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Biomedical subjects

Paul Evans

Publications and source records attributed to Paul Evans.

13 recordsLinked to original sources

Investigating the effects of reduced size on the properties of ferroelectrics.

A series of experiments has been undertaken to understand more about the fundamental origin of the thickness-induced permittivity collapse often observed in conventional thin film ferroelectric heterostructures. The various experiments are discussed, highlighting the eventual need to examine permittivity collapse in thin film single crystal material. It has been seen that dielectric collapse is not a direct consequence of reduced size, and neither is it a consequence of unavoidable physics associated with the ferroelectric-electrode boundary. Research on three-dimensional shape-constrained ferroelectrics, emphasizing self-assembled structures based on nanoporous alumina templates and on FIB-milled single crystals, is also presented, and appears to represent an exciting area for ongoing research.

Computer Simulation↗

Unfolding crystallins: the destabilizing role of a beta-hairpin cysteine in betaB2-crystallin by simulation and experiment.

The thermodynamic and kinetic stabilities of the eye lens family of betagamma-crystallins are important factors in the etiology of senile cataract. They control the chance of proteins unfolding, which can lead to aggregation and loss of transparency. betaB2-Crystallin orthologs are of low stability and comprise two typical betagamma-crystallin domains, although, uniquely, the N-terminal domain has a cysteine in one of the conserved folded beta-hairpins. Using high-temperature (500 K) molecular dynamics simulations with explicit solvent on the N-terminal domain of rodent betaB2-crystallin, we have identified in silico local flexibility in this folded beta-hairpin. We have shown in vitro using two-domain human betaB2-crystallin that replacement of this cysteine with a more usual aromatic residue (phenylalanine) results in a gain in conformational stability and a reduction in the rate of unfolding. We have used principal components analysis to visualize and cluster the coordinates from eight separate simulated unfolding trajectories of both the wild-type and the C50F mutant N-terminal domains. These data, representing fluctuations around the native well, show that although the mutant and wild-type appear to behave similarly over the early time period, the wild type appears to explore a different region of conformational space. It is proposed that the advantage of having this low-stability cysteine may be correlated with a subunit-exchange mechanism that allows betaB2-crystallin to interact with a range of other beta-crystallin subunits.

Circular Dichroism↗

Detecting stem debonding in total hip arthroplasty.

In total hip arthroplasty, cemented femoral components combined with contemporary insertion techniques have an excellent track record of reliable long-term success. Certain cemented stem designs, however, have high failure rates. As osteolysis and bone destruction are rapid and progressive with certain designs, early detection of failure is imperative. We describe a case in which the common failure pattern of debonding is evident after radiographic evaluation with stress application. Although a single-leg stance was used in this case, a modified standing view might also be used.

Aged↗

Reactions of some cyclopentenones with selected cysteine derivatives and biological activities of the product thioethers.

The conjugate addition reaction between glutathione, N-Boc-cysteine methyl ester, N-acetyl cysteine methyl ester and N-acetyl cysteine and several substituted cyclopentenones is described. The reversibility of this process was demonstrated by thio-adduct metathesis on treatment of the adduct with a different cysteinyl derivative. The levels at which these compounds inhibit the function of nuclear factor kappa B (NF-kappaB) and potentiate heat shock factor (HSF) are reported and the possible relevance of these studies concerning the antiviral and anti-inflammatory activities of the cyclopentenone prostanoids is discussed.

Cyclopentanes↗

Biomedical applications of synchrotron radiation circular dichroism spectroscopy: identification of mutant proteins associated with disease and development of a reference database for fold motifs.

Synchrotron radiation circular dichroism (SRCD) spectroscopy is an emerging technique in structural biology with particular value for accurate secondary structure determination, monitoring protein folding and kinetics, and drug discovery. This paper discusses new biomedical applications of SRCD, notably the identification of conformational changes associated with a mutant protein that causes disease, and the development of methods for identification of fold motifs in the context of structural genomics programmes. In addition, it presents for the first time, very low wavelength (below 154 nm) data for a protein in aqueous solution, demonstrating the presence of heretofore-unseen electronic transitions.

Animals↗

Relationship between academic achievement and student performance on the Comprehensive Osteopathic Medical Licensing Examination-USA level 2.

The Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) is a three-part examination used for licensing osteopathic physicians. The relationship between performance on this examination and prior student academic performance has been unclear. This study explores the relationship between COMLEX-USA level 2 scores and student academic performance at Oklahoma State University College of Osteopathic Medicine (OSU-COM). All first-time examination candidates from OSU-COM had a formal, weeklong board review in March 2000, and all passed the examination. Predictions about COMLEX-USA scores generated by the academic dean's office at OSU-COM underestimated student examination performance; results suggest a significant correlation between level 2 performance with (1) level 1 performance (.751); (2) grade point average (GPA) in basic science (.659); (3) total GPA (.672); and (4) Medical College Admission Test (MCAT) scores (.406). The correlation of level 2 scores to clinical GPA (.269) was lower but still significant. Results of this study suggest that performance on COMLEX-USA level 2 is strongly correlated with prior student academic performance in this population.

Educational Measurement↗

Relations between academic performance by medical students and COMLEX-USA Level 2: a multisite analysis.

The Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) is a national medical licensing examination for physicians earning the doctor of osteopathic medicine (DO) degree. Little has been published regarding the validity of this relatively new, high-stakes examination. The purpose of this study was to examine the validity of COMLEX-USA Level 2, which is given to fourth-year osteopathic medical students and focuses on clinically relevant content. Nineteen osteopathic medical schools were asked to submit Level 2 scores and associated academic information, including predictions by deans or deans' representatives regarding whether each student would pass the examination. Twelve of the 17 schools that had students eligible to take the Level 2 examination provided data for 1254 (80%) of 1577 first-time test takers in March 2000. The overall mean score of study participants was 533.35, with a pass rate of 91.98%. The highest average correlation with COMLEX-USA Level 2 performance was with COMLEX-USA Level 1 scores (r = 0.76), followed by basic science grade point average (GPA) (r = .66), total GPA as a fourth-year student (r = .65), and clinical GPA (r = .36). Students identified as being at highest risk received the lowest mean score (427.54) and were most likely to fail Level 2. COMLEX-USA Level 2 scores are moderately to highly related to academic achievement in osteopathic medical schools.

Educational Status↗

Job categories and their effect on exposure to fungal alpha-amylase and inhalable dust in the U.K. baking industry.

Enzymes in flour improver, in particular fungal alpha-amylase, are known to be a significant cause of respiratory allergy in the baking industry. This study measured total inhalable dust and fungal alpha-amylase exposures in U.K. bakeries, mills, and a flour improver production and packing facility and determined whether assignment of job description could identify individuals with the highest exposures to fungal alpha-amylase and inhalable dust. A total of 117 personal samples were taken for workers in 19 bakeries, 2 mills, and a flour improver production and packing facility and were analyzed using a monoclonal based immunoassay. Occupational hygiene surveys were undertaken for each site to assign job description and identify individuals who worked directly with flour improvers. Analysis of exposure data identified that mixers and weighers from large bakeries had the highest exposures to both inhalable dust and fungal alpha-amylase among the different categories of bakery workers (p<.01). Currently, the maximum exposure limit for flour dust in the United Kingdom is 10 mg/m(3) (8-hour time-weighted average reference period). In this study 25% of the total dust results for bakers exceeded 10 mg/m(3), and interestingly, 63% of the individuals with exposure levels exceeding 10 mg/m(3) were weighers and mixers. Individuals who worked directly with flour improvers were exposed to higher levels of both inhalable dust and fungal alpha-amylase (p<.01) than those who were not directly handling these products. Before sensitive immunoassays were utilized for the detection of specific inhalable allergens, gravimetric analysis was often used as a surrogate. There was a weak relationship between inhalable dust and fungal alpha-amylase exposures; however, inhalable dust levels could not be used to predict amylase exposures, which highlights the importance of measuring both inhalable dust and fungal alpha-amylase exposures.

Allergens↗