156 research outputs found

    Fault ride-through enhancement of fixed speed wind turbine using bridge-type fault current limiter

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    AbstractThe interaction between wind energy turbines and the grid results in two main problems, increasing the short-circuit level and reducing the Fault Ride-Through (FRT) capability during faults. The objective of this paper is to solve these problems, for fixed speed Wind Energy Systems (WECS), utilizing the bridge-type Fault Current Limiter (FCL) with a discharging resistor. A simple cascaded control system is proposed for the FCL to regulate the terminal voltage of the generator and limit the current. The system is simulated on PSCAD/EMTDC software to evaluate the dynamic performance of the proposed WECS compensated by FCL. The simulation results show the potentials of the FCL as a simple and effective method for solving grid interconnection problems of WECS

    Four-leg active power filter control with SUI-PI controller

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    Four-leg active power filter is considered one of the greatest vital active filters that are frequently used in industrial applications, especially those that need to be controlled in each individual phase. Also, to control the neutral current that created because of a lot of unbalanced and non-linear loads. In this paper, the used active filter was controlled by a proposed control method which can achieve simplicity and intelligence at the same time. The novelty of this paper is using the proposed controller with Four-leg active power filter. This controller relies on instantaneous reactive power theory, which used to create the required currents that are injected into the network via the used active filter to remove the problems created by unbalanced and non-linear loads. It is also maintained that the current source a pure sinusoidal wave. The system is implemented on MATLAB/Simulink. The simulation results proved the preference of the proposed controller than the conventional proportional-integration controller, where it reduced the percentage of total harmonic distortion for the current source

    Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights

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    Aparajita Sarkar,1 Kareem Imad Fanous,1 Isra Marei,2 Hong Ding,2 Moncef Ladjimi,3 Ross MacDonald,4 Morley D Hollenberg,5 Todd J Anderson,6 Michael A Hill,7 Chris R Triggle2 1Department of Medical Education, Weill Cornell Medicine-Qatar, Doha, Qatar; 2Department of Pharmacology & Medical Education, Weill Cornell Medicine- Qatar, Doha, Qatar; 3Department of Biochemistry & Medical Education, Weill Cornell Medicine-Qatar, Doha, Qatar; 4Health Sciences Library, Weill Cornell Medicine-Qatar, Doha, Qatar; 5Department of Physiology & Pharmacology, and Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 6Department of Cardiac Sciences and Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 7Dalton Cardiovascular Research Center & Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USACorrespondence: Aparajita Sarkar; Chris R Triggle, Email [email protected]; [email protected]: Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people worldwide for the treatment of type 2 diabetes (T2D). Metformin is used off-label for the treatment of polycystic ovary syndrome (PCOS) and for pre-diabetes and weight loss. Metformin is a safe, inexpensive drug with side effects mostly limited to gastrointestinal issues. Prospective clinical data from the United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, demonstrated that metformin not only has excellent therapeutic efficacy as an anti-diabetes drug but also that good glycemic control reduced the risk of micro- and macro-vascular complications, especially in obese patients and thereby reduced the risk of diabetes-associated cardiovascular disease (CVD). Based on a long history of clinical use and an excellent safety record metformin has been investigated to be repurposed for numerous other diseases including as an anti-aging agent, Alzheimer’s disease and other dementias, cancer, COVID-19 and also atrial fibrillation (AF). AF is the most frequently diagnosed cardiac arrythmia and its prevalence is increasing globally as the population ages. The argument for repurposing metformin for AF is based on a combination of retrospective clinical data and in vivo and in vitro pre-clinical laboratory studies. In this review, we critically evaluate the evidence that metformin has cardioprotective actions and assess whether the clinical and pre-clinical evidence support the use of metformin to reduce the risk and treat AF. Keywords: metformin, atrial fibrillation, AMPK, hyperglycemia, hypoglycemia, cardiac metabolism, cardiovascular protection, atrial remodelin

    Synthesis, characterization, biological applications, and molecular docking studies of amino-phenol-derived mixed-ligand complexes with Fe(III), Cr(III), and La(III) ions

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    A new series of Fe(III), Cr(III), and La(III) mixed-ligand complexes, resulting from the interaction of 2-aminophenol with 2-hydroxy acetophenone (HL1) as primary ligand and L- histidine (L2) as a secondary ligand, has been investigated using various physicochemical studies such as elemental analyses, molar conductivity, magnetic moment, infrared, UV/Vis, 1H NMR, and mass spectroscopic techniques. The microanalytical results indicate that the mixed ligand complexes were designed in a 1:1:1 M ratio. The electronic spectral data indicated that all the synthesized complexes have an octahedral structure. The disc diffusion assay was used to determine the disc inhibition zone (IZ, mm) and minimum inhibitory concentration (MIC, g/mL) of the investigated compounds against the growth of the pathogenic bacterial strains S. aureus, E. faecalis, P. aeruginosa, Klebsiella sp., and E. coli. The MTT test was used to determine the cytotoxicity of these reported compounds against the human hepatocellular liver cancer (HEPG-2) cell lines. The molecular docking study for the compounds against the EGFR tyrosine kinase receptor (PDB code: 1 M17) was conducted to examine the interactions in protein–ligand complexes. Furthermore, the biological activity of the ligand was investigated using quantitative structure–activity relationship studies (QSAR)

    Analytical techniques for multiplex analysis of protein biomarkers

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    Introduction: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. Areas covered: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. Expert commentary: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine

    Gene Expression Profiling of Embryonic Human Neural Stem Cells and Dopaminergic Neurons from Adult Human Substantia Nigra

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    Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation. The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells

    Multidimensional Characterization and Differentiation of Neurons in the Anteroventral Cochlear Nucleus

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    Multiple parallel auditory pathways ascend from the cochlear nucleus. It is generally accepted that the origin of these pathways are distinct groups of neurons differing in their anatomical and physiological properties. In extracellular in vivo recordings these neurons are typically classified on the basis of their peri-stimulus time histogram. In the present study we reconsider the question of classification of neurons in the anteroventral cochlear nucleus (AVCN) by taking a wider range of response properties into account. The study aims at a better understanding of the AVCN's functional organization and its significance as the source of different ascending auditory pathways. The analyses were based on 223 neurons recorded in the AVCN of the Mongolian gerbil. The range of analysed parameters encompassed spontaneous activity, frequency coding, sound level coding, as well as temporal coding. In order to categorize the unit sample without any presumptions as to the relevance of certain response parameters, hierarchical cluster analysis and additional principal component analysis were employed which both allow a classification on the basis of a multitude of parameters simultaneously. Even with the presently considered wider range of parameters, high number of neurons and more advanced analytical methods, no clear boundaries emerged which would separate the neurons based on their physiology. At the current resolution of the analysis, we therefore conclude that the AVCN units more likely constitute a multi-dimensional continuum with different physiological characteristics manifested at different poles. However, more complex stimuli could be useful to uncover physiological differences in future studies

    PP13, Maternal ABO Blood Groups and the Risk Assessment of Pregnancy Complications

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    Placental Protein 13 (PP13), an early biomarker of preeclampsia, is a placenta-specific galectin that binds beta-galactosides, building-blocks of ABO blood-group antigens, possibly affecting its bioavailability in blood.We studied PP13-binding to erythrocytes, maternal blood-group effect on serum PP13 and its performance as a predictor of preeclampsia and intrauterine growth restriction (IUGR). Datasets of maternal serum PP13 in Caucasian (n = 1078) and Hispanic (n = 242) women were analyzed according to blood groups. In vivo, in vitro and in silico PP13-binding to ABO blood-group antigens and erythrocytes were studied by PP13-immunostainings of placental tissue-microarrays, flow-cytometry of erythrocyte-bound PP13, and model-building of PP13--blood-group H antigen complex, respectively. Women with blood group AB had the lowest serum PP13 in the first trimester, while those with blood group B had the highest PP13 throughout pregnancy. In accordance, PP13-binding was the strongest to blood-group AB erythrocytes and weakest to blood-group B erythrocytes. PP13-staining of maternal and fetal erythrocytes was revealed, and a plausible molecular model of PP13 complexed with blood-group H antigen was built. Adjustment of PP13 MoMs to maternal ABO blood group improved the prediction accuracy of first trimester maternal serum PP13 MoMs for preeclampsia and IUGR.ABO blood group can alter PP13-bioavailability in blood, and it may also be a key determinant for other lectins' bioavailability in the circulation. The adjustment of PP13 MoMs to ABO blood group improves the predictive accuracy of this test

    Biological properties of extracellular vesicles and their physiological functions

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    MarĂ­a Yåñez-MĂł#, Pia R.-M. Siljander#, Zoraida Andreu, Apolonija Bedina Zavec, Francesc E. BorrĂ s, Edit I. Buzas, Krisztina Buzas, Enriqueta Casal, Francesco Cappello, Joana Carvalho, Eva ColĂĄs, Anabela Cordeiro-da Silva, Stefano Fais, Juan M. Falcon-Perez, Irene M. Ghobrial, Bernd Giebel, Mario Gimona, Michael Graner, Ihsan Gursel, Mayda Gursel, Niels H. H. Heegaard, An Hendrix30, Peter Kierulf, Katsutoshi Kokubun, Maja Kosanovic, Veronika Kralj-Iglic, Eva-Maria KrĂ€mer-Albers, Saara Laitinen, Cecilia LĂ€sser, Thomas Lener, ErzsĂ©bet Ligeti, Aija Linē, Georg Lipps, Alicia Llorente, Jan Lötvall, Mateja Manček-Keber, Antonio Marcilla, Maria Mittelbrunn, Irina Nazarenko, Esther N.M. Nolte-‘t Hoen, Tuula A. Nyman, Lorraine O'Driscoll, Mireia Olivan, Carla Oliveira, Éva PĂĄllinger, Hernando A. del Portillo, Jaume ReventĂłs, Marina Rigau, Eva Rohde, Marei Sammar, Francisco SĂĄnchez-Madrid, N. SantarĂ©m1, Katharina Schallmoser, Marie Stampe Ostenfeld, Willem Stoorvogel, Roman Stukelj, Susanne G. Van der Grein, M. Helena Vasconcelos, Marca H. M. Wauben and Olivier De WeverIn the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells.While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.Peer reviewe
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