Freiwilliger Verzicht auf Essen und Trinken – zur ethischen Lagebestimmung eines ambivalenten Begriffs

Ethik in der Medizin - Wie ist der Freiwillige Verzicht auf Essen und Trinken und eine medizinische Begleitung dabei ethisch zu bewerten? Die ethische Bewertung des Freiwilligen Verzichts auf Essen...     

Charakterisierung des Delaminationsverhaltens von Schichtverbunden unter Mode I- und Mode II-Belastungen

Characterization of the delamination behaviour of composites under mode I- and mode II-loading In order to determine fracture toughness properties of fibre-reinforced polymers the „Double Cantilever Beam”︁-test (DCB) has been used for mode I loading and the „End Notched Flexure”︁-test (ENF) for mode II loading. By these methods the energy release rate G and the corresponding R-curve (crack resistance curve) have been measured which characterise the crack resistance of the material against delamination. Especially the influence of fibre coatings, different structures of the laminate, and matrix modifiers on fracture toughness have been examined for epoxy as well as for thermoplastic composites (polyamide and polypropylene/glass fibres).     

Order-induced strengthening in Ni4Mo

Polycrystalline samples of Ni₄Mo have been examined at various stages of isothermal ageing at 700° C. The mechanical properties were measured on initially disordered samples at various stages of the ordering process. These properties were correlated with microstructural observations such as domain size, degree of order and fracture characteristics. The correlations are rationalised in terms of a model for the ordering process and its effect on dislocation motion.     

Reactivity of the human thioltransferase (glutaredoxin) C7S, C25S, C78S, C82S mutant and NMR solution structure of its glutathionyl mixed disulfide intermediate reflect catalytic specificity

Human thioltransferase (TTase) is a 12 kDa thiol-disulfide oxidoreductase that appears to play a critical role in maintaining the redox environment of the cell. TTase acts as a potent and specific reducing agent for protein-S-S-glutathione mixed disulfides (protein-SSG) likely formed during oxidative stress or as redox intermediates in signal transduction pathways. Accordingly, the catalytic cycle of thioltransferase itself involves a covalent glutathionyl enzyme disulfide intermediate (TTase-C22-SSG). To understand the molecular basis of TTase specificity for the glutathione moiety, we engineered a quadruple Cys to Ser mutant of human TTase (C7S, C25S, C78S, and C82S) which retains only the active site cysteine residue (C22), and we solved its high-resolution NMR solution structure in the mixed disulfide intermediate with glutathione (QM-TTase-SSG). This mutant which cannot form a C22-S-S-C25 intramolecular disulfide displays the same catalytic efficiency (Vmax/KM) and specificity for glutathionyl mixed disulfide substrates as wild-type TTase, indicating that the Cys-25-SH moiety is not required for catalysis or glutathionyl specificity. The structure of human thioltransferase is characterized by a thioredoxin-like fold which comprises a four-stranded central beta-sheet flanked on each side by alpha-helices. The disulfide-adducted glutathione in the TTase-SSG complex has an extended conformation and is localized in a cleft near the protein surface encompassing the residues from helices-alpha2,alpha3, the active site loop, and the loop connecting helix-alpha3 and strand-beta3. Numerous van der Waals and electrostatic interactions between the protein and the glutathione moiety are identified as contributing to stabilization of the complex and confering the substrate specificity. Comparison of the human thioltransferase with other thiol-disulfide oxidoreductases reveals structural and functional differences.     

Mechanism of Al2CuLi (T 1) nucleation and growth

Conventional strain contrast transmission electron microscopy (CTEM) and high-resolution transmission electron microscopy (HRTEM) were performed to establish the nucleation and growth mechanism of Al₂CuLi (T₁) precipitates in an Al-Li-Cu alloy. It is shown that the growth mechanism ofT ₁ precipitate plates occurs by the diffusional glide of growth ledges composed of b = 1/6〈112〉 partial dislocations on 111 matrix planes and that the growth ledges migrate by the ledge-kink mechanism, as previously suggested by Cassadaet al. 1 for this system.T ₁ plate nucleation is modeled as the dissociation of a perfect b = 1/2〈110〉 matrix dislocation in the vicinity of a dislocation jog. The coordinated dissociation of the dislocation line segments on each side of the sessile jog provides the displacement necessary for the formation of a new hexagonal plate or plate ledge. Strain contrast analysis of the Burgers vector of plate edges and the edges of growth ledges indicates the stacking of partial dislocations is of mixed displacement. Formerly Graduate Student, Department of Materials Science, University of Virginia,     

Aspects of transition cow metabolomics—Part I: Effects of a metaphylactic butaphosphan and cyanocobalamin treatment on the metabolome in liver,blood, and urine in cows with different liver metabotypes

Dairy cows in modern production systems are at risk to develop metabolic disorders during the transition period. Reasons for individual differences in susceptibility, as well as the underlying pathomechanisms, are still only partially understood. The development of metaphylactic treatment protocols is needed. In this context, an on-farm prospective 3-fold blinded randomized study involving 80 German Holstein cows was performed throughout 1 yr. The trial involved a thorough recording of the production and clinical traits, clinical chemistry, and liver biopsies and blood and urine sampling at d 14 (mean: 12 d, range: 1–26 d) antepartum (AP), and d 7 (7, 4–13) and 28 (28, 23–34) postpartum (PP) for metabolomics analyses. Two groups received a treatment with butaphosphan and cyanocobalamin (BCC) at either the dosage recommended by the manufacturer or the double dosage (5 or 10 mL/100 kg of body weight 10% butaphosphan and 0.005% cyanocobalamin (Catosal, Bayer Animal Health), n = 20 in each group, parity: 4.2 ± 2.0 and 3.4 ± 1.3, respectively (mean ± SD)] and one group a placebo treatment (NaCl 0.9%, n = 40, parity: 4.0 ± 1.9). The animals were treated at 6 time points (7, 6, and 5 d AP, and 1, 2, and 3 d PP) via intravenous injection. Mass spectroscopy-based targeted metabolomics analysis of blood plasma and liver samples were performed using the AbsoluteIDQ p180 kit (Biocrates Life Sciences), whereas the urine samples were analyzed by nuclear magnetic resonance spectroscopy. Statistical analysis was performed using multivariate [partial least squares discriminant analysis (PLS-DA)] and univariate methods (linear mixed model). Multivariate data analysis (PLS-DA plots) of the liver metabolome revealed 3 different metabotypes (A = medium, B = minor, C = large alterations in liver metabolome profile between AP and PP status). Metabotype B animals were characterized by higher PP lipomobilization (stronger PP body condition decrease and higher blood bilirubin, fatty acids, gamma-glutamyltransferase, and triglyceride levels) and a higher occurrence of transition cow diseases, compared with the animals in metabotype C. Analysis of the feeding data showed that the period of metabotype B animals (calving in a distinct time frame) was characterized by a decreased grass silage quality. The PP liver metabolome of the metabotype C animals was characterized by higher concentrations of AA, acylcarnitines, lysoPC and sphingomyelins compared with metabotype B. For the metaphylactic treatment with BCC a dose-dependent effect was confirmed, differing between the metabotypes. In all matrices and metabotypes at various time points significant treatment effects were observed, with different profiles in clinical chemistry and as well in metabolomics data. The most clear-cut treatment effect was observed in metabotype B in the liver at 7 d PP, characterized by an increase in several acylcarnitines and phosphatidylcholines, indicating a more efficient influx and oxidation of fatty acids in mitochondria and thereby an increase in energy supply and more efficient triglyceride export in the liver. The results from the liver metabolomics analysis support the application of an indication-based metaphylactic treatment with BCC.     

Toward 19F magnetic resonance thermometry: spin–lattice and spin–spin-relaxation times and temperature dependence of fluorinated drugs at 9.4 T

Magnetic Resonance Materials in Physics, Biology and Medicine - This study examines the influence of the environmental factor temperature on the 19F NMR characteristics of fluorinated compounds in...