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Results for “High-performance computing”

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PubMed1992

Optimization of the separation of the Rp and Sp diastereomers of phosphate-methylated DNA and RNA dinucleotides.

The separation by reversed-phase high-performance liquid chromatography of Rp and Sp diastereomers of phosphate-methylated DNA and RNA dinucleotides was studied with respect to pH, organic modifier type and concentration and reversed-phase packing material. Drylab G was used to deduce optimum conditions. On the basis of the observed discrepancies between the computer predictions and experimental results, the gradient operation procedure with volatile buffers was improved. By repetitive chromatography on a 250 x 22 mm I.D. reversed-phase column, fourteen diastereomeric pairs were obtained in at least 97% purity and 60% yield, in amounts of 10-100 mg.

Acetonitriles↗

PubMed1978

High-performance liquid chromatographic assay for suprofen, a potent new analgesic, in plasma.

A simple, rapid, high-performance liquid chromatographic (HPLC) determination of therapeutic levels of suprofen, a potent new analgesic, in human plasma is described. After a simple extraction, the compound is analyzed by HPLC using a reversed-phase column and a UV detector. Quantitation is accomplished using an external standard; peak areas are determined by computer. An average recovery of 80.0 +/- 8.5% SD of the drug was obtained over the 0.2-20.0-microgram/ml range. Maximum sensitivity is approximately 0.1 microgram/ml. No interference is encountered from any known metabolite of suprofen.

Chromatography, High Pressure Liquid↗

PubMed1992

The way to adequate control of microbial processes passes via real-time knowledge-based supervision.

Knowledge-based supervision is viewed as a major tool for achieving high-performance control of microbial processes. By providing an adequate insight into the integral state of the cell culture, knowledge-based supervisory systems allow for monitoring and handling various important phenomena which usually remain outside the scope of the conventional control approach. The present paper focuses on the development of a computer system for knowledge-based supervision of bioprocesses. Its application to the control of fed-batch cultivation of recombinant Escherichia coli for phenylalanine production is also discussed.

Biotechnology↗

PubMed1979

High-performance liquid chromatographic assay for the antiprotozoal agent, tinidazole, in human plasma.

A rapid and specific high-performance liquid chromatographic (HPLC) assay for the quantitative determination of tinidazole in human plasma is described. After a simple extraction procedure, the compound is analyzed by HPLC using a reversed-phase column and a UV detector. Quantitation is accomplished using an external standard, and peak areas are determined with an integrating computer. The average recovery of tinidazole over a concentration range of 0.20-20.0 microgram/ml was 86.9 +/- 2.8% SD. The maximum sensitivity of the assay is approximately 0.10 microgram/ml; it is suitable for use in pharmacokinetic studies following administration of therapeutic levels of tinidazole to humans.

Chromatography, High Pressure Liquid↗

PubMed1977

Sampling and extra-column effects in high-performance liquid chromatography; influence of peak skew on plate count calculations.

Chromatographic resolution and analysis accuracy can be seriously affected by broadening of very sharp bands associated with both high-performance size-exclusion chromatography and other liquid chromatography methods using less than 5 micron particles. The effect on column plate count by extra-column band broadening from injection systems, detectors, connectors and "guard" columns is discussed and exemplified with experimental data. The special cases of tailing and doublet peaks for a single species are investigated. These effects are eliminated by a special sample injection technique. Computer simulation studies demonstrated that serious errors can result from calculating column plate count with non-Gaussian peaks. The maximum allowable peak tailing is suggested and a new method for quantitating peak skew is proposed.

Chromatography, High Pressure Liquid↗

PubMed1990

High-performance liquid chromatography.

Gas chromatography has developed over the past 25 years or so into one of the most extensively used on-line analytical techniques in industrial process control and optimization. Liquid chromatography, and its several individual techniques, is firmly established in the laboratory, but its on-line process use has not developed as rapidly as GC. At the present time, only three companies (Applied Automation Inc., Dionex Corp., and Millipore Corp.) are active in this area. Nevertheless, substantial growth in on-line process LC is predicted for the next few years. The techniques of HPLC (normal-phase and reversed-phase), IEC, and SEC have great potential in industry as on-line analytical techniques, including the new field of biotechnology. Computer-based, multistream, multicomponent systems should find extensive use in pilot-plant investigations, where their ability to gather large amounts of data (on-line rather than by laboratory testing) could have important implications. In bioprocess control, undoubtedly the greatest challenge will come in the area of sample-handling technique. On-line chromatography has traditionally involved the sampling and conditioning of fairly conventional process gases and liquids. One exception is in the plastics and elastomers areas, where on-line SEC has been used for polymer MWD measurement. Here the sample is more difficult to handle, and some specialized techniques have been used. In biotechnology, we are treading new ground; nevertheless, it is hoped that some of the experience in sample handling gained in industry over the past 25 years will be of use in this new field.

Chromatography, High Pressure Liquid↗

PubMed2025

CaXML: Chemistry-informed machine learning explains mutual changes between protein conformations and calcium ions in calcium-binding proteins using structural and topological features.

Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes. However, it is unclear whether the limited experimental data available can be effectively used to train models to accurately predict the charges of calcium-binding protein variants. Here, we developed a chemistry-informed, machine-learning algorithm that implements a game theoretic approach to explain the output of a machine-learning model without the prerequisite of an excessively large database for high-performance prediction of atomic charges. We used the ab initio electronic structure data representing calcium ions and the structures of the disordered segments of calcium-binding peptides with surrounding water molecules to train several explainable models. Network theory was used to extract the topological features of atomic interactions in the structurally complex data dictated by the coordination chemistry of a calcium ion, a potent indicator of its charge state in protein. Our design created a computational tool of CaXML, which provided a framework of explainable machine learning model to annotate ionic charges of calcium ions in calcium-binding proteins in response to the chemical changes in an environment. Our framework will provide new insights into protein design for engineering functionality based on the limited size of scientific data in a genome space.

Machine Learning↗

PubMedDate not supplied

Profiling of endogenous brain peptides and small proteins: methodology, computer-assisted analysis, and application to aging and lesion models.

Significant advances in the technology for the isolation of peptides and small proteins have permitted their identification as biologic markers and enhanced the study of the posttranslational life of proteins. The protocol described here examined large numbers of tissue-derived peptides and small proteins, extracted in low pH and boiled so that proteolysis was interrupted. These were then fractionated batchwise using size exclusion and ion-exchange chromatography. Profiles of species in the peptide pools were then generated on reverse-phase high-performance liquid chromatography (HPLC). The HPLC profiles were evaluated with chromatographic analysis software to identify and quantify peptide peaks and with data compilation programs to sort this information into spreadsheets for comparison of profiles among groups. Using rodent brain, the effects of postmortem delay or age were examined. Postmortem delay produced limited alterations to the profiles, but the effect of age was more pronounced. Many changes were apparent until 12 months, after which the profiles became more constant. Additional peptide profiling of the hippocampus demonstrated changes in peptide content as a function of perforant pathway ablation. The major strengths of HPLC-mediated peptide profiling are that it lends itself to automation and can be used to detect changes in peptides and small proteins among experimental groups or subjects without any prior assumptions concerning which ones might be altered.

Aged↗

PubMed1979

Simultaneous microdetermination of capsaicin and its four analogues by using high-performance liquid chromatography and gas chromatography--mass spectrometry.

An improved method is described for the simultaneous determination of capsaicin and its analogues at levels from nanograms to micrograms using high-performance liquid chromatography (HPLC) and gas chromatography--mass spectrometry. This method consists of two steps: firstly, purification and determination of total capsaicinoid by HPLC, and secondly, the simultaneous determination of capsaicin and its analogues by mass chromatography (MC) or mass fragmentography (MF). Crude extracts of capsaicinoid were purified with a Zorbax SIL column. Total capsaicinoid was detected at 235 nm and measured automatically by a microcomputer. It was collected, evaporated, trimethylsilylated and subjected to MC or MF. After monitoring the molecular ions of trimethylsilyl derivatives of capsaicinoid and the internal standard, the absolute contents of each analogue were determined by computer. By using this method, capsaicin and all of its analogues can be determined simultaneously at levels from micrograms to nanograms without any interferences from other components.

Capsaicin↗

PubMed1977

High-performance liquid chromatographic determination of chlordiazepoxide and major related impurities in pharmaceuticals.

A rapid, precise, forward-phase (adsorption) high-performance liquid chromatographic procedure is presented for the determination of chlordiazepoxide and two common impurities, 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide and 2-amino-5-chlorobenzophenone, in commercial formulations and for the determination of the benzophenone in the chlordiazepoxide drug substance. The method involves simultaneous quantitation of chlordiazepoxide and the 1,3-dihhydro impurity, followed by quantitation of the benzophenone from a separate sample extract using a second mobile phase. A single microparticulate silica gel column is used throughout. Nitrazepam and o-dinitrobenzene are the internal standards, Quantitation is by peak area using a computing integrator, except that the peak due to the benzophenone is quantitated by peak height. The described procedure is of equivalent precision, but superior accuracy, to the BP 1973 spectrophotometric procedure for the analysis of chlordiazepoxide in chlordiazepoxide formulations. Quantitation of the 1,3-dihydro and the benzophenone impurities at levels as low as 6.3 and 0.9 ng, respectively, is demonstrated.

Benzodiazepinones↗

PubMed2025

Columba: fast approximate pattern matching with optimized search schemes.

MOTIVATION: Aligning sequencing reads to reference genomes is a fundamental task in bioinformatics. Aligners can be classified as lossy or lossless: lossy aligners prioritize speed by reporting only one or a few high-scoring alignments, whereas lossless aligners output all optimal alignments, ensuring completeness and sensitivity. RESULTS: This paper introduces Columba, a high-performance lossless aligner tailored for Illumina sequencing data. Columba processes single or paired-end reads in FASTQ format and outputs alignments in SAM format. By utilizing advanced search schemes and bit-parallel alignment techniques, Columba achieves exceptional speed. Columba is available in two variants. The first, based on the bidirectional FM-index, prioritizes speed. The second, Columba RLC, uses run-length compression using a bidirectional move structure, significantly reducing memory usage for large, repetitive datasets like pan-genomes. Benchmarks on the human genome, as well as bacterial and human pan-genome datasets, demonstrate that Columba is much faster than existing lossless aligners and even competitive with lossy tools. We integrated Columba into the OptiType HLA genotyping pipeline, where it substantially reduced computational time while maintaining accuracy. These results position Columba as a versatile, state-of-the-art tool for high-sensitivity genomic analyses. AVAILABILITY AND IMPLEMENTATION: The source code of Columba is available at https://github.com/biointec/columba under AGPL license. Scripts to reproduce the benchmarks and analyses are available at https://doi.org/10.5281/zenodo.15849246.

Software↗

PubMed1975

A mathematical model of the ventilatory control system to carbon dioxide with special reference to athletes and nonathletes.

The ventilatory response curve (VRC) as a function of alveolar and arterial pCO2 was recorded in 6 high-performance athletes and 6 nonathletes. The best fit to the data points could be found for an equation of the form (see article) showing that the results are strongly related to a Gaussian probability density function (PDF). After normalizing the equation to a form (see article) (M = mean value of PDF), sigma, A and M could be determined for both groups. Sigma and A are smaller in the athletic group, whereas M did not show any systematic difference. Regarding the respiratory center consisting of functional "elements" responding indirectly to variable pCO2 it can be concluded that the frequency distribution of the different active elements is greater and spread over a wider pCO2 range in the nonathletes with the same mean value in both groups. Using Loeschcke's model (1960), the open loop gain factor for different V CO2 as a function of p(A)CO2 was computed; the gain factor showed a maximum in the physiological range of pCO2.

Adult↗

PubMed1977

Development and use of analytical systems based on mass spectrometry.

Contemporary analytical systems based on mass spectrometry include as components a gas chromatograph, a mass spectrometer, and a computer. The form of operation is usually in electron impact ionization mode for identification and structural studies, and in chemical ionization mode for quantitative analyses. Important stages in the development of these systems included the design of "molecule separators" for the concentration of solutes in the gas phase, the use of mass spectrometers as specific ion detectors, the introduction of chemical ionization techniques, and the development of computer-based operation, data acquisition, and data analysis capabilities. A current line of investigation is concerned with the design and use of systems based on atmospheric pressure ionization. Samples are ionized in a small reaction chamber external to the low-pressure region of a quadrupole mass analyzer. The primary source of electrons is a 63Ni foil or a corona discharge. The ionization process leading to positive ions involves a sequence of ion molecule reactions, usually electrons leads to carrier gas ions leads to reagent ions leads to sample component ions. Negative ions may be formed by direct electron attachment, or by ion molecule reactions that include new types of elimination reactions. The source will accept a variety of gases and solvents. The sample may be introduced in the gas phase without solvents, by probe injection, or in the effluent stream from a gas chromatograph. Samples may be introduced in the liquid phase in solvents by injection after the fashion of gas chromatography or in the effluent stream from a high-performance liquid chromatograph. The novel aspects of atmospheric pressure ionization mass spectrometry lie in its versatility and high sensitivity of detection. Few clinical chemistry laboratories now use these systems. Significant future uses are likely to be in analytical work involving therapeutic drug monitoring and studies of drug metabolism, and in analyses for environmental biohazards including pesticides, herbicides, polyhalobiphenyls, dibenzodioxins, and other toxic compounds.

Anions↗

PubMed1992

On-line measurement in biotechnology: exploitation, objectives and benefits.

Sound data biologically relevant are prerequisites when developing high-performance bioprocesses. Understanding of physiological regulation as well as sophisticated control strategies are highly dependent on the observability of the culture, i.e. the generation and exploitation of suited signals even under complex environmental measurement conditions. Against this background, the increasing number of analytical systems is very supportive and, accordingly, an appropriate handling of sensors and measured data is of decisive importance. This article reports on practical experience with routines for maintenance, service and calibration of hardware sensors which improve the quality of measurements significantly. Verification and validation of signals is outlined in order to make the value of data exploitation tools obvious. A method for the characterization of information is introduced by practical examples of Saccharomyces cerevisiae cultures when explaining the specific properties of extracting biological information from raw data. Finally, examples for advantageous exploitation of on-line data are given.

Biosensing Techniques↗

PubMed1978

Quantitative thin-layer and high-performance liquid chromatographic determination of the diuretic agent 2-chloro-5-[44-hydroxy-3-methyl-2-(methylimino)-4-thiazolidinyl]benzenesulphonamide hydrochloride in serum and urine.

Sensitive and specific thin-layer (TLC) and high-performance liquid chromatographic (HPLC) methods were developed for the determination of the diuretic agent 2-chloro-5-[4-hydroxy-3-methyl-2-(methylimino)-4-thiazolidinyl]benzenesulphonamide hydrochloride (HOE 740). HOE 740 can be determined in serum by HPLC. The detection is performed at a very short wavelength (202 nm), resulting in a detection limit of 10 ng/ml. By TLC only urine levels that are normally high can be determined directly (the detection limit is 70 ng/ml). For the determination of the lower serum levels it is necessary to convert the drug into its dehydration product, which has a higher absorbance and gives sufficient sensitivity (the detection limit is 10 ng/ml). Serum levels determined by the two methods correlate well. Some pharmacokinetic and excretion-kinetic data were computed using two-compartment open models.

Chromatography, High Pressure Liquid↗

PubMed2025

Vcfexpress: flexible, rapid user-expressions to filter and format VCFs.

MOTIVATION: Variant call format (VCF) files are the standard output format for various software tools that identify genetic variation from DNA sequencing experiments. Downstream analyses require the ability to query, filter, and modify them simply and efficiently. Several tools are available to perform these operations from the command line, including BCFTools, vembrane, slivar, and others. RESULTS: Here, we introduce vcfexpress, a new, high-performance toolset for the analysis of VCF files, written in the Rust programming language. It is nearly as fast as BCFTools, but adds functionality to execute user expressions in the lua programming language for precise filtering and reporting of variants from a VCF or BCF file. We demonstrate performance and flexibility by comparing vcfexpress to other tools using the vembrane benchmark. AVAILABILITY AND IMPLEMENTATION: vcfexpress is available under the MIT license at https://github.com/brentp/vcfexpress with code used for the manuscript deposited in https://doi.org/10.5281/zenodo.14756838.

Software↗

PubMed1992

Pharmacokinetics and metabolism of 4'-iodo-4'-deoxy-doxorubicin in humans.

PURPOSE: 4'-iodo-4'-deoxydoxorubicin is a new anthracycline that currently is under clinical evaluation. To improve the management of future trials, we have determined its pharmacokinetics and metabolism during a phase I/II study and have tried to relate the parameters obtained to the hematologic toxicity of the drug in terms of the survival of blood cells. PATIENTS AND METHODS: The pharmacologic study included 19 patients who were entered at dose levels that ranged between 6 and 90 mg/m2; nine patients were treated at 80 mg/m2, which is close to the maximum recommended dose level. Blood sampling was performed from the end of the bolus infusion to 48 hours after treatment. Drug and metabolites were extracted and analyzed by high-performance liquid chromatography (HPLC), and the data were processed by nonlinear fitting to multicompartment models. RESULTS: Plasma concentrations were best fitted to a three-compartment model with half-lives of 5.2 minutes, 0.79 hours, and 10.3 hours. The total body clearance and volume of distribution at steady state were high (350 L/h/m2 and 2,065 L/m2). The drug was metabolized extensively to a 13-dihydroderivative, 4'-iodo-4'-deoxy-doxorubicinol; the mean area under the curve (AUC) ratio metabolite/parent drug was the highest observed ever for an anthracycline (12.1 +/- 7.4); the metabolite was cleared from the plasma with an elimination half-life of 15.3 hours. The AUCs of the parent compound and its metabolite were related linearly to the dose administered, and showed no saturation phenomenon. Urinary excretion was studied in nine patients and showed a cumulative elimination of less than 6% of the dose administered, two thirds of which were eliminated in the first 12 hours after injection. Ninety-three percent to 100% of the elimination of fluorescent compounds occurred in the form of the metabolite. Drug concentration in five tumor samples showed a rapid uptake of the drug from plasma and a preferential uptake of the parent drug compared with the metabolite. Blood cell counts after 4'-iodo-4'-deoxydoxorubicin treatment showed significant correlations among the surviving fractions of both granulocytes and platelets and the AUCs of the parent drug and its metabolite; the most significant correlations were obtained for the granulocytes and the metabolite. Significant correlations between AUCs and blood-cell survivals were maintained, even if only the nine patients treated at the dose of 80 mg/m2 were taken into account for the computation. CONCLUSIONS: Our results especially show that myelosuppression that is induced by 4'-iodo-4'-deoxydoxorubicin can be well predicted by the measure of the AUC of the drug and its metabolite. This could be used for the further development of the drug toward high-dosage schedules.

Blood Platelets↗

PubMed1992

Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy.

In order to quantify effects of an experimental chemotherapy, MCF7 cells were studied with 14C-fluorodeoxyglucose (FDG) and high-performance liquid chromatography (HPLC). Uptake measurements were performed 1 and 4 hr after the end of a therapy with hexadecylphosphocholine (HPC). A dose- and time-dependent increase of the FDG uptake after therapy was observed, with a maximum at 1 hr after therapy. These data were used to develop a new metabolic design of combination treatment. Several time-dose combinations of HPC and deoxyglucose (DOG) were analyzed for their effects on growth inhibition. The combinations using DOG in the period of pronounced enhancement of FDG uptake (1 hr after HPC treatment) were found to be the most effective with an improvement of up to 520% in growth inhibition. This metabolic design of combination treatment may also be applied in vivo, and PET can be used to optimize the time and dose schedule of the modified treatment protocol.

Antineoplastic Agents↗