关键词： Data mining   Gene expression   Genetic association study   Transcriptomics  

摘要： Genome-wide association studies have identified thousands of noncoding variants associated with human traits and diseases. However, the functional interpretation of these variants is a major challenge. Here, we constructed a multi-tissue atlas of human 3 ' UTR alternative polyadenylation (APA) quantitative trait loci (3 ' aQTLs), containing approximately 0.4 million common genetic variants associated with the APA of target genes, identified in 46 tissues isolated from 467 individuals (Genotype-Tissue Expression Project). Mechanistically, 3 ' aQTLs can alter poly(A) motifs, RNA secondary structure and RNA-binding protein-binding sites, leading to thousands of APA changes. Our CRISPR-based experiments indicate that such 3 ' aQTLs can alter APA regulation. Furthermore, we demonstrate that mapping 3 ' aQTLs can identify APA regulators, such as La-related protein 4. Finally, 3 ' aQTLs are colocalized with approximately 16.1% of trait-associated variants and are largely distinct from other QTLs, such as expression QTLs. Together, our findings show that 3 ' aQTLs contribute substantially to the molecular mechanisms underlying human complex traits and diseases. A multi-tissue atlas of alternative polyadenylation (APA) quantitative trait loci (3 ' aQTLs) identifies approximately 0.4 million common genetic variants associated with the APA of target genes. Approximately 16% of trait-associated variants colocalize with 3 ' aQTLs.

关键词： Sustainable material   Decision-making   Multi-criteria decision making   Earth-retaining wall   Life cycle assessment   Life cycle cost  

摘要： This research aims to assess the sustainability of the most common earth-retaining walls (Gravity Walls and Cantilever Walls) in terms of environmental impacts, economic issues, and their combination. Gravity walls observed in this study consist of Gabion Wall, Crib Wall, and Rubble Masonry Wall, while Cantilever Walls include Reinforced Concrete Wall. Six different criteria were taken into account, including global warming potential, fossil depletion potential, eutrophication potential, acidification potential, human toxicity potential, and cost. To achieve the aim of this study, life cycle assessments, life cycle costs, and multi-criteria decision-making methods were implemented. The results showed that the most environmental-friendly option among all alternatives was the Gabion Wall, followed by the Rubble Masonry Wall. However, in terms of economic aspects, the Cantilever Concrete Wall was the best option, costing about 17% less than the Gabion Wall. On the other hand, the results of multi-criteria decision-making showed that the Gabion Wall was the most sustainable choice. This study addressed the research gap by carrying out a sustainability assessment of different retaining walls while considering cost and environmental impacts at the same time.

关键词： alternative pathway   complement   malignant hypertension   malignant nephrosclerosis   thrombotic microangiopathy  

摘要： Background. Malignant nephrosclerosis, defined as renal microangiopathy in the setting of severe hypertension, remains a critical renal emergency leading to end-stage renal disease despite aggressive anti-hypertensive treatment. Recently, activation of the complement alternative pathway (AP) has been reported to play a prominent role in the pathogenesis of malignant nephrosclerosis. However, subsequent study failed to recapitulate the findings of genetic complement abnormalities in the disease. This study aimed to determine the presence of AP activation and genetic complement defects and establish their correlations to renal microangiopathy lesions, clinical features and prognosis in patients with malignant nephrosclerosis. Methods. Fifty patients with malignant hypertension and concomitant thrombotic microangiopathy (TMA) proven by renal biopsy were investigated;25 cases of kidney donors who received zero-hour allograft biopsies were used as normal controls. Various renal TMA lesions in patients with malignant nephrosclerosis were reviewed and evaluated using a semi-quantitative scoring system. Deposition of C5b-9, C3a, C5a, C4d and mannose-binding lectin was assessed by immunohistochemistry. Co-localization of C5b-9 and CD34 was detected by confocal microscopy. Complement factor B (FB), factor P (FP;properdin), factor D (FD), factor H (FH), C3a and C5a levels were quantified by enzyme-linked immonosorbent assay in plasma and urine samples of patients with malignant nephrosclerosis and controls. Genetic abnormalities of complement components were analysed by whole-exome sequencing. Results. Renal biopsies of malignant nephrosclerosis showed identical histopathological and ultrastructural features to atypical haemolytic uraemic syndrome. C5b-9, C3a and C5a deposits were found along the walls of arteries/arterioles and glomerular capillaries and localized in the endothelial cells. Elevated plasma and urinary levels of FB, FP, FD, C3a and C5a as well as decreased FH l

关键词： Opioid receptor   Alternative splicing   Evolutionary conservation   Gene enrichment  

摘要： The article "Alternative Splicing of Opioid Receptor Genes Shows a Conserved Pattern for 6TM Receptor Variants", written by Marjo Piltonen, Andrey Krokhotin, Marc Parisien, Pierre Berube, Haig Djambazian, Rob Sladek, Nikolay V. Dokholyan, Svetlana A. Shabalina and Luda Diatchenko was originally published electronically on the publisher's internet portal on October 3, 2020 without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on October 27, 2020 to (c) The Author(s) 2020 and the article is forthwith distributed 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, .

关键词： akali activation   aluminosilicates   amorphous   modeling   model   solubility  

摘要： Efforts to reduce the carbon footprint associated with cement and concrete production have resulted in a number of promising lower-emission alternatives. Still, research has emphasized a small subset of potentially useful precursor materials. With the goal of expanding the precursor pool, this work presents results of parallel literature mining and rate modeling activities. As a result of literature mining, materials with appropriate SiO2, Al2O3, and CaO concentrations were assembled into a comprehensive, representative ternary diagram. 23 000+ materials were extracted from 7000 journal articles, and 7500 materials from 6000 articles with 80 <= SiO2 + Al2O3 + CaO <= 105 wt% automatically classified. Both supervised and semi-supervised models were used for dissolution rate prediction of glassy materials with all models pulling from a single data set (n = 802 reported dissolution rates from 105 different glasses). Supervised modeling utilized linear and decision tree regressions to determine features most predictive of dissolution rate, resulting in log-linear relationships between rate and pH, inverse temperature (1/K), and non-bridging oxygen per tetrahedron (NBO/T). Semi-supervised modeling was observed to be more robust to broader feature inclusion, providing similar predictive ability with a relatively larger set of descriptive features. Most importantly, results indicated that models trained on data from disparate scientific communities were adequately predictive (RMSE approximate to 1), particularly under pH >= 7 conditions relevant to the cement and alkali activation communities.

摘要： Background Yoga as alternative form of therapy has shown positive impact on pulmonary functions, exercise capacity, behavioral changes, and inflammation in non-trauma patients. However, the efficacy of Yoga has not been studied in chest trauma patients. Methods This randomized controlled trial was conducted at level-1 Trauma Centre. Isolated chest injury patients were randomized into either standard physiotherapy or Yogatherapy groups. Patients in physiotherapy group received conventional chest physiotherapy and Yogatherapy group received a set of Yogic exercises in addition to conventional chest physiotherapy. Primary outcome measure was changes in pulmonary function tests (PFT) at 4 weeks of discharge. Secondary outcomes were changes in quality of life (QoL), respiratory muscle strength and endurance, chest wall mobility, and levels of cytokines at 4 weeks. Data were analyzed using STATA v14.0. Results A total of 89 eligible patients were randomized to physiotherapy (n = 46) and Yoga therapy (n = 43) groups. Demographic characteristics were comparable in both the groups. There were statistically significant improvements in PFT in the Yogatherapy group compared with physiotherapy with an increase in Forced vital capacity (p = 0.02) and Forced expiratory volume (p = 0.01) at 4 weeks. In addition, there were significant improvement in physical component of QoL, respiratory muscle endurance (p = 0.003) and axillary cirtometry (p = 0.009) in the Yogatherapy group. However, no statistically significant difference in the trends of cytokine markers seen between the groups. Conclusion Yoga was found to be effective in improving pulmonary functions and QoL in patients with chest trauma. (Trial registered at ***/clinicaltrials/***, numberREF/2016/05/011,287).

关键词： Earth rotation variations   Geodetic instrumentation   Rheology: mantle  

摘要： Until now, the polar motion resonance (PMR) complex frequency has been determined in the seasonal and retrograde diurnal band of the polar motion. In this study, this resonance is studied in the prograde diurnal band, where polar motion is mainly composed of periodic terms caused by the diurnal oceanic tide. The resonance parameters (period and quality factor) are encompassed in the frequency transfer function between generating tidal potential and polar motion, and can be estimated accordingly. To this aim, we gather three published sets of prograde diurnal terms determined from Global Navigation Satellite System (GNSS) and Very Long Baseline Interferometry (VLBI), to which we append our own estimates based upon a processing of the VLBI delays over the period 1990-2020. Then, by fitting the PMR parameters so that the prograde diurnal terms match the corresponding components of the tide generating potential, we obtained a resonance period of about 401 d and an equivalent quality factor of -22, differing from those reigning in the seasonal band (P-PMR approximate to 431 d;Q(PMR) approximate to 56-255) and in the retrograde diurnal band (P-PMR approximate to 380 d;Q(PMR) approximate to -10). Our estimates confirm strikingly the theoretical prediction derived from the tidal ocean angular momentum derived from the FES 2014 ocean tide model.

关键词： plasma   RNA   SARS-CoV-2   COVID-19  

摘要： We present the case of an inpatient with pneumonia and repeatedly negative nasopharyngeal SARS-CoV-2 testing. In such challenging cases, alternative diagnostic options include lower respiratory tract and plasma SARS-CoV-2 RNA testing, of which the latter may be particularly useful where bronchoscopy is deferred due to clinical factors or transmission risk. (c) 2021 Published by Elsevier Inc.

关键词： Biosurfactants   Sophorolipids   Rhamnolipids   Solid-phase extraction   UHPLC-MS   MS  

摘要： Biosurfactants have been investigated as potential alternatives for synthetic surfactants in several areas, for example, in environmental and pharmaceutical fields. In that regard, extensive research has been carried out with sophorolipids and rhamnolipids that also present various biological properties with therapeutic significance. These biosurfactants are obtained as complex mixtures of slightly different molecules, and thus when studying these microbial glycolipids, the ability to identify and purify the produced compounds is of extreme importance. This study aimed to develop improved methodologies for the identification, separation, and purification of sophorolipids and rhamnolipids. Therefore, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was modified to ensure faster characterization of both sophorolipids and rhamnolipids, enabling the identification and fragmentation pattern description of 10 and 13 congeners, respectively. The separation and purification of these biosurfactants was achieved with novel reversed-phase solid-phase extraction methods guaranteeing the isolation of different glycolipids, including those considered for their significant biological activity (e.g. antimicrobial, anticancer). It was possible to isolate sophorolipids and rhamnolipids with purity of 94% and 99%, respectively. The methods presented herein can be easily implemented and are expected to make purification of these biosurfactants easier, facilitating the study of their individual properties in further works.

摘要： PurposeTo explore validity evidence for the use of entrustable professional activities (EPAs) as an assessment framework in medical education. MethodFormative assessments on the 13 Core EPAs for entering residency were collected for 4 cohorts of students over a 9- to 12-month longitudinal integrated clerkship as part of the Education in Pediatrics Across the Continuum pilot at the University of Minnesota Medical School. The students requested assessments from clinical supervisors based on direct observation while engaging in patient care together. Based on each observation, the faculty member rated the student on a 9-point scale corresponding to levels of supervision required. Six EPAs were included in the present analyses. Student ratings were depicted as curves describing their performance over time;regression models were employed to fit the curves. The unit of analyses for the learning curves was observations rather than individual students. Results(1) Frequent assessments on EPAs provided a developmental picture of competence consistent with the negative exponential learning curve theory;(2) This finding was true across a variety of EPAs and across students;and (3) The time to attain the threshold level of performance on the EPA for entrustment varied by student and EPA. ConclusionsThe results provide validity evidence for an EPA-based program of assessment. Students assessed using multiple observations performing the Core EPAs for entering residency demonstrate classic developmental progression toward the desired level of competence resulting in entrustment decisions. Future work with larger data samples will allow further psychometric analyses of assessment of EPAs.