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PubMed1978

Cell membrane potential and resistance in liver.

1. Isolated segments of mouse liver were placed in a Perspex bath through which physiological saline solutions of varying composition were circulated. Two microelectrodes were inserted in different liver cells under microscopic control allowing measurement of distance between the two micro-electrode tips. Current pulses were injected through one of these electrodes, causing electrotonic potential changes in nearby cells by current spread through intercellular junctions. These electrotonic potential changes were recorded with the second micro-electrode. The spatial decrement of the amplitude of the electrotonzpotential changes and their dependence on extracellular ion concentrations were analysed by three-dimensional cable analysis, modified to account for the geometry of the tissue. 2. During exposure to control solution the mean resting cell membrane potential was -37 mV, the space constant for intracellular current spread (lambda3 = square root of Rm/chrRi) was 390 micron and Ri, a measure which includes the intracellular resistivity and the junctional resistances, was 1.4 komegacm. From these values, and an estimate of tissue cell membrane density (chi) obtained by others, the specific membrane resistance (Rm) was calculated to be 5.1 komegacm2. 3. Replacement of extracellular Na+ by K+ resulted in a large depolarization and a large decrease in the membrane resistance. Replacement of extracellular Na+ by choline resulted in a small transient hyperpolarization and a small increase in the membrane resistance. Replacement of extracellular Cl- by methylsulphate or sulphate or of NaCl by sucrose resulted in a small transient depolarization and a large increase in the membrane resistance. 4. Glucagon (10(-7) M) and adrenaline (10(-5) M) evoked membrane hyperpolarization and reduction of membrane resistance (Rm). 5. The resting membrane ion conductance can be considered to consist of three components, Cl conductance (GCl), GK and GNa. The results suggest that GCl greater than GK greater than GNa. Changes in extracellular ion concentrations specifically alter the permeability properties of the cell membrane. The glucagon action can be explained in part by an increase in GK.

Animals↗
PubMed1984

A count-dependent filter for smoothing flow cytometric histograms.

An adaptive count-dependent algorithm for smoothing statistically limited histograms has been developed. It considers both the spatial frequency limitations of the measurement system (described by the measurement system point spread function) and the reliability of the measured data (indicated by the effective number of counts influencing each channel of the histogram. Windows for smoothing flow cytometric histograms are derived from an assumed Gaussian-shaped point spread function (PSF) with a constant coefficient of variation. The windows are developed by scaling the variances of the Gaussian functions inversely with the statistical reliability of the data contained in each channel of the measured histogram. The reliability of this data is determined by taking the square root of the number of counts influencing the value tabulated for each channel. Using the algorithm, a smoothed version of the measured histogram may be developed from a linear sum of the products of the individual scaled Gaussian functions and the original measured histogram. Data are presented demonstrating the advantages of count-dependent smoothing over non-count-dependent smoothing using synthesized DNA histograms as a function of sample size.

Cell Cycle↗
PubMed2006

Probing the effects of the well-mixed assumption on viral infection dynamics.

Viral kinetics have been extensively studied in the past through the use of spatially well-mixed ordinary differential equations describing the time evolution of the diseased state. However, emerging spatial structures such as localized populations of dead cells might adversely affect the spread of infection, similar to the manner in which a counter-fire can stop a forest fire from spreading. In a previous publication [Beauchemin, C., Samuel, J., Tuszynski, J., 2005. A simple cellular automaton model for influenza A viral infections. J. Theor. Biol. 232(2), 223-234], a simple two-dimensional cellular automaton model was introduced and shown to be accurate enough to model an uncomplicated infection with influenza A. Here, this model is used to investigate the effects of relaxing the well-mixed assumption. Particularly, the effects of the initial distribution of infected cells, the regeneration rule for dead epithelial cells, and the proliferation rule for immune cells are explored and shown to have an important impact on the development and outcome of the viral infection in our model.

Animals↗
PubMed2001

Is aggregation of beta-amyloid peptides a mis-functioning of a current interaction process?

In a previous study, Hughes et al. [Proc. Natl. Acad. Sci. USA 93 (1996) 2065-2070] demonstrated that the amyloid peptide is able to interact with itself in a two-hybrid system and that interaction is specific. They further supported that the method could be used to define the sequences that might be important in nucleation-dependent aggregation. The sequence of the amyloid peptide can be split into four clusters, two hydrophilic (1-16 and 22-28) and two hydrophobic (17-21 and 29-42). We designed by molecular modeling and tested by the two-hybrid approach, series of mutations spread all over the sequence and changing the distribution of hydrophobicity and/or the spatial hindrance. In the two-hybrid assay, interaction of native Abeta is reproduced. Screening of mutations demonstrates that the C-domain (residues 29-40 (42)), the median domain (residues 17-22) and the N-domain (1-16) are all crucial for interaction. This demonstrates that almost all fragments of the amyloid peptide but a loop (residues 23-28) and the C-term amino acid are important for the native interaction. We support that the folded three-dimensional (3D) structure is the Abeta-Abeta interacting species, that the whole sequence is involved in that 3D fold which has a low secondary structure propensity and a high susceptibility to mutations and thus should have a low stability. The native fold of Abeta could be stabilized in Abeta-Abeta complexes which could in other circumstances facilitate the nucleation event of aggregation that leads to the formation of stable senile plaques.

Amino Acid Sequence↗
PubMed2003

A modeling and convolution method to measure compositional variations in strained alloy quantum dots.

We have developed a method to quantitatively measure the absolute composition of nanometer sized capped quantum dots in semiconductor alloys. The method uses spatially resolved electron energy-loss spectroscopy in a scanning transmission electron microscope to measure compositional profiles across the center of the quantum dot and the adjacent nanometer wide wetting layer. The measurements from the wetting layer are used to derive a spatial broadening function which includes the effects of probe size, instabilities and beam spreading in the sample. This broadening function is employed to simulate compositional profiles from the quantum dots. Information on the dimensions of dots is extracted from annular dark-field images. The method is applied to In(y)Ga(1-y)As (y = 0.5) quantum dots grown on a GaAs substrate. In this system, a simple truncated cone model is found to give an adequate description of the compositional variations across the dot. We find a substantial enrichment in In at the center of the dots, in agreement with theoretical predictions.

Journal Article↗
PubMed1990

Accuracy and precision of the computerized brain atlas programme for localization and quantification in positron emission tomography.

The computerized brain atlas programme (CBA) provides a powerful tool for the anatomical analysis of functional images obtained with positron emission tomography (PET). With a repertoire of simple transformations, the data base of the CBA is first adapted to the anatomy of the subject's brain represented as a set of magnetic resonance (MR) or computed tomography (CT) images. After this, it is possible to spatially standardize (reformat) any set of tomographic images related to the subject, PET images, as well as CT and MR images, by applying the inverse atlas transformations. From these reformatted images, statistical images, such as average images and associated error images corresponding to different groups of subjects, may be produced. In all these images, anatomical structures can be localized using the atlas data base and the functional values can be evaluated quantitatively. The purpose of this study was to determine the spatial and quantitative accuracy and precision of the calculated regional mean values. Therefore, the CBA was applied to regional CBF (rCBF) measurements with [11C]fluoromethane and PET on 26 healthy male volunteers during rest and during three different physiological stimulation tasks. First, the spatial accuracy and precision of the reformation process were determined by measuring the spread of defined anatomical structures in the reformatted MR images of the subjects. Second, the mean global CBF and the mean rCBF in the average PET images were compared with the global CBF and rCBF in the original PET images. Our results demonstrate that the reformation process accurately transformed the individual brains of the subjects into the standard brain anatomy of the CBA. The precision of the reformation process had an SD of approximately 1 mm for the lateral dislocation of midline structures and approximately 2-3 mm for the dislocation of the inner and outer brain surfaces. The quantitative rCBF values of the original PET images were accurately represented in the reformatted PET images. Moreover, this study shows that the application of the CBA improves the analysis of functional PET images: (a) The average PET images had a low background noise [0.4 ml/100 g/min +/- 0.7 (SD)] compared to the mean rCBF changes specifically induced by physiological stimulation. (b) The reformatted PET images had a voxel volume of 10.9 mm3. Owing to this high sampling resolution, it was possible to differentiate the mean rCBF changes in adjacent activated fields such as the left motor hand area from the sensory hand area and the left premotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2006

Keratin expression provides novel insight into the morphogenesis and function of the companion layer in hair follicles.

Hair follicles cycle between stages of growth (anagen) and metabolic quiescence (telogen) throughout life. In mature follicles, transition from telogen back into anagen involves the activation, proliferation, and differentiation of epithelial stem cells located in the bulge, a specialization of the outer root sheath. Recent studies identified keratin 6a (K6a) transcripts as enriched in bulge epithelial stem cells in mouse skin. We used messenger RNA probes, antibodies, a LacZ reporter mouse model, and whole-mount staining assays to investigate the regulation of mK6a during mouse postnatal hair cycling, and compare it to mK75, a companion layer (Cl) marker. We find that mK75 regulation parallels that of inner root sheath (IRS) markers, with expression onset at anagen IIIa above the new hair bulb and subsequent spreading towards the bulge. Although also occurring in the Cl, mK6a expression begins at anagen IIIb in differentiating cells located proximal to the bulge, and subsequently spreads towards the hair bulb. mK6a and mK75 thus exhibit temporally distinct, and spatially opposed, expression patterns in the Cl during postnatal anagen. These findings provide novel insight into the morphogenesis and properties of the Cl, and raise the distinct possibility that it is an integral part of the IRS compartment.

Animals↗
PubMed1997

Retinotopic organization in human visual cortex and the spatial precision of functional MRI.

A method of using functional magnetic resonance imaging (fMRI) to measure retinotopic organization within human cortex is described. The method is based on a visual stimulus that creates a traveling wave of neural activity within retinotopically organized visual areas. We measured the fMRI signal caused by this stimulus in visual cortex and represented the results on images of the flattened cortical sheet. We used the method to locate visual areas and to evaluate the spatial precision of fMRI. Specifically, we: (i) identified the borders between several retinotopically organized visual areas in the posterior occipital lobe; (ii) measured the function relating cortical position to visual field eccentricity within area V1; (iii) localized activity to within 1.1 mm of visual cortex; and (iv) estimated the spatial resolution of the fMRI signal and found that signal amplitude falls to 60% at a spatial frequency of 1 cycle per 9 mm of visual cortex. This spatial resolution is consistent with a linespread whose full width at half maximum spreads across 3.5 mm of visual cortex.

Brain Mapping↗
PubMed2025

Incorporating Epidemiological Data into the Genomic Analysis of Partially Sampled Infectious Disease Outbreaks.

Pathogen genomic data are increasingly being used to investigate transmission dynamics in infectious disease outbreaks. Combining genomic data with epidemiological data should substantially increase our understanding of outbreaks, but this is highly challenging when the outbreak under study is only partially sampled, so that both genomic and epidemiological data are missing for intermediate links in the transmission chains. Here, we present a new dynamic programming algorithm to perform this task efficiently. We implement this methodology into the well-established TransPhylo framework to reconstruct partially sampled outbreaks using a combination of genomic and epidemiological data. We use simulated datasets to show that including epidemiological data can improve the accuracy of the inferred transmission links compared with inference based on genomic data only. This also allows us to estimate parameters specific to the epidemiological data (such as transmission rates between particular groups), which would otherwise not be possible. We then apply these methods to two real-world examples. First, we use genomic data from an outbreak of tuberculosis in Argentina, for which data was also available on the HIV status of sampled individuals, in order to investigate the role of HIV coinfection in the spread of this tuberculosis outbreak. Second, we use genomic and geographical data from the 2003 epidemic of avian influenza H7N7 in the Netherlands to reconstruct its spatial epidemiology. In both cases, we show that incorporating epidemiological data into the genomic analysis allows us to investigate the role of epidemiological properties in the spread of infectious diseases.

Humans↗
PubMed2001

Time-resolved imaging of spatiotemporal patterns in a one-dimensional dielectric-barrier discharge system.

A makeshift streak camera produces time-resolved images of filament patterns in a one-dimensional dielectric-barrier discharge system. The images reveal a variety of spatial and temporal structures, including temporally distinct discharge stages that occur at specific phases of the 12.5 kHz driving oscillation and spatially periodic filament arrays that are generated during the discharge stages. The data answer recent questions regarding time-averaged images of a similar system. Most notably, all but the simplest time-averaged images are due to the integration of multiple filament patterns generated in different discharge stages. Disordered states of the system are also examined. Some of these are spatially disordered but display temporal structure; others appear to lack both spatial and temporal order. Possibilities are suggested for investigations of surface-charge spreading and pattern stability in similar systems.

Journal Article↗
PubMed2006

Postischemic augmentation of conducted dilation in cerebral arterioles.

BACKGROUND AND PURPOSE: Conducted vasomotor responses likely play an important role in cerebrovascular regulation, but it is unclear how these responses may be affected by ischemia. The purpose of this study was to evaluate the hypothesis that cerebral ischemia and reperfusion (I/R) alters vascular conduction in cerebral arterioles. METHODS: Middle cerebral artery occlusion (MCAO) was induced by an intraluminal filament technique in 4 groups of rats: (A) 2-hour MCAO/24-hour reperfusion (n=14); (B) 2-hour MCAO/1-hour reperfusion (n=7); (C) 1-hour MCAO/24-hour reperfusion (n=6); and (D) 1-hour MCAO/1-hour reperfusion (n=5). Neurological status and infarction (2,3,5-triphenyltetrazolium chloride staining) were evaluated after I/R. Conducted vasomotor responses were assessed in intracerebral branches of the MCA, by following the longitudinal spread of vasodilation or vasoconstriction to localized microapplication of ATP or adenosine. RESULTS: Local microapplication of ATP evoked a biphasic constriction (17+/-3%) and dilation (7+/-2%) response, whereas adenosine elicited only dilation (11+/-2%). These local responses spread longitudinally along sham-control arterioles (1 mm conduction distance) with rapid spatial decay. Ischemia followed by 24-hour reperfusion (groups A and C) led to a marked potentiation of conducted dilation responses: dilation to ATP conducted with virtually no decay in I/R arterioles. Augmentation of conductivity was not observed in the 1-hour reperfusion groups (B and D). Moreover, I/R did not alter conducted constriction. CONCLUSIONS: Ischemia-reperfusion led to a specific augmentation of conducted vasodilation in cerebral arterioles. Presumably, enhanced conductivity may improve cerebral perfusion after ischemia.

Adenosine↗
PubMed2001

endo-Fullerene and doped diamond nanocrystallite-based models of qubits for solid-state quantum computers.

Models of encapsulated nuclear spin 1/2 1H and 31P atoms in fullerene and diamond nanocrystallite, respectively, are proposed and examined with an ab initio local density functional method for possible applications as single quantum bits (qubits) in solid-state quantum computers. A 1H atom encapsulated in a fully deuterated fullerene, C20D20, forms the first model system and ab initio calculation shows that the 1H atom is stable in its atomic state at the center of the fullerene with a barrier of about 1 eV to escape. A 31P atom positioned at the center of a diamond nanocrystallite is the second model system, and 31P atom is found to be stable at the substitutional site relative to interstitial sites by 15 eV. Vacancy formation energy is 6 eV in diamond, so the substitutional 31P atom will be stable against diffusion during the formation mechanisms within the nanocrystallite. The coupling between the nuclear spin and the weakly bound (valance) donor electron in both systems is found to be suitable for single qubit applications, whereas the spatial distributions of (valance) donor electron wave functions are found to be preferentially spread along certain lattice directions, facilitating two or more qubit applications. The feasibility of the fabrication pathways for both model solid-state qubit systems within practical quantum computers is discussed within the context of our proposed solid-state qubits.

Computer Simulation↗
PubMed2004

Linear arrays for vibro-acoustography: a numerical simulation study.

In this work, we study linear array beamforming for vibro-acoustography systems. The goal of this research is to assess the feasibility of vibro-acoustography imaging systems based on linear arrays for clinical applications. The vibro-acoustography transducer is designed with two arrays driven by two continuous-wave or tone-burst signals at slightly different frequencies. The system beamforming is modeled in a homogeneous and lossless fluid. In this model, the point-spread function (psf) of the system is obtained as the product of the spatial impulse function of each linear array. Three linear array configurations are analyzed for vibro-acoustography systems. Simulations considering 64 elements in each array are performed. Aspects related to clinical applications ofvibro-acoustography, such as system spatial resolution, sidelobes, grating lobes and image frame-rate are discussed. It is concluded that linear array transducers can produce acceptable spatial resolution for clinical applications.

Acoustics↗
PubMed1981

Microtubule-organizing centres and assembly of the double-spiral microtubule pattern in certain heliozoan axonemes.

The double-spiral microtubule pattern is established by a self-linkage procedure when axopodial axonemes reassemble after cold treatment in multinucleate Echinosphaerium nucleofilum and mononucleate Actinophrys sol. Nuclei are related spatially to axoneme morphogenesis in both organisms but in rather different ways. Microtubules grow out in all directions from discrete clumps of dense material situated close to nuclei in E. nucleofilum as axonemal assembly begins. Each clump acts as a microtubule-organizing centre (MTOC) in so far as it is associated spatially with the assembly of microtubules for a single axoneme. The dense material spreads along the sides of a developing axoneme for several micrometers, where it probably promotes further microtubule assembly as the double-spiral pattern is established. Pattern is generated as microtubules that are randomly oriented to begin with become more closely juxtaposed and aligned with each other. There are indications that juxtaposition is brought about by the contractile action of a filamentous meshwork that interconnects the microtubules. Final positioning and alignment appears to be accomplished by a 'zippering' together of adjacent portions of microtubules that proceeds in both directions along the lengths of developing axonemes as self-linkage is effected. Considerable numbers of more or less radially oriented microtubules remain and project from the surface membrane of the single central nucleus during cold treatment of A. sol. Additional tubules assemble and become associated similarly with the nuclear envelope immediately after cold treatment. Initially these microtubules are not arranged in a double-spiral pattern, which is subsequently generated by procedures similar to those outlined above for E. nucleofilum. It is suggested that the surface of the nuclear envelope may act as an MTOC.

Animals↗
PubMed2004

Static point-spread function correction dominating higher-order speckle terms at high adaptive correction.

At high adaptive correction, the randomly shifting speckles familiar in conventional astronomical imaging become organized into patterns with distinct regularities that may permit partial suppression of the image noise they produce. Mathematically, the phase exponential in the Fourier-optical imaging expression may be expanded in a Taylor series in remnant phase phi, which is small at very high correction, leading to a perturbed point-spread function (PSF) that is a sum of algebraic terms, each of distinct spatial symmetry. At sufficiently high correction, one need deal with only a few of the lowest-order terms. A first-order expansion gives an ideal PSF plus two terms, linear and quadratic, describing the two brightest, physically most relevant kinds of speckle. A second-order expansion gives three new terms, the brightest of which is primarily a static correction to the PSF, with a much smaller true speckle component. When the correction is great enough to isolate individual speckle terms, the two terms from the first-order expansion alone determine the essential physics. A general observational strategy is outlined for reducing speckle noise in highly corrected companion searches, dominated by a few speckle terms of definite spatial symmetry.

Journal Article↗
PubMed2006

Dendritic calcium spikes are tunable triggers of cannabinoid release and short-term synaptic plasticity in cerebellar Purkinje neurons.

Understanding the relationship between dendritic excitability and synaptic plasticity is vital for determining how dendrites regulate the input-output function of the neuron. Dendritic calcium spikes have been associated with the induction of long-term changes in synaptic efficacy. Here we use direct recordings from cerebellar Purkinje cell dendrites to show that synaptically activated local dendritic calcium spikes are potent triggers of cannabinoid release, producing a profound and short-term reduction in synaptic efficacy at parallel fiber synapses. Enhancing dendritic excitability by modulating dendritic large-conductance calcium-activated potassium (BK) channels improves the spread of dendritic calcium spikes and enhances cannabinoid release at the expense of spatial specificity. Our findings reveal that dendritic calcium spikes provide a local and tunable coincidence detection mechanism that readjusts synaptic gain when synchronous activity reaches a threshold, and they reveal a tight link between the regulation of dendritic excitability and the induction of synaptic plasticity.

Action Potentials↗
PubMed1999

Simultaneous recovery of size and radioactivity concentration of small spheroids with PET data.

UNLABELLED: Quantification of tumor activity is used to predict prognosis and discriminate benign from malignant lesions identified by PET. Accurate quantitation of small lesions requires correction for the partial volume effects. Such a correction is often based on the recovery coefficient (RC), which depends on the lesion size, the object-to-background ratio (OBR) and physical properties of the media. The purpose of this investigation was to determine whether a model-based optimization method to simultaneously recover the size and the activity concentration of small spheroids could improve estimates of lesion radioactivity when object size is unknown. For reference, we compared our method with a widely used approach, RC correction, that requires the object size to be known. METHODS: A three-dimensional, spatially varying, object size- and contrast-dependent Gaussian model of the point spread function (PSF) of an ECAT EXACT was developed. The observed dependence of the PSF on random coincidences and measured-peak/background activity were included in the PSF using three adjusting factors. Size and radioactivity concentration of a spheroid were estimated by adjusting size and concentration until model output best matched the image data. Elliptic and circular phantoms both containing seven hot spheroids, with OBRs ranging from 5.6 to 0 background, were evaluated. RESULTS: The proposed quantification method reduced the activity error by 11%-63% of the error obtained without correction. The greatest error reduction occurred for small spheroids. The average error in radius estimation ranged from 2% to 48%, wherein the smallest spheroid produced the largest errors. For spheroids with diameters from 8 to 22 mm, Student t test (paired, one-tail) showed the proposed method significantly improved accuracy (P < 0.05) in comparison with the RC method and also in comparison with optimization without the three adjusting factors. CONCLUSION: The model-based optimization method improved estimation of radioactivity concentration over that corrected by the RC method and that made without any correction. It also provided accurate estimation of size for spheroids larger than 6 mm in diameter.

Models, Theoretical↗
PubMed1988

Neural interactions mediating the detection of motion in the retina of the tiger salamander.

The neural circuitry underlying movement detection was inferred from studies of amacrine cells under whole-cell patch clamp in retinal slices. Cells were identified by Lucifer yellow staining. Synaptic inputs were driven by "puffing" transmitter substances at the dendrites of presynaptic cells. Spatial sensitivity profiles for amacrine cells were measured by puffing transmitter substances along the lateral spread of their processes. Synaptic pathways were separated and identified with appropriate pre- and postsynaptic pharmacological blocking agents. Two distinct amacrine cell types were found: one with narrow spread of processes that received sustained excitatory synaptic current, the other with very wide spread of processes that received transient excitatory synaptic currents. The transient currents found only in the wide-field amacrine cell were formed presynaptically at GABAB receptors. They could be blocked with baclofen, a GABAB agonist, and their time course was extended by AVA, a GABAB antagonist. Baclofen and AVA had no direct affect upon the wide-field amacrine cell, but picrotoxin blocked a separate, direct GABA input to this cell. The narrow-field amacrine cell was shown to be GABAergic by counterstaining with anti-GABA antiserum after it was filled with Lucifer yellow. Its narrow, spatial profile and sustained synaptic input are properties that closely match those of the GABAergic antagonistic signal that forms transient activity (described above), suggesting that the narrow-field amacrine cell itself is the source of the GABAergic interaction mediating transient activity in the inner plexiform layer (IPL). Other work has shown a GABAB sensitivity at some bipolar terminals, suggesting a population of bipolars as the probable site of interaction mediating transient action. The results suggest that two local populations of amacrine cell types (sustained and transient) interact with the two populations of bipolar cell types (transient forming and nontransient forming). These interactions underlie the formation of the change-detecting subunits. We suggest that local populations of these subunits converge to form the receptive fields of movement-detecting ganglion cells.

Animals↗