Risk-based DC security assessment for future DC-independent system operator

—The use of multi-terminal HVDC to integrate wind power coming from the North Sea opens de door for a new transmission system model, the DC-Independent System Operator (DC-ISO). DC-ISO will face highly stressed and varying conditions that requires new risk assessment tools to ensure security of supply. This paper proposes a novel risk-based static security assessment methodology named risk-based DC security assessment (RB-DCSA). It combines a probabilistic approach to include uncertainties and a fuzzy inference system to quantify the systemic and individual component risk associated with operational scenarios considering uncertainties. The proposed methodology is illustrated using a multi-terminal HVDC system where the variability of wind speed at the offshore wind is included

Electronic transport in gadolinium atomic-size contacts

We report on the fabrication, transport measurements, and density functional theory (DFT) calculations of atomic-size contacts made of gadolinium (Gd). Gd is known to have local moments mainly associated with f electrons. These coexist with itinerant s and d bands that account for its metallic character. Here we explore whether and how the local moments influence electronic transport properties at the atomic scale. Using both scanning tunneling microscope and lithographic mechanically controllable break junction techniques under cryogenic conditions, we study the conductance of Gd when only few atoms form the junction between bulk electrodes made of the very same material. Thousands of measurements show that Gd has an average lowest conductance, attributed to single-atom contact, below 2e2h. Our DFT calculations for monostrand chains anticipate that the f bands are fully spin polarized and insulating and that the conduction may be dominated by s, p, and d bands. We also analyze the electronic transport for model nanocontacts using the nonequilibrium Green's function formalism in combination with DFT. We obtain an overall good agreement with the experimental results for zero bias and show that the contribution to the electronic transport from the f channels is negligible and that from the d channels is marginal.B.O., C.S., J.F.R., J.J.P., and C.U. acknowledge financial support by MEC-Spain (Grant No. FIS2013-47328-C2 and MAT2016-78625-C2) and the Generalitat Valenciana under Grant No. PROMETEO/2012/011. C.S. and J.J.P. acknowledge the EU structural funds and the Comunidad de Madrid under NANOFRONTMAG-CM program Grant No. S2013/MIT-2850. J.L.L. and J.F.R. acknowledge Marie Curie ITN SPINOGRAPH FP7 under REA Grant Agreement No. 607904-13. B.O. acknowledges financial support by MEC Spain (Grant No. FIS2010-21883-C02-01) under brief stays abroad scholarship

Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution

Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases

Risk-based DC security assessment for future DC-independent system operator

—The use of multi-terminal HVDC to integrate wind power coming from the North Sea opens de door for a new transmission system model, the DC-Independent System Operator (DC-ISO). DC-ISO will face highly stressed and varying conditions that requires new risk assessment tools to ensure security of supply. This paper proposes a novel risk-based static security assessment methodology named risk-based DC security assessment (RB-DCSA). It combines a probabilistic approach to include uncertainties and a fuzzy inference system to quantify the systemic and individual component risk associated with operational scenarios considering uncertainties. The proposed methodology is illustrated using a multi-terminal HVDC system where the variability of wind speed at the offshore wind is included

Optimization of an aroma sensor for assessing grape quality for wine making

Control of the raw material has considerable influence on final wine quality. The objective of this work was to develop a sensor capable of assessing grape juice quality in the cellar. Sensor response was compared with conventional chemical analysis using multivariate data techniques. The aroma sensor array is composed of 14 metal oxide sensors (MOS) gas transducers plus a temperature and a relative humidity sensor. This work showed that the sensor could detect rotten flavours in grape juice

From bioavailability science to regulation of organic chemicals

The bioavailability of organic chemicals in soil and sediment is an important area of scientific investigation for environmental scientists, although this area of study remains only partially recognized by regulators and industries working in the environmental sector. Regulators have recently started to consider bioavailability within retrospective risk assessment frameworks for organic chemicals; by doing so, realistic decision-making with regard to polluted environments can be achieved, rather than relying on the traditional approach of using total-extractable concentrations. However, implementation remains difficult because scientific developments on bioavailability are not always translated into ready-to-use approaches for regulators. Similarly, bioavailability remains largely unexplored within prospective regulatory frameworks that address the approval and regulation of organic chemicals. This article discusses bioavailability concepts and methods, as well as possible pathways for the implementation of bioavailability into risk assessment and regulation; in addition, this article offers a simple, pragmatic and justifiable approach for use within retrospective and prospective risk assessment

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

ApoB100/LDLR-/- Hypercholesterolaemic Mice as a Model for Mild Cognitive Impairment and Neuronal Damage

Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD). Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR]) of human familial hypercholesterolaemia (FH). From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100) levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions) concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing) and impairment of the episodic-like memory (determined by the integrated memory test). This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline

Hypercholesterolemia Impaired Sperm Functionality in Rabbits

Hypercholesterolemia represents a high risk factor for frequent diseases and it has also been associated with poor semen quality that may lead to male infertility. The aim of this study was to analyze semen and sperm function in diet-induced hypercholesterolemic rabbits. Twelve adult White New Zealand male rabbits were fed ad libitum a control diet or a diet supplemented with 0.05% cholesterol. Rabbits under cholesterol-enriched diet significantly increased total cholesterol level in the serum. Semen examination revealed a significant reduction in semen volume and sperm motility in hypercholesterolemic rabbits (HCR). Sperm cell morphology was seriously affected, displaying primarily a “folded head”-head fold along the major axe-, and the presence of cytoplasmic droplet on sperm flagellum. Cholesterol was particularly increased in acrosomal region when detected by filipin probe. The rise in cholesterol concentration in sperm cells was determined quantitatively by Gas chromatographic-mass spectrometric analyses. We also found a reduction of protein tyrosine phosphorylation in sperm incubated under capacitating conditions from HCR. Interestingly, the addition of Protein Kinase A pathway activators -dibutyryl-cyclic AMP and iso-butylmethylxanthine- to the medium restored sperm capacitation. Finally, it was also reported a significant decrease in the percentage of reacted sperm in the presence of progesterone. In conclusion, our data showed that diet-induced hypercholesterolemia adversely affects semen quality and sperm motility, capacitation and acrosomal reaction in rabbits; probably due to an increase in cellular cholesterol content that alters membrane related events