53 research outputs found

    Two-dimensional grid grammars

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    Everyone has an intuitive understanding of the concept of an algorithm. It is generally agreed that an algorithm, or effective procedure, is a finite set of instructions which meet certain requirements. All instructions must be unambiguous and must not involve any element of chance. Each instruction must be executed in a finite amount of time. It is usually not required that algorithms halt. Instead, the set of instructions must be so specifically stated that any two people executing them would perform precisely the same operations. In this thesis we first introduce a class of mathematical machines which are used to define the concept of an algorithmic computation. These Turing machines [3], which operate on one-dimensional tapes, are defined in Chapter II. We consider machines as computational devices, function evaluators, and acceptor automata for syntactically correct input. A set of instructions, called the Wang programming language, which can be assembled in such a way as to simulate a given Turing machine, is presented in Chapter III. In Chapter IV we define grammars, which are systems for generating strings of symbols with certain structured properties. The Chomsky Hierarchy of classes of restricted grammars is outlined [1]. In Chapter V we introduce a class of machines which operate in a manner similar to Turing machines but on a two-dimensional tape. We refer to this class of machines as grid machines

    Unsupervised reduction of random noise in complex data by a row-specific, sorted principal component-guided method

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    <p>Abstract</p> <p>Background</p> <p>Large biological data sets, such as expression profiles, benefit from reduction of random noise. Principal component (PC) analysis has been used for this purpose, but it tends to remove small features as well as random noise.</p> <p>Results</p> <p>We interpreted the PCs as a mere signal-rich coordinate system and sorted the squared PC-coordinates of each row in descending order. The sorted squared PC-coordinates were compared with the distribution of the ordered squared random noise, and PC-coordinates for insignificant contributions were treated as random noise and nullified. The processed data were transformed back to the initial coordinates as noise-reduced data. To increase the sensitivity of signal capture and reduce the effects of stochastic noise, this procedure was applied to multiple small subsets of rows randomly sampled from a large data set, and the results corresponding to each row of the data set from multiple subsets were averaged. We call this procedure Row-specific, Sorted PRincipal component-guided Noise Reduction (RSPR-NR). Robust performance of RSPR-NR, measured by noise reduction and retention of small features, was demonstrated using simulated data sets. Furthermore, when applied to an actual expression profile data set, RSPR-NR preferentially increased the correlations between genes that share the same Gene Ontology terms, strongly suggesting reduction of random noise in the data set.</p> <p>Conclusion</p> <p>RSPR-NR is a robust random noise reduction method that retains small features well. It should be useful in improving the quality of large biological data sets.</p

    Web scraping technologies in an API world

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    Web services are the de facto standard in biomedical data integration. However, there are data integration scenarios that cannot be fully covered by Web services. A number of Web databases and tools do not support Web services, and existing Web services do not cover for all possible user data demands. As a consequence, Web data scraping, one of the oldest techniques for extracting Web contents, is still in position to offer a valid and valuable service to a wide range of bioinformatics applications, ranging from simple extraction robots to online meta-servers. This article reviews existing scraping frameworks and tools, identifying their strengths and limitations in terms of extraction capabilities. The main focus is set on showing how straightforward it is today to set up a data scraping pipeline, with minimal programming effort, and answer a number of practical needs. For exemplification purposes, we introduce a biomedical data extraction scenario where the desired data sources, well-known in clinical microbiology and similar domains, do not offer programmatic interfaces yet. Moreover, we describe the operation of WhichGenes and PathJam, two bioinformatics meta-servers that use scraping as means to cope with gene set enrichment analysis.This work was partially funded by (i) the [TIN2009-14057-C03-02] project from the Spanish Ministry of Science and Innovation, the Plan E from the Spanish Government and the European Union from the European Regional Development Fund (ERDF), (ii) the Portugal-Spain cooperation action sponsored by the Foundation of Portuguese Universities [E 48/11] and the Spanish Ministry of Science and Innovation [AIB2010PT-00353] and (iii) the Agrupamento INBIOMED [2012/273] from the DXPCTSUG (Direccion Xeral de Promocion Cientifica e Tecnoloxica do Sistema Universitario de Galicia) from the Galician Government and the European Union from the ERDF unha maneira de facer Europa. H. L. F. was supported by a pre-doctoral fellowship from the University of Vigo

    Co-Crystal Structures of PKG Iβ (92–227) with cGMP and cAMP Reveal the Molecular Details of Cyclic-Nucleotide Binding

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    Cyclic GMP-dependent protein kinases (PKGs) are central mediators of the NO-cGMP signaling pathway and phosphorylate downstream substrates that are crucial for regulating smooth muscle tone, platelet activation, nociception and memory formation. As one of the main receptors for cGMP, PKGs mediate most of the effects of cGMP elevating drugs, such as nitric oxide-releasing agents and phosphodiesterase inhibitors which are used for the treatment of angina pectoris and erectile dysfunction, respectively. configuration, with a conserved threonine residue anchoring both cyclic phosphate and guanine moieties. The structure of CNBD-A in the absence of bound cyclic nucleotide was similar to that of the cyclic nucleotide bound structures. Surprisingly, isothermal titration calorimetry experiments demonstrated that CNBD-A binds both cGMP and cAMP with a relatively high affinity, showing an approximately two-fold preference for cGMP. conformation through its interaction with Thr193 and an unusual cis-peptide forming residues Leu172 and Cys173. Although these studies provide the first structural insights into cyclic nucleotide binding to PKG, our ITC results show only a two-fold preference for cGMP, indicating that other domains are required for the previously reported cyclic nucleotide selectivity
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