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PubMedDate not supplied

Development of computer-directed methods for the identification of hyperactivated motion using motion patterns developed by rabbit sperm during incubation under capacitation conditions.

Rabbit spermatozoa developed motions that mimicked hyperactivated motility during incubation for 16-20 hours under capacitation conditions and in several other commonly used media. Sperm from some rabbits failed to acquire this type of motility, and sperm from others failed to survive the long incubation time. Four motility patterns developed during incubation for 16-20 hours. Motility parameters measured by the CellSoft and CellTrak motion analysis systems were similar except for the average amplitude of lateral head displacement. Multivariate discriminant analysis with complementary regression analysis, and an unrelated tree structured classification method (CART), were used to derive rules, based on motility parameters, for the objective classification of sperm into the two motility classes: 1) nonhyperactivated motility and 2) hyperactivated motility or motility that mimicked hyperactivated motility. The motility parameter wobble (WOB) as superior to the commonly used parameter, linearity, as a classifier of motility types. It classified sperm into the two motility groups with 96.6% efficiency and, together with curvilinear velocity (VCL), attained classification efficiencies of 98%. The classification model produced by CART was preferred over the one obtained by discriminant analysis. The rule for motility classification was dependent on the motion analysis system used to measure the motion parameters. The rule for the CellSoft system, WOB < or = 0.78 and VCL > or = 51 microns/second, classified sperm with an efficiency of 98%, whereas the rule for the CellTrak system, WOB < or = 0.6 and VCL > or = 55 microns/second, achieved a classification efficiency of 97%. These rules should facilitate the study of sperm hyperactivation and its role in sperm function.

Animals↗
PubMed1994

MR volume segmentation of gray matter and white matter using manual thresholding: dependence on image brightness.

PURPOSE: To describe a quantitative MR imaging segmentation method for determination of the volume of cerebrospinal fluid, gray matter, and white matter in living human brain, and to determine the method's reliability. METHODS: We developed a computer method that allows rapid, user-friendly determination of cerebrospinal fluid, gray matter, and white matter volumes in a reliable manner, both globally and regionally. This method was applied to a large control population (N = 57). RESULTS: Initially, image brightness had a strong correlation with the gray-white ratio (r = .78). Bright images tended to overestimate, dim images to underestimate gray matter volumes. This artifact was corrected for by offsetting each image to an approximately equal brightness. After brightness correction, gray-white ratio was correlated with age (r = -.35). The age-dependent gray-white ratio was similar to that for the same age range in a prior neuropathology report. Interrater reliability was high (.93 intraclass correlation coefficient). CONCLUSIONS: The method described here for gray matter, white matter, and cerebrospinal fluid volume calculation is reliable and valid. A correction method for an artifact related to image brightness was developed.

Adult↗
PubMed2005

An improved, computer-based method to automatically track internal and external diameter of isolated microvessels.

OBJECTIVE: To develop an automated diameter tracking method suitable for studies of isolated, perfused microvessels (< 100 micro m internal diameter (ID)). METHODS: A diameter tracking method was implemented in conjunction with a standard PC workstation and video card. Within a user-defined window, the algorithm combined thresholding and iterative regression procedures to detect the average outer diameter (OD) of a vertically oriented microvessel. After an initial ID measurement by the user, the program continuously calculated ID based on the assumption of an incompressible vessel wall. RESULTS: The program, Vessel Track, was tested against a manual video caliper and two analog video dimension analyzers. Vessel Track was capable of accurately following arteriolar dimensions during extreme vasodilation and vasoconstriction. It provided more accurate, lower-noise recordings than either of the video dimension analyzers, particularly after strong vasoconstriction during which lumenal folds developed. Vessel Track also was capable of accurately measuring large-amplitude vasomotion in isolated lymphatic vessels at a tracking frequency of ~ 30 times/s. CONCLUSIONS: Vessel Track should be useful for automated diameter tracking of isolated arterioles, venules, and lymphatics. With suitable preparations, it provides fast, stable measurements of ID in microvessels even with irregular lumen geometry.

Algorithms↗
PubMed1992

POCKET: a computer graphics method for identifying and displaying protein cavities and their surrounding amino acids.

A new interactive graphics program is described that provides a quick and simple procedure for identifying, displaying, and manipulating the indentations, cavities, or holes in a known protein structure. These regions are defined as, e.g., the xo, yo, zo values at which a test sphere of radius r can be placed without touching the centers of any protein atoms, subject to the condition that there is some x < xo and some x > xo where the sphere does touch the protein atoms. The surfaces of these pockets are modeled using a modification of the marching cubes algorithm. This modification provides identification of each closed surface so that by "clicking" on any line of the surface, the entire surface can be selected. The surface can be displayed either as a line grid or as a solid surface. After the desired "pocket" has been selected, the amino acid residues and atoms that surround this pocket can be selected and displayed. The protein database that is input can have more than one protein "segment," allowing identification of the pockets at the interface between proteins. The use of the program is illustrated with several specific examples. The program is written in C and requires Silicon Graphics graphics routines.

Algorithms↗
PubMed2002

X-ray computed tomography methods for in vivo evaluation of local drug release systems.

Recent advances in drug delivery techniques have necessitated the development of tools for in vivo monitoring of drug distributions. Gamma emission imaging and magnetic resonance imaging suffer from problems of resolution and sensitivity, respectively. We propose that the combination of X-ray CT imaging and image analysis techniques provides an excellent method for the evaluation of the transport of platinum-containing drugs from a localized, controlled release source. We correlated local carboplatin concentration with CT intensity, producing a linear relationship with a sensitivity of 62.6 microg/mL per Hounsfield unit. As an example application, we evaluated the differences in drug transport properties between normal and ablated rabbit liver from implanted polymer millirods. The use of three-dimensional visualization provided a method of evaluating the placement of the drug delivery device in relation to the surrounding anatomy, and registration and reformatting allowed the accurate comparison of the sequence of temporal CT volumes acquired over a period of 24 h. Taking averages over radial lines extending away from the center of the implanted millirods and integrating over clinically appropriate regions, yielded information about drug release from the millirod and transport in biological tissues. Comparing implants in normal and ablated tissues, we found that ablation prior to millirod implantation greatly decreased the loss of drug from the immediate area, resulting in a higher average dose to the surrounding tissue. This work shows that X-ray CT imaging is a useful technique for the in vivo evaluation of the pharmacokinetics of platinated agents.

Animals↗
PubMed1993

A computer-assisted method for the study of the trabecular bone of the distal radius on conventional radiographs.

The procedure described is based on the acquisition and processing of x-rays of the distal radius obtained under standard conditions. An x-ray was obtained of the forearm together with an aluminum step wedge to automatically normalize the photometric values of the bone with respect to the photometric values of the reference aluminum wedge. Densitometric values for thickness (T) and a coarseness parameter (C) that depends on the trabecular bone pattern are measured on interactively selected rows and regions of interest (ROIs) of the digital image. Twenty-five women were examined and two different measurements were performed. The first measurement considers C in three sites of the radial epiphisis. The trabecular bone coarseness appears to increase from the distal to the very-very distal site and the value of C in the very distal site, which is located 1 cm distally to the distal one tenth of the radius, seems to be related to the pathological variations more than the value of C in the other sites. The second measurement is the C/T ratio of eight ROIs of 15 patients: five healthy and 10 osteoporotic women. This ratio is significantly different for the two groups in all the eight ROIs and the variations are particularly significant at 6 to 12 mm from the subchondral line.

Absorptiometry, Photon↗
PubMedDate not supplied

Applications of computers to toxicological research.

Computers are used in toxicology in two ways. They are able to manage and manipulate large amounts of data, and it is because of this that they are used quite commonly to search toxicity databases. The mechanical ability of computers has led a number of organizations to pursue their use in regulatory compliance. The cost-benefit aspect of this issue being what it is, much more effort can be expected in this area. The other major use of computers has been to support efforts to predict or estimate toxicity properties. This task has proven to be very difficult, as was expected, and progress has been mixed. Developers of systems, testing their own development, report impressive accuracy, as has been seen. The "real world" view is less felicitous. In a highly publicized, head-to-head test of some of the computer methods against human experts, accurate prediction of carcinogenicity by computer was achieved for 49-59% of the compounds, depending upon the method used. The humans, on the other hand, scored between 65% and 84%. A conclusion that could be drawn from this experiment is that with compounds which "obviously" are or are not carcinogenic, both computers and humans score well. Once obviousness recedes however, both are at a disadvantage, but humans can improvise more effectively. As research continues, the computer methods will develop better learning sets, and so there will be incremental improvements in their performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗
PubMed2002

Microspeciation in the copper(II)-L-histidylglycine system. An ESR study by the two-dimensional computer simulation method.

Twelve ESR-active (and one inactive) copper(II) complexes of L-histidylglycine (HL) were characterized via their formation (micro)constants and ESR parameters obtained by two-dimensional ESR spectroscopic evaluation in aqueous solution. In strongly acidic media, the ligand is coordinated through its N-terminal donor groups: the complex [CuLH(2)](3+) involves monodentate imidazole binding, whereas [CuLH](2+) involves bidentate ligation through the amino and imidazole N atoms. This histamine-like bonding mode also predominates in the isomers of [CuL(2)], formed at ligand excess near pH 7: in the major 4N isomer, both ligands occupy two equatorial sites, while in the 3N isomer, the second dipeptide is coordinated equatorially by the amino and axially by the imidazole groups. At above pH 3-4, deprotonation of the peptide group also starts: in approximately 60% of the molecules of [CuL](+), the peptide group is deprotonated, while in the minor isomer histamine-like coordination occurs. At higher pH, the active dimer [Cu(2)L(2)H(-2)], the mixed hydroxo complexes (the inactive [Cu(2)L(2)H(-3)](-) and the active [CuLH(-2)](-)), and the bis complexes [CuL(2)H](+) and [CuL(2)H(-1)](-) all involve tridentate equatorial ligation of the backbone by the amino and deprotonated peptide N and the carboxylate O atoms. In the active dimer, the neutral imidazole groups form bridges between CuLH(-1) units. In [CuL(2)H](+), the second ligand is bound equatorially via its imidazole group; in [CuL(2)H(-1)](-), the L ligand occupies the fourth equatorial site and an axial site through its amino and imidazole N atoms, respectively.

Amino Acids↗
PubMed2001

Computer-aided method for calculating animal configurations during social interactions from two-dimensional coordinates of color-marked body parts.

In an experiment investigating the impact of preweaning social experience on later social behavior in pigs, we were interested in the mutual spatial positions of pigs during paired social interactions. To obtain these data, we applied a different colored mark to the head and back of each of 2 pigs per group and videotaped the pigs' interactions. We used the EthoVision tracking system to provide x,y coordinates of the four colored marks every 0.2 sec. This paper describes the structure and functioning of a FoxPro program designed to clean the raw data and use it to identify the mutual body positions of the 2 animals at 0.2-sec intervals. Cleaning the data was achieved by identifying invalid data points and replacing them by interpolations. An algorithm was then applied to extract three variables from the coordinates: (1) whether the two pigs were in body contact; (2) the mutual orientation (parallel, antiparallel, or perpendicular) of the two pigs; and (3) whether the pig in the "active" position made snout contact in front of, or behind, the ear base of the other pig. Using these variables, we were able to identify five interaction types: Pig A attacks, Pig B attacks, undecided head-to-head position, "clinch" resting position, or no contact. To assess the reliability of the automatic system, a randomly chosen 5-min videotaped interaction was scored for mutual positions both visually (by 2 independent observers) and automatically. Good agreement was found between the data from the 2 observers and between each observer's data and the data from the automated system, as assessed using Cohen's kappa coefficients.

Animals↗
PubMed2005

Calculation of the hydration free energy difference between pyridine and its methyl-substituted derivatives by computer simulation methods.

The difference of the hydration free energy of pyridine and its methyl- and symmetrically dimethyl-substituted derivatives has been calculated by the method of free energy perturbation. To check the precision of the results obtained, we have repeated the calculations using thermodynamic integration over different paths. Besides the hydration free energy, the difference in the energy and entropy of hydration between pyridine and monomethyl- and dimethylpyridines has also been determined. The obtained results clearly show that the hydration free energy of the pyridine derivatives becomes more negative with each additional methyl group. However, the accuracy of the calculation does not allow us to draw any conclusion about the dependence of the hydration free energy on the location of the methyl group. The analysis of the Coulomb and Lennard-Jones contributions to the hydration free energy differences has shown the dominance of the latter term. The comparison of the hydration energy and free energy values has shown that there is a strong compensation effect between the energetic and entropic terms of the free energy. The hydration energy of the solute becomes considerably more negative with each additional methyl group due to the dispersion attraction between the methyl group and the surrounding water molecules. The introduction of a methyl group results in an approximately 30 J/(mol K) decrease of the entropy of hydration, and hence, at 300 K, the entropic contribution to the hydration free energy increases by about 9 kJ/mol. Due to their opposite signs, the entropic and energetic contributions largely cancel each other, resulting in approximately an order of magnitude smaller value for the free energy.

Computer Simulation↗
PubMed2006

Evaluation of different biological data and computational classification methods for use in protein interaction prediction.

Protein-protein interactions play a key role in many biological systems. High-throughput methods can directly detect the set of interacting proteins in yeast, but the results are often incomplete and exhibit high false-positive and false-negative rates. Recently, many different research groups independently suggested using supervised learning methods to integrate direct and indirect biological data sources for the protein interaction prediction task. However, the data sources, approaches, and implementations varied. Furthermore, the protein interaction prediction task itself can be subdivided into prediction of (1) physical interaction, (2) co-complex relationship, and (3) pathway co-membership. To investigate systematically the utility of different data sources and the way the data is encoded as features for predicting each of these types of protein interactions, we assembled a large set of biological features and varied their encoding for use in each of the three prediction tasks. Six different classifiers were used to assess the accuracy in predicting interactions, Random Forest (RF), RF similarity-based k-Nearest-Neighbor, Naïve Bayes, Decision Tree, Logistic Regression, and Support Vector Machine. For all classifiers, the three prediction tasks had different success rates, and co-complex prediction appears to be an easier task than the other two. Independently of prediction task, however, the RF classifier consistently ranked as one of the top two classifiers for all combinations of feature sets. Therefore, we used this classifier to study the importance of different biological datasets. First, we used the splitting function of the RF tree structure, the Gini index, to estimate feature importance. Second, we determined classification accuracy when only the top-ranking features were used as an input in the classifier. We find that the importance of different features depends on the specific prediction task and the way they are encoded. Strikingly, gene expression is consistently the most important feature for all three prediction tasks, while the protein interactions identified using the yeast-2-hybrid system were not among the top-ranking features under any condition.

Computational Biology↗
PubMed1996

Guidance in the setting of drug particle size specifications to minimize variability in absorption.

PURPOSE: To provide guidance in setting particle size specifications for poorly soluble drugs to minimize variability in absorption. METHODS: A previously reported computer method was used to simulate the percent of dose absorbed as a function of solubility, absorption rate constant, dose, and particle size. RESULTS: The simulated percent of dose absorbed was tabulated over a realistic range of solubilities, absorption rate constants, and doses using drug particle sizes that might be typically found in a dosage form. CONCLUSIONS: The greatest effect of particle size on absorption was simulated for low dose- low solubility drugs. In general, the sensitivity of absorption to particle size decreased with increasing dose or solubility. At a solubility of 1 mg/mL, particle size had practically no effect on the percent of dose absorbed over the range of doses simulated (1-250 mg).

Computer Simulation↗
PubMed2026

Likelihood-based optimization enables accurate copy number estimation for paralogous genes using exome data.

MOTIVATION: Exome sequencing is widely used for genetic studies; however, accurate detection of copy number variants (CNV) in paralogous genes is challenging due to short-read mapping ambiguity and extensive copy-number variation. The human genome contains several hundred paralogous genes, many of which are known to harbor disease-associated CNVs. Existing exome CNV callers are primarily designed for rare CNV detection in uniquely mappable regions and are not well-suited for paralogous genes. METHODS: We describe a computational method (EdgeCopy) for copy number profiling of paralogous genes using whole-exome sequence data. EdgeCopy aggregates reads mapped to all copies of paralogous genes and relates observed read depth to copy number for multiple exome samples using an approximate composite likelihood function. The likelihood function is optimized using numerical optimization to obtain gene-level fractional copy number estimates that are discretized and refined using a Hidden Markov Model to obtain exon-level copy number estimates. RESULTS: Benchmarking of Edgecopy using experimental copy number data showed high concordance (mean&#x2009;=&#x2009;0.973) for six disease-associated paralogous genes. We evaluated performance using whole-exome data from approximately 2400 samples across five continental populations from the 1000 Genomes Project. EdgeCopy shows robust concordance with whole-genome sequencing based estimates (0.974-0.982) across populations and 130 paralogous genes spanning a wide range of copy-number variation. In comparison, copy number analysis using a state-of-the-art exome CNV caller failed to estimate copy number for paralogous genes with very high mapping ambiguity and showed much lower concordance (0.565) for CNV events compared to EdgeCopy (0.908). AVAILABILITY: EdgeCopy is freely available at https://github.com/vibansal-lab/edgecopy.

Humans↗
PubMed2000

Stability and electrophilicity of phosphorus analogues of arduengo carbenes--an experimental and computational study

A variety of differently substituted 1,3,2-diazaphospholenium salts and P-halogeno-1,3,2-diazaphospholenes (X = F, Cl, Br) were synthesized, and their molecular structures, bonding situation, and Lewis acid properties were characterized by experimental (single-crystal X-ray diffraction, NMR and IR/Raman spectroscopy, MS, conductometry, titrations with Lewis bases) and computational methods. Both experimental and computational investigations confirmed that the structure and bonding in the diazaphospholenium cations of OTf and BF4 salts resembles that of neutral Arduengo carbenes and that the cations should not be described as genuinely aromatic. P-Halogenodiazaphospholenes are, in contrast to earlier assumptions, molecular species with covalent P-X bonds whose bonding situation can be expressed in terms of hyperconjugation between the six pi electrons in the C2N2 unit and the sigma*(P-X) orbital. This interaction induces a weakening of the P-X bonds, whose extent depends subtly on substituent influences and contributes fundamentally to the amazing structural similarity of ionic and covalent diazaphospholene compounds. A further consequence of this effect is the unique polarizability of the P-Cl bonds in P-chlorodiazaphospholenes, which is documented in a considerable spread of P-X distances and bond orders. Measurement of the stability constants for complexes of diazaphospholene compounds with Lewis bases confirmed the lower Lewis acidities and higher stabilities of diazaphospholenium ions as compared with nonconjugated phosphenium ions; this had been inferred from computed energies of isodesmotic halide-transfer reactions, and permitted also to determine equilibrium constants for P-Cl bond dissociation reactions. The results suggest, in accord with conductance measurements, that P-chlorodiazaphospholenes dissociate in solution only to a small extent. On the basis of these findings, the unique solvatochromatic behavior of NMR chemical shifts of these compounds was attributed to solvent-dependent P-Cl bond polarization rather than to shifts in dissociation equilibria.

Journal Article↗
PubMed2001

Potential seasonal ecological challenge of heat strain among Australian Aboriginal people practicing traditional subsistence methods: a computer simulation.

It has been largely accepted that Australian Aboriginal people practicing hunting and gathering traditionally underused their objective economic possibilities by working short hours relative to nonhunter-gatherer populations. However, the possibility that their subsistence quest might have been limited by potential heat strain has not been considered for Australian hunter-gatherers. In this article the influence of work and heat load on the potential for heat strain among adult male Australian Aboriginal people is modelled. The possibility that the short working day of Arnhem Land adults reported in the literature might reflect ecologically limited work scheduling by way of potential heat strain is examined. Three climatic regions of the North of Western Australia and the Northern Territory were identified, using data available from the Australian Bureau of Meteorology. Data from the months of January, April, July, and October were used with the United States Army Heat Strain Model, along with assumptions with respect to work load and time scheduling. Predictive modelling indicates that a late start to the working day could carry considerable risks of potential heat strain during the summer, when humidity and maximum daily temperature are highest for all three climatic regions, but especially in the tropical coastal region. While extended work times may have been needed to acquire adequate food under traditional conditions, work output could have been limited by potential heat strain under some conditions likely to have prevailed.

Adaptation, Physiological↗
PubMed1986

Left thalamic infarction and disturbance of verbal memory: a clinicoanatomical study with a new method of computed tomographic stereotaxic lesion localization.

A 41-year-old right-handed man developed disturbances of language and memory after a discrete thalamic infarction. Detailed neuropsychological assessment revealed deficits in verbal fluency, word finding, confrontation naming, and anterograde memory for verbal material. High-resolution computed tomography with stereotaxic lesion localization permitted the determination of the thalamic nuclei involved in the infarction. We suggest that the patient's problem in language and verbal memory reflected a defect in memory processing for verbal material during registration, retention, and retrieval, and that this defect probably resulted from a left anterior thalamic lesion affecting the ventrolateral nucleus, centromedian-parafascicular nuclei complex, internal medullary lamina, or mamillothalamic tract.

Adult↗