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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin Yip Tam jochen H.M.Prehn Hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and fUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(fTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/fTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

The transcriptional landscape of the developmental switch from regular pollen maturation towards microspore-derived plant regeneration in barley

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The Crop Journal 2024年第4期12卷 1064-1080页

作者： Anna Nowicka Martin Kovacik Anna Maksylewicz Przemysław Kopec Ewa Dubas Monika Krzewska Agnieszka Springer Robert E.Hoffie Diaaeldin S.Daghma Zbynek Milec Ales Pecinka jochen Kumlehn Iwona Zur The franciszek Górski Institute of Plant Physiology Polish Academy of Sciences Niezapominajek 2130-239 KrakówPoland Institute of Experimental Botany of the Czech Academy of Sciences Centre of Plant Structural and Functional GenomicsŠlechtitelu3177900 OlomoucCzech Republic Department of Cell Biology and Genetics Faculty of SciencePalacky UniversityŠlechtitelu°2777900 OlomoucCzech Republic Malopolska Centre of Biotechnology Jagiellonian University30-387 KrakówPoland Leibniz Institute of Plant Genetics and Crop Plant Research(IPK)Gatersleben Corrensstraße 306466 Stadt SeelandGermany Institute for Breeding Research on Horticultural Crops Julius Kühn Institute(JKI)-Federal Research Centre for Cultivated PlantsErwin-Baur Straße 2706484 QuedlinburgGermany Global Change Research Institute Czech Academy of Sciences Beˇlidla 986/4a60300 BrnoCzech Republic

Plant formation from in vitro-cultivated microspores involves a complex network of internal and environmental ***/doubled haploids(DHs)derived from in vitro-cultured microspores are widely used in plant breeding and genetic ***,the mechanism underlying the developmental switch from regular pollen maturation towards microspore-derived plant regeneration remains poorly ***,RNA-sequencing was employed to elucidate the transcriptional landscapes of four early stages of microspore embryogenesis(ME)in barley cultivars Golden Promise and Igri,which exhibit contrasting responsiveness to microspore-derived plant *** experiments revealed fundamental regulatory networks,specific groups of genes,and transcription factor(Tf)families potentially regulating the developmental *** identified a set of candidate genes crucial for genotype-dependent responsiveness/recalcitrance to *** high-resolution temporal transcriptome atlas provides an important resource for future functional studies on the genetic control of microspore developmental transition.

关键词： Hordeum vulgare Marker gene Microspore embryogenesis Stress response Transcriptome analysis

Diagnostic delay in inflammatory bowel diseases in a German population

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World Journal of Gastroenterology 2024年第29期30卷 3465-3478页

作者： Elisabeth Blüthner Annalena Dehe Carsten Büning Britta Siegmund Matthias Prager jochen Maul Alexander Krannich Jan Preiß Bertram Wiedenmann florian Rieder Raneem Khedraki frank Tacke Andreas Sturm Anja Schirbel Department of Hepatology and Gastroenterology Campus Virchow-Klinikum and Campus CharitéMitteCharité-Universitätsmedizin BerlinBerlin 10117Germany Department of Gastroenterology Vivantes Klinikum im FriedrichshainBerlin 10249Germany Department of Internal Medicine Krankenhaus WaldfriedeBerlin 14163Germany Department of Gastroenterology Infectious Diseases and RheumatologyCharité-Universitätsmedizin BerlinBerlin 12203Germany Praxis für Gastroenterologie Berlin Zehlendorf Berlin 14195Germany Gastroenterologie am Bayrischen Platz Berlin 10825Germany Clinical Trial Office Charité-Universitätsmedizin BerlinBerlin 10117Germany Department of Gastroenterology Diabetology and HepatologyVivantes Klinikum NeuköllnBerlin 10117Germany Department of Gastroenterology Hepatology and NutritionDigestive Diseases and Surgery InstituteThe Cleveland Clinic FoundationClevelandOH 44195United States Department of Internal Medicine DRK Kliniken Berlin WestendBerlin 14050Germany Gastroenterologie im Havelland Straße der EinheitFalkensee 14612Germany

BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients *** To identify risk factors leading to prolonged diagnostic time in a German IBD *** Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD *** diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time *** The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;Performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD *** UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic *** We demonstrated that CD patients compared to UC are at risk of long diagnostic *** efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

关键词： Diagnostic time Diagnostic delay Crohn’s disease Ulcerative colitis Germany

The need for disciplinarity,interdisciplinarity and scientific societies-the cartographic perspective

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Geo-Spatial Information Science 2021年第1期24卷 160-166,I0017页

作者： jochen Schiewe Lab for Geoinformatics and Geovisualization(G2lab) HafenCity University of HamburgHamburgGermany

Do we still need Cartography?Do we still need a cartographic society?These questions,which can also be transferred to other disciplines,are answered from disciplinary and interdisciplinary perspectives-which creates an ideal connection to the networked and interdisciplinary thinking of Gottfried *** need for Cartography as a discipline is discussed based on a view on historic,current and future functions of maps and changing research and development *** respect to interdisciplinarity,Cartography shows connections to various domains while more and more relationships with young areas from the field of Computer Science are *** regard to cartographic societies,their central role and importance as networking platforms are ***,geographical and thematic granularities of societies as well as networking formats(including online versions)need to be evaluated and further developed on a constant basis.

关键词： Cartography map functions interdisciplinarity data classification point generalization professional societies

Adaptive progressive download based on the MPEG-4 file format

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2006年第z1期7卷 106-111页

作者： fRBer Nikolaus DHLA Stefan ISSING jochen Multimedia Transport Dept.Audio Fraunhofer Institute for Integrated Circuits IISErlangen 91058Germany

In this paper we describe how progressive download and adaptive streaming can be combined into a simple and efficient streaming framework. Based on the MPEG-4 file format (MP4) we use HTTP for transport and argue that these two components are sufficient for specifying an open streaming architecture. The client selects appropriate chunks from the MP4 file to be transferred based on (1) the header information (i.e. the 'moov' box) in the first part of the file and (2) his observation of network throughput. The framework is completely client driven which allows for better server scalability and reduces signalling overhead. We discuss architecture and implementation issues such as complexity, interoperability and scalability and compare to 3GPP PSS Re1-6 adaptive streaming when appropriate. Measurements from a simple MP4/HTTP streaming client are presented showing that appropriate chunks are selected such that increased reliability is achieved.

关键词： HTTP-streaming Adaptive progressive download MPEG-4 file format (MP4) Moov box

Yield Improvement and Advanced Defect Control——Driving forces for Modeling of Bulk Crystal Growth

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Journal of Rare Earths 2006年第z1期24卷 200-207页

作者： Georg mueller jochen friedrich Crystal Growth Laboratory University Erlangen-Nürnberg (WW6) and Fraunhofer Institute of Integrated Systems and Device Technology (IISB) Martensstrasse 7 D-91058 Erlangen Germany Crystal Growth Laboratory University Erlangen-Nürnberg (WW6) and Fraunhofer Institute of Integrated Systems and Device Technology (IISB) Martensstrasse 7 D-91058 Erlangen Germany

Yield improvement and advanced defect control can be identified as the driving forces for modeling of industrial bulk crystal growth. Yield improvement is mainly achieved by upscaling of the whole crystal growth apparatus and increased processing windows with more tolerances for parameter variations. Advanced defect control means on one hand a reduction of the number of deficient crystal defects and on the other hand the formation of beneficial crystal defects with a uniform distribution and well defined concentrations in the whole crystal. This "defect engineering" relates to the whole crystal growth process as well as the following cooling and optional annealing processes, respectively. These topics were illustrated in the paper by examples of modeling and experimental results of bulk growth of silicon (Si), gallium arsenide (GaAs), indium phosphide (InP) and calcium fluoride (Caf2). These examples also involve the state of the art of modeling of the most important melt growth techniques, crystal pulling (Czochralski methods) and vertical gradient freeze (Bridgman-type methods).

关键词： yield improvement advanced defect control crystal growth

Investigation of grain mass flow in a mixed flow dryer

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Particuology 2014年第1期12卷 33-39页

作者： fabian Weigler jochen Mellmann Department of Post-harvest Technology Leibniz Institute for Agricultural Engineering Potsdam-Bornim

The numerical modeling of grain drying is a topic of great relevance to post-harvest engineering. The required type of drying process depends on the quantity of grain to be dried and the required quality of the grain. The choice of the drying system depends on the operating parameters of the drying process. The granular flow pattern of the material exerts a significant influence on the drying process. Post-harvest drying of grain is essential for better storage, handling, and processing. Therefore, it is important to know the material behavior that controls the particle flow patterns of grain in the drying equipment to guarantee the product quality and to optimize the drying process conditions. The discrete element method （DEM） was applied to investigate the particle flow pattern of wheat through a mixed-flow dryer （MfD） without airflow, and the findings were compared with experimental results in this work. The investigations were performed using dry wheat with 14 wb% moisture content.

关键词： Keywords:Mixed-flow dryerGrain mass flowDiscrete element method

The Drought of Amazonia in 2023-2024

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American Journal of Climate Change 2024年第3期13卷 567-597页

作者： Jose A. Marengo Ana P. Cunha Jhan-Carlo Espinoza Rong fu jochen Schöngart Juan C. Jimenez Mabel C. Costa Joao M. Ribeiro Sly Wongchuig Siyu Zhao National Center for Monitoring and Early Warning of Natural Disasters/CEMADEN So Jos dos Campos Brazil UNESP/CEMADEN So Jos dos Campos Brazil Graduate School of International Studies Korea University Seoul South Korea Institut des Gosciences de lEnvironnement (IGE) Institut de Recherche pour le Dvelopement (IRD) Saint Martin dHeres France Instituto de Investigacin sobre la Enseanza de las Matemticas (IREM PUCP) Pontificia Universidad Catlica del Per Lima Peru Department of Atmospheric and Oceanic Sciences University of California Los Angeles Los Angeles CA USA Departament of Environmental Dynamics Instituto Nacional de Pesquisas da Amaznia (INPA) Manaus Brazil Global Change Unit (GCU) of the Image Processing Laboratory (IPL) Universitat de Valncia Estudi General (UVEG) Paterna Spain Laboratoire dEtudes en Gophysique et Ocanographie Spatiales (LEGOS) Universit de Toulouse CNES/CNRS/IRD/UT3 Toulouse France

The Amazon basin has experienced an extreme drought that started in the austral summer of 2022-23 and extends into 2024. This drought started earlier than other previous droughts. Although some rain fell during the austral summer, totals remained below average. Higher temperatures during austral winter and spring 2023, which affected most of Central South America, then aggravated drought conditions. This coincided with an intense El Niño and abnormally warm tropical North Atlantic Ocean temperatures since mid-2023. Decreased rainfall across the Amazon basin, negative anomalies in evapotranspiration (derived from latent heat) and soil moisture indicators, as well as increased temperatures during the dry-to-wet transition season, September-October-November (SON) 2023, combined to delay the onset of the wet season in the hydrological year 2023-24 by nearly two months and caused it to be uncharacteristically weak. SON 2023 registered a precipitation deficit of the order of 50 to 100 mm/month, and temperatures +3˚C higher than usual in Amazonia, leading to reduced evapotranspiration and soil moisture indicators. These processes, in turn, determined an exceptionally late onset and a lengthening of the dry season, affecting the 2023-2024 hydrological year. These changes were aggravated by a heat wave from June to December 2023. Drought-heat compound events and their consequences are the most critical natural threats to society. River levels reached record lows, or dried up completely, affecting Amazonian ecosystems. Increased risk of wildfires is another concern exacerbated by these conditions.

关键词： El Niño SST in the Tropical Atlantic Amazon Drought River Levels Heatwave Dry Season Length

围术期神经肌肉阻滞的管理:欧洲麻醉和重症监护学会临床指南

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中华麻醉学杂志 2024年第6期44卷 641-656页

作者： Thomas fuchs-Buder Carolina S.Romero Heidrun Lewald Massimo Lamperti Arash Afshari Ana-Marjia Hristovska Denis Schmartz jochen Hinkelbein Dan Longrois Maria Popp Hans Dde Boer Massimiliano Sorbello Radmilo Jankovic Peter Kranke 法国南锡大学医学院附属医院麻醉学、重症监护与围术期医学科法国南锡54000 巴伦西亚大学综合医院麻醉与重症监护科西班牙巴伦西亚46014 慕尼黑工业大学麻醉学与重症监护科德国慕尼黑80333 克利夫兰阿布扎比诊所麻醉学研究所阿联酋阿布扎比31250 哥本哈根大学医院小儿和产科麻醉科丹麦哥本哈根2100 哥本哈根大学医院麻醉学与重症监护科丹麦赫维德2650 布鲁塞尔自由大学erasme医院麻醉科比利时布鲁塞尔1070 科隆大学医院麻醉学与重症监护科德国科隆50937 巴黎大学附属比查特克劳德伯纳德医院麻醉学与重症监护医学科法国巴黎75018 维尔茨堡大学医院麻醉学、危重病医学、急诊医学和疼痛医学科德国维尔茨堡97080 格罗宁根大学医院麻醉学、疼痛医学与程序性镇静与镇痛科荷兰格罗宁根9713 GZ 卡坦尼亚大学医院麻醉与重症监护科意大利卡坦尼亚95123 尼什大学医学院尼什临床中心麻醉学与重症治疗科塞尔维亚尼什18000

近来的研究表明,由于围术期神经肌肉阻滞管理不当,肌肉松弛药(肌松药)残留阻滞及其术后并发症的发生率居高不下。需要重视神经肌肉功能监测仪、肌松药及其拮抗剂的合理应用,以利于改善神经肌肉阻滞管理。欧洲麻醉和重症监护学会(Europea... 详细信息

近来的研究表明,由于围术期神经肌肉阻滞管理不当,肌肉松弛药(肌松药)残留阻滞及其术后并发症的发生率居高不下。需要重视神经肌肉功能监测仪、肌松药及其拮抗剂的合理应用,以利于改善神经肌肉阻滞管理。欧洲麻醉和重症监护学会(European Society of Anaesthesiology and Intensive Care,ESAIC)首次发布围术期神经肌肉阻滞管理临床指南,旨在为临床医生提供最佳医疗管理的循证建议,以提高围术期患者安全。本指南主要聚焦在3个临床问题:肌松药是否有助于成人气管插管?神经肌肉阻滞深度是否影响腹部手术患者的预后?肌松药残留阻滞的诊断和治疗策略有哪些?根据PICO原则(患者、干预、对照、结局;patient,intervention,comparator,outcome;PICO)构建临床问题并进行文献检索。初始纳入的临床研究为24 000篇,采用逐步筛选策略,最终临床研究88篇纳入指南分析。应用GRADE方法学(Grading of Recommendations,Assessment,Development and Evaluation,GRADE)对结局指标证据、质量等级进行评价。运用两轮德尔菲法收集专家组建议并形成统一推荐:R1推荐应用肌松药辅助气管插管(1A)。R2推荐应用肌松药以减少气管插管导致的咽部和(或)喉部损伤(1C)。R3推荐在快速顺序诱导插管(rapid sequence induction intubation,RSII)时使用短效肌松药,例如琥珀胆碱1 mg/kg或罗库溴铵0.9~1.2 mg/kg(1B)。R4推荐在需要改善外科手术条件时,加深神经肌肉阻滞深度(1B)。R5尚无足够的证据推荐深度神经肌肉阻滞可减轻术后疼痛或降低围术期并发症的发生率(2C)。R6推荐在拇内收肌处刺激尺神经,定量监测神经肌肉阻滞深度以排除肌松药残留阻滞(1B)。R7推荐应用舒更葡糖钠逆转甾体类肌松药(罗库溴铵、维库溴铵)诱导的深、中及浅度神经肌肉阻滞(1A)。R8推荐在使用新斯的明前,TOfr自行恢复至>0.2,并继续定量监测神经肌肉功能,直至TOfr超过0.9(1C)。

关键词：神经肌肉阻滞神经肌肉功能肌松药临床指南罗库溴铵琥珀胆碱外科手术定量监测