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Computer programs for the analysis and the management of DNA sequences.

A program package is described for the management and the analysis of DNA sequence data. The programs - with the exception of a few Fortran routines - are written in the programming language APL. They are best used interactively although batch processing is possible. The package has been in constant use for about 3 years and contains programs for most of the routine problems presently found in a DNA sequencing laboratory.

Amino Acid Sequence

NOTIS: an operating theatre information system.

Solutions to straightforward resource management problems need not always involve the use of complex, specialised and expensive software solutions. Commercially available 'off the shelf' packages have increased in flexibility and ease of use, and are usually an order of magnitude cheaper than their custom designed counterparts. In response to a request for a low cost database suitable to be used on a stand-alone microcomputer system, the widely available integrated software package Smart was used. The program specification required quantification and analysis of the workload in a medium sized operating theatre suite (at 6,000 cases/year) to be undertaken. In addition to providing Database, Spreadsheet and Wordprocessor modules, each with rapid and easy exchange of data from one module to another, Smart incorporates its own programming language. This may be used to build up complex series of instructions for data manipulation, to generate menus and create a naive user front end to the finished program. Although an adequate knowledge of database construction and basic programming are necessary, professional programming skills are not required. NOTIS, the Newham Operating Theatre Information System, is a menu driven program designed to be used by clerical staff, and accepting patient data derived from within the operating theatre. At the end of each month a set of predetermined reports are produced. These reports are designed to provide information on the workload, case type and medical personnel involvement applicable to theatre managers, anaesthetists and surgical staff.

Information Systems

VTM--an image-processing system for measuring ocular torsion.

This paper reports a new, fast, accurate realization of an image-processing method of measuring ocular torsion (rotation of the eyeball around the visual axis) called Video Torsion Measurement (VTM). The method is to cross-correlate the two grey-level distributions of an arc of the iris from two separate images using a fast image processor card interfaced to an IBM-AT compatible computer. The card (Matrox MVP-AT) is supplied with a library of low-level functions for controlling the hardware operations of the board and the VTM system software, which is written in the C programming language, incorporates these low-level functions to interface with the MVP-AT board as well as carrying out the data-acquisition and processing algorithms. These programs: acquire an image of an iris illuminated by a single infrared (IR) light source; threshold this image in order to identify the pupil; calculate the pupil area and locate the centre of the pupil using a centre-of-gravity algorithm; record the grey-level distribution along an arc 256 pixels long at a selected radius from the pupil centre; carry out an FFT on this (interpolated) grey level distribution; store the parameters of this reference FFT and cross-correlate the comparable iral grey-level distribution from other test images of the same eye in order to determine the amount of torsional rotation of the test images relative to the reference image. This system is interactive and is designed for operation in a clinical testing situation with a minimum of operator intervention. The VTM system has a resolution of the order of 0.1 deg depending on the arc radius used and it has been validated in two ways: by using it to measure known torsional rotations of an artificial iris-like pattern and also by direct simultaneous comparison of measures on the same human iris images from VTM and those from the standard 35 mm photographic procedure of measuring torsion.

Eye Movements

Improved programs for DNA and protein sequence analysis on the IBM personal computer and other standard computer systems.

We have previously described programs for a variety of types of sequence analysis (1-4). These programs have now been integrated into a single package. They are written in the standard C programming language and run on virtually any computer system with a C compiler, such as the IBM/PC and other computers running under the MS/DOS and UNIX operating systems. The programs are widely distributed and may be obtained from the authors as described below.

Amino Acid Sequence

Computer program for the IBM personal computer which searches for approximate matches to short oligonucleotide sequences in long target DNA sequences.

We describe a program which may be used to find approximate matches to a short predefined DNA sequence in a larger target DNA sequence. The program predicts the usefulness of specific DNA probes and sequencing primers and finds nearly identical sequences that might represent the same regulatory signal. The program is written in the C programming language and will run on virtually any computer system with a C compiler, such as the IBM/PC and other computers running under the MS/DOS and UNIX operating systems. The program has been integrated into an existing software package for the IBM personal computer (see article by Mount and Conrad, this volume). Some examples of its use are given.

Base Sequence

[Automatic identification of structural gene fragments using a set of peptides].

A computer program is designed to facilitate the identification of coding gene's fragments using a set of peptides. The program is written on Basic programming language for personal computer "Iskra-226" (USSR). To accelerate some operations, computer code commands are used. Treatment of 50 DNA fragments by means of 10 peptides takes ca. 1 h of computer time. The program outputs list coding gene's fragments and corresponding peptides. The suggested algorithm is based on our finding that the number of false identifications of a coding gene fragments may be predicted by Poisson distribution and minimized using correct criteria. The suggested method enables one to evaluate the reliability of the true identification of DNA fragments in case of mistakes in primary structure of the gene fragments or peptides.

3',5'-Cyclic-GMP Phosphodiesterases

Language and cognitive development: a systematic behavioral program and technology for increasing the language and cognitive skills of developmentally disabled and at-risk preschool children.

Behavioral research in teaching verbal behavior to language-delayed and developmentally disabled preschool children has progressed greatly during the past 30 years. It is now possible to produce improvements in the verbal behavior of language-delayed and developmentally disabled children that previously would have been considered impossible. Not only is it possible to teach language-delayed children a wide variety of individual elements and forms of speech, such as plurals, adjectives, syntax, and grammar, but it is also possible to achieve functional language in nonverbal children and produce total recovery in some autistic and functionally mentally retarded preschool children. The results of our research with the TALK Language Development Program provide techniques, procedures, and new directions to further advance the technology of verbal behavior. First, development of a standard procedure for the analysis, reinforcement, and recording of verbal behavior provides a precise and standard method for evaluating the effect of contingencies of reinforcement on verbal behavior. Second, the TALK program, by systematizing and operationalizing the process of shaping functional language, provides a program that is relatively easily learned by therapists, teachers, speech pathologists, and others. Third, the robustness and reliability of the TALK program, as demonstrated by replication across diagnostic groups, settings, and therapists, makes it an attractive program for use with a variety of developmentally disabled children. Fourth, the identification of specific parent-child reinforcement paradigms that appear to be functionally related to language delay may facilitate research in the prevention of language delay. Finally, our research with functionally retarded children and normal infants has led to the development of a behavioral strategy and technology for the prevention of and total recovery from some cases of language delay and functional mental retardation. At least two important opportunities now exist for making a substantial social impact through the technology of verbal behavior. First, the passage of Public Law 99-457 has created a major need for effective language programs that can be used by public school teachers of handicapped preschool children. The need will increase as more programs for the birth to 3 population are mandated. This presents a major opportunity for transferring the technology of verbal behavior to other professionals who are in daily contact with young handicapped preschool children, such as teachers, speech pathologists, pediatricians, and social workers.(ABSTRACT TRUNCATED AT 400 WORDS)

Autistic Disorder

Pattern matching of biological sequences with limited storage.

Existing methods for getting the locally best matched alignments between a pair of biological sequences require O(N2) computational steps and O(N2) storage, where N is the average sequence length. An improved method is presented with which the storage requirement is greatly reduced, while the computational steps remain O(N2). Only a small number of additional steps are required to display any common sub-sequences with similarity scores greater than a given threshold. The aligments found by the algorithm are optimal in the sense that their scores are locally maximal, where each score is a sum of weights given to individual matches/replacements, insertions and deletions involved in the alignment. The algorithm was implemented in C programming language on a personal computer. Data area of 64 kbytes on random access memory and a few hundred kbytes on a disk is sufficient for comparing two protein or nucleic acid sequences of 2500 residues. The programs are particularly valuable when used in combination with fast sequence search programs.

Algorithms

A versatile computing system for sampling, manipulation and display of biological signals using high-level language.

A medium sized minicomputer system is presented as an attractive way of balancing the cost of computing equipment with that of programme development. A versatile circuit has been coupled to a computer system and programmes have been developed to control the functions of this circuit. With such a system it is possible for relatively untrained biological workers to use FORTRAN programming language to control sampling of analogue signals, manipulation of data and finally graphical presentation of results. The system is proposed for use both in anaesthetic research and in on-line monitoring of critically ill patients.

Analog-Digital Conversion

Problems in applying expert system technology to radiographic image interpretation.

A prototype expert system was developed to study the problems applying expert system technology to radiographic image interpretation. The Radiographic Image Interpretation System (RIIS) was developed on a microcomputer using Turbo Prolog, a low cost implementation of the prolog programming language. The present implementation of RIIS was developed to highlight potential problems in applying expert system technology in the evaluation of radiographic images. It was believed that the evaluation of this prototype expert system should include a large number of users unfamiliar with the program's use as this would probably be the case in clinical use of an image interpretation expert system. At present, the expert system deals with a limited domain of focal bony lesions. Twenty cases of pathologically proven bony lesions of varying difficulty were used to evaluate potential problems in the use of this expert system technology. RIIS, with the 20 sample cases, was presented as an exhibit at the 1987 Radiological Society of North America (RSNA) meeting to evaluate the potential problems with inexperienced users. These results were compared with those of experienced users. When a musculoskeletal radiologist, familiar with the programs use, provided the "proper description," the program averaged the correct diagnosis in the top five 80% of the time. During the program's use at the RSNA meeting, the program selected the correct diagnosis in the top five 22% of the time.

Bone Neoplasms

Recombinant DNA laboratory data manager using DBASE III+.

The use of recombinant DNA technology in clinical and research laboratories involves diverse information management functions such as keeping track of patient samples, blot membranes, polymerase chain reaction products and test results. We report here the use of a PC-based database manager (DBASE III+, Ashton-Tate) for the coordinated maintenance of these functions. We have implemented a menu driven interface, developed using DBASE's programming language, which provides a data entry and maintenance system. The system is easily learned by technologists and saves time and reduces data handling errors compared to a manual method. The system can rapidly look up data and produce customized worksheets or reports correlating all available clinical and laboratory information. We will provide a copy of the program disc to interested parties.

DNA, Recombinant

Mlab--a mathematical modeling tool.

An interactive interpreter called Mlab is described. One uses Mlab by typing commands. In this sense, Mlab is a programming language. It has various mathematical and graphical facilities which make it a useful tool for mathematical modeling. The curve fitting capabilities of Mlab are augmented with differential-equation-handling and matrix-manipulation capabilities which provide a powerful and civilized facility for curve fitting. Many people are engaged in this activity, and, in general, they use programs which are neither sufficiently general nor easy to use. (Some conventional programming is usually required, for example.) Mlab purports to be easier than alternate approaches. The nature of Mlab is discussed with accompanying examples. The main example is the use of curve fitting to determine molecular weight from ultracentrifuge data. This example was chosen because it exhibits a special feature of Mlab, namely the root operator, which appears in the definition of the model function.

Computers

Computer-based tutorial in MR imaging.

PURPOSE: To test the effectiveness of customized software as a teaching tool to help the novice understand basic physics concepts underlying the creation of MR images via various pulse sequences. METHODS: The authors have developed animating graphic and highly interactive electronic MR audiovisual software for the Macintosh computer in the C programming language, and have integrated it into the classroom setting for teaching MR imaging physics concepts such as T1, T2, T2*, proton density, RF excitation, TR, TE, TI, flip angle, static magnetic field strength, gradient magnetic fields, section thickness, number of phase-encoding gradients, number of excitations, field of view, intersection gap, receiver bandwidth, contrast agent(s), etc. The program interactively demonstrates the effects of these variables upon such imaging objectives as voxel dimensions, section quantity, total scanned volume, signal-to-noise ratio, contrast, contrast-to-noise ratios, resolving power, and scan acquisition time. Partial saturation, gradient echo, inversion recovery, and fat-saturation imaging techniques are included. Written posttests on the syllabus covered in our basic MR course were administered to three groups: 43 student professionals (technologist/physicist/radiologist) (control professional group) before, 149 student professionals (exposed professional group) after the addition of the tutorial software into the MR course as an integral part of the teaching process, and a group of 200 pharmaceutical sales staff with little to no prior MR or scientific background (exposed pharmaceutical group). The scores were then evaluated and compared among the groups. One hundred ten students exposed to this software also anonymously rated the software on a 1 to 5 scale (harmful to very helpful, respectively) as to their feeling regarding its role in their MR educational experience and the ease with which they were able to understand the material covered in the basic MR course curriculum. RESULTS: Mean test scores were statistically significantly lower in the Control Professional Group (60%, +/- 2.59 standard error of the mean (SEM)) than in either the Exposed Pharmaceutical (73% +/- 0.75 SEM) or Exposed Professional Groups (77% +/- 0.99 SEM). The mean subjective assessment score regarding the software was 4.8 (scale 1 to 5). CONCLUSION: This custom-developed interactive MR tutorial software is demonstrated to be effective in assisting even those new to MR imaging in understanding the concepts underlying MR imaging physics in a manner that is felt to be significantly more palatable than lectures, articles, and/or textbooks alone.

Computer-Assisted Instruction

[Language acquisition in CLP children. 3. Results].

Following part I "Fundamentals" and part II "Procedures", this third part presents the findings about language acquisition and the conditions governing this process in 315 CLP children. It has been shown that early language programs for CLP families leads to the linguistic rehabilitation of these children before they reach school age. Semantically and syntactically complex sentences at the age of 2-3 years results in good articulation at age 5-6. Early precision of articulation is usually associated with an increased risk for psychosomatic complications. The complexity of the cleft at birth is of minor importance for language acquisition, whereas early treatment, parents' compliance and avoidance of corrections and sensitizations are decisive for the successful course of the child's language development at the age of 5-6 years.

Child

Computer-aided management of hypertensive patients.

A computerized system has been developed which potentially enables a single expert physician to monitor a large number of hypertensive patients being seen at distant locations. The patients may receive their care directly from primary care physicians or nurse-physician surrogates. Primary care physicians can use the same data bank to monitor their own panels of patients. These goals are accomplished through a special purpose, interactive programming language which can be used to perform sophisticated data retrieval along different complexes of parameters. The physician is able to query the computer, via a terminal, about any group of patient he defines and have displayed to him the clinical data requested. The system is open-ended, enabling one query to lead to another. Four hundred and ninety-three patients have been entered into this program so far, including 29 patients with diastolic pressures greater than 115, 92 with diastolic pressures of 104 to 114, and 372 with diastolics of 90 to 104. Among patients who have been on therapy for at least six weeks, 80 per cent were at goal blood pressure. Ten to 14 weeks after therapy was initiated, 69 per cent of all patients in the program were at goal blood pressure. The system provides a useful means of monitoring a large hypertensive population of patients. Such a system can result in a more efficient utilization of medical personnel and can bring the consultative services of highly trained specialists to larger segments of the population.

Computers

Developing functional requesting: acquisition, durability, and generalization of effects.

This study investigated the effects of a language program called the missing-item format, on the acquisition of requesting during snack periods. The missing-item format, an assessment and training approach, develops a child's spontaneous requesting skills in everyday tasks. Generalization and response-durability measures were also collected. The missing-item format produced effects in requests for targeted snack items, but not for the majority of generalization and durability measures. A generalization training program was then implemented, using the missing-item format. As a result, a requesting repertoire that was durable and generalized across multiple settings and stimulus conditions was established in both students.

Child

Toward computerized morphometric facilities: a review of 58 software packages for computer-aided three-dimensional reconstruction, quantification, and picture generation from parallel serial sections.

This review gives an inventory of 58 computer-aided three-dimensional reconstruction applications in the domain of biomedical research. It is devoted to the formulation of a set of recommendations thought to be necessary for improved performance of software packages in this field. These recommendations can be used to select packages and to guide future developments of existing reconstruction systems. The survey is restricted to three-dimensional reconstructions based upon a series of parallel sections of an object. Subjects treated are programming languages, resolution and sampling, input preparation, realignment, local deformation of slices, numerical quantifications, topological complexity, internal representation, display complexity (hidden surfaces, shading, smoothing), structure extraction, descriptive elements, database, data compression, time efficiency of systems and algorithms, hardware configuration, input devices, input media, interactive aids, display devices, and output devices. Information for this survey comes from articles that appeared between 1965 and 1985.

Computers

Microcomputer-assisted filing system of cardiac catheterization records using a relational database management system.

To efficiently store and retrieve cardiac catheterization records, we have developed a computer-assisted database, which comprises a 16-bit microcomputer with dual floppy disk drives, a 20 MB random-access memory, hard disk drive, and a line printer. All programmings were accomplished using a relational database management system (R:base 5000, Microrim, Inc.). Data inquiry procedures could be performed with direct operational commands of the system as well as with preprogrammed command files, and final results of searches were printed out with a line printer. The major advantages of the present system described in this report include: (1) the relatively easy and rapid creation of the database, (2) ease of modification of the database structures even after the system design is finished, (3) operational commands in combination with conditional operator(s) are flexible and powerful enough to allow the end user to retrieve data based on various kinds of criteria, (4) a high-level programming language provided by the R:base automates a series of database procedures with relative ease, (5) relational capabilities of the database management system can enhance the possibility of reconstruction of a new data file from a single or several preexisting data files, and (6) the system can be realized at reasonable cost.

Cardiac Catheterization