Synthetic LV-Grid Models for Scientific Investigations

Due to the steadily increasing number of decentralized generation units, the upcoming smart meter rollout and the expected electrification of the transport sector (e-mobility), grid planning and grid operation at low-voltage (LV) level are facing major challenges. Therefore, many studies, research and demonstration projects on the above topics have been carried out in recent years, and the results and the methods developed have been published. However, the published methods usually cannot be replicated or validated, since the majority of the examination models or the scenarios used are incomprehensible to third parties. There is a lack of uniform grid models that map the German LV grids and can be used for comparative investigations, which are similar to the example of the North American distribution grid models of the IEEE. In contrast to the transmission grid, whose structure is known with high accuracy, suitable grid models for LV grids are difficult to map because of the high number of LV grids and distribution system operators. Furthermore, a detailed description of real LV grids is usually not available in scientific publications for data privacy reasons. For investigations within a research project, the most characteristic synthetic LV grid models have been created, which are based on common settlement structures and usual grid planning principles in Germany. In this work, these LV grid models, and their development are explained in detail. For the first time, comprehensible LV grid models for the middle European area are available to the public, which can be used as a benchmark for further scientific research and method developments. This document is an English version of the paper which was originally written in German1. In addition, this paper discusses a few more aspects especially on the planning process of distribution grids in Germany

Visfatin, glucose metabolism and vascular disease: a review of evidence

The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease

Primary Biliary Cholangitis: a Rare Diagnosis During Pregnancy

Primary biliary cholangitis is an autoimmune disease that mostly affects women. It is uncommon in women of childbearing age and the diagnosis during pregnancy is rare and can be challenging. Described here is a case of primary biliary cholangitis first manifesting during pregnancy, with the onset of pruritus, jaundice, biochemical liver abnormalities and positive antimitochondrial antibodies. Although treatment with ursodeoxycholic acid was started at the time of diagnosis, there was a progressive worsening of cholestatic biochemical markers throughout pregnancy. In addition, fasting hyperglycemia with polyhydramnios was diagnosed, consistent with gestational diabetes. She had a spontaneous preterm delivery at 31 weeks of gestation, of a newborn who was admitted to the neonatal intensive care unit but who subsequently had no long-term sequelae of preterm delivery. A maternal postpartum flare occurred. Treatment with ursodeoxycholic acid was well tolerated during pregnancy and lactation.info:eu-repo/semantics/publishedVersio

Mitochondrial superoxide generation induces a parkinsonian phenotype in zebrafish and huntingtin aggregation in human cells.

Superoxide generation by mitochondria respiratory complexes is a major source of reactive oxygen species (ROS) which are capable of initiating redox signaling and oxidative damage. Current understanding of the role of mitochondrial ROS in health and disease has been limited by the lack of experimental strategies to selectively induce mitochondrial superoxide production. The recently-developed mitochondria-targeted redox cycler MitoParaquat (MitoPQ) overcomes this limitation, and has proven effective in vitro and in Drosophila. Here we present an in vivo study of MitoPQ in the vertebrate zebrafish model in the context of Parkinson's disease (PD), and in a human cell model of Huntington's disease (HD). We show that MitoPQ is 100-fold more potent than non-targeted paraquat in both cells and in zebrafish in vivo. Treatment with MitoPQ induced a parkinsonian phenotype in zebrafish larvae, with decreased sensorimotor reflexes, spontaneous movement and brain tyrosine hydroxylase (TH) levels, without detectable effects on heart rate or atrioventricular coordination. Motor phenotypes and TH levels were partly rescued with antioxidant or monoaminergic potentiation strategies. In a HD cell model, MitoPQ promoted mutant huntingtin aggregation without increasing cell death, contrasting with the complex I inhibitor rotenone that increased death in cells expressing either wild-type or mutant huntingtin. These results show that MitoPQ is a valuable tool for cellular and in vivo studies of the role of mitochondrial superoxide generation in redox biology, and as a trigger or co-stressor to model metabolic and neurodegenerative disease phenotypes

Mulberry leaf lipid nanoparticles: a naturally targeted CRISPR/Cas9 oral delivery platform for alleviation of colon diseases

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (â 25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.This study was supported by the National Natural Science Foundation of China (82072060, 82360110, and 22008201), the Science and Technology Department of Jiangxi Province (20212BDH81019 and 20224BAB206073), the Fundamental Research Funds for the Central Universities (SWU-XDPY22006 and SWU-KQ22075), the Venture & Innovation Support Pro-gram for Chongqing Overseas Returnees (2205012980212766), and theScience Fund for Distinguished Young Scholars of Chongqing Municipality (2022NSCQ-JQX5279)

Improving Protein Template Recognition by Using Small-Angle X-Ray Scattering Profiles

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Small-angle x-ray scattering (SAXS) is able to extract low-resolution protein shape information without requiring a specific crystal formation. However, it has found little use in atomic-level protein structure determination due to the uncertainty of residue-level structural assignment. We developed a new algorithm, SAXSTER, to couple the raw SAXS data with protein-fold-recognition algorithms and thus improve template-based protein-structure predictions. We designed nine different matching scoring functions of template and experimental SAXS profiles. The logarithm of the integrated correlation score showed the best template recognition ability and had the highest correlation with the true template modeling (TM)-score of the target structures. We tested the method in large-scale protein-fold-recognition experiments and achieved significant improvements in prioritizing the best template structures. When SAXSTER was applied to the proteins of asymmetric SAXS profile distributions, the average TM-score of the top-ranking templates increased by 18% after homologous templates were excluded, which corresponds to a p-value < 10(-9) in Student's t-test. These data demonstrate a promising use of SAXS data to facilitate computational protein structure modeling, which is expected to work most efficiently for proteins of irregular global shape and/or multiple-domain protein complexes.1011127702781National Science Foundation [1027394]National Institute of General Medical Sciences [GM083107, GM084222]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Science Foundation [1027394]National Institute of General Medical Sciences [GM083107, GM084222]CNPq [140377/2008-5

HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus (T2DM) is a genetically heterogeneous disease, hepatocyte nuclear factor-1 homeobox A (<it>HNF1A</it>) single-nucleotide polymorphisms (SNPs) playing a minor role in its pathogenesis. <it>HNF1A </it>is a frequent cause of monogenic diabetes, albeit with early-onset. Some uncommon subgroups like late-onset autosomal dominant diabetes mellitus (LOADDM) may present peculiar inheritance patterns with a stronger familial component. This study aims to investigate the relationship of <it>HNF1A </it>SNPs with cardiovascular risk factors in this group, as well as to characterize them in contrast with classical T2DM (CT2DM).</p> <p>Methods</p> <p>eighteen LOADDM (age at onset > 40 y.o.; diabetes in 3 contiguous generations, uniparental lineage) along with 48 CT2DM patients and 42 normoglycemic controls (N group) have been evaluated for cardiovascular risk factors and SNPs of <it>HNF1A</it>.</p> <p>Results</p> <p>LOADDM showed significantly higher frequencies of SNPs A98V (22.2% vs 2.1%, p = 0.02) and S487N (72.2% vs 43.8%, p = 0.049) of <it>HNF1A </it>compared to CT2DM. I27L did not show significant difference (66.7% vs 45.8%), but associated with lower risk of hypertriglyceridemia (OR 0.16, 95% CI 0.04–0.65, p = 0.01). "Protective effect" was independent from other well-known predictive risk factors for hypertriglyceridemia, such as waist circumference (OR 1.09 per 1 cm increase, p = 0.01) and HDL (OR 0.01 per 1 mmol/l, p = 0.005), after logistic regression.</p> <p>Conclusion</p> <p>Late onset autosomal dominant diabetes mellitus is clinically indistinguishable from classical type 2 diabetes individuals. However, LOADDM group is enriched for common <it>HNF1A </it>polymorphisms A98V and S487N. I27L showed "protective effect" upon hypertriglyceridemia in this sample of individuals, suggesting a role for <it>HNF1A </it>on diabetic individuals' lipid profile. These data contribute to the understanding of the complex interactions between genes, hyperglycemia and cardiovascular risk factors development in type 2 diabetes mellitus.</p

Computer analysis of objects’ movement in image sequences: methods and applications

Computer analysis of objects’ movement in image sequences is a very complex problem, considering that it usually involves tasks for automatic detection, matching, tracking, motion analysis and deformation estimation. In spite of its complexity, this computational analysis has a wide range of important applications; for instance, in surveillance systems, clinical analysis of human gait, objects recognition, pose estimation and deformation analysis. Due to the extent of the purposes, several difficulties arise, such as the simultaneous tracking of manifold objects, their possible temporary occlusion or definitive disappearance from the image scene, changes of the viewpoints considered in images acquisition or of the illumination conditions, or even nonrigid deformations that objects may suffer in image sequences. In this paper, we present an overview of several methods that may be considered to analyze objects’ movement; namely, for their segmentation, tracking and matching in images, and for estimation of the deformation involved between images.This paper was partially done in the scope of project “Segmentation, Tracking and Motion Analysis of Deformable (2D/3D) Objects using Physical Principles”, with reference POSC/EEA-SRI/55386/2004, financially supported by FCT -Fundação para a Ciência e a Tecnologia from Portugal. The fourth, fifth and seventh authors would like to thank also the support of their PhD grants from FCT with references SFRH/BD/29012/2006, SFRH/BD/28817/2006 and SFRH/BD/12834/2003, respectively

Severe Plasmodium vivax malaria exhibits marked inflammatory imbalance

<p>Abstract</p> <p>Background</p> <p>Despite clinical descriptions of severe vivax malaria cases having been reported, data regarding immunological and inflammatory patterns are scarce. In this report, the inflammatory and immunological status of both mild and severe vivax malaria cases are compared in order to explore immunopathological events in this disease.</p> <p>Methods and Results</p> <p>Active and passive malaria case detections were performed during 2007 in Buritis, Rondônia, in the Brazilian Amazon. A total of 219 participants enrolled the study. Study individuals were classified according to the presence of <it>Plasmodium vivax </it>infection within four groups: non-infected (n = 90), asymptomatic (n = 60), mild (n = 50) and severe vivax infection (n = 19). A diagnosis of malaria was made by microscopy and molecular assays. Since at present no clear criteria define severe vivax malaria, this study adapted the consensual criteria from falciparum malaria. Patients with severe <it>P. vivax </it>infection were younger, had lived for shorter time in the endemic area, and recalled having experienced less previous malaria episodes than individuals with no malaria infection and with mild or asymptomatic infection. Strong linear trends were identified regarding increasing plasma levels of C reactive protein (CRP), serum creatinine, bilirubins and the graduation of disease severity. Plasma levels of tumour necrosis factor (TNF), interferon-gamma(IFN-gamma) and also IFN-gamma/interleukin-10 ratios were increased and exhibited a linear trend with gradual augmentation of disease severity. Both laboratory parameters of organ dysfunction and inflammatory cytokines were reduced during anti-parasite therapy in those patients with severe disease.</p> <p>Conclusion</p> <p>Different clinical presentations of vivax malaria infection present strong association with activation of pro-inflammatory responses and cytokine imbalance. These findings are of utmost importance to improve current knowledge about physiopathological concepts of this serious widespread disease.</p