119 research outputs found

    Electron-Diffraction Investigation of the Hexafluorides of Tungsten, Osmium, Iridium, Uranium, Neptunium, and Plutonium

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    An electron‐diffraction investigation has been made by the sector–microphotometer method on WF_6, OsF_6, IrF_6, UF_6, NpF_6, and PuF_6. The photographs of all these compounds reflect a phase shift which if not accounted for leads to asymmetric structures for the molecules. It sets in at smaller values of s=4πλ^(−1) sin (Ξ/2) the heavier the molecule and the greater the electron wavelength. There is good evidence for the symmetrical octahedral structure of all the compounds. The metal–fluorine distances were found to be 1.833 Å (W–F), 1.831 Å (Os–F), 1.830 Å(Ir–F), 1.996 Å (U–F), 1.981 Å (Np–F), and 1.971 Å (Pu–F), with estimated limits of error of ±0.008 Å except for ±0.010 Å for Pu–F

    Quantitation of Aortic Valvular Insufficiency Using Radioactive Tracers: An Experimental Study In Vitro

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    A method has been developed in vitro for quantitation of aortic valvular insufficiency (Al) based on the use of ladioactive traceis lo genei-ate graphic recordings of the movement of blood out of the ventricle and back again. The regurgitant fraction of stroke volume (peirent of Al) is read from this recording. The method was evaluated in a mechanical heart model by comparing Al values read from the istope recordings and Al values determined volumetrically. The recordings gave excellent agreement with the volumetric results (Corr. Coeff. .9). These in vitro results are of such quality that clinical trials seem justified

    À propos de The Practice of Liberal Pluralism de William Galston : un dialogue avec l’auteur

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    Document de travailLa publication de The Practice of Liberal Pluralism est apparue comme un Ă©vĂ©nement de premiĂšre importance dans la rĂ©flexion contemporaine sur l’apport du pluralisme au libĂ©ralisme. La pensĂ©e de William Galston a connu une Ă©volution : dans Liberal Purposes, l’accent est mis sur la critique du neutralisme et la position d’un libĂ©ralisme perfectionniste, tandis que Liberal Pluralism s’intĂ©resse au contraire aux limites de l’intervention Ă©tatique. Cette Ă©volution fait l’objet de nombreuses questions dans la discussion qui suit. The Practice of Liberal Pluralism opĂšre une synthĂšse intĂ©ressante sur ce point. Galston se dĂ©finit comme un libĂ©ral pluraliste dans la lignĂ©e de Berlin. Bien qu’il insiste sur le conflit tragique des valeurs, il minimise cet aspect dans les discussions qui suivent, et pose la possibilitĂ© consĂ©cutive d’avoir des devoirs prima facie (cf. la discussion sur sa nĂ©gation du particularisme moral). Un des arguments centraux pour justifier le pluralisme des valeurs est qu’il rend le mieux compte de la complexitĂ© de notre univers moral (cf. la discussion sur le pluralisme et le sentiment de regret). Galston endosse Ă©galement un pluralisme politique, lequel signifie que les sources d’autoritĂ© sont multiples. Le libĂ©ralisme de Galston est trĂšs tolĂ©rant Ă  l’égard des pratiques communautaires non libĂ©rales. Cette tolĂ©rance est cependant assortie de la dĂ©fense du « droit de sortie », notion qui apparaĂźt donc comme fondamentale. Dans les discussions qui suivent, Galston propose la maniĂšre adĂ©quate de comprendre l’exercice de ce droit de sortie (cf. les discussions sur les rapports entre libertĂ© expressive, droit de sortie et autonomie).The publication of The Practice of Liberal Pluralism has appeared as an event of first importance regarding contemporary theory about the relation between pluralism and liberalism. William Galston’s theory has had a visible evolution: in Liberal Purposes, the main object is a critique of neutralism and a defence of perfectionist liberalism, whereas Liberal Pluralism main concern was to draw the limits of state intervention. This evolution is the object of numerous questions in the following discussion. The Practice of Liberal Pluralism operates an interesting synthesis on this point. Galston defines himself as a liberal pluralist such as Berlin, but although he acknowledges that conflict between values can be tragic, he minimizes this aspect in the following discussions, and considers the possibility of having prima facie duties (cf. the discussion on his rejection of moral particularism). One of the main arguments for the defence of value pluralism is its capacity to explain the complexity of the moral universe (cf. the discussion on pluralism and regret). Galston endorses a political pluralism, which means that the sources of authority are multiple. Galston’s liberalism is very tolerant regarding non-liberal communitarian practices, although this tolerance is based on the defence of an exit right, which is a fundamental notion in his theory. In the following discussion Galston proposes how to understand this right of exit in an adequate manner (cf. the questions regarding expressive liberty, exit rights and autonomy)

    Electron-Diffraction Investigation of the Hexafluorides of Tungsten, Osmium, Iridium, Uranium, Neptunium, and Plutonium

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    An electron‐diffraction investigation has been made by the sector–microphotometer method on WF_6, OsF_6, IrF_6, UF_6, NpF_6, and PuF_6. The photographs of all these compounds reflect a phase shift which if not accounted for leads to asymmetric structures for the molecules. It sets in at smaller values of s=4πλ^(−1) sin (Ξ/2) the heavier the molecule and the greater the electron wavelength. There is good evidence for the symmetrical octahedral structure of all the compounds. The metal–fluorine distances were found to be 1.833 Å (W–F), 1.831 Å (Os–F), 1.830 Å(Ir–F), 1.996 Å (U–F), 1.981 Å (Np–F), and 1.971 Å (Pu–F), with estimated limits of error of ±0.008 Å except for ±0.010 Å for Pu–F

    Polo-like kinase 3 regulates CtIP during DNA double-strand break repair in G1

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    DNA double-strand breaks (DSBs) are repaired by nonhomologous end joining (NHEJ) or homologous recombination (HR). The C terminal binding protein–interacting protein (CtIP) is phosphorylated in G2 by cyclin-dependent kinases to initiate resection and promote HR. CtIP also exerts functions during NHEJ, although the mechanism phosphorylating CtIP in G1 is unknown. In this paper, we identify Plk3 (Polo-like kinase 3) as a novel DSB response factor that phosphorylates CtIP in G1 in a damage-inducible manner and impacts on various cellular processes in G1. First, Plk3 and CtIP enhance the formation of ionizing radiation-induced translocations; second, they promote large-scale genomic deletions from restriction enzyme-induced DSBs; third, they are required for resection and repair of complex DSBs; and finally, they regulate alternative NHEJ processes in Ku−/− mutants. We show that mutating CtIP at S327 or T847 to nonphosphorylatable alanine phenocopies Plk3 or CtIP loss. Plk3 binds to CtIP phosphorylated at S327 via its Polo box domains, which is necessary for robust damage-induced CtIP phosphorylation at S327 and subsequent CtIP phosphorylation at T847

    Spielen Statine eine Rolle als adjuvante Therapie bei EntzĂŒndung? / Do statins play a role as an adjuvant therapy in inflammation?

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    Despite recent advances in management of patients in intensive care units, sepsis and septic shock are the major causes of morbidity and mortality. Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious material are the first-line therapy of choice. In addition, various immunomodulatory treatments have been investigated during the past decades. However, despite promising results in studies with animal models, studies in humans with antibodies against lipopolysaccharide (LPS), tumor necrosis factor and interleukin-1 have not been successful. In addition, high doses of steroids, immunoglobulins or antibodies against LPS and cytokines did not reduce mortality, probably owing to timing and dosage of these drugs. Prophylactic administration of immunomodulatory drugs cannot be recommended due to severe adverse effects. However, owing to pleiotropic effects of statins this class of cholesterol lowering drugs has been suggested to be beneficial as adjuvant therapy for sepsis. The present review summarizes the pathophysiology of sepsis as well as experimental and clinical evidence for the use of statins in sepsis.Trotz der Fortschritte der Medizin stellen schwere EntzĂŒndungsreaktionen wie die Sepsis eine wesentliche Ursache fĂŒr MortalitĂ€t und MorbiditĂ€t auf Intensivstationen dar. Zur kausalen Therapie gehört neben der Beseitigung der auslösenden Ursache durch chirurgische Maßnahmen vor allem eine effektive Antibiose. Weiterhin werden supportive Maßnahmen wie KreislaufunterstĂŒtzung, Nierenersatztherapie, Therapie von Gerinnungsstörungen und metabolischer Entgleisung zur Therapie eingesetzt. DarĂŒber hinaus wurde in den vergangenen Jahren eine Vielzahl von immunomodulatorischen Therapien untersucht. Hierzu gehören neutralisierende Antikörper gegen Endotoxin oder proinflam-matorische Zytokine, Kortison, Immunglobuline und spezifische Gerinnungsinhibitoren. Neuere Studien weisen darauf hin, dass Statine (HMG-CoA-Reduktase-Inhibitoren) antientzĂŒndliche Wirkung haben und eine andauernde Statintherapie mit verminderter Inzidenz bakterieller Infektionen assoziiert ist. Aus diesem Grund wurden Statine als neue adjuvante Therpaie bei schweren EntzĂŒndungen und Sepsis vorgeschlagen. Im Gegensatz zu anderen antientzĂŒndlichen Therapien wĂ€re hier auch ein prophylaktischer Einsatz bei Hochrisikopatienten, zum Beispiel vor elektiven chirurgischen Eingriffen, möglich. In der vorliegenden Arbeit sind die pathophysiologischen Grundlagen der Sepsis sowie die experimentelle HintergrĂŒnde und die ersten klinischen Daten zum Einsatz der Statine bei Sepsis zusammengefasst

    Evolutionary and biomedical insights from the rhesus macaque genome

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    The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species

    Ku counteracts mobilization of PARP1 and MRN in chromatin damaged with DNA double-strand breaks

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    In mammalian cells, the main pathway for DNA double-strand breaks (DSBs) repair is classical non-homologous end joining (C-NHEJ). An alternative or back-up NHEJ (B-NHEJ) pathway has emerged which operates preferentially under C-NHEJ defective conditions. Although B-NHEJ appears particularly relevant to genomic instability associated with cancer, its components and regulation are still largely unknown. To get insights into this pathway, we have knocked-down Ku, the main contributor to C-NHEJ. Thus, models of human cell lines have been engineered in which the expression of Ku70/80 heterodimer can be significantly lowered by the conditional induction of a shRNA against Ku70. On Ku reduction in cells, resulting NHEJ competent protein extracts showed a shift from C- to B-NHEJ that could be reversed by addition of purified Ku protein. Using a cellular fractionation protocol after treatment with a strong DSBs inducer followed by western blotting or immunostaining, we established that, among C-NHEJ factors, Ku is the main counteracting factor against mobilization of PARP1 and the MRN complex to damaged chromatin. In addition, Ku limits PAR synthesis and single-stranded DNA production in response to DSBs. These data support the involvement of PARP1 and the MRN proteins in the B-NHEJ route for the repair of DNA DSBs

    IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry

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    To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats
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