一种抗NLOS的TDOA定位算法

本文提出了一种抗非视线传播(Non-Line-of-Sight)干扰的TDOA定位算法。该算法采用退火与遗传算法相结合的方式，在满足给定条件的空间内搜索源点坐标值。数值仿真表明，该算法具备抗NLOS干扰的能力，与传统TDOA算法相比，该算法无需知道各基站的非视线传播干扰分布，是一种实用有效的定位算法。     

面对油气勘探的新领域，加快石油地球物理勘探技术进步——2006年《石油地球物理勘探》评述

 《石油地球物理勘探》报道了我国石油地球物理勘探领域方法和技术的最新进展及所取得的成就，反映了我国石油地球物理勘探的科研水平和实际应用能力。面对我国新领域油气勘探的不断深入，石油地球物理勘探技术也不断地取得进步。2006年该刊共发表各类论文134篇,主要内容涉及7个方面:①野外地震采集技术;②地震资料处理方法和技术;③地震综合解释及油气预测方法和技术;④重磁电综合物探方法和技术;⑤测井技术应用;⑥地质研究;⑦专家综述和评述。     

论企业经营者年薪制的建立

社会主义市场经济条件下企业经营者年薪制的建立，使经营者的收入与经营成果紧密相联，责权利一致，是现代企业制度的要求，体现了“按劳分配，多劳多得”的社会主义分配原则。企业在实行经营者年薪制时应明确基薪标准和效益收入，完善各项管理考核制度，建立起良好的激励机制。     

水库调水调沙回顾与展望--兼论小浪底水库运用方式研究

作者简要回顾了三门峡、恒山水库调度方式和小浪底工程设计、“八五”攻关和专题研究之运用方式以及碛口、三门峡、小浪底水库联合调度方式等。提出小浪底水库调度应坚持“多年调节泥沙 ,相机排沙”运用方式 ;调控库容应大一些 ,同时要有灵活性 ;充分利用天然大水过程排沙 ,必要时也可相机造峰 ;注重水库联合调水调沙运用及有关技术问题研究     

The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics.     

Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.     

"十五"期间国内石油化学工业发展梗概

概述了我国目前石油和化学工业的现状,与发达国家相比存在的主要差距,以及"十五"期间发展思路和规划目标.     

基于SDNA-GA 优化的模糊神经网络控制

针对最新的生物DNA研究,病毒中同一DNA碱基顺序可以编码出2条或者3条不同的多肽链.在此基础上分析与模仿了重叠基因和重叠密码的机理,得到一种新的基于重叠基因编码框架,从而提高了问题求解的效率;同时,得到一种移码解读框架的DNA遗传算法(SDNA-GA)计算模型,并将其应用于一类广义隶属度型T-S模糊神经网络控制器(GTS-FNNC)的优化设计,实现了GTS-FNNC的在线学习.