The thermodynamics and statistical mechanics of protein folding

The physics of self-organization and complexity is manifested on a variety of biological scales, from large ecosystems to the molecular level. Protein molecules exhibit characteristics of complex systems in terms of their structure, dynamics, and function. Proteins have the extraordinary ability to fold to a specific functional three-dimensional shape, starting from a random coil, in a biologically relevant time. How they accomplish this is one of the secrets of life. In this work, theoretical research into understanding this remarkable behavior is discussed. Thermodynamic and statistical mechanical tools are used in order to investigate the protein folding dynamics and stability. Theoretical analyses of the results from computer simulation of the dynamics of a four-helix bundle show that the excluded volume entropic effects are very important in protein dynamics and crucial for protein stability. The dramatic effects of changing the size of sidechains imply that a strategic placement of amino acid residues with a particular size may be an important consideration in protein engineering. Another investigation deals with modeling protein structural transitions as a phase transition. Using finite size scaling theory, the nature of unfolding transition of a four-helix bundle protein was investigated and critical exponents for the transition were calculated for various hydrophobic strengths in the core. It is found that the order of the transition changes from first to higher order as the strength of the hydrophobic interaction in the core region is significantly increased. Finally, a detailed kinetic and thermodynamic analysis was carried out in a model two-helix bundle. The connection between the structural free-energy landscape and folding kinetics was quantified. I show how simple protein engineering, by changing the hydropathy of a small number of amino acids, can enhance protein folding by significantly changing the free energy landscape so that kinetic traps are removed. The results have general applicability in protein engineering as well as understanding the underlying physical mechanisms of protein folding. ^

The relationship between job structure, burnout, and coping methods among public school county bus drivers, bus aides, mechanics, and clerical workers

The purpose of this study was to examine the relationship between the structure of jobs and burnout, and to assess to what extent, if any this relationship was moderated by individual coping methods. This study was supported by the Karasek's (1998) Job Demand-Control-Support theory of work stress as well as Maslach and Leiter's (1993) theory of burnout. Coping was examined as a moderator based on the conceptualization of Lazarus and Folkman (1984). ^ Two overall overarching questions framed this study: (a) what is the relationship between job structure, as operationalized by job title, and burnout across different occupations in support services in a large municipal school district? and (b) To what extent do individual differences in coping methods moderate this relationship? ^ This study was a cross-sectional study of county public school bus drivers, bus aides, mechanics, and clerical workers (N = 253) at three bus depot locations within the same district using validated survey instruments for data collection. Hypotheses were tested using simultaneous regression analyses. ^ Findings indicated that there were statistically significant and relevant relationships among the variables of interest; job demands, job control, burnout, and ways of coping. There was a relationship between job title and physical job demands. There was no evidence to support a relationship between job title and psychological demands. Furthermore, there was a relationship between physical demands, emotional exhaustion and personal accomplishment; key indicators of burnout. ^ Results showed significant correlations between individual ways of coping as a moderator between job structure, operationalized by job title, and individual employee burnout adding empirical evidence to the occupational stress literature. Based on the findings, there are implications for theory, research, and practice. For theory and research, the findings suggest the importance of incorporating transactional models in the study of occupational stress. In the area of practice, the findings highlight the importance of enriching jobs, increasing job control, and providing individual-level training related to stress reduction.^

High-performance liquid chromatography measurement of carotenoids in human serum, etoposide in pig cerebrospinal fluid and measurement of the aggregation of xanthophylls in aqueous solutions

The present study measured a chemotherapy drug, etoposide, in pig cerebrospinal fluid after intraventricular administrations were made directly into the fourth ventricle of the brain; cytotoxic concentrations for a twenty-four hour period after infusions. The analytical method developed validates the potential treatment of malignant brain tumors. The increase in serum carotenoid concentration in 30 healthy individuals was measured after supplementation with lutein. HPLC analysis of serum levels of carotenoids showed an increase in the concentration of lutein and a constant concentration of other major serum carotenoids. An initial attempt to measure the enthalpy of aggregation of xanthophylls was conducted by using ultraviolet-visible spectroscopy. The enthalpy of lutein aggregation and AH range of zeaxanthin disordering of aggregation are reported. Monomethyl ether of lutein did not aggregate in any of the aqueous solutions.

Acoustic Manipulation and Alignment of Particles for Applications in Separation, Micro-Templating, and Device Fabrication

This dissertation studies the manipulation of particles using acoustic stimulation for applications in microfluidics and templating of devices. The term particle is used here to denote any solid, liquid or gaseous material that has properties, which are distinct from the fluid in which it is suspended. Manipulation means to take over the movements of the particles and to position them in specified locations. Using devices, microfabricated out of silicon, the behavior of particles under the acoustic stimulation was studied with the main purpose of aligning the particles at either low-pressure zones, known as the nodes or high-pressure zones, known as anti-nodes. By aligning particles at the nodes in a flow system, these particles can be focused at the center or walls of a microchannel in order to ultimately separate them. These separations are of high scientific importance, especially in the biomedical domain, since acoustopheresis provides a unique approach to separate based on density and compressibility, unparalleled by other techniques. The study of controlling and aligning the particles in various geometries and configurations was successfully achieved by controlling the acoustic waves. Apart from their use in flow systems, a stationary suspended-particle device was developed to provide controllable light transmittance based on acoustic stimuli. Using a glass compartment and a carbon-particle suspension in an organic solvent, the device responded to acoustic stimulation by aligning the particles. The alignment of light-absorbing carbon particles afforded an increase in visible light transmittance as high as 84.5%, and it was controlled by adjusting the frequency and amplitude of the acoustic wave. The device also demonstrated alignment memory rendering it energy-efficient. A similar device for suspended-particles in a monomer enabled the development of electrically conductive films. These films were based on networks of conductive particles. Elastomers doped with conductive metal particles were rendered surface conductive at particle loadings as low as 1% by weight using acoustic focusing. The resulting films were flexible and had transparencies exceeding 80% in the visible spectrum (400-800 nm) These films had electrical bulk conductivities exceeding 50 S/cm.

Acoustic manipulation and alignment of particles for applications in separation, micro-templating and device fabrication

This dissertation studies the manipulation of particles using acoustic stimulation for applications in microfluidics and templating of devices. The term particle is used here to denote any solid, liquid or gaseous material that has properties, which are distinct from the fluid in which it is suspended. Manipulation means to take over the movements of the particles and to position them in specified locations. ^ Using devices, microfabricated out of silicon, the behavior of particles under the acoustic stimulation was studied with the main purpose of aligning the particles at either low-pressure zones, known as the nodes or high-pressure zones, known as anti-nodes. By aligning particles at the nodes in a flow system, these particles can be focused at the center or walls of a microchannel in order to ultimately separate them. These separations are of high scientific importance, especially in the biomedical domain, since acoustopheresis provides a unique approach to separate based on density and compressibility, unparalleled by other techniques. The study of controlling and aligning the particles in various geometries and configurations was successfully achieved by controlling the acoustic waves. ^ Apart from their use in flow systems, a stationary suspended-particle device was developed to provide controllable light transmittance based on acoustic stimuli. Using a glass compartment and a carbon-particle suspension in an organic solvent, the device responded to acoustic stimulation by aligning the particles. The alignment of light-absorbing carbon particles afforded an increase in visible light transmittance as high as 84.5%, and it was controlled by adjusting the frequency and amplitude of the acoustic wave. The device also demonstrated alignment memory rendering it energy-efficient. A similar device for suspended-particles in a monomer enabled the development of electrically conductive films. These films were based on networks of conductive particles. Elastomers doped with conductive metal particles were rendered surface conductive at particle loadings as low as 1% by weight using acoustic focusing. The resulting films were flexible and had transparencies exceeding 80% in the visible spectrum (400-800 nm) These films had electrical bulk conductivities exceeding 50 S/cm. ^

The Relationship between Job Structure, Burnout, and Coping Methods among Public School county Bus Drivers, Bus Aides, Mechanics, and Clerical Workers

The purpose of this study was to examine the relationship between the structure of jobs and burnout, and to assess to what extent, if any this relationship was moderated by individual coping methods. This study was supported by the Karasek's (1998) Job Demand-Control-Support theory of work stress as well as Maslach and Leiter's (1993) theory of burnout. Coping was examined as a moderator based on the conceptualization of Lazarus and Folkman (1984). Two overall overarching questions framed this study: (a) what is the relationship between job structure, as operationalized by job title, and burnout across different occupations in support services in a large municipal school district? and (b) To what extent do individual differences in coping methods moderate this relationship? This study was a cross-sectional study of county public school bus drivers, bus aides, mechanics, and clerical workers (N = 253) at three bus depot locations within the same district using validated survey instruments for data collection. Hypotheses were tested using simultaneous regression analyses. Findings indicated that there were statistically significant and relevant relationships among the variables of interest; job demands, job control, burnout, and ways of coping. There was a relationship between job title and physical job demands. There was no evidence to support a relationship between job title and psychological demands. Furthermore, there was a relationship between physical demands, emotional exhaustion and personal accomplishment; key indicators of burnout. Results showed significant correlations between individual ways of coping as a moderator between job structure, operationalized by job title, and individual employee burnout adding empirical evidence to the occupational stress literature. Based on the findings, there are implications for theory, research, and practice. For theory and research, the findings suggest the importance of incorporating transactional models in the study of occupational stress. In the area of practice, the findings highlight the importance of enriching jobs, increasing job control, and providing individual-level training related to stress reduction.