The Oral Tolerance as a Complex Network Phenomenon

Date of Acceptance: 23/05/2015 Funding: MSB acknowledges the Engineering and Physical Sciences Research Council (EPSRC) - UK grant EP/I032606/1. PJM and MD received regular scholarships from the Brazilian the following agency: Higher Education Personnel Training Coordination (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) CAPES http://www.fisica.uepg.br:7080/ppgfisica​/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Highly Sensitive Electrodic Materials Based on Pt Nanoflowers Grown on Pt Nanospheres for Biosensor Development

In this work we describe the realization of monometallic nanostructures by two simple electrodeposition steps. The surface of the modified electrode was characterized by scanning electron microscopy that confirms a homogeneous deposition of Pt nanospheres decorated with Pt nanoflowers. The so obtained nanostructured sensor exhibited good amperometric response towards hydrogen peroxide sensing at +0.30 V vs Ag|AgCl|Cl-. Therefore, it is especially useful toward glucose detection with reduced interferences. Glucose oxidase was immobilized onto the nanostructured surface by cross-linking with glutaraldehyde and the biosensor was characterized by chronoamperometric method in phosphate buffer. The biosensor showed a sensitivity of 29 ± 2 μA/(mM cm2). Measurements in cell media reveal that the Pt-Pt hybrid nanostructures are promising for real-time glucose monitoring in real biosample

The Worcester Alternative School : a study in the development of an educational innovation.

<p>Graphical representation of the mean flux of walkers f(i) (black histogram) and the KO CD103⁺ (grey histogram).</p

Polynucleotide phosphorylase exonuclease and polymerase activities on single-stranded DNA ends are modulated by RecN, SsbA and RecA proteins

Bacillus subtilis pnpA gene product, polynucleotide phosphorylase (PNPase), is involved in double-strand break (DSB) repair via homologous recombination (HR) or non-homologous end-joining (NHEJ). RecN is among the first responders to localize at the DNA DSBs, with PNPase facilitating the formation of a discrete RecN focus per nucleoid. PNPase, which co-purifies with RecA and RecN, was able to degrade single-stranded (ss) DNA with a 3′ → 5′ polarity in the presence of Mn2+ and low inorganic phosphate (Pi) concentration, or to extend a 3′-OH end in the presence dNDP·Mn2+. Both PNPase activities were observed in evolutionarily distant bacteria (B. subtilis and Escherichia coli), suggesting conserved functions. The activity of PNPase was directed toward ssDNA degradation or polymerization by manipulating the Pi/dNDPs concentrations or the availability of RecA or RecN. In its dATP-bound form, RecN stimulates PNPase-mediated polymerization. ssDNA phosphorolysis catalyzed by PNPase is stimulated by RecA, but inhibited by SsbA. Our findings suggest that (i) the PNPase degradative and polymerizing activities might play a critical role in the transition from DSB sensing to end resection via HR and (ii) by blunting a 3′-tailed duplex DNA, in the absence of HR, B. subtilis PNPase might also contribute to repair via NHEJ

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Distributed Estimation through Randomized Gossip Kalman Filter

Abstract—In this paper we consider the problem of estimat-ing a random process from noisy measurements, collected by a sensor network. We analyze a distributed two–stage algorithm. The first stage is a Kalman–like estimate update, in which each agent makes use only of its own measurements. During the second phase agents communicate with their neighbors to improve their estimate. Estimate fusion is operated by running a consensus iteration. In literature it has been considered only the case of a fixed communication strategies, i.e. described by a fixed constant consensus matrix. However, in many practical cases this is just a rough model of communications in a sensor network, that usually happen according to a randomized strategy. This strategy is more properly modeled by assuming that the consensus matrices are drawn, according to a selection probability, from an alphabet of matrices compatible with the communication graph, at each time instant. This work deals therefore with randomized communication strategies and in particular with the symmetric gossip. A mean square performance analysis is carried out and an upper–bound for the trace of the estimation error variance is derived. The proposed upper–bound has to be considered the main technical contribution of the present paper, since it is based on a highly non–trivial inequality on matrix singular values, proved in the appendix. This upper–bound is a good performance assessment index and it is assumed therefore as a cost function to be minimized. We show moreover that problem of minimizing this cost function by choosing the Kalman gain and the selection probability is convex in each of the two variables separately although it is not jointly convex. Finally simulations are presented and the results discussed. I