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Computer methods in child language research: four principles for the use of archived data.

With the increasing use of computers in language research, there is a need for caution concerning several new issues of data accountability. This paper presents four principles for archive-based language research: Maximum Readability and Minimum Bias; Consistent Encoding for exhaustive computer search; Systematic Contrastiveness; and Data Comparability in elicitation, transcription and coding. These and related principles are illustrated by examples from existing computer archives, and strategies are suggested for minimizing detrimental effects of violations. Finally, the paper describes some implications of the principles for properties of a field-wide and international standard of transcription of language data.

Archives

Computational method for the design of enzymes with altered substrate specificity.

A combination of enzyme kinetics and X-ray crystallographic analysis of site-specific mutants has been used to probe the determinants of substrate specificity for the enzyme alpha-lytic protease. We now present a generalized model for understanding the effects of mutagenesis on enzyme substrate specificity. This algorithm uses a library of side-chain rotamers to sample conformation space within the binding site for the enzyme-substrate complex. The free energy of each conformation is evaluated with a standard molecular mechanics force field, modified to include a solvation energy term. This rapid energy calculation based on coarse conformation sampling quite accurately predicts the relative catalytic efficiency of over 40 different alpha-lytic protease-substrate combinations. Unlike other computational approaches, with this method it is feasible to evaluate all possible mutations within the binding site. Using this algorithm, we have successfully designed a protease that is both highly active and selective for a non-natural substrate. These encouraging results indicate that it is possible to design altered enzymes solely on the basis of empirical energy calculations.

Algorithms

A least-squares computer method for the determination of the molecular ratio of conjugates between two different proteins from the results of the amino acid analysis.

A method for the determination of the composition of a conjugate between two different proteins by amino acid analysis followed by least-squares evaluation of the concentration ratio of the two components is presented. The method is based solely on calculations and avoids the use of labeled residues. A computer program, written in BASIC, is also presented to perform the calculations.

Amino Acids

A computer method for finding common base paired helices in aligned sequences: application to the analysis of random sequences.

We describe a new computer program that identifies conserved secondary structures in aligned nucleotide sequences of related single-stranded RNAs. The program employs a series of hash tables to identify and sort common base paired helices that are located in identical positions in more than one sequence. The program gives information on the total number of base paired helices that are conserved between related sequences and provides detailed information about common helices that have a minimum of one or more compensating base changes. The program is useful in the analysis of large biological sequences. We have used it to examine the number and type of complementary segments (potential base paired helices) that can be found in common among related random sequences similar in base composition to 16S rRNA from Escherichia coli. Two types of random sequences were analyzed. One set consisted of sequences that were independent but they had the same mononucleotide composition as the 16S rRNA. The second set contained sequences that were 80% similar to one another. Different results were obtained in the analysis of these two types of random sequences. When 5 sequences that were 80% similar to one another were analyzed, significant numbers of potential helices with two or more independent base changes were observed. When 5 independent sequences were analyzed, no potential helices were found in common. The results of the analyses with random sequences were compared with the number and type of helices found in the phylogenetic model of the secondary structure of 16S ribosomal RNA. Many more helices are conserved among the ribosomal sequences than are found in common among similar random sequences. In addition, conserved helices in the 16S rRNAs are, on the average, longer than the complementary segments that are found in comparable random sequences. The significance of these results and their application in the analysis of long non-ribosomal nucleotide sequences is discussed.

Base Composition

Comparison of computer methods for taxonomy of some streptococci using gas chromatographic chemotaxonomic data.

Gas chromatographic fingerprints of eighty-three strains of Streptococcus were analysed by computer. Seven measures of association were compared for their ability to identify strains. The most effective measure was the Stack coefficient which correctly identified 68% of strains, mostly of oral origin. Clustering of strains was carried out by median, average, single-linkage, furthest neighbour, and centroid linkage, Andrew's plots, and Minimum Spanning Trees. Of the clustering methods, centroid linkage produced the most inclusive and compact clusters. Clusters of strains of S. mitis, S. mutans, S. salivarius and S. sanguis showed varying degrees of heterogeneity; while, S. milleri was comprised of three chemotypes corresponding to oral isolates, biochemically atypical vaginal isolates, and biochemically typical strains from other sources.

Chromatography, Gas

Impedance method computation of induced currents in a simple model of a child exposed to electromagnetic fields of an electric blanket.

The three dimensional impedance method has been used to calculate the distribution of induced current densities in a simple model of an 8-y-old child exposed to the electric and magnetic fields of an electric blanket. Two types of electric blankets have been modeled in the calculations, the pre-1989 conventional type and the presently available low magnetic field PTC (positive temperature coefficient) electric blanket. The purpose of this study was to calculate and compare the induced current densities in the model of the child due to the two types of blankets and also to compare the contributions to the induced currents by the electric and magnetic fields produced by the two types of blankets. The computations have shown that as expected and claimed, the induced current density in the model of the child due to the magnetic field of the low magnetic field PTC electric blanket is much lower than the induced current density due to the magnetic field of the conventional electric blanket. However, the computations have also shown that the contribution to the total current density by the electric field of the low magnetic field electric blanket is slightly higher than that due to the electric field of the conventional electric blanket. Hence, the total average induced current density due to both the electric and magnetic fields in the case of the low magnetic field PTC electric blanket is about one-third that in the case of the conventional electric blanket.

Bedding and Linens

An automatized computer-method utilizing Procomm Plus and DataEase (4.2) PC and SAS (6.06) mainframe software for isolated, perfused guinea-pig heart studies.

A powerful, time sharing and automatized method of a comprehensive data analysis for isolated, perfused guinea-pig heart studies is described. Data are collected using DataEase PC software (version 4.2) into forms with data fields specified for vital parameters consistently recorded in isolated, perfused heart studies (HR, CBF, PEAKPRESSURE, DPDT, MVO2). After running, DataEase reports the data and information is uploaded to an IBM 3081D mainframe computer on each day of heart experiment and data collection. The uploading process, the data archival and the statistical analyses are automatized by Procomm Plus commands written in Aspect Source Program (.ASP) Files for logging, data transforming and file management procedures. The ASPCOMP.EXE compiler compiles these .ASP files into Aspect Script eXecutable (.ASX) programs, which run on the PC in our laboratory and activate WYLBUR (IBM 3081D Batch-job service and Command file processor) edited files in the mainframe's electronic devices then upload, backup and save data into these files. SAS EXE files containing program instructions for the data analyzing system are then forced by Procomm Plus to operate over the data just uploaded. SAS reads the DATA files by its INFILE facility and performs comprehensive statistical analyses and produces hard output including graphics and JOB reports of dose-response- and logaritmic scale curves for delivery to team members. This computerized and automatized method developed for isolated, perfused guinea-pig heart studies is capable of performing multiple file transfer, sophisticated statistical analyses and graphic procedures after one keystroke on the PC (Alt-F5 in Procomm Plus section) and also facilitates a consistent and convenient method for planning, controlling and standardizing experiments. The method is based on an interactive computer conversation between the PC in the laboratory and the remote's WYLBUR editor. No human presence is needed; however, in case of failure, Procomm Plus gives one of the team members supervising the system a phone call in order to get human help.

Animals