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.     

Virus-Based Nanoreactors with GALT Activity for Classic Galactosemia Therapy

Enzymatic nanoreactors were obtained by galactose-1-phosphate uridylyl-transferase (GALT) encapsulation into plant virus capsids by a molecular self-assembly strategy. The aim of this work was to produce virus-like nanoparticles containing GALT for an enzyme-replacement therapy for classic galactosemia. The encapsulation efficiency and the catalytic constants of bio-nanoreactors were determined by using different GALT and virus coat protein ratios. The substrate affinity of nanoreactors was slightly lower than that of the free enzyme; the activity rate was 16 % of the GALT free enzyme. The enzymatic nanoreactors without functionalization were internalized into different cell lines including fibroblast and kidney cells, but especially into hepatocytes. The enzymatic nanoreactors are an innovative enzyme preparation with potential use for the treatment of classic galactosemia.     

A new linearly constrained minimum variance beamformer for reconstructing EEG sparse sources

Brain source imaging based on EEG aims to reconstruct the neural activities producing the scalp potentials. This includes solving the forward and inverse problems. The aim of the inverse problem is to estimate the activity of the brain sources based on the measured data and leadfield matrix computed in the forward step. Spatial filtering, also known as beamforming, is an inverse method that reconstructs the time course of the source at a particular location by weighting and linearly combining the sensor data. In this paper, we considered a temporal assumption related to the time course of the source, namely sparsity, in the Linearly Constrained Minimum Variance (LCMV) beamformer. This assumption sounds reasonable since not all brain sources are active all the time such as epileptic spikes and also some experimental protocols such as electrical stimulations of a peripheral nerve can be sparse in time. Developing the sparse beamformer is done by incorporating L1-norm regularization of the beamformer output in the relevant cost function while obtaining the filter weights. We called this new beamformer SParse LCMV (SP-LCMV). We compared the performance of the SP-LCMV with that of LCMV for both superficial and deep sources with different amplitudes using synthetic EEG signals. Also, we compared them in localization and reconstruction of sources underlying electric median nerve stimulation. Results show that the proposed sparse beamformer can enhance reconstruction of sparse sources especially in the case of sources with high amplitude spikes.     

A novel differential evolution mapping technique for generic combinatorial optimization problems

Differential evolution is primarily designed and used to solve continuous optimization problems. Therefore, it has not been widely considered as applicable for real-world problems that are characterized by permutation-based combinatorial domains. Many algorithms for solving discrete problems using differential evolution have been proposed, some of which have achieved promising results. However, to enhance their performance, they require improvements in many aspects, such as their convergence speeds, computational times and capabilities to solve large discrete problems. In this paper, we present a new mapping method that may be used with differential evolution to solve combinatorial optimization problems. This paper focuses specifically on the mapping component and its effect on the performance of differential evolution. Our method maps continuous variables to discrete ones, while at the same time, it directs the discrete solutions produced towards optimality, by using the best solution in each generation as a guide. To judge its performance, its solutions for instances of well-known discrete problems, namely: 0/1 knapsack, traveling salesman and traveling thief problems, are compared with those obtained by 8 other state-of-the-art mapping techniques. To do this, all mapping techniques are used with the same differential evolution settings. The results demonstrated that our technique significantly outperforms the other mapping methods in terms of the average error from the best-known solution for the traveling salesman problems, and achieves promising results for both the 0/1 knapsack and the traveling thief problems.     

1-甲基环丙烯结合不同保鲜袋对叶用甘薯茎尖冷藏保鲜效果的影响

目的探究1-甲基环丙烯(1-methylcyclopropylene,1-MCP)结合不同保鲜袋对叶用甘薯茎尖贮藏品质的影响,筛选最适的保鲜方式。方法以叶用甘薯茎尖为材料,经0.91μL/L1-MCP处理24h后结合聚乙烯(PE)或微孔膜(WK)保鲜袋包装,在5℃下进行贮藏,分别于0、3、6、9、12 d时对其失重率、色差、黄化率、呼吸强度、乙烯释放量、多酚氧化酶活性等指标进行测定。结果贮藏12 d后, 1-MCP+PE, 1-MCP+WK处理组的失重率分别为3.43%,2.72%,显著低于未经1-MCP处理组(P0.05),说明1-MCP处理能够有效抑制叶用甘薯茎尖失水; 1-MCP+WK处理下的L值为33.9,高于其余3种处理,表明该处理能够更好的保持叶用甘薯茎尖的亮度和新鲜感。此外,1-MCP结合保鲜袋处理能够减弱呼吸作用,降低乙烯释放量及多酚氧化酶活性。结论1-MCP处理并结合PE膜或者微孔膜包装对叶用甘薯茎尖具有良好的保鲜效果,可以有效延长其贮藏期。     

Low-memory and high-performance architectures for the CCSDS 122.0-B-1 compression standard

Two low-memory and high-performance architectures for the CCSDS 122.0-B-1 standard are proposed. They use novel memory organizations to reduce the total memory requirements in order to be implemented in a single FPGA device. The architectures were implemented in radiation-hardened and commercial FPGA devices. Based on the experimental results for the case of Virtex5QV radiation-hardened device, the throughput is 135 MSamples/sec for image with 12 bits/pixel and horizontal resolution up 8192 pixels. Also, the proposed architectures outperform the existing one in terms of the memory requirements and area.     

吐哈盆地葡北地区“两宽一高”地震勘探技术及应用效果

吐哈盆地台北凹陷圈闭落实的准确度和储层分布预测的精度一直是制约该区油气发现的关键因素。通过可控震源“两宽一高”地震采集、OVT域时间偏移、地质导向深度偏移初始模型建立及各向异性深度偏移迭代处理，在地震资料的信噪比、频带宽度和分辨率等方面明显提高的基础上，以高精度层序地层学为指导，基于高分辨率地震资料与钻井、测井资料的综合分析，识别出侏罗系6个三级层序，在三级层序格架内将研究区七克台组底部和三间房组顶部砂体识别为两个连续上升半旋回四级层序；通过构造几何属性分析及精细构造分析，揭示了本区“四带、两凹”的构造格局及形成机制；以宽频带多种反演技术为手段，对含油气层段的七克台组和三间房组砂体分布进行了预测；在综合构造分析、储层分析和油藏成藏规律分析的基础上，提出本区油气沿构造带脊线聚集，断裂系统是油气运移的优势路径，七克台组、三间房组储层在葡北构造带发育，向玉果构造带和胜北次凹减薄尖灭，葡北构造带与玉果构造带结合部位的，具有鼻状构造背景的岩性圈闭是获得油气突破的有利地区。     

<i>XRCC1</i> Arg399Gln and Arg194Trp polymorphisms regulate XRCC1 expression and chemoresistance of non-small cell lung cancer cells

X-ray repair cross-complementing protein 1 (XRCC1) could repair cisplatin-induced DNA damage. XRCC1 Arg399Gln and Arg194Trp variants alter XRCC1 expression and function, leading to changes in cancer sensitivity to cisplatin treatment. This study aimed to investigate the effects of XRCC1 Arg399Gln and Arg194Trp polymorphisms on cell viability, apoptosis and XRCC1 expression in cisplatin-sensitive A549 and cisplatin-resistant A549/DDP nonsmall cell lung cancer (NSCLC) cells. Plasmids carrying XRCC1 Arg399Gln and Arg194Trp were constructed and transfected into A549 and A549/DDP cells. RT–PCR, Western blot, MTT assay, and flow cytometry analysis were performed to assess cell viability, apoptosis, and XRCC1 expression. Compared to control cells, the viability of A549 and A549/DDP cells transfected with XRCC1 Arg399Gln and Arg194Trp was higher and the apoptosis rate was lower, and XRCC1 mRNA and protein expression levels were significantly higher. In conclusion, our results suggest that XRCC1 Arg399Gln and Arg194Trp polymorphisms change XRCC1 expression in NSCLC cells and alter the sensitivity of NSCLC to cisplatin-based chemotherapy