The Prepotential of N=2 SU(2) x SU(2) Supersymmetric Yang-Mills Theory with Bifundamental Matter

We study the non-perturbative, instanton-corrected effective action of the N=2 SU(2) x SU(2) supersymmetric Yang-Mills theory with a massless hypermultiplet in the bifundamental representation. Starting from the appropriate hyperelliptic curve, we determine the periods and the exact holomorphic prepotential in a certain weak coupling expansion. We discuss the dependence of the solution on the parameter q=L2^2/L1^2 and several other interesting properties.Comment: 14 pages, Latex, one figure; v2: minor correction

Identification of a putative <em>Litomosoides sigmodontis</em> phosphate permease, <em>Ls-ppe-1</em>, and its role in the interaction between filarial nematodes and their Wolbachia endosymbionts & Establishment of RNA interference in the rodent filaria <em>Litomosoides sigmodontis</em>, a model of human filariasis

Filariasis is a vector-borne disease that affects 200 million individuals in the tropics, a large number of them seriously, where the disease leads to blindness (onchocerciasis) or elephantiasis (lymphatic filariasis). The Wolbachia, which are mutualistic endobacteria of most filarial nematodes, are essential for embryogenesis and larval development into adults and were thus identified as new target for anti-filarial drug development. Still, little is known about the molecular details of the symbiosis between Wolbachia and its filarial host but nematode genes that respond to an anti-wolbachial treatment may play important roles in the symbiosis. Therefore, the aim of this thesis was first to screen for such genes that might be involved in the symbiosis, and second to establish RNAi in the rodent filaria Litomosoides sigmodontis to study the function of filarial genes. Differential display PCR was used to detect several candidate genes that are up-regulated upon antibiotic treatment. One of these genes, Ls-ppe-1, was confirmed to be up-regulated over the treatment time and transcripts remained elevated one month after the treatment had been stopped, demonstrating a long-term alteration in the transcriptional state of the gene. The role of Ls-ppe-1 in the symbiosis may relate to a possible direct or indirect involvement in nucleotide metabolism. In contrast to other endosymbionts that have undergone gene reduction, Wolbachia has retained the ability to synthesize nucleotides (in addition to other metabolites). Potentially the phosphate permease provides the Wolbachia with phosphate as part of the mutualistic symbiosis The mitochondrial HSP60 was found to be up-regulated in immunohistochemical stained sections of O. volvulus after the depletion of Wolbachia by doxycycline treatment. The mRNA levels of filarial hsp60 in O. volvulus, quantified by real time PCR, were significantly increased after antibiotic treatment compared to untreated control worms. The results lead to the hypothesis that the increased expression of HSP60 is due to a disruption of the homeostasis of metabolic pathways for which Wolbachia may be needed. RNAi in adult worms of the rodent filaria L. sigmodontis was established and optimized. The actin gene was successfully knocked-down, whereas the transcript levels of Ls-hsp60 and Ls-gst2, used as controls to measure off-target effects, were not reduced. Soaking of nematodes with dsRNA coding for the C. elegans yolk receptor (Ce-rme-2), which has no orthologues in filaria, did not affect Ls-act transcription, demonstrating that the reduction of Ls-act is specific and not due to toxicity of dsRNA or off-target effects. The inhibition of Ls-act persisted for 72 hours, the length of the observation time. Two additional phenotypes were seen: first, the adult nematodes observed 48 and 72 hours after the beginning of the experiment showed paralysis by being stretched out and having slower movements, second, the release of microfilariae was significantly inhibited after soaking with dsRNA. The use of lower concentrations of dsRNA than those previously reported for RNAi in B. malayi as well as the establishment of proper controls for off-target effects could make RNAi a possibility to study the function of filarial genes. However, there are issues with RNAi in filarial nematodes and other parasitic nematodes, namely that their genomes appear to lack the genes to allow spreading of the dsRNA signal from cell to cell, indicating that the process is still hit-or-miss, depending on the gene to be silenced and/or the method of delivery

Understanding the activity transport nexus in water and CO2_{2} electrolysis: State of the art, challenges and perspectives

This article reviews the challenge of expanding the current research focus on water and CO2 electrolysis from catalyst-related insights towards achieving complete understanding of the activity transport nexus within full electrolysis cells. The challenge arises from the complex interaction of a multitude of phenomena taking place at different scales that span several orders of magnitude. An overview of current research on materials and components, experiments and simulations are provided. As well as obvious differences, there are similar principles and phenomena within water and CO$_{2}$ electrolysis technologies, which are extracted. Against this background, a perspective on required future research within the individual fields, and the need for a multidisciplinary research approach across natural, materials and engineering sciences to tackle the activity transport nexus is presented

Ihr Weg zum klimaneutralen Gebäude

IHR WEG ZUM KLIMANEUTRALEN GEBÄUDE Ihr Weg zum klimaneutralen Gebäude / Braune, Anna (Rights reserved) ( -

Совершенствование системы нормирования труда рабочих

Объект исследования - ЗАО "СИБУР-Транс". Предмет исследования – система нормирования труда на предприятия. Цель ВКР ? совершенствование системы нормирования труда на предприятии для активизации трудового потенциала на повышение производительности труда работников.The object of study - CJSC "SIBUR-TRANS". Subject of research - the system of regulation of labor in the enterprise. The purpose of WRC-improving the system of regulation of labor in the enterprise to enhance the labor potential to increase productivity of workers

Gain-of-Function Variant pPro2555Arg of von Willebrand Factor Increases Aggregate Size through Altering Stem Dynamics

The multimeric plasma glycoprotein (GP) von Willebrand factor (VWF) is best known for recruiting platelets to sites of injury during primary hemostasis. Generally, mutations in the VWF gene lead to loss of hemostatic activity and thus the bleeding disorder von Willebrand disease. By employing cone and platelet aggregometry and microfluidic assays, we uncovered a platelet GPIIb/IIIa-dependent prothrombotic gain of function (GOF) for variant p.Pro2555Arg, located in the C4 domain, leading to an increase in platelet aggregate size. We performed complementary biophysical and structural investigations using circular dichroism spectra, small-angle X-ray scattering, nuclear magnetic resonance spectroscopy, molecular dynamics simulations on the single C4 domain, and dimeric wild-type and p.Pro2555Arg constructs. C4-p.Pro2555Arg retained the overall structural conformation with minor populations of alternative conformations exhibiting increased hinge flexibility and slow conformational exchange. The dimeric protein becomes disordered and more flexible. Our data suggest that the GOF does not affect the binding affinity of the C4 domain for GPIIb/IIIa. Instead, the increased VWF dimer flexibility enhances temporal accessibility of platelet-binding sites. Using an interdisciplinary approach, we revealed that p.Pro2555Arg is the first VWF variant, which increases platelet aggregate size and shows a shear-dependent function of the VWF stem region, which can become hyperactive through mutations. Prothrombotic GOF variants of VWF are a novel concept of a VWF-associated pathomechanism of thromboembolic events, which is of general interest to vascular health but not yet considered in diagnostics. Thus, awareness should be raised for the risk they pose. Furthermore, our data implicate the C4 domain as a novel antithrombotic drug target

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation