90 research outputs found

    Geometry and Mechanics

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    IASS-IACM 2008 Session: Geometry and Mechanics -- Session Organizers: Kai-Uwe BLETZINGER (TU Munich), Fehmi CIRAK (University of Cambridge) -- Keynote Lecture: "Modeling and computation of patient-specific vascular fluid-structure interaction using Isogeometric Analysis" by Yuri BAZILEVS , Victor M. CALO, Thomas J. R. HUGHES (University of Texas at Austin), Yongie ZHANG (Carnegie Mellon University) -- Keynote Lecture: "Optimal shapes of mechanically motivated surfaces" by Kai-Uwe BLETZINGER , Matthias FIRL, Johannes LINHARD, Roland WUCHNER (TU Munich) -- "Subdivision shells for nonsmooth and branching geometries" by Quan LONG, Fehmi CIRAK (University of Cambridge) -- "Water landing analyses with explicit finite element method" by John T. WANG (NASA Langley Research Center) -- "On a geometrically exact contact description for shells: From linear approximations for shells to high-order FEM" by Alexander KONYUKHOV, Karl SCHWEIZERHOF (University of Karlsruhe

    Fibroblast Growth Factor-based Signaling through Synthetic Heparan Sulfate Blocks Copolymers Studied Using High Cell Density Three-dimensional Cell Printing

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    Four well-defined heparan sulfate (HS) block copolymers containing S-domains (high sulfo group content) placed adjacent to N-domains (low sulfo group content) were chemoenzymatically synthesized and characterized. The domain lengths in these HS block co-polymers were ∼40 saccharide units. Microtiter 96-well and three-dimensional cell-based microarray assays utilizing murine immortalized bone marrow (BaF3) cells were developed to evaluate the activity of these HS block co-polymers. Each recombinant BaF3 cell line expresses only a single type of fibroblast growth factor receptor (FGFR) but produces neither HS nor fibroblast growth factors (FGFs). In the presence of different FGFs, BaF3 cell proliferation showed clear differences for the four HS block co-polymers examined. These data were used to examine the two proposed signaling models, the symmetric FGF2-HS2-FGFR2 ternary complex model and the asymmetric FGF2-HS1-FGFR2 ternary complex model. In the symmetric FGF2-HS2-FGFR2 model, two acidic HS chains bind in a basic canyon located on the top face of the FGF2-FGFR2 protein complex. In this model the S-domains at the non-reducing ends of the two HS proteoglycan chains are proposed to interact with the FGF2-FGFR2 protein complex. In contrast, in the asymmetric FGF2-HS1-FGFR2 model, a single HS chain interacts with the FGF2-FGFR2 protein complex through a single S-domain that can be located at any position within an HS chain. Our data comparing a series of synthetically prepared HS block copolymers support a preference for the symmetric FGF2-HS2-FGFR2 ternary complex model

    The MECP2 TRD domain interacts with the DNMT3A ADD domain at the H3 tail binding site

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    The DNMT3A DNA methyltransferase and MECP2 methylation reader are highly expressed in neurons. Both proteins interact via their DNMT3A ADD and MECP2 TRD domains, and the MECP2 interaction regulates the activity and subnuclear localization of DNMT3A. Here, we mapped the interface of both domains using peptide SPOT array binding, protein pull down, equilibrium peptide binding assays, and structural analyses. The region D529 D531 on the surface of the ADD domain was identified as interaction point with the TRD domain. This includes important residues of the histone H3 N terminal tail binding site to the ADD domain, explaining why TRD and H3 binding to the ADD domain is competitive. On the TRD domain, residues 214 228 containing K219 and K223 were found to be essential for the ADD interaction. This part represents a folded patch within the otherwise largely disordered TRD domain. A crystal structure analysis of ADD revealed that the identified H3 TDR lysine binding pocket is occupied by an arginine residue from a crystallographic neighbor in the ADD apoprotein structure. Finally, we show that mutations in the interface of ADD and TRD domains disrupt the cellular interaction of both proteins in NIH3T3 cells. In summary, our data show that the H3 peptide binding cleft of the ADD domain also mediates the interaction with the MECP2 TRD domain suggesting that this binding site may have a broader role also in the interaction of DNMT3A with other proteins leading to complex regulation options by competitive and PTM specific bindin

    Unexpected Course of Nonlinear Cardiac Interbeat Interval Dynamics during Childhood and Adolescence

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    The fluctuations of the cardiac interbeat series contain rich information because they reflect variations of other functions on different time scales (e.g., respiration or blood pressure control). Nonlinear measures such as complexity and fractal scaling properties derived from 24 h heart rate dynamics of healthy subjects vary from childhood to old age. In this study, the age-related variations during childhood and adolescence were addressed. In particular, the cardiac interbeat interval series was quantified with respect to complexity and fractal scaling properties. The R-R interval series of 409 healthy children and adolescents (age range: 1 to 22 years, 220 females) was analyzed with respect to complexity (Approximate Entropy, ApEn) and fractal scaling properties on three time scales: long-term (slope β of the power spectrum, log power vs. log frequency, in the frequency range 10−4 to 10−2 Hz) intermediate-term (DFA, detrended fluctuation analysis, α2) and short-term (DFA α1). Unexpectedly, during age 7 to 13 years β and ApEn were higher compared to the age <7 years and age >13 years (β: −1.06 vs. −1.21; ApEn: 0.88 vs. 0.74). Hence, the heart rate dynamics were closer to a 1/f power law and most complex between 7 and 13 years. However, DFA α1 and α2 increased with progressing age similar to measures reflecting linear properties. In conclusion, the course of long-term fractal scaling properties and complexity of heart rate dynamics during childhood and adolescence indicates that these measures reflect complex changes possibly linked to hormonal changes during pre-puberty and puberty

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

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    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

    Note sur la répartition des groupes sanguins AB, A, B et O dans divers groupes ethniques de l'Afrique Occidentale Française

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    Koerber R., Linhard J. Note sur la répartition des groupes sanguins AB, A, B et O dans divers groupes ethniques de l'Afrique Occidentale Française. In: Bulletins et Mémoires de la Société d'anthropologie de Paris, X° Série. Tome 2 fascicule 4-6, 1951. pp. 158-160

    Les groupes d'haptoglobine, moyen d'étude des populations humaines.

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    Moullec J., Fine J.-M., Linhard J. Les groupes d'haptoglobine, moyen d'étude des populations humaines.. In: Bulletins et Mémoires de la Société d'anthropologie de Paris, XI° Série. Tome 2 fascicule 1, 1961. pp. 109-124

    Phénotypes des isozymes érythrocytaires, phosphatase acide, phosphoglucomutase, adélynate kinase, adénosine désaminase, dans un échantillon de population de Dakar (Sénégal)

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    Summary. Red cell isozyme phenotypes were studied on a sample of 270 Negro blood donors living in the district of Dakar (Senegal). The gene frequencies were : — acid phosphatase : Pa 0.1963 ; Pb 0.7796 ; Pc 0.0037 ; Pr 0.0204 ; — Phosphoglucomutase : PGM\ 0.1944 ; — adenylate kinase : AK2 absent ; — adenosine deaminase : ADA2 absent (200 blood samples tested). Heterogeneity is suggested between ethnic groups, in the acid phospatase system.Résumé. Nous avons examiné un échantillon de 270 sujets sénégalais, non apparentés. Les fréquences observées pour les gènes des quatre systèmes étudiés sont : — phosphatase acide : Pa 0,1963 ; Pb 0,7796 ; Pc 0,0037 ; Pr 0,0204 ; — phosphoglucomutase : PGM2 0,1944 ; — adénylate kinase : absence de AK2 ; — adénosine désaminase : absence de ADA2 (200 échantillons). Une hétérogénéité tend à se manifester entre les divers groupes ethniques, particulièrement dans le système de phosphatase acide. Elle devra être confirmée sur un effectif plus important.Raymondjean M., Raymondjean Noémie, Diebolt Georgette, Linhard J., Moullec J. Phénotypes des isozymes érythrocytaires, phosphatase acide, phosphoglucomutase, adélynate kinase, adénosine désaminase, dans un échantillon de population de Dakar (Sénégal). In: Bulletins et Mémoires de la Société d'anthropologie de Paris, XIII° Série. Tome 2 fascicule 1, 1975. pp. 17-21
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