Robert Rogers - US grants

No abstract provided.

Perform work as a clinical center in a multicenter clinical trial to determine the effects of early intervention for chronic obstructive pulmonary disease in cigarette smokers with mild airways dysfunction.

The work being undertaken in this grant is no longer aptly described by the project title, as was made clear in the revised grant application. We are attempting to clarify what Epstein- Barr virus (EBV) does when it lies dormant (latent) in infected human B-cells. In particular, we are identifying proteins and messages made by the virus which may be involved in cell growth control. This is directly relevant to the study of cancer. In fact, EBV is found in two human cancers, Burkitt's lymphoma and nasopharyngeal carcinoma. More specifically, our work involves analysis of latent viral transcripts by northern blotting and sequence analysis of cDNA clones. We have discovered new mRNA splicing patterns which could lead to the expression of a latent-phase protein hitherto uncharacterized in the literature. We hope eventually to demonstrate a role for this putative protein either cell growth control or in viral growth control.

This project is centered on problems in physics and partial differential equations which have the common feature that nonlocal or nonconvex effects produce a lack of compactness. The problems are divided into three categories: Self-force problems in electro-magneto-elasticity, problems in viscoelasticity, and problems in the theory of compensated compactness and weak continuity.

This project involves mathematical modeling of electromagnetic and elastic materials. These materials are characterized by equilibrium configurations exhibiting multiple phases. Examples include elastic ferromagnets and rigid superconductors. The basic modeling tools will be the use of spatially nonlocal energy terms to penalize oscillations in classical states and the variance of Young-measure states. Also included are existence results for short time dynamics of materials satisfying a generalized strong ellipticity hypothesis on electromagnetic and elastic properties and existence of equilibrium solutions for elastic bodies with perfect diamagnetism (elastic superconductors.) These studies will lead to a better understanding of the mechanical properties of elastic and electromagnetic materials and composites and will have an impact on the development and synthesis of materials with optimal properties.

Laboratory experiments are being integrated into the undergraduate math curriculum. In particular, two courses are being affected - Applied Computational Mathematics and Fourier Series and PDEs - and changes are being made in other undergraduate courses on mathematical modeling, dynamical systems, and control. For example, 1) students are able to take experimental data which they have collected themselves and program and implement the routines to analyze it using discrete Fourier transforms; 2) students who have solved a PDE by separation of variables can see their solutions evolve in time and understand better the physical phenomena the equations describe; 3) students are able to compare separation of variables solutions of such problems as the Euler-Bernoulli beam and the vibrating drum head to experimental data.

9403844 Rogers This project will support an ongoing study of a family of problems in phase transitions. The problems come from three areas of application: mechanics (liquid-vapor, solid-liquid, and multiphase-solid transitions), superconductivity, and magnetism (rigid ferromagnets as well as magnetostrictive materials). The research primarily involves studying static problems of energy minimization and trying to characterize the set of metastable states (local minimizers) of the energy. The goal is to describe hysteresis (which occurs in all of these problems) in terms of these metastable states. The primary technique is to model the physical problems being studied using relaxed, nonlocal energy functionals. Stationary points and/or relative minimizers are found using techniques of integral equations, convex analysis, and methods from the calculus of variations. Numerical algorithms are developed to approximate solutions of the Euler-Lagrange equations. The most useful properties of many high-tech materials (e.g. shape memory alloys, magnetic and magnetostrictive materials, and superconductors) are caused by the material undergoing a change of "phase." Often, these phase changes do not occur smoothly, but instead, exhibit wild oscillations at a microscopic level. In the last century, there has been a great deal of empirical study of these phenomena by materials scientists. But it was only in the past decade that mathematicians began to turn these investigations into a more quantitative science. The current project aims to make quantitative predictions of the behavior of large-scale material structures based on fundamental models of the internal energy. The project combines elements of mathematical modeling, mathematical analysis, and the development and analysis of new numerical algorithms. The proposed applications are to liquid-vapor transitions, crystal growth, shape memory alloys, magnetic and magnetostrictive materials, and superc onductors.

DMS-9704621 Rogers This grant funds a program of mathematical investigations of the alpha-beta phase transition in quartz. In unstressed quartz this transition occurs at about 574 degrees Centigrade, at which point a quartz crystal undergoes a change in shape, volume, and symmetry. The high temperature beta-phase has larger volume and higher symmetry than the low-temperature alpha-phase. The alpha-beta transition can be accompanied by an interesting triangular microstructure that is quite different from the layered microstructures that are usually found in shape memory alloys and ferromagnetic materials. An interesting mathematical feature of the problem is that the microstructure is describe by the oscillation of a scalar order parameter. Order parameters have been used in many other studies of phase transitions, but they are usually hard to measure and are defined in fairly fuzzy physical terms. On the other hand, the order parameter in quartz is well defined physically and there are good techniques for measuring it. Thus, it provides an excellent test case for mathematical models using order parameters. The proposers plan to use techniques of differential equations, the calculus of variations, scientific computation, and bifurcation theory to study both standard models for quartz and models that they will propose. %%% When a material undergoes a drastic change in its fundamental properties we say it has undergone a "phase transition." The obvious examples are freezing and melting, evaporation and condensation, but more subtle atomic rearrangements are covered by the term as well. Despite the technological importance of such material changes, the mathematical theory describing them is nowhere near as well developed as theory describing the motion, deformation, and thermal properties of materials. This grant funds a program of mathematical investigations of a phase transition in quartz. The transition is caused by changing temperature and occurs at about 574 degrees Centigrade. At this temperature, a quartz crystal undergoes a change in shape, volume, and symmetry. The transition can be accompanied by an interesting microscopic triangular pattern that is quite different from the layered patterns that are usually found in shape memory alloys and ferromagnetic materials. An understanding of these microscopic patterns (called "microstructures") is widely believed to be a key to the understanding of the phase transitions that they accompany. There are a number of reasons for focusing on this particular phase transition. Quartz has a number of important industrial applications such as oscillators and optical waveguides. In addition, the transition in quartz is usually described mathematically by a quantity called an "order parameter." Order parameters have been used in many other types of phase transitions, but they are usually hard to measure and are defined in fairly fuzzy physical terms. On the other hand, the order parameter in quartz is well defined physically and there are good techniques for measuring it. Thus, quartz provides an excellent test case for mathematical models using order parameters. ***

The Lung Health Study (LHS), conducted from 1986-1994, demonstrated that a smoking intervention program in middle-aged long-term cigarette smokers can result in a highly significant beneficial effect on the rate of FEV1 decline over five years. However, FEV1 is only a surrogate marker for clinical outcomes of respiratory morbidity and mortality. The present study proposes long-term post-trial follow-up of former LHS participants to assess the incidence of morbidity and mortality from respiratory and cardiovascular diseases and other causes, as documented by hospital, clinic, and death records. A pulmonary function test 11 to 12 years after entry into the LHS is also proposed to determine long- term effects of the LHS smoking intervention program on lung function. The main objectives of the study are as follows: 1) to determine, using an intent-to-treat analysis, whether the LHS smoking intervention significantly reduces the incidence of clinically important respiratory and cardiovascular disease over a 12- to 15-year period following study enrollment; 2) to determine whether the beneficial effect of the smoking intervention program on measures of lung function persists through 11 to 12 years of follow-up; 3) to estimate the magnitude of the effects of FEV1 and FVC on the risks of cardiovascular and respiratory morbidity and mortality, after controlling for smoking history; 4) to study the role of other factors [gender, airways reactivity, weight gain, and co- morbidities] in determining the rate of decline in pulmonary function and the risks of cardiovascular and respiratory morbidity and mortality. All ten of the original LHS clinical centers plan to participate. To minimize bias, all surviving participants of the LHS will be invited to participate, giving a potential sample size of 5600.

DESCRIPTION (Applicant's abstract): The long-term objective of the proposed work is to understand signal processing as it applies to homeodynamic control of respiratory and related autonomic functions. The work focuses primarily on processing of one particular afferent signal, that of the pulmonary stretch receptor. Activation of these mechanoreceptors induces a host of motor control responses including alteration of respiratory effort, cardiac rate and output, and bronchodilatation. Clinically, alteration of the function of these and other receptors by pathophysiological conditions (e.g. pulmonary edema, congestive heart failure) may contribute to worsening of these disease states. On a more basic level, the processing of these input signals by central nervous system networks remains unclear even in the healthy state. For example, it is not known how (or what types of) information regarding the peripheral physiological signal (pulmonary distention) is encoded by single, or groups of, neurons within the central nervous system. What is known is that the nervous system analyzes this and other signals continuously in order to control the relevant functions, and that the currency of information exchange among and between neurons is their ongoing spike trains. In order to address these issues, we have developed and propose to apply a strict probabilistic measure of neural encoding and decoding schemes that quantify exactly what and how much information is transmitted by individual, defined elements in the control circuits. This is to be done by performing in vivo recordings of individual or small populations of neurons throughout the system, all while exposing the system to continuous stimulus perturbations. The subsequent analysis will systematically define the quantity and quality of pulmonary distension information present in the (1) primary afferent neurons, (2) the dorsal respiratory group neurons within the NTS, (3) the ventral respiratory group, and (4) the motor neuron population. In addition, we will determine the properties and mechanisms behind information transfer between neurons in this system, including integration and learning. The results of these studies should significantly clarify the mechanisms underlying the control strategies in this system, and contribute a base for diagnostic and therapeutic approaches to clinical treatment of pathologies thereof.

This award supports a strategic planning effort by the Treehaven Center, the primary field station of the University of Wisconsin-Stevens Point's (UWSP) College of Natural Resources (CNR). Located in northern Wisconsin 121 km north of the main campus, the station includes large indoor facilities and 560 ha of varied northern hardwood-conifer forest, wetland, and aquatic habitats. Annual use of the Center totals nearly 16,000 person-days. A nationally recognized summer field program has provided rigorous field experience in natural resources management and ecological research methods for approximately 185 CNR undergraduates annually for two decades. These students have worked with faculty and other researchers on topics ranging from carnivore and plant community dynamics, to habitat disturbance and restoration studies, and to ground- and surface-water quality monitoring. Because of growth in its programs and in its user base, the Center has exceeded the original design limitations of its facilities and operations, which are now over 20 years old.
With support from the award, the Center will undertake a 24-month collaborative planning process consisting of a targeted series of five workshops (two at UWSP, three at Treehaven), two site visits, and two breakout sessions following each of the five workshops. The planning process will involve UWSP and Treehaven faculty and non-UWSP stakeholders, including station directors, school teachers, administrators, college students, agencies (local, state , federal), environmental organizations, industry, architects, planners, Treehaven Board of Advisors, and other community members. A series of interviews, workshops, site visits, breakout sessions, and other interdisciplinary collaborations are intended to produce a master plan with both 5- and 10-year time horizons. The effort is aimed at reestablishing seamless linkages between education and research programs at the field station. The Treehaven Center mediates the synergistic juxtaposition of varied groups seeking understanding to promote sustainability through conservation. Programs aimed at K-12 teachers and students, and other programs aimed at the public, share both the facilities and a sense of purpose with the college students and researchers who also use the facility. Treehaven hosts the nation's largest field camp for natural resources undergraduates and also provides an abundance of nationally acclaimed K-12, adult, and teacher-training programming.

DESCRIPTION (provided by applicant): Respiration in mammals is a primal homeostatic process, regulating levels of oxygen (O2) and carbon dioxide (CO2) in blood and tissues and is crucial for life. Rhythmic respiratory movements must occur continuously throughout life and originate from neural activity generated by specially organized circuits in the brain stem constituting the respiratory central pattern generator (CPG). The respiratory CPG generates rhythmic patterns of motor activity that produce coordinated movements of the respiratory pump (diaphragm, thorax, and abdomen), controlling lung inflation and deflation, and upper airway muscles, controlling airflow. These coordinated rhythmic movements drive exchange and transport of O2 and CO2 that maintain physiological homeostasis of the brain and body. Uncovering complex multilevel and multiscale mechanisms operating in the respiratory system, leading to mechanistic understanding of breathing, including breathing in different disease states requires a Physiome-type approach that relies on the development and explicit implementation of multiscale computational models of particular organs and physiological functions. The specific aims of this multi-institutional project are: (1) develop a Physiome-type, predictive, multiscale computational model of neural control of breathing that links multiple physiological mechanisms and processes involved in the vital function of breathing but operating at different scales of functional and structural organization, (2) validate this model in a series of complementary experimental investigations and (3) use the model as a computational framework for formulating predictions about possible sources and mechanisms of respiratory pattern alteration associated with heart failure. The project brings together a multidisciplinary team of scientists with long standing collaboration and complementary expertise in respiration physiology, neuroscience and translational medical studies (Thomas E. Dick, Case Western Reserve University; Julian F.R. Paton, University of Bristol, UK; Robert F. Rogers, Drexel University; Jeffrey C. Smith, NINDS, NIH, intramural), mathematics, system analysis and bioengineering (Alona Ben-Tal, Massey University, NZ), and computational neuroscience and neural control (Ilya A. Rybak, Drexel University). The end result of our proposed cross-disciplinary modeling and experimental studies will be the development and implementation of a new, fully operational, multiscale model of the integrated neurophysiological control system for breathing based on the current state of physiological knowledge. This model can then be used as a computational framework for formulating predictions about possible neural mechanisms of respiratory diseases and suggesting possible treatments.

A research team from University of Wisconsin and California State University Stanislaus, in collaboration with scientists from El Salvador, Guatemala, Honduras, France, Mexico, and Spain are carrying out an integrated study of faulting and the earthquake cycle in northern Central America, at the deforming western end of the Caribbean plate. The major emphasis is to better measure and model deformation around a continental triple junction in southern Guatemala, where the Motagua and Polochic fault system terminates the Caribbean-North America plate boundary. Existing and new data from 110 campaign and continuous GPS sites in El Salvador, Guatemala, Honduras, and southern Mexico will be compiled and analyzed to create the first consistent regional-scale GPS velocity field for the western Caribbean. The new velocity field will be used to study four important topics, including: 1) how deformation is accommodated around the continental triple junction; 2) the motion and internal deformation of the Central America forearc sliver; 3) the manner in which the Jalpatagua fault and other volcanic arc faults in Guatemala accommodate this movement and interact with the magmatic arc; and 4) how extension is accommodated between the sinistral Motagua-Polochic fault system and the dextral Jalpatagua fault and the influence on subduction coupling and upper plate deformation of a 50 degree change in the dip of the subducting Cocos plate. Complementary outcrop, gravity, paleomagnetic, radiometric, and geochemical data will be collected in Guatemala and Honduras to provide a geological framework for interpreting and modeling the GPS velocity field. Forward and inverse modeling that integrates the available geodetic and structural observations and suitable earthquake constraints will be used to better understand the factors that dictate deformation in the region and optimize estimates of block rotations, fault coupling and locking depths, and strain rates and directions within quasi-rigid blocks.

Estimates of interseismic strain rates and long-term fault slip rates that will result from this work will inform risk analysis in El Salvador, Honduras, and Guatemala, where destructive earthquakes have occurred in the past 35 years. The study complements publicly funded studies of natural hazards in neighboring countries (i.e. Mexico, Nicaragua, Costa Rica) and together will substantially advance understanding of these hazards in much of Central America and southern Mexico. Training workshops to be held in Guatemala and El Salvador will target one or more techniques and will constitute a mini-forum for presenting project results and educating students, scientists, and the broader public in the host countries.