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Gabor Butora Ning Qi Wenlang Fu Truyen Nguyen Hsueh‐Cheng Huang Ian W. Davies 《Angewandte Chemie (International ed. in English)》2014,53(51):14046-14050
The cytosolic conversion of therapeutically relevant nucleosides into bioactive triphosphates is often hampered by the inefficiency of the first kinase‐mediated step. Nucleoside monophosphate prodrugs can be used to bypass this limitation. Herein we describe a novel cyclic‐disulfide class of nucleoside monophosphate prodrugs with a cytosol‐specific, reductive release trigger. The key event, a charge‐dissipating reduction‐triggered cyclodeesterification leads to robust cytosolic production of the cyclic 3′,5′‐monophosphate for downstream enzymatic processing. The antiviral competence of the platform was demonstrated with an O‐benzyl‐1,2‐dithiane‐4,5‐diol ester of 2′‐C‐methyluridine‐3′,5′‐phosphate. Both in vitro and in vivo comparison with the clinically efficacious ProTide prodrug of 2′‐deoxy‐2′‐α‐fluoro‐β‐C‐methyluridine is provided. The cytosolic specificity of the release allows for a wide range of potential applications, from tissue‐targeted drug delivery to intracellular imaging. 相似文献
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Wei-Ting Chen Wei-Chun Chen Kuang-Hua Hsueh Chen-Wei Chiu Chi-Min Shu 《Journal of Thermal Analysis and Calorimetry》2014,118(2):1085-1094
The rapid development of the petrochemical industry of Taiwan over the past four decades has resulted in a booming economy in Taiwan that drives derived industries to develop progressively. However, it has also caused many runaway reaction accidents, such as toxic gas release, fire, and explosion. It is crucial to eliminate those potential hazard factors which can induce consequent runaway reaction accidents during the life span of the manufacturing process. In response to this crucial issue, we performed a thermokinetic parameter analysis for 1,1-bis-(tert-butylperoxy)-3,3,5-trimethylcyclohexane at isothermal conditions to conduct a thermal safety assessment of chemical materials. The five isothermal temperatures, 90, 100, 110, 120, 130, and 140 °C, measured by DSC, were adopted in this study to calculate process safety parameters, including TMRad, T NR, and SADT, which can be employed in process safety parameters for the manufacturing process. A novel, green kinetic approach accompanied with non-isothermal DSC results is used to derive thermokinetic parameters in safety protocol in this study. 相似文献
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Hsi‐Jung Yu Chien‐Chang Shen Hsiu‐Mei Yi Tai‐Hung Chen Mao‐Lin Hsueh Chu‐Chieh Lin Ming‐Jaw Don 《中国化学会会志》2013,60(2):191-194
Euphorbiane ( 1 ), a novel triterpenoid exhibiting a unique skeleton, together with seven known compounds were isolated from the 95% EtOH extract of the fresh stems of Euphorbia tirucalli. The structure of 1 and relative stereochemistry were elucidated by extensive NMR and a single‐crystal X‐ray crystallographic analysis. 相似文献
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Existence of the perfect transmission resonances of spin waves in a one-dimensional Thue–Morse magnonic quasicrystal is proposed. We find that occurrence of the perfect transmission just corresponds to the repeated bandedges in the bandedge map. Frequencies at the perfect transmissions for system with arbitrary generation order can be predicted by the bandedge map of the second and third order systems using two iterative schemes. These results show that density of the perfect transmission resonance increases exponentially for increasing the order of the system. However, the perfect transmissions are kept for higher order systems even if the peaks become denser. 相似文献
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In this paper, the Taguchi method combined with fuzzy approach was applied to find the extended optimization for a multi-objective design of a miniature 2.5× zoom fold optics with liquid elements. Relative illuminance (RI) and modulation transfer function (MTF) were considered to be optimized. The experiments were simulated and the results were evaluated by the optical software tool CODE V. It was concluded that the method used in this research was successful in optimizing the values. In our proposed method, the appropriate weight of MTF and RI for the inputs of fuzzy controllers increased the MTF by 9.92%, but the RI only reduced by 0.19% in systematic wide-angle end, respectively. 相似文献
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The effects of variable changes on the optical path length (OPL) of optical elements such as a prism are generally evaluated by utilizing a ray tracing approach to determine the OPL before and after the variable change, respectively, and then applying a finite difference (FD) method to estimate the OPL gradient with respect to each individual variable. By contrast, this study constructs the gradient matrix of OPL of a prism which permits the effects of multiple variable changes to be determined in a single pass. The developed approach not only resolves the error inherent in the FD method as a result of the denominator being far smaller than the numerator, but also avoids the requirement for multiple ray tracing operations and therefore yields a substantial improvement in the computational efficiency. The validity of the proposed approach is demonstrated utilizing a Pechan prism for illustration purposes. 相似文献
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As biotechnology has made remarkable progress nowadays, there has also been a great improvement on data collection with lower cost and higher quality outcomes. More often than not investigators can obtain the measurements of many disease-related features simultaneously. When multiple potential biomarkers are available for constructing a diagnostic tool of a disease, an effective approach is to combine these biomarkers to build one single indicator. For continuous-scaled variables, the use of linear combinations is popular due to its easy interpretation. Su and Liu (J Ame Stat Assoc 88(424):1350–1355, 1993) derived the best linear combination under the criterion of the area under the receiver operating characteristic (ROC) curve, when the joint normality of biomarkers is assumed. However, in many investigations, the emphases are placed only on a limited extent of clinical relevancy, instead of the whole ROC curve. The goal of this study is to find the linear combination that maximizes the partial area under a ROC curve (pAUC) for a pre-specified range. In order to find an analytic solution, the first derivative of the pAUC under normal assumption is derived. The explicit form is so complicated, that a further validation on the Hessian matrix is difficult. On the other hand, we find that the pAUC maximizer may not be unique and local maximizers do exist in some cases. Consequently, the existing algorithms find an initial-point dependent solution and are inadequate to serve our needs. Hence, we propose a new algorithm by adopting several initial points at one time. Intensive numerical studies have been performed to show the adequacy of the proposed algorithm. Real examples are also provided for illustration. 相似文献