107 research outputs found

    The Role of Regional Connections in Planning for Future Power System Operations Under Climate Extremes

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    Identifying the sensitivity of future power systems to climate extremes must consider the concurrent effects of changing climate and evolving power systems. We investigated the sensitivity of a Western U.S. power system to isolated and combined heat and drought when it has low (5%) and moderate (31%) variable renewable energy shares, representing historic and future systems. We used an electricity operational model combined with a model of historically extreme drought (for hydropower and freshwater-reliant thermoelectric generators) over the Western U.S. and a synthetic, regionally extreme heat event in Southern California (for thermoelectric generators and electricity load). We found that the drought has the highest impact on summertime production cost (+10% to +12%), while temperature-based deratings have minimal effect (at most +1%). The Southern California heat wave scenario impacting load increases summertime regional net imports to Southern California by 10–14%, while the drought decreases them by 6–12%. Combined heat and drought conditions have a moderate effect on imports to Southern California (−2%) in the historic system and a stronger effect (+8%) in the future system. Southern California dependence on other regions decreases in the summertime with the moderate increase in variable renewable energy (−34% imports), but hourly peak regional imports are maintained under those infrastructure changes. By combining synthetic and historically driven conditions to test two infrastructures, we consolidate the importance of considering compounded heat wave and drought in planning studies and suggest that region-to-region energy transfers during peak periods are key to optimal operations under climate extremes

    Season-ahead forecasting of water storage and irrigation requirements – an application to the southwest monsoon in India

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    Water risk management is a ubiquitous challenge faced by stakeholders in the water or agricultural sector. We present a methodological framework for forecasting water storage requirements and present an application of this methodology to risk assessment in India. The application focused on forecasting crop water stress for potatoes grown during the monsoon season in the Satara district of Maharashtra. Pre-season large-scale climate predictors used to forecast water stress were selected based on an exhaustive search method that evaluates for highest ranked probability skill score and lowest root-mean-squared error in a leave-one-out cross-validation mode. Adaptive forecasts were made in the years 2001 to 2013 using the identified predictors and a non-parametric k-nearest neighbors approach. The accuracy of the adaptive forecasts (2001–2013) was judged based on directional concordance and contingency metrics such as hit/miss rate and false alarms. Based on these criteria, our forecasts were correct 9 out of 13 times, with two misses and two false alarms. The results of these drought forecasts were compared with precipitation forecasts from the Indian Meteorological Department (IMD). We assert that it is necessary to couple informative water stress indices with an effective forecasting methodology to maximize the utility of such indices, thereby optimizing water management decisions.</p

    Computational protein biomarker prediction: a case study for prostate cancer

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    BACKGROUND: Recent technological advances in mass spectrometry pose challenges in computational mathematics and statistics to process the mass spectral data into predictive models with clinical and biological significance. We discuss several classification-based approaches to finding protein biomarker candidates using protein profiles obtained via mass spectrometry, and we assess their statistical significance. Our overall goal is to implicate peaks that have a high likelihood of being biologically linked to a given disease state, and thus to narrow the search for biomarker candidates. RESULTS: Thorough cross-validation studies and randomization tests are performed on a prostate cancer dataset with over 300 patients, obtained at the Eastern Virginia Medical School using SELDI-TOF mass spectrometry. We obtain average classification accuracies of 87% on a four-group classification problem using a two-stage linear SVM-based procedure and just 13 peaks, with other methods performing comparably. CONCLUSIONS: Modern feature selection and classification methods are powerful techniques for both the identification of biomarker candidates and the related problem of building predictive models from protein mass spectrometric profiles. Cross-validation and randomization are essential tools that must be performed carefully in order not to bias the results unfairly. However, only a biological validation and identification of the underlying proteins will ultimately confirm the actual value and power of any computational predictions

    Summary of the 2012 Inductive Pulsed Plasma Thruster Development and Testing Program

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    Inductive pulsed plasma thrusters are spacecraft propulsion devices in which energy is capacitively stored and then discharged through an inductive coil. While these devices have shown promise for operation at high efficiency on a range of propellants, many technical issues remain before they can be used in flight applications. A conical theta-pinch thruster geometry was fabricated and tested to investigate potential improvements in propellant utilization relative to more common, flat-plate planar coil designs. A capacitor charging system is used to permit repetitive discharging of thrusters at multiple cycles per second, with successful testing accomplished at a repetition-rate of 5 Hz at power levels of 0.9, 1.6, and 2.5 kW. The conical theta-pinch thruster geometry was tested at cone angles of 20deg, 38deg, and 60deg, with single-pulse operation at 500 J/pulse and repetitionrate operation with the 38deg model quantified through direct thrust measurement using a hanging pendulum thrust stand. A long-lifetime valve was designed and fabricated, and initial testing was performed to measure the valve response and quantify the leak rate at beginning-of-life. Subscale design and testing of a capacitor charging system required for operation on a spacecraft is reported, providing insights into the types of components needed in the circuit topology employed. On a spacecraft, this system would accept as input a lower voltage from the spacecraft DC bus and boost the output to the high voltage required to charge the capacitors of the thruster

    Microneedle assisted transdermal delivery of zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations

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    Objective: The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of Zolmitriptan (ZMT). Methods: Two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5mm lengths) and laboratory fabricated polymeric MNs (PM) of 0.6mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77cm2 skin area (PM-3) to maintain the MN density closer to 0.6mm ADM. Scaling analyses was done using dimensionless parameters like concentration of ZMT (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). Results: Micro-injection moulding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 3.17 and 3.65 fold increase in ZMT flux values were observed with 1.5mm ADM and PM-3 applications when compared to the passive studies. Good correlations were observed between different dimensionless parameters with scaling analyses. Numerical simulations, using MATLAB and COMSOL software, based on experimental data and histological images provided information regarding the ZMT skin distribution after MN application. Discussion: Both from experimental studies and simulations, it was inferred that PM were more effective in enhancing the transdermal delivery of ZMT when compared to ADM. Conclusion: The study suggests that MN application enhances the ZMT transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement

    Multimodal behavioral treatment of migraine: An Internet-administered, randomized, controlled trial

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    Introduction. Multimodal approaches in behavioral treatment have gained recent interest, with proven efficacy for migraine. The utility of the Internet has been demonstrated for behavioral treatment of headache disorders, but not specifically for migraine. The aim of the study was to develop and evaluate an Internet-based multimodal behavior treatment (MBT) program for migraine and to test hand massage treatment as an adjunct. Methods. Eighty-three adults, 58 women and 25 men, with at least two migraine attacks a month were recruited via advertisements. An MBT program aiming at improvements in life-style and stress coping was developed for this study and, together with a diary, adapted for use over the Internet. Participants were randomized to MBT with and without hand massage and to a control group, and were followed for 11 months. Questionnaires addressing issues of quality of life (PQ23) and depressive symptoms (MADRS-S) were used. Results. A 50%, or greater, reduction in migraine frequency was found in 40% and 42% of participants of the two groups receiving MBT (with and without hand massage, respectively), who statistically were significantly more improved than participants in the control group. No effect of hand massage was detected, and gender did not show any independent contribution to the effect in a multivariate analysis. Conclusions. MBT administered over the Internet appears feasible and effective in the treatment of migraine, but no effect of hand massage was found. For increased knowledge on long-term effects and the modes of action of the present MBT program, further studies are needed

    Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms

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    YesRecent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells. Incubation with clinically-relevant concentrations of canagliflozin, but not empagliflozin or dapagliflozin activated AMPK and inhibited IL-1β-stimulated adhesion of pro-monocytic U937 cells and secretion of IL-6 and monocyte chemoattractant protein-1 (MCP-1). Inhibition of MCP-1 secretion was attenuated by expression of dominant-negative AMPK and was mimicked by the direct AMPK activator, A769662. Stimulation of cells with either canagliflozin or A769662 had no effect on IL-1β-stimulated cell surface levels of adhesion molecules or nuclear factor-κB signalling. Despite these identical effects of canagliflozin and A769662, IL-1β-stimulated IL-6/MCP-1 mRNA was inhibited by canagliflozin, but not A769662, whereas IL-1β-stimulated c-jun N-terminal kinase phosphorylation was inhibited by A769662, but not canagliflozin. These data indicate that clinically-relevant canagliflozin concentrations directly inhibit endothelial pro-inflammatory chemokine/cytokine secretion by AMPK-dependent and -independent mechanisms without affecting early IL-1β signalling.Project Grant (PG/13/82/30483 to IPS and TMP) and PhD studentships (FS/16/55/32731 and FS/14/61/31284 to DB and AS) from the British Heart Foundation and an equipment grant (BDA11/0004309 to IPS and TMP) from Diabetes UK. OJK was supported by a Scholarship from the Iraqi Ministry of Higher Education and Scientific Research. TAA was supported by a Libyan Ministry of Education PhD Studentship

    Quantifying variation in the ability of yeasts to attract Drosophila melanogaster

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    Yeasts that invade and colonise fruit significantly enhance the volatile chemical diversity of this ecosystem. These modified bouquets are thought to be more attractive to Drosophila flies than the fruit alone, but the variance of attraction in natural yeast populations is uncharacterised. Here we investigate how a range of yeast isolates affect the attraction of female D. melanogaster to fruit in a simple two choice assay comparing yeast to sterile fruit. Of the 43 yeast isolates examined, 33 were attractive and seven repellent to the flies. The results of isolate-versus-isolate comparisons provided the same relative rankings. Attractiveness varied significantly by yeast, with the strongly fermenting Saccharomyces species generally being more attractive than the mostly respiring non-Saccharomyces species (P = 0.0035). Overall the habitat (fruit or other) from which the isolates were directly sampled did not explain attraction (P = 0.2352). However, yeasts isolated from fruit associated niches were more attractive than those from non-fruit associated niches (P = 0.0188) regardless of taxonomic positioning. These data suggest that while attractiveness is primarily correlated with phylogenetic status, the ability to attract Drosophila is a labile trait among yeasts that is potentially associated with those inhabiting fruit ecosystems. Preliminary analysis of the volatiles emitted by four yeast isolates in grape juice show the presence/absence of ethanol and acetic acid were not likely explanations for the observed variation in attraction. These data demonstrate variation among yeasts for their ability to attract Drosophila in a pattern that is consistent with the hypothesis that certain yeasts are manipulating fruit odours to mediate interactions with their Drosophila dispersal agent. © 2013 Palanca et al

    Restricted Morphological and Behavioral Abnormalities following Ablation of β-Actin in the Brain

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    The local translation of β-actin is one mechanism proposed to regulate spatially-restricted actin polymerization crucial for nearly all aspects of neuronal development and function. However, the physiological significance of localized β-actin translation in neurons has not yet been demonstrated in vivo. To investigate the role of β-actin in the mammalian central nervous system (CNS), we characterized brain structure and function in a CNS-specific β-actin knock-out mouse (CNS-ActbKO). β-actin was rapidly ablated in the embryonic mouse brain, but total actin levels were maintained through upregulation of other actin isoforms during development. CNS-ActbKO mice exhibited partial perinatal lethality while survivors presented with surprisingly restricted histological abnormalities localized to the hippocampus and cerebellum. These tissue morphology defects correlated with profound hyperactivity as well as cognitive and maternal behavior impairments. Finally, we also identified localized defects in axonal crossing of the corpus callosum in CNS-ActbKO mice. These restricted defects occurred despite the fact that primary neurons lacking β-actin in culture were morphologically normal. Altogether, we identified novel roles for β-actin in promoting complex CNS tissue architecture while also demonstrating that distinct functions for the ubiquitously expressed β-actin are surprisingly restricted in vivo
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