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-
Studies of Classical and Quantum Effects in Gravity
Awarded $32,198 for the period 4/2/07 to 6/30/08
Source: National Science Foundation
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, which would have 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
-
with Eugeny Budyain, Physiology
Mathematical modeling of subsecond dopamine fluctuations in rat
brain
Awarded $12,500; $6,250 Reynolda campus, $6,250 Health
Sciences
Source: WFU Cross-Campus Collaborative Research Support
FundThe origin and functional significance of phasic dopamine transmission
in an intact mammalian brain is not clearly understood. This project
aims, first, to develop a mathematical model for the patterns of
subsecond dopamine fluctuations in brain areas that are essential
to the circuitry involved in addiction. Second, a micromotor-driven
manipulator with several significant advantages over current manual
manipulators for obtaining data from ambulatory mammals will be
developed. Results will offer critical insights into the neurobiology
underlying drug abuse and inform the development of therapeutic
agents for addicts.
- 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.
David Carroll
- Hybrid Organic-Inorganic Composite Solar Cells for Efficient, Low-Cost,
Photoelectric Energy Conversion
Awarded $86,669.47 for the period 9/1/07-8/31/08
Source: US Department of Ecology/University of South Carolina
- PlexiLight
Awarded $131,808 for the period 6/25/07 to 6/24/08
Source: PlexiLight, Inc.
PlexiLight plans to develop a revolutionary lighting source that uses nanotechnology to produce visible light directly rather than as a byproduct of heating a filament or gas. Very thin, lightweight, and energy efficient, it could serve a wide range of residential, commercial, and military applications.
- FiberCell
Awarded $292,067 for the period 6/25/07 to 6/24/08
Source: FiberCell, Inc.
Wake Forest scientists, in collaboration with New Mexico State University, plan to develop the next generation of solar cells based on a novel architecture that uses nanotechnology and optical fibers to improve efficiency.
-
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 WFU
Health Sciences’ 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: Environmental Protection Agency (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
Source: Air Force Office of Scientific Research (AFOSR), Multidisciplinary
University Research Initiative (MURI)
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.
-
with Joel Stitzel, Biomedical Engineering,
WFUSM
Development of Electrospinning Apparatus for Tissue Engineering
Awarded $ $14,700 for the period 5/6/05 to 5/15/06
Source: WFU Cross-Campus Collaborative Research
Support Fund
The team aims to purchase a negative pressure glove
box with an antechamber and to fabricate an electrospinning apparatus
for the development of vascular scaffolds. These vascular scaffolds,
when seeded with endothelial or other appropriate cells, hold promise
as vein and potential organ replacements. The investigators propose
(1) to generate vascular scaffolds from several types of protein
components by electrospinning; (2) to optimize the synthesis of
these scaffolds; and (3) to test the mechanical strength, biocompatibility,
and biochemical characteristics of the synthetic scaffolds compared
to decellularized scaffolds or native vascular vessels.
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. The program
has four specific task areas:
1. Electromagnetic Modulation.
Novel electrochromic polymers will be coupled with metamaterial
functionalities, agile coloration, and reflective technologies to
respond to ambient thermal, lighting, and threat conditions in real
time.
2. Sensor Embed Technologies. Nano-engineered material
will be used to create novel, high-sensitivity sensor systems with
self-diagnostic functions, including the ability to sense strain,
corrosion, and IR, locally and globally, and pressure transduction.
3. Macro-electronic, distributed connectivity. Organic
macro-electronics will create a networked interconnectivity among
sensors, allowing the coating system to respond autonomously to
a wide variety of stimuli.
4. Tangential functionalities. Several tangential
functionalities will be added to the coating system, including corrosion
retardation and active vibration damping.
The program teams Dr. Carroll with investigators from the University
of Florida and New Mexico State University and corporate partners
Foster Miller, Inc., and International Technology Corporation.
Coordinated through WFU, each site is responsible for developing
and integrating a component into the final coating system. The
“distributed” management structure will enhance synergistic
and shared activities among team members and rapid response to
scientific developments.
Gregory Brown Cook
-
Quasi-equilibrium BH-BH and NS-BH binary Initial Data
Awarded $35,000 for the period 11/1/07 to 10/31/08
Source: National Science Foundation
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. Aims include:
1. to test current methods for constructing equal-mass binary black
hole initial data sets and to extend them to the construction
of unequal-mass initial-data sets;
2. to construct a new, more efficient, and easier to use code for
these initial data sets, adding the ability to deal with neutron
stars as well as black holes;
3. to develop the first consistent quasi-equilibrium initial data
sets for binary systems containing a neutron star and a black hole;
and
4. to extend current initial data techniques to the computation
of quasi-equilibrium “conformal three-geometry,” considered
the last major obstacle in constructing astrophysically
realistic compact binary initial data.
Jacquelyn Fetrow (see also Computer Science)
-
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.
- 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 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.
- 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: WFU 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.
- Algebraic and Statistical Models of Redox Signaling
Awarded $254,488 for the period 4/1/07 to 3/31/08,
Year 3
Source: NIH
An interdisciplinary research group spanning the Reynolda and
Health Sciences campuses aims to develop 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 a variety
of normal and diseased conditions, including cancer, neurodegenerative
diseases, and aging. 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. These 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.
Martin Guthold
- Determining the Mechanical Properties of Single Fibrin Fibers
Awarded $225,000 for the period 7/01/07 to 06/30/10
Source: National Science Foundation
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.
- Viscoelastic properties of fibrin fibers
Awarded $10,000, Spring 2007
Source: Science Research Fund
The mechanical properties of blood clot constituents are largely
unknown, which has seriously hampered our full understanding of
clotting and development of good models. Their major structural
component
is a network of fibrin fibers that critically depends on the fibers’ mechanical
properties and the properties of the junctions between fibers.
Little is known about these nanoscopic features because a good
technique
to study them has been lacking. This project aims to develop a
novel technique, combining atomic force and fluorescence microscopy,
to
study the mechanical properties of single fibrin fibers. The tip
of the atomic force microscope (AFM) will be used to laterally
stretch fluorescently labeled fibrin fibers that are suspended
across channels
in a striated substrate, while the fluorescence microscope images
this process. This experimental design yields a well-defined, easy-to-analyze
geometry ideal for measuring stress-strain curves of fibrin fibers.
The 16 viscoelastic characteristics of fibrin fibers that define
their mechanical behavior will be quantified for several parameters,
such as temperature and fiber radius. Fibrinogen variants will
provide insights into their molecular mechanisms and the fibrin-fibrin
interactions
that affect them. This pioneering technique should apply to many
biological and nonbiological fibers and provide an entirely new
understanding of blood clots, heart attacks, strokes, and related
diseases. The
project will include two graduate and three undergraduate students.
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: National Institutes of Health (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
viscolelastic 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
- First Principles Simulations of Battery Materials
Awarded $75,000 for the period 12/15/07 to 11/30/08
Source: National Science Foundation
The growing need for portable, rechargeable batteries in a wide variety of applications has sparked development of cost-effective and reliable battery technology. This project pursues two research tracks to elucidate rechargeable battery materials. The first uses a variety of computational techniques to study the structures, ionic conductivity, and stability of solid electrolyte materials, which may provide an efficacious alternative to the liquid and polymer electrolytes recently implicated in overheating and fire problems. The research plan will initially focus on crystalline systems related to the LiPON electrolytes developed at Oak Ridge National Laboratory. Experience from the study of these well-characterized crystalline materials can then be used to tackle the computationally more challenging task of modeling the glassy forms of commercial interest in batteries and related technologies.
The second research track focuses on improving computational tools to model cathode materials that rely on multivalent transition metals. Modeling many of their basic properties requires 5-10 times improvement in current first-principles calculations. Recent clever developments in algorithms and orbital representations of correlation functionals motivate an effort toward exact exchange (EXX), or optimized effective potential formalism. This approach will be implemented in the shared general purpose electronic structure code – pwpaw, based on the projector-augmented wave (PAW) formalism, which is particularly well suited to this task. Several recent review papers have presented the challenge of developing EXX or its equivalents as the third generation or “fourth rung of Jacob’s ladder” of density functional theory. Developing the EXX capability will help electronic structure calculations numerically realize the full power of density functional theory.
A variety of available computational techniques will be used to model solid electrolyte materials to understand their ionic conductivities and their structural and chemical properties. First-principles electronic structure tools will be improved to more accurately represent cathode materials containing transition metals. Specifically, “exact exchange” formalism allows the treatment of the exchange and correlation interactions in terms of orbital representations within the framework of density functional theory, avoiding the self-interaction bias that plagues the current explicit density functionals. This work is expected to contribute to the development of battery technology and to improve computational methods. It will also provide training in computational research for several students.
-
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 http://pwpaw.wfu.edu and through various collaborations.
The PAW method combines the best features of pseudopotential and
all-electron approaches.
Daniel B. Kim-Shapiro
- with Bruce King, Chemistry
Nitric Oxide Donor Compounds for the Treatment of Hemolytic Conditions
Awarded $161,560 for the period 1/8/08 to 12/31/08
Source: National Institutes of Health
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. Lead compounds include NONOates (NO donors), nitroxyl donors, and possibly nitrated lipids and nitrites.
-
with Janice D. Wagner, Comparative Medicine
Effects of Short-Term Hyperglycemia on Arterial and Liver Redox-Active
Iron Concentrations
Awarded $15,672; $6,900 Reynolda campus,
$8,772 Health Sciences
Source: WFU Cross-Campus Collaborative Research Support Fund
Cardiovascular disease (CVD) is the primary cause
of morbidity and mortality in both Type 1 and Type 2 diabetics,
and CVD
mortality rates are 2-8-fold higher in diabetics
than nondiabetics. Only part of the problem can be explained by
typical risk factors,
such as plasma lipids and blood pressure. This project
aims to explain how hyperglycemia influences production of oxygen
free radicals in diabetic arteries and how it might
contribute
to atherosclerosis. Transition metal ions, such as
iron or copper, are excellent catalysts for producing free radicals,
and iron disturbances have been seen in diabetics.
Preliminary
results in diabetic monkeys show increases in transition
metal-catalyzed aortic protein oxidation in parallel with an increase
in atherosclerosis
after six months. Using diabetic cynomolgus monkeys,
the project will investigate how short-term hyperglycemia affects
levels
of redox-active iron species in arteries, to determine
their involvement in atherosclerotic processes, and liver, which
plays a central role in iron metabolism. Redox-active
iron
species will be measured in intact artery and liver
tissues, snap-frozen in liquid nitrogen, and kept at -80°C,
using electron paramagnetic resonance spectroscopy. Immunoblot
analysis
will measure relative amounts of proteins involved
in iron storage (ferritin), iron transport, hemoglobin, and heme
oxygenase-1
(heme breakdown).
-
Effects of Nitrite in Sickle Cell Blood
Awarded $343,920 for the period 12/1/06 to 11/30/07
Source: National Institutes of Health
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 12/1/07 to 11/30/08
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.
-
Effects of Nitric Oxide in Sickle Cell Blood
Awarded $306,206 for the period 5/1/06 to 4/30/07,
Year 5 of 5
Source: NIH
The project’s goal is to elucidate 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, much
of NO biology in both sickle cell and normal blood is not well
understood, and previous studies report contradictory results.
Results from sickle blood will be compared to those in 1) normal
blood, 2) preparations of isolated normal and sickle red blood
cells, and 3) purified hemoglobins. A variety of spectroscopic
and other biophysical tools, some developed specifically for
this project, will include microscopy, ektacytometry, ultracentrifugation,
stopped and quench-flow mixing, laser photolysis and diffraction,
chemoluminescence, electron spin resonance, nuclear magnetic
resonance, and absorption spectroscopy.
Jed Macosko
Generating DNA LOBOS: libraries of one-bead, one sequence using an
anchored polymerase chain reaction
Awarded $10,000, Fall 2006
Source: WFU Science Research FundThis project will create libraries in which each “book” is
a microscopic bead decorated with hundreds of copies of a unique
DNA sequence. These DNA libraries of one-bead, one sequence (LOBOS)
will enable a drug-screening method developed by Associate Professor
Martin Guthold that uses folded DNA strands called aptamers. In this
method, randomized DNA aptamers bind to a drug target, and the one
that binds the tightest is amplified for future use. Hundreds of
identical aptamers must be grouped together, so they can better bind
the target and be properly amplified by PCR (the polymerase chain
reaction). DNA LOBOS will satisfy these important requirements.
Richard T. Williams
- Scientific Exchange Program between Latvia and USA: Support of research
visits between University of Latvia and Wake Forest University
Source: US Embassy in Copenhagen
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