pre-frontal input by selectively inactivating pre-frontal input with halorhodopsin, and we will further determine if disrupting information transmission from OFC to the amygdala impacts complex behavior. Overall, the development of these techniques promises to transform the study of pre-frontal/amygdala interactions by elucidating how pre-frontal input can regulate the responsivity of the amygdala, a key mechanism in maintaining normal adaptive emotional responses that likely becomes dysfunctional in many psychiatric disorders. PUBLIC HEALTH RELEVANCE: This proposal involves the development of optogenetic techniques for investigating how the prefrontal cortex regulates the amygdala in order to control emotional behavior. Since most psychiatric disorders, including mood and anxiety disorders, schizophrenia, and depression involve dysfunction in these neural circuits, this project promises to lay the groundwork for developing new treatments. Show more... | National Institutes of Health | 9/24/2009 |
| NEW YORK UNIVERSITY (INC) | $496,482.00 | Grant | Trans-NIH Recovery Act Research Support Neural cell adhesion molecule (NCAM) is key in leucocyte adhesion to endothelial cells. Upon signaling by chemokines such as MCP1 leukocytes fall into the area of endothelial cells. Tethering of the endothelial cells to leukocyte cadherins is followed by cell:cell interactions such as diapedesis. The resulting sub-endothelial inflammatory processes can result in atheroma formation and atherosclerosis. However, following translation NCAM is subject to intracellular enzymatic sialylation to form polysialated NCAM (PSA-NCAM), a form of NCAM with polyhydrated alpha 2,8 sialic acid chains in the extracellular domain that interfere with cell adhesion. We have documented the presence of PSA-NCAM in the glycocalyx of human vascular endothelial cells in arteries, veins and lymphatics of all organs (10 organ systems) studied. We also have shown that expression of the two required polysialytransferases (ST8Sia II/STX and ST8Sia IV/PST) is estrogen receptor-mediated. Others have shown that the Ras pathway can also affect the formation of PSA-NCAM, explaining both early and late estrogen effects on PSA-NCAM expression. Further, the expression of PSA-NCAM isomers depletes the parent NCAM molecules, so that the adhesion (NCAM):non-adhesion (PSA-NCAM) balance is highly leveraged. In this project we will examine the role of estradiol in the adherence of leucocytes to human endothelial cells in culture and determine the cognate regulation of the two enzymes PST and STX. We will also test other agents known to affect the system; the estrogen receptor blocker fulvestrant, the selective estrogen receptor blocker tamoxifen and the Ras initiator valproic acid for their regulation of PST, STX and PSA-NCAM. Using molecular interference we well interdict the expression of each enzyme before adding the agents and observe the effect of PSA-NCAM isomer expression and leukocyte adherence. In this manner, in addition to testing the hypothesis that estrogen's cardioprotective effects are in part due to driving NCAM sialylation, we will assess whether differential effects of estradiol on the two enzymes could furtherr regulate this mechanism. Show more... | National Institutes of Health | 9/28/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $427,867.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic 06-GM-102* .Chemist/biologist collaborations facilitating tool development. The objective of this grant is to develop fluorescent chemical tags that both have high photon counts and are cell permeable and soluble to enable single-molecule detection in cells. Single-molecule imaging can now be carried out in vitro and has provided a breakthrough for understanding the molecular mechanisms of complex biological assemblies because it allows the dynamics of individual complexes to be directly observed--but in vivo single-molecule imaging has only been carried out by a handful of leading experts in the field. In our opinion a major barrier to routine single-molecule imaging in cells is the difficulty of labeling proteins selectively in cells with suitable fluorophores. The fluorescent proteins do not have high enough photon counts to be readily detected with single molecule resolution in cells, and the organic fluorophores with high photon counts developed for in vitro biophysics do not behave well in the cell. PUBLIC HEALTH RELEVANCE: Here, we propose that chemical tags including our commercial TMP-tag can provide the combination of genetic encoding and an organic fluorophore label needed for single-molecule imaging in cells. We have assembled an interdisciplinary team of a chemical biologist expert in chemical tags (PI Cornish), a physical chemist skilled in fluorescence microscopy (co-PI Kaufman), a leading biochemist studying the mechanism of the spliceosome reaction (co-PI Moore), and a cell biologist who is a pioneer in the application of state-of-the-art microscopy to cell motility (co-PI Sheetz) to meet this objective. We propose to meet this objective by (1) challenging the chemical tags for single-molecule imaging of the spliceosome in yeast cell extracts, (2) developing fluorescent chemical tags suitable for single-molecule imaging in cells, and (3) developing chemical tags with specialized properties for high-resolution imaging. Show more... | National Institutes of Health | 9/29/2009 |
| CORNELL UNIVERSITY, INC | $1,150,800.00 | Grant |
Trans-NIH Recovery Act Research Support This is a multi-PI RO1 grant designed to use multiple mouse genetic models of neural tube defects (NTDs, spina bifida and anencephaly) to investigate genetic factors confering NTD risk. Investigations will study how those gene mutations interact with environmental conditions to result in NTDs. Specifically, the project examines the interaction of NTD risk genes with the dietary supplement, folic acid, as well as with other supplements including inositol and Betane. The project will characterize the impact of these agents on multiple mouse mutants, the gene expression changes associated with these mutations in both embryonic and maternal tissues, and will use computational analyses to assess the gene-diet interactions surrounding neural tube closure. Show more...
There were 2 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 8/03/2009 |
| COMMUNITY HEALTH CARE ASSOCIATION OF NEW YORK STATE, INC. | $478,125.00 | Grant | ARRA-Health Center Integrated Services development Initiative The Community Health Care Association of New York State (CHCANYS), New York’s 38-year old Primary Care Association and home to the New York Health Choice Network (NYHCN), our statewide Health Center Controlled Network (HCCN), requests continued funding in the amount of $478,125 for the final year of this three year implementation grant. The New York Health Choice Network is a Health Information Technology (HIT) program formed by CHCANYS in partnership with six New York State health centers to facilitate the implementation of their shared strategic vision of improving health outcomes and reducing disparities by optimizing the use of electronic health records (EHR). The Network consists of six active health center members, five of which are participants in this implementation grant project. These five participants are: 1) Open Door Family Medical Centers, Ossining, NY 2) Whitney M. Young, Jr. Health Services, Albany, NY 3) Westside Health Services, Rochester, NY 4) Hometown Health Centers, Schenectady, NY 5) Hudson River Health Care, Peekskill, NY These organizations provide services to over 210,000 patients in 47 sites across upstate New York. Seventy-one percent (71.0%) of patients have incomes below the federal poverty level. Thirty-five percent (34.8%) are Hispanic/Latino, 32.9% are African American, 27.1% are White and 5.3% are Asian/Pacific Islander. Nearly half (46.4%) of patients are Medicaid beneficiaries and 26.0% are uninsured. All of the participants except Hometown Health Centers have implemented the eClinicalworks integrated practice management and electronic health record solution. Hometown Health has not made a final product decision to date. In the eighteen months since this project began, NYHCN has successfully established network architecture that provides state of the art technology to host members’ EHR related applications, offering full disaster protection while significantly reducing health centers’ costs. We’ve developed comprehensive implementation and training services that when not in use internally are in high demand from non-network members and will serve as a source of program revenue. Finance and Clinical committees are composed of an average of two representatives per health center and meet monthly to propel identified objectives aimed at quality improvement. Final vendor and developer selection have been completed and high level designs agreed upon for a Network data repository that will facilitate our quality initiatives. Throughout the next year, we expect to implement the final project participant, complete the initial phase of data repository implementation, and continue efforts to understand, implement and standardize the use of advanced EHR features to take full advantage of point-of-care clinical decision support, population based patient registries, and interoperability opportunities to further our patient centered medical home care model. Show more... | Health Resources and Services Administration | 9/14/2009 |
| CORNELL UNIVERSITY, INC | $500,000.00 | Grant | Trans-NIH Recovery Act Research Support Selective serotonin reuptake inhibitors (SSRIs) have become the mainstream therapy in psychiatric diseases. Based on their therapeutic effect in adults, they are increasingly prescribed in children and adolescents. However, there is a concern about the use of SSRIs in young patients, in particular, due to reports of increased susceptibility to suicide. Recently, in mouse models, chronic SSRI administration at an early postnatal time frame, corresponding to 3rd trimester to childhood has been shown to lead to increased anxiety in adulthood, suggesting that SSRI treatment in young mice is anxiogenic. This suggests that the developing brain responds to SSRIs very differently than the adult brain. However, rigorous examination of the effects of SSRIs on more clinically relevant postnatal time frames, encompassing late childhood through adolescence, have not been performed in these model systems. One important mechanism by which SSRIs may attenuate anxiety in adulthood is through the induction of BDNF levels in critical brain regions, such as the hippocampus, prefrontal cortex, and mesolimbic reward circuit. Although BDNF levels are stable in adults, in early postnatal life, BDNF expression is peaking and is dynamically regulated presumably due to its critical role in neural circuit maturation. BDNF exists in 2 isoforms, an initially synthesized precursor, proBDNF, and a smaller mature BDNF form. Expression of proBDNF is highest in early postnatal life, whereas mature BDNF predominates in adults. Recent studies suggest that proBDNF and mature BDNF may play divergent roles in synaptic maturation and plasticity. ProBDNF released from presynaptic sites binds to p75 to induce long term depression (LTD), and to potentially reduce spine density and dendritic complexity, whereas mature BDNF promotes long term potentiation (LTP) and enhanced dendritic morphology. We hypothesize that induction of BDNF by SSRIs in childhood and adolescence may lead to altered neuronal morphology and function, and abnormal circuitry between cortex, hippocampus, and nucleus accumbens. These studies, utilizing new technical advances in BDNF detection will allow us to determine how SSRIs, delivered during vulnerable periods during childhood and adolescence (a) perturbs BDNF levels, BDNF isoform conversion, and signaling through BDNF receptors acutely, and in adulthood; (b) induce adult anxiety and depressive phenotypes. We predict that the postnatal developmental changes in proBDNF and mature BDNF ratios may underlie critical differential effects of SSRI antidepressants on modulating structural and functional neural plasticity, leading to long-lasting abnormal behavioral responses in animals treated with SSRIs during critical childhood periods of vulnerability. Show more... | National Institutes of Health | 9/24/2009 |
| MALCOLM X II PHASE B ASSOCIATES | $629,915.00 | Grant | Section 8 Housing Assistance Payments Program Special Allocations (Recover Rental Assistance Payment | Department of Housing and Urban Development | 5/01/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $47,210.00 | Grant | Trans-NIH Recovery Act Research Support Ebola virus (EBOV) infection of humans often results in severe hemorrhagic fever which is lethal in up to 90% of infected cases. Therefore, understanding the molecular mechanisms of Ebola virus pathogenesis is essential for development of successful therapeutics. Previous work has demonstrated that EBOV VP24 prevents type I and II Interferon (IFN) signaling by binding to the specific members of the karyopherin a (KPNA) family of nuclear import proteins to prevent nuclear accumulation of STAT-1. The ability of VP24 to block IFN signaling is one example of how EBOV can suppress the host response to infection. The goal of this proposal is to test if VP24 binding to KPNAs prevents binding and subsequent nuclear translocation of additional cellular proteins. We hypothesize VP24 blocks the nuclear import of additional cellular proteins and redistributes these proteins to the cytoplasm to promote EBOV replication. To this end, we have demonstrated that the heterogeneous ribonuclear protein C1/C2 complex (hnRNP C1/C2) interacts with members of the KPNA family, and that hnRNP C1/C2 binding to KPNA1 is diminished in the presence of VP24. VP24 inhibition of hnRNP C1/C2 binding to KPNA1 is of great interest since hnRNP CI/ C2 has been shown to play an important role in the replication cycle of other RNA viruses. Therefore, the first aim of this proposal is to fully characterize the interactions between VP24, the NPI-I KPNA family members and hnRNP C1/C2 and determine if VP24/KPNA interactions are sufficient to prevent hnRNP CI/ C2 nuclear accumulation. Since hnRNP C1/C2 facilitates both viral RNA and protein synthesis in other systems, the second aim will test if hnRNP C1/C2 interacts with EBOV RNA and impacts viral replication and/or protein translation. The third aim of this proposal focuses on developing assays to screen for small molecule inhibitors against VP24 IFN antagonism. Identifying small molecular inhibitors that impair EBOV mediated IFN antagonism (and likely replication) would be very useful for treating EBOV. Show more... | National Institutes of Health | 8/14/2009 |
| THE HOSPITAL FOR SPECIAL SURGERY FUND INC | $372,857.00 | Grant | Trans-NIH Recovery Act Research Support Revision total joint arthroplasty (rTJA) for the hip or knee joint is a complex, costly procedure. Approximately 83,000 are performed annually in the US (2006 estimate). The frequency of these revision procedures is only expected to increase with the large number of primary total joint arthroplasty (pTJA) procedures that are expected to be performed in the coming years (estimated at over 4 million annually by 2030). Given that rTJA procedures have worse outcomes than pTJA including higher risk of complication, higher motality, and more frequent need for further revision surgey, there is a need to both decrease the need for these procedures, but also to optimize outcomes for these revisions. The aims of this research are to: 1) evaluate the effect of patient, and institutional factors on the need for early rTJA after pTJA; 2) identify the referral patterns for rTJA following first pTJA and predictors of these patterns; and 3) identify the effect of referral patterns on complications after rTJA. These aims will be accomplished by identifying state residents in New York and California undergoing their first pTJA between January 1, 1997 and December 31, 2006. These patients will be followed until the end of the study period for rTJA on the same joint. Those who have surgery with a different surgeon and at a different hospital will be considered 'referrals . Patients will be identified through existing hospital discharge databases for New York and California. The effects of patient and institutional (surgeon and hospital) factors will be evaluated. In order to address the 3 specific aims, these effects will be evaluated for time to rTJA, likelihood of referral, and complications following rTJA. This will be analyzed using various multivariable models for each of the 3 aims. A Cox Regression model will be used to analyze time to rTJA for Aim 1. Aims 2 and 3 will be evaluated using a multivariable repeated measures models including methods that account for the correlation of procedures performed by the same surgeon or within the same hospital. The model for Aim 2 will evaluate the predictors of referral. The model for Aim 3 will determine whether referral improves short-term outcomes, particularly rates of surgical complication, 90 day readmission, 90 day in-hospital mortality, and subsequent revision surgery. These will be compared between patients who are referred and those who are not, adjusting for potential other confounders. It is currently unknown which patients are most at risk of early rTJA from a population perspective in the US, particularly with regard to the combination of patient and institutional factors. It is also unknown what the referral patterns are for early rTJA. It is also unknown whether geographic variation exists with regard to rTJA. Finally, it is unknown whether patients who are referred for early rTJA have better outcomes than those who have their surgery with lower volume surgeons or centers. All of these questions will be explored in this study. Quickly identifying patients most at risk for early rTJA will assist in development of future research and hopefully clinical interventions to prevent these early failures. Referral patterns and trends for rTJA have direct implications for allocation of medical resources, particularly as it pertains to training and recruitment of fellowship trained arthroplasty surgeons. Furthermore, the effect of surgeon or hospital on outcomes after early rTJA are directly relevant to improving the quality of care and reducing costs associated with these complex and already costly procedures. Show more... | National Institutes of Health | 9/23/2009 |
| NEW YORK, CITY OF | $29,062,259.00 | Grant | 16.804 - Recovery Act - Justice Assistance Grants - Localities The New York City Mayor's Office of the Criminal Justice Coordinator (CJC) will serve as the applicant and administrator for the FY09 American Reinvestment and Recovery Act (ARRA) Justice Assistance Grant (JAG) program for the City of New York. In order to coordinate citywide criminal justice policy and programs, CJC works closely with the City?s public safety agencies, including Police, Fire, Correction, the District Attorneys, and other government and non-profit agencies involved in the criminal justice system. New York City intends to use ARRA JAG funds to continue essential prosecution and court, law enforcement, drug treatment and enforcement, prevention and education, corrections and community corrections, technology improvement, and crime victim programs, many of which are currently funded through FY2008 JAG funds and were previously funded through the Local Law Enforcement Block Grant (LLEBG) and the Byrne Formula grant programs. Given the state of the economy and the expressed purpose of the ARRA to both create and sustain jobs, New York City is using grant funds to sustain as many essential programs and personnel as possible. All programs involve either the preservation or creation of new jobs. Show more... | Department of Justice | 6/05/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $135,883.00 | Grant | Trans-NSF Recovery Act Research Support Anomalous local turbulent transport in plasmas will be measured directly with novel diagnostics. By measuring critical parameters, the fundamental scaling laws of transport will be compared with various theories. A key element of the project is the diagnostic uses of feedback. A first ever ion temperature fluctuation diagnostic uses an ion energy analyzer which is modulated by a feedback signal derived from the fluctuations. The cross-correlation of this measurement with the potential fluctuations yields the ion thermal transport. The chief intellectual merit of the project lies in the challenge posed in the central issue in plasma anomalous transport physics: Bohm and gyro-Bohm scaling. This will be done via novel basic physics experiments and correlated models. Many of the general concepts and methodologies, especially the experimental determination of a nonlinear turbulent system modeling via feedback, are quite extrapolatable to many problems in fluid mechanics, aerodynamics, chemical reaction systems etc. with great potential benefit. The integration of research and education will be accomplished by exposure of the students to the clearly interdisciplinary research represented by the project, containing physics, applied physics, system and control engineering both in the laboratory and in the classes. Enhancement of the infrastructure of research and education will be accomplished via collaborations with several national and international universities and laboratories. Show more... | National Science Foundation | 9/14/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $30,121.00 | Grant | Trans-NSF Recovery Act Research Support The primary focus of this theory program is on pure electron plasmas, in particular the properties of low density electron plasma equilibria. The theories developed are now being tested in several devices, not only on the Columbia Nonneutral Torus (CNT) but also on two devices in Japan. Some of the key predictions from theory have been experimentally verified, but many phenomena in CNT are still inadequately understood. The existing computational tools will be refined and applied in preparation for the next phase of the experiment, the creation of electron-positron plasmas. The development of an understanding of non-neutral plasmas confined on magnetic surfaces will be a valuable addition to basic plasma physics. It is also important for the future electron-positron (pair) plasma experiments. Electron-positron plasmas are theoretically the simplest quasi-neutral plasmas that one can study, and hence, a pair plasma experiment would provide a stringent test of our understanding of basic plasma physics. The proposed program supports one doctoral student, and it involves substantial participation by undergraduate students as well as high school students, and will continue to do so in the future. Show more... | National Science Foundation | 9/22/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $404,383.00 | Grant | Trans-NSF Recovery Act Research Support The nature of telecommunications networks is rapidly changing. Commodity smart mobile phone frameworks such as Android and Openmoko invite developers and end users to build applications, modify the behavior of the phone, and use network services in novel ways. However, while simultaneously spurring incredible innovation, the move to open systems alters the underlying performance and security assumptions upon which the network was designed. Such changes invite vulnerabilities ranging from merely vexing phone glitches to catastrophic network failures. The current infrastructure lacks the basic protections needed to protect an increasingly open network, and it is unclear what new stresses and threats open systems and services will introduce. This research analytically and experimentally investigates defensive infrastructure addressing vulnerabilities in open cellular operating systems and telecommunications networks. In this, we are exploring the requirements and design of such defenses in three coordinated efforts; a) extending and applying formal policy models for telecommunication systems, and provide tools for phone manufacturer, provider, developer, and end-user policy compliance verification, b) building a security-conscious distribution of the open-source Android operating system, and c) explore the needs and designs of overload controls in telecommunications networks needed to absorb changes in mobile phone behavior, traffic models, and the diversity of communication end- points. This research symbiotically supports educational goals at the constituent institutions by supporting graduate and undergraduate student research, and is integral to the security and network curricula. Show more... | National Science Foundation | 9/24/2009 |
| THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK INC | $175,280.00 | Grant | Trans-NSF Recovery Act Research Support Floer homology theory, a technique using partial differential equations to study problems in smooth / symplectic topology, were first introduced in the 1980's. Since then, these theories have led to many dramatic discoveries, including the resolution of the Arnold conjecture in symplectic geometry and Gordon's conjecture on lens space surgeries, but their structure remains somewhat mysterious. The focus of this project is on better understanding the structure of certain Floer homology theories. One particular goal is to continue to develop Lipshitz-Ozsvath-Thurston's theory of 'bordered Floer homology,' an effort to axiomatize Heegaard Floer homology by a type of second-order degeneration. Another goal is to construct a 'Floer homotopy type' for Lagrangian intersection Floer homology, an idea suggested by Cohen-Jones-Segal and carried out in other contexts by Manolescu, Kronheimer-Manolescu, and Sarkar. A third goal is to associate maps on knot Floer homology to knot cobordisms, hopefully leading to deep structural results about 3- and 4-dimensional Heegaard Floer theory. Most of mathematics falls into one of two categories. One category studies continuous problems, like fluid flow or minimal surface (bubble) formation, often through partial differential equations. Another studies more rigid, algebraic problems like hidden symmetries of real world objects (e.g., mosaics or particle physics theories) or mathematical objects (like groups and fields). Some of the most striking mathematics sits at the intersection of the two types, using algebraic methods to study qualitative properties of continuous systems which are quantitatively intractable. One powerful example of this method is Floer homology, which uses algebraic structures like chain complexes, Hochschild homology, and topological field theories to study certain families of partial differential equations coming from physics. Floer theory then re-interprets the results to answer questions in topology (large-scale or qualitative geometry). This project will extend several Floer homology theories by considering even deeper algebraic and topological structure to obtain stronger geometric results. Show more... | National Science Foundation | 7/13/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $500,000.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses broad challenge area (15) Translational Science and specific Challenge Topic, 15-AI-106: translational research focused on high priority pathogens and basic research focused on resistance mechanisms. The research described herein can be initiated immediately and completed within two years. The work proposed will maintain or create three full time positions and will require the purchase of products and services from the biotech industry. In the longer term, the outcome of the proposed research may stimulate the economy by greatly reducing employee absenteeism due to influenza illness and eliciting the investment of vaccine companies in the optimization and manufacture of universal influenza vaccines. Specifically, we propose the development of novel influenza vaccine constructs which have the potential to protect against a wide range of antigenically-drifted variant viruses and against multiple subtypes influenza A viruses. The design of these constructs is based on our and others' recent observations that monoclonal antibodies which bind to the conserved stalk region of the influenza A virus hemagglutinin (HA) molecule are both broadly cross-reactive and neutralizing. The identified epitope is highly conformational, comprising portions of both the HA1 and HA2 subunits, and is located in the membrane proximal region of the HA protein. During natural infection or vaccination with conventional influenza vaccines, this region of the HA molecule is thought to be masked by the membrane distal portion of HA, a bulky and highly immunogenic globular head domain. Indeed, the immune response to vaccines currently in use is predominantly targeted against the globular head of HA; since this domain is very poorly conserved, current vaccines protect only against relatively small clusters of closely related strains. We have identified a way of expressing a modified HA molecule which lacks the globular head domain and maintains the structural integrity of the stalk region. This molecule forms the basis for a new generation of influenza vaccines which will induce broadly cross- neutralizing antibodies against the conserved stalk region. Such vaccines have the potential to provide protection against epidemic strains arising over several decades, obviating the need for annual influenza vaccination. In addition, vaccines based on the conserved HA stalk domain are predicted to be effective against influenza viruses of most (perhaps all) of the 16 HA subtypes and therefore to provide protection in the event of an influenza pandemic. Show more... | National Institutes of Health | 9/25/2009 |
| NEW YORK UNIVERSITY (INC) | $499,998.00 | Grant | Trans-NIH Recovery Act Research Support Lymphoid neoplasms are among the most common malignancies in humans, and, for reasons that remain obscure, their incidence has been increasing over the past two decades. Although these disorders arise from diverse etiologies, chromosomal translocations involving the antigen receptor loci are a common underlying mechanism. B and T lymphocyte development is driven by V(D)J recombination, a process by which gene segments at the antigen receptor loci are repeatedly rearranged to create a vast repertoire of antigen receptor genes. Because V(D)J recombination entails the cleavage and joining of widely dispersed gene segments many millions of times each day, even a miniscule error rate still carries considerable risk of translocation. This risk is further increased in B cells, which undergo yet another genomic rearrangement process known as class switch recombination (CSR) to change the effector function of the immunoglobulin (Ig) molecule. Given the deleterious consequences of aberrantly repaired double strand breaks (DSBs), both V(D)J recombination and CSR must tightly regulate accessibility of substrates for cleavage and the activities of the DNA damage response and repair machineries. Although detailed genetic and biochemical studies have identified the factors involved in these processes, these 'bulk techniques cannot provide much insight into their spatiotemporal workings; only recently have microscopic techniques allowed us to view these processes as they occur in specific cells. Using 3D FISH and other techniques, my lab recently demonstrated that homologous Ig alleles physically pair up in a stage-specific manner that parallels the sequential stages of recombination of these loci. Surprisingly, this interallelic association is mediated by the V(D)J recombinase and the DNA damage checkpoint protein ATM: introduction of a double-strand break at one Ig allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin to prevent further cleavage (Hewitt et al., Nature Immunology, 2009). Notably, ATM-deficient mice and humans are prone to certain recurrent oncogenic translocations, by mechanisms that have remained unclear; our work sheds light on the spatiotemporal aspects of ATM function. We propose that homologous pairing of alleles undergoing recombination protects genomic stability by ensuring that broken ends are aligned with homologous alleles rather than in contact with other loci. We want to delve more deeply into this mechanism, investigating how ATM and the RAG proteins exert control over locus conformation and nuclear location. Show more... | National Institutes of Health | 9/29/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $358,515.00 | Grant | Trans-NIH Recovery Act Research Support This study proposes to compare surgical treatment options for localized prostate cancer (MRP vs ORP) in terms of perioperative outcomes and cost, using several large national data resources and prospectively collected data from a large-volume specialty cancer center. Specific Aim 1 is to compare perioperative outcomes, complications, and direct medical costs between RP surgical techniques in a population-based observational cohort of men treated with RP for localized prostate cancer (taken from the Surveillance, Epidemiology and End Results (SEER) population-based cancer registry linked with Medicare claims database). The outcomes for comparison include 90-day postoperative morbidity and mortality, length of hospital stay, late urinary and bowel complications, treatment of incontinence, use of postoperative radiation or androgen deprivation therapy, and direct medical costs. Multivariable methods will be used to compare outcomes between groups, adjusting for sociodemographic and clinical covariates. The cost comparison between RP surgical techniques will be accomplished by totalling all Medicare payments made within one year of surgery. Specific Aim 2 is to identify and compare medical, nonmedical, and indirect costs following ORP and MRP in a prospective cohort of RP patients. For this aim, we will prospectively identify and compare such costs in a cohort of RP patients from a large-volume, comprehensive cancer center. Data for this portion of the study will come from an electronic medical record and clinical research database (Caisis) and from a survey administered at specific intervals. The survey will focus on expenses related to home care during recovery, incontinence or erectile dysfunction, and inability to return to work. Show more... | National Institutes of Health | 9/29/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $499,884.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses the broad Challenge Area (01) Behavior, Behavioral Change, and Prevention and the specific Challenge Topic, 01-DA-106: Development of behavioral and social interventions that reduce stigma and improve quality and accessibility of health care services in low resource settings. We will evaluate a pharmacy-based pilot intervention that combines rapid HIV testing with other preventive screening services including blood pressure, glucose, and cholesterol screening. This pilot targeted to injection drug users (IDUs) who purchase syringes from pharmacies via the New York State Expanded Syringe Access Program (ESAP) - a program aimed at increasing sterile syringe access to help reduce HIV transmission. By combining HIV testing with less stigmatizing screening services and offering testing to all pharmacy patrons instead of singling out drug users, the likelihood of reducing HIV testing and drug use-associated stigma will increase. Although HIV testing is increasingly accessible and new testing technologies are available, HIV testing rates are low in the black and Hispanic community, especially among IDUs at risk for HIV and many other infectious and chronic diseases. Structural barriers (i.e., lack of health insurance) in the black and Hispanic community, especially among IDUs may limit access to regular health care/ preventive services. Access barriers are compounded by stigma associated with getting an HIV test that may identify an individual as a drug user and/or someone who engages in socially unacceptable behavior. Thus, this proposed study aims to 1) qualitatively evaluate HIV testing and chronic disease screening in pharmacies, 2) compare/contrast correlates of agreeing to a HIV test vs. not among IDU syringe customers and their peers and 3) qualitatively compare/contrast HIV testing with comprehensive screening services pharmacy (intervention) vs. HIV testing only pharmacy (control). To accomplish these aims, we propose to conduct in-depth interviews among key stakeholders to inform development of study materials, IDU/peer survey and pharmacy staff surveys. We will recruit 2 ESAP-registered Harlem pharmacies (1 intervention and 1 control) where our current work has developed the infrastructure to perform on-site screening services. Among the intervention and control pharmacies, 798 (518 non-drug using, 70 drug-using +3 networks/ drug user) pharmacy customers will be recruited. We will adapt a previously developed training module to train pharmacy personnel on how to engage pharmacy customers. Customers from the intervention pharmacy will complete a brief attitude scale on attitudes toward HIV, IDUs and stigma, watch an educational video on the importance of health screening (particularly HIV testing), participate in desired screening services and undergo a structured 20-minute ACASI that repeats the attitudes scale. Customers in the control pharmacy will only undergo HIV testing and a structured 20-minute ACASI survey. Semi-structured surveys will be administered to all pharmacy staff to ascertain impact of on-site prevention services on pharmacy personnel and business flow. We will use standard qualitative analytic techniques and GEE to account for clustering in quantitative analyses. The proposed research is highly significant in that it aims to explore a pilot intervention that involves expanding pharmacy services to include HIV testing and to determine if offering HIV testing within a comprehensive prevention approach that includes less stigmatizing screening tests (i.e., blood pressure, glucose and cholesterol screening) increases HIV testing among injection drug users who purchase syringes in pharmacies and their peers (drug-using and/or non-drug using). We will be using new HIV testing technologies and bringing technological innovations and treatment modalities to low-income communities in New York City. The full abstract for this award is available at http://projectreporter.nih.gov. Show more... | National Institutes of Health | 9/25/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $499,221.00 | Grant | Trans-NIH Recovery Act Research Support In this study, we propose to perform the first genome-wide association study (GWAS) for Immunoglobulin A Nephropathy (IgAN, OMIM %161950), an understudied disease that is a major cause of kidney failure in the U.S. and worldwide. It is the most common cause of kidney failure among Asian populations, and the most common form of primary glomerulonephritis among young Caucasians. Similar to many immune mediated disorders, IgAN is a genetically complex trait and genetic basis for disease is not known. To perform a GWAS, we have assembled the largest international case/control cohort of IgAN. This study population consists of a Chinese cohort recruited from Beijing and Shanghai ( >2,000 biopsy-documented cases of IgAN and >2,000 healthy controls) and a Caucasian/European cohort recruited the North America and Europe (>2000 biopsydocumented cases and 2000 controls), with the recruitment ongoing at four study sites. Critically, all the samples for these studies are in hand. Initial genotyping of 551 cases and 441 controls from Beijing, China (Illumina 610quad chip). Analyses of the data demonstrated absence of significant stratification (?=1.005) and revealed genome-wide significant association of IgAN with the HLA-DQA2 locus (p=9x10-8). In addition, In addition, this modest-sized cohort revealed several suggestive associations on chromosomes 7q31 (p=7x10-6), 15q13 (p=8x10-6), 4q21 (p=2x10-5), and 3q26.2 (p=3x10-5), highlighting novel candidate genes for disease. In this project, we propose to complete the genotyping of the Beijing cohort (total of 1200 IgAN cases/1200 controls) to identify common variants with modest to large effects on disease. We will next replicate these findings in independent cohorts from Shanghai (750 cases/750 controls) and Caucasians from North America/Europe (2000 cases/2000 controls). These studies will provide insight into the pathogenesis of IgAN, providing novel opportunities for development of diagnostic and therapeutic tools for this major cause of kidney failure. PUBLIC HEALTH RELEVANCE: Immunoglobulin A Nephropathy (IgAN, OMIM %161950), an understudied disease that is a major cause of kidney failure in the U.S. and worldwide. These genetic studies will provide insight into the pathogenesis of IgAN, providing novel opportunities for development of diagnostic and therapeutic tools for this major cause of kidney failure. Show more... | National Institutes of Health | 9/25/2009 |
| ROCKEFELLER UNIVERSITY, THE | $471,193.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses broad Challenge Area 06: Enabling Technologies and specific Challenge Topic 06-GM-101: Structural Analysis of Macromolecular Complexes. It focuses on the multiprotein Mediator complex, which has been implicated as a critical coactivator for transcription of essentially all RNA polymerase II-transcribed genes in eukaryotes. Through its ability to interact with both transcriptional regulators and the RNA polymerase machinery as well as through its multiple functional capabilities, Mediator is believed to be the main channel through which transcriptional signals are ultimately processed. Aberrant expression of several Mediator subunits has also been implicated in human diseases that include cancer, heart abnormalities, and neural degeneration. Despite their common evolutionary origins, the yeast and mammalian complexes have diverged considerably. Unlike the situation for the yeast Mediator, where genetic studies have highlighted important structure-function relationships and led the way for biochemical studies, technical issues have made it difficult to go beyond a gross description of the architecture of the 30-subunit mammalian complex and its function. Unaddressed issues relate to definition of the essential core of the complex and to the nature of other factors that impinge on its function under different conditions. Here we propose to undertake a systematic approach both to define the modular architecture of the core human complex (especially as it pertains to its essential functions) and to develop methods to purify the intact complex and its interacting proteins from a diverse range of biological sources. Towards these goals we aim (i) to recombinantly generate a minimal functional derivative of the modular Mediator complex; and (ii) to raise monoclonal antibodies against defined Mediator epitopes that will allow facile purification of the natural complex in association with interacting factors. Availability of these tools is thus expected to provide a jump-start to the next phase of studies in the human Mediator field. Show more... | National Institutes of Health | 9/28/2009 |
| NEW YORK, CITY OF | $6,628,688.00 | Grant | 16.808 - Recovery Act Byrne Competitive The title of this award is Enhanced Supervision and Community Reintegration. The purpose of Probation is risk management, a strategy designed to reduce an offender?s future criminal conduct. This strategy consists of risk control, the limitation of the offender?s capacity to carry out new criminal acts, risk reduction, and the diminishment of the probability that an offender will elect to commit another crime. To better fulfill its purpose, DOP will use Edward Byrne Memorial Competitive Grant funds to hire additional probation officers, supervising probation officers, branch chiefs and support staff to bring agency staffing to parity and to ensure that public safety is not compromised by increased reliance on probation services in the area of Enhance Juvenile Intake, Supervision of Adult Sex Offenders, and Forensic Mental Health. The anticipated benefits are reduced reliance on adult incarceration, juvenile placement and inpatient mental health services, as well as improved community reintegration, family engagement, and financial independence among probationers who are supporting families. Show more... | Department of Justice | 9/02/2009 |
| THE PORT AUTHORITY OF NEW YORK & NEW JERSEY | $2,858,200.00 | Grant | NATIONAL CLEAN DIESEL FUNDING ASSISTANCE PROGRAM (B) The Port Authority was awarded a national Clean Diesel Funding Assistance Program Grant in order to fund the shore power installation at the Brooklyn Cruise Terminal in Brooklyn, NY. This project will install land-side electrical infrastructure, with the general purpose of the grant being to reduce diesel emissions from the ships onboard generators and to improve the overall air quality. Show more... | Environmental Protection Agency | 7/13/2009 |
| NEW YORK UNIVERSITY (INC) | $375,817.00 | Grant | Trans-NIH Recovery Act Research Support Translation Regulation in Hippocampal LTP and LTD | National Institutes of Health | 7/20/2009 |
| NEW YORK UNIVERSITY (INC) | $422,709.00 | Grant | Trans-NIH Recovery Act Research Support This project is about regulatory T cells, which are essential components of the immune system. Through experiments conducted during the previous funding cycle we observed that in the presence of Tregs, antigen-presenting dendritic cells (DCs) are recovered at lower frequencies, have a higher turnover rate and higher apoptosis rate than in the absence of Tregs. In this renewal application we propose to explore these observations as a potential mechanism of Treg action in vivo. Other experiments conducted during the previous funding cycle led us to appreciate the importance of adaptive, peripherally generated, Foxp3+ Tregs. We propose to study the properties of adaptive Foxp3+ Tregs and verify to what degree adaptive and natural Foxp3+ Tregs are different, each covering unique aspects of the immune response. We seek to attain the following specific aims. Aim 1. To assess the effect of Foxp3+ Tregs on dendritic cells in vivo. We will test the hypothesis that Treg-mediated elimination of antigen-loaded DCs is one mechanisms of Treg action in vivo. Aim 2. To observe in real time the interactions between Tregs, Teffectors, and DCs under tolerogenic or immunogenic conditions, using two-photon intravital microscopy. Aim 3. To assess the role of adaptive Foxp3+ Tregs in chronic inflammatory conditions. We will compare the number of adaptive and natural Tregs necessary to prevent colitis, high IgE response, and spontaneous EAE. We will track the migration patterns of adaptive Tregs purified from spleen and lung tissues. Show more... | National Institutes of Health | 7/17/2009 |
| METROPOLITAN TRANSPORTATION AUTHORITY | $11,813,686.00 | Grant | ARRA Rail and Transit Security Grant Program This application is for $11,813,686 of Transportation Security Grant Program - Capital Projects funds appropriated thorugh ARRA. This grant is for costs related to enhancing the Nation's transit infrastructure to prevent, protect, respond to, and recover from threats or acts of terrorism. Specifically, this grant is for the Long Island Rail Road/New York City Transit Perimeter Protection at the Penn Station Complex, New York City. Show more... | Federal Emergency Management Agency | 9/29/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $381,375.00 | Grant | Trans-NIH Recovery Act Research Support Influenza virus causes a respiratory infection that leads to morbidity and mortality worldwide. The virus infects the respiratory epithelium and replicates rapidly to peak levels in two days. It is eventually cleared from the lungs by a strong cellular immune response. Dendritic cells play an essential role in the generation of the cellular response. Upon interaction with the virus, DCs are triggered to produce type 1 interferon and other inflammatory cytokines and increase their expression of cell surface receptors that enhance their ability to interact with T cells. This process is referred to as DC maturation and is essential for the generation of cellular immunity. In humans and mice, influenza virus triggers a strong cellular response. Surprisingly, in vitro, influenza virus is a very poor stimulator of DC maturation because the viral NS1 protein inhibits the maturation process. However, if the DCs are preexposed to interferon, the cells can overcome the viral antagonism and respond strongly. To try to better understand the process by which immunity is generated in vivo, we began to explore the cellular movements that occurred in mice infected by aerosol. We were unable to detect any inflammatory response in the animals until almost 48 hours after infection when virus replication was reaching its apex. At this point a sudden rapid generation of chemokines and cytokines, that we refer to as the inflammatory burst, occurs in the lungs. Cytokines and chemokines reach high levels in the serum. Cells in distal lymphoid compartments, particularly the bone marrow, begin to express an 'interferon signature' characterized by the upregulation of antiviral genes. Cells in the blood stream also express an interferon signature suggesting they are coming from the bone marrow and migrating into the lungs in a preactivated state. A large and prolonged influx of leukocytes into the lungs made up primarily of GR1+ monocytes occurs at this time. DCs carrying viral antigens start to arrive in the draining LN after this time point and a significant percentage of them express GR1 and CD11b markers indicating that they recently derived from monocytes. We hypothesize that replication proceeds undetected (stealth) until virus reaches very high levels in the lungs and a breakthrough occurs by some as yet unidentified event(s). Innate immunity is triggered and amplified by cell-to-cell signaling which leads to an inflammatory burst. This initiates a sequence of events, beginning with the release of soluble mediators and the recruitment of preactivated pre-DCs. The preactivation allows the cells to respond strongly and overcome the antagonism of the viral NS1 protein leading to their subsequent migration to the draining lymph nodes where they stimulate T cell activation. In this application we will test the tenets of this hypothesis by studying the events that occur in the lungs, and the activation state of the blood and bone marrow. Finally we will investigate the role that the NS1 plays in the kinetics of infection and try to override its effects. PUBLIC HEALTH RELEVANCE: The work should provide a new understanding of the mechanisms by which the immune system responds to virus infection. We propose to try to speed up the initiation of immunity by a number of mechanisms. If this succeeds it could be a viable immunotherapeutic strategy. Show more... | National Institutes of Health | 5/21/2009 |
| CORNELL UNIVERSITY, INC | $84,177.00 | Grant |
Trans-NIH Recovery Act Research Support We requested an administrative supplement to purch
There were 2 sub-recipients, vendors, and/or sub-vendors associated with this. See details |
National Institutes of Health | 8/03/2009 |
| CORNELL UNIVERSITY, INC | $110,808.00 | Grant | Trans-NIH Recovery Act Research Support The aim of the parent grant proposal is to clone the gene responsible for a new mouse craniofacial mutation, Hollow Ear (or Hol), identified by ENU mutagenesis. The Hol mutation phenocopies the Tbx1-deficient mouse mutant, but does not map to either the Tbx1 or Crkl loci, both implicated in human DiGeorge Syndrome (DGS). Thus, the gene responsible for the Hol phenotype is not Tbx1 or Crkl, but likely acts in the Tbx1 pathway in craniofacial development. The goal we had set for high-resolution mapping during the first year of grant tenure, described in the parent grant application, was to restrict the Hol-bearing interval to approximately 1 Mb, thus allowing the identification of a manageable list of candidate genes for sequencing. We have successfully reached the goal. However, the restricted 1.2 Mb Hol critical interval contains a total number of 54 genes. Of note, this genomic region has a remarkably high gene-density, which is making gene identification seriously challenging. Generally, a typical 1 Mb genomic segment contains approximately 12 genes, albeit regions with higher gene concentration have been encountered less frequently. Some appealing candidate genes described in the parent grant application were excluded from the Hol-critical region by the time we narrowed it to only 1.2 Mb. Therefore, in the absence of strongly compelling candidates among the 54 genes contained within the Hol critical segment, we have started to systematically sequence all exons contained within the interval. At the same time, we will do additional high-resolution mapping to further narrow the Hol critical region, with the goal to reduce the number of genes for sequencing. In sum: we are facing a greater challenge than we had envisaged. As a result, we will need additional financial resources and time to conclude this important research project and identify the gene responsible for the Hol phenotype. Show more... | National Institutes of Health | 9/23/2009 |
| CORNELL UNIVERSITY, INC | $78,826.00 | Grant | Trans-NIH Recovery Act Research Support This award provides additional funding for 5T32GM073546-04. This additional funding is provided under the American Recovery and Reinvestment Act of 2009 (ARRA) to support the training expenses, stipend, tuition and travel for (1) predoctoral student in the Pharmacological Sciences for a period of two years. The selected predoctoral trainee supported by this grant is Alex Hansler. Show more... | National Institutes of Health | 8/14/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $214,512.00 | Grant | Trans-NIH Recovery Act Research Support This award is issued in response to Notice OD-09-060, Recovery Act Administrative Supplements Providing Summer Research Experiences for Students and Science Educators.PROJECT SUMMARY/ABSTRACTHedgehog (Hh) proteins are secreted morphogens that regulate normal cell differentiation as well asmalignant cell growth. Covalent attachment of the fatty acid palmitate to the N-terminus of Hh iscritical for Hh function. Unlike nearly all other palmitoylated proteins, that contain thioester linkedpalmitate, palmitate is linked to Hh via amide (N-) bond. The overall goals of this research are toelucidate the enzymology and biochemical mechanism of N-palmitoylation of developmentallyimportant signaling proteins, and to understand how expression and function of N-palmitoyltransferases is regulated. We will use Hh proteins as model systems to address the following issues:1. To reconstitute N-palmitoylation using purified Hedgehog and Rasp proteins Genetic experiments in flies and mice indicate that Rasp, a multipass membrane protein, isrequired for Hh palmitoylation. To date, there is no biochemical evidence that Rasp, or its mammalianhomolog Mart-2, functions independently and catalytically as a palmitoyl transferase. We have nowsucceeded in purifying Mart -2 to homogeneity in active form. The biochemical parameters andenzymatic mechanism of Shh and Hh N-palmitoylation will be determined.2. Structure/Function analysis of Rasp/Mart-2 and Hh/Shh: How do MBOAT proteins work andhow do they recognize their substrates? Using deletion analysis and chimeric proteinsformed between Rasp and another MBOAT family member Porcupine, we will identify thetransmembrane and/or cytoplasmic loop regions of Rasp and Mart-2 that comprise the active site andare important for catalysis. We will identify the minimum N-palmitoylation sequence motif withinHh/Shh and use this information to identify other substrates for Rasp and Mart-2.3. To determine how N-Palmitoylation by Rasp/Mart-2 is regulated within the cell Subcellular localization and trafficking experiments will be performed to determine when andwhere Hh is palmitoylated. Methods to inhibit Mart-2 mediated palmitoylation will be devised. A highthroughput screen will be exploited to identify novel small molecular inhibitors of Hh palmitoylation.These reagents could potentially be clinically useful as anti-tumor agents in Hh driven malignancies.The effects of Mart-2 inhibition on growth of Shh-dependent pancreatic cancer cells will be assayed. Project Narrative/Relevance to Public Health:Hh signaling has been shown to drive the growth of many human cancers, including medulloblastoma,melanoma, and pancreatic tumors. The proposed studies will help us understand how Hh proteinswork in normal and malignant cells and will aim to develop Hh inhibitors that could potentially beclinically useful as anti-tumor agents in Hh driven malignancies. Show more... | National Institutes of Health | 8/10/2009 |
| SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH INC | $48,410.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): A T cell response is initiated by T cell receptor (TCR) activation through recognition of foreign antigen displayed on the surface of an antigen presenting cell (APC) and results in the directional secretion of certain cytokines or cytolytic factors towards the APC. Cytolytic factors cause death of an infected target cell, and cytokines stimulate other cells involved in the immune response. Directional secretion enables a T cell to specifically communicate with a target cell and is critical for effective T cell function. This is clearly demonstrated in diseases such as Griscelli syndrome and Chediak-Higashi syndrome where impaired directional secretion by T cells results in immunodeficiency. In addition, misdirected secretion could result in the death of uninfected cells or inappropriate activation of immune responses. Directional secretion requires reorientation of the T cell microtubule organizing center (MTOC) to the immune synapse (IS), the contact site with the target cell. Our understanding of MTOC reorientation has been limited by the difficulty of directiy observing the process. MTOC reorientation occurs within minutes of TCR activation, however most studies of this process are based on staining of fixed conjugates between T cells and APCs at set time points. This approach does not provide the temporal precision necessary for mechanistic study of such a rapid process. The goal of this project is to more clearly define the mechanism responsible for T cell MTOC reorientation using a photoactivatable antigen that is inactive until exposure to a short pulse of UV light. This method enables precise spatial and temporal control over T cell activation, and will be applied in single cell live imaging experiments to simultaneously observe recruitment behaviors of various fiuorescently labeled proteins and MTOC reorientation. It will also allow observation of how RNAi knockdown or chemical inhibition of a candidate protein affects MTOC reorientation and recruitment behaviors of other proteins in live T cells. Finally, a directional cytokine secretion assay will be used to determine how MTOC reorientation defects caused by knockdown or inhibition of proteins involved affects T cell function. PUBLIC HEATLH RELAVENCE: T cells play a central role in the antigen specific immune response. The ability to directionally secrete certain cytokines or cytolytic factors towards a target cell is critical for effective T cell function as it enables specific communication with a target cell. Directional secretion requires reorientation of the microtubule organizing center (MTOC) to the contact site with the target cell; however this process is poorly understood. I will investigate the mechanism of MTOC reorientation using a photo activatable antigen that provides precise control over T cell activation enables analysis with high spatial and temporal resolution. Show more... | National Institutes of Health | 6/18/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $117,004.00 | Grant | Trans-NIH Recovery Act Research Support The goals of Mount Sinai School of Medicine's Post-baccalaureate Research Education Program (PREP), for which renewed support is sought, are to: (i) increase enrollment of under-represented minority (URM) PhD and MD-PhD students in our own graduate programs and in other excellent programs. The longer-term goal is to contribute to greater URM participation in biomedical research careers at a high level of achievement. We will demonstrate to recent URM college graduates that a career in biomedical research is an exciting and achievable choice for them. The central activity in this demonstration is a cutting-edge mentored research experience, supplemented critically by special seminars, works-in-progress, journal clubs and opportunities to attend meetings, (ii) enhance PREP scholars' ability to succeed and, in significant numbers, to excel when they enter pre-doctoral programs. To achieve this, PREP scholars with be given the chance to adjust to a Graduate School/Medical Center environment as part of the supportive PREP mini-community and become full participants in the larger academic community before undertaking a full pre-doctoral course-load. PREP scholars will also have the option of taking or auditing appropriate course-work to experience the challenge of pre-doctoral academic work with a single course at a time and, when they succeed, gain confidence as well as a 'leg-up' with respect to the requirements of their next program. An array of individualized development activities will enhance the skills of each PREP scholar from their own starting points, (iii) foster later participation in translational research and reduction of health care disparities by bringing them into the intense institutional efforts in these arenas as participants and/or learners. Mount Sinai's PREP will build on the success of its first 4 years during which a large majority of the first 17 PREP scholars to complete PREP entered doctoral programs; 13 of the 17 scholars entered PhD (11) or MD-PhD (2) programs and are progressing strongly, with one more now applying to PhD programs. To further enhance this success and foster an even deeper engagement with issues of health and health care disparities, we will refine the Program elements, will carefully monitor the long-term success of the Program and evaluate the contribution of specific Program elements by collecting and analyzing both short- and longterm outcomes data. Show more... | National Institutes of Health | 7/20/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $414,434.00 | Grant | Trans-NIH Recovery Act Research Support This application is designed to identify compounds to treat Charcot-Marie-Tooth type 2E (CMT2E). CMT is the most commonly inherited neurological disorder with a reported prevalence of 1 in 2,500 people worldwide. It is found in all races and ethnic groups. CMT is slowly progressive and CMT patients suffer from degeneration of the peripheral nerves that control sensory information of the foot/leg and hand/arm. The nerve degeneration causes the subsequent degeneration of the muscles in the extremities. Among the symptoms of CMT are foot-drop, steppage gait, high arches, foot bone abnormalities, and basic problems with hand function, as well as sometimes breathing difficulties. CMT is not usually life threatening, but can cause severe disabilities. Although the genes mutated in CMT are also expressed in the central nervous system, the disorder almost never affects brain function. CMT is divided in two major types, CMT1 and CMT2, based on nerve conduction velocities, which are reduced in CMT1 and relatively normal in CMT2. In general, CMT1 is a demyelinating neuropathy caused by mutations in genes important in myelin formation, whereas CMT2 is axonal. Mutations in the neuronal intermediate filament gene, NEFL have been shown to cause a subtype of CMT2, called CMT2E. NEFL encodes the neurofilament light (NFL) protein that we have shown to be a necessary component for the assembly of neuronal intermediate filaments. Mutations in this gene are responsible for approximately 2% of all CMT cases. Neuronal intermediate filaments form the intermediate filament network in neurons and are the predominant cytoskeletal structure in the axon. Neurofilamentous aggregates both in the neuronal cell bodies and axons are seen in patients with mutations in NEFL, as well as in other neurodegenerative diseases, such as amyotrophic lateral sclerosis. We have shown that the mutant NFL proteins form aggregates in transfected neuronal and non-neuronal cells. Misassembled neurofilament aggregates are found in all transfected cells expressing the pathogenic CMT-associated NFL mutant proteins, but not in cells expressing several polymorphic variants that are non-pathogenic. We hypothesize that inhibitors of neurofilament misassembly will lead to therapies for CMT. Therefore, the goals of this proposal are to identify small molecules that inhibit misassembly and to test their effects in a mouse model of CMT2E. We will focus our attention on two of the first described mutant NFL proteins, P8R NFL and Q333P NFL that we have characterized in the most detail. Using high-throughput visual screening methodology, we will identify small molecules that inhibit neurofilament misassembly. For the second and related part of the project, we will generate knock-in mouse models of CMT2E with mutations in the Nefl gene. These mice will be characterized phenotypically and we will then test compounds identified in the visual screens for their ability to ameliorate peripheral neuropathy in these mouse models. The proposed research will identify lead compounds for the development of drugs to treat human subjects with CMT, as well as potentially other neurodegenerative diseases and it will also generate mouse models of a human hereditary neuropathy that will be of value to many other investigators in the field. PUBLIC HEALTH RELEVANCE: CMT is the most commonly inherited form of peripheral neuropathy. The goal of this project is to use chemical screening to identify novel drugs to treat one type of CMT and test them in mouse models of the disease. Show more... | National Institutes of Health | 9/25/2009 |
| MOUNT SINAI SCHOOL OF MEDICINE OF | $276,492.00 | Grant | Trans-NIH Recovery Act Research Support Individuals live within a series of hierarchical environments, and these environments are associated with health and behaviors over and beyond individual level influences such as socioeconomic status or race. In many cases, these macro-level environmental influences that affect health have been measured by investigators by using geographic information systems, in order to contextualize individuals' home and work environments. This growing area of research has lead public health researchers towards environmental level interventions to address cardiovascular health. However, because contextual studies have been primarily cross-sectional, and physical activity is often assessed without evaluating diet and vise-versa, there remain many knowledge gaps regarding the best avenues for interventions. Furthermore, how the direction for interventions may vary by age and other population demographics remain unknown. The purpose of this project is to assess the local food and physical activity environments simultaneously on the health and behaviors of urban Seniors in Brooklyn NY. Because Seniors may be more reliant on a local area for good and services and at higher risk for cardiovascular disease outcomes, our aim is to focus on individuals 65 years or older. We plan to study the intersection between the built environment and Seniors' health and behaviors in order to provide empirical evidence to direct public health interventions. Methods: We will conduct a prospective cohort study of 1,655 Seniors recruited from five areas of Brooklyn who will be seen two years after the baseline visit. The study will consist of environmental assessment of food; physical activity and transportation resources as well interviews with Seniors to gain information about attitudes, perceptions and cultural variation around nutrition, physical activity and health. We will also monitor diet, physical activity and cardiovascular disease risk factors. We will measure the influence of changes and utilization of the food and physical activity environment on individuals' behaviors and health outcomes as well as the contribution of other environmental (physical and social) and individual-level (i.e. income) factors. Conclusions: The study will provide empirical evidence of Seniors' interactions in their built environments and effect on health behaviors and health outcome. Show more... | National Institutes of Health | 8/10/2009 |
| CITY OF NEW YORK | $2,341,472.00 | Grant | ARRA - Immunization The activities proposed for ARRA funding are consistent with recent strategic and operational decisions made by the DOHMH Bureau of Immunization (BOI) to improve immunization coverage across the life span of New Yorkers by increasing the efficiency and efficacy of all programmatic and operational activities. In 2008, a strategic review of all BOI organizational units was conducted, resulting in integration or realignment of provider support activities. The review was followed by an external Bureau wide communication and IT assessment to improve efficiencies through improved communication and information technology. ARRA funding will build on the recent organizational improvements by sustaining or enhancing several key programmatic areas. First, funds will provide for the full implementation of recommendations from the 2008 communication and IT assessment by offsetting a very significant increase of 13% (from 38% to 51%) in staff salary benefits as contained in the most cost allocation agreement. Second, in anticipation of an increase in demand for the regular seasonal flu vaccination and in the forecast demand for the new HINI vaccine, funds will provide for an increase in flu outreach services and educational activities to the general public Show more... | Centers for Disease Control and Prevention | 9/22/2009 |
| NEW YORK UNIVERSITY (INC) | $54,000.00 | Grant | Trans-NIH Recovery Act Research Support Signaling by the Notch receptors has been implicated in maintenance and differentiation of the pluripotent progenitor cells in the mammalian pancreas, intestine and vasculature. Within the parent grant, we have shown that during branching morphogenesis of the murine prostate Notch signaling is localized to the forming prostate buds and distal tips, and that BMP signaling limits the number of the Notch-active domains (Grishina et al., 2005). We have also found that gain of Notch activity in the embryonic prostates leads to increase in undifferentiated progenitors, while loss of Notch signaling results in severe defects in differentiation of both the prostate ducts and smooth muscles (manuscript in preparation). Within the parent grant, we have developed four bigenic mouse systems based on two prostate specific deleters and two conditional strains to specifically address the effect of gain and loss of Notch function during embryonic and postnatal prostate development, and in adult. With this Supplement, we will employ a postdoctoral scientist for 12 months to accelerate the tempo of research and complete the goals of the parent grant in elucidating the effect of gain and loss of Notch function in embryonic and adult prostates. This analysis is essential to complete the aims of the parent grant to prove our hypotheses that Notch signaling is important for tissue organization and differentiation in the prostate epithelium and mesenchyme, and that gain of Notch activity may be the cause for benign prostate hyperplasia (prostate enlargement). This Supplement will assure the completion and publication of two research manuscripts within the aims of the parent grant, and provide the salary support and assure perspective carrier opportunities in urological research for the postdoctoral fellow. Show more... | National Institutes of Health | 9/25/2009 |
| NEW YORK UNIVERSITY (INC) | $27,000.00 | Grant | Trans-NIH Recovery Act Research Support Admnistrative supplement for 'Studies of Chondrocy | National Institutes of Health | 9/22/2009 |
| NEW YORK UNIVERSITY (INC) | $177,450.00 | Grant | Trans-NIH Recovery Act Research Support Supplemental funds were awarded to the Core sectio | National Institutes of Health | 8/24/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $50,008.00 | Grant | Trans-NIH Recovery Act Research Support We have, according to the requirements of the ADOPT supplement, appointed staff members to participate in meetings and conference calls. We have also for each role identified alternate staff members that can assist where needed. If, as the project matures, it is identified that one of the alternates would be more suitable for participation, we will make the change in assignment. Appointments are as follows: IT Infrastructure role: Benjamin May (main), Janie Weiss (alternate), Adam Wilcox (alternate) Clinical Trial Operations role: Mary Ann Kral (main), Cynthia Cabral (alternate) Show more... | National Institutes of Health | 9/29/2009 |
| NEW YORK UNIVERSITY (INC) | $93,456.00 | Grant | Trans-NIH Recovery Act Research Support The NYU Cancer Institute is committed to increasing the number of minority researchers working in cancer related areas. In section 10.7 of our P30 application we identify current programs which focus on efforts to increase the number of researchers representing underserved populations, as well as programs for mentorship of recently recruited minority junior scientists. An active program has been the Minority Internship Program. The goal of this program has been to stimulate undergraduate, graduate and postgraduate minority students' interest in working on issues related to cancer with a special focus on the effects on the underserved and immigrant populations of New York City. Currently, interns for this program are recruited from New York City colleges as well as through the New York City Department of Health and Mental Hygiene's Health Research and Training Program. The participants in the 10 week Minority Internship Program gain experience in cancer education, communication, and research. Additionally, the interns participate in a number of educational seminars and conferences. More recently NYU Cancer Institute has expanded the internship program by partnering with Prep for Prep, a non-profit community-based organization based in New York City. Prep for Prep is a highly selective leadership development program that incorporates a rigorous 14-month academic component to prepare minority students for placement in leading independent schools. Prep for Prep continues to work closely with the students through high school graduation and beyond. Established in 1978, Prep for Prep's mission is a long-term investment strategy to develop the leadership potential of able young people from segments of society grossly under-represented in the leadership pool from which all of our major institutions draw. Currently, NYU Cancer Institute sponsors three summer internships for students enrolled in the Prep for Prep program. The supplement will allow for a doubling of the number of summer internships offered to six per summer. The goal of the summer internships is to provide a meaningful internship and opportunities to learn about research related to cancer in a professional setting. The interns selected will be placed in various research areas including basic laboratory research, translational research projects and cancer disparities and outreach projects. Additionally, interns will be involved in seminar and conferences. Supplemental funding will provide funds to support laboratory costs, as well as hourly pay for the students. The goal for these interns is to use and develop communication skills, critical thinking, inter-personal skills and research experience which may encourage pursuit of careers in cancer related fields. Show more... | National Institutes of Health | 5/29/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $92,803.00 | Grant | Trans-NIH Recovery Act Research Support The purpose of this administrative supplement is 3-fold:1) to increase access for our acute stroke patients, 2) to accelerate scientific discovery in 3 internal SPOTRIAS and 3 consortium-wide SPOTRIAS clinical research studies.3) to stimulate the economy by providing employment for 1 existing and 1 additional clinical research coordinator who will assist in carrying out Specific Aims 1-3. Measures of success of this supplement (deliverables) will be: 1) increased by at least 10% the number of stroke patients being treated with IV tPA and advanced stroke care compared with the pre-supplement time period; 2) enrollment of 40 patients to our ongoing stroke studies in the supplement period.3) successful hiring and retention of the personnel listed above.Details of the plans to achieve these goals may be found in the proposal. Show more... | National Institutes of Health | 8/17/2009 |
| CORNELL UNIVERSITY, INC | $392,961.00 | Grant | Trans-NIH Recovery Act Research Support The award supports research into the study of how houmans perceive complex visual images. The expected outcome is a complete characterization of perception of a specific class of visual images, 'visual texture', characterized by their short-range structure. This will be delivered in the form of scientific papers, presentations, and publicly available software. Show more... | National Institutes of Health | 6/19/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $384,217.00 | Grant | Trans-NIH Recovery Act Research Support Notch functions to modulate cell-fate decisions during vascular development. The overall objectives are to define roles for Notch during sprouting of blood vessels and lymphatic specification and remodeling. In the first part, we explore the hypothesis that angiogenesis is regulated by cross-talk between Notch and integrin signaling pathways; that is we ask if Notch regulation of integrin expression is key to control of endothelial migration, tubulogenesis and sprouting. Our preliminary results show Notch suppresses expression of a2b1 and a6b4 integrins, known angiogenic regulators. In Aim I, we use in vitro assays to explore the consequences of Notch suppression of a2 and a6b4 expression. We propose (1) Notch suppresses a2b1 to affect endothelial migration and/or tube formation in association with collagens/laminins, and (2) Notch suppresses a6/b4 to affect endothelial migration and sprouting in association with laminins. In vitro assays will determine if one can reverse the Notch-suppression of angiogenesis by ectopic expression of a2, b4 and/or a6 integrins. In Aim II, we utilize mice to explore genetic interaction between Notch and integrins, using mice deficient in a2 integrin or defective in b4 signaling, crossed to mice defective for Notch. In the second part, we hypothesize Notch signaling is suppressed at the onset of lymphatic lineage specification, and then activated during lymphatic re-modeling. We hypothesize unique roles for Notch family members in lymphatic growth and development, with a focus on Notch1, Notch3, and Notch4. We have discovered that VEGFR-3, a lymphatic regulator, is transciptionally regulated by these three Notch receptors. In contrast, a complex regulation of Prox-1 by Notch was uncovered with opposing roles for Notch1 and Notch4. Our general strategy will use a combination of in vitro lymphangiogenesis assays and mouse modeling to define the consequences of altering Notch activity in lymphatic endothelial cells. In Aim III, we evaluate Notch function in isolated lymphatic endothelial cells with to determine if Notch regulation of VEGFR-3 and Prox1 is key to lymphatic endothelial cell behavior. In Aim IV, conditional manipulation of Notch activity in mouse models will be conducted to determine if Notch must be repressed to initiate lymphatic specification. We will also analyze Notch mutant mice and manipulate Notch in dermal lymphatic endothelial cells to determine if Notch promotes lymphangiogenesis, lymphatic remodeling or lymphatic integrity after birth. PUBLIC HEALTH RELEVANCE: Notch signaling is fundamental to proper vascular development. We present data strongly implicating Notch as a regulator of sprouting angiogenesis and lymphatic function. Thus, the studies will aid us in understanding the functions of Notch in during pathological angiogenesis and lymphatic differentiation and may assist in developing strategies and therapeutics to correct lymphatic disorders or block tumor angiogenesis or lymphangiogenesis. Show more... | National Institutes of Health | 6/01/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $726,552.00 | Grant | Trans-NIH Recovery Act Research Support New approaches to implement proven preventive and lifestyle interventions are needed to reach the NHLBI strategic plan goal to speed the translation of science into practice and reduce the public health burden of cardiovascular disease (CVD). The Family-Centered Intervention Trial for Heart Health (FIT Heart II) is an expansion of our previous work that identified family members at risk and counseled them about lifestyle and prevention during a 'motivational moment' when a loved one was hospitalized with CVD. FIT Heart II extends this research to evaluate the impact of an engaged and educated family member/caregiver to enable the hospitalized patient to increase adherence to evidenced-based preventive therapy using a rigorous randomized controlled design in a real world setting. The purpose of FIT Heart II is to evaluate the effectiveness of a novel family-centered educational and behavioral intervention in 400 hospitalized patients with CVD and their designated caregiver/prevention partner compared to a standard inpatient cardiac education protocol on patient adherence to secondary prevention guidelines one year post-hospitalization. A secondary aim is to determine the impact of this specialized intervention (SI) vs. the standard hospital educational protocol (SP) on adherence to lifestyle goals in the patient designated caregiver/prevention partner. The specific aims are to determine: 1) the difference in mean within person change in systolic blood pressure in the SI vs. SP groups from baseline to 1 year, 2) change in adherence to other secondary prevention guidelines (e.g. lipid control, lifestyle, and use of evidence-based therapies) and clinical outcomes in SI vs. SP from baseline to 1 year, 3) change in lifestyle factors (physical activity, saturated fat intake, cigarette smoking, and weight management) from baseline to 1 year in designated caregiver/prevention partners in the SI vs. SP groups , 4) the effect of the SI compared to the SP on caregiver strain and depression in the caregiver/prevention partner, 5) the feasibility of an extended family-centered educational and behavioral intervention (FIT Heart III) that reaches out to 1st and 2nd degree relatives of patients to ensure appropriate screening, lifestyle education, and referral of family members for evidenced-based risk reduction therapies. The significance of this research is that it addresses specific challenges prioritized in the NHLBI strategic plan to develop and test novel interventions to improve patient and health system behavior to improve quality of care by increasing the use of evidence-based guidelines. Unique information will be obtained about caregivers as a potential intervention to improve the preventive care and health outcomes of patients and families that suffer disproportionate disease burden. Improved adherence to evidence-based preventive therapies could have a substantial public health benefit. PUBLIC HEALTH RELEVANCE: Adherence to evidence-based secondary prevention therapies has been shown to cut the death rate due to heart disease in half and reduction in major risk factors has a similar impact. This research addresses a public health and scientific challenge to develop and test novel interventions to increase adherence to secondary prevention guidelines among patients hospitalized with cardiovascular disease by educating and engaging a caregiver/prevention partner to encourage lifestyle and medication adherence in the patient. The study will also determine the effect of educating and supporting the caregiver on their own lifestyle, risk of depression, and caregiver strain, which impacts their own cardiovascular health. Show more... | National Institutes of Health | 8/14/2009 |
| NEW YORK UNIVERSITY (INC) | $60,782.00 | Grant | Trans-NIH Recovery Act Research Support This administrative supplement award is linked to the parent grant 1R01 AG030539 entitled 'Cerebral amyloidosis and dementia that proposes the study of alternative models of neurodegeneration in close comparison with Alzheimer’s disease (AD) to identify common pathogenic mechanisms potentially amenable for similar therapeutic strategies. We hypothesized that unrelated peptides could adopt similar altered amyloidogenic configurations that trigger comparable downstream detrimental effects in neuronal cells, being capable to accelerate amyloid deposition in vivo when in conjunction with additional amyloidogenic co-factors. Accordingly, we are comparing the effect of oligomeric and fibrillar assemblies of the ABri, ADan and Abeta amyloid subunits isolated from brains with familial British and Danish dementias (FBD and FDD) –two hereditary conditions with neuropathological features similar (if not identical) to that of AD– and Alzheimer’s disease or prepared from synthetic homologues. The instrument budgeted in this administrative supplement award is critical for the biochemical purification of these amyloid assemblies as well as for their quantitative evaluation via acid hydrolysis and amino acid analysis. Show more... | National Institutes of Health | 9/11/2009 |
| NEW YORK UNIVERSITY (INC) | $70,416.00 | Grant | Trans-NIH Recovery Act Research Support DESCRIPTION (provided by applicant): The lentivirus virion infectivity factor (Vif) is an accessory protein that is required for productive replications of the virus in primary cells and some, but not all, transformed T cell lines. HIV-1 that is genetically deficient in Vif (delta-Vif) fails to replicate in nonpermissive cells as the result of the expression of the cell preotein APOBEC3G/CEM15. APOBEC3G is a member of the cytidine deaminase family of RNA editing enzymes. Simpler viruses such as murine leukemia virus do not encode Vif. Nevertheless, cloning and functional analysis showed that mouse APOBEC3G is a potent inhibitor of delta- Vif and wild-type HIV-1. Similarly, African Green monkey APOBEC3G was also active against wild-type and delta-Vif but only inhibited delta Vif but not SIVagm. These findings suggest a species=specific interaction between Vif and APOBEC3G. The goals of this project are to understand the mechanism by which APOBEC3G reduces the infectivity of delta-Vif HIV-1 and to understand how Vif alleviates this inhibition. Human: AGM chimeric APOBEC3G will be constructed and used to determine the domain that determines the interaction. HIV-1 will be adapted to replicate in cells expressing non-homologous APOBEC3G. Physical interaction of APOBEC3G and Vif with each other and with cellular factors will be detected by coimunoprecipitation. To identify a viral editing substrate for APOBEC3G, encapsidated viral RNA, viral RNA, viral mRNA, viral cDNA, and proviral DNA will be sequenced from wild-type and delta-Vif virus grown in the presence of absence of APOBEC3G. In addition, to understand the physiological role of APOBEC3G, knock-out mice will be constructed. Several immune function assays will be used to determine the effects of the deficiency on the immune system. Insights provided by these studies will have implications regarding targeting the APOBEC3G: Vif interaction for the development of novel HIV therapeutics. Such drugs would interfere with the APOBEC3G: Wif interaction without inhibiting APOBEC3G function. Show more... | National Institutes of Health | 9/25/2009 |
| TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK | $401,188.00 | Grant | Trans-NIH Recovery Act Research Support This application addresses broad Challenge Area (06) Enabling Technologies, and specific Challenge Topic, 06-NS-106: Validating new methods to study brain connectivity. Mapping the structure and function of neural circuits is an important prerequisite to understand how groups of interconnected neurons produce perceptions and drive behavior. One challenge in mapping neural circuits is to unambiguously identify synaptic partners. Traditionally, synaptic connectivity has been studied using electrophysiology and electron microscopy - methods that provide critical detail but are impossible to apply in large scale. We aim to develop and validate a system to more easily identify synapses between selectively tagged neurons in the mouse. Recently, a system named GFP Reconstitution Across Synaptic Partners (GRASP), has been developed in invertebrates to study synaptic connectivity. It relies on genetic expression of two non-functional, complementary GFP fragments that are exposed on the extracellular sides of different cell populations. GFP reconstitution, and therefore fluorescence, occurs at the sites of close contact (e.g. synapses) between these cells. GRASP has many advantages: it can be genetically targeted to specific neuronal populations, it is a fluorescent system that can be readily visualized using traditional microscopy, and can be easily adapted to answer a wide variety of different questions about synaptic connectivity of neurons. To validate this technology for use in mammalian systems, we will initially test a battery of GRASP constructs in cell culture and an insect model. The most promising combinations will then be used to generate general-use transgenic lines that can be employed in concert with the Cre/LoxP and the tet-TTA systems to control expression of GRASP in time and space. In addition, we will develop viral carriers for GRASP as an alternate means of delivery and spatial restriction. We will use GRASP to help address questions of connectivity in the mammalian taste system, thereby providing validation of its utility to study mammalian neural circuits. Ultimately we anticipate that the genetically engineered GRASP mouse lines and viral vectors generated in this study will provide a toolbox that will be of considerable value for the entire neuroscience community. PUBLIC HEALTH RELEVANCE: Mapping the structure and function of neural circuits is an important prerequisite to understand how groups of interconnected neurons produce perceptions and drive behavior. We aim to develop and validate a system to more easily identify synapses between selectively labeled neurons in the mouse. We anticipate that our genetically engineered GRASP mouse lines and viral vect |