A Hardware Efficient Random Number Generator for Nonuniform Distributions with Arbitrary Precision

Nonuniform random numbers are key for many technical applications, and designing efficient hardware implementations of non-uniform random number generators is a very active research field. However, most state-of-the-art architectures are either tailored to specific distributions or use up a lot of hardware resources. At ReConFig 2010, we have presented a new design that saves up to 48% of area compared to state-of-the-art inversion-based implementation, usable for arbitrary distributions and precision. In this paper, we introduce a more flexible version together with a refined segmentation scheme that allows to further reduce the approximation error significantly. We provide a free software tool allowing users to implement their own distributions easily, and we have tested our random number generator thoroughly by statistic analysis and two application tests

Erdbebenbeobachtung im Freistaat Sachsen : Dreijahresbericht

Der Bericht dokumentiert Ort, Datum, Magnitude und Tiefe der Erdbeben in Sachsen über einen Zeitraum von drei Jahren. Bei der Auswertung der Registrierungen werden zusätzlich zu den Online-Stationen des seismologischen Sachsennetzes auch die Stationen der Nachbarländer einbezogen, deren Standorte in der Veröffentlichung dargestellt sind. Ein besonderes Ereignis stellt dabei der Erdbebenschwarm von Oktober bis Dezember 2008 dar. Das Kapitel »Induzierte Seismizität« befasst sich mit den Untersuchungen zur bergbauinduzierten Seismizität der Uranerzgrube Schlema-Alberoda und zur Böschungsbewegung des ehemaligen Braunkohletagebaues Nachterstedt

Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development

12 pags., 4 figs., 3 tabs.SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome.Work at BMRZ is supported by the state of Hesse. Work in Covid19-NMR was supported by the Goethe Corona Funds, by the IWBEFRE-program 20007375 of state of Hesse, the DFG through CRC902: “Molecular Principles of RNA-based regulation.” and through infrastructure funds (project numbers: 277478796, 277479031, 392682309, 452632086, 70653611) and by European Union’s Horizon 2020 research and innovation program iNEXT-discovery under grant agreement No 871037. BY-COVID receives funding from the European Union’s Horizon Europe Research and Innovation Programme under grant agreement number 101046203. “INSPIRED” (MIS 5002550) project, implemented under the Action “Reinforcement of the Research and Innovation Infrastructure,” funded by the Operational Program “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and co-financed by Greece and the EU (European Regional Development Fund) and the FP7 REGPOT CT-2011-285950—“SEE-DRUG” project (purchase of UPAT’s 700 MHz NMR equipment). The support of the CERM/CIRMMP center of Instruct-ERIC is gratefully acknowledged. This work has been funded in part by a grant of the Italian Ministry of University and Research (FISR2020IP_02112, ID-COVID) and by Fondazione CR Firenze. A.S. is supported by the Deutsche Forschungsgemeinschaft [SFB902/B16, SCHL2062/2-1] and the Johanna Quandt Young Academy at Goethe [2019/AS01]. M.H. and C.F. thank SFB902 and the Stiftung Polytechnische Gesellschaft for the Scholarship. L.L. work was supported by the French National Research Agency (ANR, NMR-SCoV2-ORF8), the Fondation de la Recherche Médicale (FRM, NMR-SCoV2-ORF8), FINOVI and the IR-RMN-THC Fr3050 CNRS. Work at UConn Health was supported by grants from the US National Institutes of Health (R01 GM135592 to B.H., P41 GM111135 and R01 GM123249 to J.C.H.) and the US National Science Foundation (DBI 2030601 to J.C.H.). Latvian Council of Science Grant No. VPP-COVID-2020/1-0014. National Science Foundation EAGER MCB-2031269. This work was supported by the grant Krebsliga KFS-4903-08-2019 and SNF-311030_192646 to J.O. P.G. (ITMP) The EOSC Future project is co-funded by the European Union Horizon Programme call INFRAEOSC-03-2020—Grant Agreement Number 101017536. Open Access funding enabled and organized by Projekt DEALPeer reviewe

Aging and Chronic Sun Exposure Cause Distinct Epigenetic Changes in Human Skin

Epigenetic changes are widely considered to play an important role in aging, but experimental evidence to support this hypothesis has been scarce. We have used array-based analysis to determine genome-scale DNA methylation patterns from human skin samples and to investigate the effects of aging, chronic sun exposure, and tissue variation. Our results reveal a high degree of tissue specificity in the methylation patterns and also showed very little interindividual variation within tissues. Data stratification by age revealed that DNA from older individuals was characterized by a specific hypermethylation pattern affecting less than 1 % of the markers analyzed. Interestingly, stratification by sun exposure produced a fundamentally different pattern with a significant trend towards hypomethylation. Our results thus identify defined agerelated DNA methylation changes and suggest that these alterations might contribute to the phenotypic change

Erdbebenbeobachtung im Freistaat Sachsen : Dreijahresbericht

Der Bericht dokumentiert Ort, Datum, Magnitude und Tiefe der Erdbeben in Sachsen über einen Zeitraum von drei Jahren. Bei der Auswertung der Registrierungen werden zusätzlich zu den Online-Stationen des seismologischen Sachsennetzes auch die Stationen der Nachbarländer einbezogen, deren Standorte in der Veröffentlichung dargestellt sind. Ein besonderes Ereignis stellt dabei der Erdbebenschwarm von Oktober bis Dezember 2008 dar. Das Kapitel »Induzierte Seismizität« befasst sich mit den Untersuchungen zur bergbauinduzierten Seismizität der Uranerzgrube Schlema-Alberoda und zur Böschungsbewegung des ehemaligen Braunkohletagebaues Nachterstedt

CD4- and dynamin-dependent endocytosis of HIV-1 into plasmacytoid dendritic cells

AbstractChronic immune activation, triggered by plasmacytoid dendritic cell (PDC) interferon (IFN)-alpha production, plays an important role in HIV-1 pathogenesis. As the entry of HIV-1 seems to be important for the activation of PDC, we directly characterized the viral entry into these cells using immuno-electron microscopy, cellular fractionation, confocal imaging, and functional experiments. After attachment to PDC, viruses were taken up in an energy-dependent manner. The virions were located in compartments positive for caveolin; early endosomal antigen 1; Rab GTPases 5, 7 and 9; lysosomal-associated membrane protein 1. PDC harbored more virus in endocytic vesicles than CD4+ T cells (p<0.05). Blocking CD4 inhibited the uptake of virions into cytosolic and endosomal compartments. Dynasore, an inhibitor of dynamin-dependent endocytosis, not the fusion inhibitor T-20, reduced the HIV-1 induced IFN-alpha production. Altogether, our morphological and functional data support the role of endocytosis for the entry and IFN-alpha induction of HIV-1 in PDC

Erdbebenbeobachtung im Freistaat Sachsen : Dreijahresbericht

Der Bericht dokumentiert Ort, Datum, Magnitude und Tiefe der Erdbeben in Sachsen über einen Zeitraum von drei Jahren. Bei der Auswertung der Registrierungen werden zusätzlich zu den Online-Stationen des seismologischen Sachsennetzes auch die Stationen der Nachbarländer einbezogen, deren Standorte in der Veröffentlichung dargestellt sind. Ein besonderes Ereignis stellt dabei der Erdbebenschwarm von Oktober bis Dezember 2008 dar. Das Kapitel »Induzierte Seismizität« befasst sich mit den Untersuchungen zur bergbauinduzierten Seismizität der Uranerzgrube Schlema-Alberoda und zur Böschungsbewegung des ehemaligen Braunkohletagebaues Nachterstedt

Salt generates anti-inflammatory Th17 cells but amplifies their pathogenicity in pro-inflammatory cytokine microenvironments.

T helper cells integrate signals from their microenvironment to acquire distinct specialization programs for efficient clearance of diverse pathogens or for immunotolerance. Ionic signals have recently been demonstrated to affect T cell polarization and function. Sodium chloride (NaCl) was proposed to accumulate in peripheral tissues upon dietary intake and to promote autoimmunity via the Th17 cell axis. Here we demonstrate that high NaCl conditions induced a stable, pathogen-specific, anti-inflammatory Th17 cell fate in human T cells in vitro. The p38/MAPK pathway, involving NFAT5 and SGK1, regulated FoxP3 and interleukin (IL)-17A-expression in high-NaCl conditions. The NaCl-induced acquisition of an anti-inflammatory Th17 cell fate was confirmed in vivo in an experimental autoimmune encephalomyelitis (EAE) mouse model, which demonstrated strongly reduced disease symptoms upon transfer of T cells polarized in high NaCl conditions. However, NaCl was coopted to promote murine and human Th17 cell pathogenicity, if T cell stimulation occurred in a pro-inflammatory and TGF-β-low cytokine microenvironment. Taken together, our findings reveal a context-dependent, dichotomous role for NaCl in shaping Th17 cell pathogenicity. NaCl might therefore prove beneficial for the treatment of chronic inflammatory diseases in combination with cytokine-blocking drugs