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Apple Macintosh programs for nucleic and protein sequence analyses.

This paper describes a package of programs for handling and analyzing nucleic acid and protein sequences using the Apple Macintosh microcomputer. There are three important features of these programs: first, because of the now classical Macintosh interface the programs can be easily used by persons with little or no computer experience. Second, it is possible to save all the data, written in an editable scrolling text window or drawn in a graphic window, as files that can be directly used either as word processing documents or as picture documents. Third, sequences can be easily exchanged with any other computer. The package is composed of thirteen programs, written in Pascal programming language.

Amino Acid Sequence

MIPS: a database for protein sequences, homology data and yeast genome information.

The MIPS group (Martinsried Institute for Protein Sequences) at the Max-Planck-Institute for Biochemistry, Martinsried near Munich, Germany, collects, processes and distributes protein sequence data within the framework of the tripartite association of the PIR-International Protein Sequence Database (,). MIPS contributes nearly 50% of the data input to the PIR-International Protein Sequence Database. The database is distributed on CD-ROM together with PATCHX, an exhaustive supplement of unique, unverified protein sequences from external sources compiled by MIPS. Through its WWW server (http://www.mips.biochem.mpg.de/ ) MIPS permits internet access to sequence databases, homology data and to yeast genome information. (i) Sequence similarity results from the FASTA program () are stored in the FASTA database for all proteins from PIR-International and PATCHX. The database is dynamically maintained and permits instant access to FASTA results. (ii) Starting with FASTA database queries, proteins have been classified into families and superfamilies (PROT-FAM). (iii) The HPT (hashed position tree) data structure () developed at MIPS is a new approach for rapid sequence and pattern searching. (iv) MIPS provides access to the sequence and annotation of the complete yeast genome (), the functional classification of yeast genes (FunCat) and its graphical display, the 'Genome Browser' (). A CD-ROM based on the JAVA programming language providing dynamic interactive access to the yeast genome and the related protein sequences has been compiled and is available on request.

Academies and Institutes

Computer programs to assist in high resolution thermal denaturation and circular dichroism studies on nucleic acids.

Computer programs are described that direct the collection, processing, and graphical display of numerical data obtained from high resolution thermal denaturation (1-3) and circular dichroism (4) studies. Besides these specific applications, the programs may also be useful, either directly or as programming models, in other types of spectrophotometric studies employing computers, programming languages, or instruments similar to those described here (see Materials and Methods).

Circular Dichroism

Accurate detection of tandem repeats exposes ubiquitous reuse of biological sequences.

Tandem repetition is one of the major processes underlying genome evolution and phenotypic diversification. While newly formed tandem repeats are often easy to identify, it is more challenging to detect repeat copies as they diverge over evolutionary timescales. Existing programs for finding tandem repeats return markedly different results, and it is unclear which predictions are more correct and how much room remains for improvement. Here, we introduce DetectRepeats, a new method that uses empirical information about structural repeats to improve the accuracy of repeat detection. We show that DetectRepeats advances the state-of-the-art by finding highly divergent repeats with relatively few false positive detections. We apply DetectRepeats to genomes across the tree of life to discover an enrichment of detectable tandem repeats within different genes, genome regions, and taxa. Furthermore, we use phylogenetic reconciliation to determine that some tandem repeats continue to evolve through intra-repeat unit replacement. In this manner, tandem repeats serve as a renewable genetic resource offering a bountiful source of alternative genetic material. Our work unlocks the confident detection of ancient tandem repeats, opening a doorway to future discoveries. DetectRepeats is part of the DECIPHER package for the R programming language and available via Bioconductor.

Tandem Repeat Sequences

Epidemiologic modeling using a microcomputer spreadsheet package.

Epidemiologic modeling has provided both researchers and students with a means of studying complex disease processes as well as making intervention recommendations to decision makers. To develop more than the most elementary model, however, it has become necessary to be well versed in a computer programming language. While this has deterred many modelers in the past, with microcomputers it is now possible to develop even complex models without significant investment of time spent in learning a computer language. In addition to being affordable, many microcomputers offer "canned" spreadsheet packages which are readily adapted for epidemiologic modeling. To demonstrate this, two models were developed and run using a microcomputer spreadsheet package: 1) the classic Reed-Frost model, and 2) a modified Reed-Frost model with two intermixing subpopulations.

Animals

An object-oriented database for protein structure analysis.

An object-oriented database system has been developed which is being used to store protein structure data. The database can be queried using the logic programming language Prolog or the query language Daplex. Queries retrieve information by navigating through a network of objects which represent the primary, secondary and tertiary structures of proteins. Routines written in both Prolog and Daplex can integrate complex calculations with the retrieval of data from the database, and can also be stored in the database for sharing among users. Thus object-oriented databases are better suited to prototyping applications and answering complex queries about protein structure than relational databases. This system has been used to find loops of varying length and anchor positions when modelling homologous protein structures.

Amino Acid Sequence

Features of commercial computer software systems for medical examiners and coroners.

There are many ways of automating medical examiner and coroner offices, one of which is to purchase commercial software products specifically designed for death investigation. We surveyed four companies that offer such products and requested information regarding each company and its hardware, software, operating systems, peripheral devices, applications, networking options, programming language, querying capability, coding systems, prices, customer support, and number and size of offices using the product. Although the four products (CME2, ForenCIS, InQuest, and Medical Examiner's Software System) are similar in many respects and each can be installed on personal computers, there are differences among the products with regard to cost, applications, and the other features. Death investigators interested in office automation should explore these products to determine the usefulness of each in comparison with the others and in comparison with general-purpose, off-the-shelf databases and software adaptable to death investigation needs.

Computers

Numerical integration simulation programs for the microcomputer.

Programs for use with the Apple II Plus microcomputer that generate graphic simulations of various linear and Michaelis-Menten pharmacokinetic models are described. The programs numerically integrate sets of differential equations for appropriate pharmacokinetic models. Multiple oral (or intramuscular), intravenous bolus, or infusion doses (continuous or discontinuous) may be administered in any combination. Doses as well as pharmacokinetic parameters may be changed at the end of each simulated dosing interval. The programs can be easily modified by users familiar with the BASIC programming language and offer an economical approach to pharmacokinetic simulation.

Computers

The frequencies of HLA alleles and haplotypes and their distribution among donors and renal patients in the UNOS registry.

HLA allele and haplotype frequencies are used in transplantation, anthropology, forensic medicine, and studies of the associations between HLA factors and the immune response. The cost of determining these frequencies through family studies can be avoided by estimating them from population data. We have utilized the data in the UNOS donor registry and kidney transplant waiting list to estimate allele and haplotype frequencies for the HLA-A, -B, and -DR(B1) loci and report the allele and a portion of the haplotype data here. Using programs written in A Program Language (APL) we were able to perform all analyses on a personal computer. We have found that the distribution of haplotype frequencies varies among the races, with Caucasians having a greater number of both more common and extremely rare haplotypes. Despite the sizes of the groups studied, only one-third to two-thirds of the haplotypes theoretically possible were actually observed. Although the data confirm the well-known fact that the distributions of alleles and haplotypes varies among races, they also reveal that certain common haplotypes are shared among all racial groups and represent an opportunity for well-matched transplants between donors and recipients of different races.

Alleles

A Systematic Review of Spatial Epidemiological Modeling Approaches Applied During the COVID-19 Pandemic.

BACKGROUND: A wide range of epidemiological modeling approaches have been applied to the SARS-CoV-2 pandemic, which presents an opportunity to assess common approaches applied to specific research questions. Spatial models interrogate how heterogeneities and host movement dynamics influence local and regional patterns of disease, issues that were of great interest for understanding and controlling SARS-CoV-2. OBJECTIVE: Here we present a systematic review of spatial epidemiological modeling approaches of SARS-CoV-2. We describe common themes and highlight unique strategies, providing a foundation for researchers to devise spatial models most appropriate for future pathogens and epidemics. Our review also categorizes the research questions that were addressed with spatial models, highlights parameter estimation techniques, and describes the cyber infrastructure used for model development. METHODS: We conducted a systematic review using Web of Science and a standardized set of keywords, followed by thorough examination of abstracts and full texts to determine which studies met our inclusion criteria. To guide our description and comparisons of models, we developed a Geography, Population, Movement (GPM) framework that conceptualizes the interactions between three distinct subcomponents of any spatial model. The geographic model represents the physical arena in which the model is implemented, the intra-population model describes the transmission and disease processes that occur within distinct spatial units of the geography, and the movement model describes the algorithms that dictate how hosts move among spatial units within the geography. RESULTS: The search identified a total of 193 articles, of which 109 were included in our review. The most abundant intra-population modeling methods were agent-based (47.7%) and compartmental modeling (29.4%) approaches. Movement models ranged in complexity, with the most complex models implementing commuter movement among many points of interest in the geographic arena, which were sometimes parameterized by fine-scale mobility data. Geographic models ranged from describing microcosms, such as single classrooms, all the way up to multi-country models. Of the 63.3% of models studies that specified the programming language used, we detected ten different languages, with Matlab and Python being the most frequent, although only 30.6% of studies provided open-access code for their models. We also described eight specialized software systems that were used to construct agent-based or compartment models of COVID-19. CONCLUSIONS: Our review identified and characterized a variety of spatial modeling strategies and software that were usefully employed to address many relevant epidemiological questions for COVID-19. Future research is needed to quantitatively assess which modeling approaches are most appropriate in specific situations, to answer specific questions, or to apply to certain disease systems. Moreover, future cyberinfrastructure could help to modularize and standardize modeling approaches, which would increase transparency and reproducibility, and which would facilitate a detailed examination of which model attributes relate to model performance in a variety of contexts.

COVID-19

Scriptable access to the Caenorhabditis elegans genome sequence and other ACEDB databases.

Much of the world's genomic data are available to the community through networked databases that are accessed via Web interfaces. Although this paradigm provides browse-level access and has greatly facilitated linking between databases, it does not provide any convenient mechanism for programmatically fetching and integrating data from diverse databases. We have created a library and an application programming interface (API) named AcePerl that provides simple, direct access to ACEDB databases from the Perl programming language. With this library, programmers and computer-savvy biologists can write software to pose complex queries on local and remote ACEDB databases, retrieve the data, integrate the results, and move data objects from one database to another. In addition, a set of Web scripts running on top of AcePerl provides Web-based browsing of any local or remote ACEDB database. AcePerl and the AceBrowser Web browser run on Unix systems and are available under a license that allows for unrestricted use and redistribution. Both packages can be downloaded from URL. A Microsoft Windows port of AcePerl is in the planning stages.

Animals

Fuzzy control of mean arterial pressure in postsurgical patients with sodium nitroprusside infusion.

We developed a fuzzy control system to provide closed-loop control of mean arterial pressure (MAP) in postsurgical patients in a cardiac surgical intensive care unit setting by regulating sodium nitroprusside (SNP) infusion. The fuzzy controller, originally expert-system-based, was analytically converted to ten nonfuzzy control algorithms, which reduced execution time dramatically. The core of the control algorithms was a nonlinear proportional-integral (PI) controller whose proportional gain and integral gain adjusted continuously according to error and rate change of error of the process output. The gains became larger when process output was far from desired setpoint and smaller when process output was close to desired setpoint, resulting in more dynamic and stable control performance than the regular PI controller, especially when a linear process with time-delay or a nonlinear process was involved. The control algorithms, encoded in C programming language, were implemented to control MAP in patients. Preliminary clinical results showed that the average percentage of time in which MAP stayed between 90% and 110% of the MAP setpoint was 89.31%, with a standard deviation of 4.96%. These were calculated based on 12 patient trials, with total trial time of 95 and 13 min.

Algorithms

Use of commercial 'authoring systems' for medical education.

A recent development in computer-assisted medical instruction has been the introduction of 'authoring systems'. Authoring systems are computer programs which can allow an instructor to prepare computer-based medical instructional materials without the need to know programming languages or have more than minimal familiarity with the computer hardware. This report documents the use of a commercially available authoring system that was used to prepare a tutorial for medical student instruction. This lesson presented information about paediatric developmental disabilities in both a text and question-and-answer format. Significant improvement in knowledge was demonstrated by the pre- and post-test results of the study group compared to the control group. The control group consisted of students who did not view the tutorial but had been assigned to a paediatric developmental disabilities clinic. The medical students who viewed the tutorial generally had very favourable comments about the use of such a system for the presentation of new information.

Attitude of Health Personnel

Computer-enhanced learning in neuroanatomy.

The recent development of powerful microcomputers and the introduction of object-oriented programming languages has now made available to educationists software that can be easily used to design and develop computer-based learning material. We have developed courseware and tutorware in the field of neuroanatomy which are pedagogically structured and yet provide multiple paths of learning for the individual student. Neuroanatomy is a difficult subject to learn because of the structural intricacy and functional correlations that it entails. The courseware enables students to approach the subject at different levels of difficulty and progress at their own pace towards a comprehensive understanding of structure and function aided by text integrated with graphics, sound and animation. A significant advantage to authors of similar courseware is the option to update the contents easily when necessary in the future.

Computer-Assisted Instruction

Computer education: attitudes and opinions of first-year medical students.

Students' attitudes toward medical informatics were evaluated with self-administered questionnaires, answered by 140 (77%) first-year medical and dental students. Fourteen per cent classified their computer literacy as negligible and 49% as deficient. Ninety-six per cent had used a computer before and 59% used one regularly. Nineteen per cent had computer education in secondary school and a further 16% attended courses given by a computer company. Only 16% read regularly about informatics. These results are similar to those observed in more industrialized countries, except that high-school education is more deficient. To 93% of these students, computer literacy is important for doctors, and to 85% computers may be very useful in many areas of health care. In the opinion of 66% of students, the computer-based patient record will be available within the next 3 to 10 years. Women showed lesser computer literacy (77% computer illiteracy to 39% in men), but there were no relevant differences in attitudes, behaviour and beliefs towards medical informatics between gender, for the same level of computer literacy. Computer education in the undergraduate curriculum was demanded by 92%, and 75% of these preferred an elective course. Weekly hours suggested for lectures should be 1 (54%) or 2 (42%), and for hands-on practice 2 (54%) or 4 (31%) hours. The curriculum should include medical applications (83% of students), information science theory and technology (44%), micro-informatics (44%), bibliographic database search (27%), programming languages (23%) and statistical packages (23%). Gender, computer literacy or course did not correlate significantly with students' opinions about the contents of undergraduate education.

Attitude of Health Personnel

Pacemaker architecture: a pacemaker with an attached computer or a computer with an attached pacemaker.

Microprocessors have a major impact on cardiac pacemaker technology. The development of adaptive systems capable of responding to physiologic variables will ultimately improve the care of the individual patient. However, in order to minimize power drain, it will be necessary to incorporate certain functions into the hardware outside the microprocessor. In addition, specifically designed program languages may indeed become necessary.

Cardiac Pacing, Artificial

A simulation of microbial competition in the human colonic ecosystem.

Many investigations of the interactions of microbial competitors in the gastrointestinal tract used continuous-flow anaerobic cultures. The simulation reported here was a deterministic 11-compartment model coded by using the C programming language and based on parameters from published in vitro studies and assumptions were data were unavailable. The resource compartments were glucose, lactose and sucrose, starch, sorbose, and serine. Six microbial competitors included indigenous nonpathogenic colonizers of the human gastrointestinal tract (Escherichia coli, Enterobacter aerogenes, Bacteroids ovatus, Fusobacterium varium, and Enterococcus faecalis) and the potential human enteropathogen Salmonella typhimurium. Flows of carbon from the resources to the microbes were modified by resource and space controls. Partitioning of resources to the competitors that could utilize them was calculated at each iteration on the basis of availability of all resources by feeding preference functions. Resources did not accumulate during iterations of the model. The results of the computer simulation of microbial competition model and for various modifications of the model. The results were based on few measured parameters but may be useful in the design of user-friendly software to aid researchers in defining and manipulating the microbial ecology of colonic ecosystems as relates to food-borne disease.

Carbohydrates

Model-based compartmental analyses in nutrition research.

Kinetic tracer studies have been used extensively in understanding digestion, absorption, and whole-body metabolism of nutrients. Optimal interpretation of changes in tracer levels over time and movement across body pools often requires sophisticated data analysis. The use of model-based compartmental analysis (MCA) can yield more detailed quantitative and predictive information concerning system dynamics, compared with direct stochastic approaches. With MCA, tracer and tracee data from both experimental and literature values are fit to a model that best approximates the system on the basis of experimental data at hand. The number of compartments of the model is determined by the shape of the curve fit to the tracee and tracer data and by literature information. On this basis, MCA can yield information about compartment numbers and sizes, fractional and net turnover, as well as catabolic and synthetic rates. PC-based MCA programs are now available. Whereas earlier editions required use of a programming language, the most recent versions being developed are completely menu driven. Model-based compartmental analyses thus represent important biotechnological advances permitting maximal interpretation of kinetic data in nutrition research.

Animal Nutritional Physiological Phenomena