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BMX is a member of TEC family nonreceptor tyrosine kinase and is involved in a variety of critical physiological and pathological processes. Through combination of irreversible inhibitor design and type II inhibitor design approaches, we have discovered a highly selective and potent type II irreversible BMX kinase inhibitor compound 41 (CHMFL-BMX-078), which exhibited an IC50 of 11 nM by formation of a covalent bond with cysteine 496 residue in the DFG-out inactive conformation of BMX. It displayed a high selectivity profile (S score(1) = 0.01) against the 468 kinases/mutants in the KINOMEscan evaluation and achieved at least 40-fold selectivity over BTK kinase. Given the fact that BMX mediated signaling pathway is still not fully understood, compound 41 would serve as a useful pharmacological tool to elucidate the detailed mechanism of BMX mediated signaling pathways.

Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream mediators such as STAT5, Crkl, and ERK's phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI50 = 14 nM), KU812 (GI50 = 25 nM), and MEG-01 (GI50 = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now.

In order to evaluate the groundwater resources and aquifer system of the Jilin urban area (JUA), a groundwater numerical flow model was established by using the groundwater modeling system based on data from 190 boreholes. River stages were interpolated to control the groundwater flow field. The input parameters such as hydraulic conductivity and specific yield were based on data from 260 pumping test data. The model was calibrated by trial and error, simulated results were compared to the observed head and contour maps, which were generally in good agreement, and the root mean squared error was 0.66 m. Sensitivity analysis was carried out and recharge proved to be the most sensitive factor in this model. The water budget showed that the input was 2.07× 108 m3/a, which was smaller than the output of 2.21 × 108 m3/a. A groundwater level decline and cone of depression exist in the Songhua and Aolong river valley. The JUA aquifer systems can be well and efficiently modeled by constructing a numerical model. Based on the supply and demand analysis of water resources, the established model would finally provide a scientific basis to use the groundwater resources sustainably in JUA.

The main purpose of nuclear magnetic resonance (NMR) magnetometer is to calibrate the magnetic field. The core of the traditional NMR magnetometer is marginal oscillator, but the precision of marginal oscillator is not high enough. The paper chiefly presents a new control method to generate RF signal for a novel NMR magnetometer. The basic structure and operation principle of the novel NMR magnetometer is simply described here. In order to improve the precision of NMR magnetometer, the RF signal is generated by the Direct Digital Synthesizer (DDS) technology and the Phase Locked Loop (PLL) technology instead of the marginal oscillator. The circuit system of generating RF is designed and developed. The working performance is tested. Its precision is approximately 0.1ppm. The experimental result shows that this control method is feasible and the NMR signal can be detected clearly.

The main purpose of magnetic flux pump is to stabilize magnetic field of superconducting magnets. This paper chiefly presents a kind of control method to magnetize excitation winding and control system design for a novel high temperature superconducting(HTS) magnetic flux pump. The basic structure and operation principle of the flux pump is simply described here. According to a stated magnetizing sequence of 7-pairs of magnetic poles, we use a singlechip to control the excitation winding to be magnetized one by one. The whole control system has been designed and developed, and the working performance has been tested. The experimental result shows that by this kind of control method, magnetic flux can be smoothly pumped into the HTS closed loop system, consequently compensate the magnetic field decay and make the HTS magnet operate in persistent current mode.