12,530 research outputs found
Merrell v. Chartiers Valley School District, 855 A.2d 713 (Pa. S. Ct. 2004)
No full textCiting H. Richard Uviller & William G. Merkel, The Second Amendment in Context: The Case of the Vanishing Predicate, 76 CHI.-KENT L.REV. 403 (2000). Merrell v. Chartiers Valley School Dist., 855 A.2d 713 (Pa. Super. Ct. 2004
Oncogenic Merkel Cell Polyomavirus T Antigen Truncating Mutations are Mediated by APOBEC3 Activity in Merkel Cell Carcinoma
No full textMerkel cell carcinoma (MCC) is an aggressive skin cancer, which is frequently caused by Merkel cell polyomavirus (MCPyV). Mutations of MCPyV tumor (T) antigens are major pathologic events of virus-positive (MCPyV+) MCCs, but their source is unclear. Activation-induced cytidine deaminase (AID)/APOBEC family cytidine deaminases contribute to antiviral immunity by mutating viral genomes and are potential carcinogenic mutators. We studied the contribution of AID/APOBEC cytidine deaminases to MCPyV large T (LT) truncation events. The MCPyV LT area in MCCs was enriched with cytosine-targeting mutations, and a strong APOBEC3 mutation signature was observed in MCC sequences. AICDA and APOBEC3 expression were detected in the Finnish MCC sample cohort, and LT expression correlated with APOBEC3H and APOBEC3G. Marginal but statistically significant somatic hypermutation targeting activity was detected in the MCPyV regulatory region. Our results suggest that APOBEC3 cytidine deaminases are a plausible cause of the LT truncating mutations in MCPyV+ MCC, while the role of AID in MCC carcinogenesis is unlikely.</p
Current status of outcome measure development for clinical trials in systemic sclerosis. Report from OMERACT 6
No full textPolitical leadership under Angela Merkel
No full textTo magistrsko delo se posveča raziskovanju političnega vodenja. Natančneje naloga razišče stil vodenja nemške kanclerke Angele Merkel. Vodilno vprašanje naloge želi odgovorit na vprašanje, kaj je tisto kar definira Merkel kot voditelja. Pri čemer se naslednjo vprašanje posvečajo bolj globljemu razumevanju edinstvenosti njenega stila vodenja. Za ta namen naloga razvije celovit teoretski okvir, s katerim razloži vse relevantne koncepte. Nato pa se v sledečih poglavjih posveti semi-časovnemu pregledu njene politične kariere in njenih dosežkov. Vse od njenih začetkov v politiki, do reševanja evro krize in migrantske krize, ustvarimo slikovit prikaz njene kariere. Nato skozi metodološki okvir meta-analize opravimo pregled preučevanja njene kariere in kasneje postavimo lastno reinterpretacijo njenega stila vodenja. Kot slednje predstavimo svoje ugotovitve in odgovore na raziskovalna vprašanja.The thesis addresses the issue of political leadership. In particular, it examines the leadership style of the German chancellor Angela Merkel. The leading question the thesis aims to answer is what defines Merkel as a leader? Whereby the next questions demand a deeper understanding of the uniqueness of her leadership style. For this purpose, the thesis establishes a comprehensive theoretical framework in where all relevant concepts are explained. Afterwards the following chapters of the research are dedicated to an semi-chronological overview of her political career and its accomplishments. All the way from her starts in politics to the developments of the euro crisis and migration crisis, we establish a pictures overview of her defining moments. Through an methodological framework of an meta-analysis, the paper then evaluates contemporary leadership research of the chancellor and later establishes an comprehensive reinterpretation of her leadership style. Finally, the findings are presented in the concluding parts, where the research question receive their deserving attention
Characteristics of PA cost-effectiveness studies by the first author, setting, number of PAs & design.
No full textCharacteristics of PA cost-effectiveness studies by the first author, setting, number of PAs & design.</p
South African responses to Open Access publishing: a survey of the research community
No full textOpen access publishing offers wide benefits to the scholarly community and may also afford relief to financially embattled academic libraries. The progress of the open access model rests upon the acceptance and validation of open access journals and open archives or institutional repositories by the academic mainstream, particularly by publishing researchers. To what extent are the key actors in the South African research system aware of the advantages of open access? This article reports on the findings of a recent survey undertaken to assess the current awareness, concerns and depth of support for open access amongst local researchers, research managers and policy makers in South Africa. The study focuses on issues of quality, article or author charges and the established academic reward system. It concludes that within the prevailing framework, there is little prospect that academics would choose to publish within open access
journals. Recommendations for advocacy by the library community are proposed
Human digital merkel cells display pannexin1 immunoreactivity
No full textThis study was supported in part by a grant from Gerencia Regional de Salud de Castilla y León to JF and JAV (GRS 1882/A/18). Y. G-M. was supported by a Grant "Severo Ochoa Program" from the Govern of the Principality of Asturias (PA-18-PF-BP17-044)
Abstract 1375: Paranuclear retention of c-KIT by Merkel cell polyomavirus large T-antigen suppresses autophagy through interaction with Beclin 1 essential for Merkel cell carcinoma cell survival
No full textAbstract Merkel cell carcinoma (MCC) is a very aggressive skin cancer most commonly caused by Merkel cell polyomavirus (MCPyV). While the strong expression of the human proto-oncogene c-KIT in MCC is well established, the functional relevance of this expression is unknown. Here, we demonstrate that paranuclear presence of c-KIT suppresses autophagy which is essential for maintenance of MCC cells. Specifically, after its phosphorylation, c-KIT traffics by clathrin-dependent endocytosis to late endosomes where it is sequestered in the paranuclear compartment by the MCPyV-encoded large transforming antigen (LT) via its Vam6p binding site, which also blocks c-KIT's lysosomal degradation. In this paranuclear compartment, c-KIT interacts directly with both the BH3 and the evolutionarily conserved domain (ECD) of Beclin 1, decreasing its binding to VPS34 and increasing its binding to BCL2, resulting in suppression of autophagy. Indeed, silencing of c-KIT induces autophagy and apoptosis in MCPyV-positive MCC cell lines. It is noteworthy that the positive feedback loop of LT and c-KIT also applies in the reverse direction, as LT is degraded via autophagy. This notion explains why an autophagy-inducing peptide efficiently induces apoptosis-independent cell death and inhibits tumor growth of MCC xenografts in mice. In conclusion, we identified a novel mechanism of MCPyV LT to suppress autophagy through sequestering and stabilizing c-KIT in the paranuclear compartment, which is mandatory to maintain the oncogenic phenotype of MCC cells. Autophagy-inducing agents therefore represent a therapeutic strategy for patients with advanced MCPyV-associated MCC. Citation Format: Hao Shi, Yajie Yang, Catharina Larsson, Weng-Onn Lui. Paranuclear retention of c-KIT by Merkel cell polyomavirus large T-antigen suppresses autophagy through interaction with Beclin 1 essential for Merkel cell carcinoma cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1375
Author Co-Citation Analysis (ACA): a powerful tool for representing implicit knowledge of scholar knowledge workers
No full textIn the last decade, knowledge has emerged as one of the most important and valuable organizational assets. Gradually this importance caused to emergence of new discipline entitled ―knowledge management‖. However one of the major challenges of knowledge management is conversion implicit or tacit knowledge to explicit knowledge. Thus Making knowledge visible so that it can be better accessed, discussed, valued or generally managed is a long-standing objective in knowledge management. Accordingly in this paper author co- citation analysis (ACA) will be proposed as an efficient technique of knowledge visualization in academia (Scholar knowledge workers)
Relative (pa,pb,pa,pa−b)-difference sets in p-subgroups of SL(n,K)
No full textAbstractIn this note, we study relative (pa,pb,pa,pa−b)-relative difference sets in certain p-subgroups of SL(n,K), K=Fq, where q is a prime power
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