Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of “onco-channelopathy”. Here, we review the contribution of ion channels and transporters in multiple myeloma (MM), a hematological neoplasia characterized by the expansion of tumor plasma cells (MM cells) in the bone marrow (BM). Deregulation of ion channels sustains MM progression by modulating intracellular pathways that promote MM cells’ survival, proliferation, and drug resistance. Finally, we focus on the promising role of ion channels as therapeutic targets for the treatment of MM patients in a combination strategy with currently used anti-MM drugs to improve their cytotoxic activity and reduce adverse effects.     

A Review of Microfluidic Experimental Designs for Nanoparticle Synthesis

Microfluidics is defined as emerging science and technology based on precisely manipulating fluids through miniaturized devices with micro-scale channels and chambers. Such microfluidic systems can be used for numerous applications, including reactions, separations, or detection of various compounds. Therefore, due to their potential as microreactors, a particular research focus was noted in exploring various microchannel configurations for on-chip chemical syntheses of materials with tailored properties. Given the significant number of studies in the field, this paper aims to review the recently developed microfluidic devices based on their geometry particularities, starting from a brief presentation of nanoparticle synthesis and mixing within microchannels, further moving to a more detailed discussion of different chip configurations with potential use in nanomaterial fabrication.     

Delay-dependent robust stability criteria for uncertain neutral systems with mixed delays

This paper concerns the problem of the delay-dependent robust stability of neutral systems with mixed delays and time-varying structured uncertainties. A new method based on linear matrix inequalities is presented that makes it easy to calculate both the upper stability bounds on the delays and the free weighting matrices. Since the criteria take the sizes of the neutral- and discrete-delays into account, it is less conservative than previous methods. Numerical examples illustrate both the improvement this approach provides over previous methods and the reciprocal influences between the neutral- and discrete-delays.     

基于精细积分的(最优)控制系统设计程序包

在精细积分算法体系的基础上开发的"精细积分(最优)控制系统设计程序包PIM-CSD(Precise Integration Method-Control System Design)",不但具有高效、精确、稳定的优点,可替代Matlab控制工具箱定常控制器设计功能,而且很容易实现时变控制器功能的扩展.主要讲述精细积分程序包在LQ最优控制、Kalman滤波以及系统仿真等控制系统设计基本内容方面的功能实现,特别强调在时变控制器和滤波器的设计以及Kalman滤波微分方程的高效求解等新功能的扩展,通过与Matlab控制系统工具箱中相关功能的比较,显示出PIM-CSD在计算效率、数值精度、算法稳定性等方面的优势.最后,探讨了PIM-CSD的应用领域和发展方向.     

LDPC码的稳定中断分析

对于一个给定的信道和一个特定的ldpc码族,针对由密度进化的不稳定性而造成的稳定中断事件,本文通过研究了BEC和AWGN信道中的稳定中断概率并确切表达了在块衰弱信道中的稳定中断概率,其仿真过程给出了在删除信道中容量逼近系统是怎样跳开了在块衰弱信道中的中断限制。     

Decode‐and‐forward with full‐duplex relaying

This paper addresses the full‐duplex relaying. Some expressions for outage and average capacity of a two‐hop cooperative system with a full‐duplex relay are derived under an independent but not identically distributed Rayleigh fading environment. Using these expressions, we provide the performance analysis without Monte Carlo simulations. The impact of interference between the relay output and input is investigated. Copyright © 2011 John Wiley & Sons, Ltd.     

Antibody Therapies Targeting Complex Membrane Proteins

In analyses of protein families that may serve as drug targets, membrane-associated G-protein-coupled receptors (GPCRs) dominate, followed by ion channels, transporters, and—to a lesser extent—membrane-bound enzymes. However, various challenges put such membrane proteins among key groups of underutilized opportunities for the application of therapeutic antibodies. Antibodies hold the promise of exquisite specificity, as they are able to target even specific conformations of a particular membrane protein, as well as adaptability through engineering into various antibody formats. However, the ease of raising and isolating specific, effective antibodies targeting membrane proteins depends on many factors. In particular, the generation of specific antibodies is easier when targeting larger, simpler, extracellular domains with greater uniqueness of amino acid sequence. The rareness of such ideal conditions is illustrated by the limited number of approved biologics for targeting GPCRs and other complex membrane proteins. Challenges in developing antibodies to complex membrane proteins such as GPCRs, ion channels, transporters, and membrane-bound enzymes can be addressed by the design of the antigen, antibody-generation strategies, lead optimization technologies, and antibody modalities. A better understanding of the membrane proteins being targeted would facilitate mechanism-based drug discovery. This review describes the advantages and challenges of targeting complex membrane proteins with antibodies and discusses the preparation of membrane protein antigens and antibody generation, illustrated by select examples of success.     

Synchronization of diffusively-coupled limit cycle oscillators

We develop analytical and numerical conditions to determine whether limit cycle oscillations synchronize in diffusively coupled systems. We examine two classes of systems: reaction–diffusion PDEs with Neumann boundary conditions, and compartmental ODEs, where compartments are interconnected through diffusion terms with adjacent compartments. In both cases the uncoupled dynamics are governed by a nonlinear system that admits an asymptotically stable limit cycle. We provide two-time scale averaging methods for certifying stability of spatially homogeneous time-periodic trajectories in the presence of sufficiently small or large diffusion and develop methods using the structured singular value for the case of intermediate diffusion. We highlight cases where diffusion stabilizes or destabilizes such trajectories.     

Analysis of LDPC with optimum combining

Low density parity check (LDPC) codes have shown exceptionally good performance for single antenna systems over a wide class of channels. LDPC when implemented with a single input multiple output system with maximum ratio combining is optimum from the standpoint of maximising signal-to-noise ratio at combiner output without the presence of interferer. Optimum combining outperforms maximal ratio combining (MRC) in the presence of interferer(s). In this article, the performance of the LDPC codes with multiple receiver antennas with optimum combining in the presence of single interferer is investigated. The simulation results showed that LDPC codes of irregular construction are able to give high coding and diversity gain with optimum combining. The proposed LDPC optimum combined (LDPC–OC) system in Rayleigh fading channel in the presence of a single interferer improves the signal to interferer plus noise ratio by 2.62 dB with four receiver antennas and by 1.98 dB when the number of receiver antennas is three.