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Sample records for strict molecular clock

  1. Molecular cogs of the insect circadian clock.

    Science.gov (United States)

    Shirasu, Naoto; Shimohigashi, Yasuyuki; Tominaga, Yoshiya; Shimohigashi, Miki

    2003-08-01

    During the last five years, enormous progress has been made in understanding the molecular basis of circadian systems, mainly by molecular genetic studies using the mouse and fly. Extensive evidence has revealed that the core clock machinery involves "clock genes" and "clock proteins" functioning as molecular cogs. These participate in transcriptional/translational feedback loops and many homologous clock-components in the fruit fly Drosophila are also expressed in mammalian clock tissues with circadian rhythms. Thus, the mechanisms of the central clock seem to be conserved across animal kingdom. However, some recent studies imply that the present widely accepted molecular models of circadian clocks may not always be supported by the experimental evidence.

  2. Molecular clock in neutral protein evolution

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    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.

  3. Molecular clock on a neutral network.

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    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.

  4. A molecular clock for autoionization decay

    International Nuclear Information System (INIS)

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

    2017-01-01

    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. (paper)

  5. Molecular Cogs: Interplay between Circadian Clock and Cell Cycle.

    Science.gov (United States)

    Gaucher, Jonathan; Montellier, Emilie; Sassone-Corsi, Paolo

    2018-05-01

    The cell cycle and the circadian clock operate as biological oscillators whose timed functions are tightly regulated. Accumulating evidence illustrates the presence of molecular links between these two oscillators. This mutual interplay utilizes various coupling mechanisms, such as the use of common regulators. The connection between these two cyclic systems has unique interest in the context of aberrant cell proliferation since both of these oscillators are frequently misregulated in cancer cells. Further studies will provide deeper understanding of the detailed molecular connections between the cell cycle and the circadian clock and may also serve as a basis for the design of innovative therapeutic strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

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    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.

  7. Divergence time estimates of mammals from molecular clocks and ...

    Indian Academy of Sciences (India)

    Prakash

    2009-10-30

    Oct 30, 2009 ... Keywords. Cretaceous; Eocene; Indian Plate; molecular clocks; placental mammals ... variation is known to occur among loci on a gene, between branches on a tree, ... been proposed to explain placental mammal diversification with respect .... Figure 1. Three models (a, explosive, b, long fuse, c, short fuse).

  8. Explaining the imperfection of the molecular clock of hominid mitochondria.

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    Eva-Liis Loogväli

    Full Text Available 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 changes in the ratios of mutations belonging to different functional classes. The proportion of non-synonymous and RNA genes substitutions has reduced over hundreds of thousands of years. The highest mutation ratios corresponding to fast acceleration in the apparent substitution rate of the coding sequence have occurred after the end of the Last Ice Age. We recalibrate the molecular clock of human mtDNA as 7990 years per synonymous mutation over the mitochondrial genome. However, the distribution of substitutions at synonymous sites in human data significantly departs from a model assuming a single rate parameter and implies at least 3 different subclasses of sites. Neutral model with 3 synonymous substitution rates can explain most, if not all, of the apparent molecular clock difference between the intra- and interspecies levels. Our findings imply the sluggishness of purifying selection in removing the slightly deleterious mutations from the human as well as the Neandertal and chimpanzee populations. However, for humans, the weakness of purifying selection has been further exacerbated by the population expansions associated with the out-of Africa migration and the end of the Last Ice Age.

  9. A sense of time: how molecular clocks organize metabolism.

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    Kohsaka, Akira; Bass, Joseph

    2007-01-01

    The discovery of an internal temporal clockwork that coordinates behavior and metabolism according to the rising and setting of the sun was first revealed in flies and plants. However, in the past decade, a molecular transcription-translation feedback loop with similar properties has also been identified in mammals. In mammals, this transcriptional oscillator programs 24-hour cycles in sleep, activity and feeding within the master pacemaker neurons of the suprachiasmatic nucleus of the hypothalamus. More recent studies have shown that the core transcription mechanism is also present in other locations within the brain, in addition to many peripheral tissues. Processes ranging from glucose transport to gluconeogenesis, lipolysis, adipogenesis and mitochondrial oxidative phosphorylation are controlled through overlapping transcription networks that are tied to the clock and are thus time sensitive. Because disruption of tissue timing occurs when food intake, activity and sleep are altered, understanding how these many tissue clocks are synchronized to tick at the same time each day, and determining how each tissue 'senses time' set by these molecular clocks might open new insight into human disease, including disorders of sleep, circadian disruption, diabetes and obesity.

  10. Fossil butterflies, calibration points and the molecular clock (Lepidoptera: Papilionoidea).

    Science.gov (United States)

    Jong, Rienk DE

    2017-05-25

    Fossil butterflies are extremely rare. Yet, they are the only direct evidence of the first appearance of particular characters and as such, they are crucial for calibrating a molecular clock, from which divergence ages are estimated. In turn, these estimates, in combination with paleogeographic information, are most important in paleobiogeographic considerations. The key issue here is the correct allocation of fossils on the phylogenetic tree from which the molecular clock is calibrated.The allocation of a fossil on a tree should be based on an apomorphic character found in a tree based on extant species, similar to the allocation of a new extant species. In practice, the latter is not done, at least not explicitly, on the basis of apomorphy, but rather on overall similarity or on a phylogenetic analysis, which is not possible for most butterfly fossils since they usually are very fragmentary. Characters most often preserved are in the venation of the wings. Therefore, special attention is given to possible apomorphies in venational characters in extant butterflies. For estimation of divergence times, not only the correct allocation of the fossil on the tree is important, but also the tree itself influences the outcome as well as the correct determination of the age of the fossil. These three aspects are discussed.        All known butterfly fossils, consisting of 49 taxa, are critically reviewed and their relationship to extant taxa is discussed as an aid for correctly calibrating a molecular clock for papilionoid Lepidoptera. In this context some aspects of age estimation and biogeographic conclusions are briefly mentioned in review. Specific information has been summarized in four appendices.

  11. Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution.

    Science.gov (United States)

    Warnock, Rachel C M; Yang, Ziheng; Donoghue, Philip C J

    2017-06-28

    Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions. © 2017 The Authors.

  12. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock

    OpenAIRE

    David M. Virshup; Rajesh Narasimamurthy

    2017-01-01

    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 entr...

  13. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock.

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    Narasimamurthy, Rajesh; Virshup, David M

    2017-01-01

    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.

  14. Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock

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    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. Rooting and dating maples (Acer) with an uncorrelated-rates molecular clock: implications for north American/Asian disjunctions.

    Science.gov (United States)

    Renner, Susanne S; Grimm, Guido W; Schneeweiss, Gerald M; Stuessy, Tod F; Ricklefs, Robert E

    2008-10-01

    Simulations suggest that molecular clock analyses can correctly identify the root of a tree even when the clock assumption is severely violated. Clock-based rooting of phylogenies may be particularly useful when outgroup rooting is problematic. Here, we explore relaxed-clock rooting in the Acer/Dipteronia clade of Sapindaceae, which comprises genera of highly uneven species richness and problematic mutual monophyly. Using an approach that does not presuppose rate autocorrelation between ancestral and descendant branches and hence does not require a rooted a priori topology, we analyzed data from up to seven chloroplast loci for some 50 ingroup species. For comparison, we used midpoint and outgroup rooting and dating methods that rely on rooted input trees, namely penalized likelihood, a Bayesian autocorrelated-rates model, and a strict clock. The chloroplast sequences used here reject a single global substitution rate, and the assumption of autocorrelated rates was also rejected. The root was placed between Acer and Dipteronia by all three rooting methods, albeit with low statistical support. Analyses of Acer diversification with a lineage-through-time plot and different survival models, although sensitive to missing data, suggest a gradual decrease in the average diversification rate. The nine North American species of Acer diverged from their nearest relatives at widely different times: eastern American Acer diverged in the Oligocene and Late Miocene; western American species in the Late Eocene and Mid Miocene; and the Acer core clade, including A. saccharum, dates to the Miocene. Recent diversification in North America is strikingly rare compared to diversification in eastern Asia.

  16. Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process

    OpenAIRE

    Kishimoto, Toshihiko; Ying, Bei-Wen; Tsuru, Saburo; Iijima, Leo; Suzuki, Shingo; Hashimoto, Tomomi; Oyake, Ayana; Kobayashi, Hisaka; Someya, Yuki; Narisawa, Dai; Yomo, Tetsuya

    2015-01-01

    The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution e...

  17. Molecular basis of a novel adaptation to hypoxic-hypercapnia in a strictly fossorial mole

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    Bonaventura Joseph

    2010-07-01

    Full Text Available Abstract Background Elevated blood O2 affinity enhances survival at low O2 pressures, and is perhaps the best known and most broadly accepted evolutionary adjustment of terrestrial vertebrates to environmental hypoxia. This phenotype arises by increasing the intrinsic O2 affinity of the hemoglobin (Hb molecule, by decreasing the intracellular concentration of allosteric effectors (e.g., 2,3-diphosphoglycerate; DPG, or by suppressing the sensitivity of Hb to these physiological cofactors. Results Here we report that strictly fossorial eastern moles (Scalopus aquaticus have evolved a low O2 affinity, DPG-insensitive Hb - contrary to expectations for a mammalian species that is adapted to the chronic hypoxia and hypercapnia of subterranean burrow systems. Molecular modelling indicates that this functional shift is principally attributable to a single charge altering amino acid substitution in the β-type δ-globin chain (δ136Gly→Glu of this species that perturbs electrostatic interactions between the dimer subunits via formation of an intra-chain salt-bridge with δ82Lys. However, this replacement also abolishes key binding sites for the red blood cell effectors Cl-, lactate and DPG (the latter of which is virtually absent from the red cells of this species at δ82Lys, thereby markedly reducing competition for carbamate formation (CO2 binding at the δ-chain N-termini. Conclusions We propose this Hb phenotype illustrates a novel mechanism for adaptively elevating the CO2 carrying capacity of eastern mole blood during burst tunnelling activities associated with subterranean habitation.

  18. Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat.

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    Mitsunori Miyazaki

    Full Text Available It is well known that spontaneously hypertensive rats (SHR develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007 linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including Mck, Ttn and Mef2c. We next performed circadian time-course collections at a young age (8 weeks; pre-hypertensive and adult age (22 weeks; hypertensive to determine if clock gene expression was disrupted in gastrocnemius, heart and liver tissues prior to or after the rats became hypertensive. We found that hypertensive/hypertrophic SHR showed a dampening of peak Bmal1 and Rev-erb expression in the liver, and the clock-controlled gene Pgc1α in the gastrocnemius. In addition, the core-clock gene Clock and the muscle-specific, clock-controlled gene Myod1, no longer maintained a circadian pattern of expression in gastrocnemius from the hypertensive SHR. These findings provide a framework to suggest a mechanism whereby chronic heart failure leads to skeletal muscle pathologies; prolonged dysregulation of the molecular clock in skeletal muscle results in altered Clock, Pgc1α and Myod1 expression which in turn leads to the mis-regulation of target genes important for mechanical and metabolic function of skeletal muscle.

  19. New Evo-SETI results about civilizations and molecular clock

    Science.gov (United States)

    Maccone, Claudio

    2017-01-01

    In two recent papers (Maccone 2013, 2014) as well as in the book (Maccone 2012), this author described the Evolution of life on Earth over the last 3.5 billion years as a lognormal stochastic process in the increasing number of living Species. In (Maccone 2012, 2013), the process used was `Geometric Brownian Motion' (GBM), largely used in Financial Mathematics (Black-Sholes models). The GBM mean value, also called `the trend', always is an exponential in time and this fact corresponds to the so-called `Malthusian growth' typical of population genetics. In (Maccone 2014), the author made an important generalization of his theory by extending it to lognormal stochastic processes having an arbitrary trend m L (t), rather than just a simple exponential trend as the GBM have. The author named `Evo-SETI' (Evolution and SETI) his theory inasmuch as it may be used not only to describe the full evolution of life on Earth from RNA to modern human societies, but also the possible evolution of life on exoplanets, thus leading to SETI, the current Search for ExtraTerrestrial Intelligence. In the Evo-SETI Theory, the life of a living being (let it be a cell or an animal or a human or a Civilization of humans or even an ET Civilization) is represented by a b-lognormal, i.e. a lognormal probability density function starting at a precise instant b (`birth') then increasing up to a peak-time p, then decreasing to a senility-time s (the descending inflexion point) and then continuing as a straight line down to the death-time d (`finite b-lognormal'). (1) Having so said, the present paper describes the further mathematical advances made by this author in 2014-2015, and is divided in two halves: Part One, devoted to new mathematical results about the History of Civilizations as b-lognormals, and (2) Part Two, about the applications of the Evo-SETI Theory to the Molecular Clock, well known to evolutionary geneticists since 50 years: the idea is that our EvoEntropy grows linearly in time

  20. Circadian oscillations of molecular clock components in the cerebellar cortex of the rat

    DEFF Research Database (Denmark)

    Rath, Martin Fredensborg; Rohde, Kristian; Møller, Morten

    2012-01-01

    these genes, Per1, Per2, Per3, Cry1, Arntl, Nr1d1, and Dbp were found to exhibit circadian rhythms in a sequential temporal manner similar to that of the SCN, but with several hours of delay. The results of lesion studies indicate that the molecular oscillatory profiles of Per1, Per2, and Cry1......The central circadian clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the circadian clockwork of the SCN constitutes a self-sustained autoregulatory feedback mechanism reflected by the rhythmic expression of clock genes. However...... in the cerebellum are controlled, though possibly indirectly, by the central clock of the SCN. These data support the presence of a circadian oscillator in the cortex of the rat cerebellum....

  1. Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleus.

    Science.gov (United States)

    Besing, Rachel C; Paul, Jodi R; Hablitz, Lauren M; Rogers, Courtney O; Johnson, Russell L; Young, Martin E; Gamble, Karen L

    2015-04-01

    The suprachiasmatic nucleus (SCN) drives and synchronizes daily rhythms at the cellular level via transcriptional-translational feedback loops comprising clock genes such as Bmal1 and Period (Per). Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, phosphorylates at least 5 core clock proteins and shows diurnal variation in phosphorylation state (inactivation) of the GSK3β isoform. Whether phosphorylation of the other primary isoform (GSK3α) varies across the subjective day-night cycle is unknown. The purpose of this study was to determine if the endogenous rhythm of GSK3 (α and β) phosphorylation is critical for rhythmic BMAL1 expression and normal amplitude and periodicity of the molecular clock in the SCN. Significant circadian rhythmicity of phosphorylated GSK3 (α and β) was observed in the SCN from wild-type mice housed in constant darkness for 2 weeks. Importantly, chronic activation of both GSK3 isoforms impaired rhythmicity of the GSK3 target BMAL1. Furthermore, chronic pharmacological inhibition of GSK3 with 20 µM CHIR-99021 enhanced the amplitude and shortened the period of PER2::luciferase rhythms in organotypic SCN slice cultures. These results support the model that GSK3 activity status is regulated by the circadian clock and that GSK3 feeds back to regulate the molecular clock amplitude in the SCN. © 2015 The Author(s).

  2. Nucleotide sequences of immunoglobulin eta genes of chimpanzee and orangutan: DNA molecular clock and hominoid evolution

    Energy Technology Data Exchange (ETDEWEB)

    Sakoyama, Y.; Hong, K.J.; Byun, S.M.; Hisajima, H.; Ueda, S.; Yaoita, Y.; Hayashida, H.; Miyata, T.; Honjo, T.

    1987-02-01

    To determine the phylogenetic relationships among hominoids and the dates of their divergence, the complete nucleotide sequences of the constant region of the immunoglobulin eta-chain (C/sub eta1/) genes from chimpanzee and orangutan have been determined. These sequences were compared with the human eta-chain constant-region sequence. A molecular clock (silent molecular clock), measured by the degree of sequence divergence at the synonymous (silent) positions of protein-encoding regions, was introduced for the present study. From the comparison of nucleotide sequences of ..cap alpha../sub 1/-antitrypsin and ..beta..- and delta-globulin genes between humans and Old World monkeys, the silent molecular clock was calibrated: the mean evolutionary rate of silent substitution was determined to be 1.56 x 10/sup -9/ substitutions per site per year. Using the silent molecular clock, the mean divergence dates of chimpanzee and orangutan from the human lineage were estimated as 6.4 +/- 2.6 million years and 17.3 +/- 4.5 million years, respectively. It was also shown that the evolutionary rate of primate genes is considerably slower than those of other mammalian genes.

  3. Non-Molecular-Clock-Like Evolution following Viral Origins in Homo sapiens

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    Wendy Mok

    2007-01-01

    Full Text Available Researchers routinely adopt molecular clock assumptions in conducting sequence analyses to estimate dates for viral origins in humans. We used computational methods to examine the extent to which this practice can result in inaccurate ‘retrodiction.’ Failing to account for dynamic molecular evolution can affect greatly estimating index case dates, resulting in an overestimated age for the SARS-CoV-human infection, for instance.

  4. Iterative Calibration: A Novel Approach for Calibrating the Molecular Clock Using Complex Geological Events.

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    Loeza-Quintana, Tzitziki; Adamowicz, Sarah J

    2018-02-01

    During the past 50 years, the molecular clock has become one of the main tools for providing a time scale for the history of life. In the era of robust molecular evolutionary analysis, clock calibration is still one of the most basic steps needing attention. When fossil records are limited, well-dated geological events are the main resource for calibration. However, biogeographic calibrations have often been used in a simplistic manner, for example assuming simultaneous vicariant divergence of multiple sister lineages. Here, we propose a novel iterative calibration approach to define the most appropriate calibration date by seeking congruence between the dates assigned to multiple allopatric divergences and the geological history. Exploring patterns of molecular divergence in 16 trans-Bering sister clades of echinoderms, we demonstrate that the iterative calibration is predominantly advantageous when using complex geological or climatological events-such as the opening/reclosure of the Bering Strait-providing a powerful tool for clock dating that can be applied to other biogeographic calibration systems and further taxa. Using Bayesian analysis, we observed that evolutionary rate variability in the COI-5P gene is generally distributed in a clock-like fashion for Northern echinoderms. The results reveal a large range of genetic divergences, consistent with multiple pulses of trans-Bering migrations. A resulting rate of 2.8% pairwise Kimura-2-parameter sequence divergence per million years is suggested for the COI-5P gene in Northern echinoderms. Given that molecular rates may vary across latitudes and taxa, this study provides a new context for dating the evolutionary history of Arctic marine life.

  5. The molecular clock of neutral evolution can be accelerated or slowed by asymmetric spatial structure.

    Science.gov (United States)

    Allen, Benjamin; Sample, Christine; Dementieva, Yulia; Medeiros, Ruben C; Paoletti, Christopher; Nowak, Martin A

    2015-02-01

    Over time, a population acquires neutral genetic substitutions as a consequence of random drift. A famous result in population genetics asserts that the rate, K, at which these substitutions accumulate in the population coincides with the mutation rate, u, at which they arise in individuals: K = u. This identity enables genetic sequence data to be used as a "molecular clock" to estimate the timing of evolutionary events. While the molecular clock is known to be perturbed by selection, it is thought that K = u holds very generally for neutral evolution. Here we show that asymmetric spatial population structure can alter the molecular clock rate for neutral mutations, leading to either Ku. Our results apply to a general class of haploid, asexually reproducing, spatially structured populations. Deviations from K = u occur because mutations arise unequally at different sites and have different probabilities of fixation depending on where they arise. If birth rates are uniform across sites, then K ≤ u. In general, K can take any value between 0 and Nu. Our model can be applied to a variety of population structures. In one example, we investigate the accumulation of genetic mutations in the small intestine. In another application, we analyze over 900 Twitter networks to study the effect of network topology on the fixation of neutral innovations in social evolution.

  6. The molecular clock of neutral evolution can be accelerated or slowed by asymmetric spatial structure.

    Directory of Open Access Journals (Sweden)

    Benjamin Allen

    2015-02-01

    Full Text Available Over time, a population acquires neutral genetic substitutions as a consequence of random drift. A famous result in population genetics asserts that the rate, K, at which these substitutions accumulate in the population coincides with the mutation rate, u, at which they arise in individuals: K = u. This identity enables genetic sequence data to be used as a "molecular clock" to estimate the timing of evolutionary events. While the molecular clock is known to be perturbed by selection, it is thought that K = u holds very generally for neutral evolution. Here we show that asymmetric spatial population structure can alter the molecular clock rate for neutral mutations, leading to either Ku. Our results apply to a general class of haploid, asexually reproducing, spatially structured populations. Deviations from K = u occur because mutations arise unequally at different sites and have different probabilities of fixation depending on where they arise. If birth rates are uniform across sites, then K ≤ u. In general, K can take any value between 0 and Nu. Our model can be applied to a variety of population structures. In one example, we investigate the accumulation of genetic mutations in the small intestine. In another application, we analyze over 900 Twitter networks to study the effect of network topology on the fixation of neutral innovations in social evolution.

  7. Molecular clocks and the human condition: approaching their characterization in human physiology and disease.

    Science.gov (United States)

    Fitzgerald, G A; Yang, G; Paschos, G K; Liang, X; Skarke, C

    2015-09-01

    Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function. © 2015 John Wiley & Sons Ltd.

  8. Testing the Molecular Clock Using the Best Fossil Record: Case Studies from the Planktic Foraminifera

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    Steel, B. A.; Kucera, M.; Darling, K.

    2004-12-01

    Criticism of molecular clock studies often centres on inadequate calibration and a perceived lack of correlation between reproductive isolation and recognisable morphological evolution. Since many major groups (e.g. birds, mammals, reptiles) have a poor fossil record, it is often difficult to test and refute these limitations. Planktic foraminifera represent an exception to this rule. Deep-sea sediments are super-abundant in foraminifera, and large numbers of specimens and occurrences are easily garnered from Ocean Drilling Programme cores. Planktic foraminifera therefore represent an ideal model group with which to test and refine molecular clock studies. Since the 1990AƒAøAøâ_sA¬Aøâ_zAøs, genetic sequences (principally 18S r-RNA) have been extracted from living planktic foraminifera, and a large genetic library has developed. Our study attempts to contextualise and test molecular data, particularly AƒAøAøâ_sA¬Agenetic studies have suggested that these two AƒAøAøâ_sA¬A<Å"super-speciesAƒAøAøâ_sA¬Aøâ_zAø in fact consist of a number of isolated forms, with contrasting ecologies and longevities, which in Recent and sub-Recent sediments can be distinguished either on the basis of pore ultrastructure (Gl. siphonifera) or test colouration (Gs. ruber). In both cases, molecular clock estimates are indicative of ancient (7-11 Ma) intra-species cryptic divergences, which seem to be considerably older than fossil dates. In particular, the calculated molecular split between the two forms of Gs. ruber (AƒAøAøâ_sA¬A<Å"whiteAƒAøAøâ_sA¬Aøâ_zAø and AƒAøAøâ_sA¬A<Å"pinkAƒAøAøâ_sA¬Aøâ_zAø) of around 11 Ma is considerably discordant with the fossil date of around 0.7 Ma. At first glance, this may appear to be a classic case of molecular over-estimation, often a feature of clock models, especially where, as in the foraminifera, substitution rates may vary widely. However, there is good reason to suspect that fossil range of the

  9. Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process.

    Science.gov (United States)

    Kishimoto, Toshihiko; Ying, Bei-Wen; Tsuru, Saburo; Iijima, Leo; Suzuki, Shingo; Hashimoto, Tomomi; Oyake, Ayana; Kobayashi, Hisaka; Someya, Yuki; Narisawa, Dai; Yomo, Tetsuya

    2015-07-01

    The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.

  10. Molecular Clock of Neutral Mutations in a Fitness-Increasing Evolutionary Process.

    Directory of Open Access Journals (Sweden)

    Toshihiko Kishimoto

    2015-07-01

    Full Text Available The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution.

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

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    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.

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

    Science.gov (United States)

    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.

  13. Beyond fossil calibrations: Realities of molecular clock practices in evolutionary biology

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    Christy Anna Hipsley

    2014-05-01

    Full Text Available Molecular-based divergence dating methods, or molecular clocks, are the primary neontological tool for estimating the temporal origins of clades. While the appropriate use of vertebrate fossils as external clock calibrations has stimulated heated discussions in the paleontological community, less attention has been given to the quality and implementation of other calibration types. In lieu of appropriate fossils, many studies rely on alternative sources of age constraints based on geological events, substitution rates and heterochronous sampling, as well as dates secondarily derived from previous analyses. To illustrate the breadth and frequency of calibration types currently employed, we conducted a literature survey of over 600 articles published from 2007 to 2013. Over half of all analyses implemented one or more fossil dates as constraints, followed by geological events and secondary calibrations (15% each. Vertebrate taxa were subjects of nearly half of all studies, while invertebrates and plants together accounted for 43%, followed by viruses, protists and fungi (3% each. Current patterns in calibration practices were disproportionate to the number of discussions on their proper use, particularly regarding plants and secondarily derived dates, which are both relatively neglected. Based on our survey, we provide a comprehensive overview of the latest approaches in clock calibration, and outline strengths and weaknesses associated with each. This critique should serve as a call to action for researchers across multiple communities, particularly those working on clades for which fossil records are poor, to develop their own guidelines regarding selection and implementation of alternative calibration types. This issue is particularly relevant now, as time-calibrated phylogenies are used for more than dating evolutionary origins, but often serve as the backbone of investigations into biogeography, diversity dynamics and rates of phenotypic

  14. The rhythm of feeding : Effect of nutrients on metabolism and the molecular clock

    NARCIS (Netherlands)

    Oosterman, J.E.

    2017-01-01

    This thesis describes studies we performed to assess the relationship between nutrients and the circadian clock. We assessed the effects of sugar and fatty acids on the daily rhythmicity of hepatic clock genes and whole-body metabolism in vivo, and on circadian rhythmicity of clock genes in vitro.

  15. Dating the Time of Origin of Major Clades: Molecular Clocks and the Fossil Record

    Science.gov (United States)

    Smith, Andrew B.; Peterson, Kevin J.

    Molecular and paleontological data provide independent means of estimating when groups of organisms evolved in the geological past, but neither approach can be considered straightforward. The single most fundamental obstacle to developing an accurate estimate of times of origination from gene sequence data is variation in rates of molecular evolution, both through time and among lineages. Although various techniques have been proposed to circumvent this problem, none unambiguously allow the components of time and rate to be separated. Furthermore, problems of establishing accurate calibration points, correctly rooted phylogenies, and accurate estimates of branch length remain formidable. Conversely, paleontological dates fix only the latest possible time of divergence, and so probabilistic methods are required to set a lower boundary on origination dates. Realistic confidence intervals that take preservational biases into account are only just becoming available. Although molecular and paleontological approaches to dating often agree reasonably well, there are two notable areas of disagreement; when mammal and bird orders originated and when the major phyla originated. The discrepancy in dating bird/mammal ordinal origins probably reflects a global rock-record bias. Paleontological sampling in the Late Cretaceous is still too restricted geographically to draw any firm conclusions about the existence of a pre-Tertiary record for modern orders of bird or mammal from anywhere other than North America. Dating the time of origin of phyla is more complicated, and is confounded by both preservational biases and problems of molecular clock estimation.

  16. Divergence time estimates of mammals from molecular clocks and fossils: relevance of new fossil finds from India.

    Science.gov (United States)

    Prasad, G V R

    2009-11-01

    This paper presents a brief review of recent advances in the classification of mammals at higher levels using fossils and molecular clocks. It also discusses latest fossil discoveries from the Cretaceous - Eocene (66-55 m.y.) rocks of India and their relevance to our current understanding of placental mammal origins and diversifications.

  17. Evolutionary history of genus Macrobrachium inferred from mitochondrial markers: a molecular clock approach.

    Science.gov (United States)

    Jose, Deepak; Harikrishnan, Mahadevan

    2018-04-17

    Caridea, an infraorder of shrimps coming under Pleocyemata was first reported from the oceans before 417 million years followed by their radiation recorded during the Permian period. Hitherto, about 3877 extant caridean species were accounted within which one quarter constitute freshwater species. Freshwater prawns of genus Macrobrachium (Infraorder Caridea; Family Palaemonidae), with more than 240 species are inhabitants of diverse aquatic habitats like coastal lagoons, lakes, tropical streams, ponds and rivers. Previous studies on Macrobrachium relied on the highly variable morphological characters which were insufficient for accurate diagnosis of natural species groups. Present study focuses on the utility of molecular markers (viz. COI and 16S rRNA) for resolving the evolutionary history of genus Macrobrachium using a combination of phylogeny and timescale components. It is for the first time a molecular clock approach had been carried out towards genus Macrobrachium in a broad aspect with the incorporation of congeners inhabiting diverse geographical realms including endemic species M. striatum from South West coast of India. Molecular results obtained revealed the phylogenetic relationships between congeners of genus Macrobrachium at intra/inter-continental level along with the corresponding evolutionary time estimates.

  18. Trapped ultracold molecular ions: candidates for an optical molecular clock for a fundamental physics mission in space

    Science.gov (United States)

    Roth, B.; Koelemeij, J.; Daerr, H.; Ernsting, I.; Jorgensen, S.; Okhapkin, M.; Wicht, A.; Nevsky, A.; Schiller, S.

    2017-11-01

    Narrow ro-vibrational transitions in ultracold molecules are excellent candidates for frequency references in the near-IR to visible spectral domain and interesting systems for fundamental tests of physics, in particular for a satellite test of the gravitational redshift of clocks. We have performed laser spectroscopy of several ro-vibrational overtone transitions υ = 0 → υ = 4 in HD+ ions at around 1.4 μm. 1+1 REMPD was used as a detection method, followed by measurement of the number of remaining molecules. The molecular ions were stored in a linear radiofrequency trap and cooled to millikelvin temperatures, by sympathetic cooling using laser-cooled Be+ ions simultaneously stored in the same trap.

  19. 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.

  20. The circadian molecular clock regulates adult hippocampal neurogenesis by controlling the timing of cell-cycle entry and exit.

    Science.gov (United States)

    Bouchard-Cannon, Pascale; Mendoza-Viveros, Lucia; Yuen, Andrew; Kærn, Mads; Cheng, Hai-Ying M

    2013-11-27

    The subgranular zone (SGZ) of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs) that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adult SGZ express molecular-clock components and proliferate in a rhythmic fashion. The clock proteins PERIOD2 and BMAL1 are critical for proper control of neurogenesis. The absence of PERIOD2 abolishes the gating of cell-cycle entrance of QNPs, whereas genetic ablation of bmal1 results in constitutively high levels of proliferation and delayed cell-cycle exit. We use mathematical model simulations to show that these observations may arise from clock-driven expression of a cell-cycle inhibitor that targets the cyclin D/Cdk4-6 complex. Our findings may have broad implications for the circadian clock in timing cell-cycle events of other stem cell populations throughout the body. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  1. The Circadian Molecular Clock Regulates Adult Hippocampal Neurogenesis by Controlling the Timing of Cell-Cycle Entry and Exit

    Directory of Open Access Journals (Sweden)

    Pascale Bouchard-Cannon

    2013-11-01

    Full Text Available The subgranular zone (SGZ of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adult SGZ express molecular-clock components and proliferate in a rhythmic fashion. The clock proteins PERIOD2 and BMAL1 are critical for proper control of neurogenesis. The absence of PERIOD2 abolishes the gating of cell-cycle entrance of QNPs, whereas genetic ablation of bmal1 results in constitutively high levels of proliferation and delayed cell-cycle exit. We use mathematical model simulations to show that these observations may arise from clock-driven expression of a cell-cycle inhibitor that targets the cyclin D/Cdk4-6 complex. Our findings may have broad implications for the circadian clock in timing cell-cycle events of other stem cell populations throughout the body.

  2. Molecular mechanism of strict substrate specificity of an extradiol dioxygenase, DesB, derived from Sphingobium sp. SYK-6.

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    Keisuke Sugimoto

    Full Text Available DesB, which is derived from Sphingobium sp. SYK-6, is a type II extradiol dioxygenase that catalyzes a ring opening reaction of gallate. While typical extradiol dioxygenases show broad substrate specificity, DesB has strict substrate specificity for gallate. The substrate specificity of DesB seems to be required for the efficient growth of S. sp. SYK-6 using lignin-derived aromatic compounds. Since direct coordination of hydroxyl groups of the substrate to the non-heme iron in the active site is a critical step for the catalytic reaction of the extradiol dioxygenases, the mechanism of the substrate recognition and coordination of DesB was analyzed by biochemical and crystallographic methods. Our study demonstrated that the direct coordination between the non-heme iron and hydroxyl groups of the substrate requires a large shift of the Fe (II ion in the active site. Mutational analysis revealed that His124 and His192 in the active site are essential to the catalytic reaction of DesB. His124, which interacts with OH (4 of the bound gallate, seems to contribute to proper positioning of the substrate in the active site. His192, which is located close to OH (3 of the gallate, is likely to serve as the catalytic base. Glu377' interacts with OH (5 of the gallate and seems to play a critical role in the substrate specificity. Our biochemical and structural study showed the substrate recognition and catalytic mechanisms of DesB.

  3. Subfemtosecond electron dynamics of H{sub 2} in strong fields or the quest for the molecular clock

    Energy Technology Data Exchange (ETDEWEB)

    Staudte, A.

    2005-07-01

    In this work we have studied experimentally and theoretically hydrogen and deuterium molecules in strong laser fields. We wanted to demonstrate that control of dynamical processes on the time scale below a single laser cycle (2.7 fs) can be achieved even without using attosecond pulses just by employing the advanced experimental technique COLTRIMS. In order to do this, we have pursued two goals: 1. To examine, whether laser steered electron wavepackets can be used for laser induced electron diffraction (LIED) on molecules. 2. To demonstrate, that the double ionization of H{sub 2} can be followed with sub laser cycle temporal resolution (the molecular clock). Laser induced electron diffraction needs linearly polarized light since its mechanism relies on rescattering of the ionized electron in the molecular potential. With rescattering occurring within a few hundred attoseconds, LIED is really a process of attosecond physics. In principle, two extreme scattering geometries are possible for a homonuclear diatomic molecule like H{sub 2}: the perpendicular geometry, which corresponds to the classical double slit experiment where the electron microbunch is steered transversely to the molecular axis, and the tangential geometry with the electron moving parallel to the molecular axis. Experimental restrictions prevented us to investigate the perpendicular geometry. The molecular clock, on the other hand, employs circularly polarized light to map the absolute phase of the laser electric field onto the spatial direction of the electron momentum. Thereby, a full laser cycle is mapped onto 360 in momentum space. Thus, different electron ejection angles in the laboratory frame correspond to different ejection times. Together with the correlated kinetic energy release of the Coulomb exploding molecules an unambiguous clock running from 0-8 fs with a few 100 as resolution can be envisioned. In direct relation to this experiment, we studied the influence of the long range

  4. Transcriptome Profiling of the Lungs Reveals Molecular Clock Genes Expression Changes after Chronic Exposure to Ambient Air Particles

    Directory of Open Access Journals (Sweden)

    Pengcheng Song

    2017-01-01

    Full Text Available The symptoms of asthma, breathlessness, insomnia, etc. all have relevance to pulmonary rhythmic disturbances. Epidemiology and toxicology studies have demonstrated that exposure to ambient air particles can result in pulmonary dysfunction. However, there are no data directly supporting a link between air pollution and circadian rhythm disorder. In the present study, we found that breathing highly polluted air resulted in changes of the molecular clock genes expression in lung by transcriptome profiling analyses in a rodent model. Compared to those exposed to filtered air, in both pregnant and offspring rats in the unfiltered group, key clock genes (Per1, Per2, Per3, Rev-erbα and Dbp expression level decreased and Bmal1 expression level increased. In both rat dams and their offspring, after continuous exposure to unfiltered air, we observed significant histologic evidence for both perivascular and peribronchial inflammation, increased tissue and systemic oxidative stress in the lungs. Our results suggest that chronic exposure to particulate matter can induce alterations of clock genes expression, which could be another important pathway for explaining the feedbacks of ambient particle exposure in addition to oxidative stress and inflammation.

  5. Comparison of different strategies for using fossil calibrations to generate the time prior in Bayesian molecular clock dating.

    Science.gov (United States)

    Barba-Montoya, Jose; Dos Reis, Mario; Yang, Ziheng

    2017-09-01

    Fossil calibrations are the utmost source of information for resolving the distances between molecular sequences into estimates of absolute times and absolute rates in molecular clock dating analysis. The quality of calibrations is thus expected to have a major impact on divergence time estimates even if a huge amount of molecular data is available. In Bayesian molecular clock dating, fossil calibration information is incorporated in the analysis through the prior on divergence times (the time prior). Here, we evaluate three strategies for converting fossil calibrations (in the form of minimum- and maximum-age bounds) into the prior on times, which differ according to whether they borrow information from the maximum age of ancestral nodes and minimum age of descendent nodes to form constraints for any given node on the phylogeny. We study a simple example that is analytically tractable, and analyze two real datasets (one of 10 primate species and another of 48 seed plant species) using three Bayesian dating programs: MCMCTree, MrBayes and BEAST2. We examine how different calibration strategies, the birth-death process, and automatic truncation (to enforce the constraint that ancestral nodes are older than descendent nodes) interact to determine the time prior. In general, truncation has a great impact on calibrations so that the effective priors on the calibration node ages after the truncation can be very different from the user-specified calibration densities. The different strategies for generating the effective prior also had considerable impact, leading to very different marginal effective priors. Arbitrary parameters used to implement minimum-bound calibrations were found to have a strong impact upon the prior and posterior of the divergence times. Our results highlight the importance of inspecting the joint time prior used by the dating program before any Bayesian dating analysis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Influence of Tertiary paleoenvironmental changes on the diversification of South American mammals: a relaxed molecular clock study within xenarthrans

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    Vizcaíno Sergio F

    2004-04-01

    Full Text Available Abstract Background Comparative genomic data among organisms allow the reconstruction of their phylogenies and evolutionary time scales. Molecular timings have been recently used to suggest that environmental global change have shaped the evolutionary history of diverse terrestrial organisms. Living xenarthrans (armadillos, anteaters and sloths constitute an ideal model for studying the influence of past environmental changes on species diversification. Indeed, extant xenarthran species are relicts from an evolutionary radiation enhanced by their isolation in South America during the Tertiary era, a period for which major climate variations and tectonic events are relatively well documented. Results We applied a Bayesian approach to three nuclear genes in order to relax the molecular clock assumption while accounting for differences in evolutionary dynamics among genes and incorporating paleontological uncertainties. We obtained a molecular time scale for the evolution of extant xenarthrans and other placental mammals. Divergence time estimates provide substantial evidence for contemporaneous diversification events among independent xenarthran lineages. This correlated pattern of diversification might possibly relate to major environmental changes that occurred in South America during the Cenozoic. Conclusions The observed synchronicity between planetary and biological events suggests that global change played a crucial role in shaping the evolutionary history of extant xenarthrans. Our findings open ways to test this hypothesis further in other South American mammalian endemics like hystricognath rodents, platyrrhine primates, and didelphid marsupials.

  7. Reconstructing genealogies of serial samples under the assumption of a molecular clock using serial-sample UPGMA.

    Science.gov (United States)

    Drummond, A; Rodrigo, A G

    2000-12-01

    Reconstruction of evolutionary relationships from noncontemporaneous molecular samples provides a new challenge for phylogenetic reconstruction methods. With recent biotechnological advances there has been an increase in molecular sequencing throughput, and the potential to obtain serial samples of sequences from populations, including rapidly evolving pathogens, is fast being realized. A new method called the serial-sample unweighted pair grouping method with arithmetic means (sUPGMA) is presented that reconstructs a genealogy or phylogeny of sequences sampled serially in time using a matrix of pairwise distances. The resulting tree depicts the terminal lineages of each sample ending at a different level consistent with the sample's temporal order. Since sUPGMA is a variant of UPGMA, it will perform best when sequences have evolved at a constant rate (i.e., according to a molecular clock). On simulated data, this new method performs better than standard cluster analysis under a variety of longitudinal sampling strategies. Serial-sample UPGMA is particularly useful for analysis of longitudinal samples of viruses and bacteria, as well as ancient DNA samples, with the minimal requirement that samples of sequences be ordered in time.

  8. Strict confluent drawing

    NARCIS (Netherlands)

    Eppstein, D.; Holten, D.H.R.; Löffler, M.; Nöllenburg, M.; Speckmann, B.; Verbeek, K.A.B.

    2013-01-01

    We define strict confluent drawing, a form of confluent drawing in which the existence of an edge is indicated by the presence of a smooth path through a system of arcs and junctions (without crossings), and in which such a path, if it exists, must be unique. We prove that it is NP-complete to

  9. Strict confluent drawing

    NARCIS (Netherlands)

    Eppstein, D.; Holten, D.; Löffler, M.; Nöllenburg, M.; Speckmann, B.; Verbeek, K.A.B.

    2016-01-01

    We define strict confluent drawing, a form of confluent drawing in which the existence of an edge is indicated by the presence of a smooth path through a system of arcs and junctions (without crossings), and in which such a path, if it exists, must be unique. We prove that it is NP-complete to

  10. Quine's "Strictly Vegetarian" Analyticity

    NARCIS (Netherlands)

    Decock, L.B.

    2017-01-01

    I analyze Quine’s later writings on analyticity from a linguistic point of view. In Word and Object Quine made room for a “strictly vegetarian” notion of analyticity. In later years, he developed this notion into two more precise notions, which I have coined “stimulus analyticity” and “behaviorist

  11. Functional molecular analysis of a circadian clock gene timeless promoter from the drosophilid fly Chymomyza costata

    Czech Academy of Sciences Publication Activity Database

    Kobelková, Alena; Bajgar, Adam; Doležel, David

    2010-01-01

    Roč. 25, č. 6 (2010), s. 399-409 ISSN 0748-7304 R&D Projects: GA ČR GP204/08/P579; GA ČR(CZ) GA204/07/1032; GA AV ČR IAA500960802 Institutional research plan: CEZ:AV0Z50070508 Keywords : timeless promoter * E-box * Chymomyza costata Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.309, year: 2010

  12. Evolutionary history of the PER3 variable number of tandem repeats (VNTR): idiosyncratic aspect of primate molecular circadian clock.

    Science.gov (United States)

    Sabino, Flávia Cal; Ribeiro, Amanda Oliveira; Tufik, Sérgio; Torres, Laila Brito; Oliveira, José Américo; Mello, Luiz Eugênio Araújo Moraes; Cavalcante, Jeferson Souza; Pedrazzoli, Mario

    2014-01-01

    The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR) locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  13. Evolutionary history of the PER3 variable number of tandem repeats (VNTR: idiosyncratic aspect of primate molecular circadian clock.

    Directory of Open Access Journals (Sweden)

    Flávia Cal Sabino

    Full Text Available The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  14. Winding up the molecular clock in the genus Carabus (Coleoptera: Carabidae: assessment of methodological decisions on rate and node age estimation

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    Andújar Carmelo

    2012-03-01

    Full Text Available Abstract Background Rates of molecular evolution are known to vary across taxa and among genes, and this requires rate calibration for each specific dataset based on external information. Calibration is sensitive to evolutionary model parameters, partitioning schemes and clock model. However, the way in which these and other analytical aspects affect both the rates and the resulting clade ages from calibrated phylogenies are not yet well understood. To investigate these aspects we have conducted calibration analyses for the genus Carabus (Coleoptera, Carabidae on five mitochondrial and four nuclear DNA fragments with 7888 nt total length, testing different clock models and partitioning schemes to select the most suitable using Bayes Factors comparisons. Results We used these data to investigate the effect of ambiguous character and outgroup inclusion on both the rates of molecular evolution and the TMRCA of Carabus. We found considerable variation in rates of molecular evolution depending on the fragment studied (ranging from 5.02% in cob to 0.26% divergence/My in LSU-A, but also on analytical conditions. Alternative choices of clock model, partitioning scheme, treatment of ambiguous characters, and outgroup inclusion resulted in rate increments ranging from 28% (HUWE1 to 1000% (LSU-B and ITS2 and increments in the TMRCA of Carabus ranging from 8.4% (cox1-A to 540% (ITS2. Results support an origin of the genus Carabus during the Oligocene in the Eurasian continent followed by a Miocene differentiation that originated all main extant lineages. Conclusions The combination of several genes is proposed as the best strategy to minimise both the idiosyncratic behaviors of individual markers and the effect of analytical aspects in rate and age estimations. Our results highlight the importance of estimating rates of molecular evolution for each specific dataset, selecting for optimal clock and partitioning models as well as other methodological issues

  15. A molecular clock dates the common ancestor of European-type porcine reproductive and respiratory syndrome virus at more than 10 years before the emergence of disease

    DEFF Research Database (Denmark)

    Forsberg, Roald; Oleksiewicz, Martin B.; Krabbe Petersen, Anne Mette

    2001-01-01

    an accurate molecular clock for the European PRRSV ORF 3 gene, place the root in the genealogy, estimate the rate of nucleotide substitution, and date the most recent common viral ancestor of the data set to 1979; more than 10 years before the onset of the European epidemic. Based on these findings, we...... conclude that PRRSV virus most likely entered the pig population some time before the epidemic emergence of the virus, and hence, that emergence of European-type PRRSV is not the result of a recent species transmission event. Together, our results show that ORF3 sequencing is a valuable epidemiologic tool...... for examining the emergence and spread of PRRSV in Europe. As such, the panel of well-characterized and highly divergent ORF3 sequences described in this study provides a reference point for future molecular epidemiologic studies....

  16. Species Protection in the European Union : How Strict is Strict?

    NARCIS (Netherlands)

    Schoukens, Hendrik; Bastmeijer, Kees; Born et al., Charles-Hubert

    2015-01-01

    European Union law to protect wild species of plants and animals is generally considered as ‘strict’. Opponents of nature conservation law often pick the species protection components of the EU Bird Directive and Habitat Directive as a prime example of an unnecessary strict regulatory scheme that

  17. Efficient Strictness Analysis of Haskell

    DEFF Research Database (Denmark)

    Jensen, Kristian Damm; Hjæresen, Peter; Rosendahl, Mads

    1994-01-01

    Strictness analysis has been a living field of investigation since Mycroft's original work in 1980, and is getting increasingly significant with the still wider use of lazy functional programming languages. This paper focuses on an actual implementation of a strictness analyser for Haskell....... The analyser uses abstract interpretation with chaotic fixpoint iteration. The demand-driven nature of this iteration technique allows us to use large domains including function domains in the style of Burn et al. 1986 and Wadler 87 and retain reasonable efficiency. The implementation, furthermore, allows us...

  18. Relativistic Ideal Clock

    OpenAIRE

    Bratek, Łukasz

    2015-01-01

    Two particularly simple ideal clocks exhibiting intrinsic circular motion with the speed of light and opposite spin alignment are described. The clocks are singled out by singularities of an inverse Legendre transformation for relativistic rotators of which mass and spin are fixed parameters. Such clocks work always the same way, no matter how they move. When subject to high accelerations or falling in strong gravitational fields of black holes, the clocks could be used to test the clock hypo...

  19. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Flexible or Strict Taxonomic Organization?

    DEFF Research Database (Denmark)

    Glückstad, Fumiko Kano; Mørup, Morten

    2012-01-01

    This work compares methods for constructing feature-based ontologies that are supposed to be used for culturally-specific knowledge transfer. The methods to be compared are the Terminological Ontology (TO) [1], a method of constructing ontology based on strict principles and rules, and the Infinite...

  1. Circadian clocks, epigenetics, and cancer

    KAUST Repository

    Masri, Selma; Kinouchi, Kenichiro; Sassone-Corsi, Paolo

    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.

  2. Strictness Analysis for Attribute Grammars

    DEFF Research Database (Denmark)

    Rosendahl, Mads

    1992-01-01

    interpretation of attribute grammars. The framework is used to construct a strictness analysis for attribute grammars. Results of the analysis enable us to transform an attribute grammar such that attributes are evaluated during parsing, if possible. The analysis is proved correct by relating it to a fixpoint...... semantics for attribute grammars. An implementation of the analysis is discussed and some extensions to the analysis are mentioned....

  3. The trend to get strict

    International Nuclear Information System (INIS)

    Clarke, Chris.

    1997-01-01

    Most policy makers in the USA and Europe are committed to strict environmental liability. The polluter pays principle is seen as popular with voters and easy to defend. For the energy sector, encompassing everything from disused gas works and coal mines to refineries, tank farms and filling stations, the cost of cleaning up old sites can be huge. Within the policy commitment to strict liability there are some issues up for negotiation, however. These include such things as: available defences; the burden of proof; mechanisms for sharing liability at multi-party sites; funding of orphan shares; the protection afforded to lenders. Most governments have shown some flexibility on these issues and some examples from the USA are given. Nevertheless, in Europe the momentum towards comprehensive strict liability regimes seems unrelenting. In the Member states of the European Union, liability laws are either already in place or new laws are in preparation. The European Commission is working on proposals for an EU-wide environmental liability regime but there are formidable obstacles to overcome if it is to become EU law. In the meanwhile, the process of trying to reach agreement at an EU level is likely to strengthen the legislative drive at national level. (UK)

  4. Novel transcriptional networks regulated by CLOCK in human neurons.

    Science.gov (United States)

    Fontenot, Miles R; Berto, Stefano; Liu, Yuxiang; Werthmann, Gordon; Douglas, Connor; Usui, Noriyoshi; Gleason, Kelly; Tamminga, Carol A; Takahashi, Joseph S; Konopka, Genevieve

    2017-11-01

    The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks is driven by hub genes with human-specific patterns of expression. These data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function. © 2017 Fontenot et al.; Published by Cold Spring Harbor Laboratory Press.

  5. 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...

  6. 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...

  7. 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,...

  8. Egyptian "Star Clocks"

    Science.gov (United States)

    Symons, Sarah

    Diagonal, transit, and Ramesside star clocks are tables of astronomical information occasionally found in ancient Egyptian temples, tombs, and papyri. The tables represent the motions of selected stars (decans and hour stars) throughout the Egyptian civil year. Analysis of star clocks leads to greater understanding of ancient Egyptian constellations, ritual astronomical activities, observational practices, and pharaonic chronology.

  9. Biological Clocks & Circadian Rhythms

    Science.gov (United States)

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian…

  10. Do Caucasian and Asian clocks tick differently?

    Directory of Open Access Journals (Sweden)

    A.A. Barbosa

    Full Text Available The Period 3 and Clock genes are important components of the mammalian molecular circadian system. Studies have shown association between polymorphisms in these clock genes and circadian phenotypes in different populations. Nevertheless, differences in the pattern of allele frequency and genotyping distribution are systematically observed in studies with different ethnic groups. To investigate and compare the pattern of distribution in a sample of Asian and Caucasian populations living in Brazil, we evaluated two well-studied polymorphisms in the clock genes: a variable number of tandem repeats (VNTR in PER3 and a single nucleotide polymorphism (SNP in CLOCK. The aim of this investigation was to search for clues about human evolutionary processes related to circadian rhythms. We selected 109 Asian and 135 Caucasian descendants. The frequencies of the shorter allele (4 repeats in the PER3 gene and the T allele in the CLOCK gene among Asians (0.86 and 0.84, respectively were significantly higher than among Caucasians (0.69 and 0.71, respectively. Our results directly confirmed the different distribution of these polymorphisms between the Asian and Caucasian ethnic groups. Given the genetic differences found between groups, two points became evident: first, ethnic variations may have implications for the interpretation of results in circadian rhythm association studies, and second, the question may be raised about which evolutionary conditions shaped these genetic clock variations.

  11. Clock gene variation in Tachycineta swallows.

    Science.gov (United States)

    Dor, Roi; Cooper, Caren B; Lovette, Irby J; Massoni, Viviana; Bulit, Flor; Liljesthrom, Marcela; Winkler, David W

    2012-01-01

    Many animals use photoperiod cues to synchronize reproduction with environmental conditions and thereby improve their reproductive success. The circadian clock, which creates endogenous behavioral and physiological rhythms typically entrained to photoperiod, is well characterized at the molecular level. Recent work provided evidence for an association between Clock poly-Q length polymorphism and latitude and, within a population, an association with the date of laying and the length of the incubation period. Despite relatively high overall breeding synchrony, the timing of clutch initiation has a large impact on the fitness of swallows in the genus Tachycineta. We compared length polymorphism in the Clock poly-Q region among five populations from five different Tachycineta species that breed across a hemisphere-wide latitudinal gradient (Fig. 1). Clock poly-Q variation was not associated with latitude; however, there was an association between Clock poly-Q allele diversity and the degree of clutch size decline within breeding seasons. We did not find evidence for an association between Clock poly-Q variation and date of clutch initiation in for any of the five Tachycineta species, nor did we found a relationship between incubation duration and Clock genotype. Thus, there is no general association between latitude, breeding phenology, and Clock polymorphism in this clade of closely related birds.Figure 1Photos of Tachycineta swallows that were used in this study: A) T. bicolor from Ithaca, New York, B) T. leucorrhoa from Chascomús, Argentina, C) T. albilinea from Hill Bank, Belize, D) T. meyeni from Puerto Varas, Chile, and E) T. thalassina from Mono Lake, California, Photographers: B: Valentina Ferretti; A, C-E: David Winkler.

  12. Intact interval timing in circadian CLOCK mutants.

    Science.gov (United States)

    Cordes, Sara; Gallistel, C R

    2008-08-28

    While progress has been made in determining the molecular basis for the circadian clock, the mechanism by which mammalian brains time intervals measured in seconds to minutes remains a mystery. An obvious question is whether the interval-timing mechanism shares molecular machinery with the circadian timing mechanism. In the current study, we trained circadian CLOCK +/- and -/- mutant male mice in a peak-interval procedure with 10 and 20-s criteria. The mutant mice were more active than their wild-type littermates, but there were no reliable deficits in the accuracy or precision of their timing as compared with wild-type littermates. This suggests that expression of the CLOCK protein is not necessary for normal interval timing.

  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. Finite Metric Spaces of Strictly Negative Type

    DEFF Research Database (Denmark)

    Hjorth, Poul; Lisonek, P.; Markvorsen, Steen

    1998-01-01

    of Euclidean spaces. We prove that, if the distance matrix is both hypermetric and regular, then it is of strictly negative type. We show that the strictly negative type finite subspaces of spheres are precisely those which do not contain two pairs of antipodal points. In connection with an open problem raised...

  15. Extremely strict ideals in Banach spaces

    Indian Academy of Sciences (India)

    Abstract. Motivated by the notion of an ideal introduced by Godefroy et al. (Stu- dia Math. 104 (1993) 13–59), in this article, we introduce and study the notion of an extremely strict ideal. For a Poulsen simplex K, we show that the space of affine contin- uous functions on K is an extremely strict ideal in the space of continuous ...

  16. Atomic and gravitational clocks

    International Nuclear Information System (INIS)

    Canuto, V.M.; City Coll., New York; Goldman, I.

    1982-01-01

    Atomic and gravitational clocks are governed by the laws of electrodynamics and gravity respectively. While the strong equivalence principle (SEP) assumes that the two clocks have been synchronous at all times, recent planetary data seem to suggest a possible violation of the SEP. Past analysis of the implications of an SEP violation on different physical phenomena revealed no disagreement. However, these studies assumed that the two different clocks can be consistently constructed within the framework. The concept of scale invariance, and the physical meaning of different systems of units, are now reviewed and the construction of two clocks that do not remain synchronous-whose rates are related by a non-constant function βsub(a)-is demonstrated. The cosmological character of βsub(a) is also discussed. (author)

  17. Clock synchronization and dispersion

    International Nuclear Information System (INIS)

    Giovannetti, Vittorio; Lloyd, Seth; Maccone, Lorenzo; Wong, Franco N C

    2002-01-01

    We present a method to defeat effects of dispersion of timing signals when synchronizing clocks. It is based on the recently proposed 'conveyor belt synchronization' scheme and on the quantum dispersion cancellation effect

  18. The circadian oscillator of the cerebral cortex: molecular, biochemical and behavioral effects of deleting the Arntl clock gene in cortical neurons

    DEFF Research Database (Denmark)

    Bering, Tenna; Carstensen, Mikkel Bloss; Wörtwein, Gitta

    2018-01-01

    for normal function of the cortical circadian oscillator. Daily rhythms in running activity and temperature were not influenced, whereas the resynchronization response to experimental jet-lag exhibited minor though significant differences between genotypes. The tail-suspension test revealed significantly...... prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect...... that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry....

  19. FUNCTIONAL IMPLICATIONS OF THE CLOCK 3111T/C SINGLE-NUCLEOTIDE POLYMORPHISM

    Directory of Open Access Journals (Sweden)

    Angela Renee Ozburn

    2016-04-01

    Full Text Available Circadian rhythm disruptions are prominently associated with Bipolar Disorder (BD. Circadian rhythms are regulated by the molecular clock, a family of proteins that function together in a transcriptional-translational feedback loop. The CLOCK protein is a key transcription factor of this feedback loop, and previous studies have found that manipulations of the Clock gene are sufficient to produce manic-like behavior in mice (Roybal et al., 2007. The Clock 3111T/C single-nucleotide polymorphism (SNP; rs1801260 is a genetic variation of the human Clock gene that is significantly associated with increased frequency of manic episodes in BD patients (Benedetti et al., 2003. The 3111T/C SNP is located in the 3’ untranslated region of the Clock gene. In this study, we sought to examine the functional implications of the human Clock 3111T/C SNP by transfecting a mammalian cell line (mouse embryonic fibroblasts isolated from Clock -/- knockout mice with pcDNA plasmids containing the human Clock gene with either the T or C SNP at position 3111. We then measured circadian gene expression over a 24 hour time period. We found that the Clock3111C SNP resulted in higher mRNA levels than the Clock 3111T SNP. Further, we found that Per2, a transcriptional target of CLOCK, was also more highly expressed with Clock 3111C expression, indicating the 3’UTR SNP affects the expression, function and stability of Clock mRNA.

  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. Atomic clocks for geodesy

    Science.gov (United States)

    Mehlstäubler, Tanja E.; Grosche, Gesine; Lisdat, Christian; Schmidt, Piet O.; Denker, Heiner

    2018-06-01

    We review experimental progress on optical atomic clocks and frequency transfer, and consider the prospects of using these technologies for geodetic measurements. Today, optical atomic frequency standards have reached relative frequency inaccuracies below 10‑17, opening new fields of fundamental and applied research. The dependence of atomic frequencies on the gravitational potential makes atomic clocks ideal candidates for the search for deviations in the predictions of Einstein’s general relativity, tests of modern unifying theories and the development of new gravity field sensors. In this review, we introduce the concepts of optical atomic clocks and present the status of international clock development and comparison. Besides further improvement in stability and accuracy of today’s best clocks, a large effort is put into increasing the reliability and technological readiness for applications outside of specialized laboratories with compact, portable devices. With relative frequency uncertainties of 10‑18, comparisons of optical frequency standards are foreseen to contribute together with satellite and terrestrial data to the precise determination of fundamental height reference systems in geodesy with a resolution at the cm-level. The long-term stability of atomic standards will deliver excellent long-term height references for geodetic measurements and for the modelling and understanding of our Earth.

  2. Hyperbolic spaces are of strictly negative type

    DEFF Research Database (Denmark)

    Hjorth, Poul G.; Kokkendorff, Simon L.; Markvorsen, Steen

    2002-01-01

    We study finite metric spaces with elements picked from, and distances consistent with, ambient Riemannian manifolds. The concepts of negative type and strictly negative type are reviewed, and the conjecture that hyperbolic spaces are of strictly negative type is settled, in the affirmative....... The technique of the proof is subsequently applied to show that every compact manifold of negative type must have trivial fundamental group, and to obtain a necessary criterion for product manifolds to be of negative type....

  3. Strictly diagonal holomorphic functions on Banach spaces

    Directory of Open Access Journals (Sweden)

    O. I. Fedak

    2016-01-01

    Full Text Available In this paper we investigate the boundedness of holomorphic functionals on a Banach space with a normalized basis $\\{e_n\\}$ which have a very special form $f(x=f(0+\\sum_{n=1}^\\infty c_nx_n^n$ and which we call strictly diagonal. We consider under which conditions strictly diagonal functions are entire and uniformly continuous on every ball of a fixed radius.

  4. Decamp Clock Board Firmware

    International Nuclear Information System (INIS)

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

    2007-01-01

    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

  5. 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.

  6. Electronuclear Park, Privatization and Civil Strict Liability

    International Nuclear Information System (INIS)

    Mondello, Gerard Camille

    2008-01-01

    The civil strict liability regime of the electronuclear industry is a fundamental variable for preventing risk. Because prices of other energies as oil or gas are becoming higher and unpredictable, nuclear power becomes cost-effective and may favour the partial privatization of nuclear parks. By considering theoretical traditional liability models, we study the conditions that ensure the most efficient safety level when comparing natural monopoly situation and Bertrand duopoly. Our results are that natural monopoly is safer than duopoly only when strict liability is fully applied. We define conditions that neutralize risk for applying some privatization plan to nuclear park

  7. Finite Metric Spaces of Strictly negative Type

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    If a finite metric space is of strictly negative type then its transfinite diameter is uniquely realized by an infinite extent (“load vector''). Finite metric spaces that have this property include all trees, and all finite subspaces of Euclidean and Hyperbolic spaces. We prove that if the distance...

  8. Comparisons of mental clocks.

    Science.gov (United States)

    Paivio, A

    1978-02-01

    Subjects in three experiments were presented with pairs of clock times and were required to choose the one in which the hour and minute hand formed the smaller angle. In Experiments 1 and 2, the times were presented digitally, necessitating a transformation into symbolic representations from which the angular size difference could be inferred. The results revealed orderly symbolic distance effects so that comparison reaction time increased as the angular size difference decreased. Moreover, subjects generally reported using imagery to make the judgment, and subjects scoring high on test of imagery ability were faster than those scoring low on such tests. Experiment 3 added a direct perceptual condition in which subjects compared angles between pairs of hands on two drawn (analog) clocks, as well as a mixed condition involving one digital and one analog clock time. The results showed comparable distance effects for all conditions. In addition, reaction time increased from the perceptual, to the mixed, to the pure-digital condition. These results are consistent with predictions from an image-based dual-coding theory.

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

    Directory of Open Access Journals (Sweden)

    Yaoming Yang

    2012-06-01

    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 feedback mechanism. Previous work has focused on the role of ubiquitin ligases in the clock mechanism. Here we show a role for the rhythmically-expressed deubiquitinating enzyme ubiquitin specific peptidase 2 (USP2 in clock function. Mice with a deletion of the Usp2 gene (Usp2 KO display a longer free-running period of locomotor activity rhythms and altered responses of the clock to light. This was associated with altered expression of clock genes in synchronized Usp2 KO mouse embryonic fibroblasts and increased levels of clock protein PERIOD1 (PER1. USP2 can be coimmunoprecipitated with several clock proteins but directly interacts specifically with PER1 and deubiquitinates it. Interestingly, this deubiquitination does not alter PER1 stability. Taken together, our results identify USP2 as a new core component of the clock machinery and demonstrate a role for deubiquitination in the regulation of the circadian clock, both at the level of the core pacemaker and its response to external cues.

  10. A Group Neighborhood Average Clock Synchronization Protocol for Wireless Sensor Networks

    Science.gov (United States)

    Lin, Lin; Ma, Shiwei; Ma, Maode

    2014-01-01

    Clock synchronization is a very important issue for the applications of wireless sensor networks. The sensors need to keep a strict clock so that users can know exactly what happens in the monitoring area at the same time. This paper proposes a novel internal distributed clock synchronization solution using group neighborhood average. Each sensor node collects the offset and skew rate of the neighbors. Group averaging of offset and skew rate value are calculated instead of conventional point-to-point averaging method. The sensor node then returns compensated value back to the neighbors. The propagation delay is considered and compensated. The analytical analysis of offset and skew compensation is presented. Simulation results validate the effectiveness of the protocol and reveal that the protocol allows sensor networks to quickly establish a consensus clock and maintain a small deviation from the consensus clock. PMID:25120163

  11. A Group Neighborhood Average Clock Synchronization Protocol for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Lin Lin

    2014-08-01

    Full Text Available Clock synchronization is a very important issue for the applications of wireless sensor networks. The sensors need to keep a strict clock so that users can know exactly what happens in the monitoring area at the same time. This paper proposes a novel internal distributed clock synchronization solution using group neighborhood average. Each sensor node collects the offset and skew rate of the neighbors. Group averaging of offset and skew rate value are calculated instead of conventional point-to-point averaging method. The sensor node then returns compensated value back to the neighbors. The propagation delay is considered and compensated. The analytical analysis of offset and skew compensation is presented. Simulation results validate the effectiveness of the protocol and reveal that the protocol allows sensor networks to quickly establish a consensus clock and maintain a small deviation from the consensus clock.

  12. Dynamic Enforcement of the Strict Integrity Policy

    Institute of Scientific and Technical Information of China (English)

    ZHANGXiangfeng; LIANGHongliang; SUNYufang

    2005-01-01

    The Strict integrity policy (SIP) in Biba's integrity model is widely used in protecting information integrity, but the static integrity labels of both subjects and objects increase compatibility cost of applications and might prevent some operations that are indeed harmless.In order to improve compatibility, Dynamic enforcement of the Strict integrity policy (DESIP) is put forward. The current integrity label attribute of a subject in SIP is replaced with two attributes in DESIP, which are used to confine dynamically the range of objects a subject could be allowed to access. The new rules of access control in DESIP are given for each kind of access mode (observe,modify and invoke) together with the proofs of their valid-ity. Comparison between SIP and DESIP shows that after a sequence of operations, a subject controlled by DESIP tends to behave in a similar way as it is controlled by SIP and DESIP is more compatible than SIP.

  13. A strictly hyperbolic equilibrium phase transition model

    International Nuclear Information System (INIS)

    Allaire, G; Faccanoni, G; Kokh, S.

    2007-01-01

    This Note is concerned with the strict hyperbolicity of the compressible Euler equations equipped with an equation of state that describes the thermodynamical equilibrium between the liquid phase and the vapor phase of a fluid. The proof is valid for a very wide class of fluids. The argument only relies on smoothness assumptions and on the classical thermodynamical stability assumptions, that requires a definite negative Hessian matrix for each phase entropy as a function of the specific volume and internal energy. (authors)

  14. On Fixed Points of Strictly Causal Functions

    Science.gov (United States)

    2013-04-08

    were defined to be the functions that are strictly contracting with respect to the Cantor metric (also called the Baire distance) on signals over non...in Computer Science, pages 447–484. Springer Berlin / Heidelberg, 1992. [36] George Markowsky. Chain-complete posets and directed sets with...Journal of Logic Programming, 42(2):59–70, 2000. [53] George M. Reed and A. William Roscoe. A timed model for communicating sequential processes. In

  15. Libya: The Transition Clock

    Science.gov (United States)

    2012-03-01

    particularly important aspect will be the treat- ment of minorities such as the Berbers , who played an important role in the fighting apparently sup- ported by...will insist on the adoption of a strict inter- pretation of Shariah law, a position that led to Berber representatives walking out of at least one

  16. Prediction of GNSS satellite clocks

    International Nuclear Information System (INIS)

    Broederbauer, V.

    2010-01-01

    This thesis deals with the characterisation and prediction of GNSS-satellite-clocks. A prerequisite to develop powerful algorithms for the prediction of clock-corrections is the thorough study of the behaviour of the different clock-types of the satellites. In this context the predicted part of the IGU-clock-corrections provided by the Analysis Centers (ACs) of the IGS was compared to the IGS-Rapid-clock solutions to determine reasonable estimates of the quality of already existing well performing predictions. For the shortest investigated interval (three hours) all ACs obtain almost the same accuracy of 0,1 to 0,4 ns. For longer intervals the individual predictions results start to diverge. Thus, for a 12-hours- interval the differences range from nearly 10 ns (GFZ, CODE) until up to some 'tens of ns'. Based on the estimated clock corrections provided via the IGS Rapid products a simple quadratic polynomial turns out to be sufficient to describe the time series of Rubidium-clocks. On the other hand Cesium-clocks show a periodical behaviour (revolution period) with an amplitude of up to 6 ns. A clear correlation between these amplitudes and the Sun elevation angle above the orbital planes can be demonstrated. The variability of the amplitudes is supposed to be caused by temperature-variations affecting the oscillator. To account for this periodical behaviour a quadratic polynomial with an additional sinus-term was finally chosen as prediction model both for the Cesium as well as for the Rubidium clocks. The three polynomial-parameters as well as amplitude and phase shift of the periodic term are estimated within a least-square-adjustment by means of program GNSS-VC/static. Input-data are time series of the observed part of the IGU clock corrections. With the estimated parameters clock-corrections are predicted for various durations. The mean error of the prediction of Rubidium-clock-corrections for an interval of six hours reaches up to 1,5 ns. For the 12-hours

  17. Radioisotope clocks in archaeology

    Energy Technology Data Exchange (ETDEWEB)

    Hedges, R E.M. [Oxford Univ. (UK). Research Lab. for Archaeology

    1979-09-06

    Methods of absolute dating which use the rate of disintegration of a radioactive nucleus as the clock, are reviewed. The use of the abundant radioisotopes (/sup 40/K, Th and U) and of the rare radioisotopes (/sup 14/C, /sup 10/Be, /sup 26/Al, /sup 32/Si, /sup 36/Cl, /sup 41/Ca, /sup 53/Mn) is discussed and radiation integration techniques (fission track dating, thermoluminescence and related techniques) are considered. Specific fields of use of the various methods and their accuracy are examined.

  18. Methodologies for steering clocks

    Science.gov (United States)

    Chadsey, Harold

    1995-01-01

    One of the concerns of the PTTI community is the coordination of one time scale with another. This is accomplished through steering one clock system to another, with a goal of a zero or constant offset in time and frequency. In order to attain this goal, rate differences are calculated and allowed for by the steering algorithm. This paper will present several of these different methods of determining rate differences. Ideally, any change in rate should not cause the offset to change sign (overshoot) by any amount, but certainly not by as much as its previous absolute value. The advantages and disadvantages of each depend on the user's situation.

  19. Clocks and special relativity

    International Nuclear Information System (INIS)

    MacRoberts, D.T.

    1980-01-01

    A kinematic theory without precise definitions of the 'space' and 'time' used is an uninterpreted calculus. The definition of 'time' in special relativity is based on light propagation and the 'constant velocity of light' is a tautological consequence of the definition. When this definition is reified in a 'clock' the phenomenon of 'time dilation' occurs, in terms of the defined time, but is not reciprocal between moving systems; the postulate of relativity is not observed. The new definition of time is compatible with an ether theory without the relativity principle. The derivation of the Lorentz transformations, which requires both postulates, is purely formalistic and is not ontologically sound. (Auth.)

  20. Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks.

    Science.gov (United States)

    de Assis, Leonardo Vinícius Monteiro; Moraes, Maria Nathália; Magalhães-Marques, Keila Karoline; Kinker, Gabriela Sarti; da Silveira Cruz-Machado, Sanseray; Castrucci, Ana Maria de Lauro

    2018-04-03

    The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism's biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

  1. Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

    Directory of Open Access Journals (Sweden)

    Leonardo Vinícius Monteiro de Assis

    2018-04-01

    Full Text Available The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME and macro-environments (TMaE in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis, and the suprachiasmatic nucleus (SCN were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism’s biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

  2. 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…

  3. 7 CFR 28.441 - Strict Middling Yellow Stained Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Yellow Stained Color. 28.441 Section... Strict Middling Yellow Stained Color. Strict Middling Yellow Stained Color is color which is deeper than that of Strict Middling Tinged Color. [57 FR 34498, Aug. 5, 1992] ...

  4. 7 CFR 28.412 - Strict Middling Light Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Light Spotted Color. 28.412 Section 28... Light Spotted Color. Strict Middling Light Spotted Color is color which in spot or color, or both, is between Strict Middling Color and Strict Middling Spotted Color. ...

  5. NPAS2 Compensates for Loss of CLOCK in Peripheral Circadian Oscillators.

    Directory of Open Access Journals (Sweden)

    Dominic Landgraf

    2016-02-01

    Full Text Available Heterodimers of CLOCK and BMAL1 are the major transcriptional activators of the mammalian circadian clock. Because the paralog NPAS2 can substitute for CLOCK in the suprachiasmatic nucleus (SCN, the master circadian pacemaker, CLOCK-deficient mice maintain circadian rhythms in behavior and in tissues in vivo. However, when isolated from the SCN, CLOCK-deficient peripheral tissues are reportedly arrhythmic, suggesting a fundamental difference in circadian clock function between SCN and peripheral tissues. Surprisingly, however, using luminometry and single-cell bioluminescence imaging of PER2 expression, we now find that CLOCK-deficient dispersed SCN neurons and peripheral cells exhibit similarly stable, autonomous circadian rhythms in vitro. In CLOCK-deficient fibroblasts, knockdown of Npas2 leads to arrhythmicity, suggesting that NPAS2 can compensate for loss of CLOCK in peripheral cells as well as in SCN. Our data overturn the notion of an SCN-specific role for NPAS2 in the molecular circadian clock, and instead indicate that, at the cellular level, the core loops of SCN neuron and peripheral cell circadian clocks are fundamentally similar.

  6. A central role for ubiquitination within a circadian clock protein modification code

    Directory of Open Access Journals (Sweden)

    Katarina eStojkovic

    2014-08-01

    Full Text Available Circadian rhythms, endogenous cycles of about 24 h in physiology, are generated by a master clock located in the suprachiasmatic nucleus of the hypothalamus and other clocks located in the brain and peripheral tissues. Circadian disruption is known to increase the incidence of various illnesses, such as mental disorders, metabolic syndrome and cancer. At the molecular level, periodicity is established by a set of clock genes via autoregulatory translation-transcription feedback loops. This clock mechanism is regulated by post-translational modifications such as phosphorylation and ubiquitination, which set the pace of the clock. Ubiquitination in particular has been found to regulate the stability of core clock components, but also other clock protein functions. Mutation of genes encoding ubiquitin ligases can cause either elongation or shortening of the endogenous circadian period. Recent research has also started to uncover roles for deubiquitination in the molecular clockwork. Here we review the role of the ubiquitin pathway in regulating the circadian clock and we propose that ubiquitination is a key element in a clock protein modification code that orchestrates clock mechanisms and circadian behavior over the daily cycle.

  7. An optical clock to go

    Science.gov (United States)

    Ludlow, Andrew D.

    2018-05-01

    Bringing next-generation atomic clocks out of the lab is not an easy task, but doing so will unlock many new possibilities. As a crucial first step, a portable atomic clock has now been deployed for relativistic geodesy measurements in the Alps.

  8. High Precision Clock Bias Prediction Model in Clock Synchronization System

    Directory of Open Access Journals (Sweden)

    Zan Liu

    2016-01-01

    Full Text Available Time synchronization is a fundamental requirement for many services provided by a distributed system. Clock calibration through the time signal is the usual way to realize the synchronization among the clocks used in the distributed system. The interference to time signal transmission or equipment failures may bring about failure to synchronize the time. To solve this problem, a clock bias prediction module is paralleled in the clock calibration system. And for improving the precision of clock bias prediction, the first-order grey model with one variable (GM(1,1 model is proposed. In the traditional GM(1,1 model, the combination of parameters determined by least squares criterion is not optimal; therefore, the particle swarm optimization (PSO is used to optimize GM(1,1 model. At the same time, in order to avoid PSO getting stuck at local optimization and improve its efficiency, the mechanisms that double subgroups and nonlinear decreasing inertia weight are proposed. In order to test the precision of the improved model, we design clock calibration experiments, where time signal is transferred via radio and wired channel, respectively. The improved model is built on the basis of clock bias acquired in the experiments. The results show that the improved model is superior to other models both in precision and in stability. The precision of improved model increased by 66.4%~76.7%.

  9. Clocks around Sgr A*

    Science.gov (United States)

    Angélil, Raymond; Saha, Prasenjit

    2014-11-01

    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 black 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 time-scale ≈6 months.

  10. How do you manage early or late clock-ins? .

    Science.gov (United States)

    Marlowe, Cathy L

    2013-08-01

    My current practice has historically been very strict with hourly employees. The workday is 8:30 a.m. to 5 p.m. for most employees. They are to clock in and out at exactly those times unless overtime has been approved. (Staff working with late patients are exempt.) My business manager is constantly fighting over clock-ins 15 to 20 minutes early or late, with similar clock-outs. Staff may have a stop to make and would like to make up those 15 minutes. We do grant paid time off in an initial minimum block of 30 minutes to assist with some of this. ... The issue is not overtime, as we're well aware that we have to pay for it when appropriate. It's simply to streamline our policy and make it fair. ... I'm looking for practice policies that deal with employee variances from the 8 a.m. to 4:30 p.m. clock-ins. For example, someone wants to come in 30 minutes early in order to leave 30 minutes early for an appointment. Or someone comes in 22 minutes late due to traffic and wants either to make it up or to take the minimal half-hour paid-time-off time.

  11. CIRCADIAN CLOCK-ASSOCIATED 1 Inhibits Leaf Senescence in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yi Song

    2018-03-01

    Full Text Available Leaf senescence is an integral part of plant development, and the timing and progressing rate of senescence could substantially affect the yield and quality of crops. It has been known that a circadian rhythm synchronized with external environmental cues is critical for the optimal coordination of various physiological and metabolic processes. However, the reciprocal interactions between the circadian clock and leaf senescence in plants remain unknown. Here, through measuring the physiological and molecular senescence related markers of several circadian components mutants, we found that CIRCADIAN CLOCK-ASSOCIATED 1 inhibits leaf senescence. Further molecular and genetic studies revealed that CCA1 directly activates GLK2 and suppresses ORE1 expression to counteract leaf senescence. As plants age, the expression and periodic amplitude of CCA1 declines and thus weakens the inhibition of senescence. Our findings reveal an age-dependent circadian clock component of the process of leaf senescence.

  12. Speed control: cogs and gears that drive the circadian clock.

    Science.gov (United States)

    Zheng, Xiangzhong; Sehgal, Amita

    2012-09-01

    In most organisms, an intrinsic circadian (~24-h) timekeeping system drives rhythms of physiology and behavior. Within cells that contain a circadian clock, specific transcriptional activators and repressors reciprocally regulate each other to generate a basic molecular oscillator. A mismatch of the period generated by this oscillator with the external environment creates circadian disruption, which can have adverse effects on neural function. Although several clock genes have been extensively characterized, a fundamental question remains: how do these genes work together to generate a ~24-h period? Period-altering mutations in clock genes can affect any of multiple regulated steps in the molecular oscillator. In this review, we examine the regulatory mechanisms that contribute to setting the pace of the circadian oscillator. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Physiological links of circadian clock and biological clock of aging.

    Science.gov (United States)

    Liu, Fang; Chang, Hung-Chun

    2017-07-01

    Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.

  14. STRICT STABILITY OF IMPULSIVE SET VALUED DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    In this paper, we develop strict stability concepts of ODE to impulsive hybrid set valued differential equations. By Lyapunov’s original method, we get some basic strict stability criteria of impulsive hybrid set valued equations.

  15. Public healthcare interests require strict competition enforcement.

    Science.gov (United States)

    Loozen, Edith M H

    2015-07-01

    Several countries have introduced competition in their health systems in order to maintain the supply of high quality health care in a cost-effective manner. The introduction of competition triggers competition enforcement. Since healthcare is characterized by specific market failures, many favor healthcare-specific competition enforcement in order not only to account for the competition interest, but also for the healthcare interests. The question is whether healthcare systems based on competition can succeed when competition enforcement deviates from standard practice. This paper analyzes whether healthcare-specific competition enforcement is theoretically sound and practically effective. This is exemplified by the Dutch system that is based on regulated competition and thus crucially depends on getting competition enforcement right. Governments are responsible for correcting market failures. Markets are responsible for maximizing the public healthcare interests. By securing sufficient competitive pressure, competition enforcement makes sure they do. When interpreted according to welfare-economics, competition law takes into account both costs and benefits specific market behavior may have for healthcare. Competition agencies and judiciary are not legitimized to deviate from standard evidentiary requirements. Dutch case law shows that healthcare-specific enforcement favors the healthcare undertakings concerned, but to the detriment of public health care. Healthcare-specific competition enforcement is conceptually flawed and counterproductive. In order for healthcare systems based on competition to succeed, competition enforcement should be strict. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Neurogenetics of Drosophila circadian clock: expect the unexpected.

    Science.gov (United States)

    Jarabo, Patricia; Martin, Francisco A

    2017-12-01

    Daily biological rhythms (i.e. circadian) are a fundamental part of animal behavior. Numerous reports have shown disruptions of the biological clock in neurodegenerative disorders and cancer. In the latter case, only recently we have gained insight into the molecular mechanisms. After 45 years of intense study of the circadian rhtythms, we find surprising similarities among species on the molecular clock that governs biological rhythms. Indeed, Drosophila is one of the most widely used models in the study of chronobiology. Recent studies in the fruit fly have revealed unpredicted roles for the clock machinery in different aspects of behavior and physiology. Not only the central pacemaker cells do have non-classical circadian functions but also circadian genes work in other cells and tissues different from central clock neurons. In this review, we summarize these new evidences. We also recapitulate the most basic features of Drosophila circadian clock, including recent data about the inputs and outputs that connect the central pacemaker with other regions of the brain. Finally, we discuss the advantages and drawbacks of using natural versus laboratory conditions.

  17. Micro Mercury Ion Clock (MMIC)

    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...

  18. History of early atomic clocks

    International Nuclear Information System (INIS)

    Ramsey, N.F.

    2005-01-01

    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)

  19. 7 CFR 28.406 - Strict Good Ordinary Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Good Ordinary Color. 28.406 Section 28.406... for the Color Grade of American Upland Cotton § 28.406 Strict Good Ordinary Color. Strict Good Ordinary Color is color which is within the range represented by a set of samples in the custody of the...

  20. 7 CFR 28.404 - Strict Low Middling Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Low Middling Color. 28.404 Section 28.404... for the Color Grade of American Upland Cotton § 28.404 Strict Low Middling Color. Strict Low Middling Color is color which is within the range represented by a set of samples in the custody of the United...

  1. 7 CFR 28.402 - Strict Middling Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Color. 28.402 Section 28.402... for the Color Grade of American Upland Cotton § 28.402 Strict Middling Color. Strict Middling Color is color which is within the range represented by a set of samples in the custody of the United States...

  2. Controllable clock circuit design in PEM system

    International Nuclear Information System (INIS)

    Sun Yunhua; Wang Peihua; Hu Tingting; Feng Baotong; Shuai Lei; Huang Huan; Wei Shujun; Li Ke; Zhao Jingwei; Wei Long

    2011-01-01

    A high-precision synchronized clock circuit design will be presented, which can supply steady, reliable and anti-jamming clock signal for the data acquirement (DAQ) system of Positron Emission Mammography (PEM). This circuit design is based on the Single-Chip Microcomputer and high-precision clock chip, and can achieve multiple controllable clock signals. The jamming between the clock signals can be reduced greatly with the differential transmission. Meanwhile, the adoption of CAN bus control in the clock circuit can prompt the clock signals to be transmitted or masked simultaneously when needed. (authors)

  3. Controllable clock circuit design in PEM system

    International Nuclear Information System (INIS)

    Sun Yunhua; Wang Peilin; Hu Tingting; Feng Baotong; Shuai Lei; Huang Huan; Wei Shujun; Li Ke; Zhao Jingwei; Wei Long

    2010-01-01

    A high-precision synchronized clock circuit design will be presented, which can supply steady, reliable and anti-jamming clock signal for the data acquirement (DAQ) system of Positron Emission Mammography (PEM). This circuit design is based on the Single-Chip Microcomputer and high-precision clock chip, and can achieve multiple controllable clock signals. The jamming between the clock signals can be reduced greatly with the differential transmission. Meanwhile, the adoption of CAN bus control in the clock circuit can prompt the clock signals to be transmitted or masked simultaneously when needed. (authors)

  4. Time without clocks - an attempt

    International Nuclear Information System (INIS)

    Karpman, G.

    1978-01-01

    A definition of time intervals separating two states of systems of elementary particles and observers is attempted. The definition is founded on the notion of instant state of the system and uses no information connected with the use of a clock. Applying the definition to a classical clock and to a sample of unstable particles, results are obtained in agreement with experiment. However, if the system contains 'few' elementary particles, the properties of the time interval present some different features. (author)

  5. 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...oeaw.ac.at Nikolaus Kerö Oregano Systems, Mohsgasse 1, 1030 Wien, Austria E-mail: nikolaus.keroe@oregano.at Abstract Clock synchronization ...is a service widely used in distributed networks to coordinate data acquisition and actions. As the requirement to achieve tighter synchronization

  6. Synchronizing strict-feedback and general strict-feedback chaotic systems via a single controller

    International Nuclear Information System (INIS)

    Chen Shihua; Wang Feng; Wang Changping

    2004-01-01

    We present a systematic design procedure to synchronize a class of chaotic systems in a so-called strict-feedback form based on back-stepping procedure. This approach needs only a single controller to realize synchronization no matter how many dimensions the chaotic system contains. Furthermore, we point out that the method does not work for general strict-feedback chaotic systems, for instance, Lorenz system. Therefore, we propose three kinds of synchronization schemes for Lorenz system using the Lyapunov function method. All the three schemes avoid including divergence factor as in Ref. [Chaos, Solitons and Fractals 16 (2003) 37]. Especially in the last two schemes, we need only one state variable in controller, which has important significance in chaos synchronization used for communication purposes. Finally numerical simulations are provided to show the effectiveness and feasibility of the developed methods

  7. Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis.

    Science.gov (United States)

    Kwon, Young-Ju; Park, Mi-Jeong; Kim, Sang-Gyu; Baldwin, Ian T; Park, Chung-Mo

    2014-05-19

    The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5' splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock and environmental stress

  8. Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis

    Science.gov (United States)

    2014-01-01

    Background The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. Results We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5′ splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Conclusion Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock

  9. Animal clocks: when science meets nature.

    Science.gov (United States)

    Kronfeld-Schor, Noga; Bloch, Guy; Schwartz, William J

    2013-08-22

    Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian 'clock'), with the alternation of environmental light and darkness synchronizing (entraining) these rhythms to the natural day-night cycle. Our knowledge of the circadian system of animals at the molecular, cellular, tissue and organismal levels is remarkable, and we are beginning to understand how each of these levels contributes to the emergent properties and increased complexity of the system as a whole. For the most part, these analyses have been carried out using model organisms in standard laboratory housing, but to begin to understand the adaptive significance of the clock, we must expand our scope to study diverse animal species from different taxonomic groups, showing diverse activity patterns, in their natural environments. The seven papers in this Special Feature of Proceedings of the Royal Society B take on this challenge, reviewing the influences of moonlight, latitudinal clines, evolutionary history, social interactions, specialized temporal niches, annual variation and recently appreciated post-transcriptional molecular mechanisms. The papers emphasize that the complexity and diversity of the natural world represent a powerful experimental resource.

  10. Pitfalls of Insulin Pump Clocks

    Science.gov (United States)

    Reed, Amy J.

    2014-01-01

    The objective was to raise awareness about the importance of ensuring that insulin pumps internal clocks are set up correctly at all times. This is a very important safety issue because all commercially available insulin pumps are not GPS-enabled (though this is controversial), nor equipped with automatically adjusting internal clocks. Special attention is paid to how basal and bolus dose errors can be introduced by daylight savings time changes, travel across time zones, and am-pm clock errors. Correct setting of insulin pump internal clock is crucial for appropriate insulin delivery. A comprehensive literature review is provided, as are illustrative cases. Incorrect setting can potentially result in incorrect insulin delivery, with potential harmful consequences, if too much or too little insulin is delivered. Daylight saving time changes may not significantly affect basal insulin delivery, given the triviality of the time difference. However, bolus insulin doses can be dramatically affected. Such problems may occur when pump wearers have large variations in their insulin to carb ratio, especially if they forget to change their pump clock in the spring. More worrisome than daylight saving time change is the am-pm clock setting. If this setting is set up incorrectly, both basal rates and bolus doses will be affected. Appropriate insulin delivery through insulin pumps requires correct correlation between dose settings and internal clock time settings. Because insulin pumps are not GPS-enabled or automatically time-adjusting, extra caution should be practiced by patients to ensure correct time settings at all times. Clinicians and diabetes educators should verify the date/time of insulin pumps during patients’ visits, and should remind their patients to always verify these settings. PMID:25355713

  11. Daily rhythmicity of clock gene transcripts in atlantic cod fast skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Carlo C Lazado

    Full Text Available The classical notion of a centralized clock that governs circadian rhythmicity has been challenged with the discovery of peripheral oscillators that enable organisms to cope with daily changes in their environment. The present study aimed to identify the molecular clock components in Atlantic cod (Gadus morhua and to investigate their daily gene expression in fast skeletal muscle. Atlantic cod clock genes were closely related to their orthologs in teleosts and tetrapods. Synteny was conserved to varying degrees in the majority of the 18 clock genes examined. In particular, aryl hydrocarbon receptor nuclear translocator-like 2 (arntl2, RAR-related orphan receptor A (rora and timeless (tim displayed high degrees of conservation. Expression profiling during the early ontogenesis revealed that some transcripts were maternally transferred, namely arntl2, cryptochrome 1b and 2 (cry1b and cry2, and period 2a and 2b (per2a and per2b. Most clock genes were ubiquitously expressed in various tissues, suggesting the possible existence of multiple peripheral clock systems in Atlantic cod. In particular, they were all detected in fast skeletal muscle, with the exception of neuronal PAS (Per-Arnt-Single-minded domain-containing protein (npas1 and rora. Rhythmicity analysis revealed 8 clock genes with daily rhythmic expression, namely arntl2, circadian locomotor output cycles kaput (clock, npas2, cry2, cry3 per2a, nuclear receptor subfamily 1, group D, member 1 (nr1d1, and nr1d2a. Transcript levels of the myogenic genes myogenic factor 5 (myf5 and muscleblind-like 1 (mbnl1 strongly correlated with clock gene expression. This is the first study to unravel the molecular components of peripheral clocks in Atlantic cod. Taken together, our data suggest that the putative clock system in fast skeletal muscle of Atlantic cod has regulatory implications on muscle physiology, particularly in the expression of genes related to myogenesis.

  12. Sound Clocks and Sonic Relativity

    Science.gov (United States)

    Todd, Scott L.; Menicucci, Nicolas C.

    2017-10-01

    Sound propagation within certain non-relativistic condensed matter models obeys a relativistic wave equation despite such systems admitting entirely non-relativistic descriptions. A natural question that arises upon consideration of this is, "do devices exist that will experience the relativity in these systems?" We describe a thought experiment in which `acoustic observers' possess devices called sound clocks that can be connected to form chains. Careful investigation shows that appropriately constructed chains of stationary and moving sound clocks are perceived by observers on the other chain as undergoing the relativistic phenomena of length contraction and time dilation by the Lorentz factor, γ , with c the speed of sound. Sound clocks within moving chains actually tick less frequently than stationary ones and must be separated by a shorter distance than when stationary to satisfy simultaneity conditions. Stationary sound clocks appear to be length contracted and time dilated to moving observers due to their misunderstanding of their own state of motion with respect to the laboratory. Observers restricted to using sound clocks describe a universe kinematically consistent with the theory of special relativity, despite the preferred frame of their universe in the laboratory. Such devices show promise in further probing analogue relativity models, for example in investigating phenomena that require careful consideration of the proper time elapsed for observers.

  13. Titan's methane clock

    Science.gov (United States)

    Nixon, C. A.; Jennings, D. E.; Romani, P. N.; Teanby, N. A.; Irwin, P. G. J.; Flasar, F. M.

    2010-04-01

    Measurements of the 12C/13C and D/H isotopic ratios in Titan's methane show intriguing differences from the values recorded in the giant planets. This implies that either (1) the atmosphere was differently endowed with material at the time of formation, or (2) evolutionary processes are at work in the moon's atmosphere - or some combination of the two. The Huygens Gas Chromatograph Mass Spectrometer Instrument (GCMS) found 12CH4/13CH4 = 82 +/- 1 (Niemann et al. 2005), some 7% lower than the giant planets' value of 88 +/- 7 (Sada et al. 1996), which closely matches the terrestrial inorganic standard of 89. The Cassini Composite Infrared Spectrometer (CIRS) has previously reported 12CH4/13CH4 of 77 +/-3 based on nadir sounding, which we now revise upwards to 80 +/- 4 based on more accurate limb sounding. The CIRS and GCMS results are therefore in agreement about an overall enrichment in 13CH4 of ~10%. The value of D/H in Titan's CH4 has long been controversial: historical measurements have ranged from about 8-15 x 10-5 (e.g. Coustenis et al. 1989, Coustenis et al. 2003). A recent measurement based on CIRS limb data by Bezard et al. (2007) puts the D/H in CH4 at (13 +/- 1) x 10-5, very much greater than in Jupiter and Saturn, ~2 x 10-5 (Mahaffy et al. 1998, Fletcher et al. 2009). To add complexity, the 12C/13C and D/H vary among molecules in Titan atmosphere, typically showing enhancement in D but depletion in 13C in the daughter species (H2, C2H2, C2H6), relative to the photochemical progenitor, methane. Jennings et al. (2009) have sought to interpret the variance in carbon isotopes as a Kinetic Isotope Effect (KIE), whilst an explanation for the D/H in all molecules remains elusive (Cordier et al. 2008). In this presentation we argue that evolution of isotopic ratios in Titan's methane over time forms a ticking 'clock', somewhat analogous to isotopic ratios in geochronology. Under plausible assumptions about the initial values and subsequent replenishment, various

  14. Circadian clocks : Translation lost

    NARCIS (Netherlands)

    Roenneberg, T; Merrow, M

    2005-01-01

    One of the big questions in biological rhythms research is how a stable and precise circa-24 hour oscillation is generated on the molecular level. While increasing complexity seemed to be the key, a recent report suggests that circa-24 hour rhythms can be generated by just four molecules incubated

  15. RNAi of the circadian clock gene period disrupts the circadian rhythm but not the circatidal rhythm in the mangrove cricket

    OpenAIRE

    Takekata, Hiroki; Matsuura, Yu; Goto, Shin G.; Satoh, Aya; Numata, Hideharu

    2012-01-01

    The clock mechanism for circatidal rhythm has long been controversial, and its molecular basis is completely unknown. The mangrove cricket, Apteronemobius asahinai, shows two rhythms simultaneously in its locomotor activity: a circatidal rhythm producing active and inactive phases as well as a circadian rhythm modifying the activity intensity of circatidal active phases. The role of the clock gene period (per), one of the key components of the circadian clock in insects, was investigated in t...

  16. Advances in Time Estimation Methods for Molecular Data.

    Science.gov (United States)

    Kumar, Sudhir; Hedges, S Blair

    2016-04-01

    Molecular dating has become central to placing a temporal dimension on the tree of life. Methods for estimating divergence times have been developed for over 50 years, beginning with the proposal of molecular clock in 1962. We categorize the chronological development of these methods into four generations based on the timing of their origin. In the first generation approaches (1960s-1980s), a strict molecular clock was assumed to date divergences. In the second generation approaches (1990s), the equality of evolutionary rates between species was first tested and then a strict molecular clock applied to estimate divergence times. The third generation approaches (since ∼2000) account for differences in evolutionary rates across the tree by using a statistical model, obviating the need to assume a clock or to test the equality of evolutionary rates among species. Bayesian methods in the third generation require a specific or uniform prior on the speciation-process and enable the inclusion of uncertainty in clock calibrations. The fourth generation approaches (since 2012) allow rates to vary from branch to branch, but do not need prior selection of a statistical model to describe the rate variation or the specification of speciation model. With high accuracy, comparable to Bayesian approaches, and speeds that are orders of magnitude faster, fourth generation methods are able to produce reliable timetrees of thousands of species using genome scale data. We found that early time estimates from second generation studies are similar to those of third and fourth generation studies, indicating that methodological advances have not fundamentally altered the timetree of life, but rather have facilitated time estimation by enabling the inclusion of more species. Nonetheless, we feel an urgent need for testing the accuracy and precision of third and fourth generation methods, including their robustness to misspecification of priors in the analysis of large phylogenies and data

  17. Naming analog clocks conceptually facilitates naming digital clocks

    NARCIS (Netherlands)

    Meeuwissen, M.H.W.; Roelofs, A.P.A.; Levelt, W.J.M.

    2004-01-01

    Naming digital clocks (e.g., 2:45, say "quarter to three") requires conceptual operations on the minute and hour information displayed in the input for producing the correct relative time expression. The interplay of these conceptual operations was investigated using a repetition priming paradigm.

  18. A network of (autonomic) clock outputs

    NARCIS (Netherlands)

    Kalsbeek, A.; Perreau-Lenz, S.; Buijs, R. M.

    2006-01-01

    The circadian clock in the suprachiasmatic nuclei (SCN) is composed of thousands of oscillator neurons, each of which is dependent on the cell-autonomous action of a defined set of circadian clock genes. A major question is still how these individual oscillators are organized into a biological clock

  19. A network of (autonomic) clock outputs

    NARCIS (Netherlands)

    Kalsbeek, A.; Perreau-Lenz, S.; Buijs, R. M.

    2006-01-01

    The circadian clock in the suprachiasmatic nuclei (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. A major question is still how these individual oscillators are organized into a biological clock that

  20. 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

  1. Modal Inclusion Logic: Being Lax is Simpler than Being Strict

    DEFF Research Database (Denmark)

    Hella, Lauri; Kuusisto, Antti Johannes; Meier, Arne

    2015-01-01

    We investigate the computational complexity of the satisfiability problem of modal inclusion logic. We distinguish two variants of the problem: one for strict and another one for lax semantics. The complexity of the lax version turns out to be complete for EXPTIME, whereas with strict semantics...

  2. 7 CFR 28.426 - Strict Good Ordinary Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Good Ordinary Spotted Color. 28.426 Section 28.426 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Spotted Color. Strict Good Ordinary Spotted Color is color which is within the range represented by a set...

  3. 7 CFR 28.433 - Strict Low Middling Tinged Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Low Middling Tinged Color. 28.433 Section 28.433 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Tinged Color. Strict Low Middling Tinged Color is color which is within the range represented by a set of...

  4. 7 CFR 28.422 - Strict Middling Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Spotted Color. 28.422 Section 28.422 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Color. Strict Middling Spotted Color is color which is within the range represented by a set of samples...

  5. 7 CFR 28.424 - Strict Low Middling Spotted Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Low Middling Spotted Color. 28.424 Section 28.424 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Spotted Color. Strict Low Middling Spotted Color is color which is within the range represented by a set...

  6. 7 CFR 28.431 - Strict Middling Tinged Color.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Strict Middling Tinged Color. 28.431 Section 28.431 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards... Color. Strict Middling Tinged Color is color which is better than Middling Tinged Color. ...

  7. 43 CFR 29.7 - Imposition of strict liability.

    Science.gov (United States)

    2010-10-01

    ... LIABILITY FUND § 29.7 Imposition of strict liability. (a) Notwithstanding the provisions of any other law... prove that the damages were caused by an act of war or by the negligence of the United States or other... negligence of such damaged party. (c)(1) Strict liability for all claims arising out of any one incident...

  8. Strictly-regular number system and data structures

    DEFF Research Database (Denmark)

    Elmasry, Amr Ahmed Abd Elmoneim; Jensen, Claus; Katajainen, Jyrki

    2010-01-01

    We introduce a new number system that we call the strictly-regular system, which efficiently supports the operations: digit-increment, digit-decrement, cut, concatenate, and add. Compared to other number systems, the strictly-regular system has distinguishable properties. It is superior to the re...

  9. STRICT CONVEXITY THROUGH EQUIVALENT NORMS IN SEPARABLES BANACH SPACES

    Directory of Open Access Journals (Sweden)

    Willy Zubiaga Vera

    2016-12-01

    Full Text Available Let E be a separable Banach space with norm || . ||. In the present work, the objective is to construct a norm || . ||1 that is equivalent to || . || in E, such that || . ||1 is strictly convex. In addition it is shown that its dual conjugate norm is also strictly convex.

  10. Clock and trigger distribution for ALICE using the CRU FPGA card

    CERN Document Server

    Imrek, Jozsef

    2017-01-01

    ALICE is preparing a major upgrade for 2021. Subdetectors upgrading their DAQ electronics will use a common hardware to receive physics data: the Common Readout Unit (CRU). The same CRU will also distribute the LHC clock and trigger to many of the upgrading subdetectors (to 7800 front end cards). Requirements are strict: for the clock the allowed jitter (RMS) is typically <300ps, and <20ps for timing critical subdetectors; the allowed variation of skew is typically <1ns, and <100ps for timing critical subdetectors. A constant latency for distributing the trigger is essential. A novel approach to implement clock forwarding – using only the internal PLLs of the CRU’s onboard FPGA, without using an external jitter cleaner PLL – is presented.

  11. CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet

    Science.gov (United States)

    Introduction: The success of obesity therapy is dependent on the genetic background of the patient. Circadian Locomotor Output Cycles Kaput (CLOCK), one of the transcription factors from the positive limb of the molecular clock, is involved in metabolic alterations. Objective: To investigate whethe...

  12. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture.

    Science.gov (United States)

    Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

    2017-01-01

    Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian

  13. Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

    Directory of Open Access Journals (Sweden)

    Virginie Sabado

    2017-10-01

    Full Text Available Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF, which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the

  14. Phylogenetic footprint of the plant clock system in angiosperms: evolutionary processes of Pseudo-Response Regulators

    Directory of Open Access Journals (Sweden)

    Saito Shigeru

    2010-05-01

    Full Text Available Abstract Background Plant circadian clocks regulate many photoperiodic and diurnal responses that are conserved among plant species. The plant circadian clock system has been uncovered in the model plant, Arabidopsis thaliana, using genetics and systems biology approaches. However, it is still not clear how the clock system had been organized in the evolutionary history of plants. We recently revealed the molecular phylogeny of LHY/CCA1 genes, one of the essential components of the clock system. The aims of this study are to reconstruct the phylogenetic relationships of angiosperm clock-associated PRR genes, the partner of the LHY/CCA1 genes, and to clarify the evolutionary history of the plant clock system in angiosperm lineages. Results In the present study, to investigate the molecular phylogeny of PRR genes, we performed two approaches: reconstruction of phylogenetic trees and examination of syntenic relationships. Phylogenetic analyses revealed that PRR genes had diverged into three clades prior to the speciation of monocots and eudicots. Furthermore, copy numbers of PRR genes have been independently increased in monocots and eudicots as a result of ancient chromosomal duplication events. Conclusions Based on the molecular phylogenies of both PRR genes and LHY/CCA1 genes, we inferred the evolutionary process of the plant clock system in angiosperms. This scenario provides evolutionary information that a common ancestor of monocots and eudicots had retained the basic components required for reconstructing a clock system and that the plant circadian clock may have become a more elaborate mechanism after the speciation of monocots and eudicots because of the gene expansion that resulted from polyploidy events.

  15. Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Valérie Mongrain

    Full Text Available We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP, we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset, -6, -12, and -18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and -6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven.

  16. Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex.

    Science.gov (United States)

    Mongrain, Valérie; La Spada, Francesco; Curie, Thomas; Franken, Paul

    2011-01-01

    We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), -6, -12, and -18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and -6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven.

  17. Automatic control of clock duty cycle

    Science.gov (United States)

    Feng, Xiaoxin (Inventor); Roper, Weston (Inventor); Seefeldt, James D. (Inventor)

    2010-01-01

    In general, this disclosure is directed to a duty cycle correction (DCC) circuit that adjusts a falling edge of a clock signal to achieve a desired duty cycle. In some examples, the DCC circuit may generate a pulse in response to a falling edge of an input clock signal, delay the pulse based on a control voltage, adjust the falling edge of the input clock signal based on the delayed pulse to produce an output clock signal, and adjust the control voltage based on the difference between a duty cycle of the output clock signal and a desired duty cycle. Since the DCC circuit adjusts the falling edge of the clock cycle to achieve a desired duty cycle, the DCC may be incorporated into existing PLL control loops that adjust the rising edge of a clock signal without interfering with the operation of such PLL control loops.

  18. 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.

  19. Strategy and Aspects of Monitoring / Control Strictly in Coordinated Subsystems

    Directory of Open Access Journals (Sweden)

    William José Borges

    2012-06-01

    Full Text Available This paper aims to discuss the approach structures of the strictly coordinated theoretical framework developed by Zylbersztajn and Farina (1999 as an expanded perspective of the firm, taking into account the food supply chains as an extension of the nexus of contracts proposed by Coase (1937 and taken up by Williamson (1985. The structures stand out as strictly coordinated. Zylbersztajn and Farina (1999 turn to identifying points of common interests that encourage firms to promote contracts between themselves in a strictly coordinated way, considering the degree of asset specificity involved in the transaction and the competitive forces that determine the search for strategic positioning organizations to achieve sustainable superior results.

  20. Clocks do not tick in unison: isolation of Clock and vrille shed new light on the clockwork model of the sand fly Lutzomyia longipalpis.

    Science.gov (United States)

    Gesto, João Silveira Moledo; Rivas, Gustavo Bueno da Silva; Pavan, Marcio Galvão; Meireles-Filho, Antonio Carlos Alves; Amoretty, Paulo Roberto de; Souza, Nataly Araújo de; Bruno, Rafaela Vieira; Peixoto, Alexandre Afranio

    2015-10-06

    Behavior rhythms of insect vectors directly interfere with the dynamics of pathogen transmission to humans. The sand fly Lutzomyia longipalpis is the main vector of visceral leishmaniasis in America and concentrates its activity around dusk. Despite the accumulation of behavioral data, very little is known about the molecular bases of the clock mechanism in this species. This study aims to characterize, within an evolutionary perspective, two important circadian clock genes, Clock and vrille. We have cloned and isolated the coding sequence of L. longipalpis' genes Clock and vrille. The former is structured in eight exons and encodes a protein of 696 amino acids, and the latter comprises three exons and translates to a protein of 469 amino acids. When compared to other insects' orthologues, L. longipalpis CLOCK shows a high degree of conservation in the functional domains bHLH and PAS, but a much shorter glutamine-rich (poly-Q) C-terminal region. As for L. longipalpis VRILLE, a high degree of conservation was found in the bZIP domain. To support these observations and provide an elegant view of the evolution of both genes in insects, phylogenetic analyses based on maximum-likelihood and Bayesian inferences were performed, corroborating the previously known insect systematics. The isolation and phylogenetic analyses of Clock and vrille orthologues in L. longipalpis bring novel and important data to characterize this species' circadian clock. Interestingly, the poly-Q shortening observed in CLOCK suggests that its transcription activity might be impaired and we speculate if this effect could be compensated by other clock factors such as CYCLE.

  1. 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.

  2. Normal form and synchronization of strict-feedback chaotic systems

    International Nuclear Information System (INIS)

    Wang, Feng; Chen, Shihua; Yu Minghai; Wang Changping

    2004-01-01

    This study concerns the normal form and synchronization of strict-feedback chaotic systems. We prove that, any strict-feedback chaotic system can be rendered into a normal form with a invertible transform and then a design procedure to synchronize the normal form of a non-autonomous strict-feedback chaotic system is presented. This approach needs only a scalar driving signal to realize synchronization no matter how many dimensions the chaotic system contains. Furthermore, the Roessler chaotic system is taken as a concrete example to illustrate the procedure of designing without transforming a strict-feedback chaotic system into its normal form. Numerical simulations are also provided to show the effectiveness and feasibility of the developed methods

  3. Strict finitism and the logic of mathematical applications

    CERN Document Server

    Ye, Feng

    2011-01-01

    Exploring the logic behind applied mathematics to the physical world, this volume illustrates how radical naturalism, nominalism and strict finitism can account for the applications of classical mathematics in current theories about natural phenomena.

  4. Two examples of non strictly convex large deviations

    OpenAIRE

    De Marco, Stefano; Jacquier, Antoine; Roome, Patrick

    2016-01-01

    We present two examples of a large deviations principle where the rate function is not strictly convex. This is motivated by a model used in mathematical finance (the Heston model), and adds a new item to the zoology of non strictly convex large deviations. For one of these examples, we show that the rate function of the Cramer-type of large deviations coincides with that of the Freidlin-Wentzell when contraction principles are applied.

  5. 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.

  6. A VMEbus clock system for accelerator control

    International Nuclear Information System (INIS)

    Beechy, D.G.; McClure, C.R.

    1992-01-01

    Because an accelerator has many systems which must operate with a high degree of synchronization, a clock signal is typically generated which carries timing information to the various accelerator components. This paper discusses two VMEbus modules designed to generate and receive this clock signal. Together they implement a clock system which can generate timing markers with 200 nanosecond resolution and can generate timing delays of over one hour with one microsecond resolution. The Clock Generator module contains both a time line generator programmed to produce clock events at specific times and eight programmable input channels to produce clock events when externally triggered. Additional clock events are generated directly from the VMEbus. Generators can be cascaded for added capability. The Clock Timer module receives the signal from the generator. It can be programmed to recognize specific clock events which act as triggers to the eight timing channels on the module. Each timing channel is programmed with a 32-bit delay value. The channels are clocked at 1 MHz. At the end of the delay period, a timer channel produces an output pulse and optionally can generate a bus interrupt

  7. Strictly contractive quantum channels and physically realizable quantum computers

    International Nuclear Information System (INIS)

    Raginsky, Maxim

    2002-01-01

    We study the robustness of quantum computers under the influence of errors modeled by strictly contractive channels. A channel T is defined to be strictly contractive if, for any pair of density operators ρ, σ in its domain, parallel Tρ-Tσ parallel 1 ≤k parallel ρ-σ parallel 1 for some 0≤k 1 denotes the trace norm). In other words, strictly contractive channels render the states of the computer less distinguishable in the sense of quantum detection theory. Starting from the premise that all experimental procedures can be carried out with finite precision, we argue that there exists a physically meaningful connection between strictly contractive channels and errors in physically realizable quantum computers. We show that, in the absence of error correction, sensitivity of quantum memories and computers to strictly contractive errors grows exponentially with storage time and computation time, respectively, and depends only on the constant k and the measurement precision. We prove that strict contractivity rules out the possibility of perfect error correction, and give an argument that approximate error correction, which covers previous work on fault-tolerant quantum computation as a special case, is possible

  8. Design and implementation of fast bipolar clock drivers for CCD imaging systems in space applications

    Science.gov (United States)

    Jayarajan, Jayesh; Kumar, Nishant; Verma, Amarnath; Thaker, Ramkrishna

    2016-05-01

    Drive electronics for generating fast, bipolar clocks, which can drive capacitive loads of the order of 5-10nF are indispensable for present day Charge Coupled Devices (CCDs). Design of these high speed bipolar clocks is challenging because of the capacitive loads that have to be driven and a strict constraint on the rise and fall times. Designing drive electronics circuits for space applications becomes even more challenging due to limited number of available discrete devices, which can survive in the harsh radiation prone space environment. This paper presents the design, simulations and test results of a set of such high speed, bipolar clock drivers. The design has been tested under a thermal cycle of -15 deg C to +55 deg C under vacuum conditions and has been designed using radiation hardened components. The test results show that the design meets the stringent rise/fall time requirements of 50+/-10ns for Multiple Vertical CCD (VCCD) clocks and 20+/-5ns for Horizontal CCD (HCCD) clocks with sufficient design margins across full temperature range, with a pixel readout rate of 6.6MHz. The full design has been realized in flexi-rigid PCB with package volume of 140x160x50 mm3.

  9. 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.

  10. Sexual Differentiation of Circadian Clock Function in the Adrenal Gland.

    Science.gov (United States)

    Kloehn, Ian; Pillai, Savin B; Officer, Laurel; Klement, Claire; Gasser, Paul J; Evans, Jennifer A

    2016-05-01

    Sex differences in glucocorticoid production are associated with increased responsiveness of the adrenal gland in females. However, the adrenal-intrinsic mechanisms that establish sexual dimorphic function remain ill defined. Glucocorticoid production is gated at the molecular level by the circadian clock, which may contribute to sexual dimorphic adrenal function. Here we examine sex differences in the adrenal gland using an optical reporter of circadian clock function. Adrenal glands were cultured from male and female Period2::Luciferase (PER2::LUC) mice to assess clock function in vitro in real time. We confirm that there is a pronounced sex difference in the intrinsic capacity to sustain PER2::LUC rhythms in vitro, with higher amplitude rhythms in adrenal glands collected from males than from females. Changes in adrenal PER2::LUC rhythms over the reproductive life span implicate T as an important factor in driving sex differences in adrenal clock function. By directly manipulating hormone levels in adult mice in vivo, we demonstrate that T increases the amplitude of PER2::LUC rhythms in adrenal glands of both male and female mice. In contrast, we find little evidence that ovarian hormones modify adrenal clock function. Lastly, we find that T in vitro can increase the amplitude of PER2::LUC rhythms in male adrenals but not female adrenals, which suggests the existence of sex differences in the mechanisms of T action in vivo. Collectively these results reveal that activational effects of T alter circadian timekeeping in the adrenal gland, which may have implications for sex differences in stress reactivity and stress-related disorders.

  11. 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.

  12. The Clock gene clone and its circadian rhythms in Pelteobagrus vachelli

    Science.gov (United States)

    Qin, Chuanjie; Shao, Ting

    2015-05-01

    The Clock gene, a key molecule in circadian systems, is widely distributed in the animal kingdom. We isolated a 936-bp partial cDNA sequence of the Clock gene ( Pva-clock) from the darkbarbel catfish Pelteobagrus vachelli that exhibited high identity with Clock genes of other species of fish and animals (65%-88%). The putative domains included a basic helix-loop-helix (bHLH) domain and two period-ARNT-single-minded (PAS) domains, which were also similar to those in other species of fish and animals. Pva-Clock was primarily expressed in the brain, and was detected in all of the peripheral tissues sampled. Additionally, the pattern of Pva-Clock expression over a 24-h period exhibited a circadian rhythm in the brain, liver and intestine, with the acrophase at zeitgeber time 21:35, 23:00, and 23:23, respectively. Our results provide insight into the function of the molecular Clock of P. vachelli.

  13. 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…

  14. Space experiments with high stability clocks

    International Nuclear Information System (INIS)

    Vessot, R.F.C.

    1993-01-01

    Modern metrology depends increasingly on the accuracy and frequency stability of atomic clocks. Applications of such high-stability oscillators (or clocks) to experiments performed in space are described and estimates of the precision of these experiments are made in terms of clock performance. Methods using time-correlation to cancel localized disturbances in very long signal paths and a proposed space borne four station VLBI system are described. (TEC). 30 refs., 14 figs., 1 tab

  15. Age-Related Changes in the Expression of the Circadian Clock Protein PERIOD in Drosophila Glial Cells

    OpenAIRE

    Long, Dani M.; Giebultowicz, Jadwiga M.

    2018-01-01

    Circadian clocks consist of molecular negative feedback loops that coordinate physiological, neurological, and behavioral variables into “circa” 24-h rhythms. Rhythms in behavioral and other circadian outputs tend to weaken during aging, as evident in progressive disruptions of sleep-wake cycles in aging organisms. However, less is known about the molecular changes in the expression of clock genes and proteins that may lead to the weakening of circadian outputs. Western blot studies have demo...

  16. Convergence theorems for strictly hemi-contractive maps

    International Nuclear Information System (INIS)

    Chidume, C.E.; Osilike, M.O.

    1992-04-01

    It is proved that each of two well-known fixed point iteration methods (the Mann and the Ishikawa iteration methods) converges strongly to the fixed point of strictly hemi-contractive map in real Banach spaces with property (U, λ, m+1,m), λ is an element of R, m is an element of IN. The class of strictly hemi-contractive maps includes all strictly pseudo-contractive maps with nonempty fixed point sets; and Banach spaces with property (U, λ, m+1, m), λ is an element of R, m is an element of IN include the L p (or l p ) spaces, p≥2. Our theorems generalize important known results. (author). 22 refs

  17. Circadian Clock Dysfunction and Psychiatric Disease: Could Fruit Flies have a Say?

    Science.gov (United States)

    Zordan, Mauro Agostino; Sandrelli, Federica

    2015-01-01

    There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system leads to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here, we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e., a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia, and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes, which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions, and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease.

  18. Circadian clock dysfunction and psychiatric disease: could fruit flies have a say?

    Directory of Open Access Journals (Sweden)

    Mauro Agostino Zordan

    2015-04-01

    Full Text Available There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system lead to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e. a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease.

  19. High Performance Clocks and Gravity Field Determination

    Science.gov (United States)

    Müller, J.; Dirkx, D.; Kopeikin, S. M.; Lion, G.; Panet, I.; Petit, G.; Visser, P. N. A. M.

    2018-02-01

    Time measured by an ideal clock crucially depends on the gravitational potential and velocity of the clock according to general relativity. Technological advances in manufacturing high-precision atomic clocks have rapidly improved their accuracy and stability over the last decade that approached the level of 10^{-18}. This notable achievement along with the direct sensitivity of clocks to the strength of the gravitational field make them practically important for various geodetic applications that are addressed in the present paper. Based on a fully relativistic description of the background gravitational physics, we discuss the impact of those highly-precise clocks on the realization of reference frames and time scales used in geodesy. We discuss the current definitions of basic geodetic concepts and come to the conclusion that the advances in clocks and other metrological technologies will soon require the re-definition of time scales or, at least, clarification to ensure their continuity and consistent use in practice. The relative frequency shift between two clocks is directly related to the difference in the values of the gravity potential at the points of clock's localization. According to general relativity the relative accuracy of clocks in 10^{-18} is equivalent to measuring the gravitational red shift effect between two clocks with the height difference amounting to 1 cm. This makes the clocks an indispensable tool in high-precision geodesy in addition to laser ranging and space geodetic techniques. We show how clock measurements can provide geopotential numbers for the realization of gravity-field-related height systems and can resolve discrepancies in classically-determined height systems as well as between national height systems. Another application of clocks is the direct use of observed potential differences for the improved recovery of regional gravity field solutions. Finally, clock measurements for space-borne gravimetry are analyzed along with

  20. Effects of different per translational kinetics on the dynamics of a core circadian clock model.

    Science.gov (United States)

    Nieto, Paula S; Revelli, Jorge A; Garbarino-Pico, Eduardo; Condat, Carlos A; Guido, Mario E; Tamarit, Francisco A

    2015-01-01

    Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.

  1. Long-Term Clock Behavior of GPS IIR Satellites

    National Research Council Canada - National Science Library

    Epstein, Marvin; Dass, Todd; Rajan, John; Gilmour, Paul

    2007-01-01

    .... Rubidium clocks, as opposed to cesium clocks, have significant long-term drift. The current literature describes an initial model of drift aging for rubidium atomic clocks followed by a long-term characteristic...

  2. Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis

    OpenAIRE

    Traynard , Pauline; Feillet , Céline; Soliman , Sylvain; Delaunay , Franck; Fages , François

    2016-01-01

    International audience; Experimental observations have put in evidence autonomous self-sustained circadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell ...

  3. 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

  4. The clock paradox as a cosmological problem

    International Nuclear Information System (INIS)

    Fu, K.Y.

    1975-01-01

    In this paper the clock paradox is discussed within the framework of the general theory of relativity. It is shown that in general the aging asymmetry exists. It is also argued that the clock paradox, according to Mach's principle, is essentially a cosmological problem. (author)

  5. 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...

  6. 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).

  7. 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.

  8. Analytic properties of form factors in strictly confining models

    International Nuclear Information System (INIS)

    Csikor, F.

    1979-12-01

    An argument is presented showing that strict confinement implies the possible existence of an (unwanted) branch point at q 2 =0 in the form factors. In case of a bag extended to infinity in the relative time, the branch point is certainly there (provided that the form factor is non zero at q 2 =0). (author)

  9. Dominance on Strict Triangular Norms and Mulholland Inequality

    Czech Academy of Sciences Publication Activity Database

    Petrík, Milan

    2018-01-01

    Roč. 335, 15 March (2018), s. 3-17 ISSN 0165-0114 R&D Projects: GA ČR GJ15-07724Y Institutional support: RVO:67985807 Keywords : dominance relation * Mulholland inequality * strict triangular norm * transitivity Subject RIV: BA - General Mathematics Impact factor: 2.718, year: 2016

  10. Effects of strict prolonged bed rest on cardiorespiratory fitness

    DEFF Research Database (Denmark)

    Ried-Larsen, Mathias; Aarts, Hugo M; Joyner, Michael J

    2017-01-01

    The aim of this systematic review and meta-analysis [International Prospective Register of Systematic Reviews (PROSPERO) CRD42017055619] was to assess the effects of strict prolonged bed rest (without countermeasures) on maximal oxygen uptake (V̇o2max) and to explore sources of variation therein....

  11. Processing of visually presented clock times.

    Science.gov (United States)

    Goolkasian, P; Park, D C

    1980-11-01

    The encoding and representation of visually presented clock times was investigated in three experiments utilizing a comparative judgment task. Experiment 1 explored the effects of comparing times presented in different formats (clock face, digit, or word), and Experiment 2 examined angular distance effects created by varying positions of the hands on clock faces. In Experiment 3, encoding and processing differences between clock faces and digitally presented times were directly measured. Same/different reactions to digitally presented times were faster than to times presented on a clock face, and this format effect was found to be a result of differences in processing that occurred after encoding. Angular separation also had a limited effect on processing. The findings are interpreted within the framework of theories that refer to the importance of representational codes. The applicability to the data of Bank's semantic-coding theory, Paivio's dual-coding theory, and the levels-of-processing view of memory are discussed.

  12. Altered Rhythm of Adrenal Clock Genes, StAR and Serum Corticosterone in VIP Receptor 2-Deficient Mice

    DEFF Research Database (Denmark)

    Fahrenkrug, Jan; Georg, Birgitte; Hannibal, Jens

    2012-01-01

    oscillator based on a group of clock genes and their protein products. Mice lacking the VPAC2 receptor display disrupted circadian rhythm of physiology and behaviour, and therefore, we using real-time RT-PCR quantified (1) the mRNAs for the clock genes Per1 and Bmal1 in the adrenal gland and SCN, (2......RNA expression and serum corticosterone concentration. Double immunohistochemistry showed that the PER1 protein and StAR were co-localised in the same steroidogenic cells. Circulating corticosterone plays a role in the circadian timing system and the misaligned corticosterone rhythm in the VPAC2 receptor......The circadian time-keeping system consists of clocks in the suprachiasmatic nucleus (SCN) and in peripheral organs including an adrenal clock linked to the rhythmic corticosteroid production by regulating steroidogenic acute regulatory protein (StAR). Clock cells contain an autonomous molecular...

  13. 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.

  14. Dilatation effect of ''quantum clocks''

    International Nuclear Information System (INIS)

    Chylinski, Z.

    1981-01-01

    The relativistic dilatation effect of the life-time of unstable microparticles combined with quantum symmetry of their description results in the ''quantum-dilatation'' dilemma. It is due to the classical character of the relativity theory which here reveals itself in the classical world-line of the clock necessary in order to deduce the dilatation effect from the Lorentz transformation. It is shown how to solve this dilemma, basing on the relation continuum C 4 . Two types of measurements of time intervals, the direct and indirect one, are analyzed. The former type corresponds to the external space-time continuum, where any direct measurement takes place, and the latter, to the internal relation continuum C 4 , where the internal structures of isolated micro-systems are sunk. (author)

  15. 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.

  16. Causes and consequences of hyperexcitation in central clock neurons.

    Directory of Open Access Journals (Sweden)

    Casey O Diekman

    Full Text Available Hyperexcited states, including depolarization block and depolarized low amplitude membrane oscillations (DLAMOs, have been observed in neurons of the suprachiasmatic nuclei (SCN, the site of the central mammalian circadian (~24-hour clock. The causes and consequences of this hyperexcitation have not yet been determined. Here, we explore how individual ionic currents contribute to these hyperexcited states, and how hyperexcitation can then influence molecular circadian timekeeping within SCN neurons. We developed a mathematical model of the electrical activity of SCN neurons, and experimentally verified its prediction that DLAMOs depend on post-synaptic L-type calcium current. The model predicts that hyperexcited states cause high intracellular calcium concentrations, which could trigger transcription of clock genes. The model also predicts that circadian control of certain ionic currents can induce hyperexcited states. Putting it all together into an integrative model, we show how membrane potential and calcium concentration provide a fast feedback that can enhance rhythmicity of the intracellular circadian clock. This work puts forward a novel role for electrical activity in circadian timekeeping, and suggests that hyperexcited states provide a general mechanism for linking membrane electrical dynamics to transcription activation in the nucleus.

  17. The Importance of the Circadian Clock in Regulating Plant Metabolism

    Directory of Open Access Journals (Sweden)

    Jin A Kim

    2017-12-01

    Full Text Available Carbohydrates are the primary energy source for plant development. Plants synthesize sucrose in source organs and transport them to sink organs during plant growth. This metabolism is sensitive to environmental changes in light quantity, quality, and photoperiod. In the daytime, the synthesis of sucrose and starch accumulates, and starch is degraded at nighttime. The circadian clock genes provide plants with information on the daily environmental changes and directly control many developmental processes, which are related to the path of primary metabolites throughout the life cycle. The circadian clock mechanism and processes of metabolism controlled by the circadian rhythm were studied in the model plant Arabidopsis and in the crops potato and rice. However, the translation of molecular mechanisms obtained from studies of model plants to crop plants is still difficult. Crop plants have specific organs such as edible seed and tuber that increase the size or accumulate valuable metabolites by harvestable metabolic components. Human consumers are interested in the regulation and promotion of these agriculturally significant crops. Circadian clock manipulation may suggest various strategies for the increased productivity of food crops through using environmental signal or overcoming environmental stress.

  18. NONO couples the circadian clock to the cell cycle.

    Science.gov (United States)

    Kowalska, Elzbieta; Ripperger, Juergen A; Hoegger, Dominik C; Bruegger, Pascal; Buch, Thorsten; Birchler, Thomas; Mueller, Anke; Albrecht, Urs; Contaldo, Claudio; Brown, Steven A

    2013-01-29

    Mammalian circadian clocks restrict cell proliferation to defined time windows, but the mechanism and consequences of this interrelationship are not fully understood. Previously we identified the multifunctional nuclear protein NONO as a partner of circadian PERIOD (PER) proteins. Here we show that it also conveys circadian gating to the cell cycle, a connection surprisingly important for wound healing in mice. Specifically, although fibroblasts from NONO-deficient mice showed approximately normal circadian cycles, they displayed elevated cell doubling and lower cellular senescence. At a molecular level, NONO bound to the p16-Ink4A cell cycle checkpoint gene and potentiated its circadian activation in a PER protein-dependent fashion. Loss of either NONO or PER abolished this activation and circadian expression of p16-Ink4A and eliminated circadian cell cycle gating. In vivo, lack of NONO resulted in defective wound repair. Because wound healing defects were also seen in multiple circadian clock-deficient mouse lines, our results therefore suggest that coupling of the cell cycle to the circadian clock via NONO may be useful to segregate in temporal fashion cell proliferation from tissue organization.

  19. Rhythmic expression of circadian clock genes in the preovulatory ovarian follicles of the laying hen.

    Directory of Open Access Journals (Sweden)

    Zhichao Zhang

    Full Text Available The circadian clock is reported to play a role in the ovaries in a variety of vertebrate species, including the domestic hen. However, the ovary is an organ that changes daily, and the laying hen maintains a strict follicular hierarchy. The aim of this study was to examine the spatial-temporal expression of several known canonical clock genes in the granulosa and theca layers of six hierarchy follicles. We demonstrated that the granulosa cells (GCs of the F1-F3 follicles harbored intrinsic oscillatory mechanisms in vivo. In addition, cultured granulosa cells (GCs from F1 follicles exposed to luteinizing hormone (LH synchronization displayed Per2 mRNA oscillations, whereas, the less mature GCs (F5 plus F6 displayed no circadian change in Per2 mRNA levels. Cultures containing follicle-stimulating hormone (FSH combined with LH expressed levels of Per2 mRNA that were 2.5-fold higher than those in cultures with LH or FSH alone. These results show that there is spatial specificity in the localization of clock cells in hen preovulatory follicles. In addition, our results support the hypothesis that gonadotropins provide a cue for the development of the functional cellular clock in immature GCs.

  20. Evidence for an Overlapping Role of CLOCK and NPAS2 Transcription Factors in Liver Circadian Oscillators▿

    Science.gov (United States)

    Bertolucci, Cristiano; Cavallari, Nicola; Colognesi, Ilaria; Aguzzi, Jacopo; Chen, Zheng; Caruso, Pierpaolo; Foá, Augusto; Tosini, Gianluca; Bernardi, Francesco; Pinotti, Mirko

    2008-01-01

    The mechanisms underlying the circadian control of gene expression in peripheral tissues and influencing many biological pathways are poorly defined. Factor VII (FVII), the protease triggering blood coagulation, represents a valuable model to address this issue in liver since its plasma levels oscillate in a circadian manner and its promoter contains E-boxes, which are putative DNA-binding sites for CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers and hallmarks of circadian regulation. The peaks of FVII mRNA levels in livers of wild-type mice preceded those in plasma, indicating a transcriptional regulation, and were abolished in Clock−/−; Npas2−/− mice, thus demonstrating a role for CLOCK and NPAS2 circadian transcription factors. The investigation of Npas2−/− and ClockΔ19/Δ19 mice, which express functionally defective heterodimers, revealed robust rhythms of FVII expression in both animal models, suggesting a redundant role for NPAS2 and CLOCK. The molecular bases of these observations were established through reporter gene assays. FVII transactivation activities of the NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers were (i) comparable (a fourfold increase), (ii) dampened by the negative circadian regulators PER2 and CRY1, and (iii) abolished upon E-box mutagenesis. Our data provide the first evidence in peripheral oscillators for an overlapping role of CLOCK and NPAS2 in the regulation of circadianly controlled genes. PMID:18316400

  1. DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

    Science.gov (United States)

    Liu, Xiao; Dang, Yunkun; Matsu-Ura, Toru; He, Yubo; He, Qun; Hong, Christian I; Liu, Yi

    2017-07-20

    Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism. Published by Elsevier Inc.

  2. Central and peripheral circadian clocks and their role in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ruchi Chauhan

    2017-10-01

    Full Text Available Molecular and cellular oscillations constitute an internal clock that tracks the time of day and permits organisms to optimize their behaviour and metabolism to suit the daily demands they face. The workings of this internal clock become impaired with age. In this review, we discuss whether such age-related impairments in the circadian clock interact with age-related neurodegenerative disorders, such as Alzheimer's disease. Findings from mouse and fly models of Alzheimer's disease have accelerated our understanding of the interaction between neurodegeneration and circadian biology. These models show that neurodegeneration likely impairs circadian rhythms either by damaging the central clock or by blocking its communication with other brain areas and with peripheral tissues. The consequent sleep and metabolic deficits could enhance the susceptibility of the brain to further degenerative processes. Thus, circadian dysfunction might be both a cause and an effect of neurodegeneration. We also discuss the primary role of light in the entrainment of the central clock and describe important, alternative time signals, such as food, that play a role in entraining central and peripheral circadian clocks. Finally, we propose how these recent insights could inform efforts to develop novel therapeutic approaches to re-entrain arrhythmic individuals with neurodegenerative disease.

  3. Strong Convergence Theorems for a Pair of Strictly Pseudononspreading Mappings

    Directory of Open Access Journals (Sweden)

    Bin-Chao Deng

    2013-01-01

    Full Text Available Let H be a real Hilbert space. Let T1,T2:H→H be k1-, k2-strictly pseudononspreading mappings; let αn and βn be two real sequences in (0,1. For given x0∈H, the sequence xn is generated iteratively by xn+1=βnxn+1-βnTw1αnγfxn+I-μαnBTw2xn, ∀n∈N, where Twi=1−wiI+wiTi with i=1,2 and B:H→H is strongly monotone and Lipschitzian. Under some mild conditions on parameters αn and βn, we prove that the sequence xn converges strongly to the set FixT1∩FixT2 of fixed points of a pair of strictly pseudononspreading mappings T1 and T2.

  4. Clocking In Time to Gate Memory Processes: The Circadian Clock Is Part of the Ins and Outs of Memory

    Directory of Open Access Journals (Sweden)

    Oliver Rawashdeh

    2018-01-01

    Full Text Available Learning, memory consolidation, and retrieval are processes known to be modulated by the circadian (circa: about; dies: day system. The circadian regulation of memory performance is evolutionarily conserved, independent of the type and complexity of the learning paradigm tested, and not specific to crepuscular, nocturnal, or diurnal organisms. In mammals, long-term memory (LTM formation is tightly coupled to de novo gene expression of plasticity-related proteins and posttranslational modifications and relies on intact cAMP/protein kinase A (PKA/protein kinase C (PKC/mitogen-activated protein kinase (MAPK/cyclic adenosine monophosphate response element-binding protein (CREB signaling. These memory-essential signaling components cycle rhythmically in the hippocampus across the day and night and are clearly molded by an intricate interplay between the circadian system and memory. Important components of the circadian timing mechanism and its plasticity are members of the Period clock gene family (Per1, Per2. Interestingly, Per1 is rhythmically expressed in mouse hippocampus. Observations suggest important and largely unexplored roles of the clock gene protein PER1 in synaptic plasticity and in the daytime-dependent modulation of learning and memory. Here, we review the latest findings on the role of the clock gene Period 1 (Per1 as a candidate molecular and mechanistic blueprint for gating the daytime dependency of memory processing.

  5. Transmission delays in hardware clock synchronization

    Science.gov (United States)

    Shin, Kang G.; Ramanathan, P.

    1988-01-01

    Various methods, both with software and hardware, have been proposed to synchronize a set of physical clocks in a system. Software methods are very flexible and economical but suffer an excessive time overhead, whereas hardware methods require no time overhead but are unable to handle transmission delays in clock signals. The effects of nonzero transmission delays in synchronization have been studied extensively in the communication area in the absence of malicious or Byzantine faults. The authors show that it is easy to incorporate the ideas from the communication area into the existing hardware clock synchronization algorithms to take into account the presence of both malicious faults and nonzero transmission delays.

  6. Circadian clock components in the rat neocortex

    DEFF Research Database (Denmark)

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

    2013-01-01

    in the rat neocortex. Among these, Per1, Per2, Per3, Cry1, Bmal1, Nr1d1 and Dbp were found to exhibit daily rhythms. The amplitude of circadian oscillation in neocortical clock gene expression was damped and the peak delayed as compared with the SCN. Lesions of the SCN revealed that rhythmic clock gene...... expression in the neocortex is dependent on the SCN. In situ hybridization and immunohistochemistry showed that products of the canonical clock gene Per2 are located in perikarya throughout all areas of the neocortex. These findings show that local circadian oscillators driven by the SCN reside within...... neurons of the neocortex....

  7. Growth of a Strictly Anaerobic Bacterium on Furfural (2-Furaldehyde)

    OpenAIRE

    Brune, Gerhard; Schoberth, Siegfried M.; Sahm, Hermann

    1983-01-01

    A strictly anaerobic bacterium was isolated from a continuous fermentor culture which converted the organic constituents of sulfite evaporator condensate to methane and carbon dioxide. Furfural is one of the major components of this condensate. This furfural isolate could degrade furfural as the sole source of carbon and energy in a defined mineral-vitamin-sulfate medium. Acetic acid was the major fermentation product. This organism could also use ethanol, lactate, pyruvate, or fumarate and c...

  8. The Fixed-Point Theory of Strictly Causal Functions

    Science.gov (United States)

    2013-06-09

    functions were defined to be the functions that are strictly contracting with respect to the Cantor metric (also called the Baire distance) on signals...of Lecture Notes in Computer Science, pages 447–484. Springer Berlin / Heidelberg, 1992. [36] George Markowsky. Chain-complete posets and directed...Journal of Logic Programming, 42(2):59–70, 2000. [52] George M. Reed and A. William Roscoe. A timed model for communicating sequential processes. In Laurent

  9. The endogenous circadian clock programs animals to eat at certain times of the 24-hour day: What if we ignore the clock?

    Science.gov (United States)

    Jiang, Peng; Turek, Fred W

    2018-04-16

    The discovery of the molecular mechanisms underlying the circadian clock, which functions in virtually every cell throughout the body to coordinate biological processes to anticipate and better adapt to daily rhythmic changes in the environment, is one of the major biomedical breakthroughs in the 20th century. Twenty years after this breakthrough, the biomedical community is now at a new frontier to incorporate the circadian clock mechanisms into many areas of biomedical research, as studies continue to reveal an important role of the circadian clock in a wide range of biological functions and diseases. A forefront of this exciting area is the research of interactions between the clock and energy metabolism. In this review, we summarize animal and human studies linking disruptions of the circadian clock, either environmental or genetic, to metabolic dysfunctions associated with obesity, diabetes, and other metabolic disorders. We also discuss how these advances in circadian biology may pave the way to revolutionize clinical practice in the era of precision medicine. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Regulation of circadian clock transcriptional output by CLOCK:BMAL1

    Science.gov (United States)

    Trott, Alexandra J.

    2018-01-01

    The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of 15% of the transcriptome and control the daily regulation of biological functions. The recent characterization of CLOCK:BMAL1 cistrome revealed that although CLOCK:BMAL1 binds synchronously to all of its target genes, its transcriptional output is highly heterogeneous. By performing a meta-analysis of several independent genome-wide datasets, we found that the binding of other transcription factors at CLOCK:BMAL1 enhancers likely contribute to the heterogeneity of CLOCK:BMAL1 transcriptional output. While CLOCK:BMAL1 rhythmic DNA binding promotes rhythmic nucleosome removal, it is not sufficient to generate transcriptionally active enhancers as assessed by H3K27ac signal, RNA Polymerase II recruitment, and eRNA expression. Instead, the transcriptional activity of CLOCK:BMAL1 enhancers appears to rely on the activity of ubiquitously expressed transcription factors, and not tissue-specific transcription factors, recruited at nearby binding sites. The contribution of other transcription factors is exemplified by how fasting, which effects several transcription factors but not CLOCK:BMAL1, either decreases or increases the amplitude of many rhythmically expressed CLOCK:BMAL1 target genes. Together, our analysis suggests that CLOCK:BMAL1 promotes a transcriptionally permissive chromatin landscape that primes its target genes for transcription activation rather than directly activating transcription, and provides a new framework to explain how environmental or pathological conditions can reprogram the rhythmic expression of clock-controlled genes. PMID:29300726

  11. Clock Drawing in Spatial Neglect: A Comprehensive Analysis of Clock Perimeter, Placement, and Accuracy

    Science.gov (United States)

    Chen, Peii; Goedert, Kelly M.

    2012-01-01

    Clock drawings produced by right-brain-damaged (RBD) individuals with spatial neglect often contain an abundance of empty space on the left while numbers and hands are placed on the right. However, the clock perimeter is rarely compromised in neglect patients’ drawings. By analyzing clock drawings produced by 71 RBD and 40 healthy adults, this study investigated whether the geometric characteristics of the clock perimeter reveal novel insights to understanding spatial neglect. Neglect participants drew smaller clocks than either healthy or non-neglect RBD participants. While healthy participants’ clock perimeter was close to circular, RBD participants drew radially extended ellipses. The mechanisms for these phenomena were investigated by examining the relation between clock-drawing characteristics and performance on six subtests of the Behavioral Inattention Test (BIT). The findings indicated that the clock shape was independent of any BIT subtest or the drawing placement on the test sheet and that the clock size was significantly predicted by one BIT subtest: the poorer the figure and shape copying, the smaller the clock perimeter. Further analyses revealed that in all participants, clocks decreased in size as they were placed farther from the center of the paper. However, even when neglect participants placed their clocks towards the center of the page, they were smaller than those produced by healthy or non-neglect RBD participants. These results suggest a neglect-specific reduction in the subjectively available workspace for graphic production from memory, consistent with the hypothesis that neglect patients are impaired in the ability to enlarge the attentional aperture. PMID:22390278

  12. 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

  13. Bennett clocking of quantum-dot cellular automata and the limits to binary logic scaling

    International Nuclear Information System (INIS)

    Lent, Craig S; Liu Mo; Lu Yuhui

    2006-01-01

    We examine power dissipation in different clocking schemes for molecular quantum-dot cellular automata (QCA) circuits. 'Landauer clocking' involves the adiabatic transition of a molecular cell from the null state to an active state carrying data. Cell layout creates devices which allow data in cells to interact and thereby perform useful computation. We perform direct solutions of the equation of motion for the system in contact with the thermal environment and see that Landauer's Principle applies: one must dissipate an energy of at least k B T per bit only when the information is erased. The ideas of Bennett can be applied to keep copies of the bit information by echoing inputs to outputs, thus embedding any logically irreversible circuit in a logically reversible circuit, at the cost of added circuit complexity. A promising alternative which we term 'Bennett clocking' requires only altering the timing of the clocking signals so that bit information is simply held in place by the clock until a computational block is complete, then erased in the reverse order of computation. This approach results in ultralow power dissipation without additional circuit complexity. These results offer a concrete example in which to consider recent claims regarding the fundamental limits of binary logic scaling

  14. Dynamics of the Drosophila circadian clock: theoretical anti-jitter network and controlled chaos.

    Directory of Open Access Journals (Sweden)

    Hassan M Fathallah-Shaykh

    Full Text Available BACKGROUND: Electronic clocks exhibit undesirable jitter or time variations in periodic signals. The circadian clocks of humans, some animals, and plants consist of oscillating molecular networks with peak-to-peak time of approximately 24 hours. Clockwork orange (CWO is a transcriptional repressor of Drosophila direct target genes. METHODOLOGY/PRINCIPAL FINDINGS: Theory and data from a model of the Drosophila circadian clock support the idea that CWO controls anti-jitter negative circuits that stabilize peak-to-peak time in light-dark cycles (LD. The orbit is confined to chaotic attractors in both LD and dark cycles and is almost periodic in LD; furthermore, CWO diminishes the Euclidean dimension of the chaotic attractor in LD. Light resets the clock each day by restricting each molecular peak to the proximity of a prescribed time. CONCLUSIONS/SIGNIFICANCE: The theoretical results suggest that chaos plays a central role in the dynamics of the Drosophila circadian clock and that a single molecule, CWO, may sense jitter and repress it by its negative loops.

  15. Pittendrigh: The Darwinian Clock-Watcher

    Indian Academy of Sciences (India)

    to our current understanding of how timing systems work in living organisms. .... to periodic factors in the geophysical environment. He postulated .... clocks against temperature, nutrition and light, while the latter needs maintenance of a stable.

  16. Cell-permeable Circadian Clock Proteins

    National Research Council Canada - National Science Library

    Johnson, Carl

    2002-01-01

    .... These 'biological clocks' are important to human physiology. For example, psychiatric and medical studies have shown that circadian rhythmicity is involved in some forms of depressive illness, 'jet lag', drug tolerance/efficacy, memory, and insomnia...

  17. 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.

  18. 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.

  19. Cellular Reprogramming–Turning the Clock Back

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 6. Cellular Reprogramming - Turning the Clock Back - Nobel Prize in Physiology or Medicine, 2012. Deepa Subramanyam. General Article Volume 18 Issue 6 June 2013 pp 514-521 ...

  20. A GPS Satellite Clock Offset Prediction Method Based on Fitting Clock Offset Rates Data

    Directory of Open Access Journals (Sweden)

    WANG Fuhong

    2016-12-01

    Full Text Available It is proposed that a satellite atomic clock offset prediction method based on fitting and modeling clock offset rates data. This method builds quadratic model or linear model combined with periodic terms to fit the time series of clock offset rates, and computes the model coefficients of trend with the best estimation. The clock offset precisely estimated at the initial prediction epoch is directly adopted to calculate the model coefficient of constant. The clock offsets in the rapid ephemeris (IGR provided by IGS are used as modeling data sets to perform certain experiments for different types of GPS satellite clocks. The results show that the clock prediction accuracies of the proposed method for 3, 6, 12 and 24 h achieve 0.43, 0.58, 0.90 and 1.47 ns respectively, which outperform the traditional prediction method based on fitting original clock offsets by 69.3%, 61.8%, 50.5% and 37.2%. Compared with the IGU real-time clock products provided by IGS, the prediction accuracies of the new method have improved about 15.7%, 23.7%, 27.4% and 34.4% respectively.

  1. 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.

  2. 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

    editted by Jerry Jacobson at the University of Wisconsin - Madison. The Chemistry Basics When we ask students or precollege teacher groups about the reduction and oxidation reactions that are occurring, they invariably answer that the magnesium metal is being oxidized and the copper metal is being reduced. This response is important because we use it to impress upon students and workshop participants the importance of looking carefully at the system before giving what might seem like an obvious answer. The copper cannot be reduced because there is no copper ion in solution, and transition metals cannot be reduced to anions. Given what is actually in solution, participants can conclude that hydrogen ion can be reduced to molecular hydrogen (in orange juice) or that hydrogen in the water molecule is being reduced to molecular hydrogen (in hard tap water). In distilled water, the clock does not run because the internal resistance of the solution is too high, thus forcing the current to be very small. The reactions of interest are given as eqs 1-3: oxidation: Mg -> Mg2+ + 2e- Eo = 2.37 vs. SHE (1) reduction 2H+ + 2e- -> H2 Eo = 0.00 vs. SHE (2) (acid solution) reduction (water) 2H2O + 2e- -> H2 + 2OH- Eo = -0.8277 vs. SHE (3) where Eo = the voltage under standard conditions and SHE = standard hydrogen electrode. At standard conditions, under zero load (all activities equal to one and 298 K) the cell voltage should theoretically be 2.37 V in acid (pH = 1) and about 1.54 V in neutral solution, either of which is enough to allow the clock to run. It is important to remember the IUPAC convention for electrochemical cells: that voltage of the cell equals voltage of the cathodic half-cell minus voltage of the anodic half-cell. In this case, Eo = 0.00 V - (-2.37 V) = 2.37 V The standard free energy calculation is straightforward in each case (eq 4), DeltaGo = -nFEo in which n = number of moles of electrons transferred, as dictated by the stoichiometry of the reaction (in all

  3. Optical lattice clock with Strontium atoms

    International Nuclear Information System (INIS)

    Baillard, X.

    2008-01-01

    This thesis presents the latest achievements regarding the optical lattice clock with Strontium atoms developed at LNE-SYRTE. After a review of the different types of optical clocks that are currently under development, we stress on the concept of optical lattice clock which was first imagined for Sr 87 using the 1 S 0 → 3 P 0 transition. We exhibit the features of this atom, in particular the concept of magic wavelength for the trap, and the achievable performances for this kind of clock. The second part presents the experimental aspects, insisting particularly on the ultra-stable laser used for the interrogation of the atoms which is a central part of the experiment. Among the latest improvements, an optical pumping phase and an interrogation phase using a magnetic field have been added in order to refine the evaluation of the Zeeman effect. Finally, the last part presents the experimental results. The last evaluation of the clock using Sr 87 atoms allowed us to reach a frequency accuracy of 2.6*10 -15 and a measurement in agreement with the one made at JILA (Tokyo university) at the 10 -15 level. On another hand, thanks to recent theoretical proposals, we made a measurement using the bosonic isotope Sr 88 by adapting the experimental setup. This measurement represents the first evaluation for this type of clock, with a frequency accuracy of 7*10 -14 . (author)

  4. Towards Self-Clocked Gated OCDMA Receiver

    Science.gov (United States)

    Idris, S.; Osadola, T.; Glesk, I.

    2013-02-01

    A novel incoherent OCDMA receiver with incorporated all-optical clock recovery for self-synchronization of a time gate for the multi access interferences (MAI) suppression and minimizing the effect of data time jitter in incoherent OCDMA system was successfully developed and demonstrated. The solution was implemented and tested in a multiuser environment in an out of the laboratory OCDMA testbed with two-dimensional wavelength-hopping time-spreading coding scheme and OC-48 (2.5 Gbp/s) data rate. The self-clocked all-optical time gate uses SOA-based fibre ring laser optical clock, recovered all-optically from the received OCDMA traffic to control its switching window for cleaning the autocorrelation peak from the surrounding MAI. A wider eye opening was achieved when the all-optically recovered clock from received data was used for synchronization if compared to a static approach with the RF clock being generated by a RF synthesizer. Clean eye diagram was also achieved when recovered clock is used to drive time gating.

  5. Genetic Disruption of the Core Circadian Clock Impairs Hippocampus-Dependent Memory

    Science.gov (United States)

    Wardlaw, Sarah M.; Phan, Trongha X.; Saraf, Amit; Chen, Xuanmao; Storm, Daniel R.

    2014-01-01

    Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1[superscript -/-] mice, which are arrhythmic…

  6. Selective Inhibition of Casein Kinase 1 epsilon Minimally Alters Circadian Clock Period

    Czech Academy of Sciences Publication Activity Database

    Walton, K. M.; Fisher, K.; Rubitski, D.; Marconi, M.; Meng, Q.-J.; Sládek, Martin; Adams, J.; Bass, M.; Chandrasekaran, R.; Butler, T.; Griffor, M.; Rajamohan, F.; Serpa, M.; Chen, Y.; Claffey, M.; Hastings, M.; Loudon, A.; Maywood, E.; Ohren, J.; Doran, A.; Wager, T. T.

    2009-01-01

    Roč. 330, č. 2 (2009), s. 430-439 ISSN 0022-3565 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian clock * casein kinase 1 epsilon * inhibitor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.093, year: 2009

  7. Small heterodimer partner (NROB2) coordinates nutrient signaling and the circadian clock in mice

    Science.gov (United States)

    Circadian rhythm regulates multiple metabolic processes and in turn is readily entrained by feeding-fasting cycles. However, the molecular mechanisms by which the peripheral clock senses nutrition availability remain largely unknown. Bile acids are under circadian control and also increase postprand...

  8. Modular PNML revisited: Some ideas for strict typing

    DEFF Research Database (Denmark)

    Kindler, Ekkart

    2007-01-01

    The Petri Net Markup Language (PNML) is currently standardised by ISO/IEC JTC1/SC7 WG 19 as Part 2 of ISO/IEC 15909. But, there is not yet a mechanism for structuring large Petri nets and for constructing Petri nets from modules. To this end, modular PNML has been proposed some time ago. But, mod...... of Petri net, but still has a strict type system. This paper focuses on the ideas and concepts; the technical details still need to be worked out. To this end, this paper also raises some issues and questions that need to be discussed before standardising modular PNML....

  9. Relaxation Methods for Strictly Convex Regularizations of Piecewise Linear Programs

    International Nuclear Information System (INIS)

    Kiwiel, K. C.

    1998-01-01

    We give an algorithm for minimizing the sum of a strictly convex function and a convex piecewise linear function. It extends several dual coordinate ascent methods for large-scale linearly constrained problems that occur in entropy maximization, quadratic programming, and network flows. In particular, it may solve exact penalty versions of such (possibly inconsistent) problems, and subproblems of bundle methods for nondifferentiable optimization. It is simple, can exploit sparsity, and in certain cases is highly parallelizable. Its global convergence is established in the recent framework of B -functions (generalized Bregman functions)

  10. A role for clock genes in sleep homeostasis.

    Science.gov (United States)

    Franken, Paul

    2013-10-01

    The timing and quality of both sleep and wakefulness are thought to be regulated by the interaction of two processes. One of these two processes keeps track of the prior sleep-wake history and controls the homeostatic need for sleep while the other sets the time-of-day that sleep preferably occurs. The molecular pathways underlying the latter, circadian process have been studied in detail and their key role in physiological time-keeping has been well established. Analyses of sleep in mice and flies lacking core circadian clock gene proteins have demonstrated, however, that besides disrupting circadian rhythms, also sleep homeostatic processes were affected. Subsequent studies revealed that sleep loss alters both the mRNA levels and the specific DNA-binding of the key circadian transcriptional regulators to their target sequences in the mouse brain. The fact that sleep loss impinges on the very core of the molecular circadian circuitry might explain why both inadequate sleep and disrupted circadian rhythms can similarly lead to metabolic pathology. The evidence for a role for clock genes in sleep homeostasis will be reviewed here. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Deleting the Arntl clock gene in the granular layer of the mouse cerebellum

    DEFF Research Database (Denmark)

    Bering, Tenna; Carstensen, Mikkel Bloss; Rath, Martin Fredensborg

    2017-01-01

    nucleus. It has been suggested that the cerebellar circadian oscillator is involved in food anticipation, but direct molecular evidence of the role of the circadian oscillator of the cerebellar cortex is currently unavailable. To investigate the hypothesis that the circadian oscillator of the cerebellum...... is involved in circadian physiology and food anticipation, we therefore by use of Cre-LoxP technology generated a conditional knockout mouse with the core clock gene Arntl deleted specifically in granule cells of the cerebellum, since expression of clock genes in the cerebellar cortex is mainly located...

  12. Non-strictly black body spectrum from the tunnelling mechanism

    International Nuclear Information System (INIS)

    Corda, Christian

    2013-01-01

    The tunnelling mechanism is widely used to explain Hawking radiation. However, in many cases the analysis used to obtain the Hawking temperature only involves comparing the emission probability for an outgoing particle with the Boltzmann factor. Banerjee and Majhi improved this approach by explicitly finding a black body spectrum associated with black holes. Their result, obtained using a reformulation of the tunnelling mechanism, is in contrast to that of Parikh and Wilczek, who found an emission probability that is compatible with a non-strictly thermal spectrum. Using the recently identified effective state for a black hole, we solve this contradiction via a slight modification of the analysis by Banerjee and Majhi. The final result is a non-strictly black body spectrum from the tunnelling mechanism. We also show that for an effective temperature, we can express the corresponding effective metric using Hawking’s periodicity arguments. Potential important implications for the black hole information puzzle are discussed. -- Highlights: •We review an important result by Banerjee and Majhi on the tunnelling mechanism in the framework of Hawking radiation. •This result is in contrast to another result reported by Parikh and Wilczek. •We introduce the effective state of a black hole. •We explain the contrast via a slight modification of the analysis by Banerjee and Majhi. •We discuss potential important implications for the black hole information puzzle

  13. Timing Embryo Segmentation: Dynamics and Regulatory Mechanisms of the Vertebrate Segmentation Clock

    Science.gov (United States)

    Resende, Tatiana P.; Andrade, Raquel P.; Palmeirim, Isabel

    2014-01-01

    All vertebrate species present a segmented body, easily observed in the vertebrate column and its associated components, which provides a high degree of motility to the adult body and efficient protection of the internal organs. The sequential formation of the segmented precursors of the vertebral column during embryonic development, the somites, is governed by an oscillating genetic network, the somitogenesis molecular clock. Herein, we provide an overview of the molecular clock operating during somite formation and its underlying molecular regulatory mechanisms. Human congenital vertebral malformations have been associated with perturbations in these oscillatory mechanisms. Thus, a better comprehension of the molecular mechanisms regulating somite formation is required in order to fully understand the origin of human skeletal malformations. PMID:24895605

  14. General anesthesia alters time perception by phase shifting the circadian clock.

    Science.gov (United States)

    Cheeseman, James F; Winnebeck, Eva C; Millar, Craig D; Kirkland, Lisa S; Sleigh, James; Goodwin, Mark; Pawley, Matt D M; Bloch, Guy; Lehmann, Konstantin; Menzel, Randolf; Warman, Guy R

    2012-05-01

    Following general anesthesia, people are often confused about the time of day and experience sleep disruption and fatigue. It has been hypothesized that these symptoms may be caused by general anesthesia affecting the circadian clock. The circadian clock is fundamental to our well-being because it regulates almost all aspects of our daily biochemistry, physiology, and behavior. Here, we investigated the effects of the most common general anesthetic, isoflurane, on time perception and the circadian clock using the honeybee (Apis mellifera) as a model. A 6-h daytime anesthetic systematically altered the time-compensated sun compass orientation of the bees, with a mean anticlockwise shift in vanishing bearing of 87° in the Southern Hemisphere and a clockwise shift in flight direction of 58° in the Northern Hemisphere. Using the same 6-h anesthetic treatment, time-trained bees showed a delay in the start of foraging of 3.3 h, and whole-hive locomotor-activity rhythms were delayed by an average of 4.3 h. We show that these effects are all attributable to a phase delay in the core molecular clockwork. mRNA oscillations of the central clock genes cryptochrome-m and period were delayed by 4.9 and 4.3 h, respectively. However, this effect is dependent on the time of day of administration, as is common for clock effects, and nighttime anesthesia did not shift the clock. Taken together, our results suggest that general anesthesia during the day causes a persistent and marked shift of the clock effectively inducing "jet lag" and causing impaired time perception. Managing this effect in humans is likely to help expedite postoperative recovery.

  15. Quantifying fluctuations in reversible enzymatic cycles and clocks

    Science.gov (United States)

    Wierenga, Harmen; ten Wolde, Pieter Rein; Becker, Nils B.

    2018-04-01

    Biochemical reactions are fundamentally noisy at a molecular scale. This limits the precision of reaction networks, but it also allows fluctuation measurements that may reveal the structure and dynamics of the underlying biochemical network. Here, we study nonequilibrium reaction cycles, such as the mechanochemical cycle of molecular motors, the phosphorylation cycle of circadian clock proteins, or the transition state cycle of enzymes. Fluctuations in such cycles may be measured using either of two classical definitions of the randomness parameter, which we show to be equivalent in general microscopically reversible cycles. We define a stochastic period for reversible cycles and present analytical solutions for its moments. Furthermore, we associate the two forms of the randomness parameter with the thermodynamic uncertainty relation, which sets limits on the timing precision of the cycle in terms of thermodynamic quantities. Our results should prove useful also for the study of temporal fluctuations in more general networks.

  16. Evidence for a chemical clock in oscillatory formation of UiO-66

    Science.gov (United States)

    Goesten, M. G.; de Lange, M. F.; Olivos-Suarez, A. I.; Bavykina, A. V.; Serra-Crespo, P.; Krywka, C.; Bickelhaupt, F. M.; Kapteijn, F.; Gascon, Jorge

    2016-06-01

    Chemical clocks are often used as exciting classroom experiments, where an induction time is followed by rapidly changing colours that expose oscillating concentration patterns. This type of reaction belongs to a class of nonlinear chemical kinetics also linked to chaos, wave propagation and Turing patterns. Despite its vastness in occurrence and applicability, the clock reaction is only well understood for liquid-state processes. Here we report a chemical clock reaction, in which a solidifying entity, metal-organic framework UiO-66, displays oscillations in crystal dimension and number, as shown by X-ray scattering. In rationalizing this result, we introduce a computational approach, the metal-organic molecular orbital methodology, to pinpoint interaction between the tectonic building blocks that construct the metal-organic framework material. In this way, we show that hydrochloric acid plays the role of autocatalyst, bridging separate processes of condensation and crystallization.

  17. Defence responses of arabidopsis thaliana to infection by pseudomonas syringae are regulated by the circadian clock

    KAUST Repository

    Bhardwaj, Vaibhav

    2011-10-31

    The circadian clock allows plants to anticipate predictable daily changes in abiotic stimuli, such as light; however, whether the clock similarly allows plants to anticipate interactions with other organisms is unknown. Here we show that Arabidopsis thaliana (Arabidopsis) has circadian clock-mediated variation in resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), with plants being least susceptible to infection in the subjective morning. We suggest that the increased resistance to Pst DC3000 observed in the morning in Col-0 plants results from clock-mediated modulation of pathogen associated molecular pattern (PAMP)-triggered immunity. Analysis of publicly available microarray data revealed that a large number of Arabidopsis defence-related genes showed both diurnal- and circadian-regulation, including genes involved in the perception of the PAMP flagellin which exhibit a peak in expression in the morning. Accordingly, we observed that PAMP-triggered callose deposition was significantly higher in wild-type plants inoculated with Pst DC3000 hrpA in the subjective morning than in the evening, while no such temporal difference was evident in arrhythmic plants. Our results suggest that PAMP-triggered immune responses are modulated by the circadian clock and that temporal regulation allows plants to anticipate and respond more effectively to pathogen challenges in the daytime. © 2011 Bhardwaj et al.

  18. 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....... In previous versions of this calculus, different clocks represented separate time streams and clock synchronisation was prohibited. In this paper we show that allowing clock synchronisation is safe by constructing a new model of guarded recursion and clocks. This result will greatly simplify the type theory...... by removing freshness restrictions from typing rules, and is a necessary step towards defining rewrite semantics, and ultimately implementing the calculus....

  19. Epigenetic and Posttranslational Modifications in Light Signal Transduction and the Circadian Clock in Neurospora crassa

    Directory of Open Access Journals (Sweden)

    Marco Proietto

    2015-07-01

    Full Text Available Blue light, a key abiotic signal, regulates a wide variety of physiological processes in many organisms. One of these phenomena is the circadian rhythm presents in organisms sensitive to the phase-setting effects of blue light and under control of the daily alternation of light and dark. Circadian clocks consist of autoregulatory alternating negative and positive feedback loops intimately connected with the cellular metabolism and biochemical processes. Neurospora crassa provides an excellent model for studying the molecular mechanisms involved in these phenomena. The White Collar Complex (WCC, a blue-light receptor and transcription factor of the circadian oscillator, and Frequency (FRQ, the circadian clock pacemaker, are at the core of the Neurospora circadian system. The eukaryotic circadian clock relies on transcriptional/translational feedback loops: some proteins rhythmically repress their own synthesis by inhibiting the activity of their transcriptional factors, generating self-sustained oscillations over a period of about 24 h. One of the basic mechanisms that perpetuate self-sustained oscillations is post translation modification (PTM. The acronym PTM generically indicates the addition of acetyl, methyl, sumoyl, or phosphoric groups to various types of proteins. The protein can be regulatory or enzymatic or a component of the chromatin. PTMs influence protein stability, interaction, localization, activity, and chromatin packaging. Chromatin modification and PTMs have been implicated in regulating circadian clock function in Neurospora. Research into the epigenetic control of transcription factors such as WCC has yielded new insights into the temporal modulation of light-dependent gene transcription. Here we report on epigenetic and protein PTMs in the regulation of the Neurospora crassa circadian clock. We also present a model that illustrates the molecular mechanisms at the basis of the blue light control of the circadian clock.

  20. Strict calculation of electron energy distribution functions in inhomogeneous plasmas

    International Nuclear Information System (INIS)

    Winkler, R.

    1996-01-01

    It is objective of the paper to report on strict calculations of the velocity or energy distribution function function and related macroscopic properties of the electrons from appropriate electron kinetic equations under various plasma conditions and to contribute to a better understanding of the electron behaviour in inhomogeneous plasma regions. In particular, the spatial relaxation of plasma electrons acted upon by uniform electric fields, the response of plasma electrons on spatial disturbances of the electric field, the electron kinetics under the impact of space charge field confinement in the dc column plasma and the electron velocity distribution is stronger field as occurring in the electrode regions of a dc glow discharge is considered. (author)

  1. Asymptotic state discrimination and a strict hierarchy in distinguishability norms

    Energy Technology Data Exchange (ETDEWEB)

    Chitambar, Eric [Department of Physics and Astronomy, Southern Illinois University, Carbondale, Illinois 62901 (United States); Hsieh, Min-Hsiu [Centre for Quantum Computation and Intelligent Systems (QCIS), Faculty of Engineering and Information Technology (FEIT), University of Technology Sydney - UTS, NSW 2007 (Australia)

    2014-11-15

    In this paper, we consider the problem of discriminating quantum states by local operations and classical communication (LOCC) when an arbitrarily small amount of error is permitted. This paradigm is known as asymptotic state discrimination, and we derive necessary conditions for when two multipartite states of any size can be discriminated perfectly by asymptotic LOCC. We use this new criterion to prove a gap in the LOCC and separable distinguishability norms. We then turn to the operational advantage of using two-way classical communication over one-way communication in LOCC processing. With a simple two-qubit product state ensemble, we demonstrate a strict majorization of the two-way LOCC norm over the one-way norm.

  2. Growth of a Strictly Anaerobic Bacterium on Furfural (2-Furaldehyde)

    Science.gov (United States)

    Brune, Gerhard; Schoberth, Siegfried M.; Sahm, Hermann

    1983-01-01

    A strictly anaerobic bacterium was isolated from a continuous fermentor culture which converted the organic constituents of sulfite evaporator condensate to methane and carbon dioxide. Furfural is one of the major components of this condensate. This furfural isolate could degrade furfural as the sole source of carbon and energy in a defined mineral-vitamin-sulfate medium. Acetic acid was the major fermentation product. This organism could also use ethanol, lactate, pyruvate, or fumarate and contained cytochrome c3 and desulfoviridin. Except for furfural degradation, the characteristics of the furfural isolate were remarkably similar to those of the sulfate reducer Desulfovibrio gigas. The furfural isolate has been tentatively identified as Desulfovibrio sp. strain F-1. Images PMID:16346423

  3. Effects of a strict cutoff on Quantum Field Theory

    International Nuclear Information System (INIS)

    Sturnfield, J.F.

    1987-01-01

    Standard Quantum Field Theory has a number of integrals which are infinite. Although these are eliminated for some cases by renormalization, this aspect of the theory is not fully satisfactory. A number of theories with fundamental lengths have been introduced as alternatives and it would be useful to be able to distinguish between them. In particular, the effects that a strict cutoff would have on Quantum Field Theory is studied. It is noted that care must be taken in the method used to apply a strict cutoff. This lead to considering a theory where the cutoffs are defined by restricting each internal line. This theory is only piece-wise analytic. The resulting scattering matrix is frame dependent, yet the theory still satisfies the special relativity view that all frames are subjectively identical. The renormalization of this theory is finite. The change in mass from the electron self-energy will be a spinor operator. The main distinctions of this theory from standard theory will occur at super high energies. New poles and resonances which arise from new endpoint singularities will be found. The locations of these singularities will be frame dependent. Some of these singularities will correspond to creations or interactions of the normal particles with tachyons. It will be shown that for the one loop diagram, the form of the cutoff singularities are closely related to the standard singularities. When there is more than one loop, there can appear some new type of behavior. In particular, a cube root type of behavior in the two loop self-energy diagram will be found. Also the asymptotic behavior of the ladder diagram is studied

  4. 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.

  5. Crime clocks and target performance maps

    CSIR Research Space (South Africa)

    Cooper, Antony K

    1999-12-01

    Full Text Available the period of analysis. Each segment of a pie chart represents a selected part of the day (eg: a two- or three-hour period) or a day of the week. The first and last segments in the day or week are then adjacent, ensuring that there is no artificial break... clocks We have also used crime clocks to map the proportion of crimes that occur during normal police working hours (07:00 to 16:00, Monday to Friday, in the case of the Johannesburg Area), against those that occur outside these hours. 3. Target...

  6. The Fermilab D0 Master Clock System

    International Nuclear Information System (INIS)

    Rotolo, C.; Fachin, M.; Chappa, S.; Rauch, M.; Needles, C.; Dyer, A.

    1991-11-01

    The Clock System provides bunch crossing related timing signals to various detector subsystems. Accelerator synchronization and monitoring as well as timing signal generation and distribution are discussed. The system is built using three module types implemented in Eurostandard hardware with a VME communications interface. The first two types of modules are used to facilitate synchronization with the accelerator and to generate 23 timing signals that are programmable with one RF bucket (18.8 ns) resolution and 1 ns accuracy. Fifty-four of the third module type are used to distribute the timing signals and two synchronous 53 MHz and 106 MHz clocks to various detector subsystems. 6 refs., 5 figs

  7. 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....

  8. Clock-frequency and temperature margins of a high-temperature superconductor delay-line memory

    International Nuclear Information System (INIS)

    Hattori, W.; Tahara, S.

    1999-01-01

    We have developed a 10 GHz 32-bit delay-line memory, using a semiconductor crossbar switch and a YBa 2 Cu 3 O 7-δ coplanar delay line. For use in the high-speed (≥10 GHz) cell-buffer storage of large-throughput (≥1 Tbit/s) asynchronous transfer mode (ATM) switching systems, this memory must be fairly reliable. To evaluate the reliability of the operation, therefore, we measured the clock-frequency and temperature margins and the temperature dependence of the bit-error rate. At 64 K, this memory has a capacity of 32 bits with a clock frequency of 9.89±0.11 GHz. In general, clock frequencies of communication systems are strictly managed so that the margins are less than 10 -6 . Therefore, the frequency margin of this memory (∼2x10 -2 )) is wide enough for use in communication systems. The temperature margin was 71.5±4.3 K at 10 GHz and 33 bits. This memory offered error-free operation (BER -13 ) at 71.5 ±3.5 K. These temperature margins are wide enough to be controlled by a cryocooler. These results show that the memory offers reliability and that it can be applied to high-speed ATM cell-buffer storage. (author)

  9. Fermentative Degradation of Polyethylene Glycol by a Strictly Anaerobic, Gram-Negative, Nonsporeforming Bacterium, Pelobacter venetianus sp. nov

    OpenAIRE

    1983-01-01

    The synthetic polyether polyethylene glycol (PEG) with a molecular weight of 20,000 was anaerobically degraded in enrichment cultures inoculated with mud of limnic and marine origins. Three strains (Gra PEG 1, Gra PEG 2, and Ko PEG 2) of rod-shaped, gram-negative, nonsporeforming, strictly anaerobic bacteria were isolated in mineral medium with PEG as the sole source of carbon and energy. All strains degraded dimers, oligomers, and polymers of PEG up to a molecular weight of 20,000 completely...

  10. 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.

  11. Robustness from flexibility in the fungal circadian clock

    Directory of Open Access Journals (Sweden)

    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

  12. Epigenetic control and the circadian clock: linking metabolism to neuronal responses.

    Science.gov (United States)

    Orozco-Solis, R; Sassone-Corsi, P

    2014-04-04

    Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape. Published by Elsevier Ltd.

  13. 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…

  14. Food at work around the clock

    DEFF Research Database (Denmark)

    Dahl Lassen, Anne; Beck, Anne Marie; Thorsen, Anne Vibeke

    This report brings together 12 invited presentations and outcomes of a workshop on food and meals for employees working irregular hours “around the clock”. The workshop, “Food at work around the clock – The Nordic Model”, was hosted by the National Food Institute at the Technical University...

  15. Hands Together! An Analog Clock Problem

    Science.gov (United States)

    Earnest, Darrell; Radtke, Susan; Scott, Siri

    2017-01-01

    In this article, the authors first present the Hands Together! task. The mathematics in this problem concerns the relationship of hour and minute durations as reflected in the oft-overlooked proportional movements of the two hands of an analog clock. The authors go on to discuss the importance of problem solving in general. They then consider…

  16. Analytic clock frequency selection for global DVFS

    NARCIS (Netherlands)

    Gerards, Marco Egbertus Theodorus; Hurink, Johann L.; Holzenspies, P.K.F.; Kuper, Jan; Smit, Gerardus Johannes Maria

    2014-01-01

    Computers can reduce their power consumption by decreasing their speed using Dynamic Voltage and Frequency Scaling (DVFS). A form of DVFS for multicore processors is global DVFS, where the voltage and clock frequency is shared among all processor cores. Because global DVFS is efficient and cheap to

  17. Efficient FPT Algorithms for (Strict) Compatibility of Unrooted Phylogenetic Trees.

    Science.gov (United States)

    Baste, Julien; Paul, Christophe; Sau, Ignasi; Scornavacca, Celine

    2017-04-01

    In phylogenetics, a central problem is to infer the evolutionary relationships between a set of species X; these relationships are often depicted via a phylogenetic tree-a tree having its leaves labeled bijectively by elements of X and without degree-2 nodes-called the "species tree." One common approach for reconstructing a species tree consists in first constructing several phylogenetic trees from primary data (e.g., DNA sequences originating from some species in X), and then constructing a single phylogenetic tree maximizing the "concordance" with the input trees. The obtained tree is our estimation of the species tree and, when the input trees are defined on overlapping-but not identical-sets of labels, is called "supertree." In this paper, we focus on two problems that are central when combining phylogenetic trees into a supertree: the compatibility and the strict compatibility problems for unrooted phylogenetic trees. These problems are strongly related, respectively, to the notions of "containing as a minor" and "containing as a topological minor" in the graph community. Both problems are known to be fixed parameter tractable in the number of input trees k, by using their expressibility in monadic second-order logic and a reduction to graphs of bounded treewidth. Motivated by the fact that the dependency on k of these algorithms is prohibitively large, we give the first explicit dynamic programming algorithms for solving these problems, both running in time [Formula: see text], where n is the total size of the input.

  18. Managing Hanford Site solid waste through strict acceptance criteria

    International Nuclear Information System (INIS)

    Jasen, W.G.; Pierce, R.D.; Willis, N.P.

    1993-02-01

    Various types of waste have been generated during the 50-year history of the Hanford Site. Regulatory changes in the last 20 years have provided the emphasis for better management of these wastes. Interpretations of the Atomic Energy Act of 1954 (AEA) and the Resource Conservation and Recovery Act of 1976 (RCRA) have led to the definition of a group of wastes called radioactive mixed wastes (RMW). As a result of the radioactive and hazardous properties of these wastes, strict management programs have been implemented for the management of these wastes. Solid waste management is accomplished through a systems performance approach to waste management that used best-demonstrated available technology (BDAT) and best management practices. The solid waste program at the Hanford Site strives to integrate all aspects of management relative to the treatment, storage and disposal (TSD) of solid waste. Often there are many competing and important needs. It is a difficult task to balance these needs in a manner that is both equitable and productive. Management science is used to help the process of making decisions. Tools used to support the decision making process include five-year planning, cost estimating, resource allocation, performance assessment, waste volume forecasts, input/output models, and waste acceptance criteria. The purpose of this document is to describe how one of these tools, waste acceptance criteria, has helped the Hanford Site manage solid wastes

  19. Fixed point iterations for strictly hemi-contractive maps in uniformly smooth Banach spaces

    International Nuclear Information System (INIS)

    Chidume, C.E.; Osilike, M.O.

    1993-05-01

    It is proved that the Mann iteration process converges strongly to the fixed point of a strictly hemi-contractive map in real uniformly smooth Banach spaces. The class of strictly hemi-contractive maps includes all strictly pseudo-contractive maps with nonempty fixed point sets. A related result deals with the Ishikawa iteration scheme when the mapping is Lipschitzian and strictly hemi-contractive. Our theorems generalize important known results. (author). 29 refs

  20. PDF and cAMP enhance PER stability in Drosophila clock neurons

    Science.gov (United States)

    Li, Yue; Guo, Fang; Shen, James; Rosbash, Michael

    2014-01-01

    The neuropeptide PDF is important for Drosophila circadian rhythms: pdf01 (pdf-null) animals are mostly arrhythmic or short period in constant darkness and have an advanced activity peak in light–dark conditions. PDF contributes to the amplitude, synchrony, as well as the pace of circadian rhythms within clock neurons. PDF is known to increase cAMP levels in PDR receptor (PDFR)-containing neurons. However, there is no known connection of PDF or of cAMP with the Drosophila molecular clockworks. We discovered that the mutant period gene perS ameliorates the phenotypes of pdf-null flies. The period protein (PER) is a well-studied repressor of clock gene transcription, and the perS protein (PERS) has a markedly short half-life. The result therefore suggests that the PDF-mediated increase in cAMP might lengthen circadian period by directly enhancing PER stability. Indeed, increasing cAMP levels and cAMP-mediated protein kinase A (PKA) activity stabilizes PER, in S2 tissue culture cells and in fly circadian neurons. Adding PDF to fly brains in vitro has a similar effect. Consistent with these relationships, a light pulse causes more prominent PER degradation in pdf01 circadian neurons than in wild-type neurons. The results indicate that PDF contributes to clock neuron synchrony by increasing cAMP and PKA, which enhance PER stability and decrease clock speed in intrinsically fast-paced PDFR-containing clock neurons. We further suggest that the more rapid degradation of PERS bypasses PKA regulation and makes the pace of clock neurons more uniform, allowing them to avoid much of the asynchrony caused by the absence of PDF. PMID:24707054

  1. The Circadian Clock Gene BMAL1 Coordinates Intestinal RegenerationSummary

    Directory of Open Access Journals (Sweden)

    Kyle Stokes

    2017-07-01

    Full Text Available Background & Aims: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied. Methods: We tested the timing of regeneration in the mouse intestine during the gastrointestinal syndrome. The role of the circadian clock was tested genetically using the BMAL1 loss of function mouse mutant in vivo, and in vitro using intestinal organoid culture. Results: The proliferation of the intestinal epithelium follows a 24-hour rhythm during the gastrointestinal syndrome. The circadian clock runs in the intestinal epithelium during this pathologic state, and the loss of the core clock gene, BMAL1, disrupts both the circadian clock and rhythmic proliferation. Circadian activity in the intestine involves a rhythmic production of inflammatory cytokines and subsequent rhythmic activation of the JNK stress response pathway. Conclusions: Our results show that a circadian rhythm in inflammation and regeneration occurs during the gastrointestinal syndrome. The study and treatment of radiation-induced illnesses, and other gastrointestinal illnesses, should consider 24-hour timing in physiology and pathology. Keywords: Intestine, Circadian Rhythms, Gastrointestinal Syndrome, TNF, Intestinal Stem Cells

  2. Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH.

    Science.gov (United States)

    Bruce, Kimberley D; Szczepankiewicz, Dawid; Sihota, Kiran K; Ravindraanandan, Manoj; Thomas, Hugh; Lillycrop, Karen A; Burdge, Graham C; Hanson, Mark A; Byrne, Christopher D; Cagampang, Felino R

    2016-07-01

    We have previously shown that high fat (HF) feeding during pregnancy primes the development of non-alcoholic steatohepatits (NASH) in the adult offspring. However, the underlying mechanisms are unclear. Since the endogenous molecular clock can regulate hepatic lipid metabolism, we investigated whether exposure to a HF diet during development could alter hepatic clock gene expression and contribute to NASH onset in later life. Female mice were fed either a control (C, 7%kcal fat) or HF (45%kcal fat) diet. Offspring were fed either a C or HF diet resulting in four offspring groups: C/C, C/HF, HF/C and HF/HF. NAFLD progression, cellular redox status, sirtuin expression (Sirt1, Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and clock-controlled genes involved in lipid metabolism (Rev-Erbα, Rev-Erbβ, RORα, and Srebp1c) were measured in offspring livers. Offspring fed a HF diet developed NAFLD. However HF fed offspring of mothers fed a HF diet developed NASH, coupled with significantly reduced NAD(+)/NADH (pNASH in adulthood, involving altered cellular redox status, reduced sirtuin abundance, and desynchronized clock gene expression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Strict or Graduated Punishment? Effect of Punishment Strictness on the Evolution of Cooperation in Continuous Public Goods Games

    Science.gov (United States)

    Shimao, Hajime; Nakamaru, Mayuko

    2013-01-01

    Whether costly punishment encourages cooperation is one of the principal questions in studies on the evolution of cooperation and social sciences. In society, punishment helps deter people from flouting rules in institutions. Specifically, graduated punishment is a design principle for long-enduring common-pool resource institutions. In this study, we investigate whether graduated punishment can promote a higher cooperation level when each individual plays the public goods game and has the opportunity to punish others whose cooperation levels fall below the punisher’s threshold. We then examine how spatial structure affects evolutionary dynamics when each individual dies inversely proportional to the game score resulting from the social interaction and another player is randomly chosen from the population to produce offspring to fill the empty site created after a player’s death. Our evolutionary simulation outcomes demonstrate that stricter punishment promotes increased cooperation more than graduated punishment in a spatially structured population, whereas graduated punishment increases cooperation more than strict punishment when players interact with randomly chosen opponents from the population. The mathematical analysis also supports the results. PMID:23555826

  4. Strict or graduated punishment? Effect of punishment strictness on the evolution of cooperation in continuous public goods games.

    Directory of Open Access Journals (Sweden)

    Hajime Shimao

    Full Text Available Whether costly punishment encourages cooperation is one of the principal questions in studies on the evolution of cooperation and social sciences. In society, punishment helps deter people from flouting rules in institutions. Specifically, graduated punishment is a design principle for long-enduring common-pool resource institutions. In this study, we investigate whether graduated punishment can promote a higher cooperation level when each individual plays the public goods game and has the opportunity to punish others whose cooperation levels fall below the punisher's threshold. We then examine how spatial structure affects evolutionary dynamics when each individual dies inversely proportional to the game score resulting from the social interaction and another player is randomly chosen from the population to produce offspring to fill the empty site created after a player's death. Our evolutionary simulation outcomes demonstrate that stricter punishment promotes increased cooperation more than graduated punishment in a spatially structured population, whereas graduated punishment increases cooperation more than strict punishment when players interact with randomly chosen opponents from the population. The mathematical analysis also supports the results.

  5. Does exercise training impact clock genes in patients with coronary artery disease and type 2 diabetes mellitus?

    Science.gov (United States)

    Steidle-Kloc, Eva; Schönfelder, Martin; Müller, Edith; Sixt, Sebastian; Schuler, Gerhard; Patsch, Wolfgang; Niebauer, Josef

    2016-09-01

    Recent findings revealed negative effects of deregulated molecular circadian rhythm in coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Physical exercise training (ET) has been shown to promote anti-diabetic and anti-atherogenic responses in skeletal muscle of these patients, but the role of the circadian clock-machinery remains unknown. This study investigated whether mRNA expression of clock genes in skeletal muscle of CAD and T2DM patients is influenced by physical ET intervention. Nineteen patients with CAD and T2DM (age 64 ± 5 years) were randomised to either six months of ET (four weeks of in-hospital ET followed by a five-month ambulatory programme) or usual care. At the beginning of the study, after four weeks and after six months parameters of metabolic and cardiovascular risk factors, and physical exercise capacity were assessed. Gene expression was measured in skeletal muscle biopsies by quantitative real-time polymerase chain reaction (PCR). A selection of clock genes and associated components (circadian locomoter output cycle kaput protein (CLOCK), period (PER) 1, cryptochrome (CRY) 2 and aminolevulinate-deltA-synthase-1 (ALAS1)) was reliably measured and used for further analysis. A time-dependent effect in gene expression was observed in CLOCK (p = 0.013) and a significant interaction between time and intervention was observed for ALAS1 (p = 0.032; p = 0.014) as a result of ET. This is the first study to analyse clock gene expression in skeletal muscles of patients with CAD and T2DM participating in a long-lasting exercise intervention. ET, as one of the cornerstones in prevention and rehabilitation of CAD and T2DM, exerts no effects on CLOCK genes but meaningful effects on the clock-associated gene ALAS1. © The European Society of Cardiology 2016.

  6. Age-Related Changes in the Expression of the Circadian Clock Protein PERIOD in Drosophila Glial Cells

    Directory of Open Access Journals (Sweden)

    Dani M. Long

    2018-01-01

    Full Text Available Circadian clocks consist of molecular negative feedback loops that coordinate physiological, neurological, and behavioral variables into “circa” 24-h rhythms. Rhythms in behavioral and other circadian outputs tend to weaken during aging, as evident in progressive disruptions of sleep-wake cycles in aging organisms. However, less is known about the molecular changes in the expression of clock genes and proteins that may lead to the weakening of circadian outputs. Western blot studies have demonstrated that the expression of the core clock protein PERIOD (PER declines in the heads of aged Drosophila melanogaster flies. This age-related decline in PER does not occur in the central pacemaker neurons but has been demonstrated so far in retinal photoreceptors. Besides photoreceptors, clock proteins are also expressed in fly glia, which play important roles in neuronal homeostasis and are further categorized into subtypes based on morphology and function. While previous studies of mammalian glial cells have demonstrated the presence of functional clocks in astrocytes and microglia, it is not known which glial cell types in Drosophila express clock proteins and how their expression may change in aged individuals. Here, we conducted immunocytochemistry experiments to identify which glial subtypes express PER protein suggestive of functional circadian clocks. Glial cell subtypes that showed night-time accumulation and day-time absence in PER consistent with oscillations reported in the pacemaker neurons were selected to compare the level of PER protein between young and old flies. Our data demonstrate that some glial subtypes show rhythmic PER expression and the relative PER levels become dampened with advanced age. Identification of glial cell types that display age-related dampening of PER levels may help to understand the cellular changes that contribute to the loss of homeostasis in the aging brain.

  7. Alkaliphilus crotonatoxidans sp. nov., a strictly anaerobic, crotonate-dismutating bacterium isolated from a methanogenic environment.

    Science.gov (United States)

    Cao, Xianhua; Liu, Xiaoli; Dong, Xiuzhu

    2003-07-01

    Two bacterial strains were isolated from methanogenic butyrate-oxidizing mixed cultures. The cells were straight to slightly curved, gram-positive rods that were motile by means of multiple flagella and formed endospores. Growth was observed in the temperature range 15-45 degrees C (optimum 37 degrees C) and pH range 5.5-9.0 (optimum pH 7.5). The novel isolates were strictly anaerobic chemo-organotrophs capable of utilizing yeast extract, peptone, tryptone and a variety of sugars and organic acids, but not glucose. None of the accessory electron acceptors tested (elemental sulfur, thiosulfate or fumarate) improved growth, except crotonate, which was dismutated to butyrate and acetate. The G + C content of the DNA of one of the isolates, strain B11-2T, was 30.6 mol%. Phylogenetic analysis based on 16S rDNA sequence similarity between strain B11-2T and some other strictly anaerobic, spore-forming bacteria indicated that the novel isolates represented a species in cluster XI within the low-GC gram-positive bacteria, being most closely related to Alkaliphilus transvaalensis JCM 10712T. DNA-DNA relatedness between strain B11-2T and A. transvaalensis JCM 10712T was 21%. On the basis of physiological and molecular properties, and cellular fatty acid and cell wall compositions, the novel isolates are proposed to represent a novel species of the genus Alkaliphilus, for which the name Alkaliphilus crotonatoxidans is proposed (type strain B11-2T=AS 1.2897T=JCM 11672T).

  8. Supporting Family Awareness with the Whereabouts Clock

    Science.gov (United States)

    Sellen, Abigail; Taylor, Alex S.; Kaye, Joseph ‘Jofish'; Brown, Barry; Izadi, Shahram

    We report the results of a field trial of a situated awareness device for families called the “Whereabouts Clock”. The Clock displays the location of family members using cellphone data as one of four privacy-preserving, deliberately coarse-grained categories ( HOME, WORK, SCHOOL or ELSEWHERE). The results show that awareness of others through the Clock supports not only family communication and coordination but also more emotive aspects of family life such as reassurance, connectedness, identity and social touch. We discuss how the term “awareness” means many things in practice and highlight the importance of designing not just for family activities, but in order to support the emotional, social and even moral aspects of family life.

  9. Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

    OpenAIRE

    2014-01-01

    Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1−/− mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippoca...

  10. Effects of mass defect in atomic clocks

    Science.gov (United States)

    Taichenachev, A. V.; Yudin, V. I.

    2018-01-01

    We consider some implications of the mass defect on the frequency of atomic transitions. We have found that some well-known frequency shifts (such as gravitational and quadratic Doppler shifts) can be interpreted as consequences of the mass defect, i.e., without the need for the concept of time dilation used in special and general relativity theories. Moreover, we show that the inclusion of the mass defect leads to previously unknown shifts for clocks based on trapped ions..

  11. Clock error models for simulation and estimation

    International Nuclear Information System (INIS)

    Meditch, J.S.

    1981-10-01

    Mathematical models for the simulation and estimation of errors in precision oscillators used as time references in satellite navigation systems are developed. The results, based on all currently known oscillator error sources, are directly implementable on a digital computer. The simulation formulation is sufficiently flexible to allow for the inclusion or exclusion of individual error sources as desired. The estimation algorithms, following from Kalman filter theory, provide directly for the error analysis of clock errors in both filtering and prediction

  12. Light and the human circadian clock.

    Science.gov (United States)

    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 field's pioneers, and the astonishing finding that circadian rhythms continue a self-sustained oscillation in constant conditions has become central to our understanding of entrainment.Here, we argue that we have to rethink these initial circadian dogmas to fully understand the circadian programme and how it entrains. Light is also the prominent zeitgeber for the human clock, as has been shown experimentally in the laboratory and in large-scale epidemiological studies in real life, and we hypothesise that social zeitgebers act through light entrainment via behavioural feedback loops (zeitnehmer). We show that human entrainment can be investigated in detail outside of the laboratory, by using the many 'experimental' conditions provided by the real world, such as daylight savings time, the 'forced synchrony' imposed by the introduction of time zones, or the fact that humans increasingly create their own light environment. The conditions of human entrainment have changed drastically over the past 100 years and have led to an increasing discrepancy between biological and social time (social jetlag). The increasing evidence that social jetlag has detrimental consequences for health suggests that shift-work is only an extreme form of circadian misalignment, and that the majority of the population in the industrialised world suffers from a similarly 'forced synchrony'.

  13. Analytic clock frequency selection for global DVFS

    OpenAIRE

    Gerards, Marco Egbertus Theodorus; Hurink, Johann L.; Holzenspies, P.K.F.; Kuper, Jan; Smit, Gerardus Johannes Maria

    2014-01-01

    Computers can reduce their power consumption by decreasing their speed using Dynamic Voltage and Frequency Scaling (DVFS). A form of DVFS for multicore processors is global DVFS, where the voltage and clock frequency is shared among all processor cores. Because global DVFS is efficient and cheap to implement, it is used in modern multicore processors like the IBM Power 7, ARM Cortex A9 and NVIDIA Tegra 2. This theory oriented paper discusses energy optimal DVFS algorithms for such processors....

  14. 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.

  15. GLONASS orbit/clock combination in VNIIFTRI

    Science.gov (United States)

    Bezmenov, I.; Pasynok, S.

    2015-08-01

    An algorithm and a program for GLONASS satellites orbit/clock combination based on daily precise orbits submitted by several Analytic Centers were developed. Some theoretical estimates for combine orbit positions RMS were derived. It was shown that under condition that RMS of satellite orbits provided by the Analytic Centers during a long time interval are commensurable the RMS of combine orbit positions is no greater than RMS of other satellite positions estimated by any of the Analytic Centers.

  16. Clock Genes and Altered Sleep-Wake Rhythms: Their Role in the Development of Psychiatric Disorders.

    Science.gov (United States)

    Charrier, Annaëlle; Olliac, Bertrand; Roubertoux, Pierre; Tordjman, Sylvie

    2017-04-29

    In mammals, the circadian clocks network (central and peripheral oscillators) controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder). However, the underlying mechanisms of these associations remain to be ascertained and the cause-effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep-wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders). First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep-wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.

  17. 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.

  18. Clock Genes and Altered Sleep–Wake Rhythms: Their Role in the Development of Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Annaëlle Charrier

    2017-04-01

    Full Text Available In mammals, the circadian clocks network (central and peripheral oscillators controls circadian rhythms and orchestrates the expression of a range of downstream genes, allowing the organism to anticipate and adapt to environmental changes. Beyond their role in circadian rhythms, several studies have highlighted that circadian clock genes may have a more widespread physiological effect on cognition, mood, and reward-related behaviors. Furthermore, single nucleotide polymorphisms in core circadian clock genes have been associated with psychiatric disorders (such as autism spectrum disorder, schizophrenia, anxiety disorders, major depressive disorder, bipolar disorder, and attention deficit hyperactivity disorder. However, the underlying mechanisms of these associations remain to be ascertained and the cause–effect relationships are not clearly established. The objective of this article is to clarify the role of clock genes and altered sleep–wake rhythms in the development of psychiatric disorders (sleep problems are often observed at early onset of psychiatric disorders. First, the molecular mechanisms of circadian rhythms are described. Then, the relationships between disrupted circadian rhythms, including sleep–wake rhythms, and psychiatric disorders are discussed. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.

  19. Clock distribution system for digital computers

    International Nuclear Information System (INIS)

    Loomis, H.H.; Wyman, R.H.

    1981-01-01

    An apparatus is disclosed for eliminating, in each clock distribution amplifier of a clock distribution system, sequential pulse catch-up error due to one pulse ''overtaking'' a prior clock pulse. The apparatus includes timing means to produce a periodic electromagnetic signal with a fundamental frequency having a fundamental frequency component v'01(T); an array of N signal characteristic detector means, with detector means no. 1 receiving the timing means signal and producing a change-of-state signal v1(T) in response to receipt of a signal above a predetermined threshold; N substantially identical filter means, one filter means being operatively associated with each detector means, for receiving the change-of-state signal vn(T) and producing a modified change-of-state signal v'n(T) (N 1, . . . , n) having a fundamental frequency component that is substantially proportional to v'01(T- theta n(T) with a cumulative phase shift theta n(T) having a time derivative that may be made uniformly and arbitrarily small; and with the detector means n+1 (1 < or = n< n) receiving a modified change-of-state signal vn(T) from filter means no. N and, in response to receipt of such a signal above a predetermined threshold, producing a change-of-state signal vn+1

  20. Biological timing and the clock metaphor: oscillatory and hourglass mechanisms.

    Science.gov (United States)

    Rensing, L; Meyer-Grahle, U; Ruoff, P

    2001-05-01

    Living organisms have developed a multitude of timing mechanisms--"biological clocks." Their mechanisms are based on either oscillations (oscillatory clocks) or unidirectional processes (hourglass clocks). Oscillatory clocks comprise circatidal, circalunidian, circadian, circalunar, and circannual oscillations--which keep time with environmental periodicities--as well as ultradian oscillations, ovarian cycles, and oscillations in development and in the brain, which keep time with biological timescales. These clocks mainly determine time points at specific phases of their oscillations. Hourglass clocks are predominantly found in development and aging and also in the brain. They determine time intervals (duration). More complex timing systems combine oscillatory and hourglass mechanisms, such as the case for cell cycle, sleep initiation, or brain clocks, whereas others combine external and internal periodicities (photoperiodism, seasonal reproduction). A definition of a biological clock may be derived from its control of functions external to its own processes and its use in determining temporal order (sequences of events) or durations. Biological and chemical oscillators are characterized by positive and negative feedback (or feedforward) mechanisms. During evolution, living organisms made use of the many existing oscillations for signal transmission, movement, and pump mechanisms, as well as for clocks. Some clocks, such as the circadian clock, that time with environmental periodicities are usually compensated (stabilized) against temperature, whereas other clocks, such as the cell cycle, that keep time with an organismic timescale are not compensated. This difference may be related to the predominance of negative feedback in the first class of clocks and a predominance of positive feedback (autocatalytic amplification) in the second class. The present knowledge of a compensated clock (the circadian oscillator) and an uncompensated clock (the cell cycle), as well

  1. Expression of clock genes /period/ and /timeless /in the central nervous system of the mediterranean flour moth, Ephestia kuehniella

    Czech Academy of Sciences Publication Activity Database

    Kobelková, Alena; Závodská, Radka; Šauman, Ivo; Bazalová, Olga; Doležel, David

    2015-01-01

    Roč. 30, č. 2 (2015), s. 104-116 ISSN 0748-7304 R&D Projects: GA ČR GC14-32654J Institutional support: RVO:60077344 Keywords : circadian clock * activity rhythms * eclosion rhythm Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.824, year: 2015

  2. Sleep Loss Reduces the DNA-Binding of BMAL1, CLOCK, and NPAS2 to Specific Clock Genes in the Mouse Cerebral Cortex

    OpenAIRE

    Mongrain, Valerie; La Spada, Francesco; Curie, Thomas; Franken, Paul

    2011-01-01

    We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory s...

  3. The Success Rate of Initial {sup 131I} Ablation in Differentiated Thyroid Cancer: Comparison Between Less strict and Very Strict Low Iodine Diets

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Ik Dong; Kim, Sung Hoon; Seo, Ye Young; Oh, Jin Kyoung; O, Joo Hyun; Chung, Soo Kyo [The Catholic Univ. of Korea, Seoul (Korea, Republic of)

    2012-03-15

    To decrease the risk of recurrence or metastasis in differentiated thyroid cancer (DTC), selected patients receive radioactive iodine ablation of remnant thyroid tissue or tumor. A low iodine diet can enhance uptake of radioactive iodine. We compared the success rates of radioactive iodine ablation therapy in patients who followed two different low iodine diets (LIDs). The success rates of postsurgical radioactive iodine ablation in DTC patients receiving empiric doses of 150 mCi were retrospectively reviewed. First-time radioactive iodine ablation therapy was done in 71 patients following less strict LID. Less strict LID restricted seafood, iodized salt, egg yolk, dairy products, processed meat, instant prepared meals, and multivitamins. Very strict LID additionally restricted rice, freshwater fish, spinach, and soybean products. Radioactive iodine ablation therapy was considered successful when follow up {sup 123I} whole body scan was negative and stimulated serum thyroglobulin level was less than 2.0 ng/mL. The success rate of patients following less strict LID was 80.3% and for very strict LID 75.6%. There was no statistically significant difference in the success rates between the two LID groups (P=0.48). Very strict LID may not contribute to improving the success rate of initial radioactive iodine ablation therapy at the cost of great inconvenience to the patient.

  4. Divergence time estimates of mammals from molecular clocks and ...

    Indian Academy of Sciences (India)

    Prakash

    2009-10-30

    Oct 30, 2009 ... In the last decade and a half, mammalian phylogeny and lineage divergence .... not the sudden availability of ecological niches following the KTB mass .... fish fauna, ostracods, and palynofossils (Singh et al. 2006;. Prasad et al. ... tendons and hence the functional adaptations of the animal during its life and ...

  5. Glutamine synthetase gene evolution: A good molecular clock

    International Nuclear Information System (INIS)

    Pesole, G.; Lanvave, C.; Saccone, C.; Bozzetti, M.P.; Preparata, G.

    1991-01-01

    Glutamine synthetase gene evolution in various animals, plants, and bacteria was evaluated by a general stationary Markov model. The evolutionary process proved to be unexpectedly regular even for a time span as long as that between the divergence of prokaryotes from eukaryotes. This enabled us to draw phylogenetic trees for species whose phylogeny cannot be easily reconstructed from the fossil record. The calculation of the times of divergence of the various organelle-specific enzymes led us to hypothesize that the pea and bean chloroplast genes for these enzymes originated from the duplication of nuclear genes as a result of the different metabolic needs of the various species. The data indicate that the duplication of plastid glutamine synthetase genes occurred long after the endosymbiotic events that produced the organelles themselves

  6. Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function

    DEFF Research Database (Denmark)

    Bugge, Anne Skovsø; Feng, Dan; Everett, Logan J

    2012-01-01

    of binding sites across the genome, enriched near metabolic genes. Depletion of both Rev-erbs in liver synergistically derepresses several metabolic genes as well as genes that control the positive limb of the molecular clock. Moreover, deficiency of both Rev-erbs causes marked hepatic steatosis, in contrast......-autonomous clock as well as hepatic lipid metabolism. Mouse embryonic fibroblasts were rendered arrhythmic by depletion of both Rev-erbs. In mouse livers, Rev-erbβ mRNA and protein levels oscillate with a diurnal pattern similar to that of Rev-erbα, and both Rev-erbs are recruited to a remarkably similar set...

  7. Diurnal rhythmicity of the clock genes Per1 and Per2 in the rat ovary.

    Science.gov (United States)

    Fahrenkrug, Jan; Georg, Birgitte; Hannibal, Jens; Hindersson, Peter; Gräs, Søren

    2006-08-01

    Circadian rhythms are generated by endogenous clocks in the central brain oscillator, the suprachiasmatic nucleus, and peripheral tissues. The molecular basis for the circadian clock consists of a number of genes and proteins that form transcriptional/translational feedback loops. In the mammalian gonads, clock genes have been reported in the testes, but the expression pattern is developmental rather than circadian. Here we investigated the daily expression of the two core clock genes, Per1 and Per2, in the rat ovary using real-time RT-PCR, in situ hybridization histochemistry, and immunohistochemistry. Both Per1 and Per2 mRNA displayed a statistically significant rhythmic oscillation in the ovary with a period of 24 h in: 1) a group of rats during proestrus and estrus under 12-h light,12-h dark cycles; 2) a second group of rats representing a mixture of all 4 d of the estrous cycle under 12-h light,12-h dark conditions; and 3) a third group of rats representing a mixture of all 4 d of estrous cycle during continuous darkness. Per1 mRNA was low at Zeitgeber time 0-2 and peaked at Zeitgeber time 12-14, whereas Per2 mRNA was delayed by approximately 4 h relative to Per1. By in situ hybridization histochemistry, Per mRNAs were localized to steroidogenic cells in preantral, antral, and preovulatory follicles; corpora lutea; and interstitial glandular tissue. With newly developed antisera, we substantiated the expression of Per1 and Per2 in these cells by single/double immunohistochemistry. Furthermore, we visualized the temporal intracellular movements of PER1 and PER2 proteins. These findings suggest the existence of an ovarian circadian clock, which may play a role both locally and in the hypothalamo-pituitary-ovarian axis.

  8. An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA.

    Directory of Open Access Journals (Sweden)

    Guo-Xiang Ruan

    2008-10-01

    Full Text Available The influence of the mammalian retinal circadian clock on retinal physiology and function is widely recognized, yet the cellular elements and neural regulation of retinal circadian pacemaking remain unclear due to the challenge of long-term culture of adult mammalian retina and the lack of an ideal experimental measure of the retinal circadian clock. In the current study, we developed a protocol for long-term culture of intact mouse retinas, which allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC clock gene reporter. With this in vitro assay, we studied the characteristics and location within the retina of circadian PER2::LUC rhythms, the influence of major retinal neurotransmitters, and the resetting of the retinal circadian clock by light. Retinal PER2::LUC rhythms were routinely measured from whole-mount retinal explants for 10 d and for up to 30 d. Imaging of vertical retinal slices demonstrated that the rhythmic luminescence signals were concentrated in the inner nuclear layer. Interruption of cell communication via the major neurotransmitter systems of photoreceptors and ganglion cells (melatonin and glutamate and the inner nuclear layer (dopamine, acetylcholine, GABA, glycine, and glutamate did not disrupt generation of retinal circadian PER2::LUC rhythms, nor did interruption of intercellular communication through sodium-dependent action potentials or connexin 36 (cx36-containing gap junctions, indicating that PER2::LUC rhythms generation in the inner nuclear layer is likely cell autonomous. However, dopamine, acting through D1 receptors, and GABA, acting through membrane hyperpolarization and casein kinase, set the phase and amplitude of retinal PER2::LUC rhythms, respectively. Light pulses reset the phase of the in vitro retinal oscillator and dopamine D1 receptor antagonists attenuated these phase shifts. Thus, dopamine and GABA act at the molecular level of PER

  9. Relativity theory and time perception: single or multiple clocks?

    Science.gov (United States)

    Buhusi, Catalin V; Meck, Warren H

    2009-07-22

    Current theories of interval timing assume that humans and other animals time as if using a single, absolute stopwatch that can be stopped or reset on command. Here we evaluate the alternative view that psychological time is represented by multiple clocks, and that these clocks create separate temporal contexts by which duration is judged in a relative manner. Two predictions of the multiple-clock hypothesis were tested. First, that the multiple clocks can be manipulated (stopped and/or reset) independently. Second, that an event of a given physical duration would be perceived as having different durations in different temporal contexts, i.e., would be judged differently by each clock. Rats were trained to time three durations (e.g., 10, 30, and 90 s). When timing was interrupted by an unexpected gap in the signal, rats reset the clock used to time the "short" duration, stopped the "medium" duration clock, and continued to run the "long" duration clock. When the duration of the gap was manipulated, the rats reset these clocks in a hierarchical order, first the "short", then the "medium", and finally the "long" clock. Quantitative modeling assuming re-allocation of cognitive resources in proportion to the relative duration of the gap to the multiple, simultaneously timed event durations was used to account for the results. These results indicate that the three event durations were effectively timed by separate clocks operated independently, and that the same gap duration was judged relative to these three temporal contexts. Results suggest that the brain processes the duration of an event in a manner similar to Einstein's special relativity theory: A given time interval is registered differently by independent clocks dependent upon the context.

  10. Relativity theory and time perception: single or multiple clocks?

    Directory of Open Access Journals (Sweden)

    Catalin V Buhusi

    2009-07-01

    Full Text Available Current theories of interval timing assume that humans and other animals time as if using a single, absolute stopwatch that can be stopped or reset on command. Here we evaluate the alternative view that psychological time is represented by multiple clocks, and that these clocks create separate temporal contexts by which duration is judged in a relative manner. Two predictions of the multiple-clock hypothesis were tested. First, that the multiple clocks can be manipulated (stopped and/or reset independently. Second, that an event of a given physical duration would be perceived as having different durations in different temporal contexts, i.e., would be judged differently by each clock.Rats were trained to time three durations (e.g., 10, 30, and 90 s. When timing was interrupted by an unexpected gap in the signal, rats reset the clock used to time the "short" duration, stopped the "medium" duration clock, and continued to run the "long" duration clock. When the duration of the gap was manipulated, the rats reset these clocks in a hierarchical order, first the "short", then the "medium", and finally the "long" clock. Quantitative modeling assuming re-allocation of cognitive resources in proportion to the relative duration of the gap to the multiple, simultaneously timed event durations was used to account for the results.These results indicate that the three event durations were effectively timed by separate clocks operated independently, and that the same gap duration was judged relative to these three temporal contexts. Results suggest that the brain processes the duration of an event in a manner similar to Einstein's special relativity theory: A given time interval is registered differently by independent clocks dependent upon the context.

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

    Science.gov (United States)

    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.

  12. Diamond Electron-Spin Clocks For Space Navigation and Communication

    Data.gov (United States)

    National Aeronautics and Space Administration — Precision clocks are needed in a broad range of applications, including satellite communication, high-bandwidth wireless communication, computing systems, and...

  13. The role of the mechanical clock in medieval science.

    Science.gov (United States)

    Álvarez, Víctor Pérez

    2015-03-01

    The invention and spread of the mechanical clock is a complex and multifaceted historical phenomenon. Some of these facets, such as its social impact, have been widely studied, but their scientific dimensions have often been dismissed. The mechanical clock was probably born as a scientific instrument for driving a model of the universe, and not only natural philosophers but also kings, nobles and other members of the social elites showed an interest in clocks as scientific instruments. Public clocks later spread a new way of telling time based on equal hours, laying the foundations for changes in time consciousness that would accelerate scientific thinking. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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...

  16. Electromagnetic synchronisation of clocks with finite separation in a rotating system

    International Nuclear Information System (INIS)

    Cohen, J.M.; Moses, H.E.; Rosenblum, A.; Temple Univ., Philadelphia, PA

    1984-01-01

    For clocks on the vertices of a triangle, it is shown that clock synchronisation using electromagnetic signals between finitely spaced clocks in a rotating frame leads to the same synchronisation error as a closely spaced band of clocks along the same light path. In addition, the above result is generalised to n equally spaced clocks. (author)

  17. Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina.

    Science.gov (United States)

    Namihira, M; Honma, S; Abe, H; Tanahashi, Y; Ikeda, M; Honma, K

    1999-08-13

    Circadian expression and light-responsiveness of the mammalian clock genes, Clock and BMAL1, in the rat retina were examined by in situ hydbribization under constant darkness. A small but significant daily variation was detected in the Clock transcript level, but not in BMAL1. Light increased the Clock and BMAL1 expressions significantly when examined 60 min after exposure. The light-induced gene expression was phase-dependent for Clock and peaked at ZT2, while rather constant throughout the day for BMAL1. These findings suggest that Clock and BMAL1 play different roles in the generation of circadian rhytm in the retina from those in the suprachiasmatic nucleus. Different roles are also suggested between the two genes in the photic signal transduction in the retina.

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

    International Nuclear Information System (INIS)

    Wang Junwei; Zhou Tianshou

    2010-01-01

    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 01 and clk 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.

  19. Mass defect effects in atomic clocks

    Science.gov (United States)

    Yudin, Valeriy; Taichenachev, Alexey

    2018-03-01

    We consider some implications of the mass defect on the frequency of atomic transitions. We have found that some well-known frequency shifts (the gravitational shift and motion-induced shifts such as quadratic Doppler and micromotion shifts) can be interpreted as consequences of the mass defect in quantum atomic physics, i.e. without the need for the concept of time dilation used in special and general relativity theories. Moreover, we show that the inclusion of the mass defect leads to previously unknown shifts for clocks based on trapped ions.

  20. Post-transcriptional control of the mammalian circadian clock: implications for health and disease.

    Science.gov (United States)

    Preußner, Marco; Heyd, Florian

    2016-06-01

    Many aspects of human physiology and behavior display rhythmicity with a period of approximately 24 h. Rhythmic changes are controlled by an endogenous time keeper, the circadian clock, and include sleep-wake cycles, physical and mental performance capability, blood pressure, and body temperature. Consequently, many diseases, such as metabolic, sleep, autoimmune and mental disorders and cancer, are connected to the circadian rhythm. The development of therapies that take circadian biology into account is thus a promising strategy to improve treatments of diverse disorders, ranging from allergic syndromes to cancer. Circadian alteration of body functions and behavior are, at the molecular level, controlled and mediated by widespread changes in gene expression that happen in anticipation of predictably changing requirements during the day. At the core of the molecular clockwork is a well-studied transcription-translation negative feedback loop. However, evidence is emerging that additional post-transcriptional, RNA-based mechanisms are required to maintain proper clock function. Here, we will discuss recent work implicating regulated mRNA stability, translation and alternative splicing in the control of the mammalian circadian clock, and its role in health and disease.

  1. Circadian expression of clock genes and clock-controlled genes in the rat retina

    NARCIS (Netherlands)

    Kamphuis, Willem; Cailotto, Cathy; Dijk, Frederike; Bergen, Arthur; Buijs, Ruud M.

    2005-01-01

    The circadian expression patterns of genes encoding for proteins that make up the core of the circadian clock were measured in rat retina using real-time quantitative PCR (qPCR). Transcript levels of several genes previously used for normalization of qPCR assays were determined and the effect of

  2. An association between clock genes and clock-controlled cell cycle genes in murine colorectal tumors

    Czech Academy of Sciences Publication Activity Database

    Soták, Matúš; Polidarová, Lenka; Ergang, Peter; Sumová, Alena; Pácha, Jiří

    2013-01-01

    Roč. 132, č. 5 (2013), s. 1032-1041 ISSN 0020-7136 R&D Projects: GA MZd(CZ) NS9982 Institutional research plan: CEZ:AV0Z50110509 Keywords : cancer * circadian rhythm * peripheral circadian clock Subject RIV: FE - Other Internal Medicine Disciplines Impact factor: 5.007, year: 2013

  3. DNA remodelling by Strict Partial Endoreplication in orchids, an original process in the plant kingdom.

    Science.gov (United States)

    Brown, Spencer C; Bourge, Mickaël; Maunoury, Nicolas; Wong, Maurice; Bianchi, Michele Wolfe; Lepers-Andrzejewski, Sandra; Besse, Pascale; Siljak-Yakovlev, Sonja; Dron, Michel; Satiat-Jeunemaître, Béatrice

    2017-04-13

    DNA remodelling during endoreplication appears to be a strong developmental characteristic in orchids. In this study, we analysed DNA content and nuclei in 41 species of orchids to further map the genome evolution in this plant family. We demonstrate that the DNA remodelling observed in 36 out of 41 orchids studied corresponds to strict partial endoreplication. Such process is developmentally regulated in each wild species studied. Cytometry data analyses allowed us to propose a model where nuclear states 2C, 4E, 8E, etc. form a series comprising a fixed proportion, the euploid genome 2C, plus 2 to 32 additional copies of a complementary part of the genome. The fixed proportion ranged from 89% of the genome in Vanilla mexicana down to 19% in V. pompona, the lowest value for all 148 orchids reported. Insterspecific hybridisation did not suppress this phenomenon. Interestingly, this process was not observed in mass-produced epiphytes. Nucleolar volumes grow with the number of endocopies present, coherent with high transcription activity in endoreplicated nuclei. Our analyses suggest species-specific chromatin rearrangement. Towards understanding endoreplication, V. planifolia constitutes a tractable system for isolating the genomic sequences that confer an advantage via endoreplication from those that apparently suffice at diploid level. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  4. α1B-Adrenergic receptor signaling controls circadian expression of Tnfrsf11b by regulating clock genes in osteoblasts

    Directory of Open Access Journals (Sweden)

    Takao Hirai

    2015-11-01

    Full Text Available Circadian clocks are endogenous and biological oscillations that occur with a period of <24 h. In mammals, the central circadian pacemaker is localized in the suprachiasmatic nucleus (SCN and is linked to peripheral tissues through neural and hormonal signals. In the present study, we investigated the physiological function of the molecular clock on bone remodeling. The results of loss-of-function and gain-of-function experiments both indicated that the rhythmic expression of Tnfrsf11b, which encodes osteoprotegerin (OPG, was regulated by Bmal1 in MC3T3-E1 cells. We also showed that REV-ERBα negatively regulated Tnfrsf11b as well as Bmal1 in MC3T3-E1 cells. We systematically investigated the relationship between the sympathetic nervous system and the circadian clock in osteoblasts. The administration of phenylephrine, a nonspecific α1-adrenergic receptor (AR agonist, stimulated the expression of Tnfrsf11b, whereas the genetic ablation of α1B-AR signaling led to the alteration of Tnfrsf11b expression concomitant with Bmal1 and Per2 in bone. Thus, this study demonstrated that the circadian regulation of Tnfrsf11b was regulated by the clock genes encoding REV-ERBα (Nr1d1 and Bmal1 (Bmal1, also known as Arntl, which are components of the core loop of the circadian clock in osteoblasts.

  5. Food-Anticipatory Behavior in Neonatal Rabbits and Rodents: An Update on the Role of Clock Genes

    Directory of Open Access Journals (Sweden)

    Mario Caba

    2018-05-01

    Full Text Available In mammals, the suprachiasmatic nucleus (SCN, the master circadian clock, is mainly synchronized to the environmental light/dark cycle. SCN oscillations are maintained by a molecular clockwork in which certain genes, Period 1–2, Cry1–2, Bmal1, and Clock, are rhythmically expressed. Disruption of these genes leads to a malfunctioning clockwork and behavioral and physiological rhythms are altered. In addition to synchronization of circadian rhythms by light, when subjects are exposed to food for a few hours daily, behavioral and physiological rhythms are entrained to anticipate mealtime, even in the absence of the SCN. The presence of anticipatory rhythms synchronized by food suggests the existence of an SCN-independent circadian pacemaker that might be dependent on clock genes. Interestingly, rabbit pups, unable to perceive light, suckle milk once a day, which entrains behavioral rhythms to anticipate nursing time. Mutations of clock genes, singly or in combination, affect diverse rhythms in brain activity and physiological processes, but anticipatory behavior and physiology to feeding time remains attenuated or unaffected. It had been suggested that compensatory upregulation of paralogs or subtypes genes, or even non-transcriptional mechanisms, are able to maintain circadian oscillations entrained to mealtime. In the present mini-review, we evaluate the current state of the role played by clock genes in meal anticipation and provide evidence for rabbit pups as a natural model of food-anticipatory circadian behavior.

  6. Validation of an automatic diagnosis of strict left bundle branch block criteria using 12-lead electrocardiograms

    DEFF Research Database (Denmark)

    Xia, Xiaojuan; Ruwald, Anne-Christine; Ruwald, Martin H

    2017-01-01

    AIMS: Strict left bundle branch block (LBBB) criteria were recently proposed to identify LBBB patients to benefit most from cardiac resynchronization therapy (CRT). The aim of our study was to automate identification of strict LBBB in order to facilitate its broader application. METHODS: We devel...

  7. The Effect of the Strictness of Consultation Requirements on Fraud Consultation

    NARCIS (Netherlands)

    Gold, A.H.; Knechel, W.R.; Wallage, P.

    2012-01-01

    We investigate how the strictness of a requirement to consult on potential client fraud affects auditors' propensity to consult with firm experts. We consider two specific forms of guidance about fraud consultations: (1) strict, i.e., mandatory and binding; and (2) lenient, i.e., advisory and

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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.

  9. Ultradian feeding in mice not only affects the peripheral clock in the liver, but also the master clock in the brain

    NARCIS (Netherlands)

    Sen, Satish; Raingard, Hélène; Dumont, Stéphanie; Kalsbeek, A.; Vuillez, Patrick; Challet, Etienne

    2017-01-01

    Restricted feeding during the resting period causes pronounced shifts in a number of peripheral clocks, but not the central clock in the suprachiasmatic nucleus (SCN). By contrast, daily caloric restriction impacts also the light-entrained SCN clock, as indicated by shifted oscillations of clock

  10. A Novel Method of Clock Synchronization in Distributed Systems

    Science.gov (United States)

    Li, Gun; Niu, Meng-jie; Chai, Yang-shun; Chen, Xin; Ren, Yan-qiu

    2017-04-01

    Time synchronization plays an important role in the spacecraft formation flight and constellation autonomous navigation, etc. For the application of clock synchronization in a network system, it is not always true that all the observed nodes in the network are interconnected, therefore, it is difficult to achieve the high-precision time synchronization of a network system in the condition that a certain node can only obtain the measurement information of clock from a single neighboring node, but cannot obtain it from other nodes. Aiming at this problem, a novel method of high-precision time synchronization in a network system is proposed. In this paper, each clock is regarded as a node in the network system, and based on the definition of different topological structures of a distributed system, the three control algorithms of time synchronization under the following three cases are designed: without a master clock (reference clock), with a master clock (reference clock), and with a fixed communication delay in the network system. And the validity of the designed clock synchronization protocol is proved by both stability analysis and numerical simulation.

  11. 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…

  12. The Chip-Scale Atomic Clock - Recent Development Progress

    Science.gov (United States)

    2004-09-01

    35th Annual Precise Time and Time Interval (PTTI) Meeting 467 THE CHIP-SCALE ATOMIC CLOCK – RECENT DEVELOPMENT PROGRESS R. Lutwak ...1] R. Lutwak , et al., 2003, “The Chip-Scale Atomic Clock – Coherent Population Trapping vs. Conventional Interrogation,” in

  13. 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

  14. ClockWork: a Real-Time Feasibility Analysis Tool

    NARCIS (Netherlands)

    Jansen, P.G.; Hanssen, F.T.Y.; Mullender, Sape J.

    ClockWork shows that we can improve the flexibility and efficiency of real-time kernels. We do this by proposing methods for scheduling based on so-called Real-Time Transactions. ClockWork uses Real-Time Transactions which allow scheduling decisions to be taken by the system. A programmer does not

  15. Development and entrainment of the colonic circadian clock during ontogenesis

    Czech Academy of Sciences Publication Activity Database

    Polidarová, Lenka; Olejníková, Lucie; Paušlyová, Lucia; Sládek, Martin; Soták, Matúš; Pácha, Jiří; Sumová, Alena

    2014-01-01

    Roč. 306, č. 4 (2014), G346-G356 ISSN 0193-1857 R&D Projects: GA ČR(CZ) GAP303/12/1108 Institutional support: RVO:67985823 Keywords : circadian clock * clock gene * ontogenesis * circadian entrainment Subject RIV: ED - Physiology Impact factor: 3.798, year: 2014

  16. Clock synchronisation experiment in India using symphonie satellite

    Science.gov (United States)

    Somayajulu, Y. V.; Mathur, B. S.; Banerjee, P.; Garg, S. C.; Singh, L.; Sood, P. C.; Tyagi, T. R.; Jain, C. L.; Kumar, K.

    1979-01-01

    A recent clock synchronization experiment between the National Physical Laboratory (NPL), New Delhi and Space Applications Center (SAC), Ahemedabad, in India via geostationary satellite symphonie 2, stationed at 49 E longitude, is reported. A two-way transmission using a microwave transponder considered to provide the greatest precision in synchronization of two remote clocks is described.

  17. Clock transport synchronisation and the dragging of inertial frames

    International Nuclear Information System (INIS)

    Rosenblum, Arnold

    1987-01-01

    It is shown that it is possible, by using the lack of synchronisation of clocks by clock transport synchronisation in circular orbits, to test for the dragging of inertial frames in Einstein's theory of general relativity. Possible experiments are discussed. (author)

  18. A self-interfering clock as a "which path" witness.

    Science.gov (United States)

    Margalit, Yair; Zhou, Zhifan; Machluf, Shimon; Rohrlich, Daniel; Japha, Yonathan; Folman, Ron

    2015-09-11

    In Einstein's general theory of relativity, time depends locally on gravity; in standard quantum theory, time is global-all clocks "tick" uniformly. We demonstrate a new tool for investigating time in the overlap of these two theories: a self-interfering clock, comprising two atomic spin states. We prepare the clock in a spatial superposition of quantum wave packets, which evolve coherently along two paths into a stable interference pattern. If we make the clock wave packets "tick" at different rates, to simulate a gravitational time lag, the clock time along each path yields "which path" information, degrading the pattern's visibility. In contrast, in standard interferometry, time cannot yield "which path" information. This proof-of-principle experiment may have implications for the study of time and general relativity and their impact on fundamental effects such as decoherence and the emergence of a classical world. Copyright © 2015, American Association for the Advancement of Science.

  19. 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...

  20. A New Trapped Ion Clock Based on Hg-201(+)

    Science.gov (United States)

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

    2009-01-01

    There are two stable odd isotopes of mercury with singly ionized hyperfine structure suitable for a microwave clock: Hg-199(+) and Hg-201(+). Virtually all trapped mercury ion clocks to date have used the 199 isotope. We have begun to investigate the viability of a trapped ion clock based on Hg-201(+). We have measured the unperturbed frequency of the (S-2)(sub 1/2) F = 1, m(sub F) = 0 to (S-2)(sub 1/2) F = 2, m(sub F) = 0 clock transition to be 29.9543658211(2) GHz. In this paper we describe initial measurements with Hg-201(+) and new applications to clocks and fundamental physics.

  1. Lattice-induced nonadiabatic frequency shifts in optical lattice clocks

    International Nuclear Information System (INIS)

    Beloy, K.

    2010-01-01

    We consider the frequency shift in optical lattice clocks which arises from the coupling of the electronic motion to the atomic motion within the lattice. For the simplest of three-dimensional lattice geometries this coupling is shown to affect only clocks based on blue-detuned lattices. We have estimated the size of this shift for the prospective strontium lattice clock operating at the 390-nm blue-detuned magic wavelength. The resulting fractional frequency shift is found to be on the order of 10 -18 and is largely overshadowed by the electric quadrupole shift. For lattice clocks based on more complex geometries or other atomic systems, this shift could potentially be a limiting factor in clock accuracy.

  2. Standard Clock in primordial density perturbations and cosmic microwave background

    International Nuclear Information System (INIS)

    Chen, Xingang; Namjoo, Mohammad Hossein

    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 summarize the key predictions of the Standard Clock and present an interesting candidate example in Planck 2013 data. 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. Although this candidate is not yet statistically significant, we use it to illustrate how Standard Clocks appear in Cosmic Microwave Background (CMB) and how they can be further tested by future data. We also use it to motivate more detailed theoretical model building

  3. Initial atomic coherences and Ramsey frequency pulling in fountain clocks

    Science.gov (United States)

    Gerginov, Vladislav; Nemitz, Nils; Weyers, Stefan

    2014-09-01

    In the uncertainty budget of primary atomic cesium fountain clocks, evaluations of frequency-pulling shifts of the hyperfine clock transition caused by unintentional excitation of its nearby transitions (Rabi and Ramsey pulling) have been based so far on an approach developed for cesium beam clocks. We re-evaluate this type of frequency pulling in fountain clocks and pay particular attention to the effect of initial coherent atomic states. We find significantly enhanced frequency shifts caused by Ramsey pulling due to sublevel population imbalance and corresponding coherences within the state-selected hyperfine component of the initial atom ground state. Such shifts are experimentally investigated in an atomic fountain clock and quantitative agreement with the predictions of the model is demonstrated.

  4. 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.

  5. An analysis of clock-shift experiments: is scatter increased and deflection reduced in clock-shifted homing pigeons?

    Science.gov (United States)

    Chappell

    1997-01-01

    Clock-shifting (altering the phase of the internal clock) in homing pigeons leads to a deflection in the vanishing bearing of the clock-shifted group relative to controls. However, two unexplained phenomena are common in clock-shift experiments: the vanishing bearings of the clock-shifted group are often more scattered (with a shorter vector length) than those of the control group, and the deflection of the mean bearing of the clock-shifted group from that of the controls is often smaller than expected theoretically. Here, an analysis of 55 clock-shift experiments performed in four countries over 21 years is reported. The bearings of the clock-shifted groups were significantly more scattered than those of controls and less deflected than expected, but these effects were not significantly different at familiar and unfamiliar sites. The possible causes of the effects are discussed and evaluated with reference to this analysis and other experiments. The most likely causes appear to be conflict between the directions indicated by the sun compass and either unshifted familiar visual landmarks (at familiar sites only) or the unshifted magnetic compass (possible at both familiar and unfamiliar sites).

  6. Synchronization control of cross-strict feedback hyperchaotic system based on cross active backstepping design

    International Nuclear Information System (INIS)

    Wang Jing; Gao Jinfeng; Ma Xikui

    2007-01-01

    This Letter presents a novel cross active backstepping design method for synchronization control of cross-strict feedback hyperchaotic system, in which the ordinary backstepping design is unavailable. The proposed control method, combining backstepping design and active control approach, extends the application of backstepping technique in chaos control. Based on this method, different combinations of controllers can be designed to meet the needs of different applications. The proposed method is applied to achieve chaos synchronization of two identical cross-strict feedback hyperchaotic systems. Also it is used to implement synchronization between cross-strict feedback hyperchaotic system and Roessler hyperchaotic system. Numerical examples illustrate the validity of the control method

  7. Cosmic time dilation: The clock paradox revisited

    International Nuclear Information System (INIS)

    Tomaschitz, Roman

    2004-01-01

    The relativistic time dilation is reviewed in a cosmological context. We show that a clock or twin paradox does not arise if cosmic time is properly taken into account. The receding galaxy background provides a unique frame of reference, and the proper times of geodesic as well as accelerated observers can be linked to the universal cosmic time parameter. This suggests to compare the proper time differentials of the respective observers by determining their state of motion in the galaxy grid. In this way, each observer can figure out whether his proper time is dilated or contracted relative to any other. In particular one can come to unambiguous conclusions on the aging of uniformly moving observers, without reference to asymmetries in measurement procedures or accelerations they may have undergone

  8. Polarizabilities of the beryllium clock transition

    International Nuclear Information System (INIS)

    Mitroy, J.

    2010-01-01

    The polarizabilities of the three lowest states of the beryllium atom are determined from a large basis configuration interaction calculation. The polarizabilities of the 2s 2 1 S e ground state (37.73a 0 3 ) and the 2s2p 3 P 0 o metastable state (39.04a 0 3 ) are found to be very similar in size and magnitude. This leads to an anomalously small blackbody radiation shift at 300 K of -0.018(4) Hz for the 2s 2 1 S e -2s2p 3 P 0 o clock transition. Magic wavelengths for simultaneous trapping of the ground and metastable states are also computed.

  9. Nuclear Iran: the race against the clock

    International Nuclear Information System (INIS)

    Delpech, Therese; )

    2005-01-01

    The recent election of an ultra-conservative during the Iranian presidential race seems to further distance the idea of a positive conclusion to negotiations with Tehran. Confronted with a dangerous Iranian agenda, the Europeans have been leading negotiations that have had some positive effect so far, but which also pose the risk of a useless prolongation of discussion. A race against the clock has started in August 2005 when Iran resumed a suspended uranium conversion activity in Isfahan. Time has come for the Security Council to take over - what it should have already done in 2003 - in a way that will make Moscow and, even more Beijing, step out of their somewhat ambiguous stances

  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. 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.

  12. Optical lattice clock with strontium atoms: a second generation of cold atom clocks

    International Nuclear Information System (INIS)

    Le Targat, R.

    2007-07-01

    Atomic fountains, based on a microwave transition of Cesium or Rubidium, constitute the state of the art atomic clocks, with a relative accuracy close to 10 -16 . It nevertheless appears today that it will be difficult to go significantly beyond this level with this kind of device. The use of an optical transition, the other parameters being unchanged, gives hope for a 4 or 5 orders of magnitude improvement of the stability and of the relative uncertainty on most systematic effects. As for motional effects on the atoms, they can be controlled on a very different manner if they are trapped in an optical lattice instead of experiencing a free ballistic flight stage, characteristic of fountains. The key point of this approach lies in the fact that the trap can be operated in such a way that a well chosen, weakly allowed, J=0 → J=0 clock transition can be free from light shift effects. In this respect, the strontium atom is one of the most promising candidate, the 1S 0 → 3P 0 transition has a natural width of 1 mHz, and several other easily accessible transitions can be used to efficiently laser cool atoms down to 10 μK. This thesis demonstrates the experimental feasibility of an optical lattice clock based on the strontium atom, and reports on a preliminary evaluation of the relative accuracy with the fermionic isotope 87 Sr, at a level of a few 10 -15 . (author)

  13. Natural selection against a circadian clock gene mutation in mice.

    Science.gov (United States)

    Spoelstra, Kamiel; Wikelski, Martin; Daan, Serge; Loudon, Andrew S I; Hau, Michaela

    2016-01-19

    Circadian rhythms with an endogenous period close to or equal to the natural light-dark cycle are considered evolutionarily adaptive ("circadian resonance hypothesis"). Despite remarkable insight into the molecular mechanisms driving circadian cycles, this hypothesis has not been tested under natural conditions for any eukaryotic organism. We tested this hypothesis in mice bearing a short-period mutation in the enzyme casein kinase 1ε (tau mutation), which accelerates free-running circadian cycles. We compared daily activity (feeding) rhythms, survivorship, and reproduction in six replicate populations in outdoor experimental enclosures, established with wild-type, heterozygous, and homozygous mice in a Mendelian ratio. In the release cohort, survival was reduced in the homozygote mutant mice, revealing strong selection against short-period genotypes. Over the course of 14 mo, the relative frequency of the tau allele dropped from initial parity to 20%. Adult survival and recruitment of juveniles into the population contributed approximately equally to the selection for wild-type alleles. The expression of activity during daytime varied throughout the experiment and was significantly increased by the tau mutation. The strong selection against the short-period tau allele observed here contrasts with earlier studies showing absence of selection against a Period 2 (Per2) mutation, which disrupts internal clock function, but does not change period length. These findings are consistent with, and predicted by the theory that resonance of the circadian system plays an important role in individual fitness.

  14. GPS satellite clock determination in case of inter-frequency clock biases for triple-frequency precise point positioning

    Science.gov (United States)

    Guo, Jiang; Geng, Jianghui

    2017-12-01

    Significant time-varying inter-frequency clock biases (IFCBs) within GPS observations prevent the application of the legacy L1/L2 ionosphere-free clock products on L5 signals. Conventional approaches overcoming this problem are to estimate L1/L5 ionosphere-free clocks in addition to their L1/L2 counterparts or to compute IFCBs between the L1/L2 and L1/L5 clocks which are later modeled through a harmonic analysis. In contrast, we start from the undifferenced uncombined GNSS model and propose an alternative approach where a second satellite clock parameter dedicated to the L5 signals is estimated along with the legacy L1/L2 clock. In this manner, we do not need to rely on the correlated L1/L2 and L1/L5 ionosphere-free observables which complicates triple-frequency GPS stochastic models, or account for the unfavorable time-varying hardware biases in undifferenced GPS functional models since they can be absorbed by the L5 clocks. An extra advantage over the ionosphere-free model is that external ionosphere constraints can potentially be introduced to improve PPP. With 27 days of triple-frequency GPS data from globally distributed stations, we find that the RMS of the positioning differences between our GPS model and all conventional models is below 1 mm for all east, north and up components, demonstrating the effectiveness of our model in addressing triple-frequency observations and time-varying IFCBs. Moreover, we can combine the L1/L2 and L5 clocks derived from our model to calculate precisely the L1/L5 clocks which in practice only depart from their legacy counterparts by less than 0.006 ns in RMS. Our triple-frequency GPS model proves convenient and efficient in combating time-varying IFCBs and can be generalized to more than three frequency signals for satellite clock determination.

  15. Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish.

    Science.gov (United States)

    Elbaz, Idan; Foulkes, Nicholas S; Gothilf, Yoav; Appelbaum, Lior

    2013-01-01

    The circadian clock and homeostatic processes are fundamental mechanisms that regulate sleep. Surprisingly, despite decades of research, we still do not know why we sleep. Intriguing hypotheses suggest that sleep regulates synaptic plasticity and consequently has a beneficial role in learning and memory. However, direct evidence is still limited and the molecular regulatory mechanisms remain unclear. The zebrafish provides a powerful vertebrate model system that enables simple genetic manipulation, imaging of neuronal circuits and synapses in living animals, and the monitoring of behavioral performance during day and night. Thus, the zebrafish has become an attractive model to study circadian and homeostatic processes that regulate sleep. Zebrafish clock- and sleep-related genes have been cloned, neuronal circuits that exhibit circadian rhythms of activity and synaptic plasticity have been studied, and rhythmic behavioral outputs have been characterized. Integration of this data could lead to a better understanding of sleep regulation. Here, we review the progress of circadian clock and sleep studies in zebrafish with special emphasis on the genetic and neuroendocrine mechanisms that regulate rhythms of melatonin secretion, structural synaptic plasticity, locomotor activity and sleep.

  16. Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish

    Directory of Open Access Journals (Sweden)

    Idan eElbaz

    2013-02-01

    Full Text Available The circadian clock and homeostatic processes are fundamental mechanisms that regulate sleep. Surprisingly, despite decades of research, we still do not know why we sleep. Intriguing hypotheses suggest that sleep regulates synaptic plasticity and consequently has a beneficial role in learning and memory. However, direct evidence is still limited and the molecular regulatory mechanisms remain unclear. The zebrafish provides a powerful vertebrate model system that enables simple genetic manipulation, imaging of neuronal circuits and synapses in living animals, and the monitoring of behavioral performance during day and night. Thus, the zebrafish has become an attractive model to study circadian and homeostatic processes that regulate sleep. Zebrafish clock- and sleep-related genes have been cloned, neuronal circuits that exhibit circadian rhythms of activity and synaptic plasticity have been studied, and rhythmic behavioral outputs have been characterized. Integration of this data could lead to a better understanding of sleep regulation. Here, we review the progress of circadian clock and sleep studies in zebrafish with special emphasis on the genetic and neuroendocrine mechanisms that regulate rhythms of melatonin secretion, structural synaptic plasticity, locomotor activity and sleep.

  17. Morfofunctional indices of peripheric blood for persons working within the strict radiation control area

    International Nuclear Information System (INIS)

    Nyagu, A.I.; Yukhimuk, L.N.; Egorova, D.M.; Pogontseva, I.M.

    1992-01-01

    The blood of 118 people permanently working within the area of strict radiation control has been investigated. Erythrocyte morphofunctional value has been estimated taking into consideration the erythrocyte morphological index as well as mechanical and osmotic resistivity of erythrocytes. For people permanently working within the area of strict radiation control intensity of signals of EPR for blood paramagnetic centres essentially changes. It proves profound changes in functioning of blood plasma antioxidant system for people working in the area of strict radiation control. For the people permanently working within the area of strict radiation control in peripheric blood growth of echynocytes and spherocytes as well as lowering of mechanical resistivity of erythrocytes is observed. 4 refs.; 1 fig.; 1 tab

  18. Strict deformation quantization for actions of a class of symplectic lie groups

    International Nuclear Information System (INIS)

    Bieliavsky, Pierre; Massar, Marc

    2002-01-01

    We present explicit universal strict deformation quantization formulae for actions of Iwasawa subgroups AN of SN(1, n). This answers a question raised by Rieffel in [Contemp. Math. 228 (1998), 315]. (author)

  19. A strontium lattice clock with reduced blackbody radiation shift

    Energy Technology Data Exchange (ETDEWEB)

    Al-Masoudi, Ali Khalas Anfoos

    2016-09-30

    Optical clocks have been quickly moving to the forefront of the frequency standards field due to their high spectral resolution, and therefore the potential high stability and accuracy. The accuracy and stability of the optical clocks are nowadays two orders of magnitude better than microwave Cs clocks, which realize the SI second. Envisioned applications of highly accurate optical clocks are to perform tests of fundamental physics, for example, searching for temporal drifts of the fine structure constant α, violations of the Local Position Invariance (LPI), dark matter and dark energy, or to performance relativistic geodesy. In this work, the uncertainty of a strontium lattice clock, based on the {sup 1}S{sub 0}-{sup 3}P{sub 0} transition in {sup 87}Sr, due to the blackbody radiation (BBR) shift has been reduced to less than 1 x 10{sup -18} by more than one order of magnitude compared to the previous evaluation of the BBR shift uncertainty in this clock. The BBR shift has been reduced by interrogating the atoms in a cryogenic environment. The systematic uncertainty of the cryogenic lattice clock is evaluated to be 1.3 x 10{sup -17} which is dominated by the uncertainty of the AC Stark shift of the lattice laser and the uncertainty contribution of the BBR shift is negligible. Concerning the instability of the clock, the detection noise of the clock has been measured, and a model linking noise and clock instability has been developed. This noise model shows that, in our lattice clock, quantum projection noise is reached if more than 130 atoms are interrogated. By combining the noise model with the degradation due to the Dick effect reflecting the frequency noise of the interrogation laser, the instability of the clock is estimated to be 1.6 x 10{sup -16}/√(τ/s) in regular operation. During this work, several high-accuracy comparisons to other atomic clocks have been performed, including several absolute frequency measurements. The Sr clock transition frequency

  20. 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.

  1. Geodesy and metrology with a transportable optical clock

    Science.gov (United States)

    Grotti, Jacopo; Koller, Silvio; Vogt, Stefan; Häfner, Sebastian; Sterr, Uwe; Lisdat, Christian; Denker, Heiner; Voigt, Christian; Timmen, Ludger; Rolland, Antoine; Baynes, Fred N.; Margolis, Helen S.; Zampaolo, Michel; Thoumany, Pierre; Pizzocaro, Marco; Rauf, Benjamin; Bregolin, Filippo; Tampellini, Anna; Barbieri, Piero; Zucco, Massimo; Costanzo, Giovanni A.; Clivati, Cecilia; Levi, Filippo; Calonico, Davide

    2018-05-01

    Optical atomic clocks, due to their unprecedented stability1-3 and uncertainty3-6, are already being used to test physical theories7,8 and herald a revision of the International System of Units9,10. However, to unlock their potential for cross-disciplinary applications such as relativistic geodesy11, a major challenge remains: their transformation from highly specialized instruments restricted to national metrology laboratories into flexible devices deployable in different locations12-14. Here, we report the first field measurement campaign with a transportable 87Sr optical lattice clock12. We use it to determine the gravity potential difference between the middle of a mountain and a location 90 km away, exploiting both local and remote clock comparisons to eliminate potential clock errors. A local comparison with a 171Yb lattice clock15 also serves as an important check on the international consistency of independently developed optical clocks. This campaign demonstrates the exciting prospects for transportable optical clocks.

  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. Do strict rules and moving images increase the reliability of sequential identification procedures?.

    OpenAIRE

    Valentine, Tim; Darling, Stephen; Memon, Amina

    2007-01-01

    Live identification procedures in England and Wales have been replaced by use of video, which provides a sequential presentation of facial images. Sequential presentation of photographs provides some protection to innocent suspects from mistaken identification when used with strict instructions designed to prevent relative judgements (Lindsay, Lea & Fulford, 1991). However, the current procedure in England and Wales is incompatible with these strict instructions. The reported research investi...

  4. Strict optical orthogonal codes for purely asynchronous code-division multiple-access applications

    Science.gov (United States)

    Zhang, Jian-Guo

    1996-12-01

    Strict optical orthogonal codes are presented for purely asynchronous optical code-division multiple-access (CDMA) applications. The proposed code can strictly guarantee the peaks of its cross-correlation functions and the sidelobes of any of its autocorrelation functions to have a value of 1 in purely asynchronous data communications. The basic theory of the proposed codes is given. An experiment on optical CDMA systems is also demonstrated to verify the characteristics of the proposed code.

  5. Loss of circadian clock accelerates aging in neurodegeneration-prone mutants.

    Science.gov (United States)

    Krishnan, Natraj; Rakshit, Kuntol; Chow, Eileen S; Wentzell, Jill S; Kretzschmar, Doris; Giebultowicz, Jadwiga M

    2012-03-01

    Circadian clocks generate rhythms in molecular, cellular, physiological, and behavioral processes. Recent studies suggest that disruption of the clock mechanism accelerates organismal senescence and age-related pathologies in mammals. Impaired circadian rhythms are observed in many neurological diseases; however, it is not clear whether loss of rhythms is the cause or result of neurodegeneration, or both. To address this important question, we examined the effects of circadian disruption in Drosophila melanogaster mutants that display clock-unrelated neurodegenerative phenotypes. We combined a null mutation in the clock gene period (per(01)) that abolishes circadian rhythms, with a hypomorphic mutation in the carbonyl reductase gene sniffer (sni(1)), which displays oxidative stress induced neurodegeneration. We report that disruption of circadian rhythms in sni(1) mutants significantly reduces their lifespan compared to single mutants. Shortened lifespan in double mutants was coupled with accelerated neuronal degeneration evidenced by vacuolization in the adult brain. In addition, per(01)sni(1) flies showed drastically impaired vertical mobility and increased accumulation of carbonylated proteins compared to age-matched single mutant flies. Loss of per function does not affect sni mRNA expression, suggesting that these genes act via independent pathways producing additive effects. Finally, we show that per(01) mutation accelerates the onset of brain pathologies when combined with neurodegeneration-prone mutation in another gene, swiss cheese (sws(1)), which does not operate through the oxidative stress pathway. Taken together, our data suggest that the period gene may be causally involved in neuroprotective pathways in aging Drosophila. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. A quantum analogy to the classical gravitomagnetic clock effect

    Science.gov (United States)

    Faruque, S. B.

    2018-06-01

    We present an approximation to the solution of Dirac equation in Schwarzschild field found through the use of Foldy-Wouthuysen Hamiltonian. We solve the equation for the positive energy states and found the frequencies by which the states oscillate. Difference of the periods of oscillation of the two states with two different total angular momentum quantum number j has an analogical form of the classical clock effect found in general relativity. But unlike the term that appears as clock effect in classical physics, here the term is quantized. Thus, we find a quantum analogue of the classical gravitomagnetic clock effect.

  7. 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.

  8. High-precision multi-node clock network distribution.

    Science.gov (United States)

    Chen, Xing; Cui, Yifan; Lu, Xing; Ci, Cheng; Zhang, Xuesong; Liu, Bo; Wu, Hong; Tang, Tingsong; Shi, Kebin; Zhang, Zhigang

    2017-10-01

    A high precision multi-node clock network for multiple users was built following the precise frequency transmission and time synchronization of 120 km fiber. The network topology adopts a simple star-shaped network structure. The clock signal of a hydrogen maser (synchronized with UTC) was recovered from a 120 km telecommunication fiber link and then was distributed to 4 sub-stations. The fractional frequency instability of all substations is in the level of 10 -15 in a second and the clock offset instability is in sub-ps in root-mean-square average.

  9. Clock synchronization by remote detection of correlated photon pairs

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Caleb; Lamas-Linares, AntIa; Kurtsiefer, Christian [Centre for Quantum Technologies, National University of Singapore, 3 Science Drive 2, 117543 (Singapore)], E-mail: christian.kurtsiefer@gmail.com

    2009-04-15

    In this study, we present an algorithm to detect the time and frequency differences of independent clocks based on observation of time-correlated photon pairs. This enables remote coincidence identification in entanglement-based quantum key distribution schemes without dedicated coincidence hardware, pulsed sources with a timing structure or very stable reference clocks. We discuss the method for typical operating conditions and show that the requirement for reference clock accuracy can be relaxed by about five orders of magnitude in comparison with previous schemes.

  10. Toward A Neutral Mercury Optical Lattice Clock: Determination of the Magic Wavelength for the Ultraviolet clock Transition

    International Nuclear Information System (INIS)

    Mejri, Sinda

    2012-01-01

    A lattice clock combines the advantages of ion and neutral atom based clocks, namely the recoil and first order Doppler free spectroscopy allowed by the Lamb-Dicke regime. This lattice light field shifts the energy levels of the clock transition. However a wavelength can be found where the light-shift of the clock states cancelled to first order. In this thesis, we present the latest advances in optical lattice clock with mercury atoms developed at LNE-SYRTE. After a review of the current performances of different optical clock are currently under development, we focus on the concept of optical lattice clock and the features of the mercury that make him an excellent candidate for the realization of an optical lattice clock achievement the uncertainty of the level of 10 -17 . The second part is devoted to the characterization of the mercury MOT, using a sensitive detection system, which allowed us to evaluate the temperature of different isotopes present in the MOT and have a good evidence of sub-Doppler cooling for the fermionic isotopes. The third part of this these, present the experimental aspects of the implementation and the development of the laser source required for trapping mercury atoms operating near the predicted magic wavelength. Finally, we report on the Lamb-Dicke spectroscopy of the 1S0 →3 P0 clock transition in the 199 Hg atoms confined in lattice trap. With use of the ultra-stable laser system, linked to LNE-SYRTE primary frequency reference, we have determined the center frequency of the transition for a range of lattice wavelengths and different lattice depths. Analyzing these measurement, we have carried out the first experimental determination of the magic wavelength, which is the crucial step towards achieving a highly accurate frequency standard using mercury. (author)

  11. PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP.

    Science.gov (United States)

    Yeom, Miji; Lee, HansongI; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

    2018-03-23

    Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

  12. Disruption of the Circadian Clock Alters Antioxidative Defense via the SIRT1-BMAL1 Pathway in 6-OHDA-Induced Models of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Yali Wang

    2018-01-01

    Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disease and is known to involve circadian dysfunction and oxidative stress. Although antioxidative defense is regulated by the molecular circadian clock, few studies have examined their function in PD and their regulation by silent information regulator 1 (SIRT1. We hypothesize that reduced antioxidative activity in models of PD results from dysfunction of the molecular circadian clock via the SIRT1 pathway. We treated rats and SH-SY5Y cells with 6-hydroxydopamine (6-OHDA and measured the expression of core circadian clock and associated nuclear receptor genes using real-time quantitative PCR as well as levels of SIRT1, brain and muscle Arnt-like protein 1 (BMAL1, and acetylated BMAL1 using Western blotting. We found that 6-OHDA treatment altered the expression patterns of clock and antioxidative molecules in vivo and in vitro. We also detected an increased ratio of acetylated BMAL1:BMAL1 and a decreased level of SIRT1. Furthermore, resveratrol, an activator of SIRT1, decreased the acetylation of BMAL1 and inhibited its binding with CRY1, thereby reversing the impaired antioxidative activity induced by 6-OHDA. These results suggest that a dysfunctional circadian clock contributes to an abnormal antioxidative response in PD via a SIRT1-dependent BMAL1 pathway.

  13. PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP

    Directory of Open Access Journals (Sweden)

    Miji Yeom

    2018-03-01

    Full Text Available Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1 and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

  14. PHARAO space atomic clock: new developments on the laser source

    Science.gov (United States)

    Saccoccio, Muriel; Loesel, Jacques; Coatantiec, Claude; Simon, Eric; Laurent, Philippe; Lemonde, Pierre; Maksimovic, I.; Abgrall, M.

    2017-11-01

    The PHARAO project purpose is to open the way for a new atomic clock generation in space, where laser cooling techniques and microgravity allow high frequency stability and accuracy. The French space agency, CNES is funding and managing the clock construction. The French SYRTE and LKB laboratories are scientific and technical advisers for the clock requirements and the follow-up of subsystem development in industrial companies. EADS SODERN is developing two main subsystems of the PHARAO clock: the Laser Source and the Cesium Tube where atoms are cooled, launched, selected and detected by laser beams. The Laser Source includes an optical bench and electronic devices to generate the laser beams required. This paper describes PHARAO and the role laser beams play in its principle of operation. Then we present the Laser Source design, the technologies involved, and the status of development. Lastly, we focus of a key equipment to reach the performances expected, which is the Extended Cavity Laser Diode.

  15. Time measurement - technical importance of most exact clocks

    International Nuclear Information System (INIS)

    Goebel, E.O.; Riehle, F.

    2004-01-01

    The exactness of the best atomic clocks currently shows a temporal variation of 1 second in 30 million years. This means that we have reached the point of the most exact frequency and time measurement ever. In the past, there was a trend towards increasing the exactness in an increasingly fast sequence. Will this trend continue? And who will profit from it? This article is meant to give answers to these questions. This is done by presenting first the level reached currently with the best atomic clocks and describing the research activities running worldwide with the aim of achieving even more exact clocks. In the second part, we present examples of various areas of technical subjects and research in which the most exact clocks are being applied presently and even more exact ones will be needed in the future [de

  16. The New PTB Caesium Fountain Clock CSF2

    National Research Council Canada - National Science Library

    Wynands, R; Bauch, A; Griebsch, D; Schroeder, R; Weyers, S

    2005-01-01

    At PTB a second caesium fountain clock, CSF2, is in the process of being set up. It differs from the first PTB caesium fountain standard CSF1 in a number of details, which are consecutively specified...

  17. A bunch clock for the Advanced Photon Source

    International Nuclear Information System (INIS)

    Lenkszus, F.R.; Laird, R.J.

    1997-01-01

    A bunch clock timing module has been developed for use by Advanced Photon Source beamlines. The module provides bunch pattern and timing information that can be used to trigger beamline data collection equipment. The module is fully integrated into the control system software (EPICS) which automatically loads it with the storage ring fill pattern at injection time. Fast timing outputs (1 ns FWHM) for each stored bunch are generated using the storage ring low-level rf and revolution clock as input references. Fiber-optic-based transmitters and receivers are used to transmit a 352-MHz low-level rf reference to distributed bunch clock modules. The bunch clock module is a single-width VME module and may be installed in a VME crate located near beamline instrumentation. A prototype has been in use on the SRI CAT beamline for over a year. The design and integration into the control system timing software along with measured performance results are presented

  18. 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.

  19. A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3beta.

    Science.gov (United States)

    Hirota, Tsuyoshi; Lewis, Warren G; Liu, Andrew C; Lee, Jae Wook; Schultz, Peter G; Kay, Steve A

    2008-12-30

    The circadian clock controls daily oscillations of gene expression at the cellular level. We report the development of a high-throughput circadian functional assay system that consists of luminescent reporter cells, screening automation, and a data analysis pipeline. We applied this system to further dissect the molecular mechanisms underlying the mammalian circadian clock using a chemical biology approach. We analyzed the effect of 1,280 pharmacologically active compounds with diverse structures on the circadian period length that is indicative of the core clock mechanism. Our screening paradigm identified many compounds previously known to change the circadian period or phase, demonstrating the validity of the assay system. Furthermore, we found that small molecule inhibitors of glycogen synthase kinase 3 (GSK-3) consistently caused a strong short period phenotype in contrast to the well-known period lengthening by lithium, another presumed GSK-3 inhibitor. siRNA-mediated knockdown of GSK-3beta also caused a short period, confirming the phenotype obtained with the small molecule inhibitors. These results clarify the role of GSK-3beta in the period regulation of the mammalian clockworks and highlight the effectiveness of chemical biology in exploring unidentified mechanisms of the circadian clock.

  20. Barley (Hordeum vulgare) circadian clock genes can respond rapidly to temperature in an EARLY FLOWERING 3-dependent manner

    Science.gov (United States)

    Ford, Brett; Deng, Weiwei; Clausen, Jenni; Oliver, Sandra; Boden, Scott; Hemming, Megan; Trevaskis, Ben

    2016-01-01

    An increase in global temperatures will impact future crop yields. In the cereal crops wheat and barley, high temperatures accelerate reproductive development, reducing the number of grains per plant and final grain yield. Despite this relationship between temperature and cereal yield, it is not clear what genes and molecular pathways mediate the developmental response to increased temperatures. The plant circadian clock can respond to changes in temperature and is important for photoperiod-dependent flowering, and so is a potential mechanism controlling temperature responses in cereal crops. This study examines the relationship between temperature, the circadian clock, and the expression of flowering-time genes in barley (Hordeum vulgare), a crop model for temperate cereals. Transcript levels of barley core circadian clock genes were assayed over a range of temperatures. Transcript levels of core clock genes CCA1, GI, PRR59, PRR73, PRR95, and LUX are increased at higher temperatures. CCA1 and PRR73 respond rapidly to a decrease in temperature whereas GI and PRR59 respond rapidly to an increase in temperature. The response of GI and the PRR genes to changes in temperature is lost in the elf3 mutant indicating that their response to temperature may be dependent on a functional ELF3 gene. PMID:27580625

  1. 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.

  2. Clock Face Drawing Test Performance in Children with ADHD

    Directory of Open Access Journals (Sweden)

    Ahmad Ghanizadeh

    2013-01-01

    Full Text Available  Introduction: The utility and discriminatory pattern of the clock face drawing test in ADHD is unclear. This study therefore compared Clock Face Drawing test performance in children with ADHD and controls.   Material & methods: 95 children with ADHD and 191 school children were matched for gender ratio and age. ADHD symptoms severities were assessed using DSM-IV ADHD checklist and their intellectual functioning was assessed. The participants completed three clock-drawing tasks, and the following four functions were assessed: Contour score, Numbers score, Hands setting score, and Center score    Results: All the subscales scores of the three clock drawing tests of the ADHD group were lower than that of the control group. In ADHD children, inattention and hyperactivity/impulsivity scores were not related with free drawn clock test scores. When pre-drawn contour test was performed, inattentiveness score was statistically associated with Number score. None of the other variables of age, gender, intellectual functioning, and hand use preference were associated with Numbers score. In pre-drawn clock, no association of ADHD symptoms with any CDT subscales was significant. In addition, more errors are observed with free drawn clock and Pre-drawn contour than pre-drawn clock.    Conclusion: Putting Numbers and Hands setting are more sensitive measures to screen ADHD than Contour and Center drawing. Test performance, except Hands setting, may have already reached a developmental plateau. It is probable that Hand setting deficit in children with ADHD may not decrease from age 8 to 14 years. Performance of children with ADHD is associated with the complexity of CDT.

  3. Highly Accurate Timestamping for Ethernet-Based Clock Synchronization

    OpenAIRE

    Loschmidt, Patrick; Exel, Reinhard; Gaderer, Georg

    2012-01-01

    It is not only for test and measurement of great importance to synchronize clocks of networked devices to timely coordinate data acquisition. In this context the seek for high accuracy in Ethernet-based clock synchronization has been significantly supported by enhancements to the Network Time Protocol (NTP) and the introduction of the Precision Time Protocol (PTP). The latter was even applied to instrumentation and measurement applications through the introduction of LXI....

  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. Clock face drawing test performance in children with ADHD.

    Science.gov (United States)

    Ghanizadeh, Ahmad; Safavi, Salar; Berk, Michael

    2013-01-01

    The utility and discriminatory pattern of the clock face drawing test in ADHD is unclear. This study therefore compared Clock Face Drawing test performance in children with ADHD and controls. 95 school children with ADHD and 191 other children were matched for gender ratio and age. ADHD symptoms severities were assessed using DSM-IV ADHD checklist and their intellectual functioning was assessed. The participants completed three clock-drawing tasks, and the following four functions were assessed: Contour score, Numbers score, Hands setting score, and Center score. All the subscales scores of the three clock drawing tests of the ADHD group were lower than that of the control group. In ADHD children, inattention and hyperactivity/ impulsivity scores were not related to free drawn clock test scores. When pre-drawn contour test was performed, inattentiveness score was statistically associated with Number score while none of the other variables of age, gender, intellectual functioning, and hand use preference were associated with that kind of score. In pre-drawn clock, no association of ADHD symptoms with any CDT subscales found significant. In addition, more errors are observed with free drawn clock and Pre-drawn contour than pre-drawn clock. Putting Numbers and Hands setting are more sensitive measures to screen ADHD than Contour and Center drawing. Test performance, except Hands setting, may have already reached a developmental plateau. It is probable that Hand setting deficit in children with ADHD may not decrease from age 8 to 14 years. Performance of children with ADHD is associated with complexity of CDT.

  6. Remote atomic clock synchronization via satellites and optical fibers

    OpenAIRE

    Piester, D.; Rost, M.; 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 10−15 (relative, 1 day averaging) and time scales can be synchronized...

  7. Master Clock and Time-Signal-Distribution System

    Science.gov (United States)

    Tjoelker, Robert; Calhoun, Malcolm; Kuhnle, Paul; Sydnor, Richard; Lauf, John

    2007-01-01

    A timing system comprising an electronic master clock and a subsystem for distributing time signals from the master clock to end users is undergoing development to satisfy anticipated timing requirements of NASA s Deep Space Network (DSN) for the next 20 to 30 years. This system has a modular, flexible, expandable architecture that is easier to operate and maintain than the present frequency and timing subsystem (FTS).

  8. Isolated abnormal strict morphology is not a contraindication for intrauterine insemination.

    Science.gov (United States)

    Lockwood, G M; Deveneau, N E; Shridharani, A N; Strawn, E Y; Sandlow, J I

    2015-11-01

    This study sought to investigate whether isolated abnormal strict morphology (<5% normal forms) and very low strict morphology (0-1% normal forms) affects pregnancy rates in intrauterine insemination (IUI). This was a retrospective study performed at an Academic Medical Center/Reproductive Medicine Center. Four hundred and eight couples were included for 856 IUI cycles. 70 IUI cycles were performed in couples with abnormal strict morphology and otherwise normal semen parameters. Outcomes were measured as clinical pregnancy rate per IUI cycle as documented by fetal heart activity on maternal ultrasound. Clinical pregnancy rate did not significantly differ between the group with abnormal strict morphology [11/70 (15.7%)] and the normal morphology group [39/281 (13.9%)]. Additionally, there was no significant difference between the pregnancy rate in the abnormal morphology group compared to that of our overall institutional IUI pregnancy rate [145/856 (16.9%)]. Furthermore, there was no significant difference between pregnancy rate in the very low morphology group [3/14 (21.4%)] compared to those with normal morphology or the overall IUI pregnancy rate. Patients with isolated abnormal strict morphology have clinical pregnancy rates similar to those with normal morphology for IUI. Even in those with very low normal forms, consideration of IUI for assisted reproduction should not be excluded. © 2015 American Society of Andrology and European Academy of Andrology.

  9. A European map regarding the strictness of the transfer pricing regulations

    Directory of Open Access Journals (Sweden)

    Ioana Ignat

    2017-12-01

    Full Text Available In the context in which transfer pricing may represent a mechanism through which multinationals have the possibility to move funds internationally, in order to prevent the base erosion and profit shifting between multinationals, countries over the world have adopted various transfer pricing regulations. Furthermore, some of the countries adopted stricter regulations than others. The objective of our research was to identify the level of strictness for the transfer pricing regulations from the European countries. To achieve this objective, we analyzed the transfer pricing regulations of all European countries and we built a transfer pricing strictness index, based on which we defined 4 categories of countries (where category 1 includes the countries with the least strict transfer pricing regulations and category 4 countries with the strictest regulations. After that, we illustrated how these categories are distributed on the European map. In order to collect the information, we used the transfer pricing guides issued by the Big Four companies for the year 2015. The study`s results show that the strictness of the transfer pricing regulations decreases from the west of Europe to east. Moreover, most of the countries were included in category 2, respectively category 3, meaning that the transfer pricing regulations from the European continent are not so flexible, but in the same time are not so strict.

  10. 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

    2016-08-09

    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.

  11. Shining a light on the Arabidopsis circadian clock.

    Science.gov (United States)

    Oakenfull, Rachael J; Davis, Seth J

    2017-11-01

    The circadian clock provides essential timing information to ensure optimal growth to prevailing external environmental conditions. A major time-setting mechanism (zeitgeber) in clock synchronization is light. Differing light wavelengths, intensities, and photoperiodic duration are processed for the clock-setting mechanism. Many studies on light-input pathways to the clock have focused on Arabidopsis thaliana. Photoreceptors are specific chromic proteins that detect light signals and transmit this information to the central circadian oscillator through a number of different signalling mechanisms. The most well-characterized clock-mediating photoreceptors are cryptochromes and phytochromes, detecting blue, red, and far-red wavelengths of light. Ultraviolet and shaded light are also processed signals to the oscillator. Notably, the clock reciprocally generates rhythms of photoreceptor action leading to so-called gating of light responses. Intermediate proteins, such as Phytochrome interacting factors (PIFs), constitutive photomorphogenic 1 (COP1) and EARLY FLOWERING 3 (ELF3), have been established in signalling pathways downstream of photoreceptor activation. However, the precise details for these signalling mechanisms are not fully established. This review highlights both historical and recent efforts made to understand overall light input to the oscillator, first looking at how each wavelength of light is detected, this is then related to known input mechanisms and their interactions. © 2017 John Wiley & Sons Ltd.

  12. 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.

  13. Time-of-Day Effects on Metabolic and Clock-Related Adjustments to Cold

    Directory of Open Access Journals (Sweden)

    Frederico Sander Mansur Machado

    2018-04-01

    Full Text Available BackgroundDaily cyclic changes in environmental conditions are key signals for anticipatory and adaptive adjustments of most living species, including mammals. Lower ambient temperature stimulates the thermogenic activity of brown adipose tissue (BAT and skeletal muscle. Given that the molecular components of the endogenous biological clock interact with thermal and metabolic mechanisms directly involved in the defense of body temperature, the present study evaluated the differential homeostatic responses to a cold stimulus at distinct time-windows of the light/dark-cycle.MethodsMale Wistar rats were subjected to a single episode of 3 h cold ambient temperature (4°C at one of 6 time-points starting at Zeitgeber Times 3, 7, 11, 15, 19, and 23. Metabolic rate, core body temperature, locomotor activity (LA, feeding, and drinking behaviors were recorded during control and cold conditions at each time-point. Immediately after the stimulus, rats were euthanized and both the soleus and BAT were collected for real-time PCR.ResultsDuring the light phase (i.e., inactive phase, cold exposure resulted in a slight hyperthermia (p < 0.001. Light phase cold exposure also increased metabolic rate and LA (p < 0.001. In addition, the prevalence of fat oxidative metabolism was attenuated during the inactive phase (p < 0.001. These metabolic changes were accompanied by time-of-day and tissue-specific changes in core clock gene expression, such as DBP (p < 0.0001 and REV-ERBα (p < 0.01 in the BAT and CLOCK (p < 0.05, PER2 (p < 0.05, CRY1 (p < 0.05, CRY2 (p < 0.01, and REV-ERBα (p < 0.05 in the soleus skeletal muscle. Moreover, genes involved in substrate oxidation and thermogenesis were affected in a time-of-day and tissue-specific manner by cold exposure.ConclusionThe time-of-day modulation of substrate mobilization and oxidation during cold exposure provides a clear example of the circadian modulation of physiological

  14. New strict left bundle branch block criteria reflect left ventricular activation differences

    DEFF Research Database (Denmark)

    Emerek, Kasper Janus Grønn; Risum, Niels; Hjortshøj, Søren Pihlkjær

    2015-01-01

    AIMS: Pacing lead electrical delays and strict left bundle branch block (LBBB) criteria were assessed against cardiac resynchronization therapy (CRT) outcome. METHODS: Forty-nine patients with LBBB and QRS duration >130 milliseconds underwent CRT-implantation. Sensed right ventricular to left ven....... CONCLUSION: Interventricular electrical delay predicts left ventricular remodeling after CRT and new, strict ECG criteria of LBBB are superior in predicting remodeling.......AIMS: Pacing lead electrical delays and strict left bundle branch block (LBBB) criteria were assessed against cardiac resynchronization therapy (CRT) outcome. METHODS: Forty-nine patients with LBBB and QRS duration >130 milliseconds underwent CRT-implantation. Sensed right ventricular to left...... ventricular electrical delay (RV-LV-IED) was measured. Response to CRT was defined as ≥15% decrease in left ventricular end-systolic volume. RESULTS: Eighteen of 20 (90%) patients with non-ischemic dilated cardiomyopathy (DCM) and 18 of 29 (62%) with ischemic heart disease (IHD) responded to CRT, p

  15. Actions of a separately strict cpo-monoid on pointed directed complete posets

    Directory of Open Access Journals (Sweden)

    Halimeh Moghbeli Damaneh

    2015-07-01

    Full Text Available ‎ In the present article‎, ‎we study some categorical properties of the category {$bf‎ Cpo_{Sep}$-$S$} of all {separately strict $S$-cpo's}; cpo's equipped with‎ a compatible right action of a separately strict cpo-monoid $S$ which is‎ strict continuous in each component‎. ‎In particular‎, we show that this category is reflective and coreflective in the‎ category of $S$-cpo's‎, ‎find the free and cofree functors‎, characterize products and coproducts‎. ‎Furthermore‎, ‎epimorphisms and‎  monomorphisms in {$bf Cpo_{Sep}$-$S$} are studied‎, ‎and show that‎ {$bf Cpo_{Sep}$-$S$} is not cartesian closed‎.

  16. Prediction of Navigation Satellite Clock Bias Considering Clock's Stochastic Variation Behavior with Robust Least Square Collocation

    Directory of Open Access Journals (Sweden)

    WANG Yupu

    2016-06-01

    Full Text Available In order to better express the characteristic of satellite clock bias (SCB and further improve its prediction precision, a new SCB prediction model is proposed, which can take the physical feature, cyclic variation and stochastic variation behaviors of the space-borne atomic clock into consideration by using a robust least square collocation (LSC method. The proposed model firstly uses a quadratic polynomial model with periodic terms to fit and abstract the trend term and cyclic terms of SCB. Then for the residual stochastic variation part and possible gross errors hidden in SCB data, the model employs a robust LSC method to process them. The covariance function of the LSC is determined by selecting an empirical function and combining SCB prediction tests. Using the final precise IGS SCB products to conduct prediction tests, the results show that the proposed model can get better prediction performance. Specifically, the results' prediction accuracy can enhance 0.457 ns and 0.948 ns respectively, and the corresponding prediction stability can improve 0.445 ns and 1.233 ns, compared with the results of quadratic polynomial model and grey model. In addition, the results also show that the proposed covariance function corresponding to the new model is reasonable.

  17. Vane clocking effects in an embedded compressor stage

    Science.gov (United States)

    Key, Nicole Leanne

    The objective of this research was to experimentally investigate the effects of vane clocking, the circumferential indexing of adjacent vane rows with similar vane counts, in an embedded compressor stage. Experiments were performed in the Purdue 3-Stage Compressor, which consists of an IGV followed by three stages. The IGV, Stator 1, and Stator 2 have identical vane counts of 44, and the effects of clocking were studied on Stage 2. The clocking configuration that located the upstream vane wake on the Stator 2 leading edge was identified with total pressure measurements at the inlet to Stator 2 and confirmed with measurements at the exit of Stator 2. For both loading conditions, the total temperature results showed that there was no measurable change associated with vane clocking in the amount of work done on the flow. At design loading, the change in stage efficiency with vane clocking was 0.27 points between the maximum and minimum efficiency clocking configurations. The maximum efficiency configuration was the case where the Stator 1 wake impinged on the Stator 2 leading edge. This condition produced a shallower and thinner Stator 2 wake compared to the clocking configuration that located the wake in the middle of the Stator 2 passage. By locating the Stator 1 wake at the leading edge, it dampened the Stator 2 boundary layer response to inlet fluctuations associated with the Rotor 2 wakes. At high loading, the change in Stage 2 efficiency increased to 1.07 points; however, the maximum efficiency clocking configuration was the case where the Stator 1 wake passed through the middle of the downstream vane passage. At high loading, the flow physics associated with vane clocking were different than at design loading because the location of the Stator 1 wake fluid on the Stator 2 leading edge triggered a boundary layer separation on the suction side of Stator 2 producing a wider and deeper wake. Vane clocking essentially affects the amount of interaction between the

  18. The retinal clock in mammals: role in health and disease

    Directory of Open Access Journals (Sweden)

    Felder-Schmittbuhl MP

    2017-05-01

    Full Text Available Marie-Paule Felder-Schmittbuhl,1,* Hugo Calligaro,2 Ouria Dkhissi-Benyahya2,* 1Institute of Cellular and Integratives Neurosciences, UPR3212, CNRS, Université de Strasbourg, Strasbourg, 2University of Lyon, Stem Cell and Brain Research Institute, INSERM U1208, Bron, France *These authors contributed equally to this work Abstract: The mammalian retina contains an extraordinary diversity of cell types that are highly organized into precise circuits to perceive and process visual information in a dynamic manner and transmit it to the brain. Above this builds up another level of complex dynamic, orchestrated by a circadian clock located within the retina, which allows retinal physiology, and hence visual function, to adapt to daily changes in light intensity. The mammalian retina is a remarkable model of circadian clock because it harbors photoreception, self-sustained oscillator function, and physiological outputs within the same tissue. However, the location of the retinal clock in mammals has been a matter of long debate. Current data have shown that clock properties are widely distributed among retinal cells and that the retina is composed of a network of circadian clocks located within distinct cellular layers. Nevertheless, the identity of the major pacemaker, if any, still warrants identification. In addition, the retina coordinates rhythmic behavior by providing visual input to the master hypothalamic circadian clock in the suprachiasmatic nuclei (SCN. This light entrainment of the SCN to the light/dark cycle involves a network of retinal photoreceptor cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs. Although it was considered that these photoreceptors synchronized both retinal and SCN clocks, new data challenge this view, suggesting that none of these photoreceptors is involved in photic entrainment of the retinal clock. Because circadian organization is a ubiquitous feature of the retina and controls

  19. The photon is no strict particle and nonlocality is far from being proven

    Energy Technology Data Exchange (ETDEWEB)

    Greulich, Karl Otto [Fritz Lipmann Institut, Jena (Germany)

    2010-07-01

    Two aspects of philosophical discussions on physics are the wave particle dualism and non locality including entanglement. However the strict particle aspect of the photon, in the common sense view, has never been proven. The accumulation time argument, the only experimental verification of a strictly particle like photon, has so far not yet been satisfied. Also, experiments thought to prove nonlocality have loophole which have so far not yet been safely closed, and now an even more serious loophole emerges. Thus, also nonlocality cannot be seen as proven. This demands some fine tuning of philosophical discussions on critical experiments in physics.

  20. The Fixed-Point Theory of Strictly Contracting Functions on Generalized Ultrametric Semilattices

    Directory of Open Access Journals (Sweden)

    Eleftherios Matsikoudis

    2013-08-01

    Full Text Available We introduce a new class of abstract structures, which we call generalized ultrametric semilattices, and in which the meet operation of the semilattice coexists with a generalized distance function in a tightly coordinated way. We prove a constructive fixed-point theorem for strictly contracting functions on directed-complete generalized ultrametric semilattices, and introduce a corresponding induction principle. We cite examples of application in the semantics of logic programming and timed computation, where, until now, the only tool available has been the non-constructive fixed-point theorem of Priess-Crampe and Ribenboim for strictly contracting functions on spherically complete generalized ultrametric semilattices.

  1. Strontium Optical Lattice Clock: In Quest of the Ultimate Performance

    International Nuclear Information System (INIS)

    Westergaard, Ph.G.

    2010-10-01

    This thesis presents the latest achievements regarding the Sr optical lattice clock experiment at LNESYRTE, Observatoire de Paris. After having described the general principles for optical lattice clocks and the operation of the clock in question, the emphasis is put on the features that have been added to the experiment since 2007. The most important new elements are an ultra-stable reference cavity for the clock laser, the development of a non-destructive detection technique, and the construction of a second Sr lattice clock. The ultra-stable cavity is constructed from a ULE spacer and fused silica mirrors and has shown a thermal noise floor at 6.5 * 10 -16 , placing it among the best in the world. The non-destructive detection is effectuated by a phase measurement of a weak probe beam that traverses the atoms placed in one arm of a Mach-Zender interferometer. The non-destructive aspect enables a recycling of the atoms from cycle to cycle which consequently increases the duty cycle, allowing for an increase of the stability of the clock. With these new tools the frequency stability is expected to be 2.2 * 10 -16 /√τ for an optimized sequence. The most recent comparisons between the two Sr clocks reach an accuracy level of 10 -16 after about 1000 s, and this way we have been able to characterize lattice related frequency shifts with an unprecedented accuracy. The measurements ensure a control of lattice related effects at the 10 -18 level even for trap depths as large as 50E r . (authors)

  2. Minimal tool set for a prokaryotic circadian clock.

    Science.gov (United States)

    Schmelling, Nicolas M; Lehmann, Robert; Chaudhury, Paushali; Beck, Christian; Albers, Sonja-Verena; Axmann, Ilka M; Wiegard, Anika

    2017-07-21

    Circadian clocks are found in organisms of almost all domains including photosynthetic Cyanobacteria, whereby large diversity exists within the protein components involved. In the model cyanobacterium Synechococcus elongatus PCC 7942 circadian rhythms are driven by a unique KaiABC protein clock, which is embedded in a network of input and output factors. Homologous proteins to the KaiABC clock have been observed in Bacteria and Archaea, where evidence for circadian behavior in these domains is accumulating. However, interaction and function of non-cyanobacterial Kai-proteins as well as homologous input and output components remain mainly unclear. Using a universal BLAST analyses, we identified putative KaiC-based timing systems in organisms outside as well as variations within Cyanobacteria. A systematic analyses of publicly available microarray data elucidated interesting variations in circadian gene expression between different cyanobacterial strains, which might be correlated to the diversity of genome encoded clock components. Based on statistical analyses of co-occurrences of the clock components homologous to Synechococcus elongatus PCC 7942, we propose putative networks of reduced and fully functional clock systems. Further, we studied KaiC sequence conservation to determine functionally important regions of diverged KaiC homologs. Biochemical characterization of exemplary cyanobacterial KaiC proteins as well as homologs from two thermophilic Archaea demonstrated that kinase activity is always present. However, a KaiA-mediated phosphorylation is only detectable in KaiC1 orthologs. Our analysis of 11,264 genomes clearly demonstrates that components of the Synechococcus elongatus PCC 7942 circadian clock are present in Bacteria and Archaea. However, all components are less abundant in other organisms than Cyanobacteria and KaiA, Pex, LdpA, and CdpA are only present in the latter. Thus, only reduced KaiBC-based or even simpler, solely KaiC-based timing systems

  3. More strictly protected areas are not necessarily more protective: evidence from Bolivia, Costa Rica, Indonesia, and Thailand

    International Nuclear Information System (INIS)

    Ferraro, Paul J; Hanauer, Merlin M; Miteva, Daniela A; Pattanayak, Subhrendu K; Canavire-Bacarreza, Gustavo Javier; Sims, Katharine R E

    2013-01-01

    National parks and other protected areas are at the forefront of global efforts to protect biodiversity and ecosystem services. However, not all protection is equal. Some areas are assigned strict legal protection that permits few extractive human uses. Other protected area designations permit a wider range of uses. Whether strictly protected areas are more effective in achieving environmental objectives is an empirical question: although strictly protected areas legally permit less anthropogenic disturbance, the social conflicts associated with assigning strict protection may lead politicians to assign strict protection to less-threatened areas and may lead citizens or enforcement agents to ignore the strict legal restrictions. We contrast the impacts of strictly and less strictly protected areas in four countries using IUCN designations to measure de jure strictness, data on deforestation to measure outcomes, and a quasi-experimental design to estimate impacts. On average, stricter protection reduced deforestation rates more than less strict protection, but the additional impact was not always large and sometimes arose because of where stricter protection was assigned rather than regulatory strictness per se. We also show that, in protected area studies contrasting y management regimes, there are y 2 policy-relevant impacts, rather than only y, as earlier studies have implied. (letter)

  4. Reciprocal cholinergic and GABAergic modulation of the small ventrolateral pacemaker neurons of Drosophila's circadian clock neuron network.

    Science.gov (United States)

    Lelito, Katherine R; Shafer, Orie T

    2012-04-01

    The relatively simple clock neuron network of Drosophila is a valuable model system for the neuronal basis of circadian timekeeping. Unfortunately, many key neuronal classes of this network are inaccessible to electrophysiological analysis. We have therefore adopted the use of genetically encoded sensors to address the physiology of the fly's circadian clock network. Using genetically encoded Ca(2+) and cAMP sensors, we have investigated the physiological responses of two specific classes of clock neuron, the large and small ventrolateral neurons (l- and s-LN(v)s), to two neurotransmitters implicated in their modulation: acetylcholine (ACh) and γ-aminobutyric acid (GABA). Live imaging of l-LN(v) cAMP and Ca(2+) dynamics in response to cholinergic agonist and GABA application were well aligned with published electrophysiological data, indicating that our sensors were capable of faithfully reporting acute physiological responses to these transmitters within single adult clock neuron soma. We extended these live imaging methods to s-LN(v)s, critical neuronal pacemakers whose physiological properties in the adult brain are largely unknown. Our s-LN(v) experiments revealed the predicted excitatory responses to bath-applied cholinergic agonists and the predicted inhibitory effects of GABA and established that the antagonism of ACh and GABA extends to their effects on cAMP signaling. These data support recently published but physiologically untested models of s-LN(v) modulation and lead to the prediction that cholinergic and GABAergic inputs to s-LN(v)s will have opposing effects on the phase and/or period of the molecular clock within these critical pacemaker neurons.

  5. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

    Directory of Open Access Journals (Sweden)

    Julian Lippert

    Full Text Available From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH in comparison to those of healthy controls (HC. Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG and Multiple Sleep Latency Test (MSLT. Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

  6. Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

    Science.gov (United States)

    Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

    2014-01-01

    From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

  7. Interrelationship between 3,5,3´-triiodothyronine and the circadian clock in the rodent heart.

    Science.gov (United States)

    Peliciari-Garcia, Rodrigo Antonio; Prévide, Rafael Maso; Nunes, Maria Tereza; Young, Martin Elliot

    2016-01-01

    Triiodothyronine (T3) is an important modulator of cardiac metabolism and function, often through modulation of gene expression. The cardiomyocyte circadian clock is a transcriptionally based molecular mechanism capable of regulating cardiac processes, in part by modulating responsiveness of the heart to extra-cardiac stimuli/stresses in a time-of-day (TOD)-dependent manner. Although TOD-dependent oscillations in circulating levels of T3 (and its intermediates) have been established, oscillations in T3 sensitivity in the heart is unknown. To investigate the latter possibility, euthyroid male Wistar rats were treated with vehicle or T3 at distinct times of the day, after which induction of known T3 target genes were assessed in the heart (4-h later). The expression of mRNA was assessed by real-time quantitative polymerase chain reaction (qPCR). Here, we report greater T3 induction of transcript levels at the end of the dark phase. Surprisingly, use of cardiomyocyte-specific clock mutant (CCM) mice revealed that TOD-dependent oscillations in T3 sensitivity were independent of this cell autonomous mechanism. Investigation of genes encoding for proteins that affect T3 sensitivity revealed that Dio1, Dio2 and Thrb1 exhibited TOD-dependent variations in the heart, while Thra1 and Thra2 did not. Of these, Dio1 and Thrb1 were increased in the heart at the end of the dark phase. Interestingly, we observed that T3 acutely altered the expression of core clock components (e.g. Bmal1) in the rat heart. To investigate this further, rats were injected with a single dose of T3, after which expression of clock genes was interrogated at 3-h intervals over the subsequent 24-h period. These studies revealed robust effects of T3 on oscillations of both core clock components and clock-controlled genes. In summary, the current study exposed TOD-dependent sensitivity to T3 in the heart and its effects in the circadian clock genes expression.

  8. 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...

  9. TURNING BACK THE CLOCK: INFERRING THE HISTORY OF THE EIGHT O'CLOCK ARC

    International Nuclear Information System (INIS)

    Finkelstein, Steven L.; Papovich, Casey; Rudnick, Gregory; Egami, Eiichi; Rieke, Marcia J.; Willmer, Christopher N. A.; Le Floc'h, Emeric; Rigby, Jane R.

    2009-01-01

    We present the results from an optical and near-infrared (NIR) spectroscopic study of the ultraviolet-luminous z = 2.73 galaxy, the 8 o'clock arc. Due to gravitational lensing, this galaxy is magnified by a factor of μ > 10, allowing in-depth measurements which are usually unfeasible at such redshifts. In the optical spectra, we measured the systemic redshift of the galaxy, z = 2.7322± 0.0012, using stellar photospheric lines. This differs from the redshift of absorption lines in the interstellar medium, z = 2.7302 ± 0.0006, implying gas outflows on the order of 160 km s -1 . With H- and K-band NIR spectra, we have measured nebular emission lines of Hα, Hβ, Hγ, [N II], and [O III], which have a redshift z = 2.7333 ± 0.0001, consistent with the derived systemic redshift. From the Balmer decrement, we measured the dust extinction in this galaxy to be A 5500 = 1.17 ± 36 mag. Correcting the Hα line flux for dust extinction as well as the assumed lensing factor, we measure a star formation rate (SFR) of ∼270 M sun yr -1 , which is higher than ∼85% of star-forming galaxies at z ∼ 2-3. Using combinations of all detected emission lines, we find that the 8 o'clock arc has a gas-phase metallicity of ∼0.8 Z sun , showing that enrichment at high redshift is not rare, even in blue, star-forming galaxies. Studying spectra from two of the arc components separately, we find that one component dominates both the dust extinction and SFR, although the metallicities between the two components are similar. We derive the mass via stellar population modeling, and find that the arc has a total stellar mass of ∼4.2 x 10 11 M sun , which falls on the mass-metallicity relation at z ∼ 2. Finally, we estimate the total gas mass, and find it to be only ∼12% of the stellar mass, implying that the 8 o'clock arc is likely nearing the end of a starburst.

  10. She's Strict for a Good Reason: Highly Effective Teachers in Low-Performing Urban Schools

    Science.gov (United States)

    Poplin, Mary; Rivera, John; Durish, Dena; Hoff, Linda; Kawell, Susan; Pawlak, Pat; Hinman, Ivannia Soto; Straus, Laura; Veney, Cloetta

    2011-01-01

    A study of 31 high-performing teachers in low-performing urban schools found that these teachers had certain traits in common. They were strict; they taught in traditional, explicit ways; there was little time in their classrooms when instruction was not occurring; and they moved around the room helping their students. They used very few…

  11. Detection of low numbers of microplastics in North Sea fish using strict quality assurance criteria

    NARCIS (Netherlands)

    Hermsen, E.; Pompe, R.; Besseling, E.; Koelmans, A.A.

    2017-01-01

    We investigated 400 individual fish of four North Sea species: Atlantic Herring, Sprat, Common Dab, and Whiting on ingestion of > 20 μm microplastic. Strict quality assurance criteria were followed in order to control contamination during the study. Two plastic particles were found in only 1 (a

  12. History, administration, goals, values, and long-term data of Russia's strictly protected scientific nature reserves

    Science.gov (United States)

    Martin A. Spetich; Anna E. Kvashnina; Y.D. Nukhimovskya; Olin E. Jr. Rhodes

    2009-01-01

    One of the most comprehensive attempts at biodiversity conservation in Russia and the former Soviet Union has been the establishment of an extensive network of protected natural areas. Among all types of protected areas in Russia, zapovedniks (strictly protected scientific preserve) have been the most effective in protecting biodiversity at the ecosystem scale. Russia...

  13. The Preventive Effect of Strict Gun Control Laws on Suicide and Homicide.

    Science.gov (United States)

    Lester, David; Murrell, Mary E.

    1982-01-01

    Examined state gun control laws and used a multidimensional scaling technique to study the relationship of strictness and death rates. Results showed states with stricter laws had lower suicide rates by firearms but higher rates by other means. No effect on homicide was found. (JAC)

  14. Required sample size for monitoring stand dynamics in strict forest reserves: a case study

    Science.gov (United States)

    Diego Van Den Meersschaut; Bart De Cuyper; Kris Vandekerkhove; Noel Lust

    2000-01-01

    Stand dynamics in European strict forest reserves are commonly monitored using inventory densities of 5 to 15 percent of the total surface. The assumption that these densities guarantee a representative image of certain parameters is critically analyzed in a case study for the parameters basal area and stem number. The required sample sizes for different accuracy and...

  15. ASHP therapeutic position statement on strict glycemic control in patients with diabetes.

    Science.gov (United States)

    2003-11-15

    The deleterious effects of hyperglycemia have been documented from the biochemical to the pathophysiologic level. Given the research findings and the guidelines for glycemic control established by ADA and ACE, ASHP supports and encourages strict glycemic control in all appropriate patients with diabetes mellitus to reduce the progression of chronic complications.

  16. What is your level of overconfidence? A strictly incentive compatible measurement of absolute and relative overconfidence

    NARCIS (Netherlands)

    Urbig, D.; Stauf, J.; Weitzel, U.|info:eu-repo/dai/nl/276323394

    This study contributes to the ongoing discussion on the appropriate measurement of overconfidence, in particular, its strictly incentive compatible measurement in experiments. Despite a number of significant advances in recent research, several important issues remain to be solved. These relate to

  17. Fermentative degradation of polyethylene glycol by a strictly anaerobic, gram-negative, nonsporeforming bacterium, Pelobacter venetianus sp. nov.

    Science.gov (United States)

    Schink, B; Stieb, M

    1983-06-01

    The synthetic polyether polyethylene glycol (PEG) with a molecular weight of 20,000 was anaerobically degraded in enrichment cultures inoculated with mud of limnic and marine origins. Three strains (Gra PEG 1, Gra PEG 2, and Ko PEG 2) of rod-shaped, gram-negative, nonsporeforming, strictly anaerobic bacteria were isolated in mineral medium with PEG as the sole source of carbon and energy. All strains degraded dimers, oligomers, and polymers of PEG up to a molecular weight of 20,000 completely by fermentation to nearly equal amounts of acetate and ethanol. The monomer ethylene glycol was not degraded. An ethylene glycol-fermenting anaerobe (strain Gra EG 12) isolated from the same enrichments was identified as Acetobacterium woodii. The PEG-fermenting strains did not excrete extracellular depolymerizing enzymes and were inhibited by ethylene glycol, probably owing to a blocking of the cellular uptake system. PEG, some PEG-containing nonionic detergents, 1,2-propanediol, 1,2-butanediol, glycerol, and acetoin were the only growth substrates utilized of a broad variety of sugars, organic acids, and alcohols. The isolates did not reduce sulfate, sulfur, thiosulfate, or nitrate and were independent of growth factors. In coculture with A. woodii or Methanospirillum hungatei, PEGs and ethanol were completely fermented to acetate (and methane). A marine isolate is described as the type strain of a new species, Pelobacter venetianus sp. nov. Its physiology and ecological significance, as well as the importance and possible mechanism of anaerobic polyether degradation, are discussed.

  18. The Circadian Clock-controlled Transcriptome of Developing Soybean Seeds

    Directory of Open Access Journals (Sweden)

    Karen A. Hudson

    2010-07-01

    Full Text Available A number of metabolic and physiological processes in plants are controlled by the circadian clock, which enables a plant to anticipate daily changes in the environment. Relatively little is known about circadian rhythms in developing seeds, which may be important for determining the extent and timing of nutrient storage in grain. Microarray expression profiling was used to identify genes expressed in developing soybean ( seeds that are controlled by the circadian clock. Genes with predicted functions in protein synthesis, fatty acid metabolism, and photosynthesis totaling 1.8% of the mRNAs detected in seed were found to be expressed in a circadian rhythm. Known circadian and light-controlled promoter elements were identified as over-represented in the promoters of clock-controlled seed genes, with the over-represented elements varying according to the phase of circadian expression. A subset of circadian-regulated genes were found to be expressed in different phases in developing seeds with respect to leaves from the same plants, many of which have roles in photosynthesis and carbon metabolism. These results help to characterize the genes and processes in seeds that may be regulated by the circadian clock, and provide some insight into organ-specific phasing of clock controlled gene expression.

  19. A high-precision synchronization circuit for clock distribution

    International Nuclear Information System (INIS)

    Lu Chong; Tan Hongzhou; Duan Zhikui; Ding Yi

    2015-01-01

    In this paper, a novel structure of a high-precision synchronization circuit, HPSC, using interleaved delay units and a dynamic compensation circuit is proposed. HPSCs are designed for synchronization of clock distribution networks in large-scale integrated circuits, where high-quality clocks are required. The application of a hybrid structure of a coarse delay line and dynamic compensation circuit performs roughly the alignment of the clock signal in two clock cycles, and finishes the fine tuning in the next three clock cycles with the phase error suppressed under 3.8 ps. The proposed circuit is implemented and fabricated using a SMIC 0.13 μm 1P6M process with a supply voltage at 1.2 V. The allowed operation frequency ranges from 200 to 800 MHz, and the duty cycle ranges between [20%, 80%]. The active area of the core circuits is 245 × 134 μm 2 , and the power consumption is 1.64 mW at 500 MHz. (paper)

  20. Data and clock transmission interface for the WCDA in LHAASO

    International Nuclear Information System (INIS)

    Chu, S.P.; Zhao, L.; Jiang, Z.Y.; Ma, C.; Gao, X.S.; Yang, Y.F.; Liu, S.B.; An, Q.

    2016-01-01

    The Water Cherenkov Detector Array (WCDA) is one of the major components of the Large High Altitude Air Shower Observatory (LHAASO). In the WCDA, 3600 Photomultiplier Tubes (PMTs) and the Front End Electronics (FEEs) are scattered over a 90000 m 2 area, while high precision time measurements (0.5 ns RMS) are required in the readout electronics. To meet this requirement, the clock has to be distributed to the FEEs with high precision. Due to the ''triggerless'' architecture, high speed data transfer is required based on the TCP/IP protocol. To simplify the readout electronics architecture and be consistent with the whole LHAASO readout electronics, the White Rabbit (WR) switches are used to transfer clock, data, and commands via a single fiber of about 400 meters. In this paper, a prototype of data and clock transmission interface for LHAASO WCDA is developed. The performance tests are conducted and the results indicate that the clock synchronization precision of the data and clock transmission is better than 50 ps. The data transmission throughput can reach 400 Mbps for one FEE board and 180 Mbps for 4 FEE boards sharing one up link port in WR switch, which is better than the requirement of the LHAASO WCDA.

  1. Protecting Clock Synchronization: Adversary Detection through Network Monitoring

    Directory of Open Access Journals (Sweden)

    Elena Lisova

    2016-01-01

    Full Text Available Nowadays, industrial networks are often used for safety-critical applications with real-time requirements. Such applications usually have a time-triggered nature with message scheduling as a core property. Scheduling requires nodes to share the same notion of time, that is, to be synchronized. Therefore, clock synchronization is a fundamental asset in real-time networks. However, since typical standards for clock synchronization, for example, IEEE 1588, do not provide the required level of security, it raises the question of clock synchronization protection. In this paper, we identify a way to break synchronization based on the IEEE 1588 standard, by conducting a man-in-the-middle (MIM attack followed by a delay attack. A MIM attack can be accomplished through, for example, Address Resolution Protocol (ARP poisoning. Using the AVISPA tool, we evaluate the potential to perform a delay attack using ARP poisoning and analyze its consequences showing both that the attack can, indeed, break clock synchronization and that some design choices, such as a relaxed synchronization condition mode, delay bounding, and using knowledge of environmental conditions, can make the network more robust/resilient against these kinds of attacks. Lastly, a Configuration Agent is proposed to monitor and detect anomalies introduced by an adversary performing attacks targeting clock synchronization.

  2. Including autapomorphies is important for paleontological tip-dating with clocklike data, but not with non-clock data.

    Science.gov (United States)

    Matzke, Nicholas J; Irmis, Randall B

    2018-01-01

    Tip-dating, where fossils are included as dated terminal taxa in Bayesian dating inference, is an increasingly popular method. Data for these studies often come from morphological character matrices originally developed for non-dated, and usually parsimony, analyses. In parsimony, only shared derived characters (synapomorphies) provide grouping information, so many character matrices have an ascertainment bias: they omit autapomorphies (unique derived character states), which are considered uninformative. There has been no study of the effect of this ascertainment bias in tip-dating, but autapomorphies can be informative in model-based inference. We expected that excluding autapomorphies would shorten the morphological branchlengths of terminal branches, and thus bias downwards the time branchlengths inferred in tip-dating. We tested for this effect using a matrix for Carboniferous-Permian eureptiles where all autapomorphies had been deliberately coded. Surprisingly, date estimates are virtually unchanged when autapomorphies are excluded, although we find large changes in morphological rate estimates and small effects on topological and dating confidence. We hypothesized that the puzzling lack of effect on dating was caused by the non-clock nature of the eureptile data. We confirm this explanation by simulating strict clock and non-clock datasets, showing that autapomorphy exclusion biases dating only for the clocklike case. A theoretical solution to ascertainment bias is computing the ascertainment bias correction (M k parsinf ), but we explore this correction in detail, and show that it is computationally impractical for typical datasets with many character states and taxa. Therefore we recommend that palaeontologists collect autapomorphies whenever possible when assembling character matrices.

  3. Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis.

    Science.gov (United States)

    Traynard, Pauline; Feillet, Céline; Soliman, Sylvain; Delaunay, Franck; Fages, François

    2016-11-01

    Experimental observations have put in evidence autonomous self-sustained circadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell cycle when the culture medium is enriched with growth factors, and the absence of such acceleration in confluent cells. In order to explain these observations, we study a possible entrainment of the circadian clock by the cell cycle through a regulation of clock genes around the mitosis phase. We develop a computational model and a formal specification of the observed behavior to investigate the conditions of entrainment in period and phase. We show that either the selective activation of RevErb-α or the selective inhibition of Bmal1 transcription during the mitosis phase, allow us to fit the experimental data on both period and phase, while a uniform inhibition of transcription during mitosis seems incompatible with the phase data. We conclude on the arguments favoring the RevErb-α up-regulation hypothesis and on some further predictions of the model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Fault-tolerant clock synchronization validation methodology. [in computer systems

    Science.gov (United States)

    Butler, Ricky W.; Palumbo, Daniel L.; Johnson, Sally C.

    1987-01-01

    A validation method for the synchronization subsystem of a fault-tolerant computer system is presented. The high reliability requirement of flight-crucial systems precludes the use of most traditional validation methods. The method presented utilizes formal design proof to uncover design and coding errors and experimentation to validate the assumptions of the design proof. The experimental method is described and illustrated by validating the clock synchronization system of the Software Implemented Fault Tolerance computer. The design proof of the algorithm includes a theorem that defines the maximum skew between any two nonfaulty clocks in the system in terms of specific system parameters. Most of these parameters are deterministic. One crucial parameter is the upper bound on the clock read error, which is stochastic. The probability that this upper bound is exceeded is calculated from data obtained by the measurement of system parameters. This probability is then included in a detailed reliability analysis of the system.

  5. Performance of a 229Thorium solid-state nuclear clock

    International Nuclear Information System (INIS)

    Kazakov, G A; Schreitl, M; Winkler, G; Schumm, T; Litvinov, A N; Romanenko, V I; Yatsenko, L P; Romanenko, A V

    2012-01-01

    The 7.8 eV nuclear isomer transition in 229 thorium has been suggested as a clock transition in a new type of optical frequency standard. Here we discuss the construction of a ‘solid-state nuclear clock’ from thorium nuclei implanted into single crystals transparent in the vacuum ultraviolet range. We investigate crystal-induced line shifts and broadening effects for the specific system of calcium fluoride. At liquid nitrogen temperatures, the clock performance will be limited by decoherence due to magnetic coupling of the thorium nuclei to neighboring nuclear moments, ruling out the commonly used Rabi or Ramsey interrogation schemes. We propose clock stabilization based on a fluorescence spectroscopy method and present optimized operation parameters. Taking advantage of the large number of quantum oscillators under continuous interrogation, a fractional instability level of 10 −19 might be reached within the solid-state approach. (paper)

  6. The expression of the clock gene cycle has rhythmic pattern and is affected by photoperiod in the moth Sesamia nonagrioides.

    Science.gov (United States)

    Kontogiannatos, Dimitrios; Gkouvitsas, Theodoros; Kourti, Anna

    2017-06-01

    To obtain clues to the link between the molecular mechanism of circadian and photoperiod clocks, we have cloned the circadian clock gene cycle (Sncyc) in the corn stalk borer, Sesamia nonagrioides, which undergoes facultative diapause controlled by photoperiod. Sequence analysis revealed a high degree of conservation among insects for this gene. SnCYC consists of 667 amino acids and structural analysis showed that it contains a BCTR domain in its C-terminal in addition to the common domains found in Drosophila CYC, i.e. bHLH, PAS-A, PAS-B domains. The results revealed that the sequence of Sncyc showed a similarity to that of its mammalian orthologue, Bmal1. We also investigated the expression patterns of Sncyc in the brain of larvae growing under long-day 16L: 8D (LD), constant darkness (DD) and short-day 10L: 14D (SD) conditions using qRT-PCR assays. The mRNAs of Sncyc expression was rhythmic in LD, DD and SD cycles. Also, it is remarkable that the photoperiodic conditions affect the expression patterns and/or amplitudes of circadian clock gene Sncyc. This gene is associated with diapause in S. nonagrioides, because under SD (diapause conditions) the photoperiodic signal altered mRNA accumulation. Sequence and expression analysis of cyc in S. nonagrioides shows interesting differences compared to Drosophila where this gene does not oscillate or change in expression patterns in response to photoperiod, suggesting that this species is an interesting new model to study the molecular control of insect circadian and photoperiodic clocks. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Complementary approaches to understanding the plant circadian clock

    Directory of Open Access Journals (Sweden)

    Ozgur E. Akman

    2010-02-01

    Full Text Available 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 dawn and dusk in the context of model-checking, which we use to compute how the probability distributions of key biochemical species change over time. These show that the relative variation in expression level is smallest at the time of peak expression, making peak time an optimal experimental phase marker. Building on these analyses, we use approaches from evolutionary systems biology to investigate how changes in the rate of mRNA degradation impacts the phase of a key protein likely to affect fitness. We explore how robust this circadian clock is towards such potential mutational changes in its underlying biochemistry. Our work shows that multiple approaches lead to a more complete understanding of the clock.

  8. [Elevated expression of CLOCK is associated with poor prognosis in hepatocellular carcinoma].

    Science.gov (United States)

    Li, Bo; Yang, Xiliang; Li, Jiaqi; Yang, Yi; Yan, Zhaoyong; Zhang, Hongxin; Mu, Jiao

    2018-02-01

    Objective To evaluate the expression of circadian locomotor output cycles kaput (CLOCK) and its effects on cell growth in hepatocellular carcinoma (HCC). Methods The expression of CLOCK in 158 pairs of human HCC tissues and matched noncancerous samples was detected by immunohistochemical (IHC) staining. The expression of CLOCK in HCC patients was also verified using the data from GEO and TCGA (a total of 356 cases). The relationship between CLOCK expression and clinicopathological features of HCC patients was analyzed by single factor statistical analysis. Kaplan-Meier survival curves of HCC patients were drawn to study the relationship between the expression level of CLOCK and the survival state. The effect of CLOCK on the growth of HepG2 cells was detected by MTS assay. Results The expression of CLOCK in HCC tissues was significantly higher than that in the adjacent tissues, and the up-regulation of CLOCK expression in HCC tissue was also confirmed in the public data of HCC (356 cases). HCC patients were divided into low CLOCK expression group and high CLOCK expression group. Univariate analysis showed that the expression of CLOCK was related to tumor size, TNM stage, and portal vein invasion in HCC patients. HCC patients with low CLOCK expression had longer overall survival time and relapse-free survival time than those with high CLOCK expression. The proliferation of cells significantly decreased after the expression of CLOCK was knocked down in HepG2 cells. Conclusion The expression of CLOCK in HCC tissues was much higher than that in normal liver tissues, and the high expression of CLOCK indicated the poor prognosis. The knockdown of CLOCK in HCC cells could inhibit the proliferation of HepG2 cells.

  9. Detecting a Multi-Homed Device Using Clock Skew

    Science.gov (United States)

    2016-09-01

    15]. The TCP timestamp value is determined by a virtual “timestamp clock” that is based on the frequency of operation of the device’s system clock...received [16]. Figure 8. TCP Timestamp Options Field. Source: [16]. The value of the timestamp comes from a virtual internal clock that is known as...Testing 18 One of the Raspberry Pis had an added USB 2.0 Gigabit LAN adapter that was used as its second connection to the network. The connections for

  10. Blackbody radiation shift of the Ga+ clock transition

    International Nuclear Information System (INIS)

    Cheng, Yongjun; Mitroy, J

    2013-01-01

    The blackbody radiation shift of the Ga + clock transition is computed to be −0.0140 ± 0.0062 Hz at 300 K. The small shift is consistent with the blackbody radiation shifts of the clock transitions of other group III ions which are of a similar size. The polarizabilities of the Ga + states were computed using the configuration interaction method with an underlying semi-empirical core potential. Quadrupole and non-adiabatic dipole polarizabilities were also computed. A byproduct of the analysis involved calculations of the low-lying spectrum and oscillator strengths, including polarizabilities, of the Ga 2+ ion. (paper)

  11. Recent results of the pulsed optically pumped rubidium clock

    Science.gov (United States)

    Levi, F.; Micalizio, S.; Godone, A.; Calosso, C.; Bertacco, E.

    2017-11-01

    A laboratory prototype of a pulsed optically pumped (POP) clock based on a rubidium cell with buffer gas is described. This clock has shown very interesting physical and metrological features, such as negligible light-shift, strongly reduced cavity-pulling and very good frequency stability. In this regard, an Allan deviation of σy(τ) = 1.2 τ-1/2 for measurement times up to τ = 105 s has been measured. These results confirm the interesting perspectives of such a frequency standard and make it very attractive for several technological applications, such as radionavigation.

  12. Fault-tolerant clock synchronization in distributed systems

    Science.gov (United States)

    Ramanathan, Parameswaran; Shin, Kang G.; Butler, Ricky W.

    1990-01-01

    Existing fault-tolerant clock synchronization algorithms are compared and contrasted. These include the following: software synchronization algorithms, such as convergence-averaging, convergence-nonaveraging, and consistency algorithms, as well as probabilistic synchronization; hardware synchronization algorithms; and hybrid synchronization. The worst-case clock skews guaranteed by representative algorithms are compared, along with other important aspects such as time, message, and cost overhead imposed by the algorithms. More recent developments such as hardware-assisted software synchronization and algorithms for synchronizing large, partially connected distributed systems are especially emphasized.

  13. Reference clock parameters for digital communications systems applications

    Science.gov (United States)

    Kartaschoff, P.

    1981-01-01

    The basic parameters relevant to the design of network timing systems describe the random and systematic time departures of the system elements, i.e., master (or reference) clocks, transmission links, and other clocks controlled over the links. The quantitative relations between these parameters were established and illustrated by means of numerical examples based on available measured data. The examples were limited to a simple PLL control system but the analysis can eventually be applied to more sophisticated systems at the cost of increased computational effort.

  14. The Effects of Race Conditions When Implementing Single-Source Redundant Clock Trees in Triple Modular Redundant Synchronous Architectures

    Science.gov (United States)

    Berg, Melanie D.; Kim, Hak S.; Phan, Anthony M.; Seidleck, Christina M.; Label, Kenneth A.; Pellish, Jonathan A.; Campola, Michael J.

    2016-01-01

    We present the challenges that arise when using redundant clock domains due to their time-skew. Radiation data show that a singular clock domain provides an improved triple modular redundant (TMR) scheme over redundant clocks.

  15. Animal clocks: when science meets nature

    OpenAIRE

    Kronfeld-Schor, Noga; Bloch, Guy; Schwartz, William J.

    2013-01-01

    Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian ‘clock’), with the alternation of environmental light and darkness synchronizing (entraining) these rhythms to the natural day–night cycle. Our knowledge of the circadian system of animals at the molecular, cellular, tissue and organismal levels is remarkable, and we are beginning to understand how each of these levels contributes to the emergent properties and increased complexity of th...

  16. A Hybrid P2P Overlay Network for Non-strictly Hierarchically Categorized Content

    Science.gov (United States)

    Wan, Yi; Asaka, Takuya; Takahashi, Tatsuro

    In P2P content distribution systems, there are many cases in which the content can be classified into hierarchically organized categories. In this paper, we propose a hybrid overlay network design suitable for such content called Pastry/NSHCC (Pastry for Non-Strictly Hierarchically Categorized Content). The semantic information of classification hierarchies of the content can be utilized regardless of whether they are in a strict tree structure or not. By doing so, the search scope can be restrained to any granularity, and the number of query messages also decreases while maintaining keyword searching availability. Through simulation, we showed that the proposed method provides better performance and lower overhead than unstructured overlays exploiting the same semantic information.

  17. Detection of low numbers of microplastics in North Sea fish using strict quality assurance criteria.

    Science.gov (United States)

    Hermsen, Enya; Pompe, Renske; Besseling, Ellen; Koelmans, Albert A

    2017-09-15

    We investigated 400 individual fish of four North Sea species: Atlantic Herring, Sprat, Common Dab, and Whiting on ingestion of >20μm microplastic. Strict quality assurance criteria were followed in order to control contamination during the study. Two plastic particles were found in only 1 (a Sprat) out of 400 individuals (0.25%, with a 95% confidence interval of 0.09-1.1%). The particles were identified to consist of polymethylmethacrylate (PMMA) through FTIR spectroscopy. No contamination occurred during the study, showing the method applied to be suitable for microplastic ingestion studies in biota. We discuss the low particle count for North Sea fish with those in other studies and suggest a relation between reported particle count and degree of quality assurance applied. Microplastic ingestion by fish may be less common than thought initially, with low incidence shown in this study, and other studies adhering to strict quality assurance criteria. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. S2SA preconditioning for the Sn equations with strictly non negative spatial discretization

    International Nuclear Information System (INIS)

    Bruss, D. E.; Morel, J. E.; Ragusa, J. C.

    2013-01-01

    Preconditioners based upon sweeps and diffusion-synthetic acceleration have been constructed and applied to the zeroth and first spatial moments of the 1-D S n transport equation using a strictly non negative nonlinear spatial closure. Linear and nonlinear preconditioners have been analyzed. The effectiveness of various combinations of these preconditioners are compared. In one dimension, nonlinear sweep preconditioning is shown to be superior to linear sweep preconditioning, and DSA preconditioning using nonlinear sweeps in conjunction with a linear diffusion equation is found to be essentially equivalent to nonlinear sweeps in conjunction with a nonlinear diffusion equation. The ability to use a linear diffusion equation has important implications for preconditioning the S n equations with a strictly non negative spatial discretization in multiple dimensions. (authors)

  19. A strict anaerobic extreme thermophilic hydrogen-producing culture enriched from digested household waste

    DEFF Research Database (Denmark)

    Karakashev, Dimitar Borisov; Kotay, Shireen Meher; Trably, Eric

    2009-01-01

    The aim of this study was to enrich, characterize and identify strict anaerobic extreme thermophilic hydrogen (H-2) producers from digested household solid wastes. A strict anaerobic extreme thermophilic H-2 producing bacterial culture was enriched from a lab-scale digester treating household...... wastes at 70 degrees C. The enriched mixed culture consisted of two rod-shaped bacterial members growing at an optimal temperature of 80 degrees C and an optimal pH 8.1. The culture was able to utilize glucose, galactose, mannose, xylose, arabinose, maltose, sucrose, pyruvate and glycerol as carbon...... sources. Growth on glucose produced acetate, H-2 and carbon dioxide. Maximal H-2 production rate on glucose was 1.1 mmol l(-1) h(-1) with a maximum H-2 yield of 1.9 mole H-2 per mole glucose. 16S ribosomal DNA clone library analyses showed that the culture members were phylogenetically affiliated...

  20. Weak asymptotic solution for a non-strictly hyperbolic system of conservation laws-II

    Directory of Open Access Journals (Sweden)

    Manas Ranjan Sahoo

    2016-04-01

    Full Text Available In this article we introduce a concept of entropy weak asymptotic solution for a system of conservation laws and construct the same for a prolonged system of conservation laws which is highly non-strictly hyperbolic. This is first done for Riemann type initial data by introducing $\\delta,\\delta',\\delta''$ waves along a discontinuity curve and then for general initial data by piecing together the Riemann solutions.

  1. The conditions for attaining the greatest degree of system stability with strict generator excitation control

    Energy Technology Data Exchange (ETDEWEB)

    Gruzdev, I.A.; Ekimova, M.M.; Truspekova, G.A.

    1982-01-01

    Expressions are derived for an idealized model of a complex electric power system; these expressions define the greatest level of stability of an electric power system and the optimum combination of stabilization factors with automatic excitation control in a single power system. The possibility of increasing the level of stability of an electric power system with simultaneous strict automatic excitation control of the synychronous generators in several power systems is analyzed.

  2. Oscillating perceptions: the ups and downs of the CLOCK protein in ...

    Indian Academy of Sciences (India)

    2008-12-31

    Dec 31, 2008 ... A functional mouse CLOCK protein has long been thought to be essential for mammalian circadian ... ordinated actions of the Ror families of transcriptional acti- ..... CLOCK-deficient mice expressing the mPER2::LUC fusion.

  3. The development of the time-keeping clock with TS-1 single chip microcomputer.

    Science.gov (United States)

    Zhou, Jiguang; Li, Yongan

    The authors have developed a time-keeping clock with Intel 8751 single chip microcomputer that has been successfully used in time-keeping station. The hard-soft ware design and performance of the clock are introduced.

  4. Performance Evaluation of Clock Recovery for Coherent Mode Division Multiplexed Systems

    DEFF Research Database (Denmark)

    Medeiros Diniz, Júlio César; Piels, Molly; Zibar, Darko

    2017-01-01

    The impact of mode mixing and group delay spread on clock tone quality of a 6-mode 32 GBd NRZ-QPSK MDM system is investigated. Even for low group delay spread, strong coupling causes clock tone disappearance....

  5. The mammalian circadian clock and its entrainment by stress and exercise.

    Science.gov (United States)

    Tahara, Yu; Aoyama, Shinya; Shibata, Shigenobu

    2017-01-01

    The mammalian circadian clock regulates day-night fluctuations in various physiological processes. The circadian clock consists of the central clock in the suprachiasmatic nucleus of the hypothalamus and peripheral clocks in peripheral tissues. External environmental cues, including light/dark cycles, food intake, stress, and exercise, provide important information for adjusting clock phases. This review focuses on stress and exercise as potent entrainment signals for both central and peripheral clocks, especially in regard to the timing of stimuli, types of stressors/exercises, and differences in the responses of rodents and humans. We suggest that the common signaling pathways of clock entrainment by stress and exercise involve sympathetic nervous activation and glucocorticoid release. Furthermore, we demonstrate that physiological responses to stress and exercise depend on time of day. Therefore, using exercise to maintain the circadian clock at an appropriate phase and amplitude might be effective for preventing obesity, diabetes, and cardiovascular disease.

  6. Turning Back the Clock: Inferring the History of the Eight O'clock Arc

    Science.gov (United States)

    Finkelstein, Steven L.; Papovich, Casey; Rudnick, Gregory; Egami, Eiichi; Le Floc'h, Emeric; Rieke, Marcia J.; Rigby, Jane R.; Willmer, Christopher N. A.

    2009-07-01

    We present the results from an optical and near-infrared (NIR) spectroscopic study of the ultraviolet-luminous z = 2.73 galaxy, the 8 o'clock arc. Due to gravitational lensing, this galaxy is magnified by a factor of μ > 10, allowing in-depth measurements which are usually unfeasible at such redshifts. In the optical spectra, we measured the systemic redshift of the galaxy, z = 2.7322± 0.0012, using stellar photospheric lines. This differs from the redshift of absorption lines in the interstellar medium, z = 2.7302 ± 0.0006, implying gas outflows on the order of 160 km s-1. With H- and K-band NIR spectra, we have measured nebular emission lines of Hα, Hβ, Hγ, [N II], and [O III], which have a redshift z = 2.7333 ± 0.0001, consistent with the derived systemic redshift. From the Balmer decrement, we measured the dust extinction in this galaxy to be A 5500 = 1.17 ± 36 mag. Correcting the Hα line flux for dust extinction as well as the assumed lensing factor, we measure a star formation rate (SFR) of ~270 M sun yr-1, which is higher than ~85% of star-forming galaxies at z ~ 2-3. Using combinations of all detected emission lines, we find that the 8 o'clock arc has a gas-phase metallicity of ~0.8 Z sun, showing that enrichment at high redshift is not rare, even in blue, star-forming galaxies. Studying spectra from two of the arc components separately, we find that one component dominates both the dust extinction and SFR, although the metallicities between the two components are similar. We derive the mass via stellar population modeling, and find that the arc has a total stellar mass of ~4.2 × 1011 M sun, which falls on the mass-metallicity relation at z ~ 2. Finally, we estimate the total gas mass, and find it to be only ~12% of the stellar mass, implying that the 8 o'clock arc is likely nearing the end of a starburst. Based partly on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy

  7. Frequency effect on p-nitrophenol degradation under conditions of strict acoustic and electric control

    Directory of Open Access Journals (Sweden)

    Chang-ping Zhu

    2011-03-01

    Full Text Available The process of decomposing p-nitrophenol (PNP with power ultrasound requires strict control of acoustic and electric conditions. In this study, the conditions, including acoustic power and acoustic intensity, but not ultrasonic frequency, were controlled strictly at constant levels. The absorbency and the COD concentrations of the samples were measured in order to show the variation of the sample concentration. The results show significant differences in the trend of the solution degradation rate as acoustic power increases after the PNP solution (with a concentration of 114 mg/L and a pH value of 5.4 is irradiated for 60 min with ultrasonic frequencies of 530.8 kHz, 610.6 kHz, 855.0 kHz, and 1 130.0 kHz. The degradation rate of the solution increases with time and acoustic power (acoustic intensity. On the other hand, the degradation rate of the solution is distinctly dependent on frequency when the acoustic power and intensity are strictly controlled and maintained at constant levels. The degradation rate of the PNP solution declines with ultrasonic frequencies of 530.8 kHz, 610.6 kHz, 855.0 kHz, and 1 130.0 kHz; the COD concentration, on the contrary, increase.

  8. Examination of the PCICE method in the nearly incompressible, as well as strictly incompressible, limits

    International Nuclear Information System (INIS)

    Berry, Ray A.; Martineau, Richard C.

    2007-01-01

    The conservative-form, pressure-based PCICE numerical method (Martineau and Berry, 2004) (Berry, 2006), recently developed for computing transient fluid flows of all speeds from very low to very high (with strong shocks), is simplified and generalized. Though the method automatically treats a continuous transition of compressibility, three distinct, limiting compressibility regimes are formally defined for purposes of discussion and comparison with traditional methods - the strictly incompressible limit, the nearly incompressible limit, and the fully compressible limit. The PCICE method's behavior is examined in each limiting regime. In the strictly incompressible limit the PCICE algorithm reduces to the traditional MAC-type method with velocity divergence driving the pressure Poisson equation. In the nearly incompressible limit the PCICE algorithm is found to reduce to a generalization of traditional incompressible methods, i.e. to one in which not only the velocity divergence effect, but also the density gradient effect is included as a driving function in the pressure Poisson equation. This nearly incompressible regime has received little attention, and it appears that in the past, strictly incompressible methods may have been conveniently applied to flows in this regime at the expense of ignoring a potentially important coupling mechanism. This could be significant in many important flows; for example, in natural convection flows resulting from high heat flux. In the fully compressible limit or regime, the algorithm is found to reduce to an expression equivalent to density-based methods for high-speed flow. (author)

  9. TESTING STRICT HYDROSTATIC EQUILIBRIUM IN SIMULATED CLUSTERS OF GALAXIES: IMPLICATIONS FOR A1689

    International Nuclear Information System (INIS)

    Molnar, S. M.; Umetsu, K.; Chiu, I.-N.; Chen, P.; Hearn, N.; Broadhurst, T.; Bryan, G.; Shang, C.

    2010-01-01

    Accurate mass determination of clusters of galaxies is crucial if they are to be used as cosmological probes. However, there are some discrepancies between cluster masses determined based on gravitational lensing and X-ray observations assuming strict hydrostatic equilibrium (i.e., the equilibrium gas pressure is provided entirely by thermal pressure). Cosmological simulations suggest that turbulent gas motions remaining from hierarchical structure formation may provide a significant contribution to the equilibrium pressure in clusters. We analyze a sample of massive clusters of galaxies drawn from high-resolution cosmological simulations and find a significant contribution (20%-45%) from non-thermal pressure near the center of relaxed clusters, and, in accord with previous studies, a minimum contribution at about 0.1 R vir , growing to about 30%-45% at the virial radius, R vir . Our results strongly suggest that relaxed clusters should have significant non-thermal support in their core region. As an example, we test the validity of strict hydrostatic equilibrium in the well-studied massive galaxy cluster A1689 using the latest high-resolution gravitational lensing and X-ray observations. We find a contribution of about 40% from non-thermal pressure within the core region of A1689, suggesting an alternate explanation for the mass discrepancy: the strict hydrostatic equilibrium is not valid in this region.

  10. Loss of the clock protein PER2 shortens the erythrocyte life span in mice.

    Science.gov (United States)

    Sun, Qi; Zhao, Yue; Yang, Yunxia; Yang, Xiao; Li, Minghui; Xu, Xi; Wen, Dan; Wang, Junsong; Zhang, Jianfa

    2017-07-28

    Cell proliferation and release from the bone marrow have been demonstrated to be controlled by circadian rhythms in both humans and mice. However, it is unclear whether local circadian clocks in the bone marrow influence physiological functions and life span of erythrocytes. Here, we report that loss of the clock gene Per2 significantly decreased erythrocyte life span. Mice deficient in Per2 were more susceptible to acute stresses in the erythrocytes, becoming severely anemic upon phenylhydrazine, osmotic, and H 2 O 2 challenges. 1 H NMR-based metabolomics analysis revealed that the Per2 depletion causes significant changes in metabolic profiles of erythrocytes, including increased lactate and decreased ATP levels compared with wild-type mice. The lower ATP levels were associated with hyperfunction of Na + /K + -ATPase activity in Per2 -null erythrocytes, and inhibition of Na + /K + -ATPase activity by ouabain efficiently rescued ATP levels. Per2 -null mice displayed increased levels of Na + /K + -ATPase α1 (ATP1A1) in the erythrocyte membrane, and transfection of Per2 cDNA into the erythroleukemic cell line TF-1 inhibited Atp1a1 expression. Furthermore, we observed that PER2 regulates Atp1a1 transcription through interacting with trans-acting transcription factor 1 (SP1). Our findings reveal that Per2 function in the bone marrow is required for the regulation of life span in circulating erythrocytes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. KPNB1 mediates PER/CRY nuclear translocation and circadian clock function.

    Science.gov (United States)

    Lee, Yool; Jang, A Reum; Francey, Lauren J; Sehgal, Amita; Hogenesch, John B

    2015-08-29

    Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals. However, the precise molecular mechanism is not fully understood. Here, we report that KPNB1, an importin β component of the ncRNA repressor of nuclear factor of activated T cells (NRON) ribonucleoprotein complex, mediates nuclear translocation and repressor function of the PER/CRY complex. RNAi depletion of KPNB1 traps the PER/CRY complex in the cytoplasm by blocking nuclear entry of PER proteins in human cells. KPNB1 interacts mainly with PER proteins and directs PER/CRY nuclear transport in a circadian fashion. Interestingly, KPNB1 regulates the PER/CRY nuclear entry and repressor function, independently of importin α, its classical partner. Moreover, inducible inhibition of the conserved Drosophila importin β in lateral neurons abolishes behavioral rhythms in flies. Collectively, these data show that KPNB1 is required for timely nuclear import of PER/CRY in the negative feedback regulation of the circadian clock.

  12. Drosophila: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse

    Directory of Open Access Journals (Sweden)

    Aliza K. De Nobrega

    2017-01-01

    Full Text Available Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such as Drosophila melanogaster, have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions of Drosophila as a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions between Drosophila and mammalian systems. Research in Drosophila provides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals.

  13. Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells

    International Nuclear Information System (INIS)

    Shimizu, Takashi; Hirai, Yuko; Murayama, Chiaki; Miyamoto, Akio; Miyazaki, Hitoshi; Miyazaki, Koyomi

    2011-01-01

    Highlights: → Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression. →Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom. → Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. →Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. → The expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. -- Abstract: Circadian Clock genes are associated with the estrous cycle in female animals. Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression in follicle-stimulating hormone FSH-treated granulosa cells. Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom, whereas Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. Similarly, expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. Our data provide a new insight that Per2 and Clock have different action on ovarian granulosa cell functions.

  14. Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Takashi, E-mail: shimizut@obihiro.ac.jp [Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan); Hirai, Yuko; Murayama, Chiaki; Miyamoto, Akio [Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan); Miyazaki, Hitoshi [Gene Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8572 (Japan); Miyazaki, Koyomi [Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566 (Japan)

    2011-08-19

    Highlights: {yields} Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression. {yields}Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom. {yields} Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. {yields}Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. {yields} The expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. -- Abstract: Circadian Clock genes are associated with the estrous cycle in female animals. Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression in follicle-stimulating hormone FSH-treated granulosa cells. Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom, whereas Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. Similarly, expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. Our data provide a new insight that Per2 and Clock have different action on ovarian granulosa cell functions.

  15. Mining for novel candidate clock genes in the circadian regulatory network

    OpenAIRE

    Bhargava, Anuprabha; Herzel, Hanspeter; Ananthasubramaniam, Bharath

    2015-01-01

    Background Most physiological processes in mammals are temporally regulated by means of a master circadian clock in the brain and peripheral oscillators in most other tissues. A transcriptional-translation feedback network of clock genes produces near 24 h oscillations in clock gene and protein expression. Here, we aim to identify novel additions to the clock network using a meta-analysis of public chromatin immunoprecipitation sequencing (ChIP-seq), proteomics and protein-protein interaction...

  16. System and method for clock synchronization and position determination using entangled photon pairs

    Science.gov (United States)

    Shih, Yanhua (Inventor)

    2010-01-01

    A system and method for clock synchronization and position determination using entangled photon pairs is provided. The present invention relies on the measurement of the second order correlation function of entangled states. Photons from an entangled photon source travel one-way to the clocks to be synchronized. By analyzing photon registration time histories generated at each clock location, the entangled states allow for high accuracy clock synchronization as well as high accuracy position determination.

  17. All-optical clock recovery of NRZ-DPSK signals using optical resonator-type filters

    DEFF Research Database (Denmark)

    Peucheret, Christophe; Seoane, Jorge; Ji, Hua

    2009-01-01

    It is shown how introducing a limited rise time to the driving signal enables all-optical clock recovery of NRZ-DPSK signals generated using a phase modulator. A Fabry-Perot filter is used to generate the optical clock.......It is shown how introducing a limited rise time to the driving signal enables all-optical clock recovery of NRZ-DPSK signals generated using a phase modulator. A Fabry-Perot filter is used to generate the optical clock....

  18. Timing Jitter Analysis for Clock recovery Circuits Based on an Optoelectronic Phase-Locked Loop (OPLL)

    DEFF Research Database (Denmark)

    Zibar, Darko; Mørk, Jesper; Oxenløwe, Leif Katsuo

    2005-01-01

    Timing jitter of an OPLL based clock recovery is investigated. We demonstrate how loop gain, input and VCO signal jitter, loop filter bandwidth and a loop time delay influence jitter of the extracted clock signal......Timing jitter of an OPLL based clock recovery is investigated. We demonstrate how loop gain, input and VCO signal jitter, loop filter bandwidth and a loop time delay influence jitter of the extracted clock signal...

  19. Chaotic map based key agreement with/out clock synchronization

    International Nuclear Information System (INIS)

    Han, S.; Chang, E.

    2009-01-01

    In order to address Bergamo et al.'s attack, Xiao et al. proposed a key agreement protocol using chaotic maps. Han then presented three attacks on Xiao et al.'s protocol. To enhance the security of key agreement based on chaotic maps, Chang et al. proposed a new key agreement using passphrase, which works in clock synchronization environment. However, their protocol still has some issues: one is its passphrase is not easy to remember and much longer than password; the second one is it cannot resist guessing attack if the constructed passphrase is easy to remember and also has already existed in some rational dictionaries; the third one is it cannot work without clock synchronization. In this paper, we will present two different key agreement protocols, which can resist guessing attack. The first one works in clock synchronization environment. The second one can work without clock synchronization. They both use authenticated password for secure communications. The protocols are secure against replaying attacks and a shared session key can be established.

  20. The hypothalamic clock and its control of glucose homeostasis

    NARCIS (Netherlands)

    Kalsbeek, Andries; Yi, Chun-Xia; la Fleur, Susanne E.; Fliers, Eric

    2010-01-01

    The everyday life of mammals, including humans, exhibits many behavioral, physiological and endocrine oscillations. The major timekeeping mechanism for these rhythms is contained in the central nervous system (CNS). The output of the CNS clock not only controls daily rhythms in sleep/wake (or

  1. Clock ambiguity and the emergence of physical laws

    International Nuclear Information System (INIS)

    Albrecht, Andreas; Iglesias, Alberto

    2008-01-01

    The process of identifying a time variable in time-reparameterization invariant theories results in great ambiguities about the actual laws of physics described by a given theory. A theory set up to describe one set of physical laws can equally well be interpreted as describing any other laws of physics by making a different choice of time variable or clock. In this article we demonstrate how this 'clock ambiguity' arises and then discuss how one might still hope to extract specific predictions about the laws of physics even when the clock ambiguity is present. We argue that a requirement of quasiseparability should play a critical role in such an analysis. As a step in this direction, we compare the Hamiltonian of a local quantum field theory with a completely random Hamiltonian. We find that any random Hamiltonian (constructed in a sufficiently large space) can yield a 'good enough' approximation to a local field theory. Based on this result we argue that theories that suffer from the clock ambiguity may in the end provide a viable fundamental framework for physics in which locality can be seen as a strongly favored (or predicted) emergent behavior. We also speculate on how other key aspects of known physics such as gauge symmetries and Poincare invariance might be predicted to emerge in this framework.

  2. Charge domain filter operating up to 20 MHz clock frequency

    NARCIS (Netherlands)

    Gal, R.A.J.; Wallinga, Hans

    1983-01-01

    An analog sampled data low pass third order Butterworth filter has been realised in a buried channel CCD technology. This Charge Domain Filter, composed of transversal and recursive CCD filter sections, has been tested at clock frequencies up to 20 MHz.

  3. The AGS Ggamma Meter and Calibrating the Gauss Clock

    Energy Technology Data Exchange (ETDEWEB)

    Ahrens, Leif [Brookhaven National Laboratory (BNL), Upton, NY (United States). Collider-Accelerator Dept.

    2014-03-31

    During AGS Polarized Proton acceleration periods, one output from the AGS Ggamma Meter, namely the energy (or Ggamma) calculated from the magnetic field in the AGS main magnets and the beam radius- both measured in particular instant, is used to figure out the times in the AGS magnet acceleration cycle when the beam passes through a particular set of depolarizing resonances. The resonance set occur whenever a particle’s Ggamma (energy*(G/m) becomes nearly equal to n*Qx (i.e. any integer multiplied by the horizontal betatron tune). This deliverable is why the machinery is referred to as the ''Ggamma Meter'' rather than the AGS energy meter. The Ggamma Meter takes as inputs a set of measurements of frequency (F(t)), radius (r(t)), and gauss clock counts (GCC(t)). The other energy (GgammaBr) assumes the field when the gauss clock starts counting is known. The change in field to time t is given by the measured accumulated gauss clock counts multiplied by the gauss clock calibration (gauss/GCC). In order to deal with experimental data, this calibration factor gets an added ad hoc complication, namely a correction dependent on the rate of change the counting rate. The Ggamma meter takes GCC(t) and together with the past history for this cycle calculates B(t).

  4. Insight Into the Circadian Clock Within Rat Colonic Epithelial Cells

    Czech Academy of Sciences Publication Activity Database

    Sládek, Martin; Rybová, Markéta; Jindráková, Zuzana; Zemanová, Zdeňka; Polidarová, Lenka; Mrnka, Libor; O´Neill, J.; Pácha, Jiří; Sumová, Alena

    2007-01-01

    Roč. 133, č. 4 (2007), s. 1240-1249 ISSN 0016-5085 R&D Projects: GA AV ČR(CZ) IAA500110605 Institutional research plan: CEZ:AV0Z50110509 Keywords : cirkadian clock * colon * NHE3 Subject RIV: FH - Neurology Impact factor: 11.673, year: 2007

  5. No more moody mornings : Alarm clock anticipates sleepers' emotions

    NARCIS (Netherlands)

    Wensveen, S.; Overbeeke, K.; Van Kasteren, J.

    2002-01-01

    More eloquent alternatives to the harsh tones of the oldfashioned alarm-clock bells abound, including a newsreaders voice summing up last nights disasters, or a tape of your favourite early morning music. Still, getting out of bed has its difficult moments. All this could well change in the near

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

    African Journals Online (AJOL)

    Hydrogen maser frequency standards are commonly utilised in various space geodetic techniques such as Very Long Baseline Interferometry (VLBI) as local reference clocks. The Hartebeesthoek Radio Astronomy Observatory in South Africa is currently operating two maser frequency standards i.e., an EFOS28 and an ...

  7. Clock gene evolution: seasonal timing, phylogenetic signal, or functional constraint?

    Science.gov (United States)

    Krabbenhoft, Trevor J; Turner, Thomas F

    2014-01-01

    Genetic determinants of seasonal reproduction are not fully understood but may be important predictors of organism responses to climate change. We used a comparative approach to study the evolution of seasonal timing within a fish community in a natural common garden setting. We tested the hypothesis that allelic length variation in the PolyQ domain of a circadian rhythm gene, Clock1a, corresponded to interspecific differences in seasonal reproductive timing across 5 native and 1 introduced cyprinid fishes (n = 425 individuals) that co-occur in the Rio Grande, NM, USA. Most common allele lengths were longer in native species that initiated reproduction earlier (Spearman's r = -0.70, P = 0.23). Clock1a allele length exhibited strong phylogenetic signal and earlier spawners were evolutionarily derived. Aside from length variation in Clock1a, all other amino acids were identical across native species, suggesting functional constraint over evolutionary time. Interestingly, the endangered Rio Grande silvery minnow (Hybognathus amarus) exhibited less allelic variation in Clock1a and observed heterozygosity was 2- to 6-fold lower than the 5 other (nonimperiled) species. Reduced genetic variation in this functionally important gene may impede this species' capacity to respond to ongoing environmental change.

  8. Resistor Extends Life Of Battery In Clocked CMOS Circuit

    Science.gov (United States)

    Wells, George H., Jr.

    1991-01-01

    Addition of fixed resistor between battery and clocked complementary metal oxide/semiconductor (CMOS) circuit reduces current drawn from battery. Basic idea to minimize current drawn from battery by operating CMOS circuit at lowest possible current consistent with use of simple, fixed off-the-shelf components. Prolongs lives of batteries in such low-power CMOS circuits as watches and calculators.

  9. New methods to assess circadian clocks in humans

    Czech Academy of Sciences Publication Activity Database

    Nováková, Marta; Sumová, Alena

    2014-01-01

    Roč. 52, č. 5 (2014), s. 404-412 ISSN 0019-5189 R&D Projects: GA MZd(CZ) NT11474 Grant - others:Univerzita Karlova(CZ) 22810 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : circadian * clock gene * melatonin * human Subject RIV: ED - Physiology Impact factor: 0.835, year: 2014

  10. Glutamatergic clock output stimulates melatonin synthesis at night

    NARCIS (Netherlands)

    Perreau-Lenz, Stéphanie; Kalsbeek, Andries; Pévet, Paul; Buijs, Ruud M.

    2004-01-01

    The rhythm of melatonin synthesis in the rat pineal gland is under the control of the biological clock, which is located in the suprachiasmatic nucleus of the hypothalamus (SCN). Previous studies demonstrated a daytime inhibitory influence of the SCN on melatonin synthesis, by using

  11. Optimal Infinite Runs in One-Clock Priced Timed Automata

    DEFF Research Database (Denmark)

    David, Alexandre; Ejsing-Duun, Daniel; Fontani, Lisa

    We address the problem of finding an infinite run with the optimal cost-time ratio in a one-clock priced timed automaton and pro- vide an algorithmic solution. Through refinements of the quotient graph obtained by strong time-abstracting bisimulation partitioning, we con- struct a graph with time...

  12. Sampling phase lock loop (PLL) with low power clock buffer

    NARCIS (Netherlands)

    Gao, X.; Bahai, A.; Bohsali, M.; Djabbari, A.; Klumperink, Eric A.M.; Nauta, Bram; Socci, G.

    2013-01-01

    A sampling phase locked loop (PLL) circuit includes a pull-up/down buffer configured to convert an oscillator reference clock into a square wave sampling control signal input to a sampling phase detector. The buffer circuit is configured to reduce power by controlling the switching of the pull-up

  13. The AGS Ggamma Meter and Calibrating the Gauss Clock

    International Nuclear Information System (INIS)

    Ahrens, Leif

    2014-01-01

    During AGS Polarized Proton acceleration periods, one output from the AGS Ggamma Meter, namely the energy (or Ggamma) calculated from the magnetic field in the AGS main magnets and the beam radius- both measured in particular instant, is used to figure out the times in the AGS magnet acceleration cycle when the beam passes through a particular set of depolarizing resonances. The resonance set occur whenever a particle's Ggamma (energy*(G/m) becomes nearly equal to n*Qx (i.e. any integer multiplied by the horizontal betatron tune). This deliverable is why the machinery is referred to as the ''Ggamma Meter'' rather than the AGS energy meter. The Ggamma Meter takes as inputs a set of measurements of frequency (F(t)), radius (r(t)), and gauss clock counts (GCC(t)). The other energy (GgammaBr) assumes the field when the gauss clock starts counting is known. The change in field to time t is given by the measured accumulated gauss clock counts multiplied by the gauss clock calibration (gauss/GCC). In order to deal with experimental data, this calibration factor gets an added ad hoc complication, namely a correction dependent on the rate of change the counting rate. The Ggamma meter takes GCC(t) and together with the past history for this cycle calculates B(t).

  14. Self-clocked sequential circuits: - a design example | Aghdasi ...

    African Journals Online (AJOL)

    This paper uses a design methodology for the State variable toggling through data driven clocks to implement a Direct Memory Access Controller (DMAC) as a design example. The design is simulated on software and also implemented using discrete hardware components. The methodology can be extended to parallel ...

  15. Peripheral circadian clocks are diversely affected by adrenalectomy

    Czech Academy of Sciences Publication Activity Database

    Soták, Matúš; Bryndová, Jana; Ergang, Peter; Vagnerová, Karla; Kvapilová, Pavlína; Vodička, Martin; Pácha, Jiří; Sumová, Alena

    2016-01-01

    Roč. 33, č. 5 (2016), s. 520-529 ISSN 0742-0528 R&D Projects: GA ČR(CZ) GA13-08304S Institutional support: RVO:67985823 Keywords : adrenalectomy * circadian rhythms * corticosterone * peripheral clock Subject RIV: ED - Physiology Impact factor: 2.562, year: 2016

  16. Special Relativity in Week One: 2) All Clocks Run Slow

    Science.gov (United States)

    Huggins, Elisha

    2011-01-01

    In our initial article on teaching special relativity in the first week of an introductory physics course, we used the principle of relativity and Maxwell's theory of light to derive Einstein's second postulate (that the speed of light is the same to all observers). In this paper we study thought experiments involving a light pulse clock moving…

  17. A Medieval Clock Made out of Simple Materials

    Science.gov (United States)

    Danese, B.; Oss, S.

    2008-01-01

    A cheap replica of the verge-and-foliot clock has been built from simple materials. It is a didactic tool of great power for physics teaching at every stage of schooling, in particular at university level. An account is given of its construction and its working principles, together with motivated examples of a few activities. (Contains 3 tables…

  18. Using Integer Clocks to Verify the Timing-Sync Sensor Network Protocol

    Science.gov (United States)

    Huang, Xiaowan; Singh, Anu; Smolka, Scott A.

    2010-01-01

    We use the UPPAAL model checker for Timed Automata to verify the Timing-Sync time-synchronization protocol for sensor networks (TPSN). The TPSN protocol seeks to provide network-wide synchronization of the distributed clocks in a sensor network. Clock-synchronization algorithms for sensor networks such as TPSN must be able to perform arithmetic on clock values to calculate clock drift and network propagation delays. They must be able to read the value of a local clock and assign it to another local clock. Such operations are not directly supported by the theory of Timed Automata. To overcome this formal-modeling obstacle, we augment the UPPAAL specification language with the integer clock derived type. Integer clocks, which are essentially integer variables that are periodically incremented by a global pulse generator, greatly facilitate the encoding of the operations required to synchronize clocks as in the TPSN protocol. With this integer-clock-based model of TPSN in hand, we use UPPAAL to verify that the protocol achieves network-wide time synchronization and is devoid of deadlock. We also use the UPPAAL Tracer tool to illustrate how integer clocks can be used to capture clock drift and resynchronization during protocol execution

  19. Noise in state of the art clocks and their impact for fundamental physics

    Science.gov (United States)

    Maleki, L.

    2001-01-01

    In this paper a review of the use of advanced atomic clocks in testing the fundamental physical laws will be presented. Noise sources of clocks will be discussed, together with an outline their characterization based on current models. The paper will conclude with a discussion of recent attempts to reduce the fundamental, as well as technical noise in atomic clocks.

  20. Telling time from analog and digital clocks: A multiple-route account

    NARCIS (Netherlands)

    Korvorst, M.H.W.; Roelofs, A.P.A.; Levelt, W.J.M.

    2007-01-01

    Does the naming of clocks always require conceptual preparation? To examine this question, speakers were presented with analog and digital clocks that had to be named in Dutch using either a relative (e.g., "quarter to four") or an absolute (e.g., "three forty-five") clock time expression format.

  1. A new stochastic model considering satellite clock interpolation errors in precise point positioning

    Science.gov (United States)

    Wang, Shengli; Yang, Fanlin; Gao, Wang; Yan, Lizi; Ge, Yulong

    2018-03-01

    Precise clock products are typically interpolated based on the sampling interval of the observational data when they are used for in precise point positioning. However, due to the occurrence of white noise in atomic clocks, a residual component of such noise will inevitable reside within the observations when clock errors are interpolated, and such noise will affect the resolution of the positioning results. In this paper, which is based on a twenty-one-week analysis of the atomic clock noise characteristics of numerous satellites, a new stochastic observation model that considers satellite clock interpolation errors is proposed. First, the systematic error of each satellite in the IGR clock product was extracted using a wavelet de-noising method to obtain the empirical characteristics of atomic clock noise within each clock product. Then, based on those empirical characteristics, a stochastic observation model was structured that considered the satellite clock interpolation errors. Subsequently, the IGR and IGS clock products at different time intervals were used for experimental validation. A verification using 179 stations worldwide from the IGS showed that, compared with the conventional model, the convergence times using the stochastic model proposed in this study were respectively shortened by 4.8% and 4.0% when the IGR and IGS 300-s-interval clock products were used and by 19.1% and 19.4% when the 900-s-interval clock products were used. Furthermore, the disturbances during the initial phase of the calculation were also effectively improved.

  2. THE LESSONIA NIGRESCENS SPECIES COMPLEX (LAMINARIALES, PHAEOPHYCEAE) SHOWS STRICT PARAPATRY AND COMPLETE REPRODUCTIVE ISOLATION IN A SECONDARY CONTACT ZONE(1).

    Science.gov (United States)

    Tellier, Florence; Tapia, Javier; Faugeron, Sylvain; Destombe, Christophe; Valero, Myriam

    2011-08-01

    During secondary contact between phylogenetically closely related species (sibling species) having diverged in allopatry, the maintenance of species integrity depends on intrinsic and extrinsic reproductive barriers. In kelps (Phaeophyceae), the observations of hybrids in laboratory conditions suggest that reproductive isolation is incomplete. However, not all interspecific crosses are successful, and very few hybrids have been observed in nature, despite the co-occurrence of many kelp species in sympatry. This suggests that there are reproductive barriers that maintain species integrity. In this study, we characterized the fine genetic structure of a secondary contact zone to clarify the extent of reproductive isolation between two sister species. In Lessonia nigrescens Bory (Laminariales, Phaeophyta) species complex, two cryptic species have been recently found out from gene phylogenies, and-waiting for a formal taxonomic description-we used their geographic distribution to name them (northern and southern species). We studied 12 populations, distributed along 50 km of coastline, and employed two molecular approaches, assigning individuals to phylogenetic species according to a diagnostic mitochondrial marker (351 individuals analyzed) and quantifying interspecific gene flow with four microsatellite markers (248 individuals analyzed). No hybridization or introgression was revealed, indicating complete reproductive isolation in natural conditions. Unexpectedly, our study demonstrated that the two species were strictly segregated in space. This absence of co-occurrence along the contact zone can partially explain the lack of hybridization, raising new interesting questions as to the mechanisms that limit sympatry at small spatial scales. © 2011 Phycological Society of America.

  3. 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.

  4. Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin: identification of cardiac clock-controlled genes using open access bioinformatics data.

    Directory of Open Access Journals (Sweden)

    Peter S Podobed

    Full Text Available Circadian rhythms are important for healthy cardiovascular physiology and are regulated at the molecular level by a circadian clock mechanism. We and others previously demonstrated that 9-13% of the cardiac transcriptome is rhythmic over 24 h daily cycles; the heart is genetically a different organ day versus night. However, which rhythmic mRNAs are regulated by the circadian mechanism is not known. Here, we used open access bioinformatics databases to identify 94 transcripts with expression profiles characteristic of CLOCK and BMAL1 targeted genes, using the CircaDB website and JTK_Cycle. Moreover, 22 were highly expressed in the heart as determined by the BioGPS website. Furthermore, 5 heart-enriched genes had human/mouse conserved CLOCK:BMAL1 promoter binding sites (E-boxes, as determined by UCSC table browser, circadian mammalian promoter/enhancer database PEDB, and the European Bioinformatics Institute alignment tool (EMBOSS. Lastly, we validated findings by demonstrating that Titin cap (Tcap, telethonin was targeted by transcriptional activators CLOCK and BMAL1 by showing 1 Tcap mRNA and TCAP protein had a diurnal rhythm in murine heart; 2 cardiac Tcap mRNA was rhythmic in animals kept in constant darkness; 3 Tcap and control Per2 mRNA expression and cyclic amplitude were blunted in Clock(Δ19/Δ19 hearts; 4 BMAL1 bound to the Tcap promoter by ChIP assay; 5 BMAL1 bound to Tcap promoter E-boxes by biotinylated oligonucleotide assay; and 6 CLOCK and BMAL1 induced tcap expression by luciferase reporter assay. Thus this study identifies circadian regulated genes in silico, with validation of Tcap, a critical regulator of cardiac Z-disc sarcomeric structure and function.

  5. Rate Control Efficacy in Permanent Atrial Fibrillation : Successful and Failed Strict Rate Control Against a Background of Lenient Rate Control

    NARCIS (Netherlands)

    Groenveld, Hessel F.; Tijssen, Jan G. P.; Crijns, Harry J. G. M.; Van den Berg, Maarten P.; Hillege, Hans L.; Alings, Marco; Van Veldhuisen, Dirk J.; Van Gelder, Isabelle C.

    2013-01-01

    Objectives This study sought to investigate differences in outcome between patients treated with successful strict, failed strict, and lenient rate control. Background The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation) study showed no difference in outcome between lenient and

  6. Evidence for widespread dysregulation of circadian clock progression in human cancer

    Directory of Open Access Journals (Sweden)

    Jarrod Shilts

    2018-01-01

    Full Text Available The ubiquitous daily rhythms in mammalian physiology are guided by progression of the circadian clock. In mice, systemic disruption of the clock can promote tumor growth. In vitro, multiple oncogenes can disrupt the clock. However, due to the difficulties of studying circadian rhythms in solid tissues in humans, whether the clock is disrupted within human tumors has remained unknown. We sought to determine the state of the circadian clock in human cancer using publicly available transcriptome data. We developed a method, called the clock correlation distance (CCD, to infer circadian clock progression in a group of samples based on the co-expression of 12 clock genes. Our method can be applied to modestly sized datasets in which samples are not labeled with time of day and coverage of the circadian cycle is incomplete. We used the method to define a signature of clock gene co-expression in healthy mouse organs, then validated the signature in healthy human tissues. By then comparing human tumor and non-tumor samples from twenty datasets of a range of cancer types, we discovered that clock gene co-expression in tumors is consistently perturbed. Subsequent analysis of data from clock gene knockouts in mice suggested that perturbed clock gene co-expression in human cancer is not caused solely by the inactivation of clock genes. Furthermore, focusing on lung cancer, we found that human lung tumors showed systematic changes in expression in a large set of genes previously inferred to be rhythmic in healthy lung. Our findings suggest that clock progression is dysregulated in many solid human cancers and that this dysregulation could have broad effects on circadian physiology within tumors. In addition, our approach opens the door to using publicly available data to infer circadian clock progression in a multitude of human phenotypes.

  7. The Clock mutant mouse is a novel experimental model for nocturia and nocturnal polyuria.

    Science.gov (United States)

    Ihara, Tatsuya; Mitsui, Takahiko; Nakamura, Yuki; Kira, Satoru; Miyamoto, Tatsuya; Nakagomi, Hiroshi; Sawada, Norifumi; Hirayama, Yuri; Shibata, Keisuke; Shigetomi, Eiji; Shinozaki, Yoichi; Yoshiyama, Mitsuharu; Andersson, Karl-Erik; Nakao, Atsuhito; Takeda, Masayuki; Koizumi, Schuichi

    2017-04-01

    The pathophysiologies of nocturia (NOC) and nocturnal polyuria (NP) are multifactorial and their etiologies remain unclear in a large number of patients. Clock genes exist in most cells and organs, and the products of Clock regulate circadian rhythms as representative clock genes. Clock genes regulate lower urinary tract function, and a newly suggested concept is that abnormalities in clock genes cause lower urinary tract symptoms. In the present study, we investigated the voiding behavior of Clock mutant (Clock Δ19/Δ19 ) mice in order to determine the effects of clock genes on NOC/NP. Male C57BL/6 mice aged 8-12 weeks (WT) and male C57BL/6 Clock Δ19/Δ19 mice aged 8 weeks were used. They were bred under 12 hr light/dark conditions for 2 weeks and voiding behavior was investigated by measuring water intake volume, urine volume, urine volume/void, and voiding frequency in metabolic cages in the dark and light periods. No significant differences were observed in behavior patterns between Clock Δ19/Δ19 and WT mice. Clock Δ19/Δ19 mice showed greater voiding frequencies and urine volumes during the sleep phase than WT mice. The diurnal change in urine volume/void between the dark and light periods in WT mice was absent in Clock Δ19/Δ19 mice. Additionally, functional bladder capacity was significantly lower in Clock Δ19/Δ19 mice than in WT mice. We demonstrated that Clock Δ19/Δ19 mice showed the phenotype of NOC/NP. The Clock Δ19/Δ19 mouse may be used as an animal model of NOC and NP. Neurourol. Urodynam. 36:1034-1038, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Probing charge transfer dynamics in self-assembled monolayers by core hole clock approach

    International Nuclear Information System (INIS)

    Zharnikov, Michael

    2015-01-01

    This article reviews recent progress in the application of core hole clock approach in the framework of resonant Auger electron spectroscopy to the monomolecular assembles of alkyl, oligophenyl, and oligo(phenylene–ethynylene) based molecules on Au(1 1 1) substrates, referring mostly to the work by the author et al. The major goal was to study electron transfer (ET) dynamics in these systems serving as prototypes of molecular electronics (ME) devices. The ET pathway to the conductive substrate was unambiguously defined by resonant excitation of the nitrile tailgroup attached to the molecular backbone. Characteristic ET times within the femtosecond domain were determined, along with the attenuation factors for the ET dynamics, analogous to the case of the static transport. The above parameters were found to exhibit strong dependence on the character of the molecular orbital which mediates the ET process. In addition, certain spectral features, which can be associated with an inverse ET from the molecular backbone to the excitation site, were observed upon exchange of the nitrile group by strongly electronegative nitro moiety. The reported results represent a valuable input for theory and a certain potential for applications such as ME devices where optimization of ET can have significant technological impact.

  9. Molecular Mechanisms of Circadian Regulation During Spaceflight

    Science.gov (United States)

    Zanello, S. B.; Boyle, R.

    2012-01-01

    The physiology of both vertebrates and invertebrates follows internal rhythms coordinated in phase with the 24-hour daily light cycle. This circadian clock is governed by a central pacemaker, the suprachiasmatic nucleus (SCN) in the brain. However, peripheral circadian clocks or oscillators have been identified in most tissues. How the central and peripheral oscillators are synchronized is still being elucidated. Light is the main environmental cue that entrains the circadian clock. Under the absence of a light stimulus, the clock continues its oscillation in a free-running condition. In general, three functional compartments of the circadian clock are defined. The vertebrate retina contains endogenous clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis (melatonin and dopamine), rod disk shedding, signalling pathways and gene expression. Neurons with putative local circadian rhythm generation are found among all the major neuron populations in the mammalian retina. In the mouse, clock genes and function are more localized to the inner retinal and ganglion cell layers. The photoreceptor, however, secrete melatonin which may still serve a an important circadian signal. The reception and transmission of the non-visual photic stimulus resides in a small subpopulation (1-3%) or retinal ganglion cells (RGC) that express the pigment melanopsin (Opn4) and are called intrisically photoreceptive RGC (ipRGC). Melanopsin peak absorption is at 420 nm and all the axons of the ipRGC reach the SCN. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate the risk of fatigue and health and performance decrement due to circadian rhythm disruption. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. We hypothesize that spaceflight may affect ip

  10. Gremlin-2 is a BMP antagonist that is regulated by the circadian clock

    DEFF Research Database (Denmark)

    Yeung, Ching-Yan Chloé; Gossan, Nicole; Lu, Yinhui

    2014-01-01

    knowledge of tendon gene regulation is essential for a complete understanding of FCT biology. Here we show autonomous circadian rhythms in mouse tendon and primary human tenocytes, controlled by an intrinsic molecular circadian clock. Time-series microarrays identified the first circadian transcriptome...... of murine tendon, revealing that 4.6% of the transcripts (745 genes) are expressed in a circadian manner. One of these genes was Grem2, which oscillated in antiphase to BMP signaling. Moreover, recombinant human Gremlin-2 blocked BMP2-induced phosphorylation of Smad1/5 and osteogenic differentiation...... of human tenocytes in vitro. We observed dampened Grem2 expression, deregulated BMP signaling, and spontaneously calcifying tendons in young CLOCKΔ19 arrhythmic mice and aged wild-type mice. Thus, disruption of circadian control, through mutations or aging, of Grem2/BMP signaling becomes a new focus...

  11. Byzantine-fault tolerant self-stabilizing protocol for distributed clock synchronization systems

    Science.gov (United States)

    Malekpour, Mahyar R. (Inventor)

    2010-01-01

    A rapid Byzantine self-stabilizing clock synchronization protocol that self-stabilizes from any state, tolerates bursts of transient failures, and deterministically converges within a linear convergence time with respect to the self-stabilization period. Upon self-stabilization, all good clocks proceed synchronously. The Byzantine self-stabilizing clock synchronization protocol does not rely on any assumptions about the initial state of the clocks. Furthermore, there is neither a central clock nor an externally generated pulse system. The protocol converges deterministically, is scalable, and self-stabilizes in a short amount of time. The convergence time is linear with respect to the self-stabilization period.

  12. Effect of cryopreservation and lyophilization on viability and growth of strict anaerobic human gut microbes.

    Science.gov (United States)

    Bircher, Lea; Geirnaert, Annelies; Hammes, Frederik; Lacroix, Christophe; Schwab, Clarissa

    2018-04-17

    Strict anaerobic gut microbes have been suggested as 'next-generation probiotics' for treating several intestinal disorders. The development of preservation techniques is of major importance for therapeutic application. This study investigated cryopreservation (-80°C) and lyophilization survival and storage stability (4°C for 3 months) of the strict anaerobic gut microbes Bacteroides thetaiotaomicron, Faecalibacterium prausnitzii, Roseburia intestinalis, Anaerostipes caccae, Eubacterium hallii and Blautia obeum. To improve preservation survival, protectants sucrose and inulin (both 5% w/v) were added for lyophilization and were also combined with glycerol (15% v/v) for cryopreservation. Bacterial fitness, evaluated by maximum growth rate and lag phase, viability and membrane integrity were determined using a standardized growth assay and by flow cytometry as markers for preservation resistance. Lyophilization was more detrimental to viability and fitness than cryopreservation, but led to better storage stability. Adding sucrose and inulin enhanced viability and the proportion of intact cells during lyophilization of all strains. Viability of protectant-free B. thetaiotaomicron, A. caccae and F. prausnitzii was above 50% after cryopreservation and storage and increased to above 80% if protectants were present. The addition of glycerol, sucrose and inulin strongly enhanced the viability of B. obeum, E. hallii and R. intestinalis from 0.03-2% in protectant-free cultures to 11-37%. This is the first study that quantitatively compared the effect of cryopreservation and lyophilization and the addition of selected protectants on viability and fitness of six strict anaerobic gut microbes. Our results suggest that efficiency of protectants is process- and species-specific. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  13. Strictly local one-dimensional topological quantum error correction with symmetry-constrained cellular automata

    Directory of Open Access Journals (Sweden)

    Nicolai Lang, Hans Peter Büchler

    2018-01-01

    Full Text Available Active quantum error correction on topological codes is one of the most promising routes to long-term qubit storage. In view of future applications, the scalability of the used decoding algorithms in physical implementations is crucial. In this work, we focus on the one-dimensional Majorana chain and construct a strictly local decoder based on a self-dual cellular automaton. We study numerically and analytically its performance and exploit these results to contrive a scalable decoder with exponentially growing decoherence times in the presence of noise. Our results pave the way for scalable and modular designs of actively corrected one-dimensional topological quantum memories.

  14. Single Molecule Experiments Challenge the Strict Wave-Particle Dualism of Light

    Directory of Open Access Journals (Sweden)

    Karl Otto Greulich

    2010-01-01

    Full Text Available Single molecule techniques improve our understanding of the photon and light. If the single photon double slit experiment is performed at the “single photon limit” of a multi-atom light source, faint light pulses with more than one photon hamper the interpretation. Single molecules, quantum dots or defect centres in crystals should be used as light source. “Single photon detectors” do not meet their promise―only “photon number resolving single photon detectors” do so. Particularly, the accumulation time argument, the only safe basis for the postulate of a strictly particle like photon, has so far not yet been verified.

  15. Single molecule experiments challenge the strict wave-particle dualism of light.

    Science.gov (United States)

    Greulich, Karl Otto

    2010-01-21

    Single molecule techniques improve our understanding of the photon and light. If the single photon double slit experiment is performed at the "single photon limit" of a multi-atom light source, faint light pulses with more than one photon hamper the interpretation. Single molecules, quantum dots or defect centres in crystals should be used as light source. "Single photon detectors" do not meet their promise-only "photon number resolving single photon detectors" do so. Particularly, the accumulation time argument, the only safe basis for the postulate of a strictly particle like photon, has so far not yet been verified.

  16. Strictly positive solutions for one-dimensional nonlinear problems involving the p-Laplacian

    OpenAIRE

    Kaufmann, Uriel; Medri, Ivan

    2013-01-01

    Let $\\Omega$ be a bounded open interval, and let $p>1$ and $q\\in\\left(0,p-1\\right) $. Let $m\\in L^{p^{\\prime}}\\left(\\Omega\\right) $ and $0\\leq c\\in L^{\\infty}\\left(\\Omega\\right) $. We study existence of strictly positive solutions for elliptic problems of the form $-\\left(\\left\\| u^{\\prime}\\right\\|^{p-2}u^{\\prime}\\right) ^{\\prime}+c\\left(x\\right) u^{p-1}=m\\left(x\\right) u^{q}$ in $\\Omega$, $u=0$ on $\\partial\\Omega$. We mention that our results are new even in the case $c\\equiv0$.

  17. Structural stability of Riemann solutions for strictly hyperbolic systems with three piecewise constant states

    Directory of Open Access Journals (Sweden)

    Xuefeng Wei

    2016-12-01

    Full Text Available This article concerns the wave interaction problem for a strictly hyperbolic system of conservation laws whose Riemann solutions involve delta shock waves. To cover all situations, the global solutions are constructed when the initial data are taken as three piecewise constant states. It is shown that the Riemann solutions are stable with respect to a specific small perturbation of the Riemann initial data. In addition, some interesting nonlinear phenomena are captured during the process of constructing the solutions, such as the generation and decomposition of delta shock waves.

  18. Differential maturation of rhythmic clock gene expression during early development in medaka (Oryzias latipes).

    Science.gov (United States)

    Cuesta, Ines H; Lahiri, Kajori; Lopez-Olmeda, Jose Fernando; Loosli, Felix; Foulkes, Nicholas S; Vallone, Daniela

    2014-05-01

    One key challenge for the field of chronobiology is to identify how circadian clock function emerges during early embryonic development. Teleosts such as the zebrafish are ideal models for studying circadian clock ontogeny since the entire process of development occurs ex utero in an optically transparent chorion. Medaka (Oryzias latipes) represents another powerful fish model for exploring early clock function with, like the zebrafish, many tools available for detailed genetic analysis. However, to date there have been no reports documenting circadian clock gene expression during medaka development. Here we have characterized the expression of key clock genes in various developmental stages and in adult tissues of medaka. As previously reported for other fish, light dark cycles are required for the emergence of clock gene expression rhythms in this species. While rhythmic expression of per and cry genes is detected very early during development and seems to be light driven, rhythmic clock and bmal expression appears much later around hatching time. Furthermore, the maturation of clock function seems to correlate with the appearance of rhythmic expression of these positive elements of the clock feedback loop. By accelerating development through elevated temperatures or by artificially removing the chorion, we show an earlier onset of rhythmicity in clock and bmal expression. Thus, differential maturation of key elements of the medaka clock mechanism depends on the developmental stage and the presence of the chorion.

  19. Combined orbits and clocks from IGS second reprocessing

    Science.gov (United States)

    Griffiths, Jake

    2018-05-01

    The Analysis Centers (ACs) of the International GNSS Service (IGS) have reprocessed a large global network of GPS tracking data from 1994.0 until 2014.0 or later. Each AC product time series was extended uniformly till early 2015 using their weekly operational IGS contributions so that the complete combined product set covers GPS weeks 730 through 1831. Three ACs also included GLONASS data from as early as 2002 but that was insufficient to permit combined GLONASS products. The reprocessed terrestrial frame combination procedures and results have been reported already, and those were incorporated into the ITRF2014 multi-technique global frame released in 2016. This paper describes the orbit and clock submissions and their multi-AC combinations and assessments. These were released to users in early 2017 in time for the adoption of IGS14 for generating the operational IGS products. While the reprocessing goal was to enable homogeneous modeling, consistent with the current operational procedures, to be applied retrospectively to the full history of observation data in order to achieve a more suitable reference for geophysical studies, that objective has only been partially achieved. Ongoing AC analysis changes and a lack of full participation limit the consistency and precision of the finished IG2 products. Quantitative internal measures indicate that the reprocessed orbits are somewhat less precise than current operational orbits or even the later orbits from the first IGS reprocessing campaign. That is even more apparent for the clocks where a lack of robust AC participation means that it was only possible to form combined 5-min clocks but not the 30-s satellite clocks published operationally. Therefore, retrospective precise point positioning solutions by users are not recommended using the orbits and clocks. Nevertheless, the orbits do support long-term stable user solutions when used with network processing with either double differencing or explicit clock

  20. Fault-Tolerant Self-Stabilizing Distributed Clock Synchronization Protocol for Arbitrary Digraphs

    Science.gov (United States)

    Malekpour, Mahyar R. (Inventor)

    2014-01-01

    A self-stabilizing network in the form of an arbitrary, non-partitioned digraph includes K nodes having a synchronizer executing a protocol. K-1 monitors of each node may receive a Sync message transmitted from a directly connected node. When the Sync message is received, the logical clock value for the receiving node is set to between 0 and a communication latency value (gamma) if the clock value is less than a minimum event-response delay (D). A new Sync message is also transmitted to any directly connected nodes if the clock value is greater than or equal to both D and a graph threshold (T(sub S)). When the Sync message is not received the synchronizer increments the clock value if the clock value is less than a resynchronization period (P), and resets the clock value and transmits a new Sync message to all directly connected nodes when the clock value equals or exceeds P.

  1. The effect of 8 days of strict bed rest on the incretin effect in healthy volunteers.

    Science.gov (United States)

    Nielsen, Signe Tellerup; Harder-Lauridsen, Nina Majlund; Benatti, Fabiana Braga; Wedell-Neergaard, Anne-Sophie; Lyngbæk, Mark Preben; Møller, Kirsten; Pedersen, Bente Klarlund; Krogh-Madsen, Rikke

    2016-03-15

    Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide, plasma incretin hormones [glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)], and serum glucagon were measured serially during both the OGTT and the IVGI. The incretin effect is calculated as the relative difference between the area under the curve for the insulin response during the OGTT and that of the corresponding IVGI, respectively. Concentrations of glucose, insulin, C-peptide, and GIP measured during the OGTT were higher after the bed rest intervention (all P effect (P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect. Copyright © 2016 the American Physiological Society.

  2. Optimal control of nonlinear continuous-time systems in strict-feedback form.

    Science.gov (United States)

    Zargarzadeh, Hassan; Dierks, Travis; Jagannathan, Sarangapani

    2015-10-01

    This paper proposes a novel optimal tracking control scheme for nonlinear continuous-time systems in strict-feedback form with uncertain dynamics. The optimal tracking problem is transformed into an equivalent optimal regulation problem through a feedforward adaptive control input that is generated by modifying the standard backstepping technique. Subsequently, a neural network-based optimal control scheme is introduced to estimate the cost, or value function, over an infinite horizon for the resulting nonlinear continuous-time systems in affine form when the internal dynamics are unknown. The estimated cost function is then used to obtain the optimal feedback control input; therefore, the overall optimal control input for the nonlinear continuous-time system in strict-feedback form includes the feedforward plus the optimal feedback terms. It is shown that the estimated cost function minimizes the Hamilton-Jacobi-Bellman estimation error in a forward-in-time manner without using any value or policy iterations. Finally, optimal output feedback control is introduced through the design of a suitable observer. Lyapunov theory is utilized to show the overall stability of the proposed schemes without requiring an initial admissible controller. Simulation examples are provided to validate the theoretical results.

  3. Strictly monolayer large continuous MoS2 films on diverse substrates and their luminescence properties

    International Nuclear Information System (INIS)

    Mohapatra, P. K.; Deb, S.; Singh, B. P.; Vasa, P.; Dhar, S.

    2016-01-01

    Despite a tremendous interest on molybdenum disulfide as a thinnest direct band gap semiconductor, single step synthesis of a large area purely monolayer MoS 2 film has not yet been reported. Here, we report a CVD route to synthesize a continuous film of strictly monolayer MoS 2 covering an area as large as a few cm 2 on a variety of different substrates without using any seeding material or any elaborate pretreatment of the substrate. This is achieved by allowing the growth to take place in the naturally formed gap between a piece of SiO 2 coated Si wafer and the substrate, when the latter is placed on top of the former inside a CVD reactor. We propose a qualitative model to explain why the MoS 2 films are always strictly monolayer in this method. The photoluminescence study of these monolayers shows the characteristic excitonic and trionic features associated with monolayer MoS 2 . In addition, a broad defect related luminescence band appears at ∼1.7 eV. As temperature decreases, the intensity of this broad feature increases, while the band edge luminescence reduces

  4. Motion and gravity effects in the precision of quantum clocks.

    Science.gov (United States)

    Lindkvist, Joel; Sabín, Carlos; Johansson, Göran; Fuentes, Ivette

    2015-05-19

    We show that motion and gravity affect the precision of quantum clocks. We consider a localised quantum field as a fundamental model of a quantum clock moving in spacetime and show that its state is modified due to changes in acceleration. By computing the quantum Fisher information we determine how relativistic motion modifies the ultimate bound in the precision of the measurement of time. While in the absence of motion the squeezed vacuum is the ideal state for time estimation, we find that it is highly sensitive to the motion-induced degradation of the quantum Fisher information. We show that coherent states are generally more resilient to this degradation and that in the case of very low initial number of photons, the optimal precision can be even increased by motion. These results can be tested with current technology by using superconducting resonators with tunable boundary conditions.

  5. Design of ternary clocked adiabatic static random access memory

    International Nuclear Information System (INIS)

    Wang Pengjun; Mei Fengna

    2011-01-01

    Based on multi-valued logic, adiabatic circuits and the structure of ternary static random access memory (SRAM), a design scheme of a novel ternary clocked adiabatic SRAM is presented. The scheme adopts bootstrapped NMOS transistors, and an address decoder, a storage cell and a sense amplifier are charged and discharged in the adiabatic way, so the charges stored in the large switch capacitance of word lines, bit lines and the address decoder can be effectively restored to achieve energy recovery during reading and writing of ternary signals. The PSPICE simulation results indicate that the ternary clocked adiabatic SRAM has a correct logic function and low power consumption. Compared with ternary conventional SRAM, the average power consumption of the ternary adiabatic SRAM saves up to 68% in the same conditions. (semiconductor integrated circuits)

  6. Phase Locking a Clock Oscillator to a Coherent Atomic Ensemble

    Directory of Open Access Journals (Sweden)

    R. Kohlhaas

    2015-04-01

    Full Text Available The sensitivity of an atomic interferometer increases when the phase evolution of its quantum superposition state is measured over a longer interrogation interval. In practice, a limit is set by the measurement process, which returns not the phase but its projection in terms of population difference on two energetic levels. The phase interval over which the relation can be inverted is thus limited to the interval [-π/2,π/2]; going beyond it introduces an ambiguity in the readout, hence a sensitivity loss. Here, we extend the unambiguous interval to probe the phase evolution of an atomic ensemble using coherence-preserving measurements and phase corrections, and demonstrate the phase lock of the clock oscillator to an atomic superposition state. We propose a protocol based on the phase lock to improve atomic clocks limited by local oscillator noise, and foresee the application to other atomic interferometers such as inertial sensors.

  7. Design of ternary clocked adiabatic static random access memory

    Science.gov (United States)

    Pengjun, Wang; Fengna, Mei

    2011-10-01

    Based on multi-valued logic, adiabatic circuits and the structure of ternary static random access memory (SRAM), a design scheme of a novel ternary clocked adiabatic SRAM is presented. The scheme adopts bootstrapped NMOS transistors, and an address decoder, a storage cell and a sense amplifier are charged and discharged in the adiabatic way, so the charges stored in the large switch capacitance of word lines, bit lines and the address decoder can be effectively restored to achieve energy recovery during reading and writing of ternary signals. The PSPICE simulation results indicate that the ternary clocked adiabatic SRAM has a correct logic function and low power consumption. Compared with ternary conventional SRAM, the average power consumption of the ternary adiabatic SRAM saves up to 68% in the same conditions.

  8. Variation in candidate genes CLOCK and ADCYAP1 does not consistently predict differences in migratory behavior in the songbird genus Junco [v1; ref status: indexed, http://f1000r.es/11p

    Directory of Open Access Journals (Sweden)

    Mark P Peterson

    2013-04-01

    Full Text Available Recent studies exploring the molecular genetic basis for migratory variation in animals have identified polymorphisms in two genes (CLOCK and ADCYAP1 that are linked to circadian rhythms and correlate with migratory propensity and phenology among individuals and populations. Results from these initial studies are mixed, however, and additional data are needed to assess the generality and diversity of the molecular mechanisms that regulate the biology of migration. We sequenced CLOCK and ADCYAP1 in 15 populations across the two species of the avian genus Junco, a North American lineage in which multiple recently diverged subspecies and populations range from sedentary to long-distance migrants. We found no consistent associations between allele length and migratory status across the genus for either CLOCK or ADCYAP1. However, within two subspecies groups, populations that migrate longer distances have longer CLOCK alleles on average. Additionally, there was a positive relationship between ADCYAP1 allele length and migratory restlessness (zugunruhe among individuals within one of two captive populations studied—a result similar to those reported previously within captive blackcaps (Sylvia atricapilla. We conclude that, while both ADCYAP1 and CLOCK may correlate with migratory propensity within or among certain populations or species, previously identified relationships between migratory behavior and sequence variants cannot be easily generalized across taxa.

  9. The fission time scale measured with an atomic clock

    NARCIS (Netherlands)

    Kravchuk, VL; Wilschut, HW; Hunyadi, M; Kopecky, S; Lohner, H; Rogachevskiy, A; Siemssen, RH; Krasznahorkay, A; Hamilton, JH; Ramayya, AV; Carter, HK

    2003-01-01

    We present a new direct method of measuring the fission absolute time scale using an atomic clock based on the lifetime of a vacancy in the atomic K-shell. We studied the reaction Ne-20 + Th-232 -> O-16 + U-236* at 30 MeV/u. The excitation energy of about 115 MeV in such a reaction is in the range

  10. The Chip-Scale Atomic Clock - Prototype Evaluation

    Science.gov (United States)

    2007-11-01

    39th Annual Precise Time and Time Interval (PTTI) Meeting THE CHIP-SCALE ATOMIC CLOCK – PROTOTYPE EVALUATION R. Lutwak *, A. Rashed...been supported by the Defense Advanced Research Projects Agency, Contract # NBCHC020050. REFERENCES [1] R. Lutwak , D. Emmons, W. Riley, and...D.C.), pp. 539-550. [2] R. Lutwak , D. Emmons, T. English, W. Riley, A. Duwel, M. Varghese, D. K. Serkland, and G. M. Peake, 2004, “The Chip-Scale

  11. Atomic clocks comparison by means of television chain

    International Nuclear Information System (INIS)

    Silva, J.M.

    1974-09-01

    The various methods and techniques of time and frequency dissemination are presented. One of them, the Line 10 Method, was used to compare two atomic clocks, localized in different places is a distance of more or less four-hundred kilometers. The results are compared with parallel results obtained with another method, physical transport, giving the necessary experimental basis of the applicability of the Line 10 Method in Brazil [pt

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

    Directory of Open Access Journals (Sweden)

    Harmon Frank G

    2010-06-01

    Full Text Available Abstract Background 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 flowering time. Despite recent advances in understanding the circadian system of the model plant Arabidopsis thaliana, the contribution of the circadian oscillator to important agronomic traits in Zea mays and other cereals remains poorly defined. To address this deficit, this study investigated the transcriptional landscape of the maize circadian system. Results Since transcriptional regulation is a fundamental aspect of circadian systems, genes exhibiting circadian expression were identified in the sequenced maize inbred B73. Of the over 13,000 transcripts examined, approximately 10 percent displayed circadian expression patterns. The majority of cycling genes had peak expression at subjective dawn and dusk, similar to other plant circadian systems. The maize circadian clock organized co-regulation of genes participating in fundamental physiological processes, including photosynthesis, carbohydrate metabolism, cell wall biogenesis, and phytohormone biosynthesis pathways. Conclusions Circadian regulation of the maize genome was widespread and key genes in several major metabolic pathways had circadian expression waveforms. The maize circadian clock coordinated transcription to be coincident with oncoming day or night, which was consistent with the circadian oscillator acting to prepare the plant for these major recurring environmental changes. These findings highlighted the multiple processes in maize plants under circadian regulation and, as a result, provided insight into the important contribution this regulatory system makes to agronomic traits in maize and potentially other C4 plant species.

  13. Piezoelectric Non Linear Nanomechanical Temperature and Acceleration Insensitive Clocks (PENNTAC)

    Science.gov (United States)

    2016-07-01

    relationship between the resonator Q and flicker noise when TED is largely mitigated , we measured a total of 25 resonators (11 full-anchor and 14...during this effort demonstrated the first fully integrated oven control system to mitigate the temperature effect on the reference clock. It showed...Reduction in AlN CMRs by Prolonged RF Excitation ............................................................ 13 2.6 Impact of Damping on Flicker

  14. Estimation of satellite position, clock and phase bias corrections

    Science.gov (United States)

    Henkel, Patrick; Psychas, Dimitrios; Günther, Christoph; Hugentobler, Urs

    2018-05-01

    Precise point positioning with integer ambiguity resolution requires precise knowledge of satellite position, clock and phase bias corrections. In this paper, a method for the estimation of these parameters with a global network of reference stations is presented. The method processes uncombined and undifferenced measurements of an arbitrary number of frequencies such that the obtained satellite position, clock and bias corrections can be used for any type of differenced and/or combined measurements. We perform a clustering of reference stations. The clustering enables a common satellite visibility within each cluster and an efficient fixing of the double difference ambiguities within each cluster. Additionally, the double difference ambiguities between the reference stations of different clusters are fixed. We use an integer decorrelation for ambiguity fixing in dense global networks. The performance of the proposed method is analysed with both simulated Galileo measurements on E1 and E5a and real GPS measurements of the IGS network. We defined 16 clusters and obtained satellite position, clock and phase bias corrections with a precision of better than 2 cm.

  15. A new clocking method for a charge coupled device

    International Nuclear Information System (INIS)

    Umezu, Rika; Kitamoto, Shunji; Murakami, Hiroshi

    2014-01-01

    We propose and demonstrate a new clocking method for a charge-coupled device (CCD). When a CCD is used for a photon counting detector of X-rays, its weak point is a limitation of its counting rate, because high counting rate makes non-negligible pile-up of photons. In astronomical usage, this pile-up is especially severe for an observation of a bright point-like object. One typical idea to reduce the pile-up is a parallel sum (P-sum) mode. This mode completely loses one-dimensional information. Our new clocking method, panning mode, provides complementary properties between the normal mode and the P-sum mode. We performed a simple simulation in order to investigate a pile-up probability and compared the simulated result and actual obtained event rates. Using this simulation and the experimental results, we compared the pile-up tolerance of various clocking modes including our new method and also compared their other characteristics

  16. Probing many-body interactions in an optical lattice clock

    Energy Technology Data Exchange (ETDEWEB)

    Rey, A.M., E-mail: arey@jilau1.colorado.edu [JILA, NIST and University of Colorado, Department of Physics, Boulder, CO 80309 (United States); Gorshkov, A.V. [Joint Quantum Institute, NIST and University of Maryland, Department of Physics, College Park, MD 20742 (United States); Kraus, C.V. [Institute for Quantum Optics and Quantum Information of the Austrian Academy of Sciences, A-6020 Innsbruck (Austria); Institute for Theoretical Physics, University of Innsbruck, A-6020 Innsbruck (Austria); Martin, M.J. [JILA, NIST and University of Colorado, Department of Physics, Boulder, CO 80309 (United States); Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, CA 91125 (United States); Bishof, M.; Swallows, M.D.; Zhang, X.; Benko, C.; Ye, J. [JILA, NIST and University of Colorado, Department of Physics, Boulder, CO 80309 (United States); Lemke, N.D.; Ludlow, A.D. [National Institute of Standards and Technology, Boulder, CO 80305 (United States)

    2014-01-15

    We present a unifying theoretical framework that describes recently observed many-body effects during the interrogation of an optical lattice clock operated with thousands of fermionic alkaline earth atoms. The framework is based on a many-body master equation that accounts for the interplay between elastic and inelastic p-wave and s-wave interactions, finite temperature effects and excitation inhomogeneity during the quantum dynamics of the interrogated atoms. Solutions of the master equation in different parameter regimes are presented and compared. It is shown that a general solution can be obtained by using the so called Truncated Wigner Approximation which is applied in our case in the context of an open quantum system. We use the developed framework to model the density shift and decay of the fringes observed during Ramsey spectroscopy in the JILA {sup 87}Sr and NIST {sup 171}Yb optical lattice clocks. The developed framework opens a suitable path for dealing with a variety of strongly-correlated and driven open-quantum spin systems. -- Highlights: •Derived a theoretical framework that describes many-body effects in a lattice clock. •Validated the analysis with recent experimental measurements. •Demonstrated the importance of beyond mean field corrections in the dynamics.

  17. Colour As a Signal for Entraining the Mammalian Circadian Clock

    Science.gov (United States)

    Walmsley, Lauren; Hanna, Lydia; Mouland, Josh; Martial, Franck; West, Alexander; Smedley, Andrew R.; Bechtold, David A.; Webb, Ann R.; Lucas, Robert J.; Brown, Timothy M.

    2015-01-01

    Twilight is characterised by changes in both quantity (“irradiance”) and quality (“colour”) of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue–yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision. PMID:25884537

  18. Colour as a signal for entraining the mammalian circadian clock.

    Directory of Open Access Journals (Sweden)

    Lauren Walmsley

    2015-04-01

    Full Text Available Twilight is characterised by changes in both quantity ("irradiance" and quality ("colour" of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue-yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision.

  19. Relative clock verifies endogenous bursts of human dynamics

    Science.gov (United States)

    Zhou, Tao; Zhao, Zhi-Dan; Yang, Zimo; Zhou, Changsong

    2012-01-01

    Temporal bursts are widely observed in many human-activated systems, which may result from both endogenous mechanisms like the highest-priority-first protocol and exogenous factors like the seasonality of activities. To distinguish the effects from different mechanisms is thus of theoretical significance. This letter reports a new timing method by using a relative clock, namely the time length between two consecutive events of an agent is counted as the number of other agents' events appeared during this interval. We propose a model, in which agents act either in a constant rate or with a power-law inter-event time distribution, and the global activity either keeps unchanged or varies periodically vs. time. Our analysis shows that the bursts caused by the heterogeneity of global activity can be eliminated by setting the relative clock, yet the bursts from real individual behaviors still exist. We perform extensive experiments on four large-scale systems, the search engine by AOL, a social bookmarking system —Delicious, a short-message communication network, and a microblogging system —Twitter. Seasonality of global activity is observed, yet the bursts cannot be eliminated by using the relative clock.

  20. Disordered strictly jammed binary sphere packings attain an anomalously large range of densities

    Science.gov (United States)

    Hopkins, Adam B.; Stillinger, Frank H.; Torquato, Salvatore

    2013-08-01

    Previous attempts to simulate disordered binary sphere packings have been limited in producing mechanically stable, isostatic packings across a broad spectrum of packing fractions. Here we report that disordered strictly jammed binary packings (packings that remain mechanically stable under general shear deformations and compressions) can be produced with an anomalously large range of average packing fractions 0.634≤ϕ≤0.829 for small to large sphere radius ratios α restricted to α≥0.100. Surprisingly, this range of average packing fractions is obtained for packings containing a subset of spheres (called the backbone) that are exactly strictly jammed, exactly isostatic, and also generated from random initial conditions. Additionally, the average packing fractions of these packings at certain α and small sphere relative number concentrations x approach those of the corresponding densest known ordered packings. These findings suggest for entropic reasons that these high-density disordered packings should be good glass formers and that they may be easy to prepare experimentally. We also identify an unusual feature of the packing fraction of jammed backbones (packings with rattlers excluded). The backbone packing fraction is about 0.624 over the majority of the α-x plane, even when large numbers of small spheres are present in the backbone. Over the (relatively small) area of the α-x plane where the backbone is not roughly constant, we find that backbone packing fractions range from about 0.606 to 0.829, with the volume of rattler spheres comprising between 1.6% and 26.9% of total sphere volume. To generate isostatic strictly jammed packings, we use an implementation of the Torquato-Jiao sequential linear programming algorithm [Phys. Rev. EPLEEE81539-375510.1103/PhysRevE.82.061302 82, 061302 (2010)], which is an efficient producer of inherent structures (mechanically stable configurations at the local maxima in the density landscape). The identification and