4,793 research outputs found

    Sunjammer

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    Gravity Duals of Lifshitz-like Fixed Points

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    We find candidate macroscopic gravity duals for scale-invariant but non-Lorentz invariant fixed points, which do not have particle number as a conserved quantity. We compute two-point correlation functions which exhibit novel behavior relative to their AdS counterparts, and find holographic renormalization group flows to conformal field theories. Our theories are characterized by a dynamical critical exponent zz, which governs the anisotropy between spatial and temporal scaling tλztt \to \lambda^z t, xλxx \to \lambda x; we focus on the case with z=2z=2. Such theories describe multicritical points in certain magnetic materials and liquid crystals, and have been shown to arise at quantum critical points in toy models of the cuprate superconductors. This work can be considered a small step towards making useful dual descriptions of such critical points.Comment: 17 pages, harvmac; v2 comments about behavior of metric near r=0 added (thanks to S. Hartnoll and G. Horowitz

    Management of type 2 diabetes mellitus in people with severe mental illness: an online cross-sectional survey of healthcare professionals

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    Objectives To establish healthcare professionals’ (HCPs) views about clinical roles, and the barriers and enablers to delivery of diabetes care for people with severe mental illness (SMI). Design Cross-sectional, postal and online survey. Setting Trusts within the National Health Service (NHS), mental health and diabetes charities and professional bodies. Participants HCPs who care for people with type 2 diabetes mellitus (T2DM) and/or SMI in the UK. Primary and secondary outcome measures The barriers, enablers and experiences of delivering T2DM care for people with SMI, informed by the Theoretical Domains Framework (TDF). Results Responders were 273 HCPs, primarily mental health nurses (33.7%) and psychiatrists (32.2%). Only 25% of respondents had received training in managing T2DM in people with SMI. Mental health professionals felt responsible for significantly fewer recommended diabetes care standards than physical health professionals (p<0.001). For those seeing diabetes care as part of their role, the significant barriers to its delivery in the regression analyses were a lack of knowledge (p=0.003); a need for training in communication and negotiation skills (p=0.04); a lack of optimism about the health of their clients (p=0.04) and their ability to manage T2DM in people with SMI (p=0.003); the threat of being disciplined (p=0.02); fear of working with people with a mental health condition (p=0.01); a lack of service user engagement(p=0.006) and a need for incentives (p=0.04). The significant enablers were an understanding of the need to tailor treatments (p=0.04) and goals (p=0.02) for people with SMI. Conclusions This survey indicates that despite current guidelines, diabetes care in mental health settings remains peripheral. Even when diabetes care is perceived as part of a HCP’s role, various individual and organisational barriers to delivering recommended T2DM care standards to people with SMI are experienced

    The use of antibodies to the polypyrimidine tract binding protein (PTB) to analyze the protein components that assemble on alternatively spliced pre-mRNAs that use distant branch points

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    We are using the rat beta-tropomyosin (beta-TM) gene as a model system to study the mechanism of alternative splicing. Previous studies demonstrated that the use of the muscle-specific exon is associated with the use of distant branch points located 147-153 nt upstream of the 3' splice site. In addition, at least one protein, the polypyrimidine tract binding protein (PTB), specifically interacts with critical cis-acting sequences upstream of exon 7 that are involved in blocking the use of this alternative exon in nonmuscle cells. In order to further study the role of PTB, monoclonal antibodies to PTB were prepared. Anti-PTB antibodies did not inhibit the binding of PTB to RNA because they were able to supershift RNA-PTB complexes. To determine if additional proteins interact with sequences within the pre-mRNA, 35S-met-labeled nuclear extracts from HeLa cells were mixed with RNAs and the RNA-protein complexes were recovered by immunoprecipitation using antibodies to PTB. When RNAs containing intron 6 were added to an 35S-met-labeled nuclear extract, precipitation with PTB antibodies showed a novel set of proteins. By contrast, addition of RNAs containing introns 5 or 7 gave the same results as no RNA, indicating that these RNAs are unable to form stable complexes with PTB. These results are in agreement with our previous studies demonstrating that PTB interacts with sequences within intron 6, but not with sequences within introns 5 and 7. When 35S-met-labeled HeLa nuclear extracts were mixed with biotinylated RNA containing intron 6 and the RNA-protein complexes were recovered using streptavidin-agarose beads, an identical pattern of proteins was observed when compared with the immunoprecipitation assay. Analysis of the proteins that assembled on introns 5, 6, or 7 using biotinylated RNA revealed a unique set of proteins that interact with each of these sequences. The composition of proteins interacting with sequences associated with the use of the 3' splice site of intron 6 included proteins of 30, 40, 55, 60, 65, 70, 80, and 100 kDa. Microsequencing identified two of the proteins to be Sam68 and the Far Upstream Element Binding Protein (FBP) from the c-myc gene. In addition, a comparison of the proteins that assemble on introns from the alpha- and beta-TM genes that utilize distant branch points revealed common as well as unique proteins that assemble on these introns. These studies identify a set of proteins, in addition to PTB, that are likely involved in the use of distant branch sites associated with the use of alternatively spliced introns

    Frontal alpha asymmetry in response to stressor moderates the relation between parenting hassles and child externalizing problems

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    Inequitable urban environments are associated with toxic stress and altered neural social stress processing that threatens the development of self-regulation. Some children in these environments struggle with early onset externalizing problems that are associated with a variety of negative long-term outcomes. While previous research has linked parenting daily hassles to child externalizing problems, the role of frontal alpha asymmetry (FAA) as a potential modifier of this relationship has scarcely been explored. The present study examined mother-child dyads, most of whom were living in low socioeconomic status households in an urban environment and self-identified as members of racial minority groups. Analyses focused on frustration task electroencephalography (EEG) data from 67 children (mean age = 59.0 months, SD = 2.6). Mothers reported the frequency of their daily parenting hassles and their child’s externalizing problems. Frustration task FAA moderated the relationship between parenting daily hassles and child externalizing problems, but resting FAA did not. More specifically, children with left frontal asymmetry had more externalizing problems as their mothers perceived more hassles in their parenting role, but parenting hassles and externalizing problems were not associated among children with right frontal asymmetry. These findings lend support to the motivational direction hypothesis and capability model of FAA. More generally, this study reveals how individual differences in lateralization of cortical activity in response to a stressor may confer differential susceptibility to child behavioral problems with approach motivation (i.e., left frontal asymmetry) predicting externalizing problems under conditions of parental stress

    Trisomic dose of several chromosome 21 genes perturbs haematopoietic stem and progenitor cell differentiation in Down's syndrome

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    Children with Down's syndrome (DS) have 20–50-fold higher incidence of all leukaemias (lymphoid and myeloid), for reasons not understood. As incidence of many solid tumours is much lower in DS, we speculated that disturbed early haematopoietic differentiation could be the cause of increased leukaemia risk. If a common mechanism is behind the risk of both major leukaemia types, it would have to arise before the bifurcation to myeloid and lymphoid lineages. Using the transchromosomic system (mouse embryonic stem cells (ESCs)) bearing an extra human chromosome 21 (HSA21)) we analyzed the early stages of haematopoietic commitment (mesodermal colony formation) in vitro. We observed that trisomy 21 (T21) causes increased production of haemogenic endothelial cells, haematopoietic stem cell precursors and increased colony forming potential, with significantly increased immature progenitors. Transchromosomic colonies showed increased expression of Gata-2, c-Kit and Tie-2. A panel of partial T21 ESCs allowed us to assign these effects to HSA21 sub-regions, mapped by 3.5 kbp-resolution tiling arrays. The Gata-2 increase on one side, and c-Kit and Tie-2 increases on the other, could be attributed to two different, non-overlapping HSA21 regions. Using human-specific small interfering RNA silencing, we could demonstrate that an extra copy of RUNX1, but not ETS-2 or ERG, causes an increase in Tie-2/c-Kit levels. Finally, we detected significantly increased levels of RUNX1, C-KIT and PU.1 in human foetal livers with T21. We conclude that overdose of more than one HSA21 gene contributes to the disturbance of early haematopoiesis in DS, and that one of the contributors is RUNX1. As the observed T21-driven hyperproduction of multipotential immature precursors precedes the bifurcation to lymphoid and myeloid lineages, we speculate that this could create conditions of increased chance for acquisition of pre-leukaemogenic rearrangements/mutations in both lymphoid and myeloid lineages during foetal haematopoiesis, contributing to the increased risk of both leukaemia types in DS
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