High Throughput Screening at the Nano Scale

A unique approach to master sample screening at the nano scale was launched as a joint venture project between Evotec Biosystems AG Germany and Novartis Pharma AG. The application, which provides a fully automated nano-screening platform, is composed of three module units: HPLC Nano-Fraction Collection, Micro to Nano Pipetting, and Screening. Process simulation and 3D design tools were used to evaluate not only the most performing module design, but also to reach an outstanding automation and robotic concept. The uniqueness of this application is the combination of miniaturized assay format and single molecule detection read-out, having major beneficial consequences for assay biology. Miniaturization of assays which have been shown to lead to significant savings in assay reagents and test samples. An additional benefit is the physical layout of the 2080-well Nano-Titre-Plate (NTP), which enables screening of rare compounds at low volume and an easy and fast shipment of chemical libraries to different screening sites.     

Engineering An Experimental Platform For High Throughput Reactivity Screening

The genomics revolution coupled to advances in computational power, informatics and robotics is driving drug discovery programs to produce drug candidates faster. This need has resulted in advances in high throughput methods for performing organic chemistry such as combinatorial and parallel synthesis. Yet there has not been a corollary advance in the ability to collect quantitative information on reactions that can be used to produce these drug candidates. This lack of an efficient and robust analytical method has resulted in a significant chemistry bottleneck. This work outlines a set of methods that helps address this chemistry bottleneck by using analytical constructs to detect and quantify reaction outcomes. To accomplish this, an integrated experimentalcheminformatics platform has been developed which couples an experimental design system, automated high throughput parallel and combinatorial synthesis methodology, sample processing, quantitative mass spectroscopy and automated data analysis. This platform is being used to optimize single reactions and the syntheses of whole libraries of compounds, and to generate large databases on specific reaction classes.     

Dealing With The Data Deluge In High Throughput Screening

Numerical taxonomy and pattern recognition analysis offer powerful tools that can greatly reduce the information burden of multiple-assay screening programs. These methods can be used to rationally design prescreens, identify assays with similar chemical response patterns, select reporter assays for chemical response groups, evaluate drug selectivity, and predict a drug's likely mechanism of action. When combined with assays designed to identify lead compounds with characteristics likely to cause failure at a later and more expensive stage of development, a simple 3-stage primary discovery process consisting of a rational prescreen, reporters, and clinical failure assay can reduce the number of required culture wells by more than 20-fold and can eliminate all but 1–2 drugs per 1,000 tested as leads for further evaluation and development.     

Selective Ion Extraction for High Throughput Screening with a Microfluidic Enzyme Assay

This proof-of-concept paper describes the application of selective ion extraction to an assay of protein kinase A on a microfluidic chip platform. Selective ion extraction is a flux balance technique, where a combination of independent pressure control and voltage are used to selectively extract one ion from a mixture. The assay product is completely separated and diverted into a separate channel from the waste stream containing the unconverted substrate and enzyme. By detecting only product, background noise generated by the substrate is removed which increases the signal to noise ratio and assay sensitivity. This technique is intended for adapting kinase or protease assays with low conversion rates to an on-chip reaction format for HTS screening.     

User Interfaces for Applications on a Wrist Watch

Advances in technology have made it possible to package a reasonably powerful processor and memory subsystem coupled with an ultra high-resolution display and wireless communication into a wrist watch. This introduces a set of challenges in the nature of input devices, navigation, applications, and other areas. This paper describes a wearable computing platform in a wrist watch form-factor we have developed. We built two versions: one with a low resolution liquid crystal display; and another with a ultra high resolution organic light emitting diode display. In this paper we discuss the selection of the input devices and the design of applications and user interfaces for these two prototypes, and the compare the two versions.     

An elasticity model for High Throughput Computing clusters

Different methods have been proposed to dynamically provide scientific applications with execution environments that hide the complexity of distributed infrastructures. Recently virtualization has emerged as a promising technology to provide such environments. In this work we present a generic cluster architecture that extends the classical benefits of virtual machines to the cluster level, so providing cluster consolidation, cluster partitioning and support for heterogeneous environments. Additionally the capacity of the virtual clusters can be supplemented with resources from a commercial cloud provider. The performance of this architecture has been evaluated in the execution of High Throughput Computing workloads. Results show that, in spite of the overhead induced by the virtualization and cloud layers, these virtual clusters constitute a feasible and performing HTC platform. Additionally, we propose a performance model to characterize these variable capacity (elastic) cluster environments. The model can be used to dynamically dimension the cluster using cloud resources, according to a fixed budget, or to estimate the cost of completing a given workload in a target time.     

Distributed Throughput Maximization in P2P VoD Applications

In peer-to-peer (P2P) video-on-demand (VoD) systems, a scalable source coding is a promising solution to provide heterogeneous peers with different video quality. In this paper, we present a systematic study on the throughput maximization problem in P2P VoD applications. We apply network coding to scalable P2P systems to eliminate the delivery redundancy. Since each peer receives distinct packets, a peer with a higher throughput can reconstruct the video at a higher quality. We maximize the throughput in the existing buffer-forwarding P2P VoD systems using a fully distributed algorithm. We demonstrate in the simulations that the proposed distributed algorithm achieves a higher throughput compared to the proportional allocation scheme or the equal allocation scheme. The existing buffer-forwarding architecture has a limitation in total upload capacity. Therefore we propose a hybrid-forwarding P2P VoD architecture to improve the throughput by combining the buffer-forwarding approach with the storage-forwarding approach. The throughput maximization problem in the hybrid-forwarding architecture is also solved using a fully distributed algorithm. We demonstrate that the proposed hybrid-forwarding architecture greatly improves the throughput compared to the existing buffer-forwarding architecture. In addition, by adjusting the priority weight at each peer, we can implement the differentiated throughput among different users within a video session in the buffer-forwarding architecture, and the differentiated throughput among different video sessions in the hybrid-forwarding architecture.      

用于控制的单板计算机

在控制中应用嵌入式系统的一大优势就是能够满足各种形状系数。ARM嵌入式处理器设计组的高级产品经理Haydn Povey指出:"随着控制算法呈现复杂化的趋势,相关人员正在将注意力从PLC逐渐转移到高端微控制器上。"     

用于智能交通传感网的高吞吐量仿真研究

随着交通拥堵的日益严重,智能交通系统(ITS)应运而生.传统ITS采用地埋式线圈采集信息、进行有线传输,效率低、不易维护.为了解决交通的拥挤和阻塞,提高道路的利用率,采用无线传感器网络(WSN),WSN采集和传输的是图像数据,无线传感器网络以满足高吞吐量和实时性要求.针对高吞吐量、低时延的智能交通传感网应用,提出了一种综合TDMA/FDMA的MAC调度算法Fr-Sch.利用树状拓扑,通过两条调度准则,同时对节点进行时隙和信道分配,最大化信道利用率,最少的时隙数保证无冲突通信.仿真结果表明,FT-Sch与MMSN和单信道TDMA协议相比,进一步提高吞吐量、降低延迟,明显提高了道路利用率.     

Near-Field Spot for Localized Light-Excitation of a Single Fluorescent Molecule

Zero-mode waveguides have become important tools for the detection of single molecules.There are still,however,serious challenges because large molecules need t...     

基于DFA结构的高速并行正则表达式匹配算法

针对正则表达式匹配速度低的问题,提出一种基于DFA结构的并行匹配算法.正则表达式匹配过程中,DFA的一部分状态访问次数多而另一部分状态访问次数少.因此,建立数学模型,应用马尔科夫链求解各个状态的访问概率,从而将DFA的状态分成前端和后端两个部分.通过多个前端部分共用一个后端部分的方法实现多个数据流的并行处理,达到了提高匹配速度的目的.算法分析与实验表明在多消耗60％-80％的存储空间时,能够提高4.2-4.6倍的匹配速度.     

Software-Based Failure Detection and Recovery in Programmable Network Interfaces

Emerging network technologies have complex network interfaces that have renewed concerns about network reliability. In this paper, we present an effective low-overhead fault tolerance technique to recover from network interface failures. Failure detection is based on a software watchdog timer that detects network processor hangs and a self-testing scheme that detects interface failures other than processor hangs. The proposed self-testing scheme achieves failure detection by periodically directing the control flow to go through only active software modules in order to detect errors that affect instructions in the local memory of the network interface. Our failure recovery is achieved by restoring the state of the network interface using a small backup copy containing just the right amount of information required for complete recovery. The paper shows how this technique can be made to minimize the performance impact to the host system and be completely transparent to the user.     

VoIP业务入侵检测模型

提出一种SIP信令协议的入侵检测方法,用以加强VoIP业务环境的安全。重点对基于SIP的VoIP业务环境的安全威胁和业务流量分析,利用数据挖掘算法和改进的贝叶斯算法构建针对SIP下的入侵检测模型。实验结果表明,该方法可以对VoIP业务环境下的网络攻击进行有效检测。     

基于Kerberos的Web单点登录研究

该文针对W eb环境中应用Kerberos认证协议存在的两个问题,提出了自己的解决方案。采用基于随机数的质询/响应方式取代基于时间的A uthenticator来解决重放攻击问题,采用Secure Cookies、H ttpSession等来解决W eb环境下服务器间和服务器内的安全会话问题。在此基础上设计并实现了面向W eb应用环境的单点登录系统Ti-SSO。     

High-Throughput Screening for High Affinity Antibodies

The UCB SLAM process described here has had a positive and dramatic effect on the way we select therapeutic candidate antibodies. An example of the number of cells that can be screened using UCB SLAM is shown in Table 2. UCB previously used the hybridoma method to generate antibodies for both research and for therapy.^{[5] and [6]} This method, we believed, was not particularly amenable to automation, due to the large amount of cell culture involved in both setting up the fusion and then maintaining the hybridoma cell lines, although this approach has been adopted by others.⁷ The in vitro culture of B cells, combined with the process automation has allowed many more antibodies to be screened, with hybridoma only those B cells that have fused with the myeloma are available for screening, this is only a small proportion of the total number of B cells. UCB SLAM B cell cultures can be screened a week after they are set up compared with 2–3 weeks for hybridoma. Advances in the molecular biology have allowed us to move away from the time-consuming dilution cloning of cells to select antibodies; the antibody genes can be isolated, sequenced, and recombinant antibody transiently expressed in 2 weeks. The method does not require a species specific, myeloma cell line as a fusion partner, which means there is no constraint on B cell source species. The lack of a B cell fusion event means that a highly efficient sampling of the B cell repertoire can be achieved. We have found the process to be applicable to generating research reagents, high quality antibodies to animal target antigens.⁸ These research reagents can be raised to different target antigen epitopes than used in both in vitro and in vivo mechanistic and disease models. The research reagents are a significant aid to investigate the complex biology of our targets. The lack of species-specific fusion partners makes this approach a challenge for hybridoma, particularly when there is a need to generate antibodies to mouse and rat antigens.