An integrated semiconductor device enabling non-optical genome sequencing

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.     

Stability Analysis and Performance Evaluation of Delayed Bilateral Telerobotic Systems over a Lossy Communication Channel

The focus of this paper is to address a novel control technique for stability and transparency analysis of bilateral telerobotic systems in the presence of data loss and time delay in the communication channel. Different control strategies have been reported to compensate the effects of time delay in the communication channel;however, most of them result in poor performance under data loss. First, a model for data loss is proposed using a finite series representation of a set of periodic continuous pulses.To improve the performance and data reconstruction, a holder circuits is also introduced. The passivity of the overall system is provided via the wave variable technique based on the proposed model for the data loss. The stability analysis of the system is then derived using the Lyapunov theorem under the time delay and the data loss. Finally, experimental results are given to illustrate the capability of the proposed control technique.     

Cell-free expression and in meso crystallisation of an integral membrane kinase for structure determination

Membrane proteins are key elements in cell physiology and drug targeting, but getting a high-resolution structure by crystallographic means is still enormously challenging. Novel strategies are in big demand to facilitate the structure determination process that will ultimately hasten the day when sequence information alone can provide a three-dimensional model. Cell-free or in vitro expression enables rapid access to large quantities of high-quality membrane proteins suitable for an array of applications. Despite its impressive efficiency, to date only two membrane proteins produced by the in vitro approach have yielded crystal structures. Here, we have analysed synergies of cell-free expression and crystallisation in lipid mesophases for generating an X-ray structure of the integral membrane enzyme diacylglycerol kinase to 2.28-Å resolution. The quality of cellular and cell-free-expressed kinase samples has been evaluated systematically by comparing (1) spectroscopic properties, (2) purity and oligomer formation, (3) lipid content and (4) functionality. DgkA is the first membrane enzyme crystallised based on cell-free expression. The study provides a basic standard for the crystallisation of cell-free-expressed membrane proteins and the methods detailed here should prove generally useful and contribute to accelerating the pace at which membrane protein structures are solved.     

The genome of the extremophile crucifer Thellungiella parvula

Thellungiella parvula is related to Arabidopsis thaliana and is endemic to saline, resource-poor habitats, making it a model for the evolution of plant adaptation to extreme environments. Here we present the draft genome for this extremophile species. Exclusively by next generation sequencing, we obtained the de novo assembled genome in 1,496 gap-free contigs, closely approximating the estimated genome size of 140 Mb. We anchored these contigs to seven pseudo chromosomes without the use of maps. We show that short reads can be assembled to a near-complete chromosome level for a eukaryotic species lacking prior genetic information. The sequence identifies a number of tandem duplications that, by the nature of the duplicated genes, suggest a possible basis for T. parvula's extremophile lifestyle. Our results provide essential background for developing genomically influenced testable hypotheses for the evolution of environmental stress tolerance.     

Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome

3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.     

利用模拟退火算法对200 MW供热堆堆芯核设计的优化

对 2 0 0 MW核供热堆装载模式 (燃料组件布置、可燃毒物棒根数和可燃毒物质量分数配置 )进行了优化。利用模拟退火算法和先进格林函数节块法进行多步燃耗优化计算。引入敏感性系数 ,并通过敏感性分析的方法决定优化参数 ,因此在单目标和多目标优化时均取得了明显的效果。对组件布置和可燃毒物质量分数的优化计算结果表明 ,在不改变原有的富集度和组件类型的前提下 ,与参考值相比 ,优化后的循环长度、功率峰因子和卸料燃耗均有明显的改善。该燃料管理方法不仅可用于低温堆而且也可以推广到压水堆     

也门采用溢流面板堆石坝的可行性

论述了溢流面板坝的发展概况及其特点，介绍了也门的水利工程特点，指出在也门进行溢流面板坝技术论证的必要性，以Warzan坝为实例，通过一系列数值模拟分析，论证了面板坝坝顶溢流的可行性，为也门Warzan坝的可行性设计研究提供了有实际参考价值的依据。     

Ventral neural tube cells differentiate into hepatocytes in the chick embryo

A population of ventral neural tube cells has recently been shown to migrate out of the hind brain neural tube via the vagus nerve and contribute to the developing gastrointestinal tract. Since liver is also innervated by the vagus nerve, we sought to determine if these cells also migrate into the liver. Ventral neural tube cells in the caudal hindbrain of chick embryos were tagged with a replication-deficient retroviral vector containing the LacZ gene on embryonic day 2. Embryos were processed for detection of labeled cells on embryonic day 5 and 11. Labeled cells were seen in the liver on both days and identified as hepatocytes. Previously, it was believed that all hepatocytes develop from the gut endoderm. Results of the present study show an additional source for the formation of liver cells. Received 25 August 1998; received after revision 5 November 1998; accepted 5 November 1998