David Foster - US grants
Affiliations: | Johns Hopkins University, Baltimore, MD |
Area:
Hippocampal ReplayWebsite:
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The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, David Foster is the likely recipient of the following grants.Years | Recipients | Code | Title / Keywords | Matching score |
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1975 — 1977 | Foster, David | N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Research Initiation - Kinetics of Virus Sorption On Weak Base Resins @ University of Wyoming |
0.951 |
1980 — 1982 | Foster, David | N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Research Initiation - Particulate Formation in a Turbulent, Backmixed, Gaseous Fueled Reactor @ University of Wisconsin-Madison |
0.943 |
1986 — 1997 | Foster, David M [⬀] | P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Resource Facility For Kinetic Analysis @ University of Washington This proposal is for the 5th year through the 9th year of the Resource Facility for Kinetic Analysis (RFKA) at the University of Washington. Kinetic analysis and integrated systems modeling have contributed substantially to our understanding of physiology and pathophysiology of metabolic systems in humans and animals. In recent years, many experimental biologists have become aware of the usefulness of these techniques in their research. With this has come the recognition that the discipline of kinetic modeling requires its own expertise. RFKA provides that expertise as a part of fulfilling its goals which are: 1) the development and application of modeling technology to biomedical problems, 2) the enhancement and maintenance of computer based methodologies for kinetic modeling with major emphasis on the SAAM (Simulation, Analysis and Modeling) programs, 3) the provision of service to the biomedical community via consultation in the use of modeling in the analysis of kinetic data, 4) the education and training of individuals in the use of modeling technology in biomedical research, and 5) the dissemination of our technology, expertise and accomplishments. Modeling and experimentation are both integral parts of the testing of hypotheses. Modeling is needed in the planning as well as in the analysis of experiments, and provides more focused and efficient experimental designs. By enhancing the contribution to modeling, RFKA supports this concept of an integrated experimental design. RFKA is distributed over three sites at three major universities; the Administrative Core of RFKA is located at the University of Washington. All sites take part in the functions that define a Resource, but each contributes a unique expertise in at least one area. The geographical distribution and diversity of interest in each has, over the first 2 1/2 years, facilitated a growth in collaborative and service activities. |
0.908 |
1991 — 1993 | Foster, David C | T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Fellowship in Primary Obstetrics and Gynecology @ Johns Hopkins University |
0.958 |
1995 — 1997 | Pregitzer, Kurt Foster, David Bornhorst, Theodore Reed, David Martin, Patrick |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Sger: the Gribben Buried Forest: a Unique Opportunity For Exploratory Research @ Michigan Technological University Ten thousand years ago the global climate was highly dynamic and the vegetation of North America was undergoing the most rapid reorganization of the post-glacial period. Spruce forests that once dominated much of interior North America were decreasing in extent as the climate rapidly warmed. One such forest was recently exposed by a mining company in the Upper Peninsula of Michigan. The Gribben forest was buried in-place by glacial sediment and remains intact, with completely preserved plant material, litter, humus layers, and soil profiles. Wood from this site was recently radiocarbon dated at approximately 10,000 years old. The site is part of an active mining operation and will be destroyed in the summer of 1995. The objectives of this exploratory research are to (1) sample the buried trees, litter and soil, (2) answer fundamental questions about paleo-forest composition, structure, growth and dynamics, and (3) archive samples and distribute data to the broader scientific community so that this unique opportunity to understand a 10,000 year old forest and its environment is not lost to science. This Small Grant for Exploratory Research will provide a unique opportunity to learn about the composition, structure, and dynamics of forest vegetation immediately after the glaciers receded from this area. The data will allow a direct test of assumptions of much of the conceptual framework underlying forest ecology and paleoecology. |
0.94 |
1996 — 1997 | Foster, David M [⬀] | P41Activity Code Description: Undocumented code - click on the grant title for more information. |
@ University of Washington technology /technique development; model design /development; endocrine gland /system; education; computers; cardiovascular system; biomedical resource; bioengineering /biomedical engineering; |
0.908 |
1996 — 1997 | Foster, David M [⬀] | P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Dissemination of Rfka Technology @ University of Washington technology /technique development; model design /development; education; computers; biomedical resource; bioengineering /biomedical engineering; |
0.908 |
1997 | Foster, David M [⬀] | P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Specification &Design of Saam Ii @ University of Washington technology /technique development; model design /development; statistics /biometry; computers; biomedical resource; bioengineering /biomedical engineering; |
0.908 |
1997 — 1999 | Foster, David M [⬀] | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
General Purpose Population Analysis Module For Saam Ii @ University of Washington DESCRIPTION: Population analysis is the methodology used to quantify intersubject variability in kinetic studies. In this revised research project, the applicants propose to develop a general population analysis package and to interface this package with the SAAM-II software system. This system will typically be used for the population modeling of pharmacokinetic/pharmacodynamic systems and metabolic studies using tracer kinetics. Population analysis is widely used on pharmacokinetic studies since it is the key to understanding how drugs behave in human and animals. It provides the foundation for the intelligent design of dosage regiments to treat disease processes. In metabolic studies, it is used to identify which parameters in a model change when a population of normal subjects is compared to a population of subjects with a known pathological condition. There are three significant obstacles in such modeling efforts: (i) there is no software package that includes both parameteric and nonparameteric methods, (ii) certain methods currently in use have not had the rigorous statistical and numerical analyses that one could desire, and (iii) current software is either limited in modeling capabilities or is not user friendly. This project brings together a unique group of researchers to overcome these obstacles by developing and incorporating into the SAAM-II a general purpose population analysis module. More specifically, the following three aims are proposed: 1) Develop convergent numerical algorithms for parametric and nonparameteric methods. 2) Prove consistency of algorithm in Aim-1. Investigate efficiency and robustness of these methods via simulation studies and compare with other existing methods. 3) Interface the algorithms in Aim-1 with the general model building/graphical user interface of SAAM-II. The result will be a population analysis program with general model building capabilities and a graphical user interface that is powerful, flexible and easy to use. Such programs do not currently exists. Such a package will improve the analysis of clinical trials, and resulting drug therapy and patient care. |
0.908 |
1998 — 2007 | Foster, David M [⬀] | P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Resource Facility For Population Kinetics @ University of Washington DESCRIPTION (provided by applicant): This application requests continuation of funds for years 06-10 for the Resource on Population Kinetics (RFPK-also referred to as the Resource). RFPK's major goal is the development, application and dissemination of modeling methodology and software tools for biomedical uses in defining, understanding and managing health and disease. This goal is achieved by promoting the application of integrated systems modeling in biomedical research. This is done by providing consultation in model development and experimental design, by offering educational programs, and by developing new methods for incorporation in state-of-the-art software tools. Modern methods of scientific computing, in conjunction with inexpensive and powerful hardware, are driving a dynamic paradigm shift in how state-of-the-art scientific, engineering and business research are performed. RFPK is at the forefront of this shift in the biomedical community in its ability to communicate and collaborate with diverse disciplines in order to conduct its research. This multidisciplinary group is comprised of faculty, staff, students and collaborators in various fields of medicine, mathematics, statistics, software engineering, and the pharmaceutical industry. This research model unifies concept development, experimentation, simulation and implementation. Examples of this new approach in action are the human genome project, the design of the Boeing 777, and the design of financial derivatives. Factors driving this approach are the need to understand and manage complex dynamical systems, the need for accurate descriptions of physical phenomena, and the need for efficiency in the use of funds for research and development. The full impact of this paradigm shift has not reached the biomedical research community. The problem is rooted in the absence of software tools and educational programs targeted at the development of modeling skills for this community. A program that integrates both software development and education must be designed to answer this need. RFPK addresses this need directly in its specific aims, which are to: (1) develop new modeling methodologies for biological systems; (2) specify, design, develop, test, validate and maintain new software tools incorporating cutting-edge mathematics, statistics and computer science; (3) provide service to the research community through collaboration and consultation; (4) provide educational programs for the research community in systems modeling applications; and (5) disseminate RFPK technology and expertise via diverse educational programs that integrate medicine, statistics, computer science and bioengineering in a comprehensive problem-solving approach. Making these new tools and methods available to a broad audience is a complex problem that is best accomplished on a university campus. RFPK has assembled a multidisciplinary team consisting of scientific experts in model development and testing who collaborate with mathematicians, statisticians, and software engineers. RFPK involves four major universities, all of which contribute unique expertise to the individual projects. Its Administrative Core is located at the University of Washington. |
0.908 |
1999 | Foster, David M [⬀] | P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Effect of Ethanol On Lipoprotein Kinetics Assessed by Population Analysis @ University of Washington The specific aims of this collaborative projecxt are to apply the new methods described in this aplication to obtain more accurate estimated of the population parameters of both minimal models and thus of both glucose disposal and beta-cell function in norma, obese and mominsulin-dependetn (NIDDM) subjects. Besides providing the population parameters and covariance matrix, these analyses will also permit us to indlude the covariates. For example, obesity is importnat in understanding the relation between glucose disposal and insulin secretion parameters and anthropometric variables, e.g. visceral adiposity (measured by TAC). In NIDDM, a major issue is to understand the integrated relation between glucose disposal and insulin secretion parameters in the light of other crucial variables such as blood pressure, triglyceride and FFA levels of visceral. These covariates will be included in the population analyses, and will help in our understanding of macrovascular/microvascular complita tions. |
0.908 |
1999 | Foster, David M [⬀] | P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Algorithm Development &Software Design For Population Kinetic Analysis @ University of Washington The specific are: 1. Develop convergent numerical algorithms for the parametric and nonparametric estimators in population kinetic analysis to be implemented in Project 2. 2. Analyze the statistical properties of the estimators in Specific Aim 1: consistency, asymptotic normality, asymptotic confidence regions and hypothesis testing. 3. Investigate efficiency and robustness of the estimators in Specific Aim I via simulation studies. For the parametric case, we will develop four algorithms: a "true" maximum likelihood (ML) algorithm, a Global Two Stage (GTS) algorithm, a NONMEM type algorithm, and a Lindstrom-Bates type algorithm. The ML algorithm is based on Monte Carlo integration for evaluating the objective function. The GTS, NONMEM, and Lindstrom-Bates type algorithms are all based on the extended least squares (ELS) method. For the nonparametric case, we will develop a Mallet type algorithm for mixed effects models. For the parametric case, consistency is a difficult issue. Consistency means that the estimated values converge to the true values as the number of subjects gets arbitrarily large. It is important to note that the original estimation procedures ot'NONMEM and Lindstrom-Bates are not consistent for 2eneral nonlinear models. The only algorithm that is consistent relative to the true parameter values is the true maximum likelihood algorithm. For the class of ELS algorithms we develop, there is a generalized notion of consistency, which means that the estimated values converge to the values that best approximate the model. We will investigate the required theory for the generalized consistency and asymptotic normality of these algorithms. The formulas for the asymptotic confidence intervals and hypothesis testing will follow from the same theory. For the nonparametric case, the consistency of the method, relative to the true values of the model, has already been established. What remains then is the determination of the asymptotic confidence intervals for estimated parameters such as means, medians, trimmed means, etc. At present these results have not been derived for the nonparametric case. We will use the theory of maximum likelihood estimation in infinite dimensional spaces for this purpose. Efficiency of an (unbiased) estimator is measured by the generalized variance of estimated values, with the Cramer-Rao lower bound being optimal. Relative efficiency of two estimators compares the corresponding generalized variances. Robustness measures how an algorithm performs when there are violations in the model and/or probability distribution assumptions. By utilizing Monte Carlo simulation studies, these properties can be investigated without requiring 1 asymptotic conditions. |
0.908 |
2000 — 2003 | Foster, David | N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida 0073638 |
0.951 |
2000 — 2004 | Foster, David Perfit, Michael (co-PI) [⬀] Mueller, Paul (co-PI) [⬀] Heatherington, Ann |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida 0080086 |
0.951 |
2001 — 2005 | Mueller, Paul [⬀] Heatherington, Ann Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida 0106592 |
0.951 |
2002 — 2006 | Foster, David Charles | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Vulvar Vestibulitis Trial: Desipramine-Lidocaine @ University of Rochester DESCRIPTION (provided by applicant): Studies are proposed for the subtype of vulvodynia known as vulvar vestibulitis. The first major aim of this application is to conduct a randomized, placebo-controlled, double-blinded clinical trial to study the clinical efficacy of four medical regimens: topical lidocaine, oral desipramine, topical lidocaine combined with oral desipramine and placebo. The efficacy of standard treatments for vulvar vestibulitis proven by randomized, placebo-controlled, blinded clinical trials has not been assessed. The tricyclic class of antidepressants, represented by desipramine, have gained empiric acceptance for the treatment of vulvar vestibulitis, although favorable therapeutic results have been reported by only a few retrospective studies or uncontrolled clinical trials. Although the precise mechanism of action remains undefined for tricyclic antidepressants, a "central" action through the dorsal horn and brain stem has been suggested. In contrast to oral desipramine, the long-term, topical application of lidocaine may act through a "local" mechanism. This randomized, placebo-controlled, double-blinded clinical trial is designed to determine whether "local" or "centrally-acting" treatments alone, or in combination are efficacious in treating vulvar vestibulitis. Outcome measures of success will include reduced overall pain, reduced pain to touch, reduced pain to standardized mechanical stimuli, increased pain-free intercourse, improved sexual function, improved quality-of-life as measured by psychometric tests, and adherence to active drug regimens. The second major aim of this application is to study the relationship among genetic polymorphisms of the IL-1 Receptor Antagonist locus, tissue levels of pro-inflammatory cytokines, and response to treatment of vulvar vestibulitis. Pro-inflammatory cytokines, such as interleukin-I beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), are secreted from a local cellular source and accumulate above normal levels in the region of the hymeneal ring. Recent genetic analysis finds a 53% homozygosity for allele 2 IL-1 Receptor Antagonist (IL-1 RA*2) in cases of vulvar vestibulitis, in contrast to 8.5% homozygosity in asymptomatic women. Furthermore, the IL-1 RA*2 allele has been linked to increased production of IL-1 beta in vitro. In our second aim, we will determine whether these in vitro results can be extrapolated to clinical cases of vulvar vestibulitis. Using samples from our clinical trial, we will assess the relationship between homozygosity for IL-1 RA*2, tissue levels of IL-1 beta, and TNF-alpha, and response to treatment. In summary, this project will allow us to answer several important questions about vulvar vestibulitis. Is medical treatment effective? Is centrally-acting or locally-acting treatment equally effective or is one superior to the other? Is there any benefit from combined local and systemic treatments? And finally, do genetic characteristics and tissue cytokine concentrations influence treatment response? |
0.91 |
2002 — 2007 | Clarke, Lori Foster, David Riseman, Edward Osterweil, Leon Croft, W. Bruce |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Massachusetts Amherst ABSTRACT |
0.939 |
2004 — 2006 | Mueller, Paul [⬀] Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida An EarthScope workshop in the northern Rocky Mountains (NRM) will provide an opportunity |
0.951 |
2004 — 2009 | Mueller, Paul [⬀] Perfit, Michael (co-PI) [⬀] Hodell, David (co-PI) [⬀] Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida EAR-0418905 |
0.951 |
2005 — 2007 | Foster, David | N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida Many modern plate boundaries involve convergence between the tectonic plates at highly oblique angles. These obliquely convergent systems produce transpressional orogenic belts where faulting and rock deformation occurs by a combination of shortening perpendicular to the plate boundary and shear parallel to the boundary. In transpressional orogens, rock packages typically show highly variable pressure-temperature-time paths adjacent to a central strike-slip fault zone. This project is focused on the determining the deformation and exhumation histories of deep crustal rocks in the Kaoko zone, which is the northern branch of the ca. 500 million year old Damera Orogen in Nambia. The Kaoko zone is a classic transpressional orogen that is deeply eroded so that the rock deformation processes and thermal histories of the lower and middle crust can be assessed at the surface. The kinematic and thermal history of the Kaoko zone gives insights into the tectonic processes occurring at depth along modern transpressional systems like the San Andreas Fault, California and the Alpine Fault in New Zealand. |
0.951 |
2006 — 2010 | Mueller, Paul [⬀] Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Evolution of the SW Laurentian Margin: Implications For Proterozoic Crustal Growth and Geodynamics @ University of Florida This research is directed at improving our understanding of the formation and dispersal of the Laurentian (ancestral North America) supercontinent and the relationship between these events and the episodic generation and preservation of continental crust along its southwestern margin. The southwestern margin of Laurentia is globally unique because it contains remnants of a former Archean microcontinent (Wyoming province) and two distinct Paleoproterozoic orogenic events at 1.6-1.9 billion years ago and 2.2-2.5 billion years ago, which produced new continental crust. Formation of Laurentia in the Paleoproterozoic coincides with a global period of exceptionally rapid growth of juvenile crust and aggregation of existing micrcontinents and arcs during the late Paleoproterozoic (1.6-2.0 billion years ago). This period of rapid growth was preceded, however, by a global period (2.0-2.5 billion years ago) with a pronounced paucity of preserved crust. Crust generated during this interval is less commonly preserved than crust from periods preceding and succeeding it in the global rock record. In addition, such crust is unevenly distributed among the modern continents. It is more commonly preserved in modern southern hemisphere continents, making its presence along the southwest Laurentian margin unique. To complete this research scientists from the University of Florida are conducting a detailed and integrated geochemical and structural/tectonic investigation of both the early and late Paleoproterozoic rocks preserved along a part of the southwestern margin of Laurentia. This is being accomplished by geologic mapping in two critical areas, the Highland Mountains of Montana and the Wasatch Mountains of Utah, which form the basis for sampling this crust for chemical, isotopic, and petrologic studies. This work is leading to more complete understanding of the ages and origins of crust and lithosphere generated during the Paleoproterozoic and will provide critical and unique insight into the global scale problem of low crustal production rates in the early Paleoproterozoic vs. much higher rates characteristic of the late Proterozoic and late Archean. These data are also providing new constraints on the relationship between supercontinent cycles and changes in crustal growth rates and a specific test of Proterozoic geodynamic models based on assumptions that certain features such as the Diamantina lineament of Australia or Aekit terrane in Siberia share a common geologic history with the Great Falls tectonic zone and, therefore, represent a combined feature that transects the Neoproterozoic margin of Laurentia. |
0.951 |
2006 — 2011 | Mueller, Paul [⬀] Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Development of a 4-D Model of Crustal Evolution in the Northern Rocky Mountains @ University of Florida 0545751 |
0.951 |
2008 | Foster, David M [⬀] | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Identifiability of Nonlinear Biological Models @ University of Washington DESCRIPTION (provided by applicant): Mathematical models of biological systems are essential to the quantitative understanding of physiological and pathophysiological mechanisms in humans and animals. Physiologically plausible models, the structure of which reflect available knowledge and assumptions about the systems, are usually nonlinear and characterized by a large number of unknown parameters. Examples of such models are enzyme kinetics and pharmacokinetic-pharmacodynamic models. Before performing an experiment to estimate these unknown parameters from the data, the following question arises: will the data we are about to collect (usually at a substantial expense) contain enough information to precisely and unequivocally estimate (for example, via least squares or maximum likelihood) all the unknown parameters of the postulated model? This question, set in the (theoretical) context of an error-free model structure and noise-free data, is usually referred to as the a priori global identifiability problem. Despite its theoretical nature, it is an essential, but often overlooked, prerequisite for model parameter estimation from real data. The solution of the identifiability problem is however in general very difficult, since one needs to solve a system of nonlinear algebraic equations which is increasing in number of terms and nonlinearity degree with the model order. The specific aims of this application focus on the development of an algorithm and a software tool to test a priori global identifiability of nonlinear compartmental models, a very inclusive class of ordinary nonlinear differential equation models based on conservation of mass. These models are widely used to study the kinetics of endogenous (e.g. substrates, hormones, enzymes) and exogenous (e.g., drugs, radiotracers) substances in living systems. The problem has been solved for a very limited set of models, but no solution exists in the general case. We will develop an algorithm based on computer algebra which allows to decrease the system complexity, thus providing the number of solutions for each parameter of the model. The software we propose to develop will be based on the client-server architecture paradigm, and will be open source, user-friendly and platform-independent. Such a tool would be very useful in experiment design. The software will also help in defining minimal input-output experimental configurations to assure a priori global identifiability: this is particularly important in clinical studies where severe constraints exist on experiment design, i.e. the number of inputs and outputs is limited for ethical and practical reasons. |
0.908 |
2008 — 2012 | Mueller, Paul (co-PI) [⬀] Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida Two different hypotheses for the relationship between the Congo and |
0.951 |
2009 — 2012 | Mueller, Paul [⬀] Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). |
0.951 |
2009 — 2013 | Vogl, James Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida The manner in which the Earths crust responds to tectonic and gravitational forces depends on the strength distribution of crustal rocks. It has been widely proposed that in certain settings, rocks in the lower half of the crust may be sufficiently weak that they flow laterally in response to pressure differences induced by topographic gradients. Such behavior has important implications for many processes in the continental crust, for example, the growth of mountain plateaus, formation of basins and continental shelves, and seismicity within the continents. These models, however, need to be rigorously tested through better field-based investigations. The Pioneer Mountains of Idaho, where these PIs will focus their study, expose rocks that may represent a boundary zone between strong rocks and underlying weaker flowing rocks, and if so will provide an excellent opportunity to test models that involve flow of weak lower crustal rocks. Better field documentation of the vertical changes in rocks strength will provide us with a more comprehensive view of continental deformation. |
0.951 |
2010 — 2011 | Foster, David J. | R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
High Density Tetrode Recording in Freely Behaving Mouse Models of Mental Disease @ Johns Hopkins University DESCRIPTION (provided by applicant): We aim to explore a novel experimental approach to understanding mental disease. Our long-term goal is to understand how schizophrenia affects information processing in the brain. To this end, I will apply high-density tetrode electrophysiology techniques to record in multiple animal models of schizophrenia, during free behavior. Much recent work in schizophrenia has focused on enhanced activity of the default mode network: brain regions which are particularly co-active during rest periods, and which include the hippocampus. This converges with recent work by myself and others investigating normal hippocampal function, and particularly, the phenomenon of awake replay, in which large numbers of hippocampal neurons fire in sequences that relate to ongoing task demands. For example, awake replay can "look-ahead" along spatial trajectories ahead of an exploring animal to explore hypothetical outcomes. We propose to investigate neural activity during movement and rest, in two different mouse models of schizophrenia, in order to (1) determine whether there are disruptions to rest period activity in particular, reminiscent of disruption to the default mode network, and (2) determine whether two distinct genetic mouse models of schizophrenia exhibit commonalities, especially with respect to rest period activity. Our preliminary data show that hippocampal neural activity is affected in a forebrain-specific calcineurin knockout mouse model, in a manner specific to rest periods. We are now in a position to determine the effect of these changes on awake replay. We will also consider a transgenic DISC1 mouse model, which exhibits reduced parvalbumin-immunoreactivity, as is also seen in schizophrenia patients. This is particularly interesting because parvalbumin-containing interneurons initiate and sculpt awake replay events in normal animals, and loss of such inhibition might be expected to lead to a similar outcome as observed in the calcineurin mouse. Determining how information processing in rest periods is disrupted is a key goal, which will make possible future studies to determine how disruptions to awake replay affect ongoing task performance, how heterogeneous disease mechanisms may lead to similar behavioral phenotypes, and ultimately how circuit level dysfunction may be treated therapeutically. PUBLIC HEALTH RELEVANCE: Schizophrenia is a psychiatric disorder that affects almost 1% of the world population, and represents the seventh most costly medical illness to society. This proposal seeks to explore a novel experimental approach to the disease, looking for commonalities between two genetically distinct animal models, and specifically targeting neural activity at the level of circuits using a cutting edge electrophysiological technique that allows for the simultaneous recording of hundreds of neurons in freely behaving animals. This work will pave the way for a better understanding of how similar circuit level phenotypes might arise out of diverse genetic models, and generate a novel understanding of the neural basis of mental phenomena that might be applied in the future to the diagnosis and treatment of human patients. |
0.958 |
2010 — 2014 | Foster, David J | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Role of Hippocampal Sequence Play in Learning and Decision Making @ Johns Hopkins University DESCRIPTION (provided by applicant): We aim to study how populations of neurons in the hippocampus and prefrontal cortex support navigational learning and decision-making. During awake behavior, hippocampal neurons are active in precise sequences that reflect trajectories taken in the past, and hypothetical trajectories to be taken in the future. This phenomenon is known as awake replay. The broad objective of this proposal is to investigate a possible role for awake replay in learning and decision making. Previous data together with a model suggest a framework in which replay sequences can be used to learn trajectories to reward locations, and also provide the ability to look ahead along hypothetical future trajectories during decision-making. We make use of high-density tetrode electrophysiology techniques which allow simultaneous recording of hundreds of neurons in multiple brain regions, in freely behaving animals. We record single unit and wideband EEG activity during the learning and performance of navigational tasks. Our preliminary data show that replay undergoes learning-related changes, that replay in the hippocampus is closely coordinated with activity in prefrontal cortex which is an area strongly associated with decision-making, and that replay at choice points is predictive of navigational decisions. We will pursue these preliminary results in three specific aims. Understanding how replay relates to learning will provide novel insight into offline mechanisms of learning, which are increasingly thought to be important, both in normal cognition, and in diseases such as Alzheimer's disease, autism and schizophrenia. Understanding how the hippocampus interacts with prefrontal cortex during replay will shed further light on the importance of offline activity, and also provide novel insight into the way that the hippocampus conveys specific information to areas of the brain that influence behavior. Hence, we will investigate a novel and important link between hippocampal neural activity and behavioral outcomes. Finally, understanding how hippocampal replay is organized during decision-making will provide novel insight into hippocampal memory retrieval. Understanding how the hippocampus supports memory is a major goal in medicine, given the involvement of the hippocampus in memory problems in Alzheimer's disease, Korskoff's syndrome, normal aging, stroke and temporal lobe epilepsy. Further, this study may reveal novel prefrontal mechanisms of planning and decision making, which may shed light on those brain diseases that have been associated with degraded prefrontal function, such as schizophrenia and autism. Ultimately, the search for the neural basis of memory is a fundamental goal with profound implications for the development of therapeutic targets in brain disease. PUBLIC HEALTH RELEVANCE: Despite the prevalence of memory disorders associated with damage to the hippocampus, from such conditions as Alzheimer's disease, aging, stroke and epilepsy, we lack a mechanistic understanding of how hippocampal neurons encode and retrieve memories, which could help us address these problems. However, recently developed techniques for recording from large numbers of neurons simultaneously in awake, freely behaving animals, have begun to reveal patterns of activity across hippocampal neurons that may provide a model of memory processing. This study will take these results further by asking how the retrieval of specific memories by the hippocampus drives the selection of appropriate behavior, thus shining light on the very processes that may go awry when memory fails. |
0.958 |
2011 — 2016 | Mueller, Paul [⬀] Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida The combined Alleghanian-Hercynian-Variscan orogeny (approximately 300 million years ago) marks the culmination of Earth?s most recent example of the formation and dispersal of a supercontinent (Pangea). The southern Appalachian Mountains record a critical zone in the formation of Pangea because they mark the collision of the precursors of three modern continents (North America, South America, and Africa). Pangea's subsequent rupture produced these three continents and continues with the expansion of the Atlantic Ocean. The research team of faculty and students from the University of Florida and Mississippi State University are conducting detailed geochemical investigations into the spatial distribution, ages, and geochemical compositions of a suite of granitic igneous bodies that intruded crystalline rocks that formed up to one billion years earlier in the roots of the mountain belt and are now in Georgia, Florida, Alabama, and South Carolina. These granitic bodies are the only known magmatic manifestation of the destruction of two ancient oceans (Iapetus and Rheic). Understanding the age and origin of the granitic bodies is critical to understanding the growth of continents in general and, particularly, how continental crust was exchanged during the Pangean supercontinent cycle. In particular, they are focusing on identifying the boundary and the operative tectonic and magmatic processes that characterized convergence of the continents that ultimately formed Pangea. The convergent boundary has tentatively been identified on the basis of geophysical data to occur in a zone known as the Suwannee suture; the proposed suture lies sub-parallel to the Florida-Georgia border. A new boundary was established after the rupture of Pangea, which produced the modern Atlantic Ocean and the African, South American, and North American continents. The location of this rupture is not known, but is being further constrained by this project. |
0.951 |
2012 — 2016 | Foster, David Charles Phipps, Richard P. (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Localized Vulvodynia Pathogenesis: Fibroblast, Yeast, and Melanocortin @ University of Rochester DESCRIPTION (provided by applicant): This R01 application responds to PAR-10-190: Vulvodynia - Systematic Epidemiologic, Etiologic or Therapeutic Studies. Our long-term goal is to develop an understanding of the vulvodynia pain mechanism leading to a mechanism-based disease classification and ultimately to a mechanism-based therapy. Our research team has reported a mechanistic connection between yeast products, regional fibroblast activation, pro-opiomelanocortins, and localized provoked vulvodynia (LPV). Fibroblasts are now recognized as more than structural cells as they not only respond to signals but can prodigiously produce many different biologic mediators, including those that promote pain. Fibroblasts also exhibit considerable regional specialization. We discovered that fibroblasts from the vulvar vestibule produce markedly elevated levels of pro-inflammatory, pro-pain mediators following activation with yeast cell wall products. In particular, heightened pro-inflammatory mediator responses are generated by fibroblasts from the vulvar vestibule of LPV-afflicted women. This may be related to single nucleotide polymorphisms (SNP) in the melanocortin-1 receptor (MC1R) that enhance inflammatory mediator production. We propose that the vulvar vestibule of all women possesses a unique inflammatory/pain-inducing responsiveness and that vulvodynia pain reflects an extreme but natural inflammatory phenomenon. We hypothesize that vulvodynia arises 1) in a region of the genital tract predisposed to inflammation, 2) in the presence of specific irritants such as yeast, that are 3) exacerbated by genetic predisposition. To significantly advance and impact the field, we have assembled a multidisciplinary team, experienced in LPV, fibroblast biology, and inflammation to achieve the following three aims. Specific Aim 1: To determine whether pro-inflammatory fibroblasts segregate to painful areas of the vulva. Using lower genital tract pain mapping, we will discover whether pro-inflammatory fibroblasts localize to painful anatomic regions in situ. Fibroblast strains will be developed from painful and non-painful areas of the vulva and their biosynthetic capabilities for pro-inflammatory and other mediators determined after exposure to key fibroblast activating cytokines. Specific Aim 2: To determine whether yeast or yeast products activate fibroblasts via Toll-like receptors (TLR) and whether specific MC1R SNPs modify that response. We will determine whether the LPV-afflicted patients carry a different pattern of yeast species and yeast load, and whether yeast cell wall products initiate, through toll-like receptors, a pro-inflammatory, pain-inducing response from fibroblasts derived from painful regions. Specific Aim 3: To determine whether pro-opiomelanocortin loss-of-function promotes vulvodynia. We will investigate whether loss-of-function melanocortin-1 receptor SNPs enhance site-specific fibroblast activation, and can be identified with a simple clinical measure, skin colorimetry. We will assess an anti-inflammatory melanocortin derivative with therapeutic potential for vulvodynia and investigate the underlying molecular mechanism(s). |
0.91 |
2012 — 2017 | Mueller, Paul [⬀] Foster, David |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida Earth scientists from Louisiana State University and the University of Florida are collaborating on an investigation of a unique segment of Precambrian (>550 million years old, m.y.o.) continental crust brought to the earth?s surface by the ~50 m.y.o. Sawtooth batholith in eastern Idaho. This crust is unique because it lies between some of the oldest crust in North America (exposed in SW Montana) and some of the most recent additions to the North American continent in western Idaho (Blue Mountains). This research will test a wide range of hypotheses for the formation and evolution of this crust: Is it an independent terrane accreted to North America in the recent past, or does it show geochemical ties to the old (>3000 m.y.o.) crust exposed in SW Montana? Does it record evidence of a ?vanished? episode of mountain building similar in age to the Grenville orogeny that formed much of eastern North America 1000 m.y. ago? If accreted to North America in the Precambrian, does it provide insight the fragmentation of North America that occurred 500-700 m.y.o ago? Specifically, the team will investigate the origin of metamorphosed sedimentary rocks that carry information about the nature of continental crust exposed at the time they were deposited. The temperature and pressure history of this crust, which will constrain the time at which it was appended to North America and the mechanism by which it was appended. Elemental abundances in the metamorphosed igneous rocks will give important clues to the environment in which they formed, while isotopic compositions will constrain the amount of new crust vs. recycled crust that is preserved. A large fraction of the crust that lies between the Archean (>2500 m.y.o.) crust of SW Montana and the <200 m.y.o. crust of western Idaho is buried beneath younger rocks, making the Sawtooth terrane a very important window into crustal evolution in western North America. |
0.951 |
2014 — 2017 | Manuel, Michele Foster, David Perfit, Michael (co-PI) [⬀] Dempere, Luisa (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mri: Acquisition of a High Resolution Electron Probe Micro-Analyzer @ University of Florida Non-Technical: This research contract centers on the acquisition of a new high-resolution electron probe microanalysis system with an integrated electron backscatter diffraction detector. This instrument will be the only one in the US and only one of three in the world with the capability of performing simultaneous crystallographic and chemical mapping at the sub-micron scale, and will permit trace elemental analysis with superb accuracy in a user-friendly environment. The instrument will have regional and international accessibility making it a multi-use, multi-institutional piece of state-of the-art equipment. This research program brings together a unique set of 15 researchers from 7 Florida state universities (University of Florida, University of North Florida, Florida State University, Florida A&M University, University of Central Florida, Florida International University and University of South Florida) that have one commonality: the need to understand the connection between chemistry and structure at the sub-micron scale. The central theme of this instrumentation program with regards to teaching, education and outreach is lowering institutional barriers. A multi-pronged approach has been developed to execute this objective: 1) a remote access system, 2) K-12 education modules developed for teachers to help them integrate microscopy into their classroom curricula, 3) partnerships with the on-campus NSF REU program to expose talented undergraduates to advanced microscopy techniques, where selection will be based on talent and focused on increasing diversity of women and underrepresented groups, 4) continuing education programs, and 5) strategic partnerships with 2 minority serving institutions and 5 emerging Hispanic serving institutions provide fertile ground and access to underrepresented groups to increase the impact of the proposed education and outreach initiatives. |
0.951 |
2017 — 2019 | Martin, Ellen Dutton, Andrea Foster, David Mueller, Paul (co-PI) [⬀] Perfit, Michael (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ University of Florida This project is enabling the acquisition of a state-of-the-art multi-collector inductively coupled plasma mass spectrometer (MC-ICP-MS) to support a team of researchers within the Department of Geological Sciences at the University of Florida to make significant advances for research applications in the Earth and Ocean Sciences. This instrumentation facilitates the research program of the lead investigator, who is an early career female with a research focus on Uranium-series geochemistry, a technique used widely to determine the age of materials in studies of past climate and sea level change on time scales from a human life to thousands of years. This MC-ICP-MS instrument allows the development of sea level reconstructions with high temporal accuracy and precision, to define the rates and tempo of ice sheet retreat and sea level rise during past warm climates. These reconstructions can be paired with climate data to inform future projections of sea level rise over the coming decades to millennia. Additional capabilities afforded by this instrument will significantly improve other existing research programs as well as enabling new lines of research in a wide range of Earth science applications. |
0.951 |
2017 — 2022 | Foster, David Richardson, Andrew |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ Northern Arizona University Phenology--the rhythm of the seasons--drives the progression of vegetation through its annual cycles from dormancy to activity and back to dormancy. Phenology is thus critical for many ecological processes. It also directly influences ecosystem productivity and the production of many goods and ecosystem services on which human society is reliant. Importantly, phenological rhythms are highly sensitive to year-to-year variability in weather, but they can also in turn influence weather itself. Thus, there are feedbacks between terrestrial ecosystems and the atmosphere that are phenologically-controlled. This project will use imagery from a network of digital cameras--the PhenoCam Network--to track vegetation phenology at high spatial and temporal resolution across North America, from tundra to the tropics. Together with sophisticated computer simulations, this project will then investigate phenologically-controlled ecosystem-atmosphere feedbacks across a climatic gradient from the Southwest, through the Great Plains, and into the Northeastern US. The question this project seeks to answer is, How much influence do these feedbacks have on how ecosystems work, and at what spatial and temporal scales? This question is important from the point of view of managing and sustaining healthy ecosystems. Public participation in scientific research will be achieved through collaboration with the Harvard Forest Long-Term Ecological Research Project's Schoolyard program and the Summer Research Program. Through these efforts this project will contribute to the education and training of traditionally under-represented groups. This project additionally includes interdisciplinary training and research opportunities for graduate-level students and three postdoctoral research associates. Imagery and data from PhenoCam will continue to be made publicly available, in near-real time, for research and education. |
0.951 |
2018 — 2019 | Foster, David Charles Haidaris, Constantine G (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Mechanisms of Vulvodynia Involving Dysregulation of Pro-Resolving Lipids @ University of Rochester The Focus: Localized provoked vulvodynia (LPV) is the most common cause of longstanding dyspareunia (painful sexual intercourse) in premenopausal women. Yet, LPV etiology is unclear, and no effective medical therapy exists; clinical trials report that treatments are no better in alleviating pain than placebo. LPV presents with pain to light touch limited to a defined region of the female lower genital tract termed the vulvar vestibule. The Premise: Our research team has discovered that fibroblast strains isolated from painful sites in the vulvar vestibule produce elevated levels of pro-pain and proinflammatory mediators (e.g. PGE2 and IL-6). When exposed to proinflammatory stimuli found in the vulvovaginal milieu, vestibular fibroblasts produce significantly higher levels of pro-pain signals than fibroblasts from pain-free sites a few millimeters away. This unique and intrinsic responsiveness connects innate vulvar responses to neuro-inflammation and culminates in localized, longstanding pain. Thus, LPV is likely an exacerbation of a normal anatomically-defined innate inflammatory response. Therapeutics that resolve inflammation and pain without impairing normal host defense (i.e. specialized pro-resolving mediators; SPMs) may be effective against LPV. SPMs are omega-3 and omega-6 fatty acid-derived lipids that consist of several types called, resolvins, maresins, protectins, and lipoxins. SPMs are naturally produced by the human body, have virtually no toxicity, and several are in clinical trial for inflammatory and other diseases, which could lead to faster clinical translation. Although SPMs have not been tested as an LPV therapy, we have strong supporting evidence that these lipids will be effective against LPV. Organizing Hypothesis: We hypothesize that SPMs will effectively modulate the LPV pathologic response and in turn, will successfully resolve LPV-associated neuro-inflammatory pain. Here, we will identify SPMs that are effective in reducing levels of proinflammatory mediators associated with LPV pain, define the mechanisms whereby SPMs act, their role(s) in LPV disease, and test therapeutic candidates in a preclinical LPV model. Specific Aim 1: Investigate the role of SPMs in blunting proinflammatory/pro-pain responses in vulvar fibroblasts, tissues, and fluids from controls and patients with LPV. Specific Aim 2: Determine the mechanism(s) that govern SPM production, responsiveness, and therapeutic potential in vulvar fibroblasts. Specific Aim 3: Evaluate the efficacy of SPMs in alleviating pain using a novel preclinical LPV mouse model. Impact on the field: We will make a significant step forward in identifying potential therapeutic agents that could not only reduce excessive proinflammatory signaling and pain in the context of LPV, but also in other chronic inflammatory conditions. Furthermore, we will strengthen the methodological basis for preclinical analgesia testing in LPV and identify SPM molecules that could be readily translated to clinical trials/use. No effective LPV therapies exist, making our work vital to improving treatment of this crippling condition. |
0.91 |