2,973 research outputs found
Pupils with social, emotional and mental health special needs: Perceptions of how restrictive physical interventions impact their relationships with teaching staff
Positive teacher-child relationships (TCRs) are vital for pupil well-being and are especially important for at-risk children. This qualitative study investigated the impact of restrictive physical interventions (RPIs) on TCRs in focus groups comprising ten boys aged 9-11 years attending two special schools in England. We examined the immediate and post incident impact of RPIs on the TCRs of two groups: students who have experienced RPIs and those who have witnessed RPIs. A range of consequences for student well-being, educational support and the TCR were identified. The implications of current study findings for the prevention and implementation of RPIs are discussed
Conditions for Analysis of Native Protein Structures Using Uniform Field Drift Tube Ion Mobility Mass Spectrometry and Characterization of Stable Calibrants for TWIM-MS
Determination of collisional cross sections (CCS) by travelling wave ion mobility mass spectrometry (TWIM-MS) requires calibration against standards for which the CCS has been measured previously by drift tube ion mobility mass spectrometry (DTIM-MS). The different extents of collisional activation in TWIM-MS and DTIM-MS can give rise to discrepancies in the CCS of calibrants across the two platforms. Furthermore, the conditions required to ionize and transmit large, folded proteins and assemblies may variably affect the structure of the calibrants and analytes. Stable hetero-oligomeric phospholipase A2 (PDx) and its subunits were characterized as calibrants for TWIM-MS. Conditions for acquisition of native-like TWIM (Synapt G1 HDMS) and DTIM (Agilent 6560 IM-Q-TOF) mass spectra were optimized to ensure the spectra exhibited similar charge state distributions. CCS measurements (DTIM-MS) for ubiquitin, cytochrome c, holo-myoglobin, serum albumin and glutamate dehydrogenase were in good agreement with other recent results determined using this and other DTIM-MS instruments. PDx and its β and γ subunits were stable across a wide range of cone and trap voltages in TWIM-MS and were stable in the presence of organic solvents. The CCS of PDx and its subunits were determined by DTIM-MS and were used as calibrants in determination of CCS of native-like cytochrome c, holo-myoglobin, carbonic anhydrase, serum albumin and haemoglobin in TWIM-MS. The CCS values were in good agreement with those measured by DTIM-MS where available. These experiments demonstrate conditions for analysis of native-like proteins using a commercially available DTIM-MS instrument, characterize robust calibrants for TWIM-MS, and present CCS values determined by DTIM-MS and TWIM-MS for native proteins to add to the current literature database
Consumer insights and the importance of competitiveness Factors for mature and developing destinations
This article aims to understand the importance of various destination attributes to the competitiveness of tourism destinations from a consumer perspective, while at the same time contrasting these in a mature versus developing destination. A sample of Australian-based domestic tourists were surveyed to assess the relative importance of tourism destination competitiveness (TDC) attributes in the context of developing and mature destinations. This research firstly appears to verify that the importance of many TDC elements, highlighted by consumers, is not dissimilar from other stakeholder-based TDC studies. Furthermore, this research effort established that in terms of attribute performance, relative destination immaturity may well constrain a developing destination’s ability to satisfy the needs of consumers
Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening
Computational techniques such as structure-based virtual screening require carefully prepared 3D models of potential small-molecule ligands. Though powerful, existing commercial programs for virtual-library preparation have restrictive and/or expensive licenses. Freely available alternatives, though often effective, do not fully account for all possible ionization, tautomeric, and ring-conformational variants. We here present Gypsum-DL, a free, robust open-source program that addresses these challenges. As input, Gypsum-DL accepts virtual compound libraries in SMILES or flat SDF formats. For each molecule in the virtual library, it enumerates appropriate ionization, tautomeric, chiral, cis/trans isomeric, and ring-conformational forms. As output, Gypsum-DL produces an SDF file containing each molecular form, with 3D coordinates assigned. To demonstrate its utility, we processed 1558 molecules taken from the NCI Diversity Set VI and 56,608 molecules taken from a Distributed Drug Discovery (D3) combinatorial virtual library. We also used 4463 high-quality protein-ligand complexes from the PDBBind database to show that Gypsum-DL processing can improve virtual-screening pose prediction. Gypsum-DL is available free of charge under the terms of the Apache License, Version 2.0
Frenetic: A High-Level Language for OpenFlow Networks
Network administrators must configure network devices to simultaneously provide several interrelated services such as routing, load balancing, traffic monitoring, and access control. Unfortunately, most interfaces for programming networks are defined at the low level of abstraction supported by the underlying hardware, leading to complicated programs with subtle bugs. We present Frenetic, a high-level language for OpenFlow networks that enables writing programs in a declarative and compositional style, with a simple "program like you see every packet" abstraction. Building on ideas from functional programming, Frenetic offers a rich pattern algebra for classifying packets into traffic streams and a suite of operators for transforming streams. The run-time system efficiently manages the low-level details of (un)installing packet-processing rules in the switches. We describe the design of Frenetic, an implementation on top of OpenFlow, and experiments and example programs that validate our design choices.Office of Naval Research grant N00014-09-1-0770 "Networks Opposing Botnets
Forgiveness and Prayer
Forgiveness and prayer are both topics of contemporary social science research, but they are not often considered together. The present study investigates how Christian respondents portray prayer when describing the process of interpersonal forgiveness. Just over half of the respondents mentioned prayer as an important part of forgiveness at their first opportunity in a structured interview protocol. Prayer responses were coded as inward, upward, or outward, with inward prayers being the most common. The narrative descriptions of inward prayer resemble Worthington\u27s (2001, 2003) REACH model of the forgiveness process
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A Spontaneous Fatp4/Scl27a4 Splice Site Mutation in a New Murine Model for Congenital Ichthyosis
Congenital ichthyoses are life-threatening conditions in humans. We describe here the identification and molecular characterization of a novel recessive mutation in mice that results in newborn lethality with severe congenital lamellar ichthyosis. Mutant newborns have a taut, shiny, non-expandable epidermis that resembles cornified manifestations of autosomal-recessive congenital ichthyosis in humans. The skin is stretched so tightly that the newborn mice are immobilized. The genetic defect was mapped to a region near the proximal end of chromosome 2 by SNP analysis, suggesting Fatp4/Slc27a4 as a candidate gene. FATP4 mutations in humans cause ichthyosis prematurity syndrome (IPS), and mutations of Fatp4 in mice have previously been found to cause a phenotype that resembles human congenital ichthyoses. Characterization of the Fatp4 cDNA revealed a fusion of exon 8 to exon 10, with deletion of exon 9. Genomic sequencing identified an A to T mutation in the splice donor sequence at the 3′-end of exon 9. Loss of exon 9 results in a frame shift mutation upstream from the conserved very long-chain acyl-CoA synthase (VLACS) domain. Histological studies revealed that the mutant mice have defects in keratinocyte differentiation, along with hyperproliferation of the stratum basale of the epidermis, a hyperkeratotic stratum corneum, and reduced numbers of secondary hair follicles. Since Fatp4 protein is present primarily at the stratum granulosum and the stratum spinosum, the hyperproliferation and the alterations in hair follicle induction suggest that very long chain fatty acids, in addition to being required for normal cornification, may influence signals from the stratum corneum to the basal cells that help to orchestrate normal skin differentiation
Different conformations and packing motifs in the crystal structures of four thiophene--carbohydrazide--pyridine derivatives
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Interpopulation hybridization results in widespread viability selection across the genome in Tigriopus californicus
<p>Abstract</p> <p>Background</p> <p>Genetic interactions within hybrids influence their overall fitness. Understanding the details of these interactions can improve our understanding of speciation. One experimental approach is to investigate deviations from Mendelian expectations (segregation distortion) in the inheritance of mapped genetic markers. In this study, we used the copepod <it>Tigriopus californicus</it>, a species which exhibits high genetic divergence between populations and a general pattern of reduced fitness in F2 interpopulation hybrids. Previous studies have implicated both nuclear-cytoplasmic and nuclear-nuclear interactions in causing this fitness reduction. We identified and mapped population-diagnostic single nucleotide polymorphisms (SNPs) and used these to examine segregation distortion across the genome within F2 hybrids.</p> <p>Results</p> <p>We generated a linkage map which included 45 newly elucidated SNPs and 8 population-diagnostic microsatellites used in previous studies. The map, the first available for the Copepoda, was estimated to cover 75% of the genome and included markers on all 12 <it>T. californicus </it>chromosomes. We observed little segregation distortion in newly hatched F2 hybrid larvae (fewer than 10% of markers at p < 0.05), but strikingly higher distortion in F2 hybrid adult males (45% of markers at p < 0.05). Hence, segregation distortion was primarily caused by selection against particular genetic combinations which acted between hatching and maturity. Distorted markers were not distributed randomly across the genome but clustered on particular chromosomes. In contrast to other studies in this species we found little evidence for cytonuclear coadaptation. Instead, different linkage groups exhibited markedly different patterns of distortion, which appear to have been influenced by nuclear-nuclear epistatic interactions and may also reflect genetic load carried within the parental lines.</p> <p>Conclusion</p> <p>Adult male F2 hybrids between two populations of <it>T. californius </it>exhibit dramatic segregation distortion across the genome. Distorted loci are clustered within specific linkage groups, and the direction of distortion differs between chromosomes. This segregation distortion is due to selection acting between hatching and adulthood.</p
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