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Two hits a.e better tha. one:ra.iona. dua. stra.egy efficiently fights neurobla.toma

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Signa. Tra.sduction a.d Ta.geted Thera.y 2024年第5期9卷 1802-1804页

作者： Ja.ques Zimmer Ca.ille Rolin markus Ollert Depa.tment of Infection a.d Immunity Luxembourg Institute of HealthEsch-sur-AlzetteLuxembourg University of Luxembourg Esch-sur-AlzetteLuxembourg Depa.tment of Derma.ology a.d a.lergy Center Odense Research Center for Anaphylaxis(ORCA)University of Southern DenmarkOdenseDenmark

The recently published la.dma.k pa.er by Berga.gio et *** Roberto Chia.le’s group in Ca.cer Cell1 investiga.es a. elega.t double-hit stra.egy to improve a.ti-ca.cer *** importa.t a.proa.h demonstra.es in a.preclinica. model tha. chimeric a.tigen receptor(Ca.)-T cell trea.ment ca. be rendered more efficient by increa.ing the cell surfa.e expression of the Ca. ta.get structure via.a.sma.l molecule.

关键词： neurobla.toma Ca.cer

Linking IL-10 signa.ing with lipid meta.olic progra.s in ma.ropha.es:dysregula.ed cera.ide homeosta.is drives colitis

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Signa. Tra.sduction a.d Ta.geted Thera.y 2024年第7期9卷 2835-2836页

作者： Imke a.reya.markus F.Neura.h Depa.tment of Medicine 1 University Hospital of ErlangenFriedrich-Alexander University Erlangen-NürnbergErlangenGermany Deutsches Zentrum Immunthera.ie(DZI) ErlangenGermany

In a.recent study published in Na.ure,York a.d coworkers identified the immunometa.olic regula.ion of mono-unsa.ura.ed fa.ty a.id(MUFa.pools a.d the subsequent increa.e in sphingolipid biosynthesis in TLR2-a.tiva.ed ma.ropha.es a. a. importa.t link between impa.red IL-10 signa.ing a.d the development of intestina. infla.ma.ion.1 Thus,ta.geted interference with the newly identified IL-10/MUFa.sphingolipid a.is a.pea.s a. a.promising stra.egy to restore immunometa.olic homeosta.is in the intestine of pa.ients with infla.ma.ory bowel disea.es(IBD).

关键词： homeosta.is impa.red intestine

Structure of serotonin receptors:molecula. underpinning of receptor a.tiva.ion a.d modula.ion

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Signa. Tra.sduction a.d Ta.geted Thera.y 2021年第7期6卷 1950-1952页

作者： markus Zweckstetter a.exa.der Ditya.ev Evgeni Ponima.kin Tra.sla.iona. Structura. Biology Group German Center for Neurodegenerative Diseases(DZNE)GottingenGermany Depa.tment for NMR-ba.ed Structura. Biology Max Planck Institute for Biophysical ChemistryGottingenGermany Molecula. Neuropla.ticity Group German Center for Neurodegenerative Diseases(DZNE)MagdeburgGermany Medica. Fa.ulty Otto-von-Guericke UniversityMagdeburgGermany Center for Beha.iora. Bra.n Sciences(CBBS) MagdeburgGermany Depa.tment of Cellula. Neurophysiology Hannover Medical SchoolHannoverGermany

The structura. ba.is of the regula.ion of serotonin(5-hydroxy-trypta.ine,5-HT)receptors by liga.ds a.d lipids is only emerging.a.recent study by Xu a.d collea.ues1 published in Na.ure a.dresses this issue by resolving five structures of 5-HT;receptor-G protein *** include 5-HT1a.in the a.osta.e,*** bound to a.liga.d,5-HT1a.a.d 5-HT1D bound to serotonin or the a.ypica. a.tipsychotic a.ipipra.ole(for 5-HT1a.,a.d 5-HT1E bound to its selective a.onist BRL-54443.

关键词： serotonin lipids a.ypica.

a.plica.ion of semi-a.a.ytica. finite element method to a.a.yze the bea.ing ca.a.ity of a.pha.t pa.ements under moving loa.s

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Frontiers of Structura. a.d Civil Engineering 2018年第2期12卷 215-221页

作者： Pengfei LIU Da.ei Wa.G Frederic OTTO markus OESER Institute of Highwa. Engineering RWTH Aachen University Aachen D52074 Germany

To fa.ilita.e long term infra.tructure a.set ma.a.ement systems, it is necessa.y to determine the bea.ing ca.a.ity of pa.ements. Currently it is common to conduct such mea.urements in a.sta.iona.y ma.ner, however the eva.ua.ion with sta.iona.y loa.ing does not correspond to rea.ity a.tendency towa.ds continuous a.d high speed mea.urements in recent yea.s ca. be observed. The computa.iona. progra. Sa.EM wa. developed with the objective of eva.ua.ing the dyna.ic response of a.pha.t under moving loa.s a.d is ba.ed on a.semi-a.a.ytic element method. In this resea.ch project Sa.EM is compa.ed to commercia. finite element softwa.e a.a.US a.d field mea.urements to verify the computa.iona. a.cura.y. The computa.iona. a.cura.y of Sa.EM wa. found to be high enough to be via.le whilst boa.ting a.computa.iona. time fa. shorter tha. a.a.US. Thus, Sa.EM a.pea.s to be a.fea.ible a.proa.h to determine the dyna.ic response of pa.ements under dyna.ic loa.s a.d is a.useful tool for infra.tructure a.ministra.ions to a.a.yze the pa.ement bea.ing ca.a.ity.

关键词： semi-a.a.ytica. finite element method bea.ing ca.a.ity a.pha.t pa.ements moving loa.s dyna.ic response

Compressive deforma.ion of ultra.ong a.yloid fibrils

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a.ta.Mecha.ica.Sinica 2010年第6期26卷 977-986页

作者： Ra.fa.lla.Pa.a.cone Steven Cra.ford markus J.Buehler La.ora.ory for a.omistic a.d Molecula. Mecha.ics

Involved in va.ious neurodegenera.ive disea.es, a.yloid fibrils a.d pla.ues fea.ure a.hiera.chica. structure, ra.ging from the a.omistic to the micrometer *** the a.omistic level,a.dense a.d orga.ized hydrogen bond network is resembled in a.beta.sheet rich seconda.y structure, which drives a.rema.ka.le stiffness in the ra.ge of 10-20GPa.la.ger tha. ma.y other biologica. na.ofibrils, a.result confirmed by both experiment a.d ***, the understa.ding of how these exceptiona. mecha.ica. properties tra.sfer from the a.omistic to the na.osca.e rema.ns *** we report a.multisca.e a.a.ysis tha., from the a.omistic-level structure of a.single fibril,extends to the mesosca.e level,rea.hing size sca.es of hundreds of *** use pa.a.eters directly derived from full a.omistic simula.ions of a.（1-40） a.yloid fibrils to pa.a.eterize a.mesoscopic coa.se-gra.ned model,which is used to reproduce the ela.tic properties of a.yloid *** then a.ply our mesoscopic model in a. a.a.ysis of the buckling beha.ior of a.yloid fibrils with different lengths a.d report a.compa.ison with predictions from continuum bea. theory. a. importa.t implica.ion of our results is a.severe reduction of the effective modulus due to buckling,a. effect tha. could be importa.t to interpret experimenta. results of ultra.ong a.yloid *** model represents a.powerful tool to mecha.ica.ly cha.a.terize molecula. structures on the order of hundreds of na.ometers to micrometers on the ba.is of the underlying a.omistic *** work provides insight into structura. a.d mecha.ica. properties of a.yloid fibrils a.d ma. ena.le further a.a.ysis of la.ger-sca.e a.semblies such a. a.yloidogenic bundles or pla.ues a. found in disea.e sta.es.

关键词： a.yloid Coa.se-gra.n Molecula. simula.ion Na.omecha.ics Ma.eriomics

Va.ida.ing neura. networks for spectroscopic cla.sifica.ion on a.universa. synthetic da.a.et

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npj Computa.iona. Ma.eria.s 2023年第1期9卷 1325-1336页

作者： Ja. Schuetzke Na.ha. J.Szyma.ski markus Reischl Institute for a.toma.ion a.d a.plied Informa.ics Karlsruhe Institute of TechnologyKarlsruhe 76131Germany Depa.tment of Ma.eria.s Science&Engineering Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Depa.tment of Ma.eria.s Science&Engineering UC BerkeleyBerkeleyCA 94720USA

To a.d the development of ma.hine lea.ning models for a.toma.ed spectroscopic da.a.cla.sifica.ion,we crea.ed a.universa. synthetic da.a.et for the va.ida.ion of their *** da.a.et mimics the cha.a.teristic a.pea.a.ce of experimenta. mea.urements from techniques such a. X-ra. diffra.tion,nuclea. ma.netic resona.ce,a.d Ra.a. spectroscopy a.ong *** a.plied eight neura. network a.chitectures to cla.sify a.tificia. spectra.eva.ua.ing their a.ility to ha.dle common experimenta. *** a.l models a.hieved over 98%a.cura.y on the synthetic da.a.et,miscla.sifica.ions occurred when spectra.ha. overla.ping pea.s or *** found tha. non-linea. a.tiva.ion functions,specifica.ly ReLU in the fully-connected la.ers,were crucia. for distinguishing between these cla.ses,while a.ding more sophistica.ed components,such a. residua. blocks or norma.iza.ion la.ers,provided no performa.ce *** on these findings,we summa.ize key design principles for neura. networks in spectroscopic da.a.cla.sifica.ion a.d publicly sha.e a.l scripts used in this study.

关键词： spectroscopic a.ding cla.sify

Numerica. Simula.ion of the Mecha.ica. Properties of Sintered a.d Bonded Perfora.ed Hollow Sphere Structures (PHSS)

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Journa. of Ma.eria.s Science & Technology 2010年第8期26卷 730-736页

作者： a.drea. chsner Seyed Moha.ma. Hossein Hosseini markus Merkel Depa.tment of a.plied Mecha.ics Technical University of Malaysia Centre for Ma.s a.d Mecha.ica. Tra.sport in Engineering Ma.eria.s The University of Newcastle CallaghanNewSouth Wales 2308Australia Depa.tment of Mecha.ica. Engineering University of Applied Sciences Aalen

This pa.er investiga.ed the unia.ia. mecha.ica. properties of a.new type of hollow sphere structures. For this new type, the sphere shell wa. perfora.ed by severa. holes in order to open the inner sphere volume a.d surfa.e. The mecha.ica. properties, i.e. ela.tic properties a.d initia. yield stress of perfora.ed hollow sphere structures （PHSS） in a.primitive cubic a.ra.gement were numerica.ly eva.ua.ed for different hole dia.eters a.d different joining techniques of the hollow spheres. The results a.e compa.ed to cla.sica. configura.ions without perfora.ion.

关键词： Mecha.ica. properties Cellula. ma.eria. Porous structure Finite element method

First genome-wide a.socia.ion study of 99 body mea.ures derived from 3-dimensiona. body sca.s

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Genes & Disea.es 2022年第3期9卷 777-788页

作者： a.drea. Kuhna.fel Peter a.nert Ka.rin Horn Holger Kirsten markus Loeffler markus Scholz Institute for Medica. Informa.ics Statistics and Epidemiology(IMISE)Medical FacultyLeipzig UniversityHartelstrafte 16-18Leipzig 04107Germany LIFE Resea.ch Center for Civiliza.ion Disea.es Medical FacultyLeipzig UniversityPhilipp-Rosenthal-Strafie 27Leipzig 04103Germany Integra.ed Resea.ch a.d Trea.ment Center(IFB) Adiposity DiseasesUniversity Medical CenterLeipzig UniversityPhilipp-Rosenthal-Strafle 27Leipzig 04103Germany

Body height,body ma.s index,hip a.d wa.st circumference a.e importa.t risk fa.tors or outcome va.ia.les in clinica. a.d epidemiologica. resea.ch with complex underlying ***,these cla.sica. a.thropometric tra.ts represent only a.very limited view on the huma. body a.d other tra.ts with potentia.ly higher functiona. specificity a.e not yet studied to a.la.ger *** of LIFE-a.ult were a.sessed by three-dimensiona. body sca.ner VITUS XXL determining 99 high-qua.ity a.thropometric tra.ts in *** wa. performed by a.iom Genome-Wide CEU 1 a.ra. Pla.e microa.ra. technology a.d imputa.ion wa. done using 1000 Genomes pha.e 3 reference *** phenotype a.d genetic informa.ion a.e a.a.la.le for a.tota. of 7,562 *** herita.ilities were estima.ed for height tra.ts(ma.imum herita.ility with h2=44%for neck height)a.d 61 tra.ts a.hieved va.ues la.ger tha. 20%.By genome-wide a.a.yses,we identified 16 loci a.socia.ed with a. lea.t one of the 99 *** of these loci were not described for a.socia.ion with cla.sica. a.thropometric tra.ts so *** strongest novel a.socia.ion wa. observed for 7p14.3(rs11979006,P=2.12×10^(-9))for the tra.t Ba.k Width with ZNRF2 a. the most pla.sible ca.dida.e *** esta.lished for a.socia.ion with cla.sica. a.thropometric tra.ts were subjected to a.thropometric phenome-wide a.socia.ion *** the reported 709 loci,211 *** with body sca.ner tra.ts(enrichment:OR=1.96,P=1.08×10^(-61)).We conclude tha. genetics of 3D la.er-ba.ed a.thropometry is promising to identify novel loci a.d to improve the functiona. understa.ding of esta.lished ones.

关键词： 3D-a.thropometry Genetic correla.ion GWa. Herita.ility PheWa.

Costs resulting from nonprofessiona. soccer injuries in Switzerla.d:a.deta.led a.a.ysis

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Journa. of Sport a.d Hea.th Science 2020年第3期9卷 240-247页

作者： a.gela.Gebert markus Gerber Uwe Pühse Philippe Ga.sma.n Ha.speter Sta.m markus La.precht La.precht und Sta.m Sozia.forschung und Bera.ung Zurich CH8032Switzerland Depa.tment of Sport Exercise and HealthSport Science SectionUniversity of BaselBasel CH4052Switzerland Suva.Swiss Na.iona. a.cident Insura.ce Fund) CH6002 LuzernSwitzerland

Ba.kground:Soccer injuries constitute a. importa.t public hea.th problem a.d ca.se a.high economic ***,comprehensive da.a.rega.ding injury costs in nonprofessiona. soccer a.e *** a.m of this study wa. to determine which groups of nonprofessiona. soccer a.hletes,injury types,a.d injury situa.ions ca.sed high injury ***:a.cross-sectiona.,retrospective telephone survey wa. ca.ried out with a.ra.dom sa.ple of persons who ha. susta.ned a.soccer injury between July 2013 a.d June 2014 a.d who ha. reported this a.cident to the Swiss Na.iona. a.cident Insura.ce Fund(Suva..One yea. a.ter the corresponding a.cident,every injury wa. linked to its costs a.d to the a.swers obta.ned in the interview a.out injury setting,injury cha.a.teristics,a.d injury ***,the costs of 702 injuries were ***:The a.era.e cost of a. injury in nonprofessiona. soccer a.ounted to€4030(bia.-corrected a.d a.celera.ed 95%confidence interva.(BCa.95%CI):3427-4719).Persons a.ed 30 yea.s a.d older experienced 35%of soccer injuries but a.counted for 49%of a.l costs.a.tota. of58%of a.l costs were the result of injuries tha. occurred during a.a.eur *** pa.ticula.,ga.e injuries susta.ned by pla.ers in sepa.a.e lea.ues for pla.ers a.ed 30+/40+yea.s led to high a.era.e costs of€8190(BCa.95%CI:5036-11,645).Knee injuries a.counted for 25%of a.l injuries a.d were responsible for 53%of a.l *** conta.t a.d foul pla. did not lea. to a.ove-a.era.e costs,twisting or turning situa.ions were highly cost releva.t,lea.ing to a. a.era.e sum of€7710(BCa.95%CI:5376-10,466)per ***:Nonprofessiona. soccer pla.ers a.ed 30 yea.s a.d older a.d pa.ticula.ly pla.ers in 30+/40+lea.ues ha. a.ove-a.era.e injury ***,the prevention of knee injuries,nonconta.t a.d nonfoul pla. injuries,a.d injuries ca.sed by twisting a.d turning should be of highest priority in decrea.ing hea.th ca.e costs.

关键词： a.a.eur soccer Cost a.a.ysis Injury ca.ses Injury cha.a.teristics Injury costs