2,011 research outputs found

    Heterogeneity in thymic emigrants: implications for thymectomy and immunosenescence.

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    The development of mature, antigen-inexperienced (naive) T cells begins in the thymus and continues after export into the periphery. Post-thymic maturation of naive T cells, in humans, coincides with the progressive loss of markers such as protein tyrosine kinase 7 (PTK7) and platelet endothelial cell adhesion molecule-1 (CD31). As a consequence, subpopulations of naive T cells can be recognised raising questions about the processes that give rise to the loss of these markers and their exact relationship to recent thymic emigrants (RTE). Here, we combine a mathematical survival analysis approach and data from healthy and thymectomised humans to understand the apparent persistence of populations of 'veteran' PTK7 (+) T cells in thymectomised individuals. We show that a model of heterogeneity in rates of maturation, possibly linked to natural variation in TCR signalling thresholds or affinity for self-antigens, can explain the data. This model of maturation predicts that the average post-thymic age of PTK7 (+) T cells will increase linearly with the age of the host suggesting that, despite the immature phenotype, PTK7 (+) cells do not necessarily represent a population of RTE. Further, the model predicts an accelerated increase in the average post-thymic age of residual PTK7 (+) T cells following thymectomy and may also explain in part the prematurely aged phenotype of the naive T cell pool in individuals thymectomised early in life

    The Goldfish as a Model for Studying Neuroestrogen Synthesis, Localization, and Action in the Brain and Visual System

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    Organizational and activational effects of estrogen (E) in the central nervous system (CNS) are exerted directly by circulating E and indirectly after aromatization of circulating androgen to E in the brain itself. Understanding an environmental chemical's ability to disrupt E-dependent neural processes, therefore, requires attention to both pathways. Because aromatase (Aro) is highly expressed in teleost brain, when compared to mammals and other vertebrates, fish are technically advantageous for localization and regulation studies and may also provide a model in which the functional consequences of brain-derived (neuro-)E synthesis are exaggerated. Recently, Aro was immunolocalized in cell bodies and fiber projections of second- and third-order neurons of the goldfish retina and in central visual processing areas. Authentic Aro enzyme activity was verified biochemically, suggesting a heretofore unrecognized role of sex steroids in the visual system. Initial studies show that in vivo treatment with aromatizable androgen or E increases calmodulin synthesis and calmodulin protein in retina and also affects retinal protein and DNA. Whether there are related changes in the processing of visual information that is essential for seasonal reproduction or in the generative and regenerative capacity of the goldfish visual system requires further investigation. IMAGES.National Science Foundation (DCB8916809

    The Intimate Geographies of Panic Disorder: Parsing Anxiety through Psychopharmacological Dissection

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    The category of panic disorder was significantly indebted to early psychopharmacological experiments (in the late 1950s and early 1960s) by the psychiatrist Donald Klein, in collaboration with Max Fink. Klein’s technique of “psychopharmacological dissection” underpinned his transformation of clinical accounts of anxiety and was central in effecting the shift from agoraphobic anxiety (with its spatial imaginary of city squares and streets) to panic. This technique disaggregated the previously unitary affect of anxiety—as advanced in psychoanalytic accounts—into two physiological and phenomenological kinds. “Psychopharmacological dissection” depended on particular modes of clinical observation to assess drug action and to interpret patient behavior. The “intimate geographies” out of which panic disorder emerged comprised both the socio-spatial dynamics of observation on the psychiatric ward and Klein’s use of John Bowlby’s model of separation anxiety—as it played out between the dyad of infant and mother—to interpret his adult patients’ affectively disordered behavior. This essay, in offering a historical geography of mid-twentieth-century anxiety and panic, emphasizes the importance of socio-spatial setting in understanding how clinical and scientific experimentation opens up new ways in which affects can be expressed, shaped, observed, and understood

    CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation

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    CD40 is a 48-kDa phosphorylated transmembrane glycoprotein belonging to the TNF receptor superfamily. CD40 has been demonstrated on a range of cell types, and it has an important role in adaptive immunity and inflammation. CD40 has recently been described on platelets but platelet activation by CD40 has not been described. In the present study, we use flow cytometry and immunoblotting to confirm that platelets constitutively express surface CD40. CD40 mRNA was undetectable, suggesting that the protein is synthesized early in platelet differentiation by megakaryocytes. Ligation of platelet CD40 with recombinant soluble CD40L trimer (sCD40LT) caused increased platelet CD62P expression, -granule and dense granule release, and the classical morphological changes associated with platelet activation. CD40 ligation also caused Ăź3 integrin activation, although this was not accompanied by platelet aggregation. These actions were abrogated by the CD40L blocking antibody TRAP-1 and the CD40 blocking antibodies M2 and M3, showing that activation was mediated by CD40L binding to platelet CD40. Ăź3 integrin blockade with eptifibatide had no effect, indicating that outside-in signaling via IIbĂź3 was not contributing to these CD40-mediated effects. CD40 ligation led to enhanced platelet-leukocyte adhesion, which is important in the recruitment of leukocytes to sites of thrombosis or inflammation. Our results support a role for CD40-mediated platelet activation in thrombosis, inflammation, and atherosclerosis

    Reservoir Performance History Matching Using Type-Curves.

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    Recently, decline-curve analysis has expanded to permit engineers to analyze a petroleum reservoir directly in regard to its fluid-flow characteristics and its volumetric extent using rate-time type-curves of the constant terminal pressure solution of the diffusivity equation. This analysis is of enormous value to reservoir managers whose goal is to maximize oil and gas production from a petroleum reservoir. Reservoir extent, continuity, and flow capacity are paramount characteristics that are considered when developing models that predict reservoir performance while using alternative depletion strategies, such as during fluid-injection projects or enhanced recovery. Reservoir producing conditions to which this technique can be readily applied are those whose actual bottom-hole flowing pressure (BHFP) closely approximates a constant value. Most wells, however, produce with variable BHFP. The work presented here focuses on an alternative rate-cumulative type-curve format whereby variable BHFP is incorporated into dimensionless variables containing both the production rate and the cumulative production providing a unified approach that can be applied to any reasonable variability in the producing rate or flowing pressure history. The proposed method, with application to single phase and multiphase flow, provides the practicing engineer a better method for decline curve analysis and therefore propagates better reservoir characterization from production data

    SUBTLE CUES AND HIDDEN ASSUMPTIONS: AN ACTION RESEARCH STUDY OF TEACHER QUESTIONING PATTERNS IN 7TH AND 8TH GRADE MATHEMATICS CLASSROOMS

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    This action research project explores the link between a teacher's questioning patterns and the modes of thinking, analyzing, evaluating and communicating that are developed in his 7th and 8th grade math students. The highly qualitative analysis focuses on three videotaped lessons from his 7th and 8th grade classrooms, and evaluates the lessons according to four categories or "lenses": cognitive demand, task completion, self-efficacy, and metacognitive activity. It then seeks to identify and codify the predominant questioning pattern used in each lesson, and connect this pattern to the levels of success exhibited in each of the four categories. Four principal patterns are observed and discussed in the lessons: Unilateral Inquiry Response Evaluation, Multilateral Inquiry Response Evaluation, Inquiry Response Collection, and Inquiry Response Revoicing Controversy. The fourth pattern is proposed as a tool for managing classroom discourse that involves a variety of (sometimes competing) student opinions

    Plasmonic-photonic crystal coupled nanolaser

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    We propose and demonstrate a hybrid photonic-plasmonic nanolaser that combines the light harvesting features of a dielectric photonic crystal cavity with the extraordinary confining properties of an optical nano-antenna. In that purpose, we developed a novel fabrication method based on multi-step electron-beam lithography. We show that it enables the robust and reproducible production of hybrid structures, using fully top down approach to accurately position the antenna. Coherent coupling of the photonic and plasmonic modes is highlighted and opens up a broad range of new hybrid nanophotonic devices
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