939 research outputs found

    Proposed reference models for atomic oxygen in the terrestrial atmosphere

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    A provisional Atomic Oxygen Reference model was derived from average monthly ozone profiles and the MSIS-86 reference model atmosphere. The concentrations are presented in tabular form for the altitude range 40 to 130 km

    The informed road map to prevention of Alzheimer disease: A call to arms

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    Alzheimer disease (AD) prevention trials hold the promise to delay or prevent cognitive decline and dementia onset by intervening before significant neuronal damage occurs. In recent years, the first AD prevention trials have launched and are yielding important findings on the biology of targeting asymptomatic AD pathology. However, there are limitations that impact the design of these prevention trials, including the translation of animal models that recapitulate key stages and multiple pathological aspects of the human disease, missing target validation in asymptomatic disease, uncertain causality of the association of pathophysiologic changes with cognitive and clinical symptoms, and limited biomarker validation for novel targets. The field is accelerating advancements in key areas including the development of highly specific and quantitative biomarker measures for AD pathology, increasing our understanding of the course and relationship of amyloid and tau pathology in asymptomatic through symptomatic stages, and the development of powerful interventions that can slow or reverse AD amyloid pathology. We review the current status of prevention trials and propose key areas of needed research as a call to basic and translational scientists to accelerate AD prevention. Specifically, we review (1) sporadic and dominantly inherited primary and secondary AD prevention trials, (2) proposed targets, mechanisms, and drugs including the amyloid, tau, and inflammatory pathways and combination treatments, (3) the need for more appropriate prevention animal models and experiments, and (4) biomarkers and outcome measures needed to design human asymptomatic prevention trials. We conclude with actions needed to effectively move prevention targets and trials forward

    Spatial transcriptomics identifies spatially dysregulated expression of <i>GRM3</i> and <i>USP47</i> in amyotrophic lateral sclerosis

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    Research Funding Medical Research Council. Grant Number: MR/L016400/1 Biogen Academy of Medical Sciences. Grant Number: 210JMG 3102 R45620 MND Scotland Engineering and Physical Sciences Research CouncilPeer reviewedPublisher PD

    Phenoconversion from probable rapid eye movement sleep behavior disorder to mild cognitive impairment to dementia in a population-based sample

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    © 2017 The Authors Introduction Rapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes. Methods Fifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed. Results Over 6.4 ± 2.9 years, six of the 14 participants with MCI developed additional neurodegenerative signs, five of whom had Lewy body disease features. Four of them progressed to dementia at a mean age 84.8 ± 4.9 years, three of whom met the criteria for probable dementia with Lewy bodies. One subject with PD developed MCI, but not dementia. Discussion Our findings from the population-based sample of Olmsted County, Minnesota, residents suggest that a substantial number of RBD patients tend to develop overt synucleinopathy features over time, and RBD patients who develop MCI and subsequent dementia have clinical features most consistent with dementia with Lewy bodies

    Gallin; an antimicrobial peptide member of a new avian defensin family, the ovodefensins, has been subject to recent gene duplication

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    Background: Egg white must provide nutrients and protection to the developing avian embryo. One way in which this is achieved is an arsenal of antimicrobial proteins and peptides which are essentially extensions of the innate immune system. Gallin is a recently identified member of a family of peptides that are found in egg white. The function of this peptide family has not been identified and they are potentially antimicrobial. Results: We have confirmed that there are at least 3 forms of the gallin gene in the chicken genome in 3 separate lines of chicken, all the forms are expressed in the tubular cells of the magnum region of the oviduct, consistent with its presence in egg white. mRNA expression levels are in the order 10,000 times greater in the magnum than the shell gland. The conservation between the multiple forms of gallin in the chicken genome compared with the conservation between gallin and other avian gallin like peptides, suggests that the gene duplication has occurred relatively recently in the chicken lineage. The gallin peptide family contains a six cysteine motif (C-X-5-C-X-3-C-X-11-CX3-C-C) found in all defensins, and is most closely related to avian beta-defensins, although the cysteine spacing differs. Further support for the classification comes from the presence of a glycine at position 10 in the 41 amino acid peptide. Recombinant gallin inhibited the growth of Escherischia coli (E. coli) at a concentration of 0.25 mu M confirming it as part of the antimicrobial innate immune system in avian species. Conclusions: The relatively recent evolution of multiple forms of a member of a new defensin related group of peptides that we have termed ovodefensins, may be an adaptation to increase expression or the first steps in divergent evolution of the gene in chickens. The potent antimicrobial activity of the peptide against E. coli increases our understanding of the antimicrobial strategies of the avian innate immune system particularly those of the egg white and the evolution of the defensin family. The potential of this peptide and others in the family can now be investigated in a number of novel antimicrobial role

    Slow early growers have more muscle in relation to adult activity: evidence from Cebu, Philippines

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    Adult skeletal muscle mass (SMM) protects against type 2 diabetes but little is known about its developmental antecedents. We examined whether pace of early weight gain predicted adult SMM in a birth cohort from Cebu City, Philippines. Additionally, we examined whether increases in SMM associated with adult muscle-building exercise varied according to early growth

    First International Workshop on Grid Simulator Testing of Wind Turbine Drivetrains: Workshop Proceedings

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    This report summarizes the proceedings of the First International Workshop on Grid Simulator Testing of Wind Turbine Drivetrains, held from June 13 to 14, 2013, at the National Renewable Energy Laboratory's National Wind Technology Center, located south of Boulder, Colorado. The workshop was sponsored by the U.S. Department of Energy and cohosted by the National Renewable Energy Laboratory and Clemson University under ongoing collaboration via a cooperative research and development agreement. The purpose of the workshop was to provide a forum to discuss the research, testing needs, and state-of-the-art apparatuses involved in grid compliance testing of utility-scale wind turbine generators. This includes both dynamometer testing of wind turbine drivetrains ('ground testing') and field testing grid-connected wind turbines. Four sessions followed by discussions in which all attendees of the workshop were encouraged to participate comprised the workshop
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