Novel Design of RNA Aptamers as Cancer Inhibitors and Diagnosis Targeting the Tyrosine Kinase Domain of the NT-3 Growth Factor Receptor Using a Computational Sequence-Based Approach

Aptamers, the nucleic acid analogs of antibodies, bind to their target molecules with remarkable specificity and sensitivity, making them promising diagnostic and therapeutic tools. The systematic evolution of ligands by exponential enrichment (SELEX) is time-consuming and expensive. However, regardless of those issues, it is the most used in vitro method for selecting aptamers. Therefore, recent studies have used computational approaches to reduce the time and cost associated with the synthesis and selection of aptamers. In an effort to present the potential of computational techniques in aptamer selection, a simple sequence-based method was used to design a 69-nucleotide long aptamer (mod_09) with a relatively stable structure (with a minimum free energy of −32.2 kcal/mol) and investigate its binding properties to the tyrosine kinase domain of the NT-3 growth factor receptor, for the first time, by employing computational modeling and docking tools.     

In Vitro–In Vivo Correlation of Tianeptine Sodium Sustained-Release Dual-Layer Tablets

Tianeptine tablets are currently marketed to be designed for immediate-release tablets. The tianeptine has a short half-life, making it difficult to design for sustained-release tablets and achieve bioequivalence with the tianeptine immediate-release tablet (Stablon^®). We established the in vitro–in vivo correlation (IVIVC) of three formulations of tianeptine sustained-release tablets according to their granule size. To evaluate sustained drug release, in vitro tests were performed in pH 1.2 media for 24 h. In vivo pharmacokinetic analysis was performed following oral administration of reference drug and test drug to beagle dogs. The dissolution profile revealed delayed release as the size of the granules increased. The dissolution results were confirmed in pharmacokinetic analysis, showing that the half-life was delayed as granule size increased. The final formulation and reference drug showed an equivalent area under the curve (AUC). Through this, IVIVC was established according to the size of the tianeptine sodium granules, which is the purpose of this study, and was used to predict in vivo pharmacokinetics from the formulation composition. This approach may be useful for determining optimal formulation compositions to achieve the desired pharmacokinetics when developing new formulations.     

Exploring the Parallel G-Quadruplex Nucleic Acid World: A Spectroscopic and Computational Investigation on the Binding of the c-myc Oncogene NHE III1 Region by the Phytochemical Polydatin

Trans-polydatin (tPD), the 3-β-D-glucoside of the well-known nutraceutical trans-resveratrol, is a natural polyphenol with documented anti-cancer, anti-inflammatory, cardioprotective, and immunoregulatory effects. Considering the anticancer activity of tPD, in this work, we aimed to explore the binding properties of this natural compound with the G-quadruplex (G4) structure formed by the Pu22 [d(TGAGGGTGGGTAGGGTGGGTAA)] DNA sequence by exploiting CD spectroscopy and molecular docking simulations. Pu22 is a mutated and shorter analog of the G4-forming sequence known as Pu27 located in the promoter of the c-myc oncogene, whose overexpression triggers the metabolic changes responsible for cancer cells transformation. The binding of tPD with the parallel Pu22 G4 was confirmed by CD spectroscopy, which showed significant changes in the CD spectrum of the DNA and a slight thermal stabilization of the G4 structure. To gain a deeper insight into the structural features of the tPD-Pu22 complex, we performed an in silico molecular docking study, which indicated that the interaction of tPD with Pu22 G4 may involve partial end-stacking to the terminal G-quartet and H-bonding interactions between the sugar moiety of the ligand and deoxynucleotides not included in the G-tetrads. Finally, we compared the experimental CD profiles of Pu22 G4 with the corresponding theoretical output obtained using DichroCalc, a web-based server normally used for the prediction of proteins’ CD spectra starting from their “.pdb” file. The results indicated a good agreement between the predicted and the experimental CD spectra in terms of the spectral bands’ profile even if with a slight bathochromic shift in the positive band, suggesting the utility of this predictive tool for G4 DNA CD investigations.     

中国共产党建党百年来的社会政策探索

自1921年成立至今中国共产党已经走过了一百年的辉煌历程。以人民为中心、为人民谋利益、与时俱进地解决中国人民的生存和发展（即民生）问题是中国共产党人的初心使命和矢志不渝的追求。社会政策作为国家解决民生问题的制度化举措自中国共产党成立以来一直受到关注和重视,但在中国革命、建设和改革等不同历史时期党对社会政策角色的运用会根据时代的特点、具体国情的变化、解决民生方针策略的需要做出调整和改变。建党百年来中国共产党解决民生问题按路径划分大致经历了三个阶段,在不同阶段党对社会政策角色的运用会发生相应的变化：党的成立至新中国成立前系党为解决民生问题创造政治前提阶段,社会政策被作为政治动员的重要手段（1921−1949）;新中国成立至1978年系党为解决民生问题创造经济前提（基础）阶段,社会政策依附经济体制,服务于经济发展（1949−1978）;改革开放以来系党在中国特色社会主义市场经济条件下为解决效率与公平的矛盾不断加大保障和改善民生的力度、民生事业不断取得新的进步阶段,社会政策相对独立发展,其地位和作用不断强化（1978年至今）。建党百年来党对社会政策的探索提供了丰富的经验和启示,对其加以科学总结具有重要的理论和现实意义。     

探寻社会学理论发展的非经验主义道路

默顿倡导以中层理论为中介来联结社会学的经验研究和一般理论研究,推动社会学理论的合理发展,这一倡导具有合理性。但是默顿试图通过以经验研究为基础优先发展中层理论,然后再通过对中层理论进行归纳来形成一般理论这种经验主义策略进而实现这一目标的想法却可能是错误的。正如中层理论并非从经验事实中归纳得来一样,一般理论也难以从中层理论中归纳而来。我们需要探索一条非经验主义的社会学理论发展道路。     

郡县制国家现代化：中央政府如何扩大公共事务治理职能

郡县制国家的传统职能是“管人”,但是在当代,为了适应现代世界,需要加强和完善“管事”的职能。然而,加强“管事”的职能遇到的一大障碍,是“管事”与“管人”通常难以分开,带来管事与管人的冲突。在全国性公共事务上,面对管事与管人的冲突,郡县制国家的一种改革方向,即建立中央统一管理与地方属地管理相结合的体制,既扩大中央政府的治理职能,同时又发挥纵向约束机制的作用,从而能改善全国性公共事务治理。此种中央统一管理与地方属地管理相结合的体制,通常不是中央政府事先设计出来的,而是在改革过程中,经由中央政府与地方政府的策略性互动过程,逐渐建立起来的。因此,郡县制国家蕴含着一种潜力,即在公共事务治理上,包括地方公共事务和全国性公共事务,可以引入和发挥“纵向约束机制”的作用,使得国家既保持“管人”的基本体制不变,又能提高治理能力。     

汉语言说者如何切入当代西方知识论—一种基于人工智能与儒家“正名论”的混合视角

肇始于“盖蒂尔问题”的当代西方的知识论研究与近代西方的认识论研究不同：前者更聚焦于知识证成之规范性维度,后者更聚焦于知识构成的事实性维度。除了专业的分析哲学专家之外,汉语哲学界对于现代西方知识论（而不是近代西方认识论）的接受度并不高。这在相当程度上可能是因为,基于英语思维的西方研究者对于“知识”“信念”“证成”等核心概念的理解方式与基于汉语思维的中国读者的理解方式有所不同。不过,我们也不能由此忽略现代西方知识论研究的两面性：一方面,现代西方知识论的很多典型话题的设置与展开方式的确是受到了“二战”后英语文化的特殊性的影响;另一方面,西方知识论学者对于信念证成的规范性状态的探究,对于各种非西方文明的合理性对话框架的构建依然具有一定的辐射意义。在这样的情况下,我们中国的知识论研究者就需要两个中介性步骤,以便将西方知识论的话题设置方式与研究方式中过分偏向于西方文化的特点予以过滤：第一,通过人工智能对于信念证成过程的机器复验,来反过来检测西方知识论理论的某些“伪普遍性”（特别是通过对于“框架问题”的揭露来体现西方命题逻辑在处理语义相关性方面所暴露出来的无能）;第二,通过对于以“正名论”为代表的汉语证成方式（以及在其背后起作用的基于词项之基本性的信息加工过程）的现代化重构,为一种能够兼容中西思维并能够为机器复演的可能性敞开自身的新知识论打下基础。这样,我们才能有希望将目前英语世界中流行的知识论研究,真正改造为具有“世界哲学”气息的知识论研究。     

“东方经济”与中国乡村工业化的社会学机制—重访史国衡的个旧矿城研究

本文对“魁阁”社会学家史国衡1940年代在美访学期间的一部未刊稿《个旧矿城》进行了梳理与讨论。史国衡的个旧研究呈现了一个将产业、民情与治理相结合的综合进路,通过对个旧锡业兴衰的个案分析,揭示了传统“东方经济”模式的独特特征以及决定中国乡村工业化成败的社会学机制,同时也以个旧经验对现代化理论、人际关系学派等当时美国社会科学主流范式提出了反思。《个旧矿城》与另一部更为人所熟知的著作《昆厂劳工》共同构成了史国衡关于中国工业化研究的姊妹篇,“工业化的社会基础”是其中一以贯之的核心线索。对史国衡个旧矿城研究的“再发现”,有助于我们重新认识中国早期社会学的工业研究传统,同时也提示我们,当下的乡村工业化乃至乡村振兴仍然需要重视产业的社会基础,处理好经济转型与社会重组之间的辩证关系。     

柱几何Rayleigh-Taylor不稳定性的数值模拟

给出了柱几何中流体力学方程组及其在数值模拟中采用的计算方法。对二维柱几何Rayleigh-Taylor不稳定性进行数值模拟,在线性阶段与线性理论符合得很好;不稳定性增长进入非线性区域的阈值依赖于界面的位置,并且明显不同于平面情况。     

An efficient method for computing the QTAIM topology of a scalar field: The electron density case

An efficient method for computing the quantum theory of atoms in molecules (QTAIM) topology of the electron density (or other scalar field) is presented. A modified Newton–Raphson algorithm was implemented for finding the critical points (CP) of the electron density. Bond paths were constructed with the second‐order Runge–Kutta method. Vectorization of the present algorithm makes it to scale linearly with the system size. The parallel efficiency decreases with the number of processors (from 70% to 50%) with an average of 54%. The accuracy and performance of the method are demonstrated by computing the QTAIM topology of the electron density of a series of representative molecules. Our results show that our algorithm might allow to apply QTAIM analysis to large systems (carbon nanotubes, polymers, fullerenes) considered unreachable until now. © 2012 Wiley Periodicals, Inc.