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A control study to evaluate a computer-based microarray experiment design recommendation system for gene-regulation pathways discovery.

The main topic of this paper is evaluating a system that uses the expected value of experimentation for discovering causal pathways in gene expression data. By experimentation we mean both interventions (e.g., a gene knock-out experiment) and observations (e.g., passively observing the expression level of a "wild-type" gene). We introduce a system called GEEVE (causal discovery in Gene Expression data using Expected Value of Experimentation), which implements expected value of experimentation in discovering causal pathways using gene expression data. GEEVE provides the following assistance, which is intended to help biologists in their quest to discover gene-regulation pathways: Recommending which experiments to perform (with a focus on "knock-out" experiments) using an expected value of experimentation (EVE) method. Recommending the number of measurements (observational and experimental) to include in the experimental design, again using an EVE method. Providing a Bayesian analysis that combines prior knowledge with the results of recent microarray experimental results to derive posterior probabilities of gene regulation relationships. In recommending which experiments to perform (and how many times to repeat them) the EVE approach considers the biologist's preferences for which genes to focus the discovery process. Also, since exact EVE calculations are exponential in time, GEEVE incorporates approximation methods. GEEVE is able to combine data from knock-out experiments with data from wild-type experiments to suggest additional experiments to perform and then to analyze the results of those microarray experimental results. It models the possibility that unmeasured (latent) variables may be responsible for some of the statistical associations among the expression levels of the genes under study. To evaluate the GEEVE system, we used a gene expression simulator to generate data from specified models of gene regulation. Using the simulator, we evaluated the GEEVE system using a randomized control study that involved 10 biologists, some of whom used GEEVE and some of whom did not. The results show that biologists who used GEEVE reached correct causal assessments about gene regulation more often than did those biologists who did not use GEEVE. The GEEVE users also reached their assessments in a more cost-effective manner.

Animals↗

Development of a specimen holder for in situ generation of pure in-plane magnetic fields in a transmission electron microscope.

As the development of quantised storage media progresses, detailed knowledge is required about the magnetisation reversal behaviour of sub-micron sized magnetic structures in external magnetic fields. Using the Lorentz mode of transmission electron microscopy (LTEM) the magnetic microstructure of thin film samples can be imaged with high spatial resolution. A novel approach for in situ magnetising experiments is described which combines the development of a custom-made sample holder which generates two orthogonal in-plane components of magnetic field in the specimen plane with the benefit of computer-controlled variation of the field. We present a specimen stage suitable for a Philips CM30 Twin/LTEM, which allows the generation of well-defined magnetic in-plane fields in the TEM.

Electromagnetic Fields↗

Concepts to automate the theoretical design of effective antisense oligonucleotides.

Among the large number of possible antisense species against a given target RNA, only a small number shows effective suppression of the target gene in living cells. In the case of short-chain antisense oligonucleotides (asON) which usually comprise less than approximately 25 nucleotides, local structures of the target RNA seem to be of particular importance for the extent of gene suppression. Experimental approaches to identify promising local target sequences and, hence, complementary asON sequences, have provided tools to define asON that are biologically active at higher than statistical probability. However, experimental protocols are expensive, time consuming, and are associated with intrinsic basic and technical limitations. As insights into the structure-function relationship of asON as well as the role of sequence motifs increase, it becomes feasible to consider computer-based theoretical approaches for the design of effective asON. In the following we describe how individual steps of the theoretical design of asON may be automated by establishing and implementing suitable algorithms.

Algorithms↗

Vortex core identification in viscous hydrodynamics.

We describe a software package designed for the investigation of topological fluid dynamics with a novel algorithm for locating and tracking vortex cores. The package is equipped with modules for generating desired vortex knots and links and evolving them according to the Navier-Stokes equations, while tracking and visualizing them. The package is parallelized using a message passing interface for a multiprocessor environment and makes use of a computational steering library for dynamic user intervention.

Algorithms↗

Quality of reporting of diagnostic accuracy studies.

PURPOSE: To evaluate quality of reporting in diagnostic accuracy articles published in 2000 in journals with impact factor of at least 4 by using items of Standards for Reporting of Diagnostic Accuracy (STARD) statement published later in 2003. MATERIALS AND METHODS: English-language articles on primary diagnostic accuracy studies in 2000 were identified with validated search strategy in MEDLINE. Articles published in journals with impact factor of 4 or higher that regularly publish articles on diagnostic accuracy were selected. Two independent reviewers evaluated quality of reporting by using STARD statement, which consists of 25 items and encourages use of a flow diagram. Total STARD score for each article was calculated by summing number of reported items. Subgroup analyses were performed for study design (case-control or cohort study) by using Student t tests for continuous outcomes and chi(2) tests for dichotomous outcomes. RESULTS: Included were 124 articles published in 2000 in 12 journals: 33 case-control and 91 cohort studies. Only 41% of articles (51 of 124) reported on more than 50% of STARD items, while no articles reported on more than 80%. A flow chart was presented in two articles. Assessment of reporting on individual items of STARD statement revealed wide variation, with some items described in 11% of articles and others in 92%. Mean STARD score (0-25 points available) was 11.9 (range, 3.5-19.5). Mean difference in STARD score between cohort studies and case-control studies was 1.53 (95% confidence interval: 0.24, 2.82). CONCLUSION: Quality of reporting in diagnostic accuracy articles published in 2000 is less than optimal, even in journals with high impact factor. Authors, editors, and reviewers should pay more attention to reporting by checking STARD statement items and including a flow diagram to represent study design and patient flow.

Case-Control Studies↗

RealSpot: software validating results from DNA microarray data analysis with spot images.

The spot images from DNA microarray highly affect the discovery of biological knowledge from gene expression data. However, results from quality analysis, normalization, differential expression, and cluster analysis are rarely validated with spot images in current data analysis methods or software packages. We designed RealSpot, a software package, to validate the results by directly associating spot quality and data with spot images in a spreadsheet table. RealSpot splits hybridization images into individual spots stored in a spreadsheet table. It subsequently associates microarray data with spot images and performs data validation through the standard table operation such as sorting, searching, and editing. RealSpot has several built-in functions to facilitate data validation, including spot quality analysis, data organization, one-way ANOVA, gene ontology association, verification, import, and export. We used RealSpot to evaluate 77 slides (30,000 features each) from real hybridization experiments and to validate results from each step of data analysis. It took approximately 10 min to validate results of spot quality after initial evaluation and correct approximately 0.3% of falsely assigned qualities of 10,000 spots. We validated 1,641 of 2,110 differentially expressed genes identified by SAM analysis in approximately 1/2 h by comparing each gene with its respective spot image. Furthermore, we found that 6 of 48 genes in one cluster from k-mean clustering method showed inconsistent trends of spot images. RealSpot is efficient for validating microarray results and thus helpful for improving the reliability of the whole microarray experiment for experimentalists.

Algorithms↗

An educational hypertext system supporting radiographic image quality.

Understanding the physical and technical factors affecting image characteristics is an essential learning task in the process of optimizing radiographic image quality. The goal of the present effort is the design of a stand-alone software application acting as an educational aid to radiology residents and radiographers. The application is organized in three modules, each one offering a different approach to the learning task. The core of the system is a hypertext database management system composed of text, digitized radiographs, graphics and animations. User orientation, linking, indexing, and annotation are some of the facilities offered in pursuing topics of interest.

Computer Graphics↗

[Research on real-time data collection and demonstration system for acupuncture manipulation].

OBJECTIVE: To apply the real-time data collection and demonstration system for acupuncture manipulation to quantitative analysis of acupuncture manipulation for acupuncture teaching and research. METHODS: The real-time observation and analysis of parameter changes of acupuncture manipulation were implemented by this system. RESULTS: During the course of lifting and thrusting manipulation, the needle body moved in a uniform variable motion, and the action force was still kept while the arrival of Qi was achieved. During the course of twirling manipulation, the variations of twirling number and radian caused the changes of resistance moment, and this reaction was related to the body response. During the course of rotating and shaking manipulation, the radius for rotating and shaking was related to such factors as the force, the action point and the direction. CONCLUSION: The real-time data collection and demonstration system for acupuncture manipulation can provide a new experimental method for quantitative data analysis, standardized research and teaching demonstration of acupuncture.

Acupuncture↗

An open and flexible framework for computer aided surgical training.

During the past year we have developed a new surgical skills training application called LapSim. We intend to describe the design, architecture and concepts of the software framework we have developed concurrently with the application. The framework is based on the concept of a classroom with students and teachers. Students, courses and results are stored in a centralized database and can be retrieved for review or modification. The students can also monitor their progress relative to other students or experts.

Computer Systems↗

[The development of an oral biomechanical testing instrument].

An oral biomechanical testing instrument, which is portable, powered with batteries and controlled by single chip microcomputer, was described. The instrument was characterized by its multichannel, high accuracy, low power dissipation, wide rage of force measurement and stable performance. It can be used for acquisiting, displaying and storing data. And it may be expected to be an ideal instrument for oral biomechanical measurements.

Diagnosis, Oral↗

[An experimental study of the computer-controlled equipment for delivering volatile anesthetic agent].

Our newly-designed computer-controlled equipment for delivering volatile anesthetic agent uses the subminiature singlechip processor as the central controlling unit. The variables, such as anesthesia method, anesthetic agent, the volume of respiratory loop, age of patient, sex, height, weight, environment temperature and the grade of ASA are all input from the keyboard. The anesthetic dosage, calculated by the singlechip processor, is converted into the signals controlling the pump to accurately deliver anesthetic agent into respiratory loop. We have designed an electrocircuit for the equipment to detect the status of the pump's operation, so we can assure of the safety and the stability of the equipment. The output precision of the equipment, with a good anti-jamming capability, is 1-2% for high flow anesthesia and 1-5% for closed-circuit anesthesia and its self-detecting working is reliable.

Anesthesia, Closed-Circuit↗

Teaching problem handling in general practice: a computer assisted learning software package for medical students.

A computer assisted learning software package for medical students, EnMesh, designed to increase understanding of the problem-handling skills needed in general practice has been developed at the University of Liverpool. Users access the system anonymously and respond in sequence to problems in the form of clinical vignettes. Responses to each problem, in the form of up to six two-line text statements, are generated by the user with a simple word processing facility. Users compare their responses with those of established general practitioners, searching for similar or matching ideas. After completing not less than four problems users are provided with feedback on their performance in relation to the physical, psychological and social dimensions of the problems. The frequency with which the system is being used and the results of self scoring are monitored by a parallel teacher programme. The programmes are designed to run on a wide range of microcomputers. EnMesh was designed to provide an informal learning resource within an established clinical course. The challenge of valid problems, the option to respond anonymously, self scoring and feedback on performance are features designed to attract student participation in computer assisted learning. Although in EnMesh the expert data is categorized in three dimensions, in designing such software the number of categories is limited solely by the range of responses which feedback is required to reflect.

Computer-Assisted Instruction↗

Prosthetic heart valves--the integration of analysis with design.

In this paper some of the issues associated with the application of computational fluid dynamics (CFD) to the design of prosthetic heart valves are discussed. The intentions are to emphasise that, for best effect, the analysis should integrate smoothly into the design process, and to illustrate the usefulness of the technique in providing detailed spatial and temporal resolution of quantities that are otherwise difficult to measure. The vehicle for the discussion is a chronological review of some valve analyses performed by the Sheffield group over the period from 1990 to 1994.

Biomedical Engineering↗

POPED, a software for optimal experiment design in population kinetics.

Population kinetic analysis is the methodology used to quantify inter-subject variability in kinetic studies. It entails the collection of (possibly sparse) data from dynamic experiments in a group of subjects and their quantitative interpretation by means of a mathematical model. This methodology is widely used in the pharmaceutical industry (where it is termed "pharmacokinetic population analysis") and recently it is becoming increasingly used in other areas of biomedical research. Unlike traditional kinetic studies, where the number of subjects can be quite small, population kinetic studies require large numbers of subjects. It is, therefore, of great interest to design these studies in the most efficient manner possible, to maximize the information content provided by the data. In this paper we propose an algorithm and a computer program, POPED, for the optimal design of a population kinetic experiment. In particular, the number of samples for each subject and the design of the individual sampling strategies, i.e. the number and location of the time points at which the output variable is sampled, will be considered. Among the various criteria proposed in the literature, D and ED optimality are the ones implemented in our software program, since they are the most widely used. A brief description of the techniques employed to perform design optimization is given, together with some details on their actual implementation. Some examples are then presented to show the program usage and the results provided.

Algorithms↗

Recent enhancements to the MARS15 code.

The MARS code is under continuous development and has recently undergone substantial improvements that further increase its reliability and predictive power in numerous shielding, accelerator, detector and space applications. The major developments and new features of the MARS15 (2004) version described in this paper concern an extended list of elementary particles and arbitrary heavy ions and their interaction cross sections, inclusive and exclusive nuclear event generators, module for modelling particle electromagnetic interactions, enhanced geometry and histogramming options, improved MAD-MARS Beam Line Builder, enhanced graphical user interface and an MPI-based parallelisation of the code.

Algorithms↗

Parallelising the MARS15 code with MPI for shielding applications.

The MARS15 Monte Carlo code capabilities to deal with time-consuming deep penetration shielding problems and other computationally tough tasks in accelerator, detector and shielding applications, have been enhanced by a parallel processing option. It has been developed, implemented and tested on the Fermilab Accelerator Division Linux cluster and network of Sun workstations. The code uses a message passing interface MPI. It is scalable and demonstrates good performance. The general architecture of the code, specific uses of message passing and effects of a scheduling on the performance and fault tolerance are described.

Algorithms↗