88 research outputs found

    On the effect of resonances in composite Higgs phenomenology

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    We consider a generic composite Higgs model based on the coset SO(5)/SO(4) and study its phenomenology beyond the leading low-energy effective lagrangian approximation. Our basic goal is to introduce in a controllable and simple way the lowest-lying, possibly narrow, resonances that may exist is such models. We do so by proposing a criterion that we call partial UV completion. We characterize the simplest cases, corresponding respectively to a scalar in either singlet or tensor representation of SO(4) and to vectors in the adjoint of SO(4). We study the impact of these resonances on the signals associated to high-energy vector boson scattering, pointing out for each resonance the characteristic patterns of depletion and enhancement with respect to the leading-order chiral lagrangian. En route we derive the O(p^4) general chiral lagrangian and discuss its peculiar accidental and approximate symmetries.Comment: v3: a few typos corrected. Conclusions unchange

    Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

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    <p>Abstract</p> <p>Background</p> <p>Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls.</p> <p>Results</p> <p>We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level.</p> <p>Conclusions</p> <p>Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.</p

    Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women

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    The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether the functional P2RX7 SNPs are associated with lumbar spine (LS) bone mineral density (BMD), a key determinant of vertebral fracture risk, in post-menopausal women. We genotyped 506 post-menopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) for the above SNPs. Lumbar spine BMD was measured at baseline and at 6–7 year follow-up. P2RX7 genotyping was performed by homogeneous mass extension. We found association of c.946A (p.Arg307Gln) with lower LS-BMD at baseline (P=0.004, β=−0.12) and follow-up (P=0.002, β=−0.13). Further analysis showed that a combined group of subjects who had LOF SNPs (n=48) had nearly ninefold greater annualised percent change in LS-BMD than subjects who were wild type at the six SNP positions (n=84; rate of loss=−0.94%/year and −0.11%/year, respectively, P=0.0005, unpaired t-test). This is the first report that describes association of the c.946A (p.Arg307Gln) LOF SNP with low LS-BMD, and that other LOF SNPs, which result in reduced or no function of the P2X7 receptor, may contribute to accelerated bone loss. Certain polymorphic variants of P2RX7 may identify women at greater risk of developing osteoporosis

    Clustering metagenomic sequences with interpolated Markov models

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    <p>Abstract</p> <p>Background</p> <p>Sequencing of environmental DNA (often called metagenomics) has shown tremendous potential to uncover the vast number of unknown microbes that cannot be cultured and sequenced by traditional methods. Because the output from metagenomic sequencing is a large set of reads of unknown origin, clustering reads together that were sequenced from the same species is a crucial analysis step. Many effective approaches to this task rely on sequenced genomes in public databases, but these genomes are a highly biased sample that is not necessarily representative of environments interesting to many metagenomics projects.</p> <p>Results</p> <p>We present S<smcaps>CIMM</smcaps> (Sequence Clustering with Interpolated Markov Models), an unsupervised sequence clustering method. S<smcaps>CIMM</smcaps> achieves greater clustering accuracy than previous unsupervised approaches. We examine the limitations of unsupervised learning on complex datasets, and suggest a hybrid of S<smcaps>CIMM</smcaps> and supervised learning method Phymm called P<smcaps>HY</smcaps>S<smcaps>CIMM</smcaps> that performs better when evolutionarily close training genomes are available.</p> <p>Conclusions</p> <p>S<smcaps>CIMM</smcaps> and P<smcaps>HY</smcaps>S<smcaps>CIMM</smcaps> are highly accurate methods to cluster metagenomic sequences. S<smcaps>CIMM</smcaps> operates entirely unsupervised, making it ideal for environments containing mostly novel microbes. P<smcaps>HY</smcaps>S<smcaps>CIMM</smcaps> uses supervised learning to improve clustering in environments containing microbial strains from well-characterized genera. S<smcaps>CIMM</smcaps> and P<smcaps>HY</smcaps>S<smcaps>CIMM</smcaps> are available open source from <url>http://www.cbcb.umd.edu/software/scimm</url>.</p

    General Composite Higgs Models

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    We construct a general class of pseudo-Goldstone composite Higgs models, within the minimal SO(5)/SO(4) coset structure, that are not necessarily of moose-type. We characterize the main properties these models should have in order to give rise to a Higgs mass around 125 GeV. We assume the existence of relatively light and weakly coupled spin 1 and 1/2 resonances. In absence of a symmetry principle, we introduce the Minimal Higgs Potential (MHP) hypothesis: the Higgs potential is assumed to be one-loop dominated by the SM fields and the above resonances, with a contribution that is made calculable by imposing suitable generalizations of the first and second Weinberg sum rules. We show that a 125 GeV Higgs requires light, often sub-TeV, fermion resonances. Their presence can also be important for the models to successfully pass the electroweak precision tests. Interestingly enough, the latter can also be passed by models with a heavy Higgs around 320 GeV. The composite Higgs models of the moose-type considered in the literature can be seen as particular limits of our class of models.Comment: 51 pages, 12 figures, 5 appendices; v2: Corrected estimates of \delta g_b in appendix B, references fixed, several minor improvements; v3: minor improvements, to appear in JHE

    Functional Role of the Polymorphic 647 T/C Variant of ENT1 (SLC29A1) and Its Association with Alcohol Withdrawal Seizures

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    Adenosine is involved in several neurological and behavioral disorders including alcoholism. In cultured cell and animal studies, type 1 equilibrative nucleoside transporter (ENT1, slc29a1), which regulates adenosine levels, is known to regulate ethanol sensitivity and preference. Interestingly, in humans, the ENT1 (SLC29A1) gene contains a non-synonymous single nucleotide polymorphism (647 T/C; rs45573936) that might be involved in the functional change of ENT1. Our functional analysis showed that prolonged ethanol exposure increased adenosine uptake activity of mutant cells (ENT1-216Thr) compared to wild-type (ENT1-216Ile) transfected cells, which might result in reduced extracellular adenosine levels. We found that mice lacking ENT1 displayed increased propensity to ethanol withdrawal seizures compared to wild-type littermates. We further investigated a possible association of the 647C variant with alcoholism and the history of alcohol withdrawal seizures in subjects of European ancestry recruited from two independent sites. Analyses of the combined data set showed an association of the 647C variant and alcohol dependence with withdrawal seizures at the nominally significant level. Together with the functional data, our findings suggest a potential contribution of a genetic variant of ENT1 to the development of alcoholism with increased risk of alcohol withdrawal-induced seizures in humans

    The Viral and Cellular MicroRNA Targetome in Lymphoblastoid Cell Lines

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    Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus linked to a number of B cell cancers and lymphoproliferative disorders. During latent infection, EBV expresses 25 viral pre-microRNAs (miRNAs) and induces the expression of specific host miRNAs, such as miR-155 and miR-21, which potentially play a role in viral oncogenesis. To date, only a limited number of EBV miRNA targets have been identified; thus, the role of EBV miRNAs in viral pathogenesis and/or lymphomagenesis is not well defined. Here, we used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) combined with deep sequencing and computational analysis to comprehensively examine the viral and cellular miRNA targetome in EBV strain B95-8-infected lymphoblastoid cell lines (LCLs). We identified 7,827 miRNA-interaction sites in 3,492 cellular 3′UTRs. 531 of these sites contained seed matches to viral miRNAs. 24 PAR-CLIP-identified miRNA:3′UTR interactions were confirmed by reporter assays. Our results reveal that EBV miRNAs predominantly target cellular transcripts during latent infection, thereby manipulating the host environment. Furthermore, targets of EBV miRNAs are involved in multiple cellular processes that are directly relevant to viral infection, including innate immunity, cell survival, and cell proliferation. Finally, we present evidence that myc-regulated host miRNAs from the miR-17/92 cluster can regulate latent viral gene expression. This comprehensive survey of the miRNA targetome in EBV-infected B cells represents a key step towards defining the functions of EBV-encoded miRNAs, and potentially, identifying novel therapeutic targets for EBV-associated malignancies

    Development of a nurse home visitation intervention for intimate partner violence

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    <p>Abstract</p> <p>Background</p> <p>Despite an increase in knowledge about the epidemiology of intimate partner violence (IPV), much less is known about interventions to reduce IPV and its associated impairment. One program that holds promise in preventing IPV and improving outcomes for women exposed to violence is the Nurse-Family Partnership (NFP), an evidence-based nurse home visitation program for socially disadvantaged first-time mothers. The present study developed an intervention model and modification process to address IPV within the context of the NFP. This included determining the extent to which the NFP curriculum addressed the needs of women at risk for IPV or its recurrence, along with client, nurse and broader stakeholder perspectives on how best to help NFP clients cope with abusive relationships.</p> <p>Methods</p> <p>Following a preliminary needs assessment, an exploratory multiple case study was conducted to identify the core components of the proposed IPV intervention. This included qualitative interviews with purposeful samples of NFP clients and community stakeholders, and focus groups with nurse home visitors recruited from four NFP sites. Conventional content analysis and constant comparison guided data coding and synthesis. A process for developing complex interventions was then implemented.</p> <p>Results</p> <p>Based on data from 69 respondents, an IPV intervention was developed that focused on identifying and responding to IPV; assessing a client's level of safety risk associated with IPV; understanding the process of leaving and resolving an abusive relationship and system navigation. A need was identified for the intervention to include both universal elements of healthy relationships and those tailored to a woman's specific level of readiness to promote change within her life. A clinical pathway guides nurses through the intervention, with a set of facilitators and corresponding instructions for each component.</p> <p>Conclusions</p> <p>NFP clients, nurses and stakeholders identified the need for modifications to the existing NFP program; this led to the development of an intervention that includes universal and targeted components to assist NFP nurses in addressing IPV with their clients. Plans for feasibility testing and evaluation of the effectiveness of the IPV intervention embedded within the NFP, and compared to NFP-only, are discussed.</p

    School-based intervention to improve the mental health of low-income, secondary school students in Santiago, Chile (YPSA): study protocol for a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Depression is common and can have devastating effects on the life of adolescents. Psychological interventions are the first-line for treating or preventing depression among adolescents. This proposal aims to evaluate a school-based, universal psychological intervention to reduce depressive symptoms among student's aged 13-14 attending municipal state secondary schools in Santiago, Chile.</p> <p>Study design</p> <p>This is a cluster randomised controlled trial with schools as the main clusters. We compared this intervention with a control group in a study involving 22 schools, 66 classes and approximately 2,600 students. Students in the active schools attended 11 weekly and 3 booster sessions of an intervention based on cognitive-behavioural models. The control schools received their usual but enhanced counselling sessions currently included in their curriculum. Mean depression scores and indicators of levels of functioning were assessed at 3 and 12 months after the completion of the intervention in order to assess the effectiveness of the intervention. Direct and indirect costs were measured in both groups to assess the cost-effectiveness of this intervention.</p> <p>Discussion</p> <p>As far as we are aware this is the first cluster randomised controlled trial of a school intervention for depression among adolescents outside the Western world.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN19466209">ISRCTN19466209</a></p
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