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Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta

Translational Neurodegeneration 2021年第3期10卷 502-517页

作者： Fadi Rofo Jos Buijs Ronny Falk Ken Honek lars lannfelt Anna M.Lilja Nicole G.Metzendorf Tobias Gustavsson Dag Sehlin Linda Söderberg Greta Hultqvist Protein Drug Design Faculty of PharmacyUppsala University75124 UppsalaSweden Department of Immunology Genetics and PathologyUppsala University75185 UppsalaSweden Ridgeview Instruments 75237 UppsalaSweden BioArctic AB 11251 StockholmSweden Department of Public Health and Caring Sciences Uppsala University75185 UppsalaSweden

Background:Amyloid-β(Aβ)immunotherapy is a promising therapeutic strategy in the fght against Alzheimer’s disease(AD).A number of monoclonal antibodies have entered clinical trials for *** of them have failed due to the lack of efcacy or side-efects,two antibodies are currently in phase 3,and one has been approved by *** soluble intermediate aggregated species of Aβ,termed oligomers and protofbrils,are believed to be key pathogenic forms,responsible for synaptic and neuronal degeneration in ***,antibodies that can strongly and selectively bind to these soluble intermediate aggregates are of great diagnostic and therapeutic ***:We designed and recombinantly produced a hexavalent antibody based on mAb158,an Aβprotofbrilselective *** humanized version of mAb158,lecanemab(BAN2401),is currently in phase 3 clinical trials for the treatment of *** new designs involved recombinantly fusing single-chain fragment variables to the N-terminal ends of mAb158 ***-time interaction analysis with LigandTracer and surface plasmon resonance were used to evaluate the kinetic binding properties of the generated antibodies to Aβ*** ELISA setups were applied to demonstrate the binding strength of the hexavalent antibody to Aβaggregates of diferent ***,the ability of the antibodies to protect cells from Aβ-induced efects was evaluated by MTT ***:Using real-time interaction analysis with LigandTracer,the hexavalent design promoted a 40-times enhanced binding with avidity to protofbrils,and most of the added binding strength was attributed to the reduced rate of ***,ELISA experiments demonstrated that the hexavalent design also had strong binding to small oligomers,while retaining weak and intermediate binding to monomers and insoluble *** hexavalent antibody also reduced cell death induced by a mixture of soluble Aβ***:We provide a new antibody design with i

关键词： Multivalent antibodies Alzheimer’s disease Aβ Avidity Oligomers Protofbrils

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What is required for better progress in clinical and scientific andrology involving sperm assessments?

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Asian Journal of Andrology 2024年第3期26卷 229-232页

作者： lars Björndahl ANOVA Karolinska University Hospital and Karolinska Institutet Norra Stationsgatan 69 Level 4 S-113 64 Stockholm Sweden

In scientific publications based on basicsemen examination,there is a generallack of consistency and transparencyregarding laboratory techniques *** support improvements in clinicaland scientific andrology,it is essential toincrease understanding of basic physiologyand biology,and enhance compliancewith existing recommendations andinternational *** designsneed to be improved as well as transparencyof laboratory methods used and openpublication of data obtained.

关键词： transparency consistency clinical

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G protein-mediated signal transduction: a molecular choreography of G protein activation after GTP binding

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3155-3157页

作者： Evi Kostenis lars Jurgenliemke Judith Alenfelder Department of Molecular- Cellular-and PharmacobiologyInstitute of Pharmaceutical BiologyUniversity of BonnBonnGermany Graduate Training Group RTG2873 University of BonnBonnGermany

A recent report from the Skiniotis group,'published in Nature,provides fascinating insight into the molecular choreography underlying a quintessential cellular signaling mechanism:G protein-mediated signal *** time-resolved cryo-EM,the authors pieced together many sequential structural snapshots to visualize how a trimeric aβy G protein-after being convinced by its activated G protein-coupled receptor(GPCR)to release GDP-picks up GTP,to set in motion finely tuned conformational transitions that lead to the conversion into the active state and,finally,subunit dissociation as well as disengagement from the receptor.

关键词： Skin activation finally

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The role of the Arctic Monitoring and Assessment Programme(AMAP)in reducing pollution of the Arctic and around the globe

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Environmental Science and Ecotechnology 2024年第1期17卷 48-58页

作者： lars-Otto Reiersen Katrin Vorkamp Roland Kallenborn Arctic Knowledge Ltd Former Executive SecretaryArctic Monitoring and Assessment Programme(AMAP)OsloNorway Department of Environmental Science Aarhus UniversityRoskildeDenmark International Joint Research Center for Arctic Environment and Ecosystem(IJRC-AEE) Polar Academy(PA)Harbin Institute of TechnologyHarbinPR China Faculty of Chemistry Biotechnology and Food ScienceNorwegian University of Life Sciences(NMBU)ÅsNorway University of the Arctic(UArctic) RovaniemiFinland

This article presents the initiation and implementation of a systematic scientific and political cooperation in the Arctic related to environmental pollution and climate change,with a special focus on the role of the Arctic Monitoring and Assessment Programme(AMAP).The AMAP initiative has coordinated monitoring and assessments of environmental pollution across countries and parameters for the entire Arctic *** from a first scientific assessment in 1998,AMAP's work has been fundamental in recognizing,understanding and addressing environmental and human health issues in the Arctic,including those of persistent organic pollutants(POPs),mercury,radioactivity,oil,acidification and climate *** scientific results have contributed at local and international levels to define and take measures towards reducing the pollution not only in the Arctic,but of the whole globe,especially the contaminant exposure of indigenous and local communities with a traditional *** results related to climate change have documented the rapid changes in the Arctic and the strong feedback between the Arctic and the rest of the *** lessons learned from the work in the Arctic can be beneficial for other regions where contaminants may accumulate and affect local and indigenous peoples living in a traditional way,*** the *** cooperation is indispensable in reducing the longrange transported pollution in the Arctic.

关键词： Climate change Heavy metals Human health Indigenous peoples Persistent organic pollutants Radioactivity

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Gastric carboxylesterases of the edible crab Cancer pagurus (Crustacea, Decapoda) can hydrolyze biodegradable plastics

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Emerging Contaminants 2024年第1期10卷 80-89页

作者： Lukas Miksch lars Gutow Reinhard Saborowski Alfred Wegener Institute Helmholtz Centre for Polar and Marine ResearchAm Handelshafen 1227570BremerhavenGermany

A promising strategy to counteract the progressing plastic pollution of the environment can involve the replacement of persistent plastics with biodegradable *** polymers are enzymatically degradable by various hydrolytic ***,these materials can reach the environment in the same way as conventional ***,they are accessible to terrestrial,freshwater,and marine *** ingested by marine organisms,highly active enzymes in their digestive tracts may break down biodegradable *** incubated microparticles of five different biodegradable plastics,based on polylactictic acid(PLA),polybutylene succinate(PBS),polybutylene adipate terephthalate(PBAT)and polyhydroxybutyrate-co-valerate(PHBV),in-vitro with the gastric fluid of the edible crab Cancer pagurus and evaluated the hydrolysis rates by pH Stat titration.A plastic blend of PLA with PBAT showed the highest hydrolysis *** enzymes in the gastric fluid of crabs were separated by anion exchange *** with carboxylesterase activity were identified using fluorescent methylumbelliferyl(MUF)-*** fractions with high carboxylesterase activity also hydrolyzed a PLA/PBAT plastic *** showed molecular masses of 40–45 kDa as determined by native gel electrophoresis(SDS-PAGE).Our study demonstrated that digestive carboxylesterases in the gastric fluid of *** exhibit a high potential for hydrolyzing certain biodegradable *** esterases are common in the digestive tract of organisms,it seems likely that other invertebrates possess the ability to hydrolyze biodegradable plastics.

关键词： Biodegradable plastics Microplastics Crustaceans Ingestion Enzymes Enzymatic degradation

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Small molecular decoys in Alzheimer's disease

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Neural Regeneration Research 2024年第8期19卷 1658-1659页

作者： Sho Oasa Valentina L.Kouznetsova Igor F.Tsigelny lars Terenius Department of Clinical Neuroscience Center for Molecular MedicineKarolinska InstitutetStockholmSweden San Diego Supercomputer Center University of California San DiegoLa JollaCAUSA Department of Neurosciences University of California San DiegoLa JollaCAUSA Department of Clinical Neuroscience Karolinska University HospitalKarolinska InstitutetStockholmSweden

Recent progress in the treatment of Alzheimer’s disease(AD)using antibodies against amyloid sustains amyloid generation as a key process in *** formation starts with two amyloidbeta(Aβ)molecules interacting(dimer formation)followed by an accelerating build-up of socalled protofibrils,which turn into fibrils,which accumulate in the characteristic plaques.

关键词： Alzheimer decoy Aβ

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Revisiting the stretch-induced force deficit:A systematic review with multilevel meta-analysis of acute effects

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Journal of Sport and Health Science 2024年第6期13卷 805-819页

作者： Konstantin Warneke lars Hubertus Lohmann Institute of Human Movement Science Sport and HealthUniversity of GrazGraz 8010Austria Institute of Sport Science Alpen-Adria University of KlagenfurtKlagenfurt am Worthersee 9020Austria Institute of Human Movement and Exercise Physiology University of JenaJena 07749Germany

Background:When recommending avoidance of static stretching prior to athletic performance,authors and practitioners commonly refer to available systematic ***,effect sizes(ES)in previous reviews were extracted in major part from studies lacking control conditions and/or prepost testing ***,currently available reviews conducted calculations without accounting for multiple study outcomes,with ES:0.03 to 0.10,which would commonly be classified as ***:Since new meta-analytical software and controlled research articles have appeared since 2013,we revisited the available literatures and performed a multilevel meta-analysis using robust variance estimation of controlled prepost trials to provide updated ***,previous research described reduced electromyography activity—also attributable to fatiguing training routines—as being responsible for decreased subsequent *** second part of this study opposed stretching and alternative interventions sufficient to induce general fatigue to examine whether static stretching induces higher performance losses compared to other exercise ***:Including 83 studies with more than 400 ES from 2012 participants,our results indicate a significant,small ES for a static stretch-induced maximal strength loss(ES=0.21,p=0.003),with high magnitude ES(ES=0.84,p=0.004)for stretching durations≥60 s per bout when compared to passive *** opposed to active controls,the maximal strength loss ranges between ES:0.17 to0.28,p<0.001 and 0.040 with mostly no to small ***,stretching did not negatively influence athletic performance in general(when compared to both passive and active controls);in fact,a positive effect on subsequent jumping performance(ES=0.15,p=0.006)was found in ***:Regarding strength testing of isolated muscles(e.g.,leg extensions or calf raises),our results confirm previous ***,since no(or even positive)e

关键词： Static stretching Maximal strength Athletic performance Performance testing

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Ptycho-endoscopy on a lensless ultrathin fiber bundle tip

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Light(Science & Applications) 2024年第9期13卷 1766-1778页

作者： Pengming Song Ruihai Wang lars Loetgering Jia Liu Peter Vouras Yujin Lee Shaowei Jiang Bin Feng Andrew Maiden Changhuei Yang Guoan Zheng Department of Biomedical Engineering University of ConnecticutStorrsCT 06269USA CarlZeiss AG Carl Zeiss PromenadeJenaThuringia 07745Germany United States Department of Defense WashingtonDC 20301USA School of Electrical and Electronic Engineering Yonsei UniversitySeoul 03722Republic of Korea Department of Electronic and Electrical Engineering University of SheffieldSheffield South Yorkshire S13JDUK Diamond Light Source HarwellOxfordshire OX110DEUK Department of Electrical Engineering California Institute of TechnologyPasadenaCA 91125USA Center for Biomedical and Bioengineering Innovation University of ConnecticutStorrsCT 06269USA

Synthetic aperture radar(SAR)utilizes an aircraft-carried antenna to emit electromagnetic pulses and detect the returning *** the aircraft travels across a designated area,it synthesizes a large virtual aperture to improve image *** by SAR,we introduce synthetic aperture ptycho-endoscopy(SAPE)for micro-endoscopic imaging beyond the diffraction *** operates by hand-holding a lensless fiber bundle tip to record coherent diffraction patterns from *** fiber cores at the distal tip modulate the diffracted wavefield within a confined area,emulating the role of the‘airborne antenna’in *** handheld operation introduces positional shifts to the tip,analogous to the aircraft’s *** shifts facilitate the acquisition of a ptychogram and synthesize a large virtual aperture extending beyond the bundle’s physical *** mitigate the influences of hand motion and fiber bending through a low-rank spatiotemporal decomposition of the bundle’s modulation *** tests demonstrate the ability to resolve a 548-nm linewidth on a resolution *** achieved space-bandwidth product is~1.1 million effective pixels,representing a 36-fold increase compared to that of the original fiber ***,SAPE’s refocusing capability enables imaging over an extended depth of field exceeding 2 *** aperture synthesizing process in SAPE surpasses the diffraction limit set by the probe’s maximum collection angle,opening new opportunities for both fiber-based and distal-chip endoscopy in applications such as medical diagnostics and industrial inspection.

关键词： fiber antenna bundle

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Electrogenic sulfur oxidation mediated by cable bacteria and its ecological effects

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Environmental Science and Ecotechnology 2024年第4期20卷 34-41页

作者： Zhenyu Wang Leonid Digel Yongqiang Yuan Hui Lu Yonggang Yang Carsten Vogt Hans-Hermann Richnow lars Peter Nielsen Department of Isotope Biogeochemistry Helmholtz Centre for Environmental Research e UFZPermoserstraße 1504318LeipzigGermany Center for Electromicrobiology Department of BiologyAarhus UniversityDK-8000AarhusDenmark Key Laboratory of Karst Georesources and Environment Ministry of EducationCollege of Resources and Environmental EngineeringGuizhou UniversityGuiyang550025China School of Environmental Science and Engineering Sun Yat-Sen UniversityGuangzhou510006China School of Life Science and Engineering Foshan UniversityFoshan528225China State Key Laboratory of Applied Microbiology Southern China Institute of MicrobiologyGuangdong Academy of SciencesGuangzhou510007China

At the sediment-water interfaces,filamentous cable bacteria transport electrons from sulfide oxidation along their filaments towards oxygen or nitrate as electron *** multicellular bacteria belonging to the family Desulfobulbaceae thus form a biogeobattery that mediates redox processes between multiple *** bacteria were first reported in *** the past years,cable bacteria have been found to be widely distributed across the *** potential in shaping the surface water environments has been extensively studied but is not fully *** this review,the biogeochemical characteristics,conduction mechanisms,and geographical distribution of cable bacteria,as well as their ecological effects,are systematically reviewed and *** insights for understanding and applying the role of cable bacteria in aquatic ecology are summarized.

关键词： Cable bacteria Electrogenic sulfur oxidation Long-distance electron transfer Aquatic ecology

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Adaptive-optical 3D microscopy for microfluidic multiphase flows

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Light(Advanced Manufacturing) 2024年第3期5卷 105-119页

作者： Clemens Bilsing Erik Nützenadel Sebastian Burgmann Jürgen Czarske lars Büttner Laboratory of Measurement and Sensor System Techniques TUD Dresden University of Technology01069 DresdenGermany Chair of Fluid Mechanics Bergische Universitát Wuppertal42119 WuppertalGermany BIOLAS Laboratory of Measurement and Sensor System Techniques01069 DresdenGermany

Measurements based on optical microscopy can be severely impaired if the access exhibits variations of the refractive *** the case of fluctuating liquid-gas boundaries,refraction introduces dynamical aberrations that increase the measurement *** is prevalent at multiphase flows(***,film flows)that occur in many technical applications as for example in coating and cleaning processes and the water management in fuel *** this paper,we present a novel approach based on adaptive optics for correcting the dynamical aberrations in real time and thus reducing the measurement *** shape of the fluctuating water-air interface is sampled with a reflecting light beam(Fresnel Guide Star)and a Hartmann-Shack sensor which makes it possible to correct its influence with a deformable mirror in a closed ***-dimensional flow measurements are achieved by using a double-helix point spread *** measure the flow inside a sessile,oscillating 50-μl droplet on an opaque gas diffusion layer for fuel cells and show that the temporally varying refraction at the droplet surface causes a systematic underestimation of the flow field magnitude corresponding to the first droplet eigenmode which plays a major role in their detachment *** demonstrate that the adaptive optics correction is able to reduce this systematic ***,the adaptive optics system can pave the way to a deeper understanding of water droplet formation and detachment which can help to improve the efficiency of fuels cells.

关键词： Double-Helix point spread function Adaptive optics Particle tracking velocimetry Aberration correction Depth-resolving microscopy Closed-loop control

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