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At least 1,621 records · Page 90Linked to original sources
PubMed1994

Suppression of activated Let-60 ras protein defines a role of Caenorhabditis elegans Sur-1 MAP kinase in vulval differentiation.

The let-60 ras gene of Caenorhabditis elegans is one of the key players in a signal transduction pathway that controls the choice between vulval and epidermal differentiation in response to extracellular signals. To identify components acting downstream of let-60 ras in the vulval signaling pathway, we have identified a reduction-of-function mutation in the sur-1 gene that completely suppresses the multivulva phenotype of a hyperactive let-60 ras mutation. About 10% of animals homozygous for the sur-1 mutation also display a specific and intriguing vulval cell lineage defect. In addition, the sur-1 mutation results in a cold-sensitive egg-laying defective phenotype and a partial larval lethal phenotype. We have cloned the sur-1 gene by DNA-mediated transformation and have shown that it encodes a protein similar in overall structure to mammalian MAP kinases (ERKs). The functional homology between Sur-1 MAP kinase and mammalian MAP kinases was also demonstrated by the ability of a rat ERK2 kinase to rescue the sur-1 mutant phenotypes. Genetic double-mutant analyses place sur-1 downstream of let-60 ras but upstream of lin-1 in the vulval signaling pathway. Our results provide further evidence for the extreme conservation of Ras-mediated signaling pathway between worms and humans and for the function of MAP kinases in cell signaling processes that control cell differentiation and animal development.

ATP-Binding Cassette Transporters↗
PubMed2001

Field theory of self-organized fractal etching.

We propose a phenomenological field theoretical approach to the chemical etching of a disordered solid. The theory is based on a recently proposed dynamical etching model. Through the introduction of a set of Langevin equations for the model evolution, we are able to map the problem into a field theory related to isotropic percolation. To the best of the author's knowledge, this constitutes the first application of field theory to a problem of chemical dynamics. By using this mapping, many of the etching process critical properties are seen to be describable in terms of the percolation renormalization group fixed point. The emerging field theory has the peculiarity of being self-organized in the sense that without any parameter fine tuning the system develops fractal properties up to a certain scale controlled solely by the volume V of the etching solution. In the limit V-->infinity the upper cutoff goes to infinity and the system becomes scale invariant. We present also a finite size scaling analysis and discuss the relation of this particular etching mechanism to gradient percolation. Finally, the possibility of considering this mechanism as a generic path to self-organized criticality is analyzed, with the characteristics of being closely related to a real physical system and therefore more directly accessible to experiments.

Journal Article↗
PubMed2005

Low-temperature dynamics of kinks on Ising interfaces.

The anisotropic motion of an interface driven by its intrinsic curvature or by an external field is investigated in the context of the kinetic Ising model in both two and three dimensions. We derive in two dimensions (2D) a continuum evolution equation for the density of kinks by a time-dependent and nonlocal mapping to the asymmetric exclusion process. Whereas kinks execute random walks biased by the external field and pile up vertically on the physical 2D lattice, they execute hard-core biased random walks on a transformed 1D lattice. Their density obeys a nonlinear diffusion equation which can be transformed into the standard expression for the interface velocity, v=M [ (gamma+gamma'') kappa+H] , where M , gamma+gamma", and kappa are the interface mobility, stiffness, and curvature, respectively. In 3D, we obtain the velocity of a curved interface near the 100 orientation from an analysis of the self-similar evolution of 2D shrinking terraces. We show that this velocity is consistent with the one predicted from the 3D tensorial generalization of the law for anisotropic curvature-driven motion. In this generalization, both the interface stiffness tensor and the curvature tensor are singular at the 100 orientation. However, their product, which determines the interface velocity, is smooth. In addition, we illustrate how this kink-based kinetic description provides a useful framework for studying more complex situations by modeling the effect of immobile dilute impurities.

Journal Article↗
PubMed2001

Grazing and border-collision in piecewise-smooth systems: a unified analytical framework.

A comprehensive derivation is presented of normal form maps for grazing bifurcations in piecewise smooth models of physical processes. This links grazings with border-collisions in nonsmooth maps. Contrary to previous literature, piecewise linear maps correspond only to nonsmooth discontinuity boundaries. All other maps have either square-root or (3/2)-type singularities.

Journal Article↗
PubMed2003

Rapid routine structure determination of macromolecular assemblies using electron microscopy: current progress and further challenges.

Although the methodology of molecular microscopy has enormous potential, it is time consuming and labor intensive. The techniques required to produce a three-dimensional (3D) electron density map of a macromolecular structure normally require manual operation of an electron microscope by a skilled operator and manual supervision of the sometimes complex software needed for analysis and calculation of 3D maps. Systems to automate the process of data acquisition from an electron microscope are being developing and these systems are being integrated with specimen handling operations and post acquisition data processing. Here, the current performance of our existing systems and the future challenges involved in substantially improving both the sustained throughput and the yield of automated data collection and analysis are reported.

Algorithms↗
PubMed2001

Strain rate imaging using two-dimensional speckle tracking.

Strain rate images (SRI) of the beating heart have been proposed to identify non-contracting regions of myocardium. Initial attempts used spatial derivatives of tissue velocity (Doppler) signals. Here, an alternate method is proposed based on two-dimensional phase-sensitive speckle tracking applied to very high frame rate, real-time images. This processing can produce high resolution maps of the time derivative of the strain magnitude (i.e., square root of the strain intensity). Such images complement traditional tissue velocity images (TVI), providing a more complete description of cardiac mechanics. To test the proposed approach, SRI were both simulated and measured on a thick-walled, cylindrical, tissue-equivalent phantom modeling cardiac deformations. Real-time ultrasound images were captured during periodic phantom deformation, where the period was matched to the data capture rate of a commercial scanner mimicking high frame rate imaging of the heart. Simulation results show that SRI with spatial resolution between 1 and 2 mm are possible with an array system operating at 5 MHz. Moreover, these images are virtually free of angle-dependent artifacts present in TVI and simple strain rate maps derived from these images. Measured results clearly show that phantom regions of low deformation, which are difficult to identify on tissue velocity-derived SRI, are readily apparent with SRI generated from two-dimensional phase-sensitive speckle tracking.

Biomedical Engineering↗
PubMed1999

Decision-making for percutaneous endoscopic gastrostomy among older adults in a community setting.

OBJECTIVE: To describe clinical decision-making for percutaneous endoscopic gastrostomy from the perspective of patients, caregivers, and physicians. DESIGN: A prospective cohort study. SETTING AND PATIENTS: All patients aged 60 and older receiving percutaneous endoscopic gastrostomies in a defined community over a 16-month period. MAIN OUTCOMES MEASURES: Either patients or their surrogate decision-makers completed a semistructured face-to-face interview to map out the information gathering process, expectations, and discussants involved in the decision to proceed with gastrostomy feeding. Physicians completed a written questionnaire to determine their likelihood of recommending percutaneous endoscopic gastrostomy, their involvement in the decision-making and recommendation process, and sources of perceived pressure in the decision-making. RESULTS: We identified 100 patients who received percutaneous endoscopic gastrostomy during the study window and 82 primary care physicians who provided care in the defined community. The most common reasons for the procedure were stroke, neurologic disease, and cancer. Patients or their surrogate decision-makers reported multiple discussants, incomplete information, and considerable distress in arriving at the decision to proceed with artificial feeding. This distress was usually in the context of an acute and debilitating illness that often overshadowed the decision about artificial feeding. The decision for gastrostomy often appeared to be a "non-decision" in the sense that decision-makers perceived few alternatives. Physicians also reported considerable distress in arriving at recommendations to proceed with percutaneous endoscopic gastrostomy, including perceived pressures from families or other healthcare professionals. Physicians have clear patterns of triage for percutaneous endoscopic gastrostomy, but the assumptions underlying these patterns are not well supported by the medical literature. CONCLUSIONS: Patients, caregivers, and physicians are often compelled to make decisions about long-term enteral feeding under tragic circumstances and with incomplete information. Decision-makers typically do not perceive any acceptable alternatives. Because data on these patients' long-term functional outcomes are lacking, decision-makers appear to focus primarily on the short-term safety of the procedure and the potential for improved nutrition.

Aged↗
PubMed1998

Capacity for plasticity in the adult owl auditory system expanded by juvenile experience.

In the process of creating a multimodal map of space, auditory-visual neurons in the optic tectum establish associations between particular values of auditory spatial cues and locations in the visual field. In the barn owl, tectal neurons reveal these associations in the match between their tuning for interaural time differences (ITDs) and the locations of their visual receptive fields (VRFs). In young owls ITD-VRF associations can be adjusted by experience over a wide range, but the range of adjustment normally becomes quite restricted in adults. This normal range of adjustment in adults was greatly expanded in owls that had previously learned abnormal ITD-VRF associations as juveniles. Thus, the act of learning abnormal associations early in life leaves an enduring trace in this pathway that enables unusual functional connections to be reestablished, as needed, in adulthood, even when the associations represented by these connections have not been used for an extended period of time.

Adaptation, Physiological↗
PubMed1993

Presentation of T-cell epitopes assembled as multiple-antigen peptides to murine and human T lymphocytes.

Multiple-antigen peptide (MAP) constructs containing different T- and B-cell epitopes were assessed for their ability to be specifically recognized by murine and human T-cell clones. The different synthetic MAP constructs consisted of a malaria T-cell epitope or of a human universal tetanus toxin helper T-cell epitope collinearly synthesized with B-cell epitopes from the circumsporozoite proteins of different malaria parasites. All constructs were able to stimulate specifically T-cell clones. Interestingly, T-cell epitopes assembled as MAP constructs did not require processing for the specific stimulation of murine and human T-cell clones, as shown by retention of their stimulatory effect in the presence of glutaraldehyde-fixed antigen-presenting cells. However, processing was required for most of the synthetic constructs containing both T- and B-cell epitopes. Thus, the requirement for processing of these constructs seems to be dictated by the nature of the B-cell epitope present.

Amino Acid Sequence↗
PubMed1983

Morphogenesis of bacteriophage phi 29 of Bacillus subtilis: oriented and quantized in vitro packaging of DNA protein gp3.

The assembly of phage phi 29 occurs by a single pathway, and the DNA protein (DNA-gp3) of "packaging intermediates" can be obtained after DNase I interruption of in vitro complementation. A broad spectrum of DNA molecules of variable length was isolated from DNase I-treated proheads. Restriction endonuclease EcoRI digestion and electrophoretic analysis of these DNA molecules suggested that DNA-gp3 packaging was oriented with respect to the physical map and was a complex process. Proteinase K-treated exogenous DNA was not packaged. When exogenous DNA-gp3 was predigested with the restriction endonucleases BstEII. EcoRI, HpaI, and HpaII, the left-end fragments, ranging in size from 8 to 0.9 megadaltons, were selectively and efficiently packaged. During in vivo and in vitro assembly, DNA-gp3 is packaged into proheads, the "core-scaffolding" protein gp7 exits from the particles, and the DNA-filled heads assume the angular morphology of phage phi 29. The packaging of a 4.1-megadalton DNA-gp3 left-end fragment (one third of the genome) resulted in the exit of gp7 and the transition to angularity.

Bacillus subtilis↗
PubMed2005

Visual evaluation of perfusion computed tomography in acute stroke accurately estimates infarct volume and tissue viability.

OBJECTIVE: To establish the validity of visual interpretation of immediately processed perfusion computed tomography (CT) maps in acute stroke for prediction of final infarction. METHODS: Perfusion CT studies acquired prospectively were reprocessed within six hours of stroke onset using standard CT console software. Four contiguous 5 mm thick images were obtained and maps of time to peak (TTP) and cerebral blood volume (CBV) generated. Volumes of lesions identified only by visual inspection were measured from manually drawn regions of interest. Volumes of tissue with prolonged TTP or reduced CBV were compared with independently calculated volume of infarction on non-contrast CT (NCCT) at 24-48 hours, and with clinical severity using the NIHSS score. Arterial patency at 24-48 h was included in analyses. RESULTS: Studies were analysed from 17 patients 150 minutes (median) after stroke onset. Volume of tissue with prolonged TTP correlated with initial NIHSS (r = 0.62, p = 0.009), and with NCCT final infarct volume when arterial occlusion persisted (r = 0.953, p = 0.012). Volume of tissue with reduced CBV correlated with final infarct volume if recanalisation occurred (r = 0.835, p = 0.001). Recanalisation was associated with lower 24 h NIHSS score (6 (IQR, 5 to 9.5) v 19 (18 to 26), p = 0.027), and in 10 patients given rtPA for MCA M1 occlusion, with lower infarct volume (73 v 431 ml, p = 0.002). CONCLUSIONS: Visual evaluation of TTP and CBV maps generated by standard perfusion CT software correlated with 24-48 hour CT infarct volumes. Comparison of TTP and CBV maps yields information on tissue viability. Perfusion CT represents a practical technique to aid acute clinical decision making. Recanalisation was a crucial determinant of clinical and radiological outcome.

Adult↗
PubMed2001

Effect of meal viscosity and nutrients on satiety, intragastric dilution, and emptying assessed by MRI.

The relationship between the intragastric distribution, dilution, and emptying of meals and satiety was studied using noninvasive magnetic resonance imaging techniques in 12 healthy subjects with four polysaccharide test meals of varying viscosity and nutrient content as follows: 1) low-viscosity nonnutrient, 2) low-viscosity nutrient, 3) high-viscosity nonnutrient, and 4) high-viscosity nutrient. Increasing the nutrient content of the high-viscosity meal delayed gastric emptying from 46 +/- 9 to 76 +/- 6 min (P < 0.004), whereas increasing viscosity had a smaller effect. The volume of secretions within the stomach 60 min after ingestion was higher for the high-viscosity nutrient meal (P < 0.04). A simple model to calculate the total volume of secretion added to the test meal is presented. Color-coded dilution map images showed the heterogeneous process of progressive gastric dilution of high-viscosity meals, whereas low-viscosity meals were uniformly diluted. Fullness was found to be linearly related to total gastric volumes for the nutrient meals (R(2) = 0.98) and logarithmically related for the nonnutrient meals (R(2) = 0.96). Fullness was higher for high- compared with low-viscosity meals (P < 0.02), and with the nutrient meals this was associated with greater antral volumes (P < 0.05).

Adult↗
PubMed2001

Postlesional vestibular reorganization in frogs: evidence for a basic reaction pattern after nerve injury.

Nerve injury induces a reorganization of subcortical and cortical sensory or motor maps in mammals. A similar process, vestibular plasticity 2 mo after unilateral section of the ramus anterior of N. VIII was examined in this study in adult frogs. The brain was isolated with the branches of both N. VIII attached. Monosynaptic afferent responses were recorded in the vestibular nuclei on the operated side following ipsilateral electric stimulation either of the sectioned ramus anterior of N. VIII or of the intact posterior vertical canal nerve. Excitatory and inhibitory commissural responses were evoked by separate stimulation of each of the contralateral canal nerves in second-order vestibular neurons. The afferent and commissural responses of posterior vertical canal neurons recorded on the operated side were not altered. However, posterior canal-related afferent inputs had expanded onto part of the deprived ramus anterior neurons. Inhibitory commissural responses evoked from canal nerves on the intact side were detected in significantly fewer deprived ramus anterior neurons than in controls, but excitatory commissural inputs from the three contralateral canal nerves had expanded. This reactivation might facilitate the survival of deprived neurons and reduce the asymmetry in bilateral resting activities but implies a deterioration of the original spatial response tuning. Extensive similarities at the synaptic and network level were noted between this vestibular reorganization and the postlesional cortical and subcortical reorganization of sensory representations in mammals. We therefore suggest that nerve injury activates a fundamental neural reaction pattern that is common between sensory modalities and vertebrate species.

Animals↗
PubMed1978

The relation of localized myocardial warming to changes in cardiac surface electrograms in dogs.

We studied the relationship of the size and severity of alteration of recovery properties in localized areas to changes in cardiac surface electrograms in experiments on six open-chest dogs. Alterations in recovery properties were induced thermally because size and severity of the affected area could be controlled on the basis of physical principles which were modeled. We recorded unipolar electrograms from 75 cardiac surface sites simultaneously during stimulation of atria and pulmonary conus in control periods and in the presence of warmed areas of varying sizes and intensities. Size of the areas was controlled by the diameter of an aperture through which a light source was directed. Intensity was controlled by the light source excitation voltage. Myocardial temperature was monitored with a thermistor. The QRS, STT, and QRST deflection areas were determined by computer processing and displayed as isoarea maps. Difference maps also were determined by subtracting control QRST isoarea maps from those obtained in the presence of warmed areas. QRST area difference maps were related closely to the size and severity of the thermally induced changes in recovery properties. With areas of the same size and increasing myocardial temperatures, the magnitude of the change in QRST area increased, and the gradient of contour lines between the affected and unaffected areas increased. When myocardial temperature at the center of the warmed area was kept constant and the size of the warmed area was increased, the affected cardiac surface area increased, but the number of isoarea contours remained approximately the same. These findings suggest that the change in QRST isoarea maps may be a useful indicator of lesion size when combined with an index of lesion severity such as the QRST area change in the electrogram with the maximum change. QRST areas during both activation orders were similar, suggesting that the QRST area is independent of changes in activation sequence.

Action Potentials↗
PubMed2002

Bioinspired engineering of exploration systems for NASA and DoD.

A new approach called bioinspired engineering of exploration systems (BEES) and its value for solving pressing NASA and DoD needs are described. Insects (for example honeybees and dragonflies) cope remarkably well with their world, despite possessing a brain containing less than 0.01% as many neurons as the human brain. Although most insects have immobile eyes with fixed focus optics and lack stereo vision, they use a number of ingenious, computationally simple strategies for perceiving their world in three dimensions and navigating successfully within it. We are distilling selected insect-inspired strategies to obtain novel solutions for navigation, hazard avoidance, altitude hold, stable flight, terrain following, and gentle deployment of payload. Such functionality provides potential solutions for future autonomous robotic space and planetary explorers. A BEES approach to developing lightweight low-power autonomous flight systems should be useful for flight control of such biomorphic flyers for both NASA and DoD needs. Recent biological studies of mammalian retinas confirm that representations of multiple features of the visual world are systematically parsed and processed in parallel. Features are mapped to a stack of cellular strata within the retina. Each of these representations can be efficiently modeled in semiconductor cellular nonlinear network (CNN) chips. We describe recent breakthroughs in exploring the feasibility of the unique blending of insect strategies of navigation with mammalian visual search, pattern recognition, and image understanding into hybrid biomorphic flyers for future planetary and terrestrial applications. We describe a few future mission scenarios for Mars exploration, uniquely enabled by these newly developed biomorphic flyers.

Algorithms↗
PubMed2006

Expression of receptor for advanced glycation end products in sarcoid granulomas.

RATIONALE: The receptor for advanced glycation end products (RAGE) engages a number of ligands implicated in inflammatory processes. The RAGE coding gene maps to the 6p21.32 region, close to the genes DRB1 and BTNL2, which are associated with sarcoidosis. OBJECTIVES: We investigated a possible implication of RAGE in sarcoid granulomas. METHODS: RAGE and major ligands (N-epsilon-carboxy-methyl-lysine [CML], S100A12, and S100B) expression was investigated by immunostaining of 99 paraffin-embedded biopsies of sarcoid tissues, and expression patterns were determined. Among the three RAGE gene single-nucleotide polymorphisms investigated, -374 T/A was selected, characterized in terms of transcriptional effect (immunocytochemistry and real-time polymerase chain reaction), and its frequency was determined in DNA extracted from biopsies. MEASUREMENTS AND RESULTS: RAGE, CML, S100A12, and S100B immunoreactivity was observed in all sarcoid granulomas, although at different intensities. The degree of RAGE expression significantly correlated with the degree of S100A12 expression. The -374 TT/AT genotypes, associated with higher RAGE transcriptional activity, were more frequent in the sarcoidosis biopsy group than in control subjects, and the association was confirmed in a second, independent series of 101 patients with sarcoidosis. CONCLUSIONS: We showed the association of RAGE and its ligands with sarcoidosis and suggest that an intrinsic genetic factor could be in part involved in its expression. In Italian patients, the -374 T/A polymorphism seems to be significantly associated with this disease.

Adolescent↗
PubMed2006

Toxicoproteomics in liver injury and inflammation.

Toxicoproteomics, in applying proteomics to toxicology, seeks to identify critical proteins and pathways in biological systems responding to adverse chemical exposures and environmental stressors using global protein expression technologies. Toxicoproteomics is being exploited for the discovery of new biomarkers and toxicity signatures in target organs, such as liver, in major biological processes, such as inflammation, in mapping serum, plasma, and other biofluid proteomes, and in parallel proteomic and transcriptomic studies. The new field of toxicoproteomics is uniquely positioned toward discovery of new biomarkers and signatures of tissue injury and a better understanding of protein expression responses during toxicity and environmental disease.

Chemical and Drug Induced Liver Injury↗
PubMed2005

Combining the meiosis Gibbs sampler with the random walk approach for linkage and association studies with a general complex pedigree and multimarker loci.

A linkage analysis for finding inheritance states and haplotype configurations is an essential process for linkage and association mapping. The linkage analysis is routinely based upon observed pedigree information and marker genotypes for individuals in the pedigree. It is not feasible for exact methods to use all such information for a large complex pedigree especially when there are many missing genotypic data. Proposed Markov chain Monte Carlo approaches such as a single-site Gibbs sampler or the meiosis Gibbs sampler are able to handle a complex pedigree with sparse genotypic data; however, they often have reducibility problems, causing biased estimates. We present a combined method, applying the random walk approach to the reducible sites in the meiosis sampler. Therefore, one can efficiently obtain reliable estimates such as identity-by-descent coefficients between individuals based on inheritance states or haplotype configurations, and a wider range of data can be used for mapping of quantitative trait loci within a reasonable time.

Computer Simulation↗