Playing to win at DNA computation.
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We describe a molecular automaton, called MAYA, which encodes a version of the game of tic-tac-toe and interactively competes against a human opponent. The automaton is a Boolean network of deoxyribozymes that incorporates 23 molecular-scale logic gates and one constitutively active deoxyribozyme arrayed in nine wells (3x3) corresponding to the game board. To make a move, MAYA carries out an analysis of the input oligonucleotide keyed to a particular move by the human opponent and indicates a move by fluorescence signaling in a response well. The cycle of human player input and automaton response continues until there is a draw or a victory for the automaton. The automaton cannot be defeated because it implements a perfect strategy.
OBJECTIVES: The paper presents the findings of the evaluation of a pilot project to introduce networked information resources into clinical settings in a large NHS Trust and describes the subsequent developments of networked information within the Trust. DESIGN: The main purpose of the evaluation was to ascertain whether access to electronic journals and other resources via a networked system offered real benefits to clinical effectiveness. SETTING: Birmingham Heartlands and Solihull NHS Trust (Teaching). SUBJECTS: Medical and administrative staff at Birmingham and Solihull NHS Trust. RESULTS: The main conclusions of the evaluation were that: (1) appropriate location of terminals close to clinical areas is vital to ensure that best use is made of networked information resources; (2) rapid access to networked information services saves staff time and allows educational opportunities to be realized; (3) networked information resources enhance rather than replace existing information sources; (4) training and support are essential to maximizing the benefits of networked information services, and (5) such a network can support clinical decision making. CONCLUSIONS: With the development of clinical governance, the clinical network has assumed even greater importance within the Trust. Timely and easy access to clinical and educational information is crucial to the practice of evidence-based medicine which underpins high quality clinical care. The evaluation led to a number of recommendations which have since been used to develop the clinical network at Birmingham Heartlands and Solihull NHS Trust.
The Government in Britain is set on using the Internet to expand the provision of health information to the general public. Concerns over the quality of the health information have preoccupied commentators and organizations rather than the way users interact with health information systems. This report examines the issues surrounding the provision of electronic health information, and describes an evaluation undertaken of a commercial health website-that of Surgerydoor (http://www.surgerydoor.co.uk/), and comprises two parts. Part one outlines the literature on electronic health information evaluation. It discusses quality issues, but also redresses the imbalance by exploring other evaluative perspectives. Part two describes an evaluation of a health information Internet site in terms of its usability and appeal, undertaken as part of a Department of Health funded study on the impact of such systems.
An increasing number of ethnic minorities are expected to enter the United States workforce based on projected demographic changes. This includes American Indian/Alaskan Native (AI/AN) nurses. Sociocultural influences on sleep disturbances, sleepiness, and other aspects related to shift-work tolerance are of unrecognized importance. More minority nurses are needed to provide culturally congruent care; however, AI/AN nurses represent less than 1% of nurses located throughout the American workforce. This article aims to verify the feasibility of Internet data collection (Web-based survey) methods and instrument stability as the first part of a two-phase study comparing individual differences and shift-work-related sleep disturbances between AI/AN and White non-Hispanic (WNH) nurses. In the first phase, an Internet survey was used to reach a cross-section of AI/AN and WNH nurses. The on-line survey was composed of accepted shift-work-related instruments. Items estimating sleep disturbances, sociocultural choices, time awareness, polychronicity, morningness/ eveningness, ethnic identity, and demographic questions were asked. The survey was linked to a series of Web pages describing the study purpose, inclusion and exclusion criteria, consent form, Web survey, and the second phase of the study in which subjects were invited to participate in actigraphy measurements. The survey was pilot-tested for error codes, item confusion, length, and completion time. Forced-answer questions were added asking ethnicity, age group, license type, state where licensed, and legal name on nursing license before accessing the survey. Data were saved periodically, cued by the word "continue." The database was located on a secure server and password protected. Nurses were recruited using published articles and printed advertisements, hospital e-mail systems, national nursing organization Web sites (minoritynurse.com; NANAINA.org), nursing Web site discussion groups, snow-balling, and word of mouth. The site was accessed 656 times with the Internet survey being completed by 138 WNH and 56 AI/AN nurses meeting the inclusion criteria. Except for the polychronicity measure (PAI3), instruments measuring time awareness, chronotype, and situational sleepiness achieved acceptable reliability coefficients with Internet data collection. Using pull-down menus would improve questions asking specific times. Internet data collection with different ethnic groups is possible; however, accessing the target population may be difficult. Despite extensive recruitment efforts, few AI/AN nurses participated. Computer literacy and failing to relate to the study's purpose may have limited the interest of the AI/AN nurses. It is possible to recruit nurse shift workers and collect individual difference and sleep disturbance data through the Internet; however, the researcher must remain vigilant throughout the process.
An application of a digital storage oscilloscope for nanosecond time-resolved spectroscopic measurements is demonstrated in the range from the single-photon region to the multi-photon region. In comparison to the time-correlated single photon counting (TCSPC) method, the measurement setup can be greatly simplified by averaging the signals measured by the oscilloscope. Moreover, the multi-photon events of the fluorescence emissions can be tracked by this simple setup although there still exist some disadvantages in the dynamic range of the signal due to radio frequency noise, and the temporal response of the photo-multiplier tube. This method can simplify time-resolved optical measurements in the nanosecond range, such as fluorescence decay and time-of-flight measurements of diffusing light. Thus, this simple method will be applicable in many clinical and industrial uses.
MOTIVATION: To enhance the usefulness of the I.M.A.G.E. Consortium (Lennon et al., 1996, Genomics, 33, 151-152) cDNA clone collection by directed analysis and organization of their associated Expressed Sequence Tags (ESTs), thus enabling effective mining of the immense amounts of public cDNA information. RESULTS: This paper introduces the IMAGEne suite of tools, which clusters ESTs around known genes, then ranks each clone within a cluster. IMAGEne filters data from known gene sequence databases and the GenBank's EST database (Boguski and Shuler, 1995, Nature Genet., 10, 369-371). It applies biological criteria in connection with judicious use of the BLAST (Altschul et al., 1990, J. Mol. Biol., 215), FASTA (Pearson and Lipman, 1988, Proc. Natl Acad. Sci. USA, 85, 2444-2448; Pearson, 1990, Methods Enzymol., 183, 63-98; Gusfield, 1997, Algorithms on Strings, Trees, and Sequences, Cambridge University Press), and SIM (Huang et al., 1990, Comput. Appl. Biosci., 6, 373-381) tools to form known gene clusters. It then applies criteria derived from experienced biologists to select the best representative I.M.A.G.E. clone for a gene. The tool provides an intuitive Java interface for query and display of the gene and its associated clones, thus directing researchers in selecting a clone that will best enhance their research. An important product is a listing of clones that best represent all known genes. The listing will be used for re-arraying clones into minimally redundant Master Arrays. Both the listings and Master Arrays will be made available to the public, which will be a valuable resource to the genomic community in furthering discovery in the area of gene function.
MOTIVATION: Protein and DNA are generally represented by sequences of letters. In a number of circumstances simplified alphabets (where one or more letters would be represented by the same symbol) have proved their potential utility in several fields of bioinformatics including searching for patterns occurring at an unexpected rate, studying protein folding and finding consensus sequences in multiple alignments. The main issue addressed in this paper is the possibility of finding a general approach that would allow an exhaustive analysis of all the possible simplified alphabets, using substitution matrices like PAM and BLOSUM as a measure for scoring. RESULTS: The computational approach presented in this paper has led to a computer program called AlphaSimp (Alphabet Simplifier) that can perform an exhaustive analysis of the possible simplified amino acid alphabets, using a branch and bound algorithm together with standard or user-defined substitution matrices. The program returns a ranked list of the highest-scoring simplified alphabets. When the extent of the simplification is limited and the simplified alphabets are maintained above ten symbols the program is able to complete the analysis in minutes or even seconds on a personal computer. However, the performance becomes worse, taking up to several hours, for highly simplified alphabets. AVAILABILITY: AlphaSimp and other accessory programs are available at http://bioinformatics.cribi.unipd.it/alphasimp
SUMMARY: Orthostrapper is a program that calculates orthology support values for pairs of sequences in a multiple alignment (Storm and Sonnhammer, Bioinformatics, 18, 92-99, 2002). Here we present OrthoGUI, a web interface and display tool for Orthostrapper analysis. OrthoGUI visualizes the Orthostrapper output in both tabular and tree representations, and can also apply a clustering algorithm to identify groups of multiple orthologs, which are indicated by colour coding. AVAILABILITY: http://www.cgb.ki.se/OrthoGUI CONTACT: erik.sonnhammer@cgb.ki.se
MOTIVATION: We present a structural alignment database that is specifically targeted for use in derivation and optimization of sequence-structure alignment algorithms for homology modeling. We have paid attention to ensure that fold-space is properly sampled, that the structures involved in alignments are of significant resolution (better than 2.5 A) and the alignments are accurate and reliable. RESULTS: Alignments have been taken from the HOMSTRAD, BAliBASE and SCOP-based Gerstein databases along with alignments generated by a global structural alignment method described here. In order to discriminate between equivalent alignments from these different sources, we have developed a novel scoring function, Contact Alignment Quality score, which evaluates trial alignments by their statistical significance combined with their ability to reproduce conserved three-dimensional residue contacts. The resulting non-redundant, unbiased database contains 1927 alignments from across fold-space with high-resolution structures and a wide range of sequence identities. AVAILABILITY: The database can be interactively queried either over the web at http://abagyan.scripps.edu/lab/web/sad/show.cgi or by using MySQL, and is also available to download over the web.
MOTIVATION: Many problems in data integration in bioinformatics can be posed as one common question: Are two sets of observations generated by the same distribution? We propose a kernel-based statistical test for this problem, based on the fact that two distributions are different if and only if there exists at least one function having different expectation on the two distributions. Consequently we use the maximum discrepancy between function means as the basis of a test statistic. The Maximum Mean Discrepancy (MMD) can take advantage of the kernel trick, which allows us to apply it not only to vectors, but strings, sequences, graphs, and other common structured data types arising in molecular biology. RESULTS: We study the practical feasibility of an MMD-based test on three central data integration tasks: Testing cross-platform comparability of microarray data, cancer diagnosis, and data-content based schema matching for two different protein function classification schemas. In all of these experiments, including high-dimensional ones, MMD is very accurate in finding samples that were generated from the same distribution, and outperforms its best competitors. CONCLUSIONS: We have defined a novel statistical test of whether two samples are from the same distribution, compatible with both multivariate and structured data, that is fast, easy to implement, and works well, as confirmed by our experiments. AVAILABILITY: http://www.dbs.ifi.lmu.de/~borgward/MMD.
The ASTRAL compendium provides several databases and tools to aid in the analysis of protein structures, particularly through the use of their sequences. It is partially derived from the SCOP database of protein domains, and it includes sequences for each domain as well as other resources useful for studying these sequences and domain structures. Several major improvements have been made to the ASTRAL compendium since its initial release 2 years ago. The number of protein domain sequences included has doubled from 15 190 to 30 867, and additional databases have been added. The Rapid Access Format (RAF) database contains manually curated mappings linking the biological amino acid sequences described in the SEQRES records of PDB entries to the amino acid sequences structurally observed (provided in the ATOM records) in a format designed for rapid access by automated tools. This information is used to derive sequences for protein domains in the SCOP database. In cases where a SCOP domain spans several protein chains, all of which can be traced back to a single genetic source, a 'genetic domain' sequence is created by concatenating the sequences of each chain in the order found in the original gene sequence. Both the original-style library of SCOP sequences and a new library including genetic domain sequences are available. Selected representative subsets of each of these libraries, based on multiple criteria and degrees of similarity, are also included. ASTRAL may be accessed at http://astral.stanford.edu/.
Proteins can be formed by single or multiple domains. The process of recombination at the molecular level has generated a wide variety of multi-domain proteins with specific domain organization to cater to the functional requirements of an organism. The functional and structural costs of inserting a domain into another means that multi-domain proteins are usually formed by covalently linking the N-terminus of one domain to the C-terminus of the preceding domain. While this is true in a large proportion of multi-domain proteins, we find a significant fraction of proteins that are the result of domain insertion. The inserted domain breaks the sequence contiguity of the domain into which it is inserted leading to a novel domain organization. This web resource aims to document domain insertions in known protein structures that are classified in the SCOP database. The web server can be accessed from http://stash.mrc-lmb.cam. ac.uk/DomIns/.
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This data acquisition system records video frames onto a video tape, and simultaneously acquires biomedical data along with video time codes onto a computer hard disk to achieve a 30-min video-synchronized data recording with a summed data rate of 2.16 Mbit/s. A time-code-bridge-file created during acquisition matches each video frame-start with the corresponding index number of the acquired data. The mean synchronization accuracy of the system is 0.22 ms.
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The scalability problem in data mining involves the development of methods for handling large databases with limited computational resources such as memory and computation time. In this paper, two scalable clustering algorithms, bEMADS and gEMADS, are presented based on the Gaussian mixture model. Both summarize data into subclusters and then generate Gaussian mixtures from their data summaries. Their core algorithm, EMADS, is defined on data summaries and approximates the aggregate behavior of each subcluster of data under the Gaussian mixture model. EMADS is provably convergent. Experimental results substantiate that both algorithms can run several orders of magnitude faster than expectation-maximization with little loss of accuracy.