David Green, Ph.D. - US grants

Sensory capabilities can be measured quite precisely by an experimental approach called psychophysics, in which the subject reports whether or not a particular stimulus signal is detectable. Most psychophysical work on human subjects involves visual or auditory stimuli. A variety of precisely quantified stimulus parameters can be varied, and the subject's threshold for detection measured or computed as a probability of correct response. This Accomplishment Based Renewal will investigate a class of psychophysical tests called adaptive procedures, with the goal of improving the efficiency of such tests, which otherwise can require very large numbers of stimulus presentations to obtain reliable results. Many of the new techniques make specific assumptions about the nature of the sensory processes. This work will test these assumptions to see if they are valid, and to see if the new methods may substantially improve the measurement efficiency. Results will have impact on visual and auditory science, and on related areas of work on signal detection processing, and sensory psychology.

We want to study auditory masking, the ability of one sound to make another difficult or impossible to hear. By measuring masking using a variety of artificial (e.g., computer generated) signals, we hope to develop an exact quantitative model of auditory processing, that is, we want to simulate the auditory detection mechanism. Of special interest are temporal effects in masking. How does masking vary with the duration of the signal or the interval between the masker and the signal?

The objective of this proposed research is to study the mechanical properties of lightweight, very highly porous ceramics. Specific objectives of this research include analysis of the tensile and compressive strengths and the crack growth mechanism during failure. These results will be used to model this important class of materials and to test and modify theories for the behavior of open cell ceramic structures and sandwich structures with open cell ceramic cores. This research will concentrate on studies of cellular carbon materials, including coated materials that form sandwich structures.

coronary disorder; disease /disorder proneness /risk; atherosclerosis; young adult human (21-34); hemostasis; caucasian American; African American; gender difference; fibrinogen; coagulation factor VII; human middle age (35-64); coagulation factor VIII; von Willebrand factor; body weight; blood pressure; tobacco abuse; blood lipid; human subject;

The objective of this research is to understand how the auditory system perceives complex auditory spectra such as speech, music, or other broadband sounds. Experiments are proposed to various auditory spectra. Data from these experiments will provide detailed quantitative models of this process. A successful model of these auditory processes would provide a baseline from which to evaluate deviations from normal hearing that occur in the various hearing pathologies. The particular goal of the present experiments is to understand how the frequency of the components comprising the spectra affect these discriminating judgments. Especially important is to understand how very high frequencies influence these discrimination capacities. When the ear is damaged, either by loud noise or ototoxic drugs, the first noticeable changes occur in the higher frequency regions.

human therapy evaluation; fructose phosphate; sickle cell crisis; blood disorder chemotherapy; drug screening /evaluation; hypoxia; dosage; ischemia; drug tolerance; adenosine triphosphate; clinical research; human subject;

vascular endothelial growth factors; neoplastic growth; megakaryocytes;

Lips 9807583 Between 1990-97 the PI has observed the sudden and unexplained decline of the riparian anurans at two remote, protected sites in montane Central America. Causes of these declines are unknown, but based on over five years of personal observations, demographic data, and results of autopsies on dead frogs (by D. E. Green), the PI hypothesizes that these two declines may be attributed to two microbial pathogens: a fungus, and a virus. The PI suggests that these two sites were affected by the same agent as that which decimated the amphibians of Monteverde, Costa Rica, and that the sequential disappearance of amphibians at these three sites over the past 10 years is evidence of a highly contagious pathogen moving through the Central American isthmus. The PI will propose to organize a multidisciplinary Rapid Response and Assessment Team that would attempt to jump ahead of this apparent "front" of amphibian mortality. The team would survey the health of both the amphibian fauna and the environment to document the changes in each during a decline. Likely members would include herpetologists, pathologists, toxicologists, and endocrinologists, parasitologists, and epidemiologists. The team would survey these sites in a systematic way to determine the mechanisms of amphibian declines by surveying all life stages, measuring environmental factors thought to cause or contribute to declines, and collecting individuals for full medical diagnostic evaluations. The team would determine the geographic extent of this decline in Central and South America by surveying select upland areas where declines have occurred, and where declines are expected to occur.

This multicenter, randomized, double-blind, controlled, dose-escalation study will evaluate a humanized monoclonal antibody in patients with chronic refractory immune thrombocytopenic purpura. The antibody alters the ability of T-cells to stimulate B-cells to make autoimmune antibodies. A single 30 min IV infusion will be given to patients with ITP who have failed steroid and splenectomy therapy. Subjects will be randomized to receive escalating doses of antibody based on the results from previous lower doses. Pharmacokinetic data will be recorded as well as platelet counts and levels of anti-platelet antibody, phenotypes of peripheral blood lymphocytes and levels of serum immunoglobulins. Should the antibody prove safe and effective, future trials are planned involving a larger number of subjects.

ABSTRACT
Proposal Number: CTS-0649081
Principal Investigator: Green, David L.
Affiliation: University of Virginia Main Camous
Proposal Title: SGER: Connecting the Depletion, Wetting and Rheological Behaviors of Polymer Grafted Nanoparticles in Polymer Melts


The aim of the proposed research is to connect the thermodynamics of depletion flocculation and interfacial wetting to the dynamics of dispersing the polymer-grafted nanoparticles into semi-dilute and concentrated polymer solutions.

INTELLECTUAL MERIT:

The static and dynamic behaviors of the polymer-grafted nanoparticles will be studied in semi-dilute and concentrated polymer solutions to define a wide array of complex environments into which polymer-grafted nanoparticles are dispersed. Employing a bottom-up methodology, model systems consisting of polydimethylsiloxane (PDMS)-grafted silica nanospheres in PDMS solutions and melts will be used to regulate the interactions between the well-characterized nanoparticles. This regulation will be achieved by systematically controlling a variety of parameters such as the grafting density of PDMS on the particle surface and the chain length of the free polymer in the solution or melt. Detailed measurements will be made to connect the phase diagrams to the flow behaviors of the polymer-grafted nanoparticles and these behaviors will be contrasted against predictions from self-consistent mean-field models to compare experiment to theory. These results will be used to determine a rational basis for optimizing the end-use properties of advanced materials.


BROADER IMPACT:

The PI will utilize the Research Experience for Undergraduates program to establish a pipeline of underrepresented students for engineering graduate study at the University of Virginia. By targeting these programs to specific geographic areas and populations, the PI hopes to increase the number of woman and minority PhDs in chemical engineering.

Quantitative and mathematical approaches to biology are becoming more prevalent in both industrial and academic research. However, there remain significant barriers between the mathematical and life sciences, reinforced by the reality that college students in these programs are not typically exposed to the other discipline beyond the freshman year. This project will establish a program to train undergraduates at the interface of mathematics and biology, through a combination of course work and research experience. The program has a focus on team-based learning, with biology and math majors working together on projects jointly led by faculty from the departments of Applied Mathematics & Statistics and various Life Sciences departments.

Each year, a cohort of undergraduate students will be recruited to the program, half drawn from majors in the mathematical sciences, and half from majors in the life sciences. These students will be grouped into research teams (including both math and biology majors) that will engage in a summer of full-time research; the research projects will continue through the following year, with the students receiving academic credit. The research projects will all involve components both of mathematics and of experimental biology, and will be jointly supervised by faculty from both disciplines. As an introduction to mathematical approaches in biology, a pair of new courses will be offered: one with a focus on the analysis of experimental data, and the other with a focus on the simulation of biological systems. These courses will provide a foundation in both the theory and application of mathematical biology, with an emphasis on how mathematical models can be integrated with experimental techniques.

This combination of team-based learning, multidisciplinary research and mentoring, and novel course work, will provide a solid foundation for students to apply mathematical approaches to biological questions. This initiative will broadly impact undergraduate education at this university, serve as a model for change at other colleges and universities, and influence the broader scientific community by graduating students with a multi-disciplinary background who will take this perspective with them in their future careers.

[unreadable] DESCRIPTION (provided by applicant): The role of procoagulant hemostatic factors in atherogenesis has been enigmatic. Increased plasma concentrations of procoagulants in youth may reflect early plaque development, and rising levels of procoagulants may mirror the severity and extent of vessel wall involvement by the disease. Insight into these processes may be gained from a longitudinal study of clotting factors in subjects beginning at the earliest stages of atherosclerosis (prior to age 30), and continuing through ages 40 and 50, when subclinical and clinical evidence of disease may be recognized. Such individuals with disease in middle age may have had elevated concentrations of procoagulants in youth and a greater rate of increase in levels over time as compared to those without evidence of atherosclerosis. A unique opportunity to test this hypothesis is presented by the CARDIA study, which for the past twenty years has serially examined a cohort of men and women who were ages 18-30 at inception. In an ancillary study, we measured levels of fibrinogen, factor VII, factor VIII, and von Willebrand factor in blood samples collected 1990-91 (Year 5) and 1992-93 (Year 7). In these Year 5 and 7 samples, obtained when subjects were in their 20's and 30's, cross-sectional analyses revealed that fibrinogen was higher in women than in men, factor VIII and von Willebrand factor were higher in blacks than in whites, and associations were reported of factor VII with cholesterol and triglycerides, and fibrinogen with body mass index, cholesterol, and LDL-cholesterol. Certain correlations were confined to specific sex/race groups, such as fibrinogen with blood pressure, triglycerides, and cigarette smoking in white males. These associations between established risk factors for atherosclerosis and procoagulants suggest common links to atherogenesis. We now wish to extend our previous study to the year 20 examination (2005-6). We shall examine the associations of rate of change in hemostatic factors with clinical and laboratory evidence of atheromatous disease, such as coronary calcification and increased carotid intimal/medial thickness, as well as changes in CARDIA measured lifestyle factors such as diet, physical activity, body mass index, and smoking, and the development of hypertension, hyperlipidemia, and diabetes. In addition, we shall assess whether changes in factor VII and factor VIII coagulant activities over time are associated with particular factor VII or factor VIII haplotypes. Study of CARDIA participants offers a unique opportunity to examine longitudinal changes in hemostatic components linked to atherothrombosis and to correlate their evolution with that of other recognized coronary risk factors during the critical period preceding clinical manifestations of disease. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]

National Science Foundation - Division of Chemical &Transport Systems Particulate & Multiphase Processes Program (1415)

ABSTRACT

Proposal Number: 0644890
Principal Investigator: Green, David L.
Affiliation: University of Virginia Main Campus
Proposal Title: CAREER: Connecting the Wetting and Rheological Behaviors of Polymer Grafted Nanoparticles in Polymer Melts

Intellectual Merit:
Recent advances in grafting polymer brushes to nanoparticles surfaces permit the formulation of a wide range of advanced polymer nanocomposites in which the brush serves to prevent particle aggregation. Through recent NSF-supported research, the PI was one of the first to fundamentally connect the wetting of the brush to the uniform dispersion of nanoparticles for a model system of polydimethylsiloxane (PDMS)-grafted silica nanospheres in PDMS melts. The PDMS-grafted nanoparticles in that study were formulated by an established "grafting to" method that entailed the covalent attachment of pre-formed polymer chains directly to the nanoparticle surface. The "grafting to" method enabled the study of the impact of low-to-moderate PDMS graft densities on nanoparticle
Dispersion. The research will to employ atom transfer radical polymerization (ATRP), a recently developed "grafting from" methodology, to construct polystyrene (PS) and polymethylmethacrylate (PMMA) brushes monomer-by-monomer from the surface of monodisperse silica nanoparticles. The "grafting from" technique permits the synthesis of polymer brushes over a wider range of graft densities than the "grafting to" method. Ultimately, this set of experiments will produce systematic data that will permit quantification of the strength of attraction between nanoparticles as well as the relevant time- and length-scales that control the gelation process.

Broader Impacts: Broader impacts are three-fold. First, the calibration of self-consistent models to experimental data will permit the prediction of physical properties such as the interparticle spacing that could then be used to optimize a range of materials properties. Second, formulation of well-designed model systems will permit physicists, colloidal scientists, and rheologists to study and quantify gelation phenomena to facilitate comparisons of experimental data across of wide range of laboratories. Third, the proposed research provides an excellent medium for achieving the educational and outreach goal of exposing more students to a career in science and engineering. To this end, the PI will seek funds for a summer program to expose secondary school teachers to cutting-edge research in his lab, create demonstrations to introduce students to the fascinating properties of nanoparticles, and utilize the Research Experience for Undergraduates program to establish a pipeline of underrepresented students for engineering graduate study at the University of Virginia. By targeting these programs to specific geographic areas and populations, the PI hopes to increase the number of woman and minority PhDs in chemical engineering.

TECHNICAL SUMMARY:
The objective of the research is to elucidate and quantify how the wetting of diblock copolymers governs the dispersion of polymer droplets in immiscible polymer blends. Specifically, monodisperse polydimethylsiloxane-polyisoprene (PDMS-b-PIP) diblock copolymers will be synthesized, and these components will be added to immiscible blends of PDMS and PIP to formulate of well-defined model systems of PDMS/PMDS-b-PIP/PIP. The advantage of using these systems is that the coalescence of the droplets, which depends on the amount of copolymer at the droplet interface, can be studied in either the PDMS or PIP matrices, which are both melts at room temperature. The use of these components will help to establish whether wetting phase diagrams, which depend on the chain lengths of the block copolymers and matrix polymers, can be used to predict the rheology of the immiscible droplets. Specifically, can theoretically derived diagrams predict the regions over which droplets are unstable and coalesce or are stable and disperse? To explore this question, well-controlled rheological experiments will be performed on the model systems, and the results of these experiments will be compared to theoretical predictions of the rheological behavior of immiscible droplets in polymeric media. It is expected that the results of this research will enhance the understanding into the mechanisms that control the dispersion of polymer droplets into polymer melts. These findings should positively impact the production of engineered materials whose properties are optimized when the droplets are evenly dispersed throughout the blend.

NON-TECHNICAL SUMMARY:
Tremendous opportunities exist for researchers to create advanced, lightweight materials from immiscible polymer blends made compatible with block copolymers. Copolymers, containing blocks chemically identical to the blended components, segregate to the interface between the polymers, which should produce a fine dispersion of one polymer in another. However, fine dispersions are rarely achieved in practice, because the droplets tend to coalesce, weakening the performance of the blends. To resolve this issue, researchers from the University of Virginia (UVa) and Virginia Polytechnic Institute (VPI) will collaborate. They will synthesize and formulate systems of immiscible polymers and block copolymers of academic and industrial interest, and investigate the dispersion characteristics of these systems in well-controlled experiments. A central thrust of the research is to determine whether theoretically derived phase diagrams can be used to predict the regions over which the droplets coalesce or disperse. Preliminary findings of the collaborators indicate that phase diagrams do aid in the prediction of droplet coalescence and dispersion. Funding from the NSF will be used to cement these relationships, which are important because they can be used to provide user-friendly roadmaps to engineer advanced materials such as automotive parts, medical fabrics, and insulation products. Moreover, broader impacts from the research include using the results to enhance a course on interfacial chemistry and reaching out to local schools with the goal of increasing the number and diversity of qualified engineering and science applicants to UVa and VPI.

Upright walking is the defining feature of modern humans and their extinct fossil relatives (hominins) and understanding the transition to this unique form of locomotion is a central problem in paleoanthropology. Considerable disagreement surrounds how the functional significance of hominin fossil anatomy is interpreted, especially with regard to characteristics retained from a primitive, apelike ancestor. Some researchers reject primitive traits when reconstructing behavior from fossil hominins, considering only derived features (such as those adapted for bipedalism), while others consider both primitive and derived traits in asserting that early hominins practiced both arboreal (climbing) and bipedal behaviors. Several characteristics of the shoulder have been cited as primitive and therefore potentially indicative of climbing in members of the genus Australopithecus. This study will focus on shoulder anatomy because previous work has highlighted morphological convergence of this region based on locomotor similarities and also because several new fossils preserving the shoulder fill key gaps in the hominin fossil record. To investigate the relationship between shoulder function and anatomy, this project will use 1) an experimental approach with wild-type mice exercised under two conditions (vertical climbing and horizontal running) and a consideration of transgenic, hypermuscular mice to examine the morphological effects of different locomotor styles and increased musculature, 2) a comparative analysis of primates to examine how the development of shoulder anatomy varies with changes in function during growth, and 3) a reanalysis of early hominin fossils to develop hypotheses about the functional significance of primitive features in light of the experimental and ontogenetic results. These approaches will evaluate the relationship between locomotor activity, muscular anatomy, and shoulder skeletal development to test long-standing hypotheses about interpreting primitive features in early hominin fossil anatomy.

In addition to the doctoral student's training, this project will provide research experience to an undergraduate student assistant. This research has broader implications beyond physical anthropology in that experimentally testing the influence of different styles of locomotion on muscle development and bone shape in mice will contribute to our understanding of skeletal health and biology. Moreover, exploring the influence of locomotor differences in a model organism and morphological development in primates has the potential to transform our ability to make functional interpretations of early hominin skeletal anatomy. By examining whether or not primitive features in hominin shoulders are directly related to locomotor style, this project will shed light on developmental anatomy of the shoulder and will evaluate different theories about the origin and evolution of human bipedalism.

0923260
Green
U. Virginia

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

Technical Summary: Our objective is to acquire a small-angle x-ray scattering instrument (SAXS) to establish the X-Ray Scattering Facility for Quantum and Nanoscale Research and Education. The proposed user facility is designed to serve the robust and growing NanoScience community at the University of Virginia (UVa). Existing research thrusts are interdisciplinary, connecting the Schools of Engineering, Arts and Sciences, and Medicine in target areas including Nanomedicine, Nanoelectronics, Energy, and the Environment. The state-of-the-art facility will be established through the addition of a SAXS instrument. SAXS is a powerful technique for characterizing the size, shape, and internal structure of materials from length scales spanning 1 to 115 nm, providing critical information about the structure of materials as diverse as crystalline and amorphous nanoparticles to functional proteins. The core faculty will use the SAXS to develop new devices and processes with broad societal impact such as new quantum computing materials for smaller integrated circuits; biodegradable polymer-metal block copolymers for improved drug delivery; and amorphous/nanostructured metallic alloys for high efficiency energy conversion. The proposed instrument will be housed in Wilsdorf Hall, a $68M multidisciplinary research building completed in 2006. In conclusion, the SAXS instrument will support significant research programs, the instrument will be highly integrated into undergraduate, graduate, and postdoctoral studies, and will be used to expose underrepresented minorities to cutting-edge research as well as recruit them into UVa?s graduate science and engineering programs.

Layperson Summary: The use of x-rays impacts countless lives across multiple disciplines, most notably in medicine. In addition to familiar radiological applications, x-rays also provide critical information regarding the structure of materials over a range of sizes depending on instrument configuration. Hence, our objective is to acquire a small-angle x-ray scattering instrument (SAXS) to establish the X-Ray Scattering Facility for Quantum and Nanoscale Research and Education. The proposed user facility is designed to serve the robust and growing nanotech communities at the University of Virginia (UVa), surrounding universities, and our commercial partners. Existing research thrusts are interdisciplinary, connecting the Schools of Engineering, Arts and Sciences, and Medicine in target areas including medicine, electronics, energy, and the environment. The high-tech facility will be established by adding the SAXS apparatus to existing instrumentation, all of which will be overseen by experts in x-ray analysis. Overall, SAXS represents a state-of-the-art technique to determine the size, shape, and architecture of materials with dimensions spanning 1 nm to 100 nm. Thus, SAXS can provide important information about the structure of materials as diverse as crystalline and amorphous nanoparticles used in the mechanical reinforcement of composites as well as functional proteins involved in biological processes such as vision. To this end, the core faculty will use SAXS to develop new devices and processes with broad societal impact such as novel electronics for next generation computers; biodegradable polymers for improved drug delivery; lightweight carbon nanotube composites for ultra-responsive sensors; and nanostructured metals for high efficiency energy conversion. The proposed instrument will be housed in Wilsdorf Hall, a new $68M nanotechnology research building recently completed in 2006. In conclusion, the SAXS instrument will support significant research programs, the instrument will be highly integrated into undergraduate, graduate, and postdoctoral studies, and will be used to expose underrepresented minorities to cutting-edge research as well as recruit them into UVa?s graduate science and engineering programs.