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PubMed2005

WindowMasker: window-based masker for sequenced genomes.

MOTIVATION: Matches to repetitive sequences are usually undesirable in the output of DNA database searches. Repetitive sequences need not be matched to a query, if they can be masked in the database. RepeatMasker/Maskeraid (RM), currently the most widely used software for DNA sequence masking, is slow and requires a library of repetitive template sequences, such as a manually curated RepBase library, that may not exist for newly sequenced genomes. RESULTS: We have developed a software tool called WindowMasker (WM) that identifies and masks highly repetitive DNA sequences in a genome, using only the sequence of the genome itself. WM is orders of magnitude faster than RM because WM uses a few linear-time scans of the genome sequence, rather than local alignment methods that compare each library sequence with each piece of the genome. We validate WM by comparing BLAST outputs from large sets of queries applied to two versions of the same genome, one masked by WM, and the other masked by RM. Even for genomes such as the human genome, where a good RepBase library is available, searching the database as masked with WM yields more matches that are apparently non-repetitive and fewer matches to repetitive sequences. We show that these results hold for transcribed regions as well. WM also performs well on genomes for which much of the sequence was in draft form at the time of the analysis. AVAILABILITY: WM is included in the NCBI C++ toolkit. The source code for the entire toolkit is available at ftp://ftp.ncbi.nih.gov/toolbox/ncbi_tools++/CURRENT/. Once the toolkit source is unpacked, the instructions for building WindowMasker application in the UNIX environment can be found in file src/app/winmasker/README.build. SUPPLEMENTARY INFORMATION: Supplementary data are available at ftp://ftp.ncbi.nlm.nih.gov/pub/agarwala/windowmasker/windowmasker_suppl.pdf

Algorithms↗

PubMed1994

Presentation of colour flow maps of the peripheral circulation.

The use of continuous wave Doppler ultrasound for lower limb arterial assessment is a well established technique in most district hospitals. Patients found to have disturbances in blood flow attributable to arterial plaques are often referred for arteriographic visualization of the disease with its inherent risks and complications. The availability of colour flow mapping on modern ultrasound scanners provides a non-invasive way of detecting the size and extent of these plaques and, in some institutions, is replacing arteriography. One possible disadvantage of the use of colour flow mapping is that it does not provide a permanent record showing the relationship of the plaques to the patient's gross anatomy in the same way as arteriography. This may limit the acceptability of this technique. At Lincoln work was undertaken to develop a system for presenting images of a whole segment of a limb simultaneously along with the associated blood velocity spectrum. This was performed first by hand and then a suite of computer software was developed to automate the process. Comparisons were made between the ultrasound based images and arteriography, showing the techniques to be of similar diagnostic value. The technique provides composite images showing anatomical detail, blood flow and velocity spectra for ease of interpretation. Further studies will be undertaken in order to define patient groups where diagnostic arteriography can be avoided.

Color↗

PubMed2005

Short communication: A method for verified access when using soft copy display.

Soft copy display is a rapidly developing area. To date, most soft copy systems can be classed by their application, e.g. review or reporting. With technology convergence this distinction is becoming less defined by the hardware and more defined by the software functionality. Although it is accepted that routine quality assurance should be conducted on soft copy monitors, this would be logistically difficult to achieve if any monitor within a hospital could be used for image review or reporting. This work proposes a simple psychophysical check to ensure optimal display performance before viewing software can be run. This is in the form of a challenge/response code constructed from letters just above the threshold of detection. This verified login would act as a portal to launching the image viewing software. The developed system was tested on three different types of monitor and five observers. Results indicate that the verified login was able to control access for displays below the optimal settings but was not as sensitive for adjustments above the optimum. However it is believed this is still of value as the lower presentation will compress the display gamma curve and reduce detail contrast. It also provides a minimum level of audit and quality control that might otherwise be missing.

Computer Communication Networks↗

PubMedDate not supplied

[Artificial intelligence--the knowledge base applied to nephrology].

The idea that efficacy efficiency, and quality in medicine could not be reached without sorting the huge knowledge of medical and nursing science is very common. Engineers and computer scientists have developed medical software with great prospects for success, but currently these software applications are not so useful in clinical practice. The medical doctor and the trained nurse live the 'information age' in many daily activities, but the main benefits are not so widespread in working activities. Artificial intelligence and, particularly, export systems charm health staff because of their potential. The first part of this paper summarizes the characteristics of 'weak artificial intelligence' and of expert systems important in clinical practice. The second part discusses medical doctors' requirements and the current nephrologic knowledge bases available for artificial intelligence development.

Artificial Intelligence↗

PubMed2003

Minimum specific cost control of technological processes realized in a living objects-containing microenvironment.

The purpose of the present work is to work out an approach for the development of software and the choice of hardware structures when designing subsystems for automatic control of technological processes realized in living objects containing limited space (microenvironment). The subsystems for automatic control of the microenvironment (SACME) under development use the Devices for Air Prophylactic Treatment, Aeroionization, and Purification (DAPTAP) as execution units for increasing the level of safety and quality of agricultural raw material and foodstuffs, for reducing the losses of agricultural produce during storage and cultivation, as well as for intensifying the processes of activation of agricultural produce and industrial microorganisms. A set of interconnected SACMEs works within the framework of a general microenvironmental system (MES). In this research, the population of baker's yeast is chosen as a basic object of control under the industrial fed-batch cultivation in a bubbling bioreactor. This project is an example of a minimum cost automation approach. The microenvironment optimal control problem for baker's yeast cultivation is reduced from a profit maximum to the maximization of overall yield by the reason that the material flow-oriented specific cost correlates closely with the reciprocal value of the overall yield. Implementation of the project partially solves a local sustainability problem and supports a balance of microeconomical, microecological and microsocial systems within a technological subsystem realized in a microenvironment maintaining an optimal value of economical criterion (e.g. minimum material, flow-oriented specific cost) and ensuring: (a) economical growth (profit increase, raw material saving); (b) high security, safety and quality of agricultural raw material during storage process and of food produce during a technological process; elimination of the contact of gaseous harmful substances with a subproduct during various technological stages; (c) improvement of labour conditions for industrial personnel from an ecological point of view (positive effect of air aeroionization and purification on human organism promoting strengthened health and an increase in life duration, pulverent and gaseous chemical and biological impurity removal). An alternative aspect of a controlled living microenvironment forming is considered.

Agriculture↗

PubMed2005

SplitTester: software to identify domains responsible for functional divergence in protein family.

BACKGROUND: Many protein families have undergone functional divergence after gene duplications such that current subgroups of the family carry out overlapping but distinct biological roles. For the protein families with known functional subtypes (a functional split), we developed the software, SplitTester, to identify potential regions that are responsible for the observed distinct functional subtypes within the same protein family. RESULTS: Our software, SplitTester, takes a multiple protein sequences alignment as input, generated from protein members of two subgroups with known functional divergence. SplitTester was designed to construct the neighbor joining tree (a split cluster) from variable-sized sliding windows across the alignment in a process called split-clustering. SplitTester identifies the regions, whose split cluster is consistent with the functional split, but may be inconsistent with the phylogeny of the protein family. We hypothesize that at least some number of these identified regions, which are not following a random mutation process, are responsible for the observed functional split. To test our method, we used reverse transcriptase from a group of Pseudoviridae retrotransposons: to identify residues specific for diverged primer recognition. Candidate regions were then mapped onto the three dimensional structures of reverse transcriptase. The locations of these amino acids within the enzyme are consistent with their biological roles. CONCLUSION: SplitTester aims to identify specific domain sequences responsible for functional divergence of subgroups within a protein family. From the analysis of retroelements reverse transcriptase family, we successfully identified the regions splitting this family according to the primer specificity, implying their functions in the specific primer selection.

Algorithms↗

PubMed1998

Efficacy outcome and sex difference in learning of hypermedia programming skills.

86 occupational therapy students participated in a 20-hr, training course in hypermedia programming for selecting functions for development of rehabilitation software. Analyses showed that the training program significantly enhanced their self-efficacy in development of software for clinical practice. The students generally showed a positive attitude towards the feasibility and significance of applying hypermedia programming in occupational therapy, but no significant sex difference in programming self-efficacy was found.

Adolescent↗

PubMed2002

Evaluating Australia's National Medicines Policy using geographical mapping.

BACKGROUND: There has been a proliferation of quality use of medicines activities in Australia since the 1990s. However, knowledge of the nature and extent of these activities was lacking. A mechanism was required to map the activities to enable their coordination. AIMS: To develop a geographical mapping facility as an evaluative tool to assist the planning and implementation of Australia's policy on the quality use of medicines. METHODS: A web-based database incorporating geographical mapping software was developed. Quality use of medicines projects implemented across the country was identified from project listings funded by the Quality Use of Medicines Evaluation Program, the National Health and Medical Research Council, Mental Health Strategy, Rural Health Support, Education and Training Program, the Healthy Seniors Initiative, the General Practice Evaluation Program and the Drug Utilisation Evaluation Network. In addition, projects were identified through direct mail to persons working in the field. RESULTS: The Quality Use of Medicines Mapping Project (QUMMP) was developed, providing a Web-based database that can be continuously updated. This database showed the distribution of quality use of medicines activities by: (i) geographical region, (ii) project type, (iii) target group, (iv) stakeholder involvement, (v) funding body and (vi) evaluation method. At September 2001, the database included 901 projects. Sixty-two per cent of projects had been conducted in Australian capital cities, where approximately 63% of the population reside. Distribution of projects varied between States. In Western Australia and Queensland, 36 and 73 projects had been conducted, respectively, representing approximately two projects per 100,000 people. By comparison, in South Australia and Tasmania approximately seven projects per 100,000 people were recorded, with six per 100,000 people in Victoria and three per 100,000 people in New South Wales. Rural and remote areas of the country had more limited project activity. CONCLUSIONS: The mapping of projects by geographical location enabled easy identification of high and low activity areas. Analysis of the types of projects undertaken in each region enabled identification of target groups that had not been involved or services that had not yet been developed. This served as a powerful tool for policy planning and implementation and will be used to support the continued implementation of Australia's policy on the quality use of medicines.

Australia↗

PubMed2004

Aperture maneuver with compelled breath (AMC) for moving tumors: a feasibility study with a moving phantom.

Respiration causes target motion, which is known to be one of the technical bottlenecks in radiotherapy, especially for stereotactic radio-surgery and intensity modulated radiotherapy (IMRT). To overcome this problem, aperture maneuver with compelled breath (AMC) has been developed. In order to simulate compelled respiratory motion, a moving phantom using a ventilator was designed. As the air flow was forced to the bellows, which simulates the lungs, by a ventilator, a film connected to the ventilator moved like the respiratory target motion. A software was developed to transfer multileaf collimator motion from breathless to actual periodic breathing conditions. Static fields as well as step-and-shoot IMRT fields were modified in accordance with moving shapes to follow the target position, using the software with the controlled breathing information. Film dosimetry for a small field and for IMRT fields with a moving phantom was performed. To evaluate clinical implementation, five healthy volunteers were tested to breathe through a ventilator, and all of them could adapt the compelled breath without any difficulties. Additive margins for a moving target with AMC were not larger than 3 mm for respiratory organ motions up to 18 mm, while those with the static beam were 9 mm. For IMRT fields, large discrepancies were present between a static target and a moving target with the static beam, while they coincided well with AMC. Clinical acceptable differences between the dose distributions from a static target with the static beam and from a moving target with AMC revealed that this technique could be applied clinically.

Algorithms↗

PubMed1986

High-performance digital image analyzer for quantitative autoradiography.

A digital image-processing system was developed for high-spatial resolution analysis of autoradiograms. The system uses a linear array of charge-coupled devices operating under computer control to scan and digitize autoradiograms into 512 X 512 matrices with 256 gray levels. Software was developed to facilitate quantitative analysis of autoradiograms produced in single- and multiple-tracer studies. Because of the high output, linearity, and accuracy of the solid-state detectors, the system was found to digitize autoradiograms significantly more precisely and accurately than previously described video camera- or photomultiplier tube-based scanning densitometers.

Autoradiography↗

PubMed2003

New approaches to drug discovery and development: a mechanism-based approach to pharmaceutical research and its application to BNP7787, a novel chemoprotective agent.

Any approach applied to drug discovery and development by the medical community and pharmaceutical industry has a direct impact on the future availability of improved, novel, and curative therapies for patients with cancer. By definition, drug discovery is a complex learning process whereby research efforts are directed toward uncovering and assimilating new knowledge to create and develop a drug for the purpose of providing benefit to a defined patient population. Accordingly, a highly desirable technology or approach to drug discovery should facilitate both effective learning and the application of newly discovered observations that can be exploited for therapeutic benefit. However, some believe that drug discovery is largely accomplished by serendipity and therefore appropriately addressed by screening a large number of compounds. Clearly, this approach has not generated an abundance of new drugs for cancer patients and suggests that a tangibly different approach in drug discovery is warranted. We employ an alternative approach to drug discovery, which is based on the elucidation and exploitation of biological, pharmacological, and biochemical mechanisms that have not been previously recognized or fully understood. Mechanism-based drug discovery involves the combined application of physics-based computer simulations and laboratory experimentation. There is increasing evidence that agreement between simulations based on the laws of physics and experimental observations results in a higher probability that such observations are more accurate and better understood as compared with either approach used alone. Physics-based computer simulation applied to drug discovery is now considered by experts in the field to be one of the ultimate methodologies for drug discovery. However, the ability to perform truly comprehensive physics-based molecular simulations remains limited by several factors, including the enormous computer-processing power that is required to perform the formidable mathematical operations and data processing (e.g. memory bandwidth, data storage and retrieval). Another major consideration is the development of software that can generate an appropriate and increasingly complex physical representation of the atomic arrangements of biological systems. During the past 17 years, we have made tremendous progress in addressing some of these obstacles by developing and optimizing physics-based computer programs for the purpose of obtaining increasingly accurate and precise information and by improving the speed of computation. To perform physics-based simulations that involve complex systems of biological and pharmaceutical interest, we have developed methods that enable us to exceed Moore's law. This has been accomplished by parallel processing as well as other methods that have enabled us to study more complex and relevant molecular systems of interest. This paper provides an overview of our approach to drug discovery and describes a novel drug, currently in clinical development, which has directly resulted from the application of this approach.

Animals↗

PubMed2004

ArrayD: a general purpose software for microarray design.

BACKGROUND: Microarray is a high-throughput technology to study expression of thousands of genes in parallel. A critical aspect of microarray production is the design aimed at space optimization while maximizing the number of gene probes and their replicates to be spotted. RESULTS: We have developed a software called 'ArrayD' that offers various alternative design solutions for an array given a set of user requirements. The user feeds the following inputs: type of source plates to be used, number of gene probes to be printed, number of replicates and number of pins to be used for printing. The solutions are stored in a text file. The choice of a design solution to be used will be governed by the spotting chemistry to be used and the accuracy of the robot. CONCLUSIONS: ArrayD is a software for standard cartesian robots. The software aids users in preparing a judicious and elegant design. ArrayD is universally applicable and is available at http://www.igib.res.in/scientists/arrayd/arrayd.html.

Computational Biology↗

PubMed2006

The development and validation of the Virtual Tissue Matrix, a software application that facilitates the review of tissue microarrays on line.

BACKGROUND: The Tissue Microarray (TMA) facilitates high-throughput analysis of hundreds of tissue specimens simultaneously. However, bottlenecks in the storage and manipulation of the data generated from TMA reviews have become apparent. A number of software applications have been developed to assist in image and data management; however no solution currently facilitates the easy online review, scoring and subsequent storage of images and data associated with TMA experimentation. RESULTS: This paper describes the design, development and validation of the Virtual Tissue Matrix (VTM). Through an intuitive HTML driven user interface, the VTM provides digital/virtual slide based images of each TMA core and a means to record observations on each TMA spot. Data generated from a TMA review is stored in an associated relational database, which facilitates the use of flexible scoring forms. The system allows multiple users to record their interpretation of each TMA spot for any parameters assessed. Images generated for the VTM were captured using a standard background lighting intensity and corrective algorithms were applied to each image to eliminate any background lighting hue inconsistencies or vignetting. Validation of the VTM involved examination of inter-and intra-observer variability between microscope and digital TMA reviews. Six bladder TMAs were immunohistochemically stained for E-Cadherin, beta-Catenin and PhosphoMet and were assessed by two reviewers for the amount of core and tumour present, the amount and intensity of membrane, cytoplasmic and nuclear staining. CONCLUSION: Results show that digital VTM images are representative of the original tissue viewed with a microscope. There were equivalent levels of inter-and intra-observer agreement for five out of the eight parameters assessed. Results also suggest that digital reviews may correct potential problems experienced when reviewing TMAs using a microscope, for example, removal of background lighting variance and tint, and potential disorientation of the reviewer, which may have resulted in the discrepancies evident in the remaining three parameters.

Algorithms↗

PubMed1996

Telepathological (image transmission) configuration.

The Laboratory for Biomedical Informatics (LBMI) has developed a digital microscope control module incorporated into an image analysis system. This is now equipped with an ISDN switch box for linking up with a remote computer-based station for delivering histopathological services. The FRAME, client/server integrated software, was developed to initiate the communication link, adjust the microscope settings, acquire and transmit images. This LBMI telepathology initiative employs simple solutions to arrive at the point of prototyping and demonstrating the state of the art on the one hand and encountering the prevailing problems in order to deliberate on possible remedies on the other.

Computer Communication Networks↗

PubMed2004

Non-invasive detection of coronary artery disease by a newly developed high-frequency QRS electrocardiogram.

Compared to other non-invasive methods, the conventional 12-lead electrocardiogram (ECG) has low sensitivity and specificity for identifying coronary artery disease (CAD). We compared the newly developed high-frequency QRS electrocardiogram (HFQRS ECG, 150-250 Hz) with adenosine sestamibi myocardial perfusion study (MPI)-the most sensitive non-invasive study in cardiology practice. Using advanced 12-lead computer-based ECG software recently developed at NASA, criteria for a positive 12-lead HFQRS-ECG test for obstructive CAD were developed using 300 signal-averaged beats from patients undergoing elective coronary angiograms for evaluation of chest pain. These criteria, which rely strictly upon the presence or the absence of morphologic 'reduced amplitude zones' (RAZs) and not upon the 'root mean squared' (RMS) voltage amplitudes of the HFQRS complexes, were then applied prospectively to 18 patients undergoing MPI. Active CAD was considered present when reversible ischemic defects were present on MPI. Of the 18 patients, 9 had reversible defects on MPI (positive scan), whereas the other 9 had no reversible perfusion defects (negative scan). Patients with a positive nuclear study went on to coronary angiography confirming CAD, except in one patient who had nonobstructive coronary disease (<50% stenosis). Eight of the 18 subjects therefore had active CAD, whereas 10 were judged not to have active CAD. The 12-lead HFQRS-ECG result was consistent with nuclear scan results in 14 of 18 patients. The HFQRS-ECG and nuclear results differed in: (1) one patient who had a low score positive MPI, negative HFQRS-ECG and normal coronary angiogram; (2) one patient who had a small reversible anterior wall perfusion defect, 60% LAD lesion on angiogram but a negative HF-QRS result; and (3) two individuals who had positive HFQRS-ECG results in the face of negative nuclear scans but who did not undergo angiography. 12-lead HFQRS ECG had excellent sensitivity (87.5% based on 7/8 true positives correctly identified) and specificity (no worse than 80%, >8/10 true negatives correctly identified) for identifying CAD. 12-lead HFQRS ECG is an easily performed, inexpensive and potentially widely available technique that utilizes the same leads and electrodes as the conventional 12-lead ECG. It had accuracy comparable to MPI in this study. Resting 12-lead HFQRS ECG appears to be a very promising non-invasive technique for identifying CAD and may represent a viable alternative to many of the more expensive and time-consuming techniques presently utilized for non-invasively identifying CAD.

Aged↗

PubMed1990

[Present level of software production for the use of microcomputers, PCh's and terminals in the stomatology of the GDR].

The informatics team of the Stomatological Society of the GDR provides a complete list of presently available program packages for home, 8 and 16-bit computers and a list of the programming teams. Main developments for the use of PC's in stomatology are described as well. By establishing clear lines for the development of software, standardized user software can be guaranteed.

Dental Instruments↗

PubMed1998

Magnetic resonance imaging of cerebral central sulci: a study of monozygotic twins.

The cerebral central sulci, seat of the sensorimotor cortex, vary anatomically in form, length and depth among individuals and present a left/right asymmetry. The purpose of this work was to measure central sulcus's lengths, at the surface and in-depth, in each hemisphere of monozygotic twins in order to evaluate the influence of environmental factors on the morphometry and asymmetry of this structure. A measurement technique on MR images of the brains using 3 D software was developed. Two operators applied this technique to measure central sulcus lengths at the surface of the brain and in-depth in each hemisphere. Besides the fact that the technique developed gave high Intraclass Correlation Coefficients (ICC) for the surface lengths (mean value 0.94), and slightly less high for the in-depth length (mean value 0.87), we found a weak (from 0.57 to 0.73 for raw data) but significant ICC between homologous sulci in pairs of twins. In addition, the ICC for asymmetry indices were not significant. Hence, if central sulcus morphometry is in part genetically influenced, these results show that nongenetic factors are nonetheless important in their development.

Adult↗

PubMed1992

Real-time quantitative elemental analysis and mapping: microchemical imaging in cell physiology.

Recent advances in widely available microcomputers have made the acquisition and processing of digital quantitative X-ray maps of one to several cells readily feasible. Here we describe a system which uses a graphics-based microcomputer to acquire spectrally filtered X-ray elemental image maps that are fitted to standards, to display the image in real time, and to correct the post-acquisition image map with regard to specimen drift. Both high-resolution quantitative energy-dispersive X-ray images of freeze-dried cyrosections and low-dose quantitative bright-field images of frozen-hydrated sections can be acquired to obtain element and water content from the same intracellular regions. The software programs developed, together with the associated hardware, also allow static probe acquisition of data from selected cell regions with spectral processing and quantification performed on-line in real time. In addition, the unified design of the software program provides for off-line processing and analysing by several investigators at microcomputers remote from the microscope. The overall experimental strategy employs computer-aided imaging, combined with static probes, as an essential interactive tool of investigation for biological analysis. This type of microchemical microscopy facilitates studies in cell physiology and pathophysiology which focus on mechanisms of ionic (elemental) compartmentation, i.e. structure-function correlation at cellular and subcellular levels; it allows investigation of intracellular concentration gradients, of the heterogeneity of cell responses to stimuli, of certain fast physiological events in vivo at ultrastructural resolution, and of events occurring with low incidence or involving cell-to-cell interactions.

Animals↗