Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

High-Tg porous polyimide films with low dielectric constant derived from spiro-(adamantane-2,9′(2′,7′-diamino)-fluorene)

Porous polyimide (PI) films with low dielectric constants and excellent thermal properties have been a pressing demand for the next generation of high-performance, miniature, and ultrathin microelectronic devices. A series of novel porous PI films containing fluorenyl-adamantane groups were prepared successfully via thermolysis of poly(ethylene glycol) (PEG) added in the PI matrix. The cross-sectional morphologies of porous PI films showed closed pores with diameters ranging from 135 to 158 nm, which were uniform and regular in shape without interconnectivity. These porous PI films exhibited excellent thermal properties with a glass-transition temperature at 376 °C whereas the 5% weight loss temperature in air excess of 405 °C due to enhanced rigidity afforded by fluorenyl-adamantane groups. Accompanied by thermolysis content of PEG increasing from 0 to 20 wt %, the density of porous PI films decreased, and the corresponding porosity grew significantly from 0 to 11.48%. Depending on porosity, the dielectric constant and dielectric loss of porous PI films significantly declined from 2.89 to 2.37 and from 0.050 to 0.021, respectively. These excellent properties benefit the as-prepared porous PI films for application as interlayer dielectrics, integrated circuit chips, or multichip modules in microelectronic fields. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47313.     

四川盆地上三叠统划分对比研究

四川盆地上三叠统对比长期存在混乱，给盆地整体评价带来困难。通过岩石地层、地震地层、事件地层及高分辨率旋回地层等多种方法讨论了须家河组与香溪群各岩性段的对比关系，得出了全盆地上三叠统的对比关系；指出须四段底可近似看成等时界面；须家河组下部地层自西向东、向南逐层超覆在雷口坡组之上，上部地层在盆地西北部自东南向西北方向剥蚀层位渐次变老。文章建议四川盆地上三叠统废除“香溪群”，统一使用“须家河组”，以利于对全盆地上三叠统进行油气资源整体评价与深化研究。     

强捻棉纱针织产品的性能研究

通过对强捻棉纱针织产品进行服用性能测试，得出强捻纱织物具有良好的服用性能。     

Synthesis and characterization of conducting copolymers from aniline and o‐anisidine in HCl solutions

Conducting poly(aniline‐co‐o‐anisidine) (PAS) films with different ratios of aniline units in the polymer chain were prepared by oxidative polymerization of different molar ratios of aniline and o‐anisidine in 1 M HCl using cyclic voltammetry. Due to the much higher reactivity of o‐anisidine, the structure and properties of PASs were found to be dominated by the o‐anisidine units. The polymerization of poly‐o‐anisidine and PASs followed zero‐order kinetics with respect to formation of the polymer (film thickness) and the autocatalytic polymerization of aniline was completely inhibited. In contrast to polyaniline, a decrease in the polymerization temperature was found to increase the amount of copolymer formed and its redox charge. The presence of aniline units in PASs led to a pronounced increase in the molecular weight and conductivity, and a decrease in the solubility in organic solvents. Repetitive charging/discharging cycles showed that PASs resist degradation more than polyaniline. Copyright © 2003 Society of Chemical Industry     

热声制冷机及其改进实验研究

热声制冷作为一种很有前途的制冷方法，在国内外相关领域引起了极大兴趣。热声制冷机由声发生器、共振管、板叠及高、低温换热器等部分组成。对声驱动器的振动膜及其冷却系统、气体弹簧系统、高、低温换热器进行了初步改进，使制冷机冷端温降从原来的12℃提高到27℃左右，这是目前国内报道的最大温降。     

High brachial artery bifurcation: a report of 2 cases

High division of the brachial artery was observed in two cadavers, during routine dissection of upper extremities. In the first case, the brachial artery of the right upper extremity was divided into its two terminal branches immediately after passing between the lateral and medial roots of the median nerve and just below the origin of the profunda brachii artery. The lateral branch was the radial artery, located in the space normally occupied by the brachial artery and the medial one was the ulnar artery. In the second case, the brachial artery was divided into its two terminal branches just below the origin of the profunda brachii artery. Accurate knowledge of the relationships and course of these major arterial conduits and particularly of their variational patterns, is of considerable practical importance in the conduct of reperative surgery in the arm, forearm and hand.     

故县大坝坝基泥化性F_5断层的化学灌浆防渗加固处理

泥化软化性F_5断层是故县大坝坝基范围内最大的一条断层,位于左岸,对左坝肩的稳定极为不利,采用水泥灌浆处理无效,故改用化学灌浆处理。选用EAA化学浆材,采用“优选组合配方综合施灌”的创新施工工艺,效果良好,为今后低渗透性复杂的泥化软化性断层的防渗加固处理,提供了新的依据和途径。     

Fringe probing of an evaporating microdroplet on a hot surface

The phenomenon of droplets impacting and evaporating on a hot surface is of interest in many areas of engineering. Quantitative measurement of these processes provides great help to reveal the physics behind. A novel technique was developed to quantitatively measure the volume evolution and contact diameter of an evaporating microdroplet on a hot surface utilizing interference fringe scattering method. In this method, fine fringes produced by the interference of two coherent laser beams was scattered by the droplet and projected onto a screen. The profile and volume of the droplet can be derived from the spatial fringe spacing on the screen. The number of total fringes measurable on the screen was used to determine the instantaneous contact diameter of the microdroplet. Validation experiments demonstrated that the measurement errors are less than ±5% and ±1% for microdroplet volume and contact diameter, respectively. By using this method, the dynamic of droplet impingement, evaporation and boiling using ethanol, pure water and water solution of a surfactant (sodium dodecyl sulfate) with impact velocity of 7.5 m/s and diameters ranged from 0.19 to 0.46 mm were investigated.