Experimentelle Ermittlung der Ölströmung in tauchgeschmierten Schneckengetrieben

Forschung im Ingenieurwesen - Schneckengetriebe finden sich in verschiedenen Anwendungen als Stell- und Leistungsgetriebe. Aufgrund der Realisierbarkeit einer hohen Übersetzung bei kleinem...     

Synthesis, biochemical evaluation, and classical and three-dimensional quantitative structure-activity relationship studies of 7-substituted-1,2,3,4-tetrahydroisoquinolines and their relative affinities toward phenylethanolamine N-methyltransferase and the alpha2-adrenoceptor

7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the alpha2-adrenoceptor. To design a selective (PNMT vs alpha2-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha2-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pKi = 0.599pi - 0.0725MR + 1. 55sigmam + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha2-adrenoceptor (alpha2 pKi = 0.599pi - 0. 0542MR - 0.951sigmam + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha2-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position. These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha2-adrenoceptor affinity) inhibitors of PNMT.     

Novel TTLL5 Variants Associated with Cone-Rod Dystrophy and Early-Onset Severe Retinal Dystrophy

Variants of the TTLL5 gene, which encodes tubulin tyrosine ligase-like family member five, are a rare cause of cone dystrophy (COD) or cone-rod dystrophy (CORD). To date, only a few TTLL5 patients have been clinically and genetically described. In this study, we report five patients harbouring biallelic variants of TTLL5. Four adult patients presented either COD or CORD with onset in the late teenage years. The youngest patient had a phenotype of early onset severe retinal dystrophy (EOSRD). Genetic analysis was performed by targeted next generation sequencing of gene panels and assessment of copy number variants (CNV). We identified eight variants, of which six were novel, including two large multiexon deletions in patients with COD or CORD, while the EOSRD patient harboured the novel homozygous p.(Trp640*) variant and three distinct USH2A variants, which might explain the observed rod involvement. Our study highlights the role of TTLL5 in COD/CORD and the importance of large deletions. These findings suggest that COD or CORD patients lacking variants in known genes may harbour CNVs to be discovered in TTLL5, previously undetected by classical sequencing methods. In addition, variable phenotypes in TTLL5-associated patients might be due to the presence of additional gene defects.     

Restricted usage of T cell receptor V alpha/J alpha gene segments with different nucleotide but identical amino acid sequences in HLA-DR3+ sarcoidosis patients

Alkylation of DNA was studied after treatment with [3H]melphalan (phenylalanine mustard; 1-2 microM) using a human tumour cell line, RD, in culture, or Escherichia coli (WP2 or WP2-uvrA strains) in growth medium. After 6 h at 37 degrees C, treated cells were isolated and re-suspended in fresh growth media. Samples were taken at times up to 48 h for isolation of DNA, and in some cases also RNA and protein (which were found to be alkylated to about the same extent as DNA). Alkylated DNA was analysed as previously described (M.R. Osborne and P.D. Lawley, Chem.-Biol. Interact 89 (1993) 49-60). The four principal products, mono-7-alkylguanine (G-M-OH); mono-3-alkyladenine (A-M-OH); and the cross-linked products G-M-G and A-M-G, were identified in DNA from melphalan treated cells, and quantitatively determined. In each case, alkylation of cellular macromolecules was maximal after about 6 h. In DNA of the human tumour cell line, the relative amounts of adenine products decreased with time, most markedly with A-M-OH to 42% of the 2-h value after 48 h. In DNA of both bacterial strains, A-M-OH was virtually undetectable even at early times. Comparisons between the time course of relative decreases in amounts of these alkylpurine products and the corresponding values for alkylated DNA in vitro suggest that the adenine products are subject to removal by repair enzyme action in E. coli of either strain.     

An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo

We have analyzed in vivo effects of the murine IL-4 mutant Q116D/Y119D (QY), which forms unproductive complexes with IL-4Ralpha and is an antagonist for IL-4 and IL-13 in vitro. Treatment of BALB/c mice with QY during immunization with OVA completely inhibited synthesis of OVA-specific IgE and IgG1. BALB/c-derived knockout mice lacking either IL-4 or IL-4Ralpha also did not develop specific IgE or IgG1, but mounted a much stronger IgG2a and IgG2b response than wild-type mice. In contrast, QY treatment of normal BALB/c mice suppressed specific IgG2a, IgG2b, and IgG3 synthesis, which may indicate the development of tolerance toward the allergen. Associated with the lack of IgE synthesis in QY-treated wild-type mice and in IL-4(-/-) mice used as a control was the failure to develop immediate cutaneous hypersensitivity or anaphylactic shock upon rechallenge. Interestingly, QY treatment also inhibited humoral immune responses and allergic reactivity in SJL/J mice, a strain that did not produce IgE, but displayed IgE-independent mast cell degranulation mediated by specific IgG1. We conclude that QY inhibits Ag-specific humoral immune responses and allergic symptoms mediated either by IgE or IgG1. It needs to be clarified how QY abrogates synthesis of IgG2a, IgG2b, and IgG3, but the induction of tolerance toward nonhazardous protein Ags should be advantageous for therapy of atopic disorders and other Th2-dominated diseases.     

Redundant configuration of robotic assembly lines with stochastic failures

One of the main challenges in the operation of robotic assembly lines is the occurrence of failures. Due to the connection of the stations via a material handling system, failures at one station often result in throughput losses. To some extent, these throughput losses can be reduced by installing buffers between the stations. However, the installation of buffers requires considerable investments and scarce factory space. Due to the advances of manufacturing technologies that form the foundation of ‘Industry 4.0’, new solutions to reduce failure-related throughput losses open up. One solution is a redundant configuration, in which downstream (backup) stations automatically take over the operations of failed stations during repair time. The throughput loss in these situations depends on the allocation of operations and the assignment of backup stations. Existing approaches in the literature that consider redundancies in the configuration of automated lines neglect the resulting production rate. Instead, the lines’ level of redundancy is used as a surrogate measure for optimisation. We present a genetic algorithm for the redundant configuration of robotic assembly lines with stochastic failures to maximise the production rate of the line. In a numerical analysis, it is demonstrated that this approach allows for productivity improvements.     

Vanadium oxide nanotube spherical clusters prepared on carbon fabrics for energy storage applications

Vanadium oxide nanotubes have shown great promise as electrode materials for energy storage devices. In this study, we report the synthesis of V(2)O(5) nanotube (VNT) clusters, which form densely packed radial arrangements of VNTs on high-surface-area carbon fiber fabrics (CF). This was achieved by coating the CF with V(2)O(5) by pulsed laser deposition (PLD). Hydrothermal treatment of the PLD films in the presence of excess intercalated V(2)O(5) results in formation of well-adhered VNT clusters on the CF. The densely packed VNTs have inner and outer diameters and interlayer distances of ~24, ~70, and ~2.4 nm, respectively. Coin cell type supercapacitors (CR2032) were assembled using VNT-CF as the anode material and electrochemical properties were evaluated.     

Rechnerische Bewertung von Trocknungsverfahren für hochwassergeschädigtes Mauerwerk

Optimal drying of of flooded masonry structures. Flooding is a global phenomenon as recently highlighted by the major catastrophic events in Central and Northern Europe. When flooding occurs in an area populated by humans, it can cause substantial damage to property and threaten human life. When properties are damaged by flooding, governmental institutions, insurers and repairers are called upon to provide services to homeowners in order to return the dwellings back to a habitable state. As one prerequisite to minimize costs for rehabilitation, such services should comprise drying measures tailored to local particularities as climatic conditions and building material properties. The paper introduces a new methodology to schedule drying measures and to evaluate their success for brick masonry buildings. The capabilities of computer simulation to predict the costs of alternative drying strategies are demonstrated by means of flooded masonry for different types of brickwork frequently used in historical buildings. The numerical simulation of moisture transport in flooded brickwork masonry allows statements about the moisture release to the indoor air, the recommended duration of usage and number of air dehumidifiers, the current drying state, the total time to return the brickwork back to a dry state and the drying costs as function of time.