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Treatment of biliary tract cancer with NVP-AEW541:Mechanisms of action and resistance

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World Journal of Gastroenterology 2010年第2期16卷 156-166页

作者： Samuel Wolf Jana Lorenz joachim Mssner Marcus Wiedmann Department of Internal MedicineⅡ University of Leipzig Department of Internal MedicineⅠ St. Mary's Hospital

AIM:To investigate in vitro treatment with NVPAEW541,a small molecule inhibitor of insulin-like growth factor-1 receptor(IGF-1R),in biliary tract cancer (BTC),since this disease is associated with a poor prognosis due to wide resistance to chemotherapeutic agents and ***:Cell growth inhibition by NVP-AEW541 was studied in vitro in 7 human BTC cell lines by automated cell *** addition,the anti-tumoral mechanism of NVP-AEW541 was studied by Western blotting,cell cycle analysis and reverse transcription-polymerase chain reaction(RT-PCR).Anti-tumoral drug effect in combination with gemcitabine,5-fluorouracil(5-FU)and Polo-like kinase 1 inhibitor BI2536 was also studied. RESULTS:In vitro treatment with NVP-AEW541 suppressed growth in all human BTC cell lines,however response was lower in gallbladder *** withNVP-AEW541 was associated with dephosphorylation of IGF-1R and *** contrast,phosphorylation of p42/p44 and Stat3 and expression of Bcl-xL were inconsistently *** addition,treated cells showed cell cycle arrest at the G1/S-checkpoint and an increase in sub-G1 ***,IGF-1R and its ligands IGF-1 and IGF-2 were co-expressed in RT-PCR,suggesting an autocrine loop of tumor cell *** with gemcitabine,NVP-AEW541 exerted synergistic effects, particularly at low concentrations,while effects of combination with 5-FU or BI 2536 were only additive. CONCLUSION:Our findings suggest that NVP-AEW541 is active against BTC in vitro and potentiates the efficacy of gemcitabine.

关键词： Tyrosine kinase inhibitor Cholangiocarcinoma Gemcitabine NVP-AEW541

Modified Helicobacter test using a new test meal and a 13C-urea breath test in Helicobacter pylori positive and negative dyspepsia patients on proton pump inhibitors

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World Journal of Gastroenterology 2017年第32期23卷 5954-5961页

作者： Bojan Tepes Peter Malfertheiner joachim Labenz Sitke Aygen AM DC Rogaska Prvomajska 29 A3250 Rogaska SlatinaSlovenia Universitatsklinikum Magdeburg A.o.R Klinik für Gastroenterologie Hepatologie und Infektiologie39120 MagdeburgGermany Department of Internal Medicine and Gastroenterology Diakonie KlinikumJung-Stilling Hospital Institut für Biomedizinische Analytik und NMR-Imaging GmbH(INFAI)

AIM To determine the sensitivity and specificity of the ^(13)C-urea breath test(UBT) in patients taking proton pump inhibitors(PPIs), using a new test meal Refex. METHODS One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori(H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the ^(13)C-UBT with the new test meal was performed the next morning. RESULTS The sensitivity of the ^(13)C-UBT with a cut off 2.5‰ was92.45%(95%CI: 81.79%-97.91%) by per-protocol(PP) analysis and 78.13 %(95%CI: 66.03%-87.49%) by intention-to-treat(ITT) analysis. The specificity of the ^(13)C-UBT test was 96.00 % in the ITT population(95%CI: 86.29%-99.51%) and 97.96% in the PP population(95%CI: 89.15%-99.95%).CONCLUSION The new test meal based ^(13)C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment.

关键词： Urea breath test new test meal Proton pump inhibitors Prospective randomized clinical trial Helicobacter pylori

Numerical Modelling of Seismic Site Effects Incorporating Non-linearity and Groundwater Level Changes

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Journal of Earth Science 2010年第6期21卷 931-940页

作者： Dominik Ehret joachim Rohn Dieter Hannich Carlos Grandas Gerhard Huber Department of Applied Geology University of Erlangen-Nuremberg Department of Applied Geology University (TH) of Karlsruhe Institute of Soil and Rock Mechanics University (TH) of Karlsruhe

In the past decades, the necessity for detailed earthquake microzonation studies was recognized worldwide. Therefore, different approaches were established and applied. Unfortunately, the majority of these approaches are not based on pre-existing field data but require extensive seismic measurements and investigations. Furthermore, these approaches incorporate non-linearity inadequately and cannot take groundwater level changes into account. For this purpose, notably numerical models are most suitable. These models require a good knowledge of the local geological conditions （especially of the uppermost unconsolidated units）, information about the geotechnical parameters of these units, and a hydrogeological model of the investigated area. Most of this information can be obtained from geotechnical investigations and surveys that have already been carried out in most densely populated areas. In a case study for Bucharest City, non-linear analyses were performed using software that is based on the visco-hypoplastic constitutive law. The results indicate that groundwater level changes have an important influence on duration and amplitude of ground response and thus should be considered for seismic microzonation studies. This approach ean be used to display site effects and to identify different microzones taking different earthquake magnitudes and groundwater levels into account.

关键词： microzonation site effect visco-hypoplasticity non-linearity Bucharest Romania.

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Computer animations of color markings revealthe function of visual threat signals inNeolamprologus pulcher

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Current Zoology 2017年第1期63卷 45-54页

作者： Valentina BALZARINI Michael TABORSKY Fabienne VILLA joachim G. FROMMEN Institute of Ecology and Evolution Behavioral Ecology Division University of Bern Wohlenstrasse 50a 3032Hinterkappelen Switzerland

Visual signals, including changes in coloration and color patterns, are frequently used by animalsto convey information. During contests, body coloration and its changes can be used to assess anopponent＇s state or motivation. Communication of aggressive propensity is particularly importantin group-living animals with a stable dominance hierarchy, as the outcome of aggressive inter-actions determines the social rank of group members. Neolamprologus pulcher is a cooperativelybreeding cichlid showing frequent within-group aggression. Both sexes exhibit two vertical blackstripes on the operculum that vary naturally in shape and darkness. During frontal threat displaysthese patterns are actively exposed to the opponent, suggesting a signaling function. To investi-gate the role of operculum stripes during contests we manipulated their darkness in computeranimated pictures of the fish. We recorded the responses in behavior and stripe darkness of testsubjects to which these animated pictures were presented. Individuals with initially darker stripeswere more aggressive against the animations and showed more operculum threat *** stripes of test subjects became darker after exposure to an animation exhibiting a paleoperculum than after exposure to a dark operculum animation, highlighting the role of the dark-ness of this color pattern in opponent assessment. We conclude that （i） the black stripes on theoperculum of N. pulcherare a reliable signal of aggression and dominance, （ii） these markings playan important role in opponent assessment, and （iii） 2D computer animations are well suited to elicitbiologically meaningful short-term aggressive responses in this widely used model system ofsocial evolution.

关键词： aggression, agonistic behavior, animated pictures, cichlid fish, communication, cooperation, social, threat display.

Identification and characterization of a novel bipartite nuclear localization signal in the hepatitis B virus polymerase

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World Journal of Gastroenterology 2013年第44期19卷 8000-8010页

作者： joachim Lupberger Stephanie Schaedler Alexander Peiran Eberhard Hildt Department of Medicine Ⅱ University of Freiburg D-79106 Freiburg Germany Inserm U748 Strasbourg France Division of Virology University Goettingen37073 Goettingen Germany Division of Virology Paul-Ehrlich-InstituteD-63325 Langen Germany

AIM: To characterize the nuclear import of hepatitis B virus (HBV) polymerase (P) and its relevance for the viral life cycle.METHODS: Sequence analysis was performed to predict functional motives within P. Phosphorylation of P was analyzed by in vitro phosphorylation. Phosphorylation site and nuclear localization signal (NLS) were destroyed by site directed mutagenesis. Functionality of the identified NLS was analyzed by confocal fluorescence microscopy and characterizing the karyopherin binding. Relevance of the structural motives for viral life cycle was studied by infection of primary Tupaia hepatocytes with HBV.RESULTS: We identified by sequence alignment and functional experiments a conserved bipartite NLS containing a casein kinase II (CKII) phosphorylation site located within the terminal protein domain (TP) of the HBV polymerase. Inhibition of CKII impairs the functionality of this NLS and thereby prevents the nuclear import of the polymerase. Binding of the import factor karyopherin-α2 to the polymerase depends on its CKII-mediated phosphorylation of the bipartite NLS. In HBV-infected primary Tupaia hepatocytes CKII inhibition in the early phase (post entry phase) of the infection process prevents the establishment of the infection.CONCLUSION: Based on these data it is suggested that during HBV infection the final import of the genome complex into the nucleus is mediated by a novel bipartite NLS localized in the TP domain of HBV polymerase.

关键词： Hepatitis B virus Nuclear localization signal Casein kinase II Trafficking Replication

From micro-scale to technical dimension—Challenges in the simulation ofdense gas-particle flows

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Particuology 2009年第4期7卷 231-232页

作者： joachim Werther Ernst-Ulrich Hartge Jinghai Li Wei Ge Institute of Solids Process Engineering and Particle Technology Hamburg University of Technology Hamburg Germany State Key Laboratory of Multi-phase Complex Systems Institute of Process Engineering Chinese Academy of Sciences Beijing China

Supported by the Sino-German Center for Research Promotion, an organization jointly founded by the National Natural Science Foundation of China （NSFC） and the German Research Foundation （DFG）, a joint Sino-German workshop on particle fluid systems was held for the fourth time on May 19-20, 2008 in Hamburg. Previous workshops were held on August 30-31, 1999 in Ham- burg,

关键词： From micro-scale to technical dimension EMMS Challenges in the simulation ofdense gas-particle flows

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REMARKS ON SINO-GERMAN WORKSHOP ON CHEMICAL AND PHYSICAL INTERACTIONS BETWEEN PARTICLES AND FLUIDS

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Particuology 2005年第Z1期 143-144页

作者： joachim Werther Department of Chemical Engineering I Technical University Hamburg-Harburg Hamburg 21071 Germany

This paper presents some remarks on the perspectives of process engineering in the 21st century extracted from the discussion at the workshop. It is considered that the field will be upgraded by introducing knowledge in other fields, extended to even more applications by generalizing the relevant methods, and unified to, at least covered by, the complexity science. Transdisciplinarity is necessary to cope with this challenge.

关键词： particle-fluid interaction complexity process engineering multi-scale multi-phase multi-level

The feasibility of coating by cooling crystallization on ibuprofen naked tablets

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Frontiers of Chemical Science and Engineering 2017年第2期11卷 211-219页

作者： Fatima Mameri Ouahiba Koutchoukali Mohamed Bouhelassa Anne Hartwig Leila Nemdili joachim Ulrich University Constantine 3 Engineering Faculty of Pharmaceutical Processes 25000 Constantine Algeria Martin Luther University Halle-Wittenberg Center of Engineering Science Thermal Process Engineering D-06099 Halle Germany

Sugar spray coating is a frequently used process in the pharmaceutical industry. However, this process presents the disadvantage to form an amorphous coating around the active ingredient. A crystalline coating formed on the surface of a tablet is highly desirable. Recently, a new process of coating by cooling crystallization has been developed and applied on bisacodyl pastilles obtained by melt crystallization. In this work, we investigated the feasibility of coating by cooling crystallization on ibuprofen ＂naked tablets＂ manufactured by compression. In the first part of this work, the solubility and the metastable zone width have been determined experimentally for the coating solution because they are essential factors for any crystallization process. In the second part, the coating process is investigated on the operating conditions that affect the surface morphology and the crystal growth rate. These experimental conditions include concentration of the coating solution, degree of sub-cooling, agitation speed, retention time, and surface properties of the naked ibuprofen tablets. The results show that naked tablet coating by cooling crystallization is feasible and can be applied in the pharmaceutical industry.

关键词： coating solution crystallization ibuprofen tablets sucrose

Etching Effect on CMP of Different GaN Layers

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稀有金属材料与工程 2011年第S3期40卷 276-280页

作者： Siche Dietmar Rost Hans-joachim Schulz Tobias Albrecht Martin Institute of Crystal Growth Max-Born-Str. 2 12489 Berlin Germany

Chemical mechanical polishing (CMP) was used to etch various GaN materials, such as GaN layers on sapphire and silicon carbide substrates grown by metal-organic chemical vapor deposition and thick GaN layers grown by physical vapor transport. It was found that CMP could reveal the dislocations in GaN surfaces due to a selective etching component. After the optimization of CMP condition, the surface finish improved and the subsurface damage was almost completely removed, demonstrated by atomic force microscopy and an electron back-scattered diffraction technique. This study established the correlation between the dislocation density and film quality. The crystalline perfection and optical properties of GaN layers were characterized by high resolution X-ray diffraction and photoluminescence.

关键词： surface etch pits CMP GaN

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