Exploring Molecular Contacts of MUC1 at CIN85 Binding Interface to Address Future Drug Design Efforts

The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents.     

Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Cryptanalysis of nonlinear confusion component based encryption algorithm

Recently many substitution box based encryption algorithms ensuring privacy have been proposed. Many, chaotic map based S-boxes have been generated posing high nonlinearity and strong cryptographic properties. Encryption schemes depending on the substitution box (S-box) only are weak and easily breakable with the help of chosen plaintext and ciphertext attacks. In this work, we have completely cryptanalyzed S-box based encryption scheme successfully by two types of attacks. Cryptanalysis in both types of attacks is performed by only one selected image. Moreover, we have suggested some improvements in the algorithm to defeat attacks.     

Intrinsic Defect Limit to the Growth of Orthorhombic HfO2 and (Hf,Zr)O2 with Strong Ferroelectricity: First-Principles Insights

It is believed that promoting the fraction of ferroelectric orthorhombic phase (o-phase) through O-poor growth conditions can increase the spontaneous polarization of HfO₂ and (Hf,Zr)O₂ thin films. However, the first-principles calculations show that the growth may be limited by the easy formation of point defects in the orthorhombic and tetragonal phases of HfO₂, ZrO₂, and (Hf,Zr)O₂. Their dominant defects, O interstitial (O_i) under O-rich conditions and O vacancy (V_O) under O-poor condition, have low formation energies and quite high density (10¹⁶–10¹⁹ cm⁻³ for 800–1400 K growth temperature). Especially, O_i has negative formation energy in tetragonal HfO₂ under O-rich condition, causing non-stoichiometry and limiting the crystalline-seed formation during o-phase growth. High-density defects can cause disordering of dipole moments and increase leakage current, both diminishing the polarization. These results explain the experimental puzzle that the measured polarization is much lower than the ideal value even in O-poor thin films and highlight that controlling defects is as important as promoting the o-phase fraction for enhancing ferroelectricity. The O-intermediate condition (average of O-rich and O-poor conditions) and low growth temperature are proposed for fabricating HfO₂ and (Hf,Zr)O₂ with fewer defects, lower leakage current, and stronger ferroelectricity, which challenges the belief that O-poor condition is optimal.     

基于K-means和SOM的水下传感器数据采集方法

随着海洋资源勘探和海洋污染物监控工作的开展，水文数据的监测和采集等已经成为重要的研究方向。其中，水下无线传感器网络在水文数据采集过程中起着举足轻重的作用。本文研究的是水下无线传感器二维监测网络模型中，传感器节点数据采集的问题，其设计方法是通过自组织映射（Self-organizing mapping，SOM）对传感器节点进行路径最优化处理，结合优化的路径图形和K-means算法找到路径内部聚合点，利用聚合点和传感器的节点得到传感器通信半径内的数据采集点，最后通过SOM得到水下机器人（Autonomous underwater vehicle，AUV）到各个数据采集点采集数据的最优路径。经过实验验证，在水下1 200 m×1 750 m范围内布置52个传感器节点的情景下，数据采集点相比于传感器节点路径规划采用相同的采集顺序得到的路径优化了6.7%；对数据采集点重新进行自组织路径规划得到的路径比传感器结点路径的最优解提高了12.2%。增加传感器节点的数量，其结果也大致相同，因此采用该方法可以提高水下机器人采集数据的效率。     

电商平台产品共同购买网络的影响因素研究

共同购买网络的推荐系统应用越加广泛，仅基于网络内生结构变量研究其共同购买链接的经济意义已有局限，故加入网络口碑这一外生变量，进行更全面的分析。采用了社会网络方法中指数随机图模型进行建模，主要围绕产品销售量、产品入度、差评率和评论数4个方面因素，探究其对共同购买网络中共同购买链接形成的影响。结果显示，销售量、产品入度和评论数对共同购买链接形成的影响呈正比关系，而差评率则会显著地降低产品共同购买的几率。该指数随机图构建出的共同购买网络为在线电商平台管理网络口碑和推荐系统优化设计提供有益参考。     

Computerized morphometry analysis of epithelial fimbriae nuclear symmetry in BRCA carriers may identify patients at risk for developing ovarian cancer

Serous ovarian tumors may originate in epithelial cells of the fallopian tubes. Computerized morphometry was able to find significant alterations in the fallopian tube epithelium of healthy BRCA carriers. The purpose of this study was to identify a subgroup of BRCA carriers that may be at risk of developing serous ovarian cancer by evaluation of the epithelial nuclear symmetry in the fallopian tubes. Four groups of patients were analyzed; healthy patients, ovarian cancer patients, BRCA carriers, and BRCA noncarriers. All fallopian tubes appeared normal by H&E examination. The ImageProPlus software was used to assess the nuclear symmetry of 65 fimbriae epithelium cells and an artificial neural network algorithm aided in detecting a subpopulation among fimbriae of healthy BRCA carriers at risk for ovarian cancer. Significant differences were found between healthy patients and ovarian cancer patients, and between BRCA carriers and noncarriers. The algorithm was able to accurately predict BRCA carriers with associated ovarian cancer based on fallopian tube nuclear symmetry characteristics. These results reinforce the hypothesis that fimbriae epithelial cells of BRCA carriers may undergo early-stage changes that could predict the risk of progression toward malignancy.