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Dr. Dae-Shik Kim Dr. Atsushi Endo Dr. Francis G. Fang Dr. Kuan-Chun Huang Dr. Xingfeng Bao Dr. Hyeong-wook Choi Dr. Utpal Majumder Dr. Young Y. Shen Steven Mathieu Xiaojie Zhu Kristen Sanders Dr. Thomas Noland Dr. Ming-Hong Hao Dr. Yu Chen Dr. John Y. Wang So Yasui Karen TenDyke Jiayi Wu Christy Ingersoll Kara A. Loiacono Dr. Janna E. Hutz Dr. Nadeem Sarwar 《ChemMedChem》2021,16(11):1741-1744
A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described. 相似文献
53.
为探究北方缺水地区湿地植物物种多样性变化,选取北京市延庆区妫水河为研究区,采用物种丰富度(R),Shannon-Wiener指数(H),Simpson指数(D)和Peilou均匀度指数(J)作为植物群落多样性指标,使用方差法和典型对应分析(CCA)对不同河段和区域间湿地植物物种分布与环境因子之间的响应关系进行研究。研究结果表明:研究区现有湿地植物93种,隶属于44科76属,优势科有菊科(Asteraceae)、禾本科(Poaceae)、豆科(Fabaceae)和莎草科(Cyperaceae); 93种植物的Shannon-Wiener指数(H)小于3,Simpson指数(D)和Peilou均匀度指数(J)介于0. 5~0. 75之间,物种数量总体不多,但分布较均匀,处于中等水平;对湿地植物群落形成及生长影响较大的水质因子依次为全氮(TN)、p H和化学需氧量(COD)。 相似文献
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中国天然气勘探开发现状及物探技术需求 总被引:4,自引:0,他引:4
2000年以来,中国石油天然气集团公司在鄂尔多斯盆地、四川盆地、塔里木盆地、松辽盆地、柴达木盆地、渤海湾盆地等的天然气勘探中不断获得新的发现,初步形成了东部、中部、西部协调发展的合理布局。现阶段面临的问题是如何尽快将资源优势转化为经济优势。目前,我国天然气主要储集层为碎屑岩、碳酸盐岩和火山岩三大岩石类型。碎屑岩储层特征表现为我国中部丘陵地区的低孔、低渗的致密砂岩以及西部复杂高陡构造的孔隙砂岩;碳酸盐岩和火山岩储层普遍埋藏较深,非均质性强,缝洞单元难以刻画。因此,必须采用有针对性的地球物理勘探技术,优先发展碎屑岩气藏检测勘探技术,强化地震岩石物理等基础研究,加快碳酸盐岩、火山岩气藏检测技术攻关。同时开展高密度、多波地震勘探等前沿技术研究,为定量评价和产能建设提供技术保障。 相似文献
56.
Daifas DP Smith JP Blanchfield B Cadieux B Sanders G Austin JW 《Journal of food protection》2003,66(4):610-617
Model broth studies were carried out to investigate the effect of ethanol on the growth of proteolytic (group I) strains of Clostridium botulinum. Ethanol extended the pathogen's lag phase, decreased its exponential growth rate, and decreased its final level of growth in the stationary phase. In all cases, botulinum neurotoxin production was associated with growth. Micrographs of C. botulinum cultures grown at 37 degrees C in trypticase peptone glucose yeast extract (TPGY) broths containing 2 and 4% ethanol showed elongation of vegetative cells and interference with cell division. The inhibition of growth and toxin production at the ethanol level predicted (5.5%, wt/wt) was confirmed by microscopy and by the mouse bioassay. A subsequent study was carried out to determine the combined effect of ethanol (0 to 8% [wt/wt]), water activity (aw; 0.953 to 0.997), and pH (6.2 to 8.2) on the probability of the growth of and neurotoxin production by proteolytic strains of C. botulinum (10(3) spores per ml). Growth and neurotoxin production occurred in 1 to 3 days in TPGY broths without ethanol (0%) and in 2 to 4 days in broths containing 2% ethanol regardless of the aw or pH levels (P < 0.005). Growth and neurotoxin production were delayed by an ethanol concentration of 4% ethanol and completely inhibited by a concentration of 6%. At an ethanol concentration of 4%, the probability of growth and toxin production over 365 days (Pt) was influenced by aw and pH. After 365 days, the maximum probability of growth and toxin production (Pmax) was 1 for all but one combination. However, tau, the time it took for 50% of all eventually positive replicates for any given combination of barriers to show growth and/or turbidity, ranged from <3 to 229 days. All tubes of TPGY broths that showed no growth after 365 days were subcultured in fresh TPGY broths. In all cases, growth and toxin production occurred within 24 h at 37 degrees C, indicating the reversible (sporostatic and/or bacteriostatic) effect of ethanol on C. botulinum. 相似文献
57.
提高储层预测精度技术思路与对策 总被引:2,自引:2,他引:2
采用地质、地震、测井人员协同一体化作业,对地下地质目标进行综合预测与评价,可提高储层预测精度,降低预测结果的多解性。主要方法是针对不同的区块,采用不同的方法和对策,首先从单井储层划分对比入手,建立储层沉积模式,同时对地震数据目的层段进行精细解释,建立地层构造模式,用沉积、构造等地质规律来指导和约束反演;利用测井资料对地震资料进行精细标定,建立各井的单井波阻抗模型,建立井数据和地震数据沟通的桥梁;在严格的测井约束、地质模型约束、层位控制下进行储层反演;充分利用地质、地震反演结果、地震参数提取及分析结果、测井、测试和分析化验等资料对储层预测结果进行综合分析与评价。该方法应用于长庆、大庆、准噶尔等实际区块,取得了较好的效果。 相似文献
58.
Jinwen Xiao Peterchev A.V. Jianhui Zhang Sanders S.R. 《Solid-State Circuits, IEEE Journal of》2004,39(12):2342-2348
This paper describes a dual-mode digitally controlled buck converter IC for cellular phone applications. An architecture employing internal power management is introduced to ensure voltage compatibility between a single-cell lithium-ion battery voltage and a low-voltage integrated circuit technology. Special purpose analog and digital interface elements are developed. These include a ring-oscillator-based A/D converter (ring-ADC), which is nearly entirely synthesizable, is robust against switching noise, and has flexible resolution control, and a very low power ring-oscillator-multiplexer-based digital pulse-width modulation (PWM) generation module (ring-MUX DPWM). The chip, which includes an output power stage rated for 400 mA, occupies an active area 2 mm/sup 2/ in 0.25-/spl mu/m CMOS. Very high efficiencies are achieved over a load range of 0.1-400 mA. Measured quiescent current in PFM mode is 4 /spl mu/A. 相似文献
59.
This paper discusses the design, fabrication, and testing of a CMOS active clamp circuit, The active clamp is a linear voltage regulator, with a voltage deadband to allow for voltage ripple, that is designed to operate in parallel with a switchmode voltage regulator. Its specific function is to sink or source large transient currents to microprocessor loads, thus allowing operation with very small output capacitance. Laboratory tests on a prototype IC exhibit stable behavior with negligible overshoot with only 47 microfarads of output capacitance with loads of about nine amperes. Output impedances of 2-3 mΩ are achieved 相似文献
60.
AM Attallah H Ismail SA El Masry H Rizk A Handousa M El Bendary A Tabll F Ezzat 《Canadian Metallurgical Quarterly》1999,37(2):354-357
Schistosoma circulating antigens were used to indicate the infection intensity and to assess cure. An immunoglobulin G2a (IgG2a) mouse monoclonal antibody was used in a fast dot-enzyme-linked immunosorbent assay (ELISA; FDA) for rapid and simple diagnosis of schistosomiasis in the field. Seven hundred Egyptians were parasitologically examined for Schistosoma mansoni and other parasitic infections. A rectal biopsy was done as a "gold standard" for individuals showing no S. mansoni eggs in their feces. Egg counts were obtained by the Kato smear method for only 100 of 152 individuals with eggs in their feces. Specific anti-schistosome IgG antibodies were evaluated in sera by ELISA. Urine samples from the 700 individuals were tested by FDA for detection of the circulating antigen. The assay showed a sensitivity of 93% among 433 infected individuals and a specificity of 89% among 267 noninfected individuals. FDA showed the highest efficiency of antigen detection (91%) compared with the efficiency of antibody detection by ELISA (75%) and stool analysis (60%). In addition, FDA detected infected patients with 20 eggs/g of feces. Also, the sensitivity of FDA ranged from 90 to 94% among samples from patients with different clinical stages of schistosomiasis. All the assay steps can be completed within 30 min at room temperature for 96 urine samples. The monoclonal antibody identified a 74-kDa antigen in different antigenic extracts of S. mansoni and Schistosoma haematobium and in the urine of infected individuals. In addition, a 30-kDa degradation product was identified only in the urine samples. On the basis of these results, FDA should be used as a rapid tool for the sensitive and specific diagnosis of Schistosoma infection. 相似文献