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Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump

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World Journal of Gastroenterology 2008年第1期14卷 38-45页

作者： Yvonne Meier Tina Zodan Carmen Lang roland zimmermann Gerd A Kullak-Ublick Peter J Meier Bruno Stieger Christiane Pauli-Magnus Division of Clinical Pharmacology and Toxicology Department of Internal Medicine University Hospital Zurich Zurich Switzerland Department of Gynecology and Obstetrics University Hospital Zurich Zurich Switzerland Division of Clinical Pharmacology and Toxicology Department of Internal Medicine University Hospital Zurich Zurich Switzerland Clinical Trial Unit University Hospital Basel Basel Switzerland

AIM： To study the association of three common ABCB11 and ABCC2 polymorphisms （ABCB11： 1331T〉C→V444A; ABCC2： 3563T〉A → V1188E and 4544G 〉A → C1515Y） with intrahepatic cholestasis of pregnancy （ICP） and contraceptive-induced cholestasis （CIC）. METHODS： ABCB11 and ABCC2 genotyping data were available from four CIC patients and from 42 and 33 ICP patients, respectively. Allele-frequencies of the studied polymorphisms were compared with those in healthy pregnant controls and Caucasian individuals. Furthermore, serum bile acid levels were correlated with the presence or absence of the 1331 C allele. RESULTS： The ABCB11 1331T〉C polymorphism was significantly more frequent in cholestatic patients than in pregnant controls： C allele 76.2% （CI, 58.0-94.4） vs 51.3% （CI 35.8-66.7）, respectively （P = 0.0007）; and CC allele 57.1% （CI 36.0-78.3） vs 20% （CI 7.6-32.4）, respectively （P = 0.0065）. All four CIC patients were homozygous carriers of the C allele. In contrast, none of the studied ABCC2 polymorphism was overrepresented in ICP or CIC patients. Higher serum bile acid levels were found in carriers of the 1331CC genotype compared to carriers of the TT genotype. CONCLUSION： Our data support a role for the ABCB11 1331T〉C polymorphism as a susceptibility factor for the development of estrogen-induced cholestasis, whereas no such association was found for ABCC2. Serum bile acid and 7-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.

关键词： Cholestasis of pregnancy Contraceptive-induced cholestasis Bile salt export pump Multidrugresistance associated protein 2 Pharmacogenetics

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Five-year impact of a new departmental protocol on emergency cesarean target times

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Open Journal of Obstetrics and Gynecology 2013年第1期3卷 148-153页

作者： Visnja Korda roland zimmermann Department of Obstetrics University Hospital of Zurich Zurich Switzerland

Objective: To evaluate the impact of an emergency cesarean standard operating procedure (SOP) on the decision-to-delivery interval (DDI) and to determine whether a shorter DDI improves neonatal outcome. Methods: Retrospective analysis of emergency cesareans from 2004 (introduction of the new SOP) to 2009 in a Swiss Level 3 perinatal center. Primary endpoints were the DDI, the pathology-to-decision interval (PDI), the 5 year learning curve, and neonatal and maternal outcome. Results: In the emergency cesarean group (175 women and 188 infants), mean DDI decreased over the observation period from 15 to 9 minutes (mean 10 minutes 41 seconds), and mean PDI from 11 to 6 minutes (mean 8 minutes). Not only did the DDI not exceed 15 minutes in over 90% of cases during the 5 years, but it fell consistently below 10 minutes in the latter stages of the learning curve. Only 2/188 infants had an umbilical artery

关键词： Emergency Cesarean Delivery Decision-to-Delivery Interval Neonatal Outcome Maternal Outcome

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Dynamical behavior of a mobile system with two degrees of freedom near the resonance

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Acta Mechanica Sinica 2011年第1期27卷 7-17页

作者： Klaus zimmermann Igor Zeidis Faculty of Mechanical Engineering Technische Universitaet Ilmenau

The design of mobile robots that can move without wheels or legs is an important engineering and technological ***-propelling mechanisms consisting of a body that has contact with a rough surface and moveable internal masses are *** models of such systems are presented in this ***,a model of a vibration driven robot that moves along a rough horizontal plane with isotropic dry friction is *** is shown that by changing the off-resonance frequency detuning in sign,one can control the direction of motion of the *** addition,a locomotion system which moves in an environment with anisotropic viscous friction is *** all models,the method of averaging to obtain an algebraic equation for the steady-state＂average＂velocity of the system is used. Prototypes were constructed to compare the theoretical results with experimental ones.

关键词： Dynamics Friction Resonance Vibrationdriven systems

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Towards Cost-Effective Cloud Downloading with Tencent Big Data

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Journal of Computer Science & Technology 2015年第6期30卷 1163-1174页

作者：李振华刘刚嵇智源 Roger zimmermann School of Software Tsinghua University Beijing 100084 China Tsinghua National Laboratory for Information Science and Technology Beijing 100084 China QQXuanfeng System Group Tencent Co. Ltd Shanghai 200233 China High Technology Research and Development Center Ministry of Science and Technology Beijing 10004 China Department of Computer Science National University of Singapore Singapore 117417 Singapore

The cloud downloading scheme, first proposed by us in 2011, has effectively optimized hundreds of millions of users＇ downloading experiences. Also, people start to build a variety of useful Internet services on top of cloud downloading. In brief, by using cloud facilities to download （and cache） the requested file from the ＂best-effort＂ Internet on behalf of the user, cloud downloading ensures the data availability and remarkably enhances the data delivery speed. Although this scheme seems simple and straightforward, designing a real-world cloud downloading system involves complicated and subtle trade-offs （between deployment cost and user experience） when serving a large number of users： 1） how to plan the cloud cache capacity to achieve a high and affordable cache hit ratio, 2） how to accelerate the data delivery from the cloud to numerous users, 3） how to handle the dense user requests for highly popular files, and 4） how to judge a potential downloading failure of the cloud. This paper addresses these design trade-offs from a practical perspective, based on big data from a nationwide commercial cloud downloading system, i.e., Tencent QQXuanfeng. Its running traces help us find reasonable design strategies and parameters, and its real performances confirm the efficacy of our design. Our study provides solid experiences and valuable heuristics for the developers of similar and relevant systems.

关键词： cloud downloading cost-effective design trade-off big data

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Let’s talk about Secs: Sec61, Sec62 and Sec63 in signaltransduction, oncology and personalized medicine

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Signal Transduction and Targeted Therapy 2017年第1期2卷 229-238页

作者： Maximilian Linxweiler Bernhard Schick Richard zimmermann Department of Otorhinolaryngology Head and Neck SurgerySaarland University Medical CenterHomburgGermany Institute of Medical Biochemistry and Molecular Biology Saarland UniversityHomburgGermany

The heterotrimeric Sec61 complex and the dimeric Sec62/Sec63 complex are located in the membrane of the human endoplasmic reticulum(ER)and play a central role in translocation of nascent and newly synthesized precursor polypeptides into the *** process involves targeting of the precursors to the membrane and opening of the polypeptide conducting Sec61 channel for *** from this central role in the intracellular transport of polypeptides,several studies of the last decade uncovered additional functions of Sec proteins in intracellular signaling:Sec62 can induce ER-phagy in the process of recovery of cells from ER stress and the Sec61 channel can also act as a passive ER calcium leak ***,mutations,amplifications and an overexpression of the SEC genes were linked to various diseases including kidney and liver diseases,diabetes and human *** of the last decade could not only elucidate the functional role of Sec proteins in the pathogenesis of these diseases,but also demonstrate a relevance of Sec62 as a prognostic and predictive biomarker in head and neck cancer,prostate and lung cancer including a basis for new therapeutic *** this article,we review the current understanding of protein transport across the ER membrane as central function of Sec proteins and further focus on recent studies that gave first insights into the functional role and therapeutic relevance of Sec61,Sec62 and Sec63 in human diseases.

关键词： transport signal cancer

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Embedding compact surfaces into the 3-dimensional Euclidean space with maximum symmetry

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Science China Mathematics 2017年第9期60卷 1599-1614页

作者： WANG Chao WANG ShiCheng ZHANG YiMu zimmermann Bruno Jonsvannsveien 87B H0201Trondheim 7050Noway School of Mathematical Sciences Peking UniversityBeijing 100871China Mathematics School Jilin UniversityChangehun 130012China Dipartimento di Matematica e Geoseienze Universita degli Studi di TriesteTrieste 34100Italy

The symmetries of surfaces which can be embedded into the symmetries of the 3-dimensional Euclidean space R3 are easier to feel by human＇s intuition. We give the maximum order of finite group actions on （R3 E） among all possible embedded closed/bordered surfaces with given geometric/algebraic genus greater than 1 in R3. We also identify the topological types of the bordered surfaces realizing the maximum order, and findsimple representative embeddings for such surfaces.

关键词： finite group action extendable action symmetry of surface maximum order

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Combined inhibitors of angiogenesis and histone deacetylase:Efficacy in rat hepatoma

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World Journal of Gastroenterology 2011年第31期17卷 3623-3629页

作者： Marion Ganslmayer Annette zimmermann Steffen Zopf Christoph Herold Medical Department 1 University hospital Erlangen-Nuernberg Department of Otolaryngology University of Marburg

AIM:To evaluate the antitumoral effect of combined inhibitors of angiogenesis and histone deacetylases in an experimental rat hepatoma ***:MH7777A hepatoma cells were injected into the liver of male Buffalo *** 7 d treatment with the vascular endothelial growth factor receptor antagonist PTK787/ZK222584(PTK/ZK),the histone deacetylase inhibitor MS-275,tamoxifen(TAM) and/or retinoic acid was initiated(n ≥ 8 animals/group).Natural tumor development was shown in untreated control groups(control 1 with n = 12,control 2 with n = 8).The control groups were initiated at different time points to demonstrate the stability of the hepatoma *** documentation of possible side effects,we documented any change in body weight,loss of fur and *** 21 d treatment,the rats were *** target parameters were tumor size and metastasis ***,immunohistochemistry for the proliferating cell nuclear antigen(PCNA) and TdT-mediated dUTP-biotin nick end labeling(TUNEL) assay were ***:The control groups developed large tumor nodules with extrahepatic tumor burden in the lung and abdominal organs(control 1:6.18 cm3 ± 4.14 cm3 and control 2:8.0 cm3 ± 4.44 cm3 28 d after tumor cell injection).The tumor volume did not differ significantly in the control groups(P = 0.13).As single agents MS-275 and PTK/ZK reduced tumor volume by 58.6% ± 2.6% and 48.7% ± 3.2% vs control group 1,which was significant only for MS-275(P = 0.025).The combination of MS-275 and PTK/ZK induced a nearly complete and highly significant tumor shrinkage by 90.3% ± 1%(P = 0.005).Addition of TAM showed no further efficacy,while quadruple therapy with retinoic acid increased antitumoral efficacy(tumor reduction by 93 ± 1%) and side *** positive cells were not significantly reduced by the single agents,while dual therapy(MS-275 and PTK/ZK) and quadruple therapy reduced the PCNA-positive cell fraction significantly by 9.1 and 20.6% vs control 1(P < 0.05).Th

关键词： PTK787 ZK222584 MS-275 Hepatocellular carcinoma Histone deacetylase inhibitor

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Skyline-join query processing in distributed databases

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Frontiers of Computer Science 2016年第2期10卷 330-352页

作者： Mei BAI Junchang XIN Guoren WANG Roger zimmermann Xite WANG College of Information Science and Engineering Northeastern University Shenyang 110819 China School of Computing National University of Singapore Singapore 117417 Singapore

The skyline-join operator, as an important variant of skylines, plays an important role in multi-criteria decision making problems. However, as the data scale increases, previous methods of skyline-join queries cannot be applied to new applications. Therefore, in this paper, it is the first attempt to propose a scalable method to process skyline-join queries in distributed databases. First, a tailored distributed framework is presented to facilitate the computation of skyline-join queries. Second, the distributed skyline-join query algorithm （DSJQ） is designed to process skyline-join queries. DSJQ contains two phases. In the first phase, two filtering strategies are used to filter out unpromising tuples from the original tables. The remaining tuples are transmitted to the corresponding data nodes according a partition function, which can guarantee that the tuples with the same join value are transferred to the same node. In the second phase, we design a scheduling plan based on rotations to calculate the final skyline-join result. The scheduling plan can ensure that calculations are equally assigned to all the data nodes, and the calculations on each data node can be processed in parallel without creating a bottleneck node. Finally, the effectiveness of DSJQ is evaluated through a series of experiments.

关键词： skyline-join distributed filtering strategy scheduling plan rotation

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Analysis of the Vibrissa Parametric Resonance Causing a Signal Amplification during Whisking Behaviour

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Journal of Bionic Engineering 2016年第2期13卷 312-323页

作者： Tatiana Volkova Igor Zeidis Hartmut Witte Manuela Schmidt Klaus zimmermann Technische Universiat Ilmenau Technical Mechanics Group 98693 Max-Planck-Ring 12 Ilmenau Germany Technische Universitat Ilmenau Biomechatronics Group 98693 Max-Planck-Ring 12 Ilmenau Germany Friedrich-Schiller-Universitat Jena Institute of Systematic Zoology and Evolutionary Biology with Phyletic Museum 07743 Erbertstrafle 1 Jena Germany

The paper deals with the mechanical vibrational motion ofvibrissae during natural exploratory behaviour of mammals. The theoretical analysis is based on a mechanical model of a cylindrical beam with circular natural configuration under an applied periodic force at the tip, which corresponds to the surface roughness of an investigated object. The equation of motion of the beam is studied using the Euler-Bemoulli beam theory and asymptotic methods of mechanics. It is shown that from the me- chanical point of view the phenomenon of parametric resonance of the vibrissa is possible. It means that the amplitude of forced vibrations of a vibrissa increases exponentially with time, if it is stimulated within a specific resonance frequency range, which depends on biomechanical parameters of the vibrissa. The most intense parametric resonance occurs, when the excitation frequency is close to the doubled natural frequency of free vibrations. Thus, it may be used to distinguish and amplify specific periodic components of a complex roughness profile during texture discrimination.

关键词： vibrissa whisking vibration tactile sensor beam theory parametric resonance

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Finding the semantic similarity in single-particle diffraction images using self-supervised contrastive projection learning

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npj Computational Materials 2023年第1期9卷 2118-2126页

作者： Julian zimmermann Fabien Beguet Daniel Guthruf Bruno Langbehn Daniela Rupp ETH Zürich ZürichSwitzerland Technische Universität Berlin BerlinGermany Max-Born-Institut BerlinGermany

Single-shot coherent diffraction imaging of isolated nanosized particles has seen remarkable success in recent years,yielding in-situ measurements with ultra-high spatial and temporal *** progress of high-repetition-rate sources for intense X-ray pulses has further enabled recording datasets containing millions of diffraction images,which are needed for the structure determination of specimens with greater structural variety and dynamic *** size of the datasets,however,represents a monumental problem for their ***,we present an automatized approach for finding semantic similarities in coherent diffraction images without relying on human expert *** introducing the concept of projection learning,we extend self-supervised contrastive learning to the context of coherent diffraction imaging and achieve a dimensionality reduction producing semantically meaningful embeddings that align with physical *** method yields substantial improvements compared to previous approaches,paving the way toward real-time and large-scale analysis of coherent diffraction experiments at X-ray free-electron lasers.

关键词： projection coherent similarity

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