Fast DNA translocation through a solid-state nanopore

We report translocation experiments on double-strand DNA through a silicon oxide nanopore. Samples containing DNA fragments with seven different lengths between 2000 to 96000 basepairs have been electrophoretically driven through a 10 nm pore. We find a power-law scaling of the translocation time versus length, with an exponent of 1.26 $\pm$ 0.07. This behavior is qualitatively different from the linear behavior observed in similar experiments performed with protein pores. We address the observed nonlinear scaling in a theoretical model that describes experiments where hydrodynamic drag on the section of the polymer outside the pore is the dominant force counteracting the driving. We show that this is the case in our experiments and derive a power-law scaling with an exponent of 1.18, in excellent agreement with our data.Comment: 5 pages, 2 figures. Submitted to PR

Structural, electronic, and dynamical properties of amorphous gallium arsenide: a comparison between two topological models

We present a detailed study of the effect of local chemical ordering on the structural, electronic, and dynamical properties of amorphous gallium arsenide. Using the recently-proposed ``activation-relaxation technique'' and empirical potentials, we have constructed two 216-atom tetrahedral continuous random networks with different topological properties, which were further relaxed using tight-binding molecular dynamics. The first network corresponds to the traditional, amorphous, Polk-type, network, randomly decorated with Ga and As atoms. The second is an amorphous structure with a minimum of wrong (homopolar) bonds, and therefore a minimum of odd-membered atomic rings, and thus corresponds to the Connell-Temkin model. By comparing the structural, electronic, and dynamical properties of these two models, we show that the Connell-Temkin network is energetically favored over Polk, but that most properties are little affected by the differences in topology. We conclude that most indirect experimental evidence for the presence (or absence) of wrong bonds is much weaker than previously believed and that only direct structural measurements, i.e., of such quantities as partial radial distribution functions, can provide quantitative information on these defects in a-GaAs.Comment: 10 pages, 7 ps figures with eps

Modern Electronic Techniques Applied to Physics and Engineering

Contains reports on five research projects

Pharmacy sales data versus ward stock accounting for the surveillance of broad-spectrum antibiotic use in hospitals

<p>Abstract</p> <p>Background</p> <p>Antibiotic consumption in hospitals is commonly measured using the accumulated amount of drugs delivered from the pharmacy to ward held stocks. The reliability of this method, particularly the impact of the length of the registration periods, has not been evaluated and such evaluation was aim of the study.</p> <p>Methods</p> <p>During 26 weeks, we performed a weekly ward stock count of use of broad-spectrum antibiotics <b>- </b>that is second- and third-generation cephalosporins, carbapenems, and quinolones <b>- </b>in five hospital wards and compared the data with corresponding pharmacy sales figures during the same period. Defined daily doses (DDDs) for antibiotics were used as measurement units (WHO ATC/DDD classification). Consumption figures obtained with the two methods for different registration intervals were compared by use of intraclass correlation analysis and Bland-Altman statistics.</p> <p>Results</p> <p>Broad-spectrum antibiotics accounted for a quarter to one-fifth of all systemic antibiotics (ATC group J01) used in the hospital and varied between wards, from 12.8 DDDs per 100 bed days in a urological ward to 24.5 DDDs in a pulmonary diseases ward. For the entire study period of 26 weeks, the pharmacy and ward defined daily doses figures for all broad-spectrum antibiotics differed only by 0.2%; however, for single wards deviations varied from -4.3% to 6.9%. The intraclass correlation coefficient, pharmacy versus ward data, increased from 0.78 to 0.94 for parenteral broad-spectrum antibiotics with increasing registration periods (1-4 weeks), whereas the corresponding figures for oral broad-spectrum antibiotics (ciprofloxacin) were from 0.46 to 0.74. For all broad-spectrum antibiotics and for parenteral antibiotics, limits of agreement between the two methods showed, according to Bland-Altman statistics, a deviation of ± 5% or less from average mean DDDs at 3- and 4-weeks registration intervals. Corresponding deviation for oral antibiotics was ± 21% at a 4-weeks interval.</p> <p>Conclusions</p> <p>There is a need for caution in interpreting pharmacy sales data aggregated over short registration intervals, especially so for oral formulations. Even a one-month registration period may be too short.</p

Use of 16S ribosomal RNA gene analyses to characterize the bacterial signature associated with poor oral health in West Virginia

<p>Abstract</p> <p>Background</p> <p>West Virginia has the worst oral health in the United States, but the reasons for this are unclear. This pilot study explored the etiology of this disparity using culture-independent analyses to identify bacterial species associated with oral disease.</p> <p>Methods</p> <p>Bacteria in subgingival plaque samples from twelve participants in two independent West Virginia dental-related studies were characterized using 16S rRNA gene sequencing and Human Oral Microbe Identification Microarray (HOMIM) analysis. Unifrac analysis was used to characterize phylogenetic differences between bacterial communities obtained from plaque of participants with low or high oral disease, which was further evaluated using clustering and Principal Coordinate Analysis.</p> <p>Results</p> <p>Statistically different bacterial signatures (<it>P </it>< 0.001) were identified in subgingival plaque of individuals with low or high oral disease in West Virginia based on 16S rRNA gene sequencing. Low disease contained a high frequency of <it>Veillonella </it>and <it>Streptococcus</it>, with a moderate number of <it>Capnocytophaga</it>. High disease exhibited substantially increased bacterial diversity and included a large proportion of Clostridiales cluster bacteria (<it>Selenomonas</it>, <it>Eubacterium, Dialister</it>). Phylogenetic trees constructed using 16S rRNA gene sequencing revealed that Clostridiales were repeated colonizers in plaque associated with high oral disease, providing evidence that the oral environment is somehow influencing the bacterial signature linked to disease.</p> <p>Conclusions</p> <p>Culture-independent analyses identified an atypical bacterial signature associated with high oral disease in West Virginians and provided evidence that the oral environment influenced this signature. Both findings provide insight into the etiology of the oral disparity in West Virginia.</p

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Genome-wide association Scan of dental caries in the permanent dentition

Background: Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults. Methods: Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries. Results: Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens. Conclusions: As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment

Radiographs Reveal Exceptional Forelimb Strength in the Sabertooth Cat, Smilodon fatalis

Background: The sabertooth cat, Smilodon fatalis, was an enigmatic predator without a true living analog. Their elongate canine teeth were more vulnerable to fracture than those of modern felids, making it imperative for them to immobilize prey with their forelimbs when making a kill. As a result, their need for heavily muscled forelimbs likely exceeded that of modern felids and thus should be reflected in their skeletons. Previous studies on forelimb bones of S. fatalis found them to be relatively robust but did not quantify their ability to withstand loading. Methodology/Principal Findings: Using radiographs of the sabertooth cat, Smilodon fatalis, 28 extant felid species, and the larger, extinct American lion Panthera atrox, we measured cross-sectional properties of the humerus and femur to provide the first estimates of limb bone strength in bending and torsion. We found that the humeri of Smilodon were reinforced by cortical thickening to a greater degree than those observed in any living felid, or the much larger P. atrox. The femur of Smilodon also was thickened but not beyond the normal variation found in any other felid measured. Conclusions/Significance: Based on the cross-sectional properties of its humerus, we interpret that Smilodon was a powerful predator that differed from extant felids in its greater ability to subdue prey using the forelimbs. This enhanced forelimb strength was part of an adaptive complex driven by the need to minimize the struggles of prey in order to protec