Ashok Kumar - US grants

9512324 Kumar A scanning electron microscope and x-ray diffractometer will be acquired and utilized for multi-disciplinary research and education at the University of South Alabama. These are two basic pieces of instrumentation for materials research. The scanning electron microscope permits analysis of the microstructural characteristics of materials whereas the X-ray diffractometer identifies their crystallographic structural properties. The instrumentation will be used in support of several research programs which include laser deposition and processing of hard coatings and of high temperature superconductor films, synthesis and characterization of molecular sieve zeolites and of metal doped glassy carbon for electrocatalysis, and development of crystal growth inhibitors for medicinal purposes. The instruments will also be used to support curriculum development. Students in the Materials Science Laboratory will utilize the instruments for several experiments on the relationship between structure, properties, and processing of materials. %%% The scanning electron microscope and X-ray diffractometer are essential instruments for materials research. Both are entry level instruments, quite appropriate for undergraduate and masters level education and research programs. As such they will have a substantial positive impact upon the infrastructure at the University of South Alabama. ***

9902175
Stephenson

Description: This award is for the US-India Collaborative Research: An Ecological and Taxonomic Study of Ectomycorrhizal Fungi. Collaborators Steven L. Stephenson, Fairmont State College, West Virginia and Indian botanist Rajendra Bhatt, H.N.B. Garhwal University will undertake comprehensive studies of the ectomycorrhizal fungi associated with the forests of eastern North America and northwestern India. These forests have a number of ecologically important ectomycorrhizal-forming tree genera in common. The objectives are: 1) to compare the species composition, diversity, taxonomy, fruiting phenology, and sporocarp productivity of selected groups of these fungi, and 2) to elucidate the biological and taxonomic relationships existing between populations of fungi that appear to represent the same taxonomic entity in these two regions. This project will produce new sets of data on the phenology, productivity, and diversity of ectomycorrhizal fungi from northwestern India that will be compared with a similar body of data for the US study site.

Scope: This research is a unique opportunity for mycologists from the US and India to collaborate on a major study of ectomycorrhizal fungi in two distant regions of the world having similar assemblages of fungi. Stephenson has done preliminary research at both test sites; Bhatt has studied the fungi of the Indian forest area for much of the past decade. The project contributes to fundamental knowledge on ectomycorrhizal fungi and provides a body of new data for launching further studies. A postdoc with expertise in the techniques of modern molecular biology will make important analytical contributions to this project and will serve as a link with one of the major centers for molecular-based studies of higher fungi. The data resulting will have important implications for timber management, watershed protection, and reforestation.

Hard and wear-resistant coatings are an important segment in the US and world economy; for instance, machine tools are a $15 billion per year industry worldwide. The focus of this research program is to fabricate ultrahard coatings based on mixed amorphous/nanocrystalline (e.g., Si3N4/TiN composite coatings) phased by ion assisted pulsed laser deposition method for manufacturing applications. A lubricant will be added to reduce the friction coefficient. The research aims to elucidate the understanding of the mechanisms controlling processing structural and micro-mechanical relationships in nanostructured coatings and thereby demonstrate routes for improved mechanical properties with engineered interface and surface modification. The state-of-the-art analytical techniques will be used to evaluate the structural and mechanical properties.
The above results will be related to the mechanical and tribological properties of the coated surface, such as: critical load, elastic modulus, and friction and wear behavior against a variety of counterfaces in dry and lubricated atmospheres. The principal investigator will also involve a local high school teacher and student into the experimental works related to the research. Through this outreach activities, both the teacher and student will learn the fundamentals of the scientific principles involved as well as learning the different experimental tools related to thin film processing of materials. The efforts will be made to work with industry to achieve the objectives of the research. Results of the project will be disseminated by presentations in regional and national conferences, and published in journals.

This CAREER award integrates research into a novel method to perform solid freeform fabrication (SFF) with a broad educational plan to advance the fundamentals of SFF to students and industry personnel. The focus of the research is to design and build a solid freeform fabrication system based on a novel method for fabrication of parts and assemblies by layer by layer deposition of powder, where the powder is deposited using electrophotography. In this approach, two types of powders, a part powder and a support powder are deposited layer-by-layer into a die such that the part powder has the shape of the desired part and is surrounded by support powder. Subsequent compaction and sintering will consolidate and fuse the part powder to high density and strength while the support material remains in powder form. Advantages of this approach include the ability to use a wide range of materials, print powder in gray scales, mix powders in a controlled fashion, create composition gradients within the part and embed electronics into parts by printing circuits. The educational plan involves developing a design studio and creating new teaching tools and course materials to modernize the curriculum in the areas of computer-integrated design, analysis and SFF manufacturing. The design studio envisioned will consist of a networked computational facility equipped with design and analysis software as well as rapid-prototyping and numerical controlled machining equipment to provide hands-on experience in integrated design and rapid manufacturing.

Superhard coating systems for next generation materials applications must exhibit a combination of physical properties which include excellent thermal and chemical stability, wear resistance, high hardness, toughness, and good adhesion. The goal of this CAREER program is to develop a means by which application specific coatings can be efficiently designed, using an integrated approach tailored towards rapid scale-up and industrial production. The specific objective of this study is to understand structure-property relationships in advanced engineering superhard coating materials prepared by pulsed laser assisted physical vapor deposition (PVD) and by filament assisted chemical vapor deposition (CVD) techniques for multifunctional applications. The pulsed laser deposition (PLD) process promises a new generation of exotic coatings which have superior adhesion, near theoretical densities, and very high hardness, and which, at the same time can be deposited at low temperature. Superhard coatings of carbon nitride (CNx), cubic boron nitride (c-BN), diamond-like carbon (DLC) and microlaminate coatings of metal/ceramic materials will be fabricated by the PLD method. Very-high density CVD plasma will be explored for rapid growth of transparent diamond films at low substrate temperature with desirable microstructure that provides better mechanical properties for manufacturing applications. Evaluation of mechanical properties will include nanoindentation, adhesion and wear tests. Microstructural analyses will include X-ray diffraction analysis for lattice structure, and SEM, TEM and AFM for grain structure and lattice microstructural information. Efforts will be made to work with the industrial partners in developing potential commercial products. An important feature of the project is the training of graduate and undergraduate students in a fundamentally and technologically significant area of Materials Science research related to synthesis, structure, properties and performance. The education plan involves the development of a module on 'Thin Film Technology' that illustrates key aspects of materials processing with appropriate emphasis on synthesis, selection of materials for substrate and film, deposition processes, microstructural development, mechanical properties, kinetics and thermodynamics, and applications in industrial sectors, for instruction in cross-disciplinary fields. The module will include multimedia teaching resources and in-class demonstration. Special attempts will be made to attract students from under represented groups and to train them in multidisciplinary research.

This USF/NSF STARS GK-12 project focuses on K-5 students. The objective is to engage graduate and senior level undergraduate students in the challenge of infusing engineering and science principles in such cutting edge areas as nanotechnology, optics, and advanced manufacturing into the elementary school environment. The partnerships involve five area elementary schools, three of which predominantly serve minority students. 15 graduate and undergraduate students from diverse ethnic backgrounds will be selected as Fellows. Fellows will be trained in both pedagogy and in communication skills. The project will work closely with the School District science and mathematics coordinators and the school principals in developing and implementing a plan to help the Fellows become valuable resources to the teachers. In addition to a stipend, each mathematics and science teacher will also participate in professional development scheduled for the summer of each year. As part of the professional development, teachers will have the opportunity to participate in research experiences with researchers in engineering and the sciences.

The objective of the proposed activities under the Grant Opportunities for Academic Liaison with Industry (GOALI) with Agere Systems Inc. is to develop a strong well-integrated research and education program focused on the understanding of the mechanical and tribological properties of chemical mechanical planarization (CMP) processes for semiconductor manufacturing applications. Integration of low-k materials in the metallization structures creates severe problems during process integration. One of the major challenges in the process integration after the incorporation of low-k materials is CMP of these films due to the reduced modulus and cohesive strength. Due to the emergence of CMP as the method of choice for global planarization of dielectric and metal films, the frictional forces generated during the CMP process have assumed significant importance. Understanding the mechanical and tribological properties of complex stacks involving low-k dielectrics is critical for successful evaluation and implementation of these materials and the main goals of the proposed research are to obtain the fundamental understanding of the nature of surface planarization and identify the mechanism to control the CMP process. As part of this GOALI proposal, Agere Systems Inc. will support as in-kind services like: a) provide CMP consumables (wafer, slurry, and pad) to perform the CMP experiments, b) provide engineer/scientist from the industry to serve as a thesis/dissertation advisor, b) provide resident workspace for a graduate student together with all on-site cost of materials and supplies to support the research, c) assign one engineer/scientist (approximately 10 % of their time to work and monitor the progress of the research), e) to emphasize technology transfer and implementation of research findings in manufacturing.
This GOALI proposal aims to synergize the Agere-USF partnership by providing opportunities for faculty, postdoctoral fellows and students to conduct research and gain experience with production processes in an industrial setting. The university-industry collaboration will provide additional opportunity for students to work with industrial scientists and use of their additional state-of-the-art equipment facilities. Apart from providing hands-on experience, the proposed research will provide a unique opportunity for the students to be involved in interdisciplinary research- a must for future success. Results of the project will be disseminated by paper presentation in regional and national conferences, and published in appropriate scientific journals

This Major Research Instrumentation (MRI) award is to purchase a fully analytical JEM-2010 transmission electron microscope (TEM). The JEM-2010 is a multipurpose high-resolution analytical microscope with wide range of capabilities, such as high-resolution image observation, microarea X-ray analysis, versatile analysis by convergent-beam electron diffraction, and analysis of the atomic structure and/or bonding state of atoms. The primary TEM system will comprise: (i) a TEM with a high resolution pole piece for high resolution electron microscopy imaging (HREM) and convergent beam electron diffraction (CBED), (ii) a scanning transmission electron microscopy (STEM) accessory, (iii) an energy dispersive X-ray spectrometer (EDS), (iv) an electron energy loss spectrometer (EELS) with an energy filter, and (v) a multichannel analyzer and support computers for data acquisition, storage, and processing. This instrument is capable of high spatial resolution imaging of crystalline and amorphous structures, small-beam electron diffraction, and compositional and spectroscopic analyses of micro-and nano-scale features, all necessary tools for characterizing materials structure. Numerous new scientific investigations will be enabled with the new equipment. This instrument will support research in a variety of materials systems including nanomaterials, semiconductors, ceramics, metals, polymers, biomaterials and mesoporous materials. The proposed research projects cover a broad area of research related to synthesis and characterization of high-performance materials for manufacturing applications and TEM will provide an opportunity to conduct high-quality research to understand the microstructural properties of the materials.

The proposed TEM instrument will not only stimulate the productivity of the existing research projects related to the characterization of materials but also will be used for educational purposes. The instrument will be used in undergraduate and graduate courses, and in outreach program for minority students from local schools. It will thus allow for research training of future scientists and engineers from diverse backgrounds in current techniques of electron microscopy and state-of-the-art instrumentation. A laboratory course will be introduced and the main purpose is to provide students hands-on experience starting from sample preparations to operations of TEM. Support for a TEM instrument will also allow the development and enhancement of creative partnership with the numerous local industries, including microelectronics manufacturing, optical coating manufacturing, biomedical company, and computer hardware company. Results of the project will be disseminated by paper presentation in regional and national conferences, and published in journals.

Project Summary: Development and Testing of Practical Algorithms for Online Interpretation of Sensor Data through Wavelet Decomposition

Proposal # 0330145

Recent growth in sensor technology and its applications have made it easy to gather abundance of data. Unfortunately, the data collection rate via sensors usually far exceeds our current ability to process them. A remedy to this bottleneck situation is the development of effective and online implementable statistical algorithms for data interpretation. Furthermore, continued miniaturization of the sensors have significantly increased the sophistication of the sensor fabrication technology which itself is heavily dependent on sensors. Thus, both ends of the sensor technology (fabrication and data interpretation) stand to gain from this research.

The funding granted would allow us to 1) develop theoretical analysis needed to assess the effectiveness of online multiresolution algorithms in interpreting sensor data, and construct efficient univariate and multivariate online algorithms, 2) test online algorithms on sensor data collected from a nanoscale fabrication process, and 3) develop a new Wavelet-EWMA feedback control strategy using online sensor data analysis algorithms. Our strategy for objective #1 is to first build a mathematical model for the multiresolution data analysis scheme in order to assess performance measures such as false alarm rate, and average run length. Our testing strategy is an elaborate one. We will collect a variety of sensor data from the test bed that relate to a number of outstanding operational issues. With each of these data sets, we will not only test the performances of the algorithms, but also use the test results to provide answers to the above issues.

If successful, the mathematical analysis developed by this research would provide a strong foundation for performance assessment of wavelet based online multiscale algorithms. This science base would lead to the development of online and practically viable algorithms for sensor data analysis. Transfer of knowledge discovered through the proposed research into technological innovations will be enhanced through our collaborations with the semiconductor industry.

The objective of this project is to enhance wafer yield in IC manufacturing by enhancing the wafer scale uniformity in material removal rate during a chemical mechanical planarization process. Reduction and elimination of edge exclusion is of particular interest to this project. An integrated model based control approach will be pursued. An analytical model relating the material removal rate to the wafer - pad interface pressure and wafer backside loading profile will be developed. The model predictions will be verified first under static conditions and from material removal rate data. An active control algorithm based on the above model will be developed. In particular, the curvature control algorithm will be pursued. This will be implemented first in software, and then in hardware.

It is anticipated that this project will develop understanding to relate nano-scale nuances of the chemical mechanical planarization process to macro-scale design considerations. This will facilitate efficient optimization and control of process parameters, which is currently done mostly through trial and error iterations. Through Industry-University collaboration, the proposed project will aid in human resource development by exposing graduate and undergraduate students to novel methods of controlling nano-scale material removal processes. Currently a 3-5 mm wafer edge exclusion is used to harvest "usable" chips on wafers, and this affects about 20 percent of the chips on a 300 mm wafer. If successful, this project will directly impact and enhance the yield of such processes.

This project is a collaborative effort of the University of Louisville, an urban university with a liberal arts mission and the Kentucky State University, designated as a Historically Black College/University, to develop a concentration and certificate programs in information security. This project develops the curriculum content, faculty development, and infrastructure development in this area, including dedicated stand-alone Information Security labs for providing hands on experience for the students that provide exposure to dealing with network attacks. The collaboration enables the institutions to recruit both urban and rural students from a diverse student population for a rigorous academic program.

The objective of this research is to synthesize nanocrystalline diamond thin films with very small grain size (5-10 nm), lower surface roughness (20-30 nm) and less internal stress and utilize its extraordinary properties in various applications such as microelectromechanical systems (MEMS) and biomedical devices. The research focus will be: 1) to synthesize nanostructured (5-10nm) diamond thin films by using novel plasma chemistry; 2) to develop and apply advanced characterization techniques to understand mechanical and tribological properties of this material at the nanoscale; 3) to demonstrate potential applications in critical technologies including high fidelity MEMS and biomedical devices; 4) to model the growth and resulting properties of nanodiamond thin films important for MEMS and bioapplications. The rationale for this project is based on the fact that material properties change drastically as the grain size of the materials reduces to the nano-scale. By controlling the grain size and grain boundary structure at the nanoscale extraordinary materials properties will be achieved including high hardness, high fracture strength, high Young's modulus, extremely low friction coefficient and high wear resistance, negligible stiction, low residual stress in as-deposited films.
On a broader scale, successful completion of this research program will lead to a knowledge base for design of novel nanostructured materials and devices. The NIRT projects will provide a unique environment for the research, education and training of graduate and undergraduate students from different disciplines in interdisciplinary setting with active participation of national laboratories, industry and international collaborators. The synergism and complementary expertise of the participants will allow our group to address complex problems and facilitate sharing of ideas and results. Undergraduate and graduate students will be involved in the development and use of cutting-edge research tools and will receive excellent training at the frontiers of nanotechnology. A vigorous education and outreach program will be aggressively pursued to bring nanotechnology to pre-college students, teachers and general public. An essential and important component of this research will be the dissemination of the results through publications in journals, presentation at meetings, and directly to collaborators. This NIRT program will strive to educate next generation of scientists and engineers that will play a key role in advancing nanotechnology research and development in 21st Century.

The objective of this research is the fabrication of a variety of nano-scale structures and the preparation of transmission electron microscopy samples using focused ion beam (FIB) to support several active research projects at the University of South Florida. Among the projects supported are directed assembly of carbon nanotube devices, the study of microstructure and fracture in thin films, the preparation and characterization of conducting semi-transparent inorganic and polymeric films, the investigation of reliability issues in interconnect layers, the fabrication and characterization of nanostructured hard coatings, the fabrication of light harvesting "rectenna" array prototypes, the fabrication of magnetic nanostructures, and the fabrication RF MEMS Switch prototypes.

Broader Impacts: The proposed instrument will be installed in USF's new Nanotechnology building. This facility will provide all campus and the surrounding community with nanofabrication, materials processing, and analytical facilities. Due to its inherent versatility the proposed FIB tool will add a significant range of capabilities to USF's materials research infrastructure, enabling massively cross-disciplinary experiments previously difficult or impossible. This instrument will bring together several of the most significant materials research groups at USF's Engineering and Physics departments, facilitating experiments on new and innovative materials and device structures. The students of these groups and across campus will benefit from having a state-of-the-art research tool on their hands, allowing them to perform cutting edge research, and be involved in interdisciplinary experiments with their peers from other departments.

0512403
Bayoumi

Description:
This project supports collaborative research by Dr. Magdy Bayoumi, Director, Center for Advanced Computer Studies (CACS), University of Louisiana, Lafayette and Dr. Ayman El-Dessouki, President of the Electronics Research Institute (ERI), Cairo. They plan to develop a framework for automated scene surveillance using algorithms, architecture, and prototyping. From the technological-solution perspective, video surveillance has been widely employed for this purpose. However, the advances in this area have mainly aimed at the video sensors only. The human operator still has to analyze the images. In other words, despite the technological advances individually made for sensors, and computing power, there exists a vacuum for a fully automated system capable of scene understanding and automated surveillance. This project proposes to automate the process of tracking objects on the area of observance by comprising a network of sensors and closed circuit television cameras. It identifies threats and raises the alarm.

Intellectual Merit: the proposed activity will deepen the understanding of video surveillance, monitoring, and automatic scene understanding. The followings are the objectives/features of the proposed architecture for an automated scene understanding: Resistance to attacks; Autonomous object detection; Video detection independent of illumination changes; Tracking of objects by agents; and Object detection without waiting for a stable camera. It will attract and prepare graduate students for research in the development of novel algorithms, methods, and hardware/software prototype for scene understanding and automated surveillance.

Broader Impacts: The proposed activity will enrich the course materials offered at the CACS. It also aims to impart training to the Egyptian side through the junior researchers' visits - thus aiming to boost awareness in the scientific education. The project will promote scientific and technological cooperation between the U.S. and Egypt in the automatic video surveillance area, which is of mutual benefit to both sides. Private sector will have the chance to develop their ability to build and implement new algorithms for different tasks and can test their developed system in an already established test environment. Start up companies will get opportunities in integrating different system components and provide services for customers in need of this automated surveillance system. The PI's will collaborate with the existing university programs, such as McNair Scholars and the Louis Stokes Louisiana Alliance for Minority Participation (LS-LAMP) programs that are aimed at substantially increasing the number of underrepresented students completing degrees in science, technology, engineering, and mathematics. The project results could help in securing the country's borders and ports. The project will influence the principal investigator's efforts to educate and train manpower in the critical research areas. This project is being supported under the US-Egypt Joint Fund Program, which provides grants to scientists and engineers in both countries to carry out these cooperative activities.

Objective - The objective of this research is to investigate the non-linear properties of nano-scale active regions of barium strontium titanate (BST) thin films, their dependence upon deposition and patterning processes, and their manifestation in macro-scale observables including capacitance-voltage behavior. Important goals for this project include the development of non-linear computer-aided-design models and design techniques for BST circuits based on non-linear transmission line topologies. The approach is to use planar capacitor (varactor) structures, layered on a BST film, as the building block for more complex devices. The structures will be patterned using focused ion beam (FIB) milling to create nano-scale gaps.

Intellectual Merit - The varactors that will be developed have feature sizes on the same order of magnitude as the film's surface roughness - at this scale, the homogeneity of the film and resultant capacitance-voltage properties, switching speed and dielectric relaxation are not well understood. The exploitation of BST for microwave signal generation will require a thorough understanding of the non-linear properties and advancements in modeling methodologies.

Broader Impact - The devices that will be developed can have a great impact on society at large, as the functionality is integral to specialized systems such as military radar and many commercial telecommunications systems. Furthermore, the fundamental knowledge gained on non-linear behavior of BST will be useful to engineers and physicists working in related fields such as high-density memory. The PIs have a track-record of involving under-represented minorities in their research activities and will recruit female and minority students to perform this work.

The objective of this research is to augment the MEMS and micro/nanotechnology research programs at the University of South Florida through the acquisition of a Deep Reactive Ion Etching (DRIE) tool (configured for deep silicon, dielectric and SiC etching) and a surface profilometer. The approach is to leverage: (a) on numerous USF research and training awards, (b) an interdisciplinary research culture that has a broad social participation of faculty and students. The instrumentation described in this proposal will provide the impetus to drive research in micro/nanotechnology as well as serve as an educational spring-board for engineers and scientists of tomorrow.

Intellectual Merit: The requested instrumentation will be a major addition to the infrastructure of the research center - NNRC and the university. They would embellish the existing assortment of tools at the researchers' disposal. Proposed research will integrate developments in different research areas in a novel approach that will advance the knowledge and understanding in diverse fields, from understanding to sensing. The research tool will provide a basis for fabrication of systems for quantitative diagnosis in diverse environments.

Broader Impact: This research will train students in emerging cross-disciplinary areas. The current research activities will have continued participation of undergraduate students and underrepresented groups (minority, women). It is anticipated that over 30 minority students will benefit from the acquisition in the first year. The results of the research will be widely disseminated through inclusion in courses and modules developed by PIs, demonstrations and outreach.

Functional process variables (FPVs) play a significant role in determining the performance of various manufacturing processes. An example of FPVs is the distribution of mechanical pressure on a wafer during chemical-mechanical polishing (CMP). The analysis of the correlation among FPVs will provide, e.g., a better understanding of the complex wafer-pad-slurry interactions in the CMP process. The improved understanding could affect 20% of wafer yield and impact a revenue stream of $2.8 billion for a single wafer fab. Therefore, the objective of the project is to develop a novel methodology for the analysis of correlated FPVs in order to achieve effective monitoring and diagnosis of complex manufacturing processes. The research will first model the complex temporal and spatial variations in correlated FPVs. For temporal variations, each FPV will be decomposed into amplitude and phase components for distinguishing the timing correlation and magnitude correlation. Global-local decomposition of FPVs will be performed to discriminate global and local variations. As to the spatial variations, a nonlinear dynamics model will be used to depict the timing correlation among FPVs. A nonlinear principal component method will be developed to model the magnitude (amplitude/global/local) correlation among FPVs. Based on the FPVs modeling, statistical procedures will be developed to detect and diagnose variations in correlated FPVs. The change of timing correlation in FPVs can be diagnosed through investigating the coefficients in the nonlinear dynamics model. The change of magnitude correlation in FPVs is to be diagnosed using the principal curve regression model. The proposed methodology will be validated using the CMP tester at USF.
The collaboration with industry partners will facilitate a broad dissemination of scientific and technological discoveries in semiconductor manufacturing. It will also assist a broad array of industry to achieve better process control and continuous variation reduction. The success of the proposed project will promote teaching and learning through the development of interdisciplinary curricular materials, establishment of a CMP testbed and web-based virtual lab, and a close Industry-University collaboration. This provides opportunities to train a new highly skilled workforce in process control and quality improvement by exposing graduate/undergraduate/K-12 students to interdisciplinary training and novel methods of analyzing FPVs in micro/nano scale material removal processes. Women/minority students will be recruited through Bridges to Doctorate, Sloan fellowships, and REU (Research Experience for Undergraduate) supplements from NSF and USF College of Engineering.

The University of Louisiana at Lafayette will acquire equipment needed for CMOS-MEMS fabrication and characterization; the equipment includes a stereoscopic microscope with camera, a profilometer, a lock-in amplifier, a low distortion function generator, an oscilloscope, a spectrum analyzer, and a logic analyzer. The VLSI research group at the University's Center for Advanced Computer Studies will conduct research on Systems-on-a-chip (SOC) viewed as integrated heterogeneous technologies where the technologies range over mixed signal CMOS, CMOS-MEMS and optical devices such asVCSELs etc. on a single die or package. Applications of fabricated devices include sensors and robotics. The infrastructure will be used in research, research training and education at the University. The investigators will partner with existing programs, including McNair Scholars and the Louis Stokes Louisiana Alliance for Minority Participation to increase the participation of under-represented students in related degree programs.

The objective of this research is to optimize the chemical mechanical planarization process using experimental evaluation of mechanical reliability of low dielectric constant materials. Extensive post surface metrology, mechanical and interfacial analysis of the materials, and consumables like pad and slurry used in polishing will be done to gain a fundamental analysis of the planarization process from different perspectives. The research will investigate the roles played by the consumables on surface defect generation at the fundamental level. This investigation will allow optimization of pad design, material selection, process pressure, orbital and linear speed, chemical solution, within wafer uniformity and local planarization. Modeling of interfacial adhesion will allow optimization of process conditions, pad physical properties, and chemical additives in order to reduce within uniformity and delamination of thin film stacks. Reliability issues related to dielectric materials will provide an optimal solution for improved yield without compromising the throughput.

If successful, the finding of this investigation will result in improved equipment and process designs as well as significant reduction in design cycle time and cost. The research will have a profound impact on integration, device yield, and consumables development resulting in a significant economic payoff. The research will be integrated into existing and new courses in the investigators program and other steps will be taken to stimulate the interest of undergraduates and minority student engineers in microelectronics industries. The results will be disseminated in a timely manner through presentation at national/international conferences and publications in archival journals.

DESCRIPTION (provided by applicant): During last funding period, we identified and established that TWEAK cytokine is a major regulator of skeletal muscle mass during aging and disuse conditions. We have now obtained strong evidence suggesting that the TWEAK causes insulin resistance in skeletal muscle. However, the mechanisms by which TWEAK induces muscle atrophy or insulin resistance remain less well understood. PGC-1¿ cofactor plays a major role in regulation of skeletal muscle mass, fiber-type composition, and mitochondrial biogenesis. Our preliminary studies have shown that TWEAK suppresses the expression of PGC-1¿ and mitochondrial content and inhibits insulin signaling in skeletal muscle. We have also found that disuse conditions or type II diabetes involve the inducible expression of TWEAK receptor Fn14 (but not TWEAK itself) in skeletal muscle. Our initial analysis has revealed that both human and mouse Fn14 promoter contains CpG rich regions and that demethylation of Fn14 promoter could be a crucial event for the induction of Fn14 expression in skeletal muscle. In the next phase of this project, we will investigate the mechanisms by which TWEAK causes sarcopenia, disuse-related muscle atrophy, and insulin resistance, and how the expression of Fn14 gets up regulated in skeletal muscle in different conditions. We will address the following three specific aims: AIM I. Investigate the role of PGC-1¿ in TWEAK-mediated skeletal muscle atrophy in vivo. Hypothesis 1: TWEAK causes muscle atrophy and fiber-type switching through down-regulation of PGC-1¿ expression. AIM II. Investigate the key mechanisms by which TWEAK-Fn14 system induces insulin-resistance in adult and/or aged skeletal muscle. Hypothesis 2: TWEAK induces insulin resistance by inhibiting insulin receptor substrate (IRS1) phosphorylation and diminishing oxidative phosphorylation in skeletal muscle. AIM III: Investigate the molecular events leading to increased expression of TWEAK receptor Fn14 in skeletal muscle. Hypothesis 3: Demethylation of CpG islands in Fn14 promoter followed by binding of SP1 transcription factor triggers the expression of Fn14 in skeletal muscle in catabolic states. Successful completion of this project will provide critical insights about sarcopenia durin aging and type II diabetes and provide novel avenues for therapeutic interventions.

PROPOSAL #: 0638709
PRINCIPAL INVESTIGATOR: Geoffrey Okogbaa
INSTITUTION: University of South Florida
TITLE: Students, Teachers and Resources in the Sciences (STARS2): A USF-NSF Continuation GK-12 Project

The STARS2 GK-12 project aims at continuing engaging graduate students in reinvigorating science and engineering education at K-12 levels. The STARS2 project will support the infrastructure necessary to engage considerably more schools, K-5 students, and teachers based on the thematic focus of engineering, specifically, materials & nanotechnology. The innovative Science Summer Camp and Mentor Teacher Program, hallmarks of the STARS project will continue to be important components of STARS2.
The key intellectual merits of the STARS2 program include: 1) development of instructional materials that represent a paradigm shift from learning fact-based science to understanding the underlying mathematics, engineering, and scientific principles, 2) development of a nanoscale thinking through the exploration of scientific phenomena at the molecular level needed to create the scientific workforce of the 21st century, 3) development of a core group of science mentors who can serve as the nucleus for growth in science education, and 4) development of an innovative 5-stage plan that serves as the building blocks for the planned activities of STARS2. Another significant innovation of the STARS2 project is the design and implementation of the successful theme based summer science camps. The broader impacts of STARS2 will continue to be manifested through a highly successful program for recruitment of the Fellows from a broad spectrum of underrepresented groups in STEM, and training them to blossom into highly skilled educators, communicators, team players, and societal contributors.

The objective of the proposed research is to generate knowledge of in situ nanomanufacturing process control through multiscale nanostructure growth modeling and growth of metal-oxide nanowires with excellent optical properties. Standard statistical quality control (SQC) faces new challenges of scale effects which is unique to quality control of nanofabrication processes. Particularly, key process variables, varying with location and time, are measured at macro/micro scales. The quality characteristics of nanostructures would better be characterized as space-time random field measured in nanoscale. Relating macroscale process variables to nanoscale critical quality characteristics and defects requires multiscale model integration for in situ process control. The research therefore aims to model nanofabrication process, more specifically, nanostructure growth for in situ quality control in nanomanufacturing. Novel metal-oxide nanowires will be synthesized and characterized for wide applications in nanoscale electronic and optoelectronic devices.
Toward this goal, we propose an interdisciplinary research plan including: (1) modeling of nanostructure birth and growth processes by integrating space-time random field models with nanostructure growth mechanisms, (2) multiscale in situ quality control of nanostructure growth through macroscale modeling of growth rate difference between substrates and nanoscale modeling of growth rate difference between locally homogeneous regions within individual substrates, and (3) controlled growth of novel metal-oxide based nanowires with excellent optical properties. The experimental work will provide data for multiscale modeling of nanostructure growth processes.

The proposed work is probably the first of its kind to control nanomanufacturing process quality through multiscale modeling of nanostructure growth processes. Successful completion of the proposed research may assist to expedite the transfer of fast-developing nanotechnology from the laboratory to industry application at lower cost. The proposed metal oxide nanowire fabrication research will provide promising building blocks for novel nano devices. A new breed of nanomanufacturing engineers will be educated through an integrated education plan.

The USF STARS program is providing 25 scholarships per year to academically talented and financially needy students to increase the retention of STEM transfer students through graduation, with emphasis on students from underrepresented groups, including women, minorities, and students with disabilities. This program offers a viable transfer pathway for students at community colleges (CC) and non-Engineering degree granting (e.g. dual degree) programs into Engineering. Also, this project leverages existing student enhancement programs developed and implemented at USF to improve the recruitment and retention of STEM transfer students through graduation.

0854023
Matthews


Summary: The investigators seek to develop an in vitro assembled corneal stroma for eventual use as a replacement tissue to aid the visually impaired. The work is motivated by the ability to assemble collagen fibrils derived from Cucumaria frondosa into mimics of corneal stroma, a technique which already exists within the team. Extension of this ability to mammalian materials is an overarching goal. The research outcomes expected from the proposed work center around defining the principles by which the collagen scaffolds of extracellular matrices (ECMs) and connective tissues may be assembled for application to tissue engineering. Despite the vast amounts of data available on the mechanical properties of the macroscopic constructs formed by collagen, little is known of the mechanics at the level of the collagen molecule or fibril. These properties will be measured, as well as the interactions between the proteoglycan components of the relevant ECM, providing the information needed to rationally design in vitro equivalents of the tissue. Mechanically matching the materials used in the construction of the stroma to those of the native system will be done at the macromolecular and macroscopic scales. Through this university-industrial collaborative research project with MiMedx, Inc., the team has access to collagens and to a wealth of experience in collagen assembly and applications to tissue engineering. Additionally, the industrial collaboration provides a streamlined mechanism by which the research outcomes will be translated into patient oriented products.

Intellectual Merit: The intellectual merit is threefold. 1. For the first time, the mechanics of and interactions between the constituents of collagenous tissues will be systematically and comprehensively explored on multiple length scales, providing a complete picture of how the mechanical properties of filamentous self-organizing systems, in particular type I collagen, are derived. 2. The results will resolve the important question of how load is supported within collagenous tissues. 3. The results also will resolve how the collagen hierarchal forms are established and maintained.

Broader Impacts: 1. The results themselves will benefit those endeavoring to a. develop biomimetic materials for connective tissues, b. develop materials for use as scaffolds in tissue engineering, and c. rationally design self-organizing, three-dimensional systems constructed from nanoscale building blocks. 2. The work is highly interdisciplinary, and as such draws students with interest in biomedical engineering, material science, physics, biology, and biochemistry. The ability to recruit students from underrepresented groups is enhanced by this breadth. 3. The laboratories consist of graduate, undergraduate, and high school students. These students will have the opportunity to work jointly in an academic and an industrial setting. 4. An outreach project has been established in which the principal investigator provides young students (K-12) within the US and abroad the opportunity to participate in research experiments by remotely accessing the instrumentation from their own classroom. 5. A new interface for the atomic force microscope is being developed which will allow the visually impaired to perform force spectroscopy experiments. 6. Finally, the material under study has tremendous potential for societal benefit in its applications as a cornea replacement.

The objective of this Grant Opportunity for Academic Liaison with Industry (GOALI) collaborative research project is to investigate the material substrate-processing interfacial conditions in chemical vapor deposition (CVD)-grown diamond films on cobalt-cemented tungsten-carbide (WC-Co) tools. Coating delamination is the major life-limiting factor to diamond-coated WC-Co cutting tools. Interface engineering, by means of surface treatments and interlayer, and optimum nanocrystalline diamond (NCD) deposition are the key solutions to achieve high-quality diamond coatings for dry machining. This collaborative research will focus on the fundamental mechanisms of interface fabrications, properties and functions to enhance the substrate/coating performance over the life of the cutting tools, and will form joint tasks of modeling, characterization, and optimization of surface conditioning, interlayer interfacial preparations, and subsequent deposition processes. Validation of enhancements to interfacial performance will be demonstrated through machining analysis and wear characterization. In addition, environmental process monitoring, in both coating and dry machining with diamond coated tools, will be conducted with data collected for life-cycle inventory and environmental impact analysis.

If successful, this research will lead to breakthrough of diamond coated tools whose performance is comparable to or better than costly polycrystalline diamond tools. Engineering of interlayer and NCD coating optimization, with material characterizations and performance analysis, will further mature the diamond coated tooling technology for industrial applications. This research will also advance knowledge of interface science, critical to coating system functions, especially in harsh tribological services. The findings gained on interface characteristics and behavior modeling will also offer knowledge transformable to other coating system studies. The proposed program will also synergize universities-industry partnership by providing opportunities for faculty and students to conduct research and gain experiences with production processes in an industrial setting. The collaborations will offer opportunity to students working with industrial colleagues and use of their state-of-the-art equipment facilities.

The objective of this research is to investigate miniature radiometric sensors that conform to a surface under test and are capable of thermal imaging to varying depths via frequency adjustment. The approach is based on the use of flexible microwave antennas within which integrated circuits are embedded to detect thermal radiation in the microwave frequency range, and dynamically adjust the sensor characteristics to account for variations in the properties of the contacting surface, such as human skin. The sensors can be applied for mobile monitoring of internal body temperature, wound healing, and other physiological phenomena.

The intellectual merit of this project lies in advancements in antenna design, nanoscale ferroelectric devices and radiometer design, enabling a transformative change in passive microwave sensing. Specific advances targeted in this research include: conformable and frequency-agile antennas; impedance-sensing integrated circuits with embedded tuning networks; and a chip-scale radiometer that can be directly integrated into the antenna.

The broader impacts of the project include advancements in the general field of microwave sensor design, yielding fundamentally new approaches for subsurface biomedical monitoring. Applications extend beyond biomedical systems and include uses such as wireless sensors for structural monitoring and communications devices. The industry partnerships will enable the research team to broadly disseminate results beyond the academic and research community. The project will also engage undergraduate students, while leveraging ongoing university programs that attract underrepresented students to engineering. A new senior/graduate-level project-based course that integrates research outcomes, and includes microwave integrated circuit design and fabrication, will be developed.

DESCRIPTION (provided by applicant): Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke, and renal failure. The renin-angiotensin system plays an important role in the regulation of blood pressure. Previous studies have suggested that: (a) angiotensinogen (AGT) gene locus is associated with human essential hypertension, (b) variant -6A of the AGT gene is associated with hypertension in Caucasian and Japanese subjects and (c) over-expression of the AGT gene increases blood pressure in transgenic mice. We have found an A/G polymorphism at -217 in the human AGT gene promoter and have shown that frequency of allele A at -217 is significantly increased in African-American hypertensive patients. AGT gene is primarily expressed in the liver and we have shown that reporter constructs containing AGT gene promoter with nucleoside A at -217 have increased basal and IL-6 induced promoter activity on transient transfection in human liver cells. Although hAGT gene has seven polymorphic sites in 1.2Kb region of its promoter, variants -217A almost always occurs with -532T, -793A, and -1074T and variants -217G, -532C, -793G, and -1074G always occur together forming two haplotypes. Since allele - 6A is the predominant allele (frequency 0.85) in African-Americans, AGT gene can be subdivided into four haplotypes -6A:-217A (AA); -6A:-217G (AG); -6G:-217A (GA) and -6G:-217G (GG). However, haplotypes GA and GG are very rare leaving AA and AG as two prominent haplotypes. We have shown that: (a) frequency of AA haplotype is increased in hypertensive patients as compared to the AG haplotype and (b) reporter constructs containing AA haplotype have increased basal as well as IL-6 induced promoter activity as compared to AG haplotype. Since inflammation plays an important role in hypertension, our hypothesis is that increased transcription of AA haplotype of the AGT gene plays an important role in the development of hypertension. In order to prove this hypothesis, we have generated transgenic mice containing human renin gene and either AA or AG haplotype of the hAGT gene using knock-in strategy at the HPRT locus. We have shown that AGT mRNA and protein level is increased in double transgenic mice containing AA haplotype of the AGT gene as compared to the AG haplotype. We have also shown that double transgenic mice containing AA haplotype of the hAGT gene and hRen gene have increased blood pressure as compared to transgenic mice containing AG haplotype of the hAGT gene and hRen gene. We will now study the role of these haplotypes on blood pressure regulation in an in vivo situation in transgenic mice containing either AA or AG haplotype of the hAGT gene and hRen gene but devoid of mAGT gene. PUBLIC HEALTH RELEVANCE: Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke, and renal failure. It is estimated that hypertension affects 50 million Americans with a prevalence rate of 25-30% in the adult Caucasian population. The incidence of hypertension and complications due to hypertension are even greater in the African American population. Our studies will help us understand molecular mechanism involved in hypertension.

This collaborative project between Old Dominion University, the University of Louisiana at Lafayette, the Mid-Atlantic Maritime Academy, Marshall Community and Technical College and South Louisiana Community College is modernizing marine technology education in three major shipbuilding and maritime areas of the country. The project is developing instructional modules in lean six sigma, value stream engineering, green manufacturing and shipyard environmental footprint. The instructional modules utilize active learning instructional methodologies that have been documented to improve student learning. Fifteen community college faculty and sixty secondary school teachers are being trained in the use of these modules and subsequently integrating the modules into the curriculum at their respective institutions. The project has strong participation and support from major shipbuilding entities, including the Virginia Ship Repair Association and the American Society of Naval Engineers, who are providing input on the content and quality of the instructional modules. The project includes job placement activities for students interested in careers in shipbuilding. An independent evaluator is implementing formative and summative evaluation plans throughout the life of the project.

MRI Proposal No. 0922850

MRI: Acquisition of an Ultrahigh Analytical Thermal Filed Emission Scanning Electron Microscope for Research and Education

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)"

Abstract

This MRI proposal requests to acquire a high resolution scanning electron microscope (HRSEM) for interdisciplinary research and education at the University of South Florida (USF). The HRSEM instrument with ultrahigh-resolution and optimized analytical functionality will provide much-needed improvement to the research infrastructure at the USF. This proposal, in different ways, affects many on-going research activities and the proposed equipment will provide the opportunity to conduct high-quality research and will also allow the development and creative partnership with industry. Numerous new scientific investigations will be enabled with the new equipment. The proposed research projects cover a broad area of research related to synthesis and characterization of high-performance materials for manufacturing applications and a HRSEM will provide an opportunity to conduct high-quality research to understand the microstructural properties of the materials. Establishment of a HRSEM capability to support these activities will leverage current and future funded programs.
This project is expected to have significant impact on research, education, research training, and infrastructure building at the USF. This research will train students in emerging cross-disciplinary areas. The results of the research will be widely disseminated through inclusion in courses and modules developed by PIs, demonstrations and outreach to community colleges. Apart from providing hands-on experience and the obvious preparation for graduate studies, the proposed research will provide a unique opportunity for the students to be involved in interdisciplinary research - a must for future success. Results of the project will be disseminated by paper presentation in regional and national conferences, and published in journal.

ABSTRACT Bacterial endophthalmitis is a vision-threatening complication of penetrating eye injury and intraocular surgery, notably cataract surgery, the most common ophthalmic procedure performed in older populations in the United States. Approximately, 3 out of 1000 patients develop bacterial endophthalmitis after cataract surgery. As the aged population in the US is expected to grow dramatically, the number of cataract surgeries performed will also increase significantly, resulting in a proportional increase in the incidence of endophthalmitis. The visual properties of the retina are highly sensitive to inflammation-caused damage therefore, a rapid detection and clearance of invading pathogens is critical in minimizing retinal damage. The recent discovery presented in the preliminary data revealed that the retina responds to the TLR2 agonist Pam3Cys by producing the mediators of innate immunity, and that intravitreal injection of Pam3Cys, prior to bacterial infection, completely prevented the development of Staphylococcus aureus (SA) endophthalmitis in C57BL/6 (B6) mice. This leads to the hypothesis that TLR2 plays a critical role in retinal innate immune response to S. aureus and that activation and signaling through TLR determines the disease outcome. The objective of this proposal is to elucidate the mechanisms by which TLR2 activation prevents the development of SA endophthalmitis. Three specific aims are proposed: 1) To determine the role of TLR2 in retinal innate response against SA, and how TLR2 signaling is modulated by Pam3Cys pretreatment. The innate response will be tested in normal, TLR2 ligand, and the SA challenged B6 mouse retinas and cultured retinal (microglia, astrocytes, Muller and RPE) cells by assessing TLR-mediated cell signaling and production of proinflammatory cytokines/chemokines, 2) To determine the mechanisms of TLR2 ligand-induced stimulation of protective retinal innate immunity. Activation of TLR2 prior to infection induces protective mechanisms mainly by down- regulating proinflammatory (Th1) cytokines and up-regulating antimicrobial peptides (AMPs) in the retina upon subsequent bacterial challenge. TLR2-/- and MyD88-/- mice will be used to determine whether these mechanisms are TLR2/MyD88 dependent, active against other bacteria, and are effective in a mouse model of intravitreal injection-associated SA endophthalmitis. 3) To determine the role of cathelicidin related antimicrobial peptide (CRAMP) in retinal innate responses during SA endophthalmitis. The TLR signaling pathways involved in CRAMP induction and mechanisms by which CRAMP modulates bacterial clearance and preservation of retinal integrity, will be tested using cultured retinal cells and CRAMP knockout (Cnlp-/-) mice. Completion of these aims should provide insight into the understanding of the retinal innate response to microbial pathogens, and may lead to the identification of new therapeutic targets for preventing surgery- associated endophthalmitis.

The objective of this EAGER grant is to seek seed funding for the proof-of-concept demonstration through fabrication; testing and measurement of nanodiamond?ragioregular polyhexylthiophene (RRPHTh) conjugated polymer nanohybrid organic photovoltaic cell. Our approach is to fabricate the photovoltaic device consisting of conducting/ND-conjugated polymer/Electrolyte/Graphene/Conducting and Al/ND-RRPHThs/Graphene/conducting electrode structures. The film of nanodiamond-RRPHTh, and homologues conducting polymer structured will be exploited for fabrication of efficient organic photovoltaic cell.

Intellectual Merit: The research will develop for the first time, the photovoltaic device using nanodiamond- RRPHTh or ND-other homologous conjugated polymers nanohybrid film over entire solar spectrum. The target of the work is to enhance photoelectrochemical and solid photovoltaic (PV) effect, and eliminate the recombination of photo induced charge carriers. The investigators will analyze and compare the device with existing technologies. We will also investigate and design a new generation efficient photovoltaic cells to increase the efficiency than observed in any organic based photovoltaic devices.

Broader Impacts: Successful completion of this investigation will result photovoltaic materials displaying of high photovoltaic efficiency at low cost. This innovative research will also meet individual soldier energy requirements, communications, building and facility energy requirements and space-based electric power systems. The market that can be addressed by the proposed technology will be over $1.5B by 2013. The project will provide a unique opportunity for the students and postdocs to be involved in the interdisciplinary research. An essential and important component of this research will be the dissemination of the result through patent, publications in journals and presentations in conferences.

DESCRIPTION (provided by applicant): Skeletal muscle atrophy/wasting is a devastating complication of a wide range of diseases and conditions such as aging, disuse, chronic obstructive pulmonary disease, space travel, chronic heart failure, sepsis, and cancer. Myogenesis is the process that is required not only for the embryonic development of skeletal muscle but it is also an important element of certain types of postnatal growth and repair of injured myofibers. Impairment in myogenesis is the critical determinant of skeletal muscle-wasting in several chronic diseases and also development of rhabdomyosarcoma in children. Although significant progress has been made to understanding the processes of skeletal muscle formation and wasting, the upstream signaling events regulating skeletal muscle mass in various physiological and pathophysiological conditions remain poorly understood. We have accumulated strong evidence that supports a crucial role of TAK1/TRAF6 signaling complex in the acquisition and maintenance of skeletal muscle mass. Our preliminary studies have shown that both TRAF6 and TAK1 stimulate myogenic differentiation through novel Lysine-63-linked poly-ubiquitination mechanisms. TAK1 and TRAF6 are also required for MyoD-induced transformation of non-muscle cells into skeletal muscles. In adult skeletal muscle, the activation of TAK1/TRAF6 leads to inflammation, impairment in myofiber regeneration, and atrophy. To clearly establish the role and delineate the mechanisms of action of TAK1/TRAF6 complex in skeletal muscle, we will use genetic approaches including conditional knockout mice. Based on our preliminary data, we hypothesize that signaling through TAK1 and TRAF6 is required for the development of skeletal muscle but not for maintaining differentiated phenotype. Under stress conditions, the activation of TAK1 and TRAF6 stimulates catabolic pathways leading to skeletal muscle atrophy. To test this hypothesis, we propose to address the following three specific aims: 1) Investigate the signaling mechanisms by which TAK1 and TRAF6 regulate myogenic differentiation in cultured myoblasts; 2) Investigate the role and cellular mechanisms by which TAK1 and TRAF6 regulate skeletal muscle development in vivo; and 3) Delineate the mechanisms by which TAK1 and TRAF6 regulates regeneration and atrophy in adult skeletal muscles. Successful completion of this project will provide critical insights into the signaling mechanisms and establish TAK1 and TRAF6 as novel molecular targets to prevent skeletal muscle loss in various muscular disorders.

NON-TECHNICAL DESCRIPTION:
This project uses novel materials to address an urgent need for de-contamination of petroleum products in the Gulf of Mexico. Petroleum is a mixture of several hydrocarbons, dissolved gas molecules, organic nitrogen compounds, organic oxygen compounds, organic heavy metallics, colloidal particles and several other products. A few volatile petroleum chemicals evaporate easily, while other chemical compounds that are easily dissolved in water remain for longer periods causing harm to all aquatic animals. So, keeping in view the complete remediation from organic contaminants arising due to the oil spill, this project investigates the integration of two novel materials such as bio-surfactants and photocatalysts for the removal of organic pollutants. The presence of the bio-surfactant will increase solubility of oils in water and could lead to higher oil degradation rates. The complete removal of organic compounds will be made possible by using a graphene-based photocatalyst nanomaterial. This de-contamination supports the cleaning of the organic products as well as organic-metals contaminants from sea water. This project also supports green technology because there are no residual products remaining in the sea water after the de-contamination process. More generally, this project stimulates students interest in de-contamination awareness and nanotechnology among the students interested in obtaining master?s and doctoral degrees on subjects related to both nanotechnology and remediation science.

TECHNICAL DETAILS:
After the catastrophic oil spill in the Gulf of Mexico, de-contamination efforts include the removal of even trace molecules from petroleum products. This project works towards developing a better understanding of the complete remediation of all organic contaminants. It integrates two technologies for the removal of organic pollutants using the biosurfactant and photocatalysts-containing graphene (photocatalysts with large surface area nanoshells and graphene-doped photocatalyst with or without graphene) particles. The presence of biosurfactants could increase solubility of oils in water by leading to higher oil degradation rates, whereas the complete removal of organic compounds could be made possible by graphene-based photocatalyst nanomaterials. With funding from this Grant for Rapid Response Research (RAPID), investigators at University of South Florida, Nanotechnology Research and Educational Center (NREC) are examining the efficacy of removing oil products from sea water. This RAPID project is also examining methods and materials to clean organic products as well as organic-metal contaminants from sea water. The project is comparing de-contamination of water collected from different affected regions.

DESCRIPTION (provided by applicant): Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke, and renal failure. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the regulation of blood pressure. Inappropriate increase of aldosterone causes age-related increase in blood pressure and other cardiovascular problems. Aldosterone is synthesized in the ZG of the adrenal cortex and aldosterone synthase is the rate limiting enzyme in its biosynthesis. Aldosterone synthase is coded by Cyp11B2 gene and the human gene has a T/C polymorphism located at -344 in its promoter. Epidemiological studies have suggested that variant -344T of Cyp11B2 gene is associated with hypertension and myocardial hypertrophy. Human Cyp11B2 gene has three SNPs in 1 Kb of its promoter that are in almost complete linkage dis-equilibrium. These SNPs are rs1799998 (T/C at -344), rs10087214 (C/T at -470), rs28659182 (C/A at -663). Thus variant -344T almost always occurs with variants -470C, -663A (named haplotype-I, and variant -344C almost always occurs with variants, - 470T, -663T (named haplotype-II). We have generated transgenic mice by knocking in hCyp11B2 gene containing either haplotype-I or haplotype-II at the HPRT locus. Transgenic mice containing haplotype-I have increased hCyp11B2 mRNA level in the adrenals and kidneys as compared to transgenic animals containing haplotype-II. In addition, male transgenic animals containing haplotype-I have increased blood pressure as compared to transgenic animals containing haplotype-II of hCyp11B2 gene. High salt (4% NaCl diet) and angiotensin-II administration increases blood pressure in transgenic mice containing haplotype-I of hCyp11B2 gene as compared to haplotype-II. Therefore, our hypothesis is that transcription factors bind strongly to the nucleotide sequence of hCyp11B2 gene containing haplotype-I as compared to haplotype-II, and increase its expression. This increases tissue or plasma aldosterone level in human subjects containing haplotype-I. The long term consequence of altered regulation of aldosterone production leads to an increase in blood pressure and cardiovascular complications in human subjects containing -344T allele as compared to -344C allele. These transgenic mice will be used to understand the role of these haplotypes on blood pressure regulation in male and female animals. Transgenic mice may also be used to develop new therapeutic reagents to reduce blood pressure and cardiovascular complications.

? DESCRIPTION (provided by PI): Myoblast fusion is a critical event that is required not only for the development of skeletal muscle during embryogenesis but also for the regeneration of adult myofibers upon injury and for load-induced skeletal muscle hypertrophy. Augmenting the natural process of muscle cell fusion in existing or introduced myogenic cells has enormous therapeutic potential to treat degenerative muscle diseases. However, the mechanisms of myoblast fusion in vertebrates remain less understood. Accumulating evidence suggests that myoblast fusion in mammalian system involves the activation of specific cell signaling pathways such as MAPK, non-canonical NF-?B, canonical Wnt signaling. However, the upstream signaling mechanisms leading to their activation and how the activation of these pathways promotes myoblast fusion during myogenesis remain poorly understood. Our preliminary studies have identified that myeloid differentiation primary response gene 88 (Myd88) is a critical regulator of myoblast fusion both in vitro and in vivo. Our results show that the levels of Myd88 are increased during myogenesis. Genetic ablation of Myd88 impairs myoblast fusion whereas overexpression of Myd88 enhances the formation of myotubes in cultured myoblasts. Furthermore, we have obtained initial evidence that Myd88 regulates the activation of specific profusion signaling pathways during myogenesis. Based on our preliminary studies, we have proposed to establish the role and delineate the signaling and molecular mechanisms by which Myd88 mediates skeletal muscle formation in vitro and in vivo. Our working hypotheses are: (I) Myd88 promotes myoblast fusion in multiple conditions through augmenting the gene expression of specific profusion molecules; (II) Myd88 coordinates the activation of canonical Wnt and non-canonical NF-?B signaling to promote myoblast fusion during myogenesis; (III) Both transcriptional and post-transcriptional mechanisms regulate the levels of Myd88 in differentiating myoblasts. We will test these hypotheses by addressing the following three specific aims. Aim I: Establish the role and investigate molecular mechanisms by which Myd88 mediates myoblast fusion; Aim II: Investigate the signaling networks through which Myd88 promotes myoblast fusion; and Aim III: Investigate the mechanisms by which levels of Myd88 are increased during myogenesis. Successful completion of this project will provide critical insights into the mechanisms of myoblast fusion and will lead to the identification of novel drug targets for treatment of muscle disorders.

Project Summary The role of myeloid cells such as neutrophils in providing host defense to microbial infections is well- established; however, the contribution of monocytes/macrophages (M?) to the pathophysiology of bacterial endophthalmitis is less clear. Our preliminary studies revealed that M? depletion results in increased inflammatory mediators at the resolution phase, suggesting their involvement in the resolution of endophthalmitis. The M? perform multiple tasks, including sensing pathogens, tissue repair, and, in response to host-derived mediators, they differentiate into distinct functional phenotypes; a feature termed plasticity. The classically activated M? (M1) produce inflammatory cytokines and nitric oxide, contributing to host tissue damage. Conversely, the alternatively activated M? (M2) mediate tissue repair through the elimination of damaged cells/tissue and the production of anti-inflammatory molecules to resolve inflammation. Therefore, understanding the mechanisms governing the phenotypic switch of M? can be utilized to develop novel therapeutic strategies. Our transcriptome and metabolomics analyses of the bacteria-infected retina directed us to the identification of adenosine monophosphate-activated protein kinase (AMPK), a metabolic gene, which modulates the infiltrating myeloid cell phenotype in endophthalmitis. We discovered that mice with global deletion (knockout) of AMPK?1 (KO) developed severe endophthalmitis and pathology compared to wild type (WT) mice. M? lacking AMPK?1 maintained a low metabolic state, even in the hyper-inflammatory state. To precisely examine the role of AMPK in myeloid cells, we induced endophthalmitis in myeloid cell specific KO of AMPK?1 (LysM-KO) and observed that LysM-KO displayed exacerbated inflammation and reduced retinal function compared to WT mice, suggesting an essential role of AMPK in myeloid cells in the pathogenesis of bacterial endophthalmitis. Building on these findings, we propose to test our central hypothesis that AMPK exerts protective effects in bacterial endophthalmitis by modulating the polarization of infiltrating monocytes/M? to promote inflammation resolution and that metabolic reprograming is an underlying mechanism of the monocytes/M? phenotype switch. To test our hypothesis, in Aim 1, we will investigate the mechanisms underlying reduced AMPK activity in bacterial endophthalmitis by examining the modification of LKB1 via nitrosylation or chemical adduct formation. Aim 2 tests the hypothesis that AMPK?1 ablation enhances the activation state of myeloid cells and maintains their proinflammatory (M1) state during the resolution phase of the disease. In Aim 3, we will decipher the bioenergetic events, regulated by AMPK in M?, that polarize and maintain their pro-inflammatory nature. The anticipated results of this study will demonstrate that defective AMPK activity in myeloid cells, mainly in monocytes/M?? impacts the resolution of endophthalmitis via regulation of cellular metabolism. Also, it may provide novel therapeutic targets for the development of anti- inflammatory therapies for endophthalmitis and other microbial infections.

Abstract Loss of skeletal muscle mass is a devastating complication of a wide range of diseases and conditions. However, there is still no approved therapy to prevent muscle wasting partly because the mechanisms that regulate skeletal muscle mass remain enigmatic. Accumulating evidence suggests that an array of signaling pathways regulates skeletal muscle mass mainly through modulating the rate of protein synthesis and degradation. However, upstream signaling mechanisms that are involved in the regulation of muscle mass remain poorly understood. During the current funding of this project, we showed TRAF6 mediates muscle atrophy and inhibits muscle regeneration in a variety of catabolic conditions. We also demonstrated that TRAF6 and TAK1 are important regulators of satellite cell homeostasis in adult skeletal muscle. In contrast to TRAF6, of which activation, causes muscle wasting, we have discovered that TAK1 is essential for skeletal muscle growth and maintenance of muscle mass in adults. Inducible myofiber-specific inactivation of TAK1 in mice (henceforth TAK1mko) leads to severe muscle wasting and development of kyphosis. The positive role of TAK1 in muscle growth is also supported by our findings that the activation of TAK1 is dramatically increased in skeletal muscle undergoing hypertrophy. Our experiments also suggest that TAK1 is required for the activation of specific intracellular pathways which promote skeletal muscle growth. Moreover, our studies indicate that TAK1 may be required for the activation of autophagy/mitophagy, regulation of mitochondrial structure and function, and maintenance of redox balance in skeletal muscle of adults. Based on our preliminary data, we hypothesize that (I) TAK1 promotes skeletal muscle growth and inhibits atrophy through augmenting protein synthesis and preventing oxidative stress; (II) TAK1 induces the activation of specific intracellular signaling pathways to augment skeletal muscle mass; and (III) TAK1 is required for the activation of autophagy/mitophagy and regulation of mitochondrial dynamics (i.e. biogenesis, fusion, and fission) and respiratory function in adult skeletal muscle. To test these hypotheses, in the next phase of the project, we propose to address the following three specific aims: (1) Establish the role and investigate the molecular mechanisms by which TAK1 promotes skeletal muscle growth and prevents atrophy; (2) Investigate the signaling mechanisms by which TAK1 regulates skeletal muscle mass; and (3) Investigate the role of TAK1 in regulation of autophagy and mitochondrial content and function in adult skeletal muscle.

Project Summary Inflammation is generally considered a beneficial host response towards invading pathogens or tissue injury. Prolonged inflammation, however, can be destructive and maladaptive, leading to irreversible damage to delicate tissues. Thus, the ideal treatment approach when dealing with inflammation-sensitive tissues, such as the retina, should include immunomodulatory therapies to promote the rapid resolution of inflammation and the restoration of tissue homeostasis to minimize secondary host-mediated damage. Recently, pro-resolution- based strategies using specialized pro-resolving mediators (SPMs) have shown great potential for the treatment of multiple inflammatory diseases. We show that the intravitreal administration of resolvin D1 (RvD1), a type of SPM, in bacterial (S. aureus)-infected mouse eyes attenuated the development of endophthalmitis, with drastically reduced inflammation and tissue damage and preserved retinal function, underline the importance of RvD1-mediated pro-resolving signaling in endophthalmitis. However, unexpectedly, we discovered that RvD1 treatment failed to protect the eyes of Toll-like receptor 2 (TLR2) knockout mice from staphylococcal endophthalmitis. Moreover, we observed a direct interaction of TLR2 with the RvD1 receptor, lipoxin A4/formyl peptide receptor 2 (ALX/FPR2, referred as FPR2). This raises an interesting fundamental question, whether the molecule or signaling pathways that induce the resolution of inflammation interact with other pathways such as the TLRs, which promote the induction of inflammation. Thus, based on prior studies and our preliminary data, we hypothesize that RvD1-mediated protective innate responses in bacterial endophthalmitis are dependent on TLR2 signaling. This will be tested with three specific aims. Aim-1 will decipher the mechanisms underlying RvD1-induced protective innate responses in bacterial endophthalmitis. This will be accomplished by using pharmacological inhibitors of RvD1-mediated FPR2 signaling, as well as the use of FPR2 overexpressing transgenic (Tg) mice and FPR2 KO mice. Bone marrow chimeric studies will be performed to determine the relative contribution of FPR2 on residential vs. myeloid cells. Aim-2 will investigate the interplay of the RvD1 and TLR2 signaling pathways in promoting inflammation resolution in endophthalmitis. These studies will elucidate this novel cross-talk by determining 1) whether TLR2 deficiency alters the generation of RvD1, 2) under which conditions TLR2 and FPR2 interact physically, and 3) the consequences of this interaction on downstream signaling. Aim-3 is designed to test the efficacy of RvD1 as an adjunct therapeutic in mitigating endophthalmitis-associated vision loss. Proposed experiments include the co- administration of RvD1 with conventional antibiotics and the determination of the optimal route of delivery (topical vs. intravitreal) and a comparison of its efficacy with that of corticosteroids. Together, we believe that the mechanistic insights and the treatment strategies developed in this proposal could have a major impact on the field, not only with regards to endophthalmitis but other ocular and non-ocular infectious diseases as well.

Project Summary The most recent outbreak of Zika Virus (ZIKV) in Brazil has presented with unexpectedly severe neurological manifestations, which were not observed in prior outbreaks of ZIKV or other related flaviviruses. This prompted the WHO to declare a public health emergency of international In addition to neurologic disorders, ZIKV infection is now being increasingly associated with ocular complications such as uveitis, acute maculopathy, pigmentory retinopathy, and chorioretinal atrophy. These clinical findings make it clear that macular and chorioretinal disease can significantly impact visual outcomes in ZIKV-infected infants and adults. However, it is not yet clear whether congenital ocular complications are directly caused by ZIKV or are secondary to microcephaly. As the retina is the primary target of ZIKV in the eye, we have developed a mouse model of ZIKV-induced chorioretinal atrophy. We found that cells lining the blood-retinal barrier (BRB), the retinal pigment epithelium (RPE), are highly permissive to ZIKV. Collectively, these findings led us to postulate that ZIKV gains access to the eye by via BRB. Despite the close relationship between ZIKV and other members of the flaviviridae family, such as DENV, WNV, and JEV, it remains unclear why only ZIKV causes congenital disorders and associated complications. To address this question , we compared the transcriptome of ZIKV-infected RPE cells with the transcriptome signatures of the other related viruses. This led to the identification of ABCG1, a cholesterol membrane transporter, as a candidate gene that is specifically involved in the pathogenesis of ZIKV. In support, our preliminary data show that pharmacological inhibition of ABCG1 activity attenuated ZIKV replication in RPE cells. Thus, the overall objective of this study concern. is to determine molecular mechanisms by which ABCG1 promotes viral replication in RPE and determine the consequences of ABCG1 ablation in the pathobiology of ZIKV-induced chorioretinal atrophy. To achieve this goal, we will pursue two specific aims: Aim-1 is to determine how ZIKV-induced ABCG1 expression modulates cholesterol synthesis/efflux to promote ZIKV replication in RPE cells. Aim-2 is designed to investigate the role of ABCG1 in the pathobiology of ZIKV-induced chorioretinal atrophy in ABCG1-BEST1Cre mice harboring an RPE-specific conditional knockout. Upon completion, these aims will elucidate the role of ABCG1 in ocular ZIKV infection, particularly in the pathogenesis of chorioretinal atrophy. Given the rapid spread of ZIKV and its impact on ocular health, this work is of paramount importance for the development of drugs to treat ZIKV infection and prevent its complications.

Abstract Sex differences are evident in vulnerability to age-related cognitive decline and diseases of aging. Estradiol (E2) is protective against neurodegenerative diseases, including Alzheimer?s disease, implicating sex hormone effects on sex differences in vulnerability. However, obstacles to sex steroid treatments include closing of the therapeutic window observed as decreased effectiveness of E2 treatment with advanced age. The goal of the proposed research is to provide an understanding of the mechanisms for E2 effects on memory and the closing of the therapeutic window. Closing of the therapeutic window is marked by a decrease in E2-responseive transcription and an inability of E2 treatment to enhance N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission examined several days after treatment. Aim 1 will test the hypothesis that E2 treatment, several days prior to testing, specifically influences NMDAR-dependent episodic memory, such that it can rescue an age-related decline in episodic memory examined on the water maze and novel object recognition tasks. Aim 2 will test the hypothesis that E2 effects on memory and NMDAR function are mediated by reversal of NMDAR hypofunction, mediated by redox regulation of phosphatase/kinase activity, similar to that previously described in aging males. Thus, it is predicted that prior to closing of the therapeutic window (i.e. in animals in which E2 treatment improves cognition and increases NMDAR function), E2 treatment will promote antioxidant enzyme activity, reduce oxidative stress, and minimize redox-mediated decrease in CaMKII activity and NMDAR function. Further, following closing of the therapeutic window (i.e. for animals in which E2 does not rescue cognition and NMDAR function), E2 treatment will not promote antioxidant enzyme activity or reduce oxidative stress, and the NMDAR response and CaMKII activity will be decreased due to an oxidized redox state. Aim 3 will test the hypothesis that age- related changes in transcriptional responsiveness to E2 are due, at least in part, to epigenetic regulation through DNA methylation. It is predicted that decreased responsiveness of E2-sensitive genes will be associated with DNA hypermethylation, particularly in gene body regions (introns), and specific to CpG, relative to non-CpG methylation sites. The proposed studies will employ a powerful combination of behavioral tests that are sensitive to NMDAR function, patch-clamp recording of NMDAR synaptic responses, measures of oxidative stress and enzyme activity, transcription, and DNA methylation.

Project Summary Staphylococcus aureus (SA) accounts for 16% of all hospital-acquired infections (HAIs) and is responsible for more deaths in the U.S. annually than HIV/AIDS. The pathogen?s high morbidity and mortality are in part attributable to the fact that SA has developed resistance to many currently available antibiotics. Thus, there is an urgent need to discover/develop new therapeutic agents. Using an ocular staphylococcal infection models and an innovative genomic-based drug repurposing approach, we identified three drugs, Dequalinium Chloride (DC), Clofilium Tosylate (CT), and Glibenclamide (GLB), which can combat SA infection by modulating the genes/pathways activated during infection. Indeed, our in vitro preliminary studies revealed that both DC and CT exhibit direct bactericidal activities against SA and S. epidermidis (SE). Moreover, two drug combinations significantly reduced the expression of common inflammatory mediators, including IL-1? and TNF-?, in SA- challenged microglia, indicating the potential therapeutic effects of these drugs in staphylococcal infections. Studies outlined in the current proposal will evaluate the therapeutic efficacy of these novel drugs in vivo. In Aim-1, we will determine the therapeutic efficacy of novel drugs in mouse models of staphylococcal endophthalmitis. This will be accomplished by administering the drugs in two combinations, DC+GLB and DC+CT, at various times points post SA or SE infection in B6 mouse eyes. The drugs will also be tested in combination with the conventional antibiotic, vancomycin. The experiments will also examine the ocular toxicity of the drug combinations. Disease outcome will be measured by assessing bacterial burden, levels of inflammatory mediators, retinal tissue damage, and retinal function testing. Aim-2 is designed to investigate the molecular mechanisms underlying the therapeutic effects of the novel drugs and compare their modes of action with antibiotics. The proposed experiments include the administration of the best drug combination and a comparison of its therapeutic efficacy with that of vancomycin, followed by a comparative transcriptome and systems biology analysis of antibiotic vs. drug treated retinal tissue. Given the need for new anti-microbial therapeutic agents and the attractive features of drug repurposing, this study has considerable potential to develop novel therapies for both ocular and non-ocular staphylococcal infections.

Project Summary (Immunology) Continuing funds are requested by 17 vision scientists (holding 13 eligible NEI R01 grants) and their personnel to support three resource/service cores and an administrative core in the newly merged Department of Ophthalmology, Visual and Anatomical Sciences (former Ophthalmology and Anatomy/Cell Biology Departments). The Immunology (I-Core) will be directed by Dr. Ashok Kumar, an R01-funded investigator with significant expertise in immunological techniques. Together with the PI, and a research assistant, the environment and capability to conduct vision research at Wayne State University and affiliated institutions will be enhanced through prioritization of the work of NEI R01 funded investigators, their staff and students (graduate and fellows) in numerous aspects of Immunology. This core will ensure vision researchers have ongoing access to contemporary instrumentation and approaches in flow cytometry/FACS and other immunological assays to facilitate their research. The I-core maintains flow cytometry, western blotting, ELISA, and other capabilities that enable advanced cell analyses for a wide range of research areas. The experimentation supported by I-core will continue to provide sophisticated immunological assays and expert consultation/training to the vision research community, maximize and centralize specialized immunology research tools, and initiate and stimulate innovative research projects addressing emerging questions of eye diseases. Priority for NEI R01 funded investigators at Wayne State University (WSU) and other affiliated institutions will be provided. The I-core also provide a supportive environment to foster collaboration among NEI R01 funded investigators, clinicians, and other WSU and affiliated investigators to develop and carry out basic and translational vision research. The I-core also will provide support, at reduced priority, for new investigators, and/or others who are collecting preliminary data to be used for NEI R01 grant submission.

Project Summary/Abstract The number of elderly individuals over 65 years of age is projected to increase exponentially over the next several decades. Neurodegenerative diseases including Alzheimer?s and dementia are expected to pose a significant health and financial concern for aging individuals, their families, and society. In order to therapeutically combat neurodegenerative diseases, we have to understand age-associated alterations and delineate the mechanisms causing cognitive deficiency. Cognitive impairment in the form of reduced executive function, including attentional abilities and cognitive flexibility, is a characteristic of several psychiatric and neurodegenerative diseases as well as of cognitive aging. N-methyl-D-aspartate receptor (NMDAR) hypofunction contributes to impaired attention in schizophrenia. Furthermore, electrophysiological evidence has shown that NMDAR hypofunction in the medial prefrontal cortex (mPFC) emerges during middle age and is associated with a decline in attentional ability. Results indicate that like older humans, serine racemase RNA (SRR) declines in the mPFC of older rats with impaired cognition. Serine racemase generates D-serine, a co- agonist that regulates NMDAR function. The overall goal of this proposal is to test the hypothesis that enhancing NMDAR function through 1) upregulation of the GluN2B NMDAR subunit or 2) increased expression of SRR, in the mPFC, will restore NMDAR-mediated synaptic function and ameliorate attention and cognitive flexibility. Aim 1 will test the hypothesis that upregulation of the GluN2B subunit of NMDAR in the mPFC will restore NMDAR- mediated synaptic function and improve cognitive function. By employing specific expression vectors, we will limit the expression of the GluN2B subunit of NMDAR either to mPFC pyramidal neurons alone or in conjunction with interneurons. Behavioral performance of animals will be tested on the 5-choice serial reaction time task and the set-shifting task, and upregulation will be confirmed using electrophysiological, immunohistochemical, Western blotting, and RT-qPCR analyses. It is predicted that upregulation of GluN2B expression in the mPFC will restore NMDAR-mediated synaptic function and improve executive function. Aim 2 will test the hypothesis that a viral vector mediated increase in the expression of serine racemase, specific to pyramidal neurons or astrocytes will enhance NMDAR function and reverse cognitive deficits associated with senescence. Augmented expression, specific to pyramidal cells or astrocytes in the mPFC will be confirmed. We predict that upregulation of serine racemase will enhance NMDAR function and ameliorate attention and cognitive flexibility. The proposed studies will employ an array of powerful multidisciplinary techniques to modify specific components of mPFC circuitry testing two novel and independent hypothesis both directed at improving age-related cognitive dysfunction.

Project Summary/Abstract The proposed supplement activities will not change the parent award project. Please see the Research Strategy.

Contact PD/PI: Snyder, Katherine E. Project Summary ? Overall Core ReBUILDetroit is a partnership between institutions of higher learning in urban Detroit, comprised of University of Detroit Mercy (primary institution), Henry Ford College (pipeline Community College partner), and Wayne State University (research partner). Together these three institutions host almost half the population of college students in Detroit. The majority of our students reside in the Detroit area, are from groups underrepresented in biomedical sciences, are Pell-grant eligible, and are first generation college goers. Our students are from socio-economically disadvantaged backgrounds and graduate from K-12 school systems that often are not able to provide access to skills required to succeed in college. These students, for a combination of financial and academic reasons, are unable to complete their studies, contributing to the low six-year graduation rates. The desire and the motivation to succeed are strong even with these challenges. The ReBUILDetroit program provides opportunities to precisely this set of Scholars. The program selects students who demonstrate the desire to pursue biomedical majors and careers in biomedical research. The program commences with students entering in the summer prior to their matriculation to college. In this summer enrichment program, ReBUILDetroit Scholars become college ready, develop a network with their fellow students at the partner institutions and are exposed to research. The first year in the program provides them with course-based instruction in research methods and research projects, after which they conduct research with nationally- renowned research faculty throughout their undergraduate years. Scholars form a Learning Community and receive peer- and near-peer mentoring, dedicated academic advising from program staff, academic coaching, professional development opportunities, social networking, and financial support throughout their undergraduate years. Our Scholars have made excellent use of all of these support structures and have developed a strong sense of science-identity and belongingness. They excel academically, with greater than 90% retention from the start of the program to date as the majority of the first cohort enters the fourth (senior) year of college. Greater than 85% are on target to graduate in not six, but in four years, with STEM majors. They view themselves as reseachers and have won awards at national conferences for presentations on the outcomes of their research conducted with faculty. The majority of the first cohort is in the process of applying to graduate and professional schools as they seek graduation in May 2019. Importantly, they have developed a strong sense of belonging and have formed a network of their peers, both with their ReBUILDetroit colleagues and with their BUILD colleagues across the national consortium. The program created in the first cycle will be strengthened in the second grant cycle and continued even beyond the grant period as ReBUILDetroit scholars become the next generation of biomedical researchers pursuing careers in various sectors. Page 78 Project Summary/Abstract Contact PD/PI: Snyder, Katherine E.

PROJECT SUMMARY: Zika virus (ZIKV) is a teratogenic human pathogen that causes congenital eye and brain diseases. Affected babies exhibit vision impairment and associated ocular pathology, including loss of foveal reflex and macular pigment mottling, chorioretinal scarring, and macular atrophy. ZIKV has become endemic and local transmissions in the USA have been reported previously. The long-term effects of structural damage on vision, as well as the pathogenic processes of congenital ZIKV eye diseases are beginning to be understood. The signaling pathways governing normal eye development, which are dysregulated during ZIKV infection, are not well characterized. We recently carried out a series of experiments by establishing a ZIKV infectious ocular cell culture system and mouse models to understand the structural and molecular perturbations. For successful replication, viruses have evolved various strategies to evade innate immune response as well as to enhance the availability of cellular metabolites required to meet the heightened energy demand for viral genome synthesis. We found that the AMPK?, a cellular master energy sensor, is activated in the ZIKV-infected retinal cells. Moreover, pharmacological activation of AMPK resulted in attenuated ZIKV replication. Another interesting finding is that the YAP/TAZ factors in the tumor suppressor Hippo/SWH signaling pathway were induced early on, but degraded at later stage of ZIKV infection in RPE cells. Silencing YAP/TAZ resulted in reduced ZIKV replication. Since the energy sensor AMPK and Hippo signaling pathways control key cellular processes, including host antiviral responses, it is critical to understand the fundamental mechanism of these two pathways deregulation. We hypothesize that ZIKV modulates AMPK and Hippo signaling pathways in ocular cells to 1) increase intracellular metabolic resources, and 2) inhibit TBK1 to antagonize antiviral defense. These molecular changes can be orchestrated through viral coded factors resulting in the pathogenesis of ocular cell injury. The following specific aims will be investigated. Aim 1 focuses on systematically evaluating the role of AMPK- Hippo signaling on regulating antiviral response to ZIKV infection in RPE cells. The cross talk between these pathways will be investigated at the YAP/TAZ level. Pharmacological activation/inhibition, and gene knockout approaches in RPE cells will be carried out. Aim 2 is designed to elucidate the effect of ZIKV on Hippo and AMPK signaling pathways during retinal development. Human iPSC-derived 3D-retinal cup organoids will be used to investigate the link between retinal development and ZIKV-mediated deregulation of these key pathways. The ZIKV-encoded virulence factors regulating these pathways will be characterized. Aim 3 is to determine the effect of RPE-specific ablation of AMPK, TBK1, and Hippo signaling on the pathogenesis of ZIKV-induced chorioretinal atrophy in mice. This proposed study would yield novel insights into the pathogenesis of ZIKV in ocular diseases and identification of potential therapeutic targets.