921 research outputs found
Space Station Freedom environmental control and life support system phase 3 simplified integrated test detailed report
A description of the phase 3 simplified integrated test (SIT) conducted at the Marshall Space Flight Center (MSFC) Core Module Integration Facility (CMIF) in 1989 is presented. This was the first test in the phase 3 series integrated environmental control and life support systems (ECLSS) tests. The basic goal of the SIT was to achieve full integration of the baseline air revitalization (AR) subsystems for Space Station Freedom. Included is a description of the SIT configuration, a performance analysis of each subsystem, results from air and water sampling, and a discussion of lessons learned from the test. Also included is a full description of the preprototype ECLSS hardware used in the test
Quench Crucibles Reinforced with Metal
Improved crucibles consisting mainly of metal-reinforced ceramic ampules have been developed for use in experiments in which material specimens are heated in the crucibles to various high temperatures, then quenched by, for example, plunging the crucibles into water at room temperature. In a traditional quench crucible, the gap between the ampule and the metal cartridge impedes the transfer of heat to such a degree that the quench rate (the rate of cooling of the specimen) can be too low to produce the desired effect in the specimen. One can increase the quench rate by eliminating the metal cartridge to enable direct quenching of the ampule, but then the thermal shock of direct quenching causes cracking of the ampule. In a quench crucible of the present improved type, there is no gap and no metal cartridge in the traditional sense. Instead, there is an overlay of metal in direct contact with the ampule, as shown on the right side of the figure. Because there is no gap between the metal overlay and the ampule, the heat-transfer rate can be much greater than it is in a traditional quench crucible. The metal overlay also reinforces the ampule against cracking
The sodium channel accessory subunit Navβ1 regulates neuronal excitability through modulation of repolarizing voltage-gated K+ channels
The channel pore-forming α subunit Kv4.2 is a major constituent of A-type (I(A)) potassium currents and a key regulator of neuronal membrane excitability. Multiple mechanisms regulate the properties, subcellular targeting and cell surface expression of Kv4.2-encoded channels. In the present study, shotgun proteomic analyses of immunoprecipitated mouse brain Kv4.2 channel complexes unexpectedly identified the voltage-gated Na(+) channel accessory subunit Navβ1. Voltage-clamp and current-clamp recordings revealed that knockdown of Navβ1 decreases I(A) densities in isolated cortical neurons and that action potential waveforms are prolonged and repetitive firing is increased in Scn1b null cortical pyramidal neurons lacking Navβ1. Biochemical and voltage-clamp experiments further demonstrated that Navβ1 interacts with and increases the stability of heterologously expressed Kv4.2 protein, resulting in greater total and cell surface Kv4.2 protein expression and in larger Kv4.2-encoded current densities. Taken together, the results presented here identify Navβ1 as a component of native neuronal Kv4.2-encoded I(A) channel complexes and a novel regulator of I(A) channel densities and neuronal excitability
Online measurements of the emissions of intermediate-volatility and semi-volatile organic compounds from aircraft
A detailed understanding of the climate and air quality impacts of aviation requires measurements of the emissions of intermediate-volatility and semi-volatile organic compounds (I/SVOCs) from aircraft. Currently both the amount and chemical composition of aircraft I/SVOC emissions remain poorly characterized. Here we characterize I/SVOC emissions from aircraft, using a novel instrument for the online, quantitative measurement of the mass loading and composition of low-volatility organic vapors. Emissions from the NASA DC8 aircraft were sampled on the ground 143 m downwind of the engines and characterized as a function of engine power from idle (4% maximum rated thrust) through 85% power. Results show that I/SVOC emissions are highest during engine idle operating conditions, with decreasing but non-zero I/SVOC emissions at higher engine powers. Comparison of I/SVOC emissions with total hydrocarbon (THC) measurements, VOC measurements, and an established emissions profile indicates that I/SVOCs comprise 10–20% of the total organic gas-phase emissions at idle, and an increasing fraction of the total gas-phase organic emissions at higher powers. Positive matrix factorization of online mass spectra is used to identify three distinct types of I/SVOC emissions: aliphatic, aromatic and oxygenated. The volatility and chemical composition of the emissions suggest that unburned fuel is the dominant source of I/SVOCs at idle, while pyrolysis products make up an increasing fraction of the I/SVOCs at higher powers. Oxygenated I/SVOC emissions were detected at lower engine powers (≤30%) and may be linked to cracked, partially oxidized or unburned fuel components.United States. Dept. of Energy. Office of Science (Small Business Innovation Research Program Grant DE-SC0001666)United States. Environmental Protection Agency (National Center for Environmental Research Grant RD834560
Submerged in the mainstream? A case study of an immigrant learner in a New Zealand primary classroom
Immigrant children from diverse language backgrounds face not only linguistic challenges when enrolled in mainstream English-medium classrooms, but also difficulties adjusting to an unfamiliar learning community. The culture of primary school classrooms in New Zealand typically reflects conventions across three dimensions: interactional, instructional task performance and cognitive-academic development. All three dimensions are underpinned by the culturally specific discourse conventions involved in language socialisation. New learners may be helped by classmates or their teacher to understand and successfully use these conventions, but left on their own they may sink rather than swim. This is a case study of one Taiwanese 11-year old boy, 'John', who entered a New Zealand primary classroom midway through the school year. John's basic conversational ability was sound, but he did not possess the interactive classroom skills needed to operate in the new culture of learning. Selected from a wider study of the classroom, transcript data from audio-recorded excerpts of John's interactions over several months with his teacher and classmates are interpreted from perspectives derived from sociocultural and language socialisation theories. The article concludes with a brief consideration of the extent to which John constructed, or was constrained from constructing meaningful learning experiences, and suggestions for further research and reflection
Influence of Hydration Temperature on Durability and Mechanical Property Performance of Prestressed and Precast High-performance Concrete Beams
Concrete technology has continued to advance throughout the years to meet the demands of designers and innovative structural systems. With the advent of high-performance concrete (HPC), which contains large amounts of cementitious materials, the investigation of the impact of concrete temperature development during hydration on concrete performance is of keen interest. Match-curing technology was used to investigate the influence of concrete temperature development during hydration on the mechanical and material property performance of prestressed and precast HPC beams. These members were fabricated for use in two recently constructed HPC bridges in Texas. The investigation was conducted in conjunction with the design, instrumentation, and construction of the Louetta Road Overpass in Houston, Texas, and the North Concho River US-87 and South Orient Railroad Overpass in San Angelo, Texas. FHWA and the Texas Department of Transportation cosponsored these projects as part of the Strategic Highway Research Program to stimulate the use of HPC and to demonstrate the suitability of HPC in highway structures. The results of the study indicated that for HPCs that contain large amounts of cementitious materials, the concrete temperature during hydration can have a dramatic impact on both the mechanical and the material (durability) performance of the concrete. Temperature recommendations are provided to avoid less than optimal concrete performance on the basis of the member shapes and mix designs investigated in the study
Evaluating the role of pathogenic dementia variants in posterior cortical atrophy
Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to “posterior Alzheimer's disease (AD)” pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against ∼4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE ε4 association, and demonstrate the utility of NeuroX
"It's making contacts" : notions of social capital and implications for widening access to medical education
Acknowledgements Our thanks to the Medical Schools Council (MSC) of the UK for funding Study A; REACH Scotland for funding Study B; and Queen Mary University of London, and to the medical school applicants and students who gave their time to be interviewed. Our thanks also to Dr Sean Zhou and Dr Sally Curtis, and Manjul Medhi, for their help with data collection for studies A and B respectively. Our thanks also to Dr Lara Varpio, Uniformed Services University of the USA, for her advice and guidance on collating data sets and her comments on the draft manuscript.Peer reviewedPublisher PD
Genetically-controlled Vesicle-Associated Membrane Protein 1 expression may contribute to Alzheimer’s pathophysiology and susceptibility
Background
Alzheimer’s disease is a neurodegenerative disorder in which extracellular deposition of β-amyloid (Aβ) oligomers causes synaptic injury resulting in early memory loss, altered homeostasis, accumulation of hyperphosphorylated tau and cell death. Since proteins in the SNAP (Soluble N-ethylmaleimide-sensitive factor Attachment Protein) REceptors (SNARE) complex are essential for neuronal Aβ release at pre-synaptic terminals, we hypothesized that genetically controlled SNARE expression could alter neuronal Aß release at the synapse and hence play an early role in Alzheimer’s pathophysiology.
Results
Here we report 5 polymorphisms in Vesicle-Associated Membrane Protein 1 (VAMP1), a gene encoding a member of the SNARE complex, associated with bidirectionally altered cerebellar VAMP1 transcript levels (all p < 0.05). At the functional level, we demonstrated that control of VAMP1 expression by heterogeneous knockdown in mice resulted in up to 74% reduction in neuronal Aβ exocytosis (p < 0.001). We performed a case-control association study of the 5 VAMP1 expression regulating polymorphisms in 4,667 Alzheimer’s disease patients and 6,175 controls to determine their contribution to Alzheimer’s disease risk. We found that polymorphisms associated with increased brain VAMP1 transcript levels conferred higher risk for Alzheimer’s disease than those associated with lower VAMP1 transcript levels (p = 0.03). Moreover, we also report a modest protective association for a common VAMP1 polymorphism with Alzheimer’s disease risk (OR = 0.88, p = 0.03). This polymorphism was associated with decreased VAMP1 transcript levels (p = 0.02) and was functionally active in a dual luciferase reporter gene assay (p < 0.01).
Conclusions
Genetically regulated VAMP1 expression in the brain may modify both Alzheimer’s disease risk and may contribute to Alzheimer’s pathophysiology
Antihyperalgesia by α2-GABAA Receptors Occurs Via a Genuine Spinal Action and Does Not Involve Supraspinal Sites
Drugs that enhance GABAergic inhibition alleviate inflammatory and neuropathic pain after spinal application. This antihyperalgesia occurs mainly through GABAA receptors (GABAARs) containing α2 subunits (α2-GABAARs). Previous work indicates that potentiation of these receptors in the spinal cord evokes profound antihyperalgesia also after systemic administration, but possible synergistic or antagonistic actions of supraspinal α2-GABAARs on spinal antihyperalgesia have not yet been addressed. Here we generated two lines of GABAAR-mutated mice, which either lack α2-GABAARs specifically from the spinal cord, or, which express only benzodiazepine-insensitive α2-GABAARs at this site. We analyzed the consequences of these mutations for antihyperalgesia evoked by systemic treatment with the novel non-sedative benzodiazepine site agonist HZ166 in neuropathic and inflammatory pain. Wild-type mice and both types of mutated mice had similar baseline nociceptive sensitivities and developed similar hyperalgesia. However, antihyperalgesia by systemic HZ166 was reduced in both mutated mouse lines by about 60% and was virtually indistinguishable from that of global point-mutated mice, in which all α2-GABAARs were benzodiazepine insensitive. The major (α2-dependent) component of GABAAR-mediated antihyperalgesia was therefore exclusively of spinal origin, whereas supraspinal α2-GABAARs had neither synergistic nor antagonistic effects on antihyperalgesia. Our results thus indicate that drugs that specifically target α2-GABAARs exert their antihyperalgesic effect through enhanced spinal nociceptive control. Such drugs may therefore be well-suited for the systemic treatment of different chronic pain conditions
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