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A simple, inexpensive hardware and software protocol is described for conditioning and testing hearing of gerbils with minimal experimenter involvement. Behavioral thresholds correspond closely with data which employ nonautomated procedures. Partial source listings of the programs written in the 'C' programming language are provided.
A Zymate II robotic dissolution system was modified by addition of a liquid chromatography (LC) system equipped with an Isco ISIS autosampler. Using the Concurrent EasyLab programming language, operation of this LC system was integrated into the main robotic dissolution procedure. This enabled simultaneous dissolution sampling and LC analysis of standard and pre-pulled sample solutions. The resulting dual-tasking system effects considerable efficiency of operation and results in significant time savings. Comparison of the robotic and non-robotic data indicate good correlation and statistically insignificant differences at the 95% confidence level. Validation studies confirm linearity and precision of the quantitative LC method, accuracy and precision of volume and temperature measurements and negligible vessel-to-vessel carryover.
OBJECTIVE: To simulate a uterine contraction using a novel computer model for uterine communication and to validate the assumptions of the computer model by comparing the simulated contraction with a real uterine contraction. METHODS: The computer model assumed two known mechanisms of intercellular communication: action potential propagation and calcium wave propagation. Simulations were performed on a desktop computer using available programming language. Model validity was assessed by fitting the computer-simulated contraction to a real contraction and comparing the fit values with values measured independently. RESULTS: The simulated contraction demonstrated five characteristics that are also observed in human labor: 1) gradual onset, 2) a linear rising segment, 3) a plateau region, 4) a symmetrical fall, and 5) gradual offset. The fit values agreed well with values determined experimentally and supported the model. CONCLUSIONS: Our results support the model, strongly suggesting that intercellular communication occurs throughout the uterus by action potentials and locally within the tissue by calcium waves.
A Macintosh-based system is described for performing instrument control, data acquisition and storage operations in single-electrode whole-cell voltage clamp experiments. The system consists of a commercially available voltage clamp amplifier, multifunction input/output (I/O) board, graphical programming language (LabVIEW 2) and custom built 'virtual instrument' (VI). The I/O board is capable of fast (up to 110 ksample/s) multichannel analog-to-digital (A/D) conversion with 12-bit resolution. It can control the gain settings of the clamp unit through digital I/O lines and generate the P/N leak subtraction protocol to eliminate the linear portion of capacitive currents using analog output voltages and gating pulses. Complete voltage clamp protocols can be implemented using the on-screen front panel controls of the VI. It enables the user to visualize the acquired data, to graph sets of current-voltage (I-V) relations or to fit single-exponential functions to one current trace. To evaluate the adequacy of whole-cell recording, the total membrane capacitance (Cm), the series resistance (Rs) and the time constant (tau c) of the decay of the capacitive current are calculated using the single-exponential function fit to the data. The system is particularly well suited to the study of large quantities of transmembrane I-V relationships. Source code for the crucial elements of the VI as well as sample recordings from a cultured spinal cord neuron, illustrating system operation, are presented.
A multiple baseline design across responses was used to examine the effect of syntax training on the sentence production of 4 individuals with chronic Broca's aphasia. Subjects were trained to produce five exemplars of five sentence types from Helm's Elicited Language Program for Syntax Stimulation (Helm-Estabrooks, 1981). Generalization and maintenance of trained sentence types to novel exemplars and novel stimulus conditions served as dependent measures. In addition, five naïve judges rated subjects' responses before and following the treatment in terms of their "adequacy." Generalization to novel exemplars was demonstrated sequentially by 3 subjects (i.e., following the teaching of all five forms), and the remaining subject demonstrated generalization for three of five sentence types trained. Maintenance was variable across subjects and sentence types. Generalization across stimulus conditions was limited for all subjects. Adequacy judgments revealed improved communication skills for wh-questions but limited changes in the perceived adequacy of subjects' declarative responses. These findings indicate that the effects of syntax training procedures are limited to those grammatical constructions taught, that generalization of learned forms to novel stimulus conditions is not an automatic consequence of acquisition, and that the effect of such training on the adequacy of subjects' responses may be limited.
BACKGROUND: A retinal image performance distorted by an asymmetric or irregular corneal surface cannot be compensated for with spherocylindric glasses completely. The best-corrected visual acuity is markedly decreased and contact lens fitting often impossible. The purpose of this study was to calculate the differential height between corneal topography raw data and any regular surface with mathematical methods in order to ablate the differential height with a computer-controlled laser beam, thereafter. METHODS: A Zernike decomposition of radial degree n = 16 was realized within a clinically relevant central corneal area of 8 mm in diameter based on corneal topography raw height data of a commercially available topographer (TMS-1, Tomey, Erlangen). Any target surface could be defined by varying weighting of the Zernike coefficients. The calculated differential height ablation between the raw data and the target surface given in a polar grid was transformed to a Cartesian grid to evaluate the sleeping time at each grid position considering the characteristic ablation curve for the intended ablation of the height difference. Subsequently, differential height ablation was simulated using an automated laser beam control for a modified excimer laser (MEL60, Aesculap-Meditec, Jena). We developed software tools for Zernike decomposition of corneal topography raw height data and time-regulated automatic laser beam control of the grid positions in the higher programming language C (Borland C++ 3.1, Borland Inc., München). RESULTS: Definition of a target surface can be realized alternatively by selecting a set of Zernike coefficients or defining a spherical or spherocylindrical surface by superposition of parabolic terms in a fixed proportion creating a best-fit target surface to the raw data. In originally "relatively flat" areas, the differential height profile indicates a "relatively deep" ablation resulting in relative steepening towards the periphery of the ablation zone. The resolution of the mechanical unit of the laser beam control consisting of two linear stepping motors is 9 microns in the focal plane with a reproducibility of 5 microns. The software unit is guiding the laser beam in a meandering fashion within the ablation area considering the calculated sleeping time for each grid position. Mean overlap of the 1 mm laser spots is 70%. The laser beam diameter of 1 mm effects a peripheral transition zone of 0.5 mm. CONCLUSIONS: Zernike decomposition of corneal topography height data is an efficient tool for localizing and quantifying superficial irregularities and for directly calculating an ablation profile from created differential height data. With an automatic laser beam control a well-defined laser ablation of superficial corneal irregularities is possible, subsequently.
A concept covering the collecting and processing of obstetrical and perinatological data is described. Collecting of patient data is effected on the basis of a case history that has been drawn up in an EDP-adequate manner, which, however, can also be used in the conventional way. This procedure was chosen because for some time to come one cannot do without a document for handwritten notes to avoid duplication of work by "double tracking" and to eliminate transmission errors, and also to continue the present procedure of dealing with the patient. A commercial data base system was chosen for data collection and storage (dBase III by Ashton Tate). This relational data base has its own programming language with very powerful macro calls. Data input is effected by means of programme masks which the user can solicit via menu monitoring. The requisite hardware configuration consists of a computer with a main storage comprising 640 KB, system MS-DOS, and a hard disk of at least 20 MB. This data collection system operates in an obstetric hospital with annually more than 1,600 births and more than 1,200 entries during early pregnancy, to the satisfaction of the users. Besides compiling the usual statistical analyses and formulating research problems, the system automatically prepares the discharge reports. This rationalisation procedure compels the user to collect the data with care and also completely. On the whole, such a data collection system offers to hospitals of any size quick and easy access to data at any time, as well as optimised patient care, without additional effort and at a reasonable cost level.
To explore the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation. The active ingredients and potential targets were screened by the Systematic Pharmacological Analysis Platform of Traditional Chinese Medicine (TCMSP). Hypertension-related targets were obtained from OMIM and GeneCards databases. Common targets between drug and hypertension were screened in the Venny platform. A protein-protein interaction (PPI) network was constructed in the STRING database using intersection targets. Key targets in PPI network were analyzed by Cytoscape. R language program was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding abilities of the main active ingredients to critical targets were verified by molecular simulation. Naringenin, quercetin, kaempferol, and β-sitosterol in Lingguizhugan Decoction, and potential targets such as STAT3, AKT1, TNF, IL6, JUN, PTGS2, MMP9, CASP3, TP53, and MAPK3, were screened out. KEGG Enrichment analysis revealed that the common targets of Lingguizhugan Decoction and hypertension are mainly involved in the lipid and atherosclerosis signaling pathway, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and IL17 signaling pathway. The molecular simulation results showed that naringenin-MAPK3, quercetin-MMP9, quercetin-PTGS2, and quercetin-TP53 were the top four in the docking scores. Naringenin-MAPK3 and quercetin-MMP9 were stable, with binding free energies of -27.97 ± 1.41 kcal/mol and -21.15 ± 3.17 kcal/mol, respectively. The possible mechanism of Lingguizhugan Decoction in treating hypertension is characterized of multi-component, multi-target, and multi-pathway.Communicated by Ramaswamy H. Sarma.
A new development in computer-assisted medical education has been the introduction of hypertext authoring systems. Authoring systems are computer programs that can allow an instructor to prepare computer-based medical educational materials without the need to know programming languages. Hypertext is a database management system that lets the user connect screens of information using associative links. The authors developed a hypertext authoring system for teaching their medical students the domain of oncology. The features of the system are hierarchical structure, index browsing, and nonsequential browsing. Moreover, the student may become a writer of a hyperdocument by typing a few script commands. In this way the hierarchical structure of a document meets the needs of the reader. Although hypertext brings with it a few difficulties for the student, the authors expect that the system will become a popular mean for organizing textual information for retrieval and browsing in oncology.
MOTIVATION: The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD) is a website providing information and dynamic links for microbial metabolic pathways, enzyme reactions, and their substrates and products. The Compound, Organism, Reaction and Enzyme (CORE) object-oriented database management system was developed to contain and serve this information. RESULTS: CORE was developed using Java, an object-oriented programming language, and PSE persistent object classes from Object Design, Inc. CORE dynamically generates descriptive web pages for reactions, compounds and enzymes, and reconstructs ad hoc pathway maps starting from any UM-BBD reaction. AVAILABILITY: CORE code is available from the authors upon request. CORE is accessible through the UM-BBD at: http://www. labmed.umn.edu/umbbd/index.html.
The SAS system provides biologists with a flexible, easy to use software package for data analysis. Through a combination of data management tools, a wide variety of pre-programmed procedures for sorting, graphing, and statistical analysis and a sophisticated programming language, SAS software can perform all analytical needs for most problems. The recent availability of SAS software on mainframes other than IBM, and more recently on the microcomputer, means that most scientists can have access to the software. In this review we discuss the structure of the SAS language and demonstrate its power in the analysis of biological problems. Although to a lesser extent now than originally, the SAS system is statistically oriented and a working knowledge of statistics is recommended before using its statistical capabilities. However, all biologists will find its data management and summarization capabilities very useful.
SUMMARY: Nanopore sequencers allow sequencing data to be accessed in real-time. This allows live analysis to be performed, while the sequencing is running, reducing the turnaround time of the results. We introduce realfreq, a framework for obtaining real-time base modification frequencies while a nanopore sequencer is in operation. Realfreq calculates and allows access to the real-time base modification frequency results while the sequencer is running. We demonstrate that the data analysis rate with realfreq on a laptop computer can keep up with the output data rate of a nanopore MinION sequencer, while a desktop computer can keep up with a single PromethION 2 solo flowcell. AVAILABILITY AND IMPLEMENTATION: Realfreq is a free and open-source application implemented in C programming language and shell scripts. The source code and the documentation for realfreq can be found at https://github.com/imsuneth/realfreq. The version used for the manuscript is also available at https://doi.org/10.5281/zenodo.15128668.
MOTIVATION: Across-chromosome phasing identifies which haplotypes of different chromosomes come from the same parent. This differs from within-chromosome phasing, which uses linkage disequilibrium patterns to determine which alleles were co-inherited within each chromosome but does not match haplotypes across different chromosomes. While across-chromosome phasing can be conducted using genotypes from parents or close relatives, current methods perform poorly for samples of unrelated individuals. Here, we introduce a novel approach for across-chromosome phasing that employs a window-based SNP-similarity metric, eliminating the need for data from close relatives or detection of identical-by-descent haplotypes. RESULTS: Using UK Biobank offspring with both parents genotyped as a gold standard, we evaluated the performance of our method by phasing the offspring without using parental data. In genomic data with no within-chromosome phase errors, our algorithm achieved a mean across-chromosome phasing accuracy of 95%, with 53% of individuals phased perfectly. When data was pre-phased computationally using a standard within-chromosome phasing algorithm, mean accuracy for across-chromosome phasing dropped to 83.1%. Thus, our method is limited primarily by the accuracy of within-chromosome phasing accuracy and can approach near-perfect across-chromosome phasing accuracy as within-chromosome phasing accuracy improves. AVAILABILITY AND IMPLEMENTATION: The implementation was executed within a multi-node computational environment of University of Colorado Boulder Research Computing (Blanca Cluster: https://www.colorado.edu/rc/resources/blanca), employing parallelization techniques in the C programming language. The source code has been made publicly accessible online at https://github.com/emmanuelsapin/AcrossChromosomesPhasing, thereby facilitating reproducibility of the results for researchers with authorized access to the UK Biobank dataset.
MOTIVATION: CRISPR-Cas9 genome-editing efficiency is strongly influenced by the sequence composition and positional context of single-guide RNAs (sgRNAs). Although numerous deep learning-based models have been developed to predict Cas9 efficiency from sgRNA sequences, most operate as black boxes, offering limited insight into the sequence determinants underlying Cas9 activity. In addition, previous studies often overlook how the positional context of sequence motifs within sgRNAs influences their effects on Cas9 binding or cleavage. RESULTS: We introduce DeepCC9, an interpretable machine learning framework that combines explicit sequence feature extraction with a residual block-based deep architecture to improve interpretability and identify composition- and position-based motifs governing Cas9 genome-editing efficiency. We applied this method to multiple Cas9 variant datasets, achieving superior predictive performance compared with existing methods while enabling direct interpretation of sequence motifs and their positional effects. Our analysis uncovered 74 sequence motifs enriched or depleted at specific positions within sgRNAs and strongly associated with Cas9 efficiency, providing mechanistic insight into sequence features that influence guide performance. Together, these results establish DeepCC9 as a generalizable and interpretable framework for modeling sequence-function relationships and advancing the understanding of the sequence determinants underlying CRISPR-Cas9 genome editing. AVAILABILITY AND IMPLEMENTATION: The authors have implemented their algorithm in the Python programming language (version 3.X), which is accessible using (https://zenodo.org/records/20073890).
SUMMARY: Genome-wide association studies (GWASs) have identified thousands of genetic variants associated with complex traits and diseases. However, explaining the mechanisms underlying phenotypic variation remains challenging. Here, we introduce SNPannotator, an automated post-GWAS analysis software package designed to streamline the interpretation of GWAS findings. Our pipeline implements a multi-step process that identifies proxy variants in high linkage disequilibrium (LD) with associated lead variants, then queries comprehensive resources (including Ensembl, the GTEx Portal, the eQTL Catalog, and STRING DB) for genomic position, deleteriousness, regulatory annotations, clinical significance, trait associations, expression (eQTLs) and splicing quantitative trait loci (sQTLs), and functional enrichment analyses and compiles the results into user-friendly reports. This package is implemented in the R programming language and includes auxiliary functions for variant lookup and LD exploration. SNPannotator provides a practical framework for efficiently deriving biologically meaningful insights from GWAS data and for assisting researchers in prioritizing candidate variants for functional validation. AVAILABILITY AND IMPLEMENTATION: The SNPannotator package is available from the Comprehensive R Archive Network (CRAN) at https://cran.r-project.org/web/packages/SNPannotator. The development version and tutorial is available on GitHub (https://github.com/omicslaboratory/SNPannotator). The online version of the package is available at https://omicslab.org/snpannotator.
Three computer programs are described which may be used to translate a DNA sequence into a protein sequence, back translate the protein sequence into an ambiguous DNA sequence, and then do pattern searching in the ambiguous sequence. The programs are written in the C programming language, have been compiled to run on a microcomputer under the CP/M 80 operating system, and may be copied in binary format through a modem. They are also to become available for the IBM/PC.
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.
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.