Casein interference in bovine plasmin assays using a synthetic substrate.

Bovine plasmin (EC 3.4.21.7) activity on H-D-valyl-L-leucyl-L-lysyl-4-nitroanilide was measured by determining the change in absorbance at 405 nm. Initial rates of reactions were estimated at all combinations of the following substrate concentrations [.4, 4, and 40 times the substrate concentration at one-half maximum velocity (Vmax) (Km)] and casein concentrations [.068, .68, and 6.8 times the inhibitor constant for competitive inhibition (KI)]. By nonlinear least squares fitting of the data to an equation that described reversible enzyme kinetics, steady state kinetic parameters, maximum velocity (Vmax), substrate concentration at one-half maximum velocity (Vmax) (Km), inhibitor constant for competitive inhibition (KI), and inhibitor constant for uncompetitive inhibition (KI) were estimated. Casein fit the equation as a competitive inhibitor of bovine plasmin. This enzyme has a catalytic constant (Kcat) of .0158 change in absorbance at 405 nm/min per nM, substrate concentration at one-half maximum velocity (Vmax) (Km) of .107 mM substrate, and inhibitor constant for competitive inhibition (KI) of .86 mg/ml of casein. Bovine plasmin activity can be measured directly in bovine milk without interference from casein.     

Urinary Tract Tumor Organoids Reveal Eminent Differences in Drug Sensitivities When Compared to 2-Dimensional Culture Systems

Generation of organoids from urinary tract tumor samples was pioneered a few years ago. We generated organoids from two upper tract urothelial carcinomas and from one bladder cancer sample, and confirmed the expression of cytokeratins as urothelial antigens, vimentin as a mesenchymal marker, and fibroblast growth factor receptor 3 by immunohistochemistry. We investigated the dose response curves of two novel components, venetoclax versus {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, in comparison to the clinical standard cisplatin in organoids in comparison to the corresponding two-dimensional cultures. Normal urothelial cells and tumor lines RT4 and HT1197 served as controls. We report that upper tract urothelial carcinoma cells and bladder cancer cells in two-dimensional cultures yielded clearly different sensitivities towards venetoclax, {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, and cisplatin. Two-dimensional cultures were more sensitive at low drug concentrations, while organoids yielded higher drug efficacies at higher doses. In some two-dimensional cell viability experiments, colorimetric assays yielded different IC₅₀ toxicity levels when compared to chemiluminescence assays. Organoids exhibited distinct sensitivities towards cisplatin and to a somewhat lesser extent towards venetoclax or {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, respectively, and significantly different sensitivities towards the three drugs investigated when compared to the corresponding two-dimensional cultures. We conclude that organoids maintained inter-individual sensitivities towards venetoclax, {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, and cisplatin. The preclinical models and test systems employed may bias the results of cytotoxicity studies.     

Topic space trajectories

Scientometrics - The annual number of publications at scientific venues, for example, conferences and journals, is growing quickly. Hence, even for researchers it becomes harder and harder to keep...     

Fracture toughness of unidirectional fiber-metal laminates: crack orientation effect

Fiber-metal laminates (FMLs) are structural composites developed for aeronautical applications. The application of FMLs to structures demands a deep knowledge of a wide set of properties, including fracture toughness. The objective of this work was to evaluate the effect of crack orientation on the fracture toughness (critical J-integral and CTOD δ₅) of unidirectional FMLs. Small C(T) and SE(B) specimens with notches parallel and perpendicular to the fibers direction were tested. A study of the relation and equivalence between J_C and δ_5C, which heavily depend on the yield strength and on the stress state, was performed motivated by apparently contradictory experimental results. These results can be explained by the direction-dependent yielding properties of unidirectional FMLs. The best overall equivalence between J_C and δ_5C was obtained considering plane stress state and using the effective yield strength, both for unidirectional FMLs notched parallel and perpendicular to the fibers direction.     

Effects of supplemental dietary fatty acids on milk yield and fatty acid composition in high and medium yielding cows

The present study tested the hypothesis that supplemental dietary fatty acids (FA) affect the energy corrected milk yield in proportion to the milk production level of dairy cows, and increase both long chain FA proportion of milk FA and milk fat globule diameter. Sixteen Danish Holstein cows were divided into four 4x4 Latin squares with two squares of medium yielding cows (32.2 kg energy corrected milk (ECM)/d; 158 days in milk (DIM)) and two squares of high yielding cows (40.0 kg ECM/d; 74 DIM). Experimental length was 12 weeks, with three weeks for each of the four periods. The four treatments were no supplementation (17 g FA/kg dry matter (DM)) and three diets with supplemented FA (29, 40, and 52 g total FA/kg DM, respectively) obtained by substituting barley with Palm Fatty Acid Distillate (PFAD) fat. Diets were offered as total mixed rations with 63% grass/clover silage (DM basis). Dry matter intake decreased with increasing FA supplementation, but net energy intake was not affected. The general linear responses to 10 g/kg DM increase in FA level were 1.1 kg ECM (P<0.0001), 0.061 kg milk fat (P<0.0001), 0.012 kg milk protein (P=0.09) and 0.052 kg lactose (P=0.0002) per day, and linear responses in milk composition were 0.39 g fat (P=0.07), -0.71 g protein (P<0.0001) and 0.05 g lactose (P=0.3) per kg milk, and 0.092 microm (P<0.0001) in milk fat average globule diameter. Fatty acid supplementation decreased short- and medium-chain FA and C16:0 and increased C18:1 proportions of total FA in milk. Supplemental dietary FA increased ECM yield but not in proportion to production level as anticipated, and increased average FA chain length and milk fat globule diameter.     

3D extrusion of multi-biomaterial lattices using an environmentally informed workflow

The conventional building material palette has been proven limited in terms of adaptability to our current environmental challenges. Innovations in computational design and digital manufacturing have supported the broadening of biomaterial applications as an alternative. While biomaterials are characteristically responsive to stimuli such as temperature and humidity, their unpredictable behaviour is a hurdle to standardization and architectural utilisation. To examine the nexus between material formulation, computation and manufacturing, multi-biomaterial lattice structures were produced through an environmentally informed workflow. Customized biomaterial development resulted in three candidate biopolymer blends with varying levels of hydro-responsiveness and transparency. The computational strategy included a machine learning clustering algorithm to customise results and dictate material distribution outputs. To test the workflow, environmental data of solar radiation exposure and solar heat gain from a specific location was used to inform the material deposition via pneumatic extrusion for the design and digital fabrication of a deformation-controlled prototype of 350 mm × 350 mm. This led to a series of multi-biomaterial wall panel components that can be applied at architectural scale. In future, these techniques can support the incorporation of living elements to be embedded within the built environment for truly animate architecture.     

Notruf 110 / 112: Technische Richtlinie Notrufverbindungen (TR Notruf) 2.0

Sieben Jahre nach Herausgabe der Version 1.0 am 22.06.2011 hat die Bundesnetzagentur nunmehr Version 2.0 der TR Notruf vorgelegt. Die neue Version ?trägt insbesondere der Umstellung der Telefonnetze auf IP-Technologie Rechnung“1, indem sie erstmals Anforderungen an Notrufverbindungen beschreibt, die vollständig in IP ausgeführt werden. Diese umfassen insbesondere die Anforderungen an den IP-basierten Notrufanschluss zur Entgegennahme der 110-/112-Notrufe bei Polizei und Feuerwehr.