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At least 631 records · Page 35Linked to original sources

PubMed2006

Contrast-driven approach to intracranial segmentation using a combination of T2- and T1-weighted 3D MRI data sets.

PURPOSE: To develop a strategy for structural brain imaging when using FSL software for segmentation and subsequent volumetry. MATERIALS AND METHODS: Three-dimensional (3D) structural MRI of 1-mm isotropic resolution was performed on a 3-Tesla clinical imaging system. Prescribed signal evolution of a multiple spin-echo (SE) sequence with variable refocusing flip angle for T2 weighting, and a modified driven equilibrium Fourier transform (MDEFT) sequence were used for T1 weighting. Postprocessing included rigid-body coregistration, brain extraction, and segmentation using the tools of the FSL 3.2 software package. RESULTS: T2 weighting provided reliable delineation of the subarachnoidal space, while T1 weighting provided better segmentation of gray matter (GM) and white matter (WM). The combination of T1-weighted (T1-w) and T2-w data allowed the identification of a T2-hypointense class of "nonbrain" (NB) representing larger vessels and structures of connective tissue, as well as partial volume of bone and air-filled cavities. CONCLUSION: Brain extraction on T2-w data and subsequent segmentation of the combined T1- and T2-w intensity distribution into four classes are recommended.

Adult↗

PubMed2001

Application of fluorescence resonance energy transfer to the GroEL-GroES chaperonin reaction.

Fluorescence resonance energy transfer (FRET) is a sensitive and flexible method for studying protein-protein interactions. Here it is applied to the GroEL-GroES chaperonin system to examine the ATP-driven dynamics that underlie protein folding by this chaperone. Relying on the known structures of GroEL and GroES, sites for attachment of fluorescent probes are designed into the sequence of both proteins. Because these sites are brought close in space when GroEL and GroES form a complex, excitation energy can pass from a donor to an acceptor chromophore by FRET. While in ideal circumstances FRET can be used to measure distances, significant population heterogeneity in the donor-to-acceptor distances in the GroEL-GroES complex makes distance determination difficult. This is due to incomplete labeling of these large, oligomeric proteins and to their rotational symmetry. It is shown, however, that FRET can still be used to follow protein-protein interaction dynamics even in a case such as this, where distance measurements are either not practical or not meaningful. In this way, the FRET signal is used as a simple proximity sensor to score the interaction between GroEL and GroES. Similarly, FRET can also be used to follow interactions between GroEL and a fluorescently labeled substrate polypeptide. Thus, while knowledge of molecular structure aids enormously in the design of FRET experiments, structural information is not necessarily required if the aim is to measure the thermodynamics or kinetics of a protein interaction event by following changes in the binding proximity of two components.

Chaperonin 10↗

PubMed2005

Models of high-dimensional semantic space predict language-mediated eye movements in the visual world.

In the visual world paradigm, participants are more likely to fixate a visual referent that has some semantic relationship with a heard word, than they are to fixate an unrelated referent [Cooper, R. M. (1974). The control of eye fixation by the meaning of spoken language. A new methodology for the real-time investigation of speech perception, memory, and language processing. Cognitive Psychology, 6, 813-839]. Here, this method is used to examine the psychological validity of models of high-dimensional semantic space. The data strongly suggest that these corpus-based measures of word semantics predict fixation behavior in the visual world and provide further evidence that language-mediated eye movements to objects in the concurrent visual environment are driven by semantic similarity rather than all-or-none categorical knowledge. The data suggest that the visual world paradigm can, together with other methodologies, converge on the evidence that may help adjudicate between different theoretical accounts of the psychological semantics.

Eye Movements↗

PubMed2005

Time course of attention reveals different mechanisms for spatial and feature-based attention in area V4.

Attention can facilitate visual processing, emphasizing specific locations and highlighting stimuli containing specific features. To dissociate the mechanisms of spatial and feature-based attention, we compared the time course of visually evoked responses under different attention conditions. We recorded from single neurons in area V4 during a delayed match-to-sample task that controlled both spatial and feature-based attention. Neuronal responses increased when spatial attention was directed toward the receptive field and were modulated by the identity of the target of feature-based attention. Modulation by spatial attention was weaker during the early portion of the visual response and stronger during the later portion of the response. In contrast, modulation by feature-based attention was relatively constant throughout the response. It appears that stimulus onset transients disrupt spatial attention, but not feature attention. We conclude that spatial attention reflects a combination of stimulus-driven and goal-driven processes, while feature-based attention is purely goal driven.

Animals↗

PubMed2005

Topoisomerase II-DNA complexes trapped by ICRF-193 perturb chromatin structure.

DNA topoisomerase II (topo II) is involved in unlinking replicating DNA and organizing mitotic chromosomes. Topo II is the target of many antitumour drugs. Topo II inhibition results in extensive catenation of newly replicated DNA and may potentially perturb chromatin assembly. Here, we show that the topo II inhibitor ICRF-193 does not prevent the bulk of nucleosome deposition, but perturbs nucleosome spacing in Xenopus egg extracts. This is due to the trapping of topo II-closed clamps on the DNA rather than increased DNA catenation. Inhibition of replicative DNA decatenation has in itself little or no effect on nucleosome deposition and spacing, suggesting that DNA can easily accommodate the sharp bending constraints imposed by the co-habitation of nucleosomes and catenane nodes. Chromatin perturbation by topo II clamps may explain some dominant cellular effects of ICRF-193. Nucleosome-driven bending of precatenane nodes may facilitate their unlinking by topo II during unperturbed replication.

Animals↗

PubMed2003

A spectroelectrochemical study on perylene cation radical in polymer microchannel-microelectrode chips.

Polymer microchannel chips (depth 20 microm and width 100 microm) integrated with band electrodes were fabricated by photolithography and imprinting methods, and applied to a spectroelectrochemical study on the cation radical of perylene (Pe). A propylene carbonate solution of Pe was brought into the channel chip by pressure driven flow and Pe was oxidized at the working band electrode (WE) in the channel. Simultaneously, absorption measurements of the solution phase in the downstream side of the electrode (30 microm from WE) were conducted on the basis of space resolved spectroscopy. The decrease in the absorbance of Pe at 438 nm upon electrolysis accompanied an appearance of the absorption band around 538 nm, which was assigned to that of the Pe cation radical. When the perylene solution was introduced to the microchip at a slow flow velocity, the dimer cation radical of Pe was shown to be produced in the channel chip. The formation and disappearance processes of the monomer and dimer cation radicals of Pe in the channel were followed by flow velocity and position dependencies of the absorption spectra.

Journal Article↗

PubMed2004

Measurement of density distributions for colloidal beta-FeOOH rods in suspensions exhibiting phase separation: the role of long-range forces in smectic ordering.

We prepared monodisperse colloidal beta-FeOOH rods with length-to-width ratios L/W of 3.6-7.0 (L=210-330 nm and W=40-58 nm). Density gradients of the rods occurred in the suspensions by gravity, inducing a phase separation. The denser phase showed smectic (Sm) liquid crystalline structures exhibiting iridescent colors in a wide range of pH from 1.2 (at which the rods interact attractively) to 4.7 (repulsively). The lower density phase was disordered, but frequently emitted diffuse colors locally (at pH>2.6), implying the occurrence of short-range order. The nematic phase was not observed in the beta-FeOOH systems, being consistent with theoretical predictions. The particle density distributions were measured over the whole region of the suspensions (separated into two phases) at various pH values using a rapid freezing method. A phase diagram was determined thereby, where the critical (minimal) packing fraction of the particles for the Sm phase showed a nonlinear decrease from 0.43 to 0.12 with increasing pH. Rod-rod spacings in the Sm phase estimated experimentally at various pH were well explained using Derjaguin-Landau-Verwey-Overbeek (DLVO) type pair potentials. It is suggested that Sm ordering can be induced by attractive minima at pH<2.2, while driven by soft repulsions at pH>2.6. The former Sm ordering is expected to be the condensation-type phase transition and the latter the disorder-order transition.

Journal Article↗

PubMed2006

Dynamics of fluctuation-dominated phase ordering: hard-core passive sliders on a fluctuating surface.

We study the dynamics of a system of hard-core particles sliding downwards on a one-dimensional fluctuating interface, which in a special case can be mapped to the problem of a passive scalar advected by a Burgers fluid. Driven by the surface fluctuations, the particles show a tendency to cluster, but the hard-core interaction prevents collapse. We use numerical simulations to measure the autocorrelation function in steady state and in the aging regime, and space-time correlation functions in steady state. We have also calculated these quantities analytically in a related surface model. The steady-state autocorrelation is a scaling function of t/L(z), where L is the system size and z is the dynamic exponent. Starting from a finite intercept, the scaling function decays with a cusp, in the small argument limit. The finite value of the intercept indicates the existence of long-range order in the system. The space-time correlation, which is a function of r/L and t/L(z), is nonmonotonic in t for fixed r. The aging autocorrelation is a scaling function of t(1) and t(2) where t(1) is the waiting time and t(2) is the time difference. This scaling function decays as a power law for t(2)>>t(1); for t(1)>>t(2), it decays with a cusp as in steady state. To reconcile the occurrence of strong fluctuations in the steady state with the fact of an ordered state, we measured the distribution function of the length of the largest cluster. This shows that fluctuations never destroy ordering, but rather the system meanders from one ordered configuration to another on a relatively rapid time scale.

Journal Article↗

PubMed2000

Coping with nonstationarity by overembedding

We discuss how nonstationarity in observed time series data due to pronounced fluctuations of system parameters can be resolved by making use of embedding techniques for scalar data. If a D-dimensional deterministic system is driven by P slowly time dependent parameters, a (D+P)-dimensional manifold has to be reconstructed from the scalar time series, which is done by an m>2(D+P)-dimensional time delay embedding. We show that in this space essential aspects of determinism are restored. We demonstrate the validity of the idea heuristically, for numerical examples and for human speech data.

Journal Article↗

PubMed2004

Rare events and scale-invariant dynamics of perturbations in delayed chaotic systems.

We study the dynamics of perturbations in time-delay dynamical systems. Using a suitable space-time coordinate transformation, we find that the time evolution of the linearized perturbations (Lyapunov vector) can be described by the linear Zhang surface growth model [J. Phys. (France) 51, 2129 (1990)]], which is known to describe surface roughening driven by power-law distributed noise. As a consequence, Lyapunov vector dynamics is dominated by rare random events that lead to non-Gaussian fluctuations and multiscaling properties.

Journal Article↗

PubMed1994

Characterization of a negative retinoic acid response element in the murine Oct4 promoter.

Expression of Oct4 in embryonic stem cells is controlled by a distal upstream stem cell-specific enhancer that is deactivated during retinoic acid (RA)-induced differentiation by an indirect mechanism not involving binding of RA receptors (H. Okazawa, K. Okamoto, F. Ishino, T. Ishino-Kaneko, S. Takeda, Y. Toyoda, M. Muramatsu, and H. Hamada, EMBO J. 10:2997-3005, 1991). Here we report that in RA-treated P19 embryonal carcinoma cells the Oct4 promoter is also subject to negative regulation by RA. The minimal Oct4 promoter sequence mediating repression consists of a promoter-proximal sequence containing a GC-rich SP1 consensus-like sequence and several hormone response element half-sites that can be arranged into direct repeats with different spacing. The GC box binds a nuclear factor that is invariably present in undifferentiated and RA-treated differentiated P19 cells. By contrast, the hormone response element-containing sequence binds factors that are induced following RA treatment. Mutational analysis and competition experiments show that the functional entity binding the RA-induced factor is a direct repeat sequence with a spacing of one nucleotide, previously shown to be a binding site for COUP transcription factors (COUP-TFs). Cotransfected orphan receptors COUP-TF1, ARP-1, and EAR-2 were able to repress the activity of Oct4 promoter-driven reporters in P19 EC cells, albeit with different efficiencies. Furthermore, the negative transcriptional effect of COUP-TFs is dominant over the activating effect of the Oct4 embryonic stem cell-specific enhancer. These results show that negative regulation of Oct4 expression during RA-induced differentiation of embryonic stem cells is controlled by two different mechanisms, including deactivation of the embryonic stem cell-specific enhancer and promoter silencing by orphan nuclear hormone receptors.

Animals↗

PubMed1979

Lamellar body phospholipid content of amniotic fluid: a possible index of fetal lung maturity.

Lamellar bodies, produced by secretory cells in the alveolar epithelium, are the major source of surfactant phospholipid. As the fetal lung matures, the membranous content of the lamellar bodies is secreted into the alveolar spaces and passes into the amniotic fluid, from which it can be isolated in a morphologically recognisable form. A method is described for the rapid isolation of a lamellar body fraction from amniotic fluid using a small air-driven clinical ultracentrifuge. The lamellar body phospholipid content of amniotic fluid increases towards the end of gestation, but the time of onset and the rate of this increase show wide individual variation. Preliminary results suggest that the lamellar body phospholipid content of amniotic fluid may be a useful index of fetal lung maturity.

Amniotic Fluid↗

PubMed2000

Laser-induced gene expression in specific cells of transgenic zebrafish.

Over the past few years, a number of studies have described the generation of transgenic lines of zebrafish in which expression of reporters was driven by a variety of promoters. These lines opened up the real possibility that transgenics could be used to complement the genetic analysis of zebrafish development. Transgenic lines in which the expression of genes can be regulated both in space and time would be especially useful. Therefore, we have cloned the zebrafish promoter for the inducible hsp70 gene and made stable transgenic lines of zebrafish that express the reporter green fluorescent protein gene under the control of a hsp70 promoter. At normal temperatures, green fluorescent protein is not detectable in transgenic embryos with the exception of the lens, but is robustly expressed throughout the embryo following an increase in ambient temperature. Furthermore, we have taken advantage of the accessibility and optical clarity of the embryos to express green fluorescent protein in individual cells by focussing a sublethal laser microbeam onto them. The targeted cells appear to develop normally: cells migrate normally, neurons project axons that follow normal pathways, and progenitor cells divide and give rise to normal progeny cells. By generating other transgenic lines in which the hsp70 promoter regulates genes of interest, it should be possible to examine the in vivo activity of the gene products by laser-inducing specific cells to express them in zebrafish embryos. As a first test, we laser-induced single muscle cells to make zebrafish Sema3A1, a semaphorin that is repulsive for specific growth cones, in a hsp70-sema3A1 transgenic line of zebrafish and found that extension by the motor axons was retarded by the induced muscle.

Animals↗

PubMed1989

Two motion perception mechanisms revealed through distance-driven reversal of apparent motion.

We demonstrate two kinds of visual stimuli that exhibit motion in one direction when viewed from near and in the opposite direction from afar. These striking reversals occur because each kind of stimulus is constructed to simultaneously activate two different mechanisms: a short-range mechanism that computes motion from space-time correspondences in stimulus luminance and a long-range mechanism in which motion computations are performed, instead, on stimulus contrast that has been full-wave rectified (e.g., on the absolute value of contrast).

Journal Article↗

PubMed1973

The Stoichiometry of Respiration-driven Potassium Transport in Corn Mitochondria.

Determinations were made for corn (Zea mays L., WF9-Tms x M14) mitochondria of the stoichiometric relationship between K(+) transport and bond energy produced in respiration (K(+)/ approximately ratio). With inward pumping of potassium acetate activated by NADH oxidation, the initial rate of K(+) transported into the sucrose inaccessible space varied between 0.58 and 0.97 K(+)/ approximately , assuming 2 high energy bond equivalents per NADH oxidized. Only small amounts of H(+) were ejected. Valinomycin did not alter the ratio.Efflux pumping of K(+) in KCl media gave a K(+)/ approximately of 0.92. Substituting sucrose for KCl caused a drop in respiration and H(+) ejection, indicating a requirement for cation efflux pumping in acceptorless respiration. Valinomycin added to the KCl medium accelerated passive swelling but did not impair subsequent efflux pumping, although respiration was partially uncoupled.

Journal Article↗

PubMed1986

Heavy riboflavin synthase from Bacillus subtilis. Particle dimensions, crystal packing and molecular symmetry.

Heavy riboflavin synthase from Bacillus subtilis is an enzyme complex consisting of approximately three alpha-subunits (Mr 23.5 X 10(3)) and 60 beta-subunits (Mr 16 X 10(3)). The enzyme has been crystallized from phosphate buffer in a hexagonal crystal modification that belongs to space group P6(3)22. The asymmetric unit of the crystal cell contains ten beta-subunits. The structure of this unusual 10(6) Mr protein has been studied by small-angle X-ray scattering, electron microscopy of three-dimensional crystals, and crystallographic methods. The scattering curves can be interpreted in terms of a hollow sphere model with a ratio of inner and outer radius of 0.3:1. A diameter of 168 A was estimated from the scattering curves, in close agreement with electron microscopic studies. An aggregate with the stoichiometry beta 60, which was obtained by ligand-driven reaggregation of isolated beta-subunits, showed similar shape and dimensions, but a larger value for the ratio Ri/Ra. Electron micrographs of freeze-etched enzyme crystals showed approximately spherical molecules, which were arranged in hexagonal layers. The lattice constants found from the micrographs are in good agreement with the values derived from X-ray diffraction data. Rotation function calculations in Patterson space showed a set of peaks for 2-fold, 3-fold and 5-fold local rotation axes, accurately consistent with icosahedral symmetry and with the particle orientation A shown in the Appendix. The crystal packing can be described as follows: enzyme particles with icosahedral symmetry (point group 532) are located at points 32 of the hexagonal cell, corresponding to positions (0, 0, 0) and (0, 0, 1/2) on the 6-fold screw axes. From the data reported, it may be concluded that the enzyme structure can be described as an icosahedral capsid of 60 beta-subunits with the triangulation number T = 1. The alpha-subunits are located in the central core space of the capsid, but their spatial orientation is incompletely understood.

Bacillus subtilis↗

PubMed2002

Interactive exploration of microarray gene expression patterns in a reduced dimensional space.

The very high dimensional space of gene expression measurements obtained by DNA microarrays impedes the detection of underlying patterns in gene expression data and the identification of discriminatory genes. In this paper we show the use of projection methods such as principal components analysis (PCA) to obtain a direct link between patterns in the genes and patterns in samples. This feature is useful in the initial interactive pattern exploration of gene expression data and data-driven learning of the nature and types of samples. Using oligonucleotide microarray measurements of 40 samples from different normal human tissues, we show that distinct patterns are obtained when the genes are projected on a two-dimensional plane spanned by the loadings of the two major principal components. These patterns define the particular genes associated with a sample class (i.e., tissue). When used separately from the other genes, these class-specific (i.e., tissue-specific) genes in turn define distinct tissue patterns in the projection space spanned by the scores of the two major principal components. In this study, PCA projection facilitated discriminatory gene selection for different tissues and identified tissue-specific gene expression signatures for liver, skeletal muscle, and brain samples. Furthermore, it allowed the classification of nine new samples belonging to these three types using the linear combination of the expression levels of the tissue-specific genes determined from the first set of samples. The application of the technique to other published data sets is also discussed.

Gene Expression Profiling↗

PubMed2001

[Organization and contents of future research in pathology].

The organisation of research in Pathology in the future will be driven by the pressure for profitableness. This situation is already now leading to a continuous shifting of capacity from "non profitable" research (and teaching) to diagnostics. Since research continues to be a central future goal of the university institutes of Pathology, we have to claim that all our institutes shall have a financially incontestable research unit (at least 1 x BAT1 and 1 x BAT2, 1-2 BATV and consumables for approx. TDM75/year) and appropriate space. Additionally, academically orientated full pathologists and fellows, research assistants on grant money and M.D. students will perform research. One of the central future goals must be increase in motivation of researchers through output-orientated individual support and the enhancement of their career expectations. Research planned by politicians ("planned research") can--as "planned economy"--not be successful. Main goal of our future research efforts in the postgenomic era will be further clarification of the molecular basis of diseases. Applied research will be driven by the need for molecular classifications including individual prediction of prognosis, progression and choice and response to therapy. The future face of Pathology entirely depends on the fact, how actively this type of research is done in our labs and, consequently, how well we will be trained to do non-morphologic diagnostics on tissue in the future.

Humans↗