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.     

“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。     

Three‐dimensional computation for flow‐induced vibrations in in‐line and cross‐flow directions of a circular cylinder

We present numerical results for in‐line and cross‐flow vibrations of a circular cylinder, which is immersed in a uniform flow and is elastically supported by damper‐spring systems to compute vibrations of a rigid cylinder. In the case of a circular cylinder with a low Scruton number, it is well‐known that two types of self‐excited vibrations appear in the in‐line direction in the range of low reduced velocities. On the other hand, a cross‐flow vibration of the circular cylinder can be excited in the range of high reduced velocities. Therefore, we compute the flow‐induced vibrations of the circular cylinder in the wide range of the reduced velocities at low and high Scruton numbers and discuss about excitation mechanisms in the in‐line and cross‐flow directions. Copyright © 2011 John Wiley & Sons, Ltd.     

On the ion exchange defects in aluminosilicate lattices

Summary Samples of synthetic leucite and boron-substituted leucite are investigated by infrared spectroscopy and spectrally resolved thermoluminescence. Evidence is obtained in favour of the assumption that point defects in aluminosilicate lattices are originated by exchanges of Si⁺⁴ and Al⁺³ ions lying in different cells.     

Effect of Fe substitution on the thermal expansion of the highT c superconductor Y1Ba2Cu3O y

Thermal expansion measurements have been carried out on Fe substituted superconducting compounds Y₁Ba₂(Cu_1−x Fe _x )₃O _y (0<x<4%) using a high resolution dilatometer employing the three terminal capacitance technique. The experimental set up is sensitive enough to detect changes in α of less than 10⁻⁸K⁻¹. Results show that the jump Δα in the coefficient of linear thermal expansion at the superconducting transition temperature,T _c, increases almost linearly with Fe concentration. The normal state thermal expansion coefficient α first decreases, attains a minimum value aroundx=1% and then increases for higher Fe concentrations. The oxygen content per unit formula is almost constant up tox=1% and then increases rapidly withx. It has also been observed that the anomalous behaviour of α around 260 K observed by Meingastet al [22] for Fe concentrationx=5% is due to inadequate annealing of the sample.     

工作机械相对振动的研究

本文对工作机械的相对振动进行了理论和实验研究。分析了相对振动的激励和合成原理,提出了工件和工具同相振动和异相振动、同相域以及相对振动放大因子等概念。在此基础上指出了减小相对振动的途径,以作为设计和改造工作机械的参考。     

Effect of optical-phonon scattering on the energy distribution of hot electrons in semiconductors at low temperature

Summary The variational method is used in finding the solution of the transport equation for a system of hot electrons inn-Ge atT=20 K in the presence of high electric field. The role of the emission of optical phonons by hot electrons together with the effect of electron capture by repulsive centres on the formulation of the distribution function are studied. It is shown that the emission of optical phonons plays a dominant role in the formulation of the distribution. The influence of electron capture is very small, it may become appreciable at higher trap concentrations. The obtained distribution function is then used in calculating the capture rate of electrons by negatively charged centres. It is shown that the capture rate increases with electric field.

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Riassunto Il metodo variazionale è usato per trovare la soluzione dell'equazione di transporto per un sistema di elettroni caldi inn-Ge aT=20 K in presenza di grande campo elettrico. Si studiano il ruolo dell'emissione di fononi ottici da elettroni caldi insieme con l'effetto della cattura degli elettroni da centri di repulsione sulla formulazione della funzione di distribuzione. Si mostra che l'emissione di fononi ottici svolge un ruolo dominante nella formulazione della distribuzione. L'influenza della cattura degli elettroni è molto piccola, può diventare apprezzabile a piú grande concentrazione di trappole. La funzione di distribuzione ottenuta è quindi usata nel calcolare il rapporto di cattura degli elettroni da centri a carica negativa. Si mostra che il rapporto di cattura cresce col campo elettrico.

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Резюме Используется вариационный метод для нахождения решения транспортного уравнения для системы горячих электронов вn-Ge приT=20 К при наличии сильного электрического поля. Исследуется роля испускания оптических фононов горячими электронами и эффект эахвата электпонов отталкивающими центрами при определении функции распредения. Показывается, что испускание оптических фононов играет доминируюэую роль при образовании функции распределения. Влияние захвата электронов очень мало и становится существенным при более высоких концентрациях ловушек. Полученная функция распределения используется при вычис-лении интенсивности захвата злектпонов отрицательно заряженными центрами. Показывается, что интенсивность захвата увеличивается с возрастанием электрического поля.