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21.
22.
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
23.
Christian Veauthier Gunnar Gaede Helena Radbruch Klaus-Dieter Wernecke Friedemann Paul 《International journal of molecular sciences》2015,16(7):16514-16528
Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are lacking. From our original cohort, a cross-sectional polysomnographic (PSG) study in consecutive MS patients, we retrospectively analysed the previously unpublished data of the Nottingham Health Profile (NHP). Those MS patients suffering from sleep disorders (n = 49) showed significantly lower HRQoL compared to MS patients without sleep disorders (n = 17). Subsequently, we classified the patients into four subgroups: insomnia (n = 17), restless-legs syndrome, periodic limb movement disorder and SD due to leg pain (n = 24), obstructive sleep apnea (n = 8) and patients without sleep disorder (n = 17). OSA and insomnia patients showed significantly higher NHP values and decreased HRQoL not only for the sleep subscale but also for the “energy” and “emotional” area of the NHP. In addition, OSA patients also showed increased NHP values in the “physical abilities” area. Interestingly, we did not find a correlation between the objective PSG parameters and the subjective sleep items of the NHP. However, this study demonstrates that sleep disorders can reduce HRQoL in MS patients and should be considered as an important confounder in all studies investigating HRQoL in MS. 相似文献
24.
25.
Antti Voss Niko Hänninen Mohammad Pour-Ghaz Marko Vauhkonen Aku Seppänen 《Materials and Structures》2018,51(3):68
The development of visualizing tools to monitor unsaturated moisture flow in cement-based materials is of great importance, as most degradation processes in cement-based materials are connected to and take place in the presence moisture. This paper investigates the ability of electrical capacitance tomography (ECT) to image two-dimensional (2D) unsaturated moisture flow in cement-based materials. In ECT, the electrical permittivity distribution within an object is reconstructed based on measured capacitances between electrodes attached on the object’s surface. In a series of experiments, mortar specimens with and without discrete cracks were imaged with ECT during a 2D moisture ingress. The results show that ECT is able to monitor the evolution of the moisture flow, and to approximate the shape and position of the moisture front. These findings indicate that ECT is a viable method for monitoring and visualizing 2D unsaturated moisture flow in cement-based materials in the presence and absence of discrete cracks. 相似文献
26.
Locke Davenport Huyer Serena Mandla Yufeng Wang Scott B. Campbell Bess Yee Christian Euler Benjamin F. Lai A. Dawn Bannerman Dawn S. Y. Lin Miles Montgomery Kayla Nemr Timothy Bender Slava Epelman Radhakrishnan Mahadevan Milica Radisic 《Advanced functional materials》2021,31(6):2003341
Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA. 相似文献
27.
B. Schönfelder G. Gottstein L. S. Shvindlerman 《Metallurgical and Materials Transactions A》2006,37(6):1757-1771
While the motion of twist boundaries can be readily studied by atomistic simulations with molecular dynamics (MD) under the
action of an elastic driving force, the approach fails for tilt boundaries. This is due to the interaction of the elastic
stress with the grain boundary (GB) structure, which causes plastic strain by GB sliding. A novel concept, the orientation
correlated driving force, is introduced to circumvent this problem. It is shown that this concept can be successfully applied
to the study of the migration of tilt boundaries. The migration behavior of several twist and tilt GBs was investigated. The
transition from low-to high-angle boundaries can be captured, and a structural transition of tilt boundaries was found at
high temperatures, which also affected the migration behavior. The results compare well with experimental results of the motion
high-angle boundaries, but for low-angle boundaries, the agreement is poor.
This article is based on a presentation made in the “Hillert Symposium on Thermodynamics & Kinetics of Migrating Interfaces
in Steels and Other Complex Alloys,” December 2–3, 2004, organized by The Royal Institute of Technology in Stockholm, Sweden. 相似文献
28.
S. Büttgenbach J. Hesselbach R. Tutsch M. Berndt B. Hoxhold K. Schöttler 《Microsystem Technologies》2006,12(7):665-669
Positioning accuracies in the range of a few micrometers and below are necessary for the assembly of active micro-systems. In order to reach these accuracies, an assembly system for sensor guided micro-assembly is developed in the Collaborative Research Centre 516 “Design and manufacturing of active micro-systems”. The combination of a parallel robot with an integrated 3D vision sensor and a micro-gripper enables to reach relative positioning accuracies below 1 μm. 相似文献
29.
Kurjenniemi Janne Hämäläinen Seppo Ristaniemi Tapani 《Wireless Personal Communications》2003,27(4):337-351
In this article we consider the performance of the 3.84 Mcpstime-division duplex (TDD) mode of UTRA (Universal TerrestrialRadio Access) network. We emphasize two of the radio resourcemanagement algorithms, handover and uplink power control, whoserole in the overall system performance is studied extensively.First, a handover algorithm used in WCDMA (Wideband Code DivisionMultiple Access) standard is considered in a TDD-mode operation.This gives rise to a careful setting of different handoverparameters, and the evaluation of the effects to the systemperformance. Secondly, the specified uplink power controlalgorithm is considered. Since it is based on several user-mademeasurements which may involve both random and systematic errors acareful study about the suitability of the power control scheme iscarried out. 相似文献
30.
Detector physics and simulation of resistive plate chambers 总被引:1,自引:0,他引:1
Werner Riegler Christian Lippmann Rob Veenhof 《Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment》2003,500(1-3):144-162
We present a simulation model suited to study efficiency, timing and pulse-height spectra of Resistive Plate Chambers. After discussing the details of primary ionisation, avalanche multiplication, signal induction and frontend electronics, we apply the model to timing RPCs with time resolution down to 50 ps and trigger RPCs with time resolution of about 1 ns. 相似文献