779 research outputs found

    Can We Really Prevent Suicide?

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    Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

    The stellar and sub-stellar IMF of simple and composite populations

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    The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-

    Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

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    Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

    Structural Simplicity as a Restraint on the Structure of Amorphous Silicon

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    Understanding the structural origins of the properties of amorphous materials remains one of the most important challenges in structural science. In this study we demonstrate that local ‘structural simplicity’, embodied by the degree to which atomic environments within a material are similar to each other, is powerful concept for rationalising the structure of canonical amorphous material amorphous silicon (a-Si). We show, by restraining a reverse Monte Carlo refinement against pair distribution function (PDF) data to be simpler, that the simplest model consistent with the PDF is a continuous random network (CRN). A further effect of producing a simple model of a-Si is the generation of a (pseudo)gap in the electronic density of states, suggesting that structural ho- mogeneity drives electronic homogeneity. That this method produces models of a-Si that approach the state-of-the-art without the need for chemically specific restraints (beyond the assumption of homogeneity) suggests that simplicity-based refinement approaches may allow experiment-driven structural modelling techniques to be developed for the wide variety of amorphous semiconductors with strong local order

    Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF

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    The essential herpesvirus adaptor protein HVS ORF57, which has homologs in all other herpesviruses, promotes viral mRNA export by utilizing the cellular mRNA export machinery. ORF57 protein specifically recognizes viral mRNA transcripts, and binds to proteins of the cellular transcription-export (TREX) complex, in particular ALYREF. This interaction introduces viral mRNA to the NXF1 pathway, subsequently directing it to the nuclear pore for export to the cytoplasm. Here we have used a range of techniques to reveal the sites for direct contact between RNA and ORF57 in the absence and presence of ALYREF. A binding site within ORF57 was characterized which recognizes specific viral mRNA motifs. When ALYREF is present, part of this ORF57 RNA binding site, composed of an a-helix, binds preferentially to ALYREF. This competitively displaces viral RNA from the a-helix, but contact with RNA is still maintained by a flanking region. At the same time, the flexible N-terminal domain of ALYREF comes into contact with the viral RNA, which becomes engaged in an extensive network of synergistic interactions with both ALYREF and ORF57. Transfer of RNA to ALYREF in the ternary complex, and involvement of individual ORF57 residues in RNA recognition, were confirmed by UV cross-linking and mutagenesis. The atomic-resolution structure of the ORF57-ALYREF interface was determined, which noticeably differed from the homologous ICP27-ALYREF structure. Together, the data provides the first site-specific description of how viral mRNA is locked by a herpes viral adaptor protein in complex with cellular ALYREF, giving herpesvirus access to the cellular mRNA export machinery. The NMR strategy used may be more generally applicable to the study of fuzzy protein-protein-RNA complexes which involve flexible polypeptide regions

    Metabolic engineering of astaxanthin biosynthesis in maize endosperm and characterization of a prototype high oil hybrid

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    Maize was genetically engineered for the biosynthesis of the high value carotenoid astaxanthin in the kernel endosperm. Introduction of a β-carotene hydroxylase and a β-carotene ketolase into a white maize genetic background extended the carotenoid pathway to astaxanthin. Simultaneously, phytoene synthase, the controlling enzyme of carotenogenesis, was over-expressed for enhanced carotenoid production and lycopene ε-cyclase was knocked-down to direct more precursors into the β-branch of the extended ketocarotenoid pathway which ends with astaxanthin. This astaxanthin-accumulating transgenic line was crossed into a high oil- maize genotype in order to increase the storage capacity for lipophilic astaxanthin. The high oil astaxanthin hybrid was compared to its astaxanthin producing parent. We report an in depth metabolomic and proteomic analysis which revealed major up- or down- regulation of genes involved in primary metabolism. Specifically, amino acid biosynthesis and the citric acid cycle which compete with the synthesis or utilization of pyruvate and glyceraldehyde 3-phosphate, the precursors for carotenogenesis, were down-regulated. Nevertheless, principal component analysis demonstrated that this compositional change is within the range of the two wild type parents used to generate the high oil producing astaxanthin hybrid

    Cetuximab plus platinum-based chemotherapy in head and neck Squamous Cell Carcinoma: a retrospective study in a single Comprehensive European Cancer Institution

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    Background: The use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort. Patients and Methods: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. Results: The median patient age was 53 (37-78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316) and PFS of 8 months (CI 95%, 6.051-9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%). Conclusions: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.info:eu-repo/semantics/publishedVersio

    Self domestication and the evolution of language

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    We set out an account of how self-domestication plays a crucial role in the evolution of language. In doing so, we focus on the growing body of work that treats language structure as emerging from the process ofcultural transmission. We argue that a full recognition of the importance of cultural transmission fundamentally changes the kind ofquestionswe should be asking regarding the biological basis of language structure. If we think of language structure as reflecting an accumulated set of changes in our genome, then we might ask something like, "What are the genetic bases of language structure and why were they selected?" However, if cultural evolution can account for language structure, then this question no longer applies. Instead, we face the task of accounting for the origin of the traits that enabled that process of structure-creating cultural evolution to get started in the first place. In light of work on cultural evolution, then, the new question for biological evolution becomes, "How did those precursor traits evolve?" We identify two key precursor traits: (1) the transmission of the communication system throughlearning; and (2) the ability to infer thecommunicative intentassociated with a signal or action. We then describe two comparative case studies-the Bengalese finch and the domestic dog-in which parallel traits can be seen emerging followingdomestication. Finally, we turn to the role of domestication in human evolution. We argue that the cultural evolution of language structure has its origin in an earlier process of self-domestication.</p
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