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1.
Vlad F. Avram Imen Chamkha Eleonor sander-Frostner Johannes K. Ehinger Romulus Z. Timar Magnus J. Hansson Danina M. Muntean Eskil Elmr 《International journal of molecular sciences》2021,22(1)
Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings. 相似文献
2.
Multibody System Dynamics - The Floating Frame of Reference Formulation (FFRF) is one of the most widely used methods to analyze flexible multibody systems subjected to large rigid-body motion but... 相似文献
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Rene M. Ripken Jeffery A. Wood Johannes G. E. Gardeniers Sverine Le Gac 《化学工程与技术》2019,42(10):2179-2186
In heterogeneous catalysis, the creation of gaseous products as bubbles in a liquid phase on the catalytic surface is associated with slip phenomena. In a microreactor, the slip length at the gas‐liquid interface is in the same order of magnitude as the reactor dimensions, which can affect fluid dynamics and transport phenomena. Here, the interplay of momentum, heat and mass transfer in a microreactor, when bubbles form on the catalytic surface, was investigated using two‐dimensional simulations. The effect of bubbles on the endothermic process of aqueous‐phase reforming of a glycerol solution was evaluated in terms of conversion and conversion and temperature in the reactor. Altogether, this study highlights the impact of bubbles, not only on the transport phenomena but also on the reactor performance. 相似文献
5.
Neil Gerard Quigley Dr. Stefano Tomassi Dr. Francesco Saverio di Leva Dr. Salvatore Di Maro Dr. Frauke Richter Dr. Katja Steiger Prof. Dr. Susanne Kossatz Prof. Dr. Luciana Marinelli Dr. Johannes Notni 《Chembiochem : a European journal of chemical biology》2020,21(19):2836-2843
αvβ6 Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with αvβ6 integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the αvβ6-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH2) to enhance αvβ6 integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)3 showed a 28-fold higher αvβ6 affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC50 of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC50-based selectivity over the related integrin αvβ8 (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)3 holds promise for improved clinical PET diagnostics of carcinomas and fibrosis. 相似文献
6.
Daniel Ritzberger Johannes Höflinger Zhang Peng Du Christoph Hametner Stefan Jakubek 《International Journal of Hydrogen Energy》2021,46(21):11878-11893
In order to mitigate the degradation and prolong the lifetime of polymer electrolyte membrane fuel cells, advanced, model-based control strategies are becoming indispensable. Thereby, the availability of accurate yet computationally efficient fuel cell models is of crucial importance. Associated with this is the need to efficiently parameterize a given model to a concise and cost-effective experimental data set. A challenging task due to the large number of unknown parameters and the resulting complex optimization problem. In this work, a parameterization scheme based on the simultaneous estimation of multiple structured state space models, obtained by analytic linearization of a candidate fuel cell stack model, is proposed. These local linear models have the advantage of high computational efficiency, regaining the desired flexibility required for the typically iterative task of model parameterization. Due to the analytic derivation of the local linear models, the relation to the original parameters of the non-linear model is retained. Furthermore, the local linear models enable a straight-forward parameter significance and identifiability analysis with respect to experimental data. The proposed method is demonstrated using experimental data from a 30 kW commercial polymer electrolyte membrane fuel cell stack. 相似文献
7.
Stephan Laske Wolfgang Ziegler Markus Kainer Johannes Wuerfel Clemens Holzer 《Polymer Engineering and Science》2015,55(12):2849-2858
The low thermal stability of polylactid acid (PLA) limits its use for various applications such as microwave‐ready dishes or hot beverage packaging. Furthermore, contained items might be damaged by occurring temperature peaks during transport (e.g., shipping container internal temperature exceeds 80°C) or other usage (e.g., car dashboard heated by sun). The aim of this study was the development of a PLA compound with an operating temperature above 100°C. Therefore, different formulations (e.g., stereocomplex of PLLA and PDLA, cross‐linking of PLA or use of commercial additives) were identified and compounds with varying conditions produced and tested regarding their thermal and mechanical properties. The results showed clearly possible routes for improving the thermal properties of PLA. Using such compounds respectively processing routes and additives helps to overcome one of the most significant problems when using PLA. The higher operating temperature of this biopolymer will lead to a wider field of application and will avoid shipping hazards. POLYM. ENG. SCI., 55:2849–2858, 2015. © 2015 Society of Plastics Engineers 相似文献
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Carina Heisig Jelka Diedenhoven Christopher Jensen Helmut Gehrke Thomas Turek 《化学工程与技术》2020,43(3):484-492
The conversion of bio-based succinic acid (SA) to the value-added chemicals 1,4-butanediol (BDO), γ-butyrolactone (GBL), and tetrahydrofuran (THF) can replace the corresponding petrochemical production routes to achieve a sustainable process. The reaction network for aqueous-phase catalytic hydrogenation of succinic acid over a supported Re-Pd catalyst was identified and the reaction kinetics was determined. With the developed kinetic model, the composition of the product mixture regarding the desired products (BDO, GBL, THF) can be described as a function of educt concentration, temperature, and pressure. The maximum BDO yield was achieved at high pressure and low temperature, while low pressure and high temperature favored GBL and THF production. 相似文献
10.
Matthew D. Ward Brian L. Chaloux Michelle D. Johannes Albert Epshteyn 《Advanced materials (Deerfield Beach, Fla.)》2020,32(42):2003667
High proton conductivity is reported for unhumidified ammonium borosulfate, NH4[B(SO4)2], a solid acid coordination polymer that contains 1D, hydrogen-bonded NH4+···1∞[B(SO4)4/2]− chains. NH4[B(SO4)2] is thermally stable to 320 °C and is amenable to sintering into monolithic, polycrystalline discs at 200 °C and about 300 MPa of uniaxial pressure. Impedance spectroscopy measurements reveal ionic conductivities for sintered ammonium borosulfate of 0.1 mS cm−1 at 25 °C and up to 10 mS cm−1 at 180 °C in ambient air. No superprotonic transition is observed in the temperature range of 25–180 °C. Ab initio molecular dynamics simulations show these high conductivities are aided by free rotation of the NH4+ units and significant gyrational mobility of the SO4 tetrahedra, which, in turn, provide facile pathways for proton locomotion. High conductivities, a wide operational temperature window, and tolerance to both ambient and anhydrous conditions make NH4[B(SO4)]2 an attractive candidate electrolyte for intermediate-temperature hydrogen fuel cells that may enable operation at temperatures as high as 300 °C without active humidification. 相似文献