292 research outputs found

    Relay Communication with Real Time Microgrid Simulation

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    The development of smart grids with increasing penetration of renewable energy sources into the electrical grids have raised several technical challenges for the control and monitoring. One of these challenges is the system reliability, which depends on power grids’ resilience and high integrity of data. The protective relays play vital role in the grid reliability that involves monitoring power lines and mitigating blackouts. In a large power grid, the protective relays operate locally by controlling the opening and closing of switches (breakers) in power lines, which allows to disconnect or remove from service any part of the power system when it operates in abnormal manner that might cause damage to the rest of the system. However, these relays are prone to failures, which lead random opening/closing of the breakers. Therefore, to back up the protection systems, it is necessary to study the relays failures and it effect on a large power grid. The focus of this research is the development of Hardware-in-the-Loop (HIL) Simulation that allows to safely emulate and study the power systems and relays under different operating condition. HIL is the standard industrial method for developing and testing the most complex control, protection and monitoring systems. In this HIL simulation, we use a real-time simulator as a virtual representation of a large power system connected to a real device that is a Schweitzer relay (SEL). A host computer is used to develop a simulation model of a power system and then runs in a target that is real-time target simulator that is an opal RT system. The HIL simulation contains software/hardware interface that enable to control the virtual input to the real system (SEL) and vice-versa

    The structural basis for high affinity binding of α1-acid glycoprotein to the potent antitumor compound UCN-01

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    The α1-acid glycoprotein (AGP) is an abundant blood plasma protein with important immunomodulatory functions coupled to endogenous and exogenous ligand-binding properties. Its affinity for many drug-like structures, however, means AGP can have a significant effect on the pharmokinetics and pharmacodynamics of numerous small molecule therapeutics. Staurosporine, and its hydroxylated forms UCN-01 and UCN-02, are kinase inhibitors that have been investigated at length as antitumour compounds. Despite their potency, these compounds display poor pharmokinetics due to binding to both AGP variants, AGP1 and AGP2. The recent renewed interest in UCN-01 as a cytostatic protective agent prompted us to solve the structure of the AGP2–UCN-01 complex by X-ray crystallography, revealing for the first time the precise binding mode of UCN-01. The solution NMR suggests AGP2 undergoes a significant conformational change upon ligand binding, but also that it uses a common set of sidechains with which it captures key groups of UCN-01 and other small molecule ligands. We anticipate that this structure and the supporting NMR data will facilitate rational redesign of small molecules that could evade AGP and therefore improve tissue distribution

    Maternal concentration of polychlorinated biphenyls and dichlorodiphenyl dichlorethylene and birth weight in Michigan fish eaters: a cohort study

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    BACKGROUND: Studies on maternal exposure to polychlorinated biphenyls (PCBs) reported inconsistent findings regarding birth weight: some studies showed no effect, some reported decreased birth weight, and one study found an increase in weights. These studies used different markers of exposure, such as measurement of PCBs in maternal serum or questionnaire data on fish consumption. Additionally maternal exposures, such as dichlorodiphenyl-dichloroethylene (DDE), which are related to PCB exposure and may interfere with the PCB effect, were rarely taken into account. METHODS: Between 1973 and 1991, the Michigan Department of Community Health conducted three surveys to assess PCB and DDE serum concentrations in Michigan anglers. Through telephone interviews with parents, we gathered information on the birth characteristics of their offspring, focusing on deliveries that occurred after 1968. We used the maternal organochlorine (OC) measurement closest to the date of delivery as the exposure. Although one mother may have contributed more than one child, serum concentrations derived from measurements in different surveys could vary for different children from the same mother. The maternal DDE and PCB serum concentrations were categorized as follows: 0 -< 5 microg / L, 5 -< 15 microg / L, 15 -< 25 microg / L, ≥25 microg / L. Using repeated measurement models (Generalized Estimation Equation), we estimated the adjusted mean birth weight controlling for gender, birth order, gestational age, date of delivery as well as maternal age, height, education, and smoking status. RESULTS: We identified 168 offspring who were born after 1968 and had maternal exposure information. We found a reduced birth weight for the offspring of mothers who had a PCB concentration ≥25 microg / L (adjusted birth weight = 2,958 g, p = 0.022). This group, however, was comprised of only seven observations. The association was not reduced when we excluded preterm deliveries. The birth weight of offspring was increased in women with higher DDE concentrations when controlling for PCBs; however, this association was not statistically significant. CONCLUSION: Our results contribute to the body of evidence that high maternal serum PCB concentration may reduce the birth weight in offspring. However, only a small proportion of mothers may actually be exposed to PCB concentrations ≥25 microg / L

    Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist

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    Among the 15 extracellular domains of the mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R), domain 11 has evolved a binding site for IGF2 to negatively regulate ligand bioavailability and mammalian growth. Despite the highly evolved structural loops of the IGF2:domain 11 binding site, affinity-enhancing AB loop mutations suggest that binding is modifiable. Here we examine the extent to which IGF2:domain 11 affinity, and its specificity over IGF1, can be enhanced, and we examine the structural basis of the mechanistic and functional consequences. Domain 11 binding loop mutants were selected by yeast surface display combined with high-resolution structure-based predictions, and validated by surface plasmon resonance. We discovered previously unidentified mutations in the ligand-interacting surface binding loops (AB, CD, FG, and HI). Five combined mutations increased rigidity of the AB loop, as confirmed by NMR. When added to three independently identified CD and FG loop mutations that reduced the koff value by twofold, these mutations resulted in an overall selective 100-fold improvement in affinity. The structural basis of the evolved affinity was improved shape complementarity established by interloop (AB-CD) and intraloop (FG-FG) side chain interactions. The high affinity of the combinatorial domain 11 Fc fusion proteins functioned as ligand-soluble antagonists or traps that depleted pathological IGF2 isoforms from serum and abrogated IGF2-dependent signaling in vivo. An evolved and reengineered high-specificity M6P/IGF2R domain 11 binding site for IGF2 may improve therapeutic targeting of the frequent IGF2 gain of function observed in human cancer

    Assessment of animal hosts of pathogenic Leptospira in northern Tanzania

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    Funding: This work was supported by the Wellcome Trust (grant number 096400/Z/11/Z; https://wellcome.ac.uk/). JEBH, VPM, JAC, and SC received support from the Research Councils UK, UK Department for International Development, and UK Biotechnology and Biological Sciences Research Council (BBSRC) (grant numbers BB/J010367/1, BB/L018926, BB/L017679, BB/L018845; http://www.bbsrc.ac.uk/). JAC and VPM also received support from the US National Institutes of Health (NIH)-National Science Foundation (NSF) Ecology and Evolution of Infectious Disease program (R01TW009237; https://www.fic.nih.gov/programs/pages/ecology-infectious-diseases.aspx). MM received support from the BBSRC East of Scotland Bioscience Doctoral Training Partnership (http://www.eastscotbiodtp.ac.uk/). MJM received support from a University of Otago Frances G. Cotter Scholarship and a University of Otago MacGibbon PhD Travel Fellowship (http://www.otago.ac.nz/). VPM and JAC received support from the US National Institutes of Health National Institute for Allergy and Infectious (grant number R01 AI121378; https://www.niaid.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: Datasets supporting this manuscript are available through: http://dx.doi.org/10.5525/gla.researchdata.582. Unique sequences generated through this study are available through GenBank (accession numbers MF955862 to MF955882).Peer reviewedPublisher PD

    The summer undergraduate research experience as a work-integrated learning opportunity and potential pathway to publication in psychology

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    © 2019 Golding, Breen, Krause and Allen. Unlike disciplines which focus on skill development from year one of a bachelor's degree, training in psychology in Australia follows the scientist-practitioner model. According to this model, an undergraduate psychology degree should focus on the scientific principles underpinning the discipline and provide a foundation for the development of professional skills in graduate school. However, most Australian psychology undergraduates do not continue into graduate school, and concerns have been raised about their lack of applied skills and work-readiness. Work-integrated learning (WIL) refers to strategies aimed at providing students with practical experiences (e.g., fieldwork, placements, and internships) directly related to their course of study. The objective of WIL is to increase work-readiness. Accreditation standards coupled with the norms of the discipline have historically prevented the inclusion of typical WIL experiences in Australian undergraduate psychology degrees. However, one particular type of WIL activity-the undergraduate research experience (URE)-is particularly suited to psychology. In a typical URE, students collaborate with faculty to conduct research designed to make an original contribution to their field. The current study is a qualitative investigation of stakeholder perceptions of a competitive summer URE program ran from 2012 to 2016. Six faculty members and seven undergraduate students were engaged in semi-structured interviews about their URE experiences. Constructed themes broadly reflected the benefits and challenges of the program and included work-readiness and additional research experience, networking and teamwork, publication, quality of experience and equity of opportunities. Faculty members and students spoke favorably of their UREs in most cases, although issues of administration and financial concerns were mentioned consistently, as were concerns about the length, timing, and nature of projects. Students reported skill development and networking as two of the key benefits of their participation in the program, and article publication was seen as particularly beneficial to career prospects. Our findings suggest that student co-authored publications resulting from UREs are possible, but careful thought is required to optimize their likelihood. Overall, this research adds to a growing literature suggesting that UREs can confer a range of benefits to Australian psychology schools related to increased research capacity and student satisfaction

    Completeness and accuracy of national cancer and death registration for outcome ascertainment in trials—an ovarian cancer exemplar

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    BACKGROUND: There is a trend to increasing use of routinely collected health data to ascertain outcome measures in trials. We report on the completeness and accuracy of national ovarian cancer and death registration in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). METHODS: Of the 202,638 participants, 202,632 were successfully linked and followed through national cancer and death registries of Northern Ireland, Wales and England. Women with registrations of any of 19 pre-defined ICD-10 codes suggestive of tubo-ovarian cancer or notification of ovarian/tubal/peritoneal cancer from hospital episode statistics or trial sites were identified. Copies of hospital and primary care notes were retrieved and reviewed by an independent outcomes review committee. National registration of site and cause of death as ovarian/tubal/peritoneal cancer (C56/C57/C48) obtained up to 3 months after trial censorship was compared to that assigned by outcomes review (reference standard). RESULTS: Outcome review was undertaken in 3110 women on whom notification was received between 2001 and 2014. Ovarian cancer was confirmed in 1324 of whom 1125 had a relevant cancer registration. Sensitivity and specificity of ovarian/tubal/peritoneal cancer registration were 85.0% (1125/1324; 95% CI 83.7-86.2%) and 94.0% (1679/1786; 95% CI 93.2-94.8%), respectively. Of 2041 death registrations reviewed, 681 were confirmed to have a tubo-ovarian cancer of whom 605 had relevant death registration. Sensitivity and specificity were 88.8% (605/681; 95% CI 86.4-91.2%) and 96.7% (1482/1533, 95% CI 95.8-97.6%), respectively. When multiple electronic health record sources were considered, sensitivity for cancer site increased to 91.1% (1206/1324, 95% CI 89.4-92.5%) and for cause of death 94.0% (640/681, 95% CI 91.9-95.5%). Of 1232 with cancer registration, 8.7% (107/1232) were wrongly designated as ovarian/tubal/peritoneal cancers by the registry and 4.0% (47/1172) of confirmed tubo-ovarian cancers were mis-registered. In 656 with death registrations, 7.8% (51/656) were wrongly assigned as due to ovarian/tubal/peritoneal cancers while 6.2% (40/645) of confirmed tubo-ovarian cancer deaths were mis-registered. CONCLUSION: Follow-up of trial participants for tubo-ovarian cancer using national registry data will result in incomplete ascertainment, particularly of the site due in part to the latency of registration. This can be reduced by using other routinely collected data such as hospital episode statistics. Central adjudication by experts though resource intensive adds value by improving the accuracy of diagnoses. TRIAL REGISTRATION: ISRCTN: ISRCTN22488978 . Registered on 6 April 2000

    Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study

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    Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents
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