Syntheses of 4′-spirocyclic phosphono-nucleosides as potential inhibitors of hepatitis C virus NS5B polymerase

To discover novel nucleosides as potential antiviral agents, 4′-spirocyclic phosphono-nucleosides were designed to mimic the monophosphate of R-1479, a known nucleoside inhibitor of HCV NS5B. Bypassing the first kinase step to nucleoside monophosphate is viewed as advantageous since this phosphorylation is often observed as the rate-limiting transformation to the active NTP for many nucleosides. Efficient synthetic routes were developed with a triphenylphosphine–iodine cyclization reaction as the key step to form the tetrahydrofuran 4′-spirocycle. The desired 4′-spirocyclic phosphono-cytidine analogs 12a, 12b, and 16 were prepared in 11 steps.     

An Organotrifluoroborate for Broadly Applicable One‐Step 18F‐Labeling

A new zwitterionic organotrifluoroborate is appended to three radiosynthons that afford undergo facile bioconjugation to several clinically relevant peptides and one enzyme inhibitor. Molecularly complex bioconjugates are ¹⁸F‐labeled in a single aqueous step in rapid time (<15 min) without HPLC purification to afford tracers in good yields (>200 mCi, 20–40 %) at high specific activity (≥3 Ci/μmol) and at >98 % purity. PET imaging shows in vivo stability and tumor uptake.     

External-Radiation-Induced Local Hydroxylation Enables Remote Release of Functional Molecules in Tumors

Radiation-induced cleavage for controlled release in vivo is yet to be established. We demonstrate the use of 3,5-dihydroxybenzyl carbamate (DHBC) as a masking group that is selectively and efficiently removed by external radiation in vitro and in vivo. DHBC reacts mainly with hydroxyl radicals produced by radiation to afford hydroxylation at para/ortho positions, followed by 1,4- or 1,6-elimination to rescue the functionality of the client molecule. The reaction is rapid and can liberate functional molecules under physiological conditions. This controlled-release platform is compatible with living systems, as demonstrated by the release of a rhodol fluorophore derivative in cells and tumor xenografts. The combined benefits of the robust caging group, the good release yield, and the independence of penetration depth make DHBC derivatives attractive chemical caging moieties for use in chemical biology and prodrug activation.     

Constructing spin-adiabatic states for the modeling of spin-crossing reactions. I. A shared-orbital implementation

In the modeling of spin-crossing reactions, it has become popular to directly explore the spin-adiabatic surfaces. Specifically, through constructing spin-adiabatic states from a two-state Hamiltonian (with spin-orbit coupling matrix elements) at each geometry, one can readily employ advanced geometry optimization algorithms to acquire a “transition state” structure, where the spin crossing occurs. In this work, we report the implementation of a fully-variational spin-adiabatic approach based on Kohn-Sham density functional theory spin states (sharing the same set of molecular orbitals) and the Breit-Pauli one-electron spin-orbit operator. For three model spin-crossing reactions (predissociation of N₂O, singlet-triplet conversion in CH₂, and CO addition to Fe(CO)₄), the spin-crossing points were obtained. Our results also indicated the Breit-Pauli one-electron spin-orbit coupling can vary significantly along the reaction pathway on the spin-adiabatic energy surface. On the other hand, due to the restriction that low-spin and high-spin states share the same set of molecular orbitals, the acquired spin-adiabatic energy surface shows a cusp (ie, a first-order discontinuity) at the crossing point, which prevents the use of standard geometry optimization algorithms to pinpoint the crossing point. An extension with this restriction removed is being developed to achieve the smoothness of spin-adiabatic surfaces.     

具有一层空气隙的矩形微带天线谱域导抗法

对具有一层空气隙的矩形微带天线进行了分析，利用谱域导抗矩阵推导出谱域中的并矢格林函数，利用伽略金法导出了谐振频率的本征方程，并从基片上表面切向电场分量的傅里叶变换直接得出辐射方向图．本文计算出的谐振频率和辐射方向图与其它的理论数值及文献中的测量结果相比较，其一致性很好．     

具有两层基片的微带线的混合模分析

给出了有两层基片的微带线与频率有关的混合模分析，应用傅里叶交换域分析及新的矩阵研究推导出色散特性．除了波导波长以外，还根据功率一电流的定义计算了特征阻抗，波导波长和特征阻抗与频率的关系及其数据值结果，并将其与有关文献的结果相比较，其一致性很好．     

冲击荷载下C型G550冷弯钢的断裂机理研究

以C型G550薄壁冷弯钢构件为研究对象, 通过材料在不同应变率下的拉伸实验和数值模拟数据得到Johnson-Cook (J-C)本构模型和Johnson-Cook失效模型参数. 通过Abaqus软件模拟了不同冲击荷载作用下C型冷弯钢构件撕裂破坏的全过程, 利用落锤装置轴向冲击试验进行对比, 其实验结果与有限元数值模拟结果有良好的一致性. 此外, 对冲击试样撕裂断口进行微观形貌分析, 得到构件的断裂机理. 结果表明: 随着冲击速度的提高, 冲击力对构件的加载时间增加, 构件需要较大的塑性变形来吸收冲击能量; 冲击速度越高, 裂纹扩展功所占吸收冲击能量的比例越大, 显示出高速下裂纹扩展的能力越好; 冲击速度较高时, 以脆性断裂为主, 断口出现解理面, 甚至在高速变形时发生了绝热剪切破坏.     

ZrO2在Rh/γ-Al2O3催化剂中对NO催化还原反应的作用

测定了含ＺｒＯ２的Ｒｈ／γ－Ａｌ２Ｏ３催化剂上ＮＯ＋Ｃ２Ｈ４和ＮＯ＋Ｃ２Ｈ４＋Ｏ２的反应活恬性,并应用ＴＰＲ、ＸＲＤ、ＢＥＴ比表面等表征了ＺｒＯ２的加入方式和晶型对Ｒｈ／γ／Ａｌ２Ｏ３催化剂活性和结构的影响。结果表明,ＺｒＯ２的加入一定程度也抑制了Ｒｈ＾３＋与γ－Ａｌ２Ｏ３之间的相互作用和Ａｌ２Ｏ３的相变,提高了催化剂的热稳定性,明显提高了８５０℃老化样品的ＮＯ＋Ｃ２Ｈ４反应活性。对于ＮＯ＋Ｃ２     

Fault Diagnosis of Rolling Bearings Based on WPE by Wavelet Decomposition and ELM

The fault diagnosis classification method based on wavelet decomposition and weighted permutation entropy (WPE) by the extreme learning machine (ELM) is proposed to address the complexity and non-smoothness of rolling bearing vibration signals. The wavelet decomposition based on ‘db3’ is used to decompose the signal into four layers and extract the approximate and detailed components, respectively. Then, the WPE values of the approximate (CA) and detailed (CD) components of each layer are calculated and composed to be the feature vectors, which are finally fed into the extreme learning machine with optimal parameters for classification. The comparative study of the simulations based on WPE and permutation entropy (PE) shows that the classification method of seven kinds of signals of normal bearing signals and six types of fault states (7 mils and 14 mils) based on WPE (CA, CD) with the number of nodes in the hidden layers of ELM determined by the five-fold cross-validation has the best performances, the training accuracy can reach 100%, and the testing accuracy can reach 98.57% with 37 nodes of the hidden layer by ELM. The proposed method using WPE (CA, CD) by ELM provides guidance for the multi-classification of normal bearing signals.     

Dome效应对四孔大气相干长度仪系统性能的影响

以水平方向距仪器1 000 m的卤钨灯为光源,通过同步对比实验探究了两台四孔大气相干长度仪的系统性能。实验结果表明,由它们测得的大气相干长度的大小和总体变化趋势能够较好吻合,相关性系数均在0.94以上,具有较好的一致性。在此基础上,进一步研究了Dome效应对该系统性能的影响。该效应的影响主要表现在使大气相干长度变小,其强度则由系统沿光路方向移动的距离决定。当移动距离小于15 cm时,Dome效应较弱,不会对实验结果产生明显影响;在距离从15 cm增至55 cm的过程中,其强度不断增加,并在55 cm处达到最强,此后则不再随距离的增加而变化。在整个实验过程中,实验结果的相关系数始终在0.9以上,即Dome效应对大气相干长度的总体变化趋势没有明显影响。