367 research outputs found

    Materials science experiments in space

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    The criteria for the selection of the experimental areas and individual experiments were that the experiment or area must make a meaningful contribution to the field of material science and that the space environment was either an absolute requirement for the successful execution of the experiment or that the experiment can be more economically or more conveniently performed in space. A number of experimental areas and individual experiments were recommended for further consideration as space experiments. Areas not considered to be fruitful and others needing additional analysis in order to determine their suitability for conduct in space are also listed. Recommendations were made concerning the manner in which these materials science experiments are carried out and the related studies that should be pursued

    Combinations of Griffithsin with Other Carbohydrate-Binding Agents Demonstrate Superior Activity Against HIV Type 1, HIV Type 2, and Selected Carbohydrate-Binding Agent-Resistant HIV Type 1 Strains

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    Abstract Carbohydrate-binding agents (CBAs) are potential HIV microbicidal agents with a high genetic barrier to resistance. We wanted to evaluate whether two mannose-specific CBAs, recognizing multiple and often distinct glycan structures on the HIV envelope gp120, can interact synergistically against HIV-1, HIV-2, and HIV-1 strains that were selected for resistance against particular CBAs [i.e., 2G12 mAb and microvirin (MVN)]. Paired CBA/CBA combinations mainly showed synergistic activity against both wild-type HIV-1 and HIV-2 but also 2G12 mAb- and MVN-resistant HIV-1 strains as based on the median effect principle with combination indices (CIs) ranging between 0.29 and 0.97. Upon combination, an increase in antiviral potency of griffithsin (GRFT) up to ?12-fold (against HIV-1), ?8-fold (against HIV-2), and ?6-fold (against CBA-resistant HIV-1) was observed. In contrast, HHA/GNA combinations showed additive activity against wild-type HIV-1 and HIV-2 strains, but remarkable synergy with HHA and GNA was observed against 2G12 mAb- and MVN-resistant HIV-1 strains (CI, 0.64 and 0.49, respectively). Overall, combinations of GRFT and other CBAs showed synergistic activity against HIV-1, HIV-2, and even against certain CBA-resistant HIV-1 strains. The CBAs tested appear to have distinct binding patterns on the gp120 envelope and therefore do not necessarily compete with each other's glycan binding sites on gp120. As a result, there might be no steric hindrance between two different CBAs in their competition for glycan binding (except for the HHA/GNA combination). These data are encouraging for the use of paired CBA combinations in topical microbicide applications (e.g., creams, gels, or intravaginal rings) to prevent HIV transmission.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98459/1/aid%2E2012%2E0026.pd

    High Levels of DEK Autoantibodies in Sera of Patients With Polyarticular Juvenile Idiopathic Arthritis and With Early Disease Flares Following Cessation of Anti–Tumor Necrosis Factor Therapy

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    © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. Objective: The nuclear oncoprotein DEK is an autoantigen associated with juvenile idiopathic arthritis (JIA), especially the oligoarticular subtype. DEK is a secreted chemotactic factor. Abundant levels of DEK and DEK autoantibodies are found in inflamed synovium in JIA. We undertook this study to further characterize the nature of DEK autoantibodies in screening serum samples from 2 different cohorts that consisted mostly of patients with JIA. Methods: DEK autoantibody levels were analyzed in sera from 33 JIA patients, 13 patients with other inflammatory conditions, and 11 healthy controls, as well as in 89 serum samples from JIA patients receiving anti–tumor necrosis factor (anti-TNF) therapy. Recombinant His-tagged full-length DEK protein (1–375 amino acids [aa]) and the 187–375-aa and 1–350-aa His-tagged DEK fragments made in a baculovirus system were used for enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The C-terminal 25-aa fragment of DEK was expressed in a glutathione S-transferase–tagged vector. ELISA results were calculated as area under the curve by the trapezoidal rule. Results: DEK autoantibody levels were significantly higher in patients with polyarticular JIA than in those with oligoarticular JIA, and were higher in patients with polyarticular JIA who had more active disease after cessation of anti-TNF therapy. Immunoblotting against the C-terminal 25-aa fragment of DEK confirmed that this section of the DEK molecule is the most immunogenic domain. Conclusion: DEK autoantibody levels are higher in patients with polyarticular JIA than in those with oligoarticular JIA, and higher in patients who have disease flares after cessation of anti-TNF therapy. The C-terminal 25-aa fragment is the most immunogenic portion of DEK. These findings are significant with respect to the nature of DEK autoantibodies, their contribution to JIA pathogenesis, and their implications for JIA management

    The effects of the spontaneous presence of a spouse/partner and others on cardiovascular reactions to an acute psychological challenge

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    The presence of supportive others has been associated with attenuated cardiovascular reactivity in the laboratory. The effects of the presence of a spouse and others in a more naturalistic setting have received little attention. Blood pressure and heart rate reactions to mental stress were recorded at home in 1028 married/partnered individuals. For 112 participants, their spouse/partner was present; for 78, at least one other person was present. Women tested with a spouse/partner present showed lower magnitude systolic blood pressure and heart rate reactivity than those tested without. Individuals tested with at least one nonspousal other present also displayed attenuated reactivity. This extends the results of laboratory studies and indicates that the spontaneous presence of others is associated with a reduction in cardiovascular reactivity in an everyday environment; spouse/partner presence would appear to be especially effective for women.\ud \u

    BCC vs. HCP - The Effect of Crystal Symmetry on the High Temperature Mobility of Solid 4^4He

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    We report results of torsional oscillator (TO) experiments on solid 4^4He at temperatures above 1K. We have previously found that single crystals, once disordered, show some mobility (decoupled mass) even at these rather high temperatures. The decoupled mass fraction with single crystals is typically 20- 30%. In the present work we performed similar measurements on polycrystalline solid samples. The decoupled mass with polycrystals is much smaller, \sim 1%, similar to what is observed by other groups. In particular, we compared the properties of samples grown with the TO's rotation axis at different orientations with respect to gravity. We found that the decoupled mass fraction of bcc samples is independent of the angle between the rotation axis and gravity. In contrast, hcp samples showed a significant difference in the fraction of decoupled mass as the angle between the rotation axis and gravity was varied between zero and 85 degrees. Dislocation dynamics in the solid offers one possible explanation of this anisotropy.Comment: 10 pages, 5 figures, to appear in Journal of Low Temperature Physics - special issue on Supersolidit

    Life events and hemodynamic stress reactivity in the middle-aged and elderly

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    Recent versions of the reactivity hypothesis, which consider it to be the product of stress exposure and exaggerated haemodynamic reactions to stress that confers cardiovascular disease risk, assume that reactivity is independent of the experience of stressful life events. This assumption was tested in two substantial cohorts, one middle-aged and one elderly. Participants had to indicate from a list of major stressful life events up to six they had experienced in the previous two years. They were also asked to rate how disruptive and stressful they were, at the time of occurrence and now. Blood pressure and pulse rate were measured at rest and in response to acute mental stress. Those who rated the events as highly disruptive at the time of exposure and currently exhibited blunted systolic blood pressure reactions to acute stress. The present results suggest that acute stress reactivity may not be independent of stressful life events experience

    Randomized Controlled Trial of Mechanical Thrombectomy Versus Catheter-directed Thrombolysis for Acute Hemodynamically Stable Pulmonary Embolism: Rationale and Design of the PEERLESS Study.

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    BACKGROUND The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient's care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the Pulmonary Embolism Response Team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and non-thrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients. METHODS The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a non-randomized MT cohort for separate analysis. The primary endpoint will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary endpoints. Other key secondary endpoints include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit. IMPLICATIONS PEERLESS is the first RCT to compare two different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted

    Loneliness, social support and cardiovascular reactivity to laboratory stress

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    Self-reported or explicit loneliness and social support have been inconsistently associated with cardiovascular reactivity (CVR) to stress. The present study aimed to adapt an implicit measure of loneliness, and use it alongside the measures of explicit loneliness and social support, to investigate their correlations with CVR to laboratory stress. Twenty-five female volunteers aged between 18 and 39 years completed self-reported measures of loneliness and social support, and an Implicit Association Test (IAT) of loneliness. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) reactivity indices were measured in response to psychosocial stress induced in the laboratory. Functional support indices of social support were significantly correlated with CVR reactivity to stress. Interestingly, implicit, but not explicit, loneliness was significantly correlated with DBP reactivity after one of the stressors. No associations were found between structural support and CVR indices. Results are discussed in terms of validity of implicit versus explicit measures and possible factors that affect physiological outcomes

    ‘Race’ Talk! Tensions and Contradictions in Sport and PE

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    Background: The universal sport discourses of inclusion, belonging, meritocracy, agency, and equality are so widespread that few challenge them. It is clear from the most cursory interest in sport, PE and society that the lived reality is quite different and ambiguous. Racial disparities in the leadership and administration of sport are commonplace world wide; yet from research into ‘race’ in sport and PE the public awareness of these issues is widespread, where many know that racism takes place it is always elsewhere For many this racism is part of the game and something that enables an advantage to be stolen, for others it is trivial and not worthy of deeper thought. This paper explores the contradictions and tensions of the author’s experience of how sport and PE students talk about ‘race’. ‘Race’ talk is considered here in the context of passive everyday ‘race’ talk, dominant discourses in sporting cultures, and colour-blindness. This paper focuses on the pernicious yet persistent nature of ‘race’ talk while demystifying its multifarious, spurious, and more persuasive daily iterations. Theoretical framework: Drawing on Guinier and Torres’ (2003) ideas of resistance through political race consciousness and Bonilla-Silva’s (2010) notion of colour-blindness the semantics of ‘race’ and racialisation in sport and PE are interrogated through the prism of Critical Race Theory (CRT). Critical race scholarship has been used in sport and PE to articulate a political application of ‘race’ as a starting point for critical activism, to disrupt whiteness, and to explore the implications of ‘race’ and racism. CRT is used here to centre ‘race’ and racialised relations where disciplines have consciously or otherwise excluded them. Importantly, the centreing of ‘race’ by critical race scholars has advanced a strategic and pragmatic engagement with this slippery concept that recognises its paradoxical but symbolic location in social relations. Discussion: Before exploring ‘race’ talk in the classroom, using images from the sport media as a pedagogical tool, the paper considers how effortlessly ‘race’ is recreated and renewed. The paper then turns to explore how the effortless turn to everyday ‘race’ talk in the classroom can be viewed as an opportunity to disrupt common racialised assumptions with the potential to implicate those that passively engage in it. Further the diagnostic, aspirational and activist goals of political race consciousness are established as vehicles for a positive sociological experience in the classroom. Conclusion: The work concludes with a pragmatic consideration of the uses and dangers of passive everyday ‘race’ talk and the value of a political race consciousness in sport and PE. Part of the explanation for the perpetuation of ‘race’ talk and the relative lack of concern with its impact in education and wider society is focused on how the sovereignty of sport and PE trumps wider social concerns of ‘race’ and racism because of at least four factors 1) the liberal left discourses of sporting utopianism 2) the ‘race’ logic that pervades sport, based upon the perceived equal access and fairness of sport as it coalesces with the, 3) 'incontrovertible facts' of black and white superiority [and inferiority] in certain sports, ergo the racial justifications for patterns of activity in sport and PE 4) the racist logic of the Right perpetuated through a biological reductionism in sport and PE discourses. Keywords: ‘Race’ Talk; Critical Race Theory; Political Race Consciousnes
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