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Glucocorticoid receptor gene haplotype structure and steroid therapy outcome in IBD patients

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World Journal of Gastroenterology 2010年第31期16卷 3888-3896页

作者： Jessica Mwinyi Christa Wenger Jyrki J Eloranta gerd a.kullak-ublick Division of Clinical Pharmacology and Toxicol-ogy University Hospital Zurich

AIM: To study whether the glucocorticoid receptor (GR/ NR3C1) gene haplotypes influence the steroid therapy outcome in inflammatory bowel disease (IBD). METHODS: We sequenced all coding exons and flanking intronic sequences of the NR3C1 gene in 181 IBD patients, determined the single nucleotide polymorphisms, and predicted the NR3C1 haplotypes. Furthermore, we investigated whether certain NR3C1 haplotypes are significantly associated with steroid therapy outcomes. RESULTS: We detected 13 NR3C1 variants, which led to the formation of 17 different haplotypes with a certainty of > 95% in 173 individuals. The three most commonly occurring haplotypes were included in the association analysis of the influence of haplotype on steroid therapy outcome or IBD activity. None of the NR3C1 haplotypes showed statistically signifi cant association with glucocorticoid therapy success. CONCLUSION: NR3C1 haplotypes are not related to steroid therapy outcome.

关键词： Inflammatory bowel disease Steroid therapy Glucocorticoid receptor Pharmacogenetics Haplotype analysis

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

A Hierarchy of Compatibility and Comeasurability Levels in Quantum Logics with Unique Conditional Probabilities

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Communications in Theoretical Physics 2010年第12期54卷 974-980页

作者： gerd Niestegge Zillertalstrasse 39 81373 Muenchen Germany

In the quantum mechanical Hilbert space formalism, the probabilistic interpretation is a later ad-hocadd-on, more or less enforced by the experimental evidence, but not motivated by the mathematical model *** involving a clear probabilistic interpretation from the very beginning is provided by the quantum logics withunique conditional *** includes the projection lattices in von Neumann algebras and here probabilityconditionalization becomes identical with the state transition of the Lüders-von Neumann measurement *** the definition of a hierarchy of five compatibility and comeasurability levels in the abstract setting of thequantum logics with unique conditional *** meanings are: the absence of quantum interference orinfluence, the existence of a joint distribution, simultaneous measurability, and the independence of the final stateafter two successive measurements from the sequential order of these two measurements.A further level means that twoelements of the quantum logic (events) belong to the same Boolean *** the general case, the five compatibilityand comeasurability levels appear to differ, but they all coincide in the common Hilbert space formalism of quantummechanics, in von Neumann algebras, and in some other cases.

关键词： quantum measurement conditional probability quantum logic operator algebras

Epigenetic changes of DNA repair genes in cancer

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Journal of Molecular Cell Biology 2011年第1期3卷 51-58页

作者： Christoph Lahtz gerd P.Pfeifer Department of Cancer Biology Beckman Research InstituteCity of HopeDuarteCA 91010USA

‘Every Hour Hurts,The Last One Kills’.That is an old saying about getting *** day,thousands of DNA damaging events take place in each cell of our body,but efficient DNA repair systems have evolved to prevent ***,our DNA repair system and that of most other organisms are not as perfect as that of Deinococcus radiodurans,for example,which is able to repair massive amounts of DNA damage at one *** many instances,accumulation of DNA damage has been linked to cancer,and genetic deficiencies in specific DNA repair genes are associated with tumor-prone *** addition to mutations,which can be either inherited or somatically acquired,epigenetic silencing of DNA repair genes may promote *** review will summarize current knowledge of the epigenetic inactivation of different DNA repair components in human cancer.

关键词： DNA methylation DNA repair epigenetics

Multiobjective Electric Machine Optimization for Highest Reliability Demands

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CES Transactions on Electrical Machines and Systems 2020年第2期4卷 71-78页

作者： gerd Bramerdorfer Department of Electrical Drives and Power Electronics Johannes Kepler University LinzAustria

This article is about illustrating a workflow for incorporating reliability measures to typical electric machine design optimization *** measures facilitate comparing designs not only for rated conditions,but also allow to analyze their performance in the presence of unevitable ***,by additionally considering reliability or robustness as objectives compared to conventional optimization scenarios,designs featuring low parameter sensitiveness can be *** analysis of the design’s reliability as part of solving optimization problems involves a significant increase in required numerical *** minimize the associated prolongation of the runtime,an approach featuring a design of experiments based reduction of required computations and a consequent surrogate modeling technique is presented *** successful training,the metamodel can be applied for fast evaluating lots of different parameter combinations.A test problem is defined and *** on the observed findings,the necessity of incorporating robustness evaluations to machine design optimization becomes *** addition,the derived models allow for studying the impact of any tolerance-affected parameter on the machine performance in *** facilitates further beneficial studies,as for instance the analysis of selected changes of tolerance levels rather than a general minimization of the respective ranges which usually is associated with high production cost.

关键词： electric machine optimization,reliability ro-bustness,sensitivity six sigma tolerance analysis

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Robustness Criteria for Concurrent Evaluation of the Impact of Tolerances in Multiobjective Electric Machine Design Optimization

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CES Transactions on Electrical Machines and Systems 2020年第1期4卷 3-12页

作者： gerd Bramerdorfer Department of Electrical Drives and Power Electronics Johannes Kepler University LinzAustria

This article is about a comparison of different measures for determining the robustness or reliability of electric machine designs in the presence of inevitable *** selected criteria shall be suitable for concurrent evaluation in the course of solving state-of-the-art large scale multi-objective opti-mization *** the past,besides particularly customized criteria,mainly gradient based measures,worst case information,or standard deviation based quantities were *** this work,the quantile measure is introduced for electric machine design optimization and compared with the existing *** evaluation of a design’s robustness is typically examined based on finite element *** for most measures a signif-icant number of parameter combinations and thus computations are required,a surrogate model assisted approach is presented to minimize computational effort and runtime.A test problem is defined and analyzed to illustrate the differences of selected robustness *** reveal the importance of considering robustness in the optimization ***,a careful choice of appropriate measures has to be *** designs are compared and conclusions and an outlook on future activities are presented.

关键词： electric machine optimization robustness sen-sitivity six sigma tolerance analysis quantile

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Thermochemical Treatment——Technologies for Recovery and Utilisation of Materials

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过程工程学报 2006年第2期6卷 231-236页

作者： gerd Kley Rudolf Brenneis Burkart Adamczyk Franz-Georg Simon Division Waste Treatment and Remedial Eng. Federal Inst. Materials Research and Testing BAM Berlin 12200 Germany

The arc furnace technology is an ideally suited process for the treatment of hazardous and problematic waste. The operation conditions of the furnace can be adapted for optimal transformation of the waste material input into raw materials and usable products. The process can significantly reduce the impact of contaminated wastes and industrial residues, and enable material conversion and separation. Thus, the products of the process have various applications. The capability of the process is illustrated with three examples, the treatment of bottom ash and filter ash from waste incineration plants, of stainless steel slags and of chromium-containing residues from the refractory industry.

关键词：热化学处理原料分离耐火材料不锈钢

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Functional neuroanatomy in panic disorder:Status quo of the research

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World Journal of Psychiatry 2017年第1期7卷 12-33页

作者： Thomas Sobanski gerd Wagner Department of Psychiatry Psychotherapyand Psychosomatic MedicineThueringen-Kliniken GmbH Psychiatric Brain and Body Research Group Jena Department of Psychiatry and PsychotherapyJena University Hospital

AIM To provide an overview of the current research in the functional neuroanatomy of panic *** Panic disorder(PD) is a frequent psychiatric disease. Gorman et al(1989; 2000) proposed a comprehensive neuroanatomical model of PD, which suggested that fear-and anxiety-related responses are mediated by a so-called "fear network" which is centered in the amygdala and includes the hippocampus, thalamus, hypothalamus, periaqueductal gray region, locus coeruleus and other brainstem sites. We performed a systematic search by the electronic database PubMed. Thereby, the main focus was laid on recent neurofunctional, neurostructural, and neurochemical studies(from the period between January 2012 and April 2016). Within this frame, special attention was given to the emerging field of imaging genetics. RESULTS We noted that many neuroimaging studies have reinforced the role of the "fear network" regions in the pathophysiology of panic disorder. However, recent functional studies suggest abnormal activation mainly in an extended fear network comprising brainstem, anterior and midcingulate cortex(ACC and MCC), insula, and lateral as well as medial parts of the prefrontal cortex. Interestingly, differences in the amygdala activation were not as consistently reported as one would predict from the hypothesis of Gorman et al(2000). Indeed, amygdala hyperactivation seems to strongly depend on stimuli and experimental paradigms, sample heterogeneity and size, as well as on limitations of neuroimaging techniques. Advanced neurochemical studies have substantiated the major role of serotonergic, noradrenergic and glutamatergic neurotransmission in the pathophysiology of PD. However, alterations of GABAergic function in PD are still a matter of debate and also their specificity remains questionable. A promising new research approach is "imaging genetics". Imaging genetic studies are designed to evaluate the impact of genetic variations(polymorphisms) on cerebral function in reg

关键词： Panic disorder Anterior cingulate cortex Amygdala Insula Functional magnetic resonance imaging Diffusion tensor imaging Voxel-based morphometry Imaging genetics Serotonin Noradrenaline

Intraepithelial lymphocytes, scores, mimickers and challenges in diagnosing gluten-sensitive enteropathy(celiac disease)

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World Journal of Gastroenterology 2017年第4期23卷 573-589页

作者： Consolato Sergi Fan Shen gerd Bouma Tian You Hospital Wuhan University of Science and Technology Departments of Laboratory Medicine and Pathology University of AlbertaEdmonton AB T6G 2B7 Department of Gastroenterology and Hepatology Vrije Universiteit Medical Center1081 HV Amsterdam

The upper digestive tract is routinely scoped for several causes of malabsorption, and the number of duodenal biopsy specimens has increased notably in the last 10 years. Gluten-sensitive enteropathy(GSE) is an autoimmune disease, which shows an increasing prevalence worldwide and requires a joint clinicopathological approach. The classical histopathology of GSE with partial or total villous blunting is well recognized, but the classification of GSE is not straightforward. Moreover, several mimickers of GSE with intraepithelial lymphocytosis have been identified in the last 20 years, with drug interactions and medical comorbidities adding to the conundrum. In this review, we report on the normal duodenal mucosa, the clinical presentation and laboratory diagnosis of GSE, the duodenal intraepithelial lymphocytes and immunophenotype of GSE-associated lymphocytes, the GSE mimickers, the differences "across oceans" among guidelines in diagnosing GSE, and the use of a synoptic report for reporting duodenal biopsies in both children and adults in the 21^(st) century.

关键词： Gluten Duodenum Lymphocytes