307 research outputs found

    The hydrodynamics of swimming microorganisms

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    Cell motility in viscous fluids is ubiquitous and affects many biological processes, including reproduction, infection, and the marine life ecosystem. Here we review the biophysical and mechanical principles of locomotion at the small scales relevant to cell swimming (tens of microns and below). The focus is on the fundamental flow physics phenomena occurring in this inertia-less realm, and the emphasis is on the simple physical picture. We review the basic properties of flows at low Reynolds number, paying special attention to aspects most relevant for swimming, such as resistance matrices for solid bodies, flow singularities, and kinematic requirements for net translation. Then we review classical theoretical work on cell motility: early calculations of the speed of a swimmer with prescribed stroke, and the application of resistive-force theory and slender-body theory to flagellar locomotion. After reviewing the physical means by which flagella are actuated, we outline areas of active research, including hydrodynamic interactions, biological locomotion in complex fluids, the design of small-scale artificial swimmers, and the optimization of locomotion strategies.Comment: Review articl

    IRF4 and BATF are critical for CD8(+) T-cell function following infection with LCMV.

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    CD8(+) T-cell functions are critical for preventing chronic viral infections by eliminating infected cells. For healthy immune responses, beneficial destruction of infected cells must be balanced against immunopathology resulting from collateral damage to tissues. These processes are regulated by factors controlling CD8(+) T-cell function, which are still incompletely understood. Here, we show that the interferon regulatory factor 4 (IRF4) and its cooperating binding partner B-cell-activating transcription factor (BATF) are necessary for sustained CD8(+) T-cell effector function. Although Irf4(-/-) CD8(+) T cells were initially capable of proliferation, IRF4 deficiency resulted in limited CD8(+) T-cell responses after infection with the lymphocytic choriomeningitis virus. Consequently, Irf4(-/-) mice established chronic infections, but were protected from fatal immunopathology. Absence of BATF also resulted in reduced CD8(+) T-cell function, limited immunopathology, and promotion of viral persistence. These data identify the transcription factors IRF4 and BATF as major regulators of antiviral cytotoxic T-cell immunity

    Partial Wave Analysis of J/ψγ(K+Kπ+π)J/\psi \to \gamma (K^+K^-\pi^+\pi^-)

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    BES data on J/ψγ(K+Kπ+π)J/\psi \to \gamma (K^+K^-\pi^+\pi^-) are presented. The KKˉK^*\bar K^* contribution peaks strongly near threshold. It is fitted with a broad 0+0^{-+} resonance with mass M=1800±100M = 1800 \pm 100 MeV, width Γ=500±200\Gamma = 500 \pm 200 MeV. A broad 2++2^{++} resonance peaking at 2020 MeV is also required with width 500\sim 500 MeV. There is further evidence for a 2+2^{-+} component peaking at 2.55 GeV. The non-KKˉK^*\bar K^* contribution is close to phase space; it peaks at 2.6 GeV and is very different from KKˉK^{*}\bar{K^{*}}.Comment: 15 pages, 6 figures, 1 table, Submitted to PL

    Contribution of CD3(+)CD8(-) and CD3(+)CD8(+) T Cells to TNF-alpha Overexpression in Crohn Disease-Associated Perianal Fistulas and Induction of Epithelial-Mesenchymal Transition in HT-29 Cells

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    Background Fistulas represent a frequent and severe complication in patients with Crohn disease (CD). Tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, and interleukin (IL)-13 are known to trigger epithelial-mesenchymal transition (EMT), promoting fistula formation. Here, we investigated the role of T-lymphocytes (T cells) in fistula pathogenesis. Methods CD3(+)CD8(-), CD3(+)CD8(+), or CD45(+)CD3(-) cells from healthy volunteers, patients with CD, and patients with CD with perianal fistula were co-cultured with HT-29 cells. The EMT, cytokine production, and mRNA expression were analyzed. Perianal CD fistula specimens were immunohistochemically stained for cytokines and their receptors. The effect of cytokines on EMT induction was investigated using an EMT spheroid model. Results Patients with CD with fistula revealed more CD3(+)CD8(-) and less CD3(+)CD8(+) T cells in blood than healthy control patients and patients with CD without fistula. In perianal fistula specimens, CD4(+) cells-and to a lesser extent CD8(+) cells-were highly present around fistula tracts. When co-cultured with HT-29 cells, both cell subsets promoted EMT-related gene expression and TNF-alpha production in a time-dependent manner. The CD3(+)CD8(-) T cells from patients with CD with fistula also produced higher amounts of IL-13 than cells from healthy control patients or patients with CD without a fistula. We found that IL-22 and IL-22R(alpha 1) were highly expressed in perianal CD fistula specimens and that IL-22 cotreatment potentiated TNF-alpha-induced EMT in HT-29 spheroids. Conclusions Our data indicate that both CD3(+)CD8(-) and CD3(+)CD8(+) T cells play an important role in the pathogenesis of perianal CD fistulas by the secretion of TNF-alpha. Our data support clinical evidence indicating that anti-TNF-alpha therapy is effective in fistula treatment and identify IL-13 and IL-22 as possible novel therapeutic targets for fistula therapy.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

    Fabrication of CuO nanoparticle interlinked microsphere cages by solution method

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    Here we report a very simple method to convert conventional CuO powders to nanoparticle interlinked microsphere cages by solution method. CuO is dissolved into aqueous ammonia, and the solution is diluted by alcohol and dip coating onto a glass substrate. Drying at 80 °C, the nanostructures with bunchy nanoparticles of Cu(OH)2can be formed. After the substrate immerges into the solution and we vaporize the solution, hollow microspheres can be formed onto the substrate. There are three phases in the as-prepared samples, monoclinic tenorite CuO, orthorhombic Cu(OH)2, and monoclinic carbonatodiamminecopper(II) (Cu(NH3)2CO3). After annealing at 150 °C, the products convert to CuO completely. At annealing temperature above 350 °C, the hollow microspheres became nanoparticle interlinked cages

    Effective Chiral Lagrangian from Dual Resonance Models

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    Parameters of the effective chiral lagrangian (EChL) of orders O(p4)O(p^4) and O(p6)O(p^6) are extracted from low--energy behaviour of dual resonance models for ππ \pi\pi and πK\pi K scattering amplitudes. Dual resonance models are considered to be good candidates for the resonance spectrum and for hadronic scattering amplitudes in the large NcN_c limit of QCD. We discuss dual resonance models in the presence of spontaneous and explicit chiral symmetry breaking. Obtained parameters of the EChL are used to estimate chiral corrections up to the sixth order to various low--energy characteristics of ππ\pi\pi and πK\pi K scattering amplitudes.Comment: 32 pages, the references list is updated, comparison with chiral quark model is done in more detail

    Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin-dependent kinase-like 5 (CDKL5) demonstrates role in hippocampal CA1 physiology

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    Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disorder associated with severe and medically refractory early-life epilepsy, motor, cognitive, visual, and autonomic disturbances in the absence of any structural brain pathology. Analysis of genetic variants in CDD has indicated that CDKL5 kinase function is central to disease pathology. CDKL5 encodes a serine-threonine kinase with significant homology to GSK3β, which has also been linked to synaptic function. Further, Cdkl5 knock-out rodents have increased GSK3β activity and often increased long-term potentiation (LTP). Thus, development of a specific CDKL5 inhibitor must be careful to exclude cross-talk with GSK3β activity. We synthesized and characterized specific, high-affinity inhibitors of CDKL5 that do not have detectable activity for GSK3β. These compounds are very soluble in water but blood-brain barrier penetration is low. In rat hippocampal brain slices, acute inhibition of CDKL5 selectively reduces postsynaptic function of AMPA-type glutamate receptors in a dose-dependent manner. Acute inhibition of CDKL5 reduces hippocampal LTP. These studies provide new tools and insights into the role of CDKL5 as a newly appreciated key kinase necessary for synaptic plasticity. Comparisons to rodent knock-out studies suggest that compensatory changes have limited the understanding of the roles of CDKL5 in synaptic physiology, plasticity, and human neuropathology

    Using behavior-analytic implicit tests to assess sexual interests among normal and sex-offender populations

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    The development of implicit tests for measuring biases and behavioral predispositions is a recent development within psychology. While such tests are usually researched within a social-cognitive paradigm, behavioral researchers have also begun to view these tests as potential tests of conditioning histories, including in the sexual domain. The objective of this paper is to illustrate the utility of a behavioral approach to implicit testing and means by which implicit tests can be built to the standards of behavioral psychologists. Research findings illustrating the short history of implicit testing within the experimental analysis of behavior are reviewed. Relevant parallel and overlapping research findings from the field of social cognition and on the Implicit Association Test are also outlined. New preliminary data obtained with both normal and sex offender populations are described in order to illustrate how behavior-analytically conceived implicit tests may have potential as investigative tools for assessing histories of sexual arousal conditioning and derived stimulus associations. It is concluded that popular implicit tests are likely sensitive to conditioned and derived stimulus associations in the history of the test-taker rather than 'unconscious cognitions', per se

    An Observational Overview of Solar Flares

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    We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011
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