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Search Results: 1 - 10 of 471514 matches for " Christopher A. Penfold "
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Modeling Meiotic Chromosomes Indicates a Size Dependent Contribution of Telomere Clustering and Chromosome Rigidity to Homologue Juxtaposition
Christopher A. Penfold,Paul E. Brown,Neil D. Lawrence,Alastair S. H. Goldman
PLOS Computational Biology , 2012, DOI: 10.1371/journal.pcbi.1002496
Abstract: Meiosis is the cell division that halves the genetic component of diploid cells to form gametes or spores. To achieve this, meiotic cells undergo a radical spatial reorganisation of chromosomes. This reorganisation is a prerequisite for the pairing of parental homologous chromosomes and the reductional division, which halves the number of chromosomes in daughter cells. Of particular note is the change from a centromere clustered layout (Rabl configuration) to a telomere clustered conformation (bouquet stage). The contribution of the bouquet structure to homologous chromosome pairing is uncertain. We have developed a new in silico model to represent the chromosomes of Saccharomyces cerevisiae in space, based on a worm-like chain model constrained by attachment to the nuclear envelope and clustering forces. We have asked how these constraints could influence chromosome layout, with particular regard to the juxtaposition of homologous chromosomes and potential nonallelic, ectopic, interactions. The data support the view that the bouquet may be sufficient to bring short chromosomes together, but the contribution to long chromosomes is less. We also find that persistence length is critical to how much influence the bouquet structure could have, both on pairing of homologues and avoiding contacts with heterologues. This work represents an important development in computer modeling of chromosomes, and suggests new explanations for why elucidating the functional significance of the bouquet by genetics has been so difficult.
Interaction of Nuclease Colicins with Membranes: Insertion Depth Correlates with Bilayer Perturbation
Mireille Vankemmelbeke, Paul O′Shea, Richard James, Christopher N. Penfold
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046656
Abstract: Background Protein transport across cellular membranes is an important aspect of toxin biology. Escherichia coli cell killing by nuclease colicins occurs through DNA (DNases) or RNA (RNases) hydrolysis and to this end their cytotoxic domains require transportation across two sets of membranes. In order to begin to unravel the molecular mechanisms underlying the membrane translocation of colicin nuclease domains, we have analysed the membrane association of four DNase domains (E9, a charge reduction E9 mutant, E8, and E7) and one ribosomal RNase domain (E3) using a biomembrane model system. Principal Results We demonstrate, through the use of large unilamellar vesicles composed of synthetic and E. coli lipids and a membrane surface potential sensor, that the colicin nuclease domains bind anionic membranes only, with micromolar affinity and via a cooperative binding mechanism. The evaluation of the nuclease bilayer insertion depth, through a fluorescence quenching analysis using brominated lipids, indicates that the nucleases locate to differential regions in the bilayer. Colicin DNases target the interfacial region of the lipid bilayer, with the DNase E7 showing the deepest insertion, whereas the ribosomal RNase E3 penetrates into the hydrophobic core region of the bilayer. Furthermore, the membrane association of the DNase E7 and the ribosomal RNase E3 induces vesicle aggregation, lipid mixing and content leakage to a much larger extent than that of the other DNases analysed. Conclusions/Significance Our results show, for the first time, that after the initial electrostatically driven membrane association, the pleiotropic membrane effects induced by colicin nuclease domains relate to their bilayer insertion depth and may be linked to their in vivo membrane translocation.
La democracia subyugada: El hiperpresidencialismo venezolano
Revista de ciencia política (Santiago) , 2010, DOI: 10.4067/S0718-090X2010000100003
Abstract: the state of democracy in venezuela combines relatively fair, free, and electoral procedures but with distinct authoritarian features: the lack of autonomy in the judicial and legislative powers vis-à-vis an executive with extraordinary attributions; the development of complex dynamics of centralization of power by the president; the free access to oil revenues by the federal government; the absence of an independent and impartial press and the loss of transparency in the government, among others. moreover, the abnormalities in the 2009 referendum (that has allowed the emergence of the only presidential system in the region without term limits) suggest that even electoral democracy is being undermined in the country.
La democracia subyugada: El hiperpresidencialismo venezolano Venezuelan's Hiperpresidentialism: Democracy Suhjugated
Revista de Ciencia Política , 2010,
Abstract: El estado de la democracia en Venezuela combina prácticas electorales débilmente institucionalizadas aunque relativamente libres y limpias pero con claros rasgos autoritarios: la falta de autonomía de los poderes Judicial y Legislativo frente a un Ejecutivo con atribuciones extraordinarias; el desarrollo de complejas dinámicas de centralización del poder hacia la figura del Presidente; el acceso irrestricto a los recursos petroleros por parte del gobierno federal; la ausencia de una prensa imparcial e independiente y la pérdida de transparencia en el gobierno, entre otros. Las anormalidades constitucionales en el referéndum de 2009 (que permite el surgimiento del único sistema presidencial en la región con reelección ilimitada) sugieren además que incluso la democracia electoral está siendo socavada. The state of democracy in Venezuela combines relatively fair, free, and electoral procedures but with distinct authoritarian features: the lack of autonomy in the Judicial and Legislative powers vis-à-vis an Executive with extraordinary attributions; the development of complex dynamics of centralization of power by the President; the free access to oil revenues by the federal government; the absence of an independent and impartial press and the loss of transparency in the government, among others. Moreover, the abnormalities in the 2009 referendum (that has allowed the emergence of the only presidential system in the region without term limits) suggest that even electoral democracy is being undermined in the country.
Total variation superiorization schemes in proton computed tomography image reconstruction
S. N. Penfold,R. W. Schulte,Y. Censor,A. B. Rosenfeld
Physics , 2010, DOI: 10.1118/1.3504603
Abstract: Purpose: Iterative projection reconstruction algorithms are currently the preferred reconstruction method in proton computed tomography (pCT). However, due to inconsistencies in the measured data arising from proton energy straggling and multiple Coulomb scattering, noise in the reconstructed image increases with successive iterations. In the current work, we investigated the use of total variation superiorization (TVS) schemes that can be applied as an algorithmic add-on to perturbation-resilient iterative projection algorithms for pCT image reconstruction. Methods: The block-iterative diagonally relaxed orthogonal projections (DROP) algorithm was used for reconstructing Geant4 Monte Carlo simulated pCT data sets. Two TVS schemes added on to DROP were investigated; the first carried out the superiorization steps once per cycle and the second once per block. Simplifications of these schemes, involving the elimination of the computationally expensive feasibility proximity checking step of the TVS framework, were also investigated. The modulation transfer function and contrast discrimination function were used to quantify spatial and density resolution, respectively. Results: With both TVS schemes, superior spatial and density resolution was achieved compared to the standard DROP algorithm. Eliminating the feasibility proximity check improved the image quality, in particular image noise, in the once-per-block superiorization, while also halving image reconstruction time. Overall, the greatest image quality was observed when carrying out the superiorization once-per-block and eliminating the feasibility proximity check. Conclusions: The low contrast imaging made possible with TVS holds a promise for its incorporation into our future pCT studies.
Occupational Fatalities Involving Hispanic Workers in the Construction Industry  [PDF]
Christopher A. Janicak
Open Journal of Safety Science and Technology (OJSST) , 2013, DOI: 10.4236/ojsst.2013.31001

This study examined occupational fatality cases involving Hispanic workers that occurred from 2005 to 2009 in the United States. During this period, approximately 26 percent of all fatalities in the construction industry involved Hispanic workers resulting in significantly greater odds for Hispanic workers of being the victim of an occupational fatality due to falls and contact with objects. These increased odds also occurred across most age groups. Prevention measures presented include focusing efforts on construction industry trades that employ younger Hispanic workers and expose them to fall and contact with objects hazards.

Pre-operative clinical assessment for anaesthesia and the effect of HIV infection
PR Penfold, AC Lundgren
South African Medical Journal , 2008,
Abstract: Background. HIV infection is common in South Africa, often remaining clinically latent and liable to be missed during clinical pre-operative assessment, despite the patient having a severe degree of immune compromise. Objectives. The primary objective was to determine the pre-operative physical status of patients presenting for anaesthesia, and to compare this with subsequent HIV tests and the CD4 counts of the HIV-positive patients. The secondary objective was to determine the prevalence of HIV infection in this group and in selected subgroups. Method. A sample of 350 adult patients presenting for anaesthesia at Chris Hani Baragwanath Hospital were interviewed pre-operatively, examined, and their American Society of Anesthesiologists physical status grading determined. In those who were confirmed HIV positive by blood sample, a CD4 count was checked. Further data were collected to determine trends in the characteristics of HIVpositive patients. Results. HIV-positive patients were more likely to be classified as ASA 1 or 2 than ASA 3 or 4 (odds ratio (OR) 2.1). HIVpositive patients with CD4 counts >200 cells/μl were more likely to be ASA 1 or 2 (OR 3.88). Of HIV-positive patients with CD4 counts <200 cells/μl, significantly more were classified as ASA 1 or 2 than ASA 3 or 4 (p<0.0001). Three patients with CD4 counts <50 cells/μl were classified as ASA 1 or 2. The overall prevalence of HIV infection was 29.4%. Females, patients presenting for obstetric surgery, and younger age groups had higher disease prevalence rates. Patients aged 30 - 39 years (43.0%) had the highest prevalence of HIV infection; the lowest was in patients aged 60 years or older (7.7%). Conclusions. Routine clinical pre-operative assessment in patients from a population with a high HIV prevalence rate may result in asymptomatic, severe immune compromise being missed in a significant number of patients. South African Medical Journal Vol. 98 (7) 2008: pp. 545-548
Techniques in Iterative Proton CT Image Reconstruction
Scott Penfold,Yair Censor
Mathematics , 2015, DOI: 10.1007/s11220-015-0122-3
Abstract: This is a review paper on some of the physics, modeling, and iterative algorithms in proton computed tomography (pCT) image reconstruction. The primary challenge in pCT image reconstruction lies in the degraded spatial resolution resulting from multiple Coulomb scattering within the imaged object. Analytical models such as the most likely path (MLP) have been proposed to predict the scattered trajectory from measurements of individual proton location and direction before and after the object. Iterative algorithms provide a flexible tool with which to incorporate these models into image reconstruction. The modeling leads to a large and sparse linear system of equations that can efficiently be solved by projection methods-based iterative algorithms. Such algorithms perform projections of the iterates onto the hyperlanes that are represented by the linear equations of the system. They perform these projections in possibly various algorithmic structures, such as block-iterative projections (BIP), string-averaging projections (SAP). These algorithmic schemes allow flexibility of choosing blocks, strings, and other parameters. They also cater for parallel implementations which are apt to further save clock time in computations. Experimental results are presented which compare some of those algorithmic options.
Reliability of a patient survey assessing cost-related changes in health care use among high deductible health plan enrollees
Robert B Penfold, Jeffrey T Kullgren, Irina Miroshnik, Alison A Galbraith, Virginia L Hinrichsen, Tracy A Lieu
BMC Health Services Research , 2011, DOI: 10.1186/1472-6963-11-133
Abstract: We administered a cross-sectional survey to a stratified random sample of families in a New England health plan's high deductible health plan (HDHP) with ≥ $500 in annualized out-of-pocket expenditures. Enrollees were asked about their knowledge of their plan, information seeking, behavior change associated with having a deductible, experience of delay in care due in part to cost, and hypothetical delay in care due in part to cost. Initial respondents were mailed a follow-up survey within two weeks of each family returning the original survey. We computed several agreement statistics to measure the test-retest reliability for select questions. We also conducted continuity adjusted chi-square, and McNemar tests in both the original and follow-up samples to measure the degree to which our results could be reproduced. Analyses were stratified by self-reported income.The test-retest reliability was moderate for the majority of questions (0.41 - 0.60) and the level of test-retest reliability did not differ substantially across each of the broader domains of questions. The observed proportions of respondents with delayed or foregone pediatric, adult, or any family care were similar when comparing the original and follow-up surveys. In the original survey, respondents in the lower-income group were more likely to delay or forego pediatric care, adult care, or any family care. All of the tests comparing income groups in the follow-up survey produced the same result as in the original survey.In this population of HDHP beneficiaries, we found that survey questions concerning plan knowledge, information seeking, and delayed or foregone care were moderately reliable. Our results offer reassurance for researchers using survey information to study the effects cost sharing on health care utilization.Increases in health care costs have led to increases in patient cost-sharing arrangements such as high deductibles. The percentage of Americans insured by high deductible health plans
Early Exposure to Environmental Toxin Contributes to Neuronal Vulnerability and Axonal Pathology in a Model of Familial ALS  [PDF]
Grace Lee, Christopher A. Shaw
Neuroscience & Medicine (NM) , 2012, DOI: 10.4236/nm.2012.34050
Abstract: Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of endemic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of Parkinsonism and dementia in some patients led to searches for environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-environment interaction in some forms of the disease.
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