Paul R. Anderson

Quantum effects for black holes and analog black holes and the validity of the semiclassical approximation

Awarded $136,660 for the period 6/1/15 to 5/31/18

Source: National Science Foundation (NSF)

The stress tensor for free quantum fields will be computed for those spacetimes when matter undergoes spherically symmetric collapse to form a black hole. Wavepackets will be used to investigate the time-dependence of the particle production that occurs. The validity of the semiclassical approximation will be investigated for those cosmological spacetimes when quantum effects are large and when an electric field in two-dimensions decays via particle production. The density-density correlation function is computed for a Bose-Einstein condensate analog black hole, which, although treated as a one-dimensional object, has phonon excitations in the transverse directions.

Studies of particle production, vacuum polarization, and the validity of the semi-classical approximation in gravity

Awarded $41,275 for the period 6/1/13 to 5/31/14

Source: NSF

Projects study particle production, vacuum polarization, and the validity of the semi-classical approximation in various spacetimes. Studies of the early stages of black hole evaporation will be more detailed than ever before and elucidate what happens to the information about how a black hole forms. The density-density correlation function will be computed for a Bose Einstein Condensate set up as a black hole analogue.

Studies of quantum fields in cosmological and black hole spacetimes

Awarded $120,000 for the period 8/1/09 to 7/31/12

Source: NSF

Evidence indicates that, early in its history, the universe expanded or inflated exponentially, and it may be doing so again. Undergraduate and graduate student participants will be trained in numerical and analytical research techniques that will elucidate phenomena ranging from the expansion of the universe to the effects of quantum fields on black holes. If quantum fluctuations destabilize an exponentially expanding universe, predictions of its future and most inflationary scenarios will be affected. If calculations for reheating in some chaotic inflation scenarios are invalidated, then more sophisticated calculations will be necessary. Investigating particle production during and after gravitational collapse will clarify what happens to information about black-hole formation. Finding that zero-temperature black holes do not exist could have important consequences for thermodynamics.

Studies of Classical and Quantum Effects in Gravity

Awarded $32,198 for the period 4/2/07 to 6/30/08

Source: NSF

Current cosmological observations imply that the universe may have recently begun a second period of exponential expansion. This project addresses several questions with implications for accepted theory. First, it will study whether quantum fluctuations in the density and pressure of matter and radiation might be unstable during such a period, with serious consequences for the fate of the universe. The semi-classical approximation to quantum gravity, at the foundation of most models of inflation, would be invalid during at least part of this period and would have to be replaced by some more sophisticated theory.Second, the project will study whether quantum fluctuations would be large enough to invalidate the types of calculations that have previously predicted the amount of particles produced at the end of inflation in popular chaotic inflationary models. The amount of particle production determines the temperature to which the universe reheats after it finishes inflating, which largely determines its evolution.Third, the project will develop a new method to compute the self-force of a particle orbiting a nonrotating black hole and emitting scalar radiation. If successful, it could be generalized to the realistic case of a particle orbiting a rotating black hole and emitting gravitational radiation. One of the primary sources of gravitational waves for a space-based detector, like LISA, is a compact object spiraling into a super massive black hole. Its trajectory is necessary to get the waveform for the gravitational waves that are emitted and can be obtained by solving the radiation reaction problem in gravity. To date, the self-force has only been computed in cases of high symmetry, such as circular orbits or radial infall. Fourth, the project will investigate the important case of zero temperature black holes. Due to the Hawking effect, black holes radiate and can be assigned thermodynamic properties, such as temperature and entropy. Quantum effects can alter the spacetime geometry near the event horizon to change its temperature and entropy. If the project finds that zero temperature black holes cannot exist, results will have important consequences for black hole thermodynamics. Finally, the project supports undergraduate and graduate student training in both numerical and analytical research techniques.

Keith Bonin

Real-time dopamine signaling and ethanol drinking behavior

Awarded $3,261 for the period 6/1/15 to 5/31/16

Source: National Institutes of Health (NIH) / Wake Forest Health Sciences (WFHS)

The effect of dopamine release on alcohol drinking behavior is poorly understood. Experiments are designed to determine whether increased ethanol drinking can be better predicted from initial measures of accumbal dopamine signaling or adaptive changes in dopaminergic transmission. Optogenetic approaches – a radical new technology for controlling brain activity with light – will be used to test the regulatory influence of specific dopamine release patterns on appetite for, and consumption of, alcohol and to determine how glutamatergic projections from the basolateral amygdala and prefrontal cortex influence accumbal dopamine signaling and operant ethanol self-administration. This functional mapping of the microcircuitry involved in alcohol consumption will be critical for developing effective treatment strategies for abuse and addiction.

Accelerating Drug Discovery: On-chip selection of DNA-Encoded Chemical Libraries

Awarded $20,000 for the period 7/1/12 to 6/30/14

Source: NanoMedica LLC

Accelerating Drug Discovery: On-chip selection of DNA-Encoded Chemical Libraries

Awarded $100,000 for the period 7/1/12 to 6/30/14

Source: North Carolina Biotechnology Center (NCBC)

This novel, proprietary NextGeneration Sequencing-enhanced drug discovery platform promises to increase throughput of Wake Forest University’s proprietary Lab-on-Bead technology dramatically, while reducing the time required to identify new drug candidates and corresponding labor and material costs. Commercial development targets discovery of new drug leads and diagnostic reagents for treating and managing cancer.

Cell Mechanics and Protein Mobility during Neoplastic transformation

Awarded: $400,000 for the period 7/15/11 to 6/30/14

Source: NSF

Recent reports indicate that cancerous and normal cells have different physical and mechanical properties, but how these properties change for different cancer cells is ambiguous. For example, some researchers report that cancer cells are softer than normal cells, while others report they are stiffer. This project aims to determine whether these cells were at different stages in their progression from normal to cancerous (neoplastic transformation) or different tumor and cell types. Specifically, it will quantify changes in mechanical properties of human mammary endothelial (HME) cells during neoplastic transformation through particle tracking,  cell squeezing, and fluorescence recovery after photobleaching (FRAP) of membrane proteins. FRAP will also be used to determine changes in cytoplasmic and nuclear protein mobility. This work will establish how and why the mechanical properties of HME cells change as they progress from normal to cancerous, which may improve cancer diagnosis, treatment, and prognosis.

Optical Torquing and Nanofluidics

Awarded: $49,771 for the period 1/1/05 to 12/31/06

Source: Research Corporation

Research and technology are driving toward smaller scales in hope of creating faster and more powerful computers, more sensitive and accurate environmental and biological sensors, less invasive medical instruments, and more effective medicines. This project will use laser light to trap and to manipulate very small cylindrical rods or tubes, rotating them and placing them on specially prepared surfaces that will change their electrical properties. Watching how their rotation changes as they move close to a surface will elucidate surface interactions. The project will also study how the properties of the surrounding medium (water, dilute solutions of flexible rods) change the nanorods’ rotation. This research will aid novel nanodevice development, lead to a new understanding of nanofluidic flow near surfaces, and stimulate and guide experimental and computational work by others. Two undergraduates will learn cutting-edge research. The project will also greatly improve departmental capabilities in single-molecule research and encourage collaborations between researchers in different physics areas and at the Medical School.


Novel Energy Harvesting Fabric

Awarded $47,999 for the period 1/1/16 to 6/30/16

Source: Army Research Office (ARO) / Streamline Automation

No abstract.

LJus OLEV Development

Awarded $253,000 for the period 10/1/15 to 3/30/16

Source: LJus, Inc.

The investigators focus on determining ways to enhance the lumens-per-watt (LPW) output of OLEV lamps and use new analytical tools to examine the power of the interconnected system, or the reduced capacitive interconnect (RCI), throughout its circuit components. Findings will be used to maximize efficiency when the newly designed drivers are coupled to the OLEV, using larger and larger segment sizes to understand the effect of scale-up on the RCI. It will determine the limits of OLEV lifetimes and manufacturing processes.

Organic thermoelectrics: The matrix composite approach

Awarded $45,000 for the period 9/17/15 to 9/30/16

Source: Air Force Office of Scientific Research (AFOSR)/Texas A&M Engineering Experiment Station

This program is developing a lightweight, flexible, unobtrusive fabric that, when applied to large area waste-power sources, such as people, tents, transport equipment, or aircraft platforms, will generate more power than its small but efficient ceramic counterparts. It will be robust to the environment, puncture, and tear, making it ideal for military applications.

Partnership for Innovation: Accelerating innovation research – technology translation of a graphenated-carbon nanotube (g-CNT) composite for a miniature, fiber-integrated spectroscopy light source

Awarded $16,667 for the period 6/3/15 to 12/31/15

Source: NSF/Duke University

No abstract.

Ljus OLEV Development

Awarded $500,000 for the period 10/1/14 to 9/30/15

Source: LJus, Inc.

First, routes to enhance the lumens-per-watt (LPW) output of OLEV lamps will be determined. Second, new analytical tools at the NanoCenter will be used to examine the power of the interconnected system, or the reduced capacitive interconnect (RCI), throughout its circuit components. This information will be used to help mate the newly designed drivers to the OLEV at the highest possible efficacy, using larger and larger segment sizes to understand the effect of scale-up on the RCI. The extreme limits to OLEV lifetimes as well as manufacturing processes will be determined.

Power-generating coverings

Awarded $350,000 for the period 10/15/14 to 9/14/16

Source: National Aeronautics and Space Administration (NASA) / Streamline Automation

The project aims (1) to optimize solution-based ink doping of commercially sourced nanotube paper for power production and reliability, working with commercial nanotube paper sources to optimize the paper for this application; (2) to develop and optimize a process for integrating the piezo-electric component into the power-generating material; (3) to optimize the junction width and to develop folding techniques; and (4) to develop an alpha production line that includes paper handling, doping and coating, poling, folding, power management, and encapsulation as necessary.

PF-DT WOLED Development

Awarded $200,000 for the period 2/11/13 to 7/31/13

Source: CeeLite Technologies, LLC

This project examines the feasibility and commercial impact of the newly developed WFU PF-BT white-emitting homopolymer family; specifically, its performance in two device architectures: field-induced polymer electroluminescent (FIPEL) and white organic light-emitting diodes (WOLEDs).

Nanotubes in tumor imaging and therapy

Awarded $20,250 for the period 3/1/11 to 2/29/12

Source: NIH/Wake Forest Baptist Health

Wake Forest investigators have developed prototype multifunctional, multiwalled carbon nanotubes that can image and treat tumors simultaneously. They will fabricate nanotubes of different lengths, architectures, and composition to assess their effectiveness in tissue culture and mouse models. The goal is a therapy that can be precisely directed with low nonspecific toxicity, compatible with standard clinical imaging instruments, and easily cleared by the body.

Purelux Optimization

Awarded $23,543 for the period 9/1/10 to 6/30/11

Source: PureLux, Inc.

The project uses nanotechnology to produce visible light directly rather than by heating a filament or gas. Very thin, lightweight, and energy efficient, the resulting product could serve a wide range of residential, commercial, and military applications.

Hybrid Organic-Inorganic Composite Solar Cells for Efficient, Low-Cost, Photoelectric Energy Conversion

Awarded $102,500 for the period 9/1/09 to 8/31/10

Source: US Department of Energy (DOE)/University of South Carolina

This project aims to assemble, fabricate, and test organic photovoltaic devices to serve as solar cells.

Nanocomposite Distal Tips for Guidewires

Awarded $45,000 for the period 9/25/09 to 9/24/10

Source: Cook Medical

No abstract.


Awarded $18,000 for the period 7/1/10 to 7/31/10;

$2,127 for the period 8/1/10 to 8/16/10; $22,595 for the period 8/25/10 to 8/26/10

Source: PureLux, Inc.

The project will use nanotechnology to produce visible light directly rather than by heating a filament or gas. Very thin, lightweight, and energy efficient, it could serve a wide range of residential, commercial, and military applications.


Awarded $200,000 for the period 12/31/09 to 3/31/10

Source: FiberCell, Inc.

Wake Forest and New Mexico State University scientists will improve the efficiency of solar cells based on a novel architecture that uses nanotechnology and optical fibers.

Hybrid Organic-Inorganic Composite Solar Cells for Efficient, Low-Cost, Photoelectric Energy Conversion

Awarded $99,999 for the period 9/1/08 to 8/31/09

Source: DOE/USC

No abstract.

Nanocomposites for energy utilization

Awarded $11,400 for the period 11/16/08 to 11/15/09

Source: Thai Government

No abstract.

Targeted CNx NAnowire-Drug Complexes for Enhanced Chemotherapeutic Efficacy

Awarded $ for the period 9/1/08 to 9/30/09

Source: Congressionally Directed Medical Research Program

Conference for Nanomedicine

Awarded $5,000 for the period 11/1/07 to 4/8/08

Source: NCBC

The Focused Workshop in NanoMedicine: Therapeutic Hyperthemia Problems will bring approximately 100 scientists, engineers, medical researchers, and nanopharmaceutical representatives together for a three-day forum. Twelve invited and 24 contributed talks will discuss the development of nanotherapeutics used in hyperthermia treatments of disease and how it might be guided by traditional pharma. To our knowledge, this workshop will be the first nationwide that is designed to understand the integration of therapeutic development and scientific innovation for an entire class of therapeutics.

MURI: Self-Assembled Soft Optical NIMS

Awarded $115,677 for the period 10/1/09 to 9/30/10

Source: AFOSR/Kent State University

Negative Index Materials (NIMs) promise a wide variety of exciting applications, such as flat, apertureless lenses; “perfect” lenses with subwavelength resolution; novel antennas; new beam-steering devices; sensor protection strategies; novel band-gap materials; and high-density optical storage. They do not occur in nature, but inherent obstacles have been overcome using such structures as split-ring resonators, which have large negative magnetic susceptibility in the frequency range of interest. To avoid scattering, their linear dimensions must be smaller than a wavelength. Great interest is focusing on VIS NIMs, which operate in the visible range of the spectrum, but the difficulty of creating the appropriate resonant structures on the required nanometer lengths has impeded development. This multidisciplinary team aims to realize NIMs in the VIS-IR range. The materials will consist of oriented dispersions of metallic nanoparticles, forming a liquid crystal phase, in a host matrix that may also be liquid crystalline. They will be created via self-assembly of the nanoparticles with functionalized surfactant/tethers and processed to form large, thick, 3D films. As liquid crystals, these NIMs will be soft and responsive, allowing easy processing and switching.

Characterization of the Potential Toxicity of Metal Nanoparticles in Marine Ecosystems Using Oysters

Awarded $66,336 for the period 4/05/07 to 3/04/09

Source: Environmental Protection Agency (EPA)/UNC Charlotte

No abstract.

Targeting the Glycocalyx (capsule/exopolysaccaride) to Reduce Bone/Implant Related Infections

Awarded $39,696 for the period 7/1/06 to 6/30/08

Source: Orthopaedic Research Education Foundation

NANOTECH will collaborate with the WFUHS Department of Orthopedic Surgery.

Novel Carbon Nitride (CNW) Conjugates for Breast Cancer

Awarded $91,055 for the period 8/15/06 to 8/14/07

Source: Department of Defense, Congressionally Directed Medical Research Programs (CDMRP)

Recently, single-walled carbon nanotubes (SWNT) and Ag nanoshells have been shown effective in photo-ablating cultured cells. In both cases, penetrating infrared light generates heat in the nano-object to raise the temperature in surrounding cells. While promising, the applicability of these approaches to real therapeutics is limited because, in both cases, high amounts of light are required to initiate cell death in tissues. Further, these nanocarriers lack specificity or targeting modalities.Carbon-based nanoparticles can be chemically modified to selectively target breast cancer cells, and when coupled to carbon nitride nanotube variants, the resulting conjugates can be activated to photo-ablate tumors with an extraordinarily small amount of power. This program will test the concept that carbon nitride nanowires (CNWs), conjugated to Herceptin, a therapy for certain breast cancers, can selectively target and photo-thermally ablate HER2-positive breast cancer tissues, using penetrating near-infrared radiation. Initial results suggest that CNWs are far superior to SWNTs or silver nanoshells due to their metallic nature and aspect ratio. This unique property of CNWs opens a new therapeutic application at depths more clinically relevant than the simple subcutaneous limits of previous approaches and with reduced dermal injury. They can also carry multiple functionalities, such as contracting agents, for imaging the target area, which will allow them to be locally activated.

Assessment of Status and Opportunities in Nanophase Transition Metal Oxide Coatings for Air Pollution Control and Mitigation

Awarded $15,000 for the period 7/20/06 to 11/21/06

Source: EPA

The project will generate a report on the state-of-the-art in nanoscale photocatalytic coatings based on transition metal oxides. This analysis of the literature and intellectual property should answer the following questions:

  • What advantages does nanotechnology offer in developing efficient photocatalysis of pollutants?
  • What mechanisms benefit from small size, surface proximity, high fields, defect exclusion, surface trapping, and extended coherence of excited states?
  • Can nanotechnology enhance cross-sections, separate charges, or mitigate well-known tendencies toward poisoning of the catalyst in realistic environments?
  • Can we conclude that current engineering technologies for broad area thin film fabrication are sufficient for practical implementation of such nanophase materials?

The answers to these questions will identify both the opportunities and bottlenecks to implementing such technologies in air pollution control/mitigation. The project will significantly enhance EPA’s knowledge base in this important science field, and the product will serve the strategic planning process as a screening tool for future research and future NCER and SBIR solicitations.

Self-Assembled Soft Optical NIMs

Awarded $115,677 for the period 10/1/06 to 9/30/07


Negative Index Materials (NIMs) promise a wide variety of exciting applications, such as flat, apertureless lenses; “perfect” lenses with subwavelength resolution; novel antennas; new beam-steering devices; sensor protection strategies; novel band-gap materials; and high-density optical storage. They do not occur in nature, but inherent obstacles have been overcome by the use of specially constructed resonant structures, such as split ring resonators, that have large negative magnetic susceptibility in the frequency range of interest. To avoid scattering, their linear dimensions must be smaller than a wavelength. Their tremendous scientific and technological potential has generated great interest in VIS NIMs, which operate in the visible range of the spectrum, but none have been yet realized, due to the difficulty of creating the appropriate resonant structures on the required nanometer lengths. The multidisciplinary team aims to realize NIMs in the VIS-IR range. The materials will consist of oriented dispersions of metallic nanoparticles, forming a liquid crystal phase, in a host matrix that may also be liquid crystalline. They will be created via self-assembly of the nanoparticles with functionalized surfactant/tethers and processed to form large, thick, 3D films. This strategy will optimize the materials’ response to competing factors of index magnitude, loss, dispersion, and anisotropy. As liquid crystals, these NIMs will be soft and responsive, allowing easy processing and switching.

Charge-Transfer Nanocomposites: The Effects of Scale Hierarchy

Awarded $151,000 for the period 1/1/06 to12/31/06

Source: AFOSR

This research program will first quantify charge-transfer mechanisms and time scales relevant to nanoparticulite/electro-active polymer blends (charge-transfer nanocomposites). These features will be correlated with induced morphological modifications, modifications to optical absorption cross-sections, and localization effects. The program will then examine electronic and optical phenomena associated with degrees of matrix order and disorder, or scale hierarchy, to determine if nanotube/host interactions are modified when the nanoparticles are ordered over length scales commensurate with polarons/excitons or the wavelength of incident light. Finally, the program will integrate nanotube-based matrix composites into organic photovoltaic devices and organic optical sensing devices, such as CCDs (charge-coupled devices), which are used in digital and video cameras and optical scanners, and photodiodes.

Agile Response Coatings

Awarded $1,443,000 for the period 4/1/05 to 3/31/08

Source: AFOSR

For twenty years, US forces have increasingly been required to respond to asymmetric situational threats, and Air Force technologies must perform multirole surveillance and tactical tasks. Reliance on slower, long-term, unmanned platforms with search-and-destroy capabilities like the Global Hawk system and stealth insertion using manned vehicles like the F-117 and B-2 demands agile coloration that can sense ambient thermal and lighting conditions; novel materials solutions to deterioration in aging and long-term deployed systems; and the ability to monitor all operational aspects of vehicle integrity, including structural and air frame components during flight. The Agile Response Coatings (ARC) program aims to develop a single coating system that biomimetically responds to its surroundings and airframe integrity, using sensing and electromagnetic modulation technologies based on novel nanostructured materials.

Samuel Cho (see also COMPUTER SCIENCE)

Extrapolating the concept of protein corona for understanding nanoparticles at large

Awarded $93,491for the period 8/15/12 to 7/31/15

Source: NSF/Clemson University

These studies aim to decipher the basic mechanisms of biocorona formation using molecular dynamics (MD) simulations (Cho lab) validated by experiment (Ke lab). Results will translate well-established theoretical and simulation approaches from protein folding to NanoEHS for great educational, economic, and environmental benefits. The Cho lab develops and performs MD simulations to examine the formation of AgNP-biocoronas at molecular resolution and to define the main determinants, such as time, free energy, and stability. Their GPU-optimized approaches perform 10-100x faster than traditional CPU approaches that preclude simulations at the relevant time and length scales. The Ke lab will validate these calculations experimentally; then additional simulations will guide the design of new NP-biocorona simulations. The Cho lab will also model NP binding interactions with proteins and glucose.

Gregory Brown Cook

Quasi-equilibrium BH-BH and NS-BH binary Initial Data

Awarded $35,000 for the period 10/8/08 to 10/31/09

Source: NSF

The collision of a pair of compact objects, either black holes or neutron stars, is a dramatic event that gravitational wave observatories, such as LISA and LIGO, hope soon to detect. The simulations to be performed in this project, starting from compact binary initial data, will provide the theoretical foundation for interpreting much of the data these observatories obtain. This work aims to improve the techniques and numerical tools for constructing compact binary initial data, to explore the space of interesting solutions, and to train undergraduate and graduate students.

Martin Guthold

Comprehensive Cancer Center Grant: Fall 2014

Awarded $40,000 for the period 2/1/2015 to 1/31/2016

Source: NIH/WFBH

In collaboration with the start-up company NanoMedica, LLC, this project is developing a novel drug-discovery method based on next-generation sequencing chips. DNA polonies, small colonies of identical DNA, can be exploited for high-throughput binding experiments. Flowing a fluorescently labeled protein target over the chip and observing binding events with a fluorescence microscope immediately reveals novel aptamer-target binding pairs. In a more sophisticated implementation, DNA fragments of each polony can be converted into a drug library by hybridizing DNA-encoded molecule libraries; collaborator Dr. Liu (Harvard) is providing a 13,824-member encoded macrocycle library. Proof-of-principle experiments, funded under an NIH SBIR phase-I project, had two specific aims: (1) mock drug selection with FITC-labeled DNA; and 2) selection against Scr kinase from the 13,824 member Liu library. Conducting complementary experiments will vastly increase the chances for a successful phase-II application.

Lab-on-Bead-enabled, next-generation sequencing for cancer drug discovery

Awarded $11,390 for the period 11/1/12 to 4/30/16

Source: NIH; NanoMedica LLC

This project combines an encoded macrocycle library screening and candidate molecule selection to discover new anticancer drug candidates. This next generation Lab-on-Bead sequencing and selection method is designed to discover more with less: it requires only tiny amounts of target molecules and library candidates and may ultimately be able to screen up to 108 drug candidates in less than a day.

Accelerating Drug Discovery: Front-end Library Screening for Biological Relevance

Awarded $250,000 for the period 1/1/11 to 12/31/12

Source: NCBC

The development of vast, nucleotide-encoded chemical libraries holds extraordinary promise for discovering new drug candidates, diagnostic reagents, and chemical probes, but their exploitation requires an effective selection process. This collaboration among Cancer Biology, Chemistry, and Physics teams and an NC-based commercial partner, NanoMedica, Inc., couples novel, highly efficient capillary electrophoresis and whole-cell preselection methods to create nanobeads functionalized with multiple copies of a unique, nucleic-acid-encoded chemical, followed by the identification and extraction of target-bound beads using inverted and atomic force microscopes or a micropipette system. Nanoselected candidates will be identified by PCR amplification of their coding sequences followed by validation assays.

Mechanical Properties of Native and Variant Fibrin Fibers

Awarded $20,000 for the period 7/1/09 to 6/30/10

Source: American Heart Association

This project studies the mechanical properties of individual fibrin fibers and fibrin fiber junctions in a fibrin clot. The strength and failure mechanisms of branching points will be compared to those of individual fibers. The goal is to construct a realistic mechanical model of a blood clot. Atomic force microscopy will be used to record force data while stretching a fiber, and an inverted fluorescence microscope allows the manipulation to be viewed and recorded. The stress/strain curves produced can be used to determine the visco-elastic modulus, elastic modulus, force relaxation rates, modulus stiffening at high strains, and energy loss.

Determining the Mechanical Properties of Single Fibrin Fibers

Awarded $225,000 for the period 7/01/07 to 6/30/10

Source: NSF

Blood clots perform the essentially mechanical task of stemming blood flow. However, the mechanical properties of clot constituents are largely unknown. Besides platelets, which initially aggregate at the site of a wound, the major structural component is a branched network of fibrin fibers. A novel technique, combining atomic force and fluorescence microscopy in a single instrument, will be used to systematically study the mechanical properties of single fibrin fibers and a variety of mutants under a variety of conditions.

George Holzwarth

Kinesin Force-Velocity in Curves when 1, 2, or 3 Motors Transport a Single Load

Awarded $5,013 for the period 8/1/07 to 7/31/08

Source: NIH

The project’s long-term objective is to elucidate, at the molecular level, how the motor protein kinesin transports vesicles from a neuron’s cell body to its axon tip, a distance of as much as 1 meter, in only 4 days. The velocity/force relation of one kinesin motor is well understood when the motor is in solution, and the viscous work load on it is small. However, within a cell, the viscoelastic drag force opposing the motor is at least 100 times greater, so 2-5 motors are probably required to pull a single vesicle. Quantitative velocity/force curves have been obtained for 1 kinesin but not for the 2, 3, or more active motors actually needed to pull a single load in vivo, and qualitative data on the effect of multiple motors are contradictory. The project will test the hypothesis that 2 or more motors pulling a single cargo will share the load equally. It aims to measure velocity/force curves for 1, 2, and 3 kinesins over a physiologically realistic force range. Using speckled microtubules to provide numerous fiduciary marks along the length of each microtubule will greatly improve the spatial precision of tracking over classical gliding assays, which use uniformly labeled microtubules, and the temporal precision will be 0.1s or better. If the gliding microtubule can be tracked for 5-10s, the pattern of velocity changes will reveal the number of active motors. Force will be generated by viscous drag and magnetic beads bound to the gliding microtubule. The exceptional length of some neurons places exceptionally stringent demands on their vesicle transport systems and suggests that some neuronal disease may originate in a transport system failure. Mutations in microtubule motor proteins have been shown to cause disease phenotypes in Drosophila and degenerative diseases of the human nervous system. A more quantitative analysis of multiple motor mechanics will expedite the identification of degenerative diseases associated with defective transport and facilitate rational intervention.

Kinesin Force-Velocity Curves when 1, 2, or 3 motors transport a single load

Awarded $20,000 for the period 1/27/06 to 1/26/07

Source: Dreyfus Foundation

Dr. Holzwarth is one of 14 national winners of the prestigious Senior Scientist Mentor Award for 2006. Faculty with emeritus status who maintain active research programs in the chemical sciences are awarded grants of $10,000 annually for two years to support undergraduate research under their guidance. The maximum force generated by 1 kinesin motor protein molecule in vitro is 7 pN. There is indirect evidence that in cells, several kinesin motors must cooperate to move a single vesicle, because the drag force that must be overcome is 5 pN. We will measure velocity-force curves for 2, 3, or 4 kinesin motors pulling a single load in vitro against a carefully measured viscous or magnetic force.

N. A. W. Holzwarth

Computational studies of solid electrolytes

Awarded $200,000 for the period 9/1/15 to 8/31/18

Source: NSF

Stable, efficient batteries for applications ranging from micro devices to electric vehicles to renewable energy storage are urgently needed, but improvements will require innovations to cathode, anode, and electrolyte materials, their interfaces, and the integrated battery itself. This project studies several solid electrolyte systems and their interfaces with ideal electrodes using a combination of first principles and empirical computational techniques.

with Timo Thonhauser, Physics, and Akbar Salam, Chemistry

ES12: 24th Annual Workshop on Recent Developments in Electronic Structure Theory

Awarded $10,000 for the period 6/1/12 to 5/31/13

Source: US Department of Energy (DOE)

The workshop brings investigators in electronic structure theory from around the world to the WFU campus. Invited presentations and contributed posters describe new methods for computing previously inaccessible properties of materials, breakthroughs in computational efficiency and accuracy, and novel applications of these methods to the study of molecules, liquids, and solids. It represents a valuable opportunity for students, postdocs, and senior researchers to present their ideas and learn from each other. Funding contributes to its success especially by keeping participant costs low and making attendance more widely accessible.

ES12: 24th annual workshop on recent development in electronic structure theory

Awarded $5,000 for the period 5/15/12 to 5/14/13

Source: Army Research Office (ARO)

Wake Forest University will host the workshop from 5-8 June 2012 ( Organized with Timo Thonhauser, Physics, and Akbar Salam, Chemistry, it will bring together electronic structure theorists from universities, colleges, institutes, and laboratories around the world. Invited presentations and contributed posters will describe new methods for computing previously inaccessible properties of materials; breakthroughs in computational efficiency and accuracy; and novel applications to study molecules, liquids, and solids. Funding will keep participant costs low and make attendance more accessible.

First Principles Simulations of Battery Materials

Awarded $100,000 for the period 9/1/13 to 8/31/14

Source: NSF

Advances in battery capacity, safety, and stability are needed to meet projected energy storage needs. First principles simulations of their materials will provide a detailed, atomic-level understanding of their conduction mechanisms to explore optimal stoichiometries and structures. Simulations using simple atomic level models will also explore the relationship of the electrolytes’ microscopic and macroscopic properties. Another project is designed to increase the physical accuracy of the simulation techniques for materials containing the localized orbitals typically found in cathode materials. Training students to perform computational materials research is a large part of this effort. With the help of colleagues at Winston-Salem State University, it hoped that minority students will be among those attracted to this effort.

Computational Study of Transition Metal Phosphate Materials

Awarded $143,000 for the period 6/30/04 to 6/29/07

Source: NSF

This project will perform a systematic computational study of several crystalline transition metal phosphate materials exhibiting a wide range of interesting physical and chemical properties that are not completely understood. Several are naturally occurring minerals of geological interest; many have various polymorphic geometric and magnetic structures; and some, whose electrochemical properties show technological promise in the battery industry and catalysis applications, have recently generated a wealth of experimental results.

The proposed computer simulations will develop our qualitative and quantitative understanding of these materials’ structural and magnetic transformations and properties of technological interest. Because of the special properties of transition metals in narrow band gap materials, some aspects of the proposed calculations will challenge the current state-of-the-art in computational formalism and coding. In particular, their electron/electron interactions are critical for determining the materials’ properties but difficult to evaluate accurately. A tangential project will develop a new approach for examining many electron systems based on the knowledge of their electron pair states.

Computational Tools for Detailed Simulations of Materials

Awarded $336,000 for the period 7/1/04 to 6/30/09

Source: NSF

This project aims to develop computational tools for accurate and efficient modeling of the bulk and surface properties of materials for fundamental studies and technological design. The main goals are:

  1. To investigate and to incorporate several new state-of-the-art optimization and iteration acceleration methods into the materials modeling codes, such as the use of surrogate functions and dynamic accuracy techniques;
  2. To develop algorithms and codes for the efficient solution of boundary value problems arising in the study of surfaces and interfaces of materials, incorporating input from bulk simulations;
  3. To share the codes and results with the research community, providing a forum for comparing the accuracy and efficiency of the leading computational methods.

Preliminary results on the use of surrogate functions for structural optimization and the development of surface algorithms are very encouraging. Based on the so-called projector augmented wave (PAW) method of Bloechl, a code for density functional calculations of periodic solids is shared with the electronic structure community from the website and through various collaborations. The PAW method combines the best features of pseudopotential and all-electron approaches.

Oana Jurchescu

Large-area, low-cost organic thin-film transistors by laser printing

Awarded $323,000 for the period 9/1/15 to 8/31/18

Source: NSF

Organic electronics could introduce “electronics everywhere”, but commercialization is hindered by current processes. This project will be the first to fabricate organic devices by laser printing, a fast, low-cost, high-throughput method directly scalable to large-area electronics. Simultaneous deposition, patterning, and purification will slash the cost and complexity of processing.

Organic/inorganic hybrid perovskite FETs for electrically injected laser action

Awarded $50,000 for the period 9/1/15 to 10/31/16

Source: Office of Naval Research

This project will advance development of hybrid organic/inorganic halide perovskites (HOIHP) by answering basic scientific questions about charge transport in HOIHP films and single crystal field-effect transistors (FETs); the effect of the magnetic field on their current and electro-luminescence; and laser action. CW, transient, and laser action techniques will be used on electrostatically gated devices to achieve current-injecting laser action.

Summer Undergraduate Research Fellowship at NIST

Awarded $8,735 for the period 5/1/14 to 9/30/14

Source: National Institute of Standards and Technology (NIST)

The project will quantify recombination dynamics in organic photovoltaics by measuring transient and small-signal perturbation. The organic photovoltaic test structures will be fabricated by solution-based approaches, using soluble small molecule systems and nucleation additives that limit grain growth. Recombination mechanisms will be studied and quantified using transient photovoltage spectroscopy and impedance spectroscopy under light bias to correlate microstructure and recombination and the role of percent-level impurities (nucleating agents) in the semiconductor bulk.


MRI: Acquisition of an electronic beam evaporator for interdisciplinary research and education

Awarded $225,048 for the period 9/1/13 to 8/31/15

Source: NSF

Acquisition of an electron-beam evaporation system will provide a comprehensive fabrication-characterization infrastructure that will be used for over 15 research projects by over 50 students and postdoctoral fellows from WFU, Appalachian State University, Winston-Salem State University, and Forsyth Technical Community College. It will advance several nanoscience, nanotechnology, biotechnology ,and energy programs with the potential to yield transformative applications in organic electronics and spintronics, solid oxide fuel cells, solid electrolytes for Li-ion batteries, high-performance scintillators for homeland security, photocatalytic membranes for water splitting and CO2 reduction, and studies of cell mechanics and protein mobility during neoplastic transformation. It will allow new experiments to expand Physics and Chemistry syllabi, and ~150 graduate and undergraduate students will receive formal training in the 7 courses and summer workshop that use the instrument.

Acquisition of a glove-box for organic thin-film transistor fabrication

Awarded $12,000 for the period 8/26/13 to 5/31/14

Source: NSF

This supplement provides partial funding for acquisition of a nitrogen glove-box in support of an NSF-funded project that aims to improve the performance of organic thin-film transistors (OTFTs) by developing a reliable, scalable patterning method. The approach exploits the formation of a differential microstructure on contacts that have been chemically modified with self-assembled monolayers (SAMs). The SAM creates the template for film formation, but its properties rapidly degrade in contact with air, posing serious challenges for the reproducibility and reliability of results. The nitrogen glove-box allows device processing in an inert atmosphere, enhancing the quality and scope of work.

Infrared (IR) spectroscopy for electronic structure determination of future electronic devices

Awarded $118,429 for the period 10/1/14 to 9/30/15

Source: NIST

This project will establish internal photoemission (IPE) and photocurrent (PC) spectroscopy in the infrared (IR) spectral range to characterize band offsets/alignment and in-gap, electrically active defects in novel semiconductor materials and devices for future electronics. This new measurement system will enable narrow band alignment on advanced tunnel field effect transistors (TFETs), candidate alternative channels for replacement Si-CMOS technologies, advanced (Gen 2 and 3) photovoltaic devices, and other novel semiconductor materials and devices, such as printable and fixable electronics based on organic or complex metal oxide semiconductors. The team works closely with NIST to design, fabricate, and characterize novel electronic device test structures.

High-conductivity in binary organic single crystals for electronic applications

Awarded $62,182 for the period 5/2/13 to 7/31/14

Source: NSF

The study of new binary organic compounds may open a wide range of functionalities not possible with monomolecular solids, creating new electronics and optoelectronics applications. The graduate students who participate in this project will gain broad experience in a range of physical characterization techniques, device fabrication and characterization, quantum-chemical computational methods, and crystal growth. Undergraduates will be exposed to exciting interdisciplinary topics and a stimulating collaborative training environment. Results will be integrated into undergraduate and graduate courses, including special-topics courses in organic electronic materials and devices, and in public outreach activities sponsored by local science museums.

CAREER: Fundamental limits of charge transport in organic semiconductors

Awarded $400,000 for the period 5/1/13 to 4/30/18

Source: NSF

Organic electronics has the potential to expand beyond conventional silicon to offer new applications and “electronics everywhere.” While still in its infancy, it has witnessed spectacular growth and attracted great interest in industry and academia. This program aims to develop large-area, low-cost organic field-effect transistors and organic photovoltaics with unprecedented performance and reproducibility. It will use single crystals to design and implement novel materials and device architectures. Studies will elucidate charge injection and transport to enable engineering these devices by spray-deposition. Broader impacts are aligned with economic progress; project results will advance high-performance devices to spark a new technology. In addition, graduate, undergraduate, and high-school students will gain knowledge and skill sets spanning crystal growth and device design, fabrication, and characterization. Infrastructure and results will be integrated in a new course and outreach programs at the local science museum. The PI’s success will persuade girls that science careers are exciting, fulfilling, and possible.

Spintronics for novel device application and metrology advancement

Awarded $121,189 for the period 8/21/14 to 9/30/15

Source: NIST

With recent advances in technology, the demand for faster data processing and greater memory capacity is urgent in the electronics industry. Current metal oxide semi-conductor field effect transistors (MOSTFETs) are rapidly reaching their physical limit. This project exploits an alternative approach to achieve drastic improvements. Spin electronics, or spintronics, can provide greater performance with lower power consumption and integrate with current electronics technology. This project will develop novel devices by discovering materials that enable a long spin transport; developing methods for efficient spin generation and detection; and integrating spintronic functionality in current electronic systems.

NSF-NIST collaborative research on electrical and optical properties of novel binary donor-acceptor compounds

Awarded $75,126 for the period 8/1/12 to 7/21/14

Source: NSF/UNC-Chapel Hill

The seemingly-infinite variety of organic compounds presents the prospect of tailoring materials with any desired properties—truly “materials by design.” To date, monomolecular organic semiconductors, such as oligoacenes, oligothiophenes, and their derivatives, have shown the best performance, but it is becoming clear that their range of properties is rather restricted. The transition to binary- and multicomponent materials promises discovery of unexpected properties. Charge-transfer (CT) compounds (salts) composed of two different organic molecules, one acting as donor (D) and the other as acceptor (A), are an example of an organic binary system. The intermolecular interactions between D and A, especially electron transfer, allow novel functionalities. This project grows single crystals of binary compounds formed from organic or inorganic donors or acceptors and explores their physical properties to identify the most promising candidates for electronic devices, light-emitting diodes, and solar cells.

Summer Undergraduate Research Fellowship (SURF)

Awarded $8,531 for the period 5/1/12 to 9/30/12

Source: NIST

With recent advances in technology, electronics industry demand for faster data processing and higher memory capacity is urgent. The metal oxide semiconductor field-effect transistors (MOSFETs) currently in use are rapidly reaching their physical limit, and implementing faster, higher capacity requires very high energy use, which is detrimental to the environment and not economically feasible. This project focuses on an alternative approach – spin electronics, or spintronics, which is not volatile and consumes very little power. A Wake Forest Physics major, Alyssa Brigeman (2013), will spend 10 weeks this summer, working “elbow-to-elbow” with some of the world’s leaders in spintronics from the NIST NanoElectronic Device Metrology Group of the Physical Measurement Laboratory.

High-conductivity in Binary Organic Single Crystals for Electronic Applications

Awarded $54,696 for the period 8/1/11 to 7/31/12

Source: NSF

The study of new binary organic compounds could open a large range of functionalities not manifest in monomolecular solids and create new electronics and optoelectronics applications. The graduate students who participate in this project will gain broad experience in a range of physical characterization techniques, device fabrication and characterization, quantum-chemical computational methods, and crystal growth. Undergraduates will be exposed to exciting interdisciplinary topics and a stimulating collaborative training environment. Results will be integrated into courses taught by the co-PIs at the undergraduate and graduate levels, including special-topics courses in organic electronic materials and devices. They will also be used in public outreach activities sponsored by local science museums.

Patterning Organic Thin-Film Transistors by Differential Microstructure

Awarded $330,000 for period 6/1/11 to 5/31/14

Source: NSF

The ability to pattern organic thin films is crucial to manufacturing organic electronic devices with better performance and reduced power consumption. Progress has been impeded by many conceptual and practical problems related to their degradation when exposed to conventional lithography processes. This project will develop reliable, reproducible methods to simultaneously deposit and pattern organic field-effect transistors at low-cost and moderate temperatures. The presence/absence and type of self-assembled monolayers (SAMs) will promote different orientations in the organic semiconductor molecules forming the thin film. A high degree of order will enhance conductivity, while mixed orientations will lead to low conductivity regions where organic semiconductors can be selectively deposited on pretreated surfaces to achieve self-patterning at low cost. Results will elucidate physical processes that originate at organic/dielectric and metal/organic interfaces and lead to development of low-cost, high-yield methods for fabrication of high-performance organic electronic devices.

Low-cost Organic Electronics: Let Molecules Do the Work

Awarded $5,000 for the period 6/1/10 to 5/31/11

Source: Oak Ridge Associated Universities

Despite remarkable achievements in the field of organic (plastic) electronics, many problems remain. Patterning is a critical step in fabricating organic thin-film transistors (OTFTs); it reduces power consumption and increases performance by minimizing parasitic current paths. However, photolithography techniques developed for inorganic semi-conductors damage weak organic semi-conducting materials and degrade device performance. Unfortunately, methods to solve this problem limit resolution and fail when scaled to large-area processing. This project will exploit unique film-forming properties to develop novel, low-cost, large-area patterning techniques for organic electronic devices. Patterning will be efficiently induced by manipulating the chemical and physical interactions so that differential microstructure forms at the contacts, dielectric materials, or self-assembled monolayers (SAMs) on their surface. The program offers exciting collaborative and interdisciplinary research opportunities and a stimulating environment for student training.

Nondestructive deposition of electrical contacts on organic semi-conductors

Awarded $126,741 for the period 6/30/11 to 9/30/12

Source: NIST

Despite recent improvements in the performance of organic electronic devices, efficient contact deposition remains a major obstacle to reliability. Conventional methods damage the weak organic materials below the metal electrodes. This project will use nano-transfer printing (NTP), which preserves organic semi-conductor quality at the interface with metals, while its low thermal budget enables fabrication of large-area, light-weight, low-cost, flexible electronics on plastic substrates. NIST researchers have successfully used it to fabricate electronic devices; this project will fabricate high-performance organic field-effect transistors. A second goal is to fabricate devices with competitive performance and use them to gain correct information on charge injection and transport and charge trapping and detrapping in organic semi-conductors.

Daniel B. Kim-Shapiro

with S. Bruce King, CHEMISTRY

Effects of nitric oxide in sickle cell blood

Awarded $356,245 for the period 5/1/15 to 4/30/16

Source: NIH

The project investigates the biochemistry and biophysics of nitric oxide (NO) in sickle cell blood and its use as a treatment for the disease. NO may benefit patients as a vasodilator, decreasing red blood cell sickling and sickle cell adherence and improving oxygen transport. However, NO biology in both sickle cell and normal blood is not well understood, and previous studies report contradictory results. Sickle blood will be compared to 1) normal blood; 2) preparations of isolated normal and sickle red blood cells; and 3) purified hemoglobins using a variety of tools, some developed specifically for this project, including microscopy, ektacytometry, ultracentrifugation, stopped and quench-flow mixing, laser photolysis and diffraction, chemoluminescence, electron spin resonance, nuclear magnetic resonance, and absorption spectroscopy.

Antidote for Inhaled CO Poisoning Based on Mutationally Engineered Neuroglobin

Awarded $43,122 for the period 12/1/15 to 11/30/16

Source: NIH / University of Pittsburgh

Wake Forest investigators are characterizing the kinetics of CO binding to neuroglobin (Ngb) mutants. To determine Ngb association rate constants, a laser pulse photolyzes Ngb-CO, and time-resolved absorption spectroscopy monitors the kinetics of CO rebinding at the nanosecond-to-millisecond scale. Time-resolved spectroscopy is also used to examine the rate at which NO replaces CO on the Ngb to determine dissociation rate constants. Computational modeling is used to interpret the data and may indicate new Ngb mutants to test.

Exercise, weight loss, and arterial stiffness in obese older adults

Awarded $16,660 for the period 7/1/13 to 6/30/14

Source: American Heart Association/WFBH

Weight loss and aerobic exercise training are generally effective in improving arterial stiffness in middle-aged adults, but in older individuals, who are largely overweight or obese, exercise alone is ineffective, possibly due to the vasculature’s impaired ability to increase NO with exercise. This project will determine whether combining an exercise intervention with diet-induced weight loss improves arterial stiffness more than exercise alone in older, obese adults enrolled in a 5-month randomized controlled trial.

Role of nitrite reduction to NO by hemoglobin in control of fetal vascular tone

Awarded $32,880 for the period 6/1/13 to 5/31/14

Source: NIH/Loma Linda University Adventist Health and Science Center

Hypoxic/ischemic insult (HI) is a common cause of perinatal morbidity and mortality. Nitric oxide (NO) is an endogenous defense against it, dilating blood vessels to increase oxygen delivery and decreasing oxygen consumption at the mitochondrial level. Although hemoglobin rapidly scavenges free NO, limiting its half-life in blood to milliseconds, de-oxyhemoglobin can reduce nitrite to NO, which provides significant protection during HI in adults. The higher concentrations of nitrite, hemoglobin, and H+ in fetal blood favor the reaction; when hemoglobin is 40-60 percent oxygenated, compared to 0 or 100 percent, nitrite reduction is up to 60-fold greater, again suggesting high NO production from nitrite and de-oxyhemoglobin in the fetus. These studies will provide the first thorough assessment of this hypothesis and show how nitrite might be used to treat perinatal HI. Dr. Kim-Shapiro directs EPR measurements performed mainly by a graduate student and contributes to the design and analysis of experiments performed at both universities.

Storage lesions in banked blood due to disruption in nitric oxide homeostasis

Awarded $171,854 for the period 6/1/15 to 5/31/16

Source: NIH/University of Pittsburgh

Storing red blood cells can impair their functionality and integrity, contributing to poor transfusion results. This project tests the hypothesis that storage lesion is largely due to dysregulation of nitric oxide (NO) homeostasis. Cell-free hemoglobin and microparticles released during hemolysis increase NO scavenging and decrease NO production. An array of clinical, molecular biology, biophysical, and biochemical tools will be applied to characterize the NO storage lesion in vitro and in chimeric mouse models, a canine model, and human studies. Therapeutics to restore NO homeostasis will be explored in these systems.

Enzymatic activity of myoglobin as a nitrate reductase that regulates hypoxic NO

Awarded $28,175 for the period 4/1/13 to 3/31/14

Source: NIH/University of Pittsburgh

Dr. Kim-Shapiro and his team will perform kinetic analysis on myoglobin mutant proteins using electron paramagnetic resonance (EPR) and model reactions of myoglobin and nitrite in the cardiomyocyte.

Noncompetitive Supplemental Application for R37 HL58091

Awarded $10,000 for the period 3/1/10 to 4/30/10

Source: NIH

In sickle cell disease, a mutant form of hemoglobin polymerizes when exposed to low oxygen tension. The red blood cells become rigid, blocking vessels and causing significant morbidity and mortality. Sickle red blood cells are also fragile, rupturing in the circulation. For many years, this problem was not viewed as crucial, but several groups have recently proposed that efficiently released cell-free hemoglobin scavenges NO, leading to an NO-related deficiency associated with sickle cell disease. Nitric oxide (NO) is currently being tested as a treatment; synthesized in blood vessel endothelial cells, it diffuses to neighboring smooth muscle cells, where it signals muscle relaxation and vasodilation.

This project aims to elucidate how hemoglobin mutation increases red blood cell fragility and why NO scavenging is reduced in red cell-encapsulated, as opposed to cell-free, hemoglobin. Differences in how NO reacts in sickle cell and other blood will be determined, and a mechanism using the anion nitrite to restore effective NO response explored. The participating laboratories have recently shown that, contrary to the existing paradigm, nitrite acts as a vasodilator in human circulation, possibly due to a novel, allosterically controlled function of hemoglobin. The study employs an array of biophysical techniques and has developed techniques to study whole blood to assess physiologically relevant conditions.

A Multifunctional Blood Substitute (MBS) for Field Resuscitation of Polytrauma Combat Casualties with Brain Injury and Concomitant Hemorrhagic Shock

Awarded $15,000 for the period 9/15/09 to 9/14/10

Source: Army Research Office (ARO)/University of Pittsburgh

Currently, no blood substitute is FDA approved, a major problem on the battlefield. Past and current attempts scavenge endogenous nitric oxide, which is critical to vascular tone and hemostasis, among other things. This project will build on the team’s recent discovery that hemoglobin produces nitric oxide from nitrite to optimize this function in a blood substitute. In particular, combinations of oxidized and nonoxidized hemoglobin products and nitrite will be explored for their ability to produce nitric oxide activity. The Wake Forest team will use electron paramagnetic resonance (EPR) spectroscopy to analyze blood or plasma samples containing the blood substitute to determine whether Hb submicromolar amounts of these hemoglobin species can be measured in the background of millimolar quantities of (EPR silent) deoxygenated and oxygenated hemoglobin.

with Bruce King, Chemistry; Gary Miller and Jack Rejeski, Health and Exercise Science; and Janine Jennings, Psychology

Effects of Nitrite Diet on Functional Health in Older Adults: A Preliminary Study

Awarded $9,375 for the period 1/1/09 to 12/31/09

Source: WFU Science Research Fund

Until recently, nitrite was thought to be biologically inert. However, due, in part, to work in the Kim-Shapiro and King labs, it is now recognized as an important signaling molecule because it can be converted to the established signaling molecule nitric oxide (NO). Emerging evidence suggests that loss in NO bioavailability contributes to conditions associated with impaired health during aging. The long-term goal of this project is to examine the extent to which nitrite (dietary or otherwise) can improve functional health in older adults. It will test the hypothesis that nitrite can compensate for the loss in NO bioavailability with aging. Phase I will develop a diet that increases nitrite in the plasma. Phase II will explore the extent to which this diet affects older adults’ cognitive performance. Results will elucidate nitrite/NO biology and physiology and potentially improve the lives of untold numbers.

EPR Work for Cardioxyl

Awarded $3,564 for the period 2/22/08-2/21/09

Source: Cardioxyl Pharmaceuticals, Inc.

Cardioxyl Pharmaceuticals aims to develop new therapeutic agents for treating cardiovascular diseases. In this project, Wake Forest will assess whether electron paramagnetic resonance spectroscopy can be used to measure the dosing of a particular therapeutic agent.

with Bruce King, Chemistry

Nitric Oxide Donor Compounds for the Treatment of Hemolytic Conditions

Awarded $162,657 for the period 1/1/09 to 12/31/09

Source: NIH

Nitric Oxide (NO) is synthesized in the endothelial cells surrounding blood vessels and signals smooth muscles to relax and increase blood flow. Hemoglobin (Hb) actively scavenges NO. In normal physiology, its scavenging is reduced due to   its compartmentalization in red blood cells, but in several diseased conditions, including hemolytic anemias, such as sickle cell disease and paroxysmal nocturnal hemoglobinuria (PNH), thalassemia intermedia, malaria, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and cardiopulmonary bypass, Hb is released into the plasma compartment and can efficiently scavenge NO. This increased NO scavenging leads to a host of complications contributing to morbidity and mortality. Administering NO through inhalation restores normal NO responsiveness and shows promise as a treatment, but it is not practical for chronic treatment. This project tests and, to some extent, synthesizes compounds that may eventually be taken intravenously or orally. Unlike many therapeutic compounds, they will be cell-impermeable, acting in the plasma compartment to react preferentially with cell-free Hb and inactivate its NO scavenging ability.

Effects of Nitrite in Sickle Cell Blood

Awarded $343,920 for the period 12/1/06 to 11/30/07

Source: NIH

Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes when exposed to low oxygen tension. Polymerization makes the red blood cells rigid so that they block some blood vessels, leading to significant morbidity and mortality. Nitric oxide (NO) is currently being tested as a treatment for sickle cell disease due to its role as a vasodilator among other things. NO is synthesized in blood vessel endothelial cells and diffuses to neighboring smooth muscle cells, where it acts as a signaling molecule, causing muscle relaxation and vasodilation. Sickle red blood cells are also fragile, rupturing during transit. For many years, this hemolytic anemia was not viewed as critical to the disease’sl pathophysiology. However, several groups have now begun to re-examine the consequences of hemolysis and the hypothesis that released cell-free hemoglobin efficiently scavenges NO, causing a deficiency.

This project aims to elucidate 4 mechanisms: 1) How does the hemoglobin mutation lead to increased red blood cell fragility? (2) How does the reduced NO scavenging by red cell-encapsulated hemoglobin compare to cell-free hemoglobin? (3) How does NO react in sickle cell blood compared to normal blood? (4) How can an effective NO response be restored in patients using the anion nitrite? The laboratories participating in this project have recently shown that, contrary to the existing paradigm, nitrite acts as a vasodilator in human circulation, possibly due to an allosterically controlled function of hemoglobin.

The study employs an array of biophysical techniques, including electron paramagnetic resonance spectroscopy, kinetic absorption spectroscopy, laser diffraction, and computational simulations. Techniques have been developed so that these studies can be made on whole blood, to assess physiologically relevant conditions.

Nitrite and Nitric Oxide in Sickle Cell Blood

Awarded $103,680 for the period 12/1/08 to 11/30/09

Source: NIH, Independent Scientist Career Development Award

This career award will reduce Dr. Kim-Shapiro’s teaching and service load so that he can spend greater than 75% of his time on research, which focuses on the effects of nitric oxide (NO) in sickle cell blood. Patients with sickle cell anemia have been shown to have abnormal NO-related vasoactivity due to cell-free hemoglobin scavenging NO. NO therapy may restore normal NO vasoactivity. Recently published data also suggest that NO may upregulate fetal hemoglobin and thereby reduce sickling.

    Dr. Kim-Shapiro is also a key collaborator on a study of the NO-donating properties of hydroxyurea, an FDA-approved drug for sickle cell disease. He has participated in some recent studies suggesting that nitrite is converted to NO by deoxygenated hemoglobin and thus serves as a reservoir for NO in the body and will expand his studies to investigate the effects of nitrite in sickle cell blood. Finally, he plans to develop noninvasive imaging tools to study pathology of the microcirculation in patients with sickle cell disease and the effects of therapeutics.

Jed Macosko

Cellcraft: Exploring the Cell through Computer Games

Awarded $25,490 for the period 6/1/09 to 5/31/10

Source: MacArthur Foundation

The Cellcraft project is a video game in which players explore the inner workings of a cell while gaining skill in organizing, planning, coordinating, delegating, and logic. Students Anthony Pecorella and Yuri Shtridelman are the co-principal investigators.

Better, Faster Live-Cell Imaging: Motion-Enhanced DIC (MEDIC) with Fluorescence

Awarded $31,262 for the period 6/16/09 to 10/31/09

Source: NIH

All human cells contain machinery for moving submicroscopic cargo. Understanding how is crucial to improving therapies for Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) as well as the overall health of the cell. This administrative supplement creates summer jobs for K-12 teachers and undergraduate students to accelerate development of a novel light microscopy imaging system, ideal for visualizing cargo transport in living cells. In summer 2009, senior personnel and an undergraduate intern will improve the software that facilitates simultaneous fluorescence-MEDIC imaging and port it to standard PC graphics cards for wider use. Two undergraduates, one middle-, and one high-school teacher will culture neurons and smooth muscle cells in the PD/PI’s new tissue culture facility, acquiring the initial imaging data and returning in summer 2010 to perform follow-on experiments. Their effort will greatly accelerate the parent project, and they will gain cutting-edge skills that will motivate their own and their students’ careers in the biomedical sciences.

NanoSelection of Customizable Biotechnology Reagents

Awarded $20,000 for the period 12/08 to 11/30/10

Source: NanoMedica, Inc.

Biotechnology demands cost-effective, customizable reagents for such applications as detection, screening, purification, and labeling. Aptamers – single-stranded nucleic acid molecules with properties comparable to monoclonal antibodies – have clear advantages over antibody-based diagnostics. Large quantities can be created easily with high purity and reproducibility using solid-state synthesis techniques. However, screening them for specific target-binding is difficult; existing selection strategies are tedious; and commercialization is often stifled by aggressive patent enforcement. Consequently, their versatility and commercial impact have largely gone untapped.

The proposed technology offers a novel, integrated platform to accelerate the discovery of commercially useful aptamers. It avoids time and reagent costs and patent barriers by directly selecting tight-binding aptamers without using proprietary amplification cycles; eliminates the “black box” of previous screening schemes by visualizing every tight-binding event individually; and allows users to customize the strength of aptamer-target affinity.

Drug Discovery at the Nanoscopic Level: Lab-On-Bead™ Processing of Encoded Chemical Libraries

Awarded $75,000 for the period 7/1/09 to 12/31/09

Source: NCBC

Finding chemicals that bind molecular targets—even with high-throughput screening—is slow, and most candidates fail physicochemical and biological requirements. Ultrahigh-throughput screening via encoded chemical libraries could improve results with a method to quickly and sensitively screen and identify the encoded chemicals. Lab-on-Bead amplifies and reads out a nucleic acid code at the level of single nanoscopic beads. This project aims to validate Lab-on Bead in partnership with biotechnologists at Harvard University and the Université Louis Pasteur for the eventual production, with the help of NanoMedica, Inc., of bead reagent kits and microfluid instruments to discover new drugs and diagnostics.

Fred Salsbury

Targeting the MSH2-dependent apoptotic pathway

Awarded $161,409 for the period 3/1/13 to 2/28/14

Source: NIH

This project is developing lead compounds for a novel chemotherapeutic that selectively activates a cell-death pathway by binding to specific protein conformations. In addition to its medical relevance, it highlights the importance of dynamics and physics-based modeling, chemical synthesis, cell biology, and animal models in drug design

Computational biosciences, Cancer Center support grant

Awarded $11,262 for the period 2/1/16 to 1/31/17

Source: NIH/WFBH

No abstract.

Targeted approach to overcoming treatment resistance in advanced prostate cancer

Awarded $28,033 for the period 7/1/12 to 6/30/13

Source: US Department of Defense

The project’s innovative approach combines computational modeling with cell biology to identify therapeutic molecules for treating advanced prostate cancer.

with Roy Hantgan, Biochemistry

Drug, Design, Discovery and Development – Molecules to Medicines

Awarded $11,939 for the period 6/1/09 to 5/31/10


Wake Forest University will prepare 20 students per year over 3 years to lead North Carolina’s pharmaceutical and biotechnology industries in a novel curriculum that integrates classroom and laboratory learning with work and teaching experience. In the new, multidisciplinary course, Drug Discovery, Design, and Development – Molecules to Medicines, with its companion Drug Discovery VirtuaLaboratory, graduate students and advanced undergraduates in chemistry, biochemistry, and biophysics examine the scientific, medical, economic, entrepreneurial, and ethical aspects of drug development and gain hands-on experience with drug-design software. The most promising compete for 3-month internships, designed by industry partners and mentored by core faculty. These students will then gain teaching skills by sharing their knowledge and experiences in seminars; leading discussions of faculty-assigned problems; and guiding new students with the drug-discovery software.

with Ulrich Bierbach and Bruce King, Chemistry, and Roy Hantgan, Biochemistry

Molecules to Medicines: Crafting a New Interdisciplinary Curriculum in Drug Discovery

Awarded $7,500 for the period 3/18/08 to 3/19/09

Source: Camille and Henry Dreyfus Foundation

Sparked by keen student interest, Wake Forest’s mandate for entrepreneurship, and the pharmaceutical  industry’s need for cross-disciplinary scientists with critical-thinking and teamwork skills, the project prepares students in the biological, chemical, and physical sciences to pursue wider career paths. In a new course, Dreyfus funds will allow promising students, Dreyfus Discoverers, to complete internships in the pharmaceutical and biotechnology industries. They will return to serve as teaching assistants, sharing their knowledge and experiences through seminars and weekly problem sessions.

Timo Thonhauser

Kinetics and reactivity in metal organic framework materials

Awarded $109,939 for the period 6/15/15 to 5/14/16

Source: Department of Energy (DoE)/University of Texas-Dallas

This project brings together a theorist from WFU and experimentalists from UT Dallas and Rutgers to investigate metal organic framework (MOF) materials for hydrogen storage and gas separation. Research focuses on first-principles electronic structure simulations to model these materials and investigate their basic physical properties.

Novel theoretical and experimental approaches for understanding and optimizinghydrogen-sorbent interactions in metal organic framework materials

Awarded $94,990 for the period 8/15/2012 to 8/14/2013

Source: US Department of Energy (DOE)/University of Texas-Dallas

This project, part of a large effort that brings together a theorist from WFU and experimentalists from UT Dallas and Rutgers, investigates metal organic framework (MOF) materials for hydrogen storage and gas separation. Research focuses on first-principles electronic-structure simulations to model these materials and investigate their basic physical properties.

CAREER:Improving electronic structure theory

Awarded $95,570 for the period 5/7/15 to 8/31/17

Source: NSF

The research plan builds on the PI’s expertise in ab initio modeling of van der Waals interactions to address the hydrogen storage problem, a critical barrier to a hydrogen economy and an urgently needed alternative fuel. Magnesium borohydride, ammonia borane, and methane-based materials show great potential but release or store hydrogen only at impractically high or low temperatures. While they differ, they are all influenced by van der Waals interactions. The PI proposes: 1) to lower the hydrogen desorption temperature in MGBH42 by destabilization through doping; 2) to lower the desorption temperature in NH3BH3 by substitutions in the hydridic group that will lower the activation barrier; and 3) to determine whether alkanes longer than the methane in H24CH4 can be stable at higher temperatures.

The education plan addresses the economic and educational challenges and inadequate mentoring in academic science in a highly diverse region. The objectives are: 1) to work with the local science museum and schools to create an Energy Zone, including a display, demonstration, teaching module, and informal talks for the general public about alternative energy and hydrogen as fuel; and 2) to develop an interdepartmental mentoring program for graduate students and postdocs to improve their research skills and transition to independent careers.

Ab-initio materials modeling including van der Waals forces

Awarded $5,000 for the period 6/1/09 to 5/31/10

Source: Oak Ridge Associated Universities (ORAU)

The prestigious and highly competitive Ralph E. Powe Junior Faculty Enhancement Award aims to enrich the research and professional growth of young faculty in a wide variety of fields from over 120 member universities across the USA. This project develops a promising new approach to conducting quantum-mechanical simulations of water, one of the most important substances on earth and crucial to life.

Richard T. Williams

Research on scintillator materials and mechanisms: LaBr3, CeBr3, and NaI with co-doping

Awarded $76,581 for the period 2/4/16 to 2/4/18

Source: Saint-Gobain Ceramics & Plastics, Inc.

Saint-Gobain Crystals is the world’s largest manufacturer of scintillator crystals for radiation detection, imaging, and monitoring in medical, homeland security, oil-well logging, and physics research applications. The Wake Forest group works on femtosecond ultraviolet laser techniques that can measure many of the important material parameters governing nonproportionality, including the kinetic order and rate constants of nonlinear quenching by z-scan and lifetime measurements; and trapping rates by picosecond induced absorption. It has also developed a set of mathematical models that can physically link proportionality and light yield to these and other measured parameters. Understanding the effect of co-doping in LaBr3:Ce will help in the prediction and/or engineering of optimized or customized performance. The research agreement includes partial support for a graduate student and postdoc.

Scoping study on the feasibility and engineering usefulness of computational modeling of scintillator performance

Awarded $10,000 for the period 4/22/15 to 9/30/15

Source: DoE/Lawrence Berkeley National Laboratory

The Williams group works with teams at Pacific Northwest National Laboratory and Lawrence Berkeley National Laboratory for the National Nuclear Security Agency to determine whether investing in computational modeling of the anticipated energy resolution and particle discrimination of developmental materials for advanced radiation detectors is worthwhile. Wake Forest and other laboratories have shown that modeling nonlinear and complex interactions of carriers excited in high-energy particle tracks requires a very large number of material parameters. Can the input parameters be determined well enough in a broad enough range of materials to enable useful engineering studies? This part of the scoping study assesses how well first-principles calculations can cross-check or supplement gaps in experimental input parameters. NNSA will use the results to decide future emphasis and directions in computational studies supporting radiation-security monitoring.

Wake Forest University subcontract #1 from LBNL Venture – Improvement of Scintillators

Awarded $40,000 for the period 2/11/16 to 9/30/17

Source: DoE/Lawrence Berkeley National Laboratory

Dr. Williams uses ultrafast lasers to measure capture and quenching rate constants and transport coefficients in scintillator materials, so computational models can be used for their engineering and optimization.

Collaborative Research: ARI-MA: Realizing high-performance inorganic scintillators at low cost

Awarded $118,083 for the period 9/15/15 to 8/31/16

Source: US Department of Homeland Security (DHS)

In year 2 of a five-year collaborative grant from NSF and the Domestic Nuclear Detection Office of DHS, the project is developing ways to lower the cost of fielding energy-resolving nuclear radiation detectors that can distinguish elements and isotopes to enable deployment of Global Nuclear Detection Architecture for international prevention of illicit shipments of nuclear and radiological materials and to improve international nonproliferation safeguards. The collaboration brings together capabilities for ultrafast laser measurements and associated computer modeling of the physics of particle tracks at Wake Forest, advanced crystal growth at Fisk, and electronic structure calculations at Arkansas State Universities.

Research on scintillator materials and mechanisms: LaBr3 with co-doping and other topics to be determined

Awarded $90,000 for the period 6/3/13 to 6/3/15

Source: Saint-Gobain Ceramics & Plastics, Inc.

The Wake Forest group brings femtosecond ultraviolet laser techniques that can measure many of the important material parameters governing nonproportionality, including kinetic order and rate constants of nonlinear quenching by z-scan and lifetime measurements and trapping rates, as well as a set of mathematical models that can physically link proportionality and light yield to these and other measured parameters. The research agreement includes support for a graduate student.

Physics of scintillator nonproportionality

Awarded $74,999 for the period 12/20/12 to 9/30/14

Source: National Nuclear Security Administration/Lawrence Berkeley National Laboratory

Wake Forest will perform laser measurements on scintillators to develop predictive models.

Quantifying recombination dynamics in Srl2:Eu2+ with material variations: Mechanisms and scintillator optimization

Awarded $150,000 for the period 7/7/11 to 7/6/14

Source: National Nuclear Security Administration/Fisk University

High-performance scintillators for y-spectroscopy in nuclear nonproliferation applications and homeland security require excellent energy resolution to distinguish neighboring element and isotope lines with minimal time and exposure. For broad implementation, the material should also be inexpensive. The main objectives are (1) to optimize the intrinsic proportionality of light yield from SrI₂:Eu²⁺ and its variations; (2) to lower the cost of optimally performing SrI₂:Eu²⁺; and (3) to experimentally measure parameters to improve SrI₂:Eu²⁺ and to enable numerical modeling to guide discovery of new scintillators.

fs laser studies of scintillation processes and materials–high-excitation density, transient absorption probes, and role of carrier diffusion

Awarded $13,000 for the period 10/1/10 to 9/30/11

Source: DoE/Regents of the University of California

Experimental investigations seek to improve scintillator resolution by clarifying and then minimizing no-proportional response. They will measure: quenching and decay kinetics of excitations at densities up to 10^22 cm^-3 using fs laser harmonics; picosecond absorption of the important activator charge states and energy-transporting species, such as NAI:T1 and CsI:T1; and conduction electron motilities by the “time-of flight” method with carrier lifetimes checked by optical measurements.

Scientific Exchange Program between Latvia and USA: Support of research visits between University of Latvia and Wake Forest University

Source: US Embassy in Copenhagen

Evaluation of Birefringence-based PTFE Film Inspection

Awarded $12,500

Source: Gillette Company

The first stage of this project looked at what light scattering can reveal about bare metal edges. The second will examine light reflected from edges having a Teflon (PTFE) coating. The study will use several techniques that are valuable for students to learn and will be conducted by two graduate students.

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