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环境友好的无氟制冷剂——roche诊断公司研发成功使用天然制冷剂的冷冻干燥设备

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流程工业 2009年第9期 46-46,48页

作者： Dirk Scheffauer roche诊断公司的运行工程师

尽管已经有一些制冷剂能够替代产生温室气体效应的氟里昂，但它们总是不能可靠地避免引起温室气体效应的可能性。第一种无氟制冷剂的问世才真正地减轻了制冷技术给环境带来的危害，这种无氟制冷剂要求采用特殊的制冷技术。在roche诊断... 详细信息

尽管已经有一些制冷剂能够替代产生温室气体效应的氟里昂，但它们总是不能可靠地避免引起温室气体效应的可能性。第一种无氟制冷剂的问世才真正地减轻了制冷技术给环境带来的危害，这种无氟制冷剂要求采用特殊的制冷技术。在roche诊断公司的驻地Penzberg市，诞生了一套新型的、真正做到了最佳的环境保护的冷冻干燥设备。

关键词：冷冻干燥设备无氟制冷剂天然制冷剂环境友好诊断研发气体效应制冷技术

roche公司灵活式自动化在实验室中的应用

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临床检验杂志 2011年第7期29卷 496-496页

作者：王菲菲 roche诊断产品上海有限公司上海200031

自动化之所以成为实验室发展的首选方案,在于它可以改善工作流程从而提高工作效率,同时减少人工介入环节,保证结果的准确性。一些研究机构对实验室流程比例进行研究发现,样品前处理占了整个实验室一半的资源,样品分析中和分析后占了实... 详细信息

自动化之所以成为实验室发展的首选方案,在于它可以改善工作流程从而提高工作效率,同时减少人工介入环节,保证结果的准确性。一些研究机构对实验室流程比例进行研究发现,样品前处理占了整个实验室一半的资源,样品分析中和分析后占了实验室工作人员15%～20%的时间和精力，

关键词：实验室自动化医学检验

Doubling down with CAR-T cell cancer immunotherapy:a two-step recognition circuit enables discrimination between target antigen high and low cancer cells

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2280-2281页

作者： Jehad Charo Bruno Gomes hoffmann-la roche ag pharmaceutical research and early development oncologyroche innovation center zurichzurichswitzerland hoffmann-la roche ag pharmaceutical research and early development oncologyroche innovation center baselbaselswitzerland

In a recent article published in Science by Hernandez-Lopez et *** antigen receptor(CAR)expressing T(CAR-T)cells with a two-step recognition system successfully discriminated between target cells expressing high and l... 详细信息

关键词： CAR cancer

Exploring the utility of the Chasing Principle:influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

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Acta Pharmaceutica Sinica B 2019年第1期9卷 194-201页

作者： Scheyla Daniela Siqueira J?rgensen Thomas Rades Huiling Mu Kirsten Graeser Anette Müllertz Department of Pharmacy Faculty of Health and Medical Sciences University of Copenhagen roche Pharma Research and Development Therapeutic Modalities Roche Innovation Center Basel

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol(CAR), cinnarizine(CIN) or R3040 on drug solubilization in a twocompartment in vitro lipolysis model. Correlation of drug log P or solubility in SNEDDS with drug solubilization during in vitro lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1(1:1, w/w) and Kolliphor RH40, with ethanol at 10%(w/w) were used. SNEDDS were named F65, F55 and F20(numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS(F0) were also analyzed. While the ranking order of drug solubilization was F65? F55? F204F0 for CAR; F65? F554F204F0 for CIN and F65? F55? F204F0 for R3040-with higher CAR solubilization than for R3040 and CIN-the ranking of S_(eq)of CAR, CIN and R3040 in SNEDDS was F65 o F55o F20, F65? F554F20 and F654F554F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high S_(eq) in SNEDDS did not reflect high drug solubilization. As CAR(log P 3.8) showed higher solubilization than CIN(log P 5.8) and R3040(log P 10.4), a correlation between drug log P and drug solubilization was observed.

关键词： Self-nanoemulsiying drug delivery system(SNEDDS) Chasing principle Two-compartment in vitro lipolysis Rat gastrointestinal conditions Drug solubilization

The T-box Transcription Factor T-bet in Immunity and Autoimmunity

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Cellular & Molecular Immunology 2006年第2期3卷 87-95页

作者： Stanford L.Peng Inflammation Autoimmunity and Transplantation ResearchRoche Palo AltoPalo AltoCAUSA

The T-box transcription factor T-bet （Tbx21） has emerged as a key regulator of type 1-like immunity, playing critical roles in the establishment and/or maintenance of effector call fates in T and B lymphocytes, as well as dendritic cells and natural killer calls. Several autoimmune diseases, especially those classically considered related to T helper 1 （Thl） immunity, appear to require T-bet, at least as judged in mouse models. This review summarizes a current understanding of T-bet＇s role in immunity, as wall as its importance in autoimmunity, with implications for therapeutic intervention.

关键词： transcription factor arthritis lupus inflammatory bowel disease diabetes multiple sclerosis

Assembly and release of infectious hepatitis C virus involving unusual organization of the secretory pathway

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World Journal of Hepatology 2016年第19期8卷 796-814页

作者： Miriam Triyatni Edward A Berger Bertrand Saunier roche Innovation Center Roche Pharma Research and Early Development F. Hoffmann-La Roche Ltd. Molecular Structure Section Laboratory of Viral Diseases NIAID NIH Unité de Virologie Structurale Institut Pasteur and CNRS UMR 3569

AIM: To determine if calnexin(CANX), RAB1 and alphatubulin were involved in the production of hepatitis C virus(HCV) particles by baby hamster kidney-West Nile virus(BHK-WNV) cells. METHODS: Using a si RNA-based approach complemented with immuno-fluorescence confocal microscope and Western blot studies, we examined the roles of CANX, RAB1 and alpha-tubulin in the production of HCV particles by permissive BHK-WNV cells expressing HCV structural proteins or the full-length genome of HCV genotype 1a. Immuno-fluorescence studies in producer cells were performed with monoclonal antibodies against HCV structural proteins, as well as immunoglobulin from the serum of a patient recently cured from an HCV infection of same genotype. The cellular compartment stained by the serum immunoglobulin was also observedin thin section transmission electron microscopy. These findings were compared with the JFH-1 strain/Huh-7.5 cell ***: We found that CANX was necessary for the production of HCV particles by BHK-WNV cells. This process involved the recruitment of a subset of HCV proteins, detected by immunoglobulin of an HCV-cured patient, in a compartment of rearranged membranes bypassing the endoplasmic reticulum-Golgi intermediary compartment and surrounded by mitochondria. It also involved the maturation of N-linked glycans on HCV envelope proteins, which was required for assembly and/or secretion of HCV particles. The formation of this specialized compartment required RAB1; upon expression of HCV structural genes, this compartment developed large vesicles with viral particles. RAB1 and alpha-tubulin were required for the release of HCV particles. These cellular factors were also involved in the production of HCVcc in the JFH-1 strain/Huh-7.5 cell system, which involves HCV RNA replication. The secretion of HCV particles by BHK-WNV cells presents similarities with a pathway involving caspase-1; a caspase-1 inhibitor was found to suppress the production of HCV particles from

关键词： Membrane rearrangements Hepatitis C virus Flavivirus replicon Virus assembly and secretion Host cellular factors

Elevated plasma levels of N-terminal pro-brain natriuretic peptide in patients with chronic hepatitis C during interferon-based antiviral therapy

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World Journal of Gastroenterology 2006年第36期12卷 5875-5877页

作者： Jrg Bojunga Christoph Sarrazin Georg Hess Stefan Zeuzem Internal Medicine Ⅱ Saarland University Hospital 66421 Homburg/Saar Germany roche Diagnostics 68305 Mannheim Germany

AIM: To investigate plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), an established marker of cardiac function, in patients with chronic hepatitis C during interferon-based antiviral therapy. METHODS: Using a sandwich immunoassay, plasma levels of NT-proBNP were determined in 48 patients with chronic hepatitis C at baseline, wk 24 and 48 during antiviral therapy and at wk 72 during ***: Plasma NT-proBNP concentrations were significantly increased (P < 0.05) at wk 24, 48 and 72 compared to the baseline values. NT-proBNP concentrations at baseline and wk 24 were closely correlated (r = 0.8; P < 0.001). At wk 24, 7 (14.6%) patients had NT-proBNP concentrations above 200 ng/L compared to 1 (2%) patient at baseline (P = 0.059). Six of these 7 patients had been treated with high-dose IFN-α induction therapy. In multiple regression analysis, NT-proBNP was not related to other clinical parameters, biochemical parameters of liver disease or virus load and response to ***: Elevated levels of NT-proBNP during and after interferon-based antiviral therapy of chronic hepatitis C may indicate the presence of cardiac dysfunction, which may contribute to the clinical symptoms observed in patients during therapy. Plasma levels of NT-proBNP may be used as a diagnostic tool and for guiding therapy in patients during interferon-based antiviral therapy.

关键词： Hepatitis C N-terminal pro-brain natriuretic peptide Interferon Cardiomyopathy Treatment side effects

Integrated platform for mechanistic mitochondrial toxicity assessment: fluoroquinolones as an example

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Integrated platform for mechanistic mitochondrial toxicity a...

Investigating Genotype 1a HCV Drug Resistance in NS5A Region via Bayesian Inference

中国毒理学会第七次全国会员代表大会暨中国毒理学会第六次中青年学者科技论坛

作者： Tianyi Jiang Xiaoqin Wu Meifang Zhang Waikwong Wu Jianxun Xie Stefan Kustermann roche Innovation Center Shanghai roche Innovation Center Basel

Drug-induced mitochondrial dysfunction can contribute to organ toxicity and has resulted in a considerable number of market withdrawals. Therefore a robust screening strategy is essential to identify potential mitochondrial liability at the early stages of drug development. It is particularly mandated for antibiotics as they bear inherent risk of mitochondrial toxicity due to the similarity

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Tsinghua Science and Technology 2015年第5期20卷 484-490页

作者： Yao Fu Gang Chen Lizhi Fu Jing Zhang bioinformatics scientist in Bina Technologies Roche Redwood City CA 94065 USA the financial service industry Department of Mathematics & Statistics Georgia State University the Department of Statistics Yale University

Hepatitis C virus（HCV） treatment is on the cutting edge of medicine. Due to the high rate of mutations and low fidelity of HCV replication, resistant strains quickly become dominant in a viral population under the selection pressure of a drug. In this paper, we examined the drug resistance mechanism in the NS5 A region of genotype1 a HCV virus by comparing the sequence data from interferon-ribavirin treated and untreated patients. To find the drug resistance difference, we used innovative Bayesian probability models to detect mutation combinations and inferred detailed interaction structures of these mutations. We aim to provide reference to drug design and mutation mechanism understanding through our work.

关键词： Bayesian model Hepatitis C virus(HCV) drug resistance NS5A