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.     

基于图像识别的铜转炉吹炼造渣期渣含Fe预测模型研究

铜转炉吹炼是火法炼铜的关键工序,其终点判断与炉寿、铜产率和直收率紧密相关,目前现有人工经验、仪器测定和物料平衡法等终点判断方法均存在一定的局限性。理论上铜转炉吹炼造渣期终点与渣含Fe是否达标有关,而不同Fe含量渣样呈现不同的图像特征,鉴于此,基于图形识别的特征向量提取原理,分别采用卷积神经网络(CNN)算法与支持向量机(SVM)算法,构建了铜转炉吹炼造渣期渣含Fe预测模型,为图像识别技术在铜转炉吹炼终点判断中的应用奠定数模基础。两种模型的实例分析表明,卷积神经网络的训练集预测准确率98%,测试集预测准确率约50%;支持向量机模型的训练集预测准确率99%,测试集预测准确率62%。     

Intelligent optimal control for lead-zinc sintering process state

The intelligent integrated predictive model of synthetical permeability was established using the fuzzy classifier to combine the time sequence predictive model with the craftwork parameter predictive model. Then, the estimation model of bum-through point（BTP） based on pipe stress point（PSP） method and the predictive model of BTP were proposed. The optimal control of permeability and heat states was implemented by using the fuzzy expert controller with self-studying mechanism. The application of the intelligent control technique suppresses 17% of the fluctuation of synthetical permeability and 12% of the fluctuation of BTP, stabilizes the output and quality of sinter and settles the basis for the optimization of output and quality of sintering process.     

闭式叶盘叶身加工切触点规划算法研究与实现

闭式整体叶盘是现代高推重比航空发动机采用的新结构。在对闭式整体叶盘叶身造型方法分析的基础上，提出基于叶片防扭曲高质量造型的等误差切触点规划算法，详细描述了算法中边界参数点确定、切削行参数划分、走刀步长确定和型值点网格化四个步骤，给出了该算法的在UGCAD系统中的实现及工程应用实例。实践证明，该算法可以保证加工质量、提高加工效率、节省系统资源，具有较强的工程实践意义。     

数控系统加减速控制与程序段终点速度规划

加减速控制是CNC系统的关键技术之一。以前的加减速控制技术通常或单独采用前加减速控制，或单独采用后加减速控制。本文提出一种采用前加减速控制，同时结合运用后加减速控制算法原理的策略并且在加工前选择速度曲线模型，以提高数控系统的加工精度、实时性和通用性。同时本文进一步分析了在数控系统加工过程中，在程序段终点处存在速度无规则突跳的现象，讨论了该现象所带来的问题并提出了解决这些问题的办法。     

Elastic-plastic analytical solution for centric crack loaded by two pairs of point shear forces in finite plate

1 Introduction A great number of cracks exist in metal materials. Their existence and interaction often lead to high stress concentration and become the source of weakening and failure of metal materials[1- 4]. The elastic-plastic analysis for a cracked p…     

逆向工程中的一种编号点及其识别方法

对机械逆向工程中运用到的一种点的编码方式进行了简单的阐述和特征化，并详细介绍了运用区域搜索进行目标分割以及运用查找特性表并结合矩不变量的一种识别的算法。     

点扩展函数与采样频率及量化精度对图像边缘的影响分析

文章在建立理想边缘成像模型的基础上,分析研究了一般成像系统的点扩展函数与空间采样频率的关系及对图像边缘定位精度的影响,给出了边缘定位误差.同时,还分析研究了量化精度对图像边缘的移位影响,给出了移位误差.最后,给出了本文的分析研究在零件视觉精密检测的应用情况.