137 research outputs found
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Session B2: An Overview of the Ice Harbor Turbine Replacement Project
Abstract:
In March of 2010 the US Army Corps of Engineers’ (USACE) awarded a contract to Voith Hydro to design and supply new turbine runners for installation at the Ice Harbor Lock and Dam located on the Lower Snake River within the State of Washington, USA. The contract included design and supply of both a fixed and an adjustable blade turbine runner for replacement of two failing units within the six unit powerhouse. The new turbine runners were to be designed for “safer” fish passage as a primary goal, and increased efficiency as a secondary goal. The hydraulic design of both runner types was a collaborative effort by the USACE’s Walla Walla District (NWW), Engineer Research and Development Center (ERDC), Hydroelectric Design Center (HDC), National Marine Fisheries Service (NMFS) and Voith Hydro. The design criteria and the design evaluation process were developed by the USACE over years of both field and laboratory research through the Turbine Survival Program. The two runner types were designed through an iterative process of Computational Fluid Dynamic Model analysis, performance model testing for power, efficiency and cavitation, and physical hydraulic model testing for evaluation of the turbine passage environment. This presentation provides a broad overview of the research, design criteria and guidelines, the design and evaluation process, and future biological field testing efforts supporting the Ice Harbor turbine runner replacement project
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Technoeconomic and life-cycle analysis of single-step catalytic conversion of wet ethanol into fungible fuel blendstocks
Micro-Hall Magnetometry Studies of Thermally Assisted and Pure Quantum Tunneling in Single Molecule Magnet Mn12-Acetate
We have studied the crossover between thermally assisted and pure quantum
tunneling in single crystals of high spin (S=10) uniaxial single molecule
magnet Mn12-acetate using micro-Hall effect magnetometry. Magnetic hysteresis
experiments have been used toinvestigate the energy levels that determine the
magnetization reversal as a function of magnetic field and temperature. These
experiments demonstrate that the crossover occurs in a narrow (~0.1 K) or broad
(~1 K) temperature interval depending on the magnitude and direction of the
applied field. For low external fields applied parallel to the easy axis, the
energy levels that dominate the tunneling shift abruptly with temperature. In
the presence of a transverse field and/or large longitudinal field these energy
levels change with temperature more gradually. A comparison of our experimental
results with model calculations of this crossover suggest that there are
additional mechanisms that enhance the tunneling rate of low lying energy
levels and broaden the crossover for small transverse fields.Comment: 5 pages, 5 figure
PTEN Depletion Decreases Disease Severity and Modestly Prolongs Survival in a Mouse Model of Spinal Muscular Atrophy.
Spinal muscular atrophy (SMA) is the second most common genetic cause of death in childhood. However, no effective treatment is available to halt disease progression. SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene. We previously reported that PTEN depletion leads to an increase in survival of SMN-deficient motor neurons. Here, we aimed to establish the impact of PTEN modulation in an SMA mouse model in vivo. Initial experiments using intramuscular delivery of adeno-associated vector serotype 6 (AAV6) expressing shRNA against PTEN in an established mouse model of severe SMA (SMNΔ7) demonstrated the ability to ameliorate the severity of neuromuscular junction pathology. Subsequently, we developed self-complementary AAV9 expressing siPTEN (scAAV9-siPTEN) to allow evaluation of the effect of systemic suppression of PTEN on the disease course of SMA in vivo. Treatment with a single injection of scAAV9-siPTEN at postnatal day 1 resulted in a modest threefold extension of the lifespan of SMNΔ7 mice, increasing mean survival to 30 days, compared to 10 days in untreated mice. Our data revealed that systemic PTEN depletion is an important disease modifier in SMNΔ7 mice, and therapies aimed at lowering PTEN expression may therefore offer a potential therapeutic strategy for SMA
Single-Neuron Level One-Photon Voltage Imaging With Sparsely Targeted Genetically Encoded Voltage Indicators
Voltage imaging of many neurons simultaneously at single-cell resolution is hampered by the difficulty of detecting small voltage signals from overlapping neuronal processes in neural tissue. Recent advances in genetically encoded voltage indicator (GEVI) imaging have shown single-cell resolution optical voltage recordings in intact tissue through imaging naturally sparse cell classes, sparse viral expression, soma restricted expression, advanced optical systems, or a combination of these. Widespread sparse and strong transgenic GEVI expression would enable straightforward optical access to a densely occurring cell type, such as cortical pyramidal cells. Here we demonstrate that a recently described sparse transgenic expression strategy can enable single-cell resolution voltage imaging of cortical pyramidal cells in intact brain tissue without restricting expression to the soma. We also quantify the functional crosstalk in brain tissue and discuss optimal imaging rates to inform future GEVI experimental design
Differentiated neuroprogenitor cells incubated with human or canine adenovirus, or lentiviral vectors have distinct transcriptome profiles
Several studies have demonstrated the potential for vector-mediated gene transfer to the brain. Helper-dependent (HD) human (HAd) and canine (CAV-2) adenovirus, and VSV-G-pseudotyped self-inactivating HIV-1 vectors (LV) effectively transduce human brain cells and their toxicity has been partly analysed. However, their effect on the brain homeostasis is far from fully defined, especially because of the complexity of the central nervous system (CNS). With the goal of dissecting the toxicogenomic signatures of the three vectors for human neurons, we transduced a bona fide human neuronal system with HD-HAd, HD-CAV-2 and LV. We analysed the transcriptional response of more than 47,000 transcripts using gene chips. Chip data showed that HD-CAV-2 and LV vectors activated the innate arm of the immune response, including Toll-like receptors and hyaluronan circuits. LV vector also induced an IFN response. Moreover, HD-CAV-2 and LV vectors affected DNA damage pathways - but in opposite directions - suggesting a differential response of the p53 and ATM pathways to the vector genomes. As a general response to the vectors, human neurons activated pro-survival genes and neuron morphogenesis, presumably with the goal of re-establishing homeostasis. These data are complementary to in vivo studies on brain vector toxicity and allow a better understanding of the impact of viral vectors on human neurons, and mechanistic approaches to improve the therapeutic impact of brain-directed gene transfer
Candidate Proteins, Metabolites and Transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study
Spinal Muscular Atrophy (SMA) is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1) gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets.To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches.A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2-12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS) and to a number of secondary clinical measures.A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites) and 44 urine metabolites. No transcripts correlated with MHFMS.In this cross-sectional study, "BforSMA" (Biomarkers for SMA), candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with disease progression, and assess potential impact on clinical trial design.Clinicaltrials.gov NCT00756821
Overview of Current Drugs and Molecules in Development for Spinal Muscular Atrophy Therapy
The full text of this article can be found here: https://link.springer.com/article/10.1007/s40265-018-0868-
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