A new approach for protein design based on the relative entropy

A new effective and fast minimization approach completely based on the physical theory is proposed for protein design. The sequence space is essentially searched according to the Boltzmann distribution. In this approach, the relative entropy is used as a minimization object function. The method has been tested on an off-lattice model of proteins and the results are better than those obtained from other similar work. Therefore, it can be applied as a uniform frame for both folding and inverse folding of proteins.     

实现散射场强整形的微散射体阵列逆向设计方法

本文提出一种基于全介电微散射体的散射阵列结构逆向设计方法,用以实现散射电场强度整形.该方法基于空域傅里叶变换与角谱变换,从给定目标区域处期望实现的散射场强分布出发,逆向求得所需的感应源,再利用电磁感应源理论,逆向设计微散射体阵列,且只需通过解析计算便能够快速地求取出微散射体阵列的电磁参数值分布.基于提出的逆向设计方法,文中提供了三维情况下的具体算例,实现了给定方形面目标区域的散射场强整形.理论计算结果与全波仿真结果符合良好,表明本文提出的逆向设计方法具有可行性与有效性.     

Multiplexed sorting of libraries on libraries: A novel method for empirical protein design by affinity-driven phage enrichment on synthetic peptide arrays

Chemically synthesized peptide arrays on planar cellulose carriers are proposed as libraries of ligands suitable for the multiplexed simultaneous capture of peptide-specific acceptor proteins from a large randomly mutagenized library of acceptor proteins presented on bacteriophage M13 particles. This experimental set-up can be exploited to rapidly screen for individual new, distinct binding partners from two complementary libraries (two-dimensional screening). The technical feasibility of this empirical protein design approach was demonstrated with calmodulin as an aceptor protein using an array of mastoparan variants for multiplexed phage affinity enrichment.     

太赫兹波段超材料的制作、设计及应用

本文从制作方法、结构设计和材料选择几方面综述了超材料在太赫兹波段的电磁响应特性和潜在应用。首先,介绍了获得不同维度、具有特异电磁响应以及结构可调超材料的各种微加工制作方法,进而分析和讨论了超材料的电磁响应特性。文中指出,结构设计可以控制超材料的电磁响应特性,如各向异性、双各向异性、偏振调制、多频响应、宽带响应、不对称透射、旋光性和超吸收等。超材料的电磁响应依赖于周围微环境的介电性质,因而可用于制作对环境敏感的传感器件。此外,电光、磁光、相变、温度敏感等功能材料的引入可以获得光场、电场、磁场、温度等主动控制的太赫兹功能器件。最后,简单介绍了超材料在太赫兹波段进一步发展所面临的机遇和挑战。     

Patient-Specific Network for Personalized Breast Cancer Therapy with Multi-Omics Data

The development of new computational approaches that are able to design the correct personalized drugs is the crucial therapeutic issue in cancer research. However, tumor heterogeneity is the main obstacle to developing patient-specific single drugs or combinations of drugs that already exist in clinics. In this study, we developed a computational approach that integrates copy number alteration, gene expression, and a protein interaction network of 73 basal breast cancer samples. 2509 prognostic genes harboring a copy number alteration were identified using survival analysis, and a protein–protein interaction network considering the direct interactions was created. Each patient was described by a specific combination of seven altered hub proteins that fully characterize the 73 basal breast cancer patients. We suggested the optimal combination therapy for each patient considering drug–protein interactions. Our approach is able to confirm well-known cancer related genes and suggest novel potential drug target genes. In conclusion, we presented a new computational approach in breast cancer to deal with the intra-tumor heterogeneity towards personalized cancer therapy.     

Asymmetric MRI Magnet Design Using a Hybrid Numerical Method

This paper describes a hybrid numerical method for the design of asymmetric magnetic resonance imaging magnet systems. The problem is formulated as a field synthesis and the desired current density on the surface of a cylinder is first calculated by solving a Fredholm equation of the first kind. Nonlinear optimization methods are then invoked to fit practical magnet coils to the desired current density. The field calculations are performed using a semi-analytical method. A new type of asymmetric magnet is proposed in this work. The asymmetric MRI magnet allows the diameter spherical imaging volume to be positioned close to one end of the magnet. The main advantages of making the magnet asymmetric include the potential to reduce the perception of claustrophobia for the patient, better access to the patient by attending physicians, and the potential for reduced peripheral nerve stimulation due to the gradient coil configuration. The results highlight that the method can be used to obtain an asymmetric MRI magnet structure and a very homogeneous magnetic field over the central imaging volume in clinical systems of approximately 1.2 m in length. Unshielded designs are the focus of this work. This method is flexible and may be applied to magnets of other geometries.     

A unilateral magnet with an extended constant magnetic field gradient

Unilateral magnetic resonance (UMR) has become, in different research areas, a powerful tool to interrogate samples of arbitrary size. Numerous designs have been suggested in the literature to produce the desired magnetic field distributions, including designs which feature constant magnetic field gradients suitable for diffusion and profiling experiments. This work presents a new approach which features extended constant magnetic field gradients with a three magnet array. Constant gradients of more than 3cm extent can be achieved in a very simple, compact and safe design. Diffusion measurements from different positions over the magnet are presented in addition to practical applications for reservoir core plug characterization. The idea of a solenoid as a probe for specific measurements in UMR is introduced. Simple profiling experiments are also presented.     

光学透明频率选择表面的设计研究

以氟化镁为基底材料, 采用基底、金属网栅与频率选择表面一体化设计方法设计了一种雷达波与光学波段双带通的结构. 利用模式匹配法对设计结构的传输特性进行了仿真研究, 并将设计结果与制备样件的测试结果进行了对比分析. 结果发现: 采用一体化设计的方法设计光学透明频率选择表面, 不仅能够快速得到电场基函数而且还能够准确预估其谐振尺寸, 从而在提高计算效率的同时避免了模式互作用零点的出现. 采用一体化设计方法获得了具有稳定滤波特性的光学透明频率选择表面, 为雷达/红外双模制导头罩的电磁屏蔽技术和隐身技术提供了一种有效技术方案. 关键词： 复合制导 频率选择表面 金属网栅 一体化设计     

The characteristics of molten globule states and folding pathways strongly depend on the sequence of a protein

ABSTRACT

The majority of proteins perform their cellular function after folding into a specific and stable native structure. Additionally, for many proteins less compact ‘molten globule’ states have been observed. Current experimental observations show that the molten globule state can show varying degrees of compactness and solvent accessibility; the underlying molecular cause for this variation is not well understood. While the specificity of protein folding can be studied using protein lattice models, current design procedures for these models tend to generate sequences without molten globule-like behaviour. Here we alter the design process so the distance between the molten globule ensemble and the native structure can be steered; this allows us to design protein sequences with a wide range of folding pathways, and sequences with well-defined heat-induced molten globules. Simulating these sequences we find that (1) molten globule states are compact, but have less specific configurations compared to the folded state, (2) the nature of the molten globule state is highly sequence dependent, (3) both two-state and multi-state folding proteins may show heat-induced molten globule states, as observed in heat capacity curves. The varying nature of the molten globules and typical heat capacity curves associated with the transitions closely resemble experimental observations.     

基于时间反演技术的电磁器件端口场与内部场转换方法

随着电磁器件的集成化,器件搭载的模块、实现的功能愈发多样.各模块间的耦合难以忽略,设计难度陡然增加,传统设计方法逐渐力不从心,迫切需要寻找一种新的电磁综合设计方法.本文利用时间反演电磁波的时空同步聚焦特性,探索了将时间反演技术应用于器件设计的可能性.首先,基于通用的器件逆设计流程,利用时间反演技术、并矢格林函数及电磁学的基本原理,提出了将器件端口场分布转换为内部场分布的方法,并证明由端口期望场的时间反演场在空间某一位置获得的连续等效源的共轭分布可在端口处产生与期望场接近的场分布.且在单点频逆设计过程中,只需知道端口电场或磁场的切向分量即可完成端口场与内部场的转换.同时,借助格林函数的互易性对本文所提理论做适当变换后,进行数值仿真验证,分析讨论了不同初始信息条件下该方法的适用性.仿真结果与理论相符,证明了理论的正确性,为将时间反演技术应用于电磁器件的逆设计提供了可能.     

Genetic alloy design based on thermodynamics and kinetics

A theory-guided computational approach for alloy design is presented. Aimed at optimising the desired properties, the microstructure is designed and an alloy composition optimised accordingly, combining criteria based on thermodynamic, thermokinetic and mechanical principles. A genetic algorithm is employed as the optimisation scheme. The approach is applied to the design of ultra-high strength stainless steels. Three composition scenarios, utilising different strengthening precipitates (carbides, Cu and NiAl/Ni₃Ti), are followed. The results are compared to a variety of existing commercial high-end engineering steels, showing that the design strategy presented here may lead to significant improvements in strength beyond current levels.     

Multiscale molecular dynamics simulations of membrane remodeling by Bin/Amphiphysin/Rvs family proteins

Membrane curvature is no longer thought of as a passive property of the membrane; rather, it is considered as an active, regulated state that serves various purposes in the cell such as between cells and organelle definition. While transport is usually mediated by tiny membrane bubbles known as vesicles or membrane tubules, such communication requires complex interplay between the lipid bilayers and cytosolic proteins such as members of the Bin/Amphiphysin/Rvs(BAR) superfamily of proteins. With rapid developments in novel experimental techniques, membrane remodeling has become a rapidly emerging new field in recent years. Molecular dynamics(MD) simulations are important tools for obtaining atomistic information regarding the structural and dynamic aspects of biological systems and for understanding the physics-related aspects. The availability of more sophisticated experimental data poses challenges to the theoretical community for developing novel theoretical and computational techniques that can be used to better interpret the experimental results to obtain further functional insights. In this review, we summarize the general mechanisms underlying membrane remodeling controlled or mediated by proteins. While studies combining experiments and molecular dynamics simulations recall existing mechanistic models, concurrently, they extend the role of different BAR domain proteins during membrane remodeling processes. We review these recent findings, focusing on how multiscale molecular dynamics simulations aid in understanding the physical basis of BAR domain proteins, as a representative of membrane-remodeling proteins.     

Chemoinformatics methods for systematic comparison of molecules from natural and synthetic sources and design of hybrid libraries

Until recently, the field of diversity and library design has more or less ignored naturalproducts as a compound source. This is probably due to at least two reasons. First,combinatorial and reaction-based approaches have been major focal points in the earlydays of computational library design. In addition, a widespread view is that naturalproducts are often highly complex and not amenable to medicinal chemistry efforts. Thiscontribution introduces recent computational approaches to systematically analyzenatural molecules and bridge the gap between natural products and synthetic chemistryprograms. Large scale comparisons of natural and synthetic molecules are discussed aswell as studies designed to identify `synthetic mimics' of natural products with specificactivity. In addition, a concept for the design of natural/synthetic hybrid libraries isintroduced. Although research in this area is still in its early stages, an important lesson tobe learned from computational analyses is that there is no need to a priori `shy away'from natural products as a source for molecular design.     

微波管电子枪三维粒子模拟研究

 分析了以往电子光学模型进行电子枪模拟工作过程及存在的缺陷，指出粒子模拟方法能够全面考虑空间电荷限制和温度限制、阴极热初速、电子注非层流性等因素，研究电子注的瞬态和噪声特性，是一种更准确的电子枪模拟方法。以某电子枪为例，运用Mafia PIC模块进行了模拟计算，与实验结果对比表明Mafia粒子模拟具有相当精度，可用于指导微波管电子枪工程设计。     

核磁共振研究中蛋白质样品的同位素标记策略

在运用核磁共振技术研究蛋白质溶液三维结构和动态特性中,蛋白质的同位素标记表达是研究的关键. 至今已发展的同位素标记技术和蛋白质表达系统已获得了广泛的应用,对蛋白质的核磁共振研究起到了巨大的推动作用. 但是随着蛋白质研究的深入发展,原有的一些常规标记表达技术已不能完全适应核磁共振研究的需要. 近年来,陆续出现的一系列同位素标记新技术和蛋白质表达新系统可以满足不同物种来源的蛋白质及更高分子量的蛋白质的核磁共振研究的需要. 本文旨在对这些蛋白质标记表达新技术的方法及应用予以逐一介绍.     

基于共心球透镜的多尺度广域高分辨率计算成像系统设计

针对实时广域高分辨率成像需求,充分利用具有对称结构的多层共心球透镜视场大且各轴外视场成像效果一致性好的特点,设计基于共心球透镜的多尺度广域高分辨率计算成像系统.该系统基于计算成像原理,通过构建像差优化函数获得光学系统设计参数,结合球形分布的次级相机阵列进行全局性优化,提高系统性能的同时有效简化光学设计过程、降低系统设计难度.系统稳定性测试结果表明,该成像系统的MTF(modulation transmission function)值在截止频率处接近衍射极限,弥散斑均方根恒小于探测器像元尺寸,整机实景实时成像效果良好,无视觉可见畸变.该系统不仅有效解决了传统成像中广域和高分辨率成像矛盾的问题,而且为计算光学成像系统设计奠定了一定研究基础.     

An object-oriented designed finite-difference time-domain simulator for electromagnetic analysis and design in MRI--applications to high field analyses

This paper presents a finite-difference time-domain (FDTD) simulator for electromagnetic analysis and design applications in MRI. It is intended to be a complete FDTD model of an MRI system including all RF and low-frequency field generating units and electrical models of the patient. The program has been constructed in an object-oriented framework. The design procedure is detailed and the numerical solver has been verified against analytical solutions for simple cases and also applied to various field calculation problems. In particular, the simulator is demonstrated for inverse RF coil design, optimized source profile generation, and parallel imaging in high-frequency situations. The examples show new developments enabled by the simulator and demonstrate that the proposed FDTD framework can be used to analyze large-scale computational electromagnetic problems in modern MRI engineering.     

Advances in diversity profiling and combinatorial series design

Rapid advances in synthetic and screening technology have recently enabled the simultaneous synthesis and biological evaluation of large chemical libraries containing hundreds to tens of thousands of compounds, using molecular diversity as a means to design and prioritize experiments. This paper reviews some of the most important computational work in the field of diversity profiling and combinatorial library design, with particular emphasis on methodology and applications. It is divided into four sections that address issues related to molecular representation, dimensionality reduction, compound selection, and visualization.     

A novel method for optimization of slit Venturi dimensions through CFD simulation and RSM design

This research presents a novel comprehensive method for optimizing the design of cavitating slit Venturi for a given cavitation intensity. This method is applicable to any cavitation number and can be used to provide the Venturi geometry that is suitable for a specific application. In this paper, cavitating Venturi design process is represented in seven steps. As an example, for the cavitation number of 0.2, geometrical and operational parameters of the Venturi were determined using the proposed seven steps. During the design process, the Venturi discharge coefficient was calculated using computational fluid dynamics (CFD) simulations. Furthermore, Venturi parameters such as inlet pressure, throat area, width, length, height and divergence angle, were optimized by the combination of CFD and Response Surface Methodology (RSM). In addition to calculating the mentioned optimum parameters, other hydraulic parameters of Venturi including discharge coefficient, flowrate, throat velocity, cavitation volume and length were also determined. Finally, the proposed design method in this study was verified by conducting sets of laboratory experiments.