201 research outputs found

    Application of Conventional Feedforward and Deep Neural Networks to Power Distribution System State Estimation and State Forecasting

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    Classical neural networks such as feedforward multilayer perceptron models (MLPs) are well established as universal approximators and as such, show promise in applications such as static state estimation in power transmission systems. This research investigates the application of conventional neural networks (MLPs) and deep learning based models such as convolutional neural networks (CNNs) and long short-term memory networks (LSTMs) to mitigate challenges in power distribution system state estimation and forecasting based upon conventional analytic methods. The ability of MLPs to perform regression to perform power system state estimation will be investigated. MLPs are considered based upon their promise to learn complex functional mapping between datasets with many features. CNNs and LSTMs are considered based upon their promise to perform time-series forecasting by learning the autocorrelation of the dataset being predicted. The performance of MLPs will be presented in terms of root-mean-square error (RMSE) between actual and predicted voltage magnitude and voltage phase angles and training execution time for distribution system state estimation (DSSE). The performance of CNNs, and LSTMs will be presented in terms of RMSE between actual and predicted real power demand and execution time when performing distribution system state forecasting (DSSF). Additionally, Bayesian Optimization with Gaussian Processes are used to optimize MLPs for regression. An IEEE standard 34-bus test system is used to illustrate the proposed conventional neural network and deep learning methods and their effectiveness to perform power system state estimation and power system state forecasting respectively

    Multimedia retrieval in MultiMatch: The impact of speech transcript errors on search behaviour

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    This study discusses the findings of an evaluation study on the performance of a multimedia multimodal information access sub-system (MIAS), incorporating automatic speech recognition technology (ASR) to automatically transcribe the speech content of video soundtracks. The study’s results indicate that an information-rich but minimalist graphical interface is preferred. It was also discovered that users tend to have a misplaced confidence in the accuracy of ASR-generated speech transcripts, thus they are not inclined to conduct a systematic auditory inspection (their usual search behaviour) of a video’s soundtrack if the query term does not appear in the transcript. In order to alert the user to the possibility that a search term may be incorrectly recognised as some other word, a matching algorithm is proposed that searches for word sequences of similar phonemic structure to the query term

    Nonequilibrium and Nonlinear Dynamics in Geomaterials I : The Low Strain Regime

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    Members of a wide class of geomaterials are known to display complex and fascinating nonlinear and nonequilibrium dynamical behaviors over a wide range of bulk strains, down to surprisingly low values, e.g., 10^{-7}. In this paper we investigate two sandstones, Berea and Fontainebleau, and characterize their behavior under the influence of very small external forces via carefully controlled resonant bar experiments. By reducing environmental effects due to temperature and humidity variations, we are able to systematically and reproducibly study dynamical behavior at strains as low as 10^{-9}. Our study establishes the existence of two strain thresholds, the first, epsilon_L, below which the material is essentially linear, and the second, epsilon_M, below which the material is nonlinear but where quasiequilibrium thermodynamics still applies as evidenced by the success of Landau theory and a simple macroscopic description based on the Duffing oscillator. At strains above epsilon_M the behavior becomes truly nonequilibrium -- as demonstrated by the existence of material conditioning -- and Landau theory no longer applies. The main focus of this paper is the study of the region below the second threshold, but we also comment on how our work clarifies and resolves previous experimental conflicts, as well as suggest new directions of research.Comment: 14 pages, 15 figure

    A description of the origins, design and performance of the TRAITS-SGP Atlantic salmon Salmo salar L. cDNA microarray

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    The origins, design, fabrication and performance of an Atlantic salmon microarray are described. The microarray comprises 16 950 Atlantic salmon-derived cDNA features, printed in duplicate and mostly sourced from pre-existing expressed sequence tag (EST) collections [SALGENE and salmon genome project (SGP)] but also supplemented with cDNAs from suppression subtractive hybridization libraries and candidate genes involved in immune response, protein catabolism, lipid metabolism and the parr–smolt transformation. A preliminary analysis of a dietary lipid experiment identified a number of genes known to be involved in lipid metabolism. Significant fold change differences (as low as 1.2x) were apparent from the microarray analysis and were confirmed by quantitative real-time polymerase chain reaction analysis. The study also highlighted the potential for obtaining artefactual expression patterns as a result of cross-hybridization of similar transcripts. Examination of the robustness and sensitivity of the experimental design employed demonstrated the greater importance of biological replication over technical (dye flip) replication for identification of a limited number of key genes in the studied system. The TRAITS (TRanscriptome Analysis of Important Traits of Salmon)–salmon genome project microarray has been proven, in a number of studies, to be a powerful tool for the study of key traits of Atlantic salmon biology. It is now available for use by researchers in the wider scientific community

    Subcortical brain atrophy persists even in HAART-regulated HIV disease

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    The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy

    QUANTIFICATION OF NORMAL BRAIN AGING USING FULLY DEFORMABLE REGISTRATION

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    Over the next twenty-five years, the proportion of the population over age 65 will increase 76%; therefore understanding both the normal and pathological processes involved in the aging of the human brain is of the highest public health priority. We report here the use of a computational method that provides estimates of the “brain age” of individuals that is based solely on a high resolution Magnetic Resonance Image (MRI) of the brain of the individual, and is blinded to his or her true chronological age. The method proceeds in two phases: first, a statistical learning algorithm is used to determine the numerical MRI-based features that predict true age on a training set of 198 healthy elderly individuals; second, these features are used to predict the true age of previously-unseen individuals. In cross-validation experiments, the brain age estimates differed from true age by a mean absolute error of 5.35 years in an elderly cohort, reflecting the broad heterogeneity in structural integrity of the elderly brain. The “brain age” of female subjects was significantly lower than that of male subjects who had the same true age (3.0 years younger for 50-year-olds and 1.6 years younger for 79 year olds), reflecting the longer life expectancy of females. Across the elderly age spectrum, the “brain age” of individuals with Alzheimer's Disease (AD) was significantly higher than that of cognitively-healthy elderly subjects with equivalent true age; however, this was not the case for the subjects with mild cognitive impairment (MCI), a possible AD prodrome

    Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

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    Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection

    Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer

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    BACKGROUND: This multicentre phase I/II study was designed to determine the maximum tolerated dose of irinotecan when combined with 5-fluorouracil and folinic acid according to the Mayo Clinic schedule and to evaluate the activity of this combination as first-line therapy in patients with advanced colorectal cancer. METHODS: Sixty-three patients received irinotecan (250 or 300 mg/m(2), 30- to 90-minute intravenous infusion on day 1), immediately followed by folinic acid (20 mg/m(2)/day) and 5-fluorouracil (425 mg/m(2), 15-minute bolus infusion) days 1 to 5, every four weeks. RESULTS: Diarrhoea was dose limiting at 300 mg/m(2 )irinotecan in combination with 5-fluorouracil and folinic acid, and this was determined to be the maximum tolerated dose. Grade 3–4 neutropenia was the most frequently reported toxicity. The recommended dose of irinotecan for the phase II part of the study was 250 mg/m(2). The response rate for the evaluable patient population was 36% (13/36), and 44% (16 patients) had stable disease (including 19% of minor response). For the intention-to-treat population, the response rate was 29% (14/49) and 35% (17 patients) stable disease (including 14% of minor response). The median time to progression was 7.0 months and the median survival was 12.0 months. Grade 3–4 non-haematological drug-related toxicities included delayed diarrhoea, stomatitis, fatigue, and nausea/vomiting. There were three deaths due to septic shock that were possibly or probably treatment-related. CONCLUSIONS: This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus 5-fluorouracil/folinic acid every four weeks showed activity as first-line therapy in patients with advanced colorectal cancer. In keeping with other published results of studies using bolus 5-fluorouracil combined with irinotecan, the use of this regimen is limited by a relatively high rate of grade 3–4 neutropenia, and the combination of irinotecan and infusional 5-fluorouracil / folinic acid should remain the regimen of first choice

    A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research

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    The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science

    C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays

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    Residues in the histone substrate binding sites that differ between the KDM4 and KDM5 subfamilies were identified. Subsequently, a C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one series was designed to rationally exploit these residue differences between the histone substrate binding sites in order to improve affinity for the KDM4-subfamily over KDM5-subfamily enzymes. In particular, residues E169 and V313 (KDM4A numbering) were targeted. Additionally, the conformational restriction of the flexible pyridopyrimidinone C8-substituent was investigated. These approaches yielded potent and cell-penetrant dual KDM4/5-subfamily inhibitors including 19a (KDM4A and KDM5B Ki = 0.004 and 0.007 μM, respectively). Compound cellular profiling in two orthogonal target engagement assays revealed a significant reduction from biochemical to cell-based activity across multiple analogues; this decrease was shown to be consistent with 2OG competition, and suggest that sub-nanomolar biochemical potency will be required with C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one compounds to achieve sub-micromolar target inhibition in cells
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