638 research outputs found

    Reduced swimming performance repeatedly evolves on loss of migration in landlocked populations of alewife

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    Author Posting. © University of Chicago, 2018. This article is posted here by permission of University of Chicago Press for personal use, not for redistribution. The definitive version was published in Physiological and Biochemical Zoology 91 (2018):814–825, doi:10.1086/696877.Whole-organism performance tasks are accomplished by the integration of morphological traits and physiological functions. Understanding how evolutionary change in morphology and physiology influences whole-organism performance will yield insight into the factors that shape its own evolution. We demonstrate that nonmigratory populations of alewife (Alosa pseudoharengus) have evolved reduced swimming performance in parallel, compared with their migratory ancestor. In contrast to theoretically and empirically based predictions, poor swimming among nonmigratory populations is unrelated to the evolution of osmoregulation and occurs despite the fact that nonmigratory alewives have a more fusiform (torpedo-like) body shape than their ancestor. Our results suggest that elimination of long-distance migration from the life cycle has shaped performance more than changes in body shape and physiological regulatory capacity.Funding was provided by the University of Connecticut’s Department of Ecology and Evolutionary Biology and El Muy Viejo.2019-01-3

    Reduced swimming performance repeatedly evolves on loss of migration in landlocked populations of alewife

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    Author Posting. © University of Chicago, 2018. This article is posted here by permission of University of Chicago Press for personal use, not for redistribution. The definitive version was published in Physiological and Biochemical Zoology 91 (2018):814–825, doi:10.1086/696877.Whole-organism performance tasks are accomplished by the integration of morphological traits and physiological functions. Understanding how evolutionary change in morphology and physiology influences whole-organism performance will yield insight into the factors that shape its own evolution. We demonstrate that nonmigratory populations of alewife (Alosa pseudoharengus) have evolved reduced swimming performance in parallel, compared with their migratory ancestor. In contrast to theoretically and empirically based predictions, poor swimming among nonmigratory populations is unrelated to the evolution of osmoregulation and occurs despite the fact that nonmigratory alewives have a more fusiform (torpedo-like) body shape than their ancestor. Our results suggest that elimination of long-distance migration from the life cycle has shaped performance more than changes in body shape and physiological regulatory capacity.Funding was provided by the University of Connecticut’s Department of Ecology and Evolutionary Biology and El Muy Viejo.2019-01-3

    Test and Analysis Correlation of a Large-Scale, Orthogrid-Stiffened Metallic Cylinder without Weld Lands

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    The NASA Engineering Safety Center (NESC) Shell Buckling Knockdown Factor Project (SBKF) was established in 2007 by the NESC with the primary objective to develop analysis-based buckling design factors and guidelines for metallic and composite launch-vehicle structures.1 A secondary objective of the project is to advance technologies that have the potential to increase the structural efficiency of launch-vehicles. The SBKF Project has determined that weld-land stiffness discontinuities can significantly reduce the buckling load of a cylinder. In addition, the welding process can introduce localized geometric imperfections that can further exacerbate the inherent buckling imperfection sensitivity of the cylinder. Therefore, single-piece barrel fabrication technologies can improve structural efficiency by eliminating these weld-land issues. As part of this effort, SBKF partnered with the Advanced Materials and Processing Branch (AMPB) at NASA Langley Research Center (LaRC), the Mechanical and Fabrication Branch at NASA Marshall Space Flight Center (MSFC), and ATI Forged Products to design and fabricate an 8-ft-diameter orthogrid-stiffened seamless metallic cylinder. The cylinder was subjected to seven subcritical load sequences (load levels that are not intended to induce test article buckling or material failure) and one load sequence to failure. The purpose of this test effort was to demonstrate the potential benefits of building cylindrical structures with no weld lands using the flow-formed manufacturing process. This seamless barrel is the ninth 8-ft-diameter metallic barrel and the first single-piece metallic structure to be tested under this program

    Buckling Response of a Large-Scale, Seamless, Orthogrid-Stiffened Metallic Cylinder

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    Results from the buckling test of a compression-loaded 8-ft-diameter seamless (i.e., without manufacturing joints), orthogrid-stiffened metallic cylinder are presented. This test was used to assess the buckling response and imperfection sensitivity characteristics of a seamless cylinder. In addition, the test article and test served as a technology demonstration to show the application of the flow forming manufacturing process to build more efficient buckling-critical structures by eliminating the welded joints that are traditionally used in the manufacturing of large metallic barrels. Pretest predictions of the cylinder buckling response were obtained using a finite-element model that included measured geometric imperfections. The buckling load predicted using this model was 697,000 lb, and the test article buckled at 743,000 lb (6% higher). After the test, the model was revised to account for measured variations in skin and stiffener geometry, nonuniform loading, and material properties. The revised model predicted a buckling load of 754,000 lb, which is within 1.5% of the tested buckling load. In addition, it was determined that the load carrying capability of the seamless cylinder is approximately 28% greater than a corresponding cylinder with welded joints

    Buckling Design and Imperfection Sensitivity of Sandwich Composite Launch-Vehicle Shell Structures

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    Composite materials are increasingly being considered and used for launch-vehicle structures. For shell structures, such as interstages, skirts, and shrouds, honeycomb-core sandwich composites are often selected for their structural efficiency. Therefore, it is becoming increasingly important to understand the structural response, including buckling, of sandwich composite shell structures. Additionally, small geometric imperfections can significantly influence the buckling response, including considerably reducing the buckling load, of shell structures. Thus, both the response of the theoretically perfect structure and the buckling imperfection sensitivity must be considered during the design of such structures. To address the latter, empirically derived design factors, called buckling knockdown factors (KDFs), were developed by NASA in the 1960s to account for this buckling imperfection sensitivity during design. However, most of the test-article designs used in the development of these recommendations are not relevant to modern launch-vehicle constructions and material systems, and in particular, no composite test articles were considered. Herein, a two-part study on composite sandwich shells to (1) examine the relationship between the buckling knockdown factor and the areal mass of optimized designs, and (2) to interrogate the imperfection sensitivity of those optimized designs is presented. Four structures from recent NASA launch-vehicle development activities are considered. First, designs optimized for both strength and stability were generated for each of these structures using design optimization software and a range of buckling knockdown factors; it was found that the designed areal masses varied by between 6.1% and 19.6% over knockdown factors ranging from 0.6 to 0.9. Next, the buckling imperfection sensitivity of the optimized designs is explored using nonlinear finite-element analysis and the as-measured shape of a large-scale composite cylindrical shell. When compared with the current buckling design recommendations, the results suggest that the current recommendations are overly conservative and that the development of new recommendations could reduce the acreage areal mass of many composite sandwich shell designs by between 4% and 19%, depending on the structure

    Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

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    Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "super responders" (24-month C-peptide ≥ baseline), and "nonresponders" (12-month C-peptide < baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4+ T cells and CD4+/CD8+ T-cell ratio and increased CD16+CD56hi natural killer cells (NK), CD4+ effector memory T cells (Tem), CD4+PD-1+ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3+Helios+ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G-CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G-CSF as a prevention strategy in high-risk subjects

    A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

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    Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

    The impact of prolonged disorders of consciousness on the occupational life of family members

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    The impact of vegetative state (VS) and minimally conscious states (MCSs) on an individual is devastating. VS and MCSs may be transitional towards recovery, but may become permanent. Although devastating for the individual the nature of these conditions also has a profound effect on the family. This study examined the impact on the family member and the changes in the individuals’ occupation. Six participants (spouses, partners or parents) were recruited to the study. Mixed methods were adopted to meet the requirements of the research and participants. Data were collected at 6 and 12 months post-injury, using time diaries, a questionnaire and semi-structured interviews. At 6 months post-injury the greatest amount of carers’ time was allocated to occupations involving the person in a Disorder of Consciousness and less time to social and leisure activities. Participants had difficulty viewing the future, lacked the desire or capacity to engage in previously enjoyed activities. At 12 months those impacts were still evident although changing. The transition to balanced occupational activity is slow, requiring a number of catalysts to change. A conceptual framework for a return to balance is provided, and guidance on advice from family members to families in a similar situation is given
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