319 research outputs found

    Helium 3/Helium 4 dilution cryocooler for space

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    Prototype dilution cryocoolers based on dilution refrigeration and adiabatic demagnetization refrigeration (ADR) cycles were designed, constructed, and tested. Although devices the devices did not operate as fully functional dilution cryocoolers, important information was gathered. The porous metal phase separator was demonstrated to operate in the -1-g configuration; this phase separation is the critical element in the He-3 circulation dilution cryocooler. Improvements in instrumentation needed for additional tests and development were identified

    Brief for Amici Curiae Canavan Foundation, Claire Altman Heine Foundation, March of Dimes Foundation, Massachusetts Breast Cancer Coalition, National Organization for Rare Disorders, National Tay Sachs and Allied Diseases Organization in Support of Plaintiffs for Affirmance

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    Amicus ("friend of the court") brief written by scholars of biotechnology patent law in support of plaintiffs-appellees, supporting affirmance in AMP v. Myriad Genetics (No. 2010-1406)

    High-Risk Corneal Graft Rejection in the Setting of Previous Corneal Herpes Simplex Virus (HSV)-1 Infection

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    Acknowledgments The authors thank M. Robertson and R. Fordyce for technical support during the duration of the study. The work performed in Aberdeen was supported by grant from Action Medical Research UK (SP4328; London, England, UK), NHS Grampian Endowment grant (12/49; Aberdeen, Scotland, UK), and Saving Sight in Grampian (Charity No.SC002938; Aberdeen, Scotland, UK). The work performed in Pittsburgh was supported by a Fight for Sight Post-Doctoral Award (JEK; New York, NY, USA); unrestricted grants from the Western Pennsylvania Medical Eye Bank Foundation (Pittsburgh, PA, USA), Research to Prevent Blindness (New York, NY, USA), and the Eye and Ear Foundation of Pittsburgh (RLH; Pittsburgh, PA, USA); and National Institutes of Health Grants P30EY08098 (RLH; Bethesda, MD, USA) and EY10359 (RLH).Peer reviewedPublisher PD

    Extracellular Vesicles from Pseudomonas aeruginosa Suppress MHC-Related Molecules in Human Lung Macrophages

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    Pseudomonas aeruginosa, a Gram-negative bacterium, is one of the most common pathogens colonizing the lungs of cystic fibrosis patients. P. aeruginosa secrete extracellular vesicles (EVs) that contain LPS and other virulence factors that modulate the host\u27s innate immune response, leading to an increased local proinflammatory response and reduced pathogen clearance, resulting in chronic infection and ultimately poor patient outcomes. Lung macrophages are the first line of defense in the airway innate immune response to pathogens. Proper host response to bacterial infection requires communication between APC and T cells, ultimately leading to pathogen clearance. In this study, we investigate whether EVs secreted from P. aeruginosa alter MHC Ag expression in lung macrophages, thereby potentially contributing to decreased pathogen clearance. Primary lung macrophages from human subjects were collected via bronchoalveolar lavage and exposed to EVs isolated from P. aeruginosa in vitro. Gene expression was measured with the NanoString nCounter gene expression assay. DNA methylation was measured with the EPIC array platform to assess changes in methylation. P. aeruginosa EVs suppress the expression of 11 different MHC-associated molecules in lung macrophages. Additionally, we show reduced DNA methylation in a regulatory region of gene complement factor B (CFB) as the possible driving mechanism of widespread MHC gene suppression. Our results demonstrate MHC molecule downregulation by P. aeruginosa-derived EVs in lung macrophages, which is consistent with an immune evasion strategy employed by a prokaryote in a host-pathogen interaction, potentially leading to decreased pulmonary bacterial clearance

    A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast

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    The mammalian tumor suppressor, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), inhibits cell growth and survival by dephosphorylating phosphatidylinositol-(3,4,5)-trisphosphate (PI[3,4,5]P3). We have found a homologue of PTEN in the fission yeast, Schizosaccharomyces pombe (ptn1). This was an unexpected finding because yeast (S. pombe and Saccharomyces cerevisiae) lack the class I phosphoinositide 3-kinases that generate PI(3,4,5)P3 in higher eukaryotes. Indeed, PI(3,4,5)P3 has not been detected in yeast. Surprisingly, upon deletion of ptn1 in S. pombe, PI(3,4,5)P3 became detectable at levels comparable to those in mammalian cells, indicating that a pathway exists for synthesis of this lipid and that the S. pombe ptn1, like mammalian PTEN, suppresses PI(3,4,5)P3 levels. By examining various mutants, we show that synthesis of PI(3,4,5)P3 in S. pombe requires the class III phosphoinositide 3-kinase, vps34p, and the phosphatidylinositol-4-phosphate 5-kinase, its3p, but does not require the phosphatidylinositol-3-phosphate 5-kinase, fab1p. These studies suggest that a pathway for PI(3,4,5)P3 synthesis downstream of a class III phosphoinositide 3-kinase evolved before the appearance of class I phosphoinositide 3-kinases

    Evaluating the Current Status of American Shad Stocks in Three Virginia Rivers

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    Directed commercial fisheries for American shad Alosa sapidissima in the primary Virginia tributaries of the Chesapeake Bay have been under moratorium since 1994. Monitoring of adult American shad within these rivers has been ongoing since 1998 through a cooperative program involving commercial fishers. The monitoring program is designed to mimic traditional commercial fishing practices so that stock status can be inferred by comparing contemporary catch-per-unit-effort levels with those derived from historic logbooks. In this paper, we present analyses of the available monitoring and historic catch rate data along with updated stock status information for American shad in the James, York, and Rappahannock rivers. Two analytical methods were used to derive annual indices of relative abundance; both methods yielded very similar patterns for each river system. Comparisons of contemporary and historic indices of relative abundance suggest that American shad in the James and York rivers continue to persist at low levels of abundance. Measures of stock abundance in the Rappahannock River have been higher than the logbook reference value for much of the monitoring period. However, current moratoria and restoration strategies, which include hatchery releases of fry, the removal of obstructions blocking spawning and nursery habitat, and reductions in bycatch from other fisheries, should continue into the foreseeable future

    Exploring Human/Animal Intersections: Converging Lines of Evidence in Comparative Models of Aging

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    At a symposium convened on March 8, 2007 by the Institute on Aging at the University of Pennsylvania, researchers from the University’s Schools of Medicine and Veterinary Medicine explored the convergence of aging research emerging from the two schools. Studies in human patients, animal models, and companion animals have revealed different but complementary aspects of the aging process, ranging from fundamental biologic aspects of aging to the treatment of age-related diseases, both experimentally and in clinical practice. Participants concluded that neither animal nor human research alone will provide answers to most questions about the aging process. Instead, an optimal translational research model supports a bidirectional flow of information from animal models to clinical research

    Birth outcomes in Colorado's undocumented immigrant population

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    BACKGROUND: The birth outcomes of undocumented women have not been systematically studied on a large scale. The growing number of undocumented women giving birth in the United States has important implications for clinical care and public health policy. The objective of this study was to describe birth outcomes of undocumented immigrants in Colorado. METHODS: Retrospective descriptive study of singleton births to 5961 undocumented women using birth certificate data for 1998–1999. RESULTS: Undocumented mothers were younger, less educated, and more likely to be single. They had higher rates of anemia, were less likely to gain enough weight, and less likely to receive early prenatal care. They were much less likely to use alcohol or tobacco. Undocumented women had a lower rate of low birth weight (5.3% v 6.5%, P < .001) or preterm infants (12.9% v 14.5%; p = .001). Undocumented women experienced higher rates of labor complications including excessive bleeding (2.3% v 0.8%, p < .001) and fetal distress (8.7% v 3.6%, p < .001). CONCLUSION: Undocumented women have lower rates of preterm delivery and low birth weight infants, but higher rates of pregnancy related risk factors. Higher prevalence of some risk factors which are amenable to medical intervention reveals the need for improved prenatal care in this group
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