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At least 883 records · Page 49Linked to original sources
PubMed2003

Single-walled carbon nanotube based molecular switch tunnel junctions.

This article describes two-terminal molecular switch tunnel junctions (MSTJs) which incorporate a semiconducting, single-walled carbon nanotube (SWNT) as the bottom electrode. The nanotube interacts noncovalently with a monolayer of bistable, nondegenerate [2]catenane tetracations, self-organized by their supporting amphiphilic dimyristoylphosphatidyl anions which shield the mechanically switchable tetracations from a two-micrometer wide metallic top electrode. The resulting 0.002 micron 2 area tunnel junction addresses a nanometer wide row of approximately 2000 molecules. Active and remnant current-voltage measurements demonstrated that these devices can be reconfigurably switched and repeatedly cycled between high and low current states under ambient conditions. Control compounds, including a degenerate [2]catenane, were explored in support of the mechanical origin of the switching signature. These SWNT-based MSTJs operate like previously reported silicon-based MSTJs, but differently from similar devices incorporating bottom metal electrodes. The relevance of these results with respect to the choice of electrode materials for molecular electronics devices is discussed.

Journal Article↗
PubMed1989

A genetic switch, based on negative regulation, sharpens stripes in Drosophila embryos.

The pair-rule genes hairy, runt, even-skipped, and fushi tarazu express their mRNAs and proteins in striped patterns in the Drosophila embryo at the blastoderm stage. Previous studies have shown that the generation of these patterns depends upon products of the gap genes and upon interactions between the pair-rule genes themselves. Here we show that blocking protein synthesis induces expression of each of the pair-rule mRNAs in virtually all regions of the embryo. Our observations together with genetic studies carried out in other laboratories suggest that negative feedback between the pair-rule genes plays a key role in striped expression of pair-rule genes. We propose that stable proteins, present in all regions of the embryo, first activate transcription of these pair-rule genes constitutively. Then, various combinations of unstable proteins repress their transcription in a patterned fashion; each stripe of accumulated products of a given pair-rule gene marks a region where it was not repressed. We develop this idea in mathematical form and demonstrate that a network of mutual repression by pair-rule genes can make each blastoderm nucleus into a genetic switch with two stable states. If preexisting gap gene patterns provide initial bias to the blastoderm nuclei, then the "bistable switch behavior" of the nuclei can refine an initially weak spatial bias into a final pattern of sharp stripes.

Animals↗
PubMed2002

Theoretical calculation of the coiled-coil stability in water in the context of its possible use as a molecular rack.

The coiled-coil stability and rigidity may be of importance for molecular electronics (electronically bistable molecules). The coiled-coil binding free energy has been calculated using molecular dynamics (MD). The energy has been computed as a difference of the appropriate free energies; derived for the coiled-coil and isolated alpha-helices separately. All MD simulations have been performed using an explicit model of the solvent, whereas the continuum solvent approach has been applied to analyze the MD trajectories. The computed stability of the coiled-coil is of the order of -87 kcal/mol, i.e., about -1.2 kcal/mol per amino acid residue, and arises mainly from the electrostatic interactions and hydrophobic effect. The entropy term has been roughly estimated to be of the order of -22 kcal/mol. This assures that coiled-coil polypeptides may be used as a stable molecular scaffolding.

Amino Acid Sequence↗
PubMed1976

The sonolucent "light bulb" sign of fluid collections.

The recent introduction of gray scale ultrasound, which uses a higher power output, has made it more difficult ot assess the cystic or solid nature of sonolucent mass lesions using the cirteria developed for bistable imaging, i.e. the amount of through transmission and the strength of the posterior wall echo. However, a cyst may be reliably diagnosed if a totally echofree area is seen adjacent to an area with low-level echoes derived from tissue parenchyma. We have termed this the "light bulb sign." Visualization of the sign facilitates the decision of the optimal time for abscess drainage.

Abscess↗
PubMed1976

Biparietal diameter: a comparison of real time and conventional B scan techniques.

Real time multitransducer B scanners can greatly facilitate obstetrical ultrasound examination. To assess the accuracy and reproducibility of biparietal diameter (BPD) measurement with the real time scanner, we compared the BPD using the real time scanner with the results obtained by conventional bistable leading edge and gray scale measurements. The results show that 73 to 90 per cent of the results with the real time scanner are within 1 mm of the other measurement and 94 per cent are within 2 mm. The variance of measurements on each case with the real time scanner is not significantly greater than the variance using the other two methods. We feel that the real time scanner can be a useful tool for obstetrical examinations and is accurate in the measurement of the biparietal diameter.

Cephalometry↗
PubMed1977

Ultrasound in the evaluation of adrenal metastases.

Metastatic involvement of the adrenal glands is a frequent complication of bronchogenic carcinoma, occuring in up to 33% of these patients. Examination of ten patients with adrenal metastases revealed large adrenal masses, occuring bilaterally in five. Five of these patients were examined using the standard bistable technique. These patients demonstrated largely echofree masses with only occasional scattered internal echoes. The remaining five patients were examined with the gray scale technique. With the added resolution afforded by the use of gray scale, the masses in these patients showed a more uniform distribution of echoes. Presence of a margin between the kidney and the mass, and displacement of the kidney inferiorly, posteriorly, and laterally is used to differentiated between upper pole renal masses and those of adrenal origin. Autopsy confirmation was obtained in six of the patients.

Adrenal Gland Neoplasms↗
PubMed1977

Ultrasonic imaging of normal intrauterine fetal anatomy.

With the advent and subsequent refinement of gray scale compound scanning, we are now able to obtain in utero a more detailed look at the size, shape position, and anatomical relationships between the internal organs and vasular structures within the body of a fetus. It is now possible to visualize fetal intracranial structures, lungs, myocardium and valvular structures, liver, spleen, stomach, abdominal aorta, portal venous system, gall bladder, umbilical vein, kidneys, urinary bladder, and genitalia. Fetal extremities, including individual phalanges, are better visualized with gray scale than with bistable sonography.

Echocardiography↗
PubMed2002

Design and constraints of the Drosophila segment polarity module: robust spatial patterning emerges from intertwined cell state switches.

The Drosophila segment polarity genes constitute the last tier in the segmentation cascade; their job is to maintain the boundaries between parasegments and provide positional "read-outs" within each parasegment for the entire developmental history of the animal. These genes constitute a relatively well-defined network with a relatively well-understood patterning task. In a previous publication (von Dassow et al. 2000. Nature 406:188-192) we showed that a computer model predicts the segment polarity network to be a robust boundary-making device. Here we elaborate those findings. First, we explore the constraints among parameters that govern the network model. Second, we test architectural variants of the core network, and show that the network tolerates a wide variety of adjustments in design. Third, we evaluate several topologically identical models that incorporate more or less molecular detail, finding that more-complex models perform noticeably better than simplified ones. Fourth, we discuss two instances in which the failure of the network model to behave in a life-like fashion highlights mechanistic details that need further experimental investigation. We conclude with an explanation of how the segment polarity network can be understood as an interwoven conspiracy of simple dynamical elements, several bistable switches and a homeostat. The robustness with which the network as a whole maintains a spatial regime of stable cell state emerges from generic dynamical properties of these simple elements.

Animals↗
PubMed2003

Vibration signals from the FT joint can induce phase transitions in both directions in motoneuron pools of the stick insect walking system.

The influence of vibratory signals from the femoral chordotonal organ fCO on the activities of muscles and motoneurons in the three main leg joints of the stick insect leg, i.e., the thoraco-coxal (TC) joint, the coxa-trochanteral (CT) joint, and the femur-tibia (FT) joint, was investigated when the animal was in the active behavioral state. Vibration stimuli induced a switch in motor activity (phase transition), for example, in the FT joint motor activity switched from flexor tibiae to extensor tibiae or vice versa. Similarly, fCO vibration induced phase transitions in both directions between the motoneuron pools of the TC joint and the CT joint. There was no correlation between the directions of phase transition in different joints. Vibration stimuli presented during simultaneous fCO elongation terminated the reflex reversal motor pattern in the FT joint prematurely by activating extensor and inactivating flexor tibiae motoneurons. In legs with freely moving tibia, fCO vibration promoted phase transitions in tibial movement. Furthermore, ground vibration promoted stance-swing transitions as long as the leg was not close to its anterior extreme position during stepping. Our results provide evidence that, in the active behavioral state of the stick insect, vibration signals can access the rhythm generating or bistable networks of the three main leg joints and can promote phase transitions in motor activity in both directions. The results substantiate earlier findings on the modular structure of the single-leg walking pattern generator and indicate a new mechanism of how sensory influence can contribute to the synchronization of phase transitions in adjacent leg joints independent of the walking direction.

Animals↗
PubMed2003

Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans.

One approach to understanding behavior is to define the cellular components of neuronal circuits that control behavior. In the nematode Caenorhabditis elegans, neuronal circuits have been delineated based on patterns of synaptic connectivity derived from ultrastructural analysis. Individual cellular components of these anatomically defined circuits have previously been characterized on the sensory and motor neuron levels. In contrast, interneuron function has only been addressed to a limited extent. We describe here several classes of interneurons (AIY, AIZ, and RIB) that modulate locomotory behavior in C. elegans. Using mutant analysis as well as microsurgical mapping techniques, we found that the AIY neuron class serves to tonically modulate reversal frequency of animals in various sensory environments via the repression of the activity of a bistable switch composed of defined command interneurons. Furthermore, we show that the presentation of defined sensory modalities induces specific alterations in reversal behavior and that the AIY interneuron class mediates this alteration in locomotory behavior. We also found that the AIZ and RIB interneuron classes process odorsensory information in parallel to the AIY interneuron class. AIY, AIZ, and RIB are the first interneurons directly implicated in chemosensory signaling. Our neuronal mapping studies provide the framework for further genetic and functional dissections of neuronal circuits in C. elegans.

Animals↗
PubMed2000

Stoichiometry in producer-grazer systems: linking energy flow with element cycling.

All organisms are composed of multiple chemical elements such as carbon, nitrogen and phosphorus. While energy flow and element cycling are two fundamental and unifying principles in ecosystem theory, population models usually ignore the latter. Such models implicitly assume chemical homogeneity of all trophic levels by concentrating on a single constituent, generally an equivalent of energy. In this paper, we examine ramifications of an explicit assumption that both producer and grazer are composed of two essential elements: carbon and phosphorous. Using stoichiometric principles, we construct a two-dimensional Lotka-Volterra type model that incorporates chemical heterogeneity of the first two trophic levels of a food chain. The analysis shows that indirect competition between two populations for phosphorus can shift predator-prey interactions from a (+, -) type to an unusual (-, -) class. This leads to complex dynamics with multiple positive equilibria, where bistability and deterministic extinction of the grazer are possible. We derive simple graphical tests for the local stability of all equilibria and show that system dynamics are confined to a bounded region. Numerical simulations supported by qualitative analysis reveal that Rosenzweig's paradox of enrichment holds only in the part of the phase plane where the grazer is energy limited; a new phenomenon, the paradox of energy enrichment, arises in the other part, where the grazer is phosphorus limited. A bifurcation diagram shows that energy enrichment of producer-grazer systems differs radically from nutrient enrichment. Hence, expressing producer-grazer interactions in stoichiometrically realistic terms reveals qualitatively new dynamical behavior.

Animals↗
PubMed2002

Photoreceptor death: spatiotemporal patterns arising from one-hit death kinetics and a diffusible cell death factor.

Retinitis pigmentosa (RP) is an inherited disease affecting approximately 1:4000 individuals in North America. It is characterized clinically by the gradual apoptotic death of photoreceptor cells that occurs nonuniformly across the surface of the retina. Recently, it has been demonstrated that the time of death of many individual photoreceptors is random, a fact that must be reconciled with the spatiotemporal patterns of photoreceptor degeneration that are observed in patients with RP. One possible explanation is that a diffusible toxic factor is released by dying photoreceptors and induces adjacent cells to likewise undergo apoptosis. To determine if such a mechanism can result in patchy distributions of photoreceptor death, as frequently observed in RP patients, we studied cell attrition produced by a bistable biochemical switch in an idealized one-dimensional retina. We found that with a reasonable choice of parameter values, our model was able to produce patterns of cell death resembling those observed in RP. In the context of this model, patches on the order of histologically observable size could develop from a single release event, but their rates of formation were independent of the concentration of toxic factor released. Instead, factor concentration affected the overall rate of cell death, the number of degenerating patches, and their distribution across the retina.

Apoptosis↗
PubMed1996

How many phenotypes from one genotype? The case of Prion diseases.

The usual assumption, namely that the underlying biochemical reactions in an organism tend to a unique steady-state, is shown to be not always correct. There are certain pathway mechanisms (e.g. positive feedback) which allow the system to exists in two alternative stable steady states. This bistability implies that environmental perturbations can "switch" the system from either state to the other. Such a switch takes place at the metabolic level and hence a single genotype can display two different, alternative, phenotypes without involving any changes in gene expression. The infective transmission of Scrapie-type diseases is explained here by such a mechanism involving protein-only changes.

Animals↗
PubMed1998

Intercellular spiral waves of calcium.

Intercellular calcium waves have been observed in a large number of cell types, and are known to result from a variety of stimuli, including mechanical or hormonal stimulation. Recently, spiral intercellular waves of calcium have been observed in slices of hippocampal tissue. We use an existing model to study the properties of spiral intercellular calcium waves. Although intercellular spiral waves are well known in the context of cardiac muscle, due to the small value of the calcium diffusion coefficient intercellular calcium waves have fundamentally different properties. We show that homogenisation techniques give a good estimate for the plane wave speed, but do not describe spiral behaviour well. Using an expression for the effective diffusion coefficient we estimate the intercellular calcium permeability in liver. For the bistable equation, we derive an analytic estimate for the value of the intercellular permeability at which wave propagation fails. In the calcium wave model, we show numerically that the spiral period is first a decreasing, then an increasing, function of the intercellular permeability. We hypothesise that this is because the curvature of the spiral core is unimportant at low permeability, the period being approximately set instead by the speed of a plane wave along a line of coupled cells in one dimension.

Animals↗
PubMed1998

Bifurcation analysis of a model of mitotic control in frog eggs

Novak and Tyson have proposed a realistic mathematical model of the biochemical mechanism that regulates M-phase promoting factor (MPF), the major enzymatic activity controlling mitotic cycles in frog eggs, early embryos, and cell-free egg extracts. We use bifurcation theory and numerical methods (AUTO) to characterize the codimension-one and -two bifurcation sets in this model. Our primary bifurcation parameter is the rate constant for cyclin synthesis, which can be manipulated experimentally by adding exogenously synthesized cyclin mRNA to extracts depleted of all endogenous mRNA molecules. For the secondary bifurcation parameter we use the total amount of one of the principle regulatory enzymes in the extract (ACP, the enzyme complex that labels cyclin for degradation: Wee1, the kinase that inhibits MPF; or Cdc25. the phosphatase that activates MPF). We find a rich array of physiologically distinct behaviors exhibited by the model as these parameters are varied around values that seem plausible for frog eggs and extracts. In addition to unique, stable steady states (cell cycle arrest) and limit cycle oscillations (autonomous, periodic cell division), we find parameter combinations where the control system is bistable. For instance, an interphase-arrested state may coexist with a metaphase arrested state, or two stable limit cycles of different amplitude and period may coexist. We suggest that such strange behavior is nearly unavoidable in a complex regulatory system like the cell cycle. Perhaps cells exploit some of these exotic bifurcations for control purposes that are as yet unrecognized by physiologists. Copyright 1998 Academic Press

Journal Article↗
PubMed2000

Quantifying the dynamics of prion infection: a bifurcation analysis of Laurent's model.

Laurent (1996a, Médecine/sciences12, 774-785; 1996b, Biochem. J.318, 35-39; 1998, Bio-phys. Chem.72, 211-222) proposed a model for the dynamics of diseases of the central nervous system caused by prions. It is based on the protein-only hypothesis (Prusiner et al., 1981, Proc. Natl. Acad. Sci. U.S.A.78, 6675-6679), which assumes that infection can be spread by particular proteins (prions) that can exist in two forms that share the same sequence, but have a different structure. The normal form is harmless, while the infectious isoform of the prion protein catalyses a transconformation from the native isoform to itself within a specialized compartment of the brain cells. This paper systematically explores the model behavior with the aim of quantifying the fundamental parameters characterizing the dynamics of prion infection. To this end we use data from the literature to fix orders of magnitude for the rates of synthesis and degradation of the native form of prion protein and for the shape of the autocatalytic function. The dynamical behavior is classified with respect to two unknown parameters (bifurcation analysis): the rate of spontaneous transconformation and the rate of output of the infectious isoform from the specialized compartment. We thus find that the bistability properties evidenced by Laurent are confined to a certain range of parameters and that permanent oscillations of the two isoforms concentrations are possible. The bifurcation analysis allows us to estimate approximate ranges for the values of the two unknown parameters and consequently to derive incubation times and compare them with actual data for hamster. Also, our study predicts that the output rate of the infectious isoform is relatively insensitive to variations of model parameters.

Animals↗
PubMed2000

Modelling T-cell-mediated suppression dependent on interactions in multicellular conjugates.

Tolerance to peripheral body antigens involves multiple mechanisms, namely T-cell-mediated suppression of potentially autoimmune cells. Recent in vivo and in vitro evidence indicates that regulatory T cells suppress the response of effector T cells by a mechanism that requires the simultaneous conjugation of regulatory and effector T cells with the same antigen-presenting cell (APC). Despite this strong requirement, it is not yet clear what happens while both cells are conjugated. Several hypotheses are discussed in the literature. Suppression may result from simple competition of regulatory and effector cells for activation resources on the APC; regulatory T cells may deliver an inhibitory signal to effector T cells in the same conjugate; or effector T cells may acquire the regulatory phenotype during their interaction with regulatory T cells. The present article tries to further our understanding of T-cell-mediated suppression, and to narrow-down the number of candidate mechanisms. We propose the first general formalism describing the formation of multicellular conjugates of T cells and APCs. Using this formalism we derive three particular models, representing alternative mechanisms of T-cell-mediated suppression. For each model, we make phase plane and bifurcation analysis, and identify their pros and cons in terms of the relationship with the large body of experimental observations on T-cell-mediated suppression. We argue that accounting for the quantitative details of adoptive transfers of tolerance requires models with bistable regimes in which either regulatory cells or effectors cells dominate the steady state. From this analysis, we conclude that the most plausible mechanism of T-cell-mediated suppression requires that regulatory T cells actively inhibit the growth of effector T cells, and that the maintenance of the population of regulatory T cells is dependent on the effector T cells. The regulatory T cell population may depend on a growth factor produced by effector T cells and/or on a continuous differentiation of effector cells to the regulatory phenotype.

Antigen-Presenting Cells↗
PubMed2001

Mitochondrial modulation of intracellular Ca(2+) signaling.

IP3-mediated Ca(2+) release plays a fundamental role in many cell signaling processes and has been the subject of numerous modeling studies. Only recently has the important role that mitochondria play in the dynamics of intracellular Ca(2+) signaling begun to be considered in experimental work and in computational models. Mitochondria sequester large amounts of Ca(2+) and thus have a modulatory effect on intracellular Ca(2+) signaling, and mitochondrial uptake of Ca(2+), in turn, has a regulatory effect on mitochondrial function. Here we integrate a well-established model of IP3-mediated Ca(2+) signaling with a detailed model of mitochondrial Ca(2+) handling and metabolic function. The incorporation of mitochondria results in oscillations in a bistable formulation of the IP3 model, and increasing metabolic substrate decreases the frequency of these oscillations consistent with the literature. Ca(2+) spikes from the cytosol are communicated into mitochondria and are shown to induce realistic metabolic changes. The model has been formulated using a modular approach that is easy to modify and should serve as a useful basis for the investigation of questions regarding the interaction of these two systems.

Calcium↗