This project will develop curricular material that bridges digital media and digital art. Building on a proof-of-concept grant that produced learning units in image, sound, video processing, and multimedia programming, it is arranged around a primer, relevant to both computer science and art students; an advanced computer science module, emphasizing the mathematics and technology underlying digital media; and an advanced art module, emphasizing aesthetics and design. The web- and text-based material, divided into recombinable topics, interactive exercises, and demonstrations, stresses concepts over applications and is designed to promote students' active, informed use of digital media tools. Content, the development of an appropriate learning hierarchy, the nonlinear linking of concepts, and pedagogical effectiveness will be assessed at four external sites: a university with large digital media courses, a largely minority university, a community college, and a technology magnet high school. The material will be disseminated through a faculty development workshop, conference presentations, journal articles, and commercial publication.

Jacquelyn Fetrow (see also Physics)

• Integrin Function in Cartilage
  Awarded $7,636 for the period 8/1/07-7/31/08
  Source: National Institutes of Health/WFU Health Sciences

Results of these studies will provide new information needed to understand the molecular mechanisms by which signals generated by chondrocyte integrin receptors regulate the production of enzymes that cause excessive degradation of the cartilage matrix in arthritis and provide novel targets to inhibit the destruction.

• with Elizabeth Hiltbold, Microbiology and Immunology, WFUHS
  Modeling Networks of Dendritic Cell Maturation Induced by Bacteria
  Awarded $20,000 for the period 5/06 to 5/07
  Source: WFU Cross-Campus Collaborative Research Support Fund

  Dendritic cells (DCs) are uniquely qualified to activate naive T cells because of their ability to sense and to capture pathogens, to degrade them within the cell, and to present their antigens on the cell surface. In a process known as maturation, DCs are transformed from poor T cell stimulators to highly potent T cell activators through a series of morphological and functional changes. This process is tightly regulated at the transcriptional level, and while several aspects have been well characterized, the program that drives it remains unclear, especially in response to intact, live bacteria, a physiologically relevant stimulus.

  Most bacteria express a variety of components that stimulate several pattern-recognition receptors, and many are able to access distinct groups of receptors at several intracellular sites, including the plasma membrane, phagosomes, and even cytoplasm. The PIs hypothesize that the interactions between multiple pattern-recognition receptors that are triggered by live Listeria are critical for maximal activation of antigen-presenting cells.

  Microarray technology is a powerful methodology for systemically studying the time-course of global changes in many biological systems. The project couples this technology with computational biology to develop network models of functional classes of genes expressed when bacterial infection induces DC maturation. Completion of the two specific aims will provide the preliminary data and framework models of DC maturation necessary to develop a competitive R01 application.

• Algebraic and Statistical Models of Redox Signaling
  Awarded $254,488 for the period 4/1/07 to 3/31/08, Year 3
  Source: National Institutes of Health (NIH)

  An interdisciplinary research group spanning the Reynolda and Health Sciences campuses is developing theory, algorithms, computational tools, and research methodologies for network modeling of redox-regulated events in human cells. Recent research indicates that redox-regulated networks are central to cellular communication under various normal and diseased conditions, including aging, cancer, and neuro-degenerative diseases. This project will (1) identify a comprehensive set of cellular proteins modified at cysteine residues as a result of redox-dependent signaling; (2) correlate the concentration of a given cellular perturbant and its associated redox signal; 3) associate networks with particular perturbants; and 4) produce both topological and dynamic models of the cellular network associated with these pathways. The models will then be compared to other data on protein/protein interactions and kinase cascades to produce a more comprehensive model of cellular regulation and its biological outcomes.

• Integrated Process for Functional Site Feature Analysis
  Awarded: $167,800 for the period 8/1/07 to 7/31/08, Year 3
  Source: NSF
  
  Sequence and structural genomics projects have identified and predicted molecular functions in proteins, yet researchers still cannot determine the biological mechanisms of, for example, catalysis or substrate specificity or inhibitor binding, without detailed biochemical and biophysical analysis of each protein. While structural genomics projects are providing the necessary data, they are not being used to reveal the general principles underlying biological mechanism.

  This project uses sequence, structure, bioinformatics, and biophysical to characterize the molecular function sites of 6 protein superfamilies, with the following objectives: 1) characterizing the sequence and structure of functional site features and using the results to develop methods for clustering the peroxiredoxin family; 2) analyzing the electrostatics at peroxiredoxin functional sites and testing them experimentally; 3) integrating electrostatic, sequence, and structural information to create a robust profiling method that can identify peroxiredoxin subfamilies; and 4) using it to create active-site signatures and profiles for a well-studied and important set of protein superfamilies. The data will be made widely available.
  
  This detailed functional site analysis of 6 superfamilies will yield insights into biological mechanisms, leading to hypotheses that can be experimentally tested. In the long term, the methods will enable more accurate functional site identification from sequence. The development of general concepts for identifying and classifying molecular functional site features will advance the design of enzymes with improved, altered, or novel activity and inhibitors (or lead compounds), an early step in the drug-discovery process. Students involved in this project will gain cross-disciplinary molecular biophysics training that will fuel successful scientific careers. In addition, the project informs a new interdisciplinary molecular biophysics course in which students are introduced to computational methods and work to interpret data in terms of protein structure. Graduate and undergraduate students from biochemistry, biology, chemistry, and physics as well as researchers from a local biopharmaceutical company studied the peroxiredoxin family in this course and were introduced to the ideas and communication skills necessary in an interdisciplinary research project.

• with Jason Grayson, Microbiology & Immunology, WFUHS
  Computational Modeling of Reactive Oxygen Intermediate Signaling in CD8+ T Cells
  Awarded $15,000 for the period 5/6/05 to 5/15/06
  Source: Cross-Campus Collaborative Research Support Fund

  CD8+ T cells are critical for clearing viruses, tumors, and certain bacteria. Understanding the molecular mechanisms that control these cells’ proliferation and death is critical for optimizing HIV and cancer vaccines and developing treatments for autoimmunity. Recently, the team demonstrated that treatment with MnTBAP, an anti-oxidant, reduces both the expansion and contraction of antigen-specific CD8+ T cells in vivo during viral infection. With treatment, proliferation decreased ten-fold, while the contraction phase was almost completely blocked. This result demonstrates that increased immunological memory can be generated from a smaller expansion of virus-specific cells. Despite these intriguing results, the molecular mechanisms by which reactive oxygen intermediates (ROI) affect proliferation and death have not been determined.

  The team hypothesizes: (1) cellular proliferation pathways are very sensitive to ROI levels, but activating death pathways requires a higher and chronic level of stimulation; and (2) different levels of ROI induce different redox responses that can be identified as part of a biological network. These hypotheses will be tested by (1) identifying cellular proteins oxidized at cysteine residues by high- throughput proteomics following T cell activation in vitro; and (2) developing framework models of the proteins involved in redox signaling networks in antigen-specific CD8+ T cells and compaing their topologies for different incubation conditions and different segments of the culture cycle.

• with S. Bruce King, Chemistry
  Profiling of Redox-Sensitive Signaling Proteins
  Awarded $18,478.36 for the period 5/1/06 to 4/30/07
  Source NIH

  Reynolds Professor Fetrow will direct the bioinformatics component of this ambitious project to devise large-scale methods to identify proteins that respond to cellular redox changes. The team aims to integrate analytical protein chemistry, cell biology, and bioinformatics to test the hypothesis that redox signaling affects the initiation of cell proliferation and transformation. Successful development of this technology will lead to future broad-scale research with implications for cancer prevention and treatment.

Errin Fulp

• Integrated Scalable Parallel Firewall and Intrusion Detection System for High-Speed Networks
  Awarded $95,116 for the period 8/08/07–8/07/08
  Source: Department of Energy (DoE)

  This project aims to develop a new, scalable network firewall and Intrusion Protection System (IPS) that can manage increasing traffic loads, higher network speeds, and strict Quality of Service (QoS) requirements.

  Firewalls remain the frontline defense for securing networks that are vital to private industry, government agencies, and the military. They filter arriving or departing traffic using an ordered list of rules that dictate the action to perform on specifically matched packets, such as discard, forward, or redirect. Firewalls with IPS capabilities can also inspect packets for virus and worm signatures.

  However, firewalls must also process legitimate traffic quickly, efficiently, and never violate the desired QoS. They can easily become bottlenecks; packets must be inspected and compared against complex rule sets, tables, and signatures, which is time-consuming. As a result, the firewall and, more important, the network it protects are susceptible to Denial of Service (DoS) attacks, which attempt to saturate the firewall with legitimate traffic. Legitimate users notice poor network performance and lower QoS.

  This project addresses these crucial high-speed security problems using firewall policy optimization and parallelization. The proposed solution provides an affordable, scalable, high-speed firewall and IPS. The design is robust, can differentiate traffic streams, and well-suited to mitigate DoS attacks.

• Firewall Architectures for High-Speed Networks
  Awarded $51,334 for the period 9/15/05 to 9/14/06
  Source: Department of Energy (DOE)
  
  As network technology advances and becomes more ubiquitous, firewalls must perform important security inspections under increasing traffic loads, faster network connections, and strict quality of service (QoS) requirements that render them susceptible to ottlenecks and denial of service (DoS) attacks. This project investigates a new architecture called hierarchical firewalls in which traffic is quickly distributed among machines based on perceived threat. Traffic considered safe is promptly forwarded into the secure network, while what remains is forwarded to different machines in the hierarchy for further scrutiny. Hence, traffic is segregated and queued based on security threat, yielding minimal delays for legitimate traffic, and the system is robust and highly available, since it uses multiple machines. Preliminary results indicate that it is 6 times faster than any other current firewall system and applicable to a wide variety of agencies in the public and private sectors.

• Systematic Development of Quantum Computational Software
  Awarded $45,000 for the period 2/1/07 to 1/31/08
  Source: North Carolina Biotechnology Center

• Systematic Development of Quantum Computational Software
  Awarded $15,000 for the period 2/1/07 to 01/31/08
  Source: Targacept
  Ab initio molecular dynamics (aiMD) is one of the most powerful simulation tools for studying material and biological complex systems. First introduced in 1985 by Roberto Car and Michele Parrinello, it combines theory with numerical computation and efficient computer implementations. However, novel applications and greater need for efficiency place a tremendous burden on existing aiMD software packages, increasing their size and complexity and making them harder to change and to maintain, to the point where a programmer with deep knowledge of the application at hand, physics, and computer science is needed for even simple modification.

  QUEST, a novel software system and programming paradigm, will fundamentally change the way highly complex aiMD algorithms are implemented. Together with researchers at partner company Targacept, Inc., the Wake Forest team will demonstrate the advantages of QUEST as an enabling technology for key biotechnology applications. If successful, QUEST will greatly reduce the cost of transitioning aiMD technology to biotechnology research and provide a common language to spark further improvements.

  Funding from this collaborative grant will help to support Dr. Yonas Abraham, a postdoctoral fellow in the Department of Computer Science. A computational physicist, he is uniquely positioned to make significant contributions and has already helped to validate the feasibility of the system design. Research efforts will be complemented by Associate Professor Todd Torgersen, an expert in compiler theory, and Dr. Roberto Car and Dr. Carlo Sbraccia at Princeton University. The work is expected to have a profound impact on drug discovery and molecular recognition and to benefit the scientific community at large.

• Computational Methods for Quantum Molecular Dynamics
  Awarded $16,000 for the period 10/1/06 to 11/30/07
  Source: National Institutes of Standards and Technology (Targacept)
  
  Over the last decades, molecular dynamics and powerful computer technology have been combined to study the dynamic properties of molecules, solids, and liquids. In particular, the Car-Parrinello method, a unifying approach for electronic structure calculations based on density functional theory and classical molecular dynamics simulations, enabled more accurate studies of molecular systems without requiring an a priori choice about the nature of the system. Since its appearance in 1985, the Car-Parrinello method remains one of the most influential and widely used for first-principles molecular dynamics. However, its computational requirements are extensive. Even a very short (picosecond) simulation of a small molecule of fewer than 30 atoms requires several weeks of processing.

  This project aims to develop and to optimize high-performance software for Car-Parrinello molecular dynamics simulations that can substantially increase their length and size for life-science applications and drug design. New approaches that will increase computational and memory efficiency will be explored for both single processor and parallel implementations. In particular, top-down and performance analyses of a base Fortran implementation will seek opportunities for optimization through program transformations and parallelization. Algorithmic transformations that can further reduce the overall computational cost will be studied, focusing on an efficient, modularized implementation.

• Computational Methods for High-Resolution Imaging and Data Mining
  Awarded $50,000 for the period 2/1/03 to 1/31/04
  Source: Air Force Office of Scientific Research (AFOSR)
  
  The project aims to investigate and to apply pupil-phase engineering concepts to problems arising in atmospheric imaging. It will also develop and implement fast algorithms for data mining of large astronomical datasets. The research is conducted in close collaboration with WFU colleagues Drs. Plemmons and Torgersen, among others.

• Phase II: Practical Enhanced-Resolution Integrated Optical-Digital Imaging Camera
  Awarded $103,464 for the period 1/22/07 to 6/30/07
  Source: University of New Mexico

• DTO Advanced Imaging Seedling Project, A Practical Enhanced-Resolution Integrated Optical Imaging Camera (PERIODIC) System, Supplementary Funds
  Awarded $62,026 for the period 9/15/00 to 02/28/07
  Source: Army Research Office (ARO)
  
  
  This DTO project, A Practical Enhanced-Resolution Integrated Optical Imaging Camera (PERIODIC) System, aims to analyze, optimize, simulate, design, and fabricate a beta prototype, integrated, optical-digital, low-profile, low-cost, array-based imaging system. Considerable progress has been made in the theoretical, computational, and design/fabrication aspects, leading to the development of very promising workable prototype systems. Successful completion of this seedling effort is expected by the end of 2006, with the help of the supplemental funds, which will support two graduate and one undergraduate student, working with Professors Pauca, Plemmons, and Torgersen. Funds will also purchase additional equipment and supplies by the design and fabrication group at Catholic University (CUA).
• Post-Detection Processing and Inverse Problems in Ground-Based Imaging

  Awarded $15,000 for the period 12/31/04 to 6/30/07
  Source: AFOSR, subcontract with University of New Mexico

  High-resolution images are essential to many important defense, science, engineering, law enforcement, and commercial applications. Extracting meaningful information from degraded images is especially vital for such biometric DoD applications as integrated optical imaging systems for personnel identification using the iris.

  This project will conduct extensive, novel research in pupil phase engineering (PPE) to help develop, along with industrial partner CDM Optics Company, a reliable, easy-to-use, low-cost iris recognition system for personal verification to ensure computer network security. The primary technical goal is to make iris recognition easier to use by greatly expanding the imaging system's iris capture volume; we estimate that our methods can increase iris capture volume more than 100 times over current systems. The design of overall optical masks is a nontrivial problem and involves the numerical solution of highly nonlinear and ill-posed optimization problems with multiple design parameters.

  Dr. Plemmons serves as Senior Scientific Consultant to establish a major research and development program in ground-based imaging for the Air Force Research Laboratory, including the Maui High Performance Computing Center, which houses one of the world's largest supercomputers.

• A Practical, Enhanced-Resolution, Integrated Optical-Digital Imaging Camera (PERIODIC) System
  Awarded $97,308 for the period 7/6/05 to 8/31/06
  Source: DOE

  This project aims to design an end-to-end optimized, compact, integrated, digital camera system with a modular architecture. Novel interferometric enhancements of optical resolution and use of information theory as an optimization tool will lead to imaging-system designs that maximize information throughput. Surveillance imaging systems will be developed for intelligence agency applications.

• Innovative Computational Methods for Inverse Problems in Optical and SAR Imaging
  Awarded $51,255 for the period 6/29/05 to 2/28/06
  Source: Army Research Office (ARO)
  

  High-resolution images are essential to many important applications in defense, law enforcement, engineering, science, and medicine. The project will result in a variety of new, robust, and efficient algorithms to extract meaningful information from degraded images, packaged into reliable software for timely transfer to research laboratories and industry.

• Wavefront Coded Imaging System for Iris Recognition - Phase III
  Awarded $200,000 for the period 7/1/04 to 2/28/05
  Source: ARO

The Wake Forest Group (WFG) and CDM Optics in Boulder, Colorado, are working together to deliver a reliable, easy-to-use, low-cost iris-recognition system for computer network security. Researchers are meeting on a regular basis at appropriate sites to exchange information, review progress, and coordinate plans as the work proceeds. These highly qualified teams, working in complementary research areas, are in an ideal position to further develop effective image quality control for personal verification, using enhanced iris-recognition camera systems.

• Pupil Phase Engineering and Wavefront Coding for Iris-Recognition Systems
  Awarded $250,000 for the period 3/1/04 to 12/31/04
  Source: ARO

This joint project with industrial partner CDM Optics Company conducts extensive, novel research in pupil phase engineering (PPE) to develop reliable, easy-to-use, low-cost personal verification for computer network security, using an iris-recognition system. The primary technical goal is to greatly expand the imaging system's iris capture volume. Additional work will build on a growing understanding of the optimization strategies and requirements for iris- recognition algorithms. By phase-encoding optical images in the pupil plane and then digitally restoring them to remove certain aberrations, such as defocus, their quality can be greatly improved. The design of overall optical masks is a nontrivial problem involving the numerical solution of highly nonlinear and ill-posed optimization problems with multiple design parameters.

• with Todd Torgersen and Paul Pauca
  Enhancement of Research and Development: Novel Image Quality-Control Systems, with Applications to Personnel Identification Imaging Systems
  Awarded $786,022 for the period 9/1/03 to 12/14/04
  Source: ARO supplements

High-resolution images are essential to many defense, science, engineering, law enforcement, and medical applications. The need to extract meaningful information from degraded images is especially vital for such defense department applications as integrated optical imaging systems for personnel identification using biometrics technology, such as iris identification. Sources of image degradation vary among applications but include blur, insufficient sampling, electronic noise, and other defects. In personnel identification applications, for example, out-of-focus blur creates stringent demands on physical positioning, wasting valuable time as the subject tries to align with the camera. While sophisticated imaging systems with auto-focus mechanisms can mitigate the problem, they are noisy, bulky, and expensive. This extended project includes the following interrelated research and development activities for image quality control using pupil-phase engineering (PPE), a technique combining optical/electronic hardware with digital processing:

• Develop enhanced and cost-effective iris-recognition imaging systems using extended depth-of-focus technology;
• Develop new design and optimization strategies to maximize the critical information content in iris imagery as dictated by state-of-the-art iris-recognition algorithms;
• Develop and make available efficient software and integrated imaging systems that combine optics and signal processing for solving relevant design optimization problems in image quality control;
• Perform a preliminary investigation applying PPE to enlarge the field-of-view, decreasing restrictions on the later position of the subject's iris;
• Extend technology transfer activities to additional government agencies as well as to commercial organizations with DOD contracts.

The interdisciplinary, cross-institutional team's recent advances in technologies for optical wavefront manipulation by PPE, optical detection, and digital post-processing have opened new possibilities for imaging systems that differ dramatically in function from traditional cameras. Extensive cross-fertilization of mathematical formulations, computational techniques, and system architectures from different imaging modalities is expected to result in quantum leaps in the performance of more traditional imaging systems.

Stan Thomas, with David John
A Consortium to Promote Computational Science and High-Performance Computing
Awarded $11,250 for the period 7/1/05 to 6/30/06
Source: Appalachian State University

• Innovative Methods for High-Resolution Imaging and Feature Extraction
  Awarded $21,508 for the period 7/5/05 to 7/4/08
  Source: ARO
  
  
  Traditional imaging technologies used in many military and commercial applications rely on independently optimized imaging, processing, and feature-extraction subsystems. Large volumes of diverse data pertaining to an object or scene are collected and then digitally processed to extract high-order information, such as its location, class, and shape. However, the disjuncture of the subsystems limits overall performance. The next generation of imaging systems will require end-to-end optimization, tuning both imaging sensor and processing technologies. Data collection will then maximize performance of the digital processing algorithms for feature extraction, clustering, and classification.
  
  
  This project aims to develop integrated system designs for improved localized contrast image enhancement and classification and clustering of hyperspectral data. These two related tasks are central to several applications of interest to the Army, such as target recognition and night vision systems.

• (see also Plemmons)

William Turkett

• with Susan Sergeant, Biochemistry, WFUHS
  Integration of Neutrophil Function and Signaling Networks with Computational Modeling
  Awarded $20,000 for the period 5/06 to 5/07
  Source: WFU Cross-Campus Collaborative Research Support Fund

  Human neutrophils, a type of white blood cell, locate and kill invading microbes that can cause disease. When they interact with microbes, signal transduction events efficiently move information through them, enabling them to respond appropriately. Although individual neutrophil signaling events have been studied, the organization of their cellular signaling networks is poorly understood. Even less is understood about how signaling networks regulate neutrophil functional responses. The project’s systems biology approach integrates neutrophil function and signaling networks with computational modeling methods. It will 1) assess simultaneous signaling events and the neutrophil response at the single-cell level by flow cytometric methods, 2) develop a computational method to integrate functional and signaling data, and 3) computationally model neutrophil signaling networks in the context of the functional outcome, to begin to verify and to predict neutrophil signaling pathways.

• Lightweight Architectures for Decision-Making in Domains with Uncertainty
  Awarded $2,200 for the period 12/1/05 to 11/30/06
  Source: WFU Science Research Fund

  This research aims to develop and to evaluate a set of probabilistic algorithms that promote effective and efficient decision-making in domains that contain uncertainty and can be executed on lightweight hardware devices. These algorithms use exploitation of domain structure and run-time knowledge to significantly reduce the usual computational requirements for reasoning under uncertainty. Their ability to perform on lightweight personal computers should be a significant step toward truly mobile personal assistants and autonomous reasoning systems.

Yue-Ling Wong (see also Art)

• with Jennifer J. Burg
  Integrated Digital Media Curriculum
  Awarded $287,280 for the period 1/1/04 to 12/31/06
  Source: NSF

  This project will develop curricular material that bridges the gap between digital media and digital art. Building on a proof-of-concept grant that produced learning units in image, sound, video processing, and multimedia programming, it is arranged around a primer, relevant to both computer science and art students; an advanced computer science module, emphasizing the mathematics and technology underlying digital media; and an advanced art module, emphasizing aesthetics and design. The web- and text-based material, divided into recombinable topics, interactive exercises, and demonstrations, stresses concepts over applications and is designed to promote students' active, informed use of digital media tools. Content, the development of an appropriate learning hierarchy, the nonlinear linking of concepts, and pedagogical effectiveness will be assessed in four external sites: a university with large digital media courses, a largely minority university, a community college, and a technology magnet high school. The material will be disseminated through a faculty development workshop, conference presentations, journal articles, and commercial publication.

• The Art and Science of Digital Media: A Curriculum Development Project
  Awarded $37,276 for the period 1/1/03 to 1/1/04, Year 2 of 2
  Source: NSF

  The NSF will support software to enhance the new digital media courses the Computer Science department will be offering for both majors and nonmajors. Interactive tutorials and novel electronic delivery formats, particularly the e-book, will be investigated to help students to learn abstract concepts and cutting-edge technologies.