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活性金属部分瞬间液相连接氮化硅陶瓷的研究

金属学报 2000年第2期36卷 171-176页

作者：周飞李志章江苏理工大学材料系镇江212013 浙江大学材料系杭州310027

采用Ｔｉ／Ｃｕ／Ｔｉ多层中间层在１２７３Ｋ温度下进行氨化硅陶瓷部分瞬间液相连接，考察了保温时间对连接强度的影响，并对连接界面进行了ＳＥＭ，ＥＰＭＡ和ＸＲＤ分析．结果表明，通过Ｃｕ－Ｔｉ二元扩散促使液相与氨化硅发生界面... 详细信息

采用Ｔｉ／Ｃｕ／Ｔｉ多层中间层在１２７３Ｋ温度下进行氨化硅陶瓷部分瞬间液相连接，考察了保温时间对连接强度的影响，并对连接界面进行了ＳＥＭ，ＥＰＭＡ和ＸＲＤ分析．结果表明，通过Ｃｕ－Ｔｉ二元扩散促使液相与氨化硅发生界面反应，形成Ｓｉ_３Ｎ_４／ＴｉＮ／Ｔｉ_５Ｓｉ_３＋Ｔｉ_５Ｓｉ_４＋ＴｉＳｉ_２／ＴｉＳｉ_２＋Ｃｕ_３Ｔｉ_２（Ｓｉ）／Ｃｕ的梯度层．保温时间影响接头反应层厚度，从而影响接头的连接强度根据活性金属部分瞬间液相连接陶瓷的界面行为，建立了活性金属部分瞬间液相连接陶瓷的理论模型．该模型较好地解释了Ｔｉ／Ｃｕ／Ｔｉ和Ｔｉ／Ｎｉ／Ｔｉ连接氮化硅陶瓷的异同点和连接工艺参数的选择。

关键词：活性金属氮化硅连接强度界面反应陶瓷连接

Cellular heterogeneity in pancreatic cancer: the different faces of gremlin action

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Signal Transduction and Targeted Therapy 2022年第11期7卷 3992-3994页

作者： Aristidis Moustakas J.Matthias Löhr Rainer L.Heuchel Department of Medical Biochemistry and Microbiology Uppsala UniversityUppsalaSweden Department of Clinical Intervention and Technology(CLINTEC) Karolinska InstitutetStockholmSweden

A recent publication in Nature by Lan et al.,presented GREM1(gremlin 1)as an important regulatory node of cellular plasticity in pancreatic ductal adenocarcinoma(PDAC).1 Knockout experiments in mice point to an important role of Grem1 in retaining an epithelial,differentiated phenotype of pancreatic cancer cells presumably by inhibiting BMP signalling.

关键词： al. cancer inhibiting

Morphological alterations and redox changes associated with hepatic warm ischemia-reperfusion injury

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World Journal of Hepatology 2017年第34期9卷 1261-1269页

作者： Rim Jawad Melroy D'souza Lisa Arodin Selenius Marita Wallenberg Lundgren Olof Danielsson Greg Nowak Mikael Bjornstedt Bengt Isaksson Division of Pathology Department of Laboratory Medicine Karolinska Institutet Department of Clinical Science Intervention and Technology (CLINTEC) Division of Surgery Karolinska Institutet Karolinska University Hospital Department of Clinical Science Intervention and Technology (CLINTEC) Division of Transplantation Surgery Karolinska Institutet Karolinska University Hospital

AIM To study the effects of warm ischemia-reperfusion(I/R) injury on hepatic morphology at the ultrastructural level and to analyze the expression of the thioredoxin(TRX)and glutaredoxin(GRX) *** Eleven patients undergoing liver resection were subjected to portal triad clamping(PTC). Liver biopsies were collected at three time points; first prior to PTC(baseline), 20 min after PTC(post-ischemia) and 20 min after reperfusion(post-reperfusion). Electron microscopy and morphometry were used to study and quantify ultrastructural changes, respectively. Additionally, gene expression analysis of TRX and GRX isoforms was performed by quantitative PCR. For further validation of redox protein status, immunogold staining was performed for the isoforms GRX1 and *** Post-ischemia, a significant loss of the liver sinusoidal endothelial cell(LSEC) lining was observed(P = 0.0003) accompanied by a decrease of hepatocyte microvilli in the space of Disse. Hepatocellular morphology was well preserved apart from the appearance of crystalline mitochondrial inclusions in 7 out of 11 patients. Postreperfusion biopsies had similar features as post-ischemia with the exception of signs of a reactivation of the LSECs. No changes in the expression of redox-regulatory genes could be observed at mR NA level of the isoforms of the TRX family but immunoelectron microscopy indicated a redistribution of TRX1 within the *** At the ultrastructural level, the major impact of hepatic warm I/R injury after PTC was borne by the LSECs with detachment and reactivation at ischemia and reperfusion, respectively. Hepatocytes morphology were well preserved. Crystalline inclusions in mitochondria were observed in the hepatocyte after ischemia.

关键词： Hepatic ischemia-reperfusion injury Ischemia reperfusion injury Warm ischemia-reperfusion injury Glutaredoxins Thioredoxins Electron microscopy Oxidative stress Portal triad clamping

Mitochondria-localized β-actin is essential for priming innate antiviral immune signaling by regulating IRF3 protein stability

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Cellular & Molecular Immunology 2019年第10期16卷 837-840页

作者： Xin Xie Martin Endara-Coll Raza Mahmood Robertas Jankauskas Tamara Gjorgjieva Piergiorgio Percipalle Science Division Biology ProgramNew York University Abu Dhabi(NYUAD)P.O.Box 129188 Abu DhabiUnited Arab Emirates Department of Molecular Biosciences The Wenner-Gren InstituteStockholm UniversitySE-10691StockholmSweden New York University Center for Genomics and Systems Biology NYUNew YorkNYUSA

Antiviral innate immunity acts as a defensive barrier to viral infection in both immune and nonimmune *** viral nucleic acids present in the cytoplasm after viral replication can activate sensors such as the RIG-I-lik... 详细信息

关键词： immunity immune stability

p53 as a hub in cellular redox regulation and therapeutic target in cancer

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Journal of Molecular Cell Biology 2019年第4期11卷 330-341页

作者： Sofi E.Eriksson Sophia Ceder Vladimir J.N.Bykov Klas G.Wiman Karolinska Institutet Department of Oncology-Pathology BioClinicum Stockholm Sweden

The TP53 tumor suppressor gene encodes a DNA-binding transcription factor that regulates multiple cellular processes including cell growth and cell death. The ability of p53 to bind to DNA and activate transcription is tightly regulated by post-translational modifications and is dependent on a reducing cellular environment. Some p53 transcriptional target genes are involved in regulation of the cellular redox homeostasis, e.g. TIGAR and GLS2. A large fraction of human tumors carry TP53 mutations, most commonly missense mutations that lead to single amino acid substitutions in the core domain. Mutant p53 proteins can acquire so called gain-of-function activities and influence the cellular redox balance in various ways, for instance by binding of the Nrf2 transcription factor, a major regulator of cellular redox state. The DNA-binding core domain of p53 has 10 cysteine residues, three of which participate in holding a zinc atom that is critical for p53 structure and function. Several novel compounds that refold and reactivate missense mutant p53 bind to specific p53 cysteine residues. These compounds can also react with other thiols and target components of the cellular redox system, such as glutathione. Dual targeting of mutant p53 and redox homeostasis may allow more efficient treatment of cancer.

关键词： p53 redox regulation mutation oxidative stress Nrf2 thiols cancer therapy

Advanced small-bowel well-differentiated neuroendocrine tumours:An international survey of practice on 3rd-line treatment

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World Journal of Gastroenterology 2021年第10期27卷 976-989页

作者： Angela Lamarca Mauro Cives Louis de Mestier Joakim Crona Francesca Spada KjellÖberg Marianne Pavel Teresa Alonso-Gordoa Department of Medical Oncology European Neuroendocrine Tumor Society Centre of ExcellenceThe Christie NHS Foundation TrustUniversity of ManchesterManchester M204BXUnited Kingdom Department of Biomedical Sciences and Human Oncology University of Bari Aldo MoroBari 70121Italy Department of Gastroenterology and Pancreatology European Neuroendocrine Tumor Society Center of ExcellenceParis-Diderot UniversityClichy 75006France Department of Medical Sciences Uppsala UniversityUppsala SE-75185Sweden Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit European Institute of OncologyMilan 20141Italy Department of Endocrine Oncology Uppsala University HospitalUppsala SE-75185Sweden Department of Endocrinology Universitatsklinikum ErlangenErlangen 91054Germany Medical Oncology Department The Ramón y Cajal Health Research InstituteAlcaláUniversityUniversity Hospital Ramon y CajalMadrid 28034Spain

BACKGROUND Somatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours(Wd-SBNETs),while and peptide receptor radionuclide therapy(PRRT)is frequently used as a second-line *** treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic *** To understand current practice and rationale for decision-making by physicians in the 3rd-line setting by building an online *** Weighted average(WA)of likelihood of usage between responders(1 very unlikely;4 very likely)was used to reflect the relevance of factors *** Replies from representatives of 28 centers were received(5/8/2020-21/9/2020);medical oncologist(53.6%),gastroenterologist(17.9%);United Kingdom(21.4%),Spain(17.9%),Italy(14.3%).Majority from European Neuroendocrine Tumor Society(ENETS)Centres of Excellence(57.1%),who followed ENETS guidelines(82.1%).Generally speaking,3rd-line treatment for Wd-SBNETs was:everolimus(EVE)(66.7%),PRRT(18.5%),liver embolization(LE)(7.4%)and interferon-alpha(IFN)(3.7%);chemotherapy(0%);decision was based on clinical trial data(59.3%),or personal experience(22.2%).EVE was most likely used if Ki-67<10%(WA 3.27/4)or age<70 years(WA 3.23/4),in the 3rd-line setting(WA 3.23/4);regardless of presence/absence of carcinoid syndrome(CS),rate of progression or extent of *** was mainly utilised only if rapid progression(within 6 mo)(WA 3.35/4),Ki-6710%-20%(WA 2.77/4),negative somatostatin receptor imaging(WA 2.65/4)or high tumour burden(WA 2.77/4);temozolomide or streptozocin was used with capecitabine or 5-fluorouracil(5-FU)(57.7%),FOLFOX(5-FU combined with oxaliplatin)(23.1%).LE was selected if presence of CS(WA 3.24/4)or Ki-67<10%(WA 2.8/4),after progression to other treatments(WA 2.8/4).IFN was rarely used(WA 1.3/4).CONCLUSION Everolimus was the most frequently used therapeutic option in the t

关键词： Neuroendocrine tumour Small bowel Survey Third-line Advanced Practice

Alkaline sphingomyelinase(NPP7) in hepatobiliary diseases: A field that needs to be closely studied

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World Journal of Hepatology 2018年第2期10卷 246-253页

作者： Rui-Dong Duan Gastroenterology and Nutrition Lab Department of Clinical Sciences Lund University

Alkaline sphingomyelinase cleaves phosphocholine from sphingomyelin, platelet-activating factor, lysophosphatidylcholine, and less effectively phosphatidyl-choline. The enzyme shares no structure similarities with acid or neutral sphingomyelinase but belongs to ectonucleotide pyrophosphatase/phosphodiesterase(NPP) family and therefore is also called NPP7 nowadays. The enzyme is expressed in the intestinal mucosa in many species and additionally in human liver. The enzyme in the intestinal tract has been extensively studied but not that in human liver. Studies on intestinal alkaline sphingomyelinase show that it inhibits colonic tumorigenesis and inflammation, hydrolyses dietary sphingomyelin, and stimulates cholesterol absorption. The review aims to summarize the current knowledge on liver alkaline sphingomyelinase in human and strengthen the necessity for close study on this unique human enzyme in hepatobiliary diseases.

关键词： Sphingomyelin Alkaline sphingomyelinase Nucleotide pyrophosphatase/phosphodiesterase 7 Autotaxin Platelet-activating factor Cholangiocarcinoma Liver diseases Gallstone

基于内模原理电站锅炉汽温控制策略的工程应用

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电力系统自动化 2007年第4期31卷 97-100页

作者：王泽宁刘春勇国电南瑞科技股份有限公司江苏省南京市210003 国网新源徐州发电厂江苏省徐州市221166

针对电站锅炉汽温被控对象大滞后、大惯性的特点,设计了一种新的基于内模控制原理的过热汽温控制策略。该控制策略已成功应用于徐州电厂6号机组670t/h超高压锅炉,现场调试和机组运行结果表明,这种基于内模控制原理的控制策略具有结构简... 详细信息

针对电站锅炉汽温被控对象大滞后、大惯性的特点,设计了一种新的基于内模控制原理的过热汽温控制策略。该控制策略已成功应用于徐州电厂6号机组670t/h超高压锅炉,现场调试和机组运行结果表明,这种基于内模控制原理的控制策略具有结构简单、在线调整参数少、可以明显提高控制回路的鲁棒性及抗干扰能力。现场试验结果表明,与传统串级比例—积分—微分(PID)调节方案相比,无论对于稳态过程或动态过程,新控制策略的调节品质均有明显提高。

关键词：火电厂电站锅炉过热汽温内模控制汽温控制

Population-scale variability of the human UDP-glycosyltransferase gene family

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Journal of Genetics and Genomics 2024年第11期51卷 1228-1236页

作者： Daianna González-Padilla Mahamadou D.Camara Volker M.Lauschke Yitian Zhou Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden Center for Molecular Medicine Karolinska Institutet and University HospitalStockholmSweden Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology StuttgartGermany University of Tubingen TubingenGermany

Human UDP-glycosyltransferases(UGTs)are responsible for the glycosylation of a wide variety of endogenous substrates and commonly prescribed *** genetic polymorphisms in UGT genes are implicated in interindividual differences in drug response and cancer ***,the genetic complexity beyond these variants has not been comprehensively *** here leveraged wholeexome and whole-genome sequencing data from 141,456 unrelated individuals across 7 major human populations to provide a comprehensive profile of genetic variability across the human UGT gene ***,9666 exonic variants were observed,of which 98.9%were *** interpret the functional impact of UGT missense variants,we developed a gene family-specific variant effect *** algorithm identified a total of 1208 deleterious variants,most of which were found in African and South Asian *** analysis corroborated the predicted effects for multiple variations in substrate binding ***,our analyses provide a systematic overview of UGT variability,which can yield insights into interindividual differences in phase 2 metabolism and facilitate the translation of sequencing data into personalized predictions of UGT substrate disposition.

关键词： UDP-Glycosyltransferases Genetic variants Populations Drug response Cancer risk Pharmacogenomics