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Contains fulltext : 290373.pdf (Publisher’s version ) (Open Access) 43 p.

Item does not contain fulltext 01 juli 2022

Supplemental material, sj-docx-1-jdr-10.1177_00220345211034766 for Robert Frank: A Pioneer and Visionary Scientist in Oral Medicine by C. Taddei-Gross, A.M. Musset, Y. Haikel and A. Bloch-Zupan in Journal of Dental Research

Item does not contain fulltext 24 november 2021

Illuminating the functional part of the genome of livestock species has the potential to facilitate precision breeding and to accelerate improvements. Identifying functional and potentially deleterious mutations can provide breeders with crucial information to tackle inbreeding depression or to increase the overall health of their populations and animal welfare. By performing Genome Wide Association Studies (GWAS) the genome can be interrogated for mutations that co-occur with a phenotype of interest. However, every GWAS delivers a large number of potentially functionally important single nucleotide polymorphisms (SNPs). The exact effect of each of these SNPs is often not known, especially for SNPs in noncoding sequences. Investigating each candidate SNP variantin detail is laborious and, eventually, infeasible, given the sheer number of variants. Thus, there is a strong need for approaches to select the most promising SNP candidates. Prioritizing variants, in particular, SNPs, has seen major developments in recent years which led to several discoveries and insights inheritable diseases of humans. Despite their great economical value, for livestock and other non-human species, this development is lagging behind.A major contributing factor to the deficit in prioritization tools for non-human species is a lack of genomic annotations. In this thesis, we translated one of the currently popular SNP prioritization tools, CADD (Combined Annotation-Dependent Depletion), to mouse (mCADD) and performed an experiment in which we simulated a decrease in the number of available genomic annotations.These results showed that following the CADD approach to predict the putative deleteriousness of SNPs is meaningful in a non-human species, even when fewer genomic annotations are available than for the human case. This motivated us to build various CADD-like SNP prioritization tools for livestock species, in particular for pig (pCADD) and chicken (chCADD). We validated the pig prioritization tool on a set of well-known functional pig variants. Further, we showed how functional and non-functional parts of the pig genome are scored differently by pCADD. In collaboration with the breeding industry, we built upon the pCADD scores and implemented them in a pipeline to identify likely causal variants in GWAS. To this end, we utilized SNPs that were found significant in GWAS based on SNP-array data and found variants with high pCADD scores in whole genome sequence data that are in linkage disequilibrium with high GWAS-scoring SNPs. Thus, these pCADD-identified SNPs are likely (causal) functional candidates for the phenotypes tested. We also identified several expression quantitative loci (eQTL) variants, SNPs that explain observed differences in gene expression, which we were able to validate using RNA-seq data. This demonstrated the power of this new tool and its usefulness in identifying novel, functional variants. For chicken, we used the chCADD to interrogate highly conserved elements in the chicken genome. Here we found that, despite being highly conserved, not all parts of these elements might be functionally active. chCADD differentiates between regions within each conserved element that are predicted to be functionally different. Taken together, the results presented in this thesis demonstrate SNP prioritization can successfully be done in non-human species, which can greatly assist breeders and animal geneticists in their work to illuminate the functional genome.

ZusammenfassungDie neue S3-Leitlinie Colitis stellt aktuelle und evidenzbasierte Empfehlungen zur Behandlung der Colitis ulcerosa zur Verfügung. Sie ersetzt damit die Vorläuferversion von 2011. Neben den neuesten Erkenntnissen zu Diagnostik und Therapie werden insbesondere infektiologische Probleme, chirurgische und Ernährungsmaßnahmen aufgegriffen. Unter der Federführung der DGVS wurde die Leitlinie gemeinsam mit 10 weiteren Fachgesellschaften und Patientenvertretern erarbeitet mit dem Ziel, eine optimale interdisziplinäre Versorgung der Patienten zu gewährleisten.

Genetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all, studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioral traits, we set out to develop a mouse model of the human 5-HTT-LPR. Here we describe the creation and characterization of a set of mouse lines with single-copy human transgenes carrying the short and long 5-HTT-LPR variants. Although we were not able to detect differences in expression between the short and long variants, we encountered several technical issues concerning the design of our humanized mice that are likely to have influenced our findings. Our study serves as a cautionary note for future studies aimed at studying human transgene regulation in the context of the living mouse.

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Contains fulltext : 144854.pdf (Publisher’s version ) (Closed access) This study draws on an active audience perspective to develop a better understanding of mass audiences' attraction towards popular management ideas. It focuses on audience members' own experiences and, in particular, what audience activities actually play a role in shaping mass attraction, and how the deployment of these activities may vary. Analysing 65 in-depth interviews with management practitioners in their role as audience members of guru seminars, the authors identify different key consumption activities, and explain how individual management practitioners may shift in consumption orientation throughout the communication process. This paper argues that such a broader and more dynamic understanding of consumption activity is essential in understanding the success and impact of management ideas, and opens several fruitful research directions. 25 december 2014 19 p.

The aim of this chapter is to investigate the relationship between tracking and migrant student performance and compare the results of native-born people, and first and second generation migrants. We combine two insights: the need to take into account school level variables when estimating the strength of the relationship between education systems and student performance and the need to include country of origin to correctly estimate models for migrant students. We use pisa 2009 data for 15 oecd countries, running analyses for native-born students, first and second generation migrants. We find that both first and second generation migrant students in educational systems with many tracks have equal or higher scores than students in systems with only one track. In an extended sample, the influence of the educational system on migrant students is absent, while for native-born students the influence remains substantial.

86 patients with significant main coronary artery stenosis (greater than 50%) were divided into 61 with stable and 25 with unstable angina pectoris. The coronary morphology (isolated main coronary artery stenosis, degree of stenosis, additional vessel disease) and the left ventricular function (ejection fraction, left ventricular end-diastolic pressure) were the same in both groups. Deaths due to coronary angiography amounted to 2.3% and involved two patients with unstable angina. 82% (n = 50) of the patients with stable angina and 83% (n = 19) with unstable angina were considered operable. 69% of the stable and 74% of the unstable group were actually revascularised. Operative deaths amounted to 3.4% and again involved two patients with unstable angina. During an average post-operative follow-up period of 38 months 5% of the operated and 28% of the non-operated patients died (P less than 0.05). The investigation demonstrated that for patients with main coronary artery stenosis operability in stable angina is no different from that in unstable angina. Angiographic and operative deaths in patients with unstable symptomatology, however, were markedly higher than in those with stable angina.

Hintergrund. Das Auftreten einer Hamolyse bei alkoholtoxischem Leberschaden in Verbindung mit einer sekundaren Hyperlipidamie wird als Zieve-Syndrom bezeichnet. Uber damit in Zusammenhang stehende Netzhautveranderungen wurde bisher nicht berichtet. Patient. Ein 44-jahriger Diabetiker stellte sich zur Routinekontrolle beim Augenarzt vor. Die Sehscharfe war beidseitig gut (1,0/0,8). Ophthalmoskopisch imponierte beidseitig eine ausgepragte Lipaemia retinalis mit cremefarbenen Netzhautgefasen sowie peripapillaren Cotton-wool-Herden mit vereinzelten Blutungen. Anamnestisch bekannt war eine Fettleberhepatitis bei jahrelangem Athanolabusus. Seit einem Monat bestand eine vermehrte Ubelkeit mit Erbrechen. Paraklinisch waren eine gemischte Hyperlipidamie mit hochgradig lipamischem Serum und eine schwere Anamie auffallig. Der Patient wurde zur weiteren Diagnostik und Therapie stationar in der Inneren Klinik aufgenommen. Hier erfolgte wegen der Anamie eine Bluttransfusion. Die extrem erhohten Cholesterin- und Triglyzeridwerte im Serum konnten durch medikamentose Einstellung der Hyperlipidamie deutlich reduziert werden. Die Kontrolluntersuchung des Augenhintergrundes 3 Wochen nach Therapiebeginn zeigte eine regelrechte Gefasfullung und in Ruckbildung befindliche Cotton-wool-Herde. Einen Monat spater lies sich kein pathologischer Netzhautbefund mehr feststellen. Schlussfolgerungen. Die beobachteten Netzhautveranderungen sind auf die Kombination von schwerer Anamie und Hyperlipidamie zuruckzufuhren und waren wegweisend fur die weitere internistische Diagnostik. Nach Behandlung der Grunderkrankung waren die Veranderungen ohne funktionelle Beeintrachtigung komplett reversibel.

Beschrieben werden 3 Falle einer akuten segmentalen hamorrhagischen antibiotikaassoziierten Kolitis bei drei jungen Mannern im Alter von 30–33 Jahren, die wegen eines Infekts der oberen Luftwege, einer Tonsillitis oder im Rahmen einer HP-Eradikationstherapie oral mit Ampicillin oder Amoxicillin behandelt worden waren. Alle drei zeigten akut einsetzende krampfartige Bauchschmerzen und blutige Durchfalle, endoskopisch fand sich eine rechtsseitige segmentale hamorrhagische Kolitis, kein pathologischer Keimnachweis im Stuhl. Die histopathologische Untersuchung erbrachte den Befund eines Schleimhautodems mit fleckformigen oberflachlich betonten Einblutungen und eines schutteren mononuklearen Infiltrats der Lamina propria. Das Deckepithel war partiell desquamiert und wies intraepitheliale Ansammlungen von Erythrozyten auf. Bei allen Patienten kam es zu spontaner Restitution nach Absetzen der Medikation. Die diagnostischen Kriterien und deren Grenzen werden unter Berucksichtigung der vorliegenden Literatur diskutiert.

Contains fulltext : 111974.pdf (Publisher’s version ) (Open Access) 03 mei 2012

Item does not contain fulltext Paper accepted at the Academy of Management, 07 augustus 2012

Item does not contain fulltext Paper presented at the 28th EGOS Colloquium, 05 juli 2012

Item does not contain fulltext 30 mei 2012

Contains fulltext : 111977.pdf (Publisher’s version ) (Open Access) 17 p.

Item does not contain fulltext Paper presented at the "Jahrestagung der Elterninitiative gegen psychische Abhängigkeit", 13-15 May., 14 mei 2011

Item does not contain fulltext Paper presented at the 31st Conference of the ISSR on “Religion and Economy in a Global World” , 30 June - 3 July., 02 juli 2011

Item does not contain fulltext Paper presented at the 27th EGOS Colloquium, 7-9 July 2011, Gothenburg., 07 juli 2011

Contains fulltext : 95422.pdf (Publisher’s version ) (Open Access) 14 p.

Contains fulltext : 95211.pdf (Publisher’s version ) (Closed access) 72 p.

Contains fulltext : 86968.pdf ( ) (Open Access)

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De enorme aantrekkingskracht van managementboeken en goeroeseminars wekt de suggestie dat managers veelal als makke schapen achter elke managementgoeroe aan lopen. Bestaand onderzoek naar dit fenomeen kijkt echter vooral naar de goeroe zelf terwijl de manager hierin onderbelicht blijft. Dit artikel richt zich op de manier waarop managers goeroeseminars ‘consumeren’. Door middel van een serie diepte-interviews met 37 deelnemers aan verschillende goeroeseminars en vier veldexperts laten we zien hoe cliënten als passieve ontvangers én als actieve consumenten kunnen worden gezien. Hieruit volgt dat managers niet over één kam kunnen worden geschoren wat betreft hun activiteiten die zij ontplooien in relatie tot goeroeseminars en de potentiële impact van populaire goeroe-ideeën. Op basis hiervan ontwikkelen we vier perspectieven over de goeroe-cliëntrelatie die bij kunnen dragen aan een beter begrip van de rol en waarde van goeroes in de huidige bedrijfskundige gemeenschap.

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Contains fulltext : 68818pre.pdf (Author’s version preprint ) (Closed access) 291 p.

BACKGROUND: Andermann syndrome (OMIM 218000) is an autosomal recessive motor-sensory neuropathy associated with developmental and neurodegenerative defects. The cerebral MRI reveals a variable degree of agenesis of the corpus callosum. Recently, truncating mutations of the KCC3 gene (also known as SLC12A6) have been associated with Andermann syndrome. METHODS: The authors assessed clinically and genetically three isolated cases from Germany and Turkey with symptoms consistent with Andermann syndrome. RESULTS: The authors detected four novel mutations within the KCC3 gene in their patients: two different truncating mutations in the first patient, a homozygous truncating mutation in the second, and a homozygous missense mutation in the third patient. In contrast to the classic phenotype of the Andermann syndrome linked to truncating KCC3 mutations the phenotype and the course of the disease linked to the missense mutation appeared to be different (i.e., showing additional features like diffuse and widespread white matter abnormalities). CONCLUSIONS: Not only truncating but also missense mutations of the KCC3 gene are associated with Andermann syndrome. Different types of KCC3 mutations may determine different clinical phenotypes.

pp120/HA4 is a hepatocyte membrane glycoprotein phosphorylated by the insulin receptor tyrosine kinase. In this study, we have investigated the role of pp120/HA4 in insulin action. Transfection of antisense pp120/HA4 cDNA in H35 hepatoma cells resulted in inhibition of pp120/HA4 expression and was associated with a 2-3-fold decrease in the rate of insulin internalization. Furthermore, insulin internalization in NIH 3T3 fibroblasts co-transfected with insulin receptors and pp120/HA4 was increased 2-fold compared with cells expressing insulin receptors alone. In contrast, no effect on internalization was observed in cells overexpressing a naturally occurring splice variant of pp120/HA4 that lacks the phosphorylation sites in the intracellular domain. Insulin internalization was also unaffected in cells expressing three site-directed mutants of pp120/HA4 in which the sites of phosphorylation by the insulin receptor kinase had been removed (Y488F, Y488F/Y513F, and S503A). Our data suggest that pp120/HA4 is part of a complex of proteins required for receptor-mediated internalization of insulin. It is possible that this function is regulated by insulin-induced phosphorylation of the intracellular domain of pp120/HA4.

A new approach to solve quasicrystalline atomic structures in 3-dimensional (3D) real space is presented: The atomic pair distribution function (PDF) of face centred icosahedral Ho9Mg26Zn65 [a(6D) = 2x5.18(3)A was obtained from in-house X-ray diffraction data (MoKa1). Starting with rational approximant models, derived from 1/1- and 2/1-Al-Mg-Zn, its local and medium range structure was refined (r < 27A; R = 12.9%) using the PDF data. 85% of all atoms show Frank-Kasper (FK) type coordinations. Basic structural unit is the 3-shell, 104-atom Bergman cluster (d = 15A comprising a void at its center. The clusters are interconnected sharing common edges and hexagonal faces of the 3rd shells. The remaining space is filled by some glue atoms (9% of all atoms), yielding an almost tetrahedrally close packed structure. All Ho atoms are surrounded by 16 neighbours (FK-polyhedron "P"). Most of them (89%) are situated in the 2nd shell (pentagon dodecahedron), the other act as glue atoms. As a result and as can be expected for real matter, local atomic coordinations in quasicrystals are similar compared to common crystalline intermetallic compounds. From our results, the long range quasiperiodic structure of icosahedral Mg-Zn-RE (RE = Y and some rare earths) is anticipated to be a canonical cell tiling (CCT, after Henely) decorated with Bergman clusters., 33 pages, 12 figures, to appear in Phys. Rev. B (2003)

Evaporation residue cross sections have been measured with neutron-rich radioactive $^{132}$Sn beams on $^{64}$Ni in the vicinity of the Coulomb barrier. The average beam intensity was $2\times 10^{4}$ particles per second and the smallest cross section measured was less than 5 mb. Large subbarrier fusion enhancement was observed. Coupled-channels calculations taking into account inelastic excitation and neutron transfer underpredict the measured cross sections below the barrier., Comment: 4 pages including 1 table and 3 figures

Wegen einer Komplikation bei der perkutanen transluminalen koronaren Angioplastie (PTCA) muste bei 5 Patienten notfallmasig ein aortokoronarer Bypass angelegt werden. Zeimal war eine Dissektion, einmal eine Koronarembolie und bei 1 Patienten die «Ablōsung» eines atheromatōsen Plaque die Ursache der Perfusionsstōrung. Bei 1 Patienten trat 45 Minuten nach primar erfolgreicher Dilatation ein thrombotischer Verschlus auf. Bei 4 Patienten mit erhaltenem koronaren Restflus war postoperativ (mittlere Revaskularisationszeit 137 Minuten) eine Infarzierung nicht nachweisbar. Der Patient mit Gefasverschlus erlitt trotz sofortiger Operation eine Vorderwandinfarzierung. Ein Patient verstarb 28 Stunden nach problemloser Revaskularisation am anaphylaktischen Schock nach einer Novalgin®-Injektion. Durch einen akuten aortokoronaren Bypass kann bei Patienten mit einer akuten Ischamie wahrend der PTCA—im speziellen bei erhaltenem koronarem Restflus—die Entwicklung eines Myokardinfarktes verhindert werden.