175 research outputs found

    Indicators of School Crime and Safety: 2012

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    Our nation's schools should be safe havens for teaching and learning, free of crime and violence. Any instance of crime or violence at school not only affects the individuals involved, but also may disrupt the educational process and affect bystanders, the school itself, and the surrounding community.Establishing reliable indicators of the current state of school crime and safety across the nation and regularly updating and monitoring these indicators is important in ensuring the safety of our nation's students. This is the aim of Indicators of School Crime and Safety. This report is the fifteenth in a series of annual publications produced jointly by the National Center for Education Statistics (NCES), Institute of Education Sciences (IES), in the U.S. Department of Education, and the Bureau of Justice Statistics (BJS) in the U.S. Department of Justice. This report presents the most recent data available on school crime and student safety. The indicators in this report are based on information drawn from a variety of data sources, including national surveys of students, teachers, and principals. Sources include results from the School-Associated Violent Deaths Study, sponsored by the U.S. Department of Education, the Department of Justice, and the Centers for Disease Control and Prevention; the National Crime Victimization Survey and School Crime Supplement to the survey, sponsored by the BJS and NCES, respectively; the Youth Risk Behavior Survey, sponsored by the Centers for Disease Control and Prevention; and the Schools and Staffing Survey and School Survey on Crime and Safety, both sponsored by NCES. The most recent data collection for each indicator varied by survey, from 2007 to 2011. Each data source has an independent sample design, data collection method, and questionnaire design, or is the result of a universe data collection. All comparisons described in this report are statistically significant at the .05 level. Additional information about methodology and the datasets analyzed in this report may be found in appendix A. This report covers topics such as victimization, teacher injury, bullying and cyber-bullying, school conditions, fights, weapons, availability and student use of drugs and alcohol, and student perceptions of personal safety at school. Indicators of crime and safety are compared across different population subgroups and over time. Data on crimes that occur away from school are offered as a point of comparison where available

    Application of BRET to monitor ligand binding to GPCRs

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    Bioluminescence resonance energy transfer (BRET) is a well-established method for investigating protein-protein interactions. Here we present a BRET approach to monitor ligand binding to G protein–coupled receptors (GPCRs) on the surface of living cells made possible by the use of fluorescent ligands in combination with a bioluminescent protein (NanoLuc) that can be readily expressed on the N terminus of GPCRs

    Patient and Public Involvement Toolkit : Involving LGBTQ+ Unpaid Carers

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    Impactful social care research that achieves to influence policy and practice needs to draw upon and be informed by the very social groups it wishes to benefit. There is a gap in a resource for co-productions in research and practice when it comes to LGBTQ+ people, and especially when these are unpaid carers – this is a unique challenge because current best practice indicates that the carer and the person cared for need to be perceived and considered as a unit. Therefore researchers and policy makers need to consider intersectional impacts and implications, that reflect the needs of the LGBTQ+ person and that of the person they care for, who may or may not be LGBTQ+, too. The leadership of LGBTQ+ individuals and communities in research, policy and practice that concerns those being impacted upon is vital. This project aimed to address a gap in the resources available to support co-production in research and practice. Its focus was on the vital role of unpaid carers as equal partners in developing research that addresses how to provide more tailored support. Our philosophy aimed to take account of the many different identities held by LGBTQ+ unpaid carers and to capitalise on the assets, knowledge and skills that they bring to caring and how best to improve it. The development of the toolkit involved developing processes and outcomes in relation to: Community engagement and consultation Identifying and building capacity for research collaboration Resources for training, supervision and support of LGBTQ+ unpaid carers; Peer networking and peer support Evaluation and capturing best practices Community knowledge exchang

    Development of SYK NanoBRET cellular target engagement assays for gain–of–function variants

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    Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase that is activated by phosphorylation events downstream of FcR, B-cell and T-cell receptors, integrins, and C-type lectin receptors. When the tandem Src homology 2 (SH2) domains of SYK bind to phosphorylated immunoreceptor tyrosine-based activation motifs (pITAMs) contained within these immunoreceptors, or when SYK is phosphorylated in interdomain regions A and B, SYK is activated. SYK gain-of-function (GoF) variants were previously identified in six patients that had higher levels of phosphorylated SYK and phosphorylated downstream proteins JNK and ERK. Furthermore, the increased SYK activation resulted in the clinical manifestation of immune dysregulation, organ inflammation, and a predisposition for lymphoma. The knowledge that the SYK GoF variants have enhanced activity was leveraged to develop a SYK NanoBRET cellular target engagement assay in intact live cells with constructs for the SYK GoF variants. Herein, we developed a potent SYK-targeted NanoBRET tracer using a SYK donated chemical probe, MRL-SYKi, that enabled a NanoBRET cellular target engagement assay for SYK GoF variants, SYK(S550Y), SYK(S550F), and SYK(P342T). We determined that ATP-competitive SYK inhibitors bind potently to these SYK variants in intact live cells. Additionally, we demonstrated that MRL-SYKi can effectively reduce the catalytic activity of SYK variants, and the phosphorylation levels of SYK(S550Y) in an epithelial cell line (SW480) stably expressing SYK(S550Y)

    Development of Cell Permeable NanoBRET Probes for the Measurement of PLK1 Target Engagement in Live Cells

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    PLK1 is a protein kinase that regulates mitosis and is both an important oncology drug target and a potential antitarget of drugs for the DNA damage response pathway or anti-infective host kinases. To expand the range of live cell NanoBRET target engagement assays to include PLK1, we developed an energy transfer probe based on the anilino-tetrahydropteridine chemotype found in several selective PLK inhibitors. Probe 11 was used to configure NanoBRET target engagement assays for PLK1, PLK2, and PLK3 and measure the potency of several known PLK inhibitors. In-cell target engagement for PLK1 was in good agreement with the reported cellular potency for the inhibition of cell proliferation. Probe 11 enabled the investigation of the promiscuity of adavosertib, which had been described as a dual PLK1/WEE1 inhibitor in biochemical assays. Live cell target engagement analysis of adavosertib via NanoBRET demonstrated PLK activity at micromolar concentrations but only selective engagement of WEE1 at clinically relevant doses

    Discovery of a Selective Inhibitor of Doublecortin Like Kinase 1

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    Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool to investigate DCLK1 biology and establish its role in cancer

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    De (con)formar a formar com: o currículo vivido no curso de ambientação institucional do IFES.

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    Made available in DSpace on 2016-08-29T11:11:55Z (GMT). No. of bitstreams: 1 tese_6910_Danusa Simon Robers.pdf: 15821358 bytes, checksum: 00ded04d356da9b697727d54ce47365b (MD5) Previous issue date: 2013-09-20A pesquisa buscou um mergulho no cotidiano do Curso de Ambientação Institucional (CAI) do Instituto Federal de Educação do Espírito Santo (Ifes), para problematizar as redes de saberesfazeres que são tecidas pelos sujeitos que realizam o currículo do curso, ou seja, todos aqueles que, de forma mais direta ou indireta, estão envolvidos na tessitura e compartilhamento das redes cotidianas desses currículos. Com a pesquisa com os cotidianos, este trabalho objetivou tecer redes de conversações com os servidoresalunos, gestores e servidoresprofessores, tendo Alves, Azevedo, Carvalho, Certeau, Ferraço, Foucault, Ginzburg, Maturana e Perez como os principais intercessores teóricos com os quais se dialogou ao longo da pesquisa. Procura discutir um pouco daquilo que acontece no cotidiano dos módulos do curso, numa tentativa de tradução dessas conversaspesquisas, apontando a necessidade de problematizar: que sentidos e/ou processos de formação profissional que apostam na produção de uma vida bonita são potencializados com o currículo realizado no Curso de Ambientação Institucional do Ifes? Fundamentouse em narrativas, imagens, documentos, música e poesia ao longo do texto, para tentar traduzir momentos, atravessamentos, encontros e envolvimentos que se deram ao longo da pesquisa, apresentando possibilidades de reinvenção para a produção de uma vida bonita. As imagensnarrativas dos praticantes do Curso de Ambientação Institucional têm o objetivo de não separar as discussões teóricometodológico-epistemológicas dos dados que foram produzidos com a pesquisa
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