82 research outputs found

    Does Liberalism Lack Virtue? A Critique of Alasdair MacIntyre’s Reactionary Politics

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    THE HERMENEUTICS OF POLICING: AN ANALYSIS OF LAW AND ORDER TECHNOCRACY

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    Contemporary American policing practices are marked by increasingly top-down, racialized, militarized, and pseudo-scientific features. Social scientists have played a central role in creating this political situation: social-scientific advocates of “law and order,” far from providing a value-neutral description of social reality, appear instead to have contributed to the creation of a peculiarly modern form of power

    NATURALISM AND ITS INADVERTENT DEFENDERS

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    The interpretive turn in the social sciences, although much discussed, has effectively stalled and even begun to backslide. With the publication of Interpretive Social Science: An Anti-Naturalist Approach, we provide a systema- tic defense of interpretive inquiry intended to help reinvigorate this mode of study across the human sciences. This defense, unfortunately, needs to be deployed not only against social scientists who unwittingly adopt naturalistic philosophical assumptions, but against interpretivist fellow travelers such as Michel Foucault, who occasionally do the same thing; and even against interpretivists who assume that their philosophical position is secured by using only qualitative methods, and that quantitative methods are inherently unsuitable to interpretivist purposes

    First-Time Practicum Students\u27 Lived Experiences of Case Presentations in Group Supervision: A Phenomenological Study

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    Although best practices of group supervision advise that supervisory methods match the developmental level of supervisees, research has shown that novices typically receive group supervision in the same manner as more experienced trainees. The prevalent use of case presentations in group supervision regardless of learners\u27 level of clinical experience suggests contemporary practicum courses may be overlooking beginning students\u27 unique, developmental characteristics and needs. Fifteen counseling students enrolled in CACREP-accredited master\u27s degree programs across the United States were interviewed for a phenomenological study exploring their experiences of case presentations in practicum. Synchronous interviews conducted over video conferencing examined participants\u27 emotional experiences throughout practicum, perceptions of the value of case presentations\u27 structural components (i.e., write-ups, recordings, feedback processes), and recommendations for improvement. Findings showed that participants shared similar emotions throughout practicum and appreciated the value of informal discussions and check-ins. Perceptions of the value of formal case presentations varied dramatically. Three conclusions emerged from the study: (a) practicum group supervision would be improved by maximizing the use of informal discussions; (b) formal case presentations may not be developmentally ideal for practicum due to problems relating to students\u27 clinical inexperience, time management, and quality of feedback exchange; and (c) practicum group supervision may be improved by developing students\u27 ability to provide and receive meaningful feedback. These conclusions have implications for counselor educators, supervisors, counseling programs, and practicum students. Modifications to practicum group supervision that are based on the findings of this study may improve students\u27 experiences and the outcomes of counselor training

    A framework for considering the utility of models when facing tough decisions in public health: a guideline for policy-makers

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    The COVID-19 pandemic has brought the combined disciplines of public health, infectious disease and policy modelling squarely into the spotlight. Never before have decisions regarding public health measures and their impacts been such a topic of international deliberation, from the level of individuals and communities through to global leaders. Nor have models-developed at rapid pace and often in the absence of complete information-ever been so central to the decision-making process. However, after nearly 3 years of experience with modelling, policy-makers need to be more confident about which models will be most helpful to support them when taking public health decisions, and modellers need to better understand the factors that will lead to successful model adoption and utilization. We present a three-stage framework for achieving these ends

    Hypoinsulinemia Regulates Amphetamine-Induced Reverse Transport of Dopamine

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    The behavioral effects of psychomotor stimulants such as amphetamine (AMPH) arise from their ability to elicit increases in extracellular dopamine (DA). These AMPH-induced increases are achieved by DA transporter (DAT)-mediated transmitter efflux. Recently, we have shown that AMPH self-administration is reduced in rats that have been depleted of insulin with the diabetogenic agent streptozotocin (STZ). In vitro studies suggest that hypoinsulinemia may regulate the actions of AMPH by inhibiting the insulin downstream effectors phosphotidylinositol 3-kinase (PI3K) and protein kinase B (PKB, or Akt), which we have previously shown are able to fine-tune DAT cell-surface expression. Here, we demonstrate that striatal Akt function, as well as DAT cell-surface expression, are significantly reduced by STZ. In addition, our data show that the release of DA, determined by high-speed chronoamperometry (HSCA) in the striatum, in response to AMPH, is severely impaired in these insulin-deficient rats. Importantly, selective inhibition of PI3K with LY294002 within the striatum results in a profound reduction in the subsequent potential for AMPH to evoke DA efflux. Consistent with our biochemical and in vivo electrochemical data, findings from functional magnetic resonance imaging experiments reveal that the ability of AMPH to elicit positive blood oxygen level–dependent signal changes in the striatum is significantly blunted in STZ-treated rats. Finally, local infusion of insulin into the striatum of STZ-treated animals significantly recovers the ability of AMPH to stimulate DA release as measured by high-speed chronoamperometry. The present studies establish that PI3K signaling regulates the neurochemical actions of AMPH-like psychomotor stimulants. These data suggest that insulin signaling pathways may represent a novel mechanism for regulating DA transmission, one which may be targeted for the treatment of AMPH abuse and potentially other dopaminergic disorders

    Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens

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    Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies

    A comprehensive platform for highly multiplexed mammalian functional genetic screens

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    <p>Abstract</p> <p>Background</p> <p>Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP) is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens.</p> <p>Results</p> <p>Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens.</p> <p>Conclusion</p> <p>Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray) based deconvolution methods.</p

    Global transpiration data from sap flow measurements: the SAPFLUXNET database

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    Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land?atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets,while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes.Fil: Poyatos, Rafael. Universitat Autònoma de Barcelona; EspañaFil: Granda, Víctor. Universitat Autònoma de Barcelona; EspañaFil: Flo, Víctor. Universitat Autònoma de Barcelona; EspañaFil: Adams, Mark A.. Swinburne University of Technology; Australia. University of Sydney; AustraliaFil: Adorján, Balázs. University of Debrecen; HungríaFil: Aguadé, David. Universitat Autònoma de Barcelona; EspañaFil: Aidar, Marcos P. M.. Institute of Botany; BrasilFil: Allen, Scott. University of Nevada; Estados UnidosFil: Alvarado Barrientos, M. Susana. Instituto de Ecología A.C.; MéxicoFil: Anderson Teixeira, Kristina J.. Smithsonian Tropical Research Institute; PanamáFil: Aparecido, Luiza Maria. Arizona State University; Estados Unidos. Texas A&M University; Estados UnidosFil: Arain, M. Altaf. McMaster University; CanadáFil: Aranda, Ismael. National Institute for Agricultural and Food Research and Technology; EspañaFil: Asbjornsen, Heidi. University of New Hampshire; Estados UnidosFil: Robert Baxter. Durham University; Reino UnidoFil: Beamesderfer, Eric. McMaster University; Canadá. Northern Arizona University; Estados UnidosFil: Carter Berry, Z.. Chapman University; Estados UnidosFil: Berveiller, Daniel. Université Paris Saclay; Francia. Centre National de la Recherche Scientifique; FranciaFil: Blakely, Bethany. University of Illinois at Urbana-Champaign; Estados UnidosFil: Boggs, Johnny. United States Forest Service; Estados UnidosFil: Gil Bohrer. Ohio State University; Estados UnidosFil: Bolstad, Paul V.. University of Minnesota; Estados UnidosFil: Bonal, Damien. Université de Lorraine; FranciaFil: Bracho, Rosvel. University of Florida; Estados UnidosFil: Brito, Patricia. Universidad de La Laguna; EspañaFil: Brodeur, Jason. McMaster University; CanadáFil: Casanoves, Fernando. Centro Agronómico Tropical de Investigación y Enseñanza; Costa RicaFil: Chave, Jérôme. Université Paul Sabatier; FranciaFil: Chen, Hui. Xiamen University; ChinaFil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Tecnológica Nacional. Facultad Regional Santa Cruz. Centro de Investigaciones y Transferencia de Santa Cruz. Universidad Nacional de la Patagonia Austral. Centro de Investigaciones y Transferencia de Santa Cruz; Argentin
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