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匹配条件: “ Klaus Ruether” ,找到相关结果约4576条。
Multi-locus stepwise regression: a haplotype-based algorithm for finding genetic associations applied to atopic dermatitis
Sven Knüppel, Jorge Esparza-Gordillo, Ingo Marenholz, Hermann-Georg Holzhütter, Anja Bauerfeind, Andreas Ruether, Stephan Weidinger, Young-Ae Lee, Klaus Rohde
BMC Medical Genetics , 2012, DOI: 10.1186/1471-2350-13-8
Abstract: Our proposed multi-locus stepwise regression starts with an evaluation of all pair-wise SNP combinations and then extends each SNP combination stepwise by one SNP from the region, carrying out haplotype regression in each step. The best associated haplotype patterns are kept for the next step and must be corrected for multiple testing at the end. These haplotypes should also be replicated in an independent data set. We applied the method to a region of 259 SNPs from the epidermal differentiation complex (EDC) on chromosome 1q21 of a German GWAS using a case control set (1,914 individuals) and to 268 families with at least two affected children as replication.A 4-SNP haplotype pattern with high statistical significance in the case control set (p = 4.13 × 10-7 after Bonferroni correction) could be identified which remained significant in the family set after Bonferroni correction (p = 0.0398). Further analysis revealed that this pattern reflects mainly the effect of the well-known FLG gene; however, a FLG-independent haplotype in case control set (OR = 1.71, 95% CI: 1.32-2.23, p = 5.6 × 10-5) and family set (OR = 1.68, 95% CI: 1.18-2.38, p = 2.19 × 10-3) could be found in addition.Our approach is a useful tool for finding allele combinations associated with diseases beyond single SNP analysis in chromosomal candidate regions.Single marker association analysis has been widely used to identify genetic risk factors involved in the genetics of complex diseases [1]. Previous studies have suggested that haplotypes, a collection of ordered markers along a chromosome, may be more appropriate as a unit for statistical analysis than single genetic markers [2,3]. As demonstrated by simulation studies, statistical approaches based on haplotypes can be a powerful method to characterize the genetic background of complex diseases [1,4-6]. However, since haplotypes are often not directly observable we have to use unphased genotypes to estimate haplotypes.The advent of the gene chip t
Systematic Association Mapping Identifies NELL1 as a Novel IBD Disease Gene
Andre Franke, Jochen Hampe, Philip Rosenstiel, Christian Becker, Florian Wagner, Robert H?sler, Randall D. Little, Klaus Huse, Andreas Ruether, Tobias Balschun, Michael Wittig, Abdou ElSharawy, Gabriele Mayr, Mario Albrecht, Natalie J. Prescott, Clive M. Onnie, Hélène Fournier, Tim Keith, Uwe Radelof, Matthias Platzer, Christopher G. Mathew, Monika Stoll, Michael Krawczak, Peter Nürnberg, Stefan Schreiber
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000691
Abstract: Crohn disease (CD), a sub-entity of inflammatory bowel disease (IBD), is a complex polygenic disorder. Although recent studies have successfully identified CD-associated genetic variants, these susceptibility loci explain only a fraction of the heritability of the disease. Here, we report on a multi-stage genome-wide scan of 393 German CD cases and 399 controls. Among the 116,161 single-nucleotide polymorphisms tested, an association with the known CD susceptibility gene NOD2, the 5q31 haplotype, and the recently reported CD locus at 5p13.1 was confirmed. In addition, SNP rs1793004 in the gene encoding nel-like 1 precursor (NELL1, chromosome 11p15.1) showed a consistent disease-association in independent German population- and family-based samples (942 cases, 1082 controls, 375 trios). Subsequent fine mapping and replication in an independent sample of 454 French/Canadian CD trios supported the authenticity of the NELL1 association. Further confirmation in a large German ulcerative colitis (UC) sample indicated that NELL1 is a ubiquitous IBD susceptibility locus (combined p<10?6; OR = 1.66, 95% CI: 1.30–2.11). The novel 5p13.1 locus was also replicated in the French/Canadian sample and in an independent UK CD patient panel (453 cases, 521 controls, combined p<10?6 for SNP rs1992660). Several associations were replicated in at least one independent sample, point to an involvement of ITGB6 (upstream), GRM8 (downstream), OR5V1 (downstream), PPP3R2 (downstream), NM_152575 (upstream) and HNF4G (intron).
An Enduring Concept for Security Council Reform  [PDF]
Klaus Schlichtmann
Beijing Law Review (BLR) , 2011, DOI: 10.4236/blr.2011.22010
Abstract: UN Security Council reform has been lingering over the years, since it was first seriously considered in the 1990s, after the collapse of the Soviet Union. This paper argues that enlarging the Security Council by adding new permanent and non-permanent members, while many of the Charter provisions vital for the maintenance of international peace and security and disarmament are not in effect, would be counterproductive. Instead, the composition of the Council should be reshuffled and expanded by giving a seat to a prominent member of the Global South, i.e. India, and replacing the seats of France and Britain with a single European representation. While there would be no increase or change in the number of permanent and non-permanent members, the result will be a dramatic increase in the numbers of people represented by the Permanent Five, which then will, in effect, comprise half of the world’s population projected for 2012. The underlying logic is that increasing the number of permanent members (P5) would make the Security Council not only less effective, but also prevent the realization of a fundamental purpose of the United Nations, i.e. the transition from an armed to an unarmed peace. By maintaining the number 5, the effective operation of the consensus principle required for the maintenance of international peace and security during the transition is ensured. It is maintained that the changes proposed in this paper may be regarded as “purely procedural” under Article 27 paragraph 2 of the Charter. It will be seen, however, that to trigger the process of the transition, UN Member states (other than the P5, who bear responsibility under the Charter to guarantee safe passage during the transition) must begin, one by one, to delegate “Security Sovereignty” to the Council.
Stereoscopic motion analysis in densely packed clusters: 3D analysis of the shimmering behaviour in Giant honey bees
Gerald Kastberger, Michael Maurer, Frank Weihmann, Matthias Ruether, Thomas Hoetzl, Ilse Kranner, Horst Bischof
Frontiers in Zoology , 2011, DOI: 10.1186/1742-9994-8-3
Abstract: Stereoscopic imaging provided non-invasive, automated, simultaneous, in-situ 3D measurements of hundreds of bees on the nest surface regarding their thoracic position and orientation of the body length axis. Segmentation was the basis for the stereo matching, which defined correspondences of individual bees in pairs of stereo images. Stereo-matched "agent bees" were re-identified in subsequent frames by the tracking procedure and triangulated into real-world coordinates. These algorithms were required to calculate the three spatial motion components (dx: horizontal, dy: vertical and dz: towards and from the comb) of individual bees over time.The method enables the assessment of the 3D positions of individual Giant honeybees, which is not possible with single-view cameras. The method can be applied to distinguish at the individual bee level active movements of the thoraces produced by abdominal flipping from passive motions generated by the moving bee curtain. The data provide evidence that the z-deflections of thoraces are potential cues for colony-intrinsic communication. The method helps to understand the phenomenon of collective decision-making through mechanoceptive synchronization and to associate shimmering with the principles of wave propagation. With further, minor modifications, the method could be used to study aspects of other mass phenomena that involve active and passive movements of individual agents in densely packed clusters.Giant honeybee (Apis dorsata) nests [1-7] constitute a matrix of densely clustered individuals arranged in a multi-layered stratum, the "bee curtain" [8], around a central, flat comb (Figures 1 and 2). Collective behaviours such as mass flight activity and colony defence [7,9] are affected by the functional principles of the 3D architecture of this bee curtain. Defence strategies against predatory wasps [10,11] include shimmering behaviour [3,12,13] (see Additional File 1, Movie S1), the ultimate evolutionary goals of which are n
Study protocol: Addressing evidence and context to facilitate transfer and uptake of consultation recording use in oncology: A knowledge translation implementation study
Thomas F Hack, J Dean Ruether, Lorna M Weir, Debjani Grenier, Lesley F Degner
Implementation Science , 2011, DOI: 10.1186/1748-5908-6-20
Abstract: Sixteen oncologists from cancer centres in three Canadian cities will participate in this three-phase study. The preimplementation phase will be used to identify and address those factors that are fundamental to facilitating the smooth adoption and delivery of the intervention during the implementation phase. During the implementation phase, breast and prostate cancer patients will receive a recording of their initial oncology consultation to take home. Patient interviews will be conducted in the days following the consultation to gather feedback on the benefits of the intervention. Patients will complete the Digital Recording Use Semi-Structured Interview (DRUSSI) and be invited to participate in focus groups in which their experiences with the consultation recording will be explored. Oncologists will receive a summary letter detailing the benefits voiced by their patients. The postimplementation phase includes a conceptual framework development meeting and a seven-point dissemination strategy.Consultation recording has been used in oncology, family medicine, and other medicine specialties, and despite affirming evidence and probable applications to a large number of diseases and a variety of clinical contexts, clinical adoption of this intervention has been slow. The proposed study findings will advance our conceptual knowledge of the ways to enhance uptake of consultation recordings in oncology.The time from diagnosis through to completion of therapy is challenging for newly diagnosed cancer patients. Patients have a substantial need for information, decision aids, and psychosocial support. One intervention that has proved promising in addressing these needs is providing a recording of the initial consultation [1-16]. Consultation recordings allow for memories to be refreshed, for the learning of information not recalled from the initial consultation, for a clearer understanding of one's cancer treatment [6-8], for greater confidence that critical aspects of the
Structural Brain Changes in Chronic Pain Reflect Probably Neither Damage Nor Atrophy
Rea Rodriguez-Raecke, Andreas Niemeier, Kristin Ihle, Wolfgang Ruether, Arne May
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054475
Abstract: Chronic pain appears to be associated with brain gray matter reduction in areas ascribable to the transmission of pain. The morphological processes underlying these structural changes, probably following functional reorganisation and central plasticity in the brain, remain unclear. The pain in hip osteoarthritis is one of the few chronic pain syndromes which are principally curable. We investigated 20 patients with chronic pain due to unilateral coxarthrosis (mean age 63.25±9.46 (SD) years, 10 female) before hip joint endoprosthetic surgery (pain state) and monitored brain structural changes up to 1 year after surgery: 6–8 weeks, 12–18 weeks and 10–14 month when completely pain free. Patients with chronic pain due to unilateral coxarthrosis had significantly less gray matter compared to controls in the anterior cingulate cortex (ACC), insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex. These regions function as multi-integrative structures during the experience and the anticipation of pain. When the patients were pain free after recovery from endoprosthetic surgery, a gray matter increase in nearly the same areas was found. We also found a progressive increase of brain gray matter in the premotor cortex and the supplementary motor area (SMA). We conclude that gray matter abnormalities in chronic pain are not the cause, but secondary to the disease and are at least in part due to changes in motor function and bodily integration.
Large-Scale Phenotyping of an Accurate Genetic Mouse Model of JNCL Identifies Novel Early Pathology Outside the Central Nervous System
John F. Staropoli, Larissa Haliw, Sunita Biswas, Lillian Garrett, Sabine M. H?lter, Lore Becker, Sergej Skosyrski, Patricia Da Silva-Buttkus, Julia Calzada-Wack, Frauke Neff, Birgit Rathkolb, Jan Rozman, Anja Schrewe, Thure Adler, Oliver Puk, Minxuan Sun, Jack Favor, Ildikó Racz, Raffi Bekeredjian, Dirk H. Busch, Jochen Graw, Martin Klingenspor, Thomas Klopstock, Eckhard Wolf, Wolfgang Wurst, Andreas Zimmer, Edith Lopez, Hayat Harati, Eric Hill, Daniela S. Krause, Jolene Guide, Ella Dragileva, Evan Gale, Vanessa C. Wheeler, Rose-Mary Boustany, Diane E. Brown, Sylvie Breton, Klaus Ruether, Valérie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Susan L. Cotman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0038310
Abstract: Cln3Δex7/8 mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3Δex7/8 mice. Homozygous Cln3Δex7/8 mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10–14 weeks of age. Homozygous Cln3Δex7/8 mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12–13 week old homozygous Cln3Δex7/8mice, which were also seen to a lesser extent in heterozygous Cln3Δex7/8 mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15–16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3Δex7/8 mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3Δex7/8 neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3Δex7/8 mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3Δex7/8 mice that merit further study for JNCL biomarker development.
Ultraviolet Laser Based Gas Phase Fluorination of Polystyrene  [PDF]
Simon Kibben, Klaus Vogelsang
Journal of Surface Engineered Materials and Advanced Technology (JSEMAT) , 2014, DOI: 10.4236/jsemat.2014.45034

A novel hybrid process for surface fluorination of polymers is being introduced. The process is based on ultra violet (UV) laser radiation, which on the one hand forms radicals out of an atmosphere of a partially fluorinated benzene, and on the other hand activates a polymer surface in the areas where the UV radiation hits the surface. The radicals can react with the polymer surface, hence altering the surface energy. With this process, a fluorine content of over 30% on the surface of bulk polystyrene can be achieved, while the smallest possible structure size was smaller than 1 mm.

Phase II study of neoadjuvant 5-FU + leucovorin + CPT-11 in patients with resectable liver metastases from colorectal adenocarcinoma
Oliver F Bathe, Scot Dowden, Francis Sutherland, Elijah Dixon, Charles Butts, David Bigam, Barb Walley, Dean Ruether, Scott Ernst
BMC Cancer , 2004, DOI: 10.1186/1471-2407-4-32
Abstract: This is a prospective Phase II evaluation of outcomes in patients with potentially resectable liver metastases. Patients will receive neoadjuvant chemotherapy and will undergo resection. Postoperative chemotherapy will be directed by the degree of response to preoperative chemotherapy. All patients with Stage IV colorectal adenocarcinoma isolated to the liver that have disease that is amenable to complete ablation by resection, radiofrequency ablation, and/or cryoablation will be candidates for the trial. Patients will receive CPT-11 180 mg/m2 IV (over 90 minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and calcium folinate 200 mg/m2 on days 1 and 2, every 2 weeks. Altogether, six cycles of chemotherapy will be administered. Patients will then undergo resection and/or radiofrequency ablation. Patients who had stable disease or a clinical response with preoperative chemotherapy will receive an additional 12 cycles of CPT-11 180 mg/m2 IV (over 90 minutes) on day 1 with 5-FU 400 mg/m2 bolus and 600 mg/m2 by 22 hour infusion and calcium folinate 200 mg/m2 on days 1 and 2 (given every 2 weeks). Patients with resectable disease who had progressive disease during neoadjuvant chemotherapy will receive best supportive care or an alternative agent, at the discretion of the treating physician. Those patients who are not rendered free of disease following the neoadjuvant chemotherapy and surgery will receive best supportive care or an alternative agent, at the discretion of the treating physician. The primary endpoint of the study is disease-free survival. Secondary endpoints include overall survival, safety and feasibility, response to chemotherapy, and quality of life.Colorectal cancers are the third most common cause of cancer death in North America. The liver is the most common site of metastasis. In patients with resectable liver metastases, there is a good probability of long-term survival and even cure [1]. Untreated liver metastases are almo
Signature of metastable electrons in highly charged ion surface interactions
J. Ducree,J. Mrogenda,E. Reckels,M. Ruether,A. Heinen,Ch. Vitt,M. Venier,J. Leuker,H. J. Andrae
Physics , 1997, DOI: 10.1103/PhysRevA.58.R1649
Abstract: We present autoionization spectra of metastable Ar(8+) and C(4+), N(5+), O(6+) and Ne(8+) scattering off an Al(111) surface with incident energies down to 5 eV. The unprecedented quality of the experimental data permits the observation of a unique, yet undiscovered peak in the structures originating from the metastable projectiles compared to corresponding ground state configurations. Analyzing the peak positions for different projectile species and velocities we demonstrate that the peak must be ascribed to an above-surface transition under participation of the metastable state.

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