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111.
Dr. Li Di Prof. Per Artursson Dr. Alex Avdeef Prof. Leslie Z. Benet Prof. J. Brian Houston Dr. Manfred Kansy Edward H. Kerns Prof. Hans Lennernäs Dr. Dennis A. Smith Prof. Kiyohiko Sugano 《ChemMedChem》2020,15(20):1862-1874
Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients. 相似文献
112.
Xueli Du Yuelong Wang Rongna Shi Zhiyong Mao Zhihao Yuan 《Journal of the European Ceramic Society》2018,38(10):3512-3517
The PbClxS1-x and Pb1-xBixS (x? =?0–0.05) bulks were fabricated with a facile method of hydrothermal synthesis and microwave sintering, and the effect of anionic and cationic donors on the thermoelectric performance of PbS was investigated. Although Cl? and Bi3+ both effectively improved the thermoelectric properties of n-type PbS, more excellent thermoelectric performance was obtained from Cl? doped samples because of higher electrical property and lower thermal conductivity at higher temperature (T? >?600?K). The thermoelectric figure of merit (ZT) reaches 1.04 for PbCl0.015S0.985 at 800?K and increases with temperature increasing without sign of saturation, which is probably the highest value ever reported for single-phase polycrystalline n-type PbS. The results also indicate that the hydrothermal synthesis and microwave sintering can realize anion doping as well as cation doping for n-type PbS at low cost, and PbS should be a robust alternative for PbTe thermoelectric materials. 相似文献
113.
David L. Wood Jeffrey D. Quass Jianlin Li Shabbir Ahmed David Ventola Claus Daniel 《Drying Technology》2018,36(2):234-244
Processing lithium-ion battery (LIB) electrode dispersions with water as the solvent during primary drying offers many advantages over N-methylpyrrolidone (NMP). An in-depth analysis of the comparative drying costs of LIB electrodes is discussed for both NMP- and water-based dispersion processing in terms of battery pack $/kWh. Electrode coating manufacturing and capital equipment cost savings are compared for water vs. conventional NMP organic solvent processing. A major finding of this work is that the total electrode manufacturing costs, whether water- or NMP-based, contribute about 8–9% of the total pack cost. However, it was found that up to a 2?×?reduction in electrode processing (drying and solvent recovery) cost can be expected along with a $3–6?M savings in associated plant capital equipment (for a plant producing 100,000 10-kWh Plug-in Hybrid Electric Vehicle (PHEV) batteries) using water as the electrode solvent. This paper shows a different perspective in that the most important benefits of aqueous electrode processing actually revolve around capital equipment savings and environmental stewardship and not processing cost savings. 相似文献
114.
Min-Kyung Kang Soo-Il Kim Su Yeon Oh Woojin Na Young-Hee Kang 《International journal of molecular sciences》2020,21(22)
Podocyte injury inevitably results in leakage of proteins from the glomerular filter and is vital in the pathogenesis of diabetic nephropathy (DN). The underlying mechanisms of podocyte injury facilitate finding of new therapeutic targets for DN treatment and prevention. Tangeretin is an O-polymethoxylated flavone present in citrus peels with anti-inflammatory and antioxidant properties. This study investigated the renoprotective effects of tangeretin on epithelial-to-mesenchymal transition-mediated podocyte injury and fibrosis through oxidative stress and hypoxia caused by hyperglycemia. Mouse podocytes were incubated in media containing 33 mM glucose in the absence and presence of 1–20 μM tangeretin for up to 6 days. The in vivo animal model employed db/db mice orally administrated with 10 mg/kg tangeretin for 8 weeks. Non-toxic tangeretin inhibited glucose-induced expression of the mesenchymal markers of N-cadherin and α-smooth muscle actin in podocytes. However, the reduced induction of the epithelial markers of E-cadherin and P-cadherin was restored by tangeretin in diabetic podocytes. Further, tangeretin enhanced the expression of the podocyte slit diaphragm proteins of nephrin and podocin down-regulated by glucose stimulation. The transmission electron microscopic images revealed that foot process effacement and loss of podocytes occurred in diabetic mouse glomeruli. However, oral administration of 10 mg/kg tangeretin reduced urine albumin excretion and improved foot process effacement of diabetic podocytes through inhibiting loss of slit junction and adherenes junction proteins. Glucose enhanced ROS production and HIF-1α induction in podocytes, leading to induction of oxidative stress and hypoxia. Similarly, in diabetic glomeruli reactive oxygen species (ROS) production and HIF-1α induction were observed. Furthermore, hypoxia-evoking cobalt chloride induced epithelial-to-mesenchymal transition (EMT) process and loss of slit diaphragm proteins and junction proteins in podocytes, which was inhibited by treating submicromolar tangeretin. Collectively, these results demonstrate that tangeretin inhibited podocyte injury and fibrosis through blocking podocyte EMT caused by glucose-induced oxidative stress and hypoxia. 相似文献
115.
Seyed Ali Maghami 《热应力杂志》2015,38(2):250-270
Thermal bending analysis of doubly curved laminated shell panels with general boundary conditions and laminations is presented. The equations of equilibrium are derived in the form of two coupled sets of ordinary differential equations based on a general shell theory and solved through the state-space approach in a repeated manner. It is depicted that the results of the present method are in great agreement with analytical solutions. Cylindrical shell panels with general boundary conditions and laminations, where no analytical solution is available, are solved. It is found that the present method exhibits a high convergence rate as well as presenting accurate results in all cases. 相似文献
116.
基于深度学习的人体姿态估计方法旨在通过构建合适的神经网络,直接从二维的图像特征中回归出人体姿态信息。主要按照2D人体姿态估计到3D人体姿态估计的顺序,并从单人检测与多人检测、稀疏的关节点检测与密集的模型构建等方面,对近年来基于深度学习的人体姿态估计方法进行系统介绍,从而初步了解如何通过深度学习的方法得到人体姿态的各个要素,包括肢体部件的相对朝向和比例尺度、骨骼关节点的位置坐标和连接关系,甚至更为复杂的人体蒙皮模型信息。最后,对当前研究面临的挑战以及未来的热点动向进行概述,清晰地呈现出该领域的发展脉络。 相似文献
117.
118.
This study addresses the thermo‐diffusion and the diffusion‐thermo phenomena in a semi‐infinite absorbent channel whose walls are contracting/expanding, with heat source/sink effects. The governing partial differential equations with suitable boundary conditions are transformed to a system of dimensionless ordinary differential equations. An analytic solution of the problem has been found using a technique called homotopy analysis method (HAM). HAM gives consistently valid answers to the problem over an extensive variety of parameters and also provides better accuracy. To validate the analytical results, a comparison has been presented with a numerical solution calculated by using the parallel shooting method. The effects of dimensionless parameters, that is, deformation parameter, Reynolds number, Soret and Dufour numbers, and heat source/sink parameter on the expressions of velocity, temperature, and concentration profiles are analyzed graphically to understand the physics of the deformable channel. It has been noted that the velocity across the channel is higher for the expanding channel, as compared to that for the contracting channel. Also the Soret and Dufour number increases the temperature of the fluid, and decreases the concentration. The temperature profile has an increasing behavior in the case of heat source, and a decreasing behavior in the case of heat sink. 相似文献
119.
Midori Umekawa Kaito Hamada Naoto Isono Shuichi Karita 《Journal of Applied Glycoscience》2020,67(4):103
Hexokinases catalyze glucose phosphorylation at the first step in glycolysis in eukaryotes. In the budding yeast Saccharomyces cerevisiae , three enzymes for glucose phosphorylation have long been known: Hxk1, Hxk2, and Glk1. In this study, we focus on Emi2, a previously uncharacterized hexokinase-like protein of S. cerevisiae . Our data show that the recombinant Emi2 protein (rEmi2), expressed in Escherichia coli , possesses glucose-phosphorylating activity in the presence of ATP and Mg 2+ . It was also found that rEmi2 phosphorylates not only glucose but also fructose, mannose and glucosamine in vitro . In addition, we examined changes in the level of endogenous Emi2 protein in S. cerevisiae in the presence or absence of glucose and a non-fermentable carbon source. We found that the expression of Emi2 protein is tightly suppressed during proliferation in high glucose, while it is strongly upregulated in response to glucose limitation and the presence of a non-fermentable carbon source. Our data suggest that the expression of the endogenous Emi2 protein in S. cerevisiae is regulated under the control of Hxk2 in response to glucose availability in the environment. 相似文献
120.
Oliwia Metryka Daniel Wasilkowski Anna Nowak Magorzata Adamczyk-Habrajska Agnieszka Mrozik 《International journal of molecular sciences》2020,21(23)
Due to the systematic increase in the production of nanomaterials (NMs) and their applications in many areas of life, issues associated with their toxicity are inevitable. In particular, the performance of heterogeneous NMs, such as nanocomposites (NCs), is unpredictable as they may inherit the properties of their individual components. Therefore, the purpose of this work was to assess the biological activity of newly synthesized Cu/TiO2-NC and the parent nanoparticle substrates Cu-NPs and TiO2-NPs on the bacterial viability, antioxidant potential and fatty acid composition of the reference Escherichia coli and Bacillus subtilis strains. Based on the toxicological parameters, it was found that B. subtilis was more sensitive to NMs than E. coli. Furthermore, Cu/TiO2-NC and Cu-NPs had an opposite effect on both strains, while TiO2-NPs had a comparable mode of action. Simultaneously, the tested strains exhibited varied responses of the antioxidant enzymes after exposure to the NMs, with Cu-NPs having the strongest impact on their activity. The most considerable alternations in the fatty acid profiles were found after the bacteria were exposed to Cu/TiO2-NC and Cu-NPs. Microscopic images indicated distinct interactions of the NMs with the bacterial outer layers, especially in regard to B. subtilis. Cu/TiO2-NC generally proved to have less distinctive antimicrobial properties on B. subtilis than E. coli compared to its parent components. Presumably, the biocidal effects of the tested NMs can be attributed to the induction of oxidative stress, the release of metal ions and specific electrochemical interactions with the bacterial cells. 相似文献