Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Generative models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,585 records · Page 88Linked to original sources
PubMed1997

Multichannel wavelet-type decomposition of evoked potentials: model-based recognition of generator activity.

Scalp recording of electrical events allows the evaluation of human cerebral function, but contributions of the specific brain structures generating the recorded activity are ambiguous. This problem is ill-posed and cannot be solved without physiological constraints based on the spatio-temporal characteristics of the generators' activity. In our model-based analysis of evoked potentials for the purpose of generator activity detection, multichannel scalp-recorded signals are decomposed into a combination of wavelets, each of which can describe the neural mass coherent activity of cell assemblies. Elimination of contributions of specific generators and/or distributed background activity can produce physiologically motivated time-frequency filtering. The decomposition and filtering procedures are demonstrated by three examples; simulation of the surface manifestation of known intracranial generators; decomposition and reconstruction of auditory brainstem evoked potentials which reflect the differences among generators of these potentials; and cognitive components of evoked potentials which are diminished in the averaged recording but are clearly detected in single-trial signals.

Algorithms↗
PubMed1982

A two compartment model of the stepping generator: analysis of the roles of a stage-setter and a rhythm generator.

Recent studies on locomotion of the mesencephalic cat demonstrated that activation of the spinal stepping generator and the postural control system are dependent phenomena (Mori et al., 1978, 1980). This has motivated the construction of a new model of the stepping generator to account for interactions with the postural control system. The present model consists of two main compartments, the rhythm generator and the stage-setter. The rhythm generator generates rhythmic bursting discharges of extensor and flexor alpha motoneurons. The function of the stage-setter is to set and reset the excitability of extensor alpha motoneuron to a number of desired levels. This study analyzes interactions in this model between rhythm generating and postural control system. By adding a concept of "stage-setting" to the rhythm generator model, we succeed in simulating a variety of locomotor patterns observed in the mesencephalic cat, including "stepping automatism" (Mori et al., 1979).

Animals↗
PubMed2005

A polymerization-depolymerization model that accurately generates the self-sustained oscillatory system involved in bacterial division site placement.

Determination of the proper site for division in Escherichia coli and other bacteria involves a unique spatial oscillatory system in which membrane-associated structures composed of the MinC, MinD and MinE proteins oscillate rapidly between the two cell poles. In vitro evidence indicates that this involves ordered cycles of assembly and disassembly of MinD polymers. We propose a mathematical model to explain this behavior. Unlike previous attempts, the present approach is based on the expected behavior of polymerization-depolymerization systems and incorporates current knowledge of the biochemical properties of MinD and MinE. Simulations based on the model reproduce all of the known topological and temporal characteristics of the in vivo oscillatory system.

Adenosine Triphosphatases↗
PubMed1999

Wet air oxidation of oily wastes generated aboard ships: kinetic modeling.

Ships are floating industrial plants which generate great amounts of toxic and hazardous wastes. Nevertheless, a feasible model for the management of such wastes has not been developed yet. This work studies the feasibility of treating those wastes aboard the ship by means of aqueous oxidation at high pressures and temperatures. Wet air oxidation has proved to be a very efficient technology for the treatment of those residual currents, resulting in destruction efficiencies of greater than 90% of initial COD and 99.9% of oil/greases content. A kinetic model for the oxidation process, based on a series-parallel reaction pathway, is proposed and is shown to fit the experimental results.

Kinetics↗
PubMed2000

Molecular dynamics generation of nonarbitrary membrane models reveals lipid orientational correlations.

This report addresses the following problems associated with the generation of computer models of phospholipid bilayer membranes using molecular dynamics simulations: arbitrary initial structures and short equilibration periods, an Ewald-induced strong coupling of phospholipids, uncertainty regarding which value should be used for surface tension to alleviate the problem of the small size of the membrane, and simultaneous realization of both order parameters and the surface area. We generated a computer model of the liquid-crystalline L-alpha-dimyristoylphosphatidylcholine (DMPC) bilayer, starting from a configuration based on a crystal structure (rather than from an arbitrary structure). To break the crystalline structure, a 20-ps high-temperature pulse of 510 K (but not 450 or 480 K) was effective. The system finally obtained is an all-atom model, with Ewald summation to evaluate Coulombic interactions and a constant surface tension of 35 dynes/cm/water-membrane interface, equilibrated for 12 ns (over 50 ns total calculation time), which reproduces all of the experimentally observed parameters examined in this work. Furthermore, this model shows the presence of significant orientational correlations between neighboring alkyl chains and between shoulder vectors (which show the orientations of the lipids about their long axes) of neighboring DMPCs.

Computer Simulation↗
PubMed2002

Unsteady aerodynamic force generation by a model fruit fly wing in flapping motion.

A computational fluid-dynamic analysis was conducted to study the unsteady aerodynamics of a model fruit fly wing. The wing performs an idealized flapping motion that emulates the wing motion of a fruit fly in normal hovering flight. The Navier-Stokes equations are solved numerically. The solution provides the flow and pressure fields, from which the aerodynamic forces and vorticity wake structure are obtained. Insights into the unsteady aerodynamic force generation process are gained from the force and flow-structure information. Considerable lift can be produced when the majority of the wing rotation is conducted near the end of a stroke or wing rotation precedes stroke reversal (rotation advanced), and the mean lift coefficient can be more than twice the quasi-steady value. Three mechanisms are responsible for the large lift: the rapid acceleration of the wing at the beginning of a stroke, the absence of stall during the stroke and the fast pitching-up rotation of the wing near the end of the stroke. When half the wing rotation is conducted near the end of a stroke and half at the beginning of the next stroke (symmetrical rotation), the lift at the beginning and near the end of a stroke becomes smaller because the effects of the first and third mechanisms above are reduced. The mean lift coefficient is smaller than that of the rotation-advanced case, but is still 80 % larger than the quasi-steady value. When the majority of the rotation is delayed until the beginning of the next stroke (rotation delayed), the lift at the beginning and near the end of a stroke becomes very small or even negative because the effect of the first mechanism above is cancelled and the third mechanism does not apply in this case. The mean lift coefficient is much smaller than in the other two cases.

Animals↗
PubMed2005

A model for surface EMG generation in volume conductors with spherical inhomogeneities.

Most models for surface electromyography (EMG) signal generation are based on the assumption of space-invariance of the system in the direction of source propagation. This assumption implies the same shape of the potential distribution generated by a source in any location along the propagation direction. In practice, the surface EMG generation system is not space invariant and, therefore, the surface signal detected along the direction of the muscle fibers may significantly change shape along the propagation path. An important class of nonspace invariant systems is that of volume conductors inhomogeneous in the direction of source propagation. In this paper, we focused on inhomogeneities introduced by the presence of spheres of different conductivities with respect to the tissue where they are located. This effect may prove helpful to model the presence of glands, vessels, or local changes in the conductivity of a tissue. We present an approximate analytical solution that accounts for an arbitrary number of spheres in an arbitrary complex volume conductor. As a representative example, we propose the solution for a planar layered volume conductor, comprised of fat and muscle layers with spherical inhomogeneities inside the fat layer. The limitations of the approximations introduced are discussed. The model is computationally fast and constitutes an advanced means for the analysis and interpretation of surface EMG signal features.

Action Potentials↗
PubMed1994

Mathematical modelling for the generation of L-[3-2H,3-13C]lactic acid isotopomers by erythrocytes exposed to either D-[1-13C]glucose or D-[6-13C]glucose in the presence of 2H2O.

The production of C3-trisdeuterated, bisdeuterated, monodeuterated or non-deuterated L-[3-13C]lactate by human erythrocytes exposed to either D-[1-13C]glucose or D-[6-13C]glucose in the presence of 2H2O can be assessed by 13C NMR spectroscopy. Such a deuteration may occur at the level of the reactions catalyzed by phosphoglucoisomerase, phosphomannoisomerase, pyruvate kinase and glutamate-pyruvate transaminase. In this report, a mathematical model is proposed for the analysis of experimental data. It allows to estimate the relative extent of deuteration at each step of D-glucose metabolism. This approach may thus provide novel information on the extent of back-and-forth interconversion of either hexose 6-phosphates in both the phosphoglucoisomerase and phosphomannoisomerase reactions or pyruvate and L-alanine in the reaction catalyzed by glutamate-pyruvate transaminase.

Alanine Transaminase↗
PubMed2006

A modified tyrosinase-related protein 2 epitope generates high-affinity tumor-specific T cells but does not mediate therapeutic efficacy in an intradermal tumor model.

The generation of tumor-specific T cells is hampered by the presentation of poorly immunogenic tumor-specific epitopes by the tumor. Here, we demonstrate that, although CD8+ T cells specific for the self/tumor Ag tyrosinase-related protein 2 (TRP2) are readily detected in tumor-bearing hosts, vaccination of either tumor-bearing or naive mice with an epitope derived from TRP2 fails to generate significant numbers of tetramer-staining TRP2-specific T cells or antitumor immunity. We identified an altered peptide epitope, called deltaV, which elicits T cell responses that are cross-reactive to the wild-type TRP2 epitope. Immunization with deltaV generates T cells with increased affinity for TRP2 compared with immunization with the wild-type TRP2 epitope, although TRP2 immunization often generates a greater number of TRP2-specific T cells based on intracellular IFN-gamma analysis. Despite generating higher affinity responses, deltaV immunization alone fails to provide any greater therapeutic efficacy against tumor growth than TRP2 immunization. This lack of tumor protection is most likely a result of both the deletion of high affinity and functional tolerance induction of lower affinity TRP2-specific T cells. Our data contribute to a growing literature demonstrating the ability of variant peptide epitopes to generate higher affinity T cell responses against tumor-specific Ags. However, consistent with most clinical data, simple generation of higher affinity T cells is insufficient to mediate tumor immunity.

Animals↗
PubMed1999

Population-based investigations of drug relative clearance using nonlinear mixed-effect modelling from information generated during the routine clinical care of patients.

Interpatient variability in drug disposition and response is a therapeutic premise, and thus evaluation and management of such variability are the basis for individualized pharmacotherapy. If the mathematical approach to determining drug doses were accurate and practical, the use of calculated doses could reduce the potential for toxicity and decrease the need for repetitious drug assays. The major strength of the population pharmacokinetics approach is that useful information can be extracted from sparse data collected during routine clinical care. Population pharmacokinetics can be defined as the study of the variability in serum drug concentrations between individuals when standard dosage regimens are administered. An approach to population pharmacokinetic data analysis has been implemented in the Nonlinear Mixed Effects Model (NONMEM) computer program. This report shows the feasibility of using a simple pharmacokinetic screen approach to estimate the population mean relative drug clearance and detecting drug-drug interaction by use of NONMEM. In clinical application of multiple trough screen or multiple peak screen, the variability of drug relative clearance within the population is assessed and a mathematical relationship between drug relative clearance and individual patient characteristics, such as age, body weight, gender, disease state or drug interaction with concomitant drug is derived. In this report I describe this approach and its application using several examples previously reported by us and others.

Electronic Data Processing↗
PubMed1998

Mechanisms and experimental models of seizure generation.

Over the past year evidence has accumulated against the idea that seizures require re-entrant activity between spatially separate structures. Seizures in vivo typically do involve interconnected, spatially separate brain regions, but they often show no net phase lag around the putative circuit. In many cases seizure-like events can arise from localized regions such as the entorhinal cortex or hippocampus proper, through mechanisms that are starting to be identified.

Animals↗
PubMed2000

Model for the generation of toroidal and poloidal magnetic fields in a laser-produced plasma.

A mechanism of simultaneous generation of toroidal and poloidal magnetic fields in an underdense region of a laser-produced plasma is discussed. The mechanism relies on the fact that at least a part of the incident transverse mode of the laser field undergoes a linear conversion into a longitudinal mode in the thermal plasma. It involves the conversion of ordered kinetic motion of the charged particles in the presence of the field into the energy of the induced magnetic fields both in poloidal and toroidal directions. The analysis is based on obtaining perturbative solutions of the two-fluid model of a hot nondissipative plasma. Our numerical results show that both the toroidal and poloidal fields increase with the laser intensity, and that the former dominates over the latter. Further, the toroidal fields decrease with increasing pulse lengths and increase rather slowly with an increase in laser wavelengths. However, the poloidal fields seem to be insensitive to the laser pulse lengths but they increase exponentially with the laser wavelengths. Finally, toroidal fields have a tendency to decrease as the critical surface is approached. The poloidal fields show a contrary behavior.

Journal Article↗
PubMed1985

A common biochemical pattern in preneoplastic hepatocyte nodules generated in four different models in the rat.

Hepatocyte nodules, structures consistently seen in every model of liver carcinogenesis well before the first appearance of cancer, were examined with respect to some Phase I and Phase II components considered to be important in the metabolism of carcinogens and other xenobiotics. Phase I components are those related to the metabolism of xenobiotics and include microsomal cytochromes P-450 and mixed-function oxygenase activities. Phase II components are those related to the conjugation and detoxification reactions of xenobiotics and their metabolites and include glutathione S-transferases and glutathione. Nodules were induced by the resistant hepatocyte, choline-deficient, methionine-low diet, phenobarbital and orotic acid models of liver carcinogenesis. Also, nodules generated by the resistant hepatocyte model were examined after transplantation to the spleen of syngeneic animals. The hepatocyte nodules show a common biochemical pattern, consisting of decreased microsomal cytochromes P-450, cytochrome b5, and aminopyrine N-demethylase activity and increased glutathione and gamma-glutamyltransferase in whole homogenates and glutathione S-transferase activity in the cytosol. This similarity, appropriate to a resistance phenotype, adds additional support for the hypothesis that hepatocyte nodules may be a common step in liver carcinogenesis in several different models.

Aminopyrine N-Demethylase↗
PubMed1988

HT-29 cells are an in vitro model for the generation of cell polarity in epithelia during embryonic differentiation.

A monoclonal antibody that recognizes a membrane glycoprotein specific for the apical membrane of human colonic epithelial cells has been used to follow the differentiation and polarization of a cell line, HT-29, derived from a human colon adenocarcinoma. When these cells formed a polarized epithelium, the antigen was concentrated at the apical plasma membrane. It was also found intracellularly in vesicles and vacuoles. When HT-29 cells were undifferentiated and unpolarized, the antigen was not expressed significantly at the plasma membrane but was found concentrated in the membranes of intracellular vacuoles. Cells not yet organized into an epithelium may thus synthesize a membrane protein specific for their future apical membranes and store it intracellularly until the polarization process takes place. Intermediary stages of differentiation were occasionally recognized. They are characterized by a small number of cells surrounding an intercellular lumen. These lumina displayed apical membrane features (the presence of the apical antigen, of some microvilli, and of junctional complexes), although the cells were not fully differentiated. The differentiation process in HT-29 cells is apparently similar to that observed during embryonic development of the intestine. Therefore, HT-29 cells represent a useful model system to study epithelial differentiation in vitro.

Adenocarcinoma↗
PubMed1979

Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte.

The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2.

Acetaldehyde↗
PubMed2000

The respiratory central pattern generator of Lymnaea: a model, measured and malleable.

Great progress has been made, and continues to be made in our understanding of the neuronal mechanisms underlying respiration in a wide variety of model systems. The central pattern generator (CPG) controlling aerial respiration in the pond-snail Lymnaea is a particularly well-studied model. Using in vitro and semi-intact preparations, the neural circuitry that controls aerial respiration has been characterized as consisting of three identified interneurons. Furthermore, insight has been gained into the behavioural, cellular and synaptic mechanisms by which this circuit controls respiratory rhythmogenesis. It has also been demonstrated that aerial respiratory behaviour can be modified both by experience and by environmental factors. Studies have shown that, in a behavioural hierarchy, respiration is subservient to the whole-body withdrawal response that respiratory behaviour can be modified through operant conditioning, and that respiratory behaviour is altered by hypoxia. Through research on the Lymnaea respiratory CPG we are coming to a better understanding of the construction and malleability of a CPG network. The malleability of this CPG is of particular interest. No longer can neuronal networks underlying respiratory behaviour be considered hard-wired; they have inherent plasticity.

Animals↗
PubMed1978

Sequential expression of immunoglobulin on developing mouse B lymphocytes: a systematic survey that suggests a model for the generation of immunoglobulin isotype diversity.

Paired immunofluorescent staining with antibodies specific for the major isotypes of mouse immunoglobulin was used to study the ontogenetic expression of diversity of cell surface immunoglobulin. The first B lymphocytes to emerge, derived from cytoplasmic IgM+ precursors, express sIgM exclusively. Between birth and 3 days of age separate populations of sIgM+ B lymphocyte acquire a second isotype: sIgD, one of the subclasses of sIgG, or sIgA. At 3 days, all splenic B lymphocytes that bear sIg or sIgA also express sIgM, but virtually none stain for sIgD. By 7 days, a substantial porportion of sIgG+ or sIgA+ lymphocytes in spleen and most of those in lymph node express both sIgM ans sIgD. Anti-mu antibody treatment from birth prevented development of B lymphocytes expressing any isotype. These observations suggest that the immature sIgM+ B lymphocyte is the pivotal cell in the generation of the different sublines of B cells and that sIgD ig or IgA. The frequency of lymphocytes bearing only sIgG or sIgA is higher in old than in young mice, suggesting that sIgD and sIgM may be lost after stimulation by antigens. The occurrence of a nearly identical distribution of sIg isotypes on B lymphocytes from athymic, pathogen-free mice suggests that primary expression of isotype diversity does not require T cells.

Aging↗
PubMed1999

[Conditional mutagenesis--second generation knockout mice as models for internal diseases].

KNOCKOUT MICE: The generation of knockout mice has largely improved our understanding of the function of a variety of gene products. Gene inactivation experiments in mice have yielded numerous animal models for human diseases, thereby expanding our understanding of the underlying pathophysiological mechanisms. The use of conventional knockout experiments is limited if the phenotyp of gene disruption results in embryonic letality. CONDITIONAL MUTAGENESIS: Conditional mutagenesis aims to overcome this limitation by regional and temporal control of gene inactivation in mice. CRE-LOXP SYSTEM: The bacteriophage-enzyme Cre recognizes loxP-sites in the genome and excises loxP-flanked DNA-regions. Using this system loxP-sites can be introduced into intron regions of a target gene and mice can be created carrying this functional, but loxP-marked gene. When crossed with transgenic mice expressing the Cre-recombinase under control of a tissue-specific and/or inducible promoter the gene will be inactivated in vivo in a timely and regionally controlled fashion.

Animals↗