Collider phenomenology of a unified leptoquark model

We demonstrate that in a recently proposed unified leptoquark model based on the gauge group $SU(4)_C\times SU(2)_L \times U(1)_R$ one can explain $R_{K^{(*)}}$ without the need of extra heavy fermions. Low energy data, in particular lepton flavour violating $\mu$ decays and $K_L\to e \mu$, severely constrain the available parameter space. We show that in the allowed part of the parameter space (i) some of the lepton-flavour-violating tau decay branching ratios are predicted to be close to their current experimental limits. (ii) The underlying scalar leptoquarks can be probed at the LHC via their dominant decay modes into tau-leptons and electrons and the third generation quarks. (iii) The constraints from meson oscillations imply that the masses of scalar gluons, another pair of coloured multiplets around, have to be bigger than around 15 TeV and, thus, they can be probed only at a future 100 TeV collider. In both neutral and charged variants, these scalars decay predominantly into third generation quarks, with up to $O$(10%) branching ratios into family-mixed final states. Moreover, we comment on the phenomenology of the scalar gluons in the current scenarios in case that the $B$-decay anomalies eventually disappear.Comment: 18 pages, 4 figures, 2 table

Die Bedeutung der Rezeptortyrosinkinasen KIT und VEGFR-2 in der Pathogenese der akuten myeloischen Leukämie

Zielsetzung dieser Arbeit war es, die Bedeutung der Expression von Liganden wie Vaskular Endothelial Growth Factor (VEGF) und Stem Cell Factor (SCF), sowie deren Rezeptortyrosinkinasen VEGFR-1, VEGFR-2 und Stem Cell Factor Receptor KIT für die Pathogenese der akuten myeloischen Leukämie (AML) genauer zu untersuchen. In neun von zehn der untersuchten leukämischen Zelllinien konnte eine starke VEGF Expression gezeigt werden, wohingegen die VEGFR-1 und VEGFR-2 Expression auf sechs bzw. zwei Zelllinien beschränkt blieb. Um der Überexpression von Rezeptortyrosinkinasen in den untersuchten Leukämiezelllinien eine pathogenetische Relevanz zuweisen zu können, wurde mit Hilfe der spezifischen Proteintyrosinkinaseinhibitoren SU5614, STI571 und SU1498 versucht, das Wachstum dieser leukämischen Zelllinien zu hemmen. Dabei zeigte sich, dass nicht die Expression von VEGFR-2 sondern nur die Überexpression und Stimulation von KIT eine proliferative Wirkung auf die untersuchten AML Zelllinien hat. Zur Bestätigung dieser Ergebnisse wurden zusätzlich verschiedene Apoptoseassays durchgeführt, die zeigen konnten, dass durch den Einsatz des PTK-Inhibitors SU5614 darüber hinaus Apoptose induziert werden kann. Auch die biochemischen Phosphorylierungsuntersuchungen des KIT Rezeptors in Kasumi-1 und KIT Rezeptor transfizierten HEK-293 Zellen belegten eindeutig eine Hemmung der Tyrosinphosphorylierung des KIT Rezeptors durch SU5614 Inkubation und bestätigen die Bedeutung des SCF/KIT Signalweges für das Zellwachstum von KIT positiven AML Zellen

Visualizing Business Ecosystems: Applying a Collaborative Modelling Process in Two Case Studies

Business ecosystems are increasingly gaining relevance in research and practice. Because business ecosystems progressively change, enterprises are interested in analysing their ecosystem, to identify and address such changes. In order to gain a comprehensive picture of the business ecosystem, various stakeholders of the enterprise should be involved in the analysis process. We propose a collaborative approach to model and visualize the business ecosystem and we validate four central roles in the modelling process. The process consists of six steps, namely the definition of the business ecosystem focus, instantiation of the model, data collection, provision of tailored visualizations, collecting feedback and adapting the models, and using the visualization ‘to tell a story’. In this paper, we report case studies of two companies that have instantiated ecosystem models

Overproduction of Pex5p stimulates import of alcohol oxidase and dihydroxyacetone synthase in a Hansenula polymorpha pex14 null mutant

Hansenula polymorpha Delta pex14 cells are affected in peroxisomal matrix protein import and lack normal peroxisomes. Instead, they contain peroxisomal membrane remnants, which harbor a very small amount of the major peroxisomal matrix enzymes alcohol oxidase (AO) and dihydroxyacetone synthase (DHAS). The bulk of these proteins is, however, mislocated in the cytosol, Here, we show that in Delta pex14 cells overproduction of the PTS1 receptor, Pex5p, leads to enhanced import of the PTS1 proteins AO and DHAS but not of the PTS2 protein amine oxidase. The import of the PTS1 protein catalase (CAT) was not stimulated by Pex5p overproduction. The difference in import behavior of AO and CAT was not related to their PTS1, since green fluorescent protein fused to the PTS1 of either AO or CAT were both not imported in Delta pex14 cells overproducing Pex5p. When produced in a wild type control strain, both proteins were normally imported into peroxisomes. In Delta pex14 cells overproducing Pex5p, Pex5P had a dual location and was localized in the cytosol and bound to the outer surface of the peroxisomal membrane. Our results indicate that binding of Pex5p to the peroxisomal membrane and import of certain PTS1 proteins can proceed in the absence of Pex14p

Structural and Mechanistic Analysis of the Choline Sulfatase from Sinorhizobium melliloti: A Class I Sulfatase Specific for an Alkyl Sulfate Ester.

Hydrolysis of organic sulfate esters proceeds by two distinct mechanisms, water attacking at either sulfur (S-O bond cleavage) or carbon (C-O bond cleavage). In primary and secondary alkyl sulfates, attack at carbon is favored, whereas in aromatic sulfates and sulfated sugars, attack at sulfur is preferred. This mechanistic distinction is mirrored in the classification of enzymes that catalyze sulfate ester hydrolysis: arylsulfatases (ASs) catalyze S-O cleavage in sulfate sugars and arylsulfates, and alkyl sulfatases break the C-O bond of alkyl sulfates. Sinorhizobium meliloti choline sulfatase (SmCS) efficiently catalyzes the hydrolysis of alkyl sulfate choline-O-sulfate (kcat/KM=4.8×103s-1M-1) as well as arylsulfate 4-nitrophenyl sulfate (kcat/KM=12s-1M-1). Its 2.8-Å resolution X-ray structure shows a buried, largely hydrophobic active site in which a conserved glutamate (Glu386) plays a role in recognition of the quaternary ammonium group of the choline substrate. SmCS structurally resembles members of the alkaline phosphatase superfamily, being most closely related to dimeric ASs and tetrameric phosphonate monoester hydrolases. Although >70% of the amino acids between protomers align structurally (RMSDs 1.79-1.99Å), the oligomeric structures show distinctly different packing and protomer-protomer interfaces. The latter also play an important role in active site formation. Mutagenesis of the conserved active site residues typical for ASs, H218O-labeling studies and the observation of catalytically promiscuous behavior toward phosphoesters confirm the close relation to alkaline phosphatase superfamily members and suggest that SmCS is an AS that catalyzes S-O cleavage in alkyl sulfate esters with extreme catalytic proficiency