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Fenghui Han,Zhe Wang,Yijun Mao,Yiyun Zhang,Jiajian Tan 한국정밀공학회 2019 International Journal of Precision Engineering and Vol.20 No.1
Multi-hole probe (MHP), as a classical measuring instrument, continues to play an important role in the pressure and velocity measurements for industrial applications by virtue of its robust and reliable performance as well as the simple structure and low cost. But the flow directionality limitations and the low efficiency of traditional operations become obstacles to the large-scale measurements of MHPs. In this paper, an improved operating method is adopted for conventional MHPs to extend their measuring range of incidence angles, and a corresponding auto-measuring system has been developed to realize automatic calibration and measurement of MHPs for industrial large-scale flow measurements. Measurement uncertainties of the system have been experimentally analyzed, verifying a good accuracy: errors of 0.36° in pitch angle, 0.40° in yaw angle and 0.83% in velocity magnitude (95% CI). Furthermore, this auto-measuring system has been applied in the large-scale measurements on different radial inlets for industrial centrifugal compressors, which provide valuable flow information that was not previously available for industrial productions and assist with the improvement study. Analysis and applications in this paper prove that the developed system not only reduces the flow directionality limitations of conventional MHPs, but also significantly improves the experimental efficiency and the control-precision of the probe, achieves a good repeatability and ensures the reliability of the experimental data, which satisfies the requirements of large-scale measurements in industrial applications. Meanwhile, the portability of the system makes it more convenient and flexible to be applied in various industrial productions.
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Zhengqiu Zhu,Lingshan Chen,Wenjun Liu,Yiyun Wu,Chong Zou,Xinyi Zhang,Shanshan He,Yinping Wang,Bixiao Shen,Xuehui Ma,Hui Gao,Yun Luan,Hui Huang 대한초음파의학회 2022 ULTRASONOGRAPHY Vol.41 No.3
Purpose: The present study investigated the association between Systematic COronary Risk Evaluation (SCORE)-estimated cardiovascular risk and carotid stiffening in a middle-aged population using ultrafast pulse wave velocity (ufPWV).Methods: This study enrolled 683 participants without known cardiovascular disease or diabetes mellitus who underwent ufPWV measurements. Clinical interviews, physical examinations, laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity (PWV) at the beginning of systole (PWV-BS), and PWV at the end of systole (PWV-ES) were assessed. Each participant underwent an assessment of SCORE risk based on major cardiovascular risk factors (CVRFs), including age, sex, smoking, systolic blood pressure (SBP), and total cholesterol (TC). Crude and adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression were used. Overall CVRFs were adjusted to assess ORs.Results: cIMT and carotid stiffening in PWV-BS and PWV-ES were significantly different between sex subgroups (all P<0.05), but only PWV-ES increased gradually in age and SCORE-estimated risk subgroups (all P<0.05). Compared with cIMT (r=0.388, P<0.001) and PWV-BS (r=0.159, P<0.001), PWV-ES was more strongly correlated with SCORE categories (r=0.405, P<0.001). Higher PWV-ES values were associated with SCORE categories independently of sex, SBP, TC, and smoking in moderate-risk and high-risk subgroups (OR, 1.63; P<0.001 and OR, 2.12; P=0.024, respectively), but were not independent of age in all risk subgroups (all P>0.05).Conclusion: Carotid stiffening quantified by ufPWV is linked to SCORE categories, and elevated PWV-ES may aid in cardiovascular risk stratification.
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Tan, Li,Wang, Jun,Tanizaki, Junko,Huang, Zhifeng,Aref, Amir R.,Rusan, Maria,Zhu, Su-Jie,Zhang, Yiyun,Ercan, Dalia,Liao, Rachel G.,Capelletti, Marzia,Zhou, Wenjun,Hur, Wooyoung,Kim, NamDoo,Sim, Taebo,G National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.45
<P><B>Significance</B></P><P>Inhibitors of the FGF receptors (FGFRs) are currently under clinical investigation for the treatment of various cancers. All currently approved kinase inhibitors eventually are rendered useless by the emergence of drug-resistant tumors. We used structure-based drug design to develop the first, to our knowledge, selective, next-generation covalent FGFR inhibitors that can overcome the most common form of kinase inhibitor resistance, the mutation of the so-called “gatekeeper” residue located in the ATP-binding pocket. We also describe a novel kinase inhibitor design strategy that uses a single electrophile to target covalently cysteines that are located in different positions within the ATP-binding pocket. These results have important implications for the design of covalent FGFR inhibitors that can overcome clinical resistance.</P><P>The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that resistance to FGFR inhibitors can be acquired through mutations in the FGFR gatekeeper residue, as clinically observed for FGFR4 in embryonal rhabdomyosarcoma and neuroendocrine breast carcinomas. Here we report on the use of a structure-based drug design to develop two selective, next-generation covalent FGFR inhibitors, the FGFR irreversible inhibitors 2 (FIIN-2) and 3 (FIIN-3). To our knowledge, FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. Because of the conformational flexibility of the reactive acrylamide substituent, FIIN-3 has the unprecedented ability to inhibit both the EGF receptor (EGFR) and FGFR covalently by targeting two distinct cysteine residues. We report the cocrystal structure of FGFR4 with FIIN-2, which unexpectedly exhibits a “DFG-out” covalent binding mode. The structural basis for dual FGFR and EGFR targeting by FIIN3 also is illustrated by crystal structures of FIIN-3 bound with FGFR4 V550L and EGFR L858R. These results have important implications for the design of covalent FGFR inhibitors that can overcome clinical resistance and provide the first example, to our knowledge, of a kinase inhibitor that covalently targets cysteines located in different positions within the ATP-binding pocket.</P>
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