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MulBlast 1.0: a multiple alignment of BLAST output to boost protein sequence similarity analysis.

The protein sequence similarity search has become a major tool for biologists. Various efficient and rapid programs and comparison matrices have been designed and refined in order to perform the scanning task (BLAST, FASTA, Automat, etc.). However, the final step of the search, the analysis of the results, is still tedious and time consuming. In order to optimize true-positive hit screening, we have developed a program which makes a multiple alignment from the BLAST search output. Conserved sequence segments are pointed out. It makes the recognition of already known as well as new sequence patterns easier. It allows at a glance a rapid identification of significant similarities, protein family signature and new sequence motifs. This alignment is written in a compatible format for the GCG programs LineUp and ProfileMake.

Algorithms↗

Integrated databases and computer systems for studying eukaryotic gene expression.

MOTIVATION: The goal of the work was to develop a WWW-oriented computer system providing a maximal integration of informational and software resources on the regulation of gene expression and navigation through them. Rapid growth of the variety and volume of information accumulated in the databases on regulation of gene expression necessarily requires the development of computer systems for automated discovery of the knowledge that can be further used for analysis of regulatory genomic sequences. RESULTS: The GeneExpress system developed includes the following major informational and software modules: (1) Transcription Regulation (TRRD) module, which contains the databases on transcription regulatory regions of eukaryotic genes and TRRD Viewer for data visualization; (2) Site Activity Prediction (ACTIVITY), the module for analysis of functional site activity and its prediction; (3) Site Recognition module, which comprises (a) B-DNA-VIDEO system for detecting the conformational and physicochemical properties of DNA sites significant for their recognition, (b) Consensus and Weight Matrices (ConsFrec) and (c) Transcription Factor Binding Sites Recognition (TFBSR) systems for detecting conservative contextual regions of functional sites and their recognition; (4) Gene Networks (GeneNet), which contains an object-oriented database accumulating the data on gene networks and signal transduction pathways, and the Java-based Viewer for exploration and visualization of the GeneNet information; (5) mRNA Translation (Leader mRNA), designed to analyze structural and contextual properties of mRNA 5'-untranslated regions (5'-UTRs) and predict their translation efficiency; (6) other program modules designed to study the structure-function organization of regulatory genomic sequences and regulatory proteins. AVAILABILITY: GeneExpress is available at http://wwwmgs.bionet.nsc. ru/systems/GeneExpress/ and the links to the mirror site(s) can be found at http://wwwmgs.bionet.nsc.ru/mgs/links/mirrors.html+ ++.

Algorithms↗

TreeGeneBrowser: phylogenetic data mining of gene sequences from public databases.

MOTIVATION: Sequence databases represent an enormous resource of phylogenetic information, but there is a lack of tools for accessing that information in order to assess the amount of evolutionary information in these databases that may be suitable for phylogenetic reconstruction and for identifying areas of the taxonomy that are under-represented for specific gene sequences. RESULTS: We have developed TreeGeneBrowser which allows inspection and evaluation of gene sequence data for phylogenetic reconstruction. This program improves the efficiency of identification of genes that may be useful for particular phylogenetic studies and identifies taxa and taxonomic branches that are under-represented in sequence databases.

Algorithms↗

A greedier approach for finding tag SNPs.

MOTIVATION: Recent studies have shown that a small subset of Single Nucleotide Polymorphisms (SNPs) (called tag SNPs) is sufficient to capture the haplotype patterns in a high linkage disequilibrium region. To find the minimum set of tag SNPs, exact algorithms for finding the optimal solution could take exponential time. On the other hand, approximation algorithms are more efficient but may fail to find the optimal solution. RESULTS: We propose a hybrid method that combines the ideas of the branch-and-bound method and the greedy algorithm. This method explores larger solution space to obtain a better solution than a traditional greedy algorithm. It also allows the user to adjust the efficiency of the program and quality of solutions. This algorithm has been implemented and tested on a variety of simulated and biological data. The experimental results indicate that our program can find better solutions than previous methods. This approach is quite general since it can be used to adapt other greedy algorithms to solve their corresponding problems. AVAILABILITY: The program is available upon request.

Algorithms↗

GH3, a novel proapoptotic domain in Drosophila Grim, promotes a mitochondrial death pathway.

Grim encodes a protein required for programmed cell death in Drosophila. The Grim N-terminus induces apoptosis by disrupting IAP blockage of caspases; however, N-terminally-deleted Grim retains pro apoptotic activity. We describe GH3, a 15 amino acid internal Grim domain absolutely required for its proapoptotic activity and sufficient to induce cell death when fused to heterologous carrier proteins. A GH3 homology region is present in the Drosophila proapoptotic proteins Reaper and Sickle. The GH3 domain and the homologous regions in Reaper and Sickle are predicted to be structured as amphipathic alpha-helixes. During apoptosis induction, Grim colocalizes with mitochondria and cytochrome c in a GH3-dependent but N-terminal- and caspase activity-independent manner. When Grim is overexpressed in vivo, both the N-terminal and the GH3 domains are equally necessary, and cooperate for apoptosis induction. The N-terminal and GH3 Grim domains thus activate independent apoptotic pathways that synergize to induce programmed cell death efficiently.

Amino Acid Sequence↗

Analysis of effects of tRNA:message stability on frameshift frequency at the Escherichia coli RF2 programmed frameshift site.

The codon that is in-frame prior to +1 frameshifting at the E.coli prfB (RF2 gene) frameshift site is randomized to create thirty-two variants. These alleles vary 1000-fold in frameshift-dependent expression in fusions to lacZ. Frameshifting is more frequent at sites where the in-frame codon ends in uridine, as if third position wobble pairs to message uridine facilitate slippage into the +1 frame. Consistent with other studies of programmed frameshift sites, efficient frameshifting depends on stable message:tRNA base pairs after rephasing. For complexes with mispairs, frameshift frequency depends on the nature, number, and position of mispairs. Central purine:purine mispairs are especially inhibitory. Relative stabilities of +1 rephased complexes are estimated from published data on the stabilities of tRNA:tRNA complexes. Stability correlates with frameshifting over its entire range, which suggests that stability is an important determinant of the probability of translation of the rephased complex.

Alleles↗

ICDS database: interrupted CoDing sequences in prokaryotic genomes.

Unrecognized frameshifts, in-frame stop codons and sequencing errors lead to Interrupted CoDing Sequence (ICDS) that can seriously affect all subsequent steps of functional characterization, from in silico analysis to high-throughput proteomic projects. Here, we describe the Interrupted CoDing Sequence database containing ICDS detected by a similarity-based approach in 80 complete prokaryotic genomes. ICDS can be retrieved by species browsing or similarity searches via a web interface (http://www-bio3d-igbmc.u-strasbg.fr/ICDS/). The definition of each interrupted gene is provided as well as the ICDS genomic localization with the surrounding sequence. Furthermore, to facilitate the experimental characterization of ICDS, we propose optimized primers for re-sequencing purposes. The database will be regularly updated with additional data from ongoing sequenced genomes. Our strategy has been validated by three independent tests: (i) ICDS prediction on a benchmark of artificially created frameshifts, (ii) comparison of predicted ICDS and results obtained from the comparison of the two genomic sequences of Bacillus licheniformis strain ATCC 14580 and (iii) re-sequencing of 25 predicted ICDS of the recently sequenced genome of Mycobacterium smegmatis. This allows us to estimate the specificity and sensitivity (95 and 82%, respectively) of our program and the efficiency of primer determination.

Bacillus↗

Systematic analysis of bicistronic reporter assay data.

Bicistronic reporter assay systems have become a mainstay of molecular biology. While the assays themselves encompass a broad range of diverse and unrelated experimental protocols, the numerical data garnered from these experiments often have similar statistical properties. In general, a primary dataset measures the paired expression of two internally controlled reporter genes. The expression ratio of these two genes is then normalized to an external control reporter. The end result is a 'ratio of ratios' that is inherently sensitive to propagation of the error contributed by each of the respective numerical components. The statistical analysis of this data therefore requires careful handling in order to control for the propagation of error and its potentially misleading effects. A careful survey of the literature found no consistent method for the statistical analysis of data generated from these important and informative assay systems. In this report, we present a detailed statistical framework for the systematic analysis of data obtained from bicistronic reporter assay systems. Specifically, a dual luciferase reporter assay was employed to measure the efficiency of four programmed -1 frameshift signals. These frameshift signals originate from the L-A virus, the SARS-associated Coronavirus and computationally identified frameshift signals from two Saccharomyces cerevisiae genes. Furthermore, these statistical methods were applied to prove that the effects of anisomycin on programmed -1 frameshifting are statistically significant. A set of Microsoft Excel spreadsheets, which can be used as templates for data generated by dual reporter assay systems, and an online tutorial are available at our website (http://dinmanlab.umd.edu/statistics). These spreadsheets could be easily adapted to any bicistronic reporter assay system.

Data Interpretation, Statistical↗

The role of universal distribution of vitamin A capsules in combatting vitamin A deficiency in Bangladesh.

Vitamin A deficiency is a major public health problem among preschool-aged children in many developing countries. In Bangladesh, a national nutritional surveillance system was initiated in 1990 to monitor 1) the occurrence of vitamin A deficiency by history of night blindness and 2) the routine coverage of national twice-yearly prophylactic vitamin A capsule (VAC) distribution. This study comprised data collected from June 1990 to August 1994. The VAC distribution had a mean coverage rate of 48.7% (95% confidence interval (CI) 48.4-49.0) in the rural areas; the coverage rate in the urban slums was 93.7% (95% CI 93.4-94.0). In the rural areas, the mean prevalence of night blindness was 0.86% (95% CI 0.81-0.91) and the bimonthly prevalence of night blindness ranged from 0.50% (95% CI 0.32-0.77) to 1.48% (95% CI 1.19-1.85), while in the urban slums the mean prevalence was 0.22% (95% CI 0.18-0.28) and the bimonthly prevalence ranged from zero to 0.62% (95% CI 0.27-1.37). The efficiency of VAC distribution was 27% (95% CI 17.6-35.3) in the rural areas and 77.8% (95% CI 61.8-87.1) in the urban slums. After adjustment for multiple potentially confounding factors, VAC receipt by individual children reduced the risk of night blindness in both rural and urban areas (rural areas: odds ratio (OR) = 0.74, 95% CI 0.63-0.87; urban slums: OR = 0.39, 95% CI 0.19-0.82). Breastfeeding was a protective factor for night blindness in both rural (OR = 0.53, 95% CI 0.42-0.67) and urban (OR = 0.32, 95% CI 0.15-0.66) areas. Night blindness was inversely related to the level of routinely attained coverage, and the degree of protection was associated with the time interval between the moment of VAC receipt and the moment of data collection. Although the prevalence of vitamin A deficiency in Bangladesh has been considerably lower in the 1990s than it was in the 1980s, it is still prevalent at all socioeconomic levels. Supplementation with high-dose VACs is an effective strategy for reducing night blindness, but the efficiency of the program will improve when coverage in the rural areas increases.

Bangladesh↗

A new approach to the design of a sequence with the highest affinity for a molecular surface.

We describe an algorithm to design the primary structures for peptides which must have the strongest binding to a given molecular surface. This problem cannot be solved by a direct combinatorial sorting, because of an enormous number of possible primary and spatial structures. The approach to solve this problem is to describe a state of each residue by two variables: (i) amino acid type and (ii) 3-D coordinate, and to minimize binding energy over all these variables simultaneously. For short chains which have no long-range interactions within themselves, this minimization can be done easily and efficiently by dynamic programming. We also discuss the problem of how to estimate specificity of binding and how to deduce a sequence with maximal specificity for a given surface. We show that this sequence can be deduced by the same algorithm after some modification of energetic parameters.

Algorithms↗

Teamwork in home infusion therapy: the relationship between nursing and pharmacy.

To admit a client to a home infusion therapy program effectively and efficiently, all of the parties involved must take part in the planning process and decision making. The registered nurse and pharmacist are not the only players on the home healthcare team involved in planning for home infusion therapy, but their relationship is especially critical for a smooth transition to the home setting. Good communication between the nurse and pharmacist and a basic understanding of responsibilities are keys to successful coordination of care delivery. But communication can be challenging when the pharmacist and nurse do not work in the same physical location, which is often the case.

Community Health Nursing↗

Strategies to promote medication adherence in children with asthma.

Asthma, the most common chronic disease in childhood, continues to be associated with high rates of morbidity and mortality, despite improved treatment protocols. Lack of adherence to individual treatment plans has been implicated in these poor outcomes. The purpose of this article is to assist the nurse in identifying obstacles that might limit adherence to treatment, and offer practical suggestions for promoting adherence in pediatric patients. The reasons that children and children's families fail to adhere to individual treatment plans include financial barriers, misconceptions about asthma, cultural influences, and mistaken health beliefs. In addition, family education about asthma management can be inadequate. An efficiently run asthma program, which includes family education, easy telephone access to the provider, prompt attention during exacerbations, and frequent follow-up, can improve adherence. By eliminating barriers to adherence and maintaining open communication and consistent positive support, nurses can help children with asthma attain and maintain the highest quality of life.

Anti-Asthmatic Agents↗

The "third" dimension in craniofacial surgery.

A new method for reconstruction of a three-dimensional surface from a sequence of high-resolution axial CT scans has been developed. This algorithm is realized as a set of computer programs that can operate on commercially available CT scanners or evaluation consoles. The program is both efficient and easy to implement. No operator intervention is required. The images produced simulate photographs of the skull. Frontal, lateral, oblique, bird's eye, worm's eye, and rear views are generated. As with photographs and conventional radiographs, each of these projections uniquely displays specific anatomic details. This method of osseous surface reconstruction is now routinely applied to all patients evaluated for major craniofacial reconstruction at our institution. The images are useful in defining aberrant anatomy, planning surgical procedures, and evaluating the results of such operations. This method replaces an inexact concept in the surgeon's imagination with a three-dimensional image of the craniofacial skeleton.

Adolescent↗

Effectiveness of screening for cervical cancer in an inpatient hospital setting.

OBJECTIVE: To estimate the effectiveness of an inpatient, hospital-based cervical cancer screening program at a single institution. METHODS: Between January 1999 and December 2002, 1,117 women admitted to the Johns Hopkins Hospital underwent Papanicolaou (Pap) test screening during their hospital stay. In that time period, 111,933 women were screened at all of the combined Hopkins outpatient clinics. We compared rates of abnormal Pap tests in these cohorts (retrospective cohort study). Our main outcome measure was the prevalence of abnormal Pap tests among the screening population by age group, ethnicity, and insurance status compared between our outpatient and inpatient populations. RESULTS: The prevalence of abnormal Pap tests in the inpatient cohort was twice as high as that in the outpatient setting (15.5% versus 7%). The prevalence of high-grade squamous intraepithelial lesions (HSIL), the immediate precursor lesion to cervical cancer, was nearly 5-fold higher in the inpatient cohort compared with the outpatient cohort (3% versus 0.7%). In multivariable models, younger women had greater risk for all types of abnormal Pap tests, and black women had greater risk for HSIL. Previous abnormal Pap and human immunodeficiency virus-positive status were associated with all abnormal tests and with HSIL results. CONCLUSIONS: A hospital-based, inpatient Pap test program is an efficient strategy for targeting limited screening funds toward women at high risk of invasive cervical cancer. LEVEL OF EVIDENCE: II-2

Adolescent↗

Re-evaluating selective screening criteria for chlamydial infection among women in the U S Pacific Northwest.

OBJECTIVES: Screening women for Chlamydia trachomatis (CT) infection using selective screening criteria has been operational in the northwestern United States (Region X) since 1988. Changes in the field, including declines in CT prevalence, introduction of sensitive laboratory tests, and budgetary pressures necessitate reevaluating the selective screening approach to ensure program credibility and efficiency. GOALS: The goals of this study were to assess 1). performance of screening criteria in Region X, 2). predictors of CT infection, and 3). optimization of these criteria. STUDY DESIGN: We conducted cross-sectional analysis of 409882 CT test records of women from 1998 to 2000 using multivariate logistic regression and sensitivity and efficiency analyses. RESULTS: Young age (<25 yrs), cervical signs of infection, and recent exposure to or history of chlamydial infection were strongly associated with testing positive. Behavioral risks showed a weak association with infection. Currently used selective screening criteria were sensitive but not efficient. Criteria weighted toward young age, exposure to chlamydia, or cervicitis would increase criteria efficiency by nearly 25% in some settings while detecting >90% of infections. CONCLUSION: Evaluating selective screening criteria can result in modifications that could increase screening efficiency.

Adolescent↗

Correlation between the Carbon Isotope Discrimination in Leaf Starch and Sugars of C(3) Plants and the Ratio of Intercellular and Atmospheric Partial Pressures of Carbon Dioxide.

Carbon isotope discrimination (Delta) was analyzed in leaf starch and soluble sugars, which represent most of the recently fixed carbon. Plants of three C(3) species (Populus nigra L. x P. deltoides Marsh., Gossypium hirsutum L. and Phaseolus vulgaris L.) were kept in the dark for 24 hours to decrease contents of starch and sugar in leaves. Then gas exchange measurements were made with constant conditions for 8 hours, and subsequently starch and soluble sugars were extracted for analysis of carbon isotope composition. The ratio of intercellular, p(i), and atmospheric, p(a), partial pressures of CO(2), was calculated from gas exchange measurements, integrated over time and weighted by assimilation rate, for comparison with the carbon isotope ratios in soluble sugars and starch. Carbon isotope discrimination in soluble sugars correlated strongly (r = 0.93) with p(i)/p(a) in all species, as did Delta in leaf starch (r = 0.84). Starch was found to contain significantly more (13)C than soluble sugar, and possible explanations are discussed. The strong correlation found between Delta and p(i)/p(a) suggests that carbon isotope analysis in leaf starch and soluble sugars may be used for monitoring, indirectly, the average of p(i)/p(a) weighted by CO(2) assimilation rate, over a day. Because p(i)/p(a) has a negative correlation with transpiration efficiency (mol CO(2)/mol H(2)O) of isolated plants, Delta in starch and sugars may be used to predict differences in this efficiency. This new method may be useful in ecophysiological studies and in selection for improved transpiration efficiency in breeding programs for C(3) species.

Journal Article↗

Complaints management--in-depth review.

Introduces the Complaints Manager program from Health-TEC to address the problems involved in complaints management and control in the health service. Shows the main screens available for data input. Demonstrates the wide range of reports which can be generated. Suggests that the Complaints Manager program provides an efficient and low-cost means of keeping complaints under control.

Cost-Benefit Analysis↗

Simulation and animation of sensor-driven robots.

Most simulation and animation systems utilized in robotics are concerned with simulation of the robot and its environment without simulation of sensors. These systems have difficulty in handling robots that utilize sensory feedback in their operation. In this paper, a new design of an environment for simulation, animation, and visualization of sensor-driven robots is presented. As sensor technology advances, increasing numbers of robots are equipped with various types of sophisticated sensors. The main goal of creating the visualization environment is to aid the automatic robot programming and off-line programming capabilities of sensor-driven robots. The software system will help the users visualize the motion and reaction of the sensor-driven robot under their control program. Therefore, the efficiency of the software development is increased, the reliability of the software and the operation safety of the robot are ensured, and the cost of new software development is reduced. Conventional computer-graphics-based robot simulation and animation software packages lack of capabilities for robot sensing simulation. This paper describes a system designed to overcome this deficiency.

Artificial Intelligence↗