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PubMed2000

[Ultrasound elastography of the prostate. A new technique for tumor detection].

AIM: Prostate tumours are often of harder consistency than the surrounding tissue. During digital rectal examination, this fact can be used not only to detect hypertrophy but also localized hardenings. The examination by digital palpation is inaccurate and, even in combination with PSA-value and a transrectal ultrasonic examination, the result is often not reliable. Ultrasound elastography enables us to measure and visualize the elastic properties of a tissue region and is a useful supplement to the examination by digital palpation. Ultrasound elastography is able to measure and visualize the elastic properties of a tissue region, therefore it is a useful supplement to commonly used diagnostic procedures. METHOD: We have developed a new system for elastographic prostate diagnosis which can be used during the transrectal ultrasonic examination. During the examination a sequence of ultrasonic images is acquired while the organ is slightly compressed by the ultrasound probe. Using numerical analysis of image pairs for the acquired sequence we calculate the tissue strain which represents the spatial elasticity distribution of a specific cross-section of the organ. This enables us to distinguish hard areas in the tissue. Image artifacts resulting from lateral motion components, i.e., orthogonal to the direction of the applied force, are compensated for by a special approach. RESULTS: We present results obtained from a typical elastography phantom and also the first in vivo images from patients who were undergoing radical prostatectomy. Our images prove that ultrasound elastography has the potential to detect malignant tissue areas, which are inconspicuous in the B-mode image. Our findings are confirmed by the corresponding histological specimens.

Elasticity↗

PubMed2006

Extended treatment of charge response kernel comprising the density functional theory and charge regulation procedures.

We propose an extended treatment of the charge response kernel (CRK), (partial differential Q(a)/partial differential V(b)), which describes the response of partial charges on atomic sites to external electrostatic potential, on the basis of the density functional theory (DFT) via the coupled perturbed Kohn-Sham equations. The present CRK theory incorporates regulation procedures in the definition of partial charges to avoid unphysical large fluctuation of the CRK on "buried" sites. The CRKs of some alcohol and organic molecules, methanol, ethanol, propanol, butanol, dimethylsulfoxide (DMSO), and tetrahydrofuran (THF) were calculated, demonstrating that the new CRK model at the DFT level has greatly improved the performance of accuracy in comparison with that at the Hartree-Fock level previously proposed. The CRK model was also applied to investigate spatial nonlocality of the charge response through alkyl chain sequences. The CRK model at the DFT level enables us to construct a nonempirical strategy for polarizable molecular modeling, with practical reliability and robustness.

Journal Article↗

PubMed1992

Lateral masking as a determinant of global dominance.

The term compound letter refers to a large (global) letter made up of small (local) letters. Reaction time to identify local letters is longer when local and global letters are different than when they are the same (the global dominance effect). The possible contribution of lateral masking to this effect was investigated. Lateral masking denotes reduced probability of identifying a stimulus when it is closely surrounded by other stimuli (as is the case for the local items in a compound stimulus). Three experiments were conducted in which the dependent measure was percentage of correct responses, rather than reaction time. In experiment 1 compound letters were used; accuracy of performance yielded evidence of global dominance such as obtained with reaction time measures. In experiments 2 and 3 the strength of lateral masking in geometrical forms was varied by varying the density of their component items. In agreement with earlier suggestions based on indirect evidence, the results directly implicated lateral masking as an important determinant of global dominance. However, lateral masking could not account fully for the experimental outcome. Factors beyond lateral masking, such as global precedence in the processing sequence or inhibitory interactions among low and high spatial-frequency components of the compound images are required in order to provide a comprehensive account of global dominance effects.

Cognition↗

PubMed2005

The structure of dimeric ROCK I reveals the mechanism for ligand selectivity.

ROCK or Rho-associated kinase, a serine/threonine kinase, is an effector of Rho-dependent signaling and is involved in actin-cytoskeleton assembly and cell motility and contraction. The ROCK protein consists of several domains: an N-terminal region, a kinase catalytic domain, a coiled-coil domain containing a RhoA binding site, and a pleckstrin homology domain. The C-terminal region of ROCK binds to and inhibits the kinase catalytic domains, and this inhibition is reversed by binding RhoA, a small GTPase. Here we present the structure of the N-terminal region and the kinase domain. In our structure, two N-terminal regions interact to form a dimerization domain linking two kinase domains together. This spatial arrangement presents the kinase active sites and regulatory sequences on a common face affording the possibility of both kinases simultaneously interacting with a dimeric inhibitory domain or with a dimeric substrate. The kinase domain adopts a catalytically competent conformation; however, no phosphorylation of active site residues is observed in the structure. We also determined the structures of ROCK bound to four different ATP-competitive small molecule inhibitors (Y-27632, fasudil, hydroxyfasudil, and H-1152P). Each of these compounds binds with reduced affinity to cAMP-dependent kinase (PKA), a highly homologous kinase. Subtle differences exist between the ROCK- and PKA-bound conformations of the inhibitors that suggest that interactions with a single amino acid of the active site (Ala215 in ROCK and Thr183 in PKA) determine the relative selectivity of these compounds. Hydroxyfasudil, a metabolite of fasudil, may be selective for ROCK over PKA through a reversed binding orientation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2003

Is slowness a learning principle of the visual cortex?

Slow feature analysis is an algorithm for extracting slowly varying features from a quickly varying signal. It has been shown in network simulations on one-dimensional stimuli that visual invariances to shift and other transformations can be learned in an unsupervised fashion based on slow feature analysis. More recently, we have shown that slow feature analysis applied to image sequences generated from natural images using a range of spatial transformations results in units that share many properties with complex and hypercomplex cells of the primary visual cortex. We find cells responsive to Gabor stimuli with phase invariance, sharpened or widened orientation or frequency tuning, secondary response lobes, end-stopping, and cells selective for direction of motion. These results indicate that slowness may be an important principle of self-organization in the visual cortex.

Journal Article↗

PubMed1994

High expression of 92-kD type IV collagenase (gelatinase B) in the osteoclast lineage during mouse development.

cDNA clones for murine 92 kD type IV collagenase (gelatinase B) were generated for the determination of its primary structure and for analysis of temporal and spatial expression in vivo. The mouse enzyme has 72% sequence identity with the human counterpart, the major difference being the presence of a 16-residue segment absent from the human enzyme. In situ hybridization analyses of embryonic and postnatal mouse tissues revealed intense signals in cells of the osteoclast cell lineage. Clear expression above background was not observed in macrophages, polymorphonuclear leukocytes, monocytes, or epithelial cells which have been shown to express the gene in vitro in cell cultures. Expression of the gene was first observed at early stage of cartilage and tooth development at E13, where signals were seen transiently in surrounding mesenchymal cells. At later developmental stages and postnatally strong expression was seen in large cells at the surface of bones. These cells were presumably osteoclasts as their location correlated with that of TRAP positive cells. Signals above background were not observed in a number of other tissues studied. The results represent the first demonstration of a highly osteoclast specific extracellular proteinase. The results suggest that during normal development of embryonic organs the 92-kD type IV collagenase does not have a major role in basement membrane degradation, but is rather mainly used for the turnover of bone matrix, possibly as a gelatinase required for the removal of denatured collagen fragments (gelatin) generated by interstitial collagenase.

Amino Acid Sequence↗

PubMed1995

Possible active site of the sweet-tasting protein thaumatin.

Epitopes on thaumatin and monellin were studied using the PEPSCAN-technology. The antibodies used were raised against thaumatin. Only antibodies that, in an ELISA, both recognized thaumatin and monellin were used in the PEPSCAN-analyses. On thaumatin two major overlapping epitopes were identified. On monellin no epitopes could be identified. The identified epitope region on thaumatin shares structural features with various peptide and protein sweeteners. It contains an aspartame-like site which is formed by Asp21 and Phe80, tips of the two extruding loops KGDAALDAGGR19-29 and CKRFGRPP77-84, which are spatially positioned next to each other. Furthermore, sub-sequences of the KGDAALDAGGR19-29 loop are similar to peptide-sweeteners such as L-Asp-D-Ala-L-Ala-methyl ester and L-Asp-D-Ala-Gly-methyl ester. Since the aspartame-like Asp21-Phe80 site and the peptide-sweetener-like sequences are also not present in non-sweet thaumatin-like proteins it is postulated that the KGDAALDAGGR19-29- and CKRFGRPP77-84 loop contain important sweet-taste determinants. This region has previously not been implicated as a sweet-taste determinant of thaumatin.

Amino Acid Sequence↗

PubMed2002

An epidemic pattern of murder.

The dates and places of 105 suspected or proven murders committed by Dr H. Shipman of Hyde in Greater Manchester between 1984 and 1998 were subjected to epidemiological analysis. These interim data were assembled through a variety of media sources and were based upon court proceedings and police investigations. The analysis revealed a significant excess of case pairs separated jointly by distances <0.6 km and by times <7 days. These sequences were also associated with purely geographical groupings within spatial diameters <0.2 km, but with longer time intervals. This was confirmed by an extended analysis of case triplets occurring within short times and distances. They showed a significant excess. These clusters were probably generated by a combination of psychopathic obsession, of local opportunity, and of caution; and in similar circumstances could occur again. The findings demand the regular display of mortality data in a format permitting the intuitive recognition of similar phenomena elsewhere.

Antisocial Personality Disorder↗

PubMed1999

Magnetic resonance imaging-based stereotactic localization of the globus pallidus and subthalamic nucleus.

OBJECTIVE: To optimize the accuracy of initial stereotactic targeting for movement disorders surgery, we performed stereotactic localization of the internal segment of the globus pallidus (GPi) and subthalamic nucleus (STN) using magnetic resonance imaging protocols in which the borders of these nuclei were directly visualized. METHODS: Fifty-one consecutive cases using the pallidal target and six using the subthalamic target were studied. Localization of these nuclei was performed using the Leksell stereotactic head frame and inversion recovery sequences (GPi) or T2-weighted spin echo sequences (STN). Targeting accuracy and individual variation in the spatial coordinates of these structures were independently measured by identification of nuclear boundaries during multiple microelectrode penetrations. RESULTS: The lateral and vertical coordinates of an atlas-defined point in the GPi, with respect to the line between the anterior and posterior commissures, was highly variable. Initial targeting the GPi based on direct visualization of the target boundaries (external medullary lamina and optic tract) resulted in greater precision than would be expected using fixed anterior and posterior commissure-based coordinates. Initial targeting the STN using magnetic resonance imaging was sufficiently precise to place the initial microelectrode penetration within STN in all six cases. CONCLUSION: Magnetic resonance imaging-based initial stereotactic targeting of the GPi, based on direct visualization of the target boundaries, is useful to improve target accuracy over that of purely indirect anterior and posterior commissure-based targeting methods. Initial targeting of the STN was reliably accomplished by direct visualization. However, there remains sufficient variability that the final target location in both GPi and STN required electrophysiological mapping in all cases.

Brain Mapping↗

PubMed2001

A new approach to analysing texture-defined motion.

It has been widely accepted that standard low-level computational approaches to motion processing cannot extract texture-defined motion without applying some pre-processing nonlinearity. This has motivated accounts of motion perception in which luminance- and texture-defined motion are processed by separate mechanisms. Here, we introduce a novel method of image description where motion sequences may be described in terms of their local spatial and temporal gradients. This allows us to assess the local velocity information available to standard low-level motion mechanisms. Our analysis of several texture-motion stimuli shows that the information indicating correct texture-motion velocity and/or direction is present in the raw luminance measures. This raises the possibility that luminance-motion and texture-motion may be processed by the same cortical mechanisms. Our analysis offers a way of looking at texture-motion processing that is, to our knowledge, new and original.

Electrophysiology↗

PubMed2005

Observation of flux reversal in a symmetric optical thermal ratchet.

We demonstrate that a cycle of three holographic optical trapping patterns can implement a thermal ratchet for diffusing colloidal spheres and that the ratchet-driven transport displays flux reversal as a function of the cycle frequency and the intertrap separation. Unlike previously described ratchet models, the approach we describe involves three equivalent states, each of which is locally and globally spatially symmetric, with spatiotemporal symmetry being broken by the sequence of states.

Journal Article↗

PubMed1993

Quantitative colorimetric analysis of liquid crystal films (LCF) for phantom dosimetry in microwave hyperthermia.

A fully quantitative analysis of liquid crystal film (LCF) color patterns, in phantom thermal dosimetry for microwave hyperthermia, is presented. An accurate determination of absorption rate density (ARD) is achieved by color image computer processing. This work is proven to be an improvement upon the semi-quantitative or qualitative descriptions of LCF colors performed essentially by visual analysis of photographs. Temperature-induced chromatic distributions are acquired as R, G, B (red, green, blue) signals by a CCD camera connected to a PC frame grabber board. These data, stored into three 512 x 512 memory buffers, are then converted to H, S, I (hue, saturation, intensity) colorimetric system. Provided a suitable calibration of the LCF, the H quantity can be transformed to temperature using a monotonic relationship. In this way, a temperature accuracy lower than 0.2 degrees C and a spatial resolution less than 1 mm are obtained. A sequence of thermal maps can be acquired and stored on disk at a maximum rate of 1 image/2 s, and then the ARD is calculated at each pixel of the map using the least squares method.

Calibration↗

PubMed2005

Spatiotemporal video segmentation based on graphical models.

This paper proposes a probabilistic framework for spatiotemporal segmentation of video sequences. Motion information, boundary information from intensity segmentation, and spatial connectivity of segmentation are unified in the video segmentation process by means of graphical models. A Bayesian network is presented to model interactions among the motion vector field, the intensity segmentation field, and the video segmentation field. The notion of the Markov random field is used to encourage the formation of continuous regions. Given consecutive frames, the conditional joint probability density of the three fields is maximized in an iterative way. To effectively utilize boundary information from the intensity segmentation, distance transformation is employed in local objective functions. Experimental results show that the method is robust and generates spatiotemporally coherent segmentation results. Moreover, the proposed video segmentation approach can be viewed as the compromise of previous motion based approaches and region merging approaches.

Algorithms↗

PubMedDate not supplied

T cell recognition of lysozyme. III. Recognition of the 'surface-simulation' synthetic antigenic sites.

In previous studies from this laboratory the antigenic sites of lysozyme were found to be composed of spatially adjacent surface residues that are mostly distant in sequence (i.e. discontinuous sites). For synthetic mimicking of the sites, we introduced the concept of 'surface-simulation' synthesis by which the binding site residues are linked directly via peptide bonds with appropriate spacing and directionality into a single peptide which does not exist in the protein but mimics a surface region of it. In the present report T cell recognition of the surface-simulation synthetic antigenic sites has been explored in a mouse strain, B10.BR, that is a high responder to lysozyme. The discontinuous antigenic sites of lysozyme also had the capacity to stimulate proliferation of T cells driven by native lysozyme in long-term cultures. Thus, in addition to the four continuous T sites that we have recently reported, T cell recognition of lysozyme also involves discontinuous sites. This is the first clear demonstration that, contrary to a long-held impression, T cell recognition is not restricted only to sequence features, but can also be directed to protein discontinuous surface areas of high conformational dependency.

Animals↗

PubMed1991

Cross-regulatory interactions between the proneural achaete and scute genes of Drosophila.

The achaete (ac) and scute (sc) genes of Drosophila allow cells to become sensory organ mother cells. Although ac and sc have similar patterns of expression, deletion of either gene removes specific subsets of sensory organs. This specificity was shown to reside in the peculiar regulation of ac and sc expression. These genes are first activated in complementary spatial domains in response to different cis-regulatory sequences. Each gene product then stimulates expression of the other gene, thus generating similar patterns of expression. Therefore, removal of one gene leads to the absence of both proneural gene products and sensory organs in the sites specified by its cis-regulatory sequences.

Animals↗

PubMed2004

Peripheral vasculature: whole-body MR angiography with midfemoral venous compression--initial experience.

Five volunteers and 10 patients suspected of having peripheral vascular disease underwent multistation contrast material-enhanced three-dimensional whole-body magnetic resonance (MR) angiography. The first examination, based on standard protocol, lasted 72 seconds, while the following two examinations, performed with a high-spatial-resolution T1-weighted gradient-recalled-echo sequence for the last two stations (lower extremities) lasted 170 seconds. In the second high-resolution examination, midfemoral venous compression was used. Intraindividual comparison showed the high-resolution protocol with venous compression resulted in the best qualitative and quantitative image quality through higher signal-to-noise and contrast-to-noise ratios in the calf arteries. Despite prolonged acquisition times, there was no venous contamination. The data suggest that midfemoral venous compression should be incorporated in multistation protocols of the lower extremities to improve depiction of calf arteries without disturbing venous overlap.

Adult↗

PubMed1989

mRNAs and a cloned histone gene are differentially expressed during anther and pollen development in rice (Oryza sativa L.).

Spatial and temporal changes in the distribution of mRNA sequences during anther and pollen development in rice (Oryza sativa) were investigated by in situ hybridization with [3H]polyuridylic acid ([3H]poly(U)) and a cloned rice histone gene probe. Annealing of sections with [3H]poly(U) showed that poly(A)-containing RNA (poly(A)+RNA) was uniformly distributed in the cells of the anther primordium. During the formation of the archesporial initial, the primary parietal cell, the primary sporogenous cell and tapetum, there was no differential accumulation of poly(A)+RNA in their progenitor cells. Preparatory to meiosis, there was a sharp decrease in poly(A)+RNA concentration in the epidermis and middle layer of the anther wall, although the label persisted in the endothecium, tapetum and microsporocytes. Poly(A)+RNA concentration decreased in these cell types during meiosis and attained very low levels in the disintegrating tapetum and the persistent endothecium of the post-meiotic anther. Pollen development was characterized by the absence of [3H]poly(U) binding sites in the uninucleate microspores and by their presence in the vegetative and generative cells of the bicellular pollen grain. In anther sections hybridized with [3H]histone probe, gene expression was only detected in the endothecium of the premeiotic anther and in the bicellular pollen grains.

Genes↗

PubMed1991

Retinobenzoic acids and nuclear retinoic acid receptors.

Retinoids (retinoic acid and its analogs) are widely involved in the control of cell proliferation, cell differentiation and embryonic development. A series of potent and novel synthetic retinoids named retinobenzoic acids has been developed. Retinobenzoic acids have proven to be useful tools in the investigation of the molecular mechanisms of retinoidal actions. Retinoids elicit their biological effects by binding to and activating specific nuclear receptors for retinoids (RAR's) which belong to the steroid/thyroid nuclear receptor superfamily. Recent investigations concerning the structure and function of nuclear receptors, namely of RAR's, are reviewed. Three subtypes of RAR (RAR-alpha, RAR-beta and RAR-gamma) have been identified so far. Each RAR is considered to play particular roles in the retinoidal actions. The role of each RAR is discussed in relation to their features and to the structure-activity relationships of retinoids. RAR's act as retinoid-dependent transcription factors which bind to a specific site of the gene and control its expression. Recent progress in the investigation of the interaction of RAR's with the responsive genes and with nuclear co-factors is reviewed. The diversity of retinoidal actions are possibly explained by the diversity of RAR's in their structure and in their spatial and temporal distribution, by the diversity of base sequences which interact with RAR's, by the diversity of cell type-specifically determined hierarchy of gene expression, and by the diversity of the nuclear factors which interact with RAR's.

Animals↗