Emt Driven By Tgf-B Is A Significant Mediator Of Stenosis In Tissue Engineered Vascular Grafts

The development of an autologous tissue engineered vascular graft (TEVG) holds great promise for improving outcomes in congenital heart surgery. The first clinical trial showed that this approach is safe and effective but that the primary mode of failure is stenosis. In a C57BL/6 mouse model of unseeded TEVGs implanted as inferior vena cava interposition grafts, neovessels form in 2 weeks and patent grafts show endothelial and smooth muscle cell (SMC) layers, but occluded grafts show accumulation of SMCs. This suggests stenosis results from abnormal SMC in-growth in the neointima. Studies on fibrosis have shown that resident endothelial cells (EC) contribute to fibroblast accumulation through endothelial-mesenchymal transition (EMT). We utilized transgenic EC lineage-tracing mouse models to track the occurrence of EMT in our TEVG and found an increased percentage of cells co-expressing LacZ and smooth muscle actin in occluded grafts, suggesting that EMT contributes to occlusion in our TEVG. We hypothesized that ECs in our TEVG undergo EMT driven by TGF-B to contribute to stenosis. Immunohistochemistry and qRT-PCR showed higher expression of TGF-B in occluded compared to patent grafts. In vivo expression of a soluble FGF trap virus to increase TGF-B signaling and thus increase EMT was found to result in a significantly increased stenosis rate in our TEVG. We next modulated this pathway by intraperitoneal administration of a small molecule inhibitor of TGF-B receptor type 1 (SB431542). Grafts from treated mice had significantly increased patency rates and internal diameters at 2 weeks compared to controls while maintaining normal neovessel architecture. We then designed a novel local delivery system for this TGF-B R1 inhibitor in our grafts and showed that local drug delivery inhibits stenosis without cell seeding and maintains normal neovessel formation. These results suggest that EMT under the control of TGF-B is a significant mediator of stenosis and that modulation of this pathway by local drug delivery might be useful in next generation TEVGs

Solar rejection in laser based underwater communication systems

This article provides a numerical study of the expected improvements in an underwater optical system given by a single-mode laser diode operating within a Fraunhofer line in a coastal water type. The system performance is examined for a silicon PIN direct-detection receiver in the euphotic zone. The solar irradiance, modelled as white noise, is evaluated when using a lithium niobate interference and a birefringent filter with different field-of-view (FOV) characteristics in a clear sky situation. The results of this analysis show the inverse dependence of the signal-to-noise (SNR) on the FOV, along with the significant improvement in the receiver sensitivity given by a narrow optical bandpass filter (OBPF)

Laser Based Underwater Communication Systems

We report on recent progress in the field of visible light communications including direct modulation of blue laser devices at data rates beyond 10 Gbit/s, and the transmission of 2.5 Gbit/s OOK data through water. We also discuss the advantages of operating with single mode laser devices and matched filtering at the receiver in the context of applications with significant solar background. The system performance for two types of direct-detection receivers, a PIN detector and less conventional silicon Photomultiplier technology will be presented

Rehearsal and pedometer reactivity in children.

The main purpose of this study was to investigate whether rehearsal, defined as the tendency to recurrently ruminate over upsetting aversive experiences, had an effect on pedometry reactivity. A total of 156 Hong Kong Chinese children aged 9–12 years were recruited. Participants completed the Rehearsal Scale for Children-Chinese (RSC-C; Ling, Maxwell, Masters, & McManus, 2010) and wore the pedometers for 3 consecutive weeks. The mean number of steps was significantly higher in Week 1 than in Week 3. High rehearsers showed a larger decrease in mean number of steps from Week 1 to Week 3 than low rehearsers. Future physical activity intervention studies should adjust for reactivity in their baseline measurements and should further examine the relationship between habitual PA and individual propensities for rehearsal

Search Engine for Antimicrobial Resistance: A Cloud Compatible Pipeline and Web Interface for Rapidly Detecting Antimicrobial Resistance Genes Directly from Sequence Data.

BACKGROUND: Antimicrobial resistance remains a growing and significant concern in human and veterinary medicine. Current laboratory methods for the detection and surveillance of antimicrobial resistant bacteria are limited in their effectiveness and scope. With the rapidly developing field of whole genome sequencing beginning to be utilised in clinical practice, the ability to interrogate sequencing data quickly and easily for the presence of antimicrobial resistance genes will become increasingly important and useful for informing clinical decisions. Additionally, use of such tools will provide insight into the dynamics of antimicrobial resistance genes in metagenomic samples such as those used in environmental monitoring. RESULTS: Here we present the Search Engine for Antimicrobial Resistance (SEAR), a pipeline and web interface for detection of horizontally acquired antimicrobial resistance genes in raw sequencing data. The pipeline provides gene information, abundance estimation and the reconstructed sequence of antimicrobial resistance genes; it also provides web links to additional information on each gene. The pipeline utilises clustering and read mapping to annotate full-length genes relative to a user-defined database. It also uses local alignment of annotated genes to a range of online databases to provide additional information. We demonstrate SEAR's application in the detection and abundance estimation of antimicrobial resistance genes in two novel environmental metagenomes, 32 human faecal microbiome datasets and 126 clinical isolates of Shigella sonnei. CONCLUSIONS: We have developed a pipeline that contributes to the improved capacity for antimicrobial resistance detection afforded by next generation sequencing technologies, allowing for rapid detection of antimicrobial resistance genes directly from sequencing data. SEAR uses raw sequencing data via an intuitive interface so can be run rapidly without requiring advanced bioinformatic skills or resources. Finally, we show that SEAR is effective in detecting antimicrobial resistance genes in metagenomic and isolate sequencing data from both environmental metagenomes and sequencing data from clinical isolates.This research was funded by GlaxoSmithKline, the Centre for Environment, Fisheries and Aquaculture Science and the Biotechnology and Biological Sciences Research Council under an industrial CASE studentship. The funder Centre for Environment, Fisheries and Aquaculture Science provided support in the form of salaries, research materials and facilities for authors DVJ and CBA, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder GlaxoSmithKline provided support in the form of salaries for author JR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version. It was first published by PLOS at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133492

Clinical progression of progressive supranuclear palsy: impact of trials bias and phenotype variants.

Funder: Cambridge Brain BankProgressive supranuclear palsy causes diverse clinical presentations, including classical Richardson's syndrome and several variant phenotypes. Clinical trials of disease-modifying therapies have recently been completed, with more planned for the next 2 years. However, many people with progressive supranuclear palsy do not meet eligibility criteria for these clinical trials. Understanding clinical progression with different phenotypes would improve trial design and enhance the accuracy of risk-benefit and cost-benefit assessments of new treatments for progressive supranuclear palsy. We set out to determine rates of motor and cognitive progression of possible, probable and definite progressive supranuclear palsy, with different phenotypes, from a representative cohort in a regional UK healthcare service. Longitudinal clinical data from people with Richardson's syndrome and variant phenotypes were analysed using linear mixed-modelling, using both the full and modified versions of the Progressive Supranuclear Palsy Rating Scale, Mini-Mental State Examination and the revised Addenbrooke's Cognitive Examination. Subgroup analyses considered patients meeting recent Phase II trial entry criteria and patients with neuropathological confirmation. Two hundred and twenty-seven patients [male = 59%, mean age (±standard deviation), 71.8 (±7.0) years] were followed for a mean 21.6 (±15.6) months. One hundred and seventy-four (77%) had Richardson's syndrome at the outset, 25 had cortical variant presentations (13%, frontal, corticobasal, speech and language variants) and 28 had subcortical variant presentations (14%, parkinsonism, postural instability and gait freezing variants). Across all participants, annual progression in Richardson's syndrome was faster than variant phenotypes on the Mini-Mental State Examination (-1.8 versus -0.9/year, P = 0.005) and revised Addenbrooke's Cognitive Examination (-5.3 versus -3.0/year, P = 0.01) but not the Progressive Supranuclear Palsy Rating Scale (9.0 versus 7.1/year, P = 0.2) nor the modified Progressive Supranuclear Palsy Rating Scale (2.7 versus 2.3/year, P = 0.4). However, for those with more than 1 years' follow-up, a significant difference was observed between Richardson's syndrome and variant phenotypes in Progressive Supranuclear Palsy Rating Scale (8.7 versus 6.3/year, P = 0.04). Survival was longer in variant phenotypes than Richardson's syndrome [7.3 (±3.9) versus 5.6 (±2.0) years, P = 0.02]. Pathologically confirmed cases (n = 49) supported these findings. Patients meeting basic trial-eligibility criteria (n = 129) progressed faster on the Progressive Supranuclear Palsy Rating Scale than trial-not-eligible patients (10.1 versus 6.1/year, P = 0.001). In conclusion, phenotypes other than Richardson's syndrome show slower progression and longer survival. Trial criteria do not select representative progressive supranuclear palsy cases. This has implications for trial design, and application of trial results to clinically more diverse patient populations

New tools for self-organized pattern formation

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A decrease in photoperiod shortly after first feeding influences the development of Atlantic salmon (Salmo salar)

Four groups of Atlantic salmon fry (n=2000) were exposed to continuous light (LD24:0) from first feeding on 18th April 2001, after which they were exposed to either an 8 or 12 week period of short days (LD10:14) starting on either the 21st May or the 18th June. Each group was then returned to LD24:0 until the conclusion of the experiment the following March. In August 200 fish per treatment were individually PIT tagged. All groups were maintained under an ambient temperature regime. The highest levels of sexual maturation in 0+ male parr were recorded in the 12 week/May group (>11% of the entire male and female population), with the lowest levels (6%) in the 8 week/May and 8 week/June groups (

Inter-sample contamination detection using mixture deconvolution comparison

© 2019 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (February 2019) in accordance with the publisher’s archiving policyA recent publication has provided the ability to compare two mixed DNA profiles and consider their probability of occurrence if they do, compared to if they do not, have a common contributor. This ability has applications to both quality assurance (to test for sample to sample contamination) and for intelligence gathering purposes (did the same unknown offender donate DNA to multiple samples). We use a mixture to mixture comparison tool to investigate the prevalence of sample to sample contamination that could occur from two laboratory mechanisms, one during DNA extraction and one during electrophoresis. By carrying out pairwise comparisons of all samples (deconvoluted using probabilistic genotyping software STRmix™) within extraction or run batches we identify any potential common DNA donors and investigate these with respect to their risk of contamination from the two proposed mechanisms. While not identifying any contamination, we inadvertently find a potential intelligence link between samples, showing the use of a mixture to mixture comparison tool for investigative purposes