4,450 research outputs found

    Multi-agent coalition formation in power transmission planning

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    Deregulation and restructuring have become unavoidable trends to the power industry recently in order to increase its efficiency, to reduce operation costs, or to provide customers better services. The once centralized system planning and management must be remodeled to reflect the changes in the market environment. We have proposed and developed a multi-agent based system to assist players, such as, owners of power generation stations, owners of transmission lines, and groups of consumers, in the same market to select partners to form coalitions. The system provides users with a cooperation plan and its associated cost allocation plan for the users to support their decision making process. Bilateral Shapley Value (BSV) was selected as the theoretical foundation to develop the system. The multi-agent system was developed by the combination of IDEAS and Tcl/Tk.published_or_final_versio

    Towards an Efficient Finite Element Method for the Integral Fractional Laplacian on Polygonal Domains

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    We explore the connection between fractional order partial differential equations in two or more spatial dimensions with boundary integral operators to develop techniques that enable one to efficiently tackle the integral fractional Laplacian. In particular, we develop techniques for the treatment of the dense stiffness matrix including the computation of the entries, the efficient assembly and storage of a sparse approximation and the efficient solution of the resulting equations. The main idea consists of generalising proven techniques for the treatment of boundary integral equations to general fractional orders. Importantly, the approximation does not make any strong assumptions on the shape of the underlying domain and does not rely on any special structure of the matrix that could be exploited by fast transforms. We demonstrate the flexibility and performance of this approach in a couple of two-dimensional numerical examples

    Drug Repurposing for the Treatment of COVID-19: A Knowledge Graph Approach

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    Identifying effective drug treatments for COVID-19 is essential to reduce morbidity and mortality. Although a number of existing drugs have been proposed as potential COVID-19 treatments, effective data platforms and algorithms to prioritize drug candidates for evaluation and application of knowledge graph for drug repurposing have not been adequately explored. A COVID-19 knowledge graph by integrating 14 public bioinformatic databases containing information on drugs, genes, proteins, viruses, diseases, symptoms and their linkages is developed. An algorithm is developed to extract hidden linkages connecting drugs and COVID-19 from the knowledge graph, to generate and rank proposed drug candidates for repurposing as treatments for COVID-19 by integrating three scores for each drug: motif scores, knowledge graph PageRank scores, and knowledge graph embedding scores. The knowledge graph contains over 48 000 nodes and 13 37 000 edges, including 13 563 molecules in the DrugBank database. From the 5624 molecules identified by the motif-discovery algorithms, ranking results show that 112 drug molecules had the top 2% scores, of which 50 existing drugs with other indications approved by health administrations reported. The proposed drug candidates serve to generate hypotheses for future evaluation in clinical trials and observational studies

    Safety of an inactivated, whole-virion COVID-19 vaccine (CoronaVac) in people aged 60 years or older in Hong Kong: a modified self-controlled case series

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    BACKGROUND: Because evidence on the safety of COVID-19 vaccines in older adults is scarce, we aimed to evaluate the incidence and risk of adverse events after CoronaVac (Sinovac Biotech) vaccination in adults aged 60 years or older. METHODS: In this modified self-controlled case series, we enrolled adults aged 60 years or older who had received at least one dose of CoronaVac in Hong Kong between Feb 23, 2021, and Jan 31, 2022. We extracted population-based, electronic health record data from the clinical management system of the Hospital Authority on adverse events of special interest (from Jan 1, 2005, to Feb 23, 2022) and patients' demographic information (from Jan 1, 2018, to Jan 31, 2022), previous diagnoses (from Jan 1, 2018, to Jan 31, 2022), medication history (from Jan 1, 2018, to Jan 31, 2022), and laboratory tests, including those for SARS-CoV-2 infection (from Jan 1, 2018, to Jan 31, 2022). Details of vaccination status were provided by the Department of Health of the Hong Kong Government and were linked to data from the Hospital Authority with identity card numbers or passport numbers. Our outcomes were the overall incidence of any adverse event of special interest and the incidence rates of 30 adverse events of special interest, as suggested by the WHO Global Advisory Committee on Vaccine Safety, in the inpatient setting within 21 days (2 days for anaphylaxis) of either the first, second, or third CoronaVac dose compared with a baseline period. Individuals who had a history of a particular event between Jan 1, 2005, and Feb 23, 2021, were excluded from the corresponding analysis. We evaluated the risk of an adverse event of special interest using conditional Poisson regression, adjusting for seasonal effects. FINDINGS: Of 1 253 497 individuals who received at least one dose of CoronaVac during the study period, 622 317 (49·6%) were aged at least 60 years and were included in the analysis. Our analysis sample received 1 229 423 doses of CoronaVac and had a mean age of 70·40 years (SD 8·10). 293 086 (47·1%) of 622 317 participants were men and 329 231 (52·9%) were women. The incidence of individual adverse events of interest ranged from 0·00 per 100 000 people to 57·49 per 100 000 people (thromboembolism). The first and third doses of CoronaVac were not associated with a significant excess risk of an adverse event of special interest within 21 days (or 2 days for anaphylaxis) of vaccination. After the second dose, the only significantly increased risk was for anaphylaxis (adjusted incidence rate ratio 2·61, 95% CI 1·08–6·31; risk difference per 100 000 people 0·61, 95% CI 0·03–1·81). INTERPRETATION: Because older age is associated with poor outcomes after SARS-CoV-2 infection, the benefits of CoronaVac vaccination in older adults outweigh the risks in regions where COVID-19 is prevalent. Ongoing monitoring of vaccine safety is warranted. FUNDING: The Food and Health Bureau of the Government, Hong Kong Special Administrative Region, China and AIR@InnoHK, administered by the Innovation and Technology Commission. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section

    Temperature Dependence of Spin-Split Peaks in Transverse Electron Focusing

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    We present experimental results of transverse electron-focusing measurements performed using n-type GaAs. In the presence of a small transverse magnetic field (B⊥), electrons are focused from the injector to detector leading to focusing peaks periodic in B⊥. We show that the odd-focusing peaks exhibit a split, where each sub-peak represents a population of a particular spin branch emanating from the injector. The temperature dependence reveals that the peak splitting is well defined at low temperature whereas it smears out at high temperature indicating the exchange-driven spin polarisation in the injector is dominant at low temperatures

    Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

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    Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

    Universality of pseudogap and emergent order in lightly doped Mott insulators

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    It is widely believed that high-temperature superconductivity in the cuprates emerges from doped Mott insulators. The physics of the parent state seems deceivingly simple: The hopping of the electrons from site to site is prohibited because their on-site Coulomb repulsion U is larger than the kinetic energy gain t. When doping these materials by inserting a small percentage of extra carriers, the electrons become mobile but the strong correlations from the Mott state are thought to survive; inhomogeneous electronic order, a mysterious pseudogap and, eventually, superconductivity appear. How the insertion of dopant atoms drives this evolution is not known, nor whether these phenomena are mere distractions specific to hole-doped cuprates or represent the genuine physics of doped Mott insulators. Here, we visualize the evolution of the electronic states of (Sr1-xLax)2IrO4, which is an effective spin-1/2 Mott insulator like the cuprates, but is chemically radically different. Using spectroscopic-imaging STM, we find that for doping concentration of x=5%, an inhomogeneous, phase separated state emerges, with the nucleation of pseudogap puddles around clusters of dopant atoms. Within these puddles, we observe the same glassy electronic order that is so iconic for the underdoped cuprates. Further, we illuminate the genesis of this state using the unique possibility to localize dopant atoms on topographs in these samples. At low doping, we find evidence for much deeper trapping of carriers compared to the cuprates. This leads to fully gapped spectra with the chemical potential at mid-gap, which abruptly collapse at a threshold of around 4%. Our results clarify the melting of the Mott state, and establish phase separation and electronic order as generic features of doped Mott insulators.Comment: This version contains the supplementary information and small updates on figures and tex

    Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

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    The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

    Adiposity has differing associations with incident coronary heart disease and mortality in the Scottish population: cross-sectional surveys with follow-up

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    Objective: Investigation of the association of excess adiposity with three different outcomes: all-cause mortality, coronary heart disease (CHD) mortality and incident CHD. Design: Cross-sectional surveys linked to hospital admissions and death records. Subjects: 19 329 adults (aged 18–86 years) from a representative sample of the Scottish population. Measurements: Gender-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality, CHD mortality and incident CHD. Separate models incorporating the anthropometric measurements body mass index (BMI), waist circumference (WC) or waist–hip ratio (WHR) were created adjusted for age, year of survey, smoking status and alcohol consumption. Results: For both genders, BMI-defined obesity (greater than or equal to30 kg m−2) was not associated with either an increased risk of all-cause mortality or CHD mortality. However, there was an increased risk of incident CHD among the obese men (hazard ratio (HR)=1.78; 95% confidence interval=1.37–2.31) and obese women (HR=1.93; 95% confidence interval=1.44–2.59). There was a similar pattern for WC with regard to the three outcomes; for incident CHD, the HR=1.70 (1.35–2.14) for men and 1.71 (1.28–2.29) for women in the highest WC category (men greater than or equal to102 cm, women greater than or equal to88 cm), synonymous with abdominal obesity. For men, the highest category of WHR (greater than or equal to1.0) was associated with an increased risk of all-cause mortality (1.29; 1.04–1.60) and incident CHD (1.55; 1.19–2.01). Among women with a high WHR (greater than or equal to0.85) there was an increased risk of all outcomes: all-cause mortality (1.56; 1.26–1.94), CHD mortality (2.49; 1.36–4.56) and incident CHD (1.76; 1.31–2.38). Conclusions: In this study excess adiposity was associated with an increased risk of incident CHD but not necessarily death. One possibility is that modern medical intervention has contributed to improved survival of first CHD events. The future health burden of increased obesity levels may manifest as an increase in the prevalence of individuals living with CHD and its consequences

    A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

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    Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283
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