Role of Membrane GM1 on Early Neuronal Membrane Actions of Aβ During Onset of Alzheimer\u27s Disease

The ability of beta-amyloid peptide (Aβ) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aβ was dependent on GM1levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aβ clustering at the membrane (Aβ fluorescent-punctas/20 μm, control = 16.2 ± 1.1 vs. D-PDMP = 6.4 ± 0.4, p \u3c 0.001). Interestingly, membrane perforation with Aβ occurred with a slower time course when the GM1 content was diminished (time to establish perforated configuration (TEPC) (min): control = 7.8 ± 2 vs. low GM1 = 12.1 ± 0.5, p \u3c 0.01), suggesting that the presence of GM1 in the membrane can modulate the distribution and the membrane perforation by Aβ. On the other hand, increasing GM1 facilitated the membrane perforation (TEPC: control = 7.8 ± 2 vs. GM1 = 6.2 ± 1 min, p \u3c 0.05). Additionally, using Cholera Toxin Subunit-B (CTB) to block the interaction of Aβ with GM1 attenuated membrane perforation significantly. Furthermore, pretreatment with CTB decreased the membrane association of Aβ (fluorescent-punctas/20 μm, Aβ: control = 14.8 ± 2.5 vs. CTB = 8 ± 1.4, p \u3c 0.05), suggesting that GM1 also plays a role in both association of Aβ with the membrane and in perforation. In addition, blockade of the Aβ association with CTB inhibited synaptotoxicity. Taken together, our results strongly suggest that membrane lipid composition can affect the ability of Aβ to associate and subsequently perforate the plasma membrane thereby modulating its neurotoxicity in hippocampal neurons

Separation of bitumen from Utah tar sands by a hot water digestion-flotation technique

Journal ArticleTar sand deposits in the state of Utah contain more than 25 billion bbl of in-place bitumen. Although 30 times smaller than the well-known Athabasca tar sands, Utah tar sands do represent a significant domestic energy resource comparable to the national crude oil reserves (31.3 billion bbl). Based upon a detailed analysis of the physical and chemical properties of both the bitumen and the sand, a hot-water separation process for Utah tar sands is currently being developed in our laboratories at the University of Utah. This process involves intense agitation of the tar sand in a hot caustic solution and subsequent separation of the bitumen by a modified froth flotation technique. Experimental results with an Asphalt Ridge, Utah, tar sand sample indicated that percent solids and caustic concentration were the two most important variables controlling the performance of the digestion stage. These variables were identified by means of an experimental factorial design, in which coefficients of separation greater than 0.90 were realized. Although preliminary in nature, the experimental evidence gathered in this investigation seems to indicate that a hot-water separation process for Utah tar sands would allow for the efficient utilization of this important energy resource

Influência do tipo de levedura e do uso de enzima pectolítica sobre a qualidade de vinhos tintos tropicais cv. Petit verdot.

Existem leveduras com atividades metabólicas variáveis, que permitem a elaboração de vinhos com características sensoriais diferentes. A região do Vale do Submédio São Francisco vem produzindo vinhos há 20 anos, mas está ainda em busca de cultivares que sejam representativas e que possibilitem a obtenção de vinhos potenciais com qualidade e tipicidade. O objetivo deste trabalho foi avaliar a influência do tipo de levedura e do uso de enzima pectolítica, em três condições, sobre a qualidade de vinhos da cv. Petit Verdot. As plantas foram instaladas em fevereiro de 2005, enxertadas sobre o porta-enxerto R110, sistema de condução em espaldeira, solo arenoso, irrigadas por gotejamento. As uvas foram colhidas em julho/2007, apresentando sólidos solúveis totais de 24,5 (ºBrix), acidez total titulável (ATT) de 8 g.L-1 em ácido tartárico, pH 3,5 e peso médio de 100 bagas de 97,6 g. A vinificação foi realizada em frascos de vidro de 20 L, utilizando-se 15 Kg de uvas para cada tratamento. As cinco leveduras testadas foram PDM, Ever rouge e Ever cru, Fermol rouge e Fermol cru. Para cada levedura, foram realizados três tratamentos: sem adição de enzima pectolítica (25 ºC, a temperatura de fermentação), com enzima adicionada a frio (10 ºC durante 24 h) para a maceração pré-fermentação, e enzima adicionada a 25 ºC, totalizando quinze tratamentos. Após a fermentação malolática, os vinhos foram analisados, apresentando variações no teor de álcool (entre 14,2 e 15 % v/v), ATT (entre 4,4 e 7,7), pH (entre 3,9 e 4,3) e índice de polifenóis totais, IPT (entre 89,7 e 101,6). A escolha do tipo de levedura e o uso de enzimas é fundamental para a obtenção de vinhos com diferentes estilos, principalmente nas condições do Vale do São Francisco, onde se busca ainda conhecer o potencial de diferentes cultivares às condições edafo-climáticas locais

Risk assessment of an offshore wind turbine and remaining useful life estimation of the power converter. Improving availability by prioritising failures with higher risk to operation

By 2014, almost 2500 offshore wind turbines were installed in Europe representing 8GW of capacity connected to the grid and, there is a growing market penetration for the next years. Offshore wind farm operators are facing many challenges related to disparate data sources utilisation for O&M logistic optimisation. Therefore, the decision-making process needs to be based on sound analysis of the wind farm information or data available. According to several technical reports operation and maintenance (O&M) cost could reach until 30% of the levelised cost of energy (LCOE). Understanding the reliability of an offshore wind turbine and the resources required to maintain it is crucial to reduce O&M costs and thus, to reduce the levelised cost of energy (LCOE). There is a need to reduce unnecessary tasks, prioritise the most urgent tasks, improve usage of vessels, crew and technicians, reduce the cost of spare parts held and schedule preventative maintenance to minimise downtime and maximise revenue. Currently, risk assessment plays an important role in the operation and maintenance (O&M) strategies of offshore wind farms. A comprehensive failure mode and effect analysis (FMEA) has been carried out to determine critical assemblies of a generic offshore wind turbine with an induction generator, three stages gearbox and monopile foundation. The main objectives of undertaking this comprehensive FMEA was to identify those failures with significant impact on the wind turbine operation and to identify or highlight areas of risk for maintainability and availability. The FMEA is validated with; widely-used data available in the public domain; Lloyd’s Register’s experience of working with wind farm operators and; Lloyd’s Register experience of working on reliability of the mechanical system of different industrial sectors for decades. The FMEA is further augmented and updated by the use of on-going measurements from operating wind farms. Yaw system, pitch system, power converter and gearbox have been identified in the FMEA as the most critical assemblies regarding risk to the turbine operation. Power converter analysis shows high failure rates and a large proportion of undetectable failures, therefore maintenance resources have been spent on fault finding with its corresponding cost. New approaches are necessary to tackle electrical or electronic failures, especially on the power converter. To improve overall reliability, a method to estimate the remaining useful life (RUL) of a fully-rated converter in a variable speed wind turbine is proposed using data commonly available for offshore wind farm operators. Studies show that the economic impact is dominated by failures related to power electronic components such as IGBTs and capacitors due to their higher repair cost. Mathematical models have been developed to correlate turbine operation variables and environmental conditions with failure root causes to define wear and maintenance actions based on the probability of failur

Pore morphology evolution and atom distribution of doped Fe2O3 foams developed by freeze-casting after redox cycling

Chemical looping water splitting systems operate at relatively high temperatures (450-800 degree C) to produce, purify, or store hydrogen by the cyclic reduction and oxidation (redox) of a solid oxygen carrier. Therefore, to improve long-term operation, it is necessary to develop highly stable oxygen carriers with large specific surface areas. In this work, highly interconnected doped Fe2O3 foams are fabricated through the freeze-casting technique, and the aid of a submicrometric camphene-based suspension to prevent Fe sintering and pore clogging during redox operation. The influence of the dopant elements (Al and Ce) over the pore morphology evolution, and redox performances are examined. The use of an Fe2O3 porous structure with initial pore size above 100 microns shows a significant reduction of the sample densification, and the addition of Al2O3 by the co-precipitation process proves to be beneficial in preventing the generation of a core-shell structure following redox processing.Comment: 25 pages, 8 figure

Quantum dissipation due to the interaction with chaotic degrees-of-freedom and the correspondence principle

Both in atomic physics and in mesoscopic physics it is sometimes interesting to consider the energy time-dependence of a parametrically-driven chaotic system. We assume an Hamiltonian ${\cal H}(Q,P;x(t))$ where $x(t)=Vt$. The velocity $V$ is slow in the classical sense but not necessarily in the quantum-mechanical sense. The crossover (in time) from ballistic to diffusive energy-spreading is studied. The associated irreversible growth of the average energy has the meaning of dissipation. It is found that a dimensionless velocity $v_{PR}$ determines the nature of the dynamics, and controls the route towards quantal-classical correspondence (QCC). A perturbative regime and a non-perturbative semiclassical regime are distinguished.Comment: 4 pages, clear presentation of the main poin

Scars of Invariant Manifolds in Interacting Chaotic Few-Body Systems

We present a novel extension of the concept of scars for the wave functions of classically chaotic few-body systems of identical particles with rotation and permutation symmetry. Generically there exist manifolds in classical phase space which are invariant under the action of a common subgroup of these two symmetries. Such manifolds are associated with highly symmetric configurations. If sufficiently stable, the quantum motion on such manifolds displays a notable enhancement of the revival in the autocorrelation function which is not directly associated with individual periodic orbits. Rather, it indicates some degree of localization around an invariant manifold which has collective characteristics that should be experimentally observable.Comment: 4 pages, RevTeX, 4 PS/EPS-figures, uses psfig.sty, quantum computation changed, to be published in Physical Review Letter

The tumor suppressor TERE1 (UBIAD1) prenyltransferase regulates the elevated cholesterol phenotype in castration resistant prostate cancer by controlling a program of ligand dependent SXR target genes.

Castrate-Resistant Prostate Cancer (CRPC) is characterized by persistent androgen receptor-driven tumor growth in the apparent absence of systemic androgens. Current evidence suggests that CRPC cells can produce their own androgens from endogenous sterol precursors that act in an intracrine manner to stimulate tumor growth. The mechanisms by which CRPC cells become steroidogenic during tumor progression are not well defined. Herein we describe a novel link between the elevated cholesterol phenotype of CRPC and the TERE1 tumor suppressor protein, a prenyltransferase that synthesizes vitamin K-2, which is a potent endogenous ligand for the SXR nuclear hormone receptor. We show that 50% of primary and metastatic prostate cancer specimens exhibit a loss of TERE1 expression and we establish a correlation between TERE1 expression and cholesterol in the LnCaP-C81 steroidogenic cell model of the CRPC. LnCaP-C81 cells also lack TERE1 protein, and show elevated cholesterol synthetic rates, higher steady state levels of cholesterol, and increased expression of enzymes in the de novo cholesterol biosynthetic pathways than the non-steroidogenic prostate cancer cells. C81 cells also show decreased expression of the SXR nuclear hormone receptor and a panel of directly regulated SXR target genes that govern cholesterol efflux and steroid catabolism. Thus, a combination of increased synthesis, along with decreased efflux and catabolism likely underlies the CRPC phenotype: SXR might coordinately regulate this phenotype. Moreover, TERE1 controls synthesis of vitamin K-2, which is a potent endogenous ligand for SXR activation, strongly suggesting a link between TERE1 levels, K-2 synthesis and SXR target gene regulation. We demonstrate that following ectopic TERE1 expression or induction of endogenous TERE1, the elevated cholesterol levels in C81 cells are reduced. Moreover, reconstitution of TERE1 expression in C81 cells reactivates SXR and switches on a suite of SXR target genes that coordinately promote both cholesterol efflux and androgen catabolism. Thus, loss of TERE1 during tumor progression reduces K-2 levels resulting in reduced transcription of SXR target genes. We propose that TERE1 controls the CPRC phenotype by regulating the endogenous levels of Vitamin K-2 and hence the transcriptional control of a suite of steroidogenic genes via the SXR receptor. These data implicate the TERE1 protein as a previously unrecognized link affecting cholesterol and androgen accumulation that could govern acquisition of the CRPC phenotype

Episodic photic zone euxinia in the northeastern Panthalassic Ocean during the end-Triassic extinction

Severe changes in ocean redox, nutrient cycling, and marine productivity accompanied most Phanerozoic mass extinctions. However, evidence for marine photic zone euxinia (PZE) as a globally important extinction mechanism for the end-Triassic extinction (ETE) is currently lacking. Fossil molecular (biomarker) and nitrogen isotopic records from a sedimentary sequence in western Canada provide the first conclusive evidence of PZE and disrupted biogeochemistry in neritic waters of the Panthalassic Ocean during the end Triassic. Increasing water-column stratification and deoxygenation across the ETE led to PZE in the Early Jurassic, paralleled by a perturbed nitrogen cycle and ecological turnovers among noncalcifying groups, including eukaryotic algae and prokaryotic plankton. If such conditions developed widely in the Panthalassic Ocean, PZE might have been a potent mechanism for the ETE.National Science Foundation (U.S.) (Grant EAR-1147402)Exobiology Program (U.S.) (Grants NNX09AM88G and NNA08CN84A)American Association of Petroleum Geologists (Grant-In-Aid)Mary-Hill and Bevan M. French Fund for Impact Geolog