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The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice
(2018)
The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.
Analyzing thermodynamic non-equilibrium processes, like the laminar and turbulent fluid flow, the dissipation is a key parameter with a characteristic minimum condition. That is applied to characterize laminar and turbulent behaviour of the Couette flow, including its transition in both directions. The Couette flow is chosen as the only flow form with constant shear stress over the flow profile, being laminar, turbulent or both. The local dissipation defines quantitative and stable criteria for the transition and the existence of turbulence. There are basic results: The Navier Stokes equations cannot describe the experimental flow profiles of the turbulent Couette flow. But they are used to quantify the dissipation of turbulent fluctuation. The dissipation minimum requires turbulent structures reaching maximum macroscopic dimensions, describing turbulence as a “non-local” phenomenon. At the transition the Couette flow profiles and the shear stress change by a factor ≅ 5 due to a change of the “apparent” turbulent viscosity by a calculated factor ≅ 27. The resulting difference of the laminar and the turbulent profiles results in two different Reynolds numbers and different loci of transition, which are identified by calculation.
The Effect of Openings on Out-of-Plane Capacity of Masonry Infilled Reinforced Concrete Frames
(2018)
The Carologistics team participates in the RoboCup Logistics League for the seventh year. The RCLL requires precise vision,
manipulation and path planning, as well as complex high-level decision
making and multi-robot coordination. We outline our approach with an
emphasis on recent modifications to those components.
The team members in 2018 are David Bosen, Christoph Gollok, Mostafa
Gomaa, Daniel Habering, Till Hofmann, Nicolas Limpert, Sebastian Schönitz,
Morian Sonnet, Carsten Stoffels, and Tarik Viehmann.
This paper is based on the last year’s team description.
In this paper the results of a techno-economic analysis of improved and optimized molten salt solar tower plants (MSSTP plants) are presented. The potential improvements that were analyzed include different receiver designs, different designs of the HTF-system and plant control, increased molten salt temperatures (up to 640°C) and multi-tower systems. Detailed technological and economic models of the solar field, solar receiver and high temperature fluid system (HTF-system) were developed and used to find potential improvements compared to a reference plant based on Solar Two technology and up-to-date cost estimations. The annual yield model calculates the annual outputs and the LCOE of all variants. An improved external tubular receiver and improved HTF-system achieves a significant decrease of LCOE compared to the reference. This is caused by lower receiver cost as well as improvements of the HTF-system and plant operation strategy, significantly reducing the plant own consumption. A novel star receiver shows potential for further cost decrease. The cavity receiver concepts result in higher LCOE due to their high investment cost, despite achieving higher efficiencies. Increased molten salt temperatures seem possible with an adapted, closed loop HTF-system and achieve comparable results to the original improved system (with 565°C) under the given boundary conditions. In this analysis all multi tower systems show lower economic viability compared to single tower systems, caused by high additional cost for piping connections and higher cost of the receivers.
REFERENCES
The overall energy efficiency of ventilation systems can be improved by considering not only single components, but by considering as well the interplay between every part of the system. With the help of the method "TOR" ("Technical Operations Research"), which was developed at the Chair of Fluid Systems at TU Darmstadt, it is possible to improve the energy efficiency of the whole system by considering all possible design choices programmatically. We show the ability of this systematic design approach with a ventilation system for buildings as a use case example.
Based on a Mixed-Integer Nonlinear Program (MINLP) we model the ventilation system. We use binary variables to model the selection of different pipe diameters. Multiple fans are model with the help of scaling laws. The whole system is represented by a graph, where the edges represent the pipes and fans and the nodes represents the source of air for cooling and the sinks, that have to be cooled. At the beginning, the human designer chooses a construction kit of different suitable fans and pipes of different diameters and different load cases. These boundary conditions define a variety of different possible system topologies. It is not possible to consider all topologies by hand. With the help of state of the art solvers, on the other side, it is possible to solve this MINLP.
Next to this, we also consider the effects of malfunctions in different components. Therefore, we show a first approach to measure the resilience of the shown example use case. Further, we compare the conventional approach with designs that are more resilient. These more resilient designs are derived by extending the before mentioned model with further constraints, that consider explicitly the resilience of the overall system. We show that it is possible to design resilient systems with this method already in the early design stage and compare the energy efficiency and resilience of these different system designs.