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Sample records for clocks confers robust

  1. Synergism of coupled subsarcolemmal Ca2+ clocks and sarcolemmal voltage clocks confers robust and flexible pacemaker function in a novel pacemaker cell model.

    Science.gov (United States)

    Maltsev, Victor A; Lakatta, Edward G

    2009-03-01

    Recent experimental studies have demonstrated that sinoatrial node cells (SANC) generate spontaneous, rhythmic, local subsarcolemmal Ca(2+) releases (Ca(2+) clock), which occur during late diastolic depolarization (DD) and interact with the classic sarcolemmal voltage oscillator (membrane clock) by activating Na(+)-Ca(2+) exchanger current (I(NCX)). This and other interactions between clocks, however, are not captured by existing essentially membrane-delimited cardiac pacemaker cell numerical models. Using wide-scale parametric analysis of classic formulations of membrane clock and Ca(2+) cycling, we have constructed and initially explored a prototype rabbit SANC model featuring both clocks. Our coupled oscillator system exhibits greater robustness and flexibility than membrane clock operating alone. Rhythmic spontaneous Ca(2+) releases of sarcoplasmic reticulum (SR)-based Ca(2+) clock ignite rhythmic action potentials via late DD I(NCX) over much broader ranges of membrane clock parameters [e.g., L-type Ca(2+) current (I(CaL)) and/or hyperpolarization-activated ("funny") current (I(f)) conductances]. The system Ca(2+) clock includes SR and sarcolemmal Ca(2+) fluxes, which optimize cell Ca(2+) balance to increase amplitudes of both SR Ca(2+) release and late DD I(NCX) as SR Ca(2+) pumping rate increases, resulting in a broad pacemaker rate modulation (1.8-4.6 Hz). In contrast, the rate modulation range via membrane clock parameters is substantially smaller when Ca(2+) clock is unchanged or lacking. When Ca(2+) clock is disabled, the system parametric space for fail-safe SANC operation considerably shrinks: without rhythmic late DD I(NCX) ignition signals membrane clock substantially slows, becomes dysrhythmic, or halts. In conclusion, the Ca(2+) clock is a new critical dimension in SANC function. A synergism of the coupled function of Ca(2+) and membrane clocks confers fail-safe SANC operation at greatly varying rates.

  2. Robustness from flexibility in the fungal circadian clock

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    Akman Ozgur E

    2010-06-01

    Full Text Available Abstract Background Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa. Results The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq gene inhibits its transcriptional activator white collar-1 (wc-1, interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on

  3. International Conference on Robust Statistics

    CERN Document Server

    Filzmoser, Peter; Gather, Ursula; Rousseeuw, Peter

    2003-01-01

    Aspects of Robust Statistics are important in many areas. Based on the International Conference on Robust Statistics 2001 (ICORS 2001) in Vorau, Austria, this volume discusses future directions of the discipline, bringing together leading scientists, experienced researchers and practitioners, as well as younger researchers. The papers cover a multitude of different aspects of Robust Statistics. For instance, the fundamental problem of data summary (weights of evidence) is considered and its robustness properties are studied. Further theoretical subjects include e.g.: robust methods for skewness, time series, longitudinal data, multivariate methods, and tests. Some papers deal with computational aspects and algorithms. Finally, the aspects of application and programming tools complete the volume.

  4. Robustness of synthetic circadian clocks to multiple environmental changes.

    Science.gov (United States)

    Gurevich, Lilia; Cohen-Luria, Rivka; Wagner, Nathaniel; Ashkenasy, Gonen

    2015-04-04

    A molecular network that mimics circadian clocks from cyanobacteria is constructed in silico. Simulating its oscillatory behaviour under variable conditions reveals its robustness relative to networks of alternative topologies. The principles for synthetic chemical circadian networks to work properly are consequently highlighted.

  5. Tissue-intrinsic dysfunction of circadian clock confers transplant arteriosclerosis.

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    Cheng, Bo; Anea, Ciprian B; Yao, Lin; Chen, Feng; Patel, Vijay; Merloiu, Ana; Pati, Paramita; Caldwell, R William; Fulton, David J; Rudic, R Daniel

    2011-10-11

    The suprachiasmatic nucleus of the brain is the circadian center, relaying rhythmic environmental and behavioral information to peripheral tissues to control circadian physiology. As such, central clock dysfunction can alter systemic homeostasis to consequently impair peripheral physiology in a manner that is secondary to circadian malfunction. To determine the impact of circadian clock function in organ transplantation and dissect the influence of intrinsic tissue clocks versus extrinsic clocks, we implemented a blood vessel grafting approach to surgically assemble a chimeric mouse that was part wild-type (WT) and part circadian clock mutant. Arterial isografts from donor WT mice that had been anastamosed to common carotid arteries of recipient WT mice (WT:WT) exhibited no pathology in this syngeneic transplant strategy. Similarly, when WT grafts were anastamosed to mice with disrupted circadian clocks, the structural features of the WT grafts immersed in the milieu of circadian malfunction were normal and absent of lesions, comparable to WT:WT grafts. In contrast, aortic grafts from Bmal1 knockout (KO) or Period-2,3 double-KO mice transplanted into littermate control WT mice developed robust arteriosclerotic disease. These lesions observed in donor grafts of Bmal1-KO were associated with up-regulation in T-cell receptors, macrophages, and infiltrating cells in the vascular grafts, but were independent of hemodynamics and B and T cell-mediated immunity. These data demonstrate the significance of intrinsic tissue clocks as an autonomous influence in experimental models of arteriosclerotic disease, which may have implications with regard to the influence of circadian clock function in organ transplantation.

  6. International Conference on Robust Statistics 2015

    CERN Document Server

    Basu, Ayanendranath; Filzmoser, Peter; Mukherjee, Diganta

    2016-01-01

    This book offers a collection of recent contributions and emerging ideas in the areas of robust statistics presented at the International Conference on Robust Statistics 2015 (ICORS 2015) held in Kolkata during 12–16 January, 2015. The book explores the applicability of robust methods in other non-traditional areas which includes the use of new techniques such as skew and mixture of skew distributions, scaled Bregman divergences, and multilevel functional data methods; application areas being circular data models and prediction of mortality and life expectancy. The contributions are of both theoretical as well as applied in nature. Robust statistics is a relatively young branch of statistical sciences that is rapidly emerging as the bedrock of statistical analysis in the 21st century due to its flexible nature and wide scope. Robust statistics supports the application of parametric and other inference techniques over a broader domain than the strictly interpreted model scenarios employed in classical statis...

  7. Robustness of circadian clocks to daylight fluctuations: hints from the picoeucaryote Ostreococcus tauri.

    Directory of Open Access Journals (Sweden)

    Quentin Thommen

    Full Text Available The development of systemic approaches in biology has put emphasis on identifying genetic modules whose behavior can be modeled accurately so as to gain insight into their structure and function. However, most gene circuits in a cell are under control of external signals and thus, quantitative agreement between experimental data and a mathematical model is difficult. Circadian biology has been one notable exception: quantitative models of the internal clock that orchestrates biological processes over the 24-hour diurnal cycle have been constructed for a few organisms, from cyanobacteria to plants and mammals. In most cases, a complex architecture with interlocked feedback loops has been evidenced. Here we present the first modeling results for the circadian clock of the green unicellular alga Ostreococcus tauri. Two plant-like clock genes have been shown to play a central role in the Ostreococcus clock. We find that their expression time profiles can be accurately reproduced by a minimal model of a two-gene transcriptional feedback loop. Remarkably, best adjustment of data recorded under light/dark alternation is obtained when assuming that the oscillator is not coupled to the diurnal cycle. This suggests that coupling to light is confined to specific time intervals and has no dynamical effect when the oscillator is entrained by the diurnal cycle. This intriguing property may reflect a strategy to minimize the impact of fluctuations in daylight intensity on the core circadian oscillator, a type of perturbation that has been rarely considered when assessing the robustness of circadian clocks.

  8. Robust circadian clocks from coupled protein-modification and transcription–translation cycles

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    Zwicker, David; Lubensky, David K.; ten Wolde, Pieter Rein

    2010-01-01

    The cyanobacterium Synechococcus elongatus uses both a protein phosphorylation cycle and a transcription–translation cycle to generate circadian rhythms that are highly robust against biochemical noise. We use stochastic simulations to analyze how these cycles interact to generate stable rhythms in growing, dividing cells. We find that a protein phosphorylation cycle by itself is robust when protein turnover is low. For high decay or dilution rates (and compensating synthesis rates), however, the phosphorylation-based oscillator loses its integrity. Circadian rhythms thus cannot be generated with a phosphorylation cycle alone when the growth rate, and consequently the rate of protein dilution, is high enough; in practice, a purely posttranslational clock ceases to function well when the cell doubling time drops below the 24-h clock period. At higher growth rates, a transcription–translation cycle becomes essential for generating robust circadian rhythms. Interestingly, although a transcription–translation cycle is necessary to sustain a phosphorylation cycle at high growth rates, a phosphorylation cycle can dramatically enhance the robustness of a transcription–translation cycle at lower protein decay or dilution rates. In fact, the full oscillator built from these two tightly intertwined cycles far outperforms not just each of its two components individually, but also a hypothetical system in which the two parts are coupled as in textbook models of coupled phase oscillators. Our analysis thus predicts that both cycles are required to generate robust circadian rhythms over the full range of growth conditions. PMID:21149676

  9. Robust circadian clocks from coupled protein-modification and transcription-translation cycles.

    Science.gov (United States)

    Zwicker, David; Lubensky, David K; ten Wolde, Pieter Rein

    2010-12-28

    The cyanobacterium Synechococcus elongatus uses both a protein phosphorylation cycle and a transcription-translation cycle to generate circadian rhythms that are highly robust against biochemical noise. We use stochastic simulations to analyze how these cycles interact to generate stable rhythms in growing, dividing cells. We find that a protein phosphorylation cycle by itself is robust when protein turnover is low. For high decay or dilution rates (and compensating synthesis rates), however, the phosphorylation-based oscillator loses its integrity. Circadian rhythms thus cannot be generated with a phosphorylation cycle alone when the growth rate, and consequently the rate of protein dilution, is high enough; in practice, a purely posttranslational clock ceases to function well when the cell doubling time drops below the 24-h clock period. At higher growth rates, a transcription-translation cycle becomes essential for generating robust circadian rhythms. Interestingly, although a transcription-translation cycle is necessary to sustain a phosphorylation cycle at high growth rates, a phosphorylation cycle can dramatically enhance the robustness of a transcription-translation cycle at lower protein decay or dilution rates. In fact, the full oscillator built from these two tightly intertwined cycles far outperforms not just each of its two components individually, but also a hypothetical system in which the two parts are coupled as in textbook models of coupled phase oscillators. Our analysis thus predicts that both cycles are required to generate robust circadian rhythms over the full range of growth conditions.

  10. Numerical models based on a minimal set of sarcolemmal electrogenic proteins and an intracellular Ca(2+) clock generate robust, flexible, and energy-efficient cardiac pacemaking.

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    Maltsev, Victor A; Lakatta, Edward G

    2013-06-01

    Recent evidence supports the idea that robust and, importantly, FLEXIBLE automaticity of cardiac pacemaker cells is conferred by a coupled system of membrane ion currents (an "M-clock") and a sarcoplasmic reticulum (SR)-based Ca(2+) oscillator ("Ca(2+)clock") that generates spontaneous diastolic Ca(2+) releases. This study identified numerical models of a human biological pacemaker that features robust and flexible automaticity generated by a minimal set of electrogenic proteins and a Ca(2+)clock. Following the Occam's razor principle (principle of parsimony), M-clock components of unknown molecular origin were excluded from Maltsev-Lakatta pacemaker cell model and thirteen different model types of only 4 or 5 components were derived and explored by a parametric sensitivity analysis. The extended ranges of SR Ca(2+) pumping (i.e. Ca(2+)clock performance) and conductance of ion currents were sampled, yielding a large variety of parameter combination, i.e. specific model sets. We tested each set's ability to simulate autonomic modulation of human heart rate (minimum rate of 50 to 70bpm; maximum rate of 140 to 210bpm) in response to stimulation of cholinergic and β-adrenergic receptors. We found that only those models that include a Ca(2+)clock (including the minimal 4-parameter model "ICaL+IKr+INCX+Ca(2+)clock") were able to reproduce the full range of autonomic modulation. Inclusion of If or ICaT decreased the flexibility, but increased the robustness of the models (a relatively larger number of sets did not fail during testing). The new models comprised of components with clear molecular identity (i.e. lacking IbNa & Ist) portray a more realistic pacemaking: A smaller Na(+) influx is expected to demand less energy for Na(+) extrusion. The new large database of the reduced coupled-clock numerical models may serve as a useful tool for the design of biological pacemakers. It will also provide a conceptual basis for a general theory of robust, flexible, and energy

  11. Dynamic interactions of an intracellular Ca2+ clock and membrane ion channel clock underlie robust initiation and regulation of cardiac pacemaker function.

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    Maltsev, Victor A; Lakatta, Edward G

    2008-01-15

    For almost half a century it has been thought that the initiation of each heartbeat is driven by surface membrane voltage-gated ion channels (M clocks) within sinoatrial nodal cells. It has also been assumed that pacemaker cell automaticity is initiated at the maximum diastolic potential (MDP). Recent experimental evidence based on confocal cell imaging and supported by numerical modelling, however, shows that initiation of cardiac impulse is a more complex phenomenon and involves yet another clock that resides under the sarcolemma. This clock is the sarcoplasmic reticulum (SR): it generates spontaneous, but precisely timed, rhythmic, submembrane, local Ca(2+) releases (LCR) that appear not at the MDP but during the late, diastolic depolarization (DD). The Ca(2+) clock and M clock dynamically interact, defining a novel paradigm of robust cardiac pacemaker function and regulation. Rhythmic LCRs during the late DD activate inward Na(+)/Ca(2+) exchanger currents and ignite action potentials, which in turn induceCa(2+) transients and SR depletions, resetting the Ca(2+) clock. Both basal and reserve protein kinaseA-dependent phosphorylation of Ca(2+) cycling proteins control the speed and amplitude of SR Ca(2+) cycling to regulate the beating rate by strongly coupled Ca(2+) and M clocks.

  12. A Robust Approach for Clock Offset Estimation in Wireless Sensor Networks

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    Kim Jang-Sub

    2010-01-01

    Full Text Available The maximum likelihood estimators (MLEs for the clock phase offset assuming a two-way message exchange mechanism between the nodes of a wireless sensor network were recently derived assuming Gaussian and exponential network delays. However, the MLE performs poorly in the presence of non-Gaussian or nonexponential network delay distributions. Currently, there is a need to develop clock synchronization algorithms that are robust to the distribution of network delays. This paper proposes a clock offset estimator based on the composite particle filter (CPF to cope with the possible asymmetries and non-Gaussianity of the network delay distributions. Also, a variant of the CPF approach based on the bootstrap sampling (BS is shown to exhibit good performance in the presence of reduced number of observations. Computer simulations illustrate that the basic CPF and its BS-based variant present superior performance than MLE under general random network delay distributions such as asymmetric Gaussian, exponential, Gamma, Weibull as well as various mixtures.

  13. Short-lived Her proteins drive robust synchronized oscillations in the zebrafish segmentation clock.

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    Ay, Ahmet; Knierer, Stephan; Sperlea, Adriana; Holland, Jack; Özbudak, Ertuğrul M

    2013-08-01

    Oscillations are prevalent in natural systems. A gene expression oscillator, called the segmentation clock, controls segmentation of precursors of the vertebral column. Genes belonging to the Hes/her family encode the only conserved oscillating genes in all analyzed vertebrate species. Hes/Her proteins form dimers and negatively autoregulate their own transcription. Here, we developed a stochastic two-dimensional multicellular computational model to elucidate how the dynamics, i.e. period, amplitude and synchronization, of the segmentation clock are regulated. We performed parameter searches to demonstrate that autoregulatory negative-feedback loops of the redundant repressor Her dimers can generate synchronized gene expression oscillations in wild-type embryos and reproduce the dynamics of the segmentation oscillator in different mutant conditions. Our model also predicts that synchronized oscillations can be robustly generated as long as the half-lives of the repressor dimers are shorter than 6 minutes. We validated this prediction by measuring, for the first time, the half-life of Her7 protein as 3.5 minutes. These results demonstrate the importance of building biologically realistic stochastic models to test biological models more stringently and make predictions for future experimental studies.

  14. Numerical models based on a minimal set of sarcolemmal electrogenic proteins and an intracellular Ca2+ clock generate robust, flexible, and energy-efficient cardiac pacemaking

    Science.gov (United States)

    Maltsev, Victor A.; Lakatta, Edward G.

    2015-01-01

    Recent evidence supports the idea that robust and, importantly, FLEXIBLE automaticity of cardiac pacemaker cells is conferred by a coupled system of membrane ion currents (an “M-clock”) and a sarcoplasmic reticulum (SR)-based Ca2+ oscillator (“Ca2+clock”) that generates spontaneous diastolic Ca2+ releases. This study identified numerical models of a human biological pacemaker that features robust and flexible automaticity generated by a minimal set of electrogenic proteins and a Ca2+clock. Following the Occam’s razor principle (principle of parsimony), M-clock components of unknown molecular origin were excluded from Maltsev-Lakatta pacemaker cell model and thirteen different model types of only 4 or 5 components were derived and explored by a parametric sensitivity analysis. The extended ranges of SR Ca2+ pumping (i.e. Ca2+clock performance) and conductance of ion currents were sampled, yielding a large variety of parameter combination, i.e. specific model sets. We tested each set’s ability to simulate autonomic modulation of human heart rate (minimum rate of 50 to 70 bpm; maximum rate of 140 to 210 bpm) in response to stimulation of cholinergic and β-adrenergic receptors. We found that only those models that include a Ca2+clock (including the minimal 4-parameter model “ICaL+IKr+INCX+Ca2+clock”) were able to reproduce the full range of autonomic modulation. Inclusion of If or ICaT decreased the flexibility, but increased the robustness of the models (a relatively larger number of sets did not fail during testing). The new models comprised of components with clear molecular identity (i.e. lacking IbNa & Ist) portray a more realistic pacemaking: A smaller Na+ influx is expected to demand less energy for Na+ extrusion. The new large database of the reduced coupled-clock numerical models may serve as a useful tool for the design of biological pacemakers. It will also provide a conceptual basis for a general theory of robust, flexible, and energy

  15. Stochastic models of cellular circadian rhythms in plants help to understand the impact of noise on robustness and clock structure

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    Maria Luisa eGuerriero

    2014-10-01

    Full Text Available Rhythmic behavior is essential for plants; for example, daily (circadian rhythms control photosynthesis and seasonal rhythms regulate their life cycle. The core of the circadian clock is a genetic network that coordinates the expression of specific clock genes in a circadian rhythm reflecting the 24-hour day/night cycle.Circadian clocks exhibit stochastic noise due to the low copy numbers of clock genes and the consequent cell-to-cell variation: this intrinsic noise plays a major role in circadian clocks by inducing more robust oscillatory behavior. Another source of noise is the environment, which causes variation in temperature and light intensity: this extrinsic noise is part of the requirement for the structural complexity of clock networks.Advances in experimental techniques now permit single-cell measurements and the development of single-cell models. Here we present some modeling studies showing the importance of considering both types of noise in understanding how plants adapt to regular and irregular light variations. Stochastic models have proven useful for understanding the effect of regular variations. By contrast, the impact of irregular variations and the interaction of different noise sources are less studied.

  16. Robust and flexible response of the Ostreococcus tauri circadian clock to light/dark cycles of varying photoperiod.

    Science.gov (United States)

    Thommen, Quentin; Pfeuty, Benjamin; Corellou, Florence; Bouget, François-Yves; Lefranc, Marc

    2012-09-01

    The green microscopic alga Ostreococcus tauri has recently emerged as a promising model for understanding how circadian clocks, which drive the daily biological rhythms of many organisms, synchronize to the day/night cycle in changing weather and seasons. Here, we analyze translational reporter time series data for the central clock genes CCA1 and TOC1 for a wide range of daylight durations (photoperiods). The variation of temporal expression profiles with day duration is complex, with the two protein peaks tracking different times of the day. Nevertheless, all profiles are accurately reproduced by a simple two-gene transcriptional loop model whose parameters depend on light only through the photoperiod value. We show that this non-intuitive behavior allows the circadian clock to combine flexibility and robustness with respect to daylight fluctuations.

  17. Defining the robust behaviour of the plant clock gene circuit with absolute RNA timeseries and open infrastructure.

    Science.gov (United States)

    Flis, Anna; Fernández, Aurora Piñas; Zielinski, Tomasz; Mengin, Virginie; Sulpice, Ronan; Stratford, Kevin; Hume, Alastair; Pokhilko, Alexandra; Southern, Megan M; Seaton, Daniel D; McWatters, Harriet G; Stitt, Mark; Halliday, Karen J; Millar, Andrew J

    2015-10-01

    Our understanding of the complex, transcriptional feedback loops in the circadian clock mechanism has depended upon quantitative, timeseries data from disparate sources. We measure clock gene RNA profiles in Arabidopsis thaliana seedlings, grown with or without exogenous sucrose, or in soil-grown plants and in wild-type and mutant backgrounds. The RNA profiles were strikingly robust across the experimental conditions, so current mathematical models are likely to be broadly applicable in leaf tissue. In addition to providing reference data, unexpected behaviours included co-expression of PRR9 and ELF4, and regulation of PRR5 by GI. Absolute RNA quantification revealed low levels of PRR9 transcripts (peak approx. 50 copies cell(-1)) compared with other clock genes, and threefold higher levels of LHY RNA (more than 1500 copies cell(-1)) than of its close relative CCA1. The data are disseminated from BioDare, an online repository for focused timeseries data, which is expected to benefit mechanistic modelling. One data subset successfully constrained clock gene expression in a complex model, using publicly available software on parallel computers, without expert tuning or programming. We outline the empirical and mathematical justification for data aggregation in understanding highly interconnected, dynamic networks such as the clock, and the observed design constraints on the resources required to make this approach widely accessible. © 2015 The Authors.

  18. Evolution of robust circadian clocks in Drosophila melanogaster populations reared in constant dark for over 330 generations

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    Shindey, Radhika; Varma, Vishwanath; Nikhil, K. L.; Sharma, Vijay Kumar

    2016-10-01

    Robustness is considered to be an important feature of biological systems which may evolve when the functionality of a trait is associated with higher fitness across multiple environmental conditions. Thus, the ability to maintain stable biological phenotypes across environments is thought to be of adaptive value. Previously, we have reported higher intrinsic activity levels (activity levels of free-running rhythm in constant darkness) and power of rhythm (as assessed by amplitude of the periodogram) in Drosophila melanogaster populations (stocks) reared in constant darkness (DD stocks) as compared to those reared in constant light (LL stocks) and 12:12-h light-dark cycles (LD stocks) for over 19 years (˜330 generations). In the current study, we intended to examine whether the enhanced levels of activity observed in DD stocks persist under various environments such as photoperiods, ambient temperatures, non-24-h light-dark (LD) cycles, and semi-natural conditions (SN). We found that DD stocks largely retain their phenotype of enhanced activity levels across most of the above-mentioned environments suggesting the evolution of robust circadian clocks in DD stocks. Furthermore, we compared the peak activity levels of the three stocks across different environmental conditions relative to their peaks in constant darkness and found that the change in peak activity levels upon entrainment was not significantly different across the three stocks for any of the examined environmental conditions. This suggests that the enhancement of activity levels in DD stocks is not due to differential sensitivity to environment. Thus, these results suggest that rearing in constant darkness (DD) leads to evolution of robust circadian clocks suggesting a possible adaptive value of possessing such rhythms under constant dark environments.

  19. Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness

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    Marciano, David C.; Lua, Rhonald C.; Herman, Christophe; Lichtarge, Olivier

    2016-01-01

    Negative autoregulation is universally found across organisms. In the bacterium Escherichia coli, transcription factors often repress their own expression to form a negative feedback network motif that enables robustness to changes in biochemical parameters. Here we present a simple phenomenological model of a negative feedback transcription factor repressing both itself and another target gene. The strength of the negative feedback is characterized by three parameters: the cooperativity in self-repression, the maximal expression rate of the transcription factor, and the apparent dissociation constant of the transcription factor binding to its own promoter. Analysis of the model shows that the target gene levels are robust to mutations in the transcription factor, and that the robustness improves as the degree of cooperativity in self-repression increases. The prediction is tested in the LexA transcriptional network of E. coli by altering cooperativity in self-repression and promoter strength. Indeed, we find robustness is correlated with the former. Considering the proposed importance of gene regulation in speciation, parameters governing a transcription factor’s robustness to mutation may have significant influence on a cell or organism’s capacity to evolve. PMID:27391757

  20. Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness

    Science.gov (United States)

    Marciano, David C.; Lua, Rhonald C.; Herman, Christophe; Lichtarge, Olivier

    2016-06-01

    Negative autoregulation is universally found across organisms. In the bacterium Escherichia coli, transcription factors often repress their own expression to form a negative feedback network motif that enables robustness to changes in biochemical parameters. Here we present a simple phenomenological model of a negative feedback transcription factor repressing both itself and another target gene. The strength of the negative feedback is characterized by three parameters: the cooperativity in self-repression, the maximal expression rate of the transcription factor, and the apparent dissociation constant of the transcription factor binding to its own promoter. Analysis of the model shows that the target gene levels are robust to mutations in the transcription factor, and that the robustness improves as the degree of cooperativity in self-repression increases. The prediction is tested in the LexA transcriptional network of E. coli by altering cooperativity in self-repression and promoter strength. Indeed, we find robustness is correlated with the former. Considering the proposed importance of gene regulation in speciation, parameters governing a transcription factor's robustness to mutation may have significant influence on a cell or organism's capacity to evolve.

  1. International Conference on Robust Rank-Based and Nonparametric Methods

    CERN Document Server

    McKean, Joseph

    2016-01-01

    The contributors to this volume include many of the distinguished researchers in this area. Many of these scholars have collaborated with Joseph McKean to develop underlying theory for these methods, obtain small sample corrections, and develop efficient algorithms for their computation. The papers cover the scope of the area, including robust nonparametric rank-based procedures through Bayesian and big data rank-based analyses. Areas of application include biostatistics and spatial areas. Over the last 30 years, robust rank-based and nonparametric methods have developed considerably. These procedures generalize traditional Wilcoxon-type methods for one- and two-sample location problems. Research into these procedures has culminated in complete analyses for many of the models used in practice including linear, generalized linear, mixed, and nonlinear models. Settings are both multivariate and univariate. With the development of R packages in these areas, computation of these procedures is easily shared with r...

  2. Genes confer similar robustness to environmental, stochastic, and genetic perturbations in yeast.

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    Ben Lehner

    Full Text Available Gene inactivation often has little or no apparent consequence for the phenotype of an organism. This property-enetic (or mutational robustness-is pervasive, and has important implications for disease and evolution, but is not well understood. Dating back to at least Waddington, it has been suggested that mutational robustness may be related to the requirement to withstand environmental or stochastic perturbations. Here I show that global quantitative data from yeast are largely consistent with this idea. Considering the effects of mutations in all nonessential genes shows that genes that confer robustness to environmental or stochastic change also buffer the effects of genetic change, and with similar efficacy. This means that selection during evolution for environmental or stochastic robustness (also referred to as canalization may frequently have the side effect of increasing genetic robustness. A dynamic environment may therefore promote the evolution of phenotypic complexity. It also means that "hub" genes in genetic interaction (synthetic lethal networks are generally genes that confer environmental resilience and phenotypic stability.

  3. The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer's disease.

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    Chen, Ko-Fan; Possidente, Bernard; Lomas, David A; Crowther, Damian C

    2014-04-01

    Circadian behavioural deficits, including sleep irregularity and restlessness in the evening, are a distressing early feature of Alzheimer's disease (AD). We have investigated these phenomena by studying the circadian behaviour of transgenic Drosophila expressing the amyloid beta peptide (Aβ). We find that Aβ expression results in an age-related loss of circadian behavioural rhythms despite ongoing normal molecular oscillations in the central clock neurons. Even in the absence of any behavioural correlate, the synchronised activity of the central clock remains protective, prolonging lifespan, in Aβ flies just as it does in control flies. Confocal microscopy and bioluminescence measurements point to processes downstream of the molecular clock as the main site of Aβ toxicity. In addition, there seems to be significant non-cell-autonomous Aβ toxicity resulting in morphological and probably functional signalling deficits in central clock neurons.

  4. A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation

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    Beril Kiragasi

    2017-06-01

    Full Text Available Homeostatic signaling systems are thought to interface with other forms of plasticity to ensure flexible yet stable levels of neurotransmission. The role of neurotransmitter receptors in this process, beyond mediating neurotransmission itself, is not known. Through a forward genetic screen, we have identified the Drosophila kainate-type ionotropic glutamate receptor subunit DKaiR1D to be required for the retrograde, homeostatic potentiation of synaptic strength. DKaiR1D is necessary in presynaptic motor neurons, localized near active zones, and confers robustness to the calcium sensitivity of baseline synaptic transmission. Acute pharmacological blockade of DKaiR1D disrupts homeostatic plasticity, indicating that this receptor is required for the expression of this process, distinct from developmental roles. Finally, we demonstrate that calcium permeability through DKaiR1D is necessary for baseline synaptic transmission, but not for homeostatic signaling. We propose that DKaiR1D is a glutamate autoreceptor that promotes robustness to synaptic strength and plasticity with active zone specificity.

  5. Robustness

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Narasimhan, Harikrishna

    2012-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of structures......, a theoretical and risk-based framework is presented which facilitates the quantification of robustness, and thus supports the formulation of pre-normative guidelines....

  6. Cellular robustness conferred by genetic crosstalk underlies resistance against chemotherapeutic drug doxorubicin in fission yeast.

    Directory of Open Access Journals (Sweden)

    Zoey Tay

    Full Text Available Doxorubicin is an anthracycline antibiotic that is among one of the most commonly used chemotherapeutic agents in the clinical setting. The usage of doxorubicin is faced with many problems including severe side effects and chemoresistance. To overcome these challenges, it is important to gain an understanding of the underlying molecular mechanisms with regards to the mode of action of doxorubicin. To facilitate this aim, we identified the genes that are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe. We further demonstrated interplay between factors controlling various aspects of chromosome metabolism, mitochondrial respiration and membrane transport. In the nucleus we observed that the subunits of the Ino80, RSC, and SAGA complexes function in the similar epistatic group that shares significant overlap with the homologous recombination genes. However, these factors generally act in synergistic manner with the chromosome segregation regulator DASH complex proteins, possibly forming two major arms for regulating doxorubicin resistance in the nucleus. Simultaneous disruption of genes function in membrane efflux transport or the mitochondrial respiratory chain integrity in the mutants defective in either Ino80 or HR function resulted in cumulative upregulation of drug-specific growth defects, suggesting a rewiring of pathways that synergize only when the cells is exposed to the cytotoxic stress. Taken together, our work not only identified factors that are required for survival of the cells in the presence of doxorubicin but has further demonstrated that an extensive molecular crosstalk exists between these factors to robustly confer doxorubicin resistance.

  7. Cellular robustness conferred by genetic crosstalk underlies resistance against chemotherapeutic drug doxorubicin in fission yeast.

    Science.gov (United States)

    Tay, Zoey; Eng, Ru Jun; Sajiki, Kenichi; Lim, Kim Kiat; Tang, Ming Yi; Yanagida, Mitsuhiro; Chen, Ee Sin

    2013-01-01

    Doxorubicin is an anthracycline antibiotic that is among one of the most commonly used chemotherapeutic agents in the clinical setting. The usage of doxorubicin is faced with many problems including severe side effects and chemoresistance. To overcome these challenges, it is important to gain an understanding of the underlying molecular mechanisms with regards to the mode of action of doxorubicin. To facilitate this aim, we identified the genes that are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe. We further demonstrated interplay between factors controlling various aspects of chromosome metabolism, mitochondrial respiration and membrane transport. In the nucleus we observed that the subunits of the Ino80, RSC, and SAGA complexes function in the similar epistatic group that shares significant overlap with the homologous recombination genes. However, these factors generally act in synergistic manner with the chromosome segregation regulator DASH complex proteins, possibly forming two major arms for regulating doxorubicin resistance in the nucleus. Simultaneous disruption of genes function in membrane efflux transport or the mitochondrial respiratory chain integrity in the mutants defective in either Ino80 or HR function resulted in cumulative upregulation of drug-specific growth defects, suggesting a rewiring of pathways that synergize only when the cells is exposed to the cytotoxic stress. Taken together, our work not only identified factors that are required for survival of the cells in the presence of doxorubicin but has further demonstrated that an extensive molecular crosstalk exists between these factors to robustly confer doxorubicin resistance.

  8. The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Ko-Fan Chen

    2014-04-01

    Full Text Available Circadian behavioural deficits, including sleep irregularity and restlessness in the evening, are a distressing early feature of Alzheimer’s disease (AD. We have investigated these phenomena by studying the circadian behaviour of transgenic Drosophila expressing the amyloid beta peptide (Aβ. We find that Aβ expression results in an age-related loss of circadian behavioural rhythms despite ongoing normal molecular oscillations in the central clock neurons. Even in the absence of any behavioural correlate, the synchronised activity of the central clock remains protective, prolonging lifespan, in Aβ flies just as it does in control flies. Confocal microscopy and bioluminescence measurements point to processes downstream of the molecular clock as the main site of Aβ toxicity. In addition, there seems to be significant non-cell-autonomous Aβ toxicity resulting in morphological and probably functional signalling deficits in central clock neurons.

  9. High finesse optical fiber cavities: optimal alignment and robust stabilization (Conference Presentation)

    Science.gov (United States)

    Ratschbacher, Lothar; Gallego, Jose; Ghosh, Sutapa; Alavi, Seyed; Alt, Wolfgang; Martinez-Dorantes, Miguel; Meschede, Dieter

    2016-04-01

    Fiber Fabry-Perot cavities, formed by micro-machined mirrors on the end-facets of optical fibers, are used in an increasing number of technical and scientific applications. Some of the most promising areas of application of these optical micro-resonators with high finesse and small mode volume are in the field of quantum communication and information. The resonator-enhanced light-matter interaction, for instance, provide basis for the realization of efficient optical interfaces between stationary matter-based quantum nodes and flying single-photon qubits. To date fiber Fabry-Perot cavities have been successfully applied in experiments interfacing single photons with a wide range of quantum systems, including cold atoms, ions and solid state emitters as well as quantum optomechanical experiments. Here we address some important practical questions that arise during the experimental implementation of high finesse fiber Fabry-Perot cavities: How can optimal fiber cavity alignment be achieved and how can the efficiency of coupling light from the optical fibers to the cavity mode and vice versa be characterized? How should optical fiber cavities be constructed and stabilized to fulfill their potential for miniaturization and integration into robust scientific and technological devices that can operate outside of dedicated laboratory environments in the future? The first two questions we answer with an analytic mode matching calculation that relates the alignment dependent fiber-to-cavity mode-matching efficiency to the easily measurable dip in the reflected light power at the cavity resonance. Our general analysis provides a simple recipe for the optimal alignment of fiber Fabry-Perot cavities and moreover for the first time explains the asymmetry in their reflective line shapes. The latter question we explore by investigating a novel, intrinsically rigid fiber cavity design that makes use of the high passive stability of a monolithic cavity spacer and employs thermal

  10. Draper Clock-Synchronization Protocol in SAL

    Data.gov (United States)

    National Aeronautics and Space Administration — In 1973, Daly, Hpokins, and McKenna (from Draper Lab.) presented a fault-tolerant digital clocking system at the FTCS conference. This is probably one of the first...

  11. Intranasal immunization with inactivated feline calicivirus particles confers robust protection against homologous virus and suppression against heterologous virus in cats.

    Science.gov (United States)

    Sato, Hiroaki; Sehata, Go; Okada, Nobutaka; Iwamoto, Kayo; Masubuchi, Katsuo; Kainuma, Risa; Noda, Tatsuki; Igarashi, Tatsuhiko; Sawada, Takuo; Noro, Taichi; Oishi, Eiji

    2017-07-01

    The protective efficacy of intranasal (IN) administration of inactivated feline calicivirus (FCV) vaccine against homologous or heterologous FCV infection was investigated. Groups of cats immunized with the experimental inactivated, non-adjuvanted FCV vaccine via either the IN or subcutaneous (SC) route were exposed to homologous or highly heterologous FCV. Both the IN and SC immunization protocols established robust protection against homologous FCV infection. Although neither immunization regimen conferred protection against the heterologous strain, clinical scores and virus titres of oral swabs were lower in cats in the IN group compared to those in the SC group, accompanying a faster neutralizing antibody response against the heterologous virus in cats in the IN group. The IN group secreted more IgA specific to FCV proteins in oral washes (lavage fluids from the oral cavity) than the SC group. IN immunization with an inactivated whole FCV particle, which protects cats from homologous virus exposure and shortens the period of heterologous virus shedding, may serve as a better platform for anti-FCV vaccine.

  12. Body Clock

    Institute of Scientific and Technical Information of China (English)

    刘洪毓

    2000-01-01

    “Body clocks” are biological methods of controling body activities.Every living thing has one. In humans, a body clock controls normal periods of sleeping and waking. It controls the time swhen you are most likely to feel pain.Eating, sleeping and exercising at about the same time each day will help keep body activities normal. But changes in your life, a new job, for example, destroy the balance and thus cause health problems.

  13. Lego clocks: building a clock from parts.

    Science.gov (United States)

    Brunner, Michael; Simons, Mirre J P; Merrow, Martha

    2008-06-01

    A new finding opens up speculation that the molecular mechanism of circadian clocks in Synechococcus elongatus is composed of multiple oscillator systems (Kitayama and colleagues, this issue, pp. 1513-1521), as has been described in many eukaryotic clock model systems. However, an alternative intepretation is that the pacemaker mechanism-as previously suggested-lies primarily in the rate of ATP hydrolysis by the clock protein KaiC.

  14. Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage.

    Science.gov (United States)

    Dodd, Antony N; Salathia, Neeraj; Hall, Anthony; Kévei, Eva; Tóth, Réka; Nagy, Ferenc; Hibberd, Julian M; Millar, Andrew J; Webb, Alex A R

    2005-07-22

    Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long- and short-circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.

  15. Robust integration schemes for junction-based modulators in a 200mm CMOS compatible silicon photonic platform (Conference Presentation)

    Science.gov (United States)

    Szelag, Bertrand; Abraham, Alexis; Brision, Stéphane; Gindre, Paul; Blampey, Benjamin; Myko, André; Olivier, Segolene; Kopp, Christophe

    2017-05-01

    Silicon photonic is becoming a reality for next generation communication system addressing the increasing needs of HPC (High Performance Computing) systems and datacenters. CMOS compatible photonic platforms are developed in many foundries integrating passive and active devices. The use of existing and qualified microelectronics process guarantees cost efficient and mature photonic technologies. Meanwhile, photonic devices have their own fabrication constraints, not similar to those of cmos devices, which can affect their performances. In this paper, we are addressing the integration of PN junction Mach Zehnder modulator in a 200mm CMOS compatible photonic platform. Implantation based device characteristics are impacted by many process variations among which screening layer thickness, dopant diffusion, implantation mask overlay. CMOS devices are generally quite robust with respect to these processes thanks to dedicated design rules. For photonic devices, the situation is different since, most of the time, doped areas must be carefully located within waveguides and CMOS solutions like self-alignment to the gate cannot be applied. In this work, we present different robust integration solutions for junction-based modulators. A simulation setup has been built in order to optimize of the process conditions. It consist in a Mathlab interface coupling process and device electro-optic simulators in order to run many iterations. Illustrations of modulator characteristic variations with process parameters are done using this simulation setup. Parameters under study are, for instance, X and Y direction lithography shifts, screening oxide and slab thicknesses. A robust process and design approach leading to a pn junction Mach Zehnder modulator insensitive to lithography misalignment is then proposed. Simulation results are compared with experimental datas. Indeed, various modulators have been fabricated with different process conditions and integration schemes. Extensive

  16. Single-dose immunization with virus replicon particles confers rapid robust protection against Rift Valley fever virus challenge.

    Science.gov (United States)

    Dodd, Kimberly A; Bird, Brian H; Metcalfe, Maureen G; Nichol, Stuart T; Albariño, César G

    2012-04-01

    Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. The potential for RVFV introduction outside the area of endemicity highlights the need for fast-acting, safe, and efficacious vaccines. Here, we demonstrate a robust system for the reverse genetics generation of a RVF virus replicon particle (VRP(RVF)) vaccine candidate. Using a mouse model, we show that VRP(RVF) immunization provides the optimal balance of safety and single-dose robust efficacy. VRP(RVF) can actively synthesize viral RNA and proteins but lacks structural glycoprotein genes, preventing spread within immunized individuals and reducing the risk of vaccine-induced pathogenicity. VRP(RVF) proved to be completely safe following intracranial inoculation of suckling mice, a stringent test of vaccine safety. Single-dose subcutaneous immunization with VRP(RVF), although it is highly attenuated, completely protected mice against a virulent RVFV challenge dose which was 100,000-fold greater than the 50% lethal dose (LD(50)). Robust protection from lethal challenge was observed by 24 h postvaccination, with 100% protection induced in as little as 96 h. We show that a single subcutaneous VRP(RVF) immunization initiated a systemic antiviral state followed by an enhanced adaptive response. These data contrast sharply with the much-reduced survivability and immune responses observed among animals immunized with nonreplicating viral particles, indicating that replication, even if confined to the initially infected cells, contributes substantially to protective efficacy at early and late time points postimmunization. These data demonstrate that replicon vaccines successfully bridge the gap between safety and efficacy and provide insights into the kinetics of antiviral protection from RVFV infection.

  17. The molecular clock as a metabolic rheostat.

    Science.gov (United States)

    Perelis, M; Ramsey, K M; Bass, J

    2015-09-01

    Circadian clocks are biologic oscillators present in all photosensitive species that produce 24-h cycles in the transcription of rate-limiting metabolic enzymes in anticipation of the light-dark cycle. In mammals, the clock drives energetic cycles to maintain physiologic constancy during the daily switch in behavioural (sleep/wake) and nutritional (fasting/feeding) states. A molecular connection between circadian clocks and tissue metabolism was first established with the discovery that 24-h transcriptional rhythms are cell-autonomous and self-sustained in most tissues and comprise a robust temporal network throughout the body. A major window in understanding how the clock is coupled to metabolism was opened with discovery of metabolic syndrome pathologies in multi-tissue circadian mutant mice including susceptibility to diet-induced obesity and diabetes. Using conditional transgenesis and dynamic metabolic testing, we have pinpointed tissue-specific roles of the clock in energy and glucose homeostasis, with our most detailed understanding of this process in endocrine pancreas. Here, we review evidence for dynamic regulation of insulin secretion and oxidative metabolic functions by the clock transcription pathway to regulate homeostatic responses to feeding and fasting. These studies indicate that clock transcription is a determinant of tissue function and provide a reference for understanding molecular pathologies linking circadian desynchrony to metabolic disease.

  18. Optical Clocks in Space

    CERN Document Server

    Schiller, S; Nevsky, A; Koelemeij, J C J; Wicht, A; Gill, P; Klein, H A; Margolis, H S; Mileti, G; Sterr, U; Riehle, F; Peik, E; Tamm, C; Ertmer, W; Rasel, E; Klein, V; Salomon, C; Tino, G M; Lemonde, P; Holzwarth, R; Hänsch, T W; Tamm, Chr.

    2007-01-01

    The performance of optical clocks has strongly progressed in recent years, and accuracies and instabilities of 1 part in 10^18 are expected in the near future. The operation of optical clocks in space provides new scientific and technological opportunities. In particular, an earth-orbiting satellite containing an ensemble of optical clocks would allow a precision measurement of the gravitational redshift, navigation with improved precision, mapping of the earth's gravitational potential by relativistic geodesy, and comparisons between ground clocks.

  19. Constitutive Activity of the Arabidopsis MAP Kinase 3 Confers Resistance to Pseudomonas syringae and Drives Robust Immune Responses

    KAUST Repository

    Lang, Julien

    2017-08-02

    Mitogen Activated Protein Kinases (MAPKs) are known to be important mediators of plant responses to biotic and abiotic stresses. In a recent report, we enlarged the understanding of the Arabidopsis thaliana MPK3 functions showing that the expression of a constitutively active (CA) form of the protein led to auto-immune phenotypes. CA-MPK3 plants are dwarf and display defense responses that are characterized by the accumulation of salicylic acid and phytoalexins as well as by the upregulation of several defense genes. Consistently with these data, we present here results demonstrating that, compared to wild type controls, CA-MPK3 plants are more resistant to the hemibiotrophic pathogen Pseudomonas syringae DC3000. Based on our previous work, we also discuss the mechanisms of robust plant immunity controlled by sustained MPK3 activity, focusing especially on the roles of disease resistance proteins.

  20. Optimizing passive quantum clocks

    Science.gov (United States)

    Mullan, Michael; Knill, Emanuel

    2014-10-01

    We describe protocols for passive atomic clocks based on quantum interrogation of the atoms. Unlike previous techniques, our protocols are adaptive and take advantage of prior information about the clock's state. To reduce deviations from an ideal clock, each interrogation is optimized by means of a semidefinite program for atomic state preparation and measurement whose objective function depends on the prior information. Our knowledge of the clock's state is maintained according to a Bayesian model that accounts for noise and measurement results. We implement a full simulation of a running clock with power-law noise models and find significant improvements by applying our techniques.

  1. Drosophila microRNAs 263a/b confer robustness during development by protecting nascent sense organs from apoptosis.

    Science.gov (United States)

    Hilgers, Valérie; Bushati, Natascha; Cohen, Stephen M

    2010-06-15

    miR-263a/b are members of a conserved family of microRNAs that are expressed in peripheral sense organs across the animal kingdom. Here we present evidence that miR-263a and miR-263b play a role in protecting Drosophila mechanosensory bristles from apoptosis by down-regulating the pro-apoptotic gene head involution defective. Both microRNAs are expressed in the bristle progenitors, and despite a difference in their seed sequence, they share this key common target. In miR-263a and miR-263b deletion mutants, loss of bristles appears to be sporadic, suggesting that the role of the microRNAs may be to ensure robustness of the patterning process by promoting survival of these functionally specified cells. In the context of the retina, this mechanism ensures that the interommatidial bristles are protected during the developmentally programmed wave of cell death that prunes excess cells in order to refine the pattern of the pupal retina.

  2. Drosophila microRNAs 263a/b confer robustness during development by protecting nascent sense organs from apoptosis.

    Directory of Open Access Journals (Sweden)

    Valérie Hilgers

    Full Text Available miR-263a/b are members of a conserved family of microRNAs that are expressed in peripheral sense organs across the animal kingdom. Here we present evidence that miR-263a and miR-263b play a role in protecting Drosophila mechanosensory bristles from apoptosis by down-regulating the pro-apoptotic gene head involution defective. Both microRNAs are expressed in the bristle progenitors, and despite a difference in their seed sequence, they share this key common target. In miR-263a and miR-263b deletion mutants, loss of bristles appears to be sporadic, suggesting that the role of the microRNAs may be to ensure robustness of the patterning process by promoting survival of these functionally specified cells. In the context of the retina, this mechanism ensures that the interommatidial bristles are protected during the developmentally programmed wave of cell death that prunes excess cells in order to refine the pattern of the pupal retina.

  3. Optical clock networks

    Science.gov (United States)

    Riehle, Fritz

    2017-01-01

    Within the last decade, optical atomic clocks have surpassed the best cesium clocks, which are used to realize the unit of time and frequency, in terms of accuracy and stability by about two orders of magnitude. When remote optical atomic clocks are connected by links without degradation in the clock signals, an optical clock network is formed, with distinct advantages for the dissemination of time, geodesy, astronomy and basic and applied research. Different approaches for time and frequency transfer in the microwave and optical regime, via satellites and free-space links, optical fibre links, or transportable optical atomic clocks, can be used to form a hybrid clock network that may allow a future redefinition of the unit of time based on an optical reference transition.

  4. GPS Composite Clock Analysis

    OpenAIRE

    Wright, James R.

    2008-01-01

    The GPS composite clock defines GPS time, the timescale used today in GPS operations. GPS time is illuminated by examination of its role in the complete estimation and control problem relative to UTC/TAI. The phase of each GPS clock is unobservable from GPS pseudorange measurements, and the mean phase of the GPS clock ensemble (GPS time) is unobservable. A new and useful observability definition is presented, together with new observability theorems, to demonstrate explicitly that GPS time is...

  5. Temperature regulates transcription in the zebrafish circadian clock.

    Directory of Open Access Journals (Sweden)

    Kajori Lahiri

    2005-11-01

    Full Text Available It has been well-documented that temperature influences key aspects of the circadian clock. Temperature cycles entrain the clock, while the period length of the circadian cycle is adjusted so that it remains relatively constant over a wide range of temperatures (temperature compensation. In vertebrates, the molecular basis of these properties is poorly understood. Here, using the zebrafish as an ectothermic model, we demonstrate first that in the absence of light, exposure of embryos and primary cell lines to temperature cycles entrains circadian rhythms of clock gene expression. Temperature steps drive changes in the basal expression of certain clock genes in a gene-specific manner, a mechanism potentially contributing to entrainment. In the case of the per4 gene, while E-box promoter elements mediate circadian clock regulation, they do not direct the temperature-driven changes in transcription. Second, by studying E-box-regulated transcription as a reporter of the core clock mechanism, we reveal that the zebrafish clock is temperature-compensated. In addition, temperature strongly influences the amplitude of circadian transcriptional rhythms during and following entrainment by light-dark cycles, a property that could confer temperature compensation. Finally, we show temperature-dependent changes in the expression levels, phosphorylation, and function of the clock protein, CLK. This suggests a mechanism that could account for changes in the amplitude of the E-box-directed rhythm. Together, our results imply that several key transcriptional regulatory elements at the core of the zebrafish clock respond to temperature.

  6. Precision Clock Evaluation Facility

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Tests and evaluates high-precision atomic clocks for spacecraft, ground, and mobile applications. Supports performance evaluation, environmental testing,...

  7. Clocked combustor can array

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won-Wook; McMahan, Kevin Weston; Srinivasan, Shiva Kumar

    2017-01-17

    The present application provides a clocked combustor can array for coherence reduction in a gas turbine engine. The clocked combustor can array may include a number of combustor cans positioned in a circumferential array. A first set of the combustor cans may have a first orientation and a second set of the combustor cans may have a second orientation.

  8. Clocked combustor can array

    Science.gov (United States)

    Kim, Won-Wook; McMahan, Kevin Weston; Srinivasan, Shiva Kumar

    2017-01-17

    The present application provides a clocked combustor can array for coherence reduction in a gas turbine engine. The clocked combustor can array may include a number of combustor cans positioned in a circumferential array. A first set of the combustor cans may have a first orientation and a second set of the combustor cans may have a second orientation.

  9. Active optical clock

    Institute of Scientific and Technical Information of China (English)

    CHEN JingBiao

    2009-01-01

    This article presents the principles and techniques of active optical clock, a special laser combining the laser physics of one-atom laser, bad-cavity gas laser, super-cavity stabilized laser and optical atomic clock together. As a simple example, an active optical clock based on thermal strontium atomic beam shows a quantum-limited linewidth of 0.51 Hz, which is insensitive to laser cavity-length noise, and may surpass the recorded narrowest 6.7 Hz of Hg ion optical clock and 1.5 Hz of very recent optical lattice clock. The estimated 0.1 Hz one-second instability and 0.27 Hz uncertainty are limited only by the rela-tivistic Doppler effect, and can be improved by cold atoms.

  10. Optical Lattice Clocks

    Science.gov (United States)

    Oates, Chris

    2012-06-01

    Since they were first proposed in 2003 [1], optical lattice clocks have become one of the leading technologies for the next generation of atomic clocks, which will be used for advanced timing applications and in tests of fundamental physics [2]. These clocks are based on stabilized lasers whose frequency is ultimately referenced to an ultra-narrow neutral atom transition (natural linewidths magic'' value so as to yield a vanishing net AC Stark shift for the clock transition. As a result lattice clocks have demonstrated the capability of generating high stability clock signals with small absolute uncertainties (˜ 1 part in 10^16). In this presentation I will first give an overview of the field, which now includes three different atomic species. I will then use experiments with Yb performed in our laboratory to illustrate the key features of a lattice clock. Our research has included the development of state-of-the-art optical cavities enabling ultra-high-resolution optical spectroscopy (1 Hz linewidth). Together with the large atom number in the optical lattice, we are able to achieve very low clock instability (< 0.3 Hz in 1 s) [3]. Furthermore, I will show results from some of our recent investigations of key shifts for the Yb lattice clock, including high precision measurements of ultracold atom-atom interactions in the lattice and the dc Stark effect for the Yb clock transition (necessary for the evaluation of blackbody radiation shifts). [4pt] [1] H. Katori, M. Takamoto, V. G. Pal'chikov, and V. D. Ovsiannikov, Phys. Rev. Lett. 91, 173005 (2003). [0pt] [2] Andrei Derevianko and Hidetoshi Katori, Rev. Mod. Phys. 83, 331 (2011). [0pt] [3] Y. Y. Jiang, A. D. Ludlow, N. D. Lemke, R. W. Fox, J. A. Sherman, L.-S. Ma, and C. W. Oates, Nature Photonics 5, 158 (2011).

  11. Optical Clocks and Relativity

    Science.gov (United States)

    Chou, C. W.; Hume, D. B.; Rosenband, T.; Wineland, D. J.

    2010-09-01

    Observers in relative motion or at different gravitational potentials measure disparate clock rates. These predictions of relativity have previously been observed with atomic clocks at high velocities and with large changes in elevation. We observed time dilation from relative speeds of less than 10 meters per second by comparing two optical atomic clocks connected by a 75-meter length of optical fiber. We can now also detect time dilation due to a change in height near Earth’s surface of less than 1 meter. This technique may be extended to the field of geodesy, with applications in geophysics and hydrology as well as in space-based tests of fundamental physics.

  12. Quantum Clock Synchronization a Multi-Party Protocol

    CERN Document Server

    Krco, M; Krco, Marko; Paul, Prabasaj

    2001-01-01

    We present a multi-party quantum clock synchronization protocol that utilizes shared prior entanglement and broadcast of classical information to synchronize spatially separated clocks. Notably, it is necessary only for any one party to publish classical information. Consequently, the efficacy of the method is independent of the relative location of the parties. The suggested protocol is robust and does not require precise sequencing of procedural steps.

  13. Stable clocks and general relativity

    CERN Document Server

    Will, C M

    1995-01-01

    We survey the role of stable clocks in general relativity. Clock comparisons have provided important tests of the Einstein Equivalence Principle, which underlies metric gravity. These include tests of the isotropy of clock comparisons (verification of local Lorentz invariance) and tests of the homogeneity of clock comparisons (verification of local position invariance). Comparisons of atomic clocks with gravitational clocks test the Strong Equivalence Principle by bounding cosmological variations in Newton's constant. Stable clocks also play a role in the search for gravitational radiation: comparision of atomic clocks with the binary pulsar's orbital clock has verified gravitational-wave damping, and phase-sensitive detection of waves from inspiralling compact binaries using laser interferometric gravitational observatories will facilitate extraction of useful source information from the data. Stable clocks together with general relativity have found important practical applications in navigational systems s...

  14. Resetting Biological Clocks

    Science.gov (United States)

    Winfree, Arthur T.

    1975-01-01

    Reports on experiments conducted on two biological clocks, in organisms in the plant and animal kingdoms, which indicate that biological oscillation can be arrested by a single stimulus of a definite strength delivered at the proper time. (GS)

  15. Resetting Biological Clocks

    Science.gov (United States)

    Winfree, Arthur T.

    1975-01-01

    Reports on experiments conducted on two biological clocks, in organisms in the plant and animal kingdoms, which indicate that biological oscillation can be arrested by a single stimulus of a definite strength delivered at the proper time. (GS)

  16. On clocks and clouds

    Directory of Open Access Journals (Sweden)

    M. K. Witte

    2013-09-01

    Full Text Available Cumulus clouds exhibit a life cycle that consists of: (a the growth phase (increasing size, most notably in the vertical direction; (b the mature phase (growth ceases; any precipitation that develops is strongest during this period; and (c the dissipation phase (cloud dissipates because of precipitation and/or entrainment; no more dynamical support. Although radar can track clouds over time and give some sense of the age of a cloud, most aircraft in situ measurements lack temporal context. We use large eddy simulations of trade wind cumulus cloud fields from cases during the Barbados Oceanographic and Meteorological Experiment (BOMEX and Rain In Cumulus over the Ocean (RICO campaigns to demonstrate a potential cumulus cloud "clock". We find that the volume-averaged total water mixing ratio rt is a useful cloud clock for the 12 clouds studied. A cloud's initial rt is set by the subcloud mixed-layer mean rt and decreases monotonically from the initial value due primarily to entrainment. The clock is insensitive to aerosol loading, environmental sounding and extrinsic cloud properties such as lifetime and volume. In some cases (more commonly for larger clouds, multiple pulses of buoyancy occur, which complicate the cumulus clock by replenishing rt. The clock is most effectively used to classify clouds by life phase.

  17. Optical atomic clocks

    CERN Document Server

    Poli, N; Gill, P; Tino, G M

    2014-01-01

    In the last ten years extraordinary results in time and frequency metrology have been demonstrated. Frequency-stabilization techniques for continuous-wave lasers and femto-second optical frequency combs have enabled a rapid development of frequency standards based on optical transitions in ultra-cold neutral atoms and trapped ions. As a result, today's best performing atomic clocks tick at an optical rate and allow scientists to perform high-resolution measurements with a precision approaching a few parts in $10^{18}$. This paper reviews the history and the state of the art in optical-clock research and addresses the implementation of optical clocks in a possible future redefinition of the SI second as well as in tests of fundamental physics.

  18. Relativistic quantum clocks

    CERN Document Server

    Lock, Maximilian P E

    2016-01-01

    The conflict between quantum theory and the theory of relativity is exemplified in their treatment of time. We examine the ways in which their conceptions differ, and describe a semiclassical clock model combining elements of both theories. The results obtained with this clock model in flat spacetime are reviewed, and the problem of generalizing the model to curved spacetime is discussed, before briefly describing an experimental setup which could be used to test of the model. Taking an operationalist view, where time is that which is measured by a clock, we discuss the conclusions that can be drawn from these results, and what clues they contain for a full quantum relativistic theory of time.

  19. The circadian clock goes genomic.

    Science.gov (United States)

    Staiger, Dorothee; Shin, Jieun; Johansson, Mikael; Davis, Seth J

    2013-06-24

    Large-scale biology among plant species, as well as comparative genomics of circadian clock architecture and clock-regulated output processes, have greatly advanced our understanding of the endogenous timing system in plants.

  20. SRC: Smart Reminder Clock

    Science.gov (United States)

    Kasim, Shahreen; Hafit, Hanayanti; Leong, Tan Hua; Hashim, Rathiah; Ruslai, Husni; Jahidin, Kamaruzzaman; Syafwan Arshad, Mohammad

    2016-11-01

    Nowadays, some people facing the problem to wake up in the morning. This was result to absence of the classes, meetings, and even exams. The aim of this project is to develop an android application that can force the user to wake up. The method used in this application are pedometer and Short Message Service (SMS) function. This application need the user to take their smartphone and walk about 10 steps to disable it, when the alarm clock is activated. After that, when the alarm clock was rang, this alarm application has automatically send a message to the users’ friends or parents phone to wake them up.

  1. Gravitomagnetism, clocks and geometry

    CERN Document Server

    Tartaglia, A

    2001-01-01

    New techniques to evaluate the clock effect using light are described. These are based on the flatness of the cylindrical surface containing the world lines of the rays constrained to move on circular trajectories about a spinning mass. The effect of the angular momentum of the source is manifested in the fact that inertial observers must be replaced by local non rotating observers. Starting from this an exact formula for circular trajectories is found. Numerical estimates for the Earth environment show that light would be a better probe than actual clocks to evidence the angular momentum influence. The advantages of light in connection with some principle experiments are shortly reviewed.

  2. Redox rhythm reinforces the circadian clock to gate immune response.

    Science.gov (United States)

    Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

    2015-07-23

    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

  3. Ultrastable optical clock with two cold-atom ensembles

    Science.gov (United States)

    Schioppo, M.; Brown, R. C.; McGrew, W. F.; Hinkley, N.; Fasano, R. J.; Beloy, K.; Yoon, T. H.; Milani, G.; Nicolodi, D.; Sherman, J. A.; Phillips, N. B.; Oates, C. W.; Ludlow, A. D.

    2017-01-01

    Atomic clocks based on optical transitions are the most stable, and therefore precise, timekeepers available. These clocks operate by alternating intervals of atomic interrogation with the 'dead' time required for quantum state preparation and readout. This non-continuous interrogation of the atom system results in the Dick effect, an aliasing of frequency noise from the laser interrogating the atomic transition. Despite recent advances in optical clock stability that have been achieved by improving laser coherence, the Dick effect has continually limited the performance of optical clocks. Here we implement a robust solution to overcome this limitation: a zero-dead-time optical clock that is based on the interleaved interrogation of two cold-atom ensembles. This clock exhibits vanishingly small Dick noise, thereby achieving an unprecedented fractional frequency instability assessed to be for an averaging time τ in seconds. We also consider alternate dual-atom-ensemble schemes to extend laser coherence and reduce the standard quantum limit of clock stability, achieving a spectroscopy line quality factor of Q > 4 × 1015.

  4. Crime clocks and target performance maps

    CSIR Research Space (South Africa)

    Cooper, Antony K

    1999-12-01

    Full Text Available the boundaries 3rd Annual Crime Mapping Research Conference 11 - 14 December 1999, Orlando, Florida Panel: Mapping around the world Crime clocks and target performance maps AK Cooper, TC Gilfillan, MA Potgieter, PMU Schmitz and PM du Plessis Division.... In an American context, a CAS Block could be equated to a Beat. Using the centroids and/or faces of the CAS Blocks, one can readily map the crime data using a GIS. Figure 1: Location of the study area Traditionally, automated crime mapping and analysis...

  5. Sagnac interferometry with a single atomic clock

    CERN Document Server

    Stevenson, R; Bishop, T; Lesanovsky, I; Fernholz, T

    2015-01-01

    We theoretically discuss an implementation of a Sagnac interferometer with cold atoms. In contrast to currently existing schemes our protocol does not rely on any free propagation of atoms. Instead it is based on superpositions of fully confined atoms and state-dependent transport along a closed path. Using Ramsey sequences for an atomic clock, the accumulated Sagnac phase is encoded in the resulting population imbalance between two internal (clock) states. Using minimal models for the above protocol we analytically quantify limitations arising from atomic dynamics and finite temperature. We discuss an actual implementation of the interferometer with adiabatic radio-frequency potentials that is inherently robust against common mode noise as well as phase noise from the reference oscillator.

  6. Decamp Clock Board Firmware

    Energy Technology Data Exchange (ETDEWEB)

    Vicente, J. de; Castilla, J.; Martinez, G.

    2007-09-27

    Decamp (Dark Energy Survey Camera) is a new instrument designed to explore the universe aiming to reveal the nature of Dark Energy. The camera consists of 72 CCDs and 520 Mpixels. The readout electronics of DECam is based on the Monsoon system. Monsoon is a new image acquisition system developed by the NOAO (National Optical Astronomical Observatory) for the new generation of astronomical cameras. The Monsoon system uses three types of boards inserted in a Eurocard format based crate: master control board, acquisition board and clock board. The direct use of the Monsoon system for DECam readout electronics requires nine crates mainly due to the high number of clock boards needed. Unfortunately, the available space for DECam electronics is constrained to four crates at maximum. The major drawback to achieve such desired compaction degree resides in the clock board signal density. This document describes the changes performed at CIEMAT on the programmable logic of the Monsoon clock board aiming to meet such restricted space constraints. (Author) 5 refs.

  7. Cyclotomic quantum clock

    CERN Document Server

    Rosu, H C

    2003-01-01

    In the wake of our recent work on cyclotomic effects in quantum phase locking [M. Planat and H. C. Rosu, Phys. Lett. A 315, 1 (2003)], we briefly discuss here a cyclotomic extension of the Salecker and Wigner quantum clock. We also hint on a possible cyclotomic structure of time at the Planck scales

  8. Transcriptional oscillation of canonical clock genes in mouse peripheral tissues

    Directory of Open Access Journals (Sweden)

    Nakahata Yasukazu

    2004-10-01

    Full Text Available Abstract Background The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms from prokaryotes to humans. Identification of clock genes has allowed us to study the molecular bases for circadian behaviors and temporal physiological processes such as hormonal secretion, and has prompted the idea that molecular clocks reside not only in a central pacemaker, the suprachiasmatic nuclei (SCN of hypothalamus in mammals, but also in peripheral tissues, even in immortalized cells. Furthermore, previous molecular dissection revealed that the mechanism of circadian oscillation at a molecular level is based on transcriptional regulation of clock and clock-controlled genes. Results We systematically analyzed the mRNA expression of clock and clock-controlled genes in mouse peripheral tissues. Eight genes (mBmal1, mNpas2, mRev-erbα, mDbp, mRev-erbβ, mPer3, mPer1 and mPer2; given in the temporal order of the rhythm peak showed robust circadian expressions of mRNAs in all tissues except testis, suggesting that these genes are core molecules of the molecular biological clock. The bioinformatics analysis revealed that these genes have one or a combination of 3 transcriptional elements (RORE, DBPE, and E-box, which are conserved among human, mouse, and rat genome sequences, and indicated that these 3 elements may be responsible for the biological timing of expression of canonical clock genes. Conclusions The observation of oscillatory profiles of canonical clock genes is not only useful for physiological and pathological examination of the circadian clock in various organs but also important for systematic understanding of transcriptional regulation on a genome-wide basis. Our finding of the oscillatory expression of canonical clock genes with a temporal order provides us an interesting hypothesis, that cyclic timing of all clock and clock-controlled genes may be dependent on several transcriptional elements

  9. Relativity and Al^+ Optical Clocks

    Science.gov (United States)

    Chou, Chin-Wen; Hume, David B.; Wineland, David J.; Rosenband, Till

    2010-03-01

    We have constructed an optical clock based on quantum logic spectroscopy of an Al+ ion that has a fractional frequency inaccuracy of 8.6x10-18. The frequency of the ^1S0^3P0 clock transition is compared to that of a previously constructed Al^+ optical clock with a statistical measurement uncertainty of 7.0x10-18. The two clocks exhibit a relative stability of 2.8x10-15&-1/2circ;, and a fractional frequency difference of -1.8x10-17, consistent with the accuracy limit of the older clock. By comparing the frequencies of the clocks, we have observed relativistic effects, such as time dilation due to velocities less than 10 m/s and the gravitational red shift from a 0.33 m height change of one of the clocks.

  10. Ultra-stable optical clock with two cold-atom ensembles

    CERN Document Server

    Schioppo, M; McGrew, W F; Hinkley, N; Fasano, R J; Beloy, K; Yoon, T H; Milani, G; Nicolodi, D; Sherman, J A; Phillips, N B; Oates, C W; Ludlow, A D

    2016-01-01

    Atomic clocks based on optical transitions are the most stable, and therefore precise, timekeepers available. These clocks operate by alternating intervals of atomic interrogation with dead time required for quantum state preparation and readout. This non-continuous interrogation of the atom system results in the Dick effect, an aliasing of frequency noise of the laser interrogating the atomic transition. Despite recent advances in optical clock stability achieved by improving laser coherence, the Dick effect has continually limited optical clock performance. Here we implement a robust solution to overcome this limitation: a zero-dead-time optical clock based on the interleaved interrogation of two cold-atom ensembles. This clock exhibits vanishingly small Dick noise, thereby achieving an unprecedented fractional frequency instability of $6 \\times 10^{-17} / \\sqrt{\\tau}$ for an averaging time $\\tau$ in seconds. We also consider alternate dual-atom-ensemble schemes to extend laser coherence and reduce the stan...

  11. Round the clock librarianship

    OpenAIRE

    1995-01-01

    The concept of Round the Clock Librarianship (ROCLOLIB) is one such opportunity of terminal and critical importance to librarians, which helps people (clients) in general and reassures them about the professional commitment and devotedness of librarians. Although the concept is old, it is an exercise here to analyse its importance for the overall image and status of the practice/occupation. The chapter discusses the proposal of opening Libraries for 24 Hours. It also points out the reasons fo...

  12. Miniaturized optical system for atomic fountain clock

    Institute of Scientific and Technical Information of China (English)

    Lü De-Sheng; Qu Qiu-Zhi; Wang Bin; Zhao Jian-Bo; Li Tang; Liu Liang; Wang Yu-Zhu

    2011-01-01

    Using modularized components, we have built a miniaturized optical system for 87Rb atomic fountain clock that is fitted on an 80 cm × 60 cm optical breadboard. Compared with the conventional optical setup on the table, our system is more compact, more robust and miniaturized. Taking advantage of this system, laser beams are transmitted through eight optical fibre patch cords from the optical breadboard to an ultra high vacuum system. This optical setup has operated for five months in our fountain system and required no alignment.

  13. High-Performance Coherent Population Trapping Clock with Polarization Modulation

    Science.gov (United States)

    Yun, Peter; Tricot, François; Calosso, Claudio Eligio; Micalizio, Salvatore; François, Bruno; Boudot, Rodolphe; Guérandel, Stéphane; de Clercq, Emeric

    2017-01-01

    We demonstrate a vapor-cell atomic-clock prototype based on a continuous-wave interrogation and double-modulation coherent population trapping (DM-CPT) technique. The DM-CPT technique uses a synchronous modulation of polarization and the relative phase of a bichromatic laser beam in order to increase the number of atoms trapped in a dark state, i.e., a nonabsorbing state. The narrow resonance, observed in the transmission of a Cs vapor cell, is used as a narrow frequency discriminator in an atomic clock. A detailed characterization of the CPT resonance versus numerous parameters is reported. A short-term fractional-frequency stability of 3.2 ×10-13τ-1 /2 up to a 100-s averaging time is measured. These performances are more than one order of magnitude better than industrial Rb clocks and are comparable to those of the best laboratory-prototype vapor-cell clocks. The noise-budget analysis shows that the short- and midterm frequency stability is mainly limited by the power fluctuations of the microwave used to generate the bichromatic laser. These preliminary results demonstrate that the DM-CPT technique is well suited for the development of a high-performance atomic clock, with the potential compact and robust setup due to its linear architecture. This clock could find future applications in industry, telecommunications, instrumentation, or global navigation satellite systems.

  14. Radium single-ion optical clock

    CERN Document Server

    Versolato, O O; Jungmann, K; Timmermans, R G E; Willmann, L; Wilschut, H W

    2011-01-01

    We explore the potential of the electric quadrupole transitions $7s\\,^2S_{1/2}$ - $6d\\,^2D_{3/2}$, $6d\\,^2D_{5/2}$ in radium isotopes as single-ion optical frequency standards. The frequency shifts of the clock transitions due to external fields and the corresponding uncertainties are calculated. Several competitive $^A$Ra$^+$ candidates with $A=$ 223 - 229 are identified. In particular, we show that the transition $7s\\,^2S_{1/2}\\,(F=2,m_F=0)$ - $6d\\,^2D_{3/2}\\,(F=0,m_F=0)$ at 828 nm in $^{223}$Ra$^+$, with no linear Zeeman and electric quadrupole shifts, stands out as a relatively simple case, which could be exploited as a compact, robust, and low-cost atomic clock operating at a fractional frequency uncertainty of $10^{-17}$. With more experimental effort, the $^{223,225,226}$Ra$^+$ clocks could be pushed to a projected performance reaching the $10^{-18}$ level.

  15. Microchip-Based Trapped-Atom Clocks

    CERN Document Server

    Vuletic, Vladan; Schleier-Smith, Monika H

    2011-01-01

    This is a chapter of a recently published book entitled Atom Chips, edited by Jakob Reichel and Vladan Vuletic. The contents of this chapter include: Basic Principles; Atomic-Fountain versus Trapped-Atom Clocks; Optical-Transition Clocks versus Microwave Clocks; Clocks with Magnetically Trapped Atoms--Fundamental Limits and Experimental Demonstrations; Readout in Trapped-Atom Clocks; and Spin Squeezing.

  16. Circadian clocks and breast cancer

    OpenAIRE

    Blakeman, Victoria; Jack L. Williams; Meng, Qing-Jun; Streuli, Charles H

    2016-01-01

    Circadian clocks respond to environmental time cues to coordinate 24-hour oscillations in almost every tissue of the body. In the breast, circadian clocks regulate the rhythmic expression of numerous genes. Disrupted expression of circadian genes can alter breast biology and may promote cancer. Here we overview circadian mechanisms, and the connection between the molecular clock and breast biology. We describe how disruption of circadian genes contributes to cancer via multiple mechanisms, an...

  17. Molecular clock in neutral protein evolution

    Directory of Open Access Journals (Sweden)

    Wilke Claus O

    2004-08-01

    Full Text Available Abstract Background A frequent observation in molecular evolution is that amino-acid substitution rates show an index of dispersion (that is, ratio of variance to mean substantially larger than one. This observation has been termed the overdispersed molecular clock. On the basis of in silico protein-evolution experiments, Bastolla and coworkers recently proposed an explanation for this observation: Proteins drift in neutral space, and can temporarily get trapped in regions of substantially reduced neutrality. In these regions, substitution rates are suppressed, which results in an overall substitution process that is not Poissonian. However, the simulation method of Bastolla et al. is representative only for cases in which the product of mutation rate μ and population size Ne is small. How the substitution process behaves when μNe is large is not known. Results Here, I study the behavior of the molecular clock in in silico protein evolution as a function of mutation rate and population size. I find that the index of dispersion decays with increasing μNe, and approaches 1 for large μNe . This observation can be explained with the selective pressure for mutational robustness, which is effective when μNe is large. This pressure keeps the population out of low-neutrality traps, and thus steadies the ticking of the molecular clock. Conclusions The molecular clock in neutral protein evolution can fall into two distinct regimes, a strongly overdispersed one for small μNe, and a mostly Poissonian one for large μNe. The former is relevant for the majority of organisms in the plant and animal kingdom, and the latter may be relevant for RNA viruses.

  18. Daily oscillation and photoresponses of clock gene, Clock, and clock-associated gene, arylalkylamine N-acetyltransferase gene transcriptions in the rat pineal gland.

    Science.gov (United States)

    Wang, Guo-Qing; Du, Yu-Zhen; Tong, Jian

    2007-01-01

    This study was conducted to investigate the circadian rhythms and light responses of Clock and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat pineal gland under the environmental conditions of a 12 h light (05:00-17:00 h): 12 h-dark (17:00-05:00 h) cycle (LD) and constant darkness (DD). The pineal gland of Sprague-Dawley rats housed under a LD regime (n=42) for four weeks and of a regime (n=42) for eight weeks were sampled at six different times, every 4 h (n=7 animals per time point), during a 24 h period. Total RNA was extracted from each sample, and the semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine temporal changes in mRNA levels of Clock and NAT genes during different circadian or zeitgeber times. The data and parameters were analyzed by the cosine function software, Clock Lab software, and the amplitude F test was used to reveal the circadian rhythm. In the DD or LD condition, both the Clock and NAT mRNA levels in the pineal gland showed robust circadian oscillation (ppineal gland were significantly reduced (ppineal gland (p>0.05). These findings indicate that the transcriptions of Clock and NAT genes in the pineal gland not only show remarkably synchronous endogenous circadian rhythmic changes, but also respond to the ambient light signal in a reduced manner.

  19. A Light Clock Satisfying the Clock Hypothesis of Special Relativity

    Science.gov (United States)

    West, Joseph

    2007-01-01

    The design of the FMEL, a floor-mirrored Einstein-Langevin "light clock", is introduced. The clock provides a physically intuitive manner to calculate and visualize the time dilation effects for a spatially extended set of observers (an accelerated "frame") undergoing unidirectional acceleration or observers on a rotating cylinder of constant…

  20. Clocks and cardiovascular function

    Science.gov (United States)

    McLoughlin, Sarah C.; Haines, Philip; FitzGerald, Garret A.

    2016-01-01

    Circadian clocks in central and peripheral tissues enable the temporal synchronization and organization of molecular and physiological processes of rhythmic animals, allowing optimum functioning of cells and organisms at the most appropriate time of day. Disruption of circadian rhythms, from external or internal forces, leads to widespread biological disruption and is postulated to underlie many human conditions, such as the incidence and timing of cardiovascular disease. Here, we describe in vivo and in vitro methodology relevant to studying the role of circadian rhythms in cardiovascular function and dysfunction PMID:25707279

  1. A mixed relaxed clock model

    Science.gov (United States)

    2016-01-01

    Over recent years, several alternative relaxed clock models have been proposed in the context of Bayesian dating. These models fall in two distinct categories: uncorrelated and autocorrelated across branches. The choice between these two classes of relaxed clocks is still an open question. More fundamentally, the true process of rate variation may have both long-term trends and short-term fluctuations, suggesting that more sophisticated clock models unfolding over multiple time scales should ultimately be developed. Here, a mixed relaxed clock model is introduced, which can be mechanistically interpreted as a rate variation process undergoing short-term fluctuations on the top of Brownian long-term trends. Statistically, this mixed clock represents an alternative solution to the problem of choosing between autocorrelated and uncorrelated relaxed clocks, by proposing instead to combine their respective merits. Fitting this model on a dataset of 105 placental mammals, using both node-dating and tip-dating approaches, suggests that the two pure clocks, Brownian and white noise, are rejected in favour of a mixed model with approximately equal contributions for its uncorrelated and autocorrelated components. The tip-dating analysis is particularly sensitive to the choice of the relaxed clock model. In this context, the classical pure Brownian relaxed clock appears to be overly rigid, leading to biases in divergence time estimation. By contrast, the use of a mixed clock leads to more recent and more reasonable estimates for the crown ages of placental orders and superorders. Altogether, the mixed clock introduced here represents a first step towards empirically more adequate models of the patterns of rate variation across phylogenetic trees. This article is part of the themed issue ‘Dating species divergences using rocks and clocks’. PMID:27325829

  2. The circadian Clock mutation increases exploratory activity and escape-seeking behavior.

    Science.gov (United States)

    Easton, A; Arbuzova, J; Turek, F W

    2003-02-01

    Disturbances of circadian rhythms are associated with many types of mood disorders; however, it is unknown whether a dysfunctional circadian pacemaker can be the primary cause of altered emotional behavior. To test this hypothesis, male and female mice carrying a mutation of the circadian gene, Clock, were compared to wild-type mice in an array of behavioral tests used to measure exploratory activity, anxiety, and behavioral despair. Female Clock mutant mice exhibited significantly greater activity and rearing in an open field and a greater number of total arm entries in the elevated plus maze. In addition, female Clock mutant mice spent significantly more time swimming in the forced swim test than wild-type mice on both days of a 2-day test. Male Clock mutant mice also exhibited increased exploration of the open field and increased swimming in the forced swim test; however, behavioral changes were less robust in Clock mutant males compared to Clock mutant females. These changes in behavior were not dependent on the expression of a lengthened free-running period but were more or less striking depending on the testing conditions. These data indicate that the Clock mutation leads to increased exploratory behavior and increased escape-seeking behavior, and, conversely, does not result in increased anxiety or depressive-like behavior. These results suggest that the Clock gene is involved in regulating behavioral arousal, and that Clock may interact with sex hormones to produce these behavioral changes.

  3. Identification and temporal expression of putative circadian clock transcripts in the amphipod crustacean Talitrus saltator.

    Science.gov (United States)

    O'Grady, Joseph F; Hoelters, Laura S; Swain, Martin T; Wilcockson, David C

    2016-01-01

    Talitrus saltator is an amphipod crustacean that inhabits the supralittoral zone on sandy beaches in the Northeast Atlantic and Mediterranean. T. saltator exhibits endogenous locomotor activity rhythms and time-compensated sun and moon orientation, both of which necessitate at least one chronometric mechanism. Whilst their behaviour is well studied, currently there are no descriptions of the underlying molecular components of a biological clock in this animal, and very few in other crustacean species. We harvested brain tissue from animals expressing robust circadian activity rhythms and used homology cloning and Illumina RNAseq approaches to sequence and identify the core circadian clock and clock-related genes in these samples. We assessed the temporal expression of these genes in time-course samples from rhythmic animals using RNAseq. We identified a comprehensive suite of circadian clock gene homologues in T. saltator including the 'core' clock genes period (Talper), cryptochrome 2 (Talcry2), timeless (Taltim), clock (Talclk), and bmal1 (Talbmal1). In addition we describe the sequence and putative structures of 23 clock-associated genes including two unusual, extended isoforms of pigment dispersing hormone (Talpdh). We examined time-course RNAseq expression data, derived from tissues harvested from behaviourally rhythmic animals, to reveal rhythmic expression of these genes with approximately circadian period in Talper and Talbmal1. Of the clock-related genes, casein kinase IIβ (TalckIIβ), ebony (Talebony), jetlag (Taljetlag), pigment dispensing hormone (Talpdh), protein phosphatase 1 (Talpp1), shaggy (Talshaggy), sirt1 (Talsirt1), sirt7 (Talsirt7) and supernumerary limbs (Talslimb) show temporal changes in expression. We report the sequences of principle genes that comprise the circadian clock of T. saltator and highlight the conserved structural and functional domains of their deduced cognate proteins. Our sequencing data contribute to the growing inventory

  4. Development of a strontium optical lattice clock for space applications

    Science.gov (United States)

    Singh, Yeshpal

    2016-07-01

    With timekeeping being of paramount importance for modern life, much research and major scientific advances have been undertaken in the field of frequency metrology, particularly over the last few years. New Nobel-prize winning technologies have enabled a new era of atomic clocks; namely the optical clock. These have been shown to perform significantly better than the best microwave clocks reaching an inaccuracy of 1.6x10-18 [1]. With such results being found in large lab based apparatus, the focus now has shifted to portability - to enable the accuracy of various ground based clocks to be measured, and compact autonomous performance - to enable such technologies to be tested in space. This could lead to a master clock in space, improving not only the accuracy of technologies on which modern life has come to require such as GPS and communication networks. But also more fundamentally, this could lead to the redefinition of the second and tests of fundamental physics including applications in the fields of ground based and satellite geodesy, metrology, positioning, navigation, transport and logistics etc. Within the European collaboration, Space Optical Clocks (SOC2) [2-3] consisting of various institutes and industry partners across Europe we have tried to tackle this problem of miniaturisation whilst maintaining stability, accuracy (5x10-17) and robustness whilst keeping power consumption to a minimum - necessary for space applications. We will present the most recent results of the Sr optical clock in SOC2 and also the novel compact design features, new methods employed and outlook. References [1] B. J. Bloom, T. L. Nicholson, J. R. Williams, S. L. Campbell, M. Bishof, X. Zhang, W. Zhang, S. L. Bromley, and J. Ye, "An optical lattice clock with accuracy and stability at the 10-18 level," Nature 506, 71-75 (2014). [2] S. Schiller et al. "Towards Neutral-atom Space Optical Clocks (SOC2): Development of high-performance transportable and breadboard optical clocks and

  5. Experimental Investigation of Digital Compensation of DGD for 112 Gb/s PDM-QPSK Clock Recovery

    DEFF Research Database (Denmark)

    Zibar, Darko; de Oliviera, Julio Cesar R.; Ribeiro, Vitor B.

    2011-01-01

    For the first time, the impact of DGD on clock recovery for 112Gb/s PDM-QPSK is experimentally investigated and quantified. We propose and experimentally demonstrate novel digital adaptive timing error detector which is robust to DGD....

  6. Non-circadian expression masking clock-driven weak transcription rhythms in U2OS cells.

    Directory of Open Access Journals (Sweden)

    Julia Hoffmann

    Full Text Available U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not correlate with detectable rhythmic transcript levels. Luciferase fusions reveal that the circadian clock supports robust but low amplitude transcription rhythms of representative promoters. However, rhythmic transcription of these potentially clock-controlled genes is masked by non-circadian transcription that overwrites the weaker contribution of the clock in constant conditions. Our data suggest that U2OS cells harbor an intrinsically rather weak circadian oscillator. The oscillator has the potential to regulate a large number of genes. The contribution of circadian versus non-circadian transcription is dependent on the metabolic state of the cell and may determine the apparent complexity of the circadian transcriptome.

  7. Clocks around Sgr A*

    CERN Document Server

    Angélil, Raymond

    2014-01-01

    The S stars near the Galactic centre and any pulsars that may be on similar orbits, can be modelled in a unified way as clocks orbiting a black hole, and hence are potential probes of relativistic effects, including block-hole spin. The high eccentricities of many S stars mean that relativistic effects peak strongly around pericentre; for example, orbit precession is not a smooth effect but almost a kick at pericentre. We argue that concentration around pericentre will be an advantage when analysing redshift or pulse-arrival data to measure relativistic effects, because cumulative precession will be drowned out by Newtonian perturbations from other mass in the Galactic-centre region. Wavelet decomposition may be a way to disentangle relativistic effects from Newton perturbations. Assuming a plausible model for Newtonian perturbations on S2, relativity appears to be strongest in a two-year interval around pericentre, in wavelet modes of timescale approximately 6 months.

  8. Clock Genes in Glia Cells

    Science.gov (United States)

    Chi-Castañeda, Donají

    2016-01-01

    Circadian rhythms are periodic patterns in biological processes that allow the organisms to anticipate changes in the environment. These rhythms are driven by the suprachiasmatic nucleus (SCN), the master circadian clock in vertebrates. At a molecular level, circadian rhythms are regulated by the so-called clock genes, which oscillate in a periodic manner. The protein products of clock genes are transcription factors that control their own and other genes’ transcription, collectively known as “clock-controlled genes.” Several brain regions other than the SCN express circadian rhythms of clock genes, including the amygdala, the olfactory bulb, the retina, and the cerebellum. Glia cells in these structures are expected to participate in rhythmicity. However, only certain types of glia cells may be called “glial clocks,” since they express PER-based circadian oscillators, which depend of the SCN for their synchronization. This contribution summarizes the current information about clock genes in glia cells, their plausible role as oscillators and their medical implications. PMID:27666286

  9. Somitogenesis clock-wave initiation requires differential decay and multiple binding sites for clock protein.

    Directory of Open Access Journals (Sweden)

    Mark Campanelli

    2010-04-01

    Full Text Available Somitogenesis is a process common to all vertebrate embryos in which repeated blocks of cells arise from the presomitic mesoderm (PSM to lay a foundational pattern for trunk and tail development. Somites form in the wake of passing waves of periodic gene expression that originate in the tailbud and sweep posteriorly across the PSM. Previous work has suggested that the waves result from a spatiotemporally graded control protein that affects the oscillation rate of clock-gene expression. With a minimally constructed mathematical model, we study the contribution of two control mechanisms to the initial formation of this gene-expression wave. We test four biologically motivated model scenarios with either one or two clock protein transcription binding sites, and with or without differential decay rates for clock protein monomers and dimers. We examine the sensitivity of wave formation with respect to multiple model parameters and robustness to heterogeneity in cell population. We find that only a model with both multiple binding sites and differential decay rates is able to reproduce experimentally observed waveforms. Our results show that the experimentally observed characteristics of somitogenesis wave initiation constrain the underlying genetic control mechanisms.

  10. Simulating Future GPS Clock Scenarios with Two Composite Clock Algorithms

    Science.gov (United States)

    2010-11-01

    Alexandria, Virginia), pp. 223-242. [8] C. A. Greenhall, 2007, “A Kalman filter clock ensemble algorithm that admits measurement noise,” Metrologia ...43, S311-S321. [9] J. A. Davis, C. A. Greenhall, and P. W. Stacey, 2005, “A Kalman filter clock algorithm for use in the presence of flicker frequency modulation noise,” Metrologia , 42, 1-10.

  11. Circadian clock components in the rat neocortex

    DEFF Research Database (Denmark)

    Rath, Martin Fredensborg; Rohde, Kristian; Fahrenkrug, Jan

    2013-01-01

    The circadian master clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the clock of the SCN is driven by a transcriptional/posttranslational autoregulatory network with clock gene products as core elements. Recent investigations...... have shown the presence of peripheral clocks in extra-hypothalamic areas of the central nervous system. However, knowledge on the clock gene network in the cerebral cortex is limited. We here show that the mammalian clock genes Per1, Per2, Per3, Cry1, Cry2, Bmal1, Clock, Nr1d1 and Dbp are expressed...

  12. Robust Manufacturing Control

    CERN Document Server

    2013-01-01

    This contributed volume collects research papers, presented at the CIRP Sponsored Conference Robust Manufacturing Control: Innovative and Interdisciplinary Approaches for Global Networks (RoMaC 2012, Jacobs University, Bremen, Germany, June 18th-20th 2012). These research papers present the latest developments and new ideas focusing on robust manufacturing control for global networks. Today, Global Production Networks (i.e. the nexus of interconnected material and information flows through which products and services are manufactured, assembled and distributed) are confronted with and expected to adapt to: sudden and unpredictable large-scale changes of important parameters which are occurring more and more frequently, event propagation in networks with high degree of interconnectivity which leads to unforeseen fluctuations, and non-equilibrium states which increasingly characterize daily business. These multi-scale changes deeply influence logistic target achievement and call for robust planning and control ...

  13. Clock and light regulation of the CREB coactivator CRTC1 in the suprachiasmatic circadian clock.

    Science.gov (United States)

    Sakamoto, Kensuke; Norona, Frances E; Alzate-Correa, Diego; Scarberry, Daniel; Hoyt, Kari R; Obrietan, Karl

    2013-05-22

    The CREB/CRE transcriptional pathway has been implicated in circadian clock timing and light-evoked clock resetting. To date, much of the work on CREB in circadian physiology has focused on how changes in the phosphorylation state of CREB regulate the timing processes. However, beyond changes in phosphorylation, CREB-dependent transcription can also be regulated by the CREB coactivator CRTC (CREB-regulated transcription coactivator), also known as TORC (transducer of regulated CREB). Here we profiled both the rhythmic and light-evoked regulation of CRTC1 and CRTC2 in the murine suprachiasmatic nucleus (SCN), the locus of the master mammalian clock. Immunohistochemical analysis revealed rhythmic expression of CRTC1 in the SCN. CRTC1 expression was detected throughout the dorsoventral extent of the SCN in the middle of the subjective day, with limited expression during early night, and late night expression levels intermediate between mid-day and early night levels. In contrast to CRTC1, robust expression of CRTC2 was detected during both the subjective day and night. During early and late subjective night, a brief light pulse induced strong nuclear accumulation of CRTC1 in the SCN. In contrast with CRTC1, photic stimulation did not affect the subcellular localization of CRTC2 in the SCN. Additionally, reporter gene profiling and chromatin immunoprecipitation analysis indicated that CRTC1 was associated with CREB in the 5' regulatory region of the period1 gene, and that overexpression of CRTC1 leads to a marked upregulation in period1 transcription. Together, these data raise the prospect that CRTC1 plays a role in fundamental aspects of SCN clock timing and entrainment.

  14. Einstein's Clocks and Langevin's Twins

    CERN Document Server

    Weinstein, Galina

    2012-01-01

    In 1905 Einstein presented the Clock Paradox and in 1911 Paul Langevin expanded Einstein's result to human observers, the "Twin Paradox." I will explain the crucial difference between Einstein and Langevin. Einstein did not present the so-called "Twin Paradox." Later Einstein continued to speak about the clock paradox. Einstein might not have been interested in the question: what happens to the observers themselves. The reason for this could be the following; Einstein dealt with measurement procedures, clocks and measuring rods. Einstein's observers were measuring time with these clocks and measuring rods. Einstein might not have been interested in so-called biology of the observers, whether these observers were getting older, younger, or whether they have gone any other changes; these changes appeared to be out of the scope of his "Principle of relativity" or kinematics. The processes and changes occurring within observers seemed to be good for philosophical discussions. Later writers criticized Einstein's c...

  15. History of early atomic clocks

    Energy Technology Data Exchange (ETDEWEB)

    Ramsey, N.F. [Harvard Univ., Cambridge, MA (United States). Lyman Lab. of Physics

    2005-06-01

    This review of the history of early atomic clocks includes early atomic beam magnetic resonance, methods of separated and successive oscillatory fields, microwave absorption, optical pumping and atomic masers. (author)

  16. A quantum network of clocks

    Science.gov (United States)

    Kómár, P.; Kessler, E. M.; Bishof, M.; Jiang, L.; Sørensen, A. S.; Ye, J.; Lukin, M. D.

    2014-08-01

    The development of precise atomic clocks plays an increasingly important role in modern society. Shared timing information constitutes a key resource for navigation with a direct correspondence between timing accuracy and precision in applications such as the Global Positioning System. By combining precision metrology and quantum networks, we propose a quantum, cooperative protocol for operating a network of geographically remote optical atomic clocks. Using nonlocal entangled states, we demonstrate an optimal utilization of global resources, and show that such a network can be operated near the fundamental precision limit set by quantum theory. Furthermore, the internal structure of the network, combined with quantum communication techniques, guarantees security both from internal and external threats. Realization of such a global quantum network of clocks may allow construction of a real-time single international time scale (world clock) with unprecedented stability and accuracy.

  17. Variations in Phase and Amplitude of Rhythmic Clock Gene Expression across Prefrontal Cortex, Hippocampus, Amygdala, and Hypothalamic Paraventricular and Suprachiasmatic Nuclei of Male and Female Rats.

    Science.gov (United States)

    Chun, Lauren E; Woodruff, Elizabeth R; Morton, Sarah; Hinds, Laura R; Spencer, Robert L

    2015-10-01

    The molecular circadian clock is a self-regulating transcription/translation cycle of positive (Bmal1, Clock/Npas2) and negative (Per1,2,3, Cry1,2) regulatory components. While the molecular clock has been well characterized in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), only a few studies have examined both the positive and negative clock components in extra-SCN brain tissue. Furthermore, there has yet to be a direct comparison of male and female clock gene expression in the brain. This comparison is warranted, as there are sex differences in circadian functioning and disorders associated with disrupted clock gene expression. This study examined basal clock gene expression (Per1, Per2, Bmal1 mRNA) in the SCN, prefrontal cortex (PFC), rostral agranular insula, hypothalamic paraventricular nucleus (PVN), amygdala, and hippocampus of male and female rats at 4-h intervals throughout a 12:12 h light:dark cycle. There was a significant rhythm of Per1, Per2, and Bmal1 in the SCN, PFC, insula, PVN, subregions of the hippocampus, and amygdala with a 24-h period, suggesting the importance of an oscillating molecular clock in extra-SCN brain regions. There were 3 distinct clock gene expression profiles across the brain regions, indicative of diversity among brain clocks. Although, generally, the clock gene expression profiles were similar between male and female rats, there were some sex differences in the robustness of clock gene expression (e.g., females had fewer robust rhythms in the medial PFC, more robust rhythms in the hippocampus, and a greater mesor in the medial amygdala). Furthermore, females with a regular estrous cycle had attenuated aggregate rhythms in clock gene expression in the PFC compared with noncycling females. This suggests that gonadal hormones may modulate the expression of the molecular clock.

  18. Stochastic models for atomic clocks

    Science.gov (United States)

    Barnes, J. A.; Jones, R. H.; Tryon, P. V.; Allan, D. W.

    1983-01-01

    For the atomic clocks used in the National Bureau of Standards Time Scales, an adequate model is the superposition of white FM, random walk FM, and linear frequency drift for times longer than about one minute. The model was tested on several clocks using maximum likelihood techniques for parameter estimation and the residuals were acceptably random. Conventional diagnostics indicate that additional model elements contribute no significant improvement to the model even at the expense of the added model complexity.

  19. The Renaissance or the cuckoo clock.

    Science.gov (United States)

    Pines, Jonathon; Hagan, Iain

    2011-12-27

    '…in Italy, for thirty years under the Borgias, they had warfare, terror, murder and bloodshed, but they produced Michelangelo, Leonardo da Vinci and the Renaissance. In Switzerland, they had brotherly love, they had five hundred years of democracy and peace-and what did that produce? The cuckoo clock'. Orson Welles as Harry Lime: The Third Man. Orson Welles might have been a little unfair on the Swiss, after all cuckoo clocks were developed in the Schwartzwald, but, more importantly, Swiss democracy gives remarkably stable government with considerable decision-making at the local level. The alternative is the battling city-states of Renaissance Italy: culturally rich but chaotic at a higher level of organization. As our understanding of the cell cycle improves, it appears that the cell is organized more along the lines of Switzerland than Renaissance Italy, and one major challenge is to determine how local decisions are made and coordinated to produce the robust cell cycle mechanisms that we observe in the cell as a whole.

  20. Phase-Shifting Effect of Light and Exercise on the Human Circadian Clock.

    Science.gov (United States)

    1992-02-29

    E. A twin study of the circadian and pulsatile variations of plasma cortisol: evidence for genetic control of the human circadian clock. Am J Physiol...Conference on Chronobiology , Irsee, Germany, September 29-October 4, 1991. Van Cauter, E. Effects of sleep on glucose regulation. Invited Speaker. Founding

  1. Simulation of the clock framework of Gaia

    CERN Document Server

    Castaneda, J; Portell, J; García-Berro, E; Luri, X; Castaneda, Javier; Gordo, Jose P.; Portell, Jordi; Garcia-Berro, Enrique; Luri, Xavier

    2005-01-01

    Gaia will perform astrometric measurements with an unprecedented resolution. Consequently, the electronics of the Astro instrument must time tag every measurement with a precision of a few nanoseconds. Hence, it requires a high stability clock signal, for which a Rb-type spacecraft master clock has been baselined. The distribution of its signal and the generation of clock subproducts must maintain these high accuracy requirements. We have developed a software application to simulate generic clock frameworks. The most critical clock structures for Gaia have also been identified, and its master clock has been parameterised.

  2. Molecular mechanisms underlying the Arabidopsis circadian clock.

    Science.gov (United States)

    Nakamichi, Norihito

    2011-10-01

    A wide range of biological processes exhibit circadian rhythm, enabling plants to adapt to the environmental day-night cycle. This rhythm is generated by the so-called 'circadian clock'. Although a number of genetic approaches have identified >25 clock-associated genes involved in the Arabidopsis clock mechanism, the molecular functions of a large part of these genes are not known. Recent comprehensive studies have revealed the molecular functions of several key clock-associated proteins. This progress has provided mechanistic insights into how key clock-associated proteins are integrated, and may help in understanding the essence of the clock's molecular mechanisms.

  3. Circadian clocks, epigenetics, and cancer

    KAUST Repository

    Masri, Selma

    2015-01-01

    The interplay between circadian rhythm and cancer has been suggested for more than a decade based on the observations that shift work and cancer incidence are linked. Accumulating evidence implicates the circadian clock in cancer survival and proliferation pathways. At the molecular level, multiple control mechanisms have been proposed to link circadian transcription and cell-cycle control to tumorigenesis.The circadian gating of the cell cycle and subsequent control of cell proliferation is an area of active investigation. Moreover, the circadian clock is a transcriptional system that is intricately regulated at the epigenetic level. Interestingly, the epigenetic landscape at the level of histone modifications, DNA methylation, and small regulatory RNAs are differentially controlled in cancer cells. This concept raises the possibility that epigenetic control is a common thread linking the clock with cancer, though little scientific evidence is known to date.This review focuses on the link between circadian clock and cancer, and speculates on the possible connections at the epigenetic level that could further link the circadian clock to tumor initiation or progression.

  4. Circadian clock proteins and immunity.

    Science.gov (United States)

    Curtis, Anne M; Bellet, Marina M; Sassone-Corsi, Paolo; O'Neill, Luke A J

    2014-02-20

    Immune parameters change with time of day and disruption of circadian rhythms has been linked to inflammatory pathologies. A circadian-clock-controlled immune system might allow an organism to anticipate daily changes in activity and feeding and the associated risk of infection or tissue damage to the host. Responses to bacteria have been shown to vary depending on time of infection, with mice being more at risk of sepsis when challenged ahead of their activity phase. Studies highlight the extent to which the molecular clock, most notably the core clock proteins BMAL1, CLOCK, and REV-ERBα, control fundamental aspects of the immune response. Examples include the BMAL1:CLOCK heterodimer regulating toll-like receptor 9 (TLR9) expression and repressing expression of the inflammatory monocyte chemokine ligand (CCL2) as well as REV-ERBα suppressing the induction of interleukin-6. Understanding the daily rhythm of the immune system could have implications for vaccinations and how we manage infectious and inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Quantitative monitoring of relative clock wander between signal and sampling sources in asynchronous optical under-sampling system

    Institute of Scientific and Technical Information of China (English)

    Huixing Zhang; Wei Zhao

    2012-01-01

    Optical performance monitoring using asynchronous optical or electrical sampling has gained considerable attention. Relative clock wander between data signal and sampling source is a typical occurrence in such systems. A method for the quantitative monitoring of the relative clock wander in asynchronous optical under-sampling system is presented. With a series of simulations, the clock wanders recovered using this method are in good agreement with the preset clock wanders of different amounts and frequencies for both RZ and NRZ signals. Hence, the reliability and robustness of the method are proven.%Optical performance monitoring using asynchronous optical or electrical sampling has gained considerable attention.Relative clock wander between data signal and sampling source is a typical occurrence in such systems.A method for the quantitative monitoring of the relative clock wander in asynchronous optical under-sampling system is presented.With a series of simulations,the clock wanders recovered using this method are in good agreement with the preset clock wanders of different amounts and frequencies for both RZ and NRZ signals.Hence,the reliability and robustness of the method are proven.

  6. Metabolic regulation of circadian clocks.

    Science.gov (United States)

    Haydon, Michael J; Hearn, Timothy J; Bell, Laura J; Hannah, Matthew A; Webb, Alex A R

    2013-05-01

    Circadian clocks are 24-h timekeeping mechanisms, which have evolved in plants, animals, fungi and bacteria to anticipate changes in light and temperature associated with the rotation of the Earth. The current paradigm to explain how biological clocks provide timing information is based on multiple interlocking transcription-translation negative feedback loops (TTFL), which drive rhythmic gene expression and circadian behaviour of growth and physiology. Metabolism is an important circadian output, which in plants includes photosynthesis, starch metabolism, nutrient assimilation and redox homeostasis. There is increasing evidence in a range of organisms that these metabolic outputs can also contribute to circadian timing and might also comprise independent circadian oscillators. In this review, we summarise the mechanisms of circadian regulation of metabolism by TTFL and consider increasing evidence that rhythmic metabolism contributes to the circadian network. We highlight how this might be relevant to plant circadian clock function.

  7. Types for X10 Clocks

    Directory of Open Access Journals (Sweden)

    Francisco Martins

    2011-10-01

    Full Text Available X10 is a modern language built from the ground up to handle future parallel systems, from multicore machines to cluster configurations. We take a closer look at a pair of synchronisation mechanisms: finish and clocks. The former waits for the termination of parallel computations, the latter allow multiple concurrent activities to wait for each other at certain points in time. In order to better understand these concepts we study a type system for a stripped down version of X10. The main result assures that well typed programs do not run into the errors identified in the X10 language reference, namely the ClockUseException. The study will open, we hope, doors to a more flexible utilisation of clocks in the X10 language.

  8. Synchronous clock stopper for microprocessor

    Science.gov (United States)

    Kitchin, David A. (Inventor)

    1985-01-01

    A synchronous clock stopper circuit for inhibiting clock pulses to a microprocessor in response to a stop request signal, and for reinstating the clock pulses in response to a start request signal thereby to conserve power consumption of the microprocessor when used in an environment of limited power. The stopping and starting of the microprocessor is synchronized, by a phase tracker, with the occurrences of a predetermined phase in the instruction cycle of the microprocessor in which the I/O data and address lines of the microprocessor are of high impedance so that a shared memory connected to the I/O lines may be accessed by other peripheral devices. The starting and stopping occur when the microprocessor initiates and completes, respectively, an instruction, as well as before and after transferring data with a memory. Also, the phase tracker transmits phase information signals over a bus to other peripheral devices which signals identify the current operational phase of the microprocessor.

  9. Robust Scientists

    DEFF Research Database (Denmark)

    Gorm Hansen, Birgitte

    2012-01-01

    as the analytical framework for descri bing the complex relationship between academic science and its so called “external” habitat. Although relational skills and adaptability do seem to be at the heart of successful research management, the key to success does not lie with the ability to assimilate to industrial...... knowledge", Danish research policy seems to have helped develop politically and economically "robust scientists". Scientific robustness is acquired by way of three strategies: 1) tasting and discriminating between resources so as to avoid funding that erodes academic profiles and push scientists away from...... and industrial intere sts. The paper concludes by stressing the potential danger of policy habitats who have promoted the evolution of robust scientists based on a competitive system where only the fittest survive. Robust scientists, it is argued, have the potential to become a new “invasive species...

  10. Colloquium: Physics of optical lattice clocks

    CERN Document Server

    Derevianko, Andrei

    2010-01-01

    Recently invented and demonstrated, optical lattice clocks hold great promise for improving the precision of modern timekeeping. These clocks aim at the 10^-18 fractional accuracy, which translates into a clock that would neither lose or gain a fraction of a second over an estimated age of the Universe. In these clocks, millions of atoms are trapped and interrogated simultaneously, dramatically improving clock stability. Here we discuss the principles of operation of these clocks and, in particular, a novel concept of "magic" trapping of atoms in optical lattices. We also highlight recently proposed microwave lattice clocks and several applications that employ the optical lattice clocks as a platform for precision measurements and quantum information processing.

  11. A circadian clock in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Eelderink-Chen, Zheng; Mazzotta, Gabriella; Sturre, Marcel; Bosman, Jasper; Roenneberg, Till; Merrow, Martha

    2010-01-01

    Circadian timing is a fundamental biological process, underlying cellular physiology in animals, plants, fungi, and cyanobacteria. Circadian clocks organize gene expression, metabolism, and behavior such that they occur at specific times of day. The biological clocks that orchestrate these daily

  12. Agile Blocker and Clock Jitter Tolerant Low-Power Frequency Selective Receiver with Energy Harvesting Capability.

    Science.gov (United States)

    Hasan, Abul; Helaoui, Mohamed; Ghannouchi, Fadhel M

    2017-08-29

    In this article, a novel tunable, blocker and clock jitter tolerant, low power, quadrature phase shift frequency selective (QPS-FS) receiver with energy harvesting capability is proposed. The receiver's design embraces and integrates (i) the baseband to radio frequency (RF) impedance translation concept to improve selectivity over that of conventional homodyne receiver topologies and (ii) broadband quadrature phase shift circuitry in the RF path to remove an active multi-phase clock generation circuit in passive mixer (PM) receivers. The use of a single local oscillator clock signal with a passive clock division network improves the receiver's robustness against clock jitter and reduces the source clock frequency by a factor of N, compared to PM receivers using N switches (N≥4). As a consequence, the frequency coverage of the QPS-FS receiver is improved by a factor of N, given a clock source of maximum frequency; and, the power consumption of the whole receiver system can eventually be reduced. The tunable QPS-FS receiver separates the wanted RF band signal from the unwanted blockers/interferers. The desired RF signal is frequency down-converted to baseband, while the undesired blocker/interferer signals are reflected by the receiver, collected and could be energy recycled using an auxiliary energy harvesting device.

  13. Development of a strontium optical lattice clock for the SOC mission on the ISS

    CERN Document Server

    Bongs, K; Smith, L; He, W; Kock, O; Swierad, D; Hughes, J; Schiller, S; Alighanbari, S; Origlia, S; Vogt, S; Sterr, U; Lisdat, Ch; Targat, R Le; Lodewyck, J; Holleville, D; Venon, B; Bize, S; Barwood, G P; Gill, P; Hill, I R; Ovchinnikov, Y B; Poli, N; Tino, G M; Stuhler, J; Kaenders, W

    2015-01-01

    Ultra-precise optical clocks in space will allow new studies in fundamental physics and astronomy. Within an European Space Agency (ESA) program, the Space Optical Clocks (SOC) project aims to install and to operate an optical lattice clock on the International Space Station (ISS) towards the end of this decade. It would be a natural follow-on to the ACES mission, improving its performance by at least one order of magnitude. The payload is planned to include an optical lattice clock, as well as a frequency comb, a microwave link, and an optical link for comparisons of the ISS clock with ground clocks located in several countries and continents. Within the EU-FP7-SPACE-2010-1 project no. 263500, during the years 2011-2015 a compact, modular and robust strontium lattice optical clock demonstrator has been developed. Goal performance is a fractional frequency instability below 1x10^{-15}, tau^{-1/2} and a fractional inaccuracy below 5x10^{-17}. Here we describe the current status of the apparatus' development, i...

  14. Normal heart rhythm is initiated and regulated by an intracellular calcium clock within pacemaker cells.

    Science.gov (United States)

    Maltsev, Victor A; Lakatta, Edward G

    2007-10-01

    For almost half a century it has been thought that the heart rhythm originates on the surface membrane of the cardiac pacemaker cells and is driven by voltage-gated ion channels (membrane clocks). Data from several recent studies, however, conclusively show that the rhythm is initiated, sustained, and regulated by oscillatory Ca(2+) releases (Ca(2+) clock) from the sarcoplasmic reticulum, a major Ca(2+) store within sinoatrial node cells, the primary heart's pacemakers. Activation of the local oscillatory Ca(2+) releases is independent of membrane depolarisation and driven by a high level of basal state phosphorylation of Ca(2+) cycling proteins. The releases produce Ca(2+) wavelets under the cell surface membrane during the later phase of diastolic depolarisation and activate the forward mode of Na(+)/Ca(2+) exchanger resulting in inward membrane current, which ignites an action potential. Phosphorylation-dependent gradation of speed at which Ca(2+) clock cycles is the essential regulatory mechanism of normal pacemaker rate and rhythm. The robust regulation of pacemaker function is insured by tight integration of Ca(2+) and membrane clocks: the action potential shape and ion fluxes are tuned by membrane clocks to sustain operation of the Ca(2+) clock which produces timely and powerful ignition of the membrane clocks to effect action potentials.

  15. A novel protein, CHRONO, functions as a core component of the mammalian circadian clock.

    Directory of Open Access Journals (Sweden)

    Akihiro Goriki

    2014-04-01

    Full Text Available Circadian rhythms are controlled by a system of negative and positive genetic feedback loops composed of clock genes. Although many genes have been implicated in these feedback loops, it is unclear whether our current list of clock genes is exhaustive. We have recently identified Chrono as a robustly cycling transcript through genome-wide profiling of BMAL1 binding on the E-box. Here, we explore the role of Chrono in cellular timekeeping. Remarkably, endogenous CHRONO occupancy around E-boxes shows a circadian oscillation antiphasic to BMAL1. Overexpression of Chrono leads to suppression of BMAL1-CLOCK activity in a histone deacetylase (HDAC -dependent manner. In vivo loss-of-function studies of Chrono including Avp neuron-specific knockout (KO mice display a longer circadian period of locomotor activity. Chrono KO also alters the expression of core clock genes and impairs the response of the circadian clock to stress. CHRONO forms a complex with the glucocorticoid receptor and mediates glucocorticoid response. Our comprehensive study spotlights a previously unrecognized clock component of an unsuspected negative circadian feedback loop that is independent of another negative regulator, Cry2, and that integrates behavioral stress and epigenetic control for efficient metabolic integration of the clock.

  16. Association between circadian clock genes and diapause incidence in Drosophila triauraria.

    Directory of Open Access Journals (Sweden)

    Hirokazu Yamada

    Full Text Available Diapause is an adaptive response triggered by seasonal photoperiodicity to overcome unfavorable seasons. The photoperiodic clock is a system that controls seasonal physiological processes, but our knowledge about its physiological mechanisms and genetic architecture remains incomplete. The circadian clock is another system that controls daily rhythmic physiological phenomena. It has been argued that there is a connection between the two clocks. To examine the genetic connection between them, we analyzed the associations of five circadian clock genes (period, timeless, Clock, cycle and cryptochrome with the occurrence of diapause in Drosophila triauraria, which shows a robust reproductive diapause with clear photoperiodicity. Non-diapause strains found in low latitudes were compared in genetic crosses with the diapause strain, in which the diapause trait is clearly dominant. Single nucleotide polymorphism and deletion analyses of the five circadian clock genes in backcross progeny revealed that allelic differences in timeless and cryptochrome between the strains were additively associated with the differences in the incidence of diapause. This suggests that there is a molecular link between certain circadian clock genes and the occurrence of diapause.

  17. Discrete gene replication events drive coupling between the cell cycle and circadian clocks.

    Science.gov (United States)

    Paijmans, Joris; Bosman, Mark; Ten Wolde, Pieter Rein; Lubensky, David K

    2016-04-12

    Many organisms possess both a cell cycle to control DNA replication and a circadian clock to anticipate changes between day and night. In some cases, these two rhythmic systems are known to be coupled by specific, cross-regulatory interactions. Here, we use mathematical modeling to show that, additionally, the cell cycle generically influences circadian clocks in a nonspecific fashion: The regular, discrete jumps in gene-copy number arising from DNA replication during the cell cycle cause a periodic driving of the circadian clock, which can dramatically alter its behavior and impair its function. A clock built on negative transcriptional feedback either phase-locks to the cell cycle, so that the clock period tracks the cell division time, or exhibits erratic behavior. We argue that the cyanobacterium Synechococcus elongatus has evolved two features that protect its clock from such disturbances, both of which are needed to fully insulate it from the cell cycle and give it its observed robustness: a phosphorylation-based protein modification oscillator, together with its accompanying push-pull read-out circuit that responds primarily to the ratios of different phosphoform concentrations, makes the clock less susceptible to perturbations in protein synthesis; the presence of multiple, asynchronously replicating copies of the same chromosome diminishes the effect of replicating any single copy of a gene.

  18. Single-transistor-clocked flip-flop

    Science.gov (United States)

    Zhao, Peiyi; Darwish, Tarek; Bayoumi, Magdy

    2005-08-30

    The invention provides a low power, high performance flip-flop. The flip-flop uses only one clocked transistor. The single clocked transistor is shared by the first and second branches of the device. A pulse generator produces a clock pulse to trigger the flip-flop. In one preferred embodiment the device can be made as a static explicit pulsed flip-flop which employs only two clocked transistors.

  19. Synchrony dynamics during initiation, failure, and rescue of the segmentation clock.

    Science.gov (United States)

    Riedel-Kruse, Ingmar H; Müller, Claudia; Oates, Andrew C

    2007-09-28

    The "segmentation clock" is thought to coordinate sequential segmentation of the body axis in vertebrate embryos. This clock comprises a multicellular genetic network of synchronized oscillators, coupled by intercellular Delta-Notch signaling. How this synchrony is established and how its loss determines the position of segmentation defects in Delta and Notch mutants are unknown. We analyzed the clock's synchrony dynamics by varying strength and timing of Notch coupling in zebra-fish embryos with techniques for quantitative perturbation of gene function. We developed a physical theory based on coupled phase oscillators explaining the observed onset and rescue of segmentation defects, the clock's robustness against developmental noise, and a critical point beyond which synchrony decays. We conclude that synchrony among these genetic oscillators can be established by simultaneous initiation and self-organization and that the segmentation defect position is determined by the difference between coupling strength and noise.

  20. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    R Daniel Rudic

    2004-11-01

    Full Text Available Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized. We demonstrate a role for Bmal1 and Clock in the regulation of glucose homeostasis. Inactivation of the known clock components Bmal1 (Mop3 and Clock suppress the diurnal variation in glucose and triglycerides. Gluconeogenesis is abolished by deletion of Bmal1 and is depressed in Clock mutants, but the counterregulatory response of corticosterone and glucagon to insulin-induced hypoglycaemia is retained. Furthermore, a high-fat diet modulates carbohydrate metabolism by amplifying circadian variation in glucose tolerance and insulin sensitivity, and mutation of Clock restores the chow-fed phenotype. Bmal1 and Clock, genes that function in the core molecular clock, exert profound control over recovery from insulin-induced hypoglycaemia. Furthermore, asynchronous dietary cues may modify glucose homeostasis via their interactions with peripheral molecular clocks.

  1. Light and the human circadian clock

    NARCIS (Netherlands)

    Roenneberg, Till; Kantermann, Thomas; Juda, Myriam; Vetter, Céline; Allebrandt, Karla V

    2013-01-01

    The circadian clock can only reliably fulfil its function if it is stably entrained. Most clocks use the light-dark cycle as environmental signal (zeitgeber) for this active synchronisation. How we think about clock function and entrainment has been strongly influenced by the early concepts of the

  2. Light and the human circadian clock

    NARCIS (Netherlands)

    Roenneberg, Till; Kantermann, Thomas; Juda, Myriam; Vetter, Céline; Allebrandt, Karla V

    2013-01-01

    The circadian clock can only reliably fulfil its function if it is stably entrained. Most clocks use the light-dark cycle as environmental signal (zeitgeber) for this active synchronisation. How we think about clock function and entrainment has been strongly influenced by the early concepts of the f

  3. Brain clock driven by neuropeptides and second messengers

    Science.gov (United States)

    Miro-Bueno, Jesus; Sosík, Petr

    2014-09-01

    The master circadian pacemaker in mammals is localized in a small portion of the brain called the suprachiasmatic nucleus (SCN). It is unclear how the SCN produces circadian rhythms. A common interpretation is that the SCN produces oscillations through the coupling of genetic oscillators in the neurons. The coupling is effected by a network of neuropeptides and second messengers. This network is crucial for the correct function of the SCN. However, models that study a possible oscillatory behavior of the network itself have received little attention. Here we propose and analyze a model to examine this oscillatory potential. We show that an intercellular oscillator emerges in the SCN as a result of the neuropeptide and second messenger dynamics. We find that this intercellular clock can produce circadian rhythms by itself with and without genetic clocks. We also found that the model is robust to perturbation of parameters and can be entrained by light-dark cycles.

  4. Activity clocks: spreading dynamics on temporal networks of human contact

    CERN Document Server

    Gauvin, Laetitia; Cattuto, Ciro; Barrat, Alain

    2013-01-01

    Dynamical processes on time-varying complex networks are key to un- derstanding and modeling a broad variety of processes in socio-technical systems. Here we focus on empirical temporal networks of human proxim- ity and we aim at understanding the factors that, in simulation, shape the arrival time distribution of simple spreading processes. Abandoning the notion of wall-clock time in favour of node-specific clocks based on activ- ity exposes robust statistical patterns in the arrival times across different social contexts. Using randomization strategies and generative models constrained by data, we show that these patterns can be understood in terms of heterogeneous inter-event time distributions coupled with hetero- geneous numbers of events per edge. We also show, both empirically and by using a synthetic dataset, that significant deviations from the above behavior can be caused by the presence of edge classes with strong activity correlations.

  5. Biological clocks: riding the tides.

    Science.gov (United States)

    de la Iglesia, Horacio O; Johnson, Carl Hirschie

    2013-10-21

    Animals with habitats in the intertidal zone often display biological rhythms that coordinate with both the tidal and the daily environmental cycles. Two recent studies show that the molecular components of the biological clocks mediating tidal rhythms are likely different from the phylogenetically conserved components that mediate circadian (daily) rhythms.

  6. A generalized gravitomagnetic clock effect

    CERN Document Server

    Hackmann, Eva

    2014-01-01

    In General Relativity the rotation of a gravitating body like the Earth influences the motion of orbiting test particles or satellites in a non-Newtonian way. This causes e.g. a precession of the orbital plane, known as the Lense-Thirring effect, and a precession of the spin of a gyroscope, known as the Schiff effect. Here we discuss a third effect, first introduced by Cohen and Mashhoon, called the gravitomagnetic clock effect. It describes the difference in proper time of counter revolving clocks after a revolution of $2\\pi$. For two clocks on counter rotating equatorial circular orbits around the Earth the effect is about $10^{-7}$ seconds per revolution, which is quite large. We introduce a general relativistic definition of the gravitomagnetic clock effect which is valid for arbitrary pairs of orbits. This includes rotations in the same direction and different initial conditions, which is crucial if the effect can be detected with existing satellites or with payloads on non-dedicated missions. We also de...

  7. Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder.

    Science.gov (United States)

    Bunney, B G; Li, J Z; Walsh, D M; Stein, R; Vawter, M P; Cartagena, P; Barchas, J D; Schatzberg, A F; Myers, R M; Watson, S J; Akil, H; Bunney, W E

    2015-02-01

    Conventional antidepressants require 2-8 weeks for a full clinical response. In contrast, two rapidly acting antidepressant interventions, low-dose ketamine and sleep deprivation (SD) therapy, act within hours to robustly decrease depressive symptoms in a subgroup of major depressive disorder (MDD) patients. Evidence that MDD may be a circadian-related illness is based, in part, on a large set of clinical data showing that diurnal rhythmicity (sleep, temperature, mood and hormone secretion) is altered during depressive episodes. In a microarray study, we observed widespread changes in cyclic gene expression in six regions of postmortem brain tissue of depressed patients matched with controls for time-of-death (TOD). We screened 12 000 transcripts and observed that the core clock genes, essential for controlling virtually all rhythms in the body, showed robust 24-h sinusoidal expression patterns in six brain regions in control subjects. In MDD patients matched for TOD with controls, the expression patterns of the clock genes in brain were significantly dysregulated. Some of the most robust changes were seen in anterior cingulate (ACC). These findings suggest that in addition to structural abnormalities, lesion studies, and the large body of functional brain imaging studies reporting increased activation in the ACC of depressed patients who respond to a wide range of therapies, there may be a circadian dysregulation in clock gene expression in a subgroup of MDDs. Here, we review human, animal and neuronal cell culture data suggesting that both low-dose ketamine and SD can modulate circadian rhythms. We hypothesize that the rapid antidepressant actions of ketamine and SD may act, in part, to reset abnormal clock genes in MDD to restore and stabilize circadian rhythmicity. Conversely, clinical relapse may reflect a desynchronization of the clock, indicative of a reactivation of abnormal clock gene function. Future work could involve identifying specific small

  8. Unraveling the circadian clock in Arabidopsis.

    Science.gov (United States)

    Wang, Xiaoxue; Ma, Ligeng

    2013-02-01

    The circadian clock is an endogenous timing system responsible for coordinating an organism's biological processes with its environment. Interlocked transcriptional feedback loops constitute the fundamental architecture of the circadian clock. In Arabidopsis, three feedback loops, the core loop, morning loop and evening loop, comprise a network that is the basis of the circadian clock. The components of these three loops are regulated in distinct ways, including transcriptional, post-transcriptional and posttranslational mechanisms. The discovery of the DNA-binding and repressive activities of TOC1 has overturned our initial concept of its function in the circadian clock. The alternative splicing of circadian clock-related genes plays an essential role in normal functioning of the clock and enables organisms to sense environmental changes. In this review, we describe the regulatory mechanisms of the circadian clock that have been identified in Arabidopsis.

  9. Circadian clock, cell cycle and cancer

    Directory of Open Access Journals (Sweden)

    Cansu Özbayer

    2011-12-01

    Full Text Available There are a few rhythms of our daily lives that we are under the influence. One of them is characterized by predictable changes over a 24-hour timescale called circadian clock. This cellular clock is coordinated by the suprachiasmatic nucleus in the anterior hypothalamus. The clock consist of an autoregulatory transcription-translation feedback loop compose of four genes/proteins; BMAL1, Clock, Cyrptochrome, and Period. BMAL 1 and Clock are transcriptional factors and Period and Cyrptochrome are their targets. Period and Cyrptochrome dimerize in the cytoplasm to enter the nucleus where they inhibit Clock/BMAL activity.It has been demonstrate that circadian clock plays an important role cellular proliferation, DNA damage and repair mechanisms, checkpoints, apoptosis and cancer.

  10. The 1993 Gordon Research Conference on Chronobiology

    Science.gov (United States)

    Schwartz, William J.

    1993-01-01

    The study of biological timekeeping is now at a particularly fertile stage, encompassing multiple levels of biological organization, recruiting a wide array of disciplines and methodologies and uniting a host of investigators. This report summarizes a research conference on Chronobiology. Some of the topics focused on transcriptional and translational mechanisms of circadian rhythmicity, with discussions of putative 'clock genes' in cyanobacteria, algae, fungi, fruitflies, and hamsters. Cellular analysis, with emphasis on photoreceptors in frogs, neurons in molluscs, and testis in moths was addressed. New methods for investigating the circadian clock in the suprachiasmatic nucleus were introduced.

  11. Robust Chaos

    CERN Document Server

    Banerjee, S; Grebogi, C; Banerjee, Soumitro; Yorke, James A.; Grebogi, Celso

    1998-01-01

    It has been proposed to make practical use of chaos in communication, in enhancing mixing in chemical processes and in spreading the spectrum of switch-mode power suppies to avoid electromagnetic interference. It is however known that for most smooth chaotic systems, there is a dense set of periodic windows for any range of parameter values. Therefore in practical systems working in chaotic mode, slight inadvertent fluctuation of a parameter may take the system out of chaos. We say a chaotic attractor is robust if, for its parameter values there exists a neighborhood in the parameter space with no periodic attractor and the chaotic attractor is unique in that neighborhood. In this paper we show that robust chaos can occur in piecewise smooth systems and obtain the conditions of its occurrence. We illustrate this phenomenon with a practical example from electrical engineering.

  12. Robust Econometrics

    OpenAIRE

    Čίžek, Pavel; Härdle, Wolfgang Karl

    2006-01-01

    Econometrics often deals with data under, from the statistical point of view, non-standard conditions such as heteroscedasticity or measurement errors and the estimation methods need thus be either adopted to such conditions or be at least insensitive to them. The methods insensitive to violation of certain assumptions, for example insensitive to the presence of heteroscedasticity, are in a broad sense referred to as robust (e.g., to heteroscedasticity). On the other hand, there is also a mor...

  13. Entanglement of quantum clocks through gravity.

    Science.gov (United States)

    Castro Ruiz, Esteban; Giacomini, Flaminia; Brukner, Časlav

    2017-03-21

    In general relativity, the picture of space-time assigns an ideal clock to each world line. Being ideal, gravitational effects due to these clocks are ignored and the flow of time according to one clock is not affected by the presence of clocks along nearby world lines. However, if time is defined operationally, as a pointer position of a physical clock that obeys the principles of general relativity and quantum mechanics, such a picture is, at most, a convenient fiction. Specifically, we show that the general relativistic mass-energy equivalence implies gravitational interaction between the clocks, whereas the quantum mechanical superposition of energy eigenstates leads to a nonfixed metric background. Based only on the assumption that both principles hold in this situation, we show that the clocks necessarily get entangled through time dilation effect, which eventually leads to a loss of coherence of a single clock. Hence, the time as measured by a single clock is not well defined. However, the general relativistic notion of time is recovered in the classical limit of clocks.

  14. Physical Layer Ethernet Clock Synchronization

    Science.gov (United States)

    2010-11-01

    42 nd Annual Precise Time and Time Interval (PTTI) Meeting 77 PHYSICAL LAYER ETHERNET CLOCK SYNCHRONIZATION Reinhard Exel , Georg...5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...Austrian Academy of Sciences Viktor Kaplan StraÃe 2, A-2700 Wiener Neustadt, Austria 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING

  15. Inertial Frames and Clock Rates

    CERN Document Server

    Kak, Subhash

    2012-01-01

    This article revisits the historiography of the problem of inertial frames. Specifically, the case of the twins in the clock paradox is considered to see that some resolutions implicitly assume inertiality for the non-accelerating twin. If inertial frames are explicitly identified by motion with respect to the large scale structure of the universe, it makes it possible to consider the relative inertiality of different frames.

  16. Researchers Discover Plants Biological Clock

    Institute of Scientific and Technical Information of China (English)

    王全良

    1996-01-01

    Scientists who created glow-in-the-dark plants by shooting up seedlingswith firefly DNA have identified the first biological clock gene in plants. Discovery of the timepiece gene, which controls such biological rhythmsas daily leaf movements and proe openings, flower-blooming schedules andphotosynthesis cycles, could lead to a host of applications in ornamental horti-culture, agriculture and even human health. Many researchers believe that

  17. Microresonator Frequency Comb Optical Clock

    Science.gov (United States)

    2014-07-22

    Number Microresonator frequency comb optical clock Block 13: Supplementary Note © 2014 . Published in Optica , Vol. Ed. 0 1, (1) (2014), (, (1). DoD...Oscillators. http://dx.doi.org/10.1364/ OPTICA .1.000010 1. INTRODUCTION Optical frequency combs enable extraordinary measurement precision and accuracy...1, No. 1 / July 2014 / Optica 10 deviation for 1 s averaging is completely dominated by the Rb reference, and the microcomb contribution is only ɚ

  18. Cellular circadian clocks in mood disorders.

    Science.gov (United States)

    McCarthy, Michael J; Welsh, David K

    2012-10-01

    Bipolar disorder (BD) and major depressive disorder (MDD) are heritable neuropsychiatric disorders associated with disrupted circadian rhythms. The hypothesis that circadian clock dysfunction plays a causal role in these disorders has endured for decades but has been difficult to test and remains controversial. In the meantime, the discovery of clock genes and cellular clocks has revolutionized our understanding of circadian timing. Cellular circadian clocks are located in the suprachiasmatic nucleus (SCN), the brain's primary circadian pacemaker, but also throughout the brain and peripheral tissues. In BD and MDD patients, defects have been found in SCN-dependent rhythms of body temperature and melatonin release. However, these are imperfect and indirect indicators of SCN function. Moreover, the SCN may not be particularly relevant to mood regulation, whereas the lateral habenula, ventral tegmentum, and hippocampus, which also contain cellular clocks, have established roles in this regard. Dysfunction in these non-SCN clocks could contribute directly to the pathophysiology of BD/MDD. We hypothesize that circadian clock dysfunction in non-SCN clocks is a trait marker of mood disorders, encoded by pathological genetic variants. Because network features of the SCN render it uniquely resistant to perturbation, previous studies of SCN outputs in mood disorders patients may have failed to detect genetic defects affecting non-SCN clocks, which include not only mood-regulating neurons in the brain but also peripheral cells accessible in human subjects. Therefore, reporters of rhythmic clock gene expression in cells from patients or mouse models could provide a direct assay of the molecular gears of the clock, in cellular clocks that are likely to be more representative than the SCN of mood-regulating neurons in patients. This approach, informed by the new insights and tools of modern chronobiology, will allow a more definitive test of the role of cellular circadian clocks

  19. Hanle Detection for Optical Clocks

    Directory of Open Access Journals (Sweden)

    Xiaogang Zhang

    2015-01-01

    Full Text Available Considering the strong inhomogeneous spatial polarization and intensity distribution of spontaneous decay fluorescence due to the Hanle effect, we propose and demonstrate a universe Hanle detection configuration of electron-shelving method for optical clocks. Experimental results from Ca atomic beam optical frequency standard with electron-shelving method show that a designed Hanle detection geometry with optimized magnetic field direction, detection laser beam propagation and polarization direction, and detector position can improve the fluorescence collection rate by more than one order of magnitude comparing with that of inefficient geometry. With the fixed 423 nm fluorescence, the improved 657 nm optical frequency standard signal intensity is presented. The potential application of the Hanle detection geometry designed for facilitating the fluorescence collection for optical lattice clock with a limited solid angle of the fluorescence collection has been discussed. The Hanle detection geometry is also effective for ion detection in ion optical clock and quantum information experiments. Besides, a cylinder fluorescence collection structure is designed to increase the solid angle of the fluorescence collection in Ca atomic beam optical frequency standard.

  20. Molecular clock is involved in predictive circadian adjustment of renal function.

    Science.gov (United States)

    Zuber, Annie Mercier; Centeno, Gabriel; Pradervand, Sylvain; Nikolaeva, Svetlana; Maquelin, Lionel; Cardinaux, Léonard; Bonny, Olivier; Firsov, Dmitri

    2009-09-22

    Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e., distal convoluted tubule (DCT) and connecting tubule (CNT) and the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf, and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms, and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function.

  1. The Implementation of E1 Clock Recovery

    Directory of Open Access Journals (Sweden)

    Wang Ziyu

    2016-01-01

    Full Text Available Clock transform and recovery is of significant importance in microwave TDM service, and it is always extracted from the E1 line data stream in most cases. However, intrinsically uncertain delay and jitter caused by packet transmission of E1 data information, may lead to the indexes of the data recovery clock exceed the clock performance template. Through analysis of the E1 clock indexes and measuring methods, this paper proposes a new clock recovery method. The method employs two buffers, the first RAM is used as a buffer to deduct excess information, and the second FIFO is used as a buffer to recovery the clock and data. The first buffer has a feedback from the second one, and is able to actively respond to changes in the data link and requests from the second one. The test results validate the effectiveness of the method, and the corresponding scheme is also valuable for the other communication systems.

  2. The circadian clock coordinates ribosome biogenesis.

    Directory of Open Access Journals (Sweden)

    Céline Jouffe

    Full Text Available Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis.

  3. Optical to microwave clock frequency ratios with a nearly continuous strontium optical lattice clock

    CERN Document Server

    Lodewyck, Jérôme; Bookjans, Eva; Robyr, Jean-Luc; Shi, Chunyan; Vallet, Grégoire; Targat, Rodolphe Le; Nicolodi, Daniele; Coq, Yann Le; Guéna, Jocelyne; Abgrall, Michel; Rosenbusch, Peter; Bize, Sébastien

    2016-01-01

    Optical lattice clocks are at the forefront of frequency metrology. Both the instability and systematic uncertainty of these clocks have been reported to be two orders of magnitude smaller than the best microwave clocks. For this reason, a redefinition of the SI second based on optical clocks seems possible in the near future. However, the operation of optical lattice clocks has not yet reached the reliability that microwave clocks have achieved so far. In this paper, we report on the operation of a strontium optical lattice clock that spans several weeks, with more than 80% uptime. We make use of this long integration time to demonstrate a reproducible measurement of frequency ratios between the strontium clock transition and microwave Cs primary and Rb secondary frequency standards.

  4. Collisionally induced atomic clock shifts and correlations

    Energy Technology Data Exchange (ETDEWEB)

    Band, Y. B.; Osherov, I. [Departments of Chemistry and Electro-Optics and the Ilse Katz Center for Nano-Science, Ben-Gurion University, Beer-Sheva 84105 (Israel)

    2011-07-15

    We develop a formalism to incorporate exchange symmetry considerations into the calculation of collisional frequency shifts for atomic clocks using a density-matrix formalism. The formalism is developed for both fermionic and bosonic atomic clocks. Numerical results for a finite-temperature {sup 87}Sr {sup 1}S{sub 0} (F=9/2) atomic clock in a magic wavelength optical lattice are presented.

  5. Molecular Mechanisms Underlying the Arabidopsis Circadian Clock

    OpenAIRE

    Nakamichi, Norihito

    2011-01-01

    A wide range of biological processes exhibit circadian rhythm, enabling plants to adapt to the environmental day–night cycle. This rhythm is generated by the so-called ‘circadian clock’. Although a number of genetic approaches have identified >25 clock-associated genes involved in the Arabidopsis clock mechanism, the molecular functions of a large part of these genes are not known. Recent comprehensive studies have revealed the molecular functions of several key clock-associated proteins. Thi...

  6. The Square Light Clock and Special Relativity

    Science.gov (United States)

    Galli, J. Ronald; Amiri, Farhang

    2012-01-01

    A thought experiment that includes a square light clock is similar to the traditional vertical light beam and mirror clock, except it is made up of four mirrors placed at a 45[degree] angle at each corner of a square of length L[subscript 0], shown in Fig. 1. Here we have shown the events as measured in the rest frame of the square light clock. By…

  7. A Mathematical Model of the Liver Circadian Clock Linking Feeding and Fasting Cycles to Clock Function

    OpenAIRE

    Aurore Woller; Hélène Duez; Bart Staels; Marc Lefranc

    2016-01-01

    To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding and fasting cycles have been associated with clock disruption and metabolic diseases; however, the mechanisms are unclear. To address this question, we have constructed a mathematical model of the mammalian circadian clock, incorporating the metabolic sensors SIRT1 and AMPK. The clock response to various tem...

  8. Distinction between Clock and Time, and a Suggested Experiment with Different Types of Clocks in GPS

    Science.gov (United States)

    Smarandache, Florentin

    2013-03-01

    The clock is an instrument for measuring the time, instrument that may not run perfectly (accurately) under certain conditions (like, say, in strong electromagnetic field, in strong gravitational field, in extremely high or low temperature, pressure, etc.), but this does not mean that time itself runs slower or faster as Einstein's Theory of Relativity asserts. We are referring to an absolute time, i.e. time measured not with respect to ether or non-ether, but with respect to an absolute mathematical reference frame. Several types of clocks could run at a more slowly rate in a moving frame of reference than other types of clocks; it depends on the construction material and functioning principle of each type of clock. Relativists say that ``gravity slows time''. This is incorrect, since actually gravity slows today's types of clocks. And one type of clock is slowed more or less than another type of clock. Not only gravity but other (electric, magnetic, etc.) fields or various medium composition elements or structures may slow or accelerate clocks that are in that medium. The clocks used today in the satellites for the GPS necessitate a correction with respect to the Earth clocks. But in the future, when new types of clocks will be built based on different construction material and functioning principle, the correction of the GPS clocks would be different. In order to make the distinction between ``clock'' and ``time'', we suggest a Experiment # 1 with different types of clocks for the GPS clocks, in order to prove that the resulted dilation and contraction factors are different from those obtained with today's cesium atomic clock.

  9. Song I-Yeong's Armillary Clock

    Science.gov (United States)

    Kim, Sang Hyuk; Lee, Yong Sam

    In 1669 (the 10th year of the reign of King Hyeonjong), Song I-Yeong (宋以穎, 1619-1692), who was a professor of astronomy at Gwansanggam (Bureau of Astronomy), developed the armillary clock which uses the weight power system of an alarm clock. The armillary clock is a unique astronomical clock that combines the traditional armillary sphere of Joseon and the principle of a Western alarm clock. Song I-Yeong's armillary clock was repaired in 1687-1688 according to the records, and since then not much is known about the history of the armillary clock. After many years, in the early 1930s which was the Japanese colonial era, Inchon (仁村) Kim Seong-Su (金性洙, 1891-1955) purchased the armillary clock at the Insa-dong antique street and donated to the Korea University Museum of the present time (designated as National Treasure No. 230 in 1985). Currently, the armillary clock is not in operation because some of the parts are damaged or lost.

  10. Clock genes, pancreatic function, and diabetes.

    Science.gov (United States)

    Vieira, Elaine; Burris, Thomas P; Quesada, Ivan

    2014-12-01

    Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic β cells, glucose homeostasis, and diabetes.

  11. The contributions of interlocking loops and extensive nonlinearity to the properties of circadian clock models.

    Directory of Open Access Journals (Sweden)

    Treenut Saithong

    Full Text Available BACKGROUND: Sensitivity and robustness are essential properties of circadian clock systems, enabling them to respond to the environment but resist noisy variations. These properties should be recapitulated in computational models of the circadian clock. Highly nonlinear kinetics and multiple loops are often incorporated into models to match experimental time-series data, but these also impact on model properties for clock models. METHODOLOGY/PRINCIPAL FINDINGS: Here, we study the consequences of complicated structure and nonlinearity using simple Goodwin-type oscillators and the complex Arabidopsis circadian clock models. Sensitivity analysis of the simple oscillators implies that an interlocked multi-loop structure reinforces sensitivity/robustness properties, enhancing the response to external and internal variations. Furthermore, we found that reducing the degree of nonlinearity could sometimes enhance the robustness of models, implying that ad hoc incorporation of nonlinearity could be detrimental to a model's perceived credibility. CONCLUSION: The correct multi-loop structure and degree of nonlinearity are therefore critical in contributing to the desired properties of a model as well as its capacity to match experimental data.

  12. Human intestinal circadian clock: expression of clock genes in colonocytes lining the crypt.

    Science.gov (United States)

    Pardini, L; Kaeffer, B; Trubuil, A; Bourreille, A; Galmiche, J-P

    2005-01-01

    Biological clock components have been detected in many epithelial tissues of the digestive tract of mammals (oral mucosa, pancreas, and liver), suggesting the existence of peripheral circadian clocks that may be entrainable by food. Our aim was to investigate the expression of main peripheral clock genes in colonocytes of healthy humans and in human colon carcinoma cell lines. The presence of clock components was investigated in single intact colonic crypts isolated by chelation from the biopsies of 25 patients (free of any sign of colonic lesions) undergoing routine colonoscopy and in cell lines of human colon carcinoma (Caco2 and HT29 clone 19A). Per-1, per-2, and clock mRNA were detected by real-time RT-PCR. The three-dimensional distributions of PER-1, PER-2, CLOCK, and BMAL1 proteins were recorded along colonic crypts by immunofluorescent confocal imaging. We demonstrate the presence of per-1, per-2, and clock mRNA in samples prepared from colonic crypts of 5 patients and in all cell lines. We also demonstrate the presence of two circadian clock proteins, PER-1 and CLOCK, in human colonocytes on crypts isolated from 20 patients (15 patients for PER-1 and 6 for CLOCK) and in colon carcinoma cells. Establishing the presence of clock proteins in human colonic crypts is the first step toward the study of the regulation of the intestinal circadian clock by nutrients and feeding rhythms.

  13. A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

    Science.gov (United States)

    Chen, Bor-Sen; Lin, Ying-Po

    2013-01-01

    Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental

  14. Robust Scientists

    DEFF Research Database (Denmark)

    Gorm Hansen, Birgitte

    The concepts of “socially robust knowledge” and “mode 2 knowledge production” (Nowotny 2003, Gibbons et al. 1994) have migrated from STS into research policy practices. Both STS-scholars and policy makers have been known to propomote the idea that the way forward for today’s scientist is to jump...... from the ivory tower and learn how to create high-flying synergies with citizens, corporations and governments. In STS as well as in Danish research policy it has thus been argued that scientists will gain more support and enjoy greater success in their work by “externalizing” their research...... and adapting their interests to the needs of outside actors. However, when studying the concrete strategies of such successful scientists, matters seem a bit more complicated. Based on interviews with a plant biologist working in GMO the paper uses the biological concepts of field participants...

  15. Robust factorization

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Fisker, Rune; Åström, Kalle;

    2002-01-01

    Factorization algorithms for recovering structure and motion from an image stream have many advantages, but they usually require a set of well-tracked features. Such a set is in generally not available in practical applications. There is thus a need for making factorization algorithms deal...... effectively with errors in the tracked features. We propose a new and computationally efficient algorithm for applying an arbitrary error function in the factorization scheme. This algorithm enables the use of robust statistical techniques and arbitrary noise models for the individual features....... These techniques and models enable the factorization scheme to deal effectively with mismatched features, missing features, and noise on the individual features. The proposed approach further includes a new method for Euclidean reconstruction that significantly improves convergence of the factorization algorithms...

  16. Uncertainty principle in larmor clock

    Institute of Scientific and Technical Information of China (English)

    QIAO Chuan; REN Zhong-Zhou

    2011-01-01

    It is well known that the spin operators of a quantum particle must obey uncertainty relations.We use the uncertainty principle to study the Larmor clock.To avoid breaking the uncertainty principle,Larmor time can be defined as the ratio of the phase difference between a spin-up particle and a spin-down particle to the corresponding Larmor frequency.The connection between the dwell time and the Larmor time has also been confirmed.Moreover,the results show that the behavior of the Larmor time depends on the height and width of the barrier.

  17. Clock genes, chronotypes and diseases

    Directory of Open Access Journals (Sweden)

    Bogdan I. Voinescu

    2009-08-01

    Full Text Available Many common diseases in humans (such as cancer, heart disease, diabetes mellitus orpsychiatric disorders, such as depression seem to be linked to disruptions of circadian cycles and toclock genes variation. It is unlikely that such diseases to be caused by a genetic variation within a singlegene. They must be influenced by complex interactions among multiple genes, as well as environmentaland lifestyle factors. Therefore, it is important to understand how the resulting perturbations in ourcircadian biology could affect our physiological processes and susceptibility to disease. Associationsbetween the polymorphisms of the main components of the circadian molecular clock, circadian type(also known as diurnal preference or chronotype and diseases are presented.

  18. Gigabit Ethernet Asynchronous Clock Compensation FIFO

    Science.gov (United States)

    Duhachek, Jeff

    2012-01-01

    Clock compensation for Gigabit Ethernet is necessary because the clock recovered from the 1.25 Gb/s serial data stream has the potential to be 200 ppm slower or faster than the system clock. The serial data is converted to 10-bit parallel data at a 125 MHz rate on a clock recovered from the serial data stream. This recovered data needs to be processed by a system clock that is also running at a nominal rate of 125 MHz, but not synchronous to the recovered clock. To cross clock domains, an asynchronous FIFO (first-in-first-out) is used, with the write pointer (wprt) in the recovered clock domain and the read pointer (rptr) in the system clock domain. Because the clocks are generated from separate sources, there is potential for FIFO overflow or underflow. Clock compensation in Gigabit Ethernet is possible by taking advantage of the protocol data stream features. There are two distinct data streams that occur in Gigabit Ethernet where identical data is transmitted for a period of time. The first is configuration, which happens during auto-negotiation. The second is idle, which occurs at the end of auto-negotiation and between every packet. The identical data in the FIFO can be repeated by decrementing the read pointer, thus compensating for a FIFO that is draining too fast. The identical data in the FIFO can also be skipped by incrementing the read pointer, which compensates for a FIFO draining too slowly. The unique and novel features of this FIFO are that it works in both the idle stream and the configuration streams. The increment or decrement of the read pointer is different in the idle and compensation streams to preserve disparity. Another unique feature is that the read pointer to write pointer difference range changes between compensation and idle to minimize FIFO latency during packet transmission.

  19. Circadian molecular clock in lung pathophysiology.

    Science.gov (United States)

    Sundar, Isaac K; Yao, Hongwei; Sellix, Michael T; Rahman, Irfan

    2015-11-15

    Disrupted daily or circadian rhythms of lung function and inflammatory responses are common features of chronic airway diseases. At the molecular level these circadian rhythms depend on the activity of an autoregulatory feedback loop oscillator of clock gene transcription factors, including the BMAL1:CLOCK activator complex and the repressors PERIOD and CRYPTOCHROME. The key nuclear receptors and transcription factors REV-ERBα and RORα regulate Bmal1 expression and provide stability to the oscillator. Circadian clock dysfunction is implicated in both immune and inflammatory responses to environmental, inflammatory, and infectious agents. Molecular clock function is altered by exposomes, tobacco smoke, lipopolysaccharide, hyperoxia, allergens, bleomycin, as well as bacterial and viral infections. The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors. Environmental agents and redox modulation may alter the levels of REV-ERBα and RORα in lung tissue in association with a heightened DNA damage response, cellular senescence, and inflammation. A reciprocal relationship exists between the molecular clock and immune/inflammatory responses in the lungs. Molecular clock function in lung cells may be used as a biomarker of disease severity and exacerbations or for assessing the efficacy of chronotherapy for disease management. Here, we provide a comprehensive overview of clock-controlled cellular and molecular functions in the lungs and highlight the repercussions of clock disruption on the pathophysiology of chronic airway diseases and their exacerbations. Furthermore, we highlight the potential for the molecular clock as a novel chronopharmacological target for the management of lung pathophysiology.

  20. Arabidopsis circadian clock and photoperiodism: time to think about location

    OpenAIRE

    Imaizumi, Takato

    2009-01-01

    Plants possess a circadian clock that enables them to coordinate internal biological events with external daily changes. Recent studies in Arabidopsis revealed that tissue specific clock components exist and that the clock network architecture also varies within different organs. These findings indicate that the makeup of circadian clock(s) within a plant is quite variable. Plants utilize the circadian clock to measure day-length changes for regulating seasonal responses, such as flowering. T...

  1. Global synchronization of parallel processors using clock pulse width modulation

    Science.gov (United States)

    Chen, Dong; Ellavsky, Matthew R.; Franke, Ross L.; Gara, Alan; Gooding, Thomas M.; Haring, Rudolf A.; Jeanson, Mark J.; Kopcsay, Gerard V.; Liebsch, Thomas A.; Littrell, Daniel; Ohmacht, Martin; Reed, Don D.; Schenck, Brandon E.; Swetz, Richard A.

    2013-04-02

    A circuit generates a global clock signal with a pulse width modification to synchronize processors in a parallel computing system. The circuit may include a hardware module and a clock splitter. The hardware module may generate a clock signal and performs a pulse width modification on the clock signal. The pulse width modification changes a pulse width within a clock period in the clock signal. The clock splitter may distribute the pulse width modified clock signal to a plurality of processors in the parallel computing system.

  2. Fast Clock Recovery for Digital Communications

    Science.gov (United States)

    Tell, R. G.

    1985-01-01

    Circuit extracts clock signal from random non-return-to-zero data stream, locking onto clock within one bit period at 1-gigabitper-second data rate. Circuit used for synchronization in opticalfiber communications. Derives speed from very short response time of gallium arsenide metal/semiconductor field-effect transistors (MESFET's).

  3. Could Atomic clocks be affected by neutrinos?

    CERN Document Server

    Hanafi, Hanaa

    2016-01-01

    An atomic clock is a clock device that uses an electronic transition frequency of the electromagnetic spectrum of atoms as a frequency standard in order to derive a time standard since time is the reciprocal of frequency. If the electronic transition frequencies are in an "optical region", we are talking in this case about optical atomic clocks. If they are in an "microwave region" these atomic clocks are made of the metallic element cesium so they are called Cesium atomic clocks. Atomic clocks are the most accurate time and frequency standards known despite the different perturbations that can affect them, a lot of researches were made in this domain to show how the transitions can be different for different type of perturbations..Since atomic clocks are very sensitive devices, based on coherent states (A coherent state tends to loose coherence after interacting). One question can arise (from a lot of questions) which is why cosmic neutrinos are not affecting these clocks? The answer to this question requir...

  4. Internal Clock Drift Estimation in Computer Clusters

    Directory of Open Access Journals (Sweden)

    Hicham Marouani

    2008-01-01

    Full Text Available Most computers have several high-resolution timing sources, from the programmable interrupt timer to the cycle counter. Yet, even at a precision of one cycle in ten millions, clocks may drift significantly in a single second at a clock frequency of several GHz. When tracing the low-level system events in computer clusters, such as packet sending or reception, each computer system records its own events using an internal clock. In order to properly understand the global system behavior and performance, as reported by the events recorded on each computer, it is important to estimate precisely the clock differences and drift between the different computers in the system. This article studies the clock precision and stability of several computer systems, with different architectures. It also studies the typical network delay characteristics, since time synchronization algorithms rely on the exchange of network packets and are dependent on the symmetry of the delays. A very precise clock, based on the atomic time provided by the GPS satellite network, was used as a reference to measure clock drifts and network delays. The results obtained are of immediate use to all applications which depend on computer clocks or network time synchronization accuracy.

  5. Temperature influences in receiver clock modelling

    Science.gov (United States)

    Wang, Kan; Meindl, Michael; Rothacher, Markus; Schoenemann, Erik; Enderle, Werner

    2016-04-01

    In Precise Point Positioning (PPP), hardware delays at the receiver site (receiver, cables, antenna, …) are always difficult to be separated from the estimated receiver clock parameters. As a result, they are partially or fully contained in the estimated "apparent" clocks and will influence the deterministic and stochastic modelling of the receiver clock behaviour. In this contribution, using three years of data, the receiver clock corrections of a set of high-precision Hydrogen Masers (H-Masers) connected to stations of the ESA/ESOC network and the International GNSS Service (IGS) are firstly characterized concerning clock offsets, drifts, modified Allan deviations and stochastic parameters. In a second step, the apparent behaviour of the clocks is modelled with the help of a low-order polynomial and a known temperature coefficient (Weinbach, 2013). The correlations between the temperature and the hardware delays generated by different types of antennae are then analysed looking at daily, 3-day and weekly time intervals. The outcome of these analyses is crucial, if we intend to model the receiver clocks in the ground station network to improve the estimation of station-related parameters like coordinates, troposphere zenith delays and ambiguities. References: Weinbach, U. (2013) Feasibility and impact of receiver clock modeling in precise GPS data analysis. Dissertation, Leibniz Universität Hannover, Germany.

  6. Atomic clocks with suppressed blackbody radiation shift

    CERN Document Server

    Yudin, V I; Okhapkin, M V; Bagayev, S N; Tamm, Chr; Peik, E; Huntemann, N; Mehlstaubler, T E; Riehle, F

    2011-01-01

    We develop a nonstandard concept of atomic clocks where the blackbody radiation shift (BBRS) and its temperature fluctuations can be dramatically suppressed (by one to three orders of magnitude) independent of the environmental temperature. The suppression is based on the fact that in a system with two accessible clock transitions (with frequencies $\

  7. A circadian clock in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Eelderink-Chen, Zheng; Mazzotta, Gabriella; Sturre, Marcel; Bosman, Jasper; Roenneberg, Till; Merrow, Martha

    2010-01-01

    Circadian timing is a fundamental biological process, underlying cellular physiology in animals, plants, fungi, and cyanobacteria. Circadian clocks organize gene expression, metabolism, and behavior such that they occur at specific times of day. The biological clocks that orchestrate these daily cha

  8. A clock synchronization skeleton based on RTAI

    NARCIS (Netherlands)

    Huang, Y.; Visser, P.M.; Broenink, Johannes F.

    2006-01-01

    This paper presents a clock synchronization skeleton based on RTAI (Real Time Application Interface). The skeleton is a thin layer that provides unified but extendible interfaces to the underlying operating system, the synchronization algorithms and the upper level applications in need of clock

  9. "Molecular Clock" Analogs: A Relative Rates Exercise

    Science.gov (United States)

    Wares, John P.

    2008-01-01

    Although molecular clock theory is a commonly discussed facet of evolutionary biology, undergraduates are rarely presented with the underlying information of how this theory is examined relative to empirical data. Here a simple contextual exercise is presented that not only provides insight into molecular clocks, but is also a useful exercise for…

  10. Progress of the ~(87)Rb Fountain Clock

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zi-Chao; WEI Rong; SHI Chun-Yan; LV De-Sheng; LI Tang; WANG Yu-Zhu

    2009-01-01

    A fountain atomic clock based on cold ~(87)Rb atoms has been in operation in our laboratory for several months.We therefore report the design of the rubidium fountain clock including its physical package,optical system and daily operation.Ramsey fringes have been attained with the signal to noise ratio of about 100.

  11. A Mathematical Model of the Liver Circadian Clock Linking Feeding and Fasting Cycles to Clock Function

    Directory of Open Access Journals (Sweden)

    Aurore Woller

    2016-10-01

    Full Text Available To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding and fasting cycles have been associated with clock disruption and metabolic diseases; however, the mechanisms are unclear. To address this question, we have constructed a mathematical model of the mammalian circadian clock, incorporating the metabolic sensors SIRT1 and AMPK. The clock response to various temporal patterns of AMPK activation was simulated numerically, mimicking the effects of a normal diet, fasting, and a high-fat diet. The model reproduces the dampened clock gene expression and NAD+ rhythms reported for mice on a high-fat diet and predicts that this effect may be pharmacologically rescued by timed REV-ERB agonist administration. Our model thus identifies altered AMPK signaling as a mechanism leading to clock disruption and its associated metabolic effects and suggests a pharmacological approach to resetting the clock in obesity.

  12. A Mathematical Model of the Liver Circadian Clock Linking Feeding and Fasting Cycles to Clock Function.

    Science.gov (United States)

    Woller, Aurore; Duez, Hélène; Staels, Bart; Lefranc, Marc

    2016-10-18

    To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding and fasting cycles have been associated with clock disruption and metabolic diseases; however, the mechanisms are unclear. To address this question, we have constructed a mathematical model of the mammalian circadian clock, incorporating the metabolic sensors SIRT1 and AMPK. The clock response to various temporal patterns of AMPK activation was simulated numerically, mimicking the effects of a normal diet, fasting, and a high-fat diet. The model reproduces the dampened clock gene expression and NAD(+) rhythms reported for mice on a high-fat diet and predicts that this effect may be pharmacologically rescued by timed REV-ERB agonist administration. Our model thus identifies altered AMPK signaling as a mechanism leading to clock disruption and its associated metabolic effects and suggests a pharmacological approach to resetting the clock in obesity.

  13. Single electron relativistic clock interferometer

    Science.gov (United States)

    Bushev, P. A.; Cole, J. H.; Sholokhov, D.; Kukharchyk, N.; Zych, M.

    2016-09-01

    Although time is one of the fundamental notions in physics, it does not have a unique description. In quantum theory time is a parameter ordering the succession of the probability amplitudes of a quantum system, while according to relativity theory each system experiences in general a different proper time, depending on the system's world line, due to time dilation. It is therefore of fundamental interest to test the notion of time in the regime where both quantum and relativistic effects play a role, for example, when different amplitudes of a single quantum clock experience different magnitudes of time dilation. Here we propose a realization of such an experiment with a single electron in a Penning trap. The clock can be implemented in the electronic spin precession and its time dilation then depends on the radial (cyclotron) state of the electron. We show that coherent manipulation and detection of the electron can be achieved already with present day technology. A single electron in a Penning trap is a technologically ready platform where the notion of time can be probed in a hitherto untested regime, where it requires a relativistic as well as quantum description.

  14. Tectonic blocks and molecular clocks

    Science.gov (United States)

    2016-01-01

    Evolutionary timescales have mainly used fossils for calibrating molecular clocks, though fossils only really provide minimum clade age constraints. In their place, phylogenetic trees can be calibrated by precisely dated geological events that have shaped biogeography. However, tectonic episodes are protracted, their role in vicariance is rarely justified, the biogeography of living clades and their antecedents may differ, and the impact of such events is contingent on ecology. Biogeographic calibrations are no panacea for the shortcomings of fossil calibrations, but their associated uncertainties can be accommodated. We provide examples of how biogeographic calibrations based on geological data can be established for the fragmentation of the Pangaean supercontinent: (i) for the uplift of the Isthmus of Panama, (ii) the separation of New Zealand from Gondwana, and (iii) for the opening of the Atlantic Ocean. Biogeographic and fossil calibrations are complementary, not competing, approaches to constraining molecular clock analyses, providing alternative constraints on the age of clades that are vital to avoiding circularity in investigating the role of biogeographic mechanisms in shaping modern biodiversity. This article is part of the themed issue ‘Dating species divergences using rocks and clocks’. PMID:27325840

  15. Nostradamus conference

    CERN Document Server

    Rössler, Otto; Snášel, Václav; Abraham, Ajith; Corchado, Emilio; Nostradamus: Modern Methods of Prediction, Modeling and Analysis of Nonlinear Systems

    2013-01-01

    This proceeding book of Nostradamus conference (http://nostradamus-conference.org) contains accepted papers presented at this event in 2012. Nostradamus conference was held in the one of the biggest and historic city of Ostrava (the Czech Republic, http://www.ostrava.cz/en), in September 2012. Conference topics are focused on classical as well as modern methods for prediction of dynamical systems with applications in science, engineering and economy. Topics are (but not limited to): prediction by classical and novel methods, predictive control, deterministic chaos and its control, complex systems, modelling and prediction of its dynamics and much more.

  16. Research on the optical system for space optical clock at NTSC

    Science.gov (United States)

    Tian, X.; Han, J. X.; Zhang, S.; Zou, H. X.; Chang, H.

    2016-11-01

    Optical clocks surpass the primary Cs microwave clocks with excellent performances. This allows new studies both in fundamental physics and engineering. The paper presents the optical system for our space optical clock at NTSC. Different from it in the laboratory, novel approaches and techniques were used to meet the space requirement of compactness and reliability. The modular consisting of three robust subunits was developed, which was one laser sources breadboard and two optical paths systems breadboards. The compact dimension of the optical system is 540mm×440mm×130mm and the total mass was approximate 28 kilogram. The deformation of two optical paths systems was calculated under an overload test by a mechanical analysis and it could meet the requirement. It is a advancement from lab to engineering application based on the work, which provides effective foundation for improving the optical system.

  17. Laser controlled atom source for optical clocks

    Science.gov (United States)

    Kock, Ole; He, Wei; Świerad, Dariusz; Smith, Lyndsie; Hughes, Joshua; Bongs, Kai; Singh, Yeshpal

    2016-11-01

    Precision timekeeping has been a driving force in innovation, from defining agricultural seasons to atomic clocks enabling satellite navigation, broadband communication and high-speed trading. We are on the verge of a revolution in atomic timekeeping, where optical clocks promise an over thousand-fold improvement in stability and accuracy. However, complex setups and sensitivity to thermal radiation pose limitations to progress. Here we report on an atom source for a strontium optical lattice clock which circumvents these limitations. We demonstrate fast (sub 100 ms), cold and controlled emission of strontium atomic vapours from bulk strontium oxide irradiated by a simple low power diode laser. Our results demonstrate that millions of strontium atoms from the vapour can be captured in a magneto-optical trap (MOT). Our method enables over an order of magnitude reduction in scale of the apparatus. Future applications range from satellite clocks testing general relativity to portable clocks for inertial navigation systems and relativistic geodesy.

  18. A low maintenance Sr optical lattice clock

    CERN Document Server

    Hill, Ian R; Bowden, William; Bridge, Elizabeth M; Donnellan, Sean; Curtis, E Anne; Gill, Patrick

    2016-01-01

    We describe the Sr optical lattice clock apparatus at NPL with particular emphasis on techniques used to increase reliability and minimise the human requirement in its operation. Central to this is a clock-referenced transfer cavity scheme for the stabilisation of cooling and trapping lasers. We highlight several measures to increase the reliability of the clock with a view towards the realisation of an optical time-scale. The clock contributed 502 hours of data over a 25 day period (84% uptime) in a recent measurement campaign with several uninterrupted periods of more than 48 hours. An instability of $2\\times10^{-17}$ was reached after $10^5$ s of averaging in an interleaved self-comparison of the clock.

  19. Cost and Precision of Brownian Clocks

    CERN Document Server

    Barato, Andre C

    2016-01-01

    Brownian clocks are biomolecular networks that can count time. A paradigmatic example are proteins that go through a cycle thus regulating some oscillatory behaviour in a living system. Typically, such a cycle requires free energy often provided by ATP hydrolysis. We investigate the relation between the precision of such a clock and its thermodynamic costs. For clocks driven by a constant thermodynamic force, a given precision requires a minimal cost that diverges as the uncertainty of the clock vanishes. In marked contrast, we show that a clock driven by a periodic variation of an external protocol can achieve arbitrary precision at arbitrarily low cost. This result constitutes a fundamental difference between processes driven by a fixed thermodynamic force and those driven periodically. As a main technical tool, we map a periodically driven system with a deterministic protocol to one subject to an external protocol that changes in stochastic time intervals, which simplifies calculations significantly. In th...

  20. Re-verification of a Lip Synchronization Protocol using Robust Reachability

    NARCIS (Netherlands)

    Kordy, Piotr; Langerak, Rom; Polderman, Jan Willem; Bujorianu, Manuela; Fischer, Michael

    2010-01-01

    The timed automata formalism is an important model for specifying and analysing real-time systems. Robustness is the correctness of the model in the presence of small drifts on clocks or imprecision in testing guards. A symbolic algorithm for the analysis of the robustness of timed automata has been

  1. Probing entrainment of Ostreococcus tauri circadian clock by green and blue light through a mathematical modeling approach.

    Science.gov (United States)

    Thommen, Quentin; Pfeuty, Benjamin; Schatt, Philippe; Bijoux, Amandine; Bouget, François-Yves; Lefranc, Marc

    2015-01-01

    Most organisms anticipate daily environmental variations and orchestrate cellular functions thanks to a circadian clock which entrains robustly to the day/night cycle, despite fluctuations in light intensity due to weather or seasonal variations. Marine organisms are also subjected to fluctuations in light spectral composition as their depth varies, due to differential absorption of different wavelengths by sea water. Studying how light input pathways contribute to circadian clock robustness is therefore important. Ostreococcus tauri, a unicellular picoplanktonic marine green alga with low genomic complexity and simple cellular organization, has become a promising model organism for systems biology. Functional and modeling approaches have shown that a core circadian oscillator based on orthologs of Arabidopsis TOC1 and CCA1 clock genes accounts for most experimental data acquired under a wide range of conditions. Some evidence points at putative light input pathway(s) consisting of a two-component signaling system (TCS) controlled by the only two histidine kinases (HK) of O. tauri. LOV-HK is a blue light photoreceptor under circadian control, that is required for circadian clock function. An involvement of Rhodopsin-HK (Rhod-HK) is also conceivable since rhodopsin photoreceptors mediate blue to green light input in animal circadian clocks. Here, we probe the role of LOV-HK and Rhod-HK in mediating light input to the TOC1-CCA1 oscillator using a mathematical model incorporating the TCS hypothesis. This model agrees with clock gene expression time series representative of multiple environmental conditions in blue or green light, characterizing entrainment by light/dark cycles, free-running in constant light, and resetting. Experimental and theoretical results indicate that both blue and green light can reset O. tauri circadian clock. Moreover, our mathematical analysis suggests that Rhod-HK is a blue-green light receptor and drives the clock together with LOV-HK.

  2. Consensus conferences

    DEFF Research Database (Denmark)

    Nielsen, Annika Porsborg; Lassen, Jesper

    Our results point to significant national variation both in terms of the perceived aim of consensus conferences, expectations to conference outcomes, conceptions of the roles of lay people and experts, and in terms of the way in which the role of public deliberation is interpreted. Interestingly...

  3. Deciphering time measurement: the role of circadian 'clock' genes and formal experimentation in insect photoperiodism.

    Science.gov (United States)

    Saunders, D S; Bertossa, R C

    2011-05-01

    This review examines possible role(s) of circadian 'clock' genes in insect photoperiodism against a background of many decades of formal experimentation and model building. Since ovarian diapause in the genetic model organism Drosophila melanogaster has proved to be weak and variable, recent attention has been directed to species with more robust photoperiodic responses. However, no obvious consensus on the problem of time measurement in insect photoperiodism has yet to emerge and a variety of mechanisms are indicated. In some species, expression patterns of clock genes and formal experiments based on the canonical properties of the circadian system have suggested that a damped oscillator version of Pittendrigh's external coincidence model is appropriate to explain the measurement of seasonal changes in night length. In other species extreme dampening of constituent oscillators may give rise to apparently hourglass-like photoperiodic responses, and in still others there is evidence for dual oscillator (dawn and dusk) photoperiodic mechanisms of the internal coincidence type. Although the exact role of circadian rhythmicity and of clock genes in photoperiodism is yet to be settled, Bünning's general hypothesis (Bünning, 1936) remains the most persuasive unifying principle. Observed differences between photoperiodic clocks may be reflections of underlying differences in the clock genes in their circadian feedback loops. Copyright © 2011. Published by Elsevier Ltd.

  4. Coupling between the circadian clock and cell cycle oscillators: implication for healthy cells and malignant growth

    Directory of Open Access Journals (Sweden)

    Celine eFeillet

    2015-05-01

    Full Text Available Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumour growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer.

  5. Coupling between the Circadian Clock and Cell Cycle Oscillators: Implication for Healthy Cells and Malignant Growth.

    Science.gov (United States)

    Feillet, Celine; van der Horst, Gijsbertus T J; Levi, Francis; Rand, David A; Delaunay, Franck

    2015-01-01

    Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic, or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumor growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer.

  6. Circadian clocks are designed optimally

    CERN Document Server

    Hasegawa, Yoshihiko

    2014-01-01

    Circadian rhythms are acquired through evolution to increase the chances for survival by synchronizing to the daylight cycle. Reliable synchronization is realized through two trade-off properties: regularity to keep time precisely, and entrainability to synchronize the internal time with daylight. Since both properties have been tuned through natural selection, their adaptation can be formalized in the framework of mathematical optimization. By using a succinct model, we found that simultaneous optimization of regularity and entrainability entails inherent features of the circadian mechanism irrespective of model details. At the behavioral level we discovered the existence of a dead zone, a time during which light pulses neither advance nor delay the clock. At the molecular level we demonstrate the role-sharing of two light inputs, phase advance and delay, as is well observed in mammals. We also reproduce the results of phase-controlling experiments and predict molecular elements responsible for the clockwork...

  7. A computational model clarifies the roles of positive and negative feedback loops in the Drosophila circadian clock

    Science.gov (United States)

    Wang, Junwei; Zhou, Tianshou

    2010-06-01

    Previous studies showed that a single negative feedback structure should be sufficient for robust circadian oscillations. It is thus pertinent to ask why current cellular clock models almost universally have interlocked negative feedback loop (NFL) and positive feedback loop (PFL). Here, we propose a molecular model that reflects the essential features of the Drosophila circadian clock to clarify the different roles of negative and positive feedback loops. In agreement with experimental observations, the model can simulate circadian oscillations in constant darkness, entrainment by light-dark cycles, as well as phenotypes of per and clk mutants. Moreover, sustained oscillations persist when the PFL is removed, implying the crucial role of NFL for rhythm generation. Through parameter sensitivity analysis, it is revealed that incorporation of PFL increases the robustness of the system to regulatory processes in PFL itself. Such reduced models can aid understanding of the design principles of circadian clocks in Drosophila and other organisms with complex transcriptional feedback structures.

  8. Half Swing Clocking Scheme at 45nm

    Directory of Open Access Journals (Sweden)

    Sakshi Verma,

    2014-01-01

    Full Text Available Achievement of high processor speed with low power consumption is an elemental factor in processor technology, especially for hand-held devices. The need for low power has caused a major paradigm shift where power dissipation has become a important consideration as performance and area. In CMOS circuits, dynamic power consumption is proportional to the transition frequency, capacitance, and square of supply voltage. Consequentially, lowering supply voltage delivers significant power savings compromising the speed of processor. Large portion of the total power is consumed in the clocking circuitry in embedded processor technology. So clock power can be reduced using half swing of clock scheme which will cut down the power dissipation and minimum speed degradation. In Digital circuits by using double-edge triggered flip flops (DETFFs, the clock frequency can be significantly reduced ideally, in half while preserving the rate of data processing. Using lower clock frequency may translate into considerable power savings for the clocked portions of a circuit, including the clock distribution network and flip-flops. The designing is based on 45nm process technology.

  9. Iterative quantum algorithm for distributed clock synchronization

    Institute of Scientific and Technical Information of China (English)

    Wang Hong-Fu; Zhang Shou

    2012-01-01

    Clock synchronization is a well-studied problem with many practical and scientific applications.We propose an arbitrary accuracy iterative quantum algorithm for distributed clock synchronization using only three qubits.The n bits of the time difference △ between two spatially separated clocks can be deterministically extracted by communicating only O(n) messages and executing the quantum iteration process n times based on the classical feedback and measurement operations.Finally,we also give the algorithm using only two qubits and discuss the success probability of the algorithm.

  10. Using Atomic Clocks to Detect Gravitational Waves

    CERN Document Server

    Loeb, Abraham

    2015-01-01

    Atomic clocks have recently reached a fractional timing precision of $<10^{-18}$. We point out that an array of atomic clocks, distributed along the Earth's orbit around the Sun, will have the sensitivity needed to detect the time dilation effect of mHz gravitational waves (GWs), such as those emitted by supermassive black hole binaries at cosmological distances. Simultaneous measurement of clock-rates at different phases of a passing GW provides an attractive alternative to the interferometric detection of temporal variations in distance between test masses separated by less than a GW wavelength, currently envisioned for the eLISA mission.

  11. CMOS Law-jitter Clock Driver Design

    OpenAIRE

    2012-01-01

    [ANGLÈS] Design of a low-jitter, low-phase noise clock driver in 40 nm CMOS technology. The work is in the field of analog integrated circuit (IC) design in nanometer CMOS technologies. [CASTELLÀ] Diseño de un circuito integrado "clock driver" de bajo jitter y bajo ruido de fase en tecnología CMOS 40 nm. El trabajo se contextualiza en el campo del diseño de circuitos integrados analógicos en tecnologías CMOS nanométricas. [CATALÀ] Disseny d'un circuit "clock driver" de baix jitter i bai...

  12. Light clocks in strong gravitational fields

    CERN Document Server

    Punzi, Raffaele; Wohlfarth, Mattias N R

    2009-01-01

    We argue that the time measured by a light clock operating with photons rather than classical light requires a refinement of the standard clock postulate in general relativity. In the presence of a gravitational field, already the one-loop quantum corrections to classical Maxwell theory affect light propagation and the construction of observers' frames of reference. Carefully taking into account these kinematic effects, a concise geometric expression for the time shown by a light clock is obtained. This result has far-reaching implications for physics in strong gravitational fields.

  13. Sleep: the sound of a local alarm clock.

    Science.gov (United States)

    Adamantidis, Antoine R

    2015-01-05

    Besides the master clock located in the suprachiasmatic nucleus (SCN) of the brain, additional clocks are distributed across the central nervous system and the body. The role of these 'secondary' clocks remains unclear. A new study shows that the lack of an internal clock in histamine neurons profoundly perturbs sleep. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Transcripts from the Circadian Clock: Telling Time and Season

    NARCIS (Netherlands)

    K. Brand (Karl)

    2011-01-01

    textabstractWe all know it when we wake mere moments before an alarm clock is scheduled to wake us: our body clock made the alarm clock redundant. This phenomenon is driven by an endogenous timer known as the biological, or circadian clock. Each revolution of the Earth about its own axis produces pe

  15. The dynamic Allan Variance IV: characterization of atomic clock anomalies.

    Science.gov (United States)

    Galleani, Lorenzo; Tavella, Patrizia

    2015-05-01

    The number of applications where precise clocks play a key role is steadily increasing, satellite navigation being the main example. Precise clock anomalies are hence critical events, and their characterization is a fundamental problem. When an anomaly occurs, the clock stability changes with time, and this variation can be characterized with the dynamic Allan variance (DAVAR). We obtain the DAVAR for a series of common clock anomalies, namely, a sinusoidal term, a phase jump, a frequency jump, and a sudden change in the clock noise variance. These anomalies are particularly common in space clocks. Our analytic results clarify how the clock stability changes during these anomalies.

  16. The Chemical and Educational Appeal of the Orange Juice Clock

    Science.gov (United States)

    Kelter, Paul B.; Carr, James D.; Johnson, Tanya; Mauricio Castro-Acuña, Carlos

    1996-12-01

    The Orange Juice Clock, in which a galvanic cell is made from the combination of a magnesium strip, a copper strip, and juice in a beaker, has been a popular classroom, conference, and workshop demonstration for nearly 10 years. It is widely enjoyed because it shows visually how chemistry - or more precisely, electrochemistry - is responsible for the very common phenomenon of a clock ticking. The chemistry of the process can also be understood on a variety of levels, from middle school (simple electron flow in a circuit, Ohm's law) and high school (reduction/oxidation and standard cell potentials) to first-year college (cell potential at nonideal conditions) and graduate school courses (overpotential and charge transfer across interfaces.) The discussion that follows considers the recent history, chemistry, and educational uses of the demonstration. The History The demonstration was devised by one of us (PK) in 1986, after reading an activity in Hubert Alyea's 1947 compendium of chemical demonstrations from this Journal (1). In that activity, Alyea hooked a magnesium strip to the negative battery terminal of an electric bell and hooked a copper strip to the positive terminal. He placed the loose ends of the strips into a 1M 2SO4 solution and the bell rang. After trying the demonstration, it seemed to make sense to modify the electrolyte to orange juice because it is safe, readily available, and would be a mixture in which the magnesium would oxidize more slowly than in sulfuric acid. Further, a clock was substituted for the bell because a clock is easier on the ears than a bell. A video of the orange-juice clock setup is given as Figure 1. Figure 1.The orange juice clock set up. Video of orange juice clock was filmed and editted by Jerry Jacobson at the University of Wisconsin - Madison. The apparatus was presented in 1987 as part of a teacher workshop led by Irwin Talesnick, then of Queen's University in Canada. Talesnick, whose distinguished career has been

  17. Circadian and Circalunar Clock Interactions in a Marine Annelid

    Directory of Open Access Journals (Sweden)

    Juliane Zantke

    2013-10-01

    Full Text Available Life is controlled by multiple rhythms. Although the interaction of the daily (circadian clock with environmental stimuli, such as light, is well documented, its relationship to endogenous clocks with other periods is little understood. We establish that the marine worm Platynereis dumerilii possesses endogenous circadian and circalunar (monthly clocks and characterize their interactions. The RNAs of likely core circadian oscillator genes localize to a distinct nucleus of the worm’s forebrain. The worm’s forebrain also harbors a circalunar clock entrained by nocturnal light. This monthly clock regulates maturation and persists even when circadian clock oscillations are disrupted by the inhibition of casein kinase 1δ/ε. Both circadian and circalunar clocks converge on the regulation of transcript levels. Furthermore, the circalunar clock changes the period and power of circadian behavior, although the period length of the daily transcriptional oscillations remains unaltered. We conclude that a second endogenous noncircadian clock can influence circadian clock function.

  18. Deregulated expression of circadian clock and clock-controlled cell cycle genes in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rana, Sobia; Munawar, Mustafa; Shahid, Adeela; Malik, Meera; Ullah, Hafeez; Fatima, Warda; Mohsin, Shahida; Mahmood, Saqib

    2014-01-01

    Circadian rhythms are endogenous and self-sustained oscillations of multiple biological processes with approximately 24-h rhythmicity. Circadian genes and their protein products constitute the molecular components of the circadian oscillator that form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends from core clock genes to various clock-controlled genes that include various cell cycle genes. Aberrant expression of circadian clock genes, therefore, may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. The current study encompasses the investigation of simultaneous expression of four circadian clock genes (Bmal1, Clock, Per1 and Per2) and three clock-controlled cell cycle genes (Myc, Cyclin D1 and Wee1) at mRNA level and determination of serum melatonin levels in peripheral blood samples of 37 CLL (chronic lymphocytic leukemia) patients and equal number of age- and sex-matched healthy controls in order to indicate association between deregulated circadian clock and manifestation of CLL. Results showed significantly down-regulated expression of Bmal1, Per1, Per2 and Wee1 and significantly up-regulated expression of Myc and Cyclin D1 (P circadian clock genes can lead to aberrant expression of their downstream targets that are involved in cell proliferation and apoptosis and hence may result in manifestation of CLL. Moreover, shift-work and low melatonin levels may also contribute in etiology of CLL by further perturbing of circadian clock.

  19. A New Design of Clock Synchronization Algorithm

    Directory of Open Access Journals (Sweden)

    Jingmeng Liu

    2014-05-01

    Full Text Available The introduction of Ethernet makes the distributed network system more flexible and efficient, but it also makes nodes which are far apart from each other unable to work in the same time basis due to the long distance. This is not allowed for the high performance requirements of the system synchronization, such as high-precision multiaxis machining system. This paper presents a high-precision network clock synchronization algorithm, namely, optimal PI clock servo, which imposes a PI controller in order to compensate for the clock drift of each network node. Then a simulation platform established by the toolbox TrueTime is used to verify the stability of the algorithm and compare it with the clock synchronization algorithm of EtherCAT. The results show that the new synchronization algorithm has higher synchronization precision and faster convergence rate.

  20. Programmable Clock Waveform Generation for CCD Readout

    Energy Technology Data Exchange (ETDEWEB)

    Vicente, J. de; Castilla, J.; Martinez, G.; Marin, J.

    2006-07-01

    Charge transfer efficiency in CCDs is closely related to the clock waveform. In this paper, an experimental framework to explore different FPGA based clock waveform generator designs is described. Two alternative design approaches for controlling the rise/fall edge times and pulse width of the CCD clock signal have been implemented: level-control and time-control. Both approaches provide similar characteristics regarding the edge linearity and noise. Nevertheless, dissimilarities have been found with respect to the area and frequency range of application. Thus, while the time-control approach consumes less area, the level control approach provides a wider range of clock frequencies since it does not suffer capacitor discharge effect. (Author) 8 refs.

  1. The Mechanics of Mechanical Watches and Clocks

    CERN Document Server

    Du, Ruxu

    2013-01-01

    "The Mechanics of Mechanical Watches and Clocks" presents historical views and mathematical models of mechanical watches and clocks. Although now over six hundred years old, mechanical watches and clocks are still popular luxury items that fascinate many people around the world. However few have examined the theory of how they work as presented in this book. The illustrations and computer animations are unique and have never been published before. It will be of significant interest to researchers in mechanical engineering, watchmakers and clockmakers, as well as people who have an engineering background and are interested in mechanical watches and clocks. It will also inspire people in other fields of science and technology, such as mechanical engineering and electronics engineering, to advance their designs. Professor Ruxu Du works at the Chinese University of Hong Kong, China. Assistant Professor Longhan Xie works at the South China University of Technology, China.

  2. Turning Back the Aging Clock -- in Mice

    Science.gov (United States)

    ... 164250.html Turning Back the Aging Clock -- in Mice Elderly rodents treated with cellular therapy regained lost fur, became ... 2017 THURSDAY, March 23, 2017 (HealthDay News) -- Aging mice became more youthful following a new cellular therapy ...

  3. Circadian clock circuitry in colorectal cancer.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Papa, Gennaro; Piepoli, Ada

    2014-04-21

    Colorectal cancer is the most prevalent among digestive system cancers. Carcinogenesis relies on disrupted control of cellular processes, such as metabolism, proliferation, DNA damage recognition and repair, and apoptosis. Cell, tissue, organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene machinery. Dysfunction of molecular clockworks and cellular oscillators is involved in tumorigenesis, and altered expression of clock genes has been found in cancer patients. Epidemiological studies have shown that circadian disruption, that is, alteration of bodily temporal organization, is a cancer risk factor, and an increased incidence of colorectal neoplastic disease is reported in shift workers. In this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.

  4. Micro Mercury Ion Clock (MMIC) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Demonstrate micro clock based on trapped Hg ions with more than 10x size reduction and power; Fractional frequency stability at parts per 1014 level, adequate for...

  5. Modeling circadian clocks: From equations to oscillations

    National Research Council Canada - National Science Library

    Gonze, Didier

    2011-01-01

    ... (such as light and temperature) is greatly helped by mathematical modeling. In the present paper we review some mathematical models for circadian clocks, ranging from abstract, phenomenological models to the most detailed molecular models...

  6. PTTI 2030 - System Applications of Advanced Clocks

    Science.gov (United States)

    2010-11-01

    while you enjoy the freedom of hands-free driving. 42 nd Annual Precise Time and Time Interval (PTTI) Meeting 587 PLATE TECTONICS ...MONITORING Ultra-stable clocks have been recognized for some time as great tools to calibrate plate movement on the earth’s crust. In combination...position after a seismic event. The addition of multiple clocks to a worldwide monitoring system has allowed improved accuracy of these measurements

  7. Magic Wavelengths for Terahertz Clock Transitions

    OpenAIRE

    Zhou, Xiaoji; Xu, Xia; Chen, Xuzong; Chen, Jingbiao

    2010-01-01

    Magic wavelengths for laser trapping of boson isotopes of alkaline-earth Sr, Ca and Mg atoms are investigated while considering terahertz clock transitions between the $^{3}P_{0}, ^{3}P_{1}, ^{3}P_{2}$ metastable triplet states. Our calculation shows that magic wavelengths of trapping laser do exist. This result is important because those metastable states have already been used to realize accurate clocks in the terahertz frequency domain. Detailed discussions for magic wavelength for teraher...

  8. Reduced Kalman Filters for Clock Ensembles

    Science.gov (United States)

    Greenhall, Charles A.

    2011-01-01

    This paper summarizes the author's work ontimescales based on Kalman filters that act upon the clock comparisons. The natural Kalman timescale algorithm tends to optimize long-term timescale stability at the expense of short-term stability. By subjecting each post-measurement error covariance matrix to a non-transparent reduction operation, one obtains corrected clocks with improved short-term stability and little sacrifice of long-term stability.

  9. Cesium Atomic Fountain Clocks at NMIJ

    Science.gov (United States)

    2010-11-01

    Wynands and S. Weyers, 2005, “Atomic fountain clocks,” Metrologia , 42, S64-S79. [2] M. Takamoto, F. L. Hong, R. Higashi, et al., 2005, “An optical...beam of laser-cooled cesium atoms,” Physical Review, A 60, R4241-R4244. [13] V. Gerginov, N. Nemitz, S. Weyers, et al., 2010, “Uncertainty evaluation of the caesium fountain clock PTB-CSF2,” Metrologia , 47, 65-79.

  10. Zebrafish circadian clocks: cells that see light.

    Science.gov (United States)

    Tamai, T K; Carr, A J; Whitmore, D

    2005-11-01

    In the classical view of circadian clock organization, the daily rhythms of most organisms were thought to be regulated by a central, 'master' pacemaker, usually located within neural structures of the animal. However, with the results of experiments performed in zebrafish, mammalian cell lines and, more recently, mammalian tissues, this view has changed to one where clock organization is now seen as being highly decentralized. It is clear that clocks exist in the peripheral tissues of animals as diverse as Drosophila, zebrafish and mammals. In the case of Drosophila and zebrafish, these tissues are also directly light-responsive. This light sensitivity and direct clock entrainability is also true for zebrafish cell lines and early-stage embryos. Using luminescent reporter cell lines containing clock gene promoters driving the expression of luciferase and single-cell imaging techniques, we have been able to show how each cell responds rapidly to a single light pulse by being shifted to a common phase, equivalent to the early day. This direct light sensitivity might be related to the requirement for light in these cells to activate the transcription of genes involved in DNA repair. It is also clear that the circadian clock in zebrafish regulates the timing of the cell cycle, demonstrating the wide impact that this light sensitivity and daily rhythmicity has on the biology of zebrafish.

  11. Adipose Clocks: Burning the Midnight Oil.

    Science.gov (United States)

    Henriksson, Emma; Lamia, Katja A

    2015-10-01

    Circadian clocks optimize the timing of physiological processes in synchrony with daily recurring and therefore predictable changes in the environment. Until the late 1990s, circadian clocks were thought to exist only in the central nervous systems of animals; elegant studies in cultured fibroblasts and using genetically encoded reporters in Drosophila melanogaster and in mice showed that clocks are ubiquitous and cell autonomous. These findings inspired investigations of the advantages construed by enabling each organ to independently adjust its function to the time of day. Studies of rhythmic gene expression in several organs suggested that peripheral organ clocks might play an important role in optimizing metabolic physiology by synchronizing tissue-intrinsic metabolic processes to cycles of nutrient availability and energy requirements. The effects of clock disruption in liver, pancreas, muscle, and adipose tissues support that hypothesis. Adipose tissues coordinate energy storage and utilization and modulate behavior and the physiology of other organs by secreting hormones known as "adipokines." Due to behavior- and environment-driven diurnal variations in supply and demand for chemical and thermal energy, adipose tissues might represent an important peripheral location for coordinating circadian energy balance (intake, storage, and utilization) over the whole organism. Given the complexity of adipose cell types and depots, the sensitivity of adipose tissue biology to age and diet composition, and the plethora of known and yet-to-be-discovered adipokines and lipokines, we have just begun to scratch the surface of understanding the role of circadian clocks in adipose tissues.

  12. Short-term GNSS satellite clock stability

    Science.gov (United States)

    Griggs, E.; Kursinski, E. R.; Akos, D.

    2015-08-01

    Global Navigation Satellite System (GNSS) clock stability is characterized via the modified Allan deviation using active hydrogen masers as the receiver frequency reference. The high stability of the maser reference allows the GNSS clock contribution to the GNSS carrier phase variance to be determined quite accurately. Satellite clock stability for four different GNSS constellations are presented, highlighting the similarities and differences between the constellations as well as satellite blocks and clock types. Impact on high-rate applications, such as GNSS radio occultation (RO), is assessed through the calculation of the maximum carrier phase error due to clock instability. White phase noise appears to dominate at subsecond time scales. However, while we derived the theoretical contribution of white phase modulation to the modified Allan deviation, our analysis of the GNSS satellite clocks was limited to 1-200 s time scales because of inconsistencies between the subsecond results from the commercial and software-defined receivers. The rubidium frequency standards on board the Global Positioning System (GPS) Block IIF, BeiDou, and Galileo satellites show improved stability results in comparison to previous GPS blocks for time scales relevant to RO. The Globalnaya Navigatsionnaya Sputnikovaya Sistema (GLONASS) satellites are the least stable of the GNSS constellations in the short term and will need high-rate corrections to produce RO results comparable to those from the other GNSS constellations.

  13. Optical lattice clocks and frequency comparison

    Energy Technology Data Exchange (ETDEWEB)

    Katori, Hidetoshi; Takano, Tetsushi; Takamoto, Masao, E-mail: katori@amo.t.u-tokyo.ac.jp [Department of Applied Physics, University of Tokyo, Tokyo (Japan); CREST, Japan Science and Technology Agency, Saitama (Japan)

    2011-01-10

    We consider designs of optical lattice clocks in view of the quantum statistics, relevant atomic spins, and atom-lattice interactions. The first two issues lead to two optimal constructions for the clock: a one-dimensional (1D) optical lattice loaded with spin-polarized fermions and a 3D optical lattice loaded with bosons. By taking atomic multipolar interactions with the lattice fields into account, an 'atomic motion insensitive' wavelength is proposed to provide a precise definition of the 'magic wavelength'. We then present a frequency comparison of these two optical lattice clocks: spin-polarized fermionic {sup 87}Sr and bosonic {sup 88}Sr prepared in 1D and 3D optical lattices, respectively. Synchronous interrogations of these two optical lattice clocks by the same probe laser allowed canceling out its frequency noise as a common mode noise to achieve a relative stability of 3x10{sup -17} for an averaging time of {tau} = 350 s. The scheme, therefore, provides us with a powerful means to investigate intrinsic uncertainty of the clocks regardless of the probe laser stability. We discuss prospects of the synchronous operation of the clocks on the measurement of the geoid height difference and on the search of constancy of fundamental constants.

  14. Ultradian rhythm unmasked in the Pdf clock mutant of Drosophila.

    Science.gov (United States)

    Seki, Yuuichi; Tanimura, Teiichi

    2014-09-01

    A diverse range of organisms shows physiological and behavioural rhythms with various periods. Extensive studies have been performed to elucidate the molecular mechanisms of circadian rhythms with an approximately 24 h period in both Drosophila and mammals, while less attention has been paid to ultradian rhythms with shorter periods. We used a video-tracking method to monitor the movement of single flies, and clear ultradian rhythms were detected in the locomotor behaviour of wild type and clock mutant flies kept under constant dark conditions. In particular, the Pigment-dispersing factor mutant (Pdf 01) demonstrated a precise and robust ultradian rhythmicity, which was not temperature compensated. Our results suggest that Drosophila has an endogenous ultradian oscillator that is masked by circadian rhythmic behaviours.

  15. Ultradian rhythm unmasked in the Pdf clock mutant of Drosophila

    Indian Academy of Sciences (India)

    Yuuichi Seki; Teiichi Tanimura

    2014-09-01

    A diverse range of organisms shows physiological and behavioural rhythms with various periods. Extensive studies have been performed to elucidate the molecular mechanisms of circadian rhythms with an approximately 24 h period in both Drosophila and mammals, while less attention has been paid to ultradian rhythms with shorter periods. We used a video-tracking method to monitor the movement of single flies, and clear ultradian rhythms were detected in the locomotor behaviour of wild type and clock mutant flies kept under constant dark conditions. In particular, the Pigment-dispersing factor mutant (Pdf01) demonstrated a precise and robust ultradian rhythmicity, which was not temperature compensated. Our results suggest that Drosophila has an endogenous ultradian oscillator that is masked by circadian rhythmic behaviours.

  16. Systems Biology-Derived Discoveries of Intrinsic Clocks

    Science.gov (United States)

    Millius, Arthur; Ueda, Hiroki R.

    2017-01-01

    A systems approach to studying biology uses a variety of mathematical, computational, and engineering tools to holistically understand and model properties of cells, tissues, and organisms. Building from early biochemical, genetic, and physiological studies, systems biology became established through the development of genome-wide methods, high-throughput procedures, modern computational processing power, and bioinformatics. Here, we highlight a variety of systems approaches to the study of biological rhythms that occur with a 24-h period—circadian rhythms. We review how systems methods have helped to elucidate complex behaviors of the circadian clock including temperature compensation, rhythmicity, and robustness. Finally, we explain the contribution of systems biology to the transcription–translation feedback loop and posttranslational oscillator models of circadian rhythms and describe new technologies and “–omics” approaches to understand circadian timekeeping and neurophysiology. PMID:28220104

  17. A novel architecture of recovered data comparison for high speed clock and data recovery

    Science.gov (United States)

    Gao, Susan; Li, Fei; Wang, Zhigong; Cui, Hongliang

    2005-05-01

    A clock and data recovery (CDR) circuit is one of the crucial blocks in high-speed serial link communication systems. The data received in these systems are asynchronous and noisy, requiring that a clock be extracted to allow synchronous operations. Furthermore, the data must be "retimed" so that the jitter accumulated during transmission is removed. This paper presents a novel architecture of CDR, which is very tolerant to long sequences of serial ones or zeros and also robust to occasional long absence of transitions. The design is based on the fact that a basic clock recovery having a clock recovery circuit (CRC) and a data decision circuit separately would generate a high jitter clock when the received non-return-to-zero (NRZ) data with long sequences of ones or zeros. To eliminate this drawback, the proposed architecture incorporates a data circuit decision circuit within the phase-locked loop (PLL) CRC. Other than this, a new phase detector (PD) is also proposed, which was easy to accomplish and robust at high speed. This PD is functional with a random input and automatically turns to disable during both the locked state and long absence of transitions. The voltage-controlled oscillator (VCO) is also designed delicately to suppress the jitter. Due to the high stability, the jitter is highly reduced when the loop is locked. The simulation results of such CDR working at 1.25Gb/s particularly for 1000BASE-X Gigabit Ethernet by using TSMC 0.25μm technology are presented to prove the feasibility of this architecture. One more CDR based on edge detection architecture is also built in the circuit for performance comparisons.

  18. Gated Clock Implementation of Arithmetic Logic Unit (ALU

    Directory of Open Access Journals (Sweden)

    Dr. Neelam R. Prakash

    2013-05-01

    Full Text Available Low power design has emerged as one of the challenging area in today’s ASIC (Application specific integrated circuit design. With continuous decrease in transistor size, power density is increasing and there is an urgent need for reduction in total power consumption. Clock gating is one most effective technique for low power synchronous circuit design. Clock gating technique in low power design is used to reduce the dynamic power consumption. Clock signal in a synchronous circuit is used for synchronization only and hence does not carry any important information. Since clock is applied to each block of a synchronous circuit, and clock switches for every cycle, clock power is the major part of dynamic power consumption in synchronous circuits. Clock gating is a well known technique to reduce clock power. In clock gating clock to an idle block is disabled. Thus significant amount of power consumption is reduced by employing clock gating. In this paper an ALU design is proposed employing Gated clock for its operation. Design simulation has been performed on Xilinx ISE design suite, and power calculation is done by Xilinx Xpower analyzer. Results show that approximately 17% of total clock power consumption is reduced by gated clock implementation.

  19. Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2011-01-01

    robust design as well as strategies for maintaining the robustness of existing structures throughout their service life. This paper describes an overall theoretical framework for assessing robustness of structures developed within WG1 “Robustness of structures”. Robustness can be defined in different......An important aspect of the COST Action TU0601 “Robustness of structures” concerns the development of a theoretically sound basis for the assessment of robustness and acceptance criteria for structural robustness which can form the basis for development of practical relevant methods for ensuring...

  20. DESIGN OF TWO-PHASE SINUSOIDAL POWER CLOCK AND CLOCKED TRANSMISSION GATE ADIABATIC LOGIC CIRCUIT

    Institute of Scientific and Technical Information of China (English)

    Wang Pengjun; Yu Junjun

    2007-01-01

    First the research is conducted on the design of the two-phase sinusoidal power clock generator in this paper. Then the design of the new adiabatic logic circuit adopting the two-phase sinusoidal power clocks-Clocked Transmission Gate Adiabatic Logic (CTGAL) circuit is presented. This circuit makes use of the clocked transmission gates to sample the input signals, then the output loads are charged and discharged in a fully adiabatic manner by using bootstrapped N-Channel Metal Oxide Semiconductor (NMOS) and Complementary Metal Oxide Semiconductor (CMOS) latch structure.Finally, with the parameters of Taiwan Semiconductor Manufacturing Company (TSMC) 0.25 μm CMOS device, the transient energy consumption of CTGAL, Bootstrap Charge-Recovery Logic (BCRL)and Pass-transistor Adiabatic Logic (PAL) including their clock generators is simulated. The simulation result indicates that CTGAL circuit has the characteristic of remarkably low energy consumption.

  1. Mendel conference

    CERN Document Server

    2015-01-01

    This book is a collection of selected accepted papers of Mendel conference that has been held in Brno, Czech Republic in June 2015. The book contents three chapters which represent recent advances in soft computing including intelligent image processing and bio-inspired robotics.: Chapter 1: Evolutionary Computing, and Swarm intelligence, Chapter 2: Neural Networks, Self-organization, and Machine Learning, and Chapter3: Intelligent Image Processing, and Bio-inspired Robotics. The Mendel conference was established in 1995, and it carries the name of the scientist and Augustinian priest Gregor J. Mendel who discovered the famous Laws of Heredity. In 2015 we are commemorating 150 years since Mendel's lectures, which he presented in Brno on February and March 1865. The main aim of the conference was to create a periodical possibility for students, academics and researchers to exchange their ideas and novel research methods.  .

  2. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.

    Science.gov (United States)

    Ramsey, Kathryn Moynihan; Yoshino, Jun; Brace, Cynthia S; Abrassart, Dana; Kobayashi, Yumiko; Marcheva, Biliana; Hong, Hee-Kyung; Chong, Jason L; Buhr, Ethan D; Lee, Choogon; Takahashi, Joseph S; Imai, Shin-Ichiro; Bass, Joseph

    2009-05-01

    The circadian clock is encoded by a transcription-translation feedback loop that synchronizes behavior and metabolism with the light-dark cycle. Here we report that both the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT), and levels of NAD+ display circadian oscillations that are regulated by the core clock machinery in mice. Inhibition of NAMPT promotes oscillation of the clock gene Per2 by releasing CLOCK:BMAL1 from suppression by SIRT1. In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1.

  3. Conference Notification

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Roskill Information Services and Metal Events Ltd areorganizing the 2nd International Rare Earths Conference,which will be held at the Conrad Hotel in Hong Kong onFebruary 28 to March 2 2006.The program is structured tocover all the main aspects of the rare earths industry,including development of Chinese rare earth industry; trendsin rare earths demand; potential constraints on supply;research on potential capacity of rare earths supply chain.Global rare earths consumers will attend the conference.Registra...

  4. Orbitography for next generation space clocks

    CERN Document Server

    Duchayne, Loïc; Wolf, Peter

    2007-01-01

    Over the last decade of the 20th century and the first few years of the 21st, the uncertainty of atomic clocks has decreased by about two orders of magnitude, passing from the low 10^-14 to below 10^-16, in relative frequency . Space applications in fundamental physics, geodesy, time/frequency metrology, navigation etc... are among the most promising for this new generation of clocks. Onboard terrestrial or solar system satellites, their exceptional frequency stability and accuracy makes them a prime tool to test the fundamental laws of nature, and to study gravitational potentials and their evolution. In this paper, we study in more detail the requirements on orbitography compatible with operation of next generation space clocks at the required uncertainty based on a completely relativistic model. Using the ACES (Atomic Clock Ensemble in Space) mission as an example, we show that the required accuracy goal can be reached with relatively modest constraints on the orbitography of the space clock, much less str...

  5. Feasibility of an optical fiber clock

    Science.gov (United States)

    Ilinova, Ekaterina; Babb, James F.; Derevianko, Andrei

    2017-09-01

    We explore the feasibility of a fiber clock, i.e., a compact, high-precision, optical lattice atomic clock based on atoms trapped inside a hollow-core optical fiber. Such a setup offers an intriguing potential both for a substantially increased number of interrogated atoms (and thereby an improved clock stability) and for miniaturization. We evaluate the sensitivity of the 1S0-3P0 clock transition in Hg and other divalent atoms to the fiber inner core surface at nonzero temperatures. The Casimir-Polder interaction induced 1S0-3P0 transition frequency shift is calculated for the atom inside the hollow capillary as a function of atomic position, capillary material, and geometric parameters. For Hg atoms on the axis of a silica capillary with inner radius ≥15 μ m and optimally chosen thickness d ˜1 μ m , the atom-surface interaction induced 1S0-3P0 clock transition frequency shift can be kept on the level δ ν /νHg˜10-19 . We also estimate the atom loss and heating due to collisions with the buffer gas, lattice intensity noise induced heating, spontaneous photon scattering heating, and residual birefringence induced frequency shifts.

  6. Body weight, metabolism and clock genes

    Directory of Open Access Journals (Sweden)

    Zanquetta Melissa M

    2010-08-01

    Full Text Available Abstract Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus and peripheral (located in other tissues circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity.

  7. Direct laser cooling Al+ ions optical clocks

    CERN Document Server

    Zhang, J; Luo, J; Lu, Z H

    2016-01-01

    Al$^+$ ions optical clock is a very promising optical frequency standard candidate due to its extremely small blackbody radiation shift. It has been successfully demonstrated with indirect cooled, quantum-logic-based spectroscopy technique. Its accuracy is limited by second-order Doppler shift, and its stability is limited by the number of ions that can be probed in quantum logic processing. We propose a direct laser cooling scheme of Al$^+$ ions optical clocks where both the stability and accuracy of the clocks are greatly improved. In the proposed scheme, two Al$^+$ ions traps are utilized. The first trap is used to trap a large number of Al$^+$ ions to improve the stability of the clock laser, while the second trap is used to trap a single Al$^+$ ions to provide the ultimate accuracy. Both traps are cooled with a continuous wave 167 nm laser. The expected clock laser stability can reach $9.0\\times10^{-17}/\\sqrt{\\tau}$. For the second trap, in addition to 167 nm laser Doppler cooling, a second stage pulsed ...

  8. Interplay between Dioxin-Mediated Signaling and Circadian Clock: A Possible Determinant in Metabolic Homeostasis

    Directory of Open Access Journals (Sweden)

    Chun Wang

    2014-07-01

    Full Text Available The rotation of the earth on its axis creates the environment of a 24 h solar day, which organisms on earth have used to their evolutionary advantage by integrating this timing information into their genetic make-up in the form of a circadian clock. This intrinsic molecular clock is pivotal for maintenance of synchronized homeostasis between the individual organism and the external environment to allow coordinated rhythmic physiological and behavioral function. Aryl hydrocarbon receptor (AhR is a master regulator of dioxin-mediated toxic effects, and is, therefore, critical in maintaining adaptive responses through regulating the expression of phase I/II drug metabolism enzymes. AhR expression is robustly rhythmic, and physiological cross-talk between AhR signaling and circadian rhythms has been established. Increasing evidence raises a compelling argument that disruption of endogenous circadian rhythms contributes to the development of disease, including sleep disorders, metabolic disorders and cancers. Similarly, exposure to environmental pollutants through air, water and food, is increasingly cited as contributory to these same problems. Thus, a better understanding of interactions between AhR signaling and the circadian clock regulatory network can provide critical new insights into environmentally regulated disease processes. This review highlights recent advances in the understanding of the reciprocal interactions between dioxin-mediated AhR signaling and the circadian clock including how these pathways relate to health and disease, with emphasis on the control of metabolic function.

  9. Cadence Design of clock/calendar using 240*8 bit RAM using Verilog HDL

    Directory of Open Access Journals (Sweden)

    K.R.N.Karthik

    2013-06-01

    Full Text Available In the contrast of the modern day technology evolution the number of electronic components increasing on a system. New electronic control units (ECUs are not only dedicated to entertainment, but alsofor increasing safety and comfort. More and more mechanical connections are replaced by electronic ones to save energy and increase comfort and security. All these electronic devices need a way of exchanging information on a fast, reliable and robust way. As there was a tremendous change in the technology day by day mainly in the field of chip designing and the automation technology as due to this the clock speeds are also rapidly increasing along with this power measures are also increasing so to manage this situation we are moving towards the clock/calendar. The clock/calendar circuit based on 2048-bit static RAM organized as 256 words by 8 bits .Address and data are transferred serially via the two-line bidirectional I2C-bus The built in word address register is incremented automatically after each written of read data byte .Addressing pin A0 is used forprogramming the hard ware address .allowing the connection of two device to bus without additional hardware This total module can be used as a real time clock of adjustable frequencies and can also replace the purpose of the counters on the digital based applications This is designed in verilog using Xilinx and cadence 90nm inLINUX environment

  10. Methods for robustness programming

    NARCIS (Netherlands)

    Olieman, N.J.

    2008-01-01

    Robustness of an object is defined as the probability that an object will have properties as required. Robustness Programming (RP) is a mathematical approach for Robustness estimation and Robustness optimisation. An example in the context of designing a food product, is finding the best composition

  11. Model selection reveals control of cold signalling by evening-phased components of the plant circadian clock.

    Science.gov (United States)

    Keily, Jack; MacGregor, Dana R; Smith, Robert W; Millar, Andrew J; Halliday, Karen J; Penfield, Steven

    2013-10-01

    Circadian clocks confer advantages by restricting biological processes to certain times of day through the control of specific phased outputs. Control of temperature signalling is an important function of the plant oscillator, but the architecture of the gene network controlling cold signalling by the clock is not well understood. Here we use a model ensemble fitted to time-series data and a corrected Akaike Information Criterion (AICc) analysis to extend a dynamic model to include the control of the key cold-regulated transcription factors C-REPEAT BINDING FACTORs 1-3 (CBF1, CBF2, CBF3). AICc was combined with in silico analysis of genetic perturbations in the model ensemble, and selected a model that predicted mutant phenotypes and connections between evening-phased circadian clock components and CBF3 transcriptional control, but these connections were not shared by CBF1 and CBF2. In addition, our model predicted the correct gating of CBF transcription by cold only when the cold signal originated from the clock mechanism itself, suggesting that the clock has an important role in temperature signal transduction. Our data shows that model selection could be a useful method for the expansion of gene network models. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  12. Conference Report: CAQD Conference 2013

    Directory of Open Access Journals (Sweden)

    Christina Silver

    2013-05-01

    Full Text Available Nestled on the banks of the river Lahn in central Germany, the 15th CAQD conference was held at Marburg. A beautiful provincial town, it is one of very few that was spared the bombings of WWII; now providing the perfect backdrop for meeting to discuss developments in qualitative technology. This was the second international conference in the series with more than 140 delegates from 14 countries, including: Canada, Brazil, Portugal, the UK, as well as Germany. Hosted by MAGMA, the Marburg Research Group for Methodology and Evaluation, in partnership with Philipps-University Marburg, CAQD prioritizes a user-focus which balances practical and methodological workshops with conference presentations. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1302249

  13. Evolutionary links between circadian clocks and photoperiodic diapause in insects.

    Science.gov (United States)

    Meuti, Megan E; Denlinger, David L

    2013-07-01

    In this article, we explore links between circadian clocks and the clock involved in photoperiodic regulation of diapause in insects. Classical resonance (Nanda-Hamner) and night interruption (Bünsow) experiments suggest a circadian basis for the diapause response in nearly all insects that have been studied. Neuroanatomical studies reveal physical connections between circadian clock cells and centers controlling the photoperiodic diapause response, and both mutations and knockdown of clock genes with RNA interference (RNAi) point to a connection between the clock genes and photoperiodic induction of diapause. We discuss the challenges of determining whether the clock, as a functioning module, or individual clock genes acting pleiotropically are responsible for the photoperiodic regulation of diapause, and how a stable, central circadian clock could be linked to plastic photoperiodic responses without compromising the clock's essential functions. Although we still lack an understanding of the exact mechanisms whereby insects measure day/night length, continued classical and neuroanatomical approaches, as well as forward and reverse genetic experiments, are highly complementary and should enable us to decipher the diverse ways in which circadian clocks have been involved in the evolution of photoperiodic induction of diapause in insects. The components of circadian clocks vary among insect species, and diapause appears to have evolved independently numerous times, thus, we anticipate that not all photoperiodic clocks of insects will interact with circadian clocks in the same fashion.

  14. Conference Hopes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Annual conference outlines tasks for 2010 to solidify China’s economic recovery through rational investment and increasing consumptionc hina will adhere to a consistent and stable economic strategy, putting in place a proactive fiscal policy and an accommodative monetary policy for the 2010 fiscal year-the macro-economic course mapped out during China’s Central

  15. Conference proceedings

    African Journals Online (AJOL)

    abp

    2015-08-07

    Aug 7, 2015 ... African epidemiological association and 1st conference of the Cameroon society of ... International Reference Centre (CIRCB) for research on HIV/AIDS prevention and .... interests (third line regimens, clinical trials and HIV functional cure). ... sharing. Regarding Mycobacterium Tuberculosis, the efficacy of.

  16. Susceptibility of Redundant Versus Singular Clock Domains Implemented in SRAM-Based FPGA TMR Designs

    Science.gov (United States)

    Berg, Melanie D.; LaBel, Kenneth A.; Pellish, Jonathan

    2016-01-01

    We present the challenges that arise when using redundant clock domains due to their clock-skew. Radiation data show that a singular clock domain (DTMR) provides an improved TMR methodology for SRAM-based FPGAs over redundant clocks.

  17. Sugars, the clock and transition to flowering

    Directory of Open Access Journals (Sweden)

    Mohammad Reza eBolouri Moghaddam

    2013-02-01

    Full Text Available Sugars do not only act as source of energy, but they also act as signals in plants. This mini review summarizes the emerging links between sucrose-mediated signaling and the cellular networks involved in flowering time control and defense. Cross-talks with gibberellin (GA and jasmonate (JA signaling pathways are highlighted. The circadian clock fulfills a crucial role at the heart of cellular networks and the bilateral relation between sugar signaling and the clock is discussed. It is proposed that important factors controlling plant growth (DELLAs, PIFs, invertases and trehalose- 6-phosphate or T6P might fulfill central roles in the transition to flowering as well. The emerging concept of ‘sweet immunity’, modulated by the clock, might at least partly rely on a sucrose-specific signaling pathway that needs further exploration.

  18. Quantum clock: A critical discussion on spacetime

    CERN Document Server

    Burderi, Luciano; Iaria, Rosario

    2016-01-01

    We critically discuss the measure of very short time intervals. By means of a Gedankenexperiment, we describe an ideal clock based on the occurrence of completely random events. Many previous thought experiments have suggested fundamental Planck-scale limits on measurements of distance and time. Here we present a new type of thought experiment, based on a different type of clock, that provide further support for the existence of such limits. We show that the minimum time interval $\\Delta t$ that this clock can measure scales as the inverse of its size $\\Delta r$. This implies an uncertainty relation between space and time: $\\Delta r$ $\\Delta t$ $> G \\hbar / c^4$; where G, $\\hbar$ and c are the gravitational constant, the reduced Planck constant, and the speed of light, respectively. We outline and briefly discuss the implications of this uncertainty conjecture.

  19. Models of the Primordial Standard Clock

    CERN Document Server

    Chen, Xingang; Wang, Yi

    2014-01-01

    Oscillating massive fields in the primordial universe can be used as Standard Clocks. The ticks of these oscillations induce features in the density perturbations, which directly record the time evolution of the scale factor of the primordial universe, thus if detected, provide a direct evidence for the inflation scenario or the alternatives. In this paper, we construct a full inflationary model of primordial Standard Clock and study its predictions on the density perturbations. This model provides a full realization of several key features proposed previously. We compare the theoretical predictions from inflation and alternative scenarios with the Planck 2013 temperature data on Cosmic Microwave Background (CMB), and identify a statistically marginal but interesting candidate. We discuss how future CMB temperature and polarization data, non-Gaussianity analysis and Large Scale Structure data may be used to further test or constrain the Standard Clock signals.

  20. Biogeographic calibrations for the molecular clock.

    Science.gov (United States)

    Ho, Simon Y W; Tong, K Jun; Foster, Charles S P; Ritchie, Andrew M; Lo, Nathan; Crisp, Michael D

    2015-09-01

    Molecular estimates of evolutionary timescales have an important role in a range of biological studies. Such estimates can be made using methods based on molecular clocks, including models that are able to account for rate variation across lineages. All clock models share a dependence on calibrations, which enable estimates to be given in absolute time units. There are many available methods for incorporating fossil calibrations, but geological and climatic data can also provide useful calibrations for molecular clocks. However, a number of strong assumptions need to be made when using these biogeographic calibrations, leading to wide variation in their reliability and precision. In this review, we describe the nature of biogeographic calibrations and the assumptions that they involve. We present an overview of the different geological and climatic events that can provide informative calibrations, and explain how such temporal information can be incorporated into dating analyses.

  1. Sample-Clock Phase-Control Feedback

    Science.gov (United States)

    Quirk, Kevin J.; Gin, Jonathan W.; Nguyen, Danh H.; Nguyen, Huy

    2012-01-01

    To demodulate a communication signal, a receiver must recover and synchronize to the symbol timing of a received waveform. In a system that utilizes digital sampling, the fidelity of synchronization is limited by the time between the symbol boundary and closest sample time location. To reduce this error, one typically uses a sample clock in excess of the symbol rate in order to provide multiple samples per symbol, thereby lowering the error limit to a fraction of a symbol time. For systems with a large modulation bandwidth, the required sample clock rate is prohibitive due to current technological barriers and processing complexity. With precise control of the phase of the sample clock, one can sample the received signal at times arbitrarily close to the symbol boundary, thus obviating the need, from a synchronization perspective, for multiple samples per symbol. Sample-clock phase-control feedback was developed for use in the demodulation of an optical communication signal, where multi-GHz modulation bandwidths would require prohibitively large sample clock frequencies for rates in excess of the symbol rate. A custom mixedsignal (RF/digital) offset phase-locked loop circuit was developed to control the phase of the 6.4-GHz clock that samples the photon-counting detector output. The offset phase-locked loop is driven by a feedback mechanism that continuously corrects for variation in the symbol time due to motion between the transmitter and receiver as well as oscillator instability. This innovation will allow significant improvements in receiver throughput; for example, the throughput of a pulse-position modulation (PPM) with 16 slots can increase from 188 Mb/s to 1.5 Gb/s.

  2. Secure and self-stabilizing clock synchronization in sensor networks

    NARCIS (Netherlands)

    Hoepman, J.H.; Larsson, A.; Schiller, E.M.; Tsigas, P.

    2007-01-01

    In sensor networks, correct clocks have arbitrary starting offsets and nondeterministic fluctuating skews. We consider an adversary that aims at tampering with the clock synchronization by intercepting messages, replaying intercepted messages (after the adversary's choice of delay), and capturing no

  3. Analysis of the performance of hydrogen maser clocks at the ...

    African Journals Online (AJOL)

    Cilence

    clock characteristics have a direct influence on precision and accuracy of the ..... Generation Atomic Fountain Clock at NIST', Proceedings of the 2004 IEEE International ... Plag H-P, Altamimi Z, Bettadpur S, Beutler G, Beyerle G, Cazenve A, ...

  4. Unusual Maths clock or Reverse Traveling Salesman Problem

    Directory of Open Access Journals (Sweden)

    Valerij F. Ochkov

    2014-01-01

    Full Text Available The article discusses some of the mathematical problem, attached to the clock. We show how to use the clock in the classroom for mathematics to illustrate some mathematical problems 

  5. Clocking Scheme for Switched-Capacitor Circuits

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    1998-01-01

    A novel clocking scheme for switched-capacitor (SC) circuits is presented. It can enhance the understanding of SC circuits and the errors caused by MOSFET (MOS) switches. Charge errors, and techniques to make SC circuits less sensitive to them are discussed.......A novel clocking scheme for switched-capacitor (SC) circuits is presented. It can enhance the understanding of SC circuits and the errors caused by MOSFET (MOS) switches. Charge errors, and techniques to make SC circuits less sensitive to them are discussed....

  6. The Large Water-Clock of Amphiaraeion

    Science.gov (United States)

    Theodossiou, E.; Manimanis, V. N.; Katsiotis, M.; Mantarakis, P.

    2010-07-01

    A very well preserved ancient water-clock exists at the Amphiaraeion, in Oropos, Greece. The Amphiaraeion, sanctuary of the mythical oracle and deified healer Amphiaraus, was active from the pre-classic period until the 5th Century A.D. In such a place the measurement of time, both day and night, was a necessity. Therefore, time was kept with both a conical sundial and a water-clock in the shape of a fountain, which, according to the archaeologists, dates to the 4th Century B.C.

  7. The robust regulation problem with robust stability

    NARCIS (Netherlands)

    Cevik, M.K.K.; Schumacher, J.M.

    1999-01-01

    Among the most common purposes of control are the tracking of reference signals and the rejection of disturbance signals in the face of uncertainties. The related design problem is called the `robust regulation problem'. Here we investigate the trade-off between the robust regulation constraint and

  8. Immunometabolism: Is it under the eye of the clock?

    OpenAIRE

    Early, James O.; Curtis, Anne M.

    2016-01-01

    Molecular clocks allow an organism to track time of day, providing the means to anticipate and respond to the daily changes within the environment. In mammals the molecular clock consists of a network of proteins that form auto-regulatory feedback loops that drive rhythms in physiology and behavior. In recent times the extent to which the molecular clock controls key metabolic and immune pathways has begun to emerge. For example, the main clock protein BMAL1 has been linked to mitochondrial m...

  9. Scaling for Robust Assessment and Predictions of Aquatic Ecosystem Health

    Science.gov (United States)

    Abdul-Aziz, O.; Ishtiaq, K. S.

    2012-12-01

    This presentation demonstrates the development and applications of a unique scaling technique for robust assessment and predictions of aquatic ecosystem health. We developed scaling-based, robust empirical and semi-empirical models for standardizing grab samples of stream dissolved oxygen (DO) and for predicting (hindcasting and forecasting) stream DO time-series. A reference clock-time, single observation from the diurnal cycle is used as the scaling parameter to collapse hourly DO time-series of different days into a single diurnal curve, which is parameterized by developing an extended stochastic harmonic analysis (ESHA). The scaling technique was previously applied to develop an algorithm for converting grab samples of stream DO collected at any time of the day to a reference clock time. The research is extended to develop an algorithm for simulating the diurnal DO cycles at different stream sites from their corresponding single reference observations of the day. The scaling concept was tested for spatio-temporal robustness with hourly DO data for eight streams representing five distinct Level III Ecoregions of Minnesota. Estimated model parameters demonstrated notable robustness in time and space. Scaling is often used to develop robust modeling and application tools in many physical engineering disciplines. Presented research exemplifies utilization of the scaling concept in Ecological Engineering applications.

  10. Circadian clocks - the fall and rise of physiology

    NARCIS (Netherlands)

    Roenneberg, Till; Merrow, Martha

    2005-01-01

    Circadian clocks control the daily life of most light-sensitive organisms- from cyanobacteria to humans. Molecular processes generate cellular rhythmicity, and cellular clocks in animals coordinate rhythms through interaction ( known as coupling). This hierarchy of clocks generates a complex, simila

  11. SIGEF Conference

    CERN Document Server

    Terceño-Gómez, Antonio; Ferrer-Comalat, Joan; Merigó-Lindahl, José; Linares-Mustarós, Salvador

    2015-01-01

    This book is a collection of selected papers presented at the SIGEF conference, held at the Faculty of Economics and Business of the University of Girona (Spain), 06-08 July, 2015. This edition of the conference has been presented with the slogan “Scientific methods for the treatment of uncertainty in social sciences”. There are different ways for dealing with uncertainty in management. The book focuses on soft computing theories and their role in assessing uncertainty in a complex world. It gives a comprehensive overview of quantitative management topics and discusses some of the most recent developments in all the areas of business and management in soft computing including Decision Making, Expert Systems and Forgotten Effects Theory, Forecasting Models, Fuzzy Logic and Fuzzy Sets, Modelling and Simulation Techniques, Neural Networks and Genetic Algorithms and Optimization and Control. The book might be of great interest for anyone working in the area of management and business economics and might be es...

  12. Conference information

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Thermag Ⅳ- The 4th International Conference on Magnetic Refrigeration at Room Temperature of IIR Refrigeration technology is widely used today. However, traditional vapor compression/expansion refrigeration technology has some disadvantages, such as low conversion efficiency of vapor compressor, and emission of the ozonosphere depletion gas and greenhouse effect gas, etc. Magnetic refrigeration is a new cooling technology with huge potential application prospect, characterized by high efficiency, energy saving and environmental friendly.

  13. Theoretical Modeling and Simulation of Phase-Locked Loop (PLL) for Clock Data Recovery (CDR)

    CERN Document Server

    Ashari, Zainab

    2012-01-01

    Modern communication and computer systems require rapid (Gbps), efficient and large bandwidth data transfers. Agressive scaling of digital integrated systems allow buses and communication controller circuits to be integrated with the microprocessor on the same chip. The Peripheral Component Interconnect Express (PCIe) protocol handles all communcation between the central processing unit (CPU) and hardware devices. PCIe buses require efficient clock data recovery circuits (CDR) to recover clock signals embedded in data during transmission. This paper describes the theoretical modeling and simulation of a phase-locked loop (PLL) used in a CDR circuit. A simple PLL architecture for a 5 GHz CDR circuit is proposed and elaborated in this work. Simulations were carried out using a Hardware Description Language, Verilog- AMS. The effect of jitter on the proposed design is also simulated and evaluated in this work. It was found that the proposed design is robust against both input and VCO jitter.

  14. Light-shift elimination in Generalized Hyper-Ramsey quantum clocks

    CERN Document Server

    Zanon-Willette, Thomas; Arimondo, Ennio

    2015-01-01

    We present a new generation of quantum clocks absolutely free from ac Stark-shift based on generalized hyper-Ramsey resonances with separated oscillating fields. Sequences of composite laser pulses with specific selection of phases, frequency detunings and durations are combined to generate a very efficient and robust frequency locking signal with a perfect elimination of the light-shift from off resonant states. Laser phase-step modulations during interactions with electromagnetic fields are applied in order to decouple the unperturbed frequency measurement from the laser's intensity. The frequency lock point is protected against laser pulse area fluctuations and errors in potentially applied frequency shift compensations. Quantum clocks based on weakly allowed or completely forbidden optical transitions in atoms, ions, molecules and nuclei will benefit from these hyper-stable laser frequency stabilization schemes to reach relative accuracies well below the 10$^{-18}$ level.

  15. Probe light-shift elimination in generalized hyper-Ramsey quantum clocks

    Science.gov (United States)

    Zanon-Willette, T.; de Clercq, E.; Arimondo, E.

    2016-04-01

    We present an interrogation scheme for the next generation of quantum clocks to suppress frequency shifts induced by laser probing fields that are themselves based on generalized hyper-Ramsey resonances. Sequences of composite laser pulses with a specific selection of phases, frequency detunings, and durations are combined to generate a very efficient and robust frequency locking signal with an almost perfect elimination of the light shift from off-resonant states and to decouple the unperturbed frequency measurement from the laser's intensity. The frequency lock point generated from synthesized error signals using either π /4 or 3 π /4 laser phase steps during the intermediate pulse is tightly protected against large laser-pulse area variations and errors in potentially applied frequency shift compensations. Quantum clocks based on weakly allowed or completely forbidden optical transitions in atoms, ions, molecules, and nuclei will benefit from these hyperstable laser frequency stabilization schemes to reach relative accuracies below the 10-18 level.

  16. Computational analysis of mammalian cell division gated by a circadian clock: quantized cell cycles and cell size control.

    Science.gov (United States)

    Zámborszky, Judit; Hong, Christian I; Csikász Nagy, Attila

    2007-12-01

    Cell cycle and circadian rhythms are conserved from cyanobacteria to humans with robust cyclic features. Recently, molecular links between these two cyclic processes have been discovered. Core clock transcription factors, Bmal1 and Clock (Clk), directly regulate Wee1 kinase, which inhibits entry into the mitosis. We investigate the effect of this connection on the timing of mammalian cell cycle processes with computational modeling tools. We connect a minimal model of circadian rhythms, which consists of transcription-translation feedback loops, with a modified mammalian cell cycle model from Novak and Tyson (2004). As we vary the mass doubling time (MDT) of the cell cycle, stochastic simulations reveal quantized cell cycles when the activity of Wee1 is influenced by clock components. The quantized cell cycles disappear in the absence of coupling or when the strength of this link is reduced. More intriguingly, our simulations indicate that the circadian clock triggers critical size control in the mammalian cell cycle. A periodic brake on the cell cycle progress via Wee1 enforces size control when the MDT is quite different from the circadian period. No size control is observed in the absence of coupling. The issue of size control in the mammalian system is debatable, whereas it is well established in yeast. It is possible that the size control is more readily observed in cell lines that contain circadian rhythms, since not all cell types have a circadian clock. This would be analogous to an ultradian clock intertwined with quantized cell cycles (and possibly cell size control) in yeast. We present the first coupled model between the mammalian cell cycle and circadian rhythms that reveals quantized cell cycles and cell size control influenced by the clock.

  17. System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock.

    Directory of Open Access Journals (Sweden)

    Benoît Kornmann

    2007-02-01

    Full Text Available The mammalian circadian timing system consists of a master pacemaker in neurons of the suprachiasmatic nucleus (SCN and clocks of a similar molecular makeup in most peripheral body cells. Peripheral oscillators are self-sustained and cell autonomous, but they have to be synchronized by the SCN to ensure phase coherence within the organism. In principle, the rhythmic expression of genes in peripheral organs could thus be driven not only by local oscillators, but also by circadian systemic signals. To discriminate between these mechanisms, we engineered a mouse strain with a conditionally active liver clock, in which REV-ERBalpha represses the transcription of the essential core clock gene Bmal1 in a doxycycline-dependent manner. We examined circadian liver gene expression genome-wide in mice in which hepatocyte oscillators were either running or arrested, and found that the rhythmic transcription of most genes depended on functional hepatocyte clocks. However, we discovered 31 genes, including the core clock gene mPer2, whose expression oscillated robustly irrespective of whether the liver clock was running or not. By contrast, in liver explants cultured in vitro, circadian cycles of mPer2::luciferase bioluminescence could only be observed when hepatocyte oscillators were operational. Hence, the circadian cycles observed in the liver of intact animals without functional hepatocyte oscillators were likely generated by systemic signals. The finding that rhythmic mPer2 expression can be driven by both systemic cues and local oscillators suggests a plausible mechanism for the phase entrainment of subsidiary clocks in peripheral organs.

  18. The salient features of the clock

    DEFF Research Database (Denmark)

    Ebbesen, Toke Riis

    2005-01-01

    of functional semiotics is explained in short terms and then further demonstrated in the analysis of a basic mechanical alarm clock. On this ground, the digital watch and digital design products in general are characterised and three possible avenues for the interpretation of the interactive possibilities...

  19. Circadian clocks: Omnes viae Romam ducunt.

    Science.gov (United States)

    Roenneberg, T; Merrow, M

    2000-10-19

    The circadian clock in all organisms is so intimately linked to light reception that it appears as if evolution has simply wired a timer into the mechanism that processes photic information. Several recent studies have provided new insights into the role of light input pathways in the circadian system of Arabidopsis.

  20. The mammalian retina as a clock

    Science.gov (United States)

    Tosini, Gianluca; Fukuhara, Chiaki

    2002-01-01

    Many physiological, cellular, and biochemical parameters in the retina of vertebrates show daily rhythms that, in many cases, also persist under constant conditions. This demonstrates that they are driven by a circadian pacemaker. The presence of an autonomous circadian clock in the retina of vertebrates was first demonstrated in Xenopus laevis and then, several years later, in mammals. In X. laevis and in chicken, the retinal circadian pacemaker has been localized in the photoreceptor layer, whereas in mammals, such information is not yet available. Recent advances in molecular techniques have led to the identification of a group of genes that are believed to constitute the molecular core of the circadian clock. These genes are expressed in the retina, although with a slightly different 24-h profile from that observed in the central circadian pacemaker. This result suggests that some difference (at the molecular level) may exist between the retinal clock and the clock located in the suprachiasmatic nuclei of hypothalamus. The present review will focus on the current knowledge of the retinal rhythmicity and the mechanisms responsible for its control.

  1. Radium single-ion optical clock

    NARCIS (Netherlands)

    Versolato, O. O.; Wansbeek, L. W.; Jungmann, K.; Timmermans, R. G. E.; Willmann, L.; Wilschut, H. W.

    2011-01-01

    We explore the potential of the electric quadrupole transitions $7s\\,^2S_{1/2}$ - $6d\\,^2D_{3/2}$, $6d\\,^2D_{5/2}$ in radium isotopes as single-ion optical frequency standards. The frequency shifts of the clock transitions due to external fields and the corresponding uncertainties are calculated.

  2. Circadian clock proteins in prokaryotes: hidden rhythms?

    Directory of Open Access Journals (Sweden)

    Maria eLoza-Correa

    2010-12-01

    Full Text Available Circadian clock genes are vital features of eukaryotes that have evolved such that organisms can adapt to our planet’s rotation in order to anticipate the coming day or night as well as unfavorable seasons. This circadian clock uses oscillation as a timekeeping element. However, circadian clock mechanisms exist also in prokaryotes. The circadian clock of Cyanobacteria is well studied. It is regulated by a cluster of three genes: kaiA, kaiB and kaiC. In this review, we will discuss the circadian system in cyanobacteria, and provide an overview and up-dated phylogenetic analysis of prokaryotic organisms that contain the main circadian genes. It is evident that the evolution of the kai genes has been influenced by lateral transfers but further and deeper studies are needed to get an in depth understanding of the exact evolutionary history of these genes. Interestingly, Legionella pneumophila an environmental bacterium and opportunistic human pathogen that parasitizes protozoa in fresh water environments also contains kaiB and kaiC, but their functions are not known. All of the residues described for the biochemical functions of the main pacemaker KaiC in Synechoccous elongates are also conserved in the L. pneumophila KaiC protein.

  3. Biochemical basis for the biological clock

    Science.gov (United States)

    Morre, D. James; Chueh, Pin-Ju; Pletcher, Jake; Tang, Xiaoyu; Wu, Lian-Ying; Morre, Dorothy M.

    2002-01-01

    NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.

  4. Internal clock formulation of quantum mechanics

    Science.gov (United States)

    Małkiewicz, Przemysław; Miroszewski, Artur

    2017-08-01

    The basic tenet of the present work is the assumption of the lack of external and fixed time in the Universe. This assumption is best embodied by general relativity, which replaces the fixed space-time structure with the gravitational field, which is subject to dynamics. The lack of time does not imply the lack of evolution but rather brings to the forefront the role of internal clocks which are some largely arbitrary internal degrees of freedom with respect to which the evolution of timeless systems can be described. We take this idea seriously and try to understand what it implies for quantum mechanics when the fixed external time is replaced by an arbitrary internal clock. We put the issue in a solid, mathematically rigorous framework. We find that the dynamical interpretation of a quantum state of a timeless system depends on the employed internal clock. In particular, we find that the continuous spectra of well-known dynamical observables like the position of a free particle on the real line may turn discrete if measured in unusual clocks. We discuss the meaning of our result for attempts at quantization of global gravitational degrees of freedom.

  5. Circadian clocks - from genes to complex behaviour

    NARCIS (Netherlands)

    Roenneberg, Till; Merrow, Martha

    1999-01-01

    Circadian clocks control temporal structure in practically all organisms and on all levels of biology, from gene expression to complex behaviour and cognition. Over the last decades, research has begun to unravel the physiological and, more recently, molecular mechanisms that underlie this endogenou

  6. Circadian Clocks in the Immune System.

    Science.gov (United States)

    Labrecque, Nathalie; Cermakian, Nicolas

    2015-08-01

    The immune system is a complex set of physiological mechanisms whose general aim is to defend the organism against non-self-bodies, such as pathogens (bacteria, viruses, parasites), as well as cancer cells. Circadian rhythms are endogenous 24-h variations found in virtually all physiological processes. These circadian rhythms are generated by circadian clocks, located in most cell types, including cells of the immune system. This review presents an overview of the clocks in the immune system and of the circadian regulation of the function of immune cells. Most immune cells express circadian clock genes and present a wide array of genes expressed with a 24-h rhythm. This has profound impacts on cellular functions, including a daily rhythm in the synthesis and release of cytokines, chemokines and cytolytic factors, the daily gating of the response occurring through pattern recognition receptors, circadian rhythms of cellular functions such as phagocytosis, migration to inflamed or infected tissue, cytolytic activity, and proliferative response to antigens. Consequently, alterations of circadian rhythms (e.g., clock gene mutation in mice or environmental disruption similar to shift work) lead to disturbed immune responses. We discuss the implications of these data for human health and the areas that future research should aim to address.

  7. The Rubidium Atomic Clock and Basic Research

    Science.gov (United States)

    2007-12-10

    photodetector . (Chip-scale clock image from ref. 14.) 38 November 2007 Physics Today www.physicstoday.org an all-optical fashion:13 The laser field is...spectroscopy, laser chemistry, atmospheric propagation and beam control, LIDAR /LADAR remote sensing; solar cell and array testing and evaluation, battery

  8. Using circadian entrainment to find cryptic clocks

    NARCIS (Netherlands)

    Eelderink-Chen, Zheng; Olmedo, Maria; Bosman, Jasper; Merrow, Martha

    2015-01-01

    Three properties are most often attributed to the circadian clock: a ca. 24-h free-running rhythm, temperature compensation of the circadian rhythm, and its entrainment to zeitgeber cycles. Relatively few experiments, however, are performed under entrainment conditions. Rather, most chronobiology pr

  9. Current Status of the Molecular Clock Hypothesis

    Science.gov (United States)

    Hermann, Gilbert

    2003-01-01

    Molecular genetics is a rapidly changing field with new developments almost from day to day. One interesting hypothesis that has come from everyone's ability to sequence proteins and/or genes is that of the molecular clock. This hypothesis postulates that homologous sequences of DNA and thus macro molecules evolve at a constant and invariable rate…

  10. Clock Synchronization for Multihop Wireless Sensor Networks

    Science.gov (United States)

    Solis Robles, Roberto

    2009-01-01

    In wireless sensor networks, more so generally than in other types of distributed systems, clock synchronization is crucial since by having this service available, several applications such as media access protocols, object tracking, or data fusion, would improve their performance. In this dissertation, we propose a set of algorithms to achieve…

  11. Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the "master clock".

    NARCIS (Netherlands)

    Wu, Y.-H.; Fischer, D.F.; Kalsbeek, A.; Garidou-Boof, M.-L.; Vliet, J. van der; Heijningen, C. van; Liu, R.-Y.; Zhou, J.-N.; Swaab, D.F.

    2006-01-01

    The suprachiasmatic nucleus (SCN) is the "master clock" of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease (AD

  12. Disrupted light-dark cycle abolishes circadian expression of peripheral clock genes without inducing behavioral arrhythmicity in mice.

    Science.gov (United States)

    Oishi, Katsutaka; Higo-Yamamoto, Sayaka; Yamamoto, Saori; Yasumoto, Yuki

    2015-03-06

    The environmental light-dark (LD) cycle entrains the central circadian clock located in the suprachiasmatic nucleus (SCN) of mammals. The present study examined the effects of disrupted LD cycles on peripheral clocks in mice housed under a normal 12 h light-12 h dark cycle (LD 12:12) or an ultradian LD 3:3 cycle. Drinking behavior seemed to be free-running with a long period (26.03 h) under ultradian LD 3:3 cycles, in addition to light-induced direct suppression (masking effect). Core body temperature completely lost robust circadian rhythm and acquired a 6-h rhythm with a low amplitude under LD 3:3. Robust circadian expression of Per1, Per2, Clock and Bmal1 mRNAs was similarly flattened to intermediate levels in the liver, heart and white adipose tissue under LD 3:3. Robust circadian expression of Rev-erbα mRNA was completely damped in these tissues. Circadian expression of Dbp, a clock-controlled gene, was also disrupted in these tissues from mice housed under LD 3:3. The aberrant LD cycle seemed to induce the loss of circadian gene expression at the level of transcription, because rhythmic pre-mRNA expression of these genes was also abolished under LD 3:3. In addition to the direct effect of the aberrant LD cycle, abolished systemic time cues such as those of plasma corticosterone and body temperature might be involved in the disrupted expression of these circadian genes under LD 3:3. Our findings suggest that disrupted environmental LD cycles abolish the normal oscillation of peripheral clocks and induce internal desynchrony in mammals.

  13. Clock measurements to improve the geopotential determination

    Science.gov (United States)

    Lion, Guillaume; Panet, Isabelle; Delva, Pacôme; Wolf, Peter; Bize, Sébastien; Guerlin, Christine

    2017-04-01

    Comparisons between optical clocks with an accuracy and stability approaching the 10-18 in term of relative frequency shift are opening new perspectives for the direct determination of geopotential at a centimeter-level accuracy in geoid height. However, so far detailed quantitative estimates of the possible improvement in geoid determination when adding such clock measurements to existing data are lacking. In this context, the present work aims at evaluating the contribution of this new kind of direct measurements in determining the geopotential at high spatial resolution (10 km). We consider the Massif Central area, marked by smooth, moderate altitude mountains and volcanic plateaus leading to variations of the gravitational field over a range of spatial scales. In such type of region, the scarcity of gravity data is an important limitation in deriving accurate high resolution geopotential models. We summarize our methodology to assess the contribution of clock data in the geopotential recovery, in combination with ground gravity measurements. We sample synthetic gravity and disturbing potential data from a spherical harmonics geopotential model, and a topography model, up to 10 km resolution; we also build a potential control grid. From the synthetic data, we estimate the disturbing potential by least-squares collocation. Finally, we assess the quality of the reconstructed potential by comparing it to that of the control grid. We show that adding only a few clock data reduces the reconstruction bias significantly and improves the standard deviation by a factor 3. We discuss the role of different parameters, such as the effect of the data coverage and data quality on these results, the trade-off between the measurement noise level and the number of data, and the optimization of the clock data network.

  14. Maximum likelihood molecular clock comb: analytic solutions.

    Science.gov (United States)

    Chor, Benny; Khetan, Amit; Snir, Sagi

    2006-04-01

    Maximum likelihood (ML) is increasingly used as an optimality criterion for selecting evolutionary trees, but finding the global optimum is a hard computational task. Because no general analytic solution is known, numeric techniques such as hill climbing or expectation maximization (EM), are used in order to find optimal parameters for a given tree. So far, analytic solutions were derived only for the simplest model--three taxa, two state characters, under a molecular clock. Four taxa rooted trees have two topologies--the fork (two subtrees with two leaves each) and the comb (one subtree with three leaves, the other with a single leaf). In a previous work, we devised a closed form analytic solution for the ML molecular clock fork. In this work, we extend the state of the art in the area of analytic solutions ML trees to the family of all four taxa trees under the molecular clock assumption. The change from the fork topology to the comb incurs a major increase in the complexity of the underlying algebraic system and requires novel techniques and approaches. We combine the ultrametric properties of molecular clock trees with the Hadamard conjugation to derive a number of topology dependent identities. Employing these identities, we substantially simplify the system of polynomial equations. We finally use tools from algebraic geometry (e.g., Gröbner bases, ideal saturation, resultants) and employ symbolic algebra software to obtain analytic solutions for the comb. We show that in contrast to the fork, the comb has no closed form solutions (expressed by radicals in the input data). In general, four taxa trees can have multiple ML points. In contrast, we can now prove that under the molecular clock assumption, the comb has a unique (local and global) ML point. (Such uniqueness was previously shown for the fork.).

  15. Suppression of Clock Shifts at Magnetic-Field-Insensitive Transitions

    Science.gov (United States)

    Arnold, K. J.; Barrett, M. D.

    2016-10-01

    We show that it is possible to significantly reduce rank 2 tensor shifts of a clock transition by operating at a judiciously chosen magnetic-field-insensitive point. In some cases shifts are almost completely eliminated making the transition an effective J =0 to J =0 candidate. This significantly improves the feasibility of a recent proposal for clock operation with large ion crystals. For such multi-ion clocks, geometric constraints and selection rules naturally divide clock operation into two categories based on the orientation of the magnetic field. We discuss the limitations imposed on each type and how calibrations might be carried out for clock operation.

  16. Suppression of clock shifts at field-insensitive transitions

    CERN Document Server

    Arnold, Kyle J

    2016-01-01

    We show that it is possible to significantly reduce quadrupole and tensor polarizability shifts of a clock transition by operating at a judiciously chosen field-insensitive point. In some cases shifts are almost completely eliminated making the transition an effective J = 0 to J = 0 candidate. This significantly improves the feasibility of a recent proposal for clock operation with large ion crystals. For such multi-ion clocks, geometric constraints and selection rules naturally divide clock operation into two categories based on the orientation of the magnetic field. We discuss the limitations imposed on each type and how calibrations might be carried out for clock operation.

  17. Molecular-clock methods for estimating evolutionary rates and timescales.

    Science.gov (United States)

    Ho, Simon Y W; Duchêne, Sebastián

    2014-12-01

    The molecular clock presents a means of estimating evolutionary rates and timescales using genetic data. These estimates can lead to important insights into evolutionary processes and mechanisms, as well as providing a framework for further biological analyses. To deal with rate variation among genes and among lineages, a diverse range of molecular-clock methods have been developed. These methods have been implemented in various software packages and differ in their statistical properties, ability to handle different models of rate variation, capacity to incorporate various forms of calibrating information and tractability for analysing large data sets. Choosing a suitable molecular-clock model can be a challenging exercise, but a number of model-selection techniques are available. In this review, we describe the different forms of evolutionary rate heterogeneity and explain how they can be accommodated in molecular-clock analyses. We provide an outline of the various clock methods and models that are available, including the strict clock, local clocks, discrete clocks and relaxed clocks. Techniques for calibration and clock-model selection are also described, along with methods for handling multilocus data sets. We conclude our review with some comments about the future of molecular clocks.

  18. Multiple layers of posttranslational regulation refine circadian clock activity in Arabidopsis.

    Science.gov (United States)

    Seo, Pil Joon; Mas, Paloma

    2014-01-01

    The circadian clock is a cellular time-keeper mechanism that regulates biological rhythms with a period of ~24 h. The circadian rhythms in metabolism, physiology, and development are synchronized by environmental cues such as light and temperature. In plants, proper matching of the internal circadian time with the external environment confers fitness advantages on plant survival and propagation. Accordingly, plants have evolved elaborated regulatory mechanisms that precisely control the circadian oscillations. Transcriptional feedback regulation of several clock components has been well characterized over the past years. However, the importance of additional regulatory mechanisms such as chromatin remodeling, protein complexes, protein phosphorylation, and stability is only starting to emerge. The multiple layers of circadian regulation enable plants to properly synchronize with the environmental cycles and to fine-tune the circadian oscillations. This review focuses on the diverse posttranslational events that regulate circadian clock function. We discuss the mechanistic insights explaining how plants articulate a high degree of complexity in their regulatory networks to maintain circadian homeostasis and to generate highly precise waveforms of circadian expression and activity.

  19. Entangling the lattice clock: Towards Heisenberg-limited timekeeping

    CERN Document Server

    Weinstein, Jonathan D; Derevianko, Andrei

    2009-01-01

    We present a scheme for entangling the atoms of an optical lattice to reduce the quantum projection noise of a clock measurement. The divalent clock atoms are held in a lattice at a ``magic'' wavelength that does not perturb the clock frequency -- to maintain clock accuracy -- while an open-shell J=1/2 ``head'' atom is coherently transported between lattice sites via the lattice polarization. This polarization-dependent ``Archimedes' screw'' transport at magic wavelength takes advantage of the vanishing vector polarizability of the scalar, J=0, clock states of bosonic isotopes of divalent atoms. The on-site interactions between the clock atoms and the head atom are used to engineer entanglement and for clock readout.

  20. Satellite virtual atomic clock with pseudorange difference function

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Satellite atomic clocks are the basis of GPS for the control of time and frequency of navigation signals. In the Chinese Area Positioning System (CAPS), a satellite navigation system without the satellite atomic clocks onboard is successfully developed. Thus, the method of time synchronization based on satellite atomic clocks in GPS is not suitable. Satellite virtual atomic clocks are used to implement satellite navigation. With the satellite virtual atomic clocks, the time at which the signals are transmitted from the ground can be delayed into the time that the signals are transmitted from the satellites and the pseudorange measuring can be fulfilled as in GPS. Satellite virtual atomic clocks can implement the navigation, make a pseudorange difference, remove the ephemeris error, and improve the accuracy of navigation positioning. They not only provide a navigation system without satellite clocks, but also a navigation system with pseudorange difference.

  1. Arabidopsis circadian clock and photoperiodism: time to think about location.

    Science.gov (United States)

    Imaizumi, Takato

    2010-02-01

    Plants possess a circadian clock that enables them to coordinate internal biological events with external daily changes. Recent studies in Arabidopsis revealed that tissue-specific clock components exist and that the clock network architecture also varies within different organs. These findings indicate that the makeup of circadian clock(s) within a plant is quite variable. Plants utilize the circadian clock to measure day-length changes for regulating seasonal responses, such as flowering. To ensure that flowering occurs under optimum conditions, the clock regulates diurnal CONSTANS (CO) expression. Subsequently, CO protein induces FLOWERING LOCUS T (FT) expression which leads to flowering. It is emerging that both CO and FT expression are intricately controlled by groups of transcription factors with overlapping functions. Copyright 2009 Elsevier Ltd. All rights reserved.

  2. Network news: prime time for systems biology of the plant circadian clock truncated form of the title: Plant circadian clocks

    Science.gov (United States)

    McClung, C. Robertson; Gutiérrez, Rodrigo A.

    2011-01-01

    Summary Whole-transcriptome analyses have established that the plant circadian clock regulates virtually every plant biological process and most prominently hormonal and stress response pathways. Systems biology efforts have successfully modeled the plant central clock machinery and an iterative process of model refinement and experimental validation has contributed significantly to the current view of the central clock machinery. The challenge now is to connect this central clock to the output pathways for understanding how the plant circadian clock contributes to plant growth and fitness in a changing environment. Undoubtedly, systems approaches will be needed to integrate and model the vastly increased volume of experimental data in order to extract meaningful biological information. Thus, we have entered an era of systems modeling, experimental testing, and refinement. This approach, coupled with advances from the genetic and biochemical analyses of clock function, is accelerating our progress towards a comprehensive understanding of the plant circadian clock network. PMID:20889330

  3. The mammalian circadian clock protein period counteracts cryptochrome in phosphorylation dynamics of circadian locomotor output cycles kaput (CLOCK).

    Science.gov (United States)

    Matsumura, Ritsuko; Tsuchiya, Yoshiki; Tokuda, Isao; Matsuo, Takahiro; Sato, Miho; Node, Koichi; Nishida, Eisuke; Akashi, Makoto

    2014-11-14

    The circadian transcription factor CLOCK exhibits a circadian oscillation in its phosphorylation levels. Although it remains unclear whether this phosphorylation contributes to circadian rhythm generation, it has been suggested to be involved in transcriptional activity, intracellular localization, and degradative turnover of CLOCK. Here, we obtained direct evidence that CLOCK phosphorylation may be essential for autonomous circadian oscillation in clock gene expression. Importantly, we found that the circadian transcriptional repressors Cryptochrome (CRY) and Period (PER) showed an opposite effect on CLOCK phosphorylation; CRY impaired BMAL1-dependent CLOCK phosphorylation, whereas PER protected the phosphorylation against CRY. Interestingly, unlike PER1 and PER2, PER3 did not exert a protective action, which correlates with the phenotypic differences among mice lacking the Per genes. Further studies on the regulatory mechanism of CLOCK phosphorylation would thus lead to elucidation of the mechanism of CRY-mediated transcriptional repression and an understanding of the true role of PER in the negative feedback system.

  4. Conference Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Riveros, P. A.; Dutrizac, J. E. [Natural Resources Canada, Ottawa, ON (Canada)] [eds.

    2001-07-01

    This workshop is part of a continuing series of joint workshops organized by CANMET of Natural Resources Canada and the Research Directorate-General of the European Commission in the areas of sustainable metallurgical processing, recycling and environmental protection. The program presented at this conference also benefited from the organizational support of the Canadian Association of Recycling Industries. Over the past twenty years these workshops served as a valuable forum for the discussion of the technological issues associated with metallurgical processing, recycling and compliance with environmental regulations within the framework of sustainable development. The program this year was organized in five sessions. A total of 32 papers were presented. Session One emphasized the international dimension of modern research as illustrated by the Intelligent Manufacturing System (MIS) program. Session Two dealt with recycling, with special attention to the recycling of plastics and construction materials. Session Three was devoted to highlighting European efforts to treat chromium-bearing solutions or to find alternatives to chromium salts in surface treatment operations. Session Four emphasized primary and secondary zinc processing and the importance of energy conservation. The final session reviewed waste management practices and the utilization of waste materials. Opening addresses by representatives of the sponsoring organizations and a list of conference attendees and their affiliations are also included.

  5. NATO Conference

    CERN Document Server

    Lynn, W

    1975-01-01

    The contents of this volume involve selection, emendation and up-dating of papers presented at the NATO Conference "Mathe­ matical Analysis of Decision problems in Ecology" in Istanbul, Turkey, July 9-13, 1973. It was sponsored by the System Sciences Division of NATO directed by Dr. B. Bayraktar with local arrange­ ments administered by Dr. Ilhami Karayalcin, professor of the Department of Industrial Engineering at the Technical University of Istanbul. It was organized by A. Charnes, University professor across the University of Texas System, and Walter R.Lynn, Di­ rector of the School of Civil and Environmental Engineering at Cornell Unjversity. The objective of the conference was to bring together a group of leading researchers from the major sciences involved in eco­ logical problems and to present the current state of progress in research of a mathematical nature which might assist in the solu­ tion of these problems. Although their presentations are not herein recorded, the key­ note address of Dr....

  6. EGC Conferences

    CERN Document Server

    Ritschard, Gilbert; Pinaud, Bruno; Venturini, Gilles; Zighed, Djamel; Advances in Knowledge Discovery and Management

    This book is a collection of representative and novel works done in Data Mining, Knowledge Discovery, Clustering and Classification that were originally presented in French at the EGC'2012 Conference held in Bordeaux, France, on January 2012. This conference was the 12th edition of this event, which takes place each year and which is now successful and well-known in the French-speaking community. This community was structured in 2003 by the foundation of the French-speaking EGC society (EGC in French stands for ``Extraction et Gestion des Connaissances'' and means ``Knowledge Discovery and Management'', or KDM). This book is intended to be read by all researchers interested in these fields, including PhD or MSc students, and researchers from public or private laboratories. It concerns both theoretical and practical aspects of KDM. The book is structured in two parts called ``Knowledge Discovery and Data Mining'' and ``Classification and Feature Extraction or Selection''. The first part (6 chapters) deals with...

  7. Robust Solar Position Sensor for Tracking Systems

    DEFF Research Database (Denmark)

    Ritchie, Ewen; Argeseanu, Alin; Leban, Krisztina Monika

    2009-01-01

    The paper proposes a new solar position sensor used in tracking system control. The main advantages of the new solution are the robustness and the economical aspect. Positioning accuracy of the tracking system that uses the new sensor is better than 1°. The new sensor uses the ancient principle...... of the solar clock. The sensitive elements are eight ordinary photo-resistors. It is important to note that all the sensors are not selected simultaneously. It is not necessary for sensor operating characteristics to be quasi-identical because the sensor principle is based on extreme operating duty measurement...... (bright or dark). In addition, the proposed solar sensor significantly simplifies the operation of the tracking control device....

  8. Optimal Implementations for Reliable Circadian Clocks

    Science.gov (United States)

    Hasegawa, Yoshihiko; Arita, Masanori

    2014-09-01

    Circadian rhythms are acquired through evolution to increase the chances for survival through synchronizing with the daylight cycle. Reliable synchronization is realized through two trade-off properties: regularity to keep time precisely, and entrainability to synchronize the internal time with daylight. We find by using a phase model with multiple inputs that achieving the maximal limit of regularity and entrainability entails many inherent features of the circadian mechanism. At the molecular level, we demonstrate the role sharing of two light inputs, phase advance and delay, as is well observed in mammals. At the behavioral level, the optimal phase-response curve inevitably contains a dead zone, a time during which light pulses neither advance nor delay the clock. We reproduce the results of phase-controlling experiments entrained by two types of periodic light pulses. Our results indicate that circadian clocks are designed optimally for reliable clockwork through evolution.

  9. The Large Built Water Clock Of Amphiaraeion.

    Science.gov (United States)

    Theodossiou, E.; Katsiotis, M.; Manimanis, V. N.; Mantarakis, P.

    A very well preserved ancient water clock was discovered during excavations at the Amphiaraeion, in Oropos, Greece. The Amphiaraeion, a famous religious and oracle center of the deified healer Amphiaraus, was active from the pre-classic period until the replacement of the ancient religion by Christianity in the 5th Century A.D.. The foretelling was supposedly done through dreams sent by the god to the believers sleeping in a special gallery. In these dreams the god suggesting to them the therapy for their illness or the solution to their problems. The patients, then threw coins into a spring of the sanctuary. In such a place, the measurement of time was a necessity. Therefore, time was kept with both a conical sundial and a water clock in the form of a fountain. According to archeologists, the large built structure that measured the time for the sanctuary dates from the 4th Century B.C.

  10. Epigenetic drift, epigenetic clocks and cancer risk.

    Science.gov (United States)

    Zheng, Shijie C; Widschwendter, Martin; Teschendorff, Andrew E

    2016-05-01

    It is well-established that the DNA methylation landscape of normal cells undergoes a gradual modification with age, termed as 'epigenetic drift'. Here, we review the current state of knowledge of epigenetic drift and its potential role in cancer etiology. We propose a new terminology to help distinguish the different components of epigenetic drift, with the aim of clarifying the role of the epigenetic clock, mitotic clocks and active changes, which accumulate in response to environmental disease risk factors. We further highlight the growing evidence that epigenetic changes associated with cancer risk factors may play an important causal role in cancer development, and that monitoring these molecular changes in normal cells may offer novel risk prediction and disease prevention strategies.

  11. Molecular clock on a neutral network.

    Science.gov (United States)

    Raval, Alpan

    2007-09-28

    The number of fixed mutations accumulated in an evolving population often displays a variance that is significantly larger than the mean (the overdispersed molecular clock). By examining a generic evolutionary process on a neutral network of high-fitness genotypes, we establish a formalism for computing all cumulants of the full probability distribution of accumulated mutations in terms of graph properties of the neutral network, and use the formalism to prove overdispersion of the molecular clock. We further show that significant overdispersion arises naturally in evolution when the neutral network is highly sparse, exhibits large global fluctuations in neutrality, and small local fluctuations in neutrality. The results are also relevant for elucidating aspects of neutral network topology from empirical measurements of the substitution process.

  12. Regulated DNA Methylation and the Circadian Clock: Implications in Cancer

    Directory of Open Access Journals (Sweden)

    Tammy M. Joska

    2014-09-01

    Full Text Available Since the cloning and discovery of DNA methyltransferases (DNMT, there has been a growing interest in DNA methylation, its role as an epigenetic modification, how it is established and removed, along with the implications in development and disease. In recent years, it has become evident that dynamic DNA methylation accompanies the circadian clock and is found at clock genes in Neurospora, mice and cancer cells. The relationship among the circadian clock, cancer and DNA methylation at clock genes suggests a correlative indication that improper DNA methylation may influence clock gene expression, contributing to the etiology of cancer. The molecular mechanism underlying DNA methylation at clock loci is best studied in the filamentous fungi, Neurospora crassa, and recent data indicate a mechanism analogous to the RNA-dependent DNA methylation (RdDM or RNAi-mediated facultative heterochromatin. Although it is still unclear, DNA methylation at clock genes may function as a terminal modification that serves to prevent the regulated removal of histone modifications. In this capacity, aberrant DNA methylation may serve as a readout of misregulated clock genes and not as the causative agent. This review explores the implications of DNA methylation at clock loci and describes what is currently known regarding the molecular mechanism underlying DNA methylation at circadian clock genes.

  13. Photoperiodic plasticity in circadian clock neurons in insects

    Directory of Open Access Journals (Sweden)

    Sakiko eShiga

    2013-08-01

    Full Text Available Since Bünning’s observation of circadian rhythms and photoperiodism in the runner bean Phaseolus multiflorus in 1936, many studies have shown that photoperiodism is based on the circadian clock system. In insects, involvement of circadian clock genes or neurons has been recently shown in the photoperiodic control of developmental arrests, diapause. Based on molecular and neuronal studies in Drosophila melanogaster, photoperiodic changes have been reported for expression patterns of the circadian clock genes, subcellular distribution of clock proteins, fiber distribution, or the number of plausible clock neurons in different species. Photoperiod sets peaks of per or tim mRNA abundance at lights-off in Sarcophaga crassipalpis, Chymomyza costata and Protophormia terraenovae. Abundance of per and Clock mRNA changes by photoperiod in Pyrrhocoris apterus. Subcellular Per distribution in circadian clock neurons changes with photoperiod in P. terraenovae. Although photoperiodism is not known in Leucophaea maderae, under longer day length, more stomata and longer commissural fibers of circadian clock neurons have been found. These plastic changes in the circadian clock neurons could be an important constituent for photoperiodic clock mechanisms to integrate repetitive photoperiodic information and produce different outputs based on day length.

  14. Geopotential measurements with synchronously linked optical lattice clocks

    Science.gov (United States)

    Takano, Tetsushi; Takamoto, Masao; Ushijima, Ichiro; Ohmae, Noriaki; Akatsuka, Tomoya; Yamaguchi, Atsushi; Kuroishi, Yuki; Munekane, Hiroshi; Miyahara, Basara; Katori, Hidetoshi

    2016-10-01

    According to Einstein's theory of relativity, the passage of time changes in a gravitational field. On Earth, raising a clock by 1 cm increases its apparent tick rate by 1.1 parts in 1018, allowing chronometric levelling through comparison of optical clocks. Here, we demonstrate such geopotential measurements by determining the height difference of master and slave clocks separated by 15 km with an uncertainty of 5 cm. A subharmonic of the master clock laser is delivered through a telecom fibre to synchronously operate the distant clocks. Clocks operated under such phase coherence reject clock laser noise and facilitate proposals for linking clocks and interferometers. Taken over half a year, 11 measurements determine the fractional frequency difference between the two clocks to be 1,652.9(5.9) × 10-18, consistent with an independent measurement by levelling and gravimetry. Our system demonstrates a building block for an internet of clocks, which may constitute ‘quantum benchmarks’, serving as height references with dynamic responses.

  15. Incremental Placement-Based Clock Network Minimization Methodology

    Institute of Scientific and Technical Information of China (English)

    ZHOU Oiang; CAI Yici; HUANG Liang; HONG Xianlong

    2008-01-01

    Power is the major challenge threatening the progress of very large scale integration (VLSI) tech-nology development. In ultra-deep submicron VLSI designs, clock network size must be minimized to re-duce power consumption, power supply noise, and the number of clock buffers which are vulnerable to process variations. Traditional design methodologies usually let the clock router independently undertake the clock network minimization. Since clock routing is based on register locations, register placement actu-ally strongly influences the clock network size. This paper describes a clock network design methodology that optimizes register placement. For a given cell placement result, incremental modifications are per-formed based on the clock skew specifications by moving registers toward preferred locations that may re-duce the clock network size. At the same time, the side-effects to logic cell placement, such as signal net wirelength and critical path delay, are controlled. Test results on benchmark circuits show that the methodol-ogy can considerably reduce clock network size with limited impact on signal net wirelength and critical path delay.

  16. A compact model for the complex plant circadian clock

    Directory of Open Access Journals (Sweden)

    Didier eGonze

    2016-02-01

    Full Text Available The circadian clock is an endogenous timekeeper that allows organisms to anticipate and adapt to the daily variations of their environment. The plant clock is an intricate network of interlocked feedback loops, in which transcription factors regulate each other to generate oscillations with expression peaks at specific times of the day. Over the last decade, mathematical modeling approaches have been used to understand the inner workings of the clock in the model plant Arabidopsis thaliana. Those efforts have produced a number of models of ever increasing complexity. Here, we present an alternative model that combines a low number of equations and parameters, similar to the very earliest models, with the complex network structure found in more recent ones. This simple model describes the temporal evolution of the abundance of eight clock genes and captures key features of the clock on a qualitative level, namely the entrained and free-running behaviors of the wild type clock, as well as the defects found in knockout mutants (such as altered free-running periods, lack of entrainment, or changes in the expression of other clock genes. Additionally, our model produces complex responses to various light cues, such as extreme photoperiods and non-24h environmental cycles, and can describe the control of hypocotyl growth by the clock. Our model constitutes a useful tool to probe dynamical properties of the clock as well as model more clock-dependent processes.

  17. The Circadian Clock, Reward, and Memory

    OpenAIRE

    Urs eAlbrecht

    2011-01-01

    During our daily activities, we experience variations in our cognitive performance, which is often accompanied by cravings for small rewards, such as consuming coffee or chocolate. This indicates that the time of day, cognitive performance, and reward may be related to one another. This review will summarize data that describe the influence of the circadian clock on addiction and mood-related behavior and put the data into perspective in relation to memory processes.

  18. The circadian clock, reward and memory

    Directory of Open Access Journals (Sweden)

    Urs eAlbrecht

    2011-11-01

    Full Text Available During our daily activities, we experience variations in our cognitive performance, which is often accompanied by cravings for small rewards, such as consuming coffee or chocolate. This indicates that the time of day, cognitive performance and reward may be related to one another. This review will summarize data that describes the influence of the circadian clock on addiction and mood-related behavior and put the data into perspective in relation to memory processes.

  19. Analysis of detector performance in a gigahertz clock rate quantum key distribution system

    Energy Technology Data Exchange (ETDEWEB)

    Clarke, Patrick J; Collins, Robert J; Hiskett, Philip A; GarcIa-MartInez, MarIa-Jose; Krichel, Nils J; McCarthy, Aongus; Tanner, Michael G; O' Connor, John A; Natarajan, Chandra M; Hadfield, Robert H; Buller, Gerald S [Scottish Universities Physics Alliance and School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS (United Kingdom); Miki, Shigehito; Sasaki, Masahide; Wang, Zhen; Fujiwara, Mikio [National Institute of Information and Communications Technology (NICT), 4-2-1 Nukui-kitamachi, Koganei, Tokyo 184-8795 (Japan); Rech, Ivan; Ghioni, Massimo; Gulinatti, Angelo [Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Townsend, Paul D, E-mail: G.S.Buller@hw.ac.uk [Tyndall National Institute and Department of Physics, University College Cork, Cork (Ireland)

    2011-07-15

    We present a detailed analysis of a gigahertz clock rate environmentally robust phase-encoded quantum key distribution (QKD) system utilizing several different single-photon detectors, including the first implementation of an experimental resonant cavity thin-junction silicon single-photon avalanche diode. The system operates at a wavelength of 850 nm using standard telecommunications optical fibre. A general-purpose theoretical model for the performance of QKD systems is presented with reference to these experimental results before predictions are made about realistic detector developments in this system. We discuss, with reference to the theoretical model, how detector operating parameters can be further optimized to maximize key exchange rates.

  20. Clock drawing performance in cognitively normal elderly.

    Science.gov (United States)

    Hubbard, Emily J; Santini, Veronica; Blankevoort, Christiaan G; Volkers, Karin M; Barrup, Melissa S; Byerly, Laura; Chaisson, Christine; Jefferson, Angela L; Kaplan, Edith; Green, Robert C; Stern, Robert A

    2008-05-01

    The Clock Drawing Test (CDT) is a common neuropsychological measure sensitive to cognitive changes and functional skills (e.g., driving test performance) among older adults. However, normative data have not been adequately developed. We report the distribution of CDT scores using three common scoring systems [Mendez, M. F., Ala, T., & Underwood, K. L. (1992). Development of scoring criteria for the Clock Drawing Task in Alzheimer's Disease. Journal of the American Geriatrics Society, 40, 1095-1099; Cahn, D. A., Salmon, D. P., Monsch, A. U., Butters, N., Wiederholt, W. C., & Corey-Bloom, J. (1996). Screening for dementia of the Alzheimer type in the community: The utility of the Clock Drawing Test. Archives of Clinical Neuropsychology, 11(6), 529-539], among 207 cognitively normal elderly. The systems were well correlated, took little time to use, and had high inter-rater reliability. We found statistically significant differences in CDT scores based on age and WRAT-3 Reading score, a marker of education quality. We present means, standard deviations, and t- and z-scores based on these subgroups. We found that "normal" CDT performance includes a wider distribution of scores than previously reported. Our results may serve as useful comparisons for clinicians wishing to know whether their patients perform in the general range of cognitively normal elderly.

  1. A microresonator frequency comb optical clock

    CERN Document Server

    Papp, Scott B; DelHaye, Pascal; Quinlan, Franklyn; Lee, Hansuek; Vahala, Kerry J; Diddams, Scott A

    2013-01-01

    Optical-frequency combs enable measurement precision at the 20th digit, and accuracy entirely commensurate with their reference oscillator. A new direction in experiments is the creation of ultracompact frequency combs by way of nonlinear parametric optics in microresonators. We refer to these as microcombs, and here we report a silicon-chip-based microcomb optical clock that phase-coherently converts an optical-frequency reference to a microwave signal. A low-noise comb spectrum with 25 THz span is generated with a 2 mm diameter silica disk and broadening in nonlinear fiber. This spectrum is stabilized to rubidium frequency references separated by 3.5 THz by controlling two teeth 108 modes apart. The optical clocks output is the electronically countable 33 GHz microcomb line spacing, which features an absolute stability better than the rubidium transitions by the expected factor of 108. Our work demonstrates the comprehensive set of tools needed for interfacing microcombs to state-of-the-art optical clocks.

  2. Chromatin remodelling and the Arabidopsis biological clock.

    Science.gov (United States)

    Más, Paloma

    2008-02-01

    Plants, as sessile organisms, rely on accurate time measurement to synchronize their physiology and development to the most favourable time-of-day or time-of-year. The biological clock is the endogenous mechanism responsible for the integration of the photoperiodic information thus coordinating metabolism in resonance with the environmental cycle. Despite the importance of circadian clock function in plant reproduction and survival, we are still far from understanding the specific molecular mechanisms governing the rhythmic expression of clock components. Recently, we have described a new mechanism of circadian regulation that involves changes in chromatin structure at the TOC1 (TIMING OF CAB EXPRESSION 1) locus. The mechanism is defined by activators and repressors that are precisely coordinated to favor a hyper- or hypo-acetylated state of histones that leads to TOC1 transcriptional activation or repression, respectively. The clockcontrolled rhythms in histone acetylation/deacetylation at the TOC1 promoter are differentially modulated by day-length or photoperiod suggesting a mechanism by which plants ensure the phase of entrainment in physiological and developmental outputs.

  3. MUSME Conference

    CERN Document Server

    Martinez, Eusebio

    2015-01-01

    This volume contains the Proceedings of MUSME 2014, held at Huatulco in Oaxaca, Mexico, October 2014. Topics include analysis and synthesis of mechanisms; dynamics of multibody systems; design algorithms for mechatronic systems; simulation procedures and results; prototypes and their performance; robots and micromachines; experimental validations; theory of mechatronic simulation; mechatronic systems; and control of mechatronic systems. The MUSME symposium on Multibody Systems and Mechatronics was held under the auspices of IFToMM, the International Federation for Promotion of Mechanism and Machine Science, and FeIbIM, the Iberoamerican Federation of Mechanical Engineering. Since the first symposium in 2002, MUSME events have been characterised by the way they stimulate the integration between the various mechatronics and multibody systems dynamics disciplines, present a forum for facilitating contacts among researchers and students mainly in South American countries, and serve as a joint conference for the ...

  4. Robust Regression and Lasso

    CERN Document Server

    Xu, Huan; Mannor, Shie

    2008-01-01

    Lasso, or $\\ell^1$ regularized least squares, has been explored extensively for its remarkable sparsity properties. It is shown in this paper that the solution to Lasso, in addition to its sparsity, has robustness properties: it is the solution to a robust optimization problem. This has two important consequences. First, robustness provides a connection of the regularizer to a physical property, namely, protection from noise. This allows a principled selection of the regularizer, and in particular, generalizations of Lasso that also yield convex optimization problems are obtained by considering different uncertainty sets. Secondly, robustness can itself be used as an avenue to exploring different properties of the solution. In particular, it is shown that robustness of the solution explains why the solution is sparse. The analysis as well as the specific results obtained differ from standard sparsity results, providing different geometric intuition. Furthermore, it is shown that the robust optimization formul...

  5. Differential effect of fructose on fat metabolism and clock gene expression in hepatocytes vs. myotubes.

    Science.gov (United States)

    Chapnik, Nava; Rozenblit-Susan, Sigal; Genzer, Yoni; Froy, Oren

    2016-08-01

    In the liver, fructose bypasses the main rate-limiting step of glycolysis at the level of phosphofructokinase, allowing it to act as an unregulated substrate for de novo lipogenesis. It has been reported that consumption of large amounts of fructose increases de novo lipogenesis in the liver. However, the effect of fructose on ectopic deposition of muscle fat has been under dispute. Our aim was to study the effect of fructose on levels of genes and proteins involved in fatty acid oxidation and synthesis in hepatocytes vs. muscle cells. In addition, as fat accumulation leads to disruption of daily rhythms, we tested the effect of fructose treatment on clock gene expression. AML-12 hepatocytes and C2C12 myotubes were treated with fructose or glucose for 2 consecutive 24-h cycles and harvested every 6h. In contrast to glucose, fructose disrupted clock gene rhythms in hepatocytes, but in myotubes, it led to more robust rhythms. Fructose led to low levels of phosphorylated AMP-activated protein kinase (pAMPK) and high levels of LIPIN1 in hepatocytes compared with glucose. In contrast, fructose led to high pAMPK and low LIPIN1 and microsomal triacylglycerol transfer protein (MTTP) levels in myotubes compared with glucose. Analysis of fat content revealed that fructose led to less fat accumulation in myotubes compared to hepatocytes. In summary, fructose shifts metabolism towards fatty acid synthesis and clock disruption in hepatocytes, but not in myotubes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Data assimilation constrains new connections and components in a complex, eukaryotic circadian clock model

    Science.gov (United States)

    Pokhilko, Alexandra; Hodge, Sarah K; Stratford, Kevin; Knox, Kirsten; Edwards, Kieron D; Thomson, Adrian W; Mizuno, Takeshi; Millar, Andrew J

    2010-01-01

    Circadian clocks generate 24-h rhythms that are entrained by the day/night cycle. Clock circuits include several light inputs and interlocked feedback loops, with complex dynamics. Multiple biological components can contribute to each part of the circuit in higher organisms. Mechanistic models with morning, evening and central feedback loops have provided a heuristic framework for the clock in plants, but were based on transcriptional control. Here, we model observed, post-transcriptional and post-translational regulation and constrain many parameter values based on experimental data. The model's feedback circuit is revised and now includes PSEUDO-RESPONSE REGULATOR 7 (PRR7) and ZEITLUPE. The revised model matches data in varying environments and mutants, and gains robustness to parameter variation. Our results suggest that the activation of important morning-expressed genes follows their release from a night inhibitor (NI). Experiments inspired by the new model support the predicted NI function and show that the PRR5 gene contributes to the NI. The multiple PRR genes of Arabidopsis uncouple events in the late night from light-driven responses in the day, increasing the flexibility of rhythmic regulation. PMID:20865009

  7. Daily changes in ultraviolet light levels can synchronize the circadian clock of bumblebees (Bombus terrestris).

    Science.gov (United States)

    Chittka, Lars; Stelzer, Ralph J; Stanewsky, Ralf

    2013-05-01

    Endogenous circadian clocks are synchronized to the 24-h day by external zeitgebers such as daily light and temperature cycles. Bumblebee foragers show diurnal rhythms under daily light:dark cycles and short-period free-running circadian rhythms in constant light conditions in the laboratory. In contrast, during the continuous light conditions of the arctic summer, they show robust 24-h rhythms in their foraging patterns, meaning that some external zeitgeber must entrain their circadian clocks in the presence of constant light. Although the sun stays above the horizon for weeks during the arctic summer, the light quality, especially in the ultraviolet (UV) range, exhibits pronounced daily changes. Since the photoreceptors and photopigments that synchronize the circadian system of bees are not known, we tested if the circadian clocks of bumblebees (Bombus terrestris) can be entrained by daily cycles in UV light levels. Bumblebee colonies were set up in the laboratory and exposed to 12 h:12 h UV + :UV- cycles in otherwise continuous lighting conditions by placing UV filters on their foraging arenas for 12 h each day. The activity patterns of individual bees were recorded using fully automatic radiofrequency identification (RFID). We found that colonies manipulated in such a way showed synchronized 24-h rhythms, whereas simultaneously tested control colonies with no variation in UV light levels showed free-running rhythms instead. The results of our study show that bumblebee circadian rhythms can indeed be synchronized by daily cycles in ambient light spectral composition.

  8. Robust Geometric Spanners

    CERN Document Server

    Bose, Prosenjit; Morin, Pat; Smid, Michiel

    2012-01-01

    Highly connected and yet sparse graphs (such as expanders or graphs of high treewidth) are fundamental, widely applicable and extensively studied combinatorial objects. We initiate the study of such highly connected graphs that are, in addition, geometric spanners. We define a property of spanners called robustness. Informally, when one removes a few vertices from a robust spanner, this harms only a small number of other vertices. We show that robust spanners must have a superlinear number of edges, even in one dimension. On the positive side, we give constructions, for any dimension, of robust spanners with a near-linear number of edges.

  9. Robustness of Structural Systems

    DEFF Research Database (Denmark)

    Canisius, T.D.G.; Sørensen, John Dalsgaard; Baker, J.W.

    2007-01-01

    The importance of robustness as a property of structural systems has been recognised following several structural failures, such as that at Ronan Point in 1968,where the consequenceswere deemed unacceptable relative to the initiating damage. A variety of research efforts in the past decades have...... systems. Guidance is provided regarding the assessment of robustness in a framework that considers potential hazards to the system, vulnerability of system components, and failure consequences. Several proposed methods for quantifying robustness are reviewed, and guidelines for robust design...

  10. Identification, Characterization, and Diel Pattern of Expression of Canonical Clock Genes in Nephrops norvegicus (Crustacea: Decapoda) Eyestalk

    Science.gov (United States)

    Sbragaglia, Valerio; Lamanna, Francesco; M. Mat, Audrey; Rotllant, Guiomar; Joly, Silvia; Ketmaier, Valerio; de la Iglesia, Horacio O.; Aguzzi, Jacopo

    2015-01-01

    The Norway lobster, Nephrops norvegicus, is a burrowing decapod with a rhythmic burrow emergence (24 h) governed by the circadian system. It is an important resource for European fisheries and its behavior deeply affects its availability. The current knowledge of Nephrops circadian biology is phenomenological as it is currently the case for almost all crustaceans. In attempt to elucidate the putative molecular mechanisms underlying circadian gene regulation in Nephrops, we used a transcriptomics approach on cDNA extracted from the eyestalk, a structure playing a crucial role in controlling behavior of decapods. We studied 14 male lobsters under 12–12 light-darkness blue light cycle. We used the Hiseq 2000 Illumina platform to sequence two eyestalk libraries (under light and darkness conditions) obtaining about 90 millions 100-bp paired-end reads. Trinity was used for the de novo reconstruction of transcriptomes; the size at which half of all assembled bases reside in contigs (N50) was equal to 1796 (light) and 2055 (darkness). We found a list of candidate clock genes and focused our attention on canonical ones: timeless, period, clock and bmal1. The cloning of assembled fragments validated Trinity outputs. The putative Nephrops clock genes showed high levels of identity (blastx on NCBI) with known crustacean clock gene homologs such as Eurydice pulchra (period: 47%, timeless: 59%, bmal1: 79%) and Macrobrachium rosenbergii (clock: 100%). We also found a vertebrate-like cryptochrome 2. RT-qPCR showed that only timeless had a robust diel pattern of expression. Our data are in accordance with the current knowledge of the crustacean circadian clock, reinforcing the idea that the molecular clockwork of this group shows some differences with the established model in Drosophila melanogaster. PMID:26524198

  11. Identification, Characterization, and Diel Pattern of Expression of Canonical Clock Genes in Nephrops norvegicus (Crustacea: Decapoda Eyestalk.

    Directory of Open Access Journals (Sweden)

    Valerio Sbragaglia

    Full Text Available The Norway lobster, Nephrops norvegicus, is a burrowing decapod with a rhythmic burrow emergence (24 h governed by the circadian system. It is an important resource for European fisheries and its behavior deeply affects its availability. The current knowledge of Nephrops circadian biology is phenomenological as it is currently the case for almost all crustaceans. In attempt to elucidate the putative molecular mechanisms underlying circadian gene regulation in Nephrops, we used a transcriptomics approach on cDNA extracted from the eyestalk, a structure playing a crucial role in controlling behavior of decapods. We studied 14 male lobsters under 12-12 light-darkness blue light cycle. We used the Hiseq 2000 Illumina platform to sequence two eyestalk libraries (under light and darkness conditions obtaining about 90 millions 100-bp paired-end reads. Trinity was used for the de novo reconstruction of transcriptomes; the size at which half of all assembled bases reside in contigs (N50 was equal to 1796 (light and 2055 (darkness. We found a list of candidate clock genes and focused our attention on canonical ones: timeless, period, clock and bmal1. The cloning of assembled fragments validated Trinity outputs. The putative Nephrops clock genes showed high levels of identity (blastx on NCBI with known crustacean clock gene homologs such as Eurydice pulchra (period: 47%, timeless: 59%, bmal1: 79% and Macrobrachium rosenbergii (clock: 100%. We also found a vertebrate-like cryptochrome 2. RT-qPCR showed that only timeless had a robust diel pattern of expression. Our data are in accordance with the current knowledge of the crustacean circadian clock, reinforcing the idea that the molecular clockwork of this group shows some differences with the established model in Drosophila melanogaster.

  12. Self-Adaptive Clock Synchronization for Computational Grid

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ying(赵英); ZHOU WanLei(周万雷); HUANG JiuMei(黄九梅); YU Shui(余水); E.J.Lanham

    2003-01-01

    This paper presents an innovative method to synchronize physical clocks for a computational grid, in particular for a computational grid linked through the asynchronous Intranet or Internet environments. The method discussed is an asynchronous self-adaptive clock synchronization mechanism. Two strategies for clock synchronisation are introduced. (1) Use continuous time intervals to calculate the precision of clocks, which can reduce the effect of network delay efficiently. (2) Every node synchronizes its clock with its leader actively. In addition, a node self-adaptive model is presented, and the relationship between the clock precision and synchronization time is induced, hence a node can predict when it should begin the synchronization process.Detailed simulation and extension of this issue are provided at the end of the paper. The presented model is both practical and feasible.

  13. Immunometabolism: Is it under the eye of the clock?

    Science.gov (United States)

    Early, James O; Curtis, Anne M

    2016-10-01

    Molecular clocks allow an organism to track time of day, providing the means to anticipate and respond to the daily changes within the environment. In mammals the molecular clock consists of a network of proteins that form auto-regulatory feedback loops that drive rhythms in physiology and behavior. In recent times the extent to which the molecular clock controls key metabolic and immune pathways has begun to emerge. For example, the main clock protein BMAL1 has been linked to mitochondrial metabolism, mitochondrial dynamics and various host defense pathways. The molecular clock may function to integrate daily metabolic changes driven by feeding-fasting to immune function and output. Understanding how the clock intersects with metabolic pathways within immune cells to affect immune phenotypes will have broad implications for the management of metabolic, inflammatory and infectious diseases.

  14. Realization of a time-scale with an optical clock

    CERN Document Server

    Grebing, C; Dörscher, S; Häfner, S; Gerginov, V; Weyers, S; Lipphardt, B; Riehle, F; Sterr, U; Lisdat, C

    2015-01-01

    Optical clocks are not only powerful tools for prime fundamental research, but are also deemed for the re-definition of the SI base unit second as they surpass the performance of caesium atomic clocks in both accuracy and stability by more than an order of magnitude. However, an important obstacle in this transition has so far been the limited reliability of the optical clocks that made a continuous realization of a time-scale impractical. In this paper, we demonstrate how this dilemma can be resolved and that a time-scale based on an optical clock can be established that is superior to one based on even the best caesium fountain clocks. The paper also gives further proof of the international consistency of strontium lattice clocks on the $10^{-16}$ accuracy level, which is another prerequisite for a change in the definition of the second.

  15. A clock network for geodesy and fundamental science

    CERN Document Server

    Lisdat, C; Quintin, N; Shi, C; Raupach, S M F; Grebing, C; Nicolodi, D; Stefani, F; Al-Masoudi, A; Dörscher, S; Häfner, S; Robyr, J -L; Chiodo, N; Bilicki, S; Bookjans, E; Koczwara, A; Koke, S; Kuhl, A; Wiotte, F; Meynadier, F; Camisard, E; Abgrall, M; Lours, M; Legero, T; Schnatz, H; Sterr, U; Denker, H; Chardonnet, C; Coq, Y Le; Santarelli, G; Amy-Klein, A; Targat, R Le; Lodewyck, J; Lopez, O; Pottie, P -E

    2015-01-01

    Leveraging the unrivaled performance of optical clocks in applications in fundamental physics beyond the standard model, in geo-sciences, and in astronomy requires comparing the frequency of distant optical clocks truthfully. Meeting this requirement, we report on the first comparison and agreement of fully independent optical clocks separated by 700 km being only limited by the uncertainties of the clocks themselves. This is achieved by a phase-coherent optical frequency transfer via a 1415 km long telecom fiber link that enables substantially better precision than classical means of frequency transfer. The fractional precision in comparing the optical clocks of three parts in $10^{17}$ was reached after only 1000 s averaging time, which is already 10 times better and more than four orders of magnitude faster than with any other existing frequency transfer method. The capability of performing high resolution international clock comparisons paves the way for a redefinition of the unit of time and an all-optic...

  16. Clock genes in hypertension: novel insights from rodent models.

    Science.gov (United States)

    Richards, Jacob; Diaz, Alexander N; Gumz, Michelle L

    2014-10-01

    The circadian clock plays an integral role in the regulation of physiological processes, including the regulation of blood pressure. However, deregulation of the clock can lead to pathophysiological states including hypertension. Recent work has implicated the circadian clock genes in the regulation of processes in the heart, kidney, vasculature, and the metabolic organs, which are all critical in the regulation of the blood pressure. The goal of this review is to provide an introduction and general overview into the role of circadian clock genes in the regulation of blood pressure with a focus on their deregulation in the etiology of hypertension. This review will focus on the core circadian clock genes CLOCK, BMAL1, Per, and Cry.

  17. Dynamic Power Reduction of Digital Circuits by ClockGating

    Directory of Open Access Journals (Sweden)

    Varsha Dewre

    2017-04-01

    Full Text Available In this paper we have presented clock gating process for low power VLSI (very large scale integration circuit design. Clock gating is one of the most quite often used systems in RTL to shrink dynamic power consumption without affecting the performance of the design. One process involves inserting gating requisites in the RTL, which the synthesis tool translates to clock gating cells in the clock-path of a register bank. This helps to diminish the switching activity on the clock network, thereby decreasing dynamic power consumption within the design. Due to the fact the translation accomplished via the synthesis tool is solely combinational; it is referred to as combinational clock gating. This transformation does not alter the behavior of the register being gated

  18. Synthetic Spin-Orbit Coupling in an Optical Lattice Clock

    Science.gov (United States)

    Wall, Michael L.; Koller, Andrew P.; Li, Shuming; Zhang, Xibo; Cooper, Nigel R.; Ye, Jun; Rey, Ana Maria

    2016-01-01

    We propose the use of optical lattice clocks operated with fermionic alkaline-earth atoms to study spin-orbit coupling (SOC) in interacting many-body systems. The SOC emerges naturally during the clock interrogation, when atoms are allowed to tunnel and accumulate a phase set by the ratio of the "magic" lattice wavelength to the clock transition wavelength. We demonstrate how standard protocols such as Rabi and Ramsey spectroscopy that take advantage of the sub-Hertz resolution of state-of-the-art clock lasers can perform momentum-resolved band tomography and determine SOC-induced s -wave collisions in nuclear-spin-polarized fermions. With the use of a second counterpropagating clock beam, we propose a method for engineering controlled atomic transport and study how it is modified by p - and s -wave interactions. The proposed spectroscopic probes provide clean and well-resolved signatures at current clock operating temperatures.

  19. Fault-tolerant Algorithms for Tick-Generation in Asynchronous Logic: Robust Pulse Generation

    CERN Document Server

    Dolev, Danny; Lenzen, Christoph; Schmid, Ulrich

    2011-01-01

    Today's hardware technology presents a new challenge in designing robust systems. Deep submicron VLSI technology introduced transient and permanent faults that were never considered in low-level system designs in the past. Still, robustness of that part of the system is crucial and needs to be guaranteed for any successful product. Distributed systems, on the other hand, have been dealing with similar issues for decades. However, neither the basic abstractions nor the complexity of contemporary fault-tolerant distributed algorithms match the peculiarities of hardware implementations. This paper is intended to be part of an attempt striving to overcome this gap between theory and practice for the clock synchronization problem. Solving this task sufficiently well will allow to build a very robust high-precision clocking system for hardware designs like systems-on-chips in critical applications. As our first building block, we describe and prove correct a novel Byzantine fault-tolerant self-stabilizing pulse syn...

  20. Atomic fountains and optical clocks at SYRTE: status and perspectives

    CERN Document Server

    Abgrall, M; De Sarlo, L; Guéna, J; Laurent, Ph; Coq, Y Le; Targat, R Le; Lodewyck, J; Lours, M; Rosenbusch, P; Rovera, D; Bize, S

    2015-01-01

    In this article, we report on the work done with the LNE-SYRTE atomic clock ensemble during the last 10 years. We cover progress made in atomic fountains and in their application to timekeeping. We also cover the development of optical lattice clocks based on strontium and on mercury. We report on tests of fundamental physical laws made with these highly accurate atomic clocks. We also report on work relevant to a future possible redefinition of the SI second.

  1. System-wide power management control via clock distribution network

    Energy Technology Data Exchange (ETDEWEB)

    Coteus, Paul W.; Gara, Alan; Gooding, Thomas M.; Haring, Rudolf A.; Kopcsay, Gerard V.; Liebsch, Thomas A.; Reed, Don D.

    2015-05-19

    An apparatus, method and computer program product for automatically controlling power dissipation of a parallel computing system that includes a plurality of processors. A computing device issues a command to the parallel computing system. A clock pulse-width modulator encodes the command in a system clock signal to be distributed to the plurality of processors. The plurality of processors in the parallel computing system receive the system clock signal including the encoded command, and adjusts power dissipation according to the encoded command.

  2. Transcriptional repressor PRR5 directly regulates clock-output pathways

    OpenAIRE

    Nakamichi, Norihito; Kiba, Takatoshi; Kamioka, Mari; Suzuki, Takamasa; Yamashino, Takafumi; Higashiyama, Tetsuya; Sakakibara, Hitoshi; Mizuno, Takeshi

    2012-01-01

    The circadian clock is an endogenous time-keeping mechanism that enables organisms to adapt to external daily cycles. The clock coordinates biological activities with these cycles, mainly through genome-wide gene expression. However, the exact mechanism underlying regulation of circadian gene expression is poorly understood. Here we demonstrated that an Arabidopsis PSEUDO-RESPONSE REGULATOR 5 (PRR5), which acts in the clock genetic circuit, directly regulates expression timing of key transcri...

  3. The Rock Island Clock Tower, From Ordnance to Engineers

    Science.gov (United States)

    1977-05-01

    11.) The Clock Tower shows no influence of two other architectural styles which were rapidly becoming popular in 1863: the Victor ian and gothic ...the hoist and to the clock on the fifth and sixth floors. The outside of the building, however, shows more attention to architectural design than...called for on the original plans. A comparison of the Columbus plans with the Rock Island Clock Tower shows an interesting architectural shift

  4. Circadian clocks and cell division: What's the pacemaker?

    OpenAIRE

    Johnson, Carl Hirschie

    2010-01-01

    Evolution has selected a system of two intertwined cell cycles: the cell division cycle (CDC) and the daily (circadian) biological clock. The circadian clock keeps track of solar time and programs biological processes to occur at environmentally appropriate times. One of these processes is the CDC, which is often gated by the circadian clock. The intermeshing of these two cell cycles is probably responsible for the observation that disruption of the circadian system enhances susceptibility to...

  5. Chronobiology of micturition: putative role of the circadian clock.

    OpenAIRE

    Negoro, Hiromitsu; Kanematsu, Akihiro; Yoshimura, Koji; Ogawa, Osamu

    2013-01-01

    [Purpose]Mammals urinate less frequently during the sleep period than the awake period. This is modulated by a triad of factors, including decreased arousal in the brain, a decreased urine production rate in the kidneys and increased functional bladder capacity during sleep. The circadian clock is genetic transcription-translation feedback machinery. It exists in most organs and cells, termed the peripheral clock, which is orchestrated by the central clock in the suprachiasmatic nucleus of th...

  6. Student Support for EIPBN 2010 Conference

    Energy Technology Data Exchange (ETDEWEB)

    Reginald C. Farrow

    2011-03-11

    The 54th International Conference on Electron, Ion and Photon Beam Technology and Nanofabrication, 2010, held at the Egan Convention Center and Hilton in Anchorage, Alaska, June 1 to 4, 2010 was a great success in large part because financial support allowed robust participation from students. The conference brought together 444 engineers and scientists from industries and universities from all over the world to discuss recent progress and future trends. Among the emerging technologies that are within the scope of EIPBN is Nanofabrication for Energy Sources along with nanofabrication for the realization of low power integrated circuits. Every year, EIPBN provides financial support for students to attend the conference.The students gave oral and poster presentations of their research and many published peer reviewed articles in a special conference issue of the Journal of Vacuum Science and Technology B. The Department of Energy Office of Basic Energy Sciences supported 20 students from US universities with a $15,000.

  7. Acetate Kinase Isozymes Confer Robustness in Acetate Metabolism

    DEFF Research Database (Denmark)

    Chan, Siu Hung Joshua; Nørregaard, Lasse; Solem, Christian

    2014-01-01

    strains reveal that AckA1 has a higher capacity for acetate production which allows faster growth in an environment with high acetate concentration. Meanwhile, AckA2 is important for fast acetate-dependent growth at low concentration of acetate. The results demonstrate that the two ACKs have complementary...

  8. Mechanisms for Robust Cognition

    Science.gov (United States)

    Walsh, Matthew M.; Gluck, Kevin A.

    2015-01-01

    To function well in an unpredictable environment using unreliable components, a system must have a high degree of robustness. Robustness is fundamental to biological systems and is an objective in the design of engineered systems such as airplane engines and buildings. Cognitive systems, like biological and engineered systems, exist within…

  9. Mechanisms for Robust Cognition

    Science.gov (United States)

    Walsh, Matthew M.; Gluck, Kevin A.

    2015-01-01

    To function well in an unpredictable environment using unreliable components, a system must have a high degree of robustness. Robustness is fundamental to biological systems and is an objective in the design of engineered systems such as airplane engines and buildings. Cognitive systems, like biological and engineered systems, exist within…

  10. Robustness of networks

    NARCIS (Netherlands)

    Wang, H.

    2009-01-01

    Our society depends more strongly than ever on large networks such as transportation networks, the Internet and power grids. Engineers are confronted with fundamental questions such as “how to evaluate the robustness of networks for a given service?”, “how to design a robust network?”, because netwo

  11. Synthesizing genetic sequential logic circuit with clock pulse generator.

    Science.gov (United States)

    Chuang, Chia-Hua; Lin, Chun-Liang

    2014-05-28

    Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

  12. A Simple Loop for Simultaneous OTDM Demultiplexing and Clock Recovery

    Institute of Scientific and Technical Information of China (English)

    CHEN Ming; LU Dan; GONG Tao-Rong; LV Bo; WANG Mu-Guang; LI Tang-Jun; JIAN Shui-Sheng

    2009-01-01

    A simple and stable loop consisting of a pair of concatenated electroabsorption modulators (EAMs) and 10 GHz clock recovery module is presented and demonstrated experimentally for simultaneous demultiplexing and clock recovery for OTDM networks. The 1OGb/s demultiplexed signai and IOGHz recovered clock are successfully implemented from 80 Gbit/s and 160 Gbit/s OTDM signals utilizing the loop. The loop based on EAM-PLL can provide excellent tolerance range (> 5 dB) of the OSCR of the source laser, and the recovered clock signa J exhibits low rms jitter over a dynamic input optical power range of 15 dB.

  13. Experiments with a New 201Hg+ Ion Clock

    Science.gov (United States)

    Burt, E. A.; Taghavi-Larigani, S.; Lea, S. N.; Prestage, J. D.; Tjoelker, R. L.

    2009-04-01

    In this paper we describe a new clock based on 201Hg+. All previous mercury ion clocks have been based on 199Hg+. We have recently completed construction of the 201Hg+ clock and will describe modifications to the design of our existing 199Hg+ clocks to accommodate the new isotope. We will also describe initial spectroscopic measurements of the hyperfine manifold, and possible future experiments. One experiment could place a limit on variations in the strong interaction fundamental constant ratio mq/ΛQCD.REFID="9789812838223_0043FN001">

  14. Crosstalk between the Circadian Clock and Innate Immunity in Arabidopsis

    Science.gov (United States)

    Zhang, Chong; Xie, Qiguang; Anderson, Ryan G.; Ng, Gina; Seitz, Nicholas C.; Peterson, Thomas; McClung, C. Robertson; McDowell, John M.; Kong, Dongdong; Kwak, June M.; Lu, Hua

    2013-01-01

    The circadian clock integrates temporal information with environmental cues in regulating plant development and physiology. Recently, the circadian clock has been shown to affect plant responses to biotic cues. To further examine this role of the circadian clock, we tested disease resistance in mutants disrupted in CCA1 and LHY, which act synergistically to regulate clock activity. We found that cca1 and lhy mutants also synergistically affect basal and resistance gene-mediated defense against Pseudomonas syringae and Hyaloperonospora arabidopsidis. Disrupting the circadian clock caused by overexpression of CCA1 or LHY also resulted in severe susceptibility to P. syringae. We identified a downstream target of CCA1 and LHY, GRP7, a key constituent of a slave oscillator regulated by the circadian clock and previously shown to influence plant defense and stomatal activity. We show that the defense role of CCA1 and LHY against P. syringae is at least partially through circadian control of stomatal aperture but is independent of defense mediated by salicylic acid. Furthermore, we found defense activation by P. syringae infection and treatment with the elicitor flg22 can feedback-regulate clock activity. Together this data strongly supports a direct role of the circadian clock in defense control and reveal for the first time crosstalk between the circadian clock and plant innate immunity. PMID:23754942

  15. Real-time geopotentiometry with synchronously linked optical lattice clocks

    CERN Document Server

    Takano, Tetsushi; Ushijima, Ichiro; Ohmae, Noriaki; Akatsuka, Tomoya; Yamaguchi, Atsushi; Kuroishi, Yuki; Munekane, Hiroshi; Miyahara, Basara; Katori, Hidetoshi

    2016-01-01

    According to the Einstein's theory of relativity, the passage of time changes in a gravitational field. On earth, raising a clock by one centimetre increases its tick rate by 1.1 parts in 10$^{18}$, enabling optical clocks to perform precision geodesy. Here, we demonstrate geopotentiometry by determining the height difference of master and slave clocks separated by 15 km with uncertainty of 5 cm. The subharmonic of the master clock is delivered through a telecom fibre to phase-lock and synchronously interrogate the slave clock. This protocol rejects laser noise in the comparison of two clocks, which improves the stability of measuring the gravitational red shift. Such phase-coherently operated clocks facilitate proposals for linking clocks and interferometers. Over half a year, 11 measurements determine the fractional frequency difference between the two clocks to be $1,652.9(5.9)\\times 10^{-18}$, or a height difference of 1,516(5) cm, consistent with an independent measurement by levelling and gravimetry. Ou...

  16. Glucocorticoids entrain molecular clock components in human peripheral cells.

    Science.gov (United States)

    Cuesta, Marc; Cermakian, Nicolas; Boivin, Diane B

    2015-04-01

    In humans, shift work induces a desynchronization between the circadian system and the outside world, which contributes to shift work-associated medical disorders. Using a simulated night shift experiment, we previously showed that 3 d of bright light at night fully synchronize the central clock to the inverted sleep schedule, whereas the peripheral clocks located in peripheral blood mononuclear cells (PBMCs) took longer to reset. This underlines the need for testing the effects of synchronizers on both the central and peripheral clocks. Glucocorticoids display circadian rhythms controlled by the central clock and are thought to act as synchronizers of rodent peripheral clocks. In the present study, we tested whether the human central and peripheral clocks were sensitive to exogenous glucocorticoids (Cortef) administered in the late afternoon. We showed that 20 mg Cortef taken orally acutely increased PER1 expression in PBMC peripheral clocks. After 6 d of Cortef administration, the phases of central markers were not affected, whereas those of PER2-3 and BMAL1 expression in PBMCs were shifted by ∼ 9.5-11.5 h. These results demonstrate, for the first time, that human peripheral clocks are entrained by glucocorticoids. Importantly, they suggest innovative interventions for shift workers and jet-lag travelers, combining synchronizing agents for the central and peripheral clocks.

  17. The molecular clock regulates circadian transcription of tissue factor gene.

    Science.gov (United States)

    Oishi, Katsutaka; Koyanagi, Satoru; Ohkura, Naoki

    2013-02-01

    Tissue factor (TF) is involved in endotoxin-induced inflammation and mortality. We found that the circadian expression of TF mRNA, which peaked at the day to night transition (activity onset), was damped in the liver of Clock mutant mice. Luciferase reporter and chromatin immunoprecipitation analyses using embryonic fibroblasts derived from wild-type or Clock mutant mice showed that CLOCK is involved in transcription of the TF gene. Furthermore, the results of real-time luciferase reporter experiments revealed that the circadian expression of TF mRNA is regulated by clock molecules through a cell-autonomous mechanism via an E-box element located in the promoter region.

  18. Ca2+-Clock-Dependent Pacemaking in the Sinus Node Is Impaired in Mice with a Cardiac Specific Reduction in SERCA2 Abundance

    Science.gov (United States)

    Logantha, Sunil Jit R. J.; Stokke, Mathis K.; Atkinson, Andrew J.; Kharche, Sanjay R.; Parveen, Sajida; Saeed, Yawer; Sjaastad, Ivar; Sejersted, Ole M.; Dobrzynski, Halina

    2016-01-01

    Background: The sarcoplasmic reticulum Ca2+-ATPase (SERCA2) pump is an important component of the Ca2+-clock pacemaker mechanism that provides robustness and flexibility to sinus node pacemaking. We have developed transgenic mice with reduced cardiac SERCA2 abundance (Serca2 KO) as a model for investigating SERCA2's role in sinus node pacemaking. Methods and Results: In Serca2 KO mice, ventricular SERCA2a protein content measured by Western blotting was 75% (P 70% reduction in SERCA2 activity. Conclusions: Serca2 KO mice show a disrupted Ca2+-clock-dependent pacemaker mechanism contributing to impaired sinus node and atrioventricular node function. PMID:27313537

  19. Stability Transfer between Two Clock Lasers Operating at Different Wavelengths for Absolute Frequency Measurement of Clock Transition in 87Sr

    CERN Document Server

    Yamaguchi, A; Nagano, S; Li, Y; Ishijima, H; Hachisu, H; Kumagai, M; Ido, T; 10.1143/APEX.5.022701

    2012-01-01

    We demonstrated transferring the stability of one highly stable clock laser operating at 729 nm to another less stable laser operating at 698 nm. The two different wavelengths were bridged using an optical frequency comb. The improved stability of the clock laser at 698 nm enabled us to evaluate the systematic frequency shifts of the Sr optical lattice clock with shorter averaging time. We determined the absolute frequency of the clock transition 1S0 - 3P0 in 87Sr to be 429 228 004 229 873.9 (1.4) Hz referenced to the SI second on the geoid via International Atomic Time (TAI).

  20. PDF cycling in the dorsal protocerebrum of the Drosophila brain is not necessary for circadian clock function.

    Science.gov (United States)

    Kula, Elzbieta; Levitan, Edwin S; Pyza, Elzbieta; Rosbash, Michael

    2006-04-01

    In Drosophila, the neuropeptide pigment-dispersing factor (PDF) is a likely circadian molecule, secreted by central pacemaker neurons (LNvs). PDF is expressed in both small and large LNvs (sLNvs and lLNvs), and there are striking circadian oscillations of PDF staining intensity in the small cell termini, which require a functional molecular clock. This cycling may be relevant to the proposed role of PDF as a synchronizer of the clock system or as an output signal connecting pacemaker cells to locomotor activity centers. In this study, the authors use a generic neuropeptide fusion protein (atrial natriuretic factor-green fluorescent protein [ANF-GFP]) and show that it can be expressed in the same neurons as PDF itself. Yet, ANF-GFP as well as PDF itself does not manifest any cyclical accumulation in sLNv termini in adult transgenic flies. Surprisingly, the absence of detectable PDF cycling is not accompanied by any detectable behavioral pheno-type, since these transgenic flies have normal morning and evening anticipation in a light-dark cycle (LD) and are fully rhythmic in constant darkness (DD). The molecular clock is also not compromised. The results suggest that robust PDF cycling in sLNv termini plays no more than a minor role in the Drosophila circadian system and is apparently not even necessary for clock output function.

  1. Clock Synchronization in Wireless Sensor Networks: A New Model and Analysis Approach Based on Networked Control Perspective

    Directory of Open Access Journals (Sweden)

    Wang Ting

    2014-01-01

    Full Text Available Motivated by the importance of the clock synchronization in wireless sensor networks (WSNs, this paper proposes a new research approach and model approach, which quantitatively analyzes clock synchronization from the perspective of modern control theory. Two kinds of control strategies are used as examples to analyze the effect of the control strategy on clock synchronization from different perspectives, namely, the single-step optimal control and the LQG global optimal control. The proposed method establishes a state space model for clock relationship, thus making dimension extension and parameter identification easier, and is robust to changes under the condition of node failures and new nodes. And through the design of different control strategies and performance index functions, the method can satisfy various requirements of the synchronization precision, convergence speed, energy consumption and the computational complexity, and so on. Finally, the simulations show that the synchronization accuracy of the proposed method is higher than that of the existing protocol, and the former convergence speed of the synchronization error is faster.

  2. Clocks underneath: the role of peripheral clocks in the timing of female reproductive physiology

    Directory of Open Access Journals (Sweden)

    Michael T Sellix

    2013-07-01

    Full Text Available The central circadian pacemaker in the suprachiasmatic nucleus (SCN is a critical component of the neuroendocrine circuit controlling gonadotropin secretion from the pituitary gland. The SCN conveys photic information to hypothalamic targets including the gonadotropin releasing hormone (GnRH neurons. Many of these target cells are also cell autonomous clocks. It has been suggested that, rather then being singularly driven by the SCN, the timing of gonadotropin secretion depends on the activity of multiple hypothalamic oscillators. While this view provides a novel twist to an old story, it does little to diminish the central role of rhythmic hypothalamic output in this system. It is now clear that the pituitary, ovary, uterus and oviduct have functional molecular clocks. Evidence supports the notion that the clocks in these tissues contribute to the timing of events in reproductive physiology. The goal of this review is to highlight the current evidence for molecular clock function in the peripheral components of the female hypothalamo-pituitary-gonadal (HPG axis as it relates to the timing of gonadotropin secretion, ovulation and parturition.

  3. A Component-Based Conference Control Model and Implementation for Loosely Coupled Sessions

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Conference control is a very important core part to compose a complete Internet multimedia conference system and has been a hot research area over the years, but there are currently no widely accepted robust and scalable solutions and standards. This paper proposes a component-based conference control model for loosely coupled sessions in which media applications can collaborate with a Session Controller(SC) to provide the conference control. A SC prototype has been built.

  4. Improved master clock reference system at USNO

    Science.gov (United States)

    Winkler, G. M. R.

    1985-04-01

    The first phase of the NAVELEX/NRL/USNO Master Clock (MC) upgrade program has been completed with the delivery of two VLG11B hydrogen Masers to the U.S. Naval Observatory (USNO). After installation in a specially prepaid Maser Laboratory with redundant environmental control, and a ten-day burn-in operation, the masers were independently tuned. Their subsequent performance caused a review of our plans for their operational use as part of the USNO MC complex. A revised concept is the basis for system integration presently in progress.

  5. Laser Cooled Atomic Clocks in Space

    Science.gov (United States)

    Thompson, R. J.; Kohel, J.; Klipstein, W. M.; Seidel, D. J.; Maleki, L.

    2000-01-01

    The goals of the Glovebox Laser-cooled Atomic Clock Experiment (GLACE) are: (1) first utilization of tunable, frequency-stabilized lasers in space, (2) demonstrate laser cooling and trapping in microgravity, (3) demonstrate longest 'perturbation-free' interaction time for a precision measurement on neutral atoms, (4) Resolve Ramsey fringes 2-10 times narrower than achievable on Earth. The approach taken is: the use of COTS components, and the utilization of prototype hardware from LCAP flight definition experiments. The launch date is scheduled for Oct. 2002. The Microgravity Science Glovebox (MSG) specifications are reviewed, and a picture of the MSG is shown.

  6. Robustness of Structures

    DEFF Research Database (Denmark)

    Faber, M.H.; Vrouwenvelder, A.C.W.M.; Sørensen, John Dalsgaard

    2011-01-01

    In 2005, the Joint Committee on Structural Safety (JCSS) together with Working Commission (WC) 1 of the International Association of Bridge and Structural Engineering (IABSE) organized a workshop on robustness of structures. Two important decisions resulted from this workshop, namely the developm......In 2005, the Joint Committee on Structural Safety (JCSS) together with Working Commission (WC) 1 of the International Association of Bridge and Structural Engineering (IABSE) organized a workshop on robustness of structures. Two important decisions resulted from this workshop, namely...... the development of a joint European project on structural robustness under the COST (European Cooperation in Science and Technology) programme and the decision to develop a more elaborate document on structural robustness in collaboration between experts from the JCSS and the IABSE. Accordingly, a project titled...... ‘COST TU0601: Robustness of Structures’ was initiated in February 2007, aiming to provide a platform for exchanging and promoting research in the area of structural robustness and to provide a basic framework, together with methods, strategies and guidelines enhancing robustness of structures...

  7. A precise clock distribution network for MRPC-based experiments

    Science.gov (United States)

    Wang, S.; Cao, P.; Shang, L.; An, Q.

    2016-06-01

    In high energy physics experiments, the MRPC (Multi-Gap Resistive Plate Chamber) detectors are widely used recently which can provide higher-resolution measurement for particle identification. However, the application of MRPC detectors leads to a series of challenges in electronics design with large number of front-end electronic channels, especially for distributing clock precisely. To deal with these challenges, this paper presents a universal scheme of clock transmission network for MRPC-based experiments with advantages of both precise clock distribution and global command synchronization. For precise clock distributing, the clock network is designed into a tree architecture with two stages: the first one has a point-to-multipoint long range bidirectional distribution with optical channels and the second one has a fan-out structure with copper link inside readout crates. To guarantee the precision of clock frequency or phase, the r-PTP (reduced Precision Time Protocol) and the DDMTD (digital Dual Mixer Time Difference) methods are used for frequency synthesis, phase measurement and adjustment, which is implemented by FPGA (Field Programmable Gate Array) in real-time. In addition, to synchronize global command execution, based upon this clock distribution network, synchronous signals are coded with clock for transmission. With technique of encoding/decoding and clock data recovery, signals such as global triggers or system control commands, can be distributed to all front-end channels synchronously, which greatly simplifies the system design. The experimental results show that both the clock jitter (RMS) and the clock skew can be less than 100 ps.

  8. Comparison of mode estimation methods and application in molecular clock analysis

    Science.gov (United States)

    Hedges, S. Blair; Shah, Prachi

    2003-01-01

    BACKGROUND: Distributions of time estimates in molecular clock studies are sometimes skewed or contain outliers. In those cases, the mode is a better estimator of the overall time of divergence than the mean or median. However, different methods are available for estimating the mode. We compared these methods in simulations to determine their strengths and weaknesses and further assessed their performance when applied to real data sets from a molecular clock study. RESULTS: We found that the half-range mode and robust parametric mode methods have a lower bias than other mode methods under a diversity of conditions. However, the half-range mode suffers from a relatively high variance and the robust parametric mode is more susceptible to bias by outliers. We determined that bootstrapping reduces the variance of both mode estimators. Application of the different methods to real data sets yielded results that were concordant with the simulations. CONCLUSION: Because the half-range mode is a simple and fast method, and produced less bias overall in our simulations, we recommend the bootstrapped version of it as a general-purpose mode estimator and suggest a bootstrap method for obtaining the standard error and 95% confidence interval of the mode.

  9. MULTIDISCIPLINARY ROBUST OPTIMIZATION DESIGN

    Institute of Scientific and Technical Information of China (English)

    Chen Jianjiang; Xiao Renbin; Zhong Yifang; Dou Gang

    2005-01-01

    Because uncertainty factors inevitably exist under multidisciplinary design environment, a hierarchical multidisciplinary robust optimization design based on response surface is proposed. The method constructs optimization model of subsystem level and system level to coordinate the coupling among subsystems, and also the response surface based on the artificial neural network is introduced to provide information for system level optimization tool to maintain the independence of subsystems,i.e. to realize multidisciplinary parallel design. The application case of electrical packaging demonstrates that reasonable robust optimum solution can be yielded and it is a potential and efficient multidisciplinary robust optimization approach.

  10. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani

    2014-04-01

    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  11. Robustness Beamforming Algorithms

    Directory of Open Access Journals (Sweden)

    Sajad Dehghani

    2014-09-01

    Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

  12. Robustness of Structures

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard

    2008-01-01

    . According to Danish design rules robustness shall be documented for all structures in high consequence class. The design procedure to document sufficient robustness consists of: 1) Review of loads and possible failure modes / scenarios and determination of acceptable collapse extent; 2) Review......This paper describes the background of the robustness requirements implemented in the Danish Code of Practice for Safety of Structures and in the Danish National Annex to the Eurocode 0, see (DS-INF 146, 2003), (DS 409, 2006), (EN 1990 DK NA, 2007) and (Sørensen and Christensen, 2006). More...... frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new structures essential...

  13. The First Atomic Clock Program: NBS, 1947-1954

    Science.gov (United States)

    1985-12-03

    clock was being brought into operation, Lyons’ group would gladly have sacrificed something in Q for the convience of carrying the frequency...divider, while the use of small, solid samples raised hopes of a n-ortable clock. Finally, when, late in 1954 it became clear that Townes’ own "atomic

  14. Verge and Foliot Clock Escapement: A Simple Dynamical System

    Science.gov (United States)

    Denny, Mark

    2010-01-01

    The earliest mechanical clocks appeared in Europe in the 13th century. From about 1250 CE to 1670 CE, these simple clocks consisted of a weight suspended from a rope or chain that was wrapped around a horizontal axle. To tell time, the weight must fall with a slow uniform speed, but, under the action of gravity alone, such a suspended weight would…

  15. Coordination of the maize transcriptome by a conserved circadian clock

    Science.gov (United States)

    The plant circadian clock orchestrates 24-hour rhythms in internal physiological processes to coordinate these activities with daily and seasonal changes in the environment. The circadian clock has a profound impact on many aspects of plant growth and development, including biomass accumulation and ...

  16. Clock accuracy analysis for a coherent IR-UWB system

    NARCIS (Netherlands)

    Wang, X.; Young, A.; Philips, K.; Groot, H. de

    2011-01-01

    The performance of a duty-cycled coherent impulse radio UWB system is typically dominated by the accuracy of its timing references. In this paper, a timing analysis is presented for an IR-UWB system to specify the accuracy requirements for the internal clocks of the transceiver. A possible clock gen

  17. Secure and self-stabilizing clock synchronization in sensor networks

    NARCIS (Netherlands)

    Hoepman, J.H.; Larsson, A.; Schiller, E.M.; Tsigas, P.

    2011-01-01

    In sensor networks, correct clocks have arbitrary starting offsets and nondeterministic fluctuating skews. We consider an adversary that aims at tampering with the clock synchronization by intercepting messages, replaying intercepted messages (after the adversary’s choice of delay), and capturing no

  18. The circadian clock regulates auxin signaling and responses in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Michael F Covington

    2007-08-01

    Full Text Available The circadian clock plays a pervasive role in the temporal regulation of plant physiology, environmental responsiveness, and development. In contrast, the phytohormone auxin plays a similarly far-reaching role in the spatial regulation of plant growth and development. Went and Thimann noted 70 years ago that plant sensitivity to auxin varied according to the time of day, an observation that they could not explain. Here we present work that explains this puzzle, demonstrating that the circadian clock regulates auxin signal transduction. Using genome-wide transcriptional profiling, we found many auxin-induced genes are under clock regulation. We verified that endogenous auxin signaling is clock regulated with a luciferase-based assay. Exogenous auxin has only modest effects on the plant clock, but the clock controls plant sensitivity to applied auxin. Notably, we found both transcriptional and growth responses to exogenous auxin are gated by the clock. Thus the circadian clock regulates some, and perhaps all, auxin responses. Consequently, many aspects of plant physiology not previously thought to be under circadian control may show time-of-day-specific sensitivity, with likely important consequences for plant growth and environmental responses.

  19. Frequency comparison of optical lattice clocks beyond the Dick limit

    Science.gov (United States)

    Takamoto, Masao; Takano, Tetsushi; Katori, Hidetoshi

    2011-05-01

    The supreme accuracy of atomic clocks relies on the universality of atomic transition frequencies. The stability of a clock, meanwhile, measures how quickly the clock's statistical uncertainties are reduced. The ultimate measure of stability is provided by the quantum projection noise, which improves as 1/√N by measuring N uncorrelated atoms. Quantum projection noise limited stabilities have been demonstrated in caesium clocks and in single-ion optical clocks, where the quantum noise overwhelms the Dick effect attributed to local oscillator noise. Here, we demonstrate a synchronous frequency comparison of two optical lattice clocks using 87Sr and 88Sr atoms, respectively, for which the Allan standard deviation reached 1 × 10-17 in an averaging time of 1,600 s by cancelling out the Dick effect to approach the quantum projection noise limit. The scheme demonstrates the advantage of using a large number (N ~ 1,000) of atoms in optical clocks and paves the way to investigating the inherent uncertainties of clocks and relativistic geodesy on a timescale of tens of minutes.

  20. Assignment of circadian function for the Neurospora clock gene frequency

    NARCIS (Netherlands)

    Merrow, Martha; Brunner, Michael; Roenneberg, Till

    1999-01-01

    Circadian clocks consist of three elements: entrainment pathways (inputs), the mechanism generating the rhythmicity (oscillator), and the output pathways that control the circadian rhythms. It is difficult to assign molecular clock components to any one of these elements. Experiments show that input

  1. Molecular clock integration of brown adipose tissue formation and function.

    Science.gov (United States)

    Nam, Deokhwa; Yechoor, Vijay K; Ma, Ke

    2016-01-01

    The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation.

  2. The role of biological clock in glucose homeostasis 

    Directory of Open Access Journals (Sweden)

    Piotr Chrościcki

    2013-06-01

    Full Text Available The mechanism of the biological clock is based on a rhythmic expression of clock genes and clock-controlled genes. As a result of their transcripto-translational associations, endogenous rhythms in the synthesis of key proteins of various physiological and metabolic processes are created. The major timekeeping mechanism for these rhythms exists in the central nervous system. The master circadian clock, localized in suprachiasmatic nucleus (SCN, regulates multiple metabolic pathways, while feeding behavior and metabolite availability can in turn regulate the circadian clock. It is also suggested that in the brain there is a food entrainable oscillator (FEO or oscillators, resulting in activation of both food anticipatory activity and hormone secretion that control digestion processes. Moreover, most cells and tissues express autonomous clocks. Maintenance of the glucose homeostasis is particularly important for the proper function of the body, as this sugar is the main source of energy for the brain, retina, erythrocytes and skeletal muscles. Thus, glucose production and utilization are synchronized in time. The hypothalamic excited orexin neurons control energy balance of organism and modulate the glucose production and utilization. Deficiency of orexin action results in narcolepsy and weight gain, whereas glucose and amino acids can affect activity of the orexin cells. Large-scale genetic studies in rodents and humans provide evidence for the involvement of disrupted clock gene expression rhythms in the pathogenesis of obesity and type 2 diabetes. In general, the current lifestyle of the developed modern societies disturbs the action of biological clock

  3. Cryptographic Combinatorial Clock-Proxy Auctions

    Science.gov (United States)

    Parkes, David C.; Rabin, Michael O.; Thorpe, Christopher

    We present a cryptographic protocol for conducting efficient, provably correct and secrecy-preserving combinatorial clock-proxy auctions. The “clock phase” functions as a trusted auction despite price discovery: bidders submit encrypted bids, and prove for themselves that they meet activity rules, and can compute total demand and thus verify price increases without revealing any information about individual demands. In the sealed-bid “proxy phase”, all bids are revealed the auctioneer via time-lapse cryptography and a branch-and-bound algorithm is used to solve the winner-determination problem. Homomorphic encryption is used to prove the correctness of the solution, and establishes the correctness of the solution to any interested party. Still an NP-hard optimization problem, the use of homomorphic encryption imposes additional computational time on winner-determination that is linear in the size of the branch-and-bound search tree, and thus roughly linear in the original (search-based) computational time. The result is a solution that avoids, in the usual case, the exponential complexity of previous cryptographically-secure combinatorial auctions.

  4. A computational model clarifies the roles of positive and negative feedback loops in the Drosophila circadian clock

    Energy Technology Data Exchange (ETDEWEB)

    Wang Junwei, E-mail: wangjunweilj@yahoo.com.c [Cisco School of Informatics, Guangdong University of Foreign Studies, Guangzhou 510006 (China); Zhou Tianshou [School of Mathematics and Computational Science, Sun Yat-Sen University, Guangzhou 510275 (China)

    2010-06-14

    Previous studies showed that a single negative feedback structure should be sufficient for robust circadian oscillations. It is thus pertinent to ask why current cellular clock models almost universally have interlocked negative feedback loop (NFL) and positive feedback loop (PFL). Here, we propose a molecular model that reflects the essential features of the Drosophila circadian clock to clarify the different roles of negative and positive feedback loops. In agreement with experimental observations, the model can simulate circadian oscillations in constant darkness, entrainment by light-dark cycles, as well as phenotypes of per{sup 01} and clk{sup Jrk} mutants. Moreover, sustained oscillations persist when the PFL is removed, implying the crucial role of NFL for rhythm generation. Through parameter sensitivity analysis, it is revealed that incorporation of PFL increases the robustness of the system to regulatory processes in PFL itself. Such reduced models can aid understanding of the design principles of circadian clocks in Drosophila and other organisms with complex transcriptional feedback structures.

  5. Conference this! Lead Pipers compare conference experiences

    Directory of Open Access Journals (Sweden)

    Editorial Board

    2010-04-01

    Full Text Available As library travel budgets are increasingly slashed around the country, it’s a tough time for conference-going. In this group post, we compare notes about the conferences we’ve attended, which have been our favorites, and why. We hope this will generate creative ideas on good conferences (online or in-person to look forward to, and maybe offer [...

  6. Deep Coupled Integration of CSAC and GNSS for Robust PNT.

    Science.gov (United States)

    Ma, Lin; You, Zheng; Li, Bin; Zhou, Bin; Han, Runqi

    2015-09-11

    Global navigation satellite systems (GNSS) are the most widely used positioning, navigation, and timing (PNT) technology. However, a GNSS cannot provide effective PNT services in physical blocks, such as in a natural canyon, canyon city, underground, underwater, and indoors. With the development of micro-electromechanical system (MEMS) technology, the chip scale atomic clock (CSAC) gradually matures, and performance is constantly improved. A deep coupled integration of CSAC and GNSS is explored in this thesis to enhance PNT robustness. "Clock coasting" of CSAC provides time synchronized with GNSS and optimizes navigation equations. However, errors of clock coasting increase over time and can be corrected by GNSS time, which is stable but noisy. In this paper, weighted linear optimal estimation algorithm is used for CSAC-aided GNSS, while Kalman filter is used for GNSS-corrected CSAC. Simulations of the model are conducted, and field tests are carried out. Dilution of precision can be improved by integration. Integration is more accurate than traditional GNSS. When only three satellites are visible, the integration still works, whereas the traditional method fails. The deep coupled integration of CSAC and GNSS can improve the accuracy, reliability, and availability of PNT.

  7. Deep Coupled Integration of CSAC and GNSS for Robust PNT

    Directory of Open Access Journals (Sweden)

    Lin Ma

    2015-09-01

    Full Text Available Global navigation satellite systems (GNSS are the most widely used positioning, navigation, and timing (PNT technology. However, a GNSS cannot provide effective PNT services in physical blocks, such as in a natural canyon, canyon city, underground, underwater, and indoors. With the development of micro-electromechanical system (MEMS technology, the chip scale atomic clock (CSAC gradually matures, and performance is constantly improved. A deep coupled integration of CSAC and GNSS is explored in this thesis to enhance PNT robustness. “Clock coasting” of CSAC provides time synchronized with GNSS and optimizes navigation equations. However, errors of clock coasting increase over time and can be corrected by GNSS time, which is stable but noisy. In this paper, weighted linear optimal estimation algorithm is used for CSAC-aided GNSS, while Kalman filter is used for GNSS-corrected CSAC. Simulations of the model are conducted, and field tests are carried out. Dilution of precision can be improved by integration. Integration is more accurate than traditional GNSS. When only three satellites are visible, the integration still works, whereas the traditional method fails. The deep coupled integration of CSAC and GNSS can improve the accuracy, reliability, and availability of PNT.

  8. Robustness - theoretical framework

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Faber, Michael H.

    2010-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new struct...... of this fact sheet is to describe a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....

  9. Robust Nonstationary Regression

    OpenAIRE

    1993-01-01

    This paper provides a robust statistical approach to nonstationary time series regression and inference. Fully modified extensions of traditional robust statistical procedures are developed which allow for endogeneities in the nonstationary regressors and serial dependence in the shocks that drive the regressors and the errors that appear in the equation being estimated. The suggested estimators involve semiparametric corrections to accommodate these possibilities and they belong to the same ...

  10. Robustness - theoretical framework

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rizzuto, Enrico; Faber, Michael H.

    2010-01-01

    More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new struct...... of this fact sheet is to describe a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....

  11. Qualitative Robustness in Estimation

    Directory of Open Access Journals (Sweden)

    Mohammed Nasser

    2012-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Times New Roman","serif";} Qualitative robustness, influence function, and breakdown point are three main concepts to judge an estimator from the viewpoint of robust estimation. It is important as well as interesting to study relation among them. This article attempts to present the concept of qualitative robustness as forwarded by first proponents and its later development. It illustrates intricacies of qualitative robustness and its relation with consistency, and also tries to remove commonly believed misunderstandings about relation between influence function and qualitative robustness citing some examples from literature and providing a new counter-example. At the end it places a useful finite and a simulated version of   qualitative robustness index (QRI. In order to assess the performance of the proposed measures, we have compared fifteen estimators of correlation coefficient using simulated as well as real data sets.

  12. The Space Optical Clock project: status and perspectives

    Science.gov (United States)

    Schiller, Stephan; Tino, Guglielmo M.; Sterr, Uwe; Lemonde, Pierre; Görlitz, Axel; Salomon, Christophe

    The Space Optical Clocks project aims at operating lattice clocks on the ISS for tests of funda-mental physics and for providing high-accuracy comparisons of future terrestrial optical clocks. A pre-phase-A study (2007-10), funded partially by ESA and DLR, includes the implementa-tion of several optical lattice clock systems using Strontium and Ytterbium as atomic systems and their characterization. Subcomponents of clock demonstrators with the added specification of transportability and using techniques that are suitable for later space use, such as all-solid-state lasers, low power consumption, and compact dimensions, have been developed and are being validated. The talk will give a brief overview over the achieved results and outline future developments.

  13. Frequency Comparison of Two High-Accuracy Al+ Optical Clocks

    CERN Document Server

    Chou, C -W; Koelemeij, J C J; Wineland, D J; Rosenband, T

    2009-01-01

    We have constructed an optical clock with a fractional frequency inaccuracy of 8.6e-18, based on quantum logic spectroscopy of an Al+ ion. A simultaneously trapped Mg+ ion serves to sympathetically laser-cool the Al+ ion and detect its quantum state. The frequency of the 1S0->3P0 clock transition is compared to that of a previously constructed Al+ optical clock with a statistical measurement uncertainty of 7.0e-18. The two clocks exhibit a relative stability of 2.8e-15/ sqrt(tau), and a fractional frequency difference of -1.8e-17, consistent with the accuracy limit of the older clock.

  14. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock

    Directory of Open Access Journals (Sweden)

    David M. Virshup

    2017-04-01

    Full Text Available An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep–wake cycle, feeding–fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.

  15. Frequency Comparison of Two High-Accuracy Al+ Optical Clocks

    Science.gov (United States)

    Chou, C. W.; Hume, D. B.; Koelemeij, J. C. J.; Wineland, D. J.; Rosenband, T.

    2010-02-01

    We have constructed an optical clock with a fractional frequency inaccuracy of 8.6×10-18, based on quantum logic spectroscopy of an Al+ ion. A simultaneously trapped Mg+ ion serves to sympathetically laser cool the Al+ ion and detect its quantum state. The frequency of the S01↔P03 clock transition is compared to that of a previously constructed Al+ optical clock with a statistical measurement uncertainty of 7.0×10-18. The two clocks exhibit a relative stability of 2.8×10-15τ-1/2, and a fractional frequency difference of -1.8×10-17, consistent with the accuracy limit of the older clock.

  16. Miniature Optical Atomic Clock: Stabilization of a Kerr Comb Oscillator

    CERN Document Server

    Savchenkov, A A; Liang, W; Ilchenko, V S; Byrd, J; Matsko, A B; Seidel, D; Maleki, L

    2013-01-01

    Mechanical clocks consist of a pendulum and a clockwork that translates the pendulum period to displayed time. The most advanced clocks utilize optical transitions in atoms in place of the pendulum and an optical frequency comb generated by a femtosecond laser as the clockwork. The comb must be stabilized at two points along its frequency spectrum: one with a laser to lock a comb line to a transition in the atom, and another through self referencing to stabilize the frequency interval between the comb lines. This approach requires advanced techniques, so optical atomic clocks are currently laboratory devices in specialized labs. In this paper we leverage unique properties of Kerr comb oscillators for realization of optical atomic clocks in miniature form factors. In particular, we describe a clock based on D1 transition of 87Rb that fits in the palm of the hand, and can be further miniaturized to chip scale.

  17. Remote atomic clock synchronization via satellites and optical fibers

    CERN Document Server

    Piester, D; Fujieda, M; Feldmann, T; Bauch, A

    2011-01-01

    In the global network of institutions engaged with the realization of International Atomic Time (TAI), atomic clocks and time scales are compared by means of the Global Positioning System (GPS) and by employing telecommunication satellites for two-way satellite time and frequency transfer (TWSTFT). The frequencies of the state-of-the-art primary caesium fountain clocks can be compared at the level of 10e-15 (relative, 1 day averaging) and time scales can be synchronized with an uncertainty of one nanosecond. Future improvements of worldwide clock comparisons will require also an improvement of the local signal distribution systems. For example, the future ACES (atomic clock ensemble in space) mission shall demonstrate remote time scale comparisons at the uncertainty level of 100 ps. To ensure that the ACES ground instrument will be synchronized to the local time scale at PTB without a significant uncertainty contribution, we have developed a means for calibrated clock comparisons through optical fibers. An un...

  18. Hunting for topological dark matter with atomic clocks

    CERN Document Server

    Derevianko, A

    2013-01-01

    The cosmological applications of atomic clocks so far have been limited to searches of the uniform-in-time drift of fundamental constants. In this paper, we point out that a transient in time change of fundamental constants can be induced by dark matter objects that have large spatial extent, and are built from light non-Standard Model fields. The stability of this type of dark matter can be dictated by the topological reasons. We point out that correlated networks of atomic clocks, some of them already in existence, can be used as a powerful tool to search for the topological defect dark matter, thus providing another important fundamental physics application to the ever-improving accuracy of atomic clocks. During the encounter with a topological defect, as it sweeps through the network, initially synchronized clocks will become desynchronized. Time discrepancies between spatially-separated clocks are expected to exhibit a distinct signature, encoding defect's space structure and its interaction strength wit...

  19. The circadian clock and cell cycle: interconnected biological circuits.

    Science.gov (United States)

    Masri, Selma; Cervantes, Marlene; Sassone-Corsi, Paolo

    2013-12-01

    The circadian clock governs biological timekeeping on a systemic level, helping to regulate and maintain physiological processes, including endocrine and metabolic pathways with a periodicity of 24-hours. Disruption within the circadian clock machinery has been linked to numerous pathological conditions, including cancer, suggesting that clock-dependent regulation of the cell cycle is an essential control mechanism. This review will highlight recent advances on the 'gating' controls of the circadian clock at various checkpoints of the cell cycle and also how the cell cycle can influence biological rhythms. The reciprocal influence that the circadian clock and cell cycle exert on each other suggests that these intertwined biological circuits are essential and multiple regulatory/control steps have been instated to ensure proper timekeeping.

  20. Cell "circadian" cycle: new role for mammalian core clock genes.

    Science.gov (United States)

    Borgs, Laurence; Beukelaers, Pierre; Vandenbosch, Renaud; Belachew, Shibeshih; Nguyen, Laurent; Malgrange, Brigitte

    2009-03-15

    In mammals, 24 hours rhythms are organized as a biochemical network of molecular clocks that are operative in all tissues, with the master clock residing in the hypothalamic suprachiasmatic nucleus (SCN). The core pacemakers of these clocks consist of auto-regulatory transcriptional/post-transcriptional feedback loops. Several lines of evidence suggest the existence of a crosstalk between molecules that are responsible for the generation of circadian rhythms and molecules that control the cell cycle progression. In addition, highly specialized cell cycle checkpoints involved in DNA repair after damage seem also, at least in part, mediated by clock proteins. Recent studies have also highlighted a putative connection between clock protein dysfunction and cancer progression. This review discusses the intimate relation that exists between cell cycle progression and components of the circadian machinery.

  1. The quantum beat principles and applications of atomic clocks

    CERN Document Server

    Major, F

    2007-01-01

    This work attempts to convey a broad understanding of the physical principles underlying the workings of these quantum-based atomic clocks, with introductory chapters placing them in context with the early development of mechanical clocks and the introduction of electronic time-keeping as embodied in the quartz-controlled clocks. While the book makes no pretense at being a history of atomic clocks, it nevertheless takes a historical perspective in its treatment of the subject. Intended for nonspecialists with some knowledge of physics or engineering, The Quantum Beat covers a wide range of salient topics relevant to atomic clocks, treated in a broad intuitive manner with a minimum of mathematical formalism. Detailed descriptions are given of the design principles of the rubidium, cesium, hydrogen maser, and mercury ion standards; the revolutionary changes that the advent of the laser has made possible, such as laser cooling, optical pumping, the formation of "optical molasses," and the cesium "fountain" stand...

  2. Clock-turning gait synthesis for humanoid robots

    Institute of Scientific and Technical Information of China (English)

    Zhe TANG; Zengqi SUN; Hongbo LIU; Meng Joo ER

    2007-01-01

    Turning gait is a basic motion for humanoid robots.This paper presents a method for humanoid turning.i.e.clock-turning.The objective of clock-turning is to change robot direction at a stationary spot.The clock-turning planning consists of four steps:ankle trajectory generation,hip trajectory generation,knee trajectory generation,and inverse kinematics calculation.Our proposed method is based on a typical humanoid structure with 12 DOFs(degrees of freedom).The final output of clock-turning planning is 12 reference trajectories.which are used to control a humanoid robot wim 12 DOFs.ZMP(zero moment point)is used as stability criterion for the planning.Simulation experiments are conducted to verify the effectiveness of our proposed clock-turning method.

  3. Geophysical applicability of atomic clocks: direct continental geoid mapping

    CERN Document Server

    Bondarescu, Ruxandra; Hetényi, György; Boschi, Lapo; Jetzer, Philippe; Balakrishna, Jayashree; 10.1111/j.1365-246X.2012.05636.x

    2012-01-01

    The geoid is the true physical figure of the Earth, a particular equipotential surface of the gravity field of the Earth that accounts for the effect of all subsurface density variations. Its shape approximates best (in the sense of least squares) the mean level of oceans, but the geoid is more difficult to determine over continents. Satellite missions carry out distance measurements and derive the gravity field to provide geoid maps over the entire globe. However, they require calibration and extensive computations including integration, which is a non-unique operation. Here we propose a direct method and a new tool that directly measures geopotential differences on continents using atomic clocks. General Relativity Theory predicts constant clock rate at sea level, and faster (resp. slower) clock rate above (resp. below) sea level. The technology of atomic clocks is on the doorstep of reaching an accuracy level in clock rate that is equivalent to 1 cm in determining equipotential surface (including geoid) he...

  4. The molecular clock mediates leptin-regulated bone formation.

    Science.gov (United States)

    Fu, Loning; Patel, Millan S; Bradley, Allan; Wagner, Erwin F; Karsenty, Gerard

    2005-09-01

    The hormone leptin is a regulator of bone remodeling, a homeostatic function maintaining bone mass constant. Mice lacking molecular-clock components (Per and Cry), or lacking Per genes in osteoblasts, display high bone mass, suggesting that bone remodeling may also be subject to circadian regulation. Moreover, Per-deficient mice experience a paradoxical increase in bone mass following leptin intracerebroventricular infusion. Thus, clock genes may mediate the leptin-dependent sympathetic regulation of bone formation. We show that expression of clock genes in osteoblasts is regulated by the sympathetic nervous system and leptin. Clock genes mediate the antiproliferative function of sympathetic signaling by inhibiting G1 cyclin expression. Partially antagonizing this inhibitory loop, leptin also upregulates AP-1 gene expression, which promotes cyclin D1 expression, osteoblast proliferation, and bone formation. Thus, leptin determines the extent of bone formation by modulating, via sympathetic signaling, osteoblast proliferation through two antagonistic pathways, one of which involves the molecular clock.

  5. Math Clock: Perangkat Penunjuk Waktu Kreatif untuk Olahraga Otak

    Directory of Open Access Journals (Sweden)

    Galuh Boy Hertantyo

    2014-11-01

    Full Text Available Brain is one of the most vital parts for humans, with the number of brain function that is needed for the body, the brain becomes a very important part of the human body. If there is damage to the brain will certainly cause the performance of the human body will not run properly. Because of that, it’s very important to maintain brain health. There is a way to maintain brain health, for example is by doing brain exercise. Examples of brain exercise is to do simple math calculations or doing brain games like sudoku. Because of that, created a tool that can help the brain to maintain brain exercise. The tool is called math clock. Making math clock tool consists of hardware and software. The hardware consists of RTC as real time data input, ATmega328 as microcontroller and dot matrix 32x16 as a tool to display the output that has been processed by the microcontroller. The software is built using C with Arduino IDE. Math clock will process the data from RTC then processed it, in microcontroller so when output displayed on dot matrix, output will be simple mathematical operation with real time clock data on it. Test results show that, math clock is capable of displaying a simple mathematical calculation operations such as addition, subtraction, multiplication and division. The mathematical operation that display on math clock, appears to be random, so it’s not triggered by same mathematical operation. In math clock the display will change every 20 second, so in 1 minute there are 3 different kinds of mathematical operations. The results of questionnaires of 10 different students, showed 9 out of 10 students said math clock is a tool that easy to use as a clock. Math clock will be alternative for doing brain exercise every day.

  6. Postnatal ontogenesis of molecular clock in mouse striatum.

    Science.gov (United States)

    Cai, Yanning; Liu, Shu; Li, Ning; Xu, Shengli; Zhang, Yanli; Chan, Piu

    2009-04-01

    Striatum is an important brain area whose function is related to motor, emotion and motivation. Interestingly, biological and physiological circadian rhythms have been found in the striatum extensively, suggesting molecular clock machinery works efficiently therein. However, the striatal expression profiles of clock genes have not been characterized systematically. In addition, little is known about when the expression rhythms start during postnatal ontogenesis. In the present study, 24 h mRNA oscillations of 6 principle clock genes (Bmal1, Clock, Npas2, Cry1, Per1 and Rev-erb alpha) were examined in mouse striatum, at early postnatal stage (postnatal day 3), pre-weaning stage (postnatal day 14) and in adult (postnatal day 60). At P3, no daily oscillation was found for all clock genes. At P14, a significant time effect was identified only for Rev-erb alpha and Npas2. At P60, the daily oscillations of these clock genes were at least borderline significant, with peak time at Circadian time (CT) 01 for Bmal1, Clock, Npas2 and Cry1; at CT 13 for Per1; and at CT 07 for Rev-erb alpha. In addition, the overall mean mRNA levels of these clock genes also underwent a dynamic change postnatally. For Bmal1, Clock, Npas2, Per1 and Rev-erb alpha, the expression level increased throughout the postnatal ontogenesis from P3, P14 to P60. For Cry1, however, the abundance at P3 and P60 were similar while that at P14 was much lower. In conclusion, the striatal molecular clock machinery, although works efficiently in adult, develops gradually after birth in mice.

  7. The genetic basis of the circadian clock : identification of frq and FRQ as clock components in Neurospora

    NARCIS (Netherlands)

    Dunlap, Jay C.; Loros, Jennifer J.; Aronson, Benjamin D.; Merrow, Martha; Crosthwaite, Susan; Bell-Pedersen, Deborah; Johnson, Keith; Lindgren, Kristin; Garceau, Norman Y.

    1995-01-01

    Genetic approaches to the identification of clock components have succeeded in two model systems, Neurospora and Drosophila. In each organism, genes identified through screens for clock-affecting mutations (frq in Neurospora, per in Drosophila) have subsequently been shown to have characteristics of

  8. 76 FR 64083 - Reliability Technical Conference; Notice of Technical Conference

    Science.gov (United States)

    2011-10-17

    ... Energy Regulatory Commission Reliability Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, November 29... addressing risks to reliability that were identified in earlier Commission technical conferences....

  9. Stochastic Regulation of her1/7 Gene Expression Is the Source of Noise in the Zebrafish Somite Clock Counteracted by Notch Signalling.

    Directory of Open Access Journals (Sweden)

    Robert P Jenkins

    2015-11-01

    Full Text Available The somite segmentation clock is a robust oscillator used to generate regularly-sized segments during early vertebrate embryogenesis. It has been proposed that the clocks of neighbouring cells are synchronised via inter-cellular Notch signalling, in order to overcome the effects of noisy gene expression. When Notch-dependent communication between cells fails, the clocks of individual cells operate erratically and lose synchrony over a period of about 5 to 8 segmentation clock cycles (2-3 hours in the zebrafish. Here, we quantitatively investigate the effects of stochasticity on cell synchrony, using mathematical modelling, to investigate the likely source of such noise. We find that variations in the transcription, translation and degradation rate of key Notch signalling regulators do not explain the in vivo kinetics of desynchronisation. Rather, the analysis predicts that clock desynchronisation, in the absence of Notch signalling, is due to the stochastic dissociation of Her1/7 repressor proteins from the oscillating her1/7 autorepressed target genes. Using in situ hybridisation to visualise sites of active her1 transcription, we measure an average delay of approximately three minutes between the times of activation of the two her1 alleles in a cell. Our model shows that such a delay is sufficient to explain the in vivo rate of clock desynchronisation in Notch pathway mutant embryos and also that Notch-mediated synchronisation is sufficient to overcome this stochastic variation. This suggests that the stochastic nature of repressor/DNA dissociation is the major source of noise in the segmentation clock.

  10. Cryptochrome mediates light-dependent magnetosensitivity of Drosophila's circadian clock.

    Directory of Open Access Journals (Sweden)

    Taishi Yoshii

    2009-04-01

    Full Text Available Since 1960, magnetic fields have been discussed as Zeitgebers for circadian clocks, but the mechanism by which clocks perceive and process magnetic information has remained unknown. Recently, the radical-pair model involving light-activated photoreceptors as magnetic field sensors has gained considerable support, and the blue-light photoreceptor cryptochrome (CRY has been proposed as a suitable molecule to mediate such magnetosensitivity. Since CRY is expressed in the circadian clock neurons and acts as a critical photoreceptor of Drosophila's clock, we aimed to test the role of CRY in magnetosensitivity of the circadian clock. In response to light, CRY causes slowing of the clock, ultimately leading to arrhythmic behavior. We expected that in the presence of applied magnetic fields, the impact of CRY on clock rhythmicity should be altered. Furthermore, according to the radical-pair hypothesis this response should be dependent on wavelength and on the field strength applied. We tested the effect of applied static magnetic fields on the circadian clock and found that flies exposed to these fields indeed showed enhanced slowing of clock rhythms. This effect was maximal at 300 muT, and reduced at both higher and lower field strengths. Clock response to magnetic fields was present in blue light, but absent under red-light illumination, which does not activate CRY. Furthermore, cry(b and cry(OUT mutants did not show any response, and flies overexpressing CRY in the clock neurons exhibited an enhanced response to the field. We conclude that Drosophila's circadian clock is sensitive to magnetic fields and that this sensitivity depends on light activation of CRY and on the applied field strength, consistent with the radical pair mechanism. CRY is widespread throughout biological systems and has been suggested as receptor for magnetic compass orientation in migratory birds. The present data establish the circadian clock of Drosophila as a model system

  11. [Circadian rhythms and light responses of clock gene and arylalkylamine N-acetyltransferase gene expressions in the pineal gland of rats].

    Science.gov (United States)

    Wang, Guo-Qing; Du, Yu-Zhen; Tong, Jian

    2005-02-25

    This study was to investigate the circadian rhythms and light responses of Clock gene and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat pineal gland under the 12 h-light : 12 h-dark cycle condition (LD) and constant darkness (DD). Sprague-Dawley rats housed under the light regime of LD (n=36) for 4 weeks and of DD (n=36) for 8 weeks were sampled for the pineal gland once a group (n=6) every 4 h in a circadian day. The total RNA was extracted from each sample and the semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine the temporal changes in mRNA levels of Clock and NAT genes during different circadian times or zeitgeber times. The data were analysed by the cosine function software, Clock Lab software and the amplitude F test was used to reveal the circadian rhythm. The main results obtained are as follows. (1) In DD or LD condition, both of Clock and NAT genes mRNA levels in the pineal gland showed robust circadian oscillation (Ppineal gland were significantly reduced (Ppineal gland (P> 0.05). These findings suggest that the expressions of Clock and NAT genes in the pineal gland not only show remarkably synchronous endogenous circadian rhythmic changes, but also response to the ambient light signal in a reduced manner.

  12. Fake/Bogus Conferences

    DEFF Research Database (Denmark)

    Asadi, Amin; Rahbar, Nader; Rezvani, Mohammad Javad

    2017-01-01

    The main objective of the present paper is to introduce some features of fake/bogus conferences and some viable approaches to differentiate them from the real ones. These fake/bogus conferences introduce themselves as international conferences, which are multidisciplinary and indexed in major sci...... scientific digital libraries. Furthermore, most of the fake/bogus conference holders offer publishing the accepted papers in ISI journals and use other techniques in their advertisement e-mails....

  13. Modes Of The Spiral Clock Gong

    Science.gov (United States)

    Perrin, R.; Charnley, T.; Swallowe, G. M.; Banu, H.

    1993-03-01

    The modal frequencies of a spiral clock gong have been measured. The mode numbers and forms of vibrations have been identified by finite element modelling and photographic techniques; very good agreement between modelling and experiment was achieved. All modes were found to be either purely in-plane or out-of-plane. In both cases plots of log (2 n - 1) vs. log ƒ yielded curves with two distinct regions, the transition occurring where the wavelength corresponded to one turn of the spiral. Both sets of lower modes were very complex but the modal frequencies above n = 11 were found to fit a modified form of Chladni's law. It is suggested that the modified Chladni law may form the basis of many musical sounds.

  14. Clock comparison based on laser ranging technologies

    Science.gov (United States)

    Samain, Etienne

    2015-06-01

    Recent progress in the domain of time and frequency standards has required some important improvements of existing time transfer links. Several time transfer by laser link (T2L2) projects have been carried out since 1972 with numerous scientific or technological objectives. There are two projects currently under exploitation: T2L2 and Lunar Reconnaissance Orbiter (LRO). The former is a dedicated two-way time transfer experiment embedded on the satellite Jason-2 allowing for the synchronization of remote clocks with an uncertainty of 100 ps and the latter is a one-way link devoted for ranging a spacecraft orbiting around the Moon. There is also the Laser Time Transfer (LTT) project, exploited until 2012 and designed in the frame of the Chinese navigation constellation. In the context of future space missions for fundamental physics, solar system science or navigation, laser links are of prime importance and many missions based on that technology have been proposed for these purposes.

  15. A molecular clock for autoionization decay

    Science.gov (United States)

    Medišauskas, Lukas; Bello, Roger Y.; Palacios, Alicia; González-Castrillo, Alberto; Morales, Felipe; Plimak, Lev; Smirnova, Olga; Martín, Fernando; Ivanov, Misha Yu

    2017-07-01

    The ultrafast decay of highly excited electronic states is resolved with a molecular clock technique, using the vibrational motion associated to the ionic bound states as a time-reference. We demonstrate the validity of the method in the context of autoionization of the hydrogen molecule, where nearly exact full dimensional ab-initio calculations are available. The vibrationally resolved photoionization spectrum provides a time-energy mapping of the autoionization process into the bound states that is used to fully reconstruct the decay in time. A resolution of a fraction of the vibrational period is achieved. Since no assumptions are made on the underlying coupled electron-nuclear dynamics, the reconstruction procedure can be applied to describe the general problem of the decay of highly excited states in other molecular targets.

  16. Epistemically Robust Strategy Subsets

    Directory of Open Access Journals (Sweden)

    Geir B. Asheim

    2016-11-01

    Full Text Available We define a concept of epistemic robustness in the context of an epistemic model of a finite normal-form game where a player type corresponds to a belief over the profiles of opponent strategies and types. A Cartesian product X of pure-strategy subsets is epistemically robust if there is a Cartesian product Y of player type subsets with X as the associated set of best reply profiles such that the set Y i contains all player types that believe with sufficient probability that the others are of types in Y − i and play best replies. This robustness concept provides epistemic foundations for set-valued generalizations of strict Nash equilibrium, applicable also to games without strict Nash equilibria. We relate our concept to closedness under rational behavior and thus to strategic stability and to the best reply property and thus to rationalizability.

  17. Robustness in econometrics

    CERN Document Server

    Sriboonchitta, Songsak; Huynh, Van-Nam

    2017-01-01

    This book presents recent research on robustness in econometrics. Robust data processing techniques – i.e., techniques that yield results minimally affected by outliers – and their applications to real-life economic and financial situations are the main focus of this book. The book also discusses applications of more traditional statistical techniques to econometric problems. Econometrics is a branch of economics that uses mathematical (especially statistical) methods to analyze economic systems, to forecast economic and financial dynamics, and to develop strategies for achieving desirable economic performance. In day-by-day data, we often encounter outliers that do not reflect the long-term economic trends, e.g., unexpected and abrupt fluctuations. As such, it is important to develop robust data processing techniques that can accommodate these fluctuations.

  18. Robustness of Spatial Micronetworks

    CERN Document Server

    McAndrew, Thomas C; Bagrow, James P

    2015-01-01

    Power lines, roadways, pipelines and other physical infrastructure are critical to modern society. These structures may be viewed as spatial networks where geographic distances play a role in the functionality and construction cost of links. Traditionally, studies of network robustness have primarily considered the connectedness of large, random networks. Yet for spatial infrastructure physical distances must also play a role in network robustness. Understanding the robustness of small spatial networks is particularly important with the increasing interest in microgrids, small-area distributed power grids that are well suited to using renewable energy resources. We study the random failures of links in small networks where functionality depends on both spatial distance and topological connectedness. By introducing a percolation model where the failure of each link is proportional to its spatial length, we find that, when failures depend on spatial distances, networks are more fragile than expected. Accounting...

  19. Robustness - acceptance criteria

    DEFF Research Database (Denmark)

    Rizzuto, Enrico; Sørensen, John Dalsgaard; Kroon, Inger B.

    2010-01-01

    This factsheet describes the general framework on the bases of which acceptance criteria for requirements on the robustness of structures can be set. Such framework is based on the more general concept of risk-based assessment of engineering systems. The present factsheet is to be seen in conjunc......This factsheet describes the general framework on the bases of which acceptance criteria for requirements on the robustness of structures can be set. Such framework is based on the more general concept of risk-based assessment of engineering systems. The present factsheet is to be seen...... in conjunction with the one on the theoretical framework for robustness (Sørensen et al. 2009). In the present factsheet, the focus is on normative implications....

  20. Direct Repression of Evening Genes by CIRCADIAN CLOCK-ASSOCIATED1 in the Arabidopsis Circadian Clock.

    Science.gov (United States)

    Kamioka, Mari; Takao, Saori; Suzuki, Takamasa; Taki, Kyomi; Higashiyama, Tetsuya; Kinoshita, Toshinori; Nakamichi, Norihito

    2016-03-01

    The circadian clock is a biological timekeeping system that provides organisms with the ability to adapt to day-night cycles. Timing of the expression of four members of the Arabidopsis thaliana PSEUDO-RESPONSE REGULATOR(PRR) family is crucial for proper clock function, and transcriptional control of PRRs remains incompletely defined. Here, we demonstrate that direct regulation of PRR5 by CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) determines the repression state of PRR5 in the morning. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) analyses indicated that CCA1 associates with three separate regions upstream of PRR5 CCA1 and its homolog LATE ELONGATED HYPOCOTYL (LHY) suppressed PRR5 promoter activity in a transient assay. The regions bound by CCA1 in the PRR5 promoter gave rhythmic patterns with troughs in the morning, when CCA1 and LHY are at high levels. Furthermore,ChIP-seq revealed that CCA1 associates with at least 449 loci with 863 adjacent genes. Importantly, this gene set contains genes that are repressed but upregulated incca1 lhy double mutants in the morning. This study shows that direct binding by CCA1 in the morning provides strong repression of PRR5, and repression by CCA1 also temporally regulates an evening-expressed gene set that includes PRR5. © 2016 American Society of Plant Biologists. All rights reserved.

  1. Use of Very Stable Clocks in Satellite Geodesy

    Science.gov (United States)

    Hugentobler, Urs; Romanyuk, Tetyana

    2016-07-01

    Time and frequency play an essential role in satellite geodesy and navigation. Global Navigation Satellite Systems (GNSS) rely on precise measurements of signal travel times. The satellite and receiver clocks involved in measuring this time interval need to be synchronized at the picosecond level. The concept of GNSS allows for an epoch-wise synchronization of space and ground clocks, a feature which is consequently used in satellite geodesy by estimating epoch-wise clock corrections for all clocks in the system, either explicitly or implicitly by forming double differences. Ultra-stable clocks allow to estimate only few parameters for each clock, e.g., offset and drift. The much reduced number of parameters should stabilize GNSS solutions, e.g., tracking network station coordinates. On the other hand systematic errors, e.g., from troposphere or orbit modeling deficiencies or temperature induced hardware delay variations may systematically affect the solutions. The presentation shows trade-offs of modelling higly stable clocks and negative impact of error sources based on simulations.

  2. Crosstalk of clock gene expression and autophagy in aging

    Science.gov (United States)

    Kalfalah, Faiza; Janke, Linda; Schiavi, Alfonso; Tigges, Julia; Ix, Alexander; Ventura, Natascia; Boege, Fritz; Reinke, Hans

    2016-01-01

    Autophagy and the circadian clock counteract tissue degeneration and support longevity in many organisms. Accumulating evidence indicates that aging compromises both the circadian clock and autophagy but the mechanisms involved are unknown. Here we show that the expression levels of transcriptional repressor components of the circadian oscillator, most prominently the human Period homologue PER2, are strongly reduced in primary dermal fibroblasts from aged humans, while raising the expression of PER2 in the same cells partially restores diminished autophagy levels. The link between clock gene expression and autophagy is corroborated by the finding that the circadian clock drives cell-autonomous, rhythmic autophagy levels in immortalized murine fibroblasts, and that siRNA-mediated downregulation of PER2 decreases autophagy levels while leaving core clock oscillations intact. Moreover, the Period homologue lin-42 regulates autophagy and life span in the nematode Caenorhabditis elegans, suggesting an evolutionarily conserved role for Period proteins in autophagy control and aging. Taken together, this study identifies circadian clock proteins as set-point regulators of autophagy and puts forward a model, in which age-related changes of clock gene expression promote declining autophagy levels. PMID:27574892

  3. Diurnal oscillations of soybean circadian clock and drought responsive genes.

    Directory of Open Access Journals (Sweden)

    Juliana Marcolino-Gomes

    Full Text Available Rhythms produced by the endogenous circadian clock play a critical role in allowing plants to respond and adapt to the environment. While there is a well-established regulatory link between the circadian clock and responses to abiotic stress in model plants, little is known of the circadian system in crop species like soybean. This study examines how drought impacts diurnal oscillation of both drought responsive and circadian clock genes in soybean. Drought stress induced marked changes in gene expression of several circadian clock-like components, such as LCL1-, GmELF4- and PRR-like genes, which had reduced expression in stressed plants. The same conditions produced a phase advance of expression for the GmTOC1-like, GmLUX-like and GmPRR7-like genes. Similarly, the rhythmic expression pattern of the soybean drought-responsive genes DREB-, bZIP-, GOLS-, RAB18- and Remorin-like changed significantly after plant exposure to drought. In silico analysis of promoter regions of these genes revealed the presence of cis-elements associated both with stress and circadian clock regulation. Furthermore, some soybean genes with upstream ABRE elements were responsive to abscisic acid treatment. Our results indicate that some connection between the drought response and the circadian clock may exist in soybean since (i drought stress affects gene expression of circadian clock components and (ii several stress responsive genes display diurnal oscillation in soybeans.

  4. Automatic minimisation of micromotion in a 88Sr+ optical clock

    Science.gov (United States)

    Barwood, G. P.; Huang, G.; Klein, H. A.; Gill, P.

    2015-07-01

    Optical clocks based on narrow linewidth transitions in single cold ions confined in RF traps are being developed at a number of laboratories worldwide. For these ion clock systems, excess micromotion can cause both Stark and Doppler frequency shifts and also a degradation of frequency stability as a result of a reduced excitation rate to the clock transition. At NPL, we detect micromotion in our 88Sr+ optical clocks by observing the correlation between photon arrival times and the zero crossing of the RF trap drive signal. Recently, two nominally identical 88Sr+ optical clocks have been operated over several days and their frequencies compared against one another. During this time the dc voltages on the endcap and compensation voltage electrodes required to minimise the micromotion can change significantly, particularly following the loading of an ion. This paper describes an automatic method to monitor and minimise micromotion applicable to single ion clocks and which we demonstrate using our two NPL 88Sr+ ion clocks.

  5. Hunting for dark matter with GPS and atomic clocks

    Science.gov (United States)

    Derevianko, Andrei

    2015-05-01

    Atomic clocks are arguably the most accurate scientific instruments ever build. Modern clocks are astonishing timepieces guaranteed to keep time within a second over the age of the Universe. The cosmological applications of atomic clocks so far have been limited to searches of the uniform-in-time drift of fundamental constants. We point out that a transient in time change of fundamental constants (translating into clocks being sped up or slowed down) can be induced by dark matter objects that have large spatial extent, and are built from light non-Standard Model fields. The stability of this type of dark matter can be dictated by the topological reasons. We argue that correlated networks of atomic clocks, such as atomic clocks onboard satellites of the GPS constellation, can be used as a powerful tool to search for the topological defect dark matter. In other words, one could envision using GPS as a 50,000 km-aperture dark-matter detector. Similar arguments apply to terrestrial networks of atomic clocks. Details:

  6. CREB influences timing and entrainment of the SCN circadian clock.

    Science.gov (United States)

    Lee, Boyoung; Li, Aiqing; Hansen, Katelin F; Cao, Ruifeng; Yoon, Jae Hwa; Obrietan, Karl

    2010-12-01

    The transcriptional feedback circuit, which is at the core of the suprachiasmatic nucleus (SCN) circadian (i.e., 24 h) clock, is tightly coupled to both external entrainment cues, such as light, as well as rhythmic cues that arise on a system-wide level within the SCN. One potential signaling pathway by which these cues are conveyed to the molecular clock is the CREB/CRE transcriptional cascade. In this study, we employed a tetracycline-inducible CREB repressor mouse strain, in which approximately 60% of the SCN neurons express the transgene, to test CREB functionality in the clock and its effects on overt rhythmicity. We show that attenuated CREB signaling in the SCN led to a significant reduction in light-evoked clock entrainment. An examination of circadian timing revealed that CREB repressor mice exhibited normal free-running rhythms in the absence of external lighting cues. However, under conditions of constant light, which typically leads to a lengthening of the circadian period, CREB repressor mice exhibited a dramatic arrhythmic phenotype, which could be reversed with doxycycline. At a cellular level, the repression of CREB led to a significant reduction in both the expression of the circadian clock proteins PERIOD1 and PERIOD2 and the clock output hormones AVP and VIP. Together, these data support the idea that the CRE transcriptional pathway orchestrates transcriptional events that are essential for both the maintenance of SCN timing and light entrainment of the circadian clock.

  7. A molecular clock regulates angiopoietin-like protein 2 expression.

    Science.gov (United States)

    Kadomatsu, Tsuyoshi; Uragami, Shota; Akashi, Makoto; Tsuchiya, Yoshiki; Nakajima, Hiroo; Nakashima, Yukiko; Endo, Motoyoshi; Miyata, Keishi; Terada, Kazutoyo; Todo, Takeshi; Node, Koichi; Oike, Yuichi

    2013-01-01

    Various physiological and behavioral processes exhibit circadian rhythmicity. These rhythms are usually maintained by negative feedback loops of core clock genes, namely, CLOCK, BMAL, PER, and CRY. Recently, dysfunction in the circadian clock has been recognized as an important foundation for the pathophysiology of lifestyle-related diseases, such as obesity, cardiovascular disease, and some cancers. We have reported that angiopoietin-like protein 2 (ANGPTL2) contributes to the pathogenesis of these lifestyle-related diseases by inducing chronic inflammation. However, molecular mechanisms underlying regulation of ANGPTL2 expression are poorly understood. Here, we assess circadian rhythmicity of ANGPTL2 expression in various mouse tissues. We observed that ANGPTL2 rhythmicity was similar to that of the PER2 gene, which is regulated by the CLOCK/BMAL1 complex. Promoter activity of the human ANGPTL2 gene was significantly induced by CLOCK and BMAL1, an induction markedly attenuated by CRY co-expression. We also identified functional E-boxes in the ANGPTL2 promoter and observed occupancy of these sites by endogenous CLOCK in human osteosarcoma cells. Furthermore, Cry-deficient mice exhibited arrhythmic Angptl2 expression. Taken together, these data suggest that periodic expression of ANGPTL2 is regulated by a molecular clock.

  8. A molecular clock regulates angiopoietin-like protein 2 expression.

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Kadomatsu

    Full Text Available Various physiological and behavioral processes exhibit circadian rhythmicity. These rhythms are usually maintained by negative feedback loops of core clock genes, namely, CLOCK, BMAL, PER, and CRY. Recently, dysfunction in the circadian clock has been recognized as an important foundation for the pathophysiology of lifestyle-related diseases, such as obesity, cardiovascular disease, and some cancers. We have reported that angiopoietin-like protein 2 (ANGPTL2 contributes to the pathogenesis of these lifestyle-related diseases by inducing chronic inflammation. However, molecular mechanisms underlying regulation of ANGPTL2 expression are poorly understood. Here, we assess circadian rhythmicity of ANGPTL2 expression in various mouse tissues. We observed that ANGPTL2 rhythmicity was similar to that of the PER2 gene, which is regulated by the CLOCK/BMAL1 complex. Promoter activity of the human ANGPTL2 gene was significantly induced by CLOCK and BMAL1, an induction markedly attenuated by CRY co-expression. We also identified functional E-boxes in the ANGPTL2 promoter and observed occupancy of these sites by endogenous CLOCK in human osteosarcoma cells. Furthermore, Cry-deficient mice exhibited arrhythmic Angptl2 expression. Taken together, these data suggest that periodic expression of ANGPTL2 is regulated by a molecular clock.

  9. Robust global motion estimation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A global motion estimation method based on robust statistics is presented in this paper. By using tracked feature points instead of whole image pixels to estimate parameters the process speeds up. To further speed up the process and avoid numerical instability, an alterative description of the problem is given, and three types of solution to the problem are compared. By using a two step process, the robustness of the estimator is also improved. Automatic initial value selection is an advantage of this method. The proposed approach is illustrated by a set of examples, which shows good results with high speed.

  10. Advances in Robust Control.

    Science.gov (United States)

    1995-02-01

    condition that the value of r we seek is extremal. Lemma 2 Let J(r, z, i) denote the N x 2N matriz [,1 = (r) .... (r)1 [zHN (r) -’Hjv(r)J If (ro, z...Analysis of a I Real-Parameter Variation Problem," Proceedings of the American Con- trol Conference, Boston , MA, 1985. 3 48 3 1 U I II I i [8] Morton

  11. Using a transportable optical clock for chronometric levelling

    Science.gov (United States)

    Lisdat, Christian; Sterr, Uwe; Koller, Silvio; Grotti, Jacopo; Vogt, Stefan; Häfner, Sebastian; Herbers, Sofia; Al-Masoudi, Ali

    2016-07-01

    With their supreme accuracy and precision, optical clocks in combination with new methods of long-distance frequency transfer can be used to determine height differences by measuring the gravitational red shift between two clocks without accumulation of measurement errors, as in classical levelling. We are developing transportable optical clocks for this purpose that will also serve for the technology development regarding optical clocks in Space and for international comparisons between optical clocks that cannot be linked with sufficient accuracy otherwise. In this talk we will focus on the transportable strontium lattice clock that we are developing and its first evaluation. Presently, we achieve a fractional frequency instability of 3 × 10^{-17} after 1000 s averaging time, which is equivalent to a height resolution of 30 cm. The first uncertainty evaluation of the system yielded 7 × 10^{-17}. We expect rapid improvements to an uncertainty of a few parts in 10^{17}. The clock is now located within a car trailer, which requires compact and rugged lasers systems and physics package. Special care has been taken in the design of the ultra-frequency stable interrogation laser that has to achieve fractional frequency instabilities of considerably below 10^{-15}. Typical laboratory constructions of the reference resonator system used to pre-stabilize the laser frequency are not compatible with the requirement of transportability. In an actual levelling campaign, this clock will be connected via a stabilized optical fibre link with another, stationary frequency standard. The measured gravitational red shift will be compared with the ones calculated from potential differences derived with state of the art geodetic data and models. We will discuss the status of measurements of geodetic relevance with optical clocks and give an outlook on our next steps. This work is supported by QUEST, DFG (RTG 1729, CRC 1128), EU-FP7 (FACT) and EMRP (ITOC). The EMRP is jointly funded

  12. Machine learning helps identify CHRONO as a circadian clock component.

    Directory of Open Access Journals (Sweden)

    Ron C Anafi

    2014-04-01

    Full Text Available Over the last decades, researchers have characterized a set of "clock genes" that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components. We used a simple form of probabilistic machine learning to integrate biologically relevant, genome-scale data and ranked genes on their similarity to known clock components. We then used a secondary experimental screen to characterize the top candidates. We found that several physically interact with known clock components in a mammalian two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse fibroblast line (NIH 3T3. One candidate, Gene Model 129, interacts with BMAL1 and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK transcriptional complex. Given these results, we have renamed the gene CHRONO (computationally highlighted repressor of the network oscillator. Bi-molecular fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO represses by abrogating the binding of BMAL1 to its transcriptional co-activator CBP. Most importantly, CHRONO knockout mice display a prolonged free-running circadian period similar to, or more drastic than, six other clock components. We conclude that CHRONO is a functional clock component providing a new layer of control on circadian molecular dynamics.

  13. Circadian rhythms, the molecular clock, and skeletal muscle.

    Science.gov (United States)

    Lefta, Mellani; Wolff, Gretchen; Esser, Karyn A

    2011-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock mechanism found in most, if not all, cell types including skeletal muscle. The mammalian molecular clock is a complex of multiple oscillating networks that are regulated through transcriptional mechanisms, timed protein turnover, and input from small molecules. At this time, very little is known about circadian aspects of skeletal muscle function/metabolism but some progress has been made on understanding the molecular clock in skeletal muscle. The goal of this chapter is to provide the basic terminology and concepts of circadian rhythms with a more detailed review of the current state of knowledge of the molecular clock, with reference to what is known in skeletal muscle. Research has demonstrated that the molecular clock is active in skeletal muscles and that the muscle-specific transcription factor, MyoD, is a direct target of the molecular clock. Skeletal muscle of clock-compromised mice, Bmal1(-/-) and Clock(Δ19) mice, are weak and exhibit significant disruptions in expression of many genes required for adult muscle structure and metabolism. We suggest that the interaction between the molecular clock, MyoD, and metabolic factors, such as PGC-1, provide a potential system of feedback loops that may be critical for both maintenance and adaptation of skeletal muscle.

  14. Robust frequency stabilization of multiple spectroscopy lasers with large and tunable offset frequencies.

    Science.gov (United States)

    Nevsky, A; Alighanbari, S; Chen, Q-F; Ernsting, I; Vasilyev, S; Schiller, S; Barwood, G; Gill, P; Poli, N; Tino, G M

    2013-11-15

    We have demonstrated a compact, robust device for simultaneous absolute frequency stabilization of three diode lasers whose carrier frequencies can be chosen freely relative to the reference. A rigid ULE multicavity block is employed, and, for each laser, the sideband locking technique is applied. A small lock error, computer control of frequency offset, wide range of frequency offset, simple construction, and robust operation are the useful features of the system. One concrete application is as a stabilization unit for the cooling and trapping lasers of a neutral-atom lattice clock. The device significantly supports and improves the clock's operation. The laser with the most stringent requirements imposed by this application is stabilized to a line width of 70 Hz, and a residual frequency drift less than 0.5 Hz/s. The carrier optical frequency can be tuned over 350 MHz while in lock.

  15. Differential clock comparisons with phase-locked local oscillators

    CERN Document Server

    Hume, David B

    2015-01-01

    We develop protocols that circumvent the laser noise limit in the stability of optical clock comparisons by synchronous probing of two clocks using phase-locked local oscillators. This allows for probe times longer than the laser coherence time, avoids the Dick effect, and supports Heisenberg-limited scaling of measurement precision. We present a model for such frequency comparisons and develop numerical simulations of the protocol with realistic noise sources. This provides a route to reduce frequency ratio measurement durations by more than an order of magnitude as clock inaccuracies reach 1x10^-18.

  16. Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders.

    Science.gov (United States)

    Barandas, Rita; Landgraf, Dominic; McCarthy, Michael J; Welsh, David K

    2015-12-01

    Psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder are often accompanied by metabolic dysfunction symptoms, including obesity and diabetes. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In this review paper, we highlight the role of circadian clocks in glucocorticoid, dopamine, and orexin/melanin-concentrating hormone systems and describe how a dysfunction of these clocks may contribute to the simultaneous development of psychiatric and metabolic symptoms.

  17. Detection of weak frequency jumps for GNSS onboard clocks.

    Science.gov (United States)

    Huang, Xinming; Gong, Hang; Ou, Gang

    2014-05-01

    In this paper, a weak frequency jump detection method is developed for onboard clocks in global navigation satellite systems (GNSS). A Kalman filter is employed to facilitate the onboard real-time processing of atomic clock measurements, whose N-step prediction residuals are used to construct the weak frequency jump detector. Numerical simulations show that the method can successfully detect weak frequency jumps. The detection method proposed in this paper is helpful for autonomous integrity monitoring of GNSS satellite clocks, and can also be applied to other frequency anomalies with an appropriately modified detector.

  18. Standard Clock in Primordial Density Perturbations and Cosmic Microwave Background

    CERN Document Server

    Chen, Xingang

    2014-01-01

    Standard Clocks in the primordial epoch leave a special type of features in the primordial perturbations, which can be used to directly measure the scale factor of the primordial universe as a function of time a(t), thus discriminating between inflation and alternatives. We have started to search for such signals in the Planck 2013 data using the key predictions of the Standard Clock. In this Letter, we present an interesting candidate with the inflation fingerprint. Motivated by this candidate, we construct and compute full Standard Clock models and use the more complete prediction to make more extensive comparison with data.

  19. Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2

    DEFF Research Database (Denmark)

    Yang, Yaoming; Duguay, David; Bédard, Nathalie

    2012-01-01

    Endogenous 24-hour rhythms are generated by circadian clocks located in most tissues. The molecular clock mechanism is based on feedback loops involving clock genes and their protein products. Post-translational modifications, including ubiquitination, are important for regulating the clock...

  20. Complexity, Robustness, and Performance

    NARCIS (Netherlands)

    B. Visser (Bauke)

    2002-01-01

    textabstractThis paper analyses the relationship between organizational complexity ( the degree of detail of information necessary to correctly assign agents to positions), robustness (the relative loss of performance due to mis-allocated agents), and performance. More complex structures are not

  1. Robustness via Diffractal Architectures

    CERN Document Server

    Moocarme, Matthew

    2015-01-01

    When plane waves diffract through fractal-patterned apertures, the resulting far-field profiles or diffractals also exhibit iterated, self-similar features. Here we show that this specific architecture enables robust signal processing and spatial multiplexing: arbitrary parts of a diffractal contain sufficient information to recreate the entire original sparse signal.

  2. Robustness of structures

    DEFF Research Database (Denmark)

    Vrouwenvelder, T.; Sørensen, John Dalsgaard

    2009-01-01

    robustness is still an issue of controversy and poses difficulties in regard to interpretation as well as regulation. Typically modern structural design codes require that ‘the consequence of damages to structures should not be disproportional to the causes of the damages'. However, despite the importance...

  3. Robustness Envelopes of Networks

    NARCIS (Netherlands)

    Trajanovski, S.; Martín-Hernández, J.; Winterbach, W.; Van Mieghem, P.

    2013-01-01

    We study the robustness of networks under node removal, considering random node failure, as well as targeted node attacks based on network centrality measures. Whilst both of these have been studied in the literature, existing approaches tend to study random failure in terms of average-case behavior

  4. Complexity, Robustness, and Performance

    NARCIS (Netherlands)

    B. Visser (Bauke)

    2002-01-01

    textabstractThis paper analyses the relationship between organizational complexity ( the degree of detail of information necessary to correctly assign agents to positions), robustness (the relative loss of performance due to mis-allocated agents), and performance. More complex structures are not nec

  5. International Conference on Physics

    CERN Document Server

    2016-01-01

    OMICS International, (conference series) the World Class Open Access Publisher and Scientific Event Organizer is hosting “International Conference on physics” which is going to be the biggest conference dedicated to Physics. The theme “Highlighting innovations and challenges in the field of Physics” and it features a three day conference addressing the major breakthroughs, challenges and the solutions adopted. The conference will be held during June 27-29, 2016 at New Orleans, USA. Will be published in: http://physics.conferenceseries.com/

  6. Facilitating Learning at Conferences

    DEFF Research Database (Denmark)

    Ravn, Ib; Elsborg, Steen

    2011-01-01

    and facilitate a variety of simple learning techniques at thirty one- and two-day conferences of up to 300 participants each. We present ten of these techniques and data evaluating them. We conclude that if conference organizers allocate a fraction of the total conference time to facilitated processes......The typical conference consists of a series of PowerPoint presentations that tend to render participants passive. Students of learning have long abandoned the transfer model that underlies such one-way communication. We propose an al-ternative theory of conferences that sees them as a forum...... for learning, mutual inspiration and human flourishing. We offer five design principles that specify how conferences may engage participants more and hence increase their learning. In the research-and-development effort reported here, our team collaborated with conference organizers in Denmark to introduce...

  7. The learning conference

    DEFF Research Database (Denmark)

    Ravn, Ib

    2007-01-01

    Purpose: To call attention to the fact that conferences for professionals rely on massive one-way communication and hence produce little learning for delegates. To introduce an alternative, the ?learning conference,? that involves delegates in fun and productive learning processes. Design....../methodology/approach: A typical full-day conference is analyzed. It has six hours of podium talk and twenty-five minutes for delegates to become involved. What model of learning can possibly lie behind this? The transfer model, which assumes learners to be empty vessels. An alternative view is that conference delegates...... are active professionals in search of inspiration, and they also want to share knowledge with their peers at the conference. A theory of the conference as a forum for mutual inspiration and human co-flourishing is proposed, as are four design principles for a learning conference: 1. Presentations must...

  8. Inferring clocks when lacking rocks: the variable rates of molecular evolution in bacteria

    Directory of Open Access Journals (Sweden)

    Ochman Howard

    2009-09-01

    Full Text Available Abstract Background Because bacteria do not have a robust fossil record, attempts to infer the timing of events in their evolutionary history requires comparisons of molecular sequences. This use of molecular clocks is based on the assumptions that substitution rates for homologous genes or sites are fairly constant through time and across taxa. Violation of these conditions can lead to erroneous inferences and result in estimates that are off by orders of magnitude. In this study, we examine the consistency of substitution rates among a set of conserved genes in diverse bacterial lineages, and address the questions regarding the validity of molecular dating. Results By examining the evolution of 16S rRNA gene in obligate endosymbionts, which can be calibrated by the fossil record of their hosts, we found that the rates are consistent within a clade but varied widely across different bacterial lineages. Genome-wide estimates of nonsynonymous and synonymous substitutions suggest that these two measures are highly variable in their rates across bacterial taxa. Genetic drift plays a fundamental role in determining the accumulation of substitutions in 16S rRNA genes and at nonsynonymous sites. Moreover, divergence estimates based on a set of universally conserved protein-coding genes also exhibit low correspondence to those based on 16S rRNA genes. Conclusion Our results document a wide range of substitution rates across genes and bacterial taxa. This high level of variation cautions against the assumption of a universal molecular clock for inferring divergence times in bacteria. However, by applying relative-rate tests to homologous genes, it is possible to derive reliable local clocks that can be used to calibrate bacterial evolution. Reviewers This article was reviewed by Adam Eyre-Walker, Simonetta Gribaldo and Tal Pupko (nominated by Dan Graur.

  9. Clock Technology Development in the Laser Cooling and Atomic Physics (LCAP) Program

    Science.gov (United States)

    Seidel, Dave; Thompson, R. J.; Klipstein, W. M.; Kohel, J.; Maleki, L.

    2000-01-01

    This paper presents the Laser Cooling and Atomic Physics (LCAP) program. It focuses on clock technology development. The topics include: 1) Overview of LCAP Flight Projects; 2) Space Clock 101; 3) Physics with Clocks in microgravity; 4) Space Clock Challenges; 5) LCAP Timeline; 6) International Space Station (ISS) Science Platforms; 7) ISS Express Rack; 8) Space Qualification of Components; 9) Laser Configuration; 10) Clock Rate Comparisons: GPS Carrier Phase Frequency Transfer; and 11) ISS Model Views. This paper is presented in viewgraph form.

  10. Cellular Clocks : Coupled Circadian Dispatch and Cell Division Cycles

    NARCIS (Netherlands)

    Merrow, Martha; Roenneberg, Till

    2004-01-01

    Gating of cell division by the circadian clock is well known, yet its mechanism is little understood. Genetically tractable model systems have led to new hypotheses and questions concerning the coupling of these two cellular cycles.

  11. Speed of light as measured by two terrestrial stable clocks

    Science.gov (United States)

    Hsu, J. P.; Sherry, T. N.; Chiu, C. B.

    1977-01-01

    Despite the recent criticism within the special theory of relativity, there exists an arrangement of stable clocks rotating with the earth which predicts diurnal variations of the one-way speed of light, as suggested previously.

  12. Improvement of an Atomic Clock using Squeezed Vacuum

    DEFF Research Database (Denmark)

    Kruse, I.; Lange, K; Peise, Jan;

    2016-01-01

    , the vacuum noise restricts the precision of the interferometer to the standard quantum limit (SQL). Here, we propose and experimentally demonstrate a novel clock configuration that surpasses the SQL by squeezing the vacuum in the empty input state. We create a squeezed vacuum state containing an average of 0.......75 atoms to improve the clock sensitivity of 10000 atoms by 2.05+0.34−0.37  dB. The SQL poses a significant limitation for today’s microwave fountain clocks, which serve as the main time reference. We evaluate the major technical limitations and challenges for devising a next generation of fountain clocks......Since the pioneering work of Ramsey, atom interferometers are employed for precision metrology, in particular to measure time and to realize the second. In a classical interferometer, an ensemble of atoms is prepared in one of the two input states, whereas the second one is left empty. In this case...

  13. Clocked, fast electronics trigger for high energy physics

    Energy Technology Data Exchange (ETDEWEB)

    Gray, R.; Rutherfoord, J.P.

    1986-04-01

    For a Fermilab experiment we have designed and built gated-pulse-stretcher modules which allow us to clock all of the fast electronics with the accelerator rf, thus simplifying the trigger design. (orig.).

  14. Measurement of Magic Wavelengths for the ^{40}Ca^{+} Clock Transition.

    Science.gov (United States)

    Liu, Pei-Liang; Huang, Yao; Bian, Wu; Shao, Hu; Guan, Hua; Tang, Yong-Bo; Li, Cheng-Bin; Mitroy, J; Gao, Ke-Lin

    2015-06-05

    We demonstrate experimentally the existence of magic wavelengths and determine the ratio of oscillator strengths for a single trapped ion. For the first time, two magic wavelengths near 396 nm for the ^{40}Ca^{+} clock transition are measured simultaneously with high precision. By tuning the applied laser to an intermediate wavelength between transitions 4s_{1/2}→4p_{1/2} and 4s_{1/2}→4p_{3/2}, the sensitivity of the clock transition Stark shift to the oscillator strengths is greatly enhanced. Furthermore, with the measured magic wavelengths, we determine the ratio of the oscillator strengths with a deviation of less than 0.5%. Our experimental method may be applied to measure magic wavelengths for other ion clock transitions. Promisingly, the measurement of these magic wavelengths paves the way to building all-optical trapped ion clocks.

  15. Two-photon assisted clock comparison to picosecond precision

    CERN Document Server

    Zhang, Shi-Wei; Yao, Yin-Ping; Wan, Ren-Gang; Zhang, Tong-Yi

    2015-01-01

    We have experimentally demonstrated a clock comparison scheme utilizing time-correlated photon pairs generated from the spontaneous parametric down conversion process of a laser pumped beta-barium borate crystal. The coincidence of two-photon events are analyzed by the cross correlation of the two time stamp sequences. Combining the coarse and fine part of the time differences at different resolutions, a 64 ps precision for clock synchronization has been realized. We also investigate the effects of hardware devices used in the system on the precision of clock comparison. The results indicate that the detector's time jitter and the background noise will degrade the system performance. With this method, comparison and synchronization of two remote clocks could be implemented with a precision at the level of a few tens of picoseconds.

  16. Novel putative mechanisms to link circadian clocks to healthy aging.

    Science.gov (United States)

    Popa-Wagner, Aurel; Catalin, Bogdan; Buga, Ana-Maria

    2015-08-01

    The circadian clock coordinates the internal physiology to increase the homeostatic capacity thereby providing both a survival advantage to the system and an optimization of energy budgeting. Multiple-oscillator circadian mechanisms are likely to play a role in regulating human health and may contribute to the aging process. Our aim is to give an overview of how the central clock in the hypothalamus and peripheral clocks relate to aging and metabolic disorders, including hyperlipidemia and hyperglycemia. In particular, we unravel novel putative mechanisms to link circadian clocks to healthy aging. This review may lead to the design of large-scale interventions to help people stay healthy as they age by adjusting daily activities, such as feeding behavior, and or adaptation to age-related changes in individual circadian rhythms.

  17. Atomic Clocks and Variations of the FIne Structure Constant

    Science.gov (United States)

    Prestage, John D.; Tjoelker, Robert L.; Maleki, Lute

    1995-01-01

    We describe a new test for possible variations of the fine structure constant alpha by comparisons of rates between clocks based on hyperfine transitions in alkali atoms with different atomic number Z. H-maser, Cs, and Hg(+) clocks have a different dependence on alpha via relativistic contributions of order (Z-alpha)(sup 2). Recent H-maser vs Hg(+) clock comparison data improve laboratory limits on a time variation by 100-fold to give dot-alpha less than or equal to 3.7 x 10(exp -14)/yr. Future laser cooled clocks (Be(+), Rb, Cs, Hg(+), etc.), when compared, will yield the most sensitive of all tests for dot-alpha/alpha.

  18. Similarities in the circadian clock and photoperiodism in plants.

    Science.gov (United States)

    Song, Young Hun; Ito, Shogo; Imaizumi, Takato

    2010-10-01

    Plants utilize circadian clocks to synchronize their physiological and developmental events with daily and yearly changes in the environment. Recent advances in Arabidopsis research have provided a better understanding of the molecular mechanisms of the circadian clock and photoperiodism. One of the most important questions is whether the mechanisms discovered in Arabidopsis are conserved in other plant species. Through the identification of many Arabidopsis clock gene homologs and the characterization of some gene functions, a strong resemblance between the circadian clocks in plants has been observed. On the contrary, based on our recent increased knowledge of photoperiodic flowering mechanisms in cereals and other plants, the day-length sensing mechanisms appear to have diverged more between long-day plants and short-day plants. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Cellular Clocks : Coupled Circadian Dispatch and Cell Division Cycles

    NARCIS (Netherlands)

    Merrow, Martha; Roenneberg, Till

    2004-01-01

    Gating of cell division by the circadian clock is well known, yet its mechanism is little understood. Genetically tractable model systems have led to new hypotheses and questions concerning the coupling of these two cellular cycles.

  20. Superradiance on the milliHertz linewidth strontium clock transition

    CERN Document Server

    Norcia, Matthew A; Cline, Julia R K; Thompson, James K

    2016-01-01

    Today's best atomic clocks are limited by frequency noise on the lasers used to interrogate the atoms. A proposed solution to this problem is to create a superradiant laser using an optical clock transition as its gain medium. This laser would act as an active atomic clock, and would be highly immune to the fluctuations in reference cavity length that limit today's best lasers. Here, we demonstrate and characterize superradiant emission from the mHz linewidth clock transition in an ensemble of laser-cooled $^{87}$Sr atoms trapped within a high-finesse optical cavity. We measure a collective enhancement of the emission rate into the cavity mode by a factor of more than 10,000 compared to independently radiating atoms. We also demonstrate a method for seeding superradiant emission and observe interference between two independent transitions lasing simultaneously. We use this interference to characterize the relative spectral properties of the two lasing sub-ensembles.

  1. Time in motion: the molecular clock meets the microbiome.

    Science.gov (United States)

    Liang, Xue; Bushman, Frederic D; FitzGerald, Garret A

    2014-10-23

    Thaiss et al. report that the intestinal microbiota undergoes diurnal oscillation, which is controlled by host feeding time. Disruption of the host circadian clock induces dysbiosis, which is associated with host metabolic disorders.

  2. Complementary approaches to understanding the plant circadian clock

    CERN Document Server

    Akman, Ozgur E; Loewe, Laurence; Troein, Carl; 10.4204/EPTCS.19.1

    2010-01-01

    Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions. We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions. We investigate how to model the timing of...

  3. CSAC Characterization and Its Impact on GNSS Clock Augmentation Performance

    Science.gov (United States)

    Fernández, Enric; Calero, David; Parés, M. Eulàlia

    2017-01-01

    Chip Scale Atomic Clocks (CSAC) are recently-developed electronic instruments that, when used together with a Global Navigation Satellite Systems (GNSS) receiver, help improve the performance of GNSS navigation solutions in certain conditions (i.e., low satellite visibility). Current GNSS receivers include a Temperature Compensated Cristal Oscillator (TCXO) clock characterized by a short-term stability (τ = 1 s) of 10−9 s that leads to an error of 0.3 m in pseudorange measurements. The CSAC can achieve a short-term stability of 2.5 × 10−12 s, which implies a range error of 0.075 m, making for an 87.5% improvement over TCXO. Replacing the internal TCXO clock of GNSS receivers with a higher frequency stability clock such as a CSAC oscillator improves the navigation solution in terms of low satellite visibility positioning accuracy, solution availability, signal recovery (holdover), multipath and jamming mitigation and spoofing attack detection. However, CSAC suffers from internal systematic instabilities and errors that should be minimized if optimal performance is desired. Hence, for operating CSAC at its best, the deterministic errors from the CSAC need to be properly modelled. Currently, this modelling is done by determining and predicting the clock frequency stability (i.e., clock bias and bias rate) within the positioning estimation process. The research presented in this paper aims to go a step further, analysing the correlation between temperature and clock stability noise and the impact of its proper modelling in the holdover recovery time and in the positioning performance. Moreover, it shows the potential of fine clock coasting modelling. With the proposed model, an improvement in vertical positioning precision of around 50% with only three satellites can be achieved. Moreover, an increase in the navigation solution availability is also observed, a reduction of holdover recovery time from dozens of seconds to only a few can be achieved. PMID:28216600

  4. Clocking In Turbines: Remarks On Physical Nature And Geometric Requirements

    Directory of Open Access Journals (Sweden)

    Swirydczuk Jerzy

    2015-04-01

    Full Text Available The article discusses two issues relating to the clocking phenomenon in turbines, which are the physical course of stator wake deformation in rotor passages and its further interaction with downstream stator blades, and turbine geometry parameters which are believed to be most favourable for clocking. In both cases, the results presented in the article have made it possible to verify and reformulate the previously accepted opinions.

  5. Rethinking transcriptional activation in the Arabidopsis circadian clock.

    Science.gov (United States)

    Fogelmark, Karl; Troein, Carl

    2014-07-01

    Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops.

  6. A model of guarded recursion with clock synchronisation

    DEFF Research Database (Denmark)

    Bizjak, Aleš; Møgelberg, Rasmus Ejlers

    2015-01-01

    productivity to be captured in types. The calculus uses clocks representing time streams and clock quantifiers which allow limited and controlled elimination of modalities. The calculus has since been extended to dependent types by Møgelberg. Both works give denotational semantics but no rewrite semantics...... by removing freshness restrictions from typing rules, and is a necessary step towards defining rewrite semantics, and ultimately implementing the calculus....

  7. Tests of Local Position Invariance Using Continuously Running Atomic Clocks

    Science.gov (United States)

    2013-01-22

    principle) and that nongravitational measurements should be independent of the velocity of the freely falling reference frame (local Lorentz invariance...be independent of the clock composition, for example. Violation of LPI may manifest itself in an anomalous gravitational redshift of an atomic clock... violating parameters β1 and β2, the relative frequencies should vary with the gravitational potential as (ν/ν)1,2 = (β1 − β2)U/c2. (2) *steven.peil

  8. Systems biology of the clock in Neurospora crassa.

    Directory of Open Access Journals (Sweden)

    Wubei Dong

    Full Text Available A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2 that encode a transcriptional activator (as well as a blue-light receptor and an oscillator frequency (frq that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE, based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2 control were resolved into four classes, circadian only (612 genes, light-responsive only (396, both circadian and light-responsive (328, and neither circadian nor light-responsive (987. In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes.

  9. Rethinking transcriptional activation in the Arabidopsis circadian clock.

    Directory of Open Access Journals (Sweden)

    Karl Fogelmark

    2014-07-01

    Full Text Available Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops.

  10. A control theory approach to clock steering techniques.

    Science.gov (United States)

    Farina, Marcello; Galleani, Lorenzo; Tavella, Patrizia; Bittanti, Sergio

    2010-10-01

    Several clock and time scale steering methods have been developed according to different viewpoints by various time laboratories. By resorting to control theory ideas, we propose a common theoretical framework encompassing these methods. A comparison of the most common steering methodologies, namely, the classical steering approach, the GPS bang-bang method, and the linear quadratic Gaussian technique, is carried out. We believe that the use of control theory methods can potentially lead to a better understanding of clock steering algorithms.

  11. Clock reading: an underestimated topic in children with mathematics difficulties

    OpenAIRE

    2012-01-01

    Recent studies have shown that children with mathematics difficulties (MD) have weaknesses in multiple areas of mathematics. Andersson (2008), for example, recently found that children with MD perform significantly worse than other children on clock reading tasks. The present study builds on this recent finding and aims at a more profound understanding of the difficulties that children with MD experience with telling time. Therefore, clock reading abilities of 154 children with MD were compar...

  12. CSAC Characterization and Its Impact on GNSS Clock Augmentation Performance

    Directory of Open Access Journals (Sweden)

    Enric Fernández

    2017-02-01

    Full Text Available Chip Scale Atomic Clocks (CSAC are recently-developed electronic instruments that, when used together with a Global Navigation Satellite Systems (GNSS receiver, help improve the performance of GNSS navigation solutions in certain conditions (i.e., low satellite visibility. Current GNSS receivers include a Temperature Compensated Cristal Oscillator (TCXO clock characterized by a short-term stability (τ = 1 s of 10−9 s that leads to an error of 0.3 m in pseudorange measurements. The CSAC can achieve a short-term stability of 2.5 × 10−12 s, which implies a range error of 0.075 m, making for an 87.5% improvement over TCXO. Replacing the internal TCXO clock of GNSS receivers with a higher frequency stability clock such as a CSAC oscillator improves the navigation solution in terms of low satellite visibility positioning accuracy, solution availability, signal recovery (holdover, multipath and jamming mitigation and spoofing attack detection. However, CSAC suffers from internal systematic instabilities and errors that should be minimized if optimal performance is desired. Hence, for operating CSAC at its best, the deterministic errors from the CSAC need to be properly modelled. Currently, this modelling is done by determining and predicting the clock frequency stability (i.e., clock bias and bias rate within the positioning estimation process. The research presented in this paper aims to go a step further, analysing the correlation between temperature and clock stability noise and the impact of its proper modelling in the holdover recovery time and in the positioning performance. Moreover, it shows the potential of fine clock coasting modelling. With the proposed model, an improvement in vertical positioning precision of around 50% with only three satellites can be achieved. Moreover, an increase in the navigation solution availability is also observed, a reduction of holdover recovery time from dozens of seconds to only a few can be achieved.

  13. General relativistic effects in quantum interference of "clocks"

    CERN Document Server

    Zych, Magdalena; Costa, Fabio; Brukner, Časlav

    2016-01-01

    Quantum mechanics and general relativity have been each successfully tested in numerous experiments. However, the regime where both theories are jointly required to explain physical phenomena remains untested by laboratory experiments, and is also not fully understood by theory. This contribution reviews recent ideas for a new type of experiments: quantum interference of "clocks", which aim to test novel quantum effects that arise from time dilation. "Clock" interference experiments could be realised with atoms or photons in near future laboratory experiments.

  14. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    OpenAIRE

    2015-01-01

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in...

  15. Explaining the Imperfection of the Molecular Clock of Hominid Mitochondria

    OpenAIRE

    Eva-Liis Loogväli; Toomas Kivisild; Tõnu Margus; Richard Villems

    2009-01-01

    The molecular clock of mitochondrial DNA has been extensively used to date various genetic events. However, its substitution rate among humans appears to be higher than rates inferred from human-chimpanzee comparisons, limiting the potential of interspecies clock calibrations for intraspecific dating. It is not well understood how and why the substitution rate accelerates. We have analyzed a phylogenetic tree of 3057 publicly available human mitochondrial DNA coding region sequences for chang...

  16. Expanding circadian input, output, and the clock through genomic screens

    OpenAIRE

    2011-01-01

    Many aspects of mammalian physiology display circadian--or once daily--rhythms, such as heart rate, blood pressure, activity levels, metabolism, and liver regeneration. These rhythms are regulated by an entrainable, self-sustaining, cell-autonomous mechanism found in nearly every cell of the body: the circadian clock. The circadian clock itself represents a regulatory network, composed of interlocking negative feedback loops, that in turn is influenced by two other types of regulatory network...

  17. Low-cost on-chip clock jitter measurement scheme

    OpenAIRE

    Omana, Martin; Rossi, Daniele; Giaffreda, Daniele; Metra, Cecilia; Mak, T.M.; Raman, Asifur; Tam, Simon

    2014-01-01

    In this paper, we present a low-cost, on-chip clock jitter digital measurement scheme for high performance microprocessors. It enables in situ jitter measurement during the test or debug phase. It provides very high measurement resolution and accuracy, despite the possible presence of power supply noise (representing a major source of clock jitter), at low area and power costs. The achieved resolution is scalable with technology node and can in principle be increased as much as desired, at lo...

  18. A Clock Enhanced Loop for Simultaneous Error-Free Demultiplexing and Clock Recovery of 160 Gb/s OTDM Signal Single-Channel Transmission over 100 km

    Institute of Scientific and Technical Information of China (English)

    JIA Nan; LI Tang-Jun; ZHONG Kang-Ping; WANG Mu-Guang; CHEN Ming; LI Jing; CHI Jian-Feng

    2010-01-01

    @@ A simple clock enhanced loop of cascaded electro-absorption modulators(EAMs)and 10GHz clock recovery modules is presented.The intensity of harmonic of clock-frequency component is analyzed theoretically and verified experimentally in a 160Gb/s OTDM 100km transmission system.The 10GHz clock component is enhanced obviously before launching into the clock recovery module and the recovered clock signal exhibits low rms jitter of < 400 fs.Moreover,completely error-free(10-12)transmission is observed for more than two hours without using forward error correction technology.The power penalty is about 3.6dB.The proposed loop has merits of enhancing base clock component,simultaneously de-multiplexing and clock recovery,which make the performance of this loop more stable and high suppression of non-target channels.

  19. Comparing dependent robust correlations.

    Science.gov (United States)

    Wilcox, Rand R

    2016-11-01

    Let r1 and r2 be two dependent estimates of Pearson's correlation. There is a substantial literature on testing H0  : ρ1  = ρ2 , the hypothesis that the population correlation coefficients are equal. However, it is well known that Pearson's correlation is not robust. Even a single outlier can have a substantial impact on Pearson's correlation, resulting in a misleading understanding about the strength of the association among the bulk of the points. A way of mitigating this concern is to use a correlation coefficient that guards against outliers, many of which have been proposed. But apparently there are no results on how to compare dependent robust correlation coefficients when there is heteroscedasicity. Extant results suggest that a basic percentile bootstrap will perform reasonably well. This paper reports simulation results indicating the extent to which this is true when using Spearman's rho, a Winsorized correlation or a skipped correlation.

  20. A robust classic.

    Science.gov (United States)

    Kutzner, Florian; Vogel, Tobias; Freytag, Peter; Fiedler, Klaus

    2011-01-01

    In the present research, we argue for the robustness of illusory correlations (ICs, Hamilton & Gifford, 1976) regarding two boundary conditions suggested in previous research. First, we argue that ICs are maintained under extended experience. Using simulations, we derive conflicting predictions. Whereas noise-based accounts predict ICs to be maintained (Fielder, 2000; Smith, 1991), a prominent account based on discrepancy-reducing feedback learning predicts ICs to disappear (Van Rooy et al., 2003). An experiment involving 320 observations with majority and minority members supports the claim that ICs are maintained. Second, we show that actively using the stereotype to make predictions that are met with reward and punishment does not eliminate the bias. In addition, participants' operant reactions afford a novel online measure of ICs. In sum, our findings highlight the robustness of ICs that can be explained as a result of unbiased but noisy learning.

  1. Novel Register Sharing in Datapath for Structural Robustness against Delay Variation

    Science.gov (United States)

    Inoue, Keisuke; Kaneko, Mineo; Iwagaki, Tsuyoshi

    As the feature size of VLSI becomes smaller, delay variations become a serious problem in VLSI. In this paper, we propose a novel class of robustness for a datapath against delay variations, which is named structural robustness against delay variation (SRV), and propose sufficient conditions for a datapath to have SRV. A resultant circuit designed under these conditions has a larger timing margin to delay variations than previous designs without sacrificing effective computation time. In addition, under any degree of delay variations, we can always find an available clock frequency for a datapath having SRV property to operate correctly, which could be a preferable characteristic in IP-based design.

  2. Electronics for the pulsed rubidium clock: design and characterization.

    Science.gov (United States)

    Calosso, Claudio E; Micalizio, Salvatore; Godone, Aldo; Bertacco, Elio K; Levi, Filippo

    2007-09-01

    Pulsing the different operation phases of a vapor-cell clock (optical pumping, interrogation, and detection) has been recognized as one of the most effective techniques to reduce light shift and then to improve the stability perspectives of vapor cell clocks. However, in order to take full advantage of the pulsed scheme, a fast-gated electronics is required, the times involved being of the order of milliseconds. In this paper we describe the design and the implementation of the electronics that synchronizes the different phases of the clock operation, as well as of the electronics that is mainly devoted to the thermal stabilization of the clock physics package. We also report some characterization measurements, including a measurement of the clock frequency stability. In particular, in terms of Allan deviation, we measured a frequency stability of 1.2 x 10(-12) tao(-1/2) for averaging times up to tao = 10(5) s, a very interesting result by itself and also for a possible space application of such a clock.

  3. The quantum beat the physical principles of atomic clocks

    CERN Document Server

    Major, F G

    1998-01-01

    One of the indicators of the level of technological development of a society has been, throughout history, the precision of clocks it was able to build. This book examines the physical principles underlying the workings of clocks--from the earliest mechanical clocks to the present-day sophisticated clocks based on the properties of individual atoms. Intended for non-specialists with some knowledge of physics or engineering,the book treats the material in a broad intuitive manner, with a minimum of mathematical formalism. The presentation covers a broad range of salient topics relevant to the measurement of frequency and time intervals. The main focus is on electronic time-keeping: clocks based on quartz crystal oscillators and, at greater length, atomic clocks based on quantum resonance in rubidium, cesium, and hydrogen atoms, and, more recently, mercury ions. The book treats the revolutionary changes that the optical laser has wrought on atomic standards through laser cooling and optical pumping, and it disc...

  4. Experimental constraint on dark matter detection with optical atomic clocks

    Science.gov (United States)

    Wcisło, P.; Morzyński, P.; Bober, M.; Cygan, A.; Lisak, D.; Ciuryło, R.; Zawada, M.

    2016-12-01

    The total mass density of the Universe appears to be dominated by dark matter. However, beyond its gravitational interactions at the galactic scale, little is known about its nature1. Several proposals have been advanced in recent years for the detection of dark matter2-4. In particular, a network of atomic clocks could be used to search for transient indicators of hypothetical dark matter5 in the form of stable topological defects; for example, monopoles, strings or domain walls6. The clocks become desynchronized when a dark-matter object sweeps through the network. This pioneering approach5 requires a comparison between at least two distant optical atomic clocks7-9. Here, by exploiting differences in the susceptibilities of the atoms and the cavity to the fine-structure constant10,11, we show that a single optical atomic clock12 is already sensitive to dark-matter events. This implies that existing optical atomic clocks13,14 can serve as a global topological-defect dark-matter observatory, without any further developments in experimental apparatus or the need for long phase-noise-compensated optical-fibre links15. Using optical atomic clocks, we explored a new dimension of astrophysical observations by constraining the strength of atomic coupling to hypothetical dark-matter cosmic objects. Under the conditions of our experiments, the degree of constraint was found to exceed the previously reported limits16 by more than three orders of magnitude.

  5. The Molecular Circadian Clock and Alcohol-Induced Liver Injury.

    Science.gov (United States)

    Udoh, Uduak S; Valcin, Jennifer A; Gamble, Karen L; Bailey, Shannon M

    2015-10-14

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  6. A clock network for geodesy and fundamental science

    Science.gov (United States)

    Lisdat, C.; Grosche, G.; Quintin, N.; Shi, C.; Raupach, S. M. F.; Grebing, C.; Nicolodi, D.; Stefani, F.; Al-Masoudi, A.; Dörscher, S.; Häfner, S.; Robyr, J.-L.; Chiodo, N.; Bilicki, S.; Bookjans, E.; Koczwara, A.; Koke, S.; Kuhl, A.; Wiotte, F.; Meynadier, F.; Camisard, E.; Abgrall, M.; Lours, M.; Legero, T.; Schnatz, H.; Sterr, U.; Denker, H.; Chardonnet, C.; Le Coq, Y.; Santarelli, G.; Amy-Klein, A.; Le Targat, R.; Lodewyck, J.; Lopez, O.; Pottie, P.-E.

    2016-08-01

    Leveraging the unrivalled performance of optical clocks as key tools for geo-science, for astronomy and for fundamental physics beyond the standard model requires comparing the frequency of distant optical clocks faithfully. Here, we report on the comparison and agreement of two strontium optical clocks at an uncertainty of 5 × 10-17 via a newly established phase-coherent frequency link connecting Paris and Braunschweig using 1,415 km of telecom fibre. The remote comparison is limited only by the instability and uncertainty of the strontium lattice clocks themselves, with negligible contributions from the optical frequency transfer. A fractional precision of 3 × 10-17 is reached after only 1,000 s averaging time, which is already 10 times better and more than four orders of magnitude faster than any previous long-distance clock comparison. The capability of performing high resolution international clock comparisons paves the way for a redefinition of the unit of time and an all-optical dissemination of the SI-second.

  7. Circadian Clock Genes Universally Control Key Agricultural Traits.

    Science.gov (United States)

    Bendix, Claire; Marshall, Carine M; Harmon, Frank G

    2015-08-01

    Circadian clocks are endogenous timers that enable plants to synchronize biological processes with daily and seasonal environmental conditions in order to allocate resources during the most beneficial times of day and year. The circadian clock regulates a number of central plant activities, including growth, development, and reproduction, primarily through controlling a substantial proportion of transcriptional activity and protein function. This review examines the roles that alleles of circadian clock genes have played in domestication and improvement of crop plants. The focus here is on three groups of circadian clock genes essential to clock function in Arabidopsis thaliana: PSEUDO-RESPONSE REGULATORs, GIGANTEA, and the evening complex genes early flowering 3, early flowering 4, and lux arrhythmo. homologous genes from each group underlie quantitative trait loci that have beneficial influences on key agricultural traits, especially flowering time but also yield, biomass, and biennial growth habit. Emerging insights into circadian clock regulation of other fundamental plant processes, including responses to abiotic and biotic stresses, are discussed to highlight promising avenues for further crop improvement. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  8. Register Clustering Methodology for Low Power Clock Tree Synthesis

    Institute of Scientific and Technical Information of China (English)

    邓超; 蔡懿慈; 周强

    2015-01-01

    Clock networks dissipate a significant fraction of the entire chip power budget. Therefore, the optimization for power consumption of clock networks has become one of the most important objectives in high performance IC designs. In contrast to most of the traditional studies that handle this problem with clock routing or buffer insertion strategy, this paper proposes a novel register clustering methodology in generating the leaf level topology of the clock tree to reduce the power consumption. Three register clustering algorithms called KMR, KSR and GSR are developed and a comprehensive study of them is discussed in this paper. Meanwhile, a buffer allocation algorithm is proposed to satisfy the slew constraint within the clusters at a minimum cost of power consumption. We integrate our algorithms into a classical clock tree synthesis (CTS) flow to test the register clustering methodology on ISPD 2010 benchmark circuits. Experimental results show that all the three register clustering algorithms achieve more than 20% reduction in power consumption without affecting the skew and the maximum latency of the clock tree. As the most effective method among the three algorithms, GSR algorithm achieves a 31%reduction in power consumption as well as a 4%reduction in skew and a 5%reduction in maximum latency. Moreover, the total runtime of the CTS flow with our register clustering algorithms is significantly reduced by almost an order of magnitude.

  9. Time in the 10,000-Year Clock

    CERN Document Server

    Hillis, Danny; Allen, Steve; Giorgini, Jon

    2011-01-01

    The Long Now Foundation is building a mechanical clock that is designed to keep time for the next 10,000 years. The clock maintains its long-term accuracy by synchronizing to the Sun. The 10,000-Year Clock keeps track of five different types of time: Pendulum Time, Uncorrected Solar Time, Corrected Solar Time, Displayed Solar Time and Orrery Time. Pendulum Time is generated from the mechanical pendulum and adjusted according to the equation of time to produce Uncorrected Solar Time, which is in turn mechanically corrected by the Sun to create Corrected Solar Time. Displayed Solar Time advances each time the clock is wound, at which point it catches up with Corrected Solar Time. The clock uses Displayed Solar Time to compute various time indicators to be displayed, including the positions of the Sun, and Gregorian calendar date. Orrery Time is a better approximation of Dynamical Time, used to compute positions of the Moon, planets and stars and the phase of the Moon. This paper describes how the clock reckons ...

  10. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Uduak S. Udoh

    2015-10-01

    Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  11. Robust Adaptive Control.

    Science.gov (United States)

    1985-09-19

    13.2 3.6. 14.0. 1.8. 11111.52 *.6 L 3 n1 i erated ~~~m nc. AFOSR-TR- 798 s AD-A 161 349 ROBUST ADAPTIVE CONTROL * FINAL REPORT PREPARED BY: R~ OBERT L... Centre Block Computes the Norm of the [1I] Solo, V., "Time Series Recursions and Stochastc Regressors. The Rematning Elemerts Imple- Approximation

  12. Robust verification analysis

    Energy Technology Data Exchange (ETDEWEB)

    Rider, William, E-mail: wjrider@sandia.gov [Sandia National Laboratories, Center for Computing Research, Albuquerque, NM 87185 (United States); Witkowski, Walt [Sandia National Laboratories, Verification and Validation, Uncertainty Quantification, Credibility Processes Department, Engineering Sciences Center, Albuquerque, NM 87185 (United States); Kamm, James R. [Los Alamos National Laboratory, Methods and Algorithms Group, Computational Physics Division, Los Alamos, NM 87545 (United States); Wildey, Tim [Sandia National Laboratories, Center for Computing Research, Albuquerque, NM 87185 (United States)

    2016-02-15

    We introduce a new methodology for inferring the accuracy of computational simulations through the practice of solution verification. We demonstrate this methodology on examples from computational heat transfer, fluid dynamics and radiation transport. Our methodology is suited to both well- and ill-behaved sequences of simulations. Our approach to the analysis of these sequences of simulations incorporates expert judgment into the process directly via a flexible optimization framework, and the application of robust statistics. The expert judgment is systematically applied as constraints to the analysis, and together with the robust statistics guards against over-emphasis on anomalous analysis results. We have named our methodology Robust Verification. Our methodology is based on utilizing multiple constrained optimization problems to solve the verification model in a manner that varies the analysis' underlying assumptions. Constraints applied in the analysis can include expert judgment regarding convergence rates (bounds and expectations) as well as bounding values for physical quantities (e.g., positivity of energy or density). This approach then produces a number of error models, which are then analyzed through robust statistical techniques (median instead of mean statistics). This provides self-contained, data and expert informed error estimation including uncertainties for both the solution itself and order of convergence. Our method produces high quality results for the well-behaved cases relatively consistent with existing practice. The methodology can also produce reliable results for ill-behaved circumstances predicated on appropriate expert judgment. We demonstrate the method and compare the results with standard approaches used for both code and solution verification on well-behaved and ill-behaved simulations.

  13. Robust Self Tuning Controllers

    DEFF Research Database (Denmark)

    Poulsen, Niels Kjølstad

    1985-01-01

    The present thesis concerns robustness properties of adaptive controllers. It is addressed to methods for robustifying self tuning controllers with respect to abrupt changes in the plant parameters. In the thesis an algorithm for estimating abruptly changing parameters is presented. The estimator...... has several operation modes and a detector for controlling the mode. A special self tuning controller has been developed to regulate plant with changing time delay....

  14. Robustness of Interdependent Networks

    Science.gov (United States)

    Havlin, Shlomo

    2011-03-01

    In interdependent networks, when nodes in one network fail, they cause dependent nodes in other networks to also fail. This may happen recursively and can lead to a cascade of failures. In fact, a failure of a very small fraction of nodes in one network may lead to the complete fragmentation of a system of many interdependent networks. We will present a framework for understanding the robustness of interacting networks subject to such cascading failures and provide a basic analytic approach that may be useful in future studies. We present exact analytical solutions for the critical fraction of nodes that upon removal will lead to a failure cascade and to a complete fragmentation of two interdependent networks in a first order transition. Surprisingly, analyzing complex systems as a set of interdependent networks may alter a basic assumption that network theory has relied on: while for a single network a broader degree distribution of the network nodes results in the network being more robust to random failures, for interdependent networks, the broader the distribution is, the more vulnerable the networks become to random failure. We also show that reducing the coupling between the networks leads to a change from a first order percolation phase transition to a second order percolation transition at a critical point. These findings pose a significant challenge to the future design of robust networks that need to consider the unique properties of interdependent networks.

  15. The Crane Robust Control

    Directory of Open Access Journals (Sweden)

    Marek Hicar

    2004-01-01

    Full Text Available The article is about a control design for complete structure of the crane: crab, bridge and crane uplift.The most important unknown parameters for simulations are burden weight and length of hanging rope. We will use robustcontrol for crab and bridge control to ensure adaptivity for burden weight and rope length. Robust control will be designed for current control of the crab and bridge, necessary is to know the range of unknown parameters. Whole robust will be splitto subintervals and after correct identification of unknown parameters the most suitable robust controllers will be chosen.The most important condition at the crab and bridge motion is avoiding from burden swinging in the final position. Crab and bridge drive is designed by asynchronous motor fed from frequency converter. We will use crane uplift with burden weightobserver in combination for uplift, crab and bridge drive with cooperation of their parameters: burden weight, rope length and crab and bridge position. Controllers are designed by state control method. We will use preferably a disturbance observerwhich will identify burden weight as a disturbance. The system will be working in both modes at empty hook as well asat maximum load: burden uplifting and dropping down.

  16. Reduced Voltage Scaling in Clock Distribution Networks

    Directory of Open Access Journals (Sweden)

    Khader Mohammad

    2009-01-01

    Full Text Available We propose a novel circuit technique to generate a reduced voltage swing (RVS signals for active power reduction on main buses and clocks. This is achieved without performance degradation, without extra power supply requirement, and with minimum area overhead. The technique stops the discharge path on the net that is swinging low at a certain voltage value. It reduces active power on the target net by as much as 33% compared to traditional full swing signaling. The logic 0 voltage value is programmable through control bits. If desired, the reduced-swing mode can also be disabled. The approach assumes that the logic 0 voltage value is always less than the threshold voltage of the nMOS receivers, which eliminate the need of the low to high voltage translation. The reduced noise margin and the increased leakage on the receiver transistors using this approach have been addressed through the selective usage of multithreshold voltage (MTV devices and the programmability of the low voltage value.

  17. Chemical clocks for early-type galaxies

    CERN Document Server

    Carretero, C; Beckman, J E

    2007-01-01

    We present a detailed stellar population analysis of 27 massive elliptical galaxies within 4 very rich clusters at redshift z~0.2. We obtained accurate estimates of the mean luminosity-weighted ages and relative abundances of CN, Mg and Fe as functions of the galaxy velocity dispersion, sigma. Our results are compatible with a scenario in which the stellar populations of massive elliptical galaxies, independently of their environment and mass, had formation timescales shorter than ~1 Gyr. This result implies that massive elliptical galaxies have evolved passively since, at least, as long ago as z~2. For a given galaxy mass the duration of star formation is shorter in those galaxies belonging to more dense environments. Finally, we show that the abundance ratios [CN/Fe] and [Mg/Fe] are the key "chemical clocks" to infer the star formation history timescales in ellipticals. In particular, [Mg/Fe] provides an upper limit for those formation timescales, while [CN/Fe] apperars to be the most suitable parameter to ...

  18. The clock of a quantum computer

    CERN Document Server

    Apolloni, B

    2002-01-01

    If the physical agent (the 'pointer', or 'cursor', or 'clocking mechanism') that sequentially scans the T lines of a long computer program is a microscopic system, two quantum phenomena become relevant: spreading of the probability distribution of the pointer along the program lines, and scattering of the probability amplitude at the two endpoints of the physical space allowed for its motion. We show that the first effect determines an upper bound O(T sup - sup 2 sup / sup 3) on the probability of finding the pointer exactly at the END line. By adding an adequate number delta of further empty lines ('telomers'), one can store the result of the computation up to the moment in which the pointer is scattered back into the active region. This leads to a less severe upper bound O(sq root delta/T) on the probability of finding the pointer either at the END line or within the additional empty lines. Our analysis is performed in the context of Feynman's model of quantum computation, the only model, to our knowledge, ...

  19. Maternal feeding controls fetal biological clock.

    Directory of Open Access Journals (Sweden)

    Hidenobu Ohta

    Full Text Available BACKGROUND: It is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD cycle. METHODOLOGY/PRINCIPAL FINDINGS: To study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy.

  20. Power-efficient dual-edge implicit pulse-triggered flip-flop with an embedded clock-gating scheme

    Institute of Scientific and Technical Information of China (English)

    Liang GENG; Ji-zhong SHEN; Cong-yuan XU

    2016-01-01

    A novel dual-edge implicit pulse-triggered flip-flop with an embedded clock-gating scheme (DIFF-CGS) is proposed, which employs a transmission-gate-logic (TGL) based clock-gating scheme in the pulse generation stage. This scheme condi-tionally disables the inverter chain when the input data are kept unchanged, so redundant transitions of delayed clock signals and internal nodes of the latch are all eliminated, leading to low power efficiency. Based on SMIC 65 nm technology, extensive post-layout simulation results show that the proposed DIFF-CGS gains an improvement of 41.39% to 56.21% in terms of power consumption, compared with its counterparts at 10% data-switching activity. Also, full-swing operations in both implicit pulse generation and the static latch improve the robustness of the design. Thus, DIFF-CGS is suitable for low-power applications in very-large-scale integration (VLSI) designs with low data-switching activities.

  1. Synchronized human skeletal myotubes of lean, obese and type 2 diabetic patients maintain circadian oscillation of clock genes

    Science.gov (United States)

    Hansen, Jan; Timmers, Silvie; Moonen-Kornips, Esther; Duez, Helene; Staels, Bart; Hesselink, Matthijs K. C.; Schrauwen, Patrick

    2016-01-01

    Cell and animal studies have demonstrated that circadian rhythm is governed by autonomous rhythmicity of clock genes. Although disturbances in circadian rhythm have been implicated in metabolic disease development, it remains unknown whether muscle circadian rhythm is altered in human models of type 2 diabetes. Here we used human primary myotubes (HPM) to investigate if rhythmicity of clock- and metabolic gene expression is altered in donors with obesity or type 2 diabetes compared to metabolically healthy donors. HPM were obtained from skeletal muscle biopsies of four groups: type 2 diabetic patients and their BMI- and age-matched obese controls and from lean, healthy and young endurance trained athletes and their age-matched sedentary controls. HPM were differentiated for 7 days before synchronization by serum shock followed by gene expression profiling over the next 72 hours. HPM display robust circadian rhythms in clock genes, but REVERBA displayed dampened rhythmicity in type 2 diabetes. Furthermore, rhythmicity in NAMPT and SIRT1 expression was only observed in HPM from trained athletes. Rhythmicity in expression of key-regulators of carbohydrate and lipid metabolism was modest. We demonstrate that in human skeletal muscle REVERBA/B, NAMPT and SIRT1 circadian rhythms are affected in donors of sedentary life style and poor health status. PMID:27756900

  2. International Cryocooler Conference

    CERN Document Server

    Cryocoolers 13

    2005-01-01

    This is the 13th volume in the conference series. Over the years the International Cryocoolers Conference has become the preeminent worldwide conference for the presentation of the latest developments and test experiences with cryocoolers. The typical applications of this technology include cooling space and terrestrial infrared focal plane arrays, space x-ray detectors, medical applications, and a growing number of high-temperature super-capacitor applications.

  3. Expectations for Cancun Conference

    Institute of Scientific and Technical Information of China (English)

    DING ZHITAO

    2010-01-01

    Compared with the great hopes raised by the Copenhagen Climate Conference in 2009, the 2010 UN Climate Change Conference in Cancun aroused fewer expectations. However, the international community is still waiting for a positive outcome that will benefit humankind as a whole. The Cancun conference is another important opportunity for all the participants to advance the Bali Road Map negotiations after last year's meeting in Copenhagen, which failed to reach a legally binding treaty for the years beyond 2012.

  4. Conference proceedings ISES 2014

    DEFF Research Database (Denmark)

    Christensen, Janne Winther; Peerstrup Ahrendt, Line; Malmkvist, Jens

    The 10th Internatinal Equitation Science Conference is held i Denmark from August 6th - 9th 2014. This book of proceedings contaions abstracts of 35 oral and 57 poster presentations within the conference themes Equine Stress, Learning and Training as well as free papers.......The 10th Internatinal Equitation Science Conference is held i Denmark from August 6th - 9th 2014. This book of proceedings contaions abstracts of 35 oral and 57 poster presentations within the conference themes Equine Stress, Learning and Training as well as free papers....

  5. British domestic synchronous clocks 1930-1980 the rise and fall of a technology

    CERN Document Server

    Pook, Leslie Philip

    2015-01-01

    This book complements available one-make books on domestic synchronous clocks. It is also a history of science book that sets British domestic synchronous clocks, their manufacturers and technology in their social context. Part I covers the historical background, British domestic synchronous clock manufacturers and brands, how synchronous clocks work, domestic synchronous clock cases, practical advice on the servicing of domestic synchronous clocks, and analysis of the marketing and reliability of British domestic synchronous clocks. This analysis provides an explanation of the rise and eventual fall of their technology. Part II contains galleries of a selection of British domestic synchronous clocks, and of the movements with which they are fitted. There is a front and back view of each clock, together with a brief description. Views of each movement include views with the movement partly dismantled, together with a brief technical description of the movement. This profusely illustrated book is primarily fo...

  6. Robust Control of Underactuated Manipulators: Analysis and Implementation

    Science.gov (United States)

    1994-05-01

    Y Control of mechanical systems with second-order nonholonomic constraints: underactuated manipulators. Proc. of the 30th Conference on Decision and...any of a series of controllers fully developed in the literature for mechanical manipulators. Because the control of such a system is fully dependent...robust controller for underactuated manipulators. The control of such systems can be extended to the control problem of fault-tolerant robots, space

  7. Robustness of Cantor diffractals.

    Science.gov (United States)

    Verma, Rupesh; Sharma, Manoj Kumar; Banerjee, Varsha; Senthilkumaran, Paramasivam

    2013-04-08

    Diffractals are electromagnetic waves diffracted by a fractal aperture. In an earlier paper, we reported an important property of Cantor diffractals, that of redundancy [R. Verma et. al., Opt. Express 20, 8250 (2012)]. In this paper, we report another important property, that of robustness. The question we address is: How much disorder in the Cantor grating can be accommodated by diffractals to continue to yield faithfully its fractal dimension and generator? This answer is of consequence in a number of physical problems involving fractal architecture.

  8. Robust Kriged Kalman Filtering

    Energy Technology Data Exchange (ETDEWEB)

    Baingana, Brian; Dall' Anese, Emiliano; Mateos, Gonzalo; Giannakis, Georgios B.

    2015-11-11

    Although the kriged Kalman filter (KKF) has well-documented merits for prediction of spatial-temporal processes, its performance degrades in the presence of outliers due to anomalous events, or measurement equipment failures. This paper proposes a robust KKF model that explicitly accounts for presence of measurement outliers. Exploiting outlier sparsity, a novel l1-regularized estimator that jointly predicts the spatial-temporal process at unmonitored locations, while identifying measurement outliers is put forth. Numerical tests are conducted on a synthetic Internet protocol (IP) network, and real transformer load data. Test results corroborate the effectiveness of the novel estimator in joint spatial prediction and outlier identification.

  9. Robustness Metrics: Consolidating the multiple approaches to quantify Robustness

    DEFF Research Database (Denmark)

    Göhler, Simon Moritz; Eifler, Tobias; Howard, Thomas J.

    2016-01-01

    determined to be conceptually different from one another. The metrics were classified by their meaning and interpretation based on the types of information necessary to calculate the metrics. Four different classes were identified: 1) Sensitivity robustness metrics; 2) Size of feasible design space...... and to remove the ambiguities of the term robustness. By applying an exemplar metric from each class to a case study, the differences between the classes were further highlighted.These classes form the basis for the definition of four specific sub-definitions of robustness, namely the ‘robust concept’, ‘robust...

  10. Second international conference on isotopes. Conference proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, C.J. [ed.

    1997-10-01

    The Second International Conference on Isotopes (2ICI) was hosted by the Australian Nuclear Association in Sydney, NSW, Australia. The Theme of the Second Conference: Isotopes for Industry, Health and a Better Environment recognizes that isotopes have been used in these fields successfully for many years and offer prospects for increasing use in the future. The worldwide interest in the use of research reactors and accelerators and in applications of stable and radioactive isotopes, isotopic techniques and radiation in industry, agriculture, medicine, environmental studies and research in general, was considered. Other radiation issues including radiation protection and safety were also addressed. International and national overviews and subject reviews invited from leading experts were included to introduce the program of technical sessions. The invited papers were supported by contributions accepted from participants for oral and poster presentation. A Technical Exhibition was held in association with the Conference. This volume contains the full text or extended abstracts of papers number 61- to number 114

  11. Adaptive Robust Variable Selection

    CERN Document Server

    Fan, Jianqing; Barut, Emre

    2012-01-01

    Heavy-tailed high-dimensional data are commonly encountered in various scientific fields and pose great challenges to modern statistical analysis. A natural procedure to address this problem is to use penalized least absolute deviation (LAD) method with weighted $L_1$-penalty, called weighted robust Lasso (WR-Lasso), in which weights are introduced to ameliorate the bias problem induced by the $L_1$-penalty. In the ultra-high dimensional setting, where the dimensionality can grow exponentially with the sample size, we investigate the model selection oracle property and establish the asymptotic normality of the WR-Lasso. We show that only mild conditions on the model error distribution are needed. Our theoretical results also reveal that adaptive choice of the weight vector is essential for the WR-Lasso to enjoy these nice asymptotic properties. To make the WR-Lasso practically feasible, we propose a two-step procedure, called adaptive robust Lasso (AR-Lasso), in which the weight vector in the second step is c...

  12. Robust Cultural Pluralism

    Directory of Open Access Journals (Sweden)

    Richard A. Shweder

    2013-11-01

    Full Text Available In this wide ranging interview, Professor Richard A. Shweder from the Department of Comparative Human Development at the University of Chicago, discusses whether it is or is not possible to be a robust cultural pluralist and a dedicated political liberal at the same time. In this discussion, Professor Shweder offers his insights - based on over 40 years of research - on issues related to the history and re-emergence of cultural psychology; moral anthropology and psychology; the experimental method in psychological investigation and its philosophical basis; contemporary and historical cultural collisions – most notably conflicting representations of female genital surgeries; cultural diversity and inequality; and the dissemination of ideas through open access publishing and Twitter. Professor Shweder ends by offering valuable advice to young researchers in the field of cultural psychology as well as a glimpse into the larger themes of his forthcoming book, which seeks to provide answers to the question of what forms of political liberalism are most compatible with robust cultural pluralism and which are not.

  13. Scientific performance estimation of robustness and threat

    Science.gov (United States)

    Hoffman, John R.; Sorensen, Eric; Stelzig, Chad A.; Mahler, Ronald P. S.; El-Fallah, Adel I.; Alford, Mark G.

    2002-07-01

    For the last three years at this conference we have been describing the implementation of a unified, scientific approach to performance estimation for various aspects of data fusion: multitarget detection, tracking, and identification algorithms; sensor management algorithms; and adaptive data fusion algorithms. The proposed approach is based on finite-set statistics (FISST), a generalization of conventional statistics to multisource, multitarget problems. Finite-set statistics makes it possible to directly extend Shannon-type information metrics to multisource, multitarget problems in such a way that information can be defined and measured even though any given end-user may have conflicting or even subjective definitions of what informative means. In this presentation, we will show how to extend our previous results to two new problems. First, that of evaluating the robustness of multisensor, multitarget algorithms. Second, that of evaluating the performance of multisource-multitarget threat assessment algorithms.

  14. Radiation`96. Conference handbook

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The conference program includes eight invited lectures which cover a range of contemporary topics in radiation science and technology. In addition, thirty-two oral papers were presented, along with forty-five posters. The conference handbook contains one-page precis or extended abstracts of all presentations, and is a substantial compendium of current radiation research in Australia.

  15. Expectations for Cancun Conference

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Compared with the great hopes raised by the Copenhagen Climate Conference in 2009, the 2010 UN Climate Change Conference in Cancun aroused fewer expectations. However, the international community is still waiting for a positive outcome that will benefit humankind as a whole.

  16. Circadian control of metabolism and pathological consequences of clock perturbations.

    Science.gov (United States)

    Mayeuf-Louchart, Alicia; Zecchin, Mathilde; Staels, Bart; Duez, Hélène

    2017-08-02

    Most organisms have developed an autonomous time-keeping system that generates self-sustained daily fluctuations in behavior and physiological processes. These biological clocks are reset every day by light to adjust physiology to the day/night cycle generated by the rotation of the Earth. Clocks present in organs involved in glucose and lipid metabolism such as the liver, muscle, adipose tissue and pancreas are also reset by feeding cues which permits the local integration of systemic and nutritional signals to switch fuel production and utilization according to the feeding/fasting cycle. However, derangements in this finely tuned system can be induced by extended light exposure, 24/7 food availability and altered food intake patterns, repeated jet-lag and shift-working, promoting metabolic imbalances ranging from body weight gain to the development of insulin resistance and liver diseases. Here, we review recent findings on the link between the clock and metabolic fluxes to maintain whole-body homeostasis, and what clock disruption in mice has revealed about the role of the clock in metabolic regulation. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  17. Energy Efficient Global Clock Synchronization for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Vinod Namboodiri

    2010-05-01

    Full Text Available Clock synchronization is critical to many sensor networks for the success of the application as well as energyefficiency. Achieving a global time frame through localized averaging of clock values for multiple rounds till convergenceis a promising approach to clock synchronization due to the decentralized nature of computation coupled withscalability. However, it is not clear what power levels for all nodes would make the synchronization process energyefficient.Large power levels lead to faster convergence but consume a lot of energy per round of synchronization.On the other hand, smaller powers consume little energy per round, but convergence is very slow requiring a lotof rounds to achieve synchronization. In this paper we look at the problem of finding a power assignment thatachieves global clock synchronization in the most energy-efficient manner possible. We look at the problem throughtwo dimensions; rate of convergence and energy consumed per round of synchronization. A centralized algorithm ispresented that uses the path congestion of the induced communication graph to estimate which power assignmentshave good convergence properties and find one that minimizes the total energy to achieve clock synchronization.Our evaluation demonstrates that the power assignment derived from this algorithm is very energy-efficient and isapplicable for wireless communication environments with various distance-power gradients. Further, we present asimple distributed algorithm which nodes can execute locally to derive energy-efficient power levels for global clocksynchronization, and is especially useful in large-scale deployments.

  18. [Circadian clocks and energy metabolism: implications for health].

    Science.gov (United States)

    Kessler, K; Pivovarova, O; Pfeiffer, A F H

    2014-04-01

    On behavioural as well as physiological levels our daily life is regulated by the circadian clock - endogenous oscillators present in the hypothalamus and in peripheral tissues - which is believed to have evolved as an adaptation to Earth rotation around the Sun and its consequent 24 h dark-light cycle. Accumulative evidence suggests that the circadian clock plays a pivotal role for energy metabolism and energy homeostasis: many hormones, enzymes and transport systems involved in the regulation of energy metabolism have been shown to display circadian rhythms in their expression, secretion and/or activity patterns. The energy metabolism, in turn, can impact on the circadian clock - a process that is called entrainment. Thus, the circadian clock and energy metabolism are intimately intertwined. So far this interplay and its implications for health have not been understood very well. For health maintenance, however, it seems to be crucial to avoid any desynchronisation between the circadian clock and energy metabolism. Form a clinical point of view this might be important for the treatment of obesity and associated disorders and may lead to new life-style approaches. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Buffer Gas Experiments in Mercury (Hg+) Ion Clock

    Science.gov (United States)

    Chung, Sang K.; Prestage, John D.; Tjoelker, Robert L.; Maleki, Lute

    2004-01-01

    We describe the results of the frequency shifts measured from various buffer gases that might be used as a buffer gas to increase the loading efficiency and cooling of ions trapped in a small mercury ion clock. The small mass, volume and power requirement of space clock precludes the use of turbo pumps. Hence, a hermetically sealed vacuum system, incorporating a suitable getter material with a fixed amount of inert buffer gas may be a practical alternative to the groundbased system. The collision shifts of 40,507,347.996xx Hz clock transition for helium, neon and argon buffer gases were measured in the ambient earth magnetic field. In addition to the above non-getterable inert gases we also measured the frequency shifts due to getterable, molecular hydrogen and nitrogen gases which may be used as buffer gases when incorporated with a miniature ion pump. We also examined the frequency shift due to the low methane gas partial pressure in a fixed higher pressure neon buffer gas environment. Methane gas interacted with mercury ions in a peculiar way as to preserve the ion number but to relax the population difference in the two hyperfine clock states and thereby reducing the clock resonance signal. The same population relaxation was also observed for other molecular buffer gases (N H,) but at much reduced rate.

  20. Buffer Gas Experiments in Mercury (Hg+) Ion Clock

    Science.gov (United States)

    Chung, Sang K.; Prestage, John D.; Tjoelker, Robert L.; Maleki, Lute

    2004-01-01

    We describe the results of the frequency shifts measured from various buffer gases that might be used as a buffer gas to increase the loading efficiency and cooling of ions trapped in a small mercury ion clock. The small mass, volume and power requirement of space clock precludes the use of turbo pumps. Hence, a hermetically sealed vacuum system, incorporating a suitable getter material with a fixed amount of inert buffer gas may be a practical alternative to the groundbased system. The collision shifts of 40,507,347.996xx Hz clock transition for helium, neon and argon buffer gases were measured in the ambient earth magnetic field. In addition to the above non-getterable inert gases we also measured the frequency shifts due to getterable, molecular hydrogen and nitrogen gases which may be used as buffer gases when incorporated with a miniature ion pump. We also examined the frequency shift due to the low methane gas partial pressure in a fixed higher pressure neon buffer gas environment. Methane gas interacted with mercury ions in a peculiar way as to preserve the ion number but to relax the population difference in the two hyperfine clock states and thereby reducing the clock resonance signal. The same population relaxation was also observed for other molecular buffer gases (N H,) but at much reduced rate.