168 research outputs found

    Surge Pressure Mitigation in the Global Precipitation Measurement Mission Core Propulsion System

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    The Global Precipitation Measurement (GPM) mission is an international partnership between NASA and JAXA whose Core spacecraft performs cutting-edge measurements of rainfall and snowfall worldwide and unifies data gathered by a network of precipitation measurement satellites. The Core spacecraft's propulsion system is a blowdown monopropellant system with an initial hydrazine load of 545 kg in a single composite overwrapped propellant tank. At launch, the propulsion system contained propellant in the tank and manifold tubes upstream of the latch valves, with low-pressure helium gas in the manifold tubes downstream of the latch valves. The system had a relatively high beginning-of- life pressure and long downstream manifold lines; these factors created conditions that were conducive to high surge pressures. This paper discusses the GPM project's approach to surge mitigation in the propulsion system design. The paper describes the surge testing program and results, with discussions of specific difficulties encountered. Based on the results of surge testing and pressure drop analyses, a unique configuration of cavitating venturis was chosen to mitigate surge while minimizing pressure losses during thruster maneuvers. This paper concludes with a discussion of overall lessons learned with surge pressure testing for NASA Goddard spacecraft programs

    Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity.

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    Polarization of the airway epithelial cells (AECs) in the airway lumen is critical to the proper function of the mucociliary escalator and maintenance of lung health, but the cellular requirements for polarization of AECs are poorly understood. Using human AECs and cell lines, we demonstrate that cadherin-26 (CDH26) is abundantly expressed in differentiated AECs, localizes to the cell apices near ciliary membranes, and has functional cadherin domains with homotypic binding. We find a unique and non-redundant role for CDH26, previously uncharacterized in AECs, in regulation of cell-cell contact and cell integrity through maintaining cytoskeletal structures. Overexpression of CDH26 in cells with a fibroblastoid phenotype increases contact inhibition and promotes monolayer formation and cortical actin structures. CDH26 expression is also important for localization of planar cell polarity proteins. Knockdown of CDH26 in AECs results in loss of cortical actin and disruption of CRB3 and other proteins associated with apical polarity. Together, our findings uncover previously unrecognized functions for CDH26 in the maintenance of actin cytoskeleton and apicobasal polarity of AECs

    Perspective of an advocate: a case and framework for research advocacy in Africa

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    Regulatory dendritic cell treatment prevents the development of vasopressin-induced preeclampsia

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    The concept that persistent feto-placental intolerance is important in the pathogenesis of preeclampsia (PE) has been demonstrated by our lab and others. Arginine vasopressin (AVP) infusion during pregnancy induces cardiovascular, renal, and immune alterations in mice consistent with human PE. These findings identify AVP as a potential contributor to poor fetal tolerance and the development of PE. In addition to their conventional immuno-stimulatory role, dendritic cells (DCs) also play a vital role in immune tolerance. In contrast to conventional DCs, regulatory DCs (DCregs) express low levels of co-stimulatory markers, produce anti-inflammatory cytokines, induce T regulatory cells, and promote tolerance. In mice, DCregs are able to prevent pro-inflammatory responses and induce antigen-specific tolerance. Given these known functions of DCregs, we hypothesize that DCregs will prevent the development of AVP-induced PE

    Betamethasone: a novel therapeutic intervention for preeclampsia

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    The early pathogenesis of preeclampsia (PE) involves a systemic inflammatory immune response. Recent data demonstrate that increased circulating arginine vasopressin (AVP) in humans is predictive of PE and that infusion of AVP in mouse dams phenocopies the pregnancy-specific cardiovascular and immune alterations observed in human PE. Specifically, AVP suppresses anti-inflammatory cytokines and cells. Betamethasone (BMTZ), commonly given to women at risk for preterm birth, is both an AVP and immune response modulator. We hypothesize that early treatment with BMTZ will prevent the development of AVP-induced PE

    Static urine osmolality with elevated first trimester urine copeptin in human preeclampsia

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    We have previously shown that maternal plasma copeptin (CPP), as a marker of vasopressin, is highly predictive of preeclampsia (PE) in the first trimester and remains elevated throughout pregnancy. Furthermore, in maternal urine samples we demonstrated that CPP was also significantly elevated in the first trimester in women who later developed PE. Because a urine dipstick test could be easily used in the clinic, we sought to validate this finding in a new and expanded cohort of samples and to determine whether these changes persist throughout pregnancy. In addition, to begin to address the mechanism for this difference, we also assessed urine osmolality to further probe renal function

    First trimester elevation in circulating endothelin-1 and arterial stiffness are predictive of late pregnancy preeclampsia

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    Preeclampsia (PE) is characterized by late pregnancy hypertension and proteinuria. PE causes significant morbidity for the maternal-fetal unit. Circulating endothelin-1 (ET-1), a potent vasoconstrictor, is elevated at the time of diagnosis of human PE. In addition, women with PE demonstrate arterial stiffness as early as the end of the first trimester. However, it is unknown if arterial stiffness is associated with a first trimester elevation in ET-1 and post-delivery placental ET-1. We hypothesized that 1) first trimester plasma ET-1 is elevated and is associated with arterial stiffness in women who develop PE; 2) first trimester ET-1 is predictive of PE; and 3) placental ET-1 is increased in PE. To address these questions, we performed a nested case-control study in women at risk for P

    Bioinformatic Analysis and Post-Translational Modification Crosstalk Prediction of Lysine Acetylation

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    Recent proteomics studies suggest high abundance and a much wider role for lysine acetylation (K-Ac) in cellular functions. Nevertheless, cross influence between K-Ac and other post-translational modifications (PTMs) has not been carefully examined. Here, we used a variety of bioinformatics tools to analyze several available K-Ac datasets. Using gene ontology databases, we demonstrate that K-Ac sites are found in all cellular compartments. KEGG analysis indicates that the K-Ac sites are found on proteins responsible for a diverse and wide array of vital cellular functions. Domain structure prediction shows that K-Ac sites are found throughout a wide variety of protein domains, including those in heat shock proteins and those involved in cell cycle functions and DNA repair. Secondary structure prediction proves that K-Ac sites are preferentially found in ordered structures such as alpha helices and beta sheets. Finally, by mutating K-Ac sites in silico and predicting the effect on nearby phosphorylation sites, we demonstrate that the majority of lysine acetylation sites have the potential to impact protein phosphorylation, methylation, and ubiquitination status. Our work validates earlier smaller-scale studies on the acetylome and demonstrates the importance of PTM crosstalk for regulation of cellular function
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