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Inturned localizes to the proximal side of wing cells under the instruction of upstream planar polarity proteins.

Planar polarity development in the Drosophila wing is under the control of the frizzled (fz) pathway. Recent work has established that the planar polarity (PP) proteins become localized to either the distal, proximal, or both sides of wing cells. Fz and Dsh distal accumulation is thought to locally activate the cytoskeleton to form a hair . Planar polarity effector (PPE) genes such as inturned (in) are not required for the asymmetric accumulation of PP proteins, but they are required for this to influence hair polarity. in mutations result in abnormal hair polarity and are epistatic to mutations in the PP genes. We report that In localizes to the proximal side of wing cells in a PP-dependent and PP-instructive manner. We further show that the function of two other PPE genes (fuzzy and fritz) is essential for In protein localization, a finding consistent with previous genetic data that suggested these three genes function in a common process. These data indicate that accumulation of proteins at the proximal side of wing cells is a key event for the distal activation of the cytoskeleton to form a hair.

Animals↗

Triple-target microarray experiments: a novel experimental strategy.

BACKGROUND: High-throughput, parallel gene expression analysis by means of microarray technology has become a widely used technique in recent years. There are currently two main dye-labelling strategies for microarray studies based on custom-spotted cDNA or oligonucleotides arrays: (I) Dye-labelling of a single target sample with a particular dye, followed by subsequent hybridisation to a single microarray slide, (II) Dye-labelling of two different target samples with two different dyes, followed by subsequent co-hybridisation to a single microarray slide. The two dyes most frequently used for either method are Cy3 and Cy5. We propose and evaluate a novel experiment set-up utilising three differently labelled targets co-hybridised to one microarray slide. In addition to Cy3 and Cy5, this incorporates Alexa 594 as a third dye-label. We evaluate this approach in line with current data processing and analysis techniques for microarrays, and run separate analyses on Alexa 594 used in single-target, dual-target and the intended triple-target experiment set-ups (a total of 18 microarray slides). We follow this by pointing out practical applications and suitable analysis methods, and conclude that triple-target microarray experiments can add value to microarray research by reducing material costs for arrays and related processes, and by increasing the number of options for pragmatic experiment design. RESULTS: The addition of Alexa 594 as a dye-label for an additional--third--target sample works within the framework of more commonplace Cy5/Cy3 labelled target sample combinations. Standard normalisation methods are still applicable, and the resulting data can be expected to allow identification of expression differences in a biological experiment, given sufficient levels of biological replication (as is necessary for most microarray experiments). CONCLUSION: The use of three dye-labelled target samples can be a valuable addition to the standard repertoire of microarray experiment designs. The method enables direct comparison between two experimental populations as well as measuring these two populations in relation to a third reference sample, allowing comparisons within the slide and across slides. These benefits are only offset by the added level of consideration required in the experimental design and data processing of a triple-target study design. Common methods for data processing and analysis are still applicable, but there is scope for the development of custom models for triple-target data. In summary, we do not consider the triple-target approach to be a new standard, but a valuable addition to the existing microarray study toolkit.

Animals↗

Population estimates from longitudinal records in otherwise data-deficient settings.

Existing methods for estimating population parameters in settings of data deficiency do not provide techniques for analysis of commonly available longitudinal data. In setting where complete population data is unavailable, longitudinal data recorded for only a subset of the total population are often available (e.g., event registers, genealogies). In this article we present and evaluate models which derive population parameters for the population subgroup underlying such longitudinal data. Using the distribution of individual times until first recorded event within a measurement interval, population parameters are estimated which provide basic denominator data for analyzing event occurrence. The models which we derive are especially suited to records which may include migration and population growth trends. The use of the models is demonstrated and evaluated through an application to genealogical records for a nineteenth-century population. Possible extensions of these models and their major limitations are also discussed.

Adult↗

[A simple biostatistical method for meta analysis of the data on 2 x 2 table].

Meta-analysis is a method in common use for data analysis in evidence-based medicine. In this paper, based on the Mantel-Haenszel and Peto methods used for Meta-analysis of the data on 2 x 2 table, we put forward a simple calculating method for clinicians. It is useful for Meta-analysis and can be easily applied to analysis of the data from multi-studies in evidence-based medicine.

Biometry↗

Effects of resolution reduction on data analysis.

BACKGROUND: There is often a need in flow cytometry to display and analyze histograms at resolutions lower than those native to the data. It is common, for example, to analyze DNA histograms at 256-channel resolution, even though the data were acquired at 1,024 channels or more. The most common method for reducing resolution, referred to as the consecutive summation (CS) method, can introduce distortions into the shape of histograms. Peaks that were symmetric in the original data can become skewed in the reduced-resolution histogram. Data analysis can be negatively affected by the distortions produced by reducing the histogram resolution. An alternative technique for reducing histogram resolution, the unbiased summation (US) method, minimizes shape distortion. This paper describes the US method and examines the benefits it provides in the analysis of DNA histograms. METHODS: Reduced chi-square (RCS) was used to measure the response to three experimental variables in the least-squares analysis of simulated DNA histograms. For each variable (the percentage of coefficient of variation [%CV], number of events, and mean position of the G1 distribution), a test data set of 1,000 histograms was generated at 1,024-channel resolution. Histogram resolutions were reduced with each method and then analyzed with ModFit LT cell-cycle analysis software (Verity Software House, Topsham, ME). S-phase error and processor computation time of each method also were evaluated. A Monte Carlo experiment was performed to compare CS and US methods to theoretically correct reductions. RESULTS: CS method analysis results were negatively affected by changes in %CV, number of events, and G1 peak position. The US method produced consistently lower RCS values (more accurate results) within the tested ranges. The US method eliminated bias in S-phase error and had negligible impact on analysis processing speed. It improved RCS values 44.50% on average (P < 0.0002) with actual DNA histograms. Whereas the CS method became less accurate (chi-square test) as the amount of reduction increased, the US method was unaffected, producing consistently better results. CONCLUSIONS: The US method is recommended for reducing histogram resolution in modeling applications such as DNA cell-cycle analysis. It may have implications in other areas of flow cytometric data analysis.

Algorithms↗

Utility of routinely acquired primary care data for paediatric disease epidemiology and pharmacoepidemiology.

BACKGROUND: The majority of medicines prescribed for children are prescribed in primary care for common acute and chronic conditions. This is in contrast to prescribing in secondary care where the population of children admitted is small but where a large number of different medicines are prescribed to treat more serious and less common conditions. METHODS: Data on prescribing was extracted from the General Practice Administration System for Scotland (GPASS) for the year November 1999 to October 2000 and prescribing patterns for children aged 0-16 years expressed as percentages. A comparison of age specific consultations for asthma, as an example of a common paediatric condition, was also made between two separate general practice data sets, the General Practice Research Database (GRPD) and the continuous morbidity recording (CMR) subset of GPASS. RESULTS: Of 214 medicines investigated for unlicensed and off-label prescribing no unlicensed prescribing was identified. Off-label prescribing due to age was most common among younger and older children. The most common reasons for off-label prescriptions were, in order of frequency, lower than recommended dose, higher than recommended dose, below the recommended age, and unlicensed formulation. Age and gender specific consultations for asthma were similar in the two representative databases, GPRD and CMR, both showing disappearance of the male predominance in the teenage years. CONCLUSIONS: Large primary care data sets available within a unified health care system such as the UK National Health Service (NHS) are likely to be broadly compatible and produce similar results. The prescribing of off-label medicines to children is common in primary care, most commonly due to prescribing out with the recommended dosage regimen.

Adolescent↗

New insights into myosin evolution and classification.

Myosins are eukaryotic actin-dependent molecular motors important for a broad range of functions like muscle contraction, vision, hearing, cell motility, and host cell invasion of apicomplexan parasites. Myosin heavy chains consist of distinct head, neck, and tail domains and have previously been categorized into 18 different classes based on phylogenetic analysis of their conserved heads. Here we describe a comprehensive phylogenetic examination of many previously unclassified myosins, with particular emphasis on sequences from apicomplexan and other chromalveolate protists including the model organism Toxoplasma, the malaria parasite Plasmodium, and the ciliate Tetrahymena. Using different phylogenetic inference methods and taking protein domain architectures, specific amino acid polymorphisms, and organismal distribution into account, we demonstrate a hitherto unrecognized common origin for ciliate and apicomplexan class XIV myosins. Our data also suggest common origins for some apicomplexan myosins and class VI, for classes II and XVIII, for classes XII and XV, and for some microsporidian myosins and class V, thereby reconciling evolutionary history and myosin structure in several cases and corroborating the common coevolution of myosin head, neck, and tail domains. Six novel myosin classes are established to accommodate sequences from chordate metazoans (class XIX), insects (class XX), kinetoplastids (class XXI), and apicomplexans and diatom algae (classes XXII, XXIII, and XXIV). These myosin (sub)classes include sequences with protein domains (FYVE, WW, UBA, ATS1-like, and WD40) previously unknown to be associated with myosin motors. Regarding the apicomplexan "myosome," we significantly update class XIV classification, propose a systematic naming convention, and discuss possible functions in these parasites.

Animals↗

Lectindb: a plant lectin database.

Lectins, a class of carbohydrate-binding proteins, are now widely recognized to play a range of crucial roles in many cell-cell recognition events triggering several important cellular processes. They encompass different members that are diverse in their sequences, structures, binding site architectures, quaternary structures, carbohydrate affinities, and specificities as well as their larger biological roles and potential applications. It is not surprising, therefore, that the vast amount of experimental data on lectins available in the literature is so diverse, that it becomes difficult and time consuming, if not impossible to comprehend the advances in various areas and obtain the maximum benefit. To achieve an effective use of all the data toward understanding the function and their possible applications, an organization of these seemingly independent data into a common framework is essential. An integrated knowledge base ( Lectindb, http://nscdb.bic.physics.iisc.ernet.in ) together with appropriate analytical tools has therefore been developed initially for plant lectins by collating and integrating diverse data. The database has been implemented using MySQL on a Linux platform and web-enabled using PERL-CGI and Java tools. Data for each lectin pertain to taxonomic, biochemical, domain architecture, molecular sequence, and structural details as well as carbohydrate and hence blood group specificities. Extensive links have also been provided for relevant bioinformatics resources and analytical tools. Availability of diverse data integrated into a common framework is expected to be of high value not only for basic studies in lectin biology but also for basic studies in pursuing several applications in biotechnology, immunology, and clinical practice, using these molecules.

Algorithms↗

On the medical informatics structure.

This paper contributes to the discussion of R. Haux paper on essential aims and tasks of medical informatics. New views on structure of informatics and consequently medical informatics are given. Information is introduced as outside and inside information. Inside information is divided into three different types as data, evidence and knowledge. This terminology slightly differs from the commonly used terminology data, information and knowledge. Based on understanding of information as outside and inside information the field of informatics is divided into four rings, namely Information Basic Ring, Information Methodology Ring, Information Interface Ring and Information Technology Ring. Medical informatics is defined and its structure explained using four information rings. These views on informatics and medical informatics open possibilities to see more clearly where are the essential aims and tasks of medical informatics.

Europe↗

Analyzing yeast protein-protein interaction data obtained from different sources.

High-throughput methods for detecting protein interactions, such as mass spectrometry and yeast two-hybrid assays, continue to produce vast amounts of data that may be exploited to infer protein function and regulation. As this article went to press, the pool of all published interaction information on Saccharomyces cerevisiae was 15,143 interactions among 4,825 proteins, and power-law scaling supports an estimate of 20,000 specific protein interactions. To investigate the biases, overlaps, and complementarities among these data, we have carried out an analysis of two high-throughput mass spectrometry (HMS)-based protein interaction data sets from budding yeast, comparing them to each other and to other interaction data sets. Our analysis reveals 198 interactions among 222 proteins common to both data sets, many of which reflect large multiprotein complexes. It also indicates that a "spoke" model that directly pairs bait proteins with associated proteins is roughly threefold more accurate than a "matrix" model that connects all proteins. In addition, we identify a large, previously unsuspected nucleolar complex of 148 proteins, including 39 proteins of unknown function. Our results indicate that existing large-scale protein interaction data sets are nonsaturating and that integrating many different experimental data sets yields a clearer biological view than any single method alone.

Chromatography, Liquid↗

Adolescents with cancer: getting on with life.

This phenomenologic study was designed to understand and describe the experiences of adolescents living with cancer. The study was conducted with a sample of five adolescents 13 to 17 years old, who had received or were receiving treatments for cancer. Data were collected during audiotaped interviews and were analyzed for common themes. The data showed that the adolescents' overall goal was to get on with life. The teenagers responded to cancer by experiencing the illness and determining that they were normal. They developed a philosophy of being positive and redefined their social world in order to get on with life. Understanding the manner in which adolescents with cancer experience living with this illness may enable health care practitioners to provide appropriate care to the teenager with cancer. Implications for practice, research, and education are discussed.

Adaptation, Psychological↗

Design and implementation of microarray gene expression markup language (MAGE-ML).

BACKGROUND: Meaningful exchange of microarray data is currently difficult because it is rare that published data provide sufficient information depth or are even in the same format from one publication to another. Only when data can be easily exchanged will the entire biological community be able to derive the full benefit from such microarray studies. RESULTS: To this end we have developed three key ingredients towards standardizing the storage and exchange of microarray data. First, we have created a minimal information for the annotation of a microarray experiment (MIAME)-compliant conceptualization of microarray experiments modeled using the unified modeling language (UML) named MAGE-OM (microarray gene expression object model). Second, we have translated MAGE-OM into an XML-based data format, MAGE-ML, to facilitate the exchange of data. Third, some of us are now using MAGE (or its progenitors) in data production settings. Finally, we have developed a freely available software tool kit (MAGE-STK) that eases the integration of MAGE-ML into end users' systems. CONCLUSIONS: MAGE will help microarray data producers and users to exchange information by providing a common platform for data exchange, and MAGE-STK will make the adoption of MAGE easier.

Computer Simulation↗

Using a geographic information system to identify areas with potential for off-target pesticide exposure.

In many countries, numerous tests are required as part of the risk assessment process before chemical registration to protect human health and the environment from unintended effects of chemical releases. Most of these tests are not based on ecological or environmental relevance but, rather, on consistent performance in the laboratory. A conceptual approach based on Geographic Information System (GIS) technology has been developed to identify areas that are vulnerable to nontarget chemical exposure. This GIS-based approach uses wind speed, frequency of those winds, pesticide application rates, and spatial location of agricultural crops to identify areas with the highest potential for pesticide exposure. A test scenario based on an incident in Idaho (USA) was used to identify the relative magnitude of risk from off-target movement of herbicides to plants in the conterminous United States. This analysis indicated that the western portion of the Corn Belt, the central California valley, southeastern Washington, the Willamette Valley of Oregon, and agricultural areas bordering the Great Lakes are among those areas in the United States that appear to have the greatest potential for off-target movement of herbicides via drift. Agricultural areas, such as the Mississippi River Valley and the southeastern United States, appears to have less potential, possibly due to lower average wind speeds. Ecological risk assessments developed for pesticide registration would be improved by using response data from species common to high-risk areas instead of extrapolating test data from species unrelated to those areas with the highest potential for exposure.

Environmental Pollutants↗

An integrated data-warehouse-concept for clinical and biological information.

The development of medical research networks within the framework of translational research has fostered interest in the integration of clinical and biological research data in a common database. The building of one single database integrating clinical data and biological research data requires a concept which enables scientists to retrieve information and to connect known facts to new findings. Clinical parameters are collected by a Patient Data Management System and viewed in a database which also includes genomic data. This database is designed as an Entity Attribute Value model, which implicates the development of a data warehouse concept. For the realization of this project, various requirements have to be taken into account which has to be fulfilled sufficiently in order to align with international standards. Data security and protection of data privacy are most important parts of the data warehouse concept. It has to be clear how patient pseudonymization has to be carried out in order to be within the scope of data security law. To be able to evaluate the data stored in a database consisting of clinical data collected by a Patient Data Management System and genomic research data easily, a data warehouse concept based on an Entity Attribute Value datamodel has been developed.

Computer Security↗

A comparative study of two nutrient data bases.

Reported dietary intake records of 18 infants, 22 young children, and 20 women were analyzed using the nutrient data base systems of the Second National Health and Nutrition Examination Survey (NHANES II) and the Nutrient Dietary Data Analysis (NDDA) System. Significant differences between the nutrient data bases were found in the calculations of potassium and niacin for infants and of energy and nine nutrients for women and children. The energy and nutrient composition of many commonly consumed food items in the two nutrient data base systems was different, even though the systems shared common data sources. Differences in the nutrient data bases were primarily due to the timing of data base updates, as well as to the differential use of industry, private, and government food analysis sources, procedural differences in data base updating, and random data entry error. Resolution of differences among nutrient data base systems may depend upon comprehensive reviews of all data base systems or the establishment of a national nutrient data base to serve as a standard for the professional.

Child, Preschool↗

Visualization of fibrous and thread-like data.

Thread-like structures are becoming more common in modern volumetric data sets as our ability to image vascular and neural tissue at higher resolutions improves. The thread-like structures of neurons and micro-vessels pose a unique problem in visualization since they tend to be densely packed in small volumes of tissue. This makes it difficult for an observer to interpret useful patterns from the data or trace individual fibers. In this paper we describe several methods for dealing with large amounts of thread-like data, such as data sets collected using Knife-Edge Scanning Microscopy (KESM) and Serial Block-Face Scanning Electron Microscopy (SBF-SEM). These methods allow us to collect volumetric data from embedded samples of whole-brain tissue. The neuronal and microvascular data that we acquire consists of thin, branching structures extending over very large regions. Traditional visualization schemes are not sufficient to make sense of the large, dense, complex structures encountered. In this paper, we address three methods to allow a user to explore a fiber network effectively. We describe interactive techniques for rendering large sets of neurons using self-orienting surfaces implemented on the GPU. We also present techniques for rendering fiber networks in a way that provides useful information about flow and orientation. Third, a global illumination framework is used to create high-quality visualizations that emphasize the underlying fiber structure. Implementation details, performance, and advantages and disadvantages of each approach are discussed.

Anatomy, Cross-Sectional↗

Are the common reference intervals truly common? Case studies on stratifying biochemical reference data by countries using two partitioning methods.

The Harris-Boyd method, recommended for partitioning biochemical reference data into subgroups by the NCCLS, and a recently proposed new method for partitioning were compared in three case studies concerning stratification by countries (Denmark, Finland, Norway, and Sweden) of reference data collected in the Nordic Reference Interval Project (NORIP) for the enzymes alkaline phosphatase (ALP), creatine kinase (CK), and gamma-glutamyl transpeptidase (GGT). The new method is based on direct estimation of the proportions of two subgroups outside the reference limits of the combined distribution, while the Harris-Boyd method uses easy-to-calculate test parameters as correlates for these proportions. The decisions on partitioning suggested by the Harris-Boyd method deviated from those obtained by using the new method for each of the three enzymes when considering pair-wise partitioning tests. The reasons for the poor performance, as it seems to be, of the Harris-Boyd method were discussed. Stratification of reference data into more than two subgroups was considered as both a theoretical problem and a practical one, using the four country-specific distributions for each enzyme as illustration. Neither the Harris-Boyd method nor the new method seems ideal to solve the partitioning problem in the case of several subgroups. The results obtained by using prevalence-adjusted values for the proportions seemed, however, to warrant the conclusion to be made that there are no major differences in terms of the partitioning criteria between the levels of each of the three enzymes in the four countries. Because these three enzymes include those two tests (CK, GGT), which in the preliminary analyses of the project data had shown largest variation between countries, the tentative conclusion was drawn that application of common reference intervals in the Nordic countries is feasible, not only for the three enzymes examined in the present study but for all of the tests involved in the NORIP project.

Chemistry, Clinical↗

Comparison of a commercially available clinical information system with other methods of measuring critical care outcomes data.

PURPOSE: To compare the quality of data recorded by a commercially available clinical information system (CIS) to other commonly used methods for obtaining large amounts of patient data. MATERIALS AND METHODS: Five sets of clinical patient data were chosen as a cross-section of all the data collected by a CIS in our intensive care unit (ICU): 1) Length of stay in the ICU, 2) Vital signs, 3) Days of mechanical ventilation, 4) medications, and 5) diagnoses. Data generated by our ICU CIS was compared with other parallel data sets commonly used to obtain the same data for clinical research. RESULTS: When compared with our CIS, the hospital database recorded a length of stay at least 1 day longer than the actual length of stay 53% of the time. A search of 139,387 sets of vital signs showed less than 0.1% rate of suspected artifact. When compared to direct observation, our CIS correctly recorded days of mechanical ventilation in 23 of 26 patients (88%). Two other data sets, medical diagnoses and medications given showed significant differences with other commonly used databases of the same information collected outside the ICU (billing codes and pharmacy records respectively CONCLUSIONS: Compared to other commonly used data sources for clinical research, a commercially available CIS is an acceptable source of ICU patient data.

Decision Support Systems, Clinical↗