Inhibitory Monoclonal Antibodies and Their Recombinant Derivatives Targeting Surface-Exposed Carbonic Anhydrase XII on Cancer Cells

Monoclonal and recombinant antibodies are widely used for the diagnostics and therapy of cancer. They are generated to interact with cell surface proteins which are usually involved in the development and progression of cancer. Carbonic anhydrase XII (CA XII) contributes to the survival of tumors under hypoxic conditions thus is considered a candidate target for antibody-based therapy. In this study, we have generated a novel collection of monoclonal antibodies (MAbs) against the recombinant extracellular domain of CA XII produced in HEK-293 cells. Eighteen out of 24 MAbs were reactive with cellular CA XII on the surface of live kidney and lung cancer cells as determined by flow cytometry. One MAb 14D6 also inhibited the enzymatic activity of recombinant CA XII as measured by the stopped-flow assay. MAb 14D6 showed the migrastatic effect on human lung carcinoma A549 and renal carcinoma A498 cell lines in a ‘wound healing’ assay. It did not reduce the growth of multicellular lung and renal cancer spheroids but reduced the cell viability by the ATP Bioluminescence assay. Epitope mapping revealed the surface-exposed amino acid sequence (35-FGPDGENS-42) close to the catalytic center of CA XII recognized by the MAb 14D6. The variable regions of the heavy and light chains of MAb 14D6 were sequenced and their complementarity-determining regions were defined. The obtained variable sequences were used to generate recombinant antibodies in two formats: single-chain fragment variable (scFv) expressed in E. coli and scFv fused to human IgG1 Fc fragment (scFv-Fc) expressed in Chinese Hamster Ovary (CHO) cells. Both recombinant antibodies maintained the same specificity for CA XII as the parental MAb 14D6. The novel antibodies may represent promising tools for CA XII-related cancer research and immunotherapy.     

Physics‐based spectral sharpening through filter‐chart calibration

The spectral overlap of color‐sampling filters increases errors when using a diagonal matrix transform, for color correction and reduces color distinction. Spectral sharpening is a transformation of colors that was introduced to reduce color‐constancy errors when the colors are collected through spectrally overlapping filters. The earlier color‐constancy methods improved color precision when the illuminant color is changed, but they overlooked the color distinction. In this article, we introduce a new spectral sharpening technique that has a good compromise of color precision and distinction, based on real physical constraints. The spectral overlap is measured through observing a gray reference chart with a set of real and spectrally disjoint filters selected by the user. The new sharpening method enables to sharpen colors obtained by a sensor without knowing the camera response functions. Experiments with real images showed that the colors sharpened by the new method have good levels of color precision and distinction as well. The color‐constancy performance is compared with the data‐based sharpening method in terms of both precision and distinction. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 564–576, 2015     

药用辅料对CYP3A活性的影响及其对仿制药质量和疗效一致性评价的指导作用

药物制剂的处方和工艺是保证药物质量和疗效的基础，药用辅料是药物制剂处方的重要组成部分。部分药用辅料可影响CYP3A的活性，继而可能影响其底物在体内的代谢和生物利用度。在中国和美国，相对生物利用度是仿制药研究的关键内容。我国正在推进仿制药质量和疗效一致性评价。因此，了解药用辅料对CYP3A的影响及其对一致性评价的指导作用具有十分重要的现实意义。     

Type II fuzzy set-based data analytics to explore amino acid associations in protein sequences of Swine Influenza Virus

The veracity present in molecular data available in biological databases possesses new challenges for data analytics. The analysis of molecular data of various diseases can provide vital information for developing better understanding of the molecular mechanism of a disease. In this paper, an attempt has been made to propose a model that addresses the issue of veracity in data analytics for amino acid association patterns in protein sequences of Swine Influenza Virus. The veracity is caused by intra-sequential and inter-sequential biases present in the sequences due to varying degrees of relationships among amino acids. A complete dataset of 63,682 protein sequences is downloaded from NCBI and is refined. The refined dataset consists of 26,594 sequences which are employed in the present study. The type I fuzzy set is employed to explore amino acid association patterns in the dataset. The type I fuzzy support is refined to partially remove the inter-sequential biases causing veracity in data. The remaining inter-sequential biases present in refined fuzzy support are evaluated and eliminated using type II fuzzy set. Hence, it is concluded that a combination of type II fuzzy & refined fuzzy approach is the optimal approach for extracting a better picture of amino acid association patterns in the molecular dataset.     

Process monitoring method based on correlation variable classification and vine copula

Chemical processes are becoming increasingly complicated, leading to an increase in process variables and more complex relationships among them. The vine copula has a significant advantage in portraying the dependence of high-dimensional variables. However, as the dimensions increase, the vine copula model incurs a high computational load; such pressure greatly reduces model efficiency. Relationships among variables in the industrial process are complex. Different variables may be strongly or weakly associated or even independent. This paper proposes a process monitoring method based on correlation variable classification and vine copula. The weighted correlation measure is first used to divide variables into a correlated subspace and weakly correlated subspace. Then, two vine structures, C-vine and D-vine, are applied to the correlated and weakly correlated subspaces, respectively. This method takes advantage of C-vine for correlated variables and the flexibility of D-vine for weakly correlated variables. Finally, comprehensive statistics are established based on different subspaces. Monitoring results of the numerical system and the Tennessee Eastman process demonstrate the effectiveness and validity of the proposed method.     

Learning fuzzy controllers in mobile robotics with embedded preprocessing

The automatic design of controllers for mobile robots usually requires two stages. In the first stage, sensorial data are preprocessed or transformed into high level and meaningful values of variables which are usually defined from expert knowledge. In the second stage, a machine learning technique is applied to obtain a controller that maps these high level variables to the control commands that are actually sent to the robot. This paper describes an algorithm that is able to embed the preprocessing stage into the learning stage in order to get controllers directly starting from sensorial raw data with no expert knowledge involved. Due to the high dimensionality of the sensorial data, this approach uses Quantified Fuzzy Rules (QFRs), that are able to transform low-level input variables into high-level input variables, reducing the dimensionality through summarization. The proposed learning algorithm, called Iterative Quantified Fuzzy Rule Learning (IQFRL), is based on genetic programming. IQFRL is able to learn rules with different structures, and can manage linguistic variables with multiple granularities. The algorithm has been tested with the implementation of the wall-following behavior both in several realistic simulated environments with different complexity and on a Pioneer 3-AT robot in two real environments. Results have been compared with several well-known learning algorithms combined with different data preprocessing techniques, showing that IQFRL exhibits a better and statistically significant performance. Moreover, three real world applications for which IQFRL plays a central role are also presented: path and object tracking with static and moving obstacles avoidance.     

Cloud based cyber-physical systems: Network evaluation study

In recent years, the Industry 4.0 concept brings new demands and trends in different areas; one of them is distributing computational power to the cloud. This concept also introduced the Reference Architectural Model for Industry 4.0 (RAMI 4.0). The efficiency of data communications within the RAMI 4.0 model is a critical issue. Aiming to evaluate the efficiency of data communication in the Cloud Based Cyber-Physical Systems (CB-CPS), this study analyzes the periods and data amount required to communicate with individual hierarchy levels of the RAMI 4.0 model. The evaluation of the network properties of the communication protocols eligible for CB-CPS is presented. The network properties to different cloud providers and data centers’ locations have been measured and interpreted. To test the findings, an architecture for cloud control of laboratory model was proposed. It was found that the time of the day; the day of the week; and data center utilization have a negligible impact on latency. The most significant impact lies in the data center distance and the speed of the communication channel. Moreover, the communication protocol also has impact on the latency. The feasibility of controlling each level of RAMI 4.0 through cloud services was investigated. Experimental results showed that control is possible in many solutions, but these solutions mostly cannot depend just on cloud services. The intelligence on the edge of the network will play a significant role. The main contribution is a thorough evaluation of different cloud providers, locations, and communication protocols to provide recommendations sufficient for different levels of the RAMI 4.0 architecture.     

Adaptive fuzzy control for nontriangular form systems with time-varying full-state constraints

This article investigates an adaptive fuzzy tracking control problem for a class of nontriangular form systems with asymmetric time-varying full state constraints. Unknown functions are approximated by the fuzzy logic systems. A domination approach is employed to tackle the nontriangular form structure. Time-varying asymmetric barrier Lyapunov functions (ABLFs) are adopted to ensure full-state constraints satisfaction. Based on the backstepping technique and time-varying ABLFs, an adaptive controller is proposed and guarantees that all the signals in the closed-loop system are ultimately bounded and the time-varying full state constraints are met. Simulation examples are presented to further demonstrate the effectiveness of the proposed approach.     

基于感知评价的Internet语音终端流量控制

分析了影响因特网语音通信质量的主要因素，根据实时传输控制协议计算延迟、丢包率等网络参数，并利用RBF神经网络将参数映射为语音质量评分，根据评分值的变化动态地调整语音终端的编码速率，在保证一定语音质量的同时，缓解网络拥塞。实验证明了该方法的有效性。