The Critical Role of Passive Permeability in Designing Successful Drugs

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.     

Study on the Height of the Mining-Induced Water-Conducting Fracture Zone Under the Q 2l Loess Cover of the Jurassic Coal Seam in Northern Shaanxi,China

A method to calculate the height of a water-conducting fractured zone (HWCFZ) was developed based on the plate and shell theory, and the development of the HWCFZ in bedrock and Q2l loess strata is discussed in detail. First, the subsidence-deflection curve equation of the overlying stratum is theoretically derived, and then the ultimate deflection and free space height of rock strata are calculated. Moreover, the strata tensile strain is calculated by using integral calculus. In addition, the failure state of the rock is analyzed by comparing the theoretically calculated tensile strain with the experimentally measured yield tensile strain, allowing one to attain the maximum value of HWCFZ. This approach was tested at the Jinjitan coal mine; the theoretically predicted, experimentally measured, and numerically computed maximum HWCFZ values were 189.5, 187.3, and 188.5 m, respectively, demonstrating the accuracy of the proposed method. These results are highly significant for safe and environment-friendly coal mining in northwest Shaanxi, China.     

Microwave dielectric properties of SrLa[Ga1−x(Mg0.5Ti0.5)x]O4 and SrLa[Ga1−x(Zn0.5Ti0.5)x]O4 (x = 0.2-0.8) ceramics

SrLa[Ga_1−x(R_0.5Ti_0.5)_x]O₄ (R = Mg, Zn) ceramics were prepared by a standard solid state sintering method. The single-phase ceramics with K₂NiF₄-type layered perovskite structure and I4/mmm space group were obtained, indicating that SrLa(R_0.5Ti_0.5) and SrLaGaO₄ can form the unlimited solid solutions. With increasing x for R = Mg and Zn, ε_r increases monotonously, the Qf value first increases and then decreases, while τ_f increases from a negative to a positive value. The optimized microwave dielectric properties were obtained as following: ε_r = 23.3, Qf = 89 400 GHz, τ_f = −0.8 ppm/°C for SrLa[Ga_0.6(Mg_0.5Ti_0.5)_0.4]O₄ and ε_r = 23.3, Qf = 76 200 GHz, τ_f = 0.2 ppm/°C for SrLa[Ga_0.7(Zn_0.5Ti_0.5)_0.3]O₄, indicating that the present solid solution ceramics are the promising candidates as microwave resonator materials for the telecommunication applications.     

Study on wax precipitation characteristics of wax deposit in pipes

Wax deposit properties are a significant concern in pipeline pigging during waxy crude oil transportation. In the present work, the impacts of flow conditions and oil properties on the wax precipitation characteristics of wax deposits are investigated. A flow loop apparatus was developed to conduct wax deposition experiments using four crude oils collected from different field pipes. The differential scanning calorimetry (DSC) technique was employed to observe the wax precipitation characteristics of crude oil and wax deposit. The results show that the wax content and the wax appearance temperature (WAT) of the deposits increase with shear stress and radial temperature gradient, and decrease with radial wax molecule concentration gradient near the pipe wall. The DSC tests on the wax deposits revealed that the deposit wax content is strongly correlated to the oil wax content. Furthermore, an empirical correlation was developed to predict the wax content and the WAT of the wax deposit. Verification of the empirical correlation using the different oils indicated that the average relative error of the wax content prediction and average absolute error of WAT prediction were 13.2% and 3.6°C, respectively.     

Nb和时效时间对热轧中锰TRIP钢中P偏聚的影响

热轧态中锰TRIP钢首先经650 ℃退火2 h,随后在550 ℃进行等温时效热处理,采用场发射扫描电镜(FE-SEM)研究该钢中P的偏聚和时效析出行为的变化情况。结果表明,中锰TRIP钢中P在晶界的偏聚是一种非平衡偏聚现象,临界时间约为50 h,与理论计算结果48 h较为吻合。在局部偏聚区域内,C与P存在共偏聚的关系,即P偏聚量高的地方,C含量也高。而合金元素Nb具有抑制P偏聚的效果,在20~70 h时效时间内,可以相对降低6.57%~19.5%的最大P偏聚量。根据电子背散射衍射(EBSD)菊池线分析,P偏聚量低于2.28at%时,P为固溶状态,高于2.28at.%时,P为析出状态。     

Alloy optimisation of bainitic steel for large plastic mould

Based on the phase transformation theories, especially the T₀ concept of bainite transformation, alloy optimisation of bainitic steel with carbides has been carried out aiming at the produce of plastic mould with large cross-section. The effect of manganese and silicon on proeutectoid ferrite and bainite transformation is explored by dilatometric analysis, XRD and different microscopy techniques. The results show that after the alloy optimisation, the transformation of proeutectoid ferrite is suppressed and when the cooling rate is lower than 0·1°C?s^??1, the new lower bainite transformation appears by decreasing carbon capacity of austenite and promoting carbide precipitation. Industrial production proves that the optimised alloy SDP1 can meet the demand for the plastic mould with the thickness of 1050?mm.     

埋地管道泄漏内封堵装置设计与研究

针对流体输送埋地管道泄漏问题,设计了一种利用管道机器人携带封堵气囊进行快速应急封堵修复的埋地管道泄漏内封堵装置。采用矩阵变换方法建立了牵引系统驱动轮过弯方程,利用MATLAB软件对过弯方程进行了验证,同时利用ADAMS软件仿真分析过弯路径与驱动轮转角对牵引系统行走速度的影响。研究结果表明:由两个串联封堵器组成的应急封堵系统可满足复杂工况下的管道泄漏封堵要求;牵引系统驱动轮在弯管内部行走时,单轮速度呈周期性变化,但三个驱动轮整体周期运动特性一致;驱动轮转角在25°~40°时,牵引系统行走速度与驱动轮转角成正比,且转角为30°时驱动效果最好。该内封堵装置的结构设计可为管道泄漏应急封堵领域装备的研发提供重要参考。