The robustness of carbon fibre members bonded to aluminium connectors in aerial delivery systems

In this paper a framework for robust design solution of an adhesively bonded joint between a composite material and an aluminum connector is developed. To this end, an approach has been developed to automate the process of robust design by linking Ansys workbench and an in-house MATLAB code. The model employed in this study investigated the possibility of joining composite materials to aluminum components which is a problematic process in terms of preparation, implementation, etc. Before designing such a join, it is necessary to fully understand the behaviour of the proposed aluminum connector with the carbon fibre member. To achieve this, the investigation of the adhesive layer’s behaviour and the uncertainties involved in such structures was identified. The behaviour of the adhesive between the carbon fibre composite and the aluminum connector was modelled based on the assumption that this layer acts as a “spring system” within a “cohesive” zone. Initially, the properties of Permabond ET5428 BLACK adhesive were used for validating the finite element model using the obtained test data. A robust design method is then employed to identify the right adhesive for the joint which not only maximizes the debonding force and sliding distance but is also robust with respect to the variation in its mechanical properties. A wide range of adhesive properties have been employed and a robust design technique based on uncertainty analysis is proposed

The History of Urological Care and Training at Thomas Jefferson University

The Department of Urology at Thomas Jefferson University and Thomas Jefferson University Hospital is generally acknowledged as the oldest formal Department of Urology in the US, formally designated as the Department of Genitourinary Surgery in 1904. The Department has been under the direction of 8 chairmen and has trained over 144 residents and 25 fellows with over 200 Jefferson Medical College graduates specializing in urology. Thomas Jefferson University was originally founded as Jefferson Medical College in 1824. Dr. George McClelland petitioned Jefferson College at Cannonsburg (now Washington and Jefferson College) to add a medical school to their institution. While technically part of Jefferson College in western Pennsylvania, Jefferson Medical College was to be located in Philadelphia under the direction of the medical faculty. By 1838, Jefferson Medical College gained its own charter and was no longer affiliated with Jefferson College. As a proprietary school, the faculty administrated and managed all the finances of the school. This included the sale of “tickets” to attend lectures. An infirmary to treat the poor was established in 1825. This dispensary to treat indigent patients under student observation was the first instituted by any medical school in the United States. Eventually, all medical schools in the United States adopted Jefferson’s example of combining lectures with practical patient experience. In 1969 Thomas Jefferson University was established that incorporated Jefferson Medical College, the College of Allied Health Sciences, the College of Graduate Studies and the Jefferson Medical College Hospital

A Simple Supramolecular Approach to Recycling Rare Earth Elements

The rapid increase in demand for rare-earth elements reflects their crucial roles in climate critical technologies. However, the lack of simple solutions for the separation of these metals from waste materials and ores represents a significant barrier to sustainable and environmentally benign rare-earth production. We report the application of a supramolecular approach to this challenge, using a triamido-arene receptor to selectively precipitate f-elements through their encapsulation as hexanitratometalates. Single-step, near quantitative recovery of Nd/Pr directly from magnet scrap was observed without the need for pH adjustment or pretreatment of the acidic leach solution. The rare-earth nitrate was rapidly stripped from the host−guest precipitate with water and the receptor recycled for further use. Near quantitative and highly selective uptake of La−Nd and Th from lateritic rare-earth ores was also achieved with no uptake of any non-f-element. These results show that targeting f-element metalates in separations chemistry can deliver exceptional and unique selectivity that may have significant consequences in the sustainable production of the rare-earth elements

An active registry for bioinformatics web services

Summary: The EMBRACE Registry is a web portal that collects and monitors web services according to test scripts provided by the their administrators. Users are able to search for, rank and annotate services, enabling them to select the most appropriate working service for inclusion in their bioinformatics analysis tasks

Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics

The RPE65 gene encodes the isomerase of the retinoid cycle, the enzymatic pathway that underlies mammalian vision. Mutations in RPE65 disrupt the retinoid cycle and cause a congenital human blindness known as Leber congenital amaurosis (LCA). We used adeno-associated virus-2-based RPE65 gene replacement therapy to treat three young adults with RPE65-LCA and measured their vision before and up to 90 days after the intervention. All three patients showed a statistically significant increase in visual sensitivity at 30 days after treatment localized to retinal areas that had received the vector. There were no changes in the effect between 30 and 90 days. Both cone- and rod-photoreceptor-based vision could be demonstrated in treated areas. For cones, there were increases of up to 1.7 log units (i.e., 50 fold); and for rods, there were gains of up to 4.8 log units (i.e., 63,000 fold). To assess what fraction of full vision potential was restored by gene therapy, we related the degree of light sensitivity to the level of remaining photoreceptors within the treatment area. We found that the intervention could overcome nearly all of the loss of light sensitivity resulting from the biochemical blockade. However, this reconstituted retinoid cycle was not completely normal. Resensitization kinetics of the newly treated rods were remarkably slow and required 8 h or more for the attainment of full sensitivity, compared with \u3c1 h in normal eyes. Cone-sensitivity recovery time was rapid. These results demonstrate\u3edramatic, albeit imperfect, recovery of rod- and cone-photoreceptor-based vision after RPE65 gene therapy

Transition from child to adult health services for young people with cerebral palsy in Ireland: A mixed methods study protocol

Supplementary Data: This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.Copyright information © Author(s) (or their employer(s)) 2020. Introduction The transition from child to adult health services is a challenging and complex process for young people with cerebral palsy (CP). Poorly managed transition is associated with deterioration in health, increased hospitalisations and reduced quality of life. While international research identifies key practices that can improve the experience and outcomes of transition, there is a paucity of data in the Irish context. This research study aims to gain an insight into the experience of transition for young people with CP in Ireland. Methods and analysis A convergent parallel mixed-methods design will be used to collect, analyse and interpret quantitative and qualitative data. Participants will be young people aged 16–22 years with CP, their parent(s)/carer(s) and service providers. Quantitative and qualitative data will be collected through questionnaires and interviews, respectively. Quantitative data will be reported using descriptive statistics. Where sufficient data are collected, we will examine associations between the experience of transition practices and sociodemographic and CP-related factors, respectively, using appropriate regression models. Associations between service provider characteristics and provision of key transition practices may also be explored using appropriate regression models. Qualitative data will be analysed using the Framework Method. A coding matrix based on key transitional practices identified from the literature will be used to identify convergence and divergence across study components at the integration stage. Ethics and dissemination The study has been approved by the RCSI University of Medicine and Health Sciences Research Ethics Committee (REC201911010). Results will be presented to non-academic stakeholders through a variety of knowledge translation activities. Results will be published in open access, peer-reviewed journals and presented at national and international scientific conferences.Health Research Board, grant number APA-2019–004. The study sponsor is RCSI University of Medicine and Health Sciences

A ChIP-Seq Benchmark Shows That Sequence Conservation Mainly Improves Detection of Strong Transcription Factor Binding Sites

Transcription factors are important controllers of gene expression and mapping transcription factor binding sites (TFBS) is key to inferring transcription factor regulatory networks. Several methods for predicting TFBS exist, but there are no standard genome-wide datasets on which to assess the performance of these prediction methods. Also, it is believed that information about sequence conservation across different genomes can generally improve accuracy of motif-based predictors, but it is not clear under what circumstances use of conservation is most beneficial.Here we use published ChIP-seq data and an improved peak detection method to create comprehensive benchmark datasets for prediction methods which use known descriptors or binding motifs to detect TFBS in genomic sequences. We use this benchmark to assess the performance of five different prediction methods and find that the methods that use information about sequence conservation generally perform better than simpler motif-scanning methods. The difference is greater on high-affinity peaks and when using short and information-poor motifs. However, if the motifs are specific and information-rich, we find that simple motif-scanning methods can perform better than conservation-based methods.Our benchmark provides a comprehensive test that can be used to rank the relative performance of transcription factor binding site prediction methods. Moreover, our results show that, contrary to previous reports, sequence conservation is better suited for predicting strong than weak transcription factor binding sites

ELK1 Uses Different DNA Binding Modes to Regulate Functionally Distinct Classes of Target Genes

Eukaryotic transcription factors are grouped into families and, due to their similar DNA binding domains, often have the potential to bind to the same genomic regions. This can lead to redundancy at the level of DNA binding, and mechanisms are required to generate specific functional outcomes that enable distinct gene expression programmes to be controlled by a particular transcription factor. Here we used ChIP–seq to uncover two distinct binding modes for the ETS transcription factor ELK1. In one mode, other ETS transcription factors can bind regulatory regions in a redundant fashion; in the second, ELK1 binds in a unique fashion to another set of genomic targets. Each binding mode is associated with different binding site features and also distinct regulatory outcomes. Furthermore, the type of binding mode also determines the control of functionally distinct subclasses of genes and hence the phenotypic response elicited. This is demonstrated for the unique binding mode where a novel role for ELK1 in controlling cell migration is revealed. We have therefore uncovered an unexpected link between the type of binding mode employed by a transcription factor, the subsequent gene regulatory mechanisms used, and the functional categories of target genes controlled

DISPARE: DIScriminative PAttern REfinement for Position Weight Matrices

<p>Abstract</p> <p>Background</p> <p>The accurate determination of transcription factor binding affinities is an important problem in biology and key to understanding the gene regulation process. Position weight matrices are commonly used to represent the binding properties of transcription factor binding sites but suffer from low information content and a large number of false matches in the genome. We describe a novel algorithm for the refinement of position weight matrices representing transcription factor binding sites based on experimental data, including ChIP-chip analyses. We present an iterative weight matrix optimization method that is more accurate in distinguishing true transcription factor binding sites from a negative control set. The initial position weight matrix comes from JASPAR, TRANSFAC or other sources. The main new features are the discriminative nature of the method and matrix width and length optimization.</p> <p>Results</p> <p>The algorithm was applied to the increasing collection of known transcription factor binding sites obtained from ChIP-chip experiments. The results show that our algorithm significantly improves the sensitivity and specificity of matrix models for identifying transcription factor binding sites.</p> <p>Conclusion</p> <p>When the transcription factor is known, it is more appropriate to use a discriminative approach such as the one presented here to derive its transcription factor-DNA binding properties starting with a matrix, as opposed to performing <it>de novo </it>motif discovery. Generating more accurate position weight matrices will ultimately contribute to a better understanding of eukaryotic transcriptional regulation, and could potentially offer a better alternative to <it>ab initio </it>motif discovery.</p