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At least 145 records · Page 8Linked to original sources

PubMed2003

Mathematical model of the spatio-temporal dynamics of second messengers in visual transduction.

A model describing the role of transversal and longitudinal diffusion of cGMP and Ca(2+) in signaling in the rod outer segment of vertebrates is developed. Utilizing a novel notion of surface-volume reaction and the mathematical theories of homogenization and concentrated capacity, the diffusion of cGMP and Ca(2+) in the inter-disc spaces is shown to be reducible to a one-parameter family of diffusion processes taking place on a single rod cross section; whereas the diffusion in the outer shell is shown to be reducible to a diffusion on a cylindrical surface. Moreover, the exterior flux of the former serves as a source term for the latter, alleviating the assumption of a well-stirred cytosol. A previous model of visual transduction that assumes a well-stirred rod outer segment cytosol (and thus contains no spatial information) can be recovered from this model by imposing a "bulk" assumption. The model shows that upon activation of a single rhodopsin, cGMP changes are local, and exhibit both a longitudinal and a transversal component. Consequently, membrane current is also highly localized. The spatial spread of the single photon response along the longitudinal axis of the outer segment is predicted to be 3-5 microm, consistent with experimental data. This approach represents a tool to analyze point-wise signaling dynamics without requiring averaging over the entire cell by global Michaelis-Menten kinetics.

Animals↗

PubMed1997

Improved model of thromboembolic stroke and rt-PA induced reperfusion in the rat.

We report the technical details and validation of an improved rat model for thromboembolic stroke and rt-PA induced reperfusion, which closely resembles clinical embolic stroke. The middle cerebral artery (MCA) was proximally occluded by injection of twelve medium sized (1.5 x 0.35 mm), fibrin-rich autologous blood clots. On inspection, densely packed clot material was found at the ipsilateral MCA origin in all untreated animals. Autoradiographic rCBF measurements showed severe ischemic deficit throughout the ipsilateral MCA territory in untreated animals. The volume in which flow values fell below 30 ml/100 g per min was 54 +/- 14% of the hemispheric volume. In all rt-PA treated animals the proximal MCA was recanalised, and the volume with flow values below 30 ml/100 g per min was reduced to 29 +/- 17%. Histological findings paralleled the spatial spread of the CBF deficit. The rat model presented is well-suited for investigations of the specific pathophysiology of thromboembolic stroke. Furthermore it allows detailed studies of thrombolytically induced reperfusion, beyond the question of successful recanalisation.

Animals↗

PubMed1998

Dynamics of a divisive gain control in human vision.

Evidence for a divisive contrast gain control in human vision was obtained using a contrast version of the probe-on-flash technique that has been employed in the light adaptation literature. Thresholds were measured for a briefly flashed (30 ms), vertical test pattern superimposed on a cosine mask as a function of time after mask onset (SOA). Threshold elevations declined monotonically for SOAs up to 150 ms. and exhibited an exponential time course with an average time constant of 51 ms. Increment thresholds for the test as a function of mask contrast provide direct evidence that these effects are due to operation of a divisive gain control within the first 150 ms after stimulus onset. Experiments to measure the spatial spread of this gain control show it to be localized to a region of no more than 45 arc min radius.

Adaptation, Ocular↗

PubMed2002

Multipoint moss passive samplers assessment of urban airborne polycyclic aromatic hydrocarbons: concentrations profile and distribution along Warsaw main streets.

Polycyclic aromatic hydrocarbons (PAHs) distribution along 28 km of Warsaw main street have been surveyed in July 2000 using moss passive samplers as a simple and economic surrogate of direct air sampling. Altogether 74 samplers at 39 crossroads with traffic lights were placed on the lamp post approximately/=3.5 m above ground. PAHs levels determined in samplers are in range from 828 to 3573 ng/g moss dry weight. The spatial spread of pollution within this range is statistically close to normal distribution with mean value of 2332 ng/g. Variability within and between study areas are rationalized in terms of urban environmental factors. PAHs concentrations profiles across the town have appeared uniform. The dominant compounds are phenantrene, fluoranthene and pyrene. Their contribution is 49-68% of total PAHs burden.

Air Pollutants↗

PubMed2001

SEE: a tool for the visualization and analysis of rodent exploratory behavior.

The complexity of exploratory behavior creates a need for a visualization and analysis tool that will highlight regularities and help generating new hypotheses about the structure of this behavior. The hypotheses can then be formulated as algorithms that capture the patterns and quantify them. SEE is a Mathematica based software developed by us for the exploration of exploratory behavior. The raw data for SEE are a time series of the animal 's coordinates in space sampled at a rate that allows a meaningful computation of speeds. SEE permits: (i) a visualization of the path of the animal and a computation of the dynamics of activity; (ii) a decomposition of the path into several modes of motion (1st gear, 2nd gear, etc.) and a computation of the typical maximal speeds, the spatial spread, and the proportion of each of these modes; and(iii) a visualization of the location in the environment of stopping episodes, along with their dwell time. These visualizations highlight the presence of preferred places, including the animal's so-called home base, and permits a computation of the spatio-temporal diversity in the location of stopping episodes. The software also: (i) decomposes the animal's path into round trips from the home base, called 'excursions', and computes the number of stops per excursion; (ii) generates a visualization of the phase space (path+speed, traced in a three-dimensional graph) of any progression segment or list of such segments; and (iii) produces a visualization of the way places in the animal's operational world are connected to each other. SEE also permits the definition and computation of behavioral endpoints across any section of any database of raw data. The range of applicability of SEE to various experimental set ups, tracking procedures, species, and preparations is addressed in the discussion.

Animals↗

PubMed1997

Adenovirus-mediated gene transfer to the brain: methodological assessment.

The purpose of this short review is to analyse major advantages and limitations of the adenovirus (Ad), specifically with relevance to its use as a vector for gene transfer to the brain. The characteristics of Ad transduction include: the relative absence of cell type specificity; the limited spatial spread of the virus; and the long-term expression of the transgene. In the central nervous system, in contrast to that which occurs in other organs, Ad transduction in the adult does not systematically provoke cell death. Nevertheless, a proportion of the transduced cells do die, and this represents a conspicuous problem. Mechanisms leading to cell death in the brain may include immune rejection and inflammation-related toxicity, although this would not explain all of the results, and direct toxicity related to either inappropriate preparation or the transduction itself. Taking into account uncertainties concerning the innocuousness of Ad transduction, it may seem unwise to envisage Ad gene therapy for diseases that are not life-threatening and/or benefit from adequate drug or surgical treatments (e.g. Parkinson's disease or epilepsy). Ad vectors may not be easily used either in diseases displaying major immune dysfunction (e.g. multiple sclerosis). In contrast, malignant brain tumors and numerous neurodegenerative diseases (such as Huntington's, Alzheimer's diseases or amyotrophic lateral sclerosis) are directly life-threatening and deprived of any adequate treatment. They may be appropriate targets for Ad-mediated gene therapy, once both the vector and the gene of interest have been defined and optimized.

Adenoviridae↗

PubMed2000

Statistical discrimination of natural modes of motion in rat exploratory behavior.

We analyze the locomotor behavior of the rat during exploration, and show that digitally collected data (time series of positions) provide a sufficient basis for establishing that the rat uses several distinct modes of motion (first, second, third, and sometimes fourth gear). The distinction between these modes is obtained by first segmenting the time series into sequences of data points occurring between arrests (as ascertained within the resolution of the data acquisition system). The statistical distribution of the maximal amount of motion occurring within each of these episodes is then analyzed and shown to be multi modal. This enables us to decompose motion into distinct modes. In one application of this decomposition we show that the ethological ad hoc notion of stopping behavior corresponds to progression without leaving first gear. We do so by showing that the spatial spread of such progressions is confined to a small 20-50 cm range in a 6.5 m diameter arena. This provides a justification for a construct of 'staying in place'. This construct is not defined in terms of position in objective space, but purely in terms of the rat's own behavior. We test the generality of our method by applying it to mouse exploratory behavior.

Animals↗

PubMed1999

The spatio-temporal dynamics of a post-vaccination resurgence of rabies in foxes and emergency vaccination planning.

We used a simulation model to study the spatio-temporal dynamics of a potential rabies outbreak in an immunized fox population after the termination of a long-term, large-scale vaccination program with two campaigns per year one in spring and one in autumn. The 'worst-case' scenario of rabies resurgence occurs if rabies has persisted at a low prevalence despite control and has remained undetected by a customary surveillance program or if infected individuals invade to the control area. Even if the termination of a vaccination program entails such a risk of a subsequent new outbreak, prolonged vaccination of a wild host population is expensive and the declining cost-benefit ratio over time eventually makes it uneconomic. Based on the knowledge of the spatio-temporal dynamics of a potential new outbreak gained from our modelling study, we suggest "terminating but observing" to be an appropriate strategy. Simulating the decline of population immunity without revaccination, we found that a new outbreak of rabies should be detected by customary surveillance programs within two years after the termination of the control. The time until detection does not depend on whether vaccination was terminated within the fourth, fifth or sixth years of repeated biannual campaigns. But it is faster if the program was completed with an autumn campaign (because next-year dispersal then occurs after a noticeable decrease in population immunity). Finally, if a rabid fox is detected after terminating vaccination, we determine a rule for defining a circular hazard area based on the simulated spatial spread of rabies. The radius of this area should be increased with the time since the last vaccination campaign. The trade-off between the number of foxes potentially missed by the emergency treatment and the cost for the emergency measures in an enlarged hazard area was found.

Animals↗

PubMed1998

Intrastriatal and intraventricular injections of oligodeoxynucleotides in the rat brain: tissue penetration, intracellular distribution and c-fos antisense effects.

We have determined the time course, the spatial spread in brain tissue, and the intracellular distribution of biotin- and fluorescein-labeled phosphorothioate oligodeoxynucleotides (ODNs) following single injections into the rat striatum or the lateral ventricle. These time and space parameters were correlated with the ability of c-fos phosphorothioate antisense ODNs to suppress the induction of Fos protein by cocaine. A rapid and dose-dependent tissue penetration of labeled ODNs was observed following either intrastriatal or intraventricular injections of a constant sample volume. Inspection of tissue sections by confocal microscopy uncovered a distinct change in the intracellular disposition of labeled ODNs during the 24 h post-injection period. At 1, 6 and 12 h, the vast majority of the fluorescent signal was confined to the interstitial spaces throughout the zone penetrated by ODNs. Neuronal nuclei displayed faint labeling along the outer portion of the nucleus at 1 and 6 h post-injection. At these time-points, ODNs were not detected in the cytoplasm. By 16 h, ODNs were barely detectable in the extracellular space and absent from neuronal nuclei. Instead, ODNs were seen in large cytoplasmic granules of neurons throughout the tissue zone penetrated by the ODNs. Experiments with intrastriatal injections of antisense ODNs to c-fos mRNA revealed Fos suppression between 3 and 12 h, but not at 16 and 24 h. This combined analysis has revealed that (1) restricted tissue penetration by ODNs limits their antisense effects on protein expression, and (2) depletion of extracellular ODNs and sequestration of c-fos antisense ODNs into large intracellular granules coincides with the loss of their biological activity.

Animals↗

PubMed1999

Three-dimensional color Doppler: a new approach for quantitative assessment of mitral regurgitant jets.

Color Doppler echocardiography does not provide adequate information about the severity of mitral regurgitation in patients with eccentric mitral regurgitation. We have developed a new procedure for 3-dimensional (3D) color Doppler reconstruction and for segmentation of regurgitant jets. The volume of regurgitant jets was compared with jet area in 63 patients with mitral regurgitation. Mitral regurgitation was assessed by angiography, regurgitant fraction and volume by pulsed Doppler, JA by planimetry, and JV by 3-dimensional Doppler. Twenty-eight patients with central jets were compared with 35 patients with eccentric jets. In the patients with eccentric jets, JV showed significant correlations with regurgitant volume (r = 0.90; P <.01) and regurgitant fraction (r = 0.76; P < .01) and was able to separate groups with different degrees of mitral regurgitation (P <.01). Three-dimensional Doppler revealed origin, direction, and spatial spreading of complex jet geometry. JV, a new parameter of mitral regurgitation, was also capable of quantifying asymmetrical jets.

Echocardiography, Doppler, Color↗

PubMed1998

[Combined chemoradiotherapy of tumors in the child].

The high chemosensitivity of pediatric tumors along with their natural propensity for an early distant dissemination have stimulated the interest for chemo-radiation combinations in children since the mid 50s. Following the early experiments in nephroblastomas on the interaction of Actinomycin-D and radiotherapy, multiple national and international studies have been conducted since the mid 70s with considerable success: nowadays most pediatric tumors enjoy a long term survival in excess of 70%. Like their adult counterparts, these associations aim to induce an early control of the primary tumor and distant spreading (spatial cooperation) but also, more specifically in children, to limit the toxicity on normal tissues when treatment intensity can be further reduced. The association of an initial chemotherapy followed by local radiation at a dose and in a volume adapted to the response to chemotherapy along with associated prognostic factors has become widely tested in national and international studies conducted in Hodgkin's disease, Ewing's sarcoma, medulloblastomas, and brain tumors in the very young. Conversely, concomitant associations have remained limited to high-risk subgroups (parameningeal rhabdomyosarcomas for example) due to their potential hazards.

Adult↗

PubMed2003

Rapid detection of threshold VEPs.

OBJECTIVE: To determine whether a one-dimensional (1D) Laplacian analysis detects steady-state visual evoked potentials (ssVEPs) faster than the standard O(z)-F(z) montage and to establish the optimum position of Laplacian reference electrodes. METHODS: Twenty-two normal adults were shown reversing checks ranging from 1.5' to 60'. Three electrode montages were investigated: O(z)-F(z), LO-F(z) and a 1D Laplacian analysis of 3 occipital electrodes (2O(z)-(RO+LO)). RO and LO were placed symmetrically and horizontally about O(z). Five different locations for RO and LO were investigated. Recordings were analysed in the frequency domain and the presence (and detection time, DT) or absence of a ssVEP defined statistically. Effects of individual, reference electrode site and check size on DT and phase differences between recording montages were investigated. RESULTS: Laplacian analysis detected ssVEPs to small (3') checks faster than O(z)-F(z), by 12.3 and 4.1s on average with Laplacian reference electrodes at 15 and 20% of half-head circumference, respectively. The optimum position of reference electrodes was governed by the instantaneous spatial spread of the response and the noise coherence between midline and lateral electrodes. CONCLUSIONS: A 1D Laplacian analysis can reduce the time to statistical detection of ssVEPs compared to the traditional O(z)-F(z) recording for stimuli near the normal acuity threshold of adults. This in turn could be used to minimise the length of a VEP acuity assessment.

Adult↗

PubMed2002

State dependent excitability changes of spinal flexor reflex in patients with restless legs syndrome secondary to chronic renal failure.

OBJECTIVE: Periodic limb movement in sleep (PLMS) is a common dysfunction of motor control during sleep, occurring either in isolation or associated with a variety of neurological disorders including restless legs syndrome (RLS). Although the PLMS generators have not been established, their occurrence in patients with spinal cord injury and their clinical resemblance to the spinal cord flexor withdrawal reflex (FR) suggest that PLMS may originate in the circuitry that mediates the FR. The significantly increased spinal cord excitability noted in primary RLS/PLMS patients may play an important role in the pathophysiology of primary RLS. The aim of this study is to establish whether the enhanced spinal cord excitability, which is represented by a lower threshold and/or greater spatial spread of the FR, is also true for the RLS/PLMS patients whose RLS is secondary to chronic renal failure (CRF). METHODS: Twenty patients with RLS/PLMS secondary to CRF have been compared with matched controls according to the state dependent changes in FR excitability. All patients met the diagnostic criteria for RLS and PLMS. They had CRF for 5.2+/-3.5 years, and were under the hemodialysis treatment. Twenty healthy, age and sex matched subjects were tested as controls. The electrophysiological testing of the FR was performed during wakefulness (9:30-10:30 p.m.) and sleep (beginning of stage II, the first sleep cycle). RESULTS: A significant increase in FR excitability was found in RLS/PLMS patients with CRF. This abnormality was prominent during sleep, which was also true for the primary RLS. CONCLUSIONS: Our results suggest that similar neuronal pathways are involved in primary and secondary RLS/PLMS patients. Our results also support that RLS/PLMS and FR share a common spinal mechanism.

Journal Article↗

PubMed2006

The role of water coordination in binary mixtures. A study of two model amphiphilic molecules in aqueous solutions by molecular dynamics and NMR.

Two binary aqueous mixtures which contain the small amphiphilic molecules TMAO (trimethylamine-N-oxide) and TBA (tert-butyl alcohol) have been investigated by molecular dynamics simulations and NMR chemical shift and self-diffusion measurements. TMAO is an osmolyte, while TBA is a monohydrate alcohol. Both possess bulky hydrophobic groups and polar heads, namely, NO in TMAO and OH in TBA. The hydrophilic/hydrophobic content of these isosteric molecules strongly modulates the structure and dynamics of the hydration shell, which is thought to be responsible for the effects observed on proteins and phospholipids. Simulation results, especially on hydrogen-bond networking, spatial correlations, and self-diffusivity, are consistent with NMR data and agree well with previous numerical studies on similar solutions. The methods employed allow the elucidation of the microscopic features of the solutions. For TBA solutions, the hydration shell is found to have a low density and a large spatial spread, and thus, above the molar fraction of 0.03, reduction of hydrophobic hydration drives self-aggregation of the solute. This effect does not take place in TMAO solutions, where the hydration shell is more compact and stable, maintaining its structure over a wider range of solute concentrations.

Computer Simulation↗

PubMed2006

A new method for measuring the diffusion coefficient in a gas phase.

A new and fast method for measuring the diffusion coefficients of binary gas mixtures using ion mobility spectrometry (IMS) has been developed. In this method, the sample is injected as a short pulse into the flowing drift gas, forming a Gaussian concentration profile inside the drift region. This Gaussian cloud is irradiated with a fast moving swarm of electrons to create negative ions. The flash of electrons is so short that the negative ions do not move much during the exposure time. The ions then drift toward the detector, where they are collected. The collected ion signal pattern reflects the spatial distribution of the sample inside the cloud at the time of exposure. This is repeated in intervals of 300-400 ms to monitor the spatial spreading of the molecules in the drift region. Consecutive IMS spectra show the evolution of the cloud over time. The collected spectra are fit to Gaussian functions to extract diffusion coefficients. Using this method, the diffusion coefficient of O(2), CHCl(3), and C(2)H(2)Cl(2) were measured, and the results are in good agreement with the previously reported experimental data.

Journal Article↗

PubMed1998

The analysis of synaptically generated traveling waves.

Mathematical and computational models for the propagation of activity in excitatorily coupled neurons are simulated and analyzed. The basic measurable quantity--velocity--is found for a wide class of models. Numerical bifurcation techniques, asymptotic analysis, and numerical simulations are used to show that there are distinct scaling laws for the velocity as a function of a variety of parameters. In particular, the obvious linear relationships between speed and spatial spread or synaptic decay rate are shown. More surprisingly, it is shown that the velocity scales as a power law with synaptic coupling strength and that the exponent is dependent only on the rising phase of the synapse.

Animals↗

PubMedDate not supplied

Summation of spatiotemporal input patterns in leaky integrate-and-fire neurons: application to neurons in the cochlear nucleus receiving converging auditory nerve fiber input.

The response of leaky integrate-and-fire neurons is analyzed for periodic inputs whose phases vary with their spatial location. The model gives the relationship between the spatial summation distance and the degree of phase locking of the output spikes (i.e., locking to the periodic stochastic inputs, measured by the synchronization index). The synaptic inputs are modeled as an inhomogeneous Poisson process, and the analysis is carried out in the Gaussian approximation. The model has been applied to globular bushy cells of the cochlear nucleus, which receive converging inputs from auditory nerve fibers that originate at neighboring sites in the cochlea. The model elucidates the roles played by spatial summation and coincidence detection, showing how synchronization decreases with an increase in both frequency and spatial spread of inputs. It also shows under what conditions an enhancement of synchronization of the output relative to the input takes place.

Action Potentials↗

PubMed1999

Characterization of a dextran-based bifunctional calcium indicator immobilized in cells by the enzymatic addition of isoprenoid lipids.

Cellular processes can be controlled by cell-wide increases in the cytosolic Ca2+ concentration or, alternatively, by localized Ca2+ signals in micro- and nano-domains. The experimental characterization of such localized Ca2+ signals would be facilitated using an immobilized Ca2+ indicator, which could prevent the accelerated spatial spreading of Ca2+ ions that is mediated by binding to diffusible indicators. Here we characterize a dextran-based Ca2+ indicator (CAAX-green) that becomes immobilized in the cytosol by an enzyme-mediated addition of a geranylgeranyl lipid group. CAAX-green consists of a dextran backbone with an attached Ca(2+)-green as well as an 11 residue peptide ending in a C-terminal CAAX-motif. Once introduced into cells by microporation, geranylgeranyl lipid groups are attached to the CAAX peptides by cytosolic enzymes. Measurements in tumor mastcells, myocytes and fibroblasts showed that the indicator becomes membrane attached between 30 min and 1 h following incorporation into the cytoplasm. A time-dependent 10-fold reduction of the diffusion coefficient and a parallel increase in the cytosolic retention after permeabilization indicates that at least 90% of cellular CAAX-green is immobilized. The KD of the indicator in permeabilized cells is 0.65 microM. Overall, these properties make CAAX-green well suited for the investigation of localized Ca2+ signals in a variety of cell types.

Animals↗