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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 ***: 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 ***: 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 γ-glutamyl transferase levels might help to distinguish ABCB4- and ABCB11-related forms of ICP and CIC.

关键词：怀孕避孕药胆汁郁积药物反应遗传学胆汁盐

Refining Use/Misuse/Mitigation Use Cases for Security Requirements

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journal of Software Engineering and Applications 2014年第8期7卷 626-638页

作者： joshua j. pauli College of Business & Information Systems Dakota State University Madison USA

We investigate security at the same time as the functional requirements by refining and integrating use, misuse, and mitigation use cases. Security requirements rely on the interactions among normal system execution (use cases), attacks (misuse cases), and necessary security strategies (mitigation use cases), but previous approaches only use a high-level of abstraction. We use refinement to uncover details of each case and the relationships among them before integrating them. We identify and model “includes” and “extends” relationships within each refined case type, and use a condition-driven process that maintains these relationships as refinement continues. We then systematically identify and model “threatens” and “mitigates” relationships to integrate the cases at a detailed level.

关键词： Use Case Misuse Case Mitigation Use Case Requirements Security Engineering

The missing base molecules in atmospheric acid-base nucleation

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National Science Review 2022年第10期9卷 196-208页

作者： Runlong Cai Rujing Yin Chao Yan Dongsen Yang Chenjuan Deng Lubna Dada juha Kangasluoma jenni Kontkanen Roope Halonen Yan Ma Xiuhui Zhang pauli Paasonen Tuukka Pet?j? Veli-Matti Kerminen Yongchun Liu Federico Bianchi jun Zheng Lin Wang jiming Hao james N.Smith Neil M. Donahue Markku Kulmala Douglas R.Worsnop jingkun jiang State Key joint Laboratory of Environment Simulation and Pollution Control School of Environment Tsinghua University Institute for Atmospheric and Earth System Research/Physics Faculty of Science University of Helsinki Aerosol and Haze Laboratory Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical Technology Collaborative Innovation Center of Atmospheric Environment and Equipment Technology Nanjing University of Information Science and Technology Laboratory of Atmospheric Chemistry Paul Scherrer Institute Center for joint Quantum Studies and Department of Physics School of Science Tianjin University Key Laboratory of Cluster Science Ministry of Education of China School of Chemistry and Chemical Engineering Beijing Institute of Technology Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3) Department of Environmental Science and Engineering Fudan University Chemistry Department University of California Center for Atmospheric Particle Studies Carnegie Mellon University Department of Chemistry Carnegie Mellon University Aerodyne Research Inc.

Transformation of low-volatility gaseous precursors to new particles affects aerosol number concentration,cloud formation and hence the *** clustering of acid and base molecules is a major mechanism driving fast nucleation and initial growth of new particles in the ***,the acid-base cluster composition,measured using state-of-the-art mass spectrometers,cannot explain the measured high formation rate of new *** we present strong evidence for the existence of base molecules such as amines in the smallest atmospheric sulfuric acid clusters prior to their detection by mass *** demonstrate that forming(H2SO4)1(amine)1is the rate-limiting step in atmospheric H2SO4-amine nucleation and the uptake of(H2SO4)1(amine)1is a major pathway for the initial growth of *** proposed mechanism is very consistent with measured new particle formation in urban Beijing,in which dimethylamine is the key base for H2SO4nucleation while other bases such as ammonia may contribute to the growth of larger *** findings further underline the fact that strong amines,even at low concentrations and when undetected in the smallest clusters,can be crucial to particle formation in the planetary boundary layer.

关键词： new particle formation acid-base nucleation aerosol polluted urban environment

Photoluminescence of Ag-In-S/ZnS quantum dots: Excitation energy dependence and low-energy electronic structure

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Nano Research 2019年第7期12卷 1595-1603页

作者： Irina V. Martynenko Anvar S. Baimuratov Florian Weigert jose X. Soares Lorena Dhamo Philip Nickl Ilona Doerfel jutta pauli Ivan D. Rukhlenko Alexander V. Baranov Ute Resch-Genger Federal Institute for Materials Research and Testing (BAM) Unter den Eichen 8712205 BerlinGermany ITMO University 49 Kronverksky Pr.St. Petersburg197101Russia University of Porto Rua de Jorge Viterbo Ferreira2284050-313 PortoPortugal Institute of Photonics and Optical Sciences (IPOS) School of PhysicsThe University of SydneyCamperdown 2006NSWAustralia

Cd-free Ⅰ-Ⅲ-Ⅵ group semiconductor quantum dots (QDs) like Ag-ln-S and Cu-ln-S show unstructured absorption spectra with a pronounced Urbach tail,rendering the determination of their band gap energy (Eg) and the energy structure of the exciton ***,the origin of the broad photoluminescence (PL) band with lifetimes of several hundred nanoseconds is still *** encouraged us to study the excitation energy dependence (EED) of the PL maxima,PL spectral band widths,quantum yields (QYs),and decay kinetics of AlS/ZnS QDs of j different size,composition,and surface capping *** results were then correlated with the second derivatives of the corresponding absorption *** excellent match between the onset of changes in PL band position and spectral width with the minima found for the second derivatives of the absorption spectra underlines the potential of the EED approach for deriving Eg values of these ternary QDs from PL *** PL QY is,however,independent of excitation energy in the energy range *** the EED of the PL features of the AlS/ZnS QDs we could also derive a mechanism of the formation of the low-energy electronic *** was additionally confirmed by a comparison of the EED of PL data of as-synthesized and size-selected QD ensembles and the comparison of these PL data with PL spectra of single *** results indicate a strong contribution of intrinsic inhomogeneous PL broadening to the overall emission features of AlS/ZnS QDs originating from radiative transitions from a set of energy states of defects localized at different positions within the quantum dot volume,in addition to contributions from dimensional and chemical *** mechanism was confirmed by numerically modelling the absorption and PL energies with a simple mass approximation for spherical QDs and a modified donor-acceptor model,thereby utilizing the advantages of previously proposed PL mechanisms of ternary *** findings will

关键词： core/shell quantum dot silver indium sulfide defect photoluminescence photoluminescence quantum yield single-dot spectroscopy

Fully Automatic Extraction of Human Spine Curve from MR Images Using Methods of Efficient Intervertebral Disk Extraction and Vertebra Registration

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journal of Acupuncture and Tuina Science 2010年第3期8卷 195-195页

作者： Tang Z pauli j

Light metal compound casting

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Science China(Technological Sciences) 2009年第1期52卷 46-51页

作者： Konrad j. M. PAPIS joerg F. LOEFFLER Peter j. UGGOWITZER ETH Zurich Laboratory of Metal Physics and Technology Wolfgang-Pauli-Str. 10

‘Compound casting’simplifies joining processes by directly casting a metallic melt onto a solid metal substrate. A continuously metallurgic transition is very important for industrial applications, such as joint structures of spaceframe constructions in transport industry. In this project, ‘compound casting’ of light metals is investigated, aiming at weight-saving. The substrate used is a wrought aluminium alloy of type AA5xxx, containing magnesium as main alloying element. The melts are aluminium alloys, containing various alloying elements (Cu, Si, Zn), and magnesium. By replacing the natural oxygen layer with a zinc layer, the inherent wetting difficulties were avoided, and compounds with flawless interfaces were successfully produced (no contraction defects, cracks or oxides). Electron microscopy and EDX investigations as well as optical micrographs of the interfacial areas revealed their continu- ously metallic constitution. Diffusion of alloying elements leads to heat-treatable microstructures in the vicinity of the joining interfaces in Al-Al couples. This permits significant variability of mechanical properties. Without significantly cutting down on wettability, the formation of low-melting intermetallic phases (Al3Mg2 and Al12Mg17 IMPs) at the interface of Al-Mg couples was avoided by applying a protective coating to the substrate.

关键词： compound casting aluminium alloys magnesium alloys interface structure

维普期刊数据库

A nucleon-pair and boson coexistent description of nuclei

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Chinese Physics C 2017年第7期41卷 67-72页

作者：戴连荣潘峰 j.P.Draayer Department of Physics Liaoning Normal University Dalian 116029 China Department of Physics and Astronomy Louisiana State University Baton Rouge LA 70803-4001 USA

We study a mixture of s-bosons and like-nucleon pairs with the standard pairing interaction outside an inert core. Competition between the nucleon-pairs and s-bosons is investigated in this scenario. The robustness of the BCS-BEC coexistence and crossover phenomena are examined through an analysis of pf-shell nuclei with realistic single-particle energies, in which two configurations with pauli blocking of nucleon-pair orbits due to the formation of the s-bosons is taken into account. When the nucleon-pair orbits are considered to be independent of the s-bosons, the BCS-BEC crossover becomes smooth, with the number of the s-bosons noticeably more than that of the nucleon-pairs near the half-shell point, a feature that is demonstrated in the pf-shell for several values of the standard pairing interaction strength. As a further test of the robustness of the BCS-BEC coexistence and crossover phenomena in nuclei, results are given for B（E2; 01^＋→21^＋） values of even-even ^102-130 Sn with ^100Sn taken as a core and valence neutron pairs confined within the 1d（5/2）, 0g（7/2）, 1d（3/2）, 2s（1/2）, 1h（11/2）orbits in the nucleon-pair orbit and the s-boson independent approximation. The results indicate that the B（E2） values are reproduced well.

关键词： shell model interacting boson model the BCS-BEC coexistence

维普期刊数据库

Mutation Status of KRAS, BRAF, PIK3CA and Expression Level of AREG and EREG Identify Responders to Cetuximab in a Large Panel of Patient Derived Colorectal Carcinoma Xenografts of All Four UICC Stages

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journal of Cancer Therapy 2013年第2期4卷 678-693页

作者： paulina Pechanska M.Becker T.Mayr B.Hinzmann H.-P.Adams I.Klaman K.-H.Kretschmar K.Kretschmar K.Stecker R.Mantke R.pauli j.Pertschy K.Hertel K.Ridwelski K.Hellwig M.Pross C.Radke I.Fichtner j.Hoffmann A.Rosenthal Signature Diagnostics AG PotsdamGermany Experimental Pharmacology&Oncology Berlin-Buch GmbH BerlinGermany Stadtisches Klinikum Brandenburg GmbH Klinik fur Allgemein-und ViszeralchirurgieInstitut fur PathologieBrandenburg an der HavelGermany Katholisches Krankenhaus St.johann Nepomuk Klinik fur Allgemeine ChirurgieErfurtGermany HELIOS Klinikum Erfurt Institut fur PathologieErfurtGermany Klinikum Magdeburg Klinik für Allgemein-und ViszeralchirurgieInstitut fur PathologieMagdeburgGermany DRK Kliniken Berlin-Kopenik Klinik fur ChirurgieInstitut fur PathologieBerlinGermany Max Delbruck Center fur Molekulare Medizin(MDC) Experimentale PharmakologieBerlinGermany.

To advance preclinical testing of novel targeted drugs in colorectal cancer (CRC) we established a panel of 133 mouse xenograft models from fresh tumor specimens of 239 patients with CRC of all four UICC stages. A subgroup of 67 xenograft models was treated with cetuximab, bevacizumab and oxaliplatin as single agents. Mutation status of KRAS (G12, G13, A146T), BRAF (V600E) and PIK3CA (E542K, E545K, H1047R) was assessed in all xenografts by allelespecific real-time PCR. KRAS codon 61 was assessed by conventional sequencing. AREG and EREG expression levels were analyzed by real-time PCR expression assays. In the treatment experiment we observed response rates of 27% (18/67) for cetuximab, 3% (2/67) for bevacizumab, and 6% (4/67) for oxaliplatin. Classification based on KRAS, BRAF and PIK3CA mutation status identified 15 of the responders (sensitivity 83%, confidence interval at p = 0.05 (CI): 59% - 96%), and 38 nonresponders (specificity 78%, CI: 63% - 88%). If any mutation except in KRAS codon 13 were considered, the classifier reached sensitivity of 94% and specificity of 69%. We improved specificity of the classifiers to 90% and 86% respectively by adding AREG and EREG RNA expression thresholds retrospectively. In patient-derived xenograft models, we found a predictive classifier for response to cetuximab that is more accurate than established biomarkers. We confirmed its potential performance in primary human tumors. For patients, the classifier’s sensitivity promises increased response rates and its specificity limits unnecessary toxicity. Given the scope of our xenograft models across all UICC stages, this applies not only to mCRC but also to the adjuvant setting of earlier stages. The xenograft collection allows to mimic randomized phase II trials and to test novel drugs effectively as single agents or in combinations. It also enables the development of highly accurate companion diagnostics as demonstrated by us for cetuximab.

关键词： Colorectal Cancer Xenograft Mutation Biomarker Cetuximab

Exact Artificial Boundary Condition for the Poisson Equation in the Simulation of the 2D Schrodinger-Poisson System

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Communications in Computational Physics 2014年第8期16卷 764-780页

作者： Norbert j.Mauser Yong Zhang Wolfgang pauli Institute c/o Fak.Mathematik University WienOskar-Morgenstern-Platz 11090 ViennaAustria.

We study the computation of ground states and time dependent solutions of the Schr¨odinger-Poisson system(SPS)on a bounded domain in 2D(*** two space dimensions).On a disc-shaped domain,we derive exact artificial boundary conditions for the Poisson potential based on truncated Fourier series expansion inθ,and propose a second order finite difference scheme to solve the r-variable ODEs of the Fourier *** Poisson potential can be solved within O(M NlogN)arithmetic operations where M,N are the number of grid points in r-direction and the Fourier *** with the Poisson solver,a backward Euler and a semi-implicit/leap-frog method are proposed to compute the ground state and dynamics *** results are shown to confirm the accuracy and *** we make it clear that backward Euler sine pseudospectral(BESP)method in[33]can not be applied to 2D SPS simulation.

关键词： 2D Schrodinger-Poisson system exact artificial boundary condition backward Euler scheme semi-implicit/leap-frog scheme backward Euler sine pseudospectral method.