Alien Registration- Jones, Stephen D. (Houlton, Aroostook County)

https://digitalmaine.com/alien_docs/34639/thumbnail.jp

Cryogenic Propulsion Stage (CPS) Configuration in Support of NASA's Multiple Design Reference Missions (DRMs)

In support of the National Aeronautics and Space Administration's (NASA) Human Exploration and Operations Mission Directorate (HEOMD), the Space Launch System (SLS) is being designed for safe, affordable, and sustainable human and scientific exploration missions beyond Earth's or-bit (BEO). The SLS Team is tasked with developing a system capable of safely and repeatedly lofting a new fleet of spaceflight vehicles beyond Earth orbit. The Cryogenic Propulsion Stage (CPS) is a key enabler for evolving the SLS capability for BEO missions. This paper reports on the methodology and initial recommendations relative to the CPS, giving a brief retrospective of early studies on this promising propulsion hardware. This paper provides an overview of the requirements development and CPS configuration in support of NASA's multiple Design Reference Missions (DRMs)

A twin-mirrored galvanometer laser light sheet generator

A galvanometer mirror-based laser light sheet system has been developed for use in the Basic Aerodynamics Research Tunnel at NASA Langley. This system generates and positions single or multiple light sheets over aeronautical research models being tested in the low speed tunnel. This report describes a twin mirrored galvanometer laser light sheet generator and shows typical light sheet arrangements in use. With this system, illumination of smoke entrained in the flow over a delta wing model reveals the vortical flow produced by the separation of the flow at the leading edge of the model. The light sheet system has proven to be very adaptable and easy to use in sizing and positioning light sheets in wind tunnel applications

In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer.

UNLABELLED: Fenofibrate, an agonist of PPAR-alpha, in doses above 25 microM, inhibits proliferation and induces apoptosis in Ishikawa endometrial cancer cells. We show that these effects are potentiated by retinoic acid, an agonist of the retinoid-X-receptor. DNA content analysis shows that G1/S phase progression through the cell cycle is inhibited. Independent Component Analysis of gene microarray experiments demonstrated downregulation of Cyclin D1 (CCND1) and associated changes in cell cycle gene expression. Expression of PPAR-alpha mRNA was reduced by >75% using RNA-interference but this resulted in only minor changes in biological effects. A nude mouse model of endometrial carcinoma was used to investigate the effect of fenofibrate in vivo but failed to show consistent inhibition of tumour growth. CONCLUSION: The combination of fenofibrate and retinoic acid is a potent inhibitor of Ishikawa endometrial cancer cell growth in vitro

Recognising the potential of large animals for modelling neuromuscular junction physiology and disease

The aetiology and pathophysiology of many diseases of the motor unit remain poorly understood and the role of the neuromuscular junction (NMJ) in this group of disorders is particularly overlooked, especially in humans, when these diseases are comparatively rare. However, elucidating the development, function and degeneration of the NMJ is essential to uncover its contribution to neuromuscular disorders, and to explore potential therapeutic avenues to treat these devastating diseases. Until now, an understanding of the role of the NMJ in disease pathogenesis has been hindered by inherent differences between rodent and human NMJs: stark contrasts in body size and corresponding differences in associated axon length underpin some of the translational issues in animal models of neuromuscular disease. Comparative studies in large mammalian models, including examination of naturally occurring, highly prevalent animal diseases and evaluation of their treatment, might provide more relevant insights into the pathogenesis and therapy of equivalent human diseases. This review argues that large animal models offer great potential to enhance our understanding of the neuromuscular system in health and disease, and in particular, when dealing with diseases for which nerve length dependency might underly the pathogenesis

Regulation of AKT phosphorylation at Ser473 and Thr308 by endoplasmic reticulum stress modulates substrate specificity in a severity dependent manner.

Endoplasmic reticulum (ER) stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473) confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308). The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling