1,730 research outputs found
Integrated metal transistor leads
Technique that makes the metal leads integral to the transistor wafer and reduces capacitance in the device, thereby increasing its efficiency is outlined
Vibration effects on heat transfer in cryogenic systems Quarterly progress report no. 1, Jun. 1 - Aug. 31, 1966
Vibration effects on natural convection and fluid transport properties in cryogenic system
Impacts of Upstream Drought and Water Withdrawals on the Health and Survival of Downstream Estuarine Oyster Populations
Increases in the frequency, duration, and severity of regional drought pose major threats to the health and integrity of downstream ecosystems. During 2007-2008, the U.S. southeast experienced one of the most severe droughts on record. Drought and water withdrawals in the upstream watershed led to decreased freshwater input to Apalachicola Bay, Florida, an estuary that is home to a diversity of commercially and ecologically important organisms. This study applied a combination of laboratory experiments and field observations to investigate the effects of reduced freshwater input on Apalachicola oysters. Oysters suffered significant disease-related mortality under high-salinity, drought conditions, particularly during the warm summer months. Mortality was size-specific, with large oysters of commercially harvestable size being more susceptible than small oysters. A potential salinity threshold was revealed between 17 and 25 ppt, where small oysters began to suffer mortality, and large oysters exhibited an increase in mortality. These findings have important implications for watershed management, because upstream freshwater releases could be carefully timed and allocated during stressful periods of the summer to reduce disease-related oyster mortality. Integrated, forward-looking water management is needed, particularly under future scenarios of climate change and human population growth, to sustain the valuable ecosystem services on which humans depend
Vibration effects on heat transfer in cryogenic systems Quarterly progress report, Jul. 1 - Sep. 30, 1967
Water test apparatus used to determine vibration effects on heat transfer in cryogenic system
Magnetization of the Lunar Crust
Magnetic fields measured by the satellite Lunar Prospector show large scale features resulting from remanently magnetized crust. Vector data synthesized at satellite altitude from a spherical harmonic model of the lunar crustal field, and the radial component of the magnetometer data, have been used to produce spatially continuous global magnetization models for the lunar crust. The magnetization is expressed in terms of localized basis functions, with a magnetization solution selected having the smallest root-mean square magnetization for a given fit to the data, controlled by a damping parameter. Suites of magnetization models for layers with thicknesses between 10 and 50 km are able to reproduce much of the input data, with global misfits of less than 0.5 nT (within the uncertainties of the data), and some surface field estimates. The magnetization distributions show robust magnitudes for a range of model thicknesses and damping parameters, however the magnetization direction is unconstrained. These global models suggest that magnetized sources of the lunar crust can be represented by a 30 km thick magnetized layer. Average magnetization values in magnetized regions are 30-40 mA/m, similar to the measured magnetizations of the Apollo samples and significantly weaker than crustal magnetizations for Mars and the Earth. These are the first global magnetization models for the Moon, providing lower bounds on the magnitude of lunar crustal magnetization in the absence of multiple sample returns, and can be used to predict the crustal contribution to the lunar magnetic field at a particular location
A strategy to combine pathway-targeted low toxicity drugs in ovarian cancer.
Serous Ovarian Cancers (SOC) are frequently resistant to programmed cell death. However, here we describe that these programmed death-resistant cells are nonetheless sensitive to agents that modulate autophagy. Cytotoxicity is not dependent upon apoptosis, necroptosis, or autophagy resolution. A screen of NCBI yielded more than one dozen FDA-approved agents displaying perturbed autophagy in ovarian cancer. The effects were maximized via combinatorial use of the agents that impinged upon distinct points of autophagy regulation. Autophagosome formation correlated with efficacy in vitro and the most cytotoxic two agents gave similar effects to a pentadrug combination that impinged upon five distinct modulators of autophagy. However, in a complex in vivo SOC system, the pentadrug combination outperformed the best two, leaving trace or no disease and with no evidence of systemic toxicity. Targeting the autophagy pathway in a multi-modal fashion might therefore offer a clinical option for treating recalcitrant SOC
HOXA13 Is Essential for Placental Vascular Patterning and Labyrinth Endothelial Specification
In eutherian mammals, embryonic growth and survival is dependent on the formation of the placenta, an organ that facilitates the efficient exchange of oxygen, nutrients, and metabolic waste between the maternal and fetal blood supplies. Key to the placenta's function is the formation of its vascular labyrinth, a series of finely branched vessels whose molecular ontogeny remains largely undefined. In this report, we demonstrate that HOXA13 plays an essential role in labyrinth vessel formation. In the absence of HOXA13 function, placental endothelial cell morphology is altered, causing a loss in vessel wall integrity, edema of the embryonic blood vessels, and mid-gestational lethality. Microarray analysis of wild-type and mutant placentas revealed significant changes in endothelial gene expression profiles. Notably, pro-vascular genes, including Tie2 and Foxf1, exhibited reduced expression in the mutant endothelia, which also exhibited elevated expression of genes normally expressed in lymphatic or sinusoidal endothelia. ChIP analysis of HOXA13–DNA complexes in the placenta confirmed that HOXA13 binds the Tie2 and Foxf1 promoters in vivo. In vitro, HOXA13 binds sequences present in the Tie2 and Foxf1 promoters with high affinity (Kd = 27–42 nM) and HOXA13 can use these bound promoter regions to direct gene expression. Taken together, these findings demonstrate that HOXA13 directly regulates Tie2 and Foxf1 in the placental labyrinth endothelia, providing a functional explanation for the mid-gestational lethality exhibited by Hoxa13 mutant embryos as well as a novel transcriptional program necessary for the specification of the labyrinth vascular endothelia
Mind the gap? The persistence of pathological discourses in urban regeneration policy
Urban regeneration policy has historically framed policy problems using a discourse that pathologises areas and spatial communities. Since 2001 in England, and 2002 in Scotland a structural change in policy has occurred where citywide partnerships are now meant overcome structural spatial inequalities, countering pathological explanations. This paper uses historical and discourse analysis to evaluate one of the major community regeneration strategies developed by the Scottish Executive in 2002: Better Communities in Scotland: Closing the Gap. It seeks to ask whether structural change in policy was paralleled by discursive change; what discursive path dependence is evidenced? The text is placed in the historic context of UK urban renewal policies dating back to the launch of the Urban Programme in 1968 and particularly the policy discourse created by the influential Conservative government policy of 1988 New Life for Urban Scotland and the wider discourses of poverty and neighbourhood renewal policy created by Labour governments since 1997. The close textual analysis of the text shows that Better Communities in Scotland continues to pathologise spatial communities. Although this suggests a degree of historical path dependency, the historic breadth of the analysis also problematises simple historical determinism
Natural history study of glycan accumulation in large animal models of GM2 gangliosidoses
beta-hexosaminidase is an enzyme responsible for the degradation of gangliosides, glycans, and other glycoconjugates containing beta-linked hexosamines that enter the lysosome. GM2 gangliosidoses, such as Tay-Sachs and Sandhoff, are lysosomal storage disorders characterized by beta-hexosaminidase deficiency and subsequent lysosomal accumulation of its substrate metabolites. These two diseases result in neurodegeneration and early mortality in children. A significant difference between these two disorders is the accumulation in Sandhoff disease of soluble oligosaccharide metabolites that derive from N- and O-linked glycans. In this paper we describe our results from a longitudinal biochemical study of a feline model of Sandhoff disease and an ovine model of Tay-Sachs disease to investigate the accumulation of GM2/GA2 gangliosides, a secondary biomarker for phospholipidosis, bis-(monoacylglycero)-phosphate, and soluble glycan metabolites in both tissue and fluid samples from both animal models. While both Sandhoff cats and Tay-Sachs sheep accumulated significant amounts of GM2 and GA2 gangliosides compared to age-matched unaffected controls, the Sandhoff cats having the more severe disease, accumulated larger amounts of gangliosides compared to Tay-Sachs sheep in their occipital lobes. For monitoring glycan metabolites, we developed a quantitative LC/MS assay for one of these free glycans in order to perform longitudinal analysis. The Sandhoff cats showed significant disease-related increases in this glycan in brain and in other matrices including urine which may provide a useful clinical tool for measuring disease severity and therapeutic efficacy. Finally, we observed age-dependent increasing accumulation for a number of analytes, especially in Sandhoff cats where glycosphingolipid, phospholipid, and glycan levels showed incremental increases at later time points without signs of peaking. This large animal natural history study for Sandhoff and Tay-Sachs is the first of its kind, providing insight into disease progression at the biochemical level. This report may help in the development and testing of new therapies to treat these disorders
- …