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In recent decades concerns about violence and programs for the minimization of physical restraint, amongst other restrictive practices, have proliferated within mental health policy and practice. Whilst nurses are often called upon when violence occurs within mental health care settings, they often find themselves having the conflicting roles of caring and controlling. Within such situations it is service users, who are experts by experience, who perhaps can offer more meaningful insight into being restrained and thus provide a more appropriate approach in dealing with mental distress. This paper presents the findings of a narrative study of individuals' experiences of physical restraint within the mental health care system. In total 11 mental health service users, who had experienced physical restraint, were interviewed. Frank's (2010, Letting stories breathe: a socio‐narratology) guiding questions were used to undertake a dialogical narrative analysis of each story. For the purpose of this paper, four of the 11 stories are presented as these are representative of Frank's 'quest narrative'. However, whilst studies from the service user perspective regarding restraint are scarce, findings are discussed in relation to the grand narrative of restraint. The dialogical relationship between individual stories and the dominant grand narrative implies that the former has the capacity to shape and review the latter within mental health care. Adding to the growing body of evidence of restraint from service users' perspectives could enable nurses to provide more appropriate and meaningful mental health care in times of mental distress. [238]. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to report findings from interviews with seven African-heritage women attending a female genital mutilation (FGM) Clinic in the north of England, during the COVID-19 lockdown. The Clinic, established several years before the pandemic, provides specialist therapeutic support to women and girls from minority ethnic communities who are affected by harmful "traditional" practices, including FGM. The services provided by the Clinic include early interventions, peer support, community engagement and empowerment around FGM. Design/methodology/approach: Data was collected during an online focus group discussion with seven women who had received counselling for FGM, to gain insight into their lived experiences of therapeutic support during the pandemic. Findings: Using Braun and Clarke (2006) six-step thematic analysis, four superordinate themes derived from the data: consistency and continuity; safety in shared experience and creativity; feeling heard, feeling stronger; and altruism and desire for change. Research limitations/implications: It is important to recognise some limitations within this study. It is based on one focus group discussion that involved seven participants, who had experienced FGM, were living in a targeted area and whose mental health had been further compromised by the COVID-19 pandemic. Practical implications: The findings of this study indicate that it is essential to consider participants' experiences of receiving therapeutic support during the COVID-19 pandemic. It was observed that emotional stressors linked with participants' experiences of FGM may be exacerbated by those related to COVID-19. Social implications: There is a need to conduct similar research, perhaps on an individual basis, that would reach a wider sample of women from ethnic minority populations who are survivors of FGM, including those from FGM practicing communities who have been hospitalised through their deteriorating mental health. This would add to the small but growing body of evidence, to provide a better understanding of the experiences of their mental health needs during the COVID-19 pandemic and perhaps better identify effective therapeutic interventions. Originality/value: These themes provide an insight into these women's experiences of the trauma associated with FGM and receiving mental health support during the pandemic. [ABSTRACT FROM AUTHOR]

Objectives: During the COVID-19 pandemic, our mental health service experimented with working from home. The flexibility of this practice can enable improved efficiency, staff well-being and expanded operating hours in the longer term. This paper shares our experiences and makes recommendations for being a part of and leading distributed clinical teams.Conclusions: We saw a 3% increase in total appointment bookings and a 7% reduction in cancellations/non-attendance compared to the same period in 2019. Based on our experience and the literature, effective distributed teams have leaders that connect via video at least weekly; focus on transparency and output over micromanagement; prioritise staff relationships and err towards overcommunication. [ABSTRACT FROM AUTHOR]

The shared cloud-based computing paradigm has experienced enormous growth. Multitenant clouds are conventionally built atop datacenters that utilize commodity hardware connected hierarchically with standard network protocols. Piton is a 25-core manycore processor that takes a different perspective, rethinking the architecture of datacenters and specializing processor architecture for Infrastructure as a Service (IaaS) clouds. The tile-based manycore processor is designed not only as a single chip, but as a large-scale system. Up to 8,192 chips (204,800 cores) can be seamlessly connected in a flat topology, maintaining a packet-switched network fabric both on and off chip. Shared memory is supported across arbitrary cores in the system, both intrachip and interchip, enabling flexibility and fine-grained resource allocation in shared systems. Piton also targets energy efficiency, critical to datacenters, using a modified multithreaded OpenSPARC T1 core enhanced with an energy-efficient drafting mode. To further facilitate sharing and increase utility for IaaS users and providers, a novel memory traffic shaper partitions bandwidth among cores or applications. Piton reimagines the datacenter architecture, breaking down barriers between chips, nodes, and racks, and enables flexibility, performance, and energy efficiency at scale. Piton has also been open sourced as a research platform called OpenPiton to enable practical full-system manycore research. [ABSTRACT FROM PUBLISHER]

A variety of genetically encoded reporters use changes in fluorescence (or Förster) resonance energy transfer (FRET) to report on biochemical processes in living cells. The standard genetically encoded FRET pair consists of CFPs and YFPs, but many CFP-YFP reporters suffer from low FRET dynamic range, phototoxicity from the CFP excitation light and complex photokinetic events such as reversible photobleaching and photoconversion. We engineered two fluorescent proteins, Clover and mRuby2, which are the brightest green and red fluorescent proteins to date and have the highest Förster radius of any ratiometric FRET pair yet described. Replacement of CFP and YFP with these two proteins in reporters of kinase activity, small GTPase activity and transmembrane voltage significantly improves photostability, FRET dynamic range and emission ratio changes. These improvements enhance detection of transient biochemical events such as neuronal action-potential firing and RhoA activation in growth cones. [ABSTRACT FROM AUTHOR]

Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family. [ABSTRACT FROM AUTHOR]

All organic fluorophores undergo irreversible photobleaching during prolonged illumination. Although fluorescent proteins typically bleach at a substantially slower rate than many small-molecule dyes, in many cases the lack of sufficient photostability remains an important limiting factor for experiments requiring large numbers of images of single cells. Screening methods focusing solely on brightness or wavelength are highly effective in optimizing both properties, but the absence of selective pressure for photostability in such screens leads to unpredictable photobleaching behavior in the resulting fluorescent proteins. Here we describe an assay for screening libraries of fluorescent proteins for enhanced photostability. With this assay, we developed highly photostable variants of mOrange (a wavelength-shifted monomeric derivative of DsRed from Discosoma sp.) and TagRFP (a monomeric derivative of eqFP578 from Entacmaea quadricolor) that maintain most of the beneficial qualities of the original proteins and perform as reliably as Aequorea victoria GFP derivatives in fusion constructs. [ABSTRACT FROM AUTHOR]

Current models describe male-specific fruitless (fruM) as a genetic 'switch' regulating sexual behavior in Drosophila melanogaster, and they postulate that female (F) and male (M) doublesex (dsx) products control body sexual morphology. In contradiction to this simple model, we show that dsx, as well as fruM and non–sex-specific retained (retn), affect both male and female sexual behaviors. In females, both retn and dsxF contribute to female receptivity, and both genes act to repress male-like courtship activity in the presence or absence of fruM. In males, consistent with the opposing functions of dsxM and dsxF, dsxM acts as a positive factor for male courtship. retn also acts counter to fruM in the development of the male-specific muscle of Lawrence. Molecularly, retn seems to regulate sexual behavior via a previously described complex that represses zerknullt. Thus, we show that fru and dsx together act as a 'switch' system regulating behavior in the context of other developmental genes, such as retn. [ABSTRACT FROM AUTHOR]

Mutations in the Drosophila retained/dead ringer (retn) gene lead to female behavioral defects and alter a limited set of neurons in the CNS. retn is implicated as a major repressor of male courtship behavior in the absence of the fruitless (fru) male protein, retn females show fru-independent male-like courtship of males and females, and are highly resistant to courtship by males. Males mutant for retn court with normal parameters, although feminization of retn cells in males induces bisexuality. Alternatively spliced RNAs appear in the larval and pupal CNS, but none shows sex specificity. Post-embryonically, retn RNAs are expressed in a limited set of neurons in the CNS and eyes. Neural defects of retn mutant cells include mushroom body β-lobe fusion and pathfinding errors by photoreceptor and subesophageal neurons. We posit that some of these retn-expressing cells function to repress a male behavioral pathway activated by fruM. [ABSTRACT FROM AUTHOR]

Ataxin 1 (Atxl) is a foci-forming polyglutamine protein of unknown function, whose mutant form causes type 1 spinocerebellar ataxia in humans and exerts neurotoxicity in transgenic mouse and fly expressing mutant Atx1. In this study, we demonstrate that Atx1 interacts with the transcriptional corepressor SMRT (silencing mediator of retinoid and thyroid hormone receptors) and with histone deacetylase 3. Atx1 binds chromosomes and mediates transcriptional repression when tethered to DNA. Interaction with SMRT-related factors is a conserved feature of Atx1, because Atx1 also binds SMRTER, a Drosophila cognate of SMRT. Significantly, mutant Atx1 forms aggregates in Drosophila, and such mutant Atx1-mediated aggregates sequester SMRTER. Consistently, the neurodegenerative eye phenotype caused by mutant Atx1 is enhanced by a Smrter mutation and, conversely, is suppressed by a chromosomal duplication that contains the wild type Smrter gene. Together, our results suggest that Atx1 is a transcriptional factor whose mutant form exerts its deleterious effects in part by perturbing corepressor-dependent transcriptional pathways. [ABSTRACT FROM AUTHOR]

Abstract Background: The mammalian receptor protein tyrosine kinase (RTK), Anaplastic Lymphoma Kinase (ALK), was first described as the product of the t(2;5) chromosomal translocation found in non-Hodgkin's lymphoma. While the mechanism of ALK activation in non-Hodgkin's lymphoma has been examined, to date, no in vivo role for this orphan insulin receptor family RTK has been described. Results: We describe here a novel Drosophila melanogaster RTK, DAlk, which we have mapped to band 53 on the right arm of the second chromosome. Full-length DAlk cDNA encodes a phosphoprotein of 200 kDa, which shares homology not only with mammalian ALK but also with the orphan RTK LTK. Analysis of both mammalian and Drosophila ALK reveals that the ALK family of RTKs contains a newly identified MAM domain within their extracellular domains. Like its mammalian counterpart, DAlk appears to be expressed in the developing CNS by in situ analysis. However, in addition to expression of DAlk in the Drosophila brain, careful analysis reveals an additional early role for DAlk in the developing visceral mesoderm where its expression is coincident with activated ERK. Conclusion: In this paper we describe a Drosophila melanogaster Alk RTK which is expressed in the developing embryonic mesoderm and CNS. Our data provide evidence for the existence of a DAlk RTK pathway in Drosophila. We show that ERK participates in this pathway, and that it is activated by DAlk in vivo. Expression patterns of dALK, together with activated ERK, suggest that DAlk fulfils the criteria of the missing RTK pathway, leading to ERK... [ABSTRACT FROM AUTHOR]

Reports on the dual role of ultraspiracle, the Drosophila retinoid X receptor, in the ecdysone response. Difference in activating abilities of usp alleles; DNA-binding properties of ultraspiracle alleles; Basis of the USP3 and USP4 activation functions in cell culture.

This paper examines whether or not small businesses (fewer than 100 employees) can successfully pursue total quality management (TQM) beyond ISO 9000. A review of the literature on quality in small businesses shows that the benefits of ISO 9000 can far outweigh the costs of achieving registrations (even for small businesses) but also emphasizes that ISO 9000 should be viewed as a step towards TQM and not the end of the quality journey. Although many small businesses are benefiting from ISO 9000, an increasing number of small ISO businesses are not progressing towards TQM. To explore the actual impact of quality on small business, a number of small ISO 9000 businesses were surveyed. The main conclusions and recommendations arising from the thesis are that small businesses can benefit from implementing TQM. However, small TQM practitioners need to learn to be more externally focused, i.e. customer focused, to measure the financial impact of TQM on bottom line performance and to use direct methods to measure customer satisfaction. [ABSTRACT FROM AUTHOR]

Reports on the identification of a unique vertebrate nuclear receptor TIx, which is expressed exclusively in the neuroepithelium of the embryonic brain. Similarity to the product of the Drosophila terminal/gap gene tailless; In vitro DNA-binding assays; Effect of the ectopic expression of TIx in fly embryos.

Shows that native ecydysone receptor (EcR) and Ultraspiricle (USP) are co-localized on ecdysone-responsive loci of polytene chromosomes. Promotion of physical association between EcR and USP by natural ecdysones; Requirement of EcR and USP in high-affinity altered by combinatorial actions among subunits and ligands.