302 research outputs found

    Improving Power Delivery of Grid-Connected Induction Machine Based Wind Generators under Dynamic Conditions Using Feedforward Linear Neural Networks

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    In the conventional grid-connected Wind Energy Conversion System (WECS), the generator side inverter is typically controlled via Field Oriented Control (FOC), while Voltage Oriented Control (VOC) controls the grid side inverter. However, robust operation cannot be guaranteed during sudden changes in wind speeds and weak grid connections. This paper presents a novel method to improve the overall dynamic performance of on-grid induction machine-based wind generators. An online mechanical parameter estimation technique is devised using Recursive Least Squares (RLS) to compute the machine inertia and friction coefficient iteratively. An adaptive feedforward neural (AFN) controller is also proposed in the synchronous reference frame, which is constructed using the estimated parameters and the system's inverse. The output of the neural controller is added to the output of the speed PI controller in the outer loop of the FOC to enhance the speed response of the wind generator. A similar approach is taken to improve the classical VOC structure for the grid-side inverter. In this case, the RLS estimates the equivalent Thevenin's grid impedance in real-time. As for the adaptive action, two identical neural networks are integrated with the inner loop direct and quadrature axis current PI controllers. Under nominal operating conditions, it is observed that the PI+AFN provides a faster settling time for the generator's speed and torque response. Upon being subjected to variations in the wind speed, the PI+AFN outperforms the classical PI controller and attains a lower integral-time error. In addition, the proposed PI+AFN controller has a better ability to maintain the grid-side inverter stability during stochastic variations in grid impedance. One significant advantage of the proposed control approach is that no data for training or validation is required since the neural network weights are directly the output of the RLS estimator. Hardware verification for the improved FOC for wind generators using the adaptive controller is also made using the DSPACE 1007 AUTOBOX platform

    Tumor-Derived Exosome and Immune Modulation

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    Tumor cells, like most other cells, release exosomes called tumor-derived exosomes (TEX) and are vital for intercellular communication. TEX are membrane-bound extracellular vesicles (EVs), containing unique cargo reminiscent of the parent tumor cells and possess immunomodulatory functions. TEX carries factors that directly promote immunosuppression in the tumor microenvironment and indirectly attract immunosuppressive T-regulatory (Treg) cells. The tumor-secreted exosomes can transfer their cargo by multiple mechanisms like fusion, phagocytosis, and receptor-mediated endocytosis, activating the recipient cells. TEX directly engages and releases cytokines, inactivating natural killer (NK) cells and T-cells and activating apoptosis. Tumor-derived exosomes also release soluble factors to suppress dendritic cell (DC) maturation while activating the expansion of immune-suppressive cells like Myeloid-derived suppressor cells (MDSCs) and Regulatory T (Treg) cells. Several studies have shown the relevance of TEX containing tumor-associated antigens (TAA) in reducing the efficacy of cancer immunotherapy and adoptive cell therapy. Hence understanding the basic biology and mechanism of TEX-mediated immunosuppression is critical in discovering cancer biomarkers and finding better immunotherapy and cell therapy approaches. In this chapter, we have discussed TEX biogenesis, TEX\u27s structural and molecular features, TEX-mediated immunosuppression, and its relation to immunotherapy

    Correction to: Sars-Cov-2 Infection in People with Type 1 Diabetes and Hospital Admission: An Analysis of Risk Factors for England

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    The article “Sars-Cov-2 Infection in People with Type 1 Diabetes and Hospital Admission: An Analysis of Risk Factors for England”, written by Adrian H. Heald, David A. Jenkins, Richard Williams, Rajshekhar N. Mudaliar, Amber Khan, Akheel Syed, Naveed Sattar, Kamlesh Khunti, Asma Naseem, Kelly A. Bowden-Davies, J. Martin Gibson, William Ollier, on behalf of the CVD-COVID-UK/COVID-IMPACT Consortium was originally published electronically on the publisher’s Internet portal (currently SpringerLink) on August 25, 2023, without open access. Now, the article is updated with open access as This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The original article has been corrected

    Sars-Cov-2 Infection in People with Type 1 Diabetes and Hospital Admission: An Analysis of Risk Factors for England

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    Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus (coronavirus disease 2019 [COVID-19]) pandemic revealed the vulnerability of specific population groups in relation to susceptibility to acute deterioration in their health, including hospital admission and mortality. There is less data on outcomes for people with type 1 diabetes (T1D) following SARS-CoV-2 infection than for those with type 2 diabetes (T2D). In this study we set out to determine the relative likelihood of hospital admission following SARS-CoV-2 infection in people with T1D when compared to those without T1D. Methods: This study was conducted as a retrospective cohort study and utilised an all-England dataset. Electronic health record data relating to people in a national England database (NHS England’s Secure Data Environment, accessed via the BHF Data Science Centre's CVD-COVID-UK/COVID-IMPACT consortium) were analysed. The cohort consisted of patients with a confirmed SARS-CoV-2 infection, and the exposure was whether or not an individual had T1D prior to infection (77,392 patients with T1D). The patients without T1D were matched for sex, age and approximate date of the positive COVID-19 test, with three SARS-CoV-2-infected people living without diabetes (n = 223,995). Potential factors influencing the relative likelihood of the outcome of hospital admission within 28 days were ascertained using univariable and multivariable logistic regression. Results: Median age of the people living with T1D was 37 (interquartile range 25–52) years, 47.4% were female and 89.6% were of white ethnicity. Mean body mass index was 27 (standard error [SE] 0.022) kg/m2, and mean glycated haemoglobin (HbA1c) was 67.3 (SE 0.069) mmol/mol (8.3%). A significantly higher proportion of people with T1D (10.7%) versus matched non-diabetes individuals (3.9%) were admitted to hospital. In combined analysis including individuals with T1D and matched controls, multiple regression modelling indicated that the factors independently relating to a higher likelihood of hospital admission were: T1D (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.62–1.80]), age (OR 1.02, 95% CI 1.02–1.03), social deprivation (higher Townsend deprivation score: OR 1.07, 95% CI 1.06–1.08), lower estimated glomerular filtration rate (eGFR) value (OR 0.975, 95% CI 0.974–0.976), non-white ethnicity (OR black 1.19, 95% CI 1.06–1.33/OR Asian 1.21, 95% CI 1.05–1.39) and having asthma (OR 1.27, 95% CI 1.19–1.35]), chronic obstructive pulmonary disease (OR 2.10, 95% CI 1.89–2.32), severe mental illness (OR 1.83, 95% CI 1.57–2.12) or hypertension (OR 1.44, 95% CI 1.37–1.52). Conclusion: In this all-England study, we describe that, following confirmed infection with SARS-CoV-2, the risk factors for hospital admission for people living with T1D are similar to people without diabetes following confirmed SARS-CoV-2 infection, although the former were more likely to be admitted to hospital. The younger age of individuals with T1D in relation to risk stratification must be taken into account in any ongoing risk reduction strategies regarding COVID-19/future viral pandemics

    Low Prevalence of Ocular Chlamydia trachomatis Infection and Active Trachoma in the Western Division of Fiji.

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    BACKGROUND: Trachoma is the leading infectious cause of blindness and is caused by ocular infection with the bacterium Chlamydia trachomatis (Ct). While the majority of the global disease burden is found in sub-Saharan Africa, the Western Pacific Region has been identified as trachoma endemic. Population surveys carried out throughout Fiji have shown an abundance of both clinically active trachoma and trachomatous trichiasis in all divisions. This finding is at odds with the clinical experience of local healthcare workers who do not consider trachoma to be highly prevalent. We aimed to determine whether conjunctival infection with Ct could be detected in one administrative division of Fiji. METHODS: A population-based survey of 2306 individuals was conducted using the Global Trachoma Mapping Project methodology. Population prevalence of active trachoma in children and trichiasis in adults was estimated using the World Health Organization simplified grading system. Conjunctival swabs were collected from 1009 children aged 1-9 years. DNA from swabs was tested for the presence of the Ct plasmid and human endogenous control. RESULTS: The prevalence of active trachoma in 1-9 year olds was 3.4%. The age-adjusted prevalence was 2.8% (95% CI: 1.4-4.3%). The unadjusted prevalence of ocular Ct infection in 1-9 year-olds was 1.9% (19/1009), and the age-adjusted infection prevalence was 2.3% (95% CI: 0.4-2.5%). The median DNA load was 41 Ct plasmid copies per swab (min 20, first quartile 32, mean 6665, third quartile 161, max 86354). There was no association between current infection and follicular trachoma. No cases of trachomatous trichiasis were identified. DISCUSSION: The Western Division of Fiji has a low prevalence of clinical trachoma. Ocular Ct infections were observed, but they were predominantly low load infections and were not correlated with clinical signs. Our study data suggest that trachoma does not meet the WHO definition of a public health problem in this Division of Fiji, but the inconsistency with previous studies warrants further investigation

    Simultaneous non-negative matrix factorization for multiple large scale gene expression datasets in toxicology

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    Non-negative matrix factorization is a useful tool for reducing the dimension of large datasets. This work considers simultaneous non-negative matrix factorization of multiple sources of data. In particular, we perform the first study that involves more than two datasets. We discuss the algorithmic issues required to convert the approach into a practical computational tool and apply the technique to new gene expression data quantifying the molecular changes in four tissue types due to different dosages of an experimental panPPAR agonist in mouse. This study is of interest in toxicology because, whilst PPARs form potential therapeutic targets for diabetes, it is known that they can induce serious side-effects. Our results show that the practical simultaneous non-negative matrix factorization developed here can add value to the data analysis. In particular, we find that factorizing the data as a single object allows us to distinguish between the four tissue types, but does not correctly reproduce the known dosage level groups. Applying our new approach, which treats the four tissue types as providing distinct, but related, datasets, we find that the dosage level groups are respected. The new algorithm then provides separate gene list orderings that can be studied for each tissue type, and compared with the ordering arising from the single factorization. We find that many of our conclusions can be corroborated with known biological behaviour, and others offer new insights into the toxicological effects. Overall, the algorithm shows promise for early detection of toxicity in the drug discovery process

    Effect of Age of Infusion Site and Type of Rapid-Acting Analog on Pharmacodynamic Parameters of Insulin Boluses in Youth With Type 1 Diabetes Receiving Insulin Pump Therapy

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    OBJECTIVE—The purpose of this study was to examine the effect of type of insulin analog and age of insertion site on the pharmacodynamic characteristics of a standard insulin bolus in youth with type 1 diabetes receiving insulin pump therapy

    Insulin Detemir in the Treatment of Type 1 and Type 2 Diabetes

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    Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia) in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime). Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients

    Discordance in glycemic categories and regression to normality at baseline in 10,000 people in a Type 2 diabetes prevention trial

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    The world diabetes population quadrupled between 1980 and 2014 to 422 million and the enormous impact of Type 2 diabetes is recognised by the recent creation of national Type 2 diabetes prevention programmes. There is uncertainty about how to correctly risk stratify people for entry into prevention programmes, how combinations of multiple ‘at high risk’ glycemic categories predict outcome, and how the large recently defined ‘at risk’ population based on an elevated glycosylated haemoglobin (HbA1c) should be managed. We identified all 141,973 people at highest risk of diabetes in our population, and screened 10,000 of these with paired fasting plasma glucose and HbA1c for randomisation into a very large Type 2 diabetes prevention trial. Baseline discordance rate between highest risk categories was 45.6 %, and 21.3 - 37.0 % of highest risk glycaemic categories regressed to normality between paired baseline measurements (median 40 days apart). Accurate risk stratification using both fasting plasma glucose and HbA1c data, the use of paired baseline data, and awareness of diagnostic imprecision at diagnostic thresholds would avoid substantial overestimation of the true risk of Type 2 diabetes and the potential benefits (or otherwise) of intervention, in high risk subjects entering prevention trials and programmes
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