851 research outputs found
Development of N-version software samples for an experiment in software fault tolerance
The report documents the task planning and software development phases of an effort to obtain twenty versions of code independently designed and developed from a common specification. These versions were created for use in future experiments in software fault tolerance, in continuation of the experimental series underway at the Systems Validation Methods Branch (SVMB) at NASA Langley Research Center. The 20 versions were developed under controlled conditions at four U.S. universities, by 20 teams of two researchers each. The versions process raw data from a modified Redundant Strapped Down Inertial Measurement Unit (RSDIMU). The specifications, and over 200 questions submitted by the developers concerning the specifications, are included as appendices to this report. Design documents, and design and code walkthrough reports for each version, were also obtained in this task for use in future studies
Construction and use of Plasmodium falciparum phage display libraries to identify host parasite interactions
BACKGROUND: The development of Plasmodium falciparum within human erythrocytes induces a wide array of changes in the ultrastructure, function and antigenic properties of the host cell. Numerous proteins encoded by the parasite have been shown to interact with the erythrocyte membrane. The identification of new interactions between human erythrocyte and P. falciparum proteins has formed a key area of malaria research. To circumvent the difficulties provided by conventional protein techniques, a novel application of the phage display technology was utilised. METHODS: P. falciparum phage display libraries were created and biopanned against purified erythrocyte membrane proteins. The identification of interacting and in-frame amino acid sequences was achieved by sequencing parasite cDNA inserts and performing bioinformatic analyses in the PlasmoDB database. RESULTS: Following four rounds of biopanning, sequencing and bioinformatic investigations, seven P. falciparum proteins with significant binding specificity toward human erythrocyte spectrin and protein 4.1 were identified. The specificity of these P. falciparum proteins were demonstrated by the marked enrichment of the respective in-frame binding sequences from a fourth round phage display library. CONCLUSION: The construction and biopanning of P. falciparum phage display expression libraries provide a novel approach for the identification of new interactions between the parasite and the erythrocyte membrane
Creating the Thermal Environment for Safely Testing the James Webb Space Telescope at the Johnson Space Center's Chamber A
Chamber A is the largest thermal vacuum chamber at the Johnson Space Center and is one of the largest space environment chambers in the world. The chamber is 19.8 m (65 ft) in diameter and 36.6 m (120 ft) tall and is equipped with cryogenic liquid nitrogen panels (shrouds) and gaseous helium shrouds to create a simulated space environment. The chamber was originally built to support testing of the Apollo Service and Command Module for lunar missions, but underwent major modifications to be able to test the James Webb Space Telescope in a simulated deep space environment. To date seven tests have been performed in preparation of testing the flight optics for the James Webb Space Telescope (JWST). Each test has had a uniquie thermal profile and set of thermal requirements for cooling down and warming up, controlling contamination, and releasing condensed air. These range from temperatures from 335K to 15K, with tight uniformity and controllability for maintining thermal stability and pressure control. One unique requirement for two test was structurally proof loading hardware by creating thermal gradients at specific temperatures. This paper will discuss the thermal requirements and goals of the tests, the original requirements of the chamber thermal systems for planned operation, and how the new requirements were met by the team using the hardware, system flexiblilty, and engineering creativity. It will also discuss the mistakes and successes to meet the unique goals, especially when meeting the thermal proof load
The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease
Neuroprotective treatments in Parkinson's disease (PD) have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms) include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R), although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS), reactive nitrogen species (RNS), apoptosis, inflammation, and trophic factors including GDNF and BDNF
Stable oxygen and carbon isotopes of carbonates in lake sediments as a paleoflood proxy
Lake sediments are increasingly explored as reliable paleoflood archives. In addition to
established flood proxies including detrital layer thickness, chemical composition, and grain
size, we explore stable oxygen and carbon isotope data as paleoflood proxies for lakes in
catchments with carbonate bedrock geology. In a case study from Lake Mondsee (Austria),
we integrate high-resolution sediment trapping at a proximal and a distal location and stable
isotope analyses of varved lake sediments to investigate flood-triggered detrital sediment flux.
First, we demonstrate a relation between runoff, detrital sediment flux, and isotope values in
the sediment trap record covering the period 2011–2013 CE including 22 events with daily
(hourly) peak runoff ranging from 10 (24) m3 s−1 to 79 (110) m3 s−1. The three- to ten-fold
lower flood-triggered detrital sediment deposition in the distal trap is well reflected by attenuated
peaks in the stable isotope values of trapped sediments. Next, we show that all nine
flood-triggered detrital layers deposited in a sediment record from 1988 to 2013 have elevated
isotope values compared with endogenic calcite. In addition, even two runoff events that did
not cause the deposition of visible detrital layers are distinguished by higher isotope values.
Empirical thresholds in the isotope data allow estimation of magnitudes of the majority of
floods, although in some cases flood magnitudes are overestimated because local effects can
result in too-high isotope values. Hence we present a proof of concept for stable isotopes as
reliable tool for reconstructing flood frequency and, although with some limitations, even
for flood magnitudes
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Niche-Associated Activation of Rac Promotes the Asymmetric Division of <i>Drosophila</i> Female Germline Stem Cells
Background: Drosophila female germline stem cells (GSCs) reside adjacent to a cellular niche that secretes Bone Morphogenetic Protein (BMP) ligands and anchors the GSCs through adherens junctions. The GSCs divide asymmetrically such that one daughter remains in the niche as a GSC, while the other is born away from the niche and differentiates. However, given that the BMP signal can be diffusible, it remains unclear how a local extracellular asymmetry is sufficient to result in a robust pattern of asymmetric division. Methods and Findings: Here we show that GSCs are polarized with respect to the cellular niche. We first use a modified biosensor to demonstrate that the small GTPase Rac is asymmetrically activated within the GSC at the niche-GSC interface. Experiments using loss-of-function and gain-of-function mutations in Rac indicate that asymmetric Rac activity both localizes the microtubule binding protein Apc2 to orient one GSC centrosome at the niche-GSC interface during interphase and activates the Jun N-terminal kinase pathway to increase the ability of the GSC to respond to BMP ligands. Other processes act in concert with each function of Rac. Specifically, we demonstrate that the GSC cell cycle arrests at prometaphase if centrosomes are misoriented. Conclusions: Thus, the GSCs, an adult stem cell present in a cellular niche, have a niche-associated polarity that couples control of the division plane with increased response to an extracellular maintenance signal. Other processes work in parallel with the Rac-mediated polarity to ensure a robust pattern of asymmetric division. We suggest that all adult stem cells likely employ multiple, independently acting mechanisms to ensure asymmetric division to maintain tissue homeostasis.</p
Early psychiatric morbidity in a Brazilian sample of acute ischemic stroke patients
OBJECTIVE: Stroke is a major public health problem worldwide, and its neuropsychiatric sequelae are frequent and disabling. Furthermore, there is evidence that these sequelae impair recovery. Brazil has the highest stroke rates in Latin America, but data on the frequency of neuropsychiatric disorders in these patients are scarce. This study aimed to identify mental disorders among in-hospital patients with acute ischemic stroke. METHODS: The Mini International Neuropsychiatric Interview-Plus (MINI-Plus) was applied to 60 patients during the first week of hospitalization. RESULTS: Psychiatric disorders were diagnosed in 55% of the patients. A wide range of neuropsychiatric disorders have been identified, mainly mood and anxiety disorders. Specifically, we identified major depression (26.7%), alcohol abuse or dependence (11.7%), specific phobia (8.3%), generalized anxiety disorder (6.7%), psychosis (5.0%), social phobia (3.3%), adjustment disorder (3.3%) and panic disorder (1.7%). CONCLUSION: Psychiatric comorbidity should be evaluated as part of the rehabilitation of stroke patients and should be carefully examined by physicians
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