bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease
Authors: Omer Nurit , Giladi Nir , Gurevich Tanya , Bar‐Shira Anat , Gana‐Weisz Mali , Goldstein Orly , Kestenbaum Meir , Cedarbaum Jesse M. , Orr‐Urtreger Avi , Mirelman Anat , Thaler Avner 
Published: April 2020

AbstractBackgroundThe phenotype of Parkinson's disease (PD) is milder among patients with LRRK2‐PD and more severe among patients with GBA‐PD; however, whether an additive phenotypical effect occurs among dual‐mutation carriers requires validation.ObjectiveThe objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single‐mutation presentation.MethodsPatients with PD were genotyped for the G2019S‐LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA‐PD, severe GBA‐PD, LRRK2‐PD, and LRRK2+GBA‐PD. Clinical symptoms were evaluated using performance‐based measures.ResultsA total of 1090 patients with idiopathic PD, 155 patients with LRRK2‐PD, 155 patients with mild GBA‐PD, 56 patients with severe GBA‐PD, and 27 patients with LRRK2+GBA‐PD participated in this study. The patients with LRRK2‐PD and LRRK2+GBA‐PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA‐PD.ConclusionsPatients with LRRK2+GBA‐PD were symptomatically similar to patients with LRRK2‐PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation. © 2020 International Parkinson and Movement Disorder Society
CCN6 mutation detection in Chinese patients with progressive pseudo‐rheumatoid dysplasia and identification of four novel mutations
Authors: Wang Yingjie , Xiao Ke , Yang Yuemei , Wu Zhihong , Jin Jin , Qiu Guixing , Weng Xisheng , Zhao Xiuli 
Published: April 2020

AbstractBackgroundNo formal diagnostic criteria for progressive pseudo‐rheumatoid dysplasia (PPD) are available because of insufficient clinical data, which results in that PPD is often misdiagnosed with other diseases. Whole exome sequencing (WES) and Sanger sequencing were employed to reveal the novel mutations on CCN6 of five patients with PPD from China in order to increase the clinical data of PPD.MethodsFour suspected PPD pedigrees containing five patients in total were collected from 1998 to 2018 in our medical center. The phenotypes of each suspected PPD case were recorded in detail, and peripheral blood samples were collected for subsequent sequencing. Genomic DNA was extracted from peripheral blood samples, and Agilent liquid phase chip capture system was utilized for efficient enrichment of whole exome region DNA. After acquiring raw sequenced reads of whole exome region, bioinformatics analysis was completed in conjunction with reference or genome sequence (GRCh37/hg19). Sanger sequencing was performed to identify the results of WES.ResultsIn total, four novel PPD‐related mutation sites in CCN6 gene were identified including (CCN6):c.643 + 2T>C, (CCN6):c.1064_1065dupGT(p.Gln356ValfsTer33), (CCN6):c.1064G > A), and exon4:c.670dupA:p.W223fs.ConclusionOur findings increase the clinical data of PPD including the CCN6 mutation spectrum, the clinical symptoms and signs. Moreover, the study highlights the utility of WES in reaching definitive diagnoses for PPD.
The Ability of Quercetin and Ferulic Acid to Lower Stored Fat is Dependent on the Metabolic Background of Human Adipocytes
Authors: Little Robert , Houghton Michael J. , Carr Ian M. , Wabitsch Martin , Kerimi Asimina , Williamson Gary 
Published: April 2020

ScopeDietary flavonoids and phenolic acids can modulate lipid metabolism, but effects on mature human adipocytes are not well characterized.Materials and methodsHuman adipocytes are differentiated, and contain accumulated lipids, mimicking white adipocytes. They are then cultured either under conditions of actively synthesizing and accumulating additional lipids through lipogenesis (“ongoing lipogenic state”) or under conditions of maintaining but not increasing stored lipids (“lipid storage state”). Total lipid, lipidomic and transcriptomics analyses are employed to assess changes after treatment with quercetin and/or ferulic acid.ResultsIn the “lipid storage state,” a longer‐term treatment (3 doses over 72 h) with low concentrations of quercetin and ferulic acid together significantly lowered stored lipid content, modified lipid composition, and modulated genes related to lipid metabolism with a strong implication of peroxisome proliferator‐activated receptor (PPARα)/retinoid X receptor (RXRα) involvement. In the “ongoing lipogenic state,” the effect of quercetin and ferulic acid is markedly different, with fewer changes in gene expression and lipid composition, and no detectable involvement of PPARα/RXRα, with a tenfold higher concentration required to attenuate stored lipid content.ConclusionsMultiple low‐dose treatment of quercetin and ferulic acid modulates lipid metabolism in adipocytes, but the effect is dramatically dependent on the metabolic state of the cell.
Circularly polarized microstrip Yagi antenna array with tilted beam for improved monopulse characteristics
Authors: Kong Deok Kyu , Woo Daewoong , Kim Jaesik , Yoon Young J. 
Published: April 2020

AbstractAn antenna array composed of four inclined microstrip Yagi antennas is proposed for a direction finding (DF) system operated in L band. Each element antenna is designed to have a tilted beam toward a central array axis in order to have high gain in the boresight axis of the antenna array. In comparison to a patch antenna array, having the same structure, antenna array gain is improved by a 2.3 dB maximum around the array axis, monopulse slope is increased by 72% and the linearity of the slope is improved significantly. Also, axial ratio is improved by 3 dB max within ±25° from boresight.
Association of Obesity with Disease Severity Among Patients with Coronavirus Disease 2019
Authors: Kalligeros Markos , Shehadeh Fadi , Mylona Evangelia K. , Benitez Gregorio , Beckwith Curt G. , Chan Philip A. , Mylonakis Eleftherios 
Published: April 2020

ObjectiveThe aim of this study was to explore the potential association of obesity and other chronic diseases with severe outcomes, such as intensive care unit (ICU) admission and invasive mechanical ventilation (IMV), in patients hospitalized with coronavirus disease 2019 (COVID‐19).MethodsThis study analyzed a retrospective cohort of 103 patients hospitalized with COVID‐19. Demographic data, past medical history, and hospital course were collected and analyzed. A multivariate logistic regression analysis was implemented to examine associations.ResultsFrom February 17 to April 5, 103 consecutive patients were hospitalized with COVID‐19. Among them, 44 patients (42.7%) were admitted to the ICU, and 29 (65.9%) required IMV. The prevalence of obesity was 47.5% (49 of 103). In a multivariate analysis, severe obesity (BMI ≥ 35 kg/m2) was associated with ICU admission (adjusted odds ratio [aOR]: 5.39, 95% CI: 1.13‐25.64). Moreover, patients who required IMV were more likely to have had heart disease (aOR: 3.41, 95% CI: 1.05‐11.06), obesity (BMI = 30‐34.9 kg/m2; aOR: 6.85, 95% CI: 1.05‐44.82), or severe obesity (BMI ≥ 35 kg/m2; aOR: 9.99, 95% CI: 1.39‐71.69).ConclusionsIn our analysis, severe obesity (BMI ≥ 35 kg/m2) was associated with ICU admission, whereas history of heart disease and obesity (BMI ≥ 30 kg/m2) were independently associated with the use of IMV. Increased vigilance and aggressive treatment of patients with obesity and COVID‐19 are warranted.
Explore and Exploit with Heterotic Line Bundle Models
Authors: Larfors M. , Schneider R. 
Published: April 2020

AbstractWe use deep reinforcement learning to explore a class of heterotic GUT models constructed from line bundle sums over Complete Intersection Calabi Yau (CICY) manifolds. We perform several experiments where A3C agents are trained to search for such models. These agents significantly outperform random exploration, in the most favourable settings by a factor of 1700 when it comes to finding unique models. Furthermore, we find evidence that the trained agents also outperform random walkers on new manifolds. We conclude that the agents detect hidden structures in the compactification data, which is partly of general nature. The experiments scale well with h(1, 1), and may thus provide the key to model building on CICYs with large h(1, 1).
Incorporating dynamic correlation into the variational determination method of the second‐order reduced density matrix in the doubly occupied configuration interaction space
Authors: Alcoba Diego R. , Torre Alicia , Lain Luis , Oña Ofelia B. , Ríos Elías , Massaccesi Gustavo E. 
Published: April 2020

AbstractThe variational determination of the second‐order reduced density matrices arising from N‐electron doubly occupied configuration interaction wave functions has recently been proposed as a method to describe systems possessing static correlation in their ground states. In this work, we propose to combine this approach with the on‐top pair density functional theory in order to incorporate dynamic correlations and improve the description of systems possessing both types of electron correlation. The procedure requires ensuring that the second‐order reduced density matrix elements satisfy determined N‐representability variational conditions, as well as other constraints arising from the doubly‐occupied configuration interaction wave function features. An analysis of the results obtained through this method, in studies of strongly correlated many‐electron systems, shows the usefulness of our proposals.
Fault‐tolerant control of singularly perturbed systems with actuator faults and disturbances
Authors: Yang Wu , Wang Yan‐Wu , Morˇrescu Irinel‐Constantin , Liu Zhi‐Wei , Huang Yuehua 
Published: April 2020

SummaryThe article proposes several fault‐tolerant control (FTC) laws for singularly perturbed systems (SPS) with actuator faults and disturbances. One of the main challenges in this context is that the fast‐slow decomposition is not available for actuator faults and disturbances. In view of this, some conditions for the asymptotic stability of the closed‐loop dynamics are investigated by amending the composite Lyapunov approach. On top of this, a closed‐form expression of the upper bound of singular perturbation parameter (SPP) is provided. Moreover, we design several SPP‐independent composite FTC laws, which can be applied when this parameter is unknown. Finally, the chattering phenomenon is eliminated by using the continuous approximation technique. We also emphasize that, for linear SPSs, the FTC design can be formulated as a set of linear matrix inequalities, while the SPP upper bound can be obtained by solving a convex optimization problem. Two numerical examples are given to illustrate the effectiveness of the proposed methodology.
Gradation effect of cleaned quarry waste to improve size distributions of concrete constituents
Authors: Gao Furong , Ji Yongsheng , Xue Qi , Xu Zhishan , Zhou Yangmei 
Published: April 2020

AbstractA specially designed cleaning system was adopted to wash away mud but keep coarse particles and stone powders in quarry waste. Then the cleaned quarry waste was used as concrete fine aggregate. Size distributions of all concrete constituents were analyzed, and workability and compressive strength of concrete were determined to evaluate gradation effect of cleaned quarry waste to improve size distributions of concrete constituents, thus improving concrete properties. Results showed that the designed cleaning system can wash away mud and keep stone powders and coarse particles in quarry waste. The particle sizes of stone powders were between 0.075 mm and 0.15 mm, and those of coarse particles were between 0.15 mm and 4.75 mm. When the cleaned quarry waste was used, continuous size distributions of all concrete constituents were formed, which solved discontinuous size distribution problems among cement, fine, and coarse aggregates. Therefore, concrete workability was improved and compressive strengths at different ages were increased.
Single‐molecule quantification of 5‐methylcytosine and 5‐hydroxymethylcytosine in cancer genome
Authors: Du Yang , Wang Yongyao , Hu Xiao , Liu Jiyan , Diao Jiajie 
Published: April 2020

AbstractEpigenetic modifications present a great influence on tumorigenesis, and have attracted a growing body of researchers’ interests. They deal with genomic information to regulate biological pathways related to tumorigenesis and cancer development, without changing the primary base sequence of DNA. As the most important epigenetic modifications, 5‐methylcytosine (5mC) and 5‐hydroxmethylcytosine (5hmC) are the ones most widely investigated in human cancers. To expand our understanding of the roles of 5mC and 5hmC in cancers, multiple methods have been developed to detect and quantify 5mC and 5hmC. While various detection methods having been reviewed, here we focus on ultrasensitive single‐molecule techniques used in quantifying 5mC and 5hmC, including nanopore sequencing, single‐molecule real‐time sequencing, optical mapping, and single‐molecule fluorescent imaging.
Bacterial Epigenomics: Epigenetics in the Age of Population Genomics
Authors: Chen Poyin , Bandoy D. J. Darwin , Weimer Bart C. 
Published: April 2020

AbstractGenome methylation in bacteria is an area of intense interest because it has broad implications for bacteriophage resistance, replication, genomic diversity via replication fidelity, response to stress, gene expression regulation, and virulence. Increasing interest in bacterial DNA modification is coming about with investigation of host/microbe interactions and the microbiome association and coevolution with the host organism. Since the recognition of DNA methylation being important in Escherichia coli and bacteriophage resistance using restriction/modification systems, more than 43,600 restriction enzymes have been cataloged in more than 3600 different bacteria. While DNA sequencing methods have made great advances there is a dearth of method advances to examine these modifications in situ. However, the large increase in whole genome sequences has led to advances in defining the modification status of single genomes as well as mining new restriction enzymes, methyltransferases, and modification motifs. These advances provide the basis for the study of pan-epigenomes, population-scale comparisons among pangenomes to link replication fidelity and methylation status along with mutational analysis of mutLS. Newer DNA sequencing methods that include SMRT and nanopore sequencing will aid the detection of DNA modifications on the ever-increasing whole genome and metagenome sequences that are being produced. As more sequences become available, larger analyses are being done to provide insight into the role and guidance of bacterial DNA modification to bacterial survival and physiology.
Eukaryotic Pangenomes
Authors: Richard Guy-Franck 
Published: April 2020

AbstractThe first eukaryotes emerged from their prokaryotic ancestors more than 1.5 billion years ago and rapidly spread over the planet, first in the ocean, later on as land animals, plants, and fungi. Taking advantage of an expanding genome complexity and flexibility, they invaded almost all known ecological niches, adapting their body plan, physiology, and metabolism to new environments. This increase in genome complexity came along with an increase in gene repertoire, mainly from molecular reassortment of existing protein domains, but sometimes from the capture of a piece of viral genome or of a transposon sequence. With increasing sequencing and computing powers, it has become possible to undertake deciphering eukaryotic genome contents to an unprecedented scale, collecting all genes belonging to a given species, aiming at compiling all essential and dispensable genes making eukaryotic life possible.In this chapter, eukaryotic core- and pangenomes concepts will be described, as well as notions of closed or open genomes. Among all eukaryotes presently sequenced, ascomycetous yeasts are arguably the most well-described clade and the pangenome of Saccharomyces cerevisiae, Candida glabrata, Candida albicans as well as Schizosaccharomyces species will be reviewed. For scientific and economical reasons, many plant genomes have been sequenced too and the gene content of soybean, cabbage, poplar, thale cress, rice, maize, and barley will be outlined. Planktonic life forms, such as Emiliana huxleyi, a chromalveolate or Micromonas pusilla, a green alga, will be detailed and their pangenomes pictured. Mechanisms generating genetic diversity, such as interspecific hybridization, whole-genome duplications, segmental duplications, horizontal gene transfer, and single-gene duplication will be depicted and exemplified. Finally, computing approaches used to calculate core- and pangenome contents will be briefly described, as well as possible future directions in eukaryotic comparative genomics.
Pangenomes and Selection: The Public Goods Hypothesis
Authors: McInerney James O. , Whelan Fiona J. , Domingo-Sananes Maria Rosa , McNally Alan , O’Connell Mary J. 
Published: April 2020

Abstract
The evolution and structure of prokaryotic genomes are largely shaped by horizontal gene transfer. This process is so prevalent that DNA can be seen as a public good—a resource that is shared across individuals, populations, and species. The consequence is a network of DNA sharing across prokaryotic life, whose extent is becoming apparent with increased availability of genomic data. Within prokaryotic species, gene gain (via horizontal gene transfer) and gene loss results in pangenomes, the complete set of genes that make up a species. Pangenomes include core genes present in all genomes, and accessory genes whose presence varies across strains. In this chapter, we discuss how we can understand pangenomes from a network perspective under the view of DNA as a public good, how pangenomes are maintained in terms of drift and selection, and how they may differ between prokaryotic groups. We argue that niche adaptation has a major impact on pangenome structure. We also discuss interactions between accessory genes within genomes, and introduce the concepts of ‘keystone genes’, whose loss leads to concurrent loss of other genes, and ‘event horizon genes’, whose acquisition may lead to adaptation to novel niches and towards a separate, irreversible evolutionary path.
Modelling 2018 Anak Krakatoa Flank Collapse and Tsunami: Effect of Landslide Failure Mechanism and Dynamics on Tsunami Generation
Authors: Zengaffinen Thomas , Løvholt Finn , Pedersen Geir Kleivstul , Muhari Abdul 
Published: April 2020

AbstractThe 2018 Anak Krakatoa volcano flank collapse generated a tsunami that impacted the Sunda Strait coastlines. In the absence of a tsunami early warning system, it caused several hundred fatalities. There are ongoing discussions to understand how the failure mechanism of this event affected landslide dynamics and tsunami generation. In this paper, the sensitivity to different failure scenarios on the tsunami generation is investigated through numerical modelling. To this end, the rate of mass release, the landslide volume, the material yield strength, and orientation of the landslide failure plane are varied to shed light on the failure mechanism, landslide evolution, and tsunami generation. We model the landslide dynamics using the depth-averaged viscoplastic flow model BingClaw, coupled with depth-averaged long wave and shallow water type models to simulated tsunami propagation. We are able to match fairly well the observed tsunami surface elevation amplitudes and inundation heights in selected area with the numerical simulations. However, as observed by other authors, discrepancies in simulated and observed arrival times for some of the offshore gauges are found, which raises questions related to the accuracy of the available bathymetry. For this purpose, further sensitivity studies changing the bathymetric depth near the source area are carried out. With this alteration we are also able to match better the arrival times of the waves.
Increased levels of inflammatory markers in the subscapularis tendon and joint capsule in patients with subacromial impingement
Authors: Farfaras Stefanos , Roshani Leyla , Mulder Jan , Mitsios Nicholas , Hallström Erling K. , Kartus Jüri-Toomas 
Published: April 2020

AbstractPurposeTo analyze biopsy samples from the subscapularis tendon and from the joint capsule from male patients with subacromial impingement syndrome and compare them with samples from male patients with post-traumatic recurrent shoulder instability, to detect increased inflammatory activity that might be present inside the humeroscapular joint.MethodsTwenty male patients scheduled for surgery for either subacromial decompression or Bankart reconstruction were included. Four biopsies from each patient were obtained during surgery from the capsule and the subscapularis tendon. Each specimen was analyzed for TNF-α, IL-6, CD-3 and CD-72. Multiplex fluorescence immunohistochemistry was performed on histological samples from the capsule and tendon to demonstrate the level of inflammatory markers. Fluorescence microscope images were acquired using an automated scanning system. On each slide, the number of pixels was registered and used in the analyses.ResultsThe subacromial impingement syndrome group comprised eight patients, median age 53 (45–74) years, while the instability group 12, median age 27 (22–48) years (p < 0.00001). The amount of IL-6 and TNF-α was significantly higher in the subscapularis tendon of the patients with subacromial impingement syndrome compared with instability patients (p = 0.0015 andp = 0.0008 respectively). In the capsular samples, significantly higher amount of TNF-α and CD-72 was found in patients with subacromial impingement syndrome compared with instability patients (p < 0.0001 for both). On the other hand, the amount of CD-3 was significantly higher in the instability group (p = 0.0013).ConclusionsThis study provides evidence that an extended inflammatory process is present, not only in the subacromial bursa but also in the glenohumeral joint in patients with subacromial impingement syndrome.Level of evidenceLevel III.Clinical relevanceTo develop a treatment targeted towards intra-articular inflammatory cytokines appears appealing.