Self-regulating Properties Research Articles

The Human F-Box DNA Helicase FBH1 Faces Saccharomyces cerevisiae Srs2 and Postreplication Repair Pathway Roles

The Saccharomyces cerevisiae Srs2 UvrD DNA helicase controls genome integrity by preventing unscheduled recombination events. While Srs2 orthologues have been identified in prokaryotic and lower eukaryotic organisms, human orthologues of Srs2 have not been described so far. We found that the human F-box DNA helicase hFBH1 suppresses specific recombination defects of S. cerevisiae srs2 mutants, consistent with the finding that the helicase domain of hFBH1 is highly conserved with that of Srs2. Surprisingly, hFBH1 in the absence of SRS2 also suppresses the DNA damage sensitivity caused by inactivation of postreplication repair-dependent functions leading to PCNA ubiquitylation. The F-box domain of hFBH1, which is not present in Srs2, is crucial for hFBH1 functions in substituting for Srs2 and postreplication repair factors. Furthermore, our findings indicate that an intact F-box domain, acting as an SCF ubiquitin ligase, is required for the DNA damage-induced degradation of hFBH1 itself. Overall, our findings suggest that the hFBH1 helicase is a functional human orthologue of budding yeast Srs2 that also possesses self-regulation properties necessary to execute its recombination functions.

Visual Selective Attention and the Effects of Monetary Rewards

Outcomes of actions, in the form of rewards and punishments, are known to shape behavior. For example, an action followed by reward will be more readily elicited on subsequent encounters with the same stimuli and context -- a phenomenon known as the law of effect. These consequences of rewards (and punishments) are important because they reinforce adaptive behaviors at the expense of competing ones, thus increasing fitness of the organism in its environment. However, it is unknown whether similar influences regulate covert mental processes, such as visual selective attention. Visual selective attention allows privileged processing of task-relevant information, while inhibiting distracting contextual elements. Using variable monetary rewards as arbitrary feedback on performance, we tested whether acts of attentional selection, and in particular the resulting aftereffects, can be modulated by their consequences. Results show that the efficacy of visual selective attention can be sensibly adjusted by external feedback. Specifically, although lingering inhibition of distractors is robust after highly rewarded selections, it is eliminated after poorly rewarded selections. This powerful feature of visual selective attention provides attentive processes with both flexibility and self-regulation properties.

A scheduler for relative delay service differentiation

We propose a new delay-based scheduler called asRD-VC (Relative Delay VirtualClock). Since it performs a delay-based service differentiation among flow aggregates, the quality at microflow level is the same as that at aggregate level. This is not easily achievable when the service differentiation is bandwidth-based or loss-based. Unlike theEDF (Earliest Deadline First) scheduler [1], our proposed scheduler self-regulates and adapts the delays according to load changes. This characteristic permits us to implement it in an AF-likePHB providing the relative quantification service in a DiffServ network. Finally, we compare our proposedrd-vc scheduler with two important existing propositions:WTP (Waiting Time Priority) [2, 3] andex-vc (Extended VirtualClock) [4]. Both these propositions are delay-based and have self-regulation property. All three schedulers (RD-VC, WTP andEX-VC) maintain the required service differentiation among aggregates and have comparable long term average performance like mean throughput per aggregate and packet loss ratio etc. However,RD-VC and WTP take an edge overEX-VC at short-term performance like jitter. Bothrd-vc andWTP have good long term and short-term performance. Our proposedrd-vc, compared to existingWTP, has two additional characteristics, i.e. unlike WTP which is limited to architectures with one queue per Qos class, it has no limitation on implementation scope (with or without separate queues per class) and it has lower complexity. This rendersRD-VC an interesting proposition.

Do inactivation mechanisms rather than adaptation hold the key to understanding ryanodine receptor channel gating?

The use of flash photolysis of caged Ca2+ to rapidly elevate [Ca2+] at the cytosolic face of a cardiac ryanodine receptor (RyR) channel reconstituted into a bilayer gives rise to a rapid increase in open probability (Po; Gyorke and Fill 1993). This is followed by a decline in Po, which occurs much more slowly (τ = 1.3 s). After the decline in Po, the channels can be reactivated by a second Ca2+ stimulus. These results led to the suggestion that RyR channels can adapt to a maintained Ca2+ stimulus. The report was of great interest for two main reasons. First, the concept that Ca2+-induced Ca2+ release (CICR) was a process that was smoothly graded and dependent on the magnitude of the trigger rather than an all-or-nothing process was difficult to explain. Not long before the publication of the Gyorke and Fill report (1993), Stern 1992 had brought this issue to the forefront of discussions on excitation–contraction (EC) coupling in cardiac muscle. He elegantly described how global models of EC coupling needed to be discarded because they were inherently unstable and that “local control” models, where discrete units of RyR channels were activated individually, could be operating. Stern 1992 argued that diffusion of Ca2+ away from the Ca2+ activation sites on RyR, coupled with the process of “stochastic attrition,” led to the inactivation of the Ca2+ release units. The contraction of the whole- cell, therefore, resulted from the summation of the individual packets of Ca2+ released from the separate release units. Stern's local control model of cardiac EC coupling made sense of seemingly irreconcilable discrepancies and stimulated workers in the field to investigate, extend, or disprove his theory. It was at this time that Gyorke and Fill 1993 presented adaptation as a self-regulating property of RyR channels that could serve as a “molecular control mechanism for smoothly graded Ca2+-induced Ca2+-release in heart.” On the face of it, they had uncovered a mechanism that would close the RyR channels to allow reaccumulation of Ca2+ within sarcoplasmic reticulum (SR) stores, and that could explain why CICR was not an all-or-nothing positive feedback process. Gyorke and Fill's paper (1993) was closely followed by the first report of Ca2+ sparks by Cheng et al. 1993. The improved temporal and spatial resolution of in situ SR Ca2+-release events afforded by the use of the confocal microscope accelerated the integration of theoretical models of EC coupling with experimental data. Here was evidence that local control of individual Ca2+ release units could provide smoothly graded CICR. This was an exciting time for cardiac physiologists and biophysicists, and the idea that adaptation of RyR might refine existing models of EC coupling was appealing. The second reason for the interest in this work was the proposal that the phenomenon of adaptation was not merely the response of RyR to a rapid step change in [Ca2+], but that the Ca2+ spike that preceded the maintained increase in [Ca2+] itself affected channel gating (Lamb et al. 1994; Lamb and Laver 1998). Thus, Lamb and co-workers (Lamb et al. 1994; Lamb and Laver 1998) argued adaptation was the overall response of RyR channels to both the Ca2+ spike and the longer lasting increase in [Ca2+]. The idea that the Ca2+ spike influenced the occurrence of adaptation was fueled by subsequent reports that adaptation did not occur when rapid changes in cytosolic [Ca2+] were produced using methods other than flash photolysis of a caged Ca2+ compound (Schiefer et al. 1995; Sitsapesan et al. 1995; Laver and Curtis 1996). The issue was further confounded by the more recent report that Ca2+ spikes, in the absence of a maintained elevation in [Ca2+], could activate RyR channels (Zahradnikova et al. 1999), although previously Gyorke and Fill 1994 had claimed vigorously that Ca2+ spikes could not activate RyR channels. In fact, this was used as evidence indicating that the fast Ca2+ spike did not influence the effect of the more maintained change in [Ca2+] (Gyorke and Fill 1994). There are certain issues that need to be resolved before we can understand how RyR channels respond to rapid changes in [Ca2+], and before we can hope to understand how SR Ca2+ release is triggered and terminated. First, does the Ca2+ spike that precedes the maintained increase in [Ca2+] in flash photolysis experiments affect the subsequent gating behavior of RyR? Second, what is the response of the RyR channel to a maintained step increase in [Ca2+]? Finally, does the gating behavior of RyR channels and the evidence from triggered Ca2+ release in intact cells support the proposal that RyR channels adapt to a maintained increase in [Ca2+]?

Power self-regulation in double-pass high-gain laser amplifiers

Double-pass laser amplifiers can provide automatic passive regulation of the power in an optical signal. This regulation can significantly reduce the amplitude noise on a laser beam that is intended as a continuous wave light source. Analytic expressions are derived to describe the optical-noise-reduction region of double-pass amplifier operation and the dependence of the self-regulation properties on gain, saturation, and mirror reflectivity.

Characteristic features of the radiolysis of water irradiated under strictly fixed conditions and under conditions varying over a small range

A qualitative mathematical analysis of the system of differential equations that describes the radiolysis of pure water and water solutions of hydrogen, hydrogen peroxide, and oxygen is performed. It is established that in a closed volume with fixed values of external parameters (dose rate, temperature, and others) a steady state characterized by a stable singular point-type attractor is unavoidably reached. The type of attractor does not depend on the values of the external parameters, i.e., in principle the system possesses self-regulation properties with respect to them. It is shown that under real conditions, when the external parameters cannot be strictly fixed, the existence of a stationary state and a stationary concentration of the products of radiolysis of water are determined not only by the specific values of the external parameters but also by their variation in the time required to establish a stationary state. 3 figures, 1 table, 10 references.

A New WDM Amplifier Cascade for Improved Performance in Wavelength-Routed Optical Transport Networks

We propose a new wavelength-division-multiplexed (WDM) optical amplifier cascade, based on erbium-doped fiber amplifiers, gain equalizing filters, and arrays of integrated waveguide amplifiers, to ensure good performance in wavelength-routed optical transport networks without the need for a complex centralized network control. To prove its efficiency, we propose this configuration for the National Science Foundation Network and we analyze its performance under critical conditions of link failure restoration. Computed results demonstrate that the self-regulating properties of this WDM amplifier cascade make these networks robust against link failures.

A possible basic cortical microcircuit called "cascaded inhibition." Results from cortical network models and recording experiments from striate simple cells.

The robust behavior, the degree of response linearity, and the aspect of contrast gain control in visual cortical simple cells are (amongst others) the result of the interplay between excitatory and inhibitory afferent and intracortical connections. The goal of this study was to suggest a simple intracortical connection pattern, which could also play a role in other cortical substructures, in order to generically obtain these desired effects within large physiological parameter ranges. To this end we explored the degree of linearity of spatial summation in visual simple cells experimentally and in different models based on half-wave rectifying cells ("push-pull models"). Visual cortical push-pull connection schemes originated from antagonistic motor-control models. Thus, this model class is widely applicable but normally requires a rather specific design. On the other hand we showed that a more generic version of a push-pull model, the so-called cascaded inhibitory intracortical connection scheme, which we implemented in a biologically realistic simulation, naturally explains much of the experimental data. We investigated the influence of the afferent and intracortical connection structure on the measured linearity of spatial summation in simple cells. The analysis made use of the relative modulation measure, which is easy to apply but is limited to moving sinusoidal grating stimuli. We introduced two basic push-pull models, where the order of threshold nonlinearity and linear summation is reversed. Very little difference is observed with the relative modulation measure for these models. Alterative models, like half-wave squaring models, were also briefly discussed. Of all model parameters, the ratio of excitation to inhibition in the simple cell exerts the most crucial influence on the relative modulation. Linearity deteriorates as soon as excitatory and inhibitory inputs are imbalanced and the relative modulation drops. This prediction was tested experimentally by extracellular recordings from cat area 17 simple cells and we found that about 62% showed a significant deviation from linear behavior. The problem that individual basic push-pull models are hard to distinguish experimentally led us to suggest a different solution. In order to generically account for the observed behavior (e.g., imbalance of excitation versus inhibition), we suggested a rather generic version of a push-pull model where it no longer mattered about (the hard-to-distinguish) fine differences in connectivity. Thus, we introduced a new class of biophysically realistic models ("cascaded inhibition"). This model class requires very little connection specificity and is therefore highly robust against parameter variations. Up to 25 cells are connected to each target cell. Thereby a highly interconnected network is generated, which also leads to disinhibition at some parts of an individual receptive field. We showed that the performance of these models simulates the degree of linearity and its variability in recal simple cells with comparatively high accuracy. This behavior can be explained by the self-regulating properties of a cascaded inhibitory connection scheme by which the balance between excitation and inhibition at a given cell is improved by the joint network effects. The virtues and the generic design of this connection pattern, therefore, allow to speculate that it is used also in other parts of the cortex.

Living systems theory as a paradigm for organizational behavior: understanding humans, organizations, and social processes.

Living systems theories have been used to model human, organization, and communication processes. This paper attempts to describe these models and to highlight the isomorphisms among the models. Particular emphasis is given to self-regulating properties of humans as a subsystem of social systems. Attention is given to the advantages of generalizing across levels and phenomena and integrating the middle-range theories that dominate the field of organizational behavior. Three broad recommendations for future research are discussed.

Self-regulating characteristics of a cold neutron source with a closed-thermosiphon

This report describes self-regulating properties of the Kyoto University Reactor (KUR) Cold Neutron Source (CNS), which is cooled by a closed-thermosiphon loop of hydrogen, as are most of the CNS constructed recently. The circular moderator transfer tube is in a plane inclined about 14° to the horizontal plane. The hydrogen-helium cryogenic system of the CNS shows a self-regulating characteristic under thermal disturbances, if they are smaller than about 30% of the practical allowable heat load, 300 W at 25 K in our case. This self-regulating characteristic has been confirmed from Bode's diagram of the hydrogen pressure response in the reservoir tank to the heat load modulation. Due to this property, the liquid level in the moderator cell is kept almost constant during long term operation of the reactor. Measurements of the vertical distribution of the cold neutron flux from the moderator cell showed that a sufficient amount of liquid was stored in the cell and the ratio of the fraction of cold neutrons in the cold moderator to that in the ambient moderator was measured to be about 20 where the wavelengths are longer than 6 Å using liquid hydrogen as a moderator.

A new SPWM inverter with minimum filter requirement

Abstract A new sinusoidal pulsewidth modulation (SPWM) control technique for simplifying the implementation of the SPWM method and minimizing the requirement of the voltampere rating of the inverter input filter is described and analysed. With the proposed modulation scheme, the regeneration of low-order harmonics caused by the input voltage fluctuation can be suppressed and the peak fundamental output voltage can be regulated rapidly and precisely by the dual voltage feedback control. Only a minimum voltampere rating of the inverter input filter is required for avoiding overmodulation. The theoretical results of the proposed approach with open-loop self-regulating property are discussed and experimentally verified.

Novel sinusoidal pulsewidth modulation schemes for voltage-source inverters with fluctuating input voltage

The optimum waveform parameters of pulse position and pulse widths for voltage-source inverters with fluctuating input voltage are proposed. Eight types of modulation schemes are described for synthesizing the optimum low-distortion output waveforms, of which the harmonic spectra and the peak fundamental-value are almost insensitive to the input-voltage fluctuation, with a minimum voltampere rating of inverter input filter. For fluctuating inverter input voltage with insufficient filtering, the type-VII and the alternative type-III modulation schemes are found to be especially suitable for practical implementation. Detailed descriptions of the suggested circuits with dual-feedback control for implementing two such modulation schemes are given. A peak-value detector that can rapidly produce the peak value of the inverter output voltage with a minimum time constant is also proposed. The theoretical results of the proposed approaches with one-loop self-regulating property are experimentally verified and compared with the conventional method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

密閉熱サイフォン型冷中性子源の非連続モデルによる熱力学的考察

A fundamental consideration of a closed-thermosiphon type cold neutron source (CNS) has been presented on the basis of the non-equilibrium thermodynamics. In order to simplify the treatment, a discontinuous thermodynamic model consisting of two large sub-systems connected by a small transport sub-system is employed. The analyses are especially concentrated in the self-regulation property, that is, the amount of liquid hydrogen in the moderator cell can be kept almost constant against thermal disturbances from reactor output fluctuations. It is shown that this property results from a thermodynamic process producing an entropy of a total system by a temperature increment in which an evaporation in one sub-system is compensated by a liquefaction in the other sub-system linked together by a common quantity of latent heat.

Stochastic analysis of a nonlinear model for selection of biological macromolecules

A stochastic analysis of a nonlinear selection model is presented. The model, based on Eigen and Schuster's theory of selection and evolution of biological macromolecules, considers the effects of fluctuations on the individual concentrations of macromolecules as well as the total population numbers in constrained systems. Our analysis shows that one of the models most often treated deterministically (referred to as constant organization in the literature) becomes unstable when fluctuations in the total population number are considered. An alternative model which apparently has built in self-regulating properties is analyzed and proves to be stable except for some special cases of degeneracy.

Symbiosis and the origin of life.

The paper uses chemical kinetic arguments and illustrations by computer modelling to discuss the origin and evolution of life. Complex self-reproducing chemical systems cannot arise spontaneously, whereas simple auto-catalytic systems can, especially in an irradiated aqueous medium. Self-reproducing chemical particles of any complexity, in an appropriate environment, have a self-regulating property which permits long-term survival. However, loss of materials from the environment can lead to continuing decay which is circumvented by physical union between different kinds of self-reproducing particles. The increasing complexity produced by such unions (symbioses) is irreversible so that the chemical system evolves. It is suggested that evolution by successive symbioses brought about the change from simple, spontaneously arising, auto-catalytic particles to complex prokaryotic cells.

Models and Hypotheses

Complex linear appearing structures and networks (e.g. blood vessels, leaf veins, nerves) are formed reproducibly during the development of nearly every organism, but the molecular mechanism leading to such patterns is still unknown. A model is proposed in which a few simple coupled biochemical reactions are able to generate such structures. Among undifferentiated cells, a local peak of differentiation-inducing substance (activator) is formed by autocatalysis and lateral inhibition. The activator peak triggers the differentiation of the cell at that location. Due to changes in metabolism, the differentiated cell repels the activator peak and drives it to a neighbouring cell which then also differentiates. The repulsion between the activator peak and the already differentiated cells forces the activator peak to move ahead of the tip of the extending filament. Long filaments of differentiated cells may be formed, which can split, branch laterally, reconnect with each other and grow towards specific target cells. Partial differential equations describing the mutual interaction of the substances involved were presented and solved with a computer. The resulting patterns show self-regulating properties and other features found in the leaf vascular system, the pattern of tracheae in insect epidermis, and other biological networks.

Static DC to sinusoidal AC inverter using techniques of high-frequency pulse-width modulation

A dc to sinusoidal ac inverter is described in which high-frequency pulse-width modulation is used to provide a low-frequency sine-wave output without the need for either a low-frequency power transformer or for low-frequency filter components. The inverter is physically simple and has low weight and small size. From a practical viewpoint the usefulness of this inverter is further enhanced by its self-regulating property. An analysis of this circuit and its output waveform is also given which provides the mathematical basis for the experimentally observed test results. In addition to the proof of the self-regulating property, it is further proven analytically that the amplitudes of the harmonics of the sinusoidal output voltage are very small with respect to the amplitude of the fundamental voltage.