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At least 991 records · Page 55Linked to original sources
PubMed1982

A model for the speech-reception threshold in noise without and with a hearing aid.

This paper presents a summary of the main results of our current research programme on the speech-reception threshold for sentences as a function of the sound-pressure level of interfering noise. The experimental results agree with a simple quantitative model in which every hearing loss for speech is interpreted as the sum of a class-A loss (attenuation), characterized by a reduction in the levels of both speech signal and noise, and a class-D loss (distortion), comparable to a reduction in S/N ratio. The experiments confirm the model's prediction that a hearing aid can compensate for class-A hearing losses but, generally, not for class-D hearing losses. The implies that the problem of having difficulties in understanding speech in a noisy environment, which is the primary handicap of hearing-impaired subjects, is not solved by the hearing aid.

Audiometry, Speech↗
PubMed2006

T-cell motility in the early stages of the immune response modeled as a random walk amongst targets.

The transport process by which a T cell makes high-frequency encounters with antigen-presenting cells following infection is an important element of adaptive immunity. Recent experimental work has allowed in vivo cell motility to be characterized in detail. On the basis of experimental data we develop a quantitative model for encounters between T cells and antigen-presenting cells. We model this as a transport-limited chemical reaction with the dynamics dependent on physical contact between randomly moving reactants. We use asymptotic methods to calculate a time distribution which characterizes the delay before a T cell is activated and use Monte Carlo simulations to verify the analysis. We find that the density of antigen-primed dendritic cells within the lymph node paracortex must be greater than 35 cells/mm3 for a T cell to have a more than 50% chance of encountering a dendritic cell within 24 h. This density is much larger than existing estimates based on calculations which neglect the transport process. We also use simulations to compare a T cell which re-orients isotropically with a T cell which turns according to an experimentally observed distribution and find that the effects of anisotropy on the solution are small.

Animals↗
PubMed2004

Quantification of water diffusion and relaxation times of human U87 tumors in a mouse model.

Assessing the potential of anti-cancer agents can be greatly facilitated by applying MRI methods to investigations with animal models. Quantitative diffusion imaging, T1, and T2 measurements may offer valuable information for understanding properties of the tumor and for evaluating new therapeutic approaches. The human U87 high-grade glial tumor is widely used for cancer investigations in orthotopic murine models. The physiological features of this model at the cellular and sub-cellular level have not, however, been well characterized by MRI. In this study, we measured the diffusion, T1 and T2 characteristics of water in the human U87 tumor at 8.5 T in an orthotopic murine model in vivo and analyzed their detailed changes in the transition from the tumor core through the tumor periphery, and out to surrounding tissue using custom developed radial profile analysis software. For the tumor bearing mice (n = 10), the mean average apparent diffusion coefficient (ADC) of the tumor core was 1.03 +/- 0.02 ( x 10(-3) mm2/s), while in the contralateral normal brain it was 0.73 +/- 0.03 ( x 10(-3) mm2/s). The mean T1 in tumor was 2.03 +/- 0.08 s and in normal brain tissue was 1.64 +/- 0.06 s. The mean T(2) in tumor was 0.062 +/- 0.002 s and in normal brain tissue was 0.048 +/- 0.001 s. The mean ADC, T1 and T2 of the tumor compared to normal tissue were significantly different (p < 0.005).

Animals↗
PubMed2002

Molecular relaxation and microscopic structure of multilayers and superlattices of a photosensitive liquid-crystalline polymer.

We report a detailed study of photoinduced changes in the microscopic structure of monolayers, multilayers, and superlattices of a photosensitive side chain liquid crystalline polymer, deposited by the Langmuir-Schaefer technique. We probe both out-of-plane and in-plane ordering and its changes due to optical pumping of the trans-cis photoisomerization transition of the azobenzene side chain in an azopolyacrylate. Microscopic structure was studied mainly by synchrotron radiation x-ray reflectometry and grazing incidence diffraction; we also used null-ellipsometry and atomic force microscopy. Our results provide a quantitative modeling of the structural changes and corresponding relaxation times taking place as a function of confinement, temperature and optical pumping, and in particular confirm previously reported ellipsometric results on such changes as a function of sample thickness. This allows a quantitative description of the effects of reduced dimensionality on the structural transitions in this glass-forming system.

Journal Article↗
PubMed1992

A pseudoreceptor docking study of 4,5-alpha-epoxymorphinans with a range of dielectric constants.

Thirteen 4,5-epoxymorphinan mu agonists with established analgesic action were docked into an Asp-Lys-His-Phe pseudoreceptor complex under a range of distance-dependent dielectric conditions. The number of compounds with potential energies of the docked complexes that agreed in rank order with corresponding analgesic potencies was determined for each condition. Two dielectric conditions, n-decane (1.991) and ethanol (24.3), enabled the greatest number of compounds to relate to their pseudoreceptors with each having 9 and 8 successes respectively. Both of these conditions demonstrated unique influences on the types of structures that were successfully docked. For example, the morphine stereoisomer alpha-isomorphine, the geometric isomer B/C trans-morphine, and the 8-position-substituted gamma-isomorphine were successes in the n-decane condition, whereas the ethanol condition produced the substituted codeine derivatives dihydrocodeinone and dihydroxycodeinone. These findings emphasize the importance of dielectric influence when developing force-field modeled quantitative structure-activity relationships for a closely related homologous series.

Amino Acid Sequence↗
PubMed2001

Diffusion-based calibration for SPME analysis of aqueous samples.

When an SPME fiber is exposed for a short period of time to a flowing fluid sample, the amount of extracted analyte depends on its diffusion coefficient in the matrix medium, and it can be correlated to its concentration using a simple mathematical model. This work discusses the extension of this approach, already validated for gaseous samples and SPME fibers coated with strong adsorbent coatings, to the diffusion-based quantification of analytes present in aqueous samples. Dilute aqueous solutions of aromatic hydrocarbons were used as model samples and vials were modified to use conventional magnetic agitation with controlled tangential flow of the test solution around the fiber. It was demonstrated that, with proper selection of the stirring speed and sampling time, the same diffusion-based quantitative model used for gas samples could be employed. Under optimal conditions, the concentrations of the evaluated aromatic hydrocarbons were estimated with relative standard deviations between 0.8 and 3.6% and without deviation from the expected values within this precision range. Considering the extraction times involved, between 30 and 60 s, the approach here presented is the fastest possible technique for direct extraction of analytes from liquid samples.

Journal Article↗
PubMed2003

Three-component competitive adsorption model for flow-through PAC systems. 2. Model application to a PAC/membrane system.

A three-component competitive adsorption kinetic model, developed and validated in part 1 of this study, was applied to a continuous-flow PAC/membrane system to study the effects of various system and operating parameters on organic removal. The model quantitatively describes the two competitive adsorption mechanisms that occur during adsorption of trace organic compounds by powdered activated carbon (PAC) in flow-through systems where the PAC is retained in the system: pore blockage and direct competition for adsorption sites. Model simulations were conducted to investigate the effects of influent water composition, membrane cleaning water quality, PAC pore size distribution, and system operation conditions such as hydraulic retention time, membrane cleaning interval, and PAC dosing method on treatment efficiency. Effects of these factors on adsorption capacity as well as surface diffusion rate and consequent removal of the trace organic compound were discussed. It was found that optimal operating conditions for maximum trace organic compound removal must be determined on the basis of the adsorption properties and concentrations of the competing compounds in the influent. For the conditions investigated in this study, the small strongly competing compound, p-DCB, had greater impact on atrazine removal than the large pore-blocking compound, PSS-1.8k. Various process design and operating parameters had complex and interrelated effects on the impact of competitive adsorption and corresponding trace contaminant removal efficiency in hybrid PAC/membrane systems.

Adsorption↗
PubMed1978

Towards a quantitative understanding of the epidemiology of Keystone virus in the eastern United States.

The implications of the Keystone virus--Aedes atlanticus transmission cycle are explored in the context of a quantitative model. Among the variables considered are the vertical transmission rate, the effect of the virus upon vector fertility and survival, vector densities and distributions, the proportion susceptible in the vertebrate population, the attractiveness of different vertebrates to the vector and vector survival rates. The logical relationships between these several variables are explored. It is concluded that the current view of Keystone virus maintenance is quantitatively feasible, and that certain predictions may be made as to the magnitude of several parameters which have not yet been measured. Such predictions allow direct testing of the model. The general structure of the model is such that it may prove useful in describing the epidemiology of other vector-borne infections in which vertical transmission is essential for infection maintenance at certain periods of the year.

Aedes↗
PubMed1991

Model of peripheral and amblyopic hyperacuity.

Vernier thresholds rise much more rapidly in the periphery than do grating thresholds. A similar dissociation between acuity and hyperacuity has been shown to be present in strabismic but not in anisometropic amblyopia, thus leading to the suggestion that the strabismic fovea is similar to the normal periphery. Here it is shown that a quantitative model for spatial pattern discrimination, which accounts for foveal hyperacuity data, can be extended to encompass both the periphery and amblyopia if appropriate alterations are made. For the periphery it is necessary to increase the size of model receptive fields and to introduce both spatial undersampling and position irregularity (i.e. irregularity in the location of cortical filters). The strabismic fovea also requires spatial undersampling and position irregularity but no change in receptive field size. Defects in the good eye of strabismics can be explained by spatial irregularity. Finally, the anisometropic fovea requires a reduction in mechanism sensitivity but neither spatial undersampling nor position irregularity.

Amblyopia↗
PubMed1982

A stepwise mechanism for the permeation of phloretin through a lipid bilayer.

The thermodynamics of interactions between phloretin and a phosphatidylcholine (PC) vesicle membrane are characterized using equilibrium spectrophotometric titration, stopped-flow, and temperature-jump techniques. Binding of phloretin to a PC vesicle membrane is diffusion limited, with an association rate constant greater than 10(8) M-1s-1, and an interfacial activation free energy of less than 2 kcal/mol. Equilibrium binding of phloretin to a vesicle membrane is characterized by a single class of high-affinity (8 micro M), noninteracting sites. Binding is enthalpy driven (delta H = -4.9 kcal/mol) at 23 degrees C. Analysis of amplitudes of kinetic processes shows that 66 +/- 3% of total phloretin binding sites are exposed at the external vesicle surface. The rate of phloretin movement between binding sites located near the external and internal interfaces is proportional to the concentration of un-ionized phloretin, with a rate constant of 5.7 X 10(4) M-1s-1 at 23 degrees C. The rate of this process is limited by a large enthalpic (9 kcal/mol) and entropic (-31 entropy units) barrier. An analysis of the concentration dependence of the rate of transmembrane movement suggests the presence of multiple intramembrane potential barriers. Permeation of phloretin through a lipid bilayer is modeled quantitatively in terms of discrete steps: binding to a membrane surface, translocation across a series of intramembrane barriers, and dissociation from the opposite membrane surface. The permeability coefficient for phloretin is calculated as 1.9 X 10(-3) cm/s on the basis of the model presented. Structure-function relationships are examined for a number of phloretin analogues.

Flavanones↗
PubMed1979

Using systems theory to organize confusion.

This paper represents an initial step in applying to complex clinical situations the symbolic logic developed by G. Spencer Brown and elaborated by Francisco Varela. This way of modeling turns out to yield an interesting mixture of rigidity, ambiguity, and paradox, perhaps inevitable at our present level of understanding of systems containing feedback. Applying the Brown-Varela concepts seems a useful transitional step toweard the future use of more sophisticated quantitative models such as those of Powers and Forrester.

Adolescent↗
PubMed2005

A model of the coupling between grip aperture and hand transport during human prehension.

It has been repeatedly demonstrated that the opening between the index finger and thumb (grasp component) during an object-directed reach-to-grasp movement achieves maximum aperture approximately two-thirds of the way through the duration of the reaching movement (transport component). Here we offer a quantitative model of the temporal coupling between grip aperture and wrist velocity which shows experimentally that the correlation between grip aperture and object size is a sigmoidal function of movement duration. When wrist velocity reaches its peak value, the correlation between the grip aperture and the size of the goal object has reached half of the correlation that is achieved by the end of the movement.

Hand↗
PubMed1999

Brownian dynamics simulation of DNA condensation.

DNA condensation observed in vitro with the addition of polyvalent counterions is due to intermolecular attractive forces. We introduce a quantitative model of these forces in a Brownian dynamics simulation in addition to a standard mean-field Poisson-Boltzmann repulsion. The comparison of a theoretical value of the effective diameter calculated from the second virial coefficient in cylindrical geometry with some experimental results allows a quantitative evaluation of the one-parameter attractive potential. We show afterward that with a sufficient concentration of divalent salt (typically approximately 20 mM MgCl(2)), supercoiled DNA adopts a collapsed form where opposing segments of interwound regions present zones of lateral contact. However, under the same conditions the same plasmid without torsional stress does not collapse. The condensed molecules present coexisting open and collapsed plectonemic regions. Furthermore, simulations show that circular DNA in 50% methanol solutions with 20 mM MgCl(2) aggregates without the requirement of torsional energy. This confirms known experimental results. Finally, a simulated DNA molecule confined in a box of variable size also presents some local collapsed zones in 20 mM MgCl(2) above a critical concentration of the DNA. Conformational entropy reduction obtained either by supercoiling or by confinement seems thus to play a crucial role in all forms of condensation of DNA.

Biopolymers↗
PubMed1978

Implications of sex differences in the prevalences of antisocial personality, alcoholism, and criminality for familial transmission.

We describe three multifactorial models of disease transmission in which the prevalences of a disease differ in men and women. These models demonstrate explicitly how such sex differences may be caused by genetic factors, home environment, sociocultural, or other nonfamilial factors. Independent sets of family data about antisocial personality and alcoholism in the United States and criminality in Danish twins are analyzed according to these quantitative models. Relevant clinical and adoption data about these disorders are reviewed. The sex differences observed in the development of antisocial personality and of crime appear to be due to familial factors whereas the differences between male and female alcoholics are due to nonfamilial factors. The models and results are discussed in terms of their general implications for testing hypotheses about gender-related differences.

Adolescent↗
PubMed1982

A mathematical model of primary pacemaking cell in SA node of the heart.

Application of voltage-clamp techniques to cardiac primary pacemaker tissue is currently a subject of considerable interest in cardiac electrophysiology. Information regarding the electrical behavior of this type of membrane is by no means complete, yet sufficiently detailed information is available in the literature that would allow the formulation of a reasonably quantitative model to represent the electrical activity of primary pacemaker tissue. In this study the well-known McAllister-Noble-Tsien (MNT) model of the cardiac Purkinje fiber is modified to account for the electrical activity of the primary pacemaking cell (P-cell) of the sinoatrial (SA) node in the heart. Modification is accomplished by appropriately deleting (or inactivating) selected inward- or outward-current channels in the MNT model and adjusting the range of voltage dependence of the various channel-gating variables. Wherever possible, this is accomplished by taking into account voltage-clamp and other electrophysiological data from experiments on the SA node. The resultant model mimics published data quite well and is capable of characterizing the free-running behavior of the primary pacemaker as well as its response to injected currents.

Action Potentials↗
PubMed2001

Variable range hopping and electrical conductivity along the DNA double helix.

We present a model to describe electrical conductivity along the DNA double helix. In this model, DNA is considered as a one-dimensional disordered system, and electrons are transported via variable range hopping between localized states. Thermal structural fluctuations in DNA further localize electronic wave functions, giving rise to a temperature-dependent localization length. The model quantitatively explains the temperature dependence of the conductivity observed in the lambda phage DNA (lambda-DNA).

Bacteriophage lambda↗
PubMed1994

Rat and human sensory evoked potentials and the predictability of human neurotoxicity from rat data.

The development of comprehensive quantitative models as alternatives to risk assessment based on uncertainty factors will require many steps, among them consideration of the relationships between the health endpoints which are measured in laboratory animals and humans. Sensory evoked potentials are measures of sensory function which can be recorded from many species, including humans, and as such provide an opportunity for examining the extrapolation of neurotoxicity data from laboratory animals to humans. Our research strategy for investigating how well laboratory rat data predict human neurotoxic risk involves comparing parametric stimulus manipulations and drug treatments in both species. Finally, we are comparing results in humans with neurodegenerative conditions, including those induced by neurotoxicant exposure, with animal models. To date, we have focused on pattern-elicited visual evoked potentials (VEPs) recorded from pigmented rats and humans. Parametric manipulations of spatial frequency, temporal frequency and stimulus contrast revealed parallel functions, displaced for differences in absolute sensitivity. Additionally, diazepam produced similar effects in rats and human volunteers. A quantitative cross-species map was developed to illustrate the prediction of human effects from rat data. Exposure to carbon disulfide produced changes in rat VEP-derived contrast sensitivity functions, which resembled psychophysically-measured loss of visual contrast sensitivity in human workers exposed to organic solvents. The results of these continuing efforts should help indicate how well animal electrophysiological measures predict human neurotoxicity.

Animals↗
PubMed2005

Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function.

RATIONALE: The transition from initial drug use to drug addiction has been proposed to result from an allostatic decrease in reward function driven by an overactivation of brain antireward processes. OBJECTIVES: How decreased reward function explains compulsive drug use is not entirely clear at present, and is still a subject for debate. METHODS: We present a quantitative model of cocaine self-administration that integrates pharmacokinetic, pharmacodynamic, and motivational factors to address this question. The model assumes that reward system responsivity is a homeostatically regulated process where the desired level of responsivity (called the reward set point) is initially different from the baseline level. The reduction or correction of this difference or error in reward function would drive cocaine self-administration. RESULTS: Theoretical data obtained by computer simulation fit the experimental data obtained in animals self-administering cocaine (i.e., the within-session pattern of self-injections, the shape and curvature of the dose-injection function, the nonlinear relationship between drug intake and regulated drug effects). Importantly, simulation of an allostatic decrease in reward system responsivity exacerbates the initial error that drives self-administration, thereby increasing both the intake of, and the motivation for, the drug. This allostatic change manifests as a vertical shift in the dose-injection function similar to that seen in animals with escalating cocaine self-administration. CONCLUSIONS: The present model provides a satisfactory explanation of escalated drug intake and suggests a novel negative reinforcement view of addiction based on an allostatic decrease in reward function.

Adaptation, Physiological↗