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Results for “quantitative model”

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At least 199 records · Page 11Linked to original sources
PubMed1989

Negative co-operativity in Escherichia coli single strand binding protein-oligonucleotide interactions. I. Evidence and a quantitative model.

The interaction of the Escherichia coli single strand binding (SSB) protein with single-stranded DNA is complex, since a number of different binding modes have been observed, with different DNA site sizes and binding properties and the transitions among these binding modes are strongly influenced by solution conditions in vitro. Recent experiments have suggested the existence of negative co-operativity among the multiple DNA binding sites within individual SSB tetramers. In order to probe this negative co-operativity, we have examined the binding of a series of oligonucleotides of varying length, using the quenching of the intrinsic SSB protein fluorescence to monitor binding. The stoichiometries for saturation of the SSB tetramer are 4, 2, 2, 1 and 1, for the oligonucleotides, dT(pT)N-1, with N = 16, 28, 35, 56 and 70, respectively, indicating that one molecule of either dT(pT)27 or dT(pT)34 interacts with two SSB subunits, whereas one molecule of dT(pT)15 interacts with only a single subunit. Saturation of the SSB tetramer with dT(pT)15, dT(pT)34, dT(pT)69 or poly(dT) results in 85 to 90% quenching of the SSB fluorescence, whereas saturation with dT(pT)27 or dT(pT)55 results in only 80% and 72% quenching, respectively. Therefore, a single-stranded DNA of at least 64 nucleotides is required to wrap around an SSB tetramer fully and interact with all four subunits. A quenching of 50(+/- 2)% is observed upon filling only half of the subunits with either one molecule of dT(pT)34 or two molecules of dT(pT)15, which agrees with the quenching and site size observed in the (SSB)35 polynucleotide binding mode. Direct binding measurements indicate that the binding of dT(pT)27 to its second site is influenced by the oligonucleotide that occupies the first binding site (either dT(pT)27 or dT(pT)34), providing proof for the existence of a true negative co-operativity. This negative co-operativity is observed also for the binding of the shorter oligonucleotide, dT(pT)15. A statistical thermodynamic ("square") model gives an excellent description of the binding of all oligonucleotides possessing multiple sites on the SSB tetramer, based on only two interaction constants, the intrinsic binding constant, KN, and the negative co-operativity parameter, sigma N. These data indicate that the binding sites (subunits) on the unliganded SSB tetramer are all equivalent, but that a non-equivalence between dimers of subunits within the tetramer is induced upon binding ssDNA.

Bacterial Proteins↗
PubMed1985

Quantitative models of hybrid dysgenesis: rapid evolution under transposition, extrachromosomal inheritance, and fertility selection.

A model of the P-M system of hybrid dysgenesis is presented which incorporates single-site transposition of P factors in M cytotype, determination of offspring cytotype by both maternal cytotype and maternal or offspring nuclear genotype, and strong fertility selection in dysgenic individuals. The conditions required for the initial invasion of P factors into a pure M population, information concerning stable polymorphisms, and results of numerical iterations depicting the dynamic, nonequilibrium behavior of the system are summarized. While conditions for initial increase are independent of the rate of cytotype switching, the rate of evolution is accelerated by increased production of dysgenic individuals. If the transposition rate is sufficiently high to overcome the fertility barrier opposing P factors introduced into M populations, then convergence to high frequencies of the P factor occurs very rapidly. Under intense fertility depression, the phase of rapid increase may be preceded by an extended period of gradual increase at low frequencies.

Animals↗
PubMed1995

A quantitative model for simultaneous brightness induction.

The brightness that results from stimulating a particular test-region of the retina may be depressed or enhanced by simultaneous stimulation of other "inducing"-regions. The test-region brightness may be affected by contiguous inducing-regions (local contrast effects), and by non-contiguous inducing regions (long-range effects sometimes called "assimilation"). We describe a computational model for early vision that can predict the results of brightness-matching procedures commonly used to measure these phenomena. According to this model, brightness depression reflects primarily lateral inhibition that underlies local contrast effects; whereas brightness enhancement results from processes similar, in spirit, to those described in Helson's adaptation-level theory.

Contrast Sensitivity↗
PubMed1991

Qualitative and quantitative modelling of toxic effects of organophosphorous compounds to fish.

In this paper a QSAR analysis is applied with the intention of analyzing toxicity data of 20 organophosphorous compounds in terms of possible rate-limiting steps. Several aspects will be discussed and related to the physico-chemical properties of the test compounds. These are: bioconcentration factors, inhibition of acetylcholinesterase (AChE) and biotransformation in oxidative and glutathione-mediated in vitro systems. As expected, relatively simple relationships between toxicity data and Kow, as obtained for narcotic chemicals, were not obtained. The results of this study show that large differences can occur in the toxicity of the chemicals to fish, despite the fact that in vitro parameters for AChE inhibition and biotransformation are approximately equal. From these observations it is concluded that the application of general QSAR models for the estimation of toxicity data of reactive compounds that can be metabolized in vivo is as yet restricted due to our lack of knowledge of specific enzyme activities and of the role of possible extrahepatic biotransformation processes.

Animals↗
PubMed1986

Understanding metabolic alterations in space flight using quantitative models: fluid and energy balance.

This report summarizes many of the results obtained during the Skylab program, on metabolic changes during weightlessness. The examination of the data was conducted following an integrated multi-disciplinary and multi-experimental approach. Emphasis is given on several major aspects of metabolic adaptation to space flight: fluid-electrolyte regulation, mechanisms of hormone disturbances, energy balance and etiology of weight loss. The aim is to obtain a composite picture of the fluid, electrolyte and energy response to weightlessness.

Adaptation, Physiological↗
PubMed2005

Stimulant drug action in attention deficit hyperactivity disorder (ADHD): inference of neurophysiological mechanisms via quantitative modelling.

OBJECTIVE: To infer the neural mechanisms underlying tonic transitions in the electroencephalogram (EEG) in 11 adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) before and after treatment with stimulant medication. METHODS: A biophysical model was used to analyse electroencephalographic (EEG) measures of tonic brain activity at multiple scalp sites before and after treatment with medication. RESULTS: It was observed that stimulants had the affect of significantly reducing the parameter controlling activation in the intrathalamic pathway involving the thalamic reticular nucleus (TRN) and the parameter controlling excitatory cortical activity. The effect of stimulant medication was also found to be preferentially localized within subcortical nuclei projecting towards frontal and central scalp sites. CONCLUSIONS: It is suggested that the action of stimulant medication occurs via suppression of the locus coeruleus, which in turn reduces stimulation of the TRN, and improves cortical arousal. The effects localized to frontal and central sites are consistent with the occurrence of frontal delta-theta EEG abnormalities in ADHD, and existing theories of hypoarousal. SIGNIFICANCE: To our knowledge, this is the first study where a detailed biophysical model of the brain has been used to estimate changes in neurophysiological parameters underlying the effects of stimulant medication in ADHD.

Adolescent↗
PubMed2005

Current challenges in quantitative modeling of epidermal growth factor signaling.

Over the last decade, epidermal growth factor (EGF) signaling has been used repeatedly as a test-bed for pioneering computational systems biology. Recent breakthroughs in our molecular understanding of EGF signaling pose new challenges for mathematical modeling strategies. Three key areas emerge as particularly relevant: the pervasive importance of compartmentalization and endosomal trafficking; the complexity of signalosome complexes; and the regulatory influence of diffusion and spatiality. Each one of them demands a drastic change in current computational approaches. We discuss recent developments in the field that address these emerging aspects in a new generation of more realistic - and potential more useful - models of EGF signaling.

Animals↗
PubMed2005

A quantitative model for flow-induced bioluminescence in dinoflagellates.

A model is presented for the flash response of bioluminescent dinoflagellates stimulated by fluid shear. The model is based on the idea that the response of an individual cell to stimulation is inherently probabilistic, and can be modeled as a Poisson process over short time scales. A new cell parameter, the cell anxiety, is introduced to parameterize the probability of flashing. The statistical model is incorporated into a description of fully developed fluid flow in pipes and a cylindrical Couette chamber, and found to compare favorably with previously published data from experiments.

Animals↗
PubMed2001

A quantitative model for the dynamics of serum prostate-specific antigen as a marker for cancerous growth: an explanation for a medical anomaly.

Prostate-specific antigen (PSA) is an enzyme produced by both normal and cancerous prostate epithelial cells. Although PSA is the most widely used serum marker to detect and follow patients with prostatic adenocarcinoma, there are certain anomalies in the values of serum levels of PSA that are not understood. We developed a mathematical model for the dynamics of serum levels of PSA as a function of the tumor volume. Our model results show good agreement with experimental observations and provide an explanation for the existence of significant prostatic tumor mass despite a low-serum PSA. This result can be very useful in enhancing the use of serum PSA levels as a marker for cancer growth.

Adenocarcinoma↗
PubMed1977

A quantitative model of actin-myosin interaction in skeletal muscle.

Biochemical schemes for the actomyosin ATPase cycle as well as the cooperative regulation of ATPase activity are incorporated into a model of the contractile process of intact muscle. This model is shown to describe accurately the tension developed by skinned muscle fibers in the absence of Ca. This work adds to the evidence that the extrapolation of results from purified protein systems to intact muscle may be valid. Extensions to the case of Ca-activated tensions are discussed.

Actins↗
PubMed1982

A quantitative model of intersarcomere dynamics during fixed-end contractions of single frog muscle fibers.

A numerical model of a muscle fiber as 400 sarcomeres, identical except for their initial lengths, was used to simulate fixed-end tetanic contractions of frog single fibers at sarcomere lengths above the optimum. The sarcomeres were represented by a lumped model, constructed from the passive and active sarcomere length-tension curves, the force-velocity curve, and the observed active elasticity of a single frog muscle fiber. An intersarcomere force was included to prevent large disparities in lengths of neighboring sarcomeres. The model duplicated the fast rise, slow creep rise, peak, and slow decline of tension seen in tetanic contractions of stretched living fibers. Decreasing the initial non-uniformity of sarcomere length reduced the rate of rise of tension during the creep phase, but did not decrease the peak tension reached. Limitations of the model, and other processes that might contribute to the shape of the fixed end tetanic tension record are discussed. Taking account of model and experimental results, it is concluded that the distinctive features of the tension records of fixed end tetanic contraction at lengths beyond optimum can be explained by internal motion within the fiber.

Animals↗