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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell Jun Okabe Ishant Khurana thomas Karagiannis Julia J.Liang Lina Mariana thomas Loudovaris thomas kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

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Development of a Small Scale Magnetically Levitated Train as Demonstrator for Undergraduate Mechatronics Students

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Journal of Energy and Power Engineering 2013年第6期7卷 1124-1131页

作者： Rudiger Appunn thomas Herold kay Hameyer Institute of Electrical Machines RWTH Aachen University Aachen 52062 Germany

At the Institute of Electrical Machines of the Rheinisch Westfalilische Technische Hochschule Aachen University, there is a project financed by student fees for the realization of a magnetically levitated train in the scale of 1：50. Undergraduate students are supposed to get the possibility to design and build up a real train which serves as demonstrator for a mechatronic system. This project strengthens the motivation of students, since a practical demonstration of electromagnetic forces is given in addition to theoretical courses. This paper introduces the major project steps and explains the learning targets for the students. It focuses on analytical magnetic circuit design, numerical field simulation, modeling and control of a multi degree of freedom system, electronic circuit design, measurement setups and a first prototype test bench.

关键词： Electrical engineering education magnetic levitation modeling control finite element methods.

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Atlas of Oocytes, Zygotes and Embryos in Reproductive Medicine 1

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2012年

作者： Marc Van den Bergh thomas Ebner kay Elder

ISBN: (数字)9781139512183

ISBN: (纸本)9781139512183

The assessment and selection of oocytes and embryos is fundamental to the live birth rate data of all IVF units, the parameter that is used to gauge a clinic's success and credibility. This new atlas contains over 1000 high-quality images of oocytes, zygotes and embryos, presented with accompanying data on indications for treatment, stimulation type and duration, as well as short medical histories of each couple and final outcome of treatment. All images in the book can be downloaded from the accompanying CD-ROM. Structured on a patient-by-patient basis, the atlas describes 100 clinically documented case studies that follow the evolution of oocytes and zygotes between day two and day five. Pronuclear morphology and synchrony as well as embryo morphology are reported and described for each case. Written and produced by experienced embryologists, this practical atlas is an important resource for clinical embryologists and physicians in reproductive medicine.

关键词：妇产科学

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The Hong Kong consensus recommendations on the diagnosis and management of pancreatic cystic lesions

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Hepatobiliary Surgery and Nutrition 2023年第5期12卷 715-735,I0019-I0020页

作者： Tan-To Cheung Yuk Tong Lee Raymond Shing-Yan Tang Wong Hoi She Kai Chi Cheng Chin Cheung Cheung Keith Wan Hang Chiu Kenneth Siu Ho Chok Wing Sun Chow Tak Wing Lai Wai-kay Seto thomas Yau Department of Surgery Queen Mary HospitalThe University of Hong KongHong KongChina Gastroenterologist in private practice Hong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Surgery Kwong Wah HospitalHong KongChina Department of Surgery Tuen Mun HospitalHong KongChina Department of Radiology&Imaging Queen Elizabeth HospitalHong KongChina Department of Medicine The University of Hong KongHong KongChina Department of Surgery Princess Margaret HospitalHong KongChina Department of Medicine School of Clinical MedicineThe University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Background:The finding of pancreatic cystic lesions(PCL)on incidental imaging is becoming increasingly *** studies report a prevalence of 2.2-44.7%depending on the population,imaging modality and indication for imaging,and the prevalence increases with *** with PCL are at risk of developing pancreatic cancer,a disease with a poor *** publication summarizes recommendations for the diagnosis and management of PCL and post-operative pancreatic exocrine insufficiency(PEI)from a group of local ***:Clinical evidence was consolidated from narrative reviews and consensus statements formulated during two online meetings in March *** expert panel included gastroenterologists,hepatobiliary surgeons,oncologists,radiologists,and ***:Patients with PCL require careful investigation and follow-up due to the risk of malignant transformation of these *** should undergo clinical investigation and pancreas-specific imaging to classify lesions and understand the risk profile of the *** indicated,patients should undergo pancreatectomy to excise *** pancreatectomy,patients are at risk of PEI,leading to gastrointestinal dysfunction and ***,such patients should be monitored for symptoms of PEI,and promptly treated with pancreatic enzyme replacement therapy(PERT).Patients with poor response to PERT may require increases in dose,addition of a proton pump inhibitor,and/or further investigation,including tests for pancreatic *** are also at risk of new-onset diabetes mellitus after pancreatectomy;they should be screened and treated with insulin if ***:These statements are an accurate summary of our approach to the diagnosis and management of patients with PCL and will be of assistance to clinicians treating these patients in a similar clinical landscape.

关键词： Pancreatic cystic lesions pancreatic endocrine insufficiency pancreatic enzyme replacement therapy

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A multilocus molecular phylogeny for the avian genus Liocichla(Passeriformes:Leiothrichidae:Liocichla)

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Chinese Birds 2015年第3期6卷 140-152页

作者： Herman L Mays Bailey D Mc kay Dieter thomas Tietze Cheng-Te Yao Lindsey N Miller Kathleen N Moreland Fumin Lei Department of Biological Sciences Marshall University Cincinnati Museum Center American Museum of Natural History Institute of Pharmacy and Molecular Biotechnology Heidelberg University Endemic Species Research Institute Biotechnology Program Loveland High School Institute of Zoology Chinese Academy of Sciences

Background:Historically the babblers have been assigned to the family Timaliidae but several recent studies have attempted to rest the taxonomy of this diverse passerine assemblage on a more firm evolutionary *** result has been a major rearrangement of the group.A well?supported and comprehensive phylogeny for this widespread avian group is an important part of testing evolutionary and biogeographic hypotheses,especially in Asia where the babblers are a key component of many forest ***,the genus Liocichla is poorly represented in these prior studies of babbler ***:We used a multilocus molecular genetic approach to generate a phylogenetic hypothesis for all five cur?rently recognized species in the avian genus *** DNA sequence data was used to construct individ?ual gene trees using maximum likelihood and species trees were estimated from gene trees using Bayesian *** dates were obtained using a molecular clock ***:Molecular data estimate a probable window of time for the origin for the Liocichla from the mid to late Miocene,between 5.55 and 12.87 *** plumage similarities between the insular Taiwan endemic,***,and the continental *** and ***,molecular data suggest that *** is the sister taxon to all continen?tal *** continental Liocichla are comprised of two lineages;a lineage containing *** and *** and a lineage comprised of *** and *** comparatively early divergence of *** within the Liocichla may be illusory due to extinct and therefore unsampled *** and *** are parapatric with a Pleistocene split(0.07–1.88 Ma) occurring between an Eastern Himalayan *** and a Northern Indo?china distributed *** and *** underwent a similar split between the Eastern Himalaya(***) and Central China(***) divided by the Hengduan ***

关键词： Biogeography Himalayas Leiothrichidae Liocichla Phylogenetics Phylogeography Taiwan

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Engineering microparticles based on solidified stem cell secretome with an augmented pro-angiogenic factor portfolio for therapeutic angiogenesis

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Bioactive Materials 2022年第11期7卷 526-541页

作者： thomas Spater Marisa Assunçao Kwok Keung Lit Guidong Gong Xiaoling Wang Yi-Yun Chen Ying Rao Yucong Li Chi Him Kendrick Yiu Matthias W.Laschke Michael D.Menger Dan Wang Rocky S.Tuan kay-Hooi Khoo Michael Raghunath Junling Guo Anna Blocki Institute for Clinical&Experimental Surgery Saarland UniversityHomburgSaarGermany School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongShatinNew TerritoriesHong KongChina Institute for Tissue Engineering and Regenerative Medicine The Chinese University of Hong KongShatinNew TerritoriesHong KongChina BMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and EngineeringSichuan UniversityChengduSichuan610065China Bioproducts Institute Departments of Chemical and Biological EngineeringThe University of British ColumbiaVancouverBCCanada Academia Sinica Common Mass Spectrometry Facilities for Proteomics and Protein Modification Analysis and Institute of Biological ChemistryAcademia SinicaNankangTaipeiChina Shun Hing Institute of Advanced Engineering(SHIAE) Faculty of EngineeringThe Chinese University of Hong KongShatinNew TerritoriesHong KongChina Ministry of Education Key Laboratory for Regenerative Medicine School of Biomedical SciencesThe Chinese University of Hong KongShatinNew TerritoriesHong KongChina Department of Orthopaedics&Traumatology The Chinese University of Hong KongShatinNew TerritoriesHong KongHong Kong Special Administrative Region of China Institute for Chemistry and Biotechnology Zurich University of Applied SciencesWadenswilSwitzerland State Key Laboratory of Polymer Materials Engineering Sichuan UniversityChengduSichuan610065China

Tissue (re)vascularization strategies face various challenges, as therapeutic cells do not survive long enough in situ, while the administration of pro-angiogenic factors is hampered by fast clearance and insufficient ability to emulate complex spatiotemporal signaling. Here, we propose to address these limitations by engineering a functional biomaterial capable of capturing and concentrating the pro-angiogenic activities of mesenchymal stem cells (MSCs). In particular, dextran sulfate, a high molecular weight sulfated glucose polymer, supplemented to MSC cul-tures, interacts with MSC-derived extracellular matrix (ECM) components and facilitates their co-assembly and accumulation in the pericellular space. Upon decellularization, the resulting dextran sulfate-ECM hybrid material can be processed into MIcroparticles of SOlidified Secretome (MIPSOS). The insoluble format of MIPSOS protects protein components from degradation, while facilitating their sustained release. Proteomic analysis demonstrates that MIPSOS are highly enriched in pro-angiogenic factors, resulting in an enhanced pro-angiogenic bioactivity when compared to naïve MSC-derived ECM (cECM). Consequently, intravital microscopy of full-thickness skin wounds treated with MIPSOS demonstrates accelerated revascularization and healing, far superior to the ther-apeutic potential of cECM. Hence, the microparticle-based solidified stem cell secretome provides a promising platform to address major limitations of current therapeutic angiogenesis approaches.

关键词： Dextran sulfate Extracellular matrix Mesenchymal stem cells Therapeutic angiogenesis Wound healing Poly-electrolyte-driven co-assembly

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聚合型防老剂

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橡胶参考资料 1975年第9期 35-41页

作者： E.kay D.K.thomas W.W.Wright 吴同锴

在某些应用上,例如高速飞机,要求橡胶另件能在高温并且经常与流体(诸如煤油、酯等液压介质)接触的条件下长期工作。特别是高温用橡胶诸如目前在飞机上广泛应用的氟胶、硅胶甚至最终也要发生老化。这种老化,在很大程度上是热氧作用的结果... 详细信息

在某些应用上,例如高速飞机,要求橡胶另件能在高温并且经常与流体(诸如煤油、酯等液压介质)接触的条件下长期工作。特别是高温用橡胶诸如目前在飞机上广泛应用的氟胶、硅胶甚至最终也要发生老化。这种老化,在很大程度上是热氧作用的结果,如果橡胶能保持在绝氧条件下应用,则可预期使用寿命明显增加。但是从系统中排除氧通常是行不通

关键词：防老剂分子网抗老剂聚合型硫化胶

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Absolute Lymphocyte/Monocyte Ratio at Diagnosis and Interim Positron-Emission Tomography Predict Survival in Classical Hodgkin Lymphoma

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Journal of Cancer Therapy 2013年第3期4卷 452-459页

作者： Luis F. Porrata kay M. Ristow thomas M. Habermann thomas E. Witzig Joseph P. Colgan David J. Inwards Stephen M. Ansell Ivana N. Micallef Patrick B. Johnston Grzegorz Nowakowski Carrie A. Thompson Svetomir N. Markovic Division of Hematology Internal Medicine Mayo College of Medicine Rochester USA

Interim Positron-Emission Tomography (int-PET) and the peripheral blood absolute lymphocyte/monocyte ratio at di- agnosis (ALC/AMC-DX) have been shown to be predictors for progression-free survival (PFS) and time to progression (TTP) in classical Hodgkin lymphoma (cHL). Therefore, we studied if the combination of ALC/AMC-DX and the (int-PET) can further stratified PFS and TTP in cHL patients. Patients were required to be diagnosed, treated, and followed with int-PET at Mayo Clinic, Rochester, Minnesota. From 2000 until 2008, 111 cHL patients qualified for the study. The median follow-up was 2.8 years (range: 0.3 - 10.4 years). Patients with a negative int-PET (N = 98) pre- sented with a higher ALC/AMC-DX (median of 2.32, range: 0.26 - 37.5) compared with patients with a positive int-PET (N = 13) (median of 0.9, range: 0.29 - 3.10), p 1.1. Group 1 experienced superior PFS and TTP in comparison with the other groups. In conclusion, the combination of ALC/AMC-DX and the int-PET provides a simple model to assess clinical outcomes in cHL.

关键词： Classical Hodgkin Lymphoma Absolute Lymphocyte/Monocyte Ratio at Diagnosis Interim PET-Scan Progression-Free Survival Time to Progression

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冲洗蒸煮袋的交通灾害对气体阻隔性能的影响

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绿色包装 2016年第7期 61-页

作者： Kyle D. Dunno Scott Whiteside Ron thomas kay Cooksey Patrick Gerard

透明高阻隔蒸煮袋装满了水并充入氮气。本研究使用体积分别为200与400cm^3的蒸煮袋,并搭配使用oxydot~?作为一种无创测量技术监测空氧分包装。该蒸煮袋包装在开槽容器内模拟实验室运输试验小包裹和机组负荷的输送系统。评价模拟运输试... 详细信息

透明高阻隔蒸煮袋装满了水并充入氮气。本研究使用体积分别为200与400cm^3的蒸煮袋,并搭配使用oxydot~?作为一种无创测量技术监测空氧分包装。该蒸煮袋包装在开槽容器内模拟实验室运输试验小包裹和机组负荷的输送系统。评价模拟运输试验的影响,并与每个变量控制蒸煮袋进行比较。测量所有的蒸煮袋空氧含量(测控)63天。结果表明,比较模拟的运输样品的对照样品,在所有的变量中有显着差异。比较空氧体积,400cm^3袋相比200cm^3袋在小包裹中产生更少的氧气(P<0.05)。在机组负荷模拟中的两个空氧体积没有显着差异。这项研究的结果表明,包装的产品通过小包裹供应链分布,这是比那些被运送托盘更好的处理,因为这对分销渠道来说增加了空氧体积,可以免受氧气渗入的困扰。

关键词：蒸煮袋运输试验气体阻隔性无创测量比较模拟技术监测机组负荷输送系统模拟实验室变量控制

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Performance and calibration of quark/gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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Chinese Physics C 2024年第2期48卷 1-25页

作者： G. Aad B. Abbott K. Abeling N.J. Abicht S.H. Abidi A. Aboulhorma H. Abramowicz H. Abreu Y. Abulaiti B.S. Acharya C. Adam Bourdarios L. Adamczyk S.V. Addepalli M.J. Addison J. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik M.N. Agaras J. Agarwala A. Aggarwal C. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aikot M. Ait Tamlihat B. Aitbenchikh I. Aizenberg M. Akbiyik T.P.A. Åkesson A.V. Akimov D. Akiyama N.N. Akolkar K. Al Khoury G.L. Alberghi J. Albert P. Albicocco G.L. Albouy S. Alderweireldt M. Aleksa I.N. Aleksandrov C. Alexa T. Alexopoulos F. Alfonsi M. Algren M. Alhroob B. Ali H.M.J. Ali S. Ali S.W. Alibocus M. Aliev G. Alimonti W. Alkakhi C. Allaire B.M.M. Allbrooke J.F. Allen C.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso C. Alpigiani M. Alvarez Estevez A. Alvarez Fernandez M. Alves Cardoso M.G. Alviggi M. Aly Y. Amaral Coutinho A. Ambler C. Amelung M. Amerl C.G. Ames D. Amidei S.P. Amor Dos Santos K.R. Amos V. Ananiev C. Anastopoulos T. Andeen J.K. Anders S.Y. Andrean A. Andreazza S. Angelidakis A. Angerami A.V. Anisenkov A. Annovi C. Antel M.T. Anthony E. Antipov M. Antonelli F. Anulli M. Aoki T. Aoki J.A. Aparisi Pozo M.A. Aparo L. Aperio Bella C. Appelt A. Apyan N. Aranzabal S.J. Arbiol Val C. Arcangeletti A.T.H. Arce E. Arena J-F. Arguin S. Argyropoulos J.-H. Arling O. Arnaez H. Arnold G. Artoni H. Asada K. Asai S. Asai N.A. Asbah J. Assahsah K. Assamagan R. Astalos S. Atashi R.J. Atkin M. Atkinson H. Atmani P.A. Atmasiddha K. Augsten S. Auricchio A.D. Auriol V.A. Austrup G. Avolio K. Axiotis G. Azuelos D. Babal H. Bachacou K. Bachas A. Bachiu F. Backman A. Badea P. Bagnaia M. Bahmani A.J. Bailey V.R. Bailey J.T. Baines L. Baines O.K. Baker E. Bakos D. Bakshi Gupta V. Balakrishnan R. Balasubramanian E.M. Baldin P. Balek E. Ballabene F. Balli L.M. Baltes W.K. Balunas J. Balz E. Banas M. Bandieramonte A. Bandyopadhyay S. Bansal L. Barak M. Barakat E.L. Barberio D. Barberis M. Barbero M.Z. Barel K.N. Barends T. Barillari M-S. Barisits T. Barklow P. Baron D.A. Baron Mo The ATLAS Collaboration

The identification of jets originating from quarks and gluons,often referred to as quark/gluon tagging,plays an important role in various analyses performed at the Large Hadron Collider,as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced *** paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS *** taggers with high performances in rejecting jets from gluon over jets from quarks are studied:one tagger is based on requirements on the number of inner-detector tracks associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark/gluon fraction in data,by using quark/gluon-enriched subsamples defined by the jet *** in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points.

关键词： ATLAS JET QUARK GLUON TAGGING

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