76 research outputs found

    Index of names of syntaxa typified in 1994

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    Following the "Index of new names” (Theurillat & Moravec 1998), the present work collects the names of syntaxa (in the sense of the Code of phytosociological nomenclature,Barkman et al. 1986) above subassociation rank typified in 1994. The list comprises 101 names of syntaxa; three names are added to the Index 1992 (Theurillat & Moravec 1995

    Index of new names of syntaxa published in 1994

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    The present work collects the new names of syntaxa (in the sense of the Code of phytosociological nomenclature,Barkman et al. 1986) above subassociation rank found in the literature received by the Library of the Conservatoire Botanique in Geneva. For the year 1994 851 names were listed corresponding to 34 classes, 55 orders, 2 suborders, 128 alliances, 29 suballiances, and 603 associations. For each of them, an assessment of its validity is given relating to the Code of Phytosociological Nomenclature. 72 names are given to add to the Indices 1991, 1992, 1993 (Theurillat & Moravec 1994, 1995, 1996

    The Arf6 GEF GEP100/BRAG2 Regulates Cell Adhesion by Controlling Endocytosis of β1 Integrins

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    SummaryThe small GTPase Arf6 has been shown to regulate the post-endocytic trafficking of a subset of membrane proteins, including β1 integrins, and inhibition of Arf6 function impairs both cell adhesion and motility [1]. The activity of Arf GTPases is regulated by a large family of guanine nucleotide exchange factors (GEFs) [2]. Arf-GEP100/BRAG2 is a GEF with reported specificity for Arf6 in vitro [3], but it is otherwise poorly characterized. Here we report that BRAG2 exists in two ubiquitously expressed isoforms, which we call BRAG2a and BRAG2b, both of which can activate Arf6 in vivo. Depletion of endogenous BRAG2 by siRNA leads to dramatic effects in the cell periphery; one such effect is an accumulation of β1 integrin on the cell surface and a corresponding enhancement of cell attachment and spreading on fibronectin-coated substrates. In contrast, depletion of Arf6 leads to intracellular accumulation of β1 integrin and reduced adhesion and spreading. These findings suggest that Arf6 regulates both endocytosis and recycling of β1 integrins and that BRAG2 functions selectively to activate Arf6 during integrin internalization

    Use of Fluid-Ventilated, Gas-Permeable Scleral Lens for Management of Severe Keratoconjunctivitis Sicca Secondary to Chronic Graft-versus-Host Disease

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    AbstractKeratoconjunctivitis sicca (KCS) occurs in 40%-60% of patients with chronic graft-versus-host-disease (cGVHD) after allogeneic hematopoietic cell transplantation. Although immunosuppressive therapy is the primary treatment of chronic GVHD, ocular symptoms require measures to improve ocular lubrication, decrease inflammation, and maintain mucosal integrity. The liquid corneal bandage provided by a fluid-ventilated, gas-permeable scleral lens (SL) has been effective in mitigating symptoms and resurfacing corneal erosions in patients with KCS related to causes other than cGVHD. We report outcomes in 9 consecutive patients referred for SL fitting for cGVHD-related severe KCS that was refractory to standard treatments. All patients reported improvement of ocular symptoms and reduced the use of topical lubricants after SL fitting resulting from decreased evaporation. No serious adverse events or infections attributable to the SL occurred. The median Ocular Surface Disease Index improved from 81 (75-100) to 21 (6-52) within 2 weeks after SL fitting, and was 12 (2-53) at the time of last contact, 1-23 months (median, 8.0) after SL fitting. Disability related to KCS resolved in 7 patients after SL fitting. The use of SL appears to be safe and effective in patients with severe cGVHD-related KCS refractory to conventional therapies

    Treatment change as a predictor of outcome among patients with classic chronic graft-versus-host disease

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    We analyzed outcomes for 668 patients who had systemic treatment for chronic graft-versus-host disease (GVHD) to assess the utility of early treatment change for exacerbation of chronic GVHD as a surrogate for survival endpoints in clinical trials. Fifty-six percent of patients had treatment change within 2 years after diagnosis of chronic GVHD. The median onset of treatment change was 4.4 months (range, 0.3 – 50 months). The cumulative incidence of non-relapse mortality (NRM) at 2 years was 16%, and overall survival at 2 years was 74%. In time-dependent Cox models, treatment change was associated with an increase in risk of NRM (hazard ratio, 2.53; 95% CI, 1.7-3.7; p < .0001). The hazard ratio was attenuated by 6% per month of delay in treatment change. Our results confirm that exacerbation of chronic GVHD is associated with an increased risk of NRM and with decreased survival, but the strength of this association is not large enough to allow the use of early exacerbation as a surrogate for survival endpoints in clinical trials. Other measures of clinical benefit, such as response, will need to be developed as endpoints in phase II trials for patients with chronic GVHD

    Lesioning of the Striatum Reverses Motor Asymmetry in the 6-Hydroxydopamine Rodent Model of Parkinsonism

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    In the rat several paradigms of grafting of adrenal medulla into the striatum were studied following the induction of a parkinsonian model, using a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra . Direct autologous grafting of adrenal medulla into the caudate-putamen complex, a radiofrequency lesion of the striatum alone, and a radiofrequency lesion followed by delayed grafting of adrenal medulla were compared by analyzing rotational behavior. Direct grafting of adrenal medulla produced an overall reduction in apomorphine induced turning behavior by 43.5% when compared with controls. Radiofrequency lesioning of the striatum without graft showed the best improvement over control animals with a 92% reduction in the total number of rotations induced by apomorphine. Delayed grafting into the caudate lesion cavity also produced a dramatic reduction in motor asymmetry but did not improve the behavioral outcome over that of the lesion alone. Animals receiving only radiofrequency lesions exhibited a band of increased tyrosine hydroxylase like immunoreactivity bordering the lesion cavity. Graft survival was limited in the nonlesioned animals but appeared enhanced in the animals whose striatum was previously lesioned. Lesion location within the striatum influenced the behavioral outcome. Large reductions in apomorphine-induced rotations could result from small lesions of the dorso-lateral striatum. These findings indicate that selective destruction of the caudate-putamen complex without tissue transplantation produces a dramatic reduction in the motor asymmetry of 6-OHDA treated rats. Suggested explanations for the decrease in induced rotational behavior with radiofrequency lesions include a decrease in the number of striatal dopamine receptors following cell destruction and lesioninduced recovery of host dopaminergic afferents. Striatal damage in critical areas can reverse some of the motor behavior associated with the 6-OHDA model and needs to be considered when evaluating the effects of neural grafting in this model

    Ancillary Therapy and Supportive Care of Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. Ancillary Therapy and Supportive Care Working Group Report

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    AbstractThe Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of “ancillary therapy and supportive care” embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach

    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

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    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

    Astro2020 APC White Paper: The Early Career Perspective on the Coming Decade, Astrophysics Career Paths, and the Decadal Survey Process

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    In response to the need for the Astro2020 Decadal Survey to explicitly engage early career astronomers, the National Academies of Sciences, Engineering, and Medicine hosted the Early Career Astronomer and Astrophysicist Focus Session (ECFS) on October 8-9, 2018 under the auspices of Committee of Astronomy and Astrophysics. The meeting was attended by fifty six pre-tenure faculty, research scientists, postdoctoral scholars, and senior graduate students, as well as eight former decadal survey committee members, who acted as facilitators. The event was designed to educate early career astronomers about the decadal survey process, to solicit their feedback on the role that early career astronomers should play in Astro2020, and to provide a forum for the discussion of a wide range of topics regarding the astrophysics career path. This white paper presents highlights and themes that emerged during two days of discussion. In Section 1, we discuss concerns that emerged regarding the coming decade and the astrophysics career path, as well as specific recommendations from participants regarding how to address them. We have organized these concerns and suggestions into five broad themes. These include (sequentially): (1) adequately training astronomers in the statistical and computational techniques necessary in an era of "big data", (2) responses to the growth of collaborations and telescopes, (3) concerns about the adequacy of graduate and postdoctoral training, (4) the need for improvements in equity and inclusion in astronomy, and (5) smoothing and facilitating transitions between early career stages. Section 2 is focused on ideas regarding the decadal survey itself, including: incorporating early career voices, ensuring diverse input from a variety of stakeholders, and successfully and broadly disseminating the results of the survey
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