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51.
该文利用色集事先分配法、构造染色法、反证法探讨了完全三部图K4,4,p (p≥1008)的点可区别IE-全染色问题,确定了K4,4,p (p≥1008)的点可区别IE-全染色数。 相似文献
52.
Dr. Hui Qiu Richard Caldwell Dr. Lesley Liu-Bujalski Dr. Andreas Goutopoulos Reinaldo Jones Justin Potnick Dr. Brian Sherer Dr. Andrew Bender Dr. Roland Grenningloh Dr. Daigen Xu Dr. Anna Gardberg Dr. Igor Mochalkin Dr. Theresa Johnson Dr. Ariele Viacava Follis Jared Head Dr. Federica Morandi 《ChemMedChem》2019,14(2):217-223
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. 相似文献
53.
WENXI GAO QIANQIAN MA CHENYU TANG YUELI ZHAN YINONG DUAN HUIHUA NI YUNZHAO XU 《Biocell》2020,44(4):597-605
Cervical cancer (CESC) is one of the most common cancers and affects the female genital tract. Consistent HPV
infection status has been determined to be a vital cause of tumorigenesis. HPV infection may induce changes to the
immune system and limit the host’s immune response. Immunotherapy is therefore essential to improving the overall
survival of both locally advanced and recurrent CESC patients. Using 304 relevant samples from TCGA, we assessed
immune cell function in CESC patients to better understand the status of both tumor micro-environment cells and
immune cells in CESC. Functional enrichment analysis, pathway enrichment analysis, and PPI network construction
were performed to explore the differentially expressed genes (DEGs). The analysis identified 425 DEGs, which
included 295 up-regulated genes and 130 down-regulated genes. We established that upregulation of CCL5 was
correlated with significantly better survival, meaning that CCL5 expression could serve as a novel prognostic
biomarker for CESC patients. We further focused on CCL5 as a hub gene in CESC, as it had significant correlations
with increased numbers of several types of immune cells. Cell-type fractions of M1 macrophages were significantly
higher in the high-immune-scores group, which was associated with better overall survival. Finally, we concluded that
CCL5 is a promising prognostic biomarker for CESC, as well as a novel chemotherapeutic target. 相似文献
54.
京津冀协同发展战略是我国当前重点推进的国家顶层战略,河北省作为京津产业转移对接的重要基地,在产业升级、爬坡过坎中面临重要的战略任务。破解困境的突破点在于技术技能人才的培养和使用。在京津冀协同发展背景下,亟待我省政府和职业院校尤其是高等职业院校,适应经济新常态,大力推进现代职教改革,培养我省转型升级需要的高素质技术技能人才,为服务国家战略提供技术技能支撑。 相似文献
55.
Tian Xiaoying Peng Hui Luo Xuguang Nie Shiyuan Zhou Feng Peng Xiaoyan 《International Journal of Control, Automation and Systems》2020,18(4):897-910
International Journal of Control, Automation and Systems - There is a class of typical nonlinear industrial process, which can be characterized by a first-order inertia plus pure delay model in an... 相似文献
56.
刘家山排土场为民采排弃形成,已经出现大规模滑坡。为了保证上下游生产生活设施的安全,依据现场实际情况,结合现场调查,提出了削坡处理的方案。经过治理后,刘家山排土场平稳地渡过了雨季,目前处于稳定状态,达到了治理目的。 相似文献
57.
The Caputo and Caputo–Fabrizio derivative are applied to study a second‐grade nanofluid over a vertical plate. A comparative analysis is presented to study the unsteady free convection of a second‐grade nanofluid with a new time–space fractional heat conduction. The governing equations with mixed time–space fractional derivatives are non‐dimensionalized and solved numerically, and a comparison between the Caputo and the Caputo–Fabrizio models is made. It is found that the temperature is higher for the Caputo–Fabrizio fractional model than the Caputo model, but the higher velocity only exists near the vertical plate for the Caputo–Fabrizio model than the Caputo model. Moreover, the velocity for the Caputo model will exceed the Caputo–Fabrizio model as y evolves. 相似文献
58.
二氧化碳制冷技术和提升氨制冷安全体系是绿色制冷的重要支撑,北京冬奥会大量采用绿色制冷技术,不仅推动国内制冷行业可持续发展,而且将对2030年碳达峰和2060年碳中和产生深远影响. 相似文献
59.
60.
以Si-MCM-41、Al-MCM-41(1) (n(Si)/n(Al)=15)、Al-MCM-41(2) (n(Si)/n(Al)=10)以及用NH4NO3或HAc的醇溶液分别与Si-MCM-41离子交换所得的H-MCM-41(N)和H-MCM-41(H)为载体制备了系列Ru/MCM-41催化剂。采用N2吸附、XRD和H2-TPR表征了负载Ru前后催化剂的结构及Ru在各种载体表面上的分散状态。以0.5%(质量分数)苯的环己烷溶液为模型化合物,在298K、3.0MPa反应条件下,考察了上述催化剂的苯液相加氢反应性能,并与Ru/HY、Ru/H61538;和Pt/MCM-41催化剂进行了比较。结果表明,载体MCM-41的n(Si)/n(Al)和表面化学组成等性质对Ru在其表面上的分散状态、还原性及催化性能均有影响。对苯的转化率与反应时间的关系曲线进行拟合,发现其遵循一级动力学方程,加氢反应速率常数按照Ru/Al-MCM-41(2)相似文献