Ming Li - US grants

DESCRIPTION (Adapted from applicant's abstract): Insulin dependent diabetes mellitus (IDDM) is characterized by the selective destruction of B-cells of the pancreatic Islets of Langerhans. The principal investigator's previous studies suggest that a low-voltage-activated (LVA) Ca2+ channel may be involved in the process of cytokine-mediated B-cell death. In this proposal, he will test the hypothesis that "abnormal regulation of LVA calcium channels by cytokines and other factors changes B-cell calcium homeostasis, predisposing these cells to further toxicities causing B-cell destruction during insulitis." The aims of the proposed study include: 1) To identify the role of the LVA calcium channels in mediating calcium influx and apoptosis in pancreatic B-cells. LVA Ca2+ channel antagonists will be used to evaluate the role of LVA Ca2+ channels in basal, glucose- and depolarization-stimulated Ca2+ influx. The role of LVA Ca2+ channels in time- and dose-dependent DNA fragmentation and cell death induced by cytokines will also be investigated. 2) To clone the LVA channel from an insulin secreting cell line, INS-1. By using RT-PCR method, we will deduce the nucleotide sequence of the putative alpha1 subunit of the LVA Ca2+ channel and express it in Xenopus oocytes. 3) To investigate the mechanisms of LVA calcium channel regulation. The investigator will examine how cytokines and sex hormones regulate the expression of LVA Ca2+ channels in diabetic and non-diabetic animal models. This study will provide significant insight into the mechanisms of pathogenesis of selective B-cell destruction in human IDDM.

neurotransmitter transport; membrane transport proteins; chemical kinetics; glutamate transporter; serotonin transporter; cysteine; gamma aminobutyrate; conformation; Xenopus oocyte; optics; voltage /patch clamp; fluorescent dye /probe;

This award provides support for a collaborative project involving two computer scientists and a plant geneticist who will develop new methods, efficient algorithms, and software tools for several important problems in the field of bioinformatics. This supported work includes research into computational paradigms such as quartet methods, interactive systems, and approximation algorithms as applied to the evolutionary analysis of gene sequences, gene duplication, and horizontal transfer events in the genomes of chloroplasts, a DNA-containing organelle found in all plants. Additional studies will examine the information content of genomes by improving and testing a recently developed sequence entropy estimator and a distance metric for genomic sequences. Work in this area will include the application of the improved methods to sequence data from the genomes of mitochondria, viruses, chloroplasts and bacteria. Other efforts will address the important problem of simultaneous multiple sequence alignment and evolutionary tree reconstruction. The multiple sequence alignment approaches to be developed are based on the use of conserved blocks that have few or no gaps, and multiple alignments within a constant band. Work in a fourth area will develop efficient algorithms for computing short and long interspersed nuclear elements (SINES and LINES) in genomic sequences of lengths up to billions of nucleotides. Because of the large amounts of data that must be analyzed, this will require the development or adaptation of appropriate external memory algorithms.

Biological, biomedical and pharmaceutical research is undergoing a major revolution as new analytical technologies produce unprecedented amounts of genetic data. The exploration of this information is critically dependent upon the development of advanced computational and software techniques for data analysis, storage and retrieval. From this dependency, a new interdisciplinary research field, bioinformatics (or computational molecular biology) has emerged in recent years. The work supported through this award is expected to make both fundamental and applied contributions to the field. The fundamental research will explore and explicate new ideas and methods for solving algorithmic problems in bioinformatics and the applied research will involve the development and evaluation of software tools in the practice of plant genomics. Although the efforts are aimed at improving the understanding of the evolution of chloroplast genomes, the approaches should be readily extensible to analysis of all other genomes.

This Grant Opportunity for Academic Liaison with Industry (GOALI) project will involve the principal investigator and researchers at the ALCOA Technical Center (ATC). This award is to institute an integrated experimental-computational research program targeted at improving productivity and product quality. This will be accomplished by developing advanced multiple scale computational models and software for simulating failure in materials processing and subsequent process design. It will augment two newly initiated thrust areas at ATC on: (1) understanding the effect alloy microstructure and process parameters on edge cracking in cold rolling processes; and (2) improving cut-edge quality and minimize burr and debris in material shearing processes such as slitting. Furthermore, collaborations with Scientific Forming Technologies Corporation (SFTC) and Ohio Supercomputer center will elevate the simulation software to the advanced level of high performance computing needed for solving complex industrial problems.

Experimentally motivated-validated, multi-scale computer models will introduce adaptive multi-level hierarchy and represent details of material microstructure from quantitative metallography, to simulate ductile fracture. The adaptive multi-level system of computational modules will concurrently predict variables at the scales of the work-piece and model localization and ductile fracture as a phenomenon of incidence, interaction and propagation of damage across the scales. Adaptive hierarchy of computational sub-domains with varying resolutions will differentiate between non-critical and evolving critical regions and will zoom in at 'damaging hotspots' for pure microscopic simulations. Microscopic stress and damage analysis of real microstructures will be done by the specially developed Voronoi cell finite element models. The forming simulations will be coupled with design methodologies and software to predict 'optimal' microstructural constitution and process parameters. Experiments on localization and failure in deformation processing will be performed, and will include mechanical testing of notched specimens for load-displacement and fracture toughness data, and real process like cold rolling and sheet metal shearing for

Kolmogorov complexity is a modern theory of randomness
and has many applications in computer science and
other fields. The investigator is enriching this theory
and its applications by doing research in two directions.

Analyzing the average-case complexity of an algorithm
is at the heart of practical algorithm analysis.
It has been demonstrated over the past decade that
Kolmogorov complexity is a powerful tool to help analyzing the
average-case complexity and the lower bounds of algorithms.
Examples are the average case analysis of Shellsort and Heapsort.
The PI plans to continue this work to systematically develop
the tool, the Incompressibility Method. This involves comparative
studies to understand why, how, and when
the incompressibility method
works. In order to demonstrate, and to uncover,
the power of this method, this method will be used to solve
other open questions. Samples of some open questions include:
improving Shellsort average-case lower bound analysis,
average height of balanced trees, and Stack sorting lower bound.

The modern information age and the post-genomic era raises a
fundamental question: Given two sequences (genomes or English
documents), how much information do they share? For example,
given two genomes, can we measure their evolutionary distance?
The goal of this second part of the proposal is to understand
this fundamental question and develop tools.
In the past, the PI and his coauthors have partially answered this
question by defining the concept of Information Distance.
Information Distance measures the absolute
thermodynamic energy required to convert one sequence to another.
However, it does not measure evolutionary distance because
genomic evolution allows long segment deletion/insertion, cheaply.
A new theory suitable for such evolutionary distance will be
developed. To demonstrate the feasibility of this research,
some preliminary theory has been proposed and successfully applied to
construct whole genome and chain letter phylogenies when no other
method applies. More recently, this theory has also been
applied to program plagiarism detection and language classification.

The objective of this collaborative research is to enhance the scientific knowledge of material properties, modeling, and manufacturing at the scale of a few millimeters to several microns in size. The results of this project will be a viable micro-forming process. The approach will combined fundamental and applied research with respect to physical interactions between workpiece and tool, processing parameters, and scaling effects of material properties, which prevent optimized macro-forming processes to be simply miniaturized to components on the micro/meso-scale. This knowledge will then be applied to devise a micro-forming process that will produce more accurate parts faster, for less cost, and with higher aspect ratios. The research results will be validated through extensive material testing, micro-forming system testing, and comparisons between the numerical simulation and experimental results.
The knowledge gained through this research at the micro/meso-scale will lead to an effective and efficient micro-forming process. The implementation of such a micro-manufacturing process will lead to further micro-components and systems for biomedical, telecommunication, and environmental monitoring applications, which will benefit society as a whole. Also, the findings will be incorporated into university courses and disseminated through seminars, short courses, journal articles and the internet, which will contribute to the micro/meso-scale knowledge base. Finally, the undergraduate and graduate students involved with the research will benefit from the interactions amongst the academic (U New Hampshire, Northwestern U) and industry (Alcoa, GOALI partner) collaborators on this interdisciplinary project.

OCE-0451699/04521740/0452380

New Large Eddy Simulations (LES) will be conducted to investigate turbulent mixing processes in estuaries and coastal oceans. Temperature and salinity equations will be added to an advanced LES code that has been validated in engineering flows. The model will include LES equations generalized to incorporate large-scale density and pressure gradients, non-uniform meshes in two directions, allowing for fine resolution of the stratified pycnocline and other regions of interest, and an immersed-boundary method to represent variable-bottom bathymetry and curvy coastlines. This LES model will investigate three important mixing processes in estuaries: (1) asymmetric tidal mixing due to baroclinic pressure gradient and tidal straining; (2) mixing and lateral circulation in a straight, stratified channel with transversely varying bottom depth; (3) topographically-forced, localized mixing in hydraulic transitional flows near channel constrictions. Finally, we shall use the LES model to simulate a segment of the Hudson River estuary and compare the model results with recent dye-release experiments; the velocity and scalar fields obtained from the LES will be used to interpret observations collected in this partially-mixed estuary. The objectives of the proposed research are to elucidate turbulent mixing processes in stratified estuarine flows and to extend LES modeling techniques to horizontally-inhomogeneous estuarine and coastal flows affected by varying bathymetry and shoreline geometry.

Intellectual merit: Understanding turbulent mixing in stratified shear flows is a fundamental problem in physical oceanography. Partially-mixed estuaries are an excellent natural laboratory for studying stratified turbulence, and elucidating key turbulent processes affecting salt and momentum transports in estuaries will shed light on the important mixing problem. LES techniques have been used successfully to investigate oceanic boundary layers; however, they are generally limited to horizontally-homogeneous flows in simple geometries. The methodology to be developed in this project can be used to tackle a wide range of turbulent mixing problems in coastal oceanography and generate turbulence data for calibrating and improving turbulence parameterization schemes.

Broader impact: The proposed study will lead to improved representations of turbulent mixing processes in regional ocean models, which are used to predict sea level, currents, water quality, contaminant transport, and ecosystem productivity in estuarine and coastal environments of societal concerns. Biogeochemical state variables can be added into the model to investigate ecological hotspots such as harmful algal blooms in estuaries and coastal oceans. The project will provide training for a graduate student and a postdoctoral fellow to acquire advanced numerical skills for solving oceanographic problems.

bias; genetics

DESCRIPTION (provided by applicant): Tobacco is one of the most widely abused substances, killing more than 438,000 US citizens each year. Economically, smoking is responsible for about 7% of total US health care costs, or an estimated $167 billion each year. Genetic and epidemiological studies demonstrate that nicotine dependence (ND) is a complex disorder determined by genetic and environmental factors. Our previous meta-analysis of reported twin studies indicated that the weighted mean heritability for ND is 56% in adult smokers. To identify susceptibility loci for ND, we performed four genome-wide linkage studies on three independent samples, in which the African American (AA) and European American (EA) samples of the Mid-South Tobacco Family (MSTF) cohort were recruited by us during the first funding period of this grant. Our linkage analyses revealed four regions on chromosomes 9 (two regions), 11, and 18, in both the AA and EA samples of the MSTF cohort. In addition, we identified five regions on chromosomes 2, 4, 10, 12, and 17, which are specific for the EA sample, and two more regions, on chromosomes 10 and 13, that are unique to the AA sample. Considering that 1) we first reported "significant" linkage on chromosome 10 and "suggestive" linkage on chromosomes 9, 11, and 13 for ND in the AA population and 2) we have the largest collection of samples from this ethnic group in the US, in the current application, we seek support to follow up and expand our ongoing efforts in searching susceptibility genes for ND. Specifically, our aims are: 1) To perform high density association study on our AA family sample to screen for both common and rare risk variants for ND;2) To have sufficient power to detect the small effect of susceptibility loci for ND, we plan to continue our recruitment effort, with the final goal of collecting 2,000 unrelated individuals with ND and 2,000 unrelated control individuals who have tried tobacco smoking but did not develop ND symptoms;and 3) To replicate nominal significantly associated single nucleotide polymorphisms (SNPs) identified in the AA family sample from Aim 1 using 2,000 AA cases and 2,000 AA controls recruited from Aim 2. We expect that such a sample size will have sufficient power to detect 80% of true effects with an odds ratio (OR) as low as 1.3. We expect the completion of the proposed studies to greatly advance our understanding of the genetic determinants of ND in African American smokers that eventually will allow targeting of novel prevention and treatment strategies to individuals at risk. PUBLIC HEALTH RELEVANCE: This renewal application is proposed to follow up and expand our ongoing efforts in searching susceptibility genes for nicotine dependence in African-American population. Specifically, we will perform a genome-wide association study on our AA family sample and then replicate these findings in an independent case-control sample.

The research objective of this Small Grant for Exploratory Research (SGER)/Grant Opportunity for Academic Liaison with Industry (GOALI)/collaborative research project is to validate the feasibility of a novel hybrid manufacturing process which has the potential to generate complex three-dimensional thinsection parts using a three-axis CNC machine. The new hybrid process, which integrates machining and single point incremental forming into a single CNC machine tool setup, is called Deformation Machining. Combining these processes will enable new part geometries to be created that are not currently possible, and allow some complex parts now requiring a 5-axis machine tool to be fabricated using a 3-axis machine.

This new process can enable the flexible and rapid fabrication of lightweight structural components. Potential applications of this process span industries from aerospace to automotive and beyond. Aerospace applications include parts such as bulkheads, frames, spars, stringers, and wingribs. In the aerospace industry alone recurring savings will be substantial. The savings come from three areas: reduced equipment costs, reduced component weight, and increased part accuracy. These savings have been estimated based purely on replication of existing part geometry. However, even greater benefit is expected to arise because designers will gain the ability to conceive new structures which only become feasible using the advantages of deformation machining.

[unreadable] DESCRIPTION (provided by applicant): Clinical work on the mother-child relationship shows that the quality of maternal care from women with schizophrenia is generally inferior to that from healthy mothers. One important contributing factor recognized by both patients and their clinicians is antipsychotic medications. Both typical and atypical antipsychotics are reported to adversely affect maternal care. The PI's long-term goal is to understand the neurobiological and behavioral mechanisms of action of antipsychotic drugs. The objective of this R03 application is to determine the behavioral and neurochemical mechanisms underlying the adverse effects of both typical and atypical antipsychotics on maternal behavior using a rat model. The project hypothesis is that at the clinical relevant dose, the disruptive effect of antipsychotics on maternal behavior primarily reflects a suppressive effect on maternal motivation and is mediated via the dopamine D2 receptor system. Rat maternal behavior is chosen as a model system because it is an ecologically valid and complex behavior that cuts across mammalian species and shares many direct features with human mothering behaviors. Aim 1 will examine the motivational mechanism underlying the disruptive effect of antipsychotics on rat maternal behavior. Aim 2 will identify the neurochemical basis (dopamine versus serotonin) of clozapine-induced maternal behavior deficits. Specifically, the PI will seek to determine (1) whether haloperidol and clozapine at the therapeutic relevant doses (~50%-80% D2 occupancy in rodents) produce a disruption of active maternal behaviors by decreasing mother rats' motivation, as opposed to motor function or sedation; (2) to what extent clozapine (as the representative of atypical antipsychotic drugs) disrupts maternal behavior via the blocking of dopamine D2 receptors and/or 5-HT2A receptors. This project is innovative in that both behavioral (mother-pup separation, repeated drug administration and testing) and pharmacological means (chlordiazepoxide) will be employed to tease apart the specific antipsychotic effects on various distinct behavioral processes involved in rat maternal behavior. . This preclinical project is designed to determine the important psychological and neurochemical mechanisms underlying the adverse side effects of antipsychotic medication on human mothering behavior. Knowledge gained from this project is expected to enhance understanding of the extent to which antipsychotic drugs impact the quality of maternal care and the nature of such impact. Project outcomes are expected to increase the effectiveness of the evaluation of psychotropic drug uses in mothers, future drug development and clinical practice and, ultimately, positively impact the health and well-being of children of mothers with schizophrenia. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): Typical and atypical antipsychotics are the primary drugs used to treat schizophrenia. Although both groups show similar efficacy against psychosis (e.g., delusions, hallucinations), it is unclear whether atypicals as a class have intrinsic and superior benefits over typicals on symptoms related to motivation, emotion and cognition, independent of their favorable motor side effects. The PI's long-term goal is to understand the neurobiological and behavioral mechanisms of action of antipsychotic drugs. The objective of this R21 application is to use a preclinical approach to identify the extent to which two first-line atypicals (risperidone and olanzapine) exhibit an anxiolytic effect on behavioral and physiological measures of fear and anxiety, as part of broad efforts to delineate the critical differences between typical and atypical antipsychotics on non-psychotic symptoms. The project hypothesis is that risperidone and olanzapine have an intrinsic anxiolytic property in preventing the development of new fearful reactions and in extinguishing existing ones. A conditioned avoidance response model will be innovatively used to test this hypothesis. This model not only has high predictive validity for anti-"psychotic" efficacy, but also encompasses multiple measurable and non- motoric responses reflecting elements of fear and anxiety (e.g., body temperature, defecation, urination, ultrasonic vocalization), which enable evaluation of the anxiolytic properties of various antipsychotics, while carefully matching their anti-"psychotic" efficacy and teasing out any possible influence from their effects on learning or motor functions. Its reliability and sensitivity will be further validated against the elevated plus maze (the gold standard of animal model of anxiety). Aim 1 is to identify behavioral effects of repeated haloperidol (typical), risperidone, olanzapine (atypical), chlordiazepoxide (anxiolytic), citalopram (antidepressant with anxiolytic property) treatment on the acquisition of various conditioned fear responses and conditioned avoidance responding in this model. Aim 2 will explore their effects on the extinction of these responses. Aim 3 will validate this novel approach by examining the behavioral effects of repeated antipsychotic treatment on various measures of anxiety in the elevated plus maze, one of most widely used animal models of anxiety. This project is innovative in that a single behavioral paradigm will be used to concurrently identify antipsychotic and anxiolytic efficacies of the drugs, while other confounding factors (e.g., drug effects on learning, memory or motor functions) are being carefully controlled. The reliability of the data is expected to be high because a wide range of doses of typical and atypical drugs will be compared directly with anxiolytic drugs and multiple measures of fear/anxiety will be collected. Furthermore, a repeated drug treatment regimen instead of an acute one will provide better modeling of the clinical treatment condition. This project is designed to reveal the extent to which the two most widely prescribed atypical antipsychotic drugs, risperidone and olanzapine, alleviate anxiety or fear at different stages of development. Such findings are expected to have a positive impact on the development and evaluation of psychotropic drugs and on the treatment of patients with schizophrenia. [unreadable] [unreadable] [unreadable] [unreadable]

Climatic perturbations by drought-flood cycles, tropical storms, and hurricanes are increasingly important in Mid-Atlantic estuaries, leading to ecosystem-scale responses of the plankton system with significant trophic implications. Recent observations support an emerging paradigm that climate dominates nutrient enrichment in these ecosystems, explaining seasonal and interannual variability of phytoplankton floral composition, biomass (chl-a), and primary production (PP). This project will evaluate this paradigm in the two largest estuaries in the United States, Chesapeake Bay (CB) and Albemarle-Pamlico Sound-Neuse River Estuary (APS-NRE) by quantifying responses to climatic perturbations. This project will: (1) resolve long-term trends of plankton biomass/production from high variability driven by climatic forcing, such as drought-flood cycles that generate significant departures from the norm; (2) quantify the role of episodic wind and precipitation events, such as those associated with frontal passages, tropical storms, and hurricanes, that evoke consequential spikes of biomass/production outside the resolution of traditional methods. The field program will focus on event-scale forcing of phytoplankton dynamics by collecting shipboard, aircraft remote sensing, and satellite (SeaWiFS, MODIS-A) data, analyzing extensive monitoring data for CB and APS-NRE to develop context, and quantifying effects of climatic perturbations on phytoplankton dynamics as departures from long-term averages. The rapid-response sampling will be paired with numerical simulations using coupled hydrodynamic biogeochemical models based on the Regional Ocean Modeling System (ROMS). This combination of observations and modeling will be used to explore mechanistic links and test empirical relationships obtained from field data.

Intellectual Merit. Drought-flood cycles, tropical storms, and hurricanes are occurring at increasing severity and frequency, exerting significant pressures on land margin ecosystems. Research and monitoring in these ecosystems has focused singularly on eutrophication for nearly five decades. Recognition of climatic perturbations as the underlying cause of phytoplankton variability represents a significant departure from this singular focus. This project will combine observations and modeling to significantly extend our knowledge of how climate regulates phytoplankton dynamics in estuaries. Progress in calibrating and validating hydrodynamic biogeochemical models with data collected in CB and APS-NRE by this project will lead to predictive capabilities thus far unattained, allowing us to evaluate the paradigm that climatic perturbations regulate phytoplankton dynamics in estuaries.

Broader Impacts: Addressing the effects of climatic perturbations on phytoplankton dynamics in estuaries with a combination of data collection, analysis, and mechanistic modeling has societal benefits for scientists and resource managers. Applications in addition to ?basic? science include the consideration of climatic forcing in designing effective nutrient management strategies. Specific impacts include: (1) quantifying the effects of climatic perturbations on planktonic processes for important estuarine-coastal ecosystems; (2) extending empirically-based water quality criteria forward by enabling predictions of floral composition, chl-a, and PP in changing climate conditions; (3) combining observations and mechanistic models to support scenario analysis, allowing us to distinguish long-term trends from variability imposed by climate. This project will offer a graduate course in physical transport processes and plankton productivity that will benefit from this research, support two Ph.D. students, and train undergraduates in NSF REU and minority outreach programs at HPL-UMCES and IMS-UNC. The main products will be peer-reviewed publications and presentations at scientific meetings. The three PIs maintain active web sites that will be used to distribute results and data.

Intellectual Merit: This study is the first proposed field effort to quantify the role of secondary circulation in driving the estuarine exchange flow. Although recent numerical studies in a limited estuarine parameter space suggest that the lateral advection is a leading-order term in the subtidal along-channel momentum balance, it has not been confirmed by observations. Observational test of this model result is critical to the field of estuarine oceanography because it raises a fundamental question regarding the validity of the classic theory of estuarine circulation. Numerical and scaling results have suggested that the effects of lateral advection are nearly always balanced by internal stresses so that a simple theory based on the momentum balance between longitudinal pressure gradient and bottom stress provides an accurate prediction for the estuarine residual velocity. The central hypothesis is that the near cancellation between secondary flows and interfacial stress is a manifestation for a possible interaction or feedback between the advective accelerations due to secondary circulation and diffusive momentum transfer due to small-scale turbulent flows. This project will investigate the co-variability between the lateral advection and interfacial stress over the spring-neap tidal cycle and assess their roles in the estuarine exchange flow. We plan to conduct a series of field experiments in the James River estuary, complemented by ROMS (Regional Ocean Modeling System) and LES (Large Eddy Simulations) modeling simulations. Field efforts include moored and shipboard observations as well as dye-release experiments and microstructure profiling. ROMS modeling will focus on the effects of secondary circulation on the estuarine exchange flows in this wide estuary, while LES modeling will examine the interactions and possible coupling between secondary flows and small scale turbulent flows. Results obtained from this project will provide a definitive answer on the role of secondary circulation in estuarine circulation.

Broader Impacts: Estuarine dispersion is largely driven by the exchange flow and the ability to predict dispersion is critical in many applied problems such as determining the Maximum Total Daily Load (TMDL) permissible to an estuarine system. More generally, this project will yield much-needed information regarding the circulation and mixing processes in estuaries and help develop state-of-the-art numerical models for simulating estuarine flows, which are required for predicting water quality, contaminant and fish larvae transport. For the field work in the James River, we will involve participation of high school teachers and students from the areas near the estuary. Through the participation of one of the investigator at the University of Florida, this project enhances the involvement of minority groups in science. This project will also provide training to three graduate students and undergraduate interns.

The goal of this revised research proposal is to determine the pharmacologic effects of nicotine on the learning and memory deficits resulted from the presence of HIV-1 viral proteins and to define the genes and biological pathways associated with those effects by using a newly created non-infectious HIV-1 transgenic (HIV-1Tg) rat model. Although the HIV-1 genes gag and pol had been deleted, other viral genes including LTRs still kept intact and are expressed in most tissues including brain and blood of the HIV-1Tg rats. With advancing age, this HIV-1Tg rat develops clinical manifestations of human HIV disease, and, thus, mimics the infection that results from the persistent presence of HIV proteins in the host. When we examined the performance of HIV-1Tg rats in a modified Morris water maze, they showed deficits in spatial learning similar to those in patients with HIV-1 infection. Numerous epidemiological and basic research studies in both humans and rodent models reveal that nicotine can enhance cognitive abilities, indicating nicotine has neuroprotective effects. Based on these findings, we hypothesize that exposure of HIV-1Tg rats to nicotine can alter the observed learning and cognitive deficits resulted from the continuous presence of HIV-1 viral proteins in the rats. To test this hypothesis, we propose to first determine nicotine's effects in the HIV-1Tg rats at the behavioral level and then identify the genes and biological pathways that are affected by nicotine in the HIV-1Tg rats. Finally, we will characterize the specific genes and pathways that mediate nicotine's effects on HIV-1-induced learning and memory deficits. Specifically, our aims are: 1) To determine nicotine's effects on learning and memory in HIV-1Tg rats using a modified Morris water maze test with non-visual cues for navigation; 2) To identify the biological pathways that are significantly affected by nicotine in HIV-1Tg rats using high-density oligonucleotide microarray; and 3) To characterize the specific genes associated those biological pathways, including those are responsible for neuroprotection and neuroinflammation, that mediate nicotine's effects on learning and memory in HIV- 1Tg rats at both RNA and protein levels using various conventional biochemistry and molecular biology techniques. To our knowledge, this represents the first study of investigating how nicotine affects on learning and cognitive deficits resulted from the HIV-1 viral proteins in a rodent model. The data generated from the proposed studies will shed light on the molecular mechanism(s) underlying nicotine's effects on learning behaviors in the presence of HIV-1 viral proteins, and can have substantial clinical significance in the understanding and treatment of neurological dysfunctions associated with HIV infection and AIDS.

DESCRIPTION (provided by applicant): A functional adaptive immune system depends on a diverse and self-tolerant population of T lymphocytes that are generated in the thymus and maintained in the peripheral lymphoid organs. Recent studies have defined the cytokine transforming growth factor-beta (TGF-beta) as a critical regulator of thymic T cell development as well as a crucial player in peripheral T cell homeostasis, tolerance to self-antigens, and T cell differentiation during the immune responses. The long-term objective of this proposal is to elucidate the mechanisms by which TGF-beta regulates T cells. T cell defects observed in mice with T cell-specific deletion of Tgfbr2 gene are associated with abnormal expression of receptors for cytokines of the common gamma-chain receptor family including interleukin 7 (IL-7), IL-2, and IL-15. To determine the function of compromised CD127 (IL-7 receptor alpha chain) expression in TGF-beta receptor II-deficient thymocytes and naive T cells, a strain of CD127 transgenic mice will be used. To determine the role of anomalous CD122 (IL-2/15 receptor beta chain) expression in TGF-beta receptor II-deficient effector T cells, a strain of IL-15-deficient mice will be utilized. These mice will be crossed with T cell-specific TGF-beta receptor II-deficient mice, and the correction of T cell defects will be determined. Defects of TGF-beta receptor II-deficient T cells are additionally associated with abnormal expression of Gfi-1, T-bet, and Eomes, transcription factors that regulate CD127 and CD122 expression. The functions of Gfi-1, T-bet, and Eomes in control of CD127 and CD122 expression and TGF- beta receptor II-deficient T cell activity will be addressed using mice that are deficient in these transcription factors. Finally, the role of TGF-beta-activated Smad proteins in Gfi-1, T-bet, and Eomes repression in T cells will be studied. Successful completion of the projects outlined in this proposal will generate mechanistic insights into the crosstalk between TGF-beta and the common gamma-chain cytokines in T cell regulation. PUBLIC HEALTH RELEVANCE: T lymphocytes play a key role in immune-related diseases such as infection, autoimmune diseases, transplant rejection, and cancer. It has been established that the secreted molecule TGF-beta is a critical regulator of T cell differentiation and function. Experiments proposed here will define how TGF-beta controls T cells.

DESCRIPTION (provided by applicant): Antipsychotics have been in clinical use for more than half a century. Actions at various receptor sites, notably dopamine D2, serotonin 5-HT2A, and/or 5-HT1A receptors, are critically important for the therapeutic effect of antipsychotic drugs. How these actions at the neurobiological level translate into improvement of psychotic symptoms remains unresolved. The Principal Investigator's long-term goal is to understand the behavioral and neurobiological mechanisms of action of antipsychotic drugs. The objective of this application is to identify the behavioral mechanisms of antipsychotic action through a preclinical approach. The project hypothesis is that antipsychotic drugs achieve their anti-psychotic effect via a dual action: (a) selectively weakening the aberrant motivational salience of stimuli (e.g., psychotic thoughts or abnormal perceptions, internal and external cues) and (b) producing a drug interoceptive state that allows the weakening effect on motivational salience of stimuli to be maintained over time. A conditioned avoidance response (CAR) model and phencyclidine (PCP)-induced hyperlocomotion model based on repeated treatment regimens will be innovatively used to test this hypothesis. Aim 1 is designed to examine the weakening of motivational salience action in the CAR model. Aim 2 is to characterize the second proposed mechanism of antipsychotic action: the interoceptive drug state using the CAR model. Aim 3 is structured to use the phencyclidine (PCP)-induced hyperlocomotion model to cross-validate findings from the first two aims and further test our hypothesis. This project is innovative because several novel experimental manipulation techniques will be employed to characterize the exact psychological processes affected by antipsychotics and tease apart the ones relevant to antipsychotic action from irrelevant ones. In addition, multiple behavioral models sensitive to antipsychotic action will be used to cross-validate findings and test alternative hypotheses. Because antipsychotics will be directly compared with non-antipsychotics (e.g. chlordiazepoxide, fluoxetine, and citalopram), the reliability of data and the specificity of drug action will be greatly enhanced. Finally, a repeated drug treatment regimen instead of an acute one will provide better modeling of the clinical condition and ensure the mechanisms identified are applicable to clinics.

An investigation into the causes of interannual variability in estuarine salinity, stratification and circulation will be conducted using salinity observations, statistical methods, realistic 3-Dimensional hydrodynamic models, and simplified 2-Dimensional numerical models. The overall objective is to quantify interannual variability of estuarine circulation, stratification, and salinity, to explain the physical mechanisms responsible for such variability, and provide an assessment of the likely changes in these metrics in response to future climate change. Observational analysis and 3-Dimensional modeling will be focused on Chesapeake and Delaware Bays, for which (a) extensive salinity databases exist, and (b) a robust numerical model has been developed and validated. Process-oriented modeling studies will be conducted to examine how the estuaries respond to interannual variability in river runoff and shelf salinity, sea-level rise and potential changes in tidal and wind mixing. Multiple model hindcasts will be conducted in which the individual impacts of interannual variability in open-ocean sea level, river flow, shelf salinity, and meteorological forcing are assessed. Statistical models will be applied to the historical salinity data to investigate how salt intrusion length and estuarine stratification vary with river flow, shelf salinity and sea level rise. Projections of future climate impacts on these estuaries will be made by using the regional output of state-of-the art climate models that have been extensively evaluated for the Mid-Atlantic region. General insights into the sensitivity of estuarine physical processes to climate variability and change will be afforded by (1) the differing physics of Chesapeake Bay (partially mixed) and Delaware Bay (well mixed); (2) process oriented and realistic 3-Dimensional modeling studies; and (3) configuration of 2-Dimensional semi-analytical models over a large parameter space of river flow, tidal velocity amplitude, and estuarine geometry.

Intellectual Merit. Much of current estuarine research focuses on relatively short time scales (tidal, weather-related, and seasonal). Little is known of interannual variability in estuarine salinity, stratification, and circulation. The inevitability of sea-level rise and climate change demands a rigorous, physically based approach for quantifying their impacts. This project addresses that need with a collaborative effort between two teams with complementary expertise in numerical modeling, estuarine dynamics, climate change impacts, and time-series analysis.

Broader Impacts. This research project will impact the broader community of estuarine scientists and coastal managers as it will better quantify the potential impacts of climate change on estuarine salinity and stratification, factors that greatly influence water quality and the sustainability of living resources such as oysters and crabs. The long-term model simulations and analysis products will be made available to the Chesapeake and Delaware Bay management communities as they prepare for the impacts of climate change. Results will also be communicated to a broad range of stakeholders, including the general public, through several climate assessment activities underway in the Mid-Atlantic Region. Because the modeling and data analysis approaches developed here can be applied to any estuary, and because we will utilize simplified 2-Dimensional model to provide insights about the potential impacts of climate change on a broad class of estuaries, the impacts of the work extend beyond Chesapeake and Delaware Bays. Educational impacts of the proposal are through the support of graduate and post-doctoral research at the interface of the disciplines of estuarine dynamics and climate change.

Intellectual Merit: The physical workings of an estuary depend on the outcome of a contest between forces acting to stratify its waters, and forces acting to destroy this stratification. For six decades, the destructive force has been identified as the tides, which generate turbulence through ebb and flow over the rough bottom. In recent years, a new player has emerged: wind blowing over the estuary. Research has shown wind to be an effective mixer, even to the point of de-stratifying the water column. More recently, it has been found that this mixing takes place, not solely as a one-dimensional vertical process, but also through straining of the density structure in the longitudinal and lateral direction of the estuary. The driving hypothesis for this project is that, in addition to driving strong circulations along and across the estuary, it can also be a major contributor to the mixing providing the energy for the classical two-layer estuarine circulation, at least in estuaries with long fetches and weaker circulation. This project has been designed to investigate the role of wind in estuarine dynamics and to test these hypotheses. In order to examine this role, the response of the estuary to an applied wind stress must be described in three-dimensional detail, detail that has not been provided heretofore. In addition, this response must be clearly identified, separate from the underlying circulation of interest?the slower, steadier estuarine flow. Finally, this description must be scalable to the broad class of estuaries. Achieving this detail and understanding requires an extensive and intensive program of observation and analysis in combination with numerical models that have the ability to separate, dissect, integrate, and scale the multiple circulation and mixing components. The observational program in the Chesapeake Bay will involve an intensive array of instrumentation, the most novel of which is a high-resolution tower equipped with velocimeters and temperature-salinity recorders that will enable direct measurements of the stress profile. A dense array of buoys will be instrumented with meteorological sensors to measure local structure in the wind field. Finally, a scheme of multi-ship, towed-vehicle sampling is designed to provide detailed spatial pictures of the density structure with a sufficiently high repetition rate to resolve changes over a tidal cycle. A partnership with the meteorologists responsible for weather forecasting in the Chesapeake Bay region will aid both the observation and analysis of this complex, interactive system.

Broader Impacts: The circulation and enclosed nature of estuaries make them highly productive fisheries, fisheries threatened by the effects of human alteration of the landscape. Estuaries worldwide are in various states of degradation, the chief cause of which is excess nutrients delivered from agricultural runoff and municipal sewage. These nutrients over-enrich the waters and lead to oxygen sags in the lower layers, sags that deprive living resources of the ability to use this valuable habitat. In estuaries such as Chesapeake Bay and Long Island Sound, these sags can proceed to hypoxia and even anoxia, the total depletion of dissolved oxygen. Costly programs are planned and underway to restore the health of our nation's estuaries. These management programs will need to rely on an accurate description of the physics of estuarine circulation if they are to be successful. In addition, the public will need to be informed of both the problem and the efforts toward solutions if they are to provide the political and economic support necessary. To that end, this research project will engage with education and outreach efforts, especially with the COSEE Coastal Trends program and with the Horn Point Laboratory Scientist-Educator Program, and will involve a scientist-educator, who will head a team of undergraduates to develop a teaching module related to the role of estuarine circulation (including wind mixing) in the Chesapeake Bay's Dead Zone. Finally, this proposal will provide training to two graduate students pursuing PhD degrees and a Postdoctoral fellow.

ACM Special Interest Group of Multimedia, ACM Multimedia has contributed significantly to the advance of all aspects of multimedia research, technologies and applications since 1993. Through the continuous efforts of the community, ACM Multimedia has become a dynamic and comprehensive program for publication, education, and interaction, including presentation and discussion of research papers, participation in tutorials, demos, doctoral symposium, industrial grand challenge competitions, and art exhibitions. All these activities provide a unique opportunity for students to share their knowledge, experience, and their current research with internationally recognized researchers from both academia and industry. ACM Multimedia 2011 (ACM MM 2011) is to be held in Scottsdale, Arizona, November 28 - December 1, 2011 and is expected to attract many US and international attendees from academia and industry.

This award provides support for ACM MM 2011 education related events, namely the Doctoral Symposium, Face-to-face Meeting with Leading Researchers, the Open Source Competition and partial travel expenses and registration for about 20 US-based students; in particular, female and minority students and students presenting in the doctoral symposium and participating open source software competition. A Female Student Mentoring Workshop will be supported by a separate funding from the ACM SIGMM.

The intellectual merit includes the opportunity for students to learn about the cutting edge research and interact with experts in the top multimedia conference. The broad impact is to train and develop the future generation of leaders and workforce in this critical field, as well as enhancing the participation of women and minority students in multimedia research.

The ACM Multimedia proceedings are published by ACM. The student award application procedure and results will be announced at the ACM MM 2011 conference website (http://www.acmmm11.org).

Proposal #: 12-29213
PI(s): Cao, Yu; Kizza, Joseph M; Li, Ming; Tanis, Craig;
Institution: University of Tennessee Chattanooga
Title: MRI: Acquisition of HPC-B: A High Performance Computational Infrastructure for Biomedical Informatics Research
Project Proposed:
This project, from an EPSCoR state and a non-PhD granting institution, acquiring a high performance computational infrastructure to be located at U. of Tennessee, Chattanooga (UTC), aims to support, as a shared facility, five research projects involving ten investigators and 18 students (9 UG, 6 MSc and 3PhD). The proposed projects explore three requirements for a viable, productive and usable health information technology. The project addresses the need to
- Retrieve relevant information from biomedical data, with accuracy and security;
- Analyze the data; and
- Disseminate and share the data.
Biomedical records hold enormous amounts of multimodal data. Thus, the research efforts described focus on actions needed to make this data available (complete, secure, and reliable).
The proposed research questions are organized into three main thrust areas: How to
- Discover clinically and biomedically important knowledge from complex biomedical multimedia data;
- Evaluate and improve the quality and safety of health care by analyzing the large amount of clinical data; and
- Facilitate the biomedical information collection, management, exchange, and analysis with large-scale network computing platforms and telemedicine systems.
The computational infrastructure is expected to serve as an essential shared research instrument, allowing researchers to analyze, design, develop, test, and deploy large-scale and distributed computer algorithms to address a variety of computationally-intensive and data-intensive biomedical informatics research challenges.
Broader Impacts:
Due to a large potential number of users, its convincing educational plan, outreach plan, as well as expected scientific discoveries in a very important area for every society: health care, this work exhibits potential for strong broader impacts. The programs to enrich broader impact aspects will not only be felt locally, but also internationally, and help to ensure that the country maintains leadership and innovation within the addressed research domains.

The emergence of cloud computing brings a paradigm shift to the way that data is stored, accessed and utilized. Especially, outsourcing data to the public cloud enjoys unlimited resources with great economic savings for both data owners and users. However, user privacy concerns have been a major hurdle for the widespread adoption of the public cloud technology. Encryption techniques can protect the confidentiality of users' data, however, supporting effective data utilization such as search operations over encrypted data become a key challenge. Existing techniques are either too computationally expensive, or lack enough flexibility to be adopted by cloud users in practice.
This project aims at protecting user privacy in the cloud. It develops the tools to provide privacy-assured, usable, and efficient data utilization services in outsourced cloud storage systems. Specifically, it tackles the above challenges by combining cryptography with information-retrieval techniques, and focuses on three aspects: (1) the design of novel keyword search schemes over encrypted data with rich functionalities, including ranked search and multi-keyword search; (2) the design of privacy-preserving search schemes over data that are represented using various structures, such as graphs; (3) new approaches for protecting user privacy in the mobile cloud setting. This research also includes a prototyping and experimentation plan.
Ensuring user privacy is fundamental to the success of public cloud deployment. This project also develops curricula and teaches and supervises students. Materials of this project will be made available online as tutorials, software packages, and publications of general interest.

1360280
Easton
1360285
Li
1360286
Najjar

WSC-Category 1 Collaborative Proposal: Coupled Multi-scale Economic, Hydrologic, and Estuarine Modeling to Assess Impacts of Climate Change on Water Quality Management

One of the most important questions facing our society is the potential impact of climate change on water quality, water resources and ecosystem function. Confounding issues such as urban sprawl and agricultural intensification make it difficult to determine the singular effects of climate change on water quality, ecosystem function and on the costs to achieve water quality goals. In view of the challenges facing the Chesapeake Bay (urban growth, agricultural intensification, climate change) an integrated multi-disciplinary approach is critical to provide policy makers with robust and reliable information. The approach that the research team will use is to integrate key climate, hydrologic, estuarine, and economic drivers at multiple scales which will provide water management options for the Chesapeake Bay system.

One way to assess the impacts of climate change in the face of these other stressors is to develop coupled models that incorporate the pertinent controls on the water system. The overarching goal of this project is to develop a quantifiable, predictive framework that couples biogeochemical and hydrologic drivers of terrestrial nutrient export with climate change to evaluate the effects of ecosystem management on estuarine function and costs of water quality protection. To achieve this goal, the project proposes to work broadly across common regional Chesapeake Bay watershed physiographic gradients and dominant land uses (e.g., agriculture, forest and urban) using a multi-scale model evaluation of the impact of climate change and climate variability on the hydrologic, biogeochemical, and economic drivers of water quality degradation in the Chesapeake Bay estuary. Climate data will be down scaled from global and regional climate models and applied to watershed models to predict hydrologic activity and nutrient production across five test-bed watersheds where significant investments in land management (e.g., Best Management Practices) have been made. Test-bed model results will be used to populate an economic model to quantify the optimum tradeoff between water quality improvements and their associated costs. The watershed models will then be upscaled to predict hydrologic and nutrient delivery to an estuarine model to determine estuary impacts.

The goal of the project is to provide a secure foundation for a transportation system that increasingly relies on the cooperation, connectedness, and automation of vehicles to achieve increases in safety, efficiency, and capacity. The financial losses attributable to congestion in America's transportation infrastructure are more than $1 trillion annually and the parallel loss of life in vehicle collisions is 40,000 deaths per year. Cooperative, autonomous vehicles are expected to increase the throughput of vehicles; reduce emissions, fuel consumption, and injuries; extend personal transportation to the disabled and elderly; and lessen the number and size of roadways.

This project leverages a multi-disciplinary group, composed of security, transportation, control, and communication researchers to secure an automated transportation system that is available to all vehicles, trusted or not, that may experience impaired connectivity. The team is (1) developing a secure and resilient control regime for automated vehicles, (2) building a framework based on the physical layer to enable vehicles to establish peer trust, and (3) providing a trusted infrastructure the ability to securely gather and disseminate traffic and environmental data to vehicles for optimal route planning and accident avoidance using Bayesian inference on Markov models.

The proposed research will advance the knowledge in many fields: secure and resilient control, VANET security, trust establishment and management, physical-layer security, decision theory, and secure protocol design. Results from this research will be disseminated in peer-reviewed journals and conferences. The research will provide opportunities for research training for underrepresented students at undergraduate and graduate levels.

DESCRIPTION (provided by applicant): CD4+Foxp3+ regulatory T cells (Tregs) play a pivotal role in the control of immune tolerance to self-antigens, allergens, and commensals as well as immune responses to pathogens and tumors. Our recent studies have revealed that Treg function is dependent on the transcription factor forkhead box O1 (Foxo1) mediated in part by Foxo1 suppression of the proinflammatory cytokine IFN-? expression. In the first part of the project, we will explore the mechanisms of Foxo1-induced IFN-? repression in Tregs. Genome-wide analysis of Foxo1 binding sites showed that Foxo1 is recruited to the regulatory elements of Ifng and Irf1, which encodes a transcription factor that promotes IFN-? production in T cells. Foxo1 DNA binding and reporter gene assays will be performed to determine whether Foxo1 inhibits the enhancer and promoter activities of Ifng and Irf1. Proteomics studies of Foxo1-associated proteins demonstrated physical interactions between Foxo1 and the transcription factor Runx3. The precise protein domains that mediate Foxo1 interaction with Runx3 will be mapped, and their role in regulating Runx3-induced IFN-? expression will be studied. Furthermore, the in vivo functions of IRF1, IRF1-induced IL-12R?1, and Runx3 in the control of IFN-? expression and the suppressive activities of Foxo1-deficient Tregs will be determined. In the second part of the project, we will use a Toxoplasma gondii infection model to investigate whether Treg acquisition of IFN-? expression and the associated Treg functional defects are caused by the loss of Foxo1 activities. Completion of these studies will generate mechanistic insights to the novel Foxo1-dependent genetic program that controls Treg function in the immunological steady state and during infection.

The ever-growing number of wireless systems and the scarcity for available spectrum necessitates highly efficient spectrum sharing among disparate wireless networks. Many of them are heterogeneous in hardware capabilities, wireless technologies, or protocol standards. The resulting cross-technology interference (CTI) can be detrimental to the performance of co-locating networks if not properly mitigated. Current interference management approaches mostly follow the interference-avoidance paradigm, where transmissions are separated in frequency, time, or space to enable spectrum sharing, rather than to reduce or eliminate interference. This project explores cooperative interference mitigation (CIM), a new coexistence paradigm among heterogeneous multi-hop wireless networks. By exploiting recent advances in multi-input multi-output (MIMO) interference cancellation (IC) techniques, the proposed approach allows disparate networks to cooperatively cancel/mitigate their CTI to enhance everyone?s performance. This research focuses on the following objectives: 1) Develop tractable models/frameworks to analyze the theoretical limits and performance bounds of CIM for heterogeneous multi-hop networks, considering various forms of network heterogeneity; 2) Study the incentives of CIM through a novel game theoretic framework, that characterizes the conditions of mutual cooperation and thwarts selfish or malicious behavior; 3) Design distributed performance-approaching algorithms to achieve CIM and integrate them into practical network/MAC layer protocols, by exploiting machine learning tools and implicit inter-system communications. The expected outcomes also include the development of various simulation toolkits and system prototypes for experimental validation.

The integrated education plan includes cross-discipline curriculum development, student mentoring and outreach. The proposed research will have broad impacts on unplanned heterogeneous multi-hop networks that share spectrum resources, such as current and future networks in unlicensed bands, and secondary networks in TV white spaces. Applications will benefit multiple domains including healthcare, energy, emergency services and military etc. Major results will be disseminated via conference and journal publications, software packages, talks and tutorials.

? DESCRIPTION: Adolescence is a period in which the brain and various psychological functions undergo dramatic transitions. It is also the time when symptoms of a variety of severe mental disorders often manifest. In recent years, there has been a significant increase (~6 folds) in antipsychotic use in children and adolescents with schizophrenia and other severe mental illnesses. However, research on the long-term consequences of antipsychotic exposure on the brain and behavioral developments is lacking. As antipsychotic treatment is administered to patients of psychiatric illnesses, there is a need to evaluate the possible short-term and long-term impacts of antipsychotic medications on psychological functions and other aspects of brain maturation at various ages using a validated preclinical disease model of schizophrenia. The PI's long-term goal is to understand the impacts of antipsychotic treatment during adolescence on the behavioral and neurobiological functions throughout development. Previous work from the PI's laboratory shows that repeated intermittent administration of olanzapine induces a sensitization-like (increase in magnitude) effect in a conditioned avoidance response model in both adult and adolescent rats, whereas repeated intermittent administration of clozapine induces a tolerance- like (decrease in magnitude) effect. Preclinical studies also suggest that repeated antipsychotic treatment alters adolescent neurogenesis in the hippocampus. This R03 project will build upon these findings to assess olanzapine sensitization (Aim 1) and clozapine tolerance (Aim 2) and their possible link to alterations in neurogenesis in adolescent rats born from rat mothers that have been exposed to polycytidilic:polyinosinic acid (PolyI:C) - a validated rat maternal immune activation (MIA) model of schizophrenia. In addition, the project will reveal possible interactions between MIA and antipsychotic-induced changes in patterns of neurogenesis. The general approach is to generate immune activation in pregnant female rats using PolyI:C, then induce olanzapine sensitization or clozapine tolerance in the adolescent offspring through continuous drug administration, then test its expression after the animals become adults. The synthetic nucleoside bromodeoxyuridine (BrdU) will be used to identify regions of neuronal survival following antipsychotic treatments. Finally, double labeling of anti-BrdU with NeuN or glial fibrillary acidic protein antibodies is used to further confirm the differentiation of cells generated under the influence of antipsychotic treatment. This project wil not only increase our understanding of the behavioral and neurobiological mechanisms of antipsychotic action, but also allow a detailed study of the long-term impacts of such exposure on neuronal development. This project is significant as it will have implications for psychotropic drug evaluation, future drug development, and clinical practice.

The radio spectrum is becoming an increasingly valuable natural resource nowadays, while it has been shown that much of the spectrum is underutilized in existing licensed bands. To enhance spectrum utilization, dynamic spectrum access (DSA) has been envisioned as a set of promising new spectrum management paradigms, such as spectrum trading/auction and opportunistic spectrum access. While DSA and programmable cognitive radios enable a much higher flexibility of spectrum access, due to the openness of wireless medium, it is also susceptible to various forms of misuse or abuse. For example, unauthorized transmissions without a valid license, or secondary transmissions that intentionally disobey the interference constraints set by the primary users (radios). The misusers will not only gain higher throughput for themselves, but also harm the efficiency of spectrum access operations of normal users (radios). Therefore, enforcing spectrum access rules or etiquettes is crucial to ensuring the ultimate success of the DSA paradigm.

This project develops a framework for etiquette and rule enforcing in dynamic spectrum sharing environments. The main idea of the proposed research is to engage community users (radios) to detect misuse, and identify and punish unruly devices. By crowdsourcing the tasks of monitoring neighborhood radio access behaviors to many cognitive radio devices, multiple benefits can be gained: 1) the potentially large number of participating devices can result in much larger detection coverage and accuracy; 2) no pervasive dedicated trusted infrastructure or hardware is needed; and 3) the fact that every device could possibly be a monitoring device leads to a much stronger deterrence to misbehaviors. The interdisciplinary research plan consists of four major components: 1) an optimized crowdsourced passive radio traffic monitoring framework to detect access misbehavior in the vast DSA spectrum; 2) techniques to identify misbehaving cognitive radio devices using physical layer identification, even when the signal waveform can be adaptively modified; 3) techniques for immediate punishment of spectrum misuse through adaptive friendly jamming which exploits multi-functional re-configurable antennas; and 4) incentive mechanism design via auctions to ensure user participation in each task of crowdsourced etiquette enforcement. The success of this project will benefit multiple current and future application domains deploying DSA, especially those that require critical information protection, such as healthcare, transportation, energy, public services, emergency, and military services.

This award supports twelve US matriculated students to participate in IEEE International Conference on Healthcare Informatics (ICHI) Doctoral Consortium Program. Students who are selected will receive funding to cover their expenditures on registration, travel, and lodging. Students will be scheduled for a rapid-fire talk, with auto-advancing slides, to present a synopsis of their work. These rapid overviews will be followed by a poster session where participants and mentors can discuss research in greater detail. Selected participants may also be invited to give a longer oral presentation. The consortium will close with a panel discussion discussing topics relevant to doctoral students (e.g., dissertation proposal, dissertation execution, job search, and grant seeking). Awardee students will also benefit from vis-a-vis meeting with leading researchers and receive valuable guidance on direction of their dissertation, specific issues in health informatics, as well as career development. This award promotes the training and development of the future generation of leaders and workforce, as well as enhances the participation of women and minority students in in this critical field. The student award application procedure and results will be announced at the ICHI 2015 conference website (http://cs.utdallas.edu/ichi2015/).

IEEE International Conference on Healthcare Informatics (ICHI) is the premier community forum concerned with the application of computer science principles, information science principles, information technology, and communication technology to address problems in healthcare, public health, and everyday wellness. The conference highlights the most novel technical contributions in computing-oriented health informatics and the related social and ethical implications. The conference aims to (i) fertilize interdisciplinary education among healthcare informatics students, researchers, and practitioners; (ii) promote research design and methodology development in the emerging fields; and (iii) coalesce knowledge translation between academia and industry/government. Issues addressed by ICHI become increasingly important in the marketplace with availability of numerous consumer and clinician systems and services. The conference has been held four times: 2010 (IHI 2010, Washington DC, USA), 2012 (IHI 2012, Miami, Florida, USA), 2013 (ICHI 2013, Philadelphia, PA, USA), and 2014 (ICHI 2014, Verona, Italy). ICHI 2015 will be held in Dallas, Texas USA on October 21-23, 2015. The IEEE ICHI 2015 proceedings are published by IEEE.

IEEE INFOCOM is the premier forum to showcase the latest research outcomes that cover a wide range of topics in communications, data networking and wireless networks. Researchers attend this forum to identify methods of improving their work, and seek feedback from fellow researchers on their work. For students, this is a valuable avenue to interact with other top-tier researchers in very informal and friendly manner. This award will support students at U.S. institutions to attend the 2015 IEEE INFOCOM Conference on Computer Communications which will be held in Hong Kong April 26-May 1, 2015. Priority will be given to students who will benefit from attending this workshop, but are unlikely to attend due to the unavailability of travel funding. In addition, applications from female and underrepresented groups in higher education are greatly encouraged.

The requested travel funds will allow graduate students conducting research in the field to attend high-caliber technical presentations, be exposed to state-of-the-art research, and interact with leading researchers and fellow graduate students. The impact to the students' careers from attending INFOCOM 2015 is expected to be substantial, since they would be unable to attend this event without the support of this grant.

Mobile crowd sensing (MCS) arises as a new sensing paradigm based on the power of the crowd together with the ever-increasing sensing capabilities of various mobile devices. As carrying out sensing tasks can deplete the energy of battery-powered mobile devices quickly, this concern largely affects the wide deployment of MCS. Therefore, how to enhance the energy efficiency in MCS is an imperative and challenging task. Inspired by recent advances in wireless networking and energy harvesting techniques, the proposed research aims to develop joint sensing task computation and communication framework to achieve green MCS for various sensing tasks. The research project and activities have significant potential to better support newly emerging MCS applications such as healthcare, environment monitoring, traffic monitoring, social behavior monitoring, etc. The research results are expected to inspire other theoretical and systematic studies to contribute to the networking design and energy management aspects of developing energy-efficient MCS. The project plans to engage female and under-represented minority students in the research activities. The results of the project will be disseminated through publications and talks.

This project has an exciting two-year research plan focusing on fundamental challenges associated with modeling and analyzing green MCS. Observing that the energy consumed in task processing and its distribution correlates to each other, a unified framework to jointly model the energy consumption in computation and communication is proposed to strike a balance between the two to achieve energy efficiency. As renewable energy has emerged as a feasible alternative to the traditional energy sources, it is incorporated in the sensing crowd so as to decrease the on-grid energy demand from sensing devices. Dynamic energy optimization problems are then investigated to minimize energy expenditure in supporting performance-guaranteed sensing tasks, by comprehensively considering time-varying computing resource allocation, renewable energy supply, and wireless channel conditions. Moreover, some sensing devices are envisioned to be capable of transferring extra harvested renewable energy to others nearby, so as to fully explore the vacant energy and computation resources in MCS. Finally, in order to stimulate mobile devices to join MCS, incentive mechanisms and heterogeneous auction markets are developed.

This project, developing a cloud-based instrument, aims to aggregate data driven from an array of body sensors. The instrument can be used in a wide range of wearable sensor-based medical applications. The proponents investigate research challenges focused on Biomedical Body Sensor Data Acquisition, Transmission, and Analysis. Recent advances in cloud computing and sensor technologies have made feasible to develop a software instrument that is able to integrate all aspects of heterogeneous biomedical body sensor systems, from sensor data preprocessing, transmission, and critical event detection at sensor side, to data reliability evaluation and enhancement, data analysis, sensor control at data aggregator (usually a smart phone or PC), and finally data storage, retrieval, and further extensive analysis at the cloud server.

Build jointly with UT-Dallas, the instrument development includes: 1. Android developing; 2. Mobile cloud computing; 3. Cloud infrastructure and set up; 4. Cloud API and Sensor side APUI; 5. Reliability Enhancement, and 6. Event detection. Its major components include: 1. A cloud cluster to support data storage/indexing analysis; 2. APIs for sensor side data preprocessing, critical event detection, and transmission strategies based on open source platform TinyOS; 3. Mobile App development ; and 4. API for sensor data access and analysis algorithms evaluation.

The purpose of this research project is to develop a multidisciplinary research team at the California State University, Fresno to study how active travel and green infrastructures can be better planned to improve residents' mental wellbeing through a combination of crowdsourcing technology and traditional survey questionnaires and interviews. The study will focus on residents in disadvantaged communities in Fresno, California. This study aims to contribute to the field and the society in several ways. First, the findings of this study will advance understanding of the relationship between urban infrastructure, people's travel and park use behavior, and public health, particularly mental health. Second, this study will be able to propose urban policy solutions to health and infrastructure inequalities that plague many American cities, particularly those disadvantaged communities in small- and medium-sized cities. Third, this project will support a strong interdisciplinary research team at the California State University Fresno, a minority-serving institution and a federally designated Hispanic Serving Institution. In addition to this research project, the research team will facilitate local initiatives to promote public health and social equity through continuing community engagement and student training.

This research project will allow the group to build an interdisciplinary, socio-technical research team that is able to use a combination of crowdsourcing technology and traditional survey and interview to investigate the connections between active travel and green infrastructure and mental wellbeing. The crowdsourcing technology will allow the research team to collect data at finer spatial scales in a real-time fashion. An online database will also be developed to store the real-time data that will be collected through the crowdsourcing technology. The team will also engage and interview local elected officials and staff as well as residents in the studied communities. The interview will help them to understand these perspectives regarding how the active travel and green infrastructure in studied communities can be improved. A public workshop will be designed to further to broaden engagement.

Project Summary: This revised U01 research project is in response to PAR-16-214 with the Funding Opportunity Title, ?Program for Extramural/Intramural Alcohol Research Collaborations?. Sulie L. Chang, Ph.D. and Ming D. Li, Ph.D. will be the two extramural investigators at Seton Hall University, and David Goldman, M.D. will be the intramural investigator at NIAAA/NIH. For their alcohol research collaborations, they will share their unique, yet complementary, expertise and experiences as well as their research facilities and other resources. The project goal is to delineate the involvement of DNA methylation in binge ethanol (EtOH)-induced spleen atrophy during adolescence. Adolescence is an important period for maturation of various physiological functions, including immune responses. Binge alcohol drinking, defined as consumption of excessive amounts of alcohol in a short time resulting in a blood EtOH concentration (BEC) of at least 0.08 g/dl, is popular among adolescents and can lead to addictive behaviors and eventually alcoholism in adulthood. Atrophy of the spleen, a key immune organ, is highly associated with immune dysfunction. We have shown that treatment with 4.8 g/kg/d EtOH for 3 d differentially decreases the size of the spleen in 5 wk old adolescent male F344 rats, but not in adult rats. There was also a decrease in the area of the splenic white pulp and a distortion of white pulp structure in Sprague Dawley rats binge treated with EtOH. Expression of CD3, a T cell marker, was decreased. The CD3+ T cell population was also differentially decreased in F344 rats given binge EtOH. These data showed that loss of T cells might partially, account for distortions of white pulp and the overall relative spleen weight. The expression of caspase-3, a key enzyme for cell death, negatively correlated with the relative spleen weight, indicating that binge EtOH induces loss of T cells leading to distortions of the white pulp and spleen atrophy, in part, due to apoptosis. DNA methylation is an epigenetic event that operates through post-transcriptional modification of DNA by DNA methyltransferases (DNMTs) to regulate gene expressions. One of our preliminary studies showed that treatment with 5-Aza-2?-deoxycytidine (5-AZ), an inhibitor of DNA methylation, reversed binge EtOH-induced spleen atrophy. In parallel, we also found that significant decreases of DNMT1 expression in the spleens of rats given binge EtOH. The qRT-PCR array data showed that 6 genes were significantly downregulated among 84 immunity and EtOH metabolism related genes after binge drinking. Taken together, we hypothesize that DNA methylation is involved in binge EtOH-induced regulation of various target genes leading to apoptosis of T cells, distortion of white pulp, and spleen atrophy during adolescence. To test this hypothesis, in this revised application, we propose the following three aims: Aim 1 is to investigate the effects of binge EtOH consumption on spleen atrophy, and to isolate and characterize CD3+ cells for the studies in Aims 2 and 3. Aim 2 is to investigate the role of methylation in binge EtOH-induced spleen atrophy using genome bisulfite sequencing (WGBS), followed by genome-wide methylation analysis (GWMA). Aim 3 is to determine the involvement of methylation in binge EtOH-induced spleen atrophy at the gene expression and mechanistic levels by studying the expression of methylated genes, including the known EtOH regulated genes (KERGs) and WGBS identified methylated genes (WGIMGs). In addition, the methylation inhibitor, 5-AZ, will be used to confirm if methylation of these identified genes (e.g.,methylated KERGs and WGIMGs) is involved in binge-EtOH induced expression of these genes. The proposed studies have combined data-driven discovery and hypothesis-driven investigation together. We expect to identify whole-genome methylated loci in the spleens of adolescent rats subjected to a binge EtOH regimen and the methylation loci of the KERGs and WGIMGs and determine the expression and activities of the proteins encoded by these genes. With these information, we will be able to develop epigenetic-based interventions to curtail binge alcohol-induced spleen injury during adolescence.

Project Summary: As one of the key active ingredients of tobacco smoke, nicotine exerts its actions primarily on the nicotinic acetylcholine receptors (nAChRs), which are expressed on neurons, microglia, and other cells in the central nervous system (CNS). Activation of nAChRs by nicotine has various potential therapeutic immune benefits, including modulation of inflammatory responses, maintenance of immune homeostasis, and regulation of expression of pro- and anti-inflammatory factors. However, smokers have a higher rate of HIV disease progression and behavioral and cognitive complications, with differences seen between male and female smokers. It has been suggested that prolonged exposure to nicotine in HIV patients through cigarette smoking might decrease the expression and desensitize the activation of nAChRs, which could dampen nicotine's ability to mediate immune responses. During the past several years, we have conducted a series of behavioral and molecular studies using a rodent HIV-1 transgenic (HIV-1Tg) rat model to study various medical issues, including immunity, associated with HIV patients receiving combined anti-retroviral therapy (cART). We used this HIV-transgenic rat model to determine the effects of nicotine on brain function in the presence of HIV-1 proteins and found that chronic treatment with nicotine can restore the expression of many genes altered by the HIV-1 viral proteins in signaling pathways involved in immunity and other neuronal systems. In addition, we found that expression of various nAChR subunits, especially ?6, ?3, and ?4, and immune-related genes, such as interferon regulatory factor 7 (IRF7) and interleukin-1? (IL-1?), differ greatly in HIV-1Tg rats compared with F344 controls. Our findings indicate that HIV-1 proteins greatly impact CNS immunity as well as nAChR function and alter the responsiveness to nicotine in certain immune-related and nAChR-mediated signaling pathways. Based on these findings, we hypothesize that there are significant interactions between nicotine and HIV-1 proteins that affect the immune response to nicotine in the brain of HIV-1-positive individuals. To test this hypothesis, we propose the following three aims. Aim 1 is to determine the interactive effects of nicotine and HIV viral proteins on microglia and macrophages in the brain as well as cytokine production in the blood and brain of the HIV-1Tg rat. Aim 2 is to compare the interactive effects of nicotine and HIV-1 viral proteins on gene expression in three brain regions of male and female HIV-1Tg rats using RNA-seq analysis. Aim 3 is to characterize specific genes and pathways that mediate the effects of the interaction between nicotine and HIV- 1 viral proteins using various molecular techniques, including CRISPR gene editing. The proposed studies represent the first application of next-generation sequencing technique in combination with conventional molecular approaches to investigate the modulatory effects of chronic use of nicotine on CNS immunity in the presence of HIV-1 viral proteins. By combining both genomic and molecular approaches, our studies will be comprehensive and free of subjective bias and assure the value of the data for the development of new strategies for treating HIV-1 patients who use nicotine.