Bayesian hierarchical model for large-scale covariance matrix estimation.

Many bioinformatics problems implicitly depend on estimating large-scale covariance matrix. The traditional approaches tend to give rise to high variance and low accuracy due to "overfitting." We cast the large-scale covariance matrix estimation problem into the Bayesian hierarchical model framework, and introduce dependency between covariance parameters. We demonstrate the advantages of our approaches over the traditional approaches using simulations and OMICS data analysis.     

SPATIAL VARIATION PATTERNS IN THE MARINE MACROALGA XIPHOPHORA GLADIATA SSP. GLADIATA (PHAEOPHYTA). II. MORPHOLOGICAL VARIATION OVER LARGE SPATIAL SCALES1

The geographic expression of inter-regional morphological variation in Xiphophora gladiata ssp. gladiata was examined using a combination of discriminant function analyses, canonical correlation analysis and linear regression analysis. The pattern of that expression is an irregularly-stepped cline over scales of hundreds of kilometers, superimposed on a weak complex of microclines driven by exposure and (perhaps) other locally-varying environmental factors. The large-scale irregular cline is probably a response to the physico-chemical characteristics of regional water masses.     

Molecular biological databases--present and future.

The importance of databases as a research tool in molecular biology is growing steadily, and a wide range of databases relevant to genome research is currently available. However, the design of current databases is inadequate for accurate representation and analysis of the results of large-scale genome mapping and sequencing projects. A new generation of databases is required to master the challenges of the future.     

Los Alamos sequence analysis package for nucleic acids and proteins.

An interactive system for computer analysis of nucleic acid and protein sequences has been developed for the Los Alamos DNA Sequence Database. It provides a convenient way to search or verify various sequence features, e.g., restriction enzyme sites, protein coding frames, and properties of coded proteins. Further, the comprehensive analysis package on a large-scale database can be used for comparative studies on sequence and structural homologies in order to find unnoted information stored in nucleic acid sequences.     

上海市28家三甲医院双休日门诊的现状研究

通过实地调查上海市28家大型三甲医院,获取全市大型三甲医院双休日门诊的开设情况,同时对实行双休日门诊的上海某三甲综合性医院进行2008—2011年的双休日门诊开设前后的诊次分析。结果发现,上海市三甲医院大部分开设了双休日门诊,但是开始的程度和范围不一,双休日门诊在在三甲医院等优质医疗资源集中区是急需的。     

Human DNA polymorphisms and methods of analysis.

The current predominant method of analyzing base substitution polymorphisms, RFLP analysis, is likely to be gradually supplanted by methods based on PCR because of the improved sensitivity and genotyping rate. The most promising PCR methods for analysis appear to be allele-specific PCR and single-stranded conformational analysis. The single-stranded conformation approach has already been applied to the scanning of cystic fibrosis exons for new mutations. Linkage mapping projects that cover large segments of the human genome will probably rely, in the coming years, primarily on tandem repeat polymorphisms, particularly microsatellite polymorphisms. Microsatellite polymorphisms have at least a fourfold advantage over base substitution RFLPs because they are twice as informative and can be typed at at least twice the rate. The facioscapulohumeral muscular dystrophy gene was recently mapped in just 6 weeks using microsatellite polymorphisms. Because of the informativeness handicap, it will be difficult for base substitution polymorphisms to overtake tandem repeat markers for large-scale linkage mapping. Methods that allow base substitution polymorphisms to be typed at two or three times the rate of microsatellite markers would have to be developed. Most of the other applications of DNA polymorphisms described in the introduction are also increasingly likely to rely on highly informative tandem repeat markers in the future. Methods for analysis will probably be based on PCR. It is easy to envisage, for example, an automated method for large-scale DNA fingerprinting of individuals based upon a standard set of highly informative, dependable microsatellite polymorphisms. Methods for analyzing base substitution polymorphisms will continue to be important for the diagnostic detection of disease-gene alleles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Large-scale modeling of the primary visual cortex: influence of cortical architecture upon neuronal response.

A large-scale computational model of a local patch of input layer 4 [Formula: see text] of the primary visual cortex (V1) of the macaque monkey, together with a coarse-grained reduction of the model, are used to understand potential effects of cortical architecture upon neuronal performance. Both the large-scale point neuron model and its asymptotic reduction are described. The work focuses upon orientation preference and selectivity, and upon the spatial distribution of neuronal responses across the cortical layer. Emphasis is given to the role of cortical architecture (the geometry of synaptic connectivity, of the ordered and disordered structure of input feature maps, and of their interplay) as mechanisms underlying cortical responses within the model. Specifically: (i) Distinct characteristics of model neuronal responses (firing rates and orientation selectivity) as they depend upon the neuron's location within the cortical layer relative to the pinwheel centers of the map of orientation preference; (ii) A time independent (DC) elevation in cortico-cortical conductances within the model, in contrast to a "push-pull" antagonism between excitation and inhibition; (iii) The use of asymptotic analysis to unveil mechanisms which underly these performances of the model; (iv) A discussion of emerging experimental data. The work illustrates that large-scale scientific computation--coupled together with analytical reduction, mathematical analysis, and experimental data, can provide significant understanding and intuition about the possible mechanisms of cortical response. It also illustrates that the idealization which is a necessary part of theoretical modeling can outline in sharp relief the consequences of differing alternative interpretations and mechanisms--with final arbiter being a body of experimental evidence whose measurements address the consequences of these analyses.     

链霉菌CB02959中四霉素及四烯菌素的鉴定及培养基优化

【背景】四霉素(Tetramycin)和四烯菌素(Tetrin)是具有广谱抗真菌活性的四烯大环内酯类抗生素。链霉菌CB02959是一株雷纳霉素(Leinamycin)类化合物的潜在产生菌株,利用antiSMASH分析其基因组发现该菌株含有一个纳他霉素(Natamycin)类四烯大环内酯化合物的生物合成基因簇。【目的】对Streptomyces sp. CB02959中次级代谢产物进行研究,确定其是否可以产生四烯大环内酯化合物,对其发酵产物进行分离和结构鉴定,并进行初步的发酵优化以提高产量。【方法】基于生物信息学预测和高分辨质谱数据,推测CB02959中多烯化合物的结构;在不同发酵培养基中培养CB02959,确定适合大规模发酵的培养基;敲除tetrA基因以确定目标基因簇和四烯大环内酯化合物产生的相关性;分离和鉴定CB02959产生的主要代谢物的结构;通过改变培养基中葡萄糖、麦芽提取物和胰蛋白胨的含量,提高四烯大环内酯化合物的产量。【结果】通过对CB02959中纳他霉素类化合物生物合成基因簇的分析及16S rRNA基因序列的进化树分析,推测CB02959可能是一株新的四霉素和四烯菌素产生菌;在YEME发酵培养基中对CB02959进行大规模发酵,分离得到4个化合物,鉴定为四霉素A (1)、四霉素B (2)、四烯菌素A (3)、四烯菌素B (4);最后通过培养基的初步优化,将化合物1–4的产量分别提高至208.1、100.0、1 315.6、109.9 mg/L。【结论】通过基因组挖掘策略发现了一株新的四霉素和四烯菌素产生菌链霉菌CB02959,并通过培养基优化提升了其四烯大环内酯化合物的产量,此发现为这类抗真菌天然产物的后续开发奠定了基础。     

Biochemical and structural characterization of recombinant copper-metallothionein from Saccharomyces cerevisiae.

Methods were developed for large-scale purification of recombinant Cu-metallothionein (Cu-MT) for structural investigations and the determination of Cu-binding stoichiometry. Cu-MT of Saccharomyces cerevisiae overexpressed in Escherichia coli was purified using a procedure based on ion exchange and gel filtration chromatography followed by reversed-phase HPLC. The purified protein was fully characterized by electrophoresis, amino acid analysis, atomic absorption spectroscopy and elemental analysis, and was shown to contain 10 +/- 2 Cu(I) per molecule of protein. Small angle X-ray scattering measurements yielded a radius of gyration of 1.2 nm for the recombinant protein, indicating a more extended structure in solution than that derived from the recent NMR data [Peterson, C.W., Narula, S.S. & Armitage, I.A. (1996) FEBS Lett. 379, 85-93].     

Mathematical simulation and analysis of cellular metabolism and regulation.

MOTIVATION: A better understanding of the biological phenomena observed in cells requires the creation and analysis of mathematical models of cellular metabolism and physiology. The formulation and study of such models must also be simplified as far as possible to cope with the increasing complexity demanded and exponential accumulation of the metabolic reconstructions computed from sequenced genomes. RESULTS: A mathematical simulation workbench, DBsolve, has been developed to simplify the derivation and analysis of mathematical models. It combines: (i) derivation of large-scale mathematical models from metabolic reconstructions and other data sources; (ii) solving and parameter continuation of non-linear algebraic equations (NAEs), including metabolic control analysis; (iii) solving the non-linear stiff systems of ordinary differential equations (ODEs); (iv) bifurcation analysis of ODEs; (v) parameter fitting to experimental data or functional criteria based on constrained optimization. The workbench has been successfully used for dynamic metabolic modeling of some typical biochemical networks (Dolgacheva et al., Biochemistry (Moscow), 6, 1063-1068, 1996; Goldstein and Goryanin, Mol. Biol. (Moscow), 30, 976-983, 1996), including microbial glycolytic pathways, signal transduction pathways and receptor-ligand interactions. AVAILABILITY: DBsolve 5. 00 is freely available from http://websites.ntl.com/ approximately igor.goryanin. CONTACT: gzz78923@ggr.co.uk     

Exploring the nonlinear dynamics of the brain.

The growing need for a better understanding of large-scale brain dynamics has stimulated in the last decade the development of new and more advanced data analysis techniques. Progress in this domain has greatly benefited from developments in nonlinear time series analysis. This review gives a short overview of some of the nonlinear properties one may wish to infer from brain recordings and presents some examples and recent applications.     

In vitro propagation of Hedychium coronarium Koen. through axillary bud proliferation

This report describes an efficient and reproducible protocol for large-scale multiplication of Hedychium coronarium plantlets. Axillary bud explants were cultured on Murashige and Skoog medium supplemented with 3 mg/l benzylaminopurine, 3 mg/l kinetin (KIN), and 0.2 mg/l thidiazuron, yielding a maximum of 13.2 ± 0.3 number of shoots. Sub-culturing of shoots every 4 weeks on fresh multiplication medium yielded a consistent proliferation rate. Shoot clusters containing three to five shoots were successfully rooted in KIN (3 mg/l) and indole acetic acid (0.5 mg/l), yielding a maximum of 6.3 ± 0.5 number of roots. Plantlets grown in vitro were acclimatized and subsequently transferred to the field for phenotypic evaluation. Random amplified polymorphic DNA and inter-simple sequence repeat analysis has confirmed the genetic uniformity of in vitro plantlets up to 2 years. After 2 years, these plantlets were transplanted to field, and evaluation of phenotypic characteristics was done. This study is of high significance as these could be commercially utilized for large-scale production of true-to-type plantlets.     

Comparison of RFLP and morphological distances between maize Zea mays L. inbred lines. Consequences for germplasm protection purposes

 A total of 145 maize inbred lines, representative of material released in France, were differentiated using RFLP markers and a set of discriminant morphological traits in order to evaluate the use of molecular markers for large-scale germplasm diversity analysis and determination of distinctness. Several criteria are proposed with respect to choice of probes, which should give reliable results for routine studies and have a known single-locus genetic determinism to avoid redundancy. A method is proposed by which to incorporate the data from different restriction enzymes obtained with the same probe. The precision of the estimation of the genetic distance is given. The relationship between molecular and morphological distances appears to be triangular, molecular divergence behaving as a limiting factor for morphological divergence. This suggested a scheme for incorporating molecular markers in studies of distinctness. Received: 20 August 1996 / Accepted: 20 December 1996     

A relationship between gene expression and protein interactions on the proteome scale: analysis of the bacteriophage T7 and the yeast Saccharomyces cerevisiae

The relationship between the similarity of expression patterns for a pair of genes and interaction of the proteins they encode is demonstrated both for the simple genome of the bacteriophage T7 and the considerably more complex genome of the yeast Saccharomyces cerevisiae. Statistical analysis of large-scale gene expression and protein interaction data shows that protein pairs encoded by co-expressed genes interact with each other more frequently than with random proteins. Furthermore, the mean similarity of expression profiles is significantly higher for respective interacting protein pairs than for random ones. Such coupled analysis of gene expression and protein interaction data may allow evaluation of the results of large-scale gene expression and protein interaction screens as demonstrated for several publicly available datasets. The role of this link between expression and interaction in the evolution from monomeric to oligomeric protein structures is also discussed.     

Cell-free protein synthesis for proteomics.

The use of cell-free expression systems as an alternative to cell-based methods for protein production is greatly facilitating studies of protein functions. Recent improvements to cell-free systems, and the development of cell-free protein display and microarray technologies, have led to cell-free protein synthesis becoming a powerful tool for large-scale analysis of proteins. This paper reviews the most commonly used cell-free systems and their applications in proteomics.     

High-throughput behavioral analysis in C. elegans

We designed a real-time computer vision system, the Multi-Worm Tracker (MWT), which can simultaneously quantify the behavior of dozens of Caenorhabditis elegans on a Petri plate at video rates. We examined three traditional behavioral paradigms using this system: spontaneous movement on food, where the behavior changes over tens of minutes; chemotaxis, where turning events must be detected accurately to determine strategy; and habituation of response to tap, where the response is stochastic and changes over time. In each case, manual analysis or automated single-worm tracking would be tedious and time-consuming, but the MWT system allowed rapid quantification of behavior with minimal human effort. Thus, this system will enable large-scale forward and reverse genetic screens for complex behaviors.     

Synergism analysis of biochemical systems. II. Tensor formulation and treatment of stoichiometric constraints

The previous paper outlined a conceptual and mathematical framework for synergism analysis of kinetic models. Though the formalism presented there is adequate for studying simple models, the analysis of large-scale models benefits from the more effective formulation achieved in this work. The present formulation is based on simple tensor operations and takes advantage of the analogy between the formalisms for synergism and log-synergism analysis presented before. Well-known relationships of first-order sensitivity analysis and new relationships for (log-)synergism coefficients of various steady-state properties are cast in the new formal setting. The formalism is then extended to models that are subject to constraints between variables, fluxes and/or parameters. This treatment, which generalizes Reder's concept of link matrices, is applied to networks that include moiety conservation cycles [C. Reder, Metabolic control theory: a structural approach, J. Theor. Biol. 135 (1988) 175]. It is also used to take advantage of flux conservation at steady-state to simplify synergism analysis. Issues of numerical effectiveness are briefly discussed, and the theory illustrated with the study of synergistic behaviour in the metabolism of reactive oxygen species and of a scheme of dynamic channelling.     

Improved and large-scale synthesis of certain glycosyl cyanides. Synthesis of 2,5-anhydro-5-thio-D-allononitrile

The first synthesis of 2,5-anhydro-5-thio-D-allononitrile starting with L-lyxose, via a trifluoromethanesulfonic ester intermediate, has been accomplished. Methods have been developed to achieve a large-scale synthesis of 3,4,5,7-tetra-O-acetyl-2,6-anhydro-D-glycero-D-talo-heptononitrile (5). An improved procedure has been developed to synthesize 2,5-anhydro-3,4,6-tri-O-benzoyl-D-gulononitrile (9). The structures of 5 and the thioamide derivative from 9, 2,5-anhydro-3,4,6-tri-O-benzoyl-D-gulonothioamide, were confirmed by X-ray crystallographic analysis.