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.     

Achieving both large piezoelectric constant and high Curie temperature in BiFeO3-PbTiO3-BaTiO3 solid solution

The high-temperature and high-performance piezoelectric ceramics are required urgently in the petrochemical, automotive, and aerospace industries. In this work, the (0.85-x)BiFeO₃-xPbTiO₃-0.15BaTiO₃ (BF-PT-BT, x = 0.21, 0.22, 0.23, 0.24 and 0.25) piezoelectric ceramics with both high Curie temperature and large piezoelectric constant d₃₃ were presented. X-ray diffraction analysis shows that BF-PT-BT ceramics exhibit dominant perovskite structure with the coexistence of tetragonal (T) and rhombohedral (R) phases. The c/a ratio, Curie temperature, piezoelectric constant, dielectric constant and loss of the BF-PT-BT ceramics for x = 0.23 are 1.06, 546 °C, 222 pC/N, 545 and 0.013, respectively. Room temperature piezoelectric constant of BF-PT-BT ceramics is much higher than those of PbTiO₃, PbNb₂O₆ and other ABO₃ perovskite compounds (BaZrO₃, Bi(Zn, Ti)O₃, PbZrO₃ and Pb(Mg, Nb)O₃) modified ternary BiFeO₃-PbTiO₃ ceramics with similar Curie temperatures. The piezoelectric constant is almost unchanged after BF-PT-BT ceramics was annealed at 450 °C for 30 min, which is due to the stable switched non-180° domain and transformed R phase by annealing treatment.     

Microstructural evaluation and thermal oxidation behaviors of YSZ/NiCoCrAlYTa coatings deposited by different thermal techniques

In this paper, two coating techniques, the high velocity oxy-fuel (HVOF) and air plasma spray (APS) techniques, were used to deposit a bond coat of NiCoCrAlYTa on the Inconel 625 substrate, followed by applying a topcoat of yttria-stabilized zirconia (YSZ). The samples were preoxidized in an argon-controlled furnace at a temperature of 1000 °C for 12 and 24 h to characterize the microstructure of a thermally grown oxide (TGO) using the two coating techniques. The most suitable preoxidized samples were further tested for isothermal oxidation at 1000 °C for up to 120 h, and a hot corrosion test was performed at 1000 °C for up to 52 h or until spalling occurred. As-sprayed and oxidized samples prepared with different coating techniques were evaluated in terms of their microstructure using different characterization methods, such as field emission scanning electron microscopy (FESEM), variable pressure scanning electron microscopy (VPSEM), energy dispersive X-ray spectroscopy (EDS) equipped with energy dispersive X-ray and X-ray diffraction (XRD) analyses. In addition, the mechanical properties of these samples were evaluated using adhesion tests. The results show that the YSZ/NiCoCrAlYTa coating applied with the HVOF technique forms a more thin and continuous layer of TGO than that obtained when applying a YSZ/NiCoCrAlYTa coating using the APS technique, indicating that a severe brittle oxidation interface exists between the two layers. The results also indicate that the mechanical strength obtained from the adhesion test of the coated samples is observably affected by the oxidation behaviors obtained with the different deposition techniques chosen.     

Preparation and corrosion resistance of nonstoichiometric lanthanum zirconate coatings

Lanthanum zirconate is a promising thermal barrier coating material owing to its excellent thermophysical properties and La plays the key role in its corrosion resistance. Here, an amorphous precursor is used as raw feedstock material so as to synthesize lanthanum zirconate coatings with tailorable composition by atmospheric plasma spray (APS). Three lanthanum zirconate coatings of La_1.7Zr_2.3O_7.15, La_2.0Zr_2.0O_7.0 and La_2.3Zr_1.7O_6.85 are fabricated. Furthermore, the corrosion resistance of the as-sprayed coatings against CaO-MgO-Al₂O₃-SiO₂ at 1250℃ is investigated. The increased La content promotes the formation of a sealing layer of the crystalline Ca₂La₈(SiO₄)₆O₂ apatite, which slows down the penetration of molten CaO-MgO-Al₂O₃-SiO₂. Therefore, the infiltration rate of the La_2.3Zr_1.7O_6.85 coating decreased up to 42.6 % compared with the other two coatings. This work develops a feasible preparation strategy to control the La composition for the improved corrosion resistance, which is expected to guide the future coating design and synthesis for the materials with big composition changes during the APS process.     

Modeling the thermal shock induced cracking in ceramics

Prediction of surface cracking in ceramics due to quenching is performed numerically using either the coupled criterion or a cohesive zone model. Under such a thermal shock, a network of short cracks with minimal spacing between them initiate and propagate until some of them stop while the others continue propagating. The numerical implementation consists of a periodic array of cracks modeled by a representative volume element. It allows crack initiation, simultaneous propagation and period doubling to be predicted. The investigation of the crack period doubling allows a precise determination of the optimal crack spacing, which decreases with an increasing thermal shock amplitude. The predicted crack spacing results are in agreement with experimental measurements.     

Thermally driven failure of Nd:YVO4 amplifier crystals

We report on an unusual failure pattern resulting from thermally driven fracture of laser amplifier single crystals. The pattern led to some confusion with regard to the point of initiation due to the coalescence of hackle lines to a region within the fracture surface, rather than the more common divergence of hackle away from the origin. The pattern leads to new fracture terms: Hackle node - the coalescence of hackle marks to a point of prior compression. The feature is produced as a thermally-generated, centrally-located compressive region transforms to tension thereby drawing crack propagation and hackle to the compressive region, forming an internal terminus. Hackle terminus – a hackle node formed by final crack propagation within the component. As part of the analysis, the fracture toughness and slow crack growth constants of neodymium doped, yttrium ortho-vanadate (Nd:YVO₄) were measured. Nd:YVO₄ exhibits slow crack growth and is very brittle with a fracture toughness of only 0.48 MPa√m.     

金沙江上游水电站应对白格堰塞湖灾害的措施及经验

2018年10月、11月,西藏自治区昌都市江达县白格村两次发生山体滑坡造成金沙江断流并形成白格堰塞湖,给金沙江上游沿岸人民生产生活设施造成巨大安全威胁和超过百亿元的经济损失。华电金沙江上游水电开发有限公司组织所属企业及参建单位快速应对,采取撤离避让、工程防护、人工干预、生产恢复,推动后续处置、风险评估等措施,最大限度减轻了对金沙江上游叶巴滩、拉哇、巴塘、苏洼龙等在建水电站的灾害损失和后续影响,为类似灾害的处置提供借鉴经验。