Simulation of Brushless DC Motor for Performance Analysis using MATLAB/SIMULINK EnvironmentÂ

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Data compression in smart distribution systems via singular value decomposition

Electrical distribution systems have been experiencing many changes in recent times. Advances in metering system infrastructure and the deployment of a large number of smart meters in the grid will produce a big volume of data that will be required for many different applications. Despite the significant investments taking place in the communications infrastructure, this remains a bottleneck for the implementation of some applications. This paper presents a methodology for lossy data compression in smart distribution systems using the singular value decomposition technique. The proposed method is capable of significantly reducing the volume of data to be transmitted through the communications network and accurately reconstructing the original data. These features are illustrated by results from tests carried out using real data collected from metering devices at many different substations

Cardiovascular outcomes of type 2 diabetic patients treated with DPP‑4 inhibitors versus sulphonylureas as add-on to metformin in clinical practice

DPP-4 inhibitors (DPP-4i) and sulphonylureas remain the most widely prescribed add-on treatments after metformin. However, there is limited evidence from clinical practice comparing major adverse cardiovascular events (MACE) in patients prescribed these treatments, particularly among those without prior history of MACE and from vulnerable population groups. Using electronic health records from UK primary care, we undertook a retrospective cohort study with people diagnosed type-2 diabetes mellitus, comparing incidence of MACE (myocardial infarction, stroke, major cardiovascular surgery, unstable angina) and all-cause mortality among those prescribed DPP-4i versus sulphonylureas as add-on to metformin. We stratified analysis by history of MACE, age, social deprivation and comorbidities and adjusted for HbA1c, weight, smoking-status, comorbidities and medications. We identified 17,570 patients prescribed sulphonylureas and 6,267 prescribed DPP-4i between 2008–2017. Of these, 16.3% had pre-existing MACE. Primary incidence of MACE was similar in patients prescribed DPP-4i and sulphonylureas (10.3 vs 8.5 events per 1000 person-years; adjusted Hazard Ratio (adjHR): 0.94; 95%CI 0.80–1.14). For those with pre-existing MACE, rates for recurrence were higher overall, but similar between the two groups (21.8 vs 17.2 events per 1000 person-years; adjHR: 0.93; 95%CI 0.69–1.24). For those aged over 75 and with BMI less than 25 kg/m2 there was a protective effect for DPP-I, warranting further investigation. Patients initiating a DPP-4i had similar risk of cardiovascular outcomes to those initiating a sulphonylurea. This indicates the choice should be based on safety and cost, not cardiovascular prognosis, when deciding between a DPP-4i or sulphonylurea as add-on to metformin

Differential Functional Constraints on the Evolution of Postsynaptic Density Proteins in Neocortical Laminae

The postsynaptic density (PSD) is a protein dense complex on the postsynaptic membrane of excitatory synapses that is implicated in normal nervous system functions such as synaptic plasticity, and also contains an enrichment of proteins involved in neuropsychiatric disorders. It has recently been reported that the genes encoding PSD proteins evolved more slowly than other genes in the human brain, but the underlying evolutionary advantage for this is not clear. Here, we show that cortical gene expression levels could explain most of this effect, indicating that expression level is a primary contributor to the evolution of these genes in the brain. Furthermore, we identify a positive correlation between the expression of PSD genes and cortical layers, with PSD genes being more highly expressed in deep layers, likely as a result of layer-enriched transcription factors. As the cortical layers of the mammalian brain have distinct functions and anatomical projections, our results indicate that the emergence of the unique six-layered mammalian cortex may have provided differential functional constraints on the evolution of PSD genes. More superficial cortical layers contain PSD genes with less constraint and these layers are primarily involved in intracortical projections, connections that may be particularly important for evolved cognitive functions. Therefore, the differential expression and evolutionary constraint of PSD genes in neocortical laminae may be critical not only for neocortical architecture but the cognitive functions that are dependent on this structure

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

Identification of a tyrosine residue responsible for N-acetylimidazole-induced increase of activity of ecto-nucleoside triphosphate diphosphohydrolase 3

Chemical modification in combination with site-directed mutagenesis was used to identify a tyrosine residue responsible for the increase in ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) nucleotidase activity after acetylation with a tyrosine-selective reagent, N-acetylimidazole. The NTPDase3 ATPase activity is increased more than the ADPase activity by this reagent. Several fairly well conserved tyrosine residues (252, 255, and 262) that are located in or very near apyrase conserved region 4a (ACR4a) were mutated. These mutants were all active, but mutation of tyrosine 252 to either alanine or phenylalanine eliminated the activity increase observed after N-acetylimidazole treatment of the wild-type enzyme. This suggests that the acetylation of tyrosine 252 is responsible for the increased activity. Stabilization of quaternary structure has resulted in increased enzyme activities for the NTPDases. However, mutation of these three tyrosine residues did not result in global changes of tertiary or quaternary structure, as measured by Cibacron blue binding, chemical cross linking, and native gel electrophoretic analysis. Nevertheless, disruption of the oligomeric structure with the detergent Triton X-100 abolished the increase in activity induced by this reagent. In addition, mutations that abolished the N-acetylimidazole effect also attenuated the increases of enzyme activity observed after lectin and chemical cross-linking treatments, which were previously attributed to stabilization of the quaternary structure. Thus, we speculate that the acetylation of tyrosine 252 might induce a subtle conformational change in NTPDase3, resulting in the observed increase in activity

Privatization in the presence of foreign competition and strategic policies

Recent evidence shows that developing and transition economies are increasingly privatizing their public firms and also experiencing rapid growth of inward foreign direct investment (FDI). In an international mixed oligopoly with strategic tax/subsidy policies, we analyze the interaction between privatization and FDI. We find that the incentive for FDI increases with privatization. However, the possibility of FDI reduces the degree of privatization. Our paper shows that FDI policies reducing the fixed-cost of undertaking FDI may need to complement the privatization policies to attract FDI and to improve domestic welfare

Borrelia burgdorferi Requires the Alternative Sigma Factor RpoS for Dissemination within the Vector during Tick-to-Mammal Transmission

While the roles of rpoSBb and RpoS-dependent genes have been studied extensively within the mammal, the contribution of the RpoS regulon to the tick-phase of the Borrelia burgdorferi enzootic cycle has not been examined. Herein, we demonstrate that RpoS-dependent gene expression is prerequisite for the transmission of spirochetes by feeding nymphs. RpoS-deficient organisms are confined to the midgut lumen where they transform into an unusual morphotype (round bodies) during the later stages of the blood meal. We show that round body formation is rapidly reversible, and in vitro appears to be attributable, in part, to reduced levels of Coenzyme A disulfide reductase, which among other functions, provides NAD+ for glycolysis. Our data suggest that spirochetes default to an RpoS-independent program for round body formation upon sensing that the energetics for transmission are unfavorable

Programmable disorder in random DNA tilings

Scaling up the complexity and diversity of synthetic molecular structures will require strategies that exploit the inherent stochasticity of molecular systems in a controlled fashion. Here we demonstrate a framework for programming random DNA tilings and show how to control the properties of global patterns through simple, local rules. We constructed three general forms of planar network—random loops, mazes and trees—on the surface of self-assembled DNA origami arrays on the micrometre scale with nanometre resolution. Using simple molecular building blocks and robust experimental conditions, we demonstrate control of a wide range of properties of the random networks, including the branching rules, the growth directions, the proximity between adjacent networks and the size distribution. Much as combinatorial approaches for generating random one-dimensional chains of polymers have been used to revolutionize chemical synthesis and the selection of functional nucleic acids, our strategy extends these principles to random two-dimensional networks of molecules and creates new opportunities for fabricating more complex molecular devices that are organized by DNA nanostructures