3,121 research outputs found

    EpiScanpy: integrated single-cell epigenomic analysis

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    EpiScanpy is a toolkit for the analysis of single-cell epigenomic data, namely single-cell DNA methylation and single-cell ATAC-seq data. To address the modality specific challenges from epigenomics data, epiScanpy quantifies the epigenome using multiple feature space constructions and builds a nearest neighbour graph using epigenomic distance between cells. EpiScanpy makes the many existing scRNA-seq workflows from scanpy available to large-scale single-cell data from other -omics modalities, including methods for common clustering, dimension reduction, cell type identification and trajectory learning techniques, as well as an atlas integration tool for scATAC-seq datasets. The toolkit also features numerous useful downstream functions, such as differential methylation and differential openness calling, mapping epigenomic features of interest to their nearest gene, or constructing gene activity matrices using chromatin openness. We successfully benchmark epiScanpy against other scATAC-seq analysis tools and show its outperformance at discriminating cell types. The authors present epiScanpy: a computational framework for the analysis of single-cell epigenomic data, both ATAC-seq and DNA methylation data, with examples for clustering, cell type identification, trajectory learning and atlas integration - and show its performance in distinguishing cell types

    Targeting of RET oncogene by naphthalene diimide-mediated gene promoter G-quadruplex stabilization exerts anti-tumor activity in oncogene-addicted human medullary thyroid cancer

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    Medullary thyroid cancer (MTC) relies on the aberrant activation of RET proto-oncogene. Though targeted approaches (i.e., tyrosine kinase inhibitors) are available, the absence of complete responses and the onset of resistance mechanisms indicate the need for novel therapeutic interventions. Due to their role in regulation of gene expression, G-quadruplexes (G4) represent attractive targets amenable to be recognized or stabilized by small molecules. Here, we report that exposure of MTC cells to a tri-substituted naphthalene diimide (NDI) resulted in a significant antiproliferative activity paralleled by inhibition of RET expression. Biophysical analysis and gene reporter assays showed that impairment of RET expression was consequent to the NDI-mediated stabilization of the G4 forming within the gene promoter. We also showed for the first time that systemic administration of the NDI in mice xenotransplanted with MTC cells resulted in a remarkable inhibition of tumor growth in vivo. Overall, our findings indicate that NDI-dependent RET G4 stabilization represents a suitable approach to control RET transcription and delineate the rationale for the development of G4 stabilizing-based treatments for MTC as well as for other tumors in which RET may have functional and therapeutic implications

    The Grizzly, October 3, 1986

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    Berman Collection • Former Phila. Cop Anchors Security Force • Letters: Not Ones to Dampen Festive Spirits; What is this thing?; It\u27s Aluminating! • Not a Dichotomous Community • Temple Fires Conversation Perhaps More Than Unger Imagined • Grizzlies Pound Green Terrors • Hockey Upsets Temple, Falls to Lock Haven • Nolan Institutes In-Service RA Training • Soccer: Bears Choose Tri-Captains • Parker Parked in Injury Garage • Athlete of the Week: Schoenherr Shows her Stuff • Resume Workshophttps://digitalcommons.ursinus.edu/grizzlynews/1170/thumbnail.jp

    Mapping the evidence regarding school-to-work/university transition and health inequalities among young adults: a scoping review protocol

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    Introduction School-to-work/university transition is a sensitive period that can have a substantial impact on health and health behaviour over the life course. There is some indication that health and health behaviour is socially patterned in the age span of individuals in this transition (16–24 years) and that there are differences by socioeconomic position (SEP). However, evidence regarding this phenomenon has not been systematically mapped. In addition, little is known about the role of institutional characteristics (eg, of universities, workplaces) in the development of health and possible inequalities in health during this transition. Hence, the first objective of this scoping review is to systematically map the existing evidence regarding health and health behaviours (and possible health inequalities, for example, differences by SEP) in the age group of 16–24 years and during school-to-work transition noted in Germany and abroad. The second objective is to summarise the evidence on the potential effects of contextual and compositional characteristics of specific institutions entered during this life stage on health and health behaviours. Third, indicators and measures of these characteristics will be summarised. Methods and analysis We will systematically map the evidence on health inequalities during school-to-work-transitions among young adults (aged 16–24 years), following the methodological framework proposed by Arksey and O’Malley. The literature search is performed in Ovid MEDLINE, Web of Science, International Labour Organization and National Institute for Occupational Safety and Health, using a predetermined search strategy. Articles published between January 2000 and February 2020 in English or German are considered for the review. The selection process follows a two-step approach: (1) screening of titles and abstracts, and (2) screening of full texts, both steps by two independent reviewers. Any discrepancies in the selection process are resolved by a third researcher. Data extraction will be performed using a customised data extraction sheet. The results will be presented in tabular and narrative form. Ethics and dissemination Ethical approval is not required for this scoping review. The results will be published in a peer-reviewed scientific journal and presented at international conferences and project workshops.Peer Reviewe

    The Grizzly, October 3, 1986

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    Berman Collection • Former Phila. Cop Anchors Security Force • Letters: Not Ones to Dampen Festive Spirits; What is this thing?; It\u27s Aluminating! • Not a Dichotomous Community • Temple Fires Conversation Perhaps More Than Unger Imagined • Grizzlies Pound Green Terrors • Hockey Upsets Temple, Falls to Lock Haven • Nolan Institutes In-Service RA Training • Soccer: Bears Choose Tri-Captains • Parker Parked in Injury Garage • Athlete of the Week: Schoenherr Shows her Stuff • Resume Workshophttps://digitalcommons.ursinus.edu/grizzlynews/1170/thumbnail.jp

    The Grizzly, September 26, 1986

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    Mary Ann Unger\u27s Temple is the Gift of Muriel and Philip I. Berman • Kane Evaluates Alcohol Policy • Myrin Hires $20,000 Security Guard • Going a Little Haywire • Letters: Majestically situated?; My Hey Echoes • Bears Buried in Season Opener Against Franklin & Marshall • Lady Bears Fight to 2-2 • Booters Jump to 4-1 • Trauger Sweeps Up Her Opponents • Blowing the Call • Grizzly Captains • Athlete of the Week: Gwen O\u27Donohue • Bio Head Makes Small Move from Dean\u27s Office to Laboratories • Tim Ail Becomes New Food Director • Education Moveshttps://digitalcommons.ursinus.edu/grizzlynews/1169/thumbnail.jp

    Oscillations and interactions of dark and dark-bright solitons in Bose-Einstein condensates

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    Solitons are among the most distinguishing fundamental excitations in a wide range of non-linear systems such as water in narrow channels, high speed optical communication, molecular biology and astrophysics. Stabilized by a balance between spreading and focusing, solitons are wavepackets, which share some exceptional generic features like form-stability and particle-like properties. Ultra-cold quantum gases represent very pure and well-controlled non-linear systems, therefore offering unique possibilities to study soliton dynamics. Here we report on the first observation of long-lived dark and dark-bright solitons with lifetimes of up to several seconds as well as their dynamics in highly stable optically trapped 87^{87}Rb Bose-Einstein condensates. In particular, our detailed studies of dark and dark-bright soliton oscillations reveal the particle-like nature of these collective excitations for the first time. In addition, we discuss the collision between these two types of solitary excitations in Bose-Einstein condensates.Comment: 9 pages, 4 figure

    The Grizzly, September 19, 1986

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    Case\u27s Open: Kegs Closed • An Important Issue: Campus Counseling • Psych 428: Raising Patients\u27 Confidences • The Temple of Art • Letters: Is This the Way it\u27s Supposed to be?; In the Pen With an Itchy Pen • Commending Some Fine Counseling • Alcohol Opinions • Musser Hall: Not Just AC and HBO • Dr. Ken Nelson Meets Students\u27 Needs • Coming to Grips with U.C. • Staging a Revival of Sorts • Soccer Season Starts • Field Hockey Falls to Delaware • Cross-Country Team Successful at Lebanon Valley • U.C. Goes 2-2https://digitalcommons.ursinus.edu/grizzlynews/1168/thumbnail.jp

    The VMC survey - XVII : The proper motions of the Small Magellanic Cloud and the Milky Way globular cluster 47 Tucanae

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    In this study we use multi-epoch near-infrared observations from the VISTA survey of the Magellanic Cloud system (VMC) to measure the proper motion of different stellar populations in a tile of 1.5 deg sq. in size in the direction of the Galactic globular cluster 47 Tuc. We obtain the proper motion of the cluster itself, of the Small Magellanic Cloud (SMC), and of the field Milky Way stars. Stars of the three main stellar components are selected from their spatial distribution and their distribution in colour-magnitude diagrams. Their average coordinate displacement is computed from the difference between multiple Ks-band observations for stars as faint as Ks=19 mag. Proper motions are derived from the slope of the best-fitting line among 10 VMC epochs over a time baseline of ~1 yr. Background galaxies are used to calibrate the absolute astrometric reference frame. The resulting absolute proper motion of 47 Tuc is (mu_alpha cos(delta), mu_delta)=(+7.26+/-0.03, -1.25+/-0.03) mas/yr. This measurement refers to about 35000 sources distributed between 10 and 60 arcmin from the cluster centre. For the SMC we obtain (mu_alpha cos(delta), mu_delta)=(+1.16+/-0.07, -0.81+/-0.07) mas/yr from about 5250 red clump and red giant branch stars. The absolute proper motion of the Milky Way population in the line-of-sight (l =305.9, b =-44.9) of this VISTA tile is (mu_alpha cos(delta), mu_delta)=(+10.22+/-0.14, -1.27+/-0.12) mas/yr and results from about 4000 sources. Systematic uncertainties associated to the astrometric reference system are 0.18 mas/yr. Thanks to the proper motion we detect 47 Tuc stars beyond its tidal radius.Peer reviewe

    Primary tooth abscess caused by Mycobacterium bovis in an immunocompetent child

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    Bovine tuberculosis is a zoonotic disease, and although its incidence has dramatically decreased in developed countries where effective control measures are applied, it still remains a potential health hazard in the developing world. Tuberculosis of the oral cavity is extremely rare and is usually secondary to pulmonary involvement. We present the unusual case of an immunocompetent 6-year-old child residing in an urban area with primary oral tuberculosis due to Mycobacterium bovis, which was confirmed by the application of a molecular genetic approach. M. bovis belongs to Mycobacterium tuberculosis complex which comprises species with close genetic relationship, and for this reason, the use of new molecular techniques is a useful tool for the differentiation at species level of the closely related members of this complex
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