relaxed clock model: Topics by Science.gov

Sample records for relaxed clock model

Rate variation and estimation of divergence times using strict and relaxed clocks.

PubMed

Brown, Richard P; Yang, Ziheng

2011-09-26

Understanding causes of biological diversity may be greatly enhanced by knowledge of divergence times. Strict and relaxed clock models are used in Bayesian estimation of divergence times. We examined whether: i) strict clock models are generally more appropriate in shallow phylogenies where rate variation is expected to be low, ii) the likelihood ratio test of the clock (LRT) reliably informs which model is appropriate for dating divergence times. Strict and relaxed models were used to analyse sequences simulated under different levels of rate variation. Published shallow phylogenies (Black bass, Primate-sucking lice, Podarcis lizards, Gallotiinae lizards, and Caprinae mammals) were also analysed to determine natural levels of rate variation relative to the performance of the different models. Strict clock analyses performed well on data simulated under the independent rates model when the standard deviation of log rate on branches, σ, was low (≤ 0.1), but were inappropriate when σ>0.1 (95% of rates fall within 0.0082-0.0121 subs/site/Ma when σ = 0.1, for a mean rate of 0.01). The independent rates relaxed clock model performed well at all levels of rate variation, although posterior intervals on times were significantly wider than for the strict clock. The strict clock is therefore superior when rate variation is low. The performance of a correlated rates relaxed clock model was similar to the strict clock. Increased numbers of independent loci led to slightly narrower posteriors under the relaxed clock while older root ages provided proportionately narrower posteriors. The LRT had low power for σ = 0.01-0.1, but high power for σ = 0.5-2.0. Posterior means of σ2 were useful for assessing rate variation in published datasets. Estimates of natural levels of rate variation ranged from 0.05-3.38 for different partitions. Differences in divergence times between relaxed and strict clock analyses were greater in two datasets with higher σ2 for one or more partitions, supporting the simulation results. The strict clock can be superior for trees with shallow roots because of low levels of rate variation between branches. The LRT allows robust assessment of suitability of the clock model as does examination of posteriors on σ2.
Bayesian random local clocks, or one rate to rule them all

PubMed Central

2010-01-01

Background Relaxed molecular clock models allow divergence time dating and "relaxed phylogenetic" inference, in which a time tree is estimated in the face of unequal rates across lineages. We present a new method for relaxing the assumption of a strict molecular clock using Markov chain Monte Carlo to implement Bayesian modeling averaging over random local molecular clocks. The new method approaches the problem of rate variation among lineages by proposing a series of local molecular clocks, each extending over a subregion of the full phylogeny. Each branch in a phylogeny (subtending a clade) is a possible location for a change of rate from one local clock to a new one. Thus, including both the global molecular clock and the unconstrained model results, there are a total of 22n-2 possible rate models available for averaging with 1, 2, ..., 2n - 2 different rate categories. Results We propose an efficient method to sample this model space while simultaneously estimating the phylogeny. The new method conveniently allows a direct test of the strict molecular clock, in which one rate rules them all, against a large array of alternative local molecular clock models. We illustrate the method's utility on three example data sets involving mammal, primate and influenza evolution. Finally, we explore methods to visualize the complex posterior distribution that results from inference under such models. Conclusions The examples suggest that large sequence datasets may only require a small number of local molecular clocks to reconcile their branch lengths with a time scale. All of the analyses described here are implemented in the open access software package BEAST 1.5.4 (http://beast-mcmc.googlecode.com/). PMID:20807414
Relaxed clocks and inferences of heterogeneous patterns of nucleotide substitution and divergence time estimates across whales and dolphins (Mammalia: Cetacea).

PubMed

Dornburg, Alex; Brandley, Matthew C; McGowen, Michael R; Near, Thomas J

2012-02-01

Various nucleotide substitution models have been developed to accommodate among lineage rate heterogeneity, thereby relaxing the assumptions of the strict molecular clock. Recently developed "uncorrelated relaxed clock" and "random local clock" (RLC) models allow decoupling of nucleotide substitution rates between descendant lineages and are thus predicted to perform better in the presence of lineage-specific rate heterogeneity. However, it is uncertain how these models perform in the presence of punctuated shifts in substitution rate, especially between closely related clades. Using cetaceans (whales and dolphins) as a case study, we test the performance of these two substitution models in estimating both molecular rates and divergence times in the presence of substantial lineage-specific rate heterogeneity. Our RLC analyses of whole mitochondrial genome alignments find evidence for up to ten clade-specific nucleotide substitution rate shifts in cetaceans. We provide evidence that in the uncorrelated relaxed clock framework, a punctuated shift in the rate of molecular evolution within a subclade results in posterior rate estimates that are either misled or intermediate between the disparate rate classes present in baleen and toothed whales. Using simulations, we demonstrate abrupt changes in rate isolated to one or a few lineages in the phylogeny can mislead rate and age estimation, even when the node of interest is calibrated. We further demonstrate how increasing prior age uncertainty can bias rate and age estimates, even while the 95% highest posterior density around age estimates decreases; in other words, increased precision for an inaccurate estimate. We interpret the use of external calibrations in divergence time studies in light of these results, suggesting that rate shifts at deep time scales may mislead inferences of absolute molecular rates and ages.
Characterization and calibration of a viscoelastic simplified potential energy clock model for inorganic glasses

DOE PAGES

Chambers, Robert S.; Tandon, Rajan; Stavig, Mark E.

2015-07-07

In this study, to analyze the stresses and strains generated during the solidification of glass-forming materials, stress and volume relaxation must be predicted accurately. Although the modeling attributes required to depict physical aging in organic glassy thermosets strongly resemble the structural relaxation in inorganic glasses, the historical modeling approaches have been distinctly different. To determine whether a common constitutive framework can be applied to both classes of materials, the nonlinear viscoelastic simplified potential energy clock (SPEC) model, developed originally for glassy thermosets, was calibrated for the Schott 8061 inorganic glass and used to analyze a number of tests. A practicalmore » methodology for material characterization and model calibration is discussed, and the structural relaxation mechanism is interpreted in the context of SPEC model constitutive equations. SPEC predictions compared to inorganic glass data collected from thermal strain measurements and creep tests demonstrate the ability to achieve engineering accuracy and make the SPEC model feasible for engineering applications involving a much broader class of glassy materials.« less
Note: Pulsed optically pumped atomic clock based on a paraffin-coated cell

NASA Astrophysics Data System (ADS)

Lin, Haixiao; Deng, Jianliao; Lin, Jinda; Zhang, Song; Hu, Yao; Wang, Yuzhu

2018-06-01

We report on the implementation of a pulsed optically pumped atomic clock based on a paraffin-coated cell. The relaxation times are measured, with the longitudinal relaxation time, T1 = 9.7 ± 0.4 ms, and the transversal relaxation time, T2 = 0.40 ± 0.03 ms. We demonstrated that the measured frequency stability of the clock is 3.9 × 10-13 τ-1/2 (1 s ≤ τ ≤ 100 s) and reaches a value of 3.1 × 10-14 for τ = 1000 s, where τ is the averaging time. This is an unprecedented result for a paraffin-coated vapor cell clock, and it makes significant contributions toward improving the performance of the wall-coated vapor cell atomic clock.
The impact of calibration and clock-model choice on molecular estimates of divergence times.

PubMed

Duchêne, Sebastián; Lanfear, Robert; Ho, Simon Y W

2014-09-01

Phylogenetic estimates of evolutionary timescales can be obtained from nucleotide sequence data using the molecular clock. These estimates are important for our understanding of evolutionary processes across all taxonomic levels. The molecular clock needs to be calibrated with an independent source of information, such as fossil evidence, to allow absolute ages to be inferred. Calibration typically involves fixing or constraining the age of at least one node in the phylogeny, enabling the ages of the remaining nodes to be estimated. We conducted an extensive simulation study to investigate the effects of the position and number of calibrations on the resulting estimate of the timescale. Our analyses focused on Bayesian estimates obtained using relaxed molecular clocks. Our findings suggest that an effective strategy is to include multiple calibrations and to prefer those that are close to the root of the phylogeny. Under these conditions, we found that evolutionary timescales could be estimated accurately even when the relaxed-clock model was misspecified and when the sequence data were relatively uninformative. We tested these findings in a case study of simian foamy virus, where we found that shallow calibrations caused the overall timescale to be underestimated by up to three orders of magnitude. Finally, we provide some recommendations for improving the practice of molecular-clock calibration. Copyright © 2014 Elsevier Inc. All rights reserved.
Reduced-Volume Fracture Toughness Characterization for Transparent Polymers

DTIC Science & Technology

2015-03-21

Caruthers et al. (2004) developed a thermodynamically consistent, nonlinear viscoelastic bulk constitutive model based on a potential energy clock ( PEC ...except that relaxation times change. Because of its formulation, the PEC model predicts mechanical yield as a natural consequence of relaxation...softening type of behavior, but hysteresis effects are not naturally accounted for. Adolf et al. (2009) developed a method of simplifying the PEC model
The oldest platypus and its bearing on divergence timing of the platypus and echidna clades

PubMed Central

Rowe, Timothy; Rich, Thomas H.; Vickers-Rich, Patricia; Springer, Mark; Woodburne, Michael O.

2008-01-01

Monotremes have left a poor fossil record, and paleontology has been virtually mute during two decades of discussion about molecular clock estimates of the timing of divergence between the platypus and echidna clades. We describe evidence from high-resolution x-ray computed tomography indicating that Teinolophos, an Early Cretaceous fossil from Australia's Flat Rocks locality (121–112.5 Ma), lies within the crown clade Monotremata, as a basal platypus. Strict molecular clock estimates of the divergence between platypus and echidnas range from 17 to 80 Ma, but Teinolophos suggests that the two monotreme clades were already distinct in the Early Cretaceous, and that their divergence may predate even the oldest strict molecular estimates by at least 50%. We generated relaxed molecular clock models using three different data sets, but only one yielded a date overlapping with the age of Teinolophos. Morphology suggests that Teinolophos is a platypus in both phylogenetic and ecological aspects, and tends to contradict the popular view of rapid Cenozoic monotreme diversification. Whereas the monotreme fossil record is still sparse and open to interpretation, the new data are consistent with much slower ecological, morphological, and taxonomic diversification rates for monotremes than in their sister taxon, the therian mammals. This alternative view of a deep geological history for monotremes suggests that rate heterogeneities may have affected mammalian evolution in such a way as to defeat strict molecular clock models and to challenge even relaxed molecular clock models when applied to mammalian history at a deep temporal scale. PMID:18216270
The oldest platypus and its bearing on divergence timing of the platypus and echidna clades.

PubMed

Rowe, Timothy; Rich, Thomas H; Vickers-Rich, Patricia; Springer, Mark; Woodburne, Michael O

2008-01-29

Monotremes have left a poor fossil record, and paleontology has been virtually mute during two decades of discussion about molecular clock estimates of the timing of divergence between the platypus and echidna clades. We describe evidence from high-resolution x-ray computed tomography indicating that Teinolophos, an Early Cretaceous fossil from Australia's Flat Rocks locality (121-112.5 Ma), lies within the crown clade Monotremata, as a basal platypus. Strict molecular clock estimates of the divergence between platypus and echidnas range from 17 to 80 Ma, but Teinolophos suggests that the two monotreme clades were already distinct in the Early Cretaceous, and that their divergence may predate even the oldest strict molecular estimates by at least 50%. We generated relaxed molecular clock models using three different data sets, but only one yielded a date overlapping with the age of Teinolophos. Morphology suggests that Teinolophos is a platypus in both phylogenetic and ecological aspects, and tends to contradict the popular view of rapid Cenozoic monotreme diversification. Whereas the monotreme fossil record is still sparse and open to interpretation, the new data are consistent with much slower ecological, morphological, and taxonomic diversification rates for monotremes than in their sister taxon, the therian mammals. This alternative view of a deep geological history for monotremes suggests that rate heterogeneities may have affected mammalian evolution in such a way as to defeat strict molecular clock models and to challenge even relaxed molecular clock models when applied to mammalian history at a deep temporal scale.
Cross-validation to select Bayesian hierarchical models in phylogenetics.

PubMed

Duchêne, Sebastián; Duchêne, David A; Di Giallonardo, Francesca; Eden, John-Sebastian; Geoghegan, Jemma L; Holt, Kathryn E; Ho, Simon Y W; Holmes, Edward C

2016-05-26

Recent developments in Bayesian phylogenetic models have increased the range of inferences that can be drawn from molecular sequence data. Accordingly, model selection has become an important component of phylogenetic analysis. Methods of model selection generally consider the likelihood of the data under the model in question. In the context of Bayesian phylogenetics, the most common approach involves estimating the marginal likelihood, which is typically done by integrating the likelihood across model parameters, weighted by the prior. Although this method is accurate, it is sensitive to the presence of improper priors. We explored an alternative approach based on cross-validation that is widely used in evolutionary analysis. This involves comparing models according to their predictive performance. We analysed simulated data and a range of viral and bacterial data sets using a cross-validation approach to compare a variety of molecular clock and demographic models. Our results show that cross-validation can be effective in distinguishing between strict- and relaxed-clock models and in identifying demographic models that allow growth in population size over time. In most of our empirical data analyses, the model selected using cross-validation was able to match that selected using marginal-likelihood estimation. The accuracy of cross-validation appears to improve with longer sequence data, particularly when distinguishing between relaxed-clock models. Cross-validation is a useful method for Bayesian phylogenetic model selection. This method can be readily implemented even when considering complex models where selecting an appropriate prior for all parameters may be difficult.
A Kolmogorov-Smirnov test for the molecular clock based on Bayesian ensembles of phylogenies

PubMed Central

Antoneli, Fernando; Passos, Fernando M.; Lopes, Luciano R.

2018-01-01

Divergence date estimates are central to understand evolutionary processes and depend, in the case of molecular phylogenies, on tests of molecular clocks. Here we propose two non-parametric tests of strict and relaxed molecular clocks built upon a framework that uses the empirical cumulative distribution (ECD) of branch lengths obtained from an ensemble of Bayesian trees and well known non-parametric (one-sample and two-sample) Kolmogorov-Smirnov (KS) goodness-of-fit test. In the strict clock case, the method consists in using the one-sample Kolmogorov-Smirnov (KS) test to directly test if the phylogeny is clock-like, in other words, if it follows a Poisson law. The ECD is computed from the discretized branch lengths and the parameter λ of the expected Poisson distribution is calculated as the average branch length over the ensemble of trees. To compensate for the auto-correlation in the ensemble of trees and pseudo-replication we take advantage of thinning and effective sample size, two features provided by Bayesian inference MCMC samplers. Finally, it is observed that tree topologies with very long or very short branches lead to Poisson mixtures and in this case we propose the use of the two-sample KS test with samples from two continuous branch length distributions, one obtained from an ensemble of clock-constrained trees and the other from an ensemble of unconstrained trees. Moreover, in this second form the test can also be applied to test for relaxed clock models. The use of a statistically equivalent ensemble of phylogenies to obtain the branch lengths ECD, instead of one consensus tree, yields considerable reduction of the effects of small sample size and provides a gain of power. PMID:29300759
Characterization of the uncertainty of divergence time estimation under relaxed molecular clock models using multiple loci.

PubMed

Zhu, Tianqi; Dos Reis, Mario; Yang, Ziheng

2015-03-01

Genetic sequence data provide information about the distances between species or branch lengths in a phylogeny, but not about the absolute divergence times or the evolutionary rates directly. Bayesian methods for dating species divergences estimate times and rates by assigning priors on them. In particular, the prior on times (node ages on the phylogeny) incorporates information in the fossil record to calibrate the molecular tree. Because times and rates are confounded, our posterior time estimates will not approach point values even if an infinite amount of sequence data are used in the analysis. In a previous study we developed a finite-sites theory to characterize the uncertainty in Bayesian divergence time estimation in analysis of large but finite sequence data sets under a strict molecular clock. As most modern clock dating analyses use more than one locus and are conducted under relaxed clock models, here we extend the theory to the case of relaxed clock analysis of data from multiple loci (site partitions). Uncertainty in posterior time estimates is partitioned into three sources: Sampling errors in the estimates of branch lengths in the tree for each locus due to limited sequence length, variation of substitution rates among lineages and among loci, and uncertainty in fossil calibrations. Using a simple but analogous estimation problem involving the multivariate normal distribution, we predict that as the number of loci ([Formula: see text]) goes to infinity, the variance in posterior time estimates decreases and approaches the infinite-data limit at the rate of 1/[Formula: see text], and the limit is independent of the number of sites in the sequence alignment. We then confirmed the predictions by using computer simulation on phylogenies of two or three species, and by analyzing a real genomic data set for six primate species. Our results suggest that with the fossil calibrations fixed, analyzing multiple loci or site partitions is the most effective way for improving the precision of posterior time estimation. However, even if a huge amount of sequence data is analyzed, considerable uncertainty will persist in time estimates. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society of Systematic Biologists.
A reassessment of the emergence time of European bat lyssavirus type 1.

PubMed

Hughes, Gareth J

2008-12-01

The previous study of the evolutionary rates of European bat lyssavirus type 1 (EBLV-1) used a strict molecular clock to estimate substitution rates of the nucleoprotein gene and in turn times of the most recent common ancestor (tMRCA) of the entire genotype and the two major EBLV-1 lineages (EBLV-1A and EBLV-1B). The results of that study suggested that the evolutionary rate of EBLV-1 was one of the lowest recorded for RNA viruses and that genetic diversity of EBLV-1 arose 500-750 years ago. Here I have shown that the use of a relaxed molecular clock (allowing branch rates to vary within a phylogeny) shows that these previous estimates should be revised. The relaxed clock provides a significantly better fit to all datasets. The substitution rate of EBLV-1B is compatible to that expected given previous estimates for the N gene of rabies virus whilst rate estimations for EBLV-1A appear to be confounded by substantial rate variation within the phylogeny. The relaxed clock substitution rate for EBLV-1 (1.1 x 10(-4)) is higher than had been estimated previously, and closer to that expected for the N gene. Moreover, tMRCA estimates for EBLV-1 are substantially reduced using the relaxed molecular clock (70-300 years) although the differing dynamics of EBLV-1A and EBLV-1B confound the confidence in this estimate. Current diversity of both EBLV-1A and EBLV-1B appears to have emerged within the last 100 years. Reconstruction of the population histories suggests that EBLV-1B may be emerging whilst the signal derived from the EBLV-1A phylogeny may be dampened by clade-specific dynamics.
Inflation of Molecular Clock Rates and Dates: Molecular Phylogenetics, Biogeography, and Diversification of a Global Cicada Radiation from Australasia (Hemiptera: Cicadidae: Cicadettini).

PubMed

Marshall, David C; Hill, Kathy B R; Moulds, Max; Vanderpool, Dan; Cooley, John R; Mohagan, Alma B; Simon, Chris

2016-01-01

Dated phylogenetic trees are important for studying mechanisms of diversification, and molecular clocks are important tools for studies of organisms lacking good fossil records. However, studies have begun to identify problems in molecular clock dates caused by uncertainty of the modeled molecular substitution process. Here we explore Bayesian relaxed-clock molecular dating while studying the biogeography of ca. 200 species from the global cicada tribe Cicadettini. Because the available fossils are few and uninformative, we calibrate our trees in part with a cytochrome oxidase I (COI) clock prior encompassing a range of literature estimates for arthropods. We show that tribe-level analyses calibrated solely with the COI clock recover extremely old dates that conflict with published estimates for two well-studied New Zealand subclades within Cicadettini. Additional subclade analyses suggest that COI relaxed-clock rates and maximum-likelihood branch lengths become inflated relative to EF-1[Formula: see text] intron and exon rates and branch lengths as clade age increases. We present corrected estimates derived from: (i) an extrapolated EF-1[Formula: see text] exon clock derived from COI-calibrated analysis within the largest New Zealand subclade; (ii) post hoc scaling of the tribe-level chronogram using results from subclade analyses; and (iii) exploitation of a geological calibration point associated with New Caledonia. We caution that considerable uncertainty is generated due to dependence of substitution estimates on both the taxon sample and the choice of model, including gamma category number and the choice of empirical versus estimated base frequencies. Our results suggest that diversification of the tribe Cicadettini commenced in the early- to mid-Cenozoic and continued with the development of open, arid habitats in Australia and worldwide. We find that Cicadettini is a rare example of a global terrestrial animal group with an Australasian origin, with all non-Australasian genera belonging to two distal clades. Within Australia, we show that Cicadettini is more widely distributed than any other cicada tribe, diverse in temperate, arid and monsoonal habitats, and nearly absent from rainforests. We comment on the taxonomic implications of our findings for thirteen cicada genera. © The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Estimating evolutionary rates using time-structured data: a general comparison of phylogenetic methods.

PubMed

Duchêne, Sebastián; Geoghegan, Jemma L; Holmes, Edward C; Ho, Simon Y W

2016-11-15

In rapidly evolving pathogens, including viruses and some bacteria, genetic change can accumulate over short time-frames. Accordingly, their sampling times can be used to calibrate molecular clocks, allowing estimation of evolutionary rates. Methods for estimating rates from time-structured data vary in how they treat phylogenetic uncertainty and rate variation among lineages. We compiled 81 virus data sets and estimated nucleotide substitution rates using root-to-tip regression, least-squares dating and Bayesian inference. Although estimates from these three methods were often congruent, this largely relied on the choice of clock model. In particular, relaxed-clock models tended to produce higher rate estimates than methods that assume constant rates. Discrepancies in rate estimates were also associated with high among-lineage rate variation, and phylogenetic and temporal clustering. These results provide insights into the factors that affect the reliability of rate estimates from time-structured sequence data, emphasizing the importance of clock-model testing. sduchene@unimelb.edu.au or garzonsebastian@hotmail.comSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Novel non-parametric models to estimate evolutionary rates and divergence times from heterochronous sequence data.

PubMed

Fourment, Mathieu; Holmes, Edward C

2014-07-24

Early methods for estimating divergence times from gene sequence data relied on the assumption of a molecular clock. More sophisticated methods were created to model rate variation and used auto-correlation of rates, local clocks, or the so called "uncorrelated relaxed clock" where substitution rates are assumed to be drawn from a parametric distribution. In the case of Bayesian inference methods the impact of the prior on branching times is not clearly understood, and if the amount of data is limited the posterior could be strongly influenced by the prior. We develop a maximum likelihood method--Physher--that uses local or discrete clocks to estimate evolutionary rates and divergence times from heterochronous sequence data. Using two empirical data sets we show that our discrete clock estimates are similar to those obtained by other methods, and that Physher outperformed some methods in the estimation of the root age of an influenza virus data set. A simulation analysis suggests that Physher can outperform a Bayesian method when the real topology contains two long branches below the root node, even when evolution is strongly clock-like. These results suggest it is advisable to use a variety of methods to estimate evolutionary rates and divergence times from heterochronous sequence data. Physher and the associated data sets used here are available online at http://code.google.com/p/physher/.
Approximate likelihood calculation on a phylogeny for Bayesian estimation of divergence times.

PubMed

dos Reis, Mario; Yang, Ziheng

2011-07-01

The molecular clock provides a powerful way to estimate species divergence times. If information on some species divergence times is available from the fossil or geological record, it can be used to calibrate a phylogeny and estimate divergence times for all nodes in the tree. The Bayesian method provides a natural framework to incorporate different sources of information concerning divergence times, such as information in the fossil and molecular data. Current models of sequence evolution are intractable in a Bayesian setting, and Markov chain Monte Carlo (MCMC) is used to generate the posterior distribution of divergence times and evolutionary rates. This method is computationally expensive, as it involves the repeated calculation of the likelihood function. Here, we explore the use of Taylor expansion to approximate the likelihood during MCMC iteration. The approximation is much faster than conventional likelihood calculation. However, the approximation is expected to be poor when the proposed parameters are far from the likelihood peak. We explore the use of parameter transforms (square root, logarithm, and arcsine) to improve the approximation to the likelihood curve. We found that the new methods, particularly the arcsine-based transform, provided very good approximations under relaxed clock models and also under the global clock model when the global clock is not seriously violated. The approximation is poorer for analysis under the global clock when the global clock is seriously wrong and should thus not be used. The results suggest that the approximate method may be useful for Bayesian dating analysis using large data sets.
Buffer Gas Experiments in Mercury (Hg+) Ion Clock

NASA Technical Reports Server (NTRS)

Chung, Sang K.; Prestage, John D.; Tjoelker, Robert L.; Maleki, Lute

2004-01-01

We describe the results of the frequency shifts measured from various buffer gases that might be used as a buffer gas to increase the loading efficiency and cooling of ions trapped in a small mercury ion clock. The small mass, volume and power requirement of space clock precludes the use of turbo pumps. Hence, a hermetically sealed vacuum system, incorporating a suitable getter material with a fixed amount of inert buffer gas may be a practical alternative to the groundbased system. The collision shifts of 40,507,347.996xx Hz clock transition for helium, neon and argon buffer gases were measured in the ambient earth magnetic field. In addition to the above non-getterable inert gases we also measured the frequency shifts due to getterable, molecular hydrogen and nitrogen gases which may be used as buffer gases when incorporated with a miniature ion pump. We also examined the frequency shift due to the low methane gas partial pressure in a fixed higher pressure neon buffer gas environment. Methane gas interacted with mercury ions in a peculiar way as to preserve the ion number but to relax the population difference in the two hyperfine clock states and thereby reducing the clock resonance signal. The same population relaxation was also observed for other molecular buffer gases (N H,) but at much reduced rate.
Major Radiations in the Evolution of Caviid Rodents: Reconciling Fossils, Ghost Lineages, and Relaxed Molecular Clocks

PubMed Central

Pérez, María Encarnación; Pol, Diego

2012-01-01

Background Caviidae is a diverse group of caviomorph rodents that is broadly distributed in South America and is divided into three highly divergent extant lineages: Caviinae (cavies), Dolichotinae (maras), and Hydrochoerinae (capybaras). The fossil record of Caviidae is only abundant and diverse since the late Miocene. Caviids belongs to Cavioidea sensu stricto (Cavioidea s.s.) that also includes a diverse assemblage of extinct taxa recorded from the late Oligocene to the middle Miocene of South America (“eocardiids”). Results A phylogenetic analysis combining morphological and molecular data is presented here, evaluating the time of diversification of selected nodes based on the calibration of phylogenetic trees with fossil taxa and the use of relaxed molecular clocks. This analysis reveals three major phases of diversification in the evolutionary history of Cavioidea s.s. The first two phases involve two successive radiations of extinct lineages that occurred during the late Oligocene and the early Miocene. The third phase consists of the diversification of Caviidae. The initial split of caviids is dated as middle Miocene by the fossil record. This date falls within the 95% higher probability distribution estimated by the relaxed Bayesian molecular clock, although the mean age estimate ages are 3.5 to 7 Myr older. The initial split of caviids is followed by an obscure period of poor fossil record (refered here as the Mayoan gap) and then by the appearance of highly differentiated modern lineages of caviids, which evidentially occurred at the late Miocene as indicated by both the fossil record and molecular clock estimates. Conclusions The integrated approach used here allowed us identifying the agreements and discrepancies of the fossil record and molecular clock estimates on the timing of the major events in cavioid evolution, revealing evolutionary patterns that would not have been possible to gather using only molecular or paleontological data alone. PMID:23144757
Repetitive Interrogation of 2-Level Quantum Systems

NASA Technical Reports Server (NTRS)

Prestage, John D.; Chung, Sang K.

2010-01-01

Trapped ion clocks derive information from a reference atomic transition by repetitive interrogations of the same quantum system, either a single ion or ionized gas of many millions of ions. Atomic beam frequency standards, by contrast, measure reference atomic transitions in a continuously replenished "flow through" configuration where initial ensemble atomic coherence is zero. We will describe some issues and problems that can arise when atomic state selection and preparation of the quantum atomic system is not completed, that is, optical pumping has not fully relaxed the coherence and also not fully transferred atoms to the initial state. We present a simple two-level density matrix analysis showing how frequency shifts during the state-selection process can cause frequency shifts of the measured clock transition. Such considerations are very important when a low intensity lamp light source is used for state selection, where there is relatively weak relaxation and re-pumping of ions to an initial state and much weaker 'environmental' relaxation of the atomic coherence set-up in the atomic sample.

Bayesian relaxed clock estimation of divergence times in foraminifera.

PubMed

Groussin, Mathieu; Pawlowski, Jan; Yang, Ziheng

2011-10-01

Accurate and precise estimation of divergence times during the Neo-Proterozoic is necessary to understand the speciation dynamic of early Eukaryotes. However such deep divergences are difficult to date, as the molecular clock is seriously violated. Recent improvements in Bayesian molecular dating techniques allow the relaxation of the molecular clock hypothesis as well as incorporation of multiple and flexible fossil calibrations. Divergence times can then be estimated even when the evolutionary rate varies among lineages and even when the fossil calibrations involve substantial uncertainties. In this paper, we used a Bayesian method to estimate divergence times in Foraminifera, a group of unicellular eukaryotes, known for their excellent fossil record but also for the high evolutionary rates of their genomes. Based on multigene data we reconstructed the phylogeny of Foraminifera and dated their origin and the major radiation events. Our estimates suggest that Foraminifera emerged during the Cryogenian (650-920 Ma, Neo-Proterozoic), with a mean time around 770 Ma, about 220 Myr before the first appearance of reliable foraminiferal fossils in sediments (545 Ma). Most dates are in agreement with the fossil record, but in general our results suggest earlier origins of foraminiferal orders. We found that the posterior time estimates were robust to specifications of the prior. Our results highlight inter-species variations of evolutionary rates in Foraminifera. Their effect was partially overcome by using the partitioned Bayesian analysis to accommodate rate heterogeneity among data partitions and using the relaxed molecular clock to account for changing evolutionary rates. However, more coding genes appear necessary to obtain more precise estimates of divergence times and to resolve the conflicts between fossil and molecular date estimates. Copyright © 2011 Elsevier Inc. All rights reserved.
Coupled Leidenfrost states as a monodisperse granular clock

NASA Astrophysics Data System (ADS)

Liu, Rui; Yang, Mingcheng; Chen, Ke; Hou, Meiying; To, Kiwing

2016-08-01

Using an event-driven molecular dynamics simulation, we show that simple monodisperse granular beads confined in coupled columns may oscillate as a different type of granular clock. To trigger this oscillation, the system needs to be driven against gravity into a density-inverted state, with a high-density clustering phase supported from below by a gaslike low-density phase (Leidenfrost effect) in each column. Our analysis reveals that the density-inverted structure and the relaxation dynamics between the phases can amplify any small asymmetry between the columns, and lead to a giant oscillation. The oscillation occurs only for an intermediate range of the coupling strength, and the corresponding phase diagram can be universally described with a characteristic height of the density-inverted structure. A minimal two-phase model is proposed and a linear stability analysis shows that the triggering mechanism of the oscillation can be explained as a switchable two-parameter Andronov-Hopf bifurcation. Numerical solutions of the model also reproduce similar oscillatory dynamics to the simulation results.
Gas-cell atomic clocks for space: new results and alternative schemes

NASA Astrophysics Data System (ADS)

Affolderbach, C.; Breschi, E.; Schori, C.; Mileti, G.

2017-11-01

We present our development activities on compact Rubidium gas-cell atomic frequency standards, for use in space-borne and ground-based applications. We experimentally demonstrate a high-performance laser optically-pumped Rb clock for space applications such as telecommunications, science missions, and satellite navigation systems (e.g. GALILEO). Using a stabilised laser source and optimized gas cells, we reach clock stabilities as low as 1.5·10-12 τ-1/2 up to 103 s and 4·10-14 at 104 s. The results demonstrate the feasibility of a laser-pumped Rb clock reaching < 1·10-12 τ-1/2 in a compact device (<2 liters, 2 kg, 20 W), given optimization of the implemented techniques. A second activity concerns more radically miniaturized gas-cell clocks, aiming for low power consumption and a total volume around 1 cm3 , at the expense of relaxed frequency stability. Here miniaturized "chip-scale" vapour cells and use of coherent laser interrogation techniques are at the heart of the investigations.
A total-evidence approach to dating with fossils, applied to the early radiation of the hymenoptera.

PubMed

Ronquist, Fredrik; Klopfstein, Seraina; Vilhelmsen, Lars; Schulmeister, Susanne; Murray, Debra L; Rasnitsyn, Alexandr P

2012-12-01

Phylogenies are usually dated by calibrating interior nodes against the fossil record. This relies on indirect methods that, in the worst case, misrepresent the fossil information. Here, we contrast such node dating with an approach that includes fossils along with the extant taxa in a Bayesian total-evidence analysis. As a test case, we focus on the early radiation of the Hymenoptera, mostly documented by poorly preserved impression fossils that are difficult to place phylogenetically. Specifically, we compare node dating using nine calibration points derived from the fossil record with total-evidence dating based on 343 morphological characters scored for 45 fossil (4--20 complete) and 68 extant taxa. In both cases we use molecular data from seven markers (∼5 kb) for the extant taxa. Because it is difficult to model speciation, extinction, sampling, and fossil preservation realistically, we develop a simple uniform prior for clock trees with fossils, and we use relaxed clock models to accommodate rate variation across the tree. Despite considerable uncertainty in the placement of most fossils, we find that they contribute significantly to the estimation of divergence times in the total-evidence analysis. In particular, the posterior distributions on divergence times are less sensitive to prior assumptions and tend to be more precise than in node dating. The total-evidence analysis also shows that four of the seven Hymenoptera calibration points used in node dating are likely to be based on erroneous or doubtful assumptions about the fossil placement. With respect to the early radiation of Hymenoptera, our results suggest that the crown group dates back to the Carboniferous, ∼309 Ma (95% interval: 291--347 Ma), and diversified into major extant lineages much earlier than previously thought, well before the Triassic. [Bayesian inference; fossil dating; morphological evolution; relaxed clock; statistical phylogenetics.].
A Total-Evidence Approach to Dating with Fossils, Applied to the Early Radiation of the Hymenoptera

PubMed Central

Ronquist, Fredrik; Klopfstein, Seraina; Vilhelmsen, Lars; Schulmeister, Susanne; Murray, Debra L.; Rasnitsyn, Alexandr P.

2012-01-01

Abstract Phylogenies are usually dated by calibrating interior nodes against the fossil record. This relies on indirect methods that, in the worst case, misrepresent the fossil information. Here, we contrast such node dating with an approach that includes fossils along with the extant taxa in a Bayesian total-evidence analysis. As a test case, we focus on the early radiation of the Hymenoptera, mostly documented by poorly preserved impression fossils that are difficult to place phylogenetically. Specifically, we compare node dating using nine calibration points derived from the fossil record with total-evidence dating based on 343 morphological characters scored for 45 fossil (4--20 complete) and 68 extant taxa. In both cases we use molecular data from seven markers (∼5 kb) for the extant taxa. Because it is difficult to model speciation, extinction, sampling, and fossil preservation realistically, we develop a simple uniform prior for clock trees with fossils, and we use relaxed clock models to accommodate rate variation across the tree. Despite considerable uncertainty in the placement of most fossils, we find that they contribute significantly to the estimation of divergence times in the total-evidence analysis. In particular, the posterior distributions on divergence times are less sensitive to prior assumptions and tend to be more precise than in node dating. The total-evidence analysis also shows that four of the seven Hymenoptera calibration points used in node dating are likely to be based on erroneous or doubtful assumptions about the fossil placement. With respect to the early radiation of Hymenoptera, our results suggest that the crown group dates back to the Carboniferous, ∼309 Ma (95% interval: 291--347 Ma), and diversified into major extant lineages much earlier than previously thought, well before the Triassic. [Bayesian inference; fossil dating; morphological evolution; relaxed clock; statistical phylogenetics.] PMID:22723471
Evolution and dispersal of St. Louis encephalitis virus in the Americas.

PubMed

Auguste, Albert J; Pybus, Oliver G; Carrington, Christine V F

2009-07-01

Using a Bayesian coalescent approach on a dataset of 73 envelope gene sequences we estimated substitution rates and dates of divergence for St. Louis encephalitis virus (SLEV) in the Americas. We found significant rate heterogeneity among lineages, such that "relaxed" molecular clock models were much better supported than a strict molecular clock. The mean substitution rate estimated for all SLEV was 4.1x10(-4)substitutions/site/year (95% HPD 2.5-5.7)-higher than previous estimates that relied on the less well-suited strict clock. Mean substitution rates for individual lineages varied from 3.7x10(-4) to 7.2x10(-4)substitutions/site/year. For the first time we also assessed the magnitude and direction of viral gene flow within the Americas. The overall direction of gene flow during the period represented by the phylogeny is from South to North, and the region between 15 degrees N and 30 degrees N latitude appears to be the major source of virus for the rest of North America, which is consistent with migratory birds returning to their northern breeding grounds having acquired infection while wintering in the region of the Gulf of Mexico.
Estimation of divergence times in litostomatean ciliates (Ciliophora: Intramacronucleata), using Bayesian relaxed clock and 18S rRNA gene.

PubMed

Vďačný, Peter

2015-08-01

The class Litostomatea comprises a diverse assemblage of free-living and endosymbiotic ciliates. To understand diversification dynamic of litostomateans, divergence times of their main groups were estimated with the Bayesian molecular dating, a technique allowing relaxation of molecular clock and incorporation of flexible calibration points. The class Litostomatea very likely emerged during the Cryogenian around 680 Mya. The origin of the subclass Rhynchostomatia is dated to about 415 Mya, while that of the subclass Haptoria to about 654 Mya. The order Pleurostomatida, emerging about 556 Mya, was recognized as the oldest group within the subclass Haptoria. The order Spathidiida appeared in the Paleozoic about 442 Mya. The three remaining haptorian orders evolved in the Paleozoic/Mesozoic periods: Didiniida about 419 Mya, Lacrymariida about 269 Mya, and Haptorida about 194 Mya. The subclass Trichostomatia originated from a spathidiid ancestor in the Mesozoic about 260 Mya. A further goal of this study was to investigate the impact of various settings on posterior divergence time estimates. The root placement and tree topology as well as the priors of the rate-drift model, birth-death process and nucleotide substitution rate, had no significant effect on calculation of posterior divergence time estimates. However, removal of calibration points could significantly change time estimates at some nodes. Copyright © 2015 Elsevier GmbH. All rights reserved.
Short communication: phylodynamics analysis of the human immunodeficiency virus type 1 envelope gene in mother and child pairs.

PubMed

Santos, Luciane Amorim; Gray, Rebecca R; Monteiro-Cunha, Joana Paixão; Strazza, Evandra; Kashima, Simone; Santos, Edson de Souza; Araújo, Thessika Hialla Almeida; Gonçalves, Marilda de Souza; Salemi, Marco; Alcantara, Luiz Carlos Junior

2015-09-01

Characterizing the impact of HIV transmission routes on viral genetic diversity can improve the understanding of the mechanisms of virus evolution and adaptation. HIV vertical transmission can occur in utero, during delivery, or while breastfeeding. The present study investigated the phylodynamics of the HIV-1 env gene in mother-to-child transmission by analyzing one chronically infected pair from Brazil and three acutely infected pairs from Zambia, with three to five time points. Sequences from 25 clones from each sample were obtained and aligned using Clustal X. ML trees were constructed in PhyML using the best evolutionary model. Bayesian analyses testing the relaxed and strict molecular clock were performed using BEAST and a Bayesian Skyline Plot (BSP) was construed. The genetic variability of previously described epitopes was investigated and compared between each individual time point and between mother and child sequences. The relaxed molecular clock was the best-fitted model for all datasets. The tree topologies did not show differentiation in the evolutionary dynamics of the virus circulating in the mother from the viral population in the child. In the BSP, the effective population size was more constant in time in the chronically infected patients while in the acute patients it was possible to detect bottlenecks. The genetic variability within viral epitopes recognized by the human immune system was considerably higher among the chronically infected pair in comparison with acutely infected pairs. These results contribute to a better understanding of HIV-1 evolutionary dynamics in mother-to-child transmission.
How the Central American Seaway and an ancient northern passage affected flatfish diversification.

PubMed

Byrne, Lisa; Chapleau, François; Aris-Brosou, Stéphane

2018-05-21

While the natural history of flatfish has been debated for decades, the mode of diversification of this biologically and economically important group has never been elucidated. To address this question, we assembled the largest molecular data set to date, covering > 300 species (out of ca. 800 extant), from 13 of the 14 known families over nine genes, and employed relaxed molecular clocks to uncover their patterns of diversification. As the fossil record of flatfish is contentious, we used sister species distributed on both sides of the American continent to calibrate clock models based on the closure of the Central American Seaway (CAS), and on their current species range. We show that flatfish diversified in two bouts, as species that are today distributed around the Equator diverged during the closure of CAS, while those with a northern range diverged after this, hereby suggesting the existence of a post-CAS closure dispersal for these northern species, most likely along a trans-Arctic northern route, a hypothesis fully compatible with paleogeographic reconstructions.
A Methodology for the Design and Verification of Globally Asynchronous/Locally Synchronous Architectures

NASA Technical Reports Server (NTRS)

Miller, Steven P.; Whalen, Mike W.; O'Brien, Dan; Heimdahl, Mats P.; Joshi, Anjali

2005-01-01

Recent advanced in model-checking have made it practical to formally verify the correctness of many complex synchronous systems (i.e., systems driven by a single clock). However, many computer systems are implemented by asynchronously composing several synchronous components, where each component has its own clock and these clocks are not synchronized. Formal verification of such Globally Asynchronous/Locally Synchronous (GA/LS) architectures is a much more difficult task. In this report, we describe a methodology for developing and reasoning about such systems. This approach allows a developer to start from an ideal system specification and refine it along two axes. Along one axis, the system can be refined one component at a time towards an implementation. Along the other axis, the behavior of the system can be relaxed to produce a more cost effective but still acceptable solution. We illustrate this process by applying it to the synchronization logic of a Dual Fight Guidance System, evolving the system from an ideal case in which the components do not fail and communicate synchronously to one in which the components can fail and communicate asynchronously. For each step, we show how the system requirements have to change if the system is to be implemented and prove that each implementation meets the revised system requirements through modelchecking.
A clock-aided positioning algorithm based on Kalman model of GNSS receiver clock bias

NASA Astrophysics Data System (ADS)

Zhu, Lingyao; Li, Zishen; Yuan, Hong

2017-10-01

The modeling and forecasting of the receiver clock bias is of practical significance, including the improvement of positioning accuracy, etc. When the clock frequency of the receiver is stable, the model can be established according to the historical clock bias data and the clock bias of the following time can be predicted. For this, we adopted the Kalman model to predict the receiver clock bias based on the calculated clock bias data obtained from the laboratory via sliding mode. Meanwhile, the relevant clock-aided positioning algorithm was presented. The results show that: the Kalman model can be used in practical work; and that under the condition that only 3 satellite signal can be received, this clock-aided positioning results can meet the needs of civilian users, which improves the continuity of positioning in harsh conditions.
SPECabq v. 2.0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chambers, Robert S.; Neidigk, Matthew A.

Sandia SPECabq is FORTRAN code that defines the user supplied subroutines needed to perform nonlinear viscoelastic analyses in the ABAQUS commercial finite element code based on the Simplified Potential Energy Clock (SPEC) Model. The SPEC model was published in the open literature in 2009. It must be compiled and linked with the ABAQUS libraries under the user supplied subroutine option of the ABAQUS executable script. The subroutine is used to analyze the thermomechanical behavior of isotropic polymers predicting things like how a polymer may undergo stress or volume relaxation under different temperature and loading environments. This subroutine enables the ABAQUSmore » finite element code to be used for analyzing the thermo-mechanical behavior of samples and parts that are made from glassy polymers.« less
Incorporating Orienteering in School Programs.

ERIC Educational Resources Information Center

Bradford, Douglas

Orienteering has been described as being "either a serious sport, or a relaxing recreation". Orienteering can be a family affair or an individual fight against the clock. In its simplest form, orienteering can be described as a cross-country run, jog, or walk on a predetermined course, using a map and a compass to find several control points on…
Is dynamic two-dimensional anal ultrasonography useful in the assessment of anismus? A comparison with manometry.

PubMed

Murad-Regadas, Sthela Maria; Regadas, Francisco Sérgio P; Barreto, Rosilma Gorete Lima; Rodrigues, Lusmar Veras; Fernandes, Graziela Olivia da Silva; Lima, Doryane Maria dos Reis

2010-01-01

Anismus is a prevalent functional cause of outlet delay. It is characterized by symptoms of obstructed defecation associated with paradoxical contraction of the pelvic floor muscles. To evaluate the ability of two dimensional anal ultrasonography to identify anismus patients with paradoxical contraction or normal relaxation, comparing findings with manometric measurements. Forty-nine women presenting with outlet delay and a mean validated Wexner constipation score of 13.5 were included in a prospective study. Following screening with anal manometry, the patients were assigned to one of two groups: G-I -with normal relaxation and G-II -patients with anismus. Dynamic anorectal ultrasonography was used to quantifier the movement of the puborectalis muscle and to measure changes in the angle between two converging lines drawn from the 3 o'clock and the 9 o'clock positions of the endoprobe circumference to the internal border of the puborectalis muscle. The angle decreases during straining in patients with normal relaxation, but increases in patients with anismus. The agreement between the two techniques was verified with the Kappa index. In manometry, during straining the anal canal pressure decreased by 41.3% in G-I and increased by 168.6% in G-II, indicating a diagnosis of anismus for the second group. In US, during straining, the angle produced by the movement of the puborectalis muscle decreased from 63 ± 1.31 to 58 ± 1.509 degrees (P = 0.0135) in 23 of the 30 patients in G-I, indicating normal relaxation, and increased from 66 ± 0.972 to 72 ± 0.897 degrees (P = 0.0001) in 16 of the 19 patients in G-II, indicating anismus. The index of agreement between manometry and two dimensional anal ultrasonography was moderate: 77% (23/30) for G-I and 84% (16/19) for G-II. Two-dimensional dynamic anal ultrasonography showed similar results previously suggested by anal manometry at identifying patients with normal relaxation or paradoxical contraction.
Microfabricated alkali vapor cell with anti-relaxation wall coating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Straessle, R.; Pétremand, Y.; Briand, D.

2014-07-28

We present a microfabricated alkali vapor cell equipped with an anti-relaxation wall coating. The anti-relaxation coating used is octadecyltrichlorosilane and the cell was sealed by thin-film indium-bonding at a low temperature of 140 °C. The cell body is made of silicon and Pyrex and features a double-chamber design. Depolarizing properties due to liquid Rb droplets are avoided by confining the Rb droplets to one chamber only. Optical and microwave spectroscopy performed on this wall-coated cell are used to evaluate the cell's relaxation properties and a potential gas contamination. Double-resonance signals obtained from the cell show an intrinsic linewidth that is significantlymore » lower than the linewidth that would be expected in case the cell had no wall coating but only contained a buffer-gas contamination on the level measured by optical spectroscopy. Combined with further experimental evidence this proves the presence of a working anti-relaxation wall coating in the cell. Such cells are of interest for applications in miniature atomic clocks, magnetometers, and other quantum sensors.« less
A new stochastic model considering satellite clock interpolation errors in precise point positioning

NASA Astrophysics Data System (ADS)

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.
Phylogeny and temporal diversification of darters (Percidae: Etheostomatinae).

PubMed

Near, Thomas J; Bossu, Christen M; Bradburd, Gideon S; Carlson, Rose L; Harrington, Richard C; Hollingsworth, Phillip R; Keck, Benjamin P; Etnier, David A

2011-10-01

Discussions aimed at resolution of the Tree of Life are most often focused on the interrelationships of major organismal lineages. In this study, we focus on the resolution of some of the most apical branches in the Tree of Life through exploration of the phylogenetic relationships of darters, a species-rich clade of North American freshwater fishes. With a near-complete taxon sampling of close to 250 species, we aim to investigate strategies for efficient multilocus data sampling and the estimation of divergence times using relaxed-clock methods when a clade lacks a fossil record. Our phylogenetic data set comprises a single mitochondrial DNA (mtDNA) gene and two nuclear genes sampled from 245 of the 248 darter species. This dense sampling allows us to determine if a modest amount of nuclear DNA sequence data can resolve relationships among closely related animal species. Darters lack a fossil record to provide age calibration priors in relaxed-clock analyses. Therefore, we use a near-complete species-sampled phylogeny of the perciform clade Centrarchidae, which has a rich fossil record, to assess two distinct strategies of external calibration in relaxed-clock divergence time estimates of darters: using ages inferred from the fossil record and molecular evolutionary rate estimates. Comparison of Bayesian phylogenies inferred from mtDNA and nuclear genes reveals that heterospecific mtDNA is present in approximately 12.5% of all darter species. We identify three patterns of mtDNA introgression in darters: proximal mtDNA transfer, which involves the transfer of mtDNA among extant and sympatric darter species, indeterminate introgression, which involves the transfer of mtDNA from a lineage that cannot be confidently identified because the introgressed haplotypes are not clearly referable to mtDNA haplotypes in any recognized species, and deep introgression, which is characterized by species diversification within a recipient clade subsequent to the transfer of heterospecific mtDNA. The results of our analyses indicate that DNA sequences sampled from single-copy nuclear genes can provide appreciable phylogenetic resolution for closely related animal species. A well-resolved near-complete species-sampled phylogeny of darters was estimated with Bayesian methods using a concatenated mtDNA and nuclear gene data set with all identified heterospecific mtDNA haplotypes treated as missing data. The relaxed-clock analyses resulted in very similar posterior age estimates across the three sampled genes and methods of calibration and therefore offer a viable strategy for estimating divergence times for clades that lack a fossil record. In addition, an informative rank-free clade-based classification of darters that preserves the rich history of nomenclature in the group and provides formal taxonomic communication of darter clades was constructed using the mtDNA and nuclear gene phylogeny. On the whole, the appeal of mtDNA for phylogeny inference among closely related animal species is diminished by the observations of extensive mtDNA introgression and by finding appreciable phylogenetic signal in a modest sampling of nuclear genes in our phylogenetic analyses of darters.
Using Integer Clocks to Verify the Timing-Sync Sensor Network Protocol

NASA Technical Reports Server (NTRS)

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

NASA Astrophysics Data System (ADS)

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.
Simulating Future GPS Clock Scenarios with Two Composite Clock Algorithms

NASA Technical Reports Server (NTRS)

Suess, Matthias; Matsakis, Demetrios; Greenhall, Charles A.

2010-01-01

Using the GPS Toolkit, the GPS constellation is simulated using 31 satellites (SV) and a ground network of 17 monitor stations (MS). At every 15-minutes measurement epoch, the monitor stations measure the time signals of all satellites above a parameterized elevation angle. Once a day, the satellite clock estimates the station and satellite clocks. The first composite clock (B) is based on the Brown algorithm, and is now used by GPS. The second one (G) is based on the Greenhall algorithm. The composite clock of G and B performance are investigated using three ground-clock models. Model C simulates the current GPS configuration, in which all stations are equipped with cesium clocks, except for masers at USNO and Alternate Master Clock (AMC) sites. Model M is an improved situation in which every station is equipped with active hydrogen masers. Finally, Models F and O are future scenarios in which the USNO and AMC stations are equipped with fountain clocks instead of masers. Model F is a rubidium fountain, while Model O is more precise but futuristic Optical Fountain. Each model is evaluated using three performance metrics. The timing-related user range error having all satellites available is the first performance index (PI1). The second performance index (PI2) relates to the stability of the broadcast GPS system time itself. The third performance index (PI3) evaluates the stability of the time scales computed by the two composite clocks. A distinction is made between the "Signal-in-Space" accuracy and that available through a GNSS receiver.

Network news: prime time for systems biology of the plant circadian clock.

PubMed

McClung, C Robertson; Gutiérrez, Rodrigo A

2010-12-01

Whole-transcriptome analyses have established that the plant circadian clock regulates virtually every plant biological process and most prominently hormonal and stress response pathways. Systems biology efforts have successfully modeled the plant central clock machinery and an iterative process of model refinement and experimental validation has contributed significantly to the current view of the central clock machinery. The challenge now is to connect this central clock to the output pathways for understanding how the plant circadian clock contributes to plant growth and fitness in a changing environment. Undoubtedly, systems approaches will be needed to integrate and model the vastly increased volume of experimental data in order to extract meaningful biological information. Thus, we have entered an era of systems modeling, experimental testing, and refinement. This approach, coupled with advances from the genetic and biochemical analyses of clock function, is accelerating our progress towards a comprehensive understanding of the plant circadian clock network. Copyright © 2010 Elsevier Ltd. All rights reserved.
Generalized Autobalanced Ramsey Spectroscopy of Clock Transitions

NASA Astrophysics Data System (ADS)

Yudin, V. I.; Taichenachev, A. V.; Basalaev, M. Yu.; Zanon-Willette, T.; Pollock, J. W.; Shuker, M.; Donley, E. A.; Kitching, J.

2018-05-01

When performing precision measurements, the quantity being measured is often perturbed by the measurement process itself. Such measurements include precision frequency measurements for atomic clock applications carried out with Ramsey spectroscopy. With the aim of eliminating probe-induced perturbations, a method of generalized autobalanced Ramsey spectroscopy (GABRS) is presented and rigorously substantiated. The usual local-oscillator frequency control loop is augmented with a second control loop derived from secondary Ramsey sequences interspersed with the primary sequences and with a different Ramsey period. This second loop feeds back to a secondary clock variable and ultimately compensates for the perturbation of the clock frequency caused by the measurements in the first loop. We show that such a two-loop scheme can lead to perfect compensation for measurement-induced light shifts and does not suffer from the effects of relaxation, time-dependent pulse fluctuations and phase-jump modulation errors that are typical of other hyper-Ramsey schemes. Several variants of GABRS are explored based on different secondary variables including added relative phase shifts between Ramsey pulses, external frequency-step compensation, and variable second-pulse duration. We demonstrate that a universal antisymmetric error signal, and hence perfect compensation at a finite modulation amplitude, is generated only if an additional frequency step applied during both Ramsey pulses is used as the concomitant variable parameter. This universal technique can be applied to the fields of atomic clocks, high-resolution molecular spectroscopy, magnetically induced and two-photon probing schemes, Ramsey-type mass spectrometry, and the field of precision measurements. Some variants of GABRS can also be applied for rf atomic clocks using coherent-population-trapping-based Ramsey spectroscopy of the two-photon dark resonance.
Improved Short-Term Clock Prediction Method for Real-Time Positioning.

PubMed

Lv, Yifei; Dai, Zhiqiang; Zhao, Qile; Yang, Sheng; Zhou, Jinning; Liu, Jingnan

2017-06-06

The application of real-time precise point positioning (PPP) requires real-time precise orbit and clock products that should be predicted within a short time to compensate for the communication delay or data gap. Unlike orbit correction, clock correction is difficult to model and predict. The widely used linear model hardly fits long periodic trends with a small data set and exhibits significant accuracy degradation in real-time prediction when a large data set is used. This study proposes a new prediction model for maintaining short-term satellite clocks to meet the high-precision requirements of real-time clocks and provide clock extrapolation without interrupting the real-time data stream. Fast Fourier transform (FFT) is used to analyze the linear prediction residuals of real-time clocks. The periodic terms obtained through FFT are adopted in the sliding window prediction to achieve a significant improvement in short-term prediction accuracy. This study also analyzes and compares the accuracy of short-term forecasts (less than 3 h) by using different length observations. Experimental results obtained from International GNSS Service (IGS) final products and our own real-time clocks show that the 3-h prediction accuracy is better than 0.85 ns. The new model can replace IGS ultra-rapid products in the application of real-time PPP. It is also found that there is a positive correlation between the prediction accuracy and the short-term stability of on-board clocks. Compared with the accuracy of the traditional linear model, the accuracy of the static PPP using the new model of the 2-h prediction clock in N, E, and U directions is improved by about 50%. Furthermore, the static PPP accuracy of 2-h clock products is better than 0.1 m. When an interruption occurs in the real-time model, the accuracy of the kinematic PPP solution using 1-h clock prediction product is better than 0.2 m, without significant accuracy degradation. This model is of practical significance because it solves the problems of interruption and delay in data broadcast in real-time clock estimation and can meet the requirements of real-time PPP.
Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition

PubMed Central

Menon, Ramkumar; Bonney, Elizabeth A.; Condon, Jennifer; Mesiano, Sam; Taylor, Robert N.

2016-01-01

The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments. In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes. PMID:27363410
GPS/GLONASS Combined Precise Point Positioning with Receiver Clock Modeling

PubMed Central

Wang, Fuhong; Chen, Xinghan; Guo, Fei

2015-01-01

Research has demonstrated that receiver clock modeling can reduce the correlation coefficients among the parameters of receiver clock bias, station height and zenith tropospheric delay. This paper introduces the receiver clock modeling to GPS/GLONASS combined precise point positioning (PPP), aiming to better separate the receiver clock bias and station coordinates and therefore improve positioning accuracy. Firstly, the basic mathematic models including the GPS/GLONASS observation equations, stochastic model, and receiver clock model are briefly introduced. Then datasets from several IGS stations equipped with high-stability atomic clocks are used for kinematic PPP tests. To investigate the performance of PPP, including the positioning accuracy and convergence time, a week of (1–7 January 2014) GPS/GLONASS data retrieved from these IGS stations are processed with different schemes. The results indicate that the positioning accuracy as well as convergence time can benefit from the receiver clock modeling. This is particularly pronounced for the vertical component. Statistic RMSs show that the average improvement of three-dimensional positioning accuracy reaches up to 30%–40%. Sometimes, it even reaches over 60% for specific stations. Compared to the GPS-only PPP, solutions of the GPS/GLONASS combined PPP are much better no matter if the receiver clock offsets are modeled or not, indicating that the positioning accuracy and reliability are significantly improved with the additional GLONASS satellites in the case of insufficient number of GPS satellites or poor geometry conditions. In addition to the receiver clock modeling, the impacts of different inter-system timing bias (ISB) models are investigated. For the case of a sufficient number of satellites with fairly good geometry, the PPP performances are not seriously affected by the ISB model due to the low correlation between the ISB and the other parameters. However, the refinement of ISB model weakens the correlation between coordinates and ISB estimates and finally enhance the PPP performance in the case of poor observation conditions. PMID:26134106
Detecting gravitational decoherence with clocks: Limits on temporal resolution from a classical-channel model of gravity

NASA Astrophysics Data System (ADS)

Khosla, Kiran E.; Altamirano, Natacha

2017-05-01

The notion of time is given a different footing in quantum mechanics and general relativity, treated as a parameter in the former and being an observer-dependent property in the latter. From an operational point of view time is simply the correlation between a system and a clock, where an idealized clock can be modeled as a two-level system. We investigate the dynamics of clocks interacting gravitationally by treating the gravitational interaction as a classical information channel. This model, known as the classical-channel gravity (CCG), postulates that gravity is mediated by a fundamentally classical force carrier and is therefore unable to entangle particles gravitationally. In particular, we focus on the decoherence rates and temporal resolution of arrays of N clocks, showing how the minimum dephasing rate scales with N , and the spatial configuration. Furthermore, we consider the gravitational redshift between a clock and a massive particle and show that a classical-channel model of gravity predicts a finite-dephasing rate from the nonlocal interaction. In our model we obtain a fundamental limitation in time accuracy that is intrinsic to each clock.
Intracellular Calcium Dynamics and the Acceleration of Sinus Rhythm by β-Adrenergic Stimulation

PubMed Central

Joung, Boyoung; Tang, Liang; Maruyama, Mitsunori; Han, Seongwook; Chen, Zhenhui; Stucky, Marcelle; Jones, Larry R.; Fishbein, Michael C.; Weiss, James N.; Chen, Peng-Sheng; Lin, Shien-Fong

2009-01-01

Background Recent evidence indicates that membrane voltage and Ca2+ clocks jointly regulate sinoatrial node (SAN) automaticity. Here we test the hypothesis that sinus rate acceleration by β-adrenergic stimulation involves synergistic interactions between these clock mechanisms. Methods and Results We simultaneously mapped intracellular calcium (Cai) and membrane potential (Vm) in 25 isolated canine right atrium (RA), using previously described criteria of the timing of late diastolic Cai elevation (LDCAE) relative to the action potential (AP) upstroke to detect the Ca2+ clock. Before isoproterenol, the earliest pacemaking site occurred in the inferior SAN, and LDCAE was observed in only 4/25 preparations. Isoproterenol (1 μmol/L) increased sinus rate and shifted pacemaking site to superior SAN, concomitant with the appearance of LDCAE preceding the AP upstroke by 98 ± 31 ms. Caffeine had similar effects, while SR Ca2+ depletion with ryanodine and thapsigargin prevented isoproterenol-induced LDCAE and blunted sinus rate acceleration. Cai transient relaxation time during ISO was shorter in superior SAN (124 ± 34 ms) than inferior SAN (138 ± 24 ms, p = 0.01) or RA (164 ± 33 ms, p = 0.001), and was associated with a lower SR Ca2+ ATPase pump to phospholamban protein ratio in SAN than in RA. If current blockade with ZD 7288 modestly blunted, but did not prevent LDCAE or sinus rate acceleration by isoproterenol. Conclusions Acceleration of the Ca2+ clock in the superior SAN plays an important role in sinus acceleration during β-adrenergic stimulation, interacting synergistically with the voltage clock to increase sinus rate. PMID:19188501
Stabilizing Rabi oscillation of a charge qubit via the atomic clock technique

NASA Astrophysics Data System (ADS)

Yu, Deshui; Landra, Alessandro; Kwek, Leong Chuan; Amico, Luigi; Dumke, Rainer

2018-02-01

We propose a superconducting circuit-atom hybrid, where the Rabi oscillation of single excess Cooper pair in the island is stabilized via the common atomic clock technique. The noise in the superconducting circuit is mapped onto the voltage source which biases the Cooper-pair box via an inductor and a gate capacitor. The fast fluctuations of the gate charge are significantly suppressed by an inductor-capacitor resonator, leading to a long-relaxation-time Rabi oscillation. More importantly, the residual low-frequency fluctuations are further reduced by using the general feedback-control method, in which the voltage bias is stabilized via continuously measuring the dc-Stark-shift-induced atomic Ramsey signal. The stability and coherence time of the resulting charge-qubit Rabi oscillation are both enhanced. The principal structure of this Cooper-pair-box oscillator is studied in detail.
Ground control system for the midcourse space experiment UTC clock

NASA Technical Reports Server (NTRS)

Dragonette, Richard

1994-01-01

One goal of the Midcourse Space Experiment (MSX) spacecraft Operations Planning Center is to maintain the onboard satellite UTC clock (UTC(MSX)) to within 1 millisecond of UTC(APL) (the program requirement is 10 msec). The UTC(MSX) clock employs as its time base an APL built 5 MHz quartz oscillator, which is expected to have frequency instabilities (aging rate + drift rate + frequency offset) that will cause the clock to drift approximately two to ten milliseconds per day. The UTC(MSX) clock can be advanced or retarded by the APL MSX satellite ground control center by integer multiples of 1 millisecond. The MSX Operations Planning Center is developing software which records the drift of UTC(MSX) relative to UTC(APL) and which schedules the time of day and magnitude of UTC(MSX) clock updates up to 48 hours in advance. Because of the manner in which MSX spacecraft activities are scheduled, MSX clock updates are planned 24 to 48 hours in advance, and stored in the satellite's computer controller for later execution. Data will be collected on the drift of UTC(MSX) relative to UTC(APL) over a three to five day period. Approximately six times per day, the time offset between UTC(MSX) and UTC(APL) will be measured by APL with a resolution of less than 100 microseconds. From this data a second order analytical model of the clock's drift will be derived. This model will be used to extrapolate the offset of the MSX clock in time from the present to 48 hours in the future. MSX clock updates will be placed on the spacecraft's daily schedule whenever the predicted clock offset exceeds 0.5 milliseconds. The paper includes a discussion of how the empirical model of the MSX clock is derived from satellite telemetry data, as well as the algorithm used to schedule MSX clock updates based on the model.
Atomic clocks and the continuous-time random-walk

NASA Astrophysics Data System (ADS)

Formichella, Valerio; Camparo, James; Tavella, Patrizia

2017-11-01

Atomic clocks play a fundamental role in many fields, most notably they generate Universal Coordinated Time and are at the heart of all global navigation satellite systems. Notwithstanding their excellent timekeeping performance, their output frequency does vary: it can display deterministic frequency drift; diverse continuous noise processes result in nonstationary clock noise (e.g., random-walk frequency noise, modelled as a Wiener process), and the clock frequency may display sudden changes (i.e., "jumps"). Typically, the clock's frequency instability is evaluated by the Allan or Hadamard variances, whose functional forms can identify the different operative noise processes. Here, we show that the Allan and Hadamard variances of a particular continuous-time random-walk, the compound Poisson process, have the same functional form as for a Wiener process with drift. The compound Poisson process, introduced as a model for observed frequency jumps, is an alternative to the Wiener process for modelling random walk frequency noise. This alternate model fits well the behavior of the rubidium clocks flying on GPS Block-IIR satellites. Further, starting from jump statistics, the model can be improved by considering a more general form of continuous-time random-walk, and this could bring new insights into the physics of atomic clocks.
Molecular Phylogenetics and Temporal Diversification in the Genus Aeromonas Based on the Sequences of Five Housekeeping Genes

PubMed Central

Lorén, J. Gaspar; Farfán, Maribel; Fusté, M. Carmen

2014-01-01

Several approaches have been developed to estimate both the relative and absolute rates of speciation and extinction within clades based on molecular phylogenetic reconstructions of evolutionary relationships, according to an underlying model of diversification. However, the macroevolutionary models established for eukaryotes have scarcely been used with prokaryotes. We have investigated the rate and pattern of cladogenesis in the genus Aeromonas (γ-Proteobacteria, Proteobacteria, Bacteria) using the sequences of five housekeeping genes and an uncorrelated relaxed-clock approach. To our knowledge, until now this analysis has never been applied to all the species described in a bacterial genus and thus opens up the possibility of establishing models of speciation from sequence data commonly used in phylogenetic studies of prokaryotes. Our results suggest that the genus Aeromonas began to diverge between 248 and 266 million years ago, exhibiting a constant divergence rate through the Phanerozoic, which could be described as a pure birth process. PMID:24586399
Empirical and Bayesian approaches to fossil-only divergence times: A study across three reptile clades.

PubMed

Turner, Alan H; Pritchard, Adam C; Matzke, Nicholas J

2017-01-01

Estimating divergence times on phylogenies is critical in paleontological and neontological studies. Chronostratigraphically-constrained fossils are the only direct evidence of absolute timing of species divergence. Strict temporal calibration of fossil-only phylogenies provides minimum divergence estimates, and various methods have been proposed to estimate divergences beyond these minimum values. We explore the utility of simultaneous estimation of tree topology and divergence times using BEAST tip-dating on datasets consisting only of fossils by using relaxed morphological clocks and birth-death tree priors that include serial sampling (BDSS) at a constant rate through time. We compare BEAST results to those from the traditional maximum parsimony (MP) and undated Bayesian inference (BI) methods. Three overlapping datasets were used that span 250 million years of archosauromorph evolution leading to crocodylians. The first dataset focuses on early Sauria (31 taxa, 240 chars.), the second on early Archosauria (76 taxa, 400 chars.) and the third on Crocodyliformes (101 taxa, 340 chars.). For each dataset three time-calibrated trees (timetrees) were calculated: a minimum-age timetree with node ages based on earliest occurrences in the fossil record; a 'smoothed' timetree using a range of time added to the root that is then averaged over zero-length internodes; and a tip-dated timetree. Comparisons within datasets show that the smoothed and tip-dated timetrees provide similar estimates. Only near the root node do BEAST estimates fall outside the smoothed timetree range. The BEAST model is not able to overcome limited sampling to correctly estimate divergences considerably older than sampled fossil occurrence dates. Conversely, the smoothed timetrees consistently provide node-ages far older than the strict dates or BEAST estimates for morphologically conservative sister-taxa when they sit on long ghost lineages. In this latter case, the relaxed-clock model appears to be correctly moderating the node-age estimate based on the limited morphological divergence. Topologies are generally similar across analyses, but BEAST trees for crocodyliforms differ when clades are deeply nested but contain very old taxa. It appears that the constant-rate sampling assumption of the BDSS tree prior influences topology inference by disfavoring long, unsampled branches.
Empirical and Bayesian approaches to fossil-only divergence times: A study across three reptile clades

PubMed Central

Turner, Alan H.; Pritchard, Adam C.; Matzke, Nicholas J.

2017-01-01

Estimating divergence times on phylogenies is critical in paleontological and neontological studies. Chronostratigraphically-constrained fossils are the only direct evidence of absolute timing of species divergence. Strict temporal calibration of fossil-only phylogenies provides minimum divergence estimates, and various methods have been proposed to estimate divergences beyond these minimum values. We explore the utility of simultaneous estimation of tree topology and divergence times using BEAST tip-dating on datasets consisting only of fossils by using relaxed morphological clocks and birth-death tree priors that include serial sampling (BDSS) at a constant rate through time. We compare BEAST results to those from the traditional maximum parsimony (MP) and undated Bayesian inference (BI) methods. Three overlapping datasets were used that span 250 million years of archosauromorph evolution leading to crocodylians. The first dataset focuses on early Sauria (31 taxa, 240 chars.), the second on early Archosauria (76 taxa, 400 chars.) and the third on Crocodyliformes (101 taxa, 340 chars.). For each dataset three time-calibrated trees (timetrees) were calculated: a minimum-age timetree with node ages based on earliest occurrences in the fossil record; a ‘smoothed’ timetree using a range of time added to the root that is then averaged over zero-length internodes; and a tip-dated timetree. Comparisons within datasets show that the smoothed and tip-dated timetrees provide similar estimates. Only near the root node do BEAST estimates fall outside the smoothed timetree range. The BEAST model is not able to overcome limited sampling to correctly estimate divergences considerably older than sampled fossil occurrence dates. Conversely, the smoothed timetrees consistently provide node-ages far older than the strict dates or BEAST estimates for morphologically conservative sister-taxa when they sit on long ghost lineages. In this latter case, the relaxed-clock model appears to be correctly moderating the node-age estimate based on the limited morphological divergence. Topologies are generally similar across analyses, but BEAST trees for crocodyliforms differ when clades are deeply nested but contain very old taxa. It appears that the constant-rate sampling assumption of the BDSS tree prior influences topology inference by disfavoring long, unsampled branches. PMID:28187191
A Brownian model for recurrent earthquakes

USGS Publications Warehouse

Matthews, M.V.; Ellsworth, W.L.; Reasenberg, P.A.

2002-01-01

We construct a probability model for rupture times on a recurrent earthquake source. Adding Brownian perturbations to steady tectonic loading produces a stochastic load-state process. Rupture is assumed to occur when this process reaches a critical-failure threshold. An earthquake relaxes the load state to a characteristic ground level and begins a new failure cycle. The load-state process is a Brownian relaxation oscillator. Intervals between events have a Brownian passage-time distribution that may serve as a temporal model for time-dependent, long-term seismic forecasting. This distribution has the following noteworthy properties: (1) the probability of immediate rerupture is zero; (2) the hazard rate increases steadily from zero at t = 0 to a finite maximum near the mean recurrence time and then decreases asymptotically to a quasi-stationary level, in which the conditional probability of an event becomes time independent; and (3) the quasi-stationary failure rate is greater than, equal to, or less than the mean failure rate because the coefficient of variation is less than, equal to, or greater than 1/???2 ??? 0.707. In addition, the model provides expressions for the hazard rate and probability of rupture on faults for which only a bound can be placed on the time of the last rupture. The Brownian relaxation oscillator provides a connection between observable event times and a formal state variable that reflects the macromechanics of stress and strain accumulation. Analysis of this process reveals that the quasi-stationary distance to failure has a gamma distribution, and residual life has a related exponential distribution. It also enables calculation of "interaction" effects due to external perturbations to the state, such as stress-transfer effects from earthquakes outside the target source. The influence of interaction effects on recurrence times is transient and strongly dependent on when in the loading cycle step pertubations occur. Transient effects may be much stronger than would be predicted by the "clock change" method and characteristically decay inversely with elapsed time after the perturbation.
The Trade-Off Mechanism in Mammalian Circadian Clock Model with Two Time Delays

NASA Astrophysics Data System (ADS)

Yan, Jie; Kang, Xiaxia; Yang, Ling

Circadian clock is an autonomous oscillator which orchestrates the daily rhythms of physiology and behaviors. This study is devoted to explore how a positive feedback loop affects the dynamics of mammalian circadian clock. We simplify an experimentally validated mathematical model in our previous work, to a nonlinear differential equation with two time delays. This simplified mathematical model incorporates the pacemaker of mammalian circadian clock, a negative primary feedback loop, and a critical positive auxiliary feedback loop, Rev-erbα/Cry1 loop. We perform analytical studies of the system. Delay-dependent conditions for the asymptotic stability of the nontrivial positive steady state of the model are investigated. We also prove the existence of Hopf bifurcation, which leads to self-sustained oscillation of mammalian circadian clock. Our theoretical analyses show that the oscillatory regime is reduced upon the participation of the delayed positive auxiliary loop. However, further simulations reveal that the auxiliary loop can enable the circadian clock gain widely adjustable amplitudes and robust period. Thus, the positive auxiliary feedback loop may provide a trade-off mechanism, to use the small loss in the robustness of oscillation in exchange for adaptable flexibility in mammalian circadian clock. The results obtained from the model may gain new insights into the dynamics of biological oscillators with interlocked feedback loops.
The Clock mutant mouse is a novel experimental model for nocturia and nocturnal polyuria.

PubMed

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.
Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition.

PubMed

Menon, Ramkumar; Bonney, Elizabeth A; Condon, Jennifer; Mesiano, Sam; Taylor, Robert N

2016-09-01

The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments.In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Stochastic models for atomic clocks

NASA Technical Reports Server (NTRS)

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

1983-01-01

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

PubMed

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.
The relative ages of ectomycorrhizal mushrooms and their plant hosts estimated using Bayesian relaxed molecular clock analyses

PubMed Central

Hibbett, David S; Matheny, P Brandon

2009-01-01

Background Ectomycorrhizae (ECM) are symbioses formed by polyphyletic assemblages of fungi (mostly Agaricomycetes) and plants (mostly Pinaceae and angiosperms in the rosid clade). Efforts to reconstruct the evolution of the ECM habit in Agaricomycetes have yielded vastly different results, ranging from scenarios with many relatively recent origins of the symbiosis and no reversals to the free-living condition; a single ancient origin of ECM and many subsequent transitions to the free-living condition; or multiple gains and losses of the association. To test the plausibility of these scenarios, we performed Bayesian relaxed molecular clock analyses including fungi, plants, and other eukaryotes, based on the principle that a symbiosis cannot evolve prior to the origin of both partners. As we were primarily interested in the relative ages of the plants and fungi, we did not attempt to calibrate the molecular clock using the very limited fossil record of Agaricomycetes. Results Topologically constrained and unconstrained analyses suggest that the root node of the Agaricomycetes is much older than either the rosids or Pinaceae. The Agaricomycetidae, a large clade containing the Agaricales and Boletales (collectively representing 70% of Agaricomycetes), is also significantly older than the rosids. The relative age of Agaricomycetidae and Pinaceae, however, is sensitive to tree topology, and the inclusion or exclusion of the gnetophyte Welwitschia mirabilis. Conclusion The ancestor of the Agaricomycetes could not have been an ECM species because it existed long before any of its potential hosts. Within more derived clades of Agaricomycetes, there have been at least eight independent origins of ECM associations involving angiosperms, and at least six to eight origins of associations with gymnosperms. The first ECM symbioses may have involved Pinaceae, which are older than rosids, but several major clades of Agaricomycetes, such as the Boletales and Russulales, are young enough to have been plesiomorphically associated with either rosids or Pinaceae, suggesting that some contemporary ECM partnerships could be of very ancient origin. PMID:19284559

Molecular cogs of the insect circadian clock.

PubMed

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.
Noise-Induced Synchronization among Sub-RF CMOS Analog Oscillators for Skew-Free Clock Distribution

NASA Astrophysics Data System (ADS)

Utagawa, Akira; Asai, Tetsuya; Hirose, Tetsuya; Amemiya, Yoshihito

We present on-chip oscillator arrays synchronized by random noises, aiming at skew-free clock distribution on synchronous digital systems. Nakao et al. recently reported that independent neural oscillators can be synchronized by applying temporal random impulses to the oscillators [1], [2]. We regard neural oscillators as independent clock sources on LSIs; i. e., clock sources are distributed on LSIs, and they are forced to synchronize through the use of random noises. We designed neuron-based clock generators operating at sub-RF region (<1GHz) by modifying the original neuron model to a new model that is suitable for CMOS implementation with 0.25-μm CMOS parameters. Through circuit simulations, we demonstrate that i) the clock generators are certainly synchronized by pseudo-random noises and ii) clock generators exhibited phase-locked oscillations even if they had small device mismatches.
The origin and diversification of eukaryotes: problems with molecular phylogenetics and molecular clock estimation

PubMed Central

Roger, Andrew J; Hug, Laura A

2006-01-01

Determining the relationships among and divergence times for the major eukaryotic lineages remains one of the most important and controversial outstanding problems in evolutionary biology. The sequencing and phylogenetic analyses of ribosomal RNA (rRNA) genes led to the first nearly comprehensive phylogenies of eukaryotes in the late 1980s, and supported a view where cellular complexity was acquired during the divergence of extant unicellular eukaryote lineages. More recently, however, refinements in analytical methods coupled with the availability of many additional genes for phylogenetic analysis showed that much of the deep structure of early rRNA trees was artefactual. Recent phylogenetic analyses of a multiple genes and the discovery of important molecular and ultrastructural phylogenetic characters have resolved eukaryotic diversity into six major hypothetical groups. Yet relationships among these groups remain poorly understood because of saturation of sequence changes on the billion-year time-scale, possible rapid radiations of major lineages, phylogenetic artefacts and endosymbiotic or lateral gene transfer among eukaryotes. Estimating the divergence dates between the major eukaryote lineages using molecular analyses is even more difficult than phylogenetic estimation. Error in such analyses comes from a myriad of sources including: (i) calibration fossil dates, (ii) the assumed phylogenetic tree, (iii) the nucleotide or amino acid substitution model, (iv) substitution number (branch length) estimates, (v) the model of how rates of evolution change over the tree, (vi) error inherent in the time estimates for a given model and (vii) how multiple gene data are treated. By reanalysing datasets from recently published molecular clock studies, we show that when errors from these various sources are properly accounted for, the confidence intervals on inferred dates can be very large. Furthermore, estimated dates of divergence vary hugely depending on the methods used and their assumptions. Accurate dating of divergence times among the major eukaryote lineages will require a robust tree of eukaryotes, a much richer Proterozoic fossil record of microbial eukaryotes assignable to extant groups for calibration, more sophisticated relaxed molecular clock methods and many more genes sampled from the full diversity of microbial eukaryotes. PMID:16754613
Lego clocks: building a clock from parts.

PubMed

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

NASA Technical Reports Server (NTRS)

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.
Microbial DNA records historical delivery of anthropogenic mercury

PubMed Central

Poulain, Alexandre J; Aris-Brosou, Stéphane; Blais, Jules M; Brazeau, Michelle; Keller, Wendel (Bill); Paterson, Andrew M

2015-01-01

Mercury (Hg) is an anthropogenic pollutant that is toxic to wildlife and humans, but the response of remote ecosystems to globally distributed Hg is elusive. Here, we use DNA extracted from a dated sediment core to infer the response of microbes to historical Hg delivery. We observe a significant association between the mercuric reductase gene (merA) phylogeny and the timing of Hg deposition. Using relaxed molecular clock models, we show a significant increase in the scaled effective population size of the merA gene beginning ~200 years ago, coinciding with the Industrial Revolution and a coincident strong signal for positive selection acting on residues in the terminal region of the mercuric reductase. This rapid evolutionary response of microbes to changes in the delivery of anthropogenic Hg indicates that microbial genomes record ecosystem response to pollutant deposition in remote regions. PMID:26057844
KSC01padig110

NASA Image and Video Library

2001-03-02

The student team Viking Electros, from W.M. Raines High School, Jacksonville, Fla., relaxes between heats at the NASA/KSC FIRST Southeastern Regional event held March 1-3, 2001. FIRST (For Inspiration and Recognition of Science and Technology) events are held nationwide, pitting robots against each other and the clock on a playing field. Many teams are sponsored by corporations and academic institutions. There are 27 teams throughout the State of Florida who are competing. KSC, which sponsors nine teams, has held the regional event for two years
Coherent Population Trapping and Optical Ramsey Interference for Compact Rubidium Clock Development

NASA Astrophysics Data System (ADS)

Warren, Zachary Aron

Coherent population trapping (CPT) and optical Ramsey interference provide new avenues for developing compact, high-performance atomic clocks. In this work, I have studied the fundamental aspects of CPT and optical Ramsey interference for Raman clock development. This thesis research is composed of two parts: theoretical and experimental studies. The theoretical component of the research was initially based on pre-existing atomic models of a three-level ?-type system in which the phenomena of CPT and Ramsey interference are formed. This model served as a starting point for studying basic characteristics of CPT and Ramsey interference such as power dependence of CPT, effects of average detuning, and ground-state decoherence on linewidth, which directly impact the performance of the Raman clock. The basic three-level model was also used to model pulsed CPT excitation and measure light shift in Ramsey interference which imposes a fundamental limit on the long-term frequency stability of the Raman clock. The theoretical calculations illustrate reduction (or suppression) of light shift in Ramsey interference as an important advantage over CPT for Raman clock development. To make the model more accurate than an ideal three-level system, I developed a comprehensive atomic model using density-matrix equations including all sixteen Zeeman sublevels in the D1 manifold of 87Rb atoms in a vapor medium. The multi-level atomic model has been used for investigating characteristics of CPT and Ramsey interference under different optical excitation schemes pertaining to the polarization states of the frequency-modulated CPT beam in a Raman clock. It is also used to study the effects of axial and traverse magnetic fields on the contrast of CPT and Ramsey interference. More importantly, the multi-level atomic model is also used to accurately calculate light shift in Ramsey interference in the D1 manifold of 87Rb atoms by taking into account all possible off-resonant excitations and the ground-state decoherence among the Zeeman sublevels. Light shift suppression in Ramsey interference with pulse saturation is also found to be evident in this comprehensive model. In the experimental component of the research, I designed a prototype of the Raman clock using a small (2 cm in length), buffer-gas filled, and isotopically pure 87Rb cell. A fiber-coupled waveguide electro-optic modulator was used to generate the frequency-modulated CPT beam for the experiments. The experimental setup was operated either by continuous excitation or pulsed excitation for experimentally characterizing CPT and Ramsey interference under different experimental conditions and for testing different optical excitation schemes which were investigated theoretically. Several iterations of the clock physics package were developed in order to attain better frequency stability performance in the Raman clock. The experimental work also provided a basis to develop a new repeated-query technique for producing an ultra-narrow linewidth central fringe with a high S/N ratio, and suppressing the side fringes in Ramsey interference. The above described research was carried out keeping in mind compact, high-performance clock development, which relies on technologies that can be miniaturized. Vapor cell based atomic clocks are ideal candidates for compact clock technology. The CPT phenomenon, observed by Raman excitation in a vapor medium, is a promising candidate for compact, high-performance Raman clock development. However, atom-field interaction involved in a vapor medium is often more complex than other media such as cold atom or atomic beam. It is difficult to model this interaction in order to predict its influence on CPT characteristics and, hence, the performance of the Raman clock. This dissertation addresses one such problem by developing a comprehensive atomic model to investigate light shift and modification of light shift in the Raman clock, particularly with pulsed excitation. It demonstrates a clear possibility of reducing (or suppressing) the light shift associated with Ramsey interference in a vapor medium for achieving higher frequency stability in the Raman clock. Additionally, theoretical comparisons of various optical excitation techniques have been calculated to demonstrate the relative strengths and weaknesses of different schemes for Raman clock development. (Abstract shortened by ProQuest.).
Organ specificity in the plant circadian system is explained by different light inputs to the shoot and root clocks.

PubMed

Bordage, Simon; Sullivan, Stuart; Laird, Janet; Millar, Andrew J; Nimmo, Hugh G

2016-10-01

Circadian clocks allow the temporal compartmentalization of biological processes. In Arabidopsis, circadian rhythms display organ specificity but the underlying molecular causes have not been identified. We investigated the mechanisms responsible for the similarities and differences between the clocks of mature shoots and roots in constant conditions and in light : dark cycles. We developed an imaging system to monitor clock gene expression in shoots and light- or dark-grown roots, modified a recent mathematical model of the Arabidopsis clock and used this to simulate our new data. We showed that the shoot and root circadian clocks have different rhythmic properties (period and amplitude) and respond differently to light quality. The root clock was entrained by direct exposure to low-intensity light, even in antiphase to the illumination of shoots. Differences between the clocks were more pronounced in conditions where light was present than in constant darkness, and persisted in the presence of sucrose. We simulated the data successfully by modifying those parameters of a clock model that are related to light inputs. We conclude that differences and similarities between the shoot and root clocks can largely be explained by organ-specific light inputs. This provides mechanistic insight into the developing field of organ-specific clocks. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.
The sympathy of two pendulum clocks: beyond Huygens' observations.

PubMed

Peña Ramirez, Jonatan; Olvera, Luis Alberto; Nijmeijer, Henk; Alvarez, Joaquin

2016-03-29

This paper introduces a modern version of the classical Huygens' experiment on synchronization of pendulum clocks. The version presented here consists of two monumental pendulum clocks--ad hoc designed and fabricated--which are coupled through a wooden structure. It is demonstrated that the coupled clocks exhibit 'sympathetic' motion, i.e. the pendula of the clocks oscillate in consonance and in the same direction. Interestingly, when the clocks are synchronized, the common oscillation frequency decreases, i.e. the clocks become slow and inaccurate. In order to rigorously explain these findings, a mathematical model for the coupled clocks is obtained by using well-established physical and mechanical laws and likewise, a theoretical analysis is conducted. Ultimately, the sympathy of two monumental pendulum clocks, interacting via a flexible coupling structure, is experimentally, numerically, and analytically demonstrated.
A Blind Circadian Clock in Cavefish Reveals that Opsins Mediate Peripheral Clock Photoreception

PubMed Central

Cavallari, Nicola; Frigato, Elena; Vallone, Daniela; Fröhlich, Nadine; Lopez-Olmeda, Jose Fernando; Foà, Augusto; Berti, Roberto; Sánchez-Vázquez, Francisco Javier; Bertolucci, Cristiano; Foulkes, Nicholas S.

2011-01-01

The circadian clock is synchronized with the day-night cycle primarily by light. Fish represent fascinating models for deciphering the light input pathway to the vertebrate clock since fish cell clocks are regulated by direct light exposure. Here we have performed a comparative, functional analysis of the circadian clock involving the zebrafish that is normally exposed to the day-night cycle and a cavefish species that has evolved in perpetual darkness. Our results reveal that the cavefish retains a food-entrainable clock that oscillates with an infradian period. Importantly, however, this clock is not regulated by light. This comparative study pinpoints the two extra-retinal photoreceptors Melanopsin (Opn4m2) and TMT-opsin as essential upstream elements of the peripheral clock light input pathway. PMID:21909239
A molecular genetic time scale demonstrates Cretaceous origins and multiple diversification rate shifts within the order Galliformes (Aves).

PubMed

Stein, R Will; Brown, Joseph W; Mooers, Arne Ø

2015-11-01

The phylogeny of Galliformes (landfowl) has been studied extensively; however, the associated chronologies have been criticized recently due to misplaced or misidentified fossil calibrations. As a consequence, it is unclear whether any crown-group lineages arose in the Cretaceous and survived the Cretaceous-Paleogene (K-Pg; 65.5 Ma) mass extinction. Using Bayesian phylogenetic inference on an alignment spanning 14,539 bp of mitochondrial and nuclear DNA sequence data, four fossil calibrations, and a combination of uncorrelated lognormally distributed relaxed-clock and strict-clock models, we inferred a time-calibrated molecular phylogeny for 225 of the 291 extant Galliform taxa. These analyses suggest that crown Galliformes diversified in the Cretaceous and that three-stem lineages survived the K-Pg mass extinction. Ideally, characterizing the tempo and mode of diversification involves a taxonomically complete phylogenetic hypothesis. We used simple constraint structures to incorporate 66 data-deficient taxa and inferred the first taxon-complete phylogenetic hypothesis for the Galliformes. Diversification analyses conducted on 10,000 timetrees sampled from the posterior distribution of candidate trees show that the evolutionary history of the Galliformes is best explained by a rate-shift model including 1-3 clade-specific increases in diversification rate. We further show that the tempo and mode of diversification in the Galliformes conforms to a three-pulse model, with three-stem lineages arising in the Cretaceous and inter and intrafamilial diversification occurring after the K-Pg mass extinction, in the Paleocene-Eocene (65.5-33.9 Ma) or in association with the Eocene-Oligocene transition (33.9 Ma). Copyright © 2015 Elsevier Inc. All rights reserved.
Distributed Time Synchronization Algorithms and Opinion Dynamics

NASA Astrophysics Data System (ADS)

Manita, Anatoly; Manita, Larisa

2018-01-01

We propose new deterministic and stochastic models for synchronization of clocks in nodes of distributed networks. An external accurate time server is used to ensure convergence of the node clocks to the exact time. These systems have much in common with mathematical models of opinion formation in multiagent systems. There is a direct analogy between the time server/node clocks pair in asynchronous networks and the leader/follower pair in the context of social network models.
Development of diabetes does not alter behavioral and molecular circadian rhythms in a transgenic rat model of type 2 diabetes mellitus.

PubMed

Qian, Jingyi; Thomas, Anthony P; Schroeder, Analyne M; Rakshit, Kuntol; Colwell, Christopher S; Matveyenko, Aleksey V

2017-08-01

Metabolic state and circadian clock function exhibit a complex bidirectional relationship. Circadian disruption increases propensity for metabolic dysfunction, whereas common metabolic disorders such as obesity and type 2 diabetes (T2DM) are associated with impaired circadian rhythms. Specifically, alterations in glucose availability and glucose metabolism have been shown to modulate clock gene expression and function in vitro; however, to date, it is unknown whether development of diabetes imparts deleterious effects on the suprachiasmatic nucleus (SCN) circadian clock and SCN-driven outputs in vivo. To address this question, we undertook studies in aged diabetic rats transgenic for human islet amyloid polypeptide, an established nonobese model of T2DM (HIP rat), which develops metabolic defects closely recapitulating those present in patients with T2DM. HIP rats were also cross-bred with a clock gene reporter rat model (Per1:luciferase transgenic rat) to permit assessment of the SCN and the peripheral molecular clock function ex vivo. Utilizing these animal models, we examined effects of diabetes on 1 ) behavioral circadian rhythms, 2 ) photic entrainment of circadian activity, 3 ) SCN and peripheral tissue molecular clock function, and 4 ) melatonin secretion. We report that circadian activity, light-induced entrainment, molecular clockwork, as well as melatonin secretion are preserved in the HIP rat model of T2DM. These results suggest that despite the well-characterized ability of glucose to modulate circadian clock gene expression acutely in vitro, SCN clock function and key behavioral and physiological outputs appear to be preserved under chronic diabetic conditions characteristic of nonobese T2DM. Copyright © 2017 the American Physiological Society.
CSAC Characterization and Its Impact on GNSS Clock Augmentation Performance

PubMed Central

Fernández, Enric; Calero, David; Parés, M. Eulàlia

2017-01-01

Chip Scale Atomic Clocks (CSAC) are recently-developed electronic instruments that, when used together with a Global Navigation Satellite Systems (GNSS) receiver, help improve the performance of GNSS navigation solutions in certain conditions (i.e., low satellite visibility). Current GNSS receivers include a Temperature Compensated Cristal Oscillator (TCXO) clock characterized by a short-term stability (τ = 1 s) of 10−9 s that leads to an error of 0.3 m in pseudorange measurements. The CSAC can achieve a short-term stability of 2.5 × 10−12 s, which implies a range error of 0.075 m, making for an 87.5% improvement over TCXO. Replacing the internal TCXO clock of GNSS receivers with a higher frequency stability clock such as a CSAC oscillator improves the navigation solution in terms of low satellite visibility positioning accuracy, solution availability, signal recovery (holdover), multipath and jamming mitigation and spoofing attack detection. However, CSAC suffers from internal systematic instabilities and errors that should be minimized if optimal performance is desired. Hence, for operating CSAC at its best, the deterministic errors from the CSAC need to be properly modelled. Currently, this modelling is done by determining and predicting the clock frequency stability (i.e., clock bias and bias rate) within the positioning estimation process. The research presented in this paper aims to go a step further, analysing the correlation between temperature and clock stability noise and the impact of its proper modelling in the holdover recovery time and in the positioning performance. Moreover, it shows the potential of fine clock coasting modelling. With the proposed model, an improvement in vertical positioning precision of around 50% with only three satellites can be achieved. Moreover, an increase in the navigation solution availability is also observed, a reduction of holdover recovery time from dozens of seconds to only a few can be achieved. PMID:28216600
CSAC Characterization and Its Impact on GNSS Clock Augmentation Performance.

PubMed

Fernández, Enric; Calero, David; Parés, M Eulàlia

2017-02-14

Chip Scale Atomic Clocks (CSAC) are recently-developed electronic instruments that, when used together with a Global Navigation Satellite Systems (GNSS) receiver, help improve the performance of GNSS navigation solutions in certain conditions (i.e., low satellite visibility). Current GNSS receivers include a Temperature Compensated Cristal Oscillator (TCXO) clock characterized by a short-term stability ( τ = 1 s) of 10 -9 s that leads to an error of 0.3 m in pseudorange measurements. The CSAC can achieve a short-term stability of 2.5 × 10 -12 s, which implies a range error of 0.075 m, making for an 87.5% improvement over TCXO. Replacing the internal TCXO clock of GNSS receivers with a higher frequency stability clock such as a CSAC oscillator improves the navigation solution in terms of low satellite visibility positioning accuracy, solution availability, signal recovery (holdover), multipath and jamming mitigation and spoofing attack detection. However, CSAC suffers from internal systematic instabilities and errors that should be minimized if optimal performance is desired. Hence, for operating CSAC at its best, the deterministic errors from the CSAC need to be properly modelled. Currently, this modelling is done by determining and predicting the clock frequency stability (i.e., clock bias and bias rate) within the positioning estimation process. The research presented in this paper aims to go a step further, analysing the correlation between temperature and clock stability noise and the impact of its proper modelling in the holdover recovery time and in the positioning performance. Moreover, it shows the potential of fine clock coasting modelling. With the proposed model, an improvement in vertical positioning precision of around 50% with only three satellites can be achieved. Moreover, an increase in the navigation solution availability is also observed, a reduction of holdover recovery time from dozens of seconds to only a few can be achieved.
Regulatory principles and experimental approaches to the circadian control of starch turnover

PubMed Central

Seaton, Daniel D.; Ebenhöh, Oliver; Millar, Andrew J.; Pokhilko, Alexandra

2014-01-01

In many plants, starch is synthesized during the day and degraded during the night to avoid carbohydrate starvation in darkness. The circadian clock participates in a dynamic adjustment of starch turnover to changing environmental condition through unknown mechanisms. We used mathematical modelling to explore the possible scenarios for the control of starch turnover by the molecular components of the plant circadian clock. Several classes of plausible models were capable of describing the starch dynamics observed in a range of clock mutant plants and light conditions, including discriminating circadian protocols. Three example models of these classes are studied in detail, differing in several important ways. First, the clock components directly responsible for regulating starch degradation are different in each model. Second, the intermediate species in the pathway may play either an activating or inhibiting role on starch degradation. Third, the system may include a light-dependent interaction between the clock and downstream processes. Finally, the clock may be involved in the regulation of starch synthesis. We discuss the differences among the models’ predictions for diel starch profiles and the properties of the circadian regulators. These suggest additional experiments to elucidate the pathway structure, avoid confounding results and identify the molecular components involved. PMID:24335560
Standard Clock in primordial density perturbations and cosmic microwave background

NASA Astrophysics Data System (ADS)

Chen, Xingang; Namjoo, Mohammad Hossein

2014-12-01

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.
Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana

PubMed Central

Locke, James C W; Kozma-Bognár, László; Gould, Peter D; Fehér, Balázs; Kevei, Éva; Nagy, Ferenc; Turner, Matthew S; Hall, Anthony; Millar, Andrew J

2006-01-01

Our computational model of the circadian clock comprised the feedback loop between LATE ELONGATED HYPOCOTYL (LHY), CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and TIMING OF CAB EXPRESSION 1 (TOC1), and a predicted, interlocking feedback loop involving TOC1 and a hypothetical component Y. Experiments based on model predictions suggested GIGANTEA (GI) as a candidate for Y. We now extend the model to include a recently demonstrated feedback loop between the TOC1 homologues PSEUDO-RESPONSE REGULATOR 7 (PRR7), PRR9 and LHY and CCA1. This three-loop network explains the rhythmic phenotype of toc1 mutant alleles. Model predictions fit closely to new data on the gi;lhy;cca1 mutant, which confirm that GI is a major contributor to Y function. Analysis of the three-loop network suggests that the plant clock consists of morning and evening oscillators, coupled intracellularly, which may be analogous to coupled, morning and evening clock cells in Drosophila and the mouse. PMID:17102804
Mercury Atomic Frequency Standards for Space Based Navigation and Timekeeping

NASA Technical Reports Server (NTRS)

Tjoelker, R. L.; Burt, E. A.; Chung, S.; Hamell, R. L.; Prestage, J. D.; Tucker, B.; Cash, P.; Lutwak, R.

2012-01-01

A low power Mercury Atomic Frequency Standard (MAFS) has been developed and demonstrated on the path towards future space clock applications. A self contained mercury ion breadboard clock: emulating flight clock interfaces, steering a USO local oscillator, and consuming approx 40 Watts has been operating at JPL for more than a year. This complete, modular ion clock instrument demonstrates that key GNSS size, weight, and power (SWaP) requirements can be achieved while still maintaining short and long term performance demonstrated in previous ground ion clocks. The MAFS breadboard serves as a flexible platform for optimizing further space clock development and guides engineering model design trades towards fabrication of an ion clock for space flight.

It's time to swim! Zebrafish and the circadian clock.

PubMed

Vatine, Gad; Vallone, Daniela; Gothilf, Yoav; Foulkes, Nicholas S

2011-05-20

The zebrafish represents a fascinating model for studying key aspects of the vertebrate circadian timing system. Easy access to early embryonic development has made this species ideal for investigating how the clock is first established during embryogenesis. In particular, the molecular basis for the functional development of the zebrafish pineal gland has received much attention. In addition to this dedicated clock and photoreceptor organ, and unlike the situation in mammals, the clocks in zebrafish peripheral tissues and even cell lines are entrainable by direct exposure to light thus providing unique insight into the function and evolution of the light input pathway. Finally, the small size, low maintenance costs and high fecundity of this fish together with the availability of genetic tools make this an attractive model for forward genetic analysis of the circadian clock. Here, we review the work that has established the zebrafish as a valuable clock model organism and highlight the key questions that will shape the future direction of research. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
A Self-Stabilizing Byzantine-Fault-Tolerant Clock Synchronization Protocol

NASA Technical Reports Server (NTRS)

Malekpour, Mahyar R.

2009-01-01

This report presents a rapid Byzantine-fault-tolerant self-stabilizing clock synchronization protocol that is independent of application-specific requirements. It is focused on clock synchronization of a system in the presence of Byzantine faults after the cause of any transient faults has dissipated. A model of this protocol is mechanically verified using the Symbolic Model Verifier (SMV) [SMV] where the entire state space is examined and proven to self-stabilize in the presence of one arbitrary faulty node. Instances of the protocol are proven to tolerate bursts of transient failures and deterministically converge with a linear convergence time with respect to the synchronization period. This protocol does not rely on assumptions about the initial state of the system other than the presence of sufficient number of good nodes. All timing measures of variables are based on the node s local clock, and no central clock or externally generated pulse is used. The Byzantine faulty behavior modeled here is a node with arbitrarily malicious behavior that is allowed to influence other nodes at every clock tick. The only constraint is that the interactions are restricted to defined interfaces.
Detecting an atomic clock frequency anomaly using an adaptive Kalman filter algorithm

NASA Astrophysics Data System (ADS)

Song, Huijie; Dong, Shaowu; Wu, Wenjun; Jiang, Meng; Wang, Weixiong

2018-06-01

The abnormal frequencies of an atomic clock mainly include frequency jump and frequency drift jump. Atomic clock frequency anomaly detection is a key technique in time-keeping. The Kalman filter algorithm, as a linear optimal algorithm, has been widely used in real-time detection for abnormal frequency. In order to obtain an optimal state estimation, the observation model and dynamic model of the Kalman filter algorithm should satisfy Gaussian white noise conditions. The detection performance is degraded if anomalies affect the observation model or dynamic model. The idea of the adaptive Kalman filter algorithm, applied to clock frequency anomaly detection, uses the residuals given by the prediction for building ‘an adaptive factor’ the prediction state covariance matrix is real-time corrected by the adaptive factor. The results show that the model error is reduced and the detection performance is improved. The effectiveness of the algorithm is verified by the frequency jump simulation, the frequency drift jump simulation and the measured data of the atomic clock by using the chi-square test.
Demonstration of Orbit Determination for the Lunar Reconnaissance Orbiter Using One-Way Laser Ranging Data

NASA Technical Reports Server (NTRS)

Bauer, S.; Hussmann, H.; Oberst, J.; Dirkx, D.; Mao, D.; Neumann, G. A.; Mazarico, E.; Torrence, M. H.; McGarry, J. F.; Smith, D. E.;

2016-01-01

We used one-way laser ranging data from International Laser Ranging Service (ILRS) ground stations to NASA's Lunar Reconnaissance Orbiter (LRO) for a demonstration of orbit determination. In the one-way setup, the state of LRO and the parameters of the spacecraft and all involved ground station clocks must be estimated simultaneously. This setup introduces many correlated parameters that are resolved by using a priori constraints. More over the observation data coverage and errors accumulating from the dynamical and the clock modeling limit the maximum arc length. The objective of this paper is to investigate the effect of the arc length, the dynamical and modeling accuracy and the observation data coverage on the accuracy of the results. We analyzed multiple arcs using lengths of 2 and 7 days during a one-week period in Science Mission phase 02 (SM02,November2010) and compared the trajectories, the post-fit measurement residuals and the estimated clock parameters. We further incorporated simultaneous passes from multiple stations within the observation data to investigate the expected improvement in positioning. The estimated trajectories were compared to the nominal LRO trajectory and the clock parameters (offset, rate and aging) to the results found in the literature. Arcs estimated with one-way ranging data had differences of 5-30 m compared to the nominal LRO trajectory. While the estimated LRO clock rates agreed closely with the a priori constraints, the aging parameters absorbed clock modeling errors with increasing clock arc length. Because of high correlations between the different ground station clocks and due to limited clock modeling accuracy, their differences only agreed at the order of magnitude with the literature. We found that the incorporation of simultaneous passes requires improved modeling in particular to enable the expected improvement in positioning. We found that gaps in the observation data coverage over 12h (approximately equals 6 successive LRO orbits) prevented the successful estimation of arcs with lengths shorter or longer than 2 or 7 days with our given modeling.

Gene transfers can date the tree of life.

PubMed

Davín, Adrián A; Tannier, Eric; Williams, Tom A; Boussau, Bastien; Daubin, Vincent; Szöllősi, Gergely J

2018-05-01

Biodiversity has always been predominantly microbial, and the scarcity of fossils from bacteria, archaea and microbial eukaryotes has prevented a comprehensive dating of the tree of life. Here, we show that patterns of lateral gene transfer deduced from an analysis of modern genomes encode a novel and abundant source of information about the temporal coexistence of lineages throughout the history of life. We use state-of-the-art species tree-aware phylogenetic methods to reconstruct the history of thousands of gene families and demonstrate that dates implied by gene transfers are consistent with estimates from relaxed molecular clocks in Bacteria, Archaea and Eukarya. We present the order of speciations according to lateral gene transfer data calibrated to geological time for three datasets comprising 40 genomes for Cyanobacteria, 60 genomes for Archaea and 60 genomes for Fungi. An inspection of discrepancies between transfers and clocks and a comparison with mammalian fossils show that gene transfer in microbes is potentially as informative for dating the tree of life as the geological record in macroorganisms.
Transient triggering of near and distant earthquakes

USGS Publications Warehouse

Gomberg, J.; Blanpied, M.L.; Beeler, N.M.

1997-01-01

We demonstrate qualitatively that frictional instability theory provides a context for understanding how earthquakes may be triggered by transient loads associated with seismic waves from near and distance earthquakes. We assume that earthquake triggering is a stick-slip process and test two hypotheses about the effect of transients on the timing of instabilities using a simple spring-slider model and a rate- and state-dependent friction constitutive law. A critical triggering threshold is implicit in such a model formulation. Our first hypothesis is that transient loads lead to clock advances; i.e., transients hasten the time of earthquakes that would have happened eventually due to constant background loading alone. Modeling results demonstrate that transient loads do lead to clock advances and that the triggered instabilities may occur after the transient has ceased (i.e., triggering may be delayed). These simple "clock-advance" models predict complex relationships between the triggering delay, the clock advance, and the transient characteristics. The triggering delay and the degree of clock advance both depend nonlinearly on when in the earthquake cycle the transient load is applied. This implies that the stress required to bring about failure does not depend linearly on loading time, even when the fault is loaded at a constant rate. The timing of instability also depends nonlinearly on the transient loading rate, faster rates more rapidly hastening instability. This implies that higher-frequency and/or longer-duration seismic waves should increase the amount of clock advance. These modeling results and simple calculations suggest that near (tens of kilometers) small/moderate earthquakes and remote (thousands of kilometers) earthquakes with magnitudes 2 to 3 units larger may be equally effective at triggering seismicity. Our second hypothesis is that some triggered seismicity represents earthquakes that would not have happened without the transient load (i.e., accumulated strain energy would have been relieved via other mechanisms). We test this using two "new-seismicity" models that (1) are inherently unstable but slide at steady-state conditions under the background load and (2) are conditionally stable such that instability occurs only for sufficiently large perturbations. For the new-seismicity models, very small-amplitude transients trigger instability relative to the clock-advance models. The unstable steady-state models predict that the triggering delay depends inversely and nonlinearly on the transient amplitude (as in the clock-advance models). We were unable to generate delayed triggering with conditionally stable models. For both new-seismicity models, the potential for triggering is independent of when the transient load is applied or, equivalently, of the prestress (unlike in the clock-advance models). In these models, a critical triggering threshold appears to be inversely proportional to frequency. Further advancement of our understanding will require more sophisticated, quantitative models and observations that distinguish between our qualitative, yet distinctly different, model predictions.
Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

PubMed Central

Ben-Moshe, Zohar; Foulkes, Nicholas S.

2014-01-01

The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model. PMID:24839600
What is dynamics in quantum gravity?

NASA Astrophysics Data System (ADS)

Małkiewicz, Przemysław

2017-10-01

The appearance of the Hamiltonian constraint in the canonical formalism for general relativity reflects the lack of a fixed external time. The dynamics of general relativistic systems can be expressed with respect to an arbitrarily chosen internal degree of freedom, the so-called internal clock. We investigate the way in which the choice of internal clock determines the quantum dynamics and how much different quantum dynamics induced by different clocks are. We develop our method of comparison by extending the Hamilton-Jacobi theory of contact transformations to include a new type of transformation which transforms both the canonical variables and the internal clock. We employ our method to study the quantum dynamics of the Friedmann-Lemaitre model and obtain semiclassical corrections to the classical dynamics, which depend on the choice of internal clock. For a unique quantisation map we find the abundance of inequivalent semiclassical corrections induced by quantum dynamics taking place in different internal clocks. It follows that the concepts like minimal volume, maximal curvature and the number of quantum bounces, often used to describe quantum effects in cosmological models, depend on the choice of internal clock.
Noise in state of the art clocks and their impact for fundamental physics

NASA Technical Reports Server (NTRS)

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.
A Stable Clock Error Model Using Coupled First and Second Order Gauss-Markov Processes

NASA Technical Reports Server (NTRS)

Carpenter, Russell; Lee, Taesul

2008-01-01

Long data outages may occur in applications of global navigation satellite system technology to orbit determination for missions that spend significant fractions of their orbits above the navigation satellite constellation(s). Current clock error models based on the random walk idealization may not be suitable in these circumstances, since the covariance of the clock errors may become large enough to overflow flight computer arithmetic. A model that is stable, but which approximates the existing models over short time horizons is desirable. A coupled first- and second-order Gauss-Markov process is such a model.
Natural Variation of the Circadian Clock in Neurospora.

PubMed

Koritala, Bala S C; Lee, Kwangwon

2017-01-01

Most living organisms on earth experience daily and expected changes from the rotation of the earth. For an organism, the ability to predict and prepare for incoming stresses or resources is a very important skill for survival. This cellular process of measuring daily time of the day is collectively called the circadian clock. Because of its fundamental role in survival in nature, there is a great interest in studying the natural variation of the circadian clock. However, characterizing the genetic and molecular mechanisms underlying natural variation of circadian clocks remains a challenging task. In this chapter, we will summarize the progress in studying natural variation of the circadian clock in the successful eukaryotic model Neurospora, which led to discovering many design principles of the molecular mechanisms of the eukaryotic circadian clock. Despite the success of the system in revealing the molecular mechanisms of the circadian clock, Neurospora has not been utilized to extensively study natural variation. We will review the challenges that hindered the natural variation studies in Neurospora, and how they were overcome. We will also review the advantages of Neurospora for natural variation studies. Since Neurospora is the model fungal species for circadian study, it represents over 5 million species of fungi on earth. These fungi play important roles in ecosystems on earth, and as such Neurospora could serve as an important model for understanding the ecological role of natural variation in fungal circadian clocks. © 2017 Elsevier Inc. All rights reserved.
The sympathy of two pendulum clocks: beyond Huygens’ observations

PubMed Central

Peña Ramirez, Jonatan; Olvera, Luis Alberto; Nijmeijer, Henk; Alvarez, Joaquin

2016-01-01

This paper introduces a modern version of the classical Huygens’ experiment on synchronization of pendulum clocks. The version presented here consists of two monumental pendulum clocks—ad hoc designed and fabricated—which are coupled through a wooden structure. It is demonstrated that the coupled clocks exhibit ‘sympathetic’ motion, i.e. the pendula of the clocks oscillate in consonance and in the same direction. Interestingly, when the clocks are synchronized, the common oscillation frequency decreases, i.e. the clocks become slow and inaccurate. In order to rigorously explain these findings, a mathematical model for the coupled clocks is obtained by using well-established physical and mechanical laws and likewise, a theoretical analysis is conducted. Ultimately, the sympathy of two monumental pendulum clocks, interacting via a flexible coupling structure, is experimentally, numerically, and analytically demonstrated. PMID:27020903
Stable Kalman filters for processing clock measurement data

NASA Technical Reports Server (NTRS)

Clements, P. A.; Gibbs, B. P.; Vandergraft, J. S.

1989-01-01

Kalman filters have been used for some time to process clock measurement data. Due to instabilities in the standard Kalman filter algorithms, the results have been unreliable and difficult to obtain. During the past several years, stable forms of the Kalman filter have been developed, implemented, and used in many diverse applications. These algorithms, while algebraically equivalent to the standard Kalman filter, exhibit excellent numerical properties. Two of these stable algorithms, the Upper triangular-Diagonal (UD) filter and the Square Root Information Filter (SRIF), have been implemented to replace the standard Kalman filter used to process data from the Deep Space Network (DSN) hydrogen maser clocks. The data are time offsets between the clocks in the DSN, the timescale at the National Institute of Standards and Technology (NIST), and two geographically intermediate clocks. The measurements are made by using the GPS navigation satellites in mutual view between clocks. The filter programs allow the user to easily modify the clock models, the GPS satellite dependent biases, and the random noise levels in order to compare different modeling assumptions. The results of this study show the usefulness of such software for processing clock data. The UD filter is indeed a stable, efficient, and flexible method for obtaining optimal estimates of clock offsets, offset rates, and drift rates. A brief overview of the UD filter is also given.
Effects of Different PER Translational Kinetics on the Dynamics of a Core Circadian Clock Model

PubMed Central

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. PMID:25607544
Effects of different per translational kinetics on the dynamics of a core circadian clock model.

PubMed

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.
A New Navigation Satellite Clock Bias Prediction Method Based on Modified Clock-bias Quadratic Polynomial Model

NASA Astrophysics Data System (ADS)

Wang, Y. P.; Lu, Z. P.; Sun, D. S.; Wang, N.

2016-01-01

In order to better express the characteristics of satellite clock bias (SCB) and improve SCB prediction precision, this paper proposed a new SCB prediction model which can take physical characteristics of space-borne atomic clock, the cyclic variation, and random part of SCB into consideration. First, the new model employs a quadratic polynomial model with periodic items to fit and extract the trend term and cyclic term of SCB; then based on the characteristics of fitting residuals, a time series ARIMA ~(Auto-Regressive Integrated Moving Average) model is used to model the residuals; eventually, the results from the two models are combined to obtain final SCB prediction values. At last, this paper uses precise SCB data from IGS (International GNSS Service) to conduct prediction tests, and the results show that the proposed model is effective and has better prediction performance compared with the quadratic polynomial model, grey model, and ARIMA model. In addition, the new method can also overcome the insufficiency of the ARIMA model in model recognition and order determination.
Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms

PubMed Central

Gérard, Claude; Goldbeter, Albert

2012-01-01

The cell division cycle and the circadian clock represent two major cellular rhythms. These two periodic processes are coupled in multiple ways, given that several molecular components of the cell cycle network are controlled in a circadian manner. For example, in the network of cyclin-dependent kinases (Cdks) that governs progression along the successive phases of the cell cycle, the synthesis of the kinase Wee1, which inhibits the G2/M transition, is enhanced by the complex CLOCK-BMAL1 that plays a central role in the circadian clock network. Another component of the latter network, REV-ERBα, inhibits the synthesis of the Cdk inhibitor p21. Moreover, the synthesis of the oncogene c-Myc, which promotes G1 cyclin synthesis, is repressed by CLOCK-BMAL1. Using detailed computational models for the two networks we investigate the conditions in which the mammalian cell cycle can be entrained by the circadian clock. We show that the cell cycle can be brought to oscillate at a period of 24 h or 48 h when its autonomous period prior to coupling is in an appropriate range. The model indicates that the combination of multiple modes of coupling does not necessarily facilitate entrainment of the cell cycle by the circadian clock. Entrainment can also occur as a result of circadian variations in the level of a growth factor controlling entry into G1. Outside the range of entrainment, the coupling to the circadian clock may lead to disconnected oscillations in the cell cycle and the circadian system, or to complex oscillatory dynamics of the cell cycle in the form of endoreplication, complex periodic oscillations or chaos. The model predicts that the transition from entrainment to 24 h or 48 h might occur when the strength of coupling to the circadian clock or the level of growth factor decrease below critical values. PMID:22693436
The clock and wavefront model revisited.

PubMed

Murray, Philip J; Maini, Philip K; Baker, Ruth E

2011-08-21

The currently accepted interpretation of the clock and wavefront model of somitogenesis is that a posteriorly moving molecular gradient sequentially slows the rate of clock oscillations, resulting in a spatial readout of temporal oscillations. However, while molecular components of the clocks and wavefronts have now been identified in the pre-somitic mesoderm (PSM), there is not yet conclusive evidence demonstrating that the observed molecular wavefronts act to slow clock oscillations. Here we present an alternative formulation of the clock and wavefront model in which oscillator coupling, already known to play a key role in oscillator synchronisation, plays a fundamentally important role in the slowing of oscillations along the anterior-posterior (AP) axis. Our model has three parameters which can be determined, in any given species, by the measurement of three quantities: the clock period in the posterior PSM, somite length and the length of the PSM. A travelling wavefront, which slows oscillations along the AP axis, is an emergent feature of the model. Using the model we predict: (a) the distance between moving stripes of gene expression; (b) the number of moving stripes of gene expression and (c) the oscillator period profile along the AP axis. Predictions regarding the stripe data are verified using existing zebrafish data. We simulate a range of experimental perturbations and demonstrate how the model can be used to unambiguously define a reference frame along the AP axis. Comparing data from zebrafish, chick, mouse and snake, we demonstrate that: (a) variation in patterning profiles is accounted for by a single nondimensional parameter; the ratio of coupling strengths; and (b) the period profile along the AP axis is conserved across species. Thus the model is consistent with the idea that, although the genes involved in pattern propagation in the PSM vary, there is a conserved patterning mechanism across species. Copyright © 2011 Elsevier Ltd. All rights reserved.
The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity

PubMed Central

Plikus, Maksim V.; Van Spyk, Elyse Noelani; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S.; Andersen, Bogi

2015-01-01

Historically work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as liver, fat and muscle. In recent years, skin is emerging as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging and carcinogenesis. Morphologically skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration -- the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell-type specific circadian mutants. Also, due to the accessibility of the skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar UV radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. The skin also provides opportunities to interrogate clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model for investigating the role of clock in seasonal organismal behaviors. PMID:25589491
A Novel Application of Machine Learning Methods to Model Microcontroller Upset Due to Intentional Electromagnetic Interference

NASA Astrophysics Data System (ADS)

Bilalic, Rusmir

A novel application of support vector machines (SVMs), artificial neural networks (ANNs), and Gaussian processes (GPs) for machine learning (GPML) to model microcontroller unit (MCU) upset due to intentional electromagnetic interference (IEMI) is presented. In this approach, an MCU performs a counting operation (0-7) while electromagnetic interference in the form of a radio frequency (RF) pulse is direct-injected into the MCU clock line. Injection times with respect to the clock signal are the clock low, clock rising edge, clock high, and the clock falling edge periods in the clock window during which the MCU is performing initialization and executing the counting procedure. The intent is to cause disruption in the counting operation and model the probability of effect (PoE) using machine learning tools. Five experiments were executed as part of this research, each of which contained a set of 38,300 training points and 38,300 test points, for a total of 383,000 total points with the following experiment variables: injection times with respect to the clock signal, injected RF power, injected RF pulse width, and injected RF frequency. For the 191,500 training points, the average training error was 12.47%, while for the 191,500 test points the average test error was 14.85%, meaning that on average, the machine was able to predict MCU upset with an 85.15% accuracy. Leaving out the results for the worst-performing model (SVM with a linear kernel), the test prediction accuracy for the remaining machines is almost 89%. All three machine learning methods (ANNs, SVMs, and GPML) showed excellent and consistent results in their ability to model and predict the PoE on an MCU due to IEMI. The GP approach performed best during training with a 7.43% average training error, while the ANN technique was most accurate during the test with a 10.80% error.

Cryptochrome Mediates Light-Dependent Magnetosensitivity of Drosophila's Circadian Clock

PubMed Central

Yoshii, Taishi; Ahmad, Margaret; Helfrich-Förster, Charlotte

2009-01-01

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 μT, 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, cryb and cryOUT 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 for CRY-dependent magnetic sensitivity. Furthermore, given that CRY occurs in multiple tissues of Drosophila, including those potentially implicated in fly orientation, future studies may yield insights that could be applicable to the magnetic compass of migratory birds and even to potential magnetic field effects in humans. PMID:19355790
Ultrahigh-resolution spectroscopy with atomic or molecular dark resonances: Exact steady-state line shapes and asymptotic profiles in the adiabatic pulsed regime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zanon-Willette, Thomas; Clercq, Emeric de; Arimondo, Ennio

2011-12-15

Exact and asymptotic line shape expressions are derived from the semiclassical density matrix representation describing a set of closed three-level {Lambda} atomic or molecular states including decoherences, relaxation rates, and light shifts. An accurate analysis of the exact steady-state dark-resonance profile describing the Autler-Townes doublet, the electromagnetically induced transparency or coherent population trapping resonance, and the Fano-Feshbach line shape leads to the linewidth expression of the two-photon Raman transition and frequency shifts associated to the clock transition. From an adiabatic analysis of the dynamical optical Bloch equations in the weak field limit, a pumping time required to efficiently trap amore » large number of atoms into a coherent superposition of long-lived states is established. For a highly asymmetrical configuration with different decay channels, a strong two-photon resonance based on a lower states population inversion is established when the driving continuous-wave laser fields are greatly unbalanced. When time separated resonant two-photon pulses are applied in the adiabatic pulsed regime for atomic or molecular clock engineering, where the first pulse is long enough to reach a coherent steady-state preparation and the second pulse is very short to avoid repumping into a new dark state, dark-resonance fringes mixing continuous-wave line shape properties and coherent Ramsey oscillations are created. Those fringes allow interrogation schemes bypassing the power broadening effect. Frequency shifts affecting the central clock fringe computed from asymptotic profiles and related to the Raman decoherence process exhibit nonlinear shapes with the three-level observable used for quantum measurement. We point out that different observables experience different shifts on the lower-state clock transition.« less
Chronobiology of crickets: a review.

PubMed

Tomioka, Kenji

2014-10-01

Crickets provide a good model for the study of mechanisms underlying circadian rhythms and photoperiodic responses. They show clear circadian rhythms in their overt behavior and the sensitivity of the visual system. Classical neurobiological studies revealed that a pair of optic lobes is the locus of the circadian clock controlling these rhythms and that the compound eye is the major photoreceptor necessary for synchronization to environmental light cycles. The two optic lobe clocks are mutually coupled through a neural pathway and the coupling regulates an output circadian waveform and a free-running period. Recent molecular studies revealed that the cricket's clock consists of cyclic expression of so-called clock genes and that the clock mechanism is featured by both Drosophila-like and mammalian-like traits. Molecular oscillation is also observed in some extra-optic lobe tissues and depends on the optic lobe clock in a tissue dependent manner. Interestingly, the clock is also involved in adaptation to seasonally changing environment. It fits its waveform to a given photoperiod and may be an indispensable part of a photoperiodic time-measurement mechanism. With adoption of modern molecular technologies, the cricket becomes a much more important and promising model animal for the study of circadian and photoperiodic biology.
Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis.

PubMed

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.
Regulation of circadian blood pressure: from mice to astronauts.

PubMed

Agarwal, Rajiv

2010-01-01

Circadian variation is commonly seen in healthy people; aberration in these biological rhythms is an early sign of disease. Impaired circadian variation of blood pressure (BP) has been shown to be associated with greater target organ damage and with an elevated risk of cardiovascular events independent of the BP load. The purpose of this review is to examine the physiology of circadian BP variation and propose a tripartite model that explains the regulation of circadian BP. The time-keeper in mammals resides centrally in the suprachiasmatic nucleus. Apart from this central clock, molecular clocks exist in most peripheral tissues including vascular tissue and the kidney. These molecular clocks regulate sodium balance, sympathetic function and vascular tone. A physiological model is proposed that integrates our understanding of molecular clocks in mice with the circadian BP variation among humans. The master regulator in this proposed model is the sleep-activity cycle. The equivalents of peripheral clocks are endothelial and adrenergic functions. Thus, in the proposed model, the variation in circadian BP is dependent upon three major factors: physical activity, autonomic function, and sodium sensitivity. The integrated consideration of physical activity, autonomic function, and sodium sensitivity appears to explain the physiology of circadian BP variation and the pathophysiology of disrupted BP rhythms in various conditions and disease states. Our understanding of molecular clocks in mice may help to explain the provenance of blunted circadian BP variation even among astronauts.
Real-Time Distributed Embedded Oscillator Operating Frequency Monitoring

NASA Technical Reports Server (NTRS)

Pollock, Julie; Oliver, Brett; Brickner, Christopher

2012-01-01

A document discusses the utilization of embedded clocks inside of operating network data links as an auxiliary clock source to satisfy local oscillator monitoring requirements. Modem network interfaces, typically serial network links, often contain embedded clocking information of very tight precision to recover data from the link. This embedded clocking data can be utilized by the receiving device to monitor the local oscillator for tolerance to required specifications, often important in high-integrity fault-tolerant applications. A device can utilize a received embedded clock to determine if the local or the remote device is out of tolerance by using a single link. The local device can determine if it is failing, assuming a single fault model, with two or more active links. Network fabric components, containing many operational links, can potentially determine faulty remote or local devices in the presence of multiple faults. Two methods of implementation are described. In one method, a recovered clock can be directly used to monitor the local clock as a direct replacement of an external local oscillator. This scheme is consistent with a general clock monitoring function whereby clock sources are clocking two counters and compared over a fixed interval of time. In another method, overflow/underflow conditions can be used to detect clock relationships for monitoring. These network interfaces often provide clock compensation circuitry to allow data to be transferred from the received (network) clock domain to the internal clock domain. This circuit could be modified to detect overflow/underflow conditions of the buffering required and report a fast or slow receive clock, respectively.
Impaired light detection of the circadian clock in a zebrafish melanoma model

PubMed Central

Hamilton, Noémie; Diaz-de-Cerio, Natalia; Whitmore, David

2015-01-01

The circadian clock controls the timing of the cell cycle in healthy tissues and clock disruption is known to increase tumourigenesis. Melanoma is one of the most rapidly increasing forms of cancer and the precise molecular circadian changes that occur in a melanoma tumor are unknown. Using a melanoma zebrafish model, we have explored the molecular changes that occur to the circadian clock within tumors. We have found disruptions in melanoma clock gene expression due to a major impairment to the light input pathway, with a parallel loss of light-dependent activation of DNA repair genes. Furthermore, the timing of mitosis in tumors is perturbed, as well as the regulation of certain key cell cycle regulators, such that cells divide arhythmically. The inability to co-ordinate DNA damage repair and cell division is likely to promote further tumourigenesis and accelerate melanoma development. PMID:25832911
Impaired light detection of the circadian clock in a zebrafish melanoma model.

PubMed

Hamilton, Noémie; Diaz-de-Cerio, Natalia; Whitmore, David

2015-01-01

The circadian clock controls the timing of the cell cycle in healthy tissues and clock disruption is known to increase tumourigenesis. Melanoma is one of the most rapidly increasing forms of cancer and the precise molecular circadian changes that occur in a melanoma tumor are unknown. Using a melanoma zebrafish model, we have explored the molecular changes that occur to the circadian clock within tumors. We have found disruptions in melanoma clock gene expression due to a major impairment to the light input pathway, with a parallel loss of light-dependent activation of DNA repair genes. Furthermore, the timing of mitosis in tumors is perturbed, as well as the regulation of certain key cell cycle regulators, such that cells divide arhythmically. The inability to co-ordinate DNA damage repair and cell division is likely to promote further tumourigenesis and accelerate melanoma development.
Analysis of Circadian Leaf Movements.

PubMed

Müller, Niels A; Jiménez-Gómez, José M

2016-01-01

The circadian clock is a molecular timekeeper that controls a wide variety of biological processes. In plants, clock outputs range from the molecular level, with rhythmic gene expression and metabolite content, to physiological processes such as stomatal conductance or leaf movements. Any of these outputs can be used as markers to monitor the state of the circadian clock. In the model plant Arabidopsis thaliana, much of the current knowledge about the clock has been gained from time course experiments profiling expression of endogenous genes or reporter constructs regulated by the circadian clock. Since these methods require labor-intensive sample preparation or transformation, monitoring leaf movements is an interesting alternative, especially in non-model species and for natural variation studies. Technological improvements both in digital photography and image analysis allow cheap and easy monitoring of circadian leaf movements. In this chapter we present a protocol that uses an autonomous point and shoot camera and free software to monitor circadian leaf movements in tomato.
Initial atomic coherences and Ramsey frequency pulling in fountain clocks

NASA Astrophysics Data System (ADS)

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.
A remark on the GNSS single difference model with common clock scheme for attitude determination

NASA Astrophysics Data System (ADS)

Chen, Wantong

2016-09-01

GNSS-based attitude determination technique is an important field of study, in which two schemes can be used to construct the actual system: the common clock scheme and the non-common clock scheme. Compared with the non-common clock scheme, the common clock scheme can strongly improve both the reliability and the accuracy. However, in order to gain these advantages, specific care must be taken in the implementation. The cares are thus discussed, based on the generating technique of carrier phase measurement in GNSS receivers. A qualitative assessment of potential phase bias contributes is also carried out. Possible technical difficulties are pointed out for the development of single-board multi-antenna GNSS attitude systems with a common clock.
A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

PubMed Central

Flourakis, Matthieu; Kula-Eversole, Elzbieta; Hutchison, Alan L.; Han, Tae Hee; Aranda, Kimberly; Moose, Devon L.; White, Kevin P.; Dinner, Aaron R.; Lear, Bridget C.; Ren, Dejian; Diekman, Casey O.; Raman, Indira M.; Allada, Ravi

2015-01-01

Summary Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons. This current is driven by the rhythmic expression of NCA localization factor-1, linking the molecular clock to ion channel function. In the evening, basal potassium currents peak to silence clock neurons. Remarkably, daily antiphase cycles of sodium and potassium currents also drive mouse clock neuron rhythms. Thus, we reveal an evolutionarily ancient strategy for the neural mechanisms that govern daily sleep and wake. PMID:26276633
Circadian Clock Dysfunction and Psychiatric Disease: Could Fruit Flies have a Say?

PubMed Central

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. PMID:25941512
Autonomous Quantum Clocks: Does Thermodynamics Limit Our Ability to Measure Time?

NASA Astrophysics Data System (ADS)

Erker, Paul; Mitchison, Mark T.; Silva, Ralph; Woods, Mischa P.; Brunner, Nicolas; Huber, Marcus

2017-07-01

Time remains one of the least well-understood concepts in physics, most notably in quantum mechanics. A central goal is to find the fundamental limits of measuring time. One of the main obstacles is the fact that time is not an observable and thus has to be measured indirectly. Here, we explore these questions by introducing a model of time measurements that is complete and autonomous. Specifically, our autonomous quantum clock consists of a system out of thermal equilibrium—a prerequisite for any system to function as a clock—powered by minimal resources, namely, two thermal baths at different temperatures. Through a detailed analysis of this specific clock model, we find that the laws of thermodynamics dictate a trade-off between the amount of dissipated heat and the clock's performance in terms of its accuracy and resolution. Our results furthermore imply that a fundamental entropy production is associated with the operation of any autonomous quantum clock, assuming that quantum machines cannot achieve perfect efficiency at finite power. More generally, autonomous clocks provide a natural framework for the exploration of fundamental questions about time in quantum theory and beyond.
Multi-locus phylogeny and divergence time estimates of Enallagma damselflies (Odonata: Coenagrionidae).

PubMed

Callahan, Melissa S; McPeek, Mark A

2016-01-01

Reconstructing evolutionary patterns of species and populations provides a framework for asking questions about the impacts of climate change. Here we use a multilocus dataset to estimate gene trees under maximum likelihood and Bayesian models to obtain a robust estimate of relationships for a genus of North American damselflies, Enallagma. Using a relaxed molecular clock, we estimate the divergence times for this group. Furthermore, to account for the fact that gene tree analyses can overestimate ages of population divergences, we use a multi-population coalescent model to gain a more accurate estimate of divergence times. We also infer diversification rates using a method that allows for variation in diversification rate through time and among lineages. Our results reveal a complex evolutionary history of Enallagma, in which divergence events both predate and occur during Pleistocene climate fluctuations. There is also evidence of diversification rate heterogeneity across the tree. These divergence time estimates provide a foundation for addressing the relative significance of historical climatic events in the diversification of this genus. Copyright © 2015 Elsevier Inc. All rights reserved.
A Genome-Wide RNAi Screen for Modifiers of the Circadian Clock in Human Cells

PubMed Central

Zhang, Eric E.; Liu, Andrew C.; Hirota, Tsuyoshi; Miraglia, Loren J.; Welch, Genevieve; Pongsawakul, Pagkapol Y.; Liu, Xianzhong; Atwood, Ann; Huss, Jon W.; Janes, Jeff; Su, Andrew I.; Hogenesch, John B.; Kay, Steve A.

2009-01-01

Summary Two decades of research identified more than a dozen clock genes and defined a biochemical feedback mechanism of circadian oscillator function. To identify additional clock genes and modifiers, we conducted a genome-wide siRNA screen in a human cellular clock model. Knockdown of nearly a thousand genes reduced rhythm amplitude. Potent effects on period length or increased amplitude were less frequent; we found hundreds of these and confirmed them in secondary screens. Characterization of a subset of these genes demonstrated a dosage-dependent effect on oscillator function. Protein interaction network analysis showed that dozens of gene products directly or indirectly associate with known clock components. Pathway analysis revealed these genes are overrepresented for components of insulin and hedgehog signaling, the cell cycle, and the folate metabolism. Coupled with data showing many of these pathways are clock-regulated, we conclude the clock is interconnected with many aspects of cellular function. PMID:19765810
Performance Analysis of Several GPS/Galileo Precise Point Positioning Models

PubMed Central

Afifi, Akram; El-Rabbany, Ahmed

2015-01-01

This paper examines the performance of several precise point positioning (PPP) models, which combine dual-frequency GPS/Galileo observations in the un-differenced and between-satellite single-difference (BSSD) modes. These include the traditional un-differenced model, the decoupled clock model, the semi-decoupled clock model, and the between-satellite single-difference model. We take advantage of the IGS-MGEX network products to correct for the satellite differential code biases and the orbital and satellite clock errors. Natural Resources Canada’s GPSPace PPP software is modified to handle the various GPS/Galileo PPP models. A total of six data sets of GPS and Galileo observations at six IGS stations are processed to examine the performance of the various PPP models. It is shown that the traditional un-differenced GPS/Galileo PPP model, the GPS decoupled clock model, and the semi-decoupled clock GPS/Galileo PPP model improve the convergence time by about 25% in comparison with the un-differenced GPS-only model. In addition, the semi-decoupled GPS/Galileo PPP model improves the solution precision by about 25% compared to the traditional un-differenced GPS/Galileo PPP model. Moreover, the BSSD GPS/Galileo PPP model improves the solution convergence time by about 50%, in comparison with the un-differenced GPS PPP model, regardless of the type of BSSD combination used. As well, the BSSD model improves the precision of the estimated parameters by about 50% and 25% when the loose and the tight combinations are used, respectively, in comparison with the un-differenced GPS-only model. Comparable results are obtained through the tight combination when either a GPS or a Galileo satellite is selected as a reference. PMID:26102495
Performance Analysis of Several GPS/Galileo Precise Point Positioning Models.

PubMed

Afifi, Akram; El-Rabbany, Ahmed

2015-06-19

This paper examines the performance of several precise point positioning (PPP) models, which combine dual-frequency GPS/Galileo observations in the un-differenced and between-satellite single-difference (BSSD) modes. These include the traditional un-differenced model, the decoupled clock model, the semi-decoupled clock model, and the between-satellite single-difference model. We take advantage of the IGS-MGEX network products to correct for the satellite differential code biases and the orbital and satellite clock errors. Natural Resources Canada's GPSPace PPP software is modified to handle the various GPS/Galileo PPP models. A total of six data sets of GPS and Galileo observations at six IGS stations are processed to examine the performance of the various PPP models. It is shown that the traditional un-differenced GPS/Galileo PPP model, the GPS decoupled clock model, and the semi-decoupled clock GPS/Galileo PPP model improve the convergence time by about 25% in comparison with the un-differenced GPS-only model. In addition, the semi-decoupled GPS/Galileo PPP model improves the solution precision by about 25% compared to the traditional un-differenced GPS/Galileo PPP model. Moreover, the BSSD GPS/Galileo PPP model improves the solution convergence time by about 50%, in comparison with the un-differenced GPS PPP model, regardless of the type of BSSD combination used. As well, the BSSD model improves the precision of the estimated parameters by about 50% and 25% when the loose and the tight combinations are used, respectively, in comparison with the un-differenced GPS-only model. Comparable results are obtained through the tight combination when either a GPS or a Galileo satellite is selected as a reference.
Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior.

PubMed

Ben-Moshe Livne, Zohar; Alon, Shahar; Vallone, Daniela; Bayleyen, Yared; Tovin, Adi; Shainer, Inbal; Nisembaum, Laura G; Aviram, Idit; Smadja-Storz, Sima; Fuentes, Michael; Falcón, Jack; Eisenberg, Eli; Klein, David C; Burgess, Harold A; Foulkes, Nicholas S; Gothilf, Yoav

2016-11-01

The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior.
Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior

PubMed Central

Alon, Shahar; Vallone, Daniela; Tovin, Adi; Shainer, Inbal; Nisembaum, Laura G.; Aviram, Idit; Smadja-Storz, Sima; Fuentes, Michael; Falcón, Jack; Eisenberg, Eli; Klein, David C.; Burgess, Harold A.; Foulkes, Nicholas S.; Gothilf, Yoav

2016-01-01

The master circadian clock in fish has been considered to reside in the pineal gland. This dogma is challenged, however, by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light. To further examine the role of the pineal gland oscillator in the zebrafish circadian system, we generated a transgenic line in which the molecular clock is selectively blocked in the melatonin-producing cells of the pineal gland by a dominant-negative strategy. As a result, clock-controlled rhythms of melatonin production in the adult pineal gland were disrupted. Moreover, transcriptome analysis revealed that the circadian expression pattern of the majority of clock-controlled genes in the adult pineal gland is abolished. Importantly, circadian rhythms of behavior in zebrafish larvae were affected: rhythms of place preference under constant darkness were eliminated, and rhythms of locomotor activity under constant dark and constant dim light conditions were markedly attenuated. On the other hand, global peripheral molecular oscillators, as measured in whole larvae, were unaffected in this model. In conclusion, characterization of this novel transgenic model provides evidence that the molecular clock in the melatonin-producing cells of the pineal gland plays a key role, possibly as part of a multiple pacemaker system, in modulating circadian rhythms of behavior. PMID:27870848

Inheritance of Cell-Cycle Duration in the Presence of Periodic Forcing

NASA Astrophysics Data System (ADS)

Mosheiff, Noga; Martins, Bruno M. C.; Pearl-Mizrahi, Sivan; Grünberger, Alexander; Helfrich, Stefan; Mihalcescu, Irina; Kohlheyer, Dietrich; Locke, James C. W.; Glass, Leon; Balaban, Nathalie Q.

2018-04-01

Periodic forcing of nonlinear oscillators leads to a large number of dynamic behaviors. The coupling of the cell cycle to the circadian clock provides a biological realization of such forcing. A previous model of forcing leads to nontrivial relations between correlations along cell lineages. Here, we present a simplified two-dimensional nonlinear map for the periodic forcing of the cell cycle. Using high-throughput single-cell microscopy, we have studied the correlations between cell-cycle duration in discrete lineages of several different organisms, including those with known coupling to a circadian clock and those without known coupling to a circadian clock. The model reproduces the paradoxical correlations and predicts new features that can be compared with the experimental data. By fitting the model to the data, we extract the important parameters that govern the dynamics. Interestingly, the model reproduces bimodal distributions for cell-cycle duration, as well as the gating of cell division by the phase of the clock, without having been explicitly fed into the model. In addition, the model predicts that circadian coupling may increase cell-to-cell variability in a clonal population of cells. In agreement with this prediction, deletion of the circadian clock reduces variability. Our results show that simple correlations can identify systems under periodic forcing and that studies of nonlinear coupling of biological oscillators provide insight into basic cellular processes of growth.
Subordination to periodic processes and synchronization

NASA Astrophysics Data System (ADS)

Ascolani, Gianluca; Bologna, Mauro; Grigolini, Paolo

2009-07-01

We study the subordination to a process that is periodic in the natural time scale, and equivalent to a clock with N states. The rationale for this investigation is given by a set of many interacting clocks with N states. The natural time scale representation corresponds to the dynamics of an individual clock with no interaction with the other clocks of this set. We argue that the cooperation among the clocks of this set has the effect of generating a global clock, whose times of sojourn in each of its N states are described by a distribution density with an inverse power law form and power index μ<2. This is equivalent to extending the widely used subordination method from fluctuation-dissipation processes to periodic processes, thereby raising the question of whether special conditions exist of perfect synchronization, signaled by regular oscillations, and especially by oscillations with no damping. We study first the case of a Poisson subordination function. We show that in spite of the random nature of the subordination method the procedure has the effect of creating damped oscillations, whose damping vanishes in the limiting case of N≫1, thereby suggesting a condition of perfect synchronization in this limit. The Bateman’s mathematical arguments [H. Bateman, Higher Transcendental Functions, vol. III, Robert K Krieger, Publishing Company, Inc. Krim.Fr. Drive Malabar, FL; Copyright 1953 by McGraw-Hill Book Company Inc.] indicate that the condition of perfect synchronization is possible also in the non-Poisson case, with μ<2, although it may lie beyond the range of computer simulation. To make the theoretical predictions accessible to numerical simulation, we use a subordination function whose survival probability is a Mittag-Leffler exponential function. This method prevents us from directly establishing the macroscopic coherence emerging from μ=2, which generates a perfect form of 1/f noise. However, it affords indirect evidence that perfect synchronization signaled by undamped regular oscillations may be produced in this case. Furthermore, we explore a condition characterized by an excellent agreement between theory and numerical simulation, where the long-time region relaxation, with a perfect inverse power law decay, emerging from the subordination to ordinary fluctuation-dissipation processes, is replaced by exponentially damped regular oscillations.
A Simple Electromagnetic Model for the Light Clock of Special Relativity

ERIC Educational Resources Information Center

Smith, Glenn S.

2011-01-01

Thought experiments involving a light clock are common in introductory treatments of special relativity, because they provide a simple way of demonstrating the non-intuitive phenomenon of time dilation. The properties of the ray or pulse of light that is continuously reflected between the parallel mirrors of the clock are often stated vaguely and…
RAPID COMMUNICATION: Improving prediction accuracy of GPS satellite clocks with periodic variation behaviour

NASA Astrophysics Data System (ADS)

Heo, Youn Jeong; Cho, Jeongho; Heo, Moon Beom

2010-07-01

The broadcast ephemeris and IGS ultra-rapid predicted (IGU-P) products are primarily available for use in real-time GPS applications. The IGU orbit precision has been remarkably improved since late 2007, but its clock products have not shown acceptably high-quality prediction performance. One reason for this fact is that satellite atomic clocks in space can be easily influenced by various factors such as temperature and environment and this leads to complicated aspects like periodic variations, which are not sufficiently described by conventional models. A more reliable prediction model is thus proposed in this paper in order to be utilized particularly in describing the periodic variation behaviour satisfactorily. The proposed prediction model for satellite clocks adds cyclic terms to overcome the periodic effects and adopts delay coordinate embedding, which offers the possibility of accessing linear or nonlinear coupling characteristics like satellite behaviour. The simulation results have shown that the proposed prediction model outperforms the IGU-P solutions at least on a daily basis.
Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1

DOE PAGES

Michael, Alicia K.; Fribourgh, Jennifer L.; Chelliah, Yogarany; ...

2017-01-31

The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solutionmore » X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.« less
Biological timing and the clock metaphor: oscillatory and hourglass mechanisms.

PubMed

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 as relevant models, are briefly re viewed. Hourglass clocks are based on linear or exponential unidirectional processes that trigger events mainly in the course of development and aging. An important hourglass mechanism within the aging process is the limitation of cell division capacity by the length of telomeres. The mechanism of this clock is briefly reviewed. In all clock mechanisms, thresholds at which "dependent variables" are triggered play an important role.
DOE Office of Scientific and Technical Information (OSTI.GOV)

Michael, Alicia K.; Fribourgh, Jennifer L.; Chelliah, Yogarany

The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solutionmore » X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.« less
Microfabricated spin exchange relaxation free atomic magnetometer

NASA Astrophysics Data System (ADS)

Griffith, W. Clark; Jimenez-Martinez, Ricardo; Preusser, Jan; Knappe, Svenja; Kitching, John

2009-05-01

Methods first developed at NIST for MEMS-based atomic clocks have been applied to magnetic field sensors. The sensors are built around microfabricated alkali-atom vapor cells integrated with micro-optics and a VCSEL light source. Exceptional magnetic field sensitivities can be achieved in a small volume vapor cell, especially when operated in the spin-exchange relaxation free (SERF) regime. In this technique, magnetic resonance broadening due to spin-exchange collisions is suppressed under conditions of high alkali density and low magnetic fields. We have demonstrated sensitivities better than 100 fT/Hz^1/2 with a millimeter scale SERF sensor.ootnotetextV. Shah, S. Knappe, P.D.D. Schwindt, and J. Kitching, Nature Photonics, 1, 649 (2007). Adding flux concentratorsootnotetextW.C. Griffith, R. Jimenez-Martinez, V. Shah, S. Knappe, and J. Kitching, Appl. Phys. Lett., 94, 023502 (2009). around the vapor cell further improves the sensitivity to 10 fT/Hz^1/2, potentially providing a low power, noncryogenic alternative to SQUID sensors.
Investigation of Seasonal and Latitudinal Effects on the Expression of Clock Genes in Drosophila

NASA Astrophysics Data System (ADS)

Hosseini, Seyede Sanaz; Nazarimehr, Fahimeh; Jafari, Sajad

The primary goal in this work is to develop a dynamical model capturing the influence of seasonal and latitudinal variations on the expression of Drosophila clock genes. To this end, we study a specific dynamical system with strange attractors that exhibit changes of Drosophila activity in a range of latitudes and across different seasons. Bifurcations of this system are analyzed to peruse the effect of season and latitude on the behavior of clock genes. Existing experimental data collected from the activity of Drosophila melanogaster corroborate the dynamical model.
Potential Conservation of Circadian Clock Proteins in the phylum Nematoda as Revealed by Bioinformatic Searches

PubMed Central

Romanowski, Andrés; Garavaglia, Matías Javier; Goya, María Eugenia; Ghiringhelli, Pablo Daniel; Golombek, Diego Andrés

2014-01-01

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system. PMID:25396739
Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches.

PubMed

Romanowski, Andrés; Garavaglia, Matías Javier; Goya, María Eugenia; Ghiringhelli, Pablo Daniel; Golombek, Diego Andrés

2014-01-01

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.
The role of the mechanical clock in medieval science.

PubMed

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.
Crosstalk of clock gene expression and autophagy in aging

PubMed Central

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

2016-01-01

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

PubMed

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

2016-08-28

Autophagy and the circadian clock counteract tissue degeneration and support longevity in many organisms. Accumulating evidence indicates that aging compromises both the circadian clock and autophagy but the mechanisms involved are unknown. Here we show that the expression levels of transcriptional repressor components of the circadian oscillator, most prominently the human Period homologue PER2 , are strongly reduced in primary dermal fibroblasts from aged humans, while raising the expression of PER2 in the same cells partially restores diminished autophagy levels. The link between clock gene expression and autophagy is corroborated by the finding that the circadian clock drives cell-autonomous, rhythmic autophagy levels in immortalized murine fibroblasts, and that siRNA-mediated downregulation of PER2 decreases autophagy levels while leaving core clock oscillations intact. Moreover, the Period homologue lin-42 regulates autophagy and life span in the nematode Caenorhabditis elegans , suggesting an evolutionarily conserved role for Period proteins in autophagy control and aging. Taken together, this study identifies circadian clock proteins as set-point regulators of autophagy and puts forward a model, in which age-related changes of clock gene expression promote declining autophagy levels.
On-orbit frequency stability analysis of the GPS NAVSTAR-1 quartz clock and the NAVSTARs-6 and -8 rubidium clocks

NASA Technical Reports Server (NTRS)

Mccaskill, T. B.; Buisson, J. A.; Reid, W. G.

1984-01-01

An on-orbit frequency stability performance analysis of the GPS NAVSTAR-1 quartz clock and the NAVSTARs-6 and -8 rubidium clocks is presented. The clock offsets were obtained from measurements taken at the GPS monitor stations which use high performance cesium standards as a reference. Clock performance is characterized through the use of the Allan variance, which is evaluated for sample times of 15 minutes to two hours, and from one day to 10 days. The quartz and rubidium clocks' offsets were corrected for aging rate before computing the frequency stability. The effect of small errors in aging rate is presented for the NAVSTAR-8 rubidium clock's stability analysis. The analysis includes presentation of time and frequency residuals with respect to linear and quadratic models, which aid in obtaining aging rate values and identifying systematic and random effects. The frequency stability values were further processed with a time domain noise process analysis, which is used to classify random noise process and modulation type.
The circadian clock of Neurospora crassa.

PubMed

Baker, Christopher L; Loros, Jennifer J; Dunlap, Jay C

2012-01-01

Circadian clocks organize our inner physiology with respect to the external world, providing life with the ability to anticipate and thereby better prepare for major fluctuations in its environment. Circadian systems are widely represented in nearly all major branches of life, except archaebacteria, and within the eukaryotes, the filamentous fungus Neurospora crassa has served for nearly half a century as a durable model organism for uncovering the basic circadian physiology and molecular biology. Studies using Neurospora have clarified our fundamental understanding of the clock as nested positive and negative feedback loops regulated through transcriptional and post-transcriptional processes. These feedback loops are centered on a limited number of proteins that form molecular complexes, and their regulation provides a physical explanation for nearly all clock properties. This review will introduce the basics of circadian rhythms, the model filamentous fungus N. crassa, and provide an overview of the molecular components and regulation of the circadian clock. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
Flatfish monophyly refereed by the relationship of Psettodes in Carangimorphariae.

PubMed

Shi, Wei; Chen, Shixi; Kong, Xiaoyu; Si, Lizhen; Gong, Li; Zhang, Yanchun; Yu, Hui

2018-05-25

The monophyly of flatfishes has not been supported in many molecular phylogenetic studies. The monophyly of Pleuronectoidei, which comprises all but one family of flatfishes, is broadly supported. However, the Psettodoidei, comprising the single family Psettodidae, is often found to be most closely related to other carangimorphs based on substantial sequencing efforts and diversely analytical methods. In this study, we examined why this particular result is often obtained. The mitogenomes of five flatfishes were determined. Select mitogenomes of representative carangimorph species were further employed for phylogenetic and molecular clock analyses. Our phylogenetic results do not fully support Psettodes as a sister group to pleuronectoids or other carangimorphs. And results also supported the evidence of long-branch attraction between Psettodes and the adjacent clades. Two chronograms, derived from Bayesian relaxed-clock methods, suggest that over a short period in the early Paleocene, a series of important evolutionary events occurred in carangimorphs. Based on insights provided by the molecular clock, we propose the following evolutionary explanation for the difficulty in determining the phylogenetic position of Psettodes: The initial diversification of Psettodes was very close in time to the initial diversification of carangimorphs, and the primary diversification time of pleuronectoids, the other suborder of flatfishes, occurred later than that of some percomorph taxa. Additionally, the clade of Psettodes is long and naked branch, which supports the uncertainty of its phylogenetic placement. Finally, we confirmed the monophyly of flatfishes, which was accepted by most ichthyologists.
Species Radiation of Carabid Beetles (Broscini: Mecodema) in New Zealand

PubMed Central

Goldberg, Julia; Knapp, Michael; Emberson, Rowan M.; Townsend, J. Ian; Trewick, Steven A.

2014-01-01

New Zealand biodiversity has often been viewed as Gondwanan in origin and age, but it is increasingly apparent from molecular studies that diversification, and in many cases origination of lineages, postdate the break-up of Gondwanaland. Relatively few studies of New Zealand animal species radiations have as yet been reported, and here we consider the species-rich genus of carabid beetles, Mecodema. Constrained stratigraphic information (emergence of the Chatham Islands) and a substitution rate for Coleoptera were separately used to calibrate Bayesian relaxed molecular clock date estimates for diversification of Mecodema. The inferred timings indicate radiation of these beetles no earlier than the mid-Miocene with most divergences being younger, dating to the Plio-Pleistocene. A shallow age for the radiation along with a complex spatial distribution of these taxa involving many instances of sympatry implicates recent ecological speciation rather than a simplistic allopatric model. This emphasises the youthful and dynamic nature of New Zealand evolution that will be further elucidated with detailed ecological and population genetic analyses. PMID:24465949
A clock network for geodesy and fundamental science

PubMed Central

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.

2016-01-01

Leveraging the unrivalled performance of optical clocks as key tools for geo-science, for astronomy and for fundamental physics beyond the standard model requires comparing the frequency of distant optical clocks faithfully. Here, we report on the comparison and agreement of two strontium optical clocks at an uncertainty of 5 × 10−17 via a newly established phase-coherent frequency link connecting Paris and Braunschweig using 1,415 km of telecom fibre. The remote comparison is limited only by the instability and uncertainty of the strontium lattice clocks themselves, with negligible contributions from the optical frequency transfer. A fractional precision of 3 × 10−17 is reached after only 1,000 s averaging time, which is already 10 times better and more than four orders of magnitude faster than any previous long-distance clock comparison. The capability of performing high resolution international clock comparisons paves the way for a redefinition of the unit of time and an all-optical dissemination of the SI-second. PMID:27503795
A clock network for geodesy and fundamental science.

PubMed

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.

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

PubMed Central

2017-01-01

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. PMID:28637852
Meta-analysis of stratus OCT glaucoma diagnostic accuracy.

PubMed

Chen, Hsin-Yi; Chang, Yue-Cune

2014-09-01

To evaluate the diagnostic accuracy of glaucoma in different stages, different types of glaucoma, and different ethnic groups using Stratus optical coherence tomography (OCT). We searched MEDLINE to identify available articles on diagnostic accuracy of glaucoma published between January 2004 and December 2011. A PubMed (National Center for Biotechnology Information) search using medical subject headings and keywords was executed using the following terms: "diagnostic accuracy" or "receiver operator characteristic" or "area under curve" or "AUC" and "Stratus OCT" and "glaucoma." The search was subsequently limited to publications in English. The area under a receiver operator characteristic (AUC) curve was used to measure the diagnostic performance. A random-effects model was used to estimate the pooled AUC value of the 17 parameters (average retinal nerve fiber layer thickness, temporal quadrant, superior quadrant, nasal quadrant, inferior quadrant, and 1 to 12 o'clock). Meta-regression analysis was used to check the significance of some important factors: (1) glaucoma severity (five stages), (2) glaucoma types (four types), and (3) ethnicity (four categories). The orders of accuracy among those parameters were as follows: average > inferior > superior > 7 o'clock > 6 o'clock > 11 o'clock > 12 o'clock > 1 o'clock > 5 o'clock > nasal > temporal > 2 o'clock > 10 o'clock > 8 o'clock > 9 o'clock > 4 o'clock > 3 o'clock. After adjusting for the effects of age, glaucoma severity, glaucoma types, and ethnicity, the average retinal nerve fiber layer thickness provided highest accuracy compared with the other parameters of OCT. The diagnostic accuracy in Asian populations was significantly lower than that in whites and the other two ethnic types. Stratus OCT demonstrated good diagnostic capability in differentiating glaucomatous from normal eyes. However, we should be more cautious in applying this instrument in Asian groups in glaucoma management.
Relativity theory and time perception: single or multiple clocks?

PubMed

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.
Characterisation, analysis of expression and localisation of circadian clock genes from the perspective of photoperiodism in the aphid Acyrthosiphon pisum.

PubMed

Barberà, Miquel; Collantes-Alegre, Jorge Mariano; Martínez-Torres, David

2017-04-01

Aphids are typical photoperiodic insects that switch from viviparous parthenogenetic reproduction typical of long day seasons to oviparous sexual reproduction triggered by the shortening of photoperiod in autumn yielding an overwintering egg in which an embryonic diapause takes place. While the involvement of the circadian clock genes in photoperiodism in mammals is well established, there is still some controversy on their participation in insects. The availability of the genome of the pea aphid Acyrthosiphon pisum places this species as an excellent model to investigate the involvement of the circadian system in the aphid seasonal response. In the present report, we have advanced in the characterisation of the circadian clock genes and showed that these genes display extensive alternative splicing. Moreover, the expression of circadian clock genes, analysed at different moments of the day, showed a robust cycling of central clock genes period and timeless. Furthermore, the rhythmic expression of these genes was shown to be rapidly dampened under DD (continuous darkness conditions), thus supporting the model of a seasonal response based on a heavily dampened circadian oscillator. Additionally, increased expression of some of the circadian clock genes under short-day conditions suggest their involvement in the induction of the aphid seasonal response. Finally, in situ localisation of transcripts of genes period and timeless in the aphid brain revealed the site of clock neurons for the first time in aphids. Two groups of clock cells were identified: the Dorsal Neurons (DN) and the Lateral Neurons (LN), both in the protocerebrum. Copyright © 2017 Elsevier Ltd. All rights reserved.
Mechanisms of relaxation and spin decoherence in nanomagnets

NASA Astrophysics Data System (ADS)

van Tol, Johan

Relaxation in spin systems is of great interest with respect to various possible applications like quantum information processing and storage, spintronics, and dynamic nuclear polarization (DNP). The implementation of high frequencies and fields is crucial in the study of systems with large zero-field splitting or large interactions, as for example molecular magnets and low dimensional magnetic materials. Here we will focus on the implementation of pulsed Electron Paramagnetic Resonance (ERP) at multiple frequencies of 10, 95, 120, 240, and 336 GHz, and the relaxation and decoherence processes as a function of magnetic field and temperature. Firstly, at higher frequencies the direct single-phonon spin-lattice relaxation (SLR) is considerably enhanced, and will more often than not be the dominant relaxation mechanism at low temperatures, and can be much faster than at lower fields and frequencies. In principle the measurement of the SLR rates as a function of the frequency provides a means to map the phonon density of states. Secondly, the high electron spin polarization at high fields has a strong influence on the spin fluctuations in relatively concentrated spin systems, and the contribution of the electron-electron dipolar interactions to the coherence rate can be partially quenched at low temperatures. This not only allows the study of relatively concentrated spin systems by pulsed EPR (as for example magnetic nanoparticles and molecular magnets), it enables the separation of the contribution of the fluctuations of the electron spin system from other decoherence mechanisms. Besides choice of temperature and field, several strategies in sample design, pulse sequences, or clock transitions can be employed to extend the coherence time in nanomagnets. A review will be given of the decoherence mechanisms with an attempt at a quantitative comparison of experimental rates with theory.
Physiological links of circadian clock and biological clock of aging.

PubMed

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.
Ras-mediated deregulation of the circadian clock in cancer.

PubMed

Relógio, Angela; Thomas, Philippe; Medina-Pérez, Paula; Reischl, Silke; Bervoets, Sander; Gloc, Ewa; Riemer, Pamela; Mang-Fatehi, Shila; Maier, Bert; Schäfer, Reinhold; Leser, Ulf; Herzel, Hanspeter; Kramer, Achim; Sers, Christine

2014-01-01

Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARγ, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock.
Roughness exponent in two-dimensional percolation, Potts model, and clock model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redinz, Jose Arnaldo; Martins, Marcelo Lobato

We present a numerical study of the self-affine profiles obtained from configurations of the q-state Potts (with q=2,3, and 7) and p=10 clock models as well as from the occupation states for site percolation on the square lattice. The first and second order static phase transitions of the Potts model are located by a sharp change in the value of the roughness exponent {alpha} characterizing those profiles. The low temperature phase of the Potts model corresponds to flat ({alpha}{approx_equal}1) profiles, whereas its high temperature phase is associated with rough ({alpha}{approx_equal}0.5) ones. For the p=10 clock model, in addition to themore » flat (ferromagnetic) and rough (paramagnetic) profiles, an intermediate rough (0.5{lt}{alpha}{lt}1) phase{emdash}associated with a soft spin-wave one{emdash}is observed. Our results for the transition temperatures in the Potts and clock models are in agreement with the static values, showing that this approach is able to detect the phase transitions in these models directly from the spin configurations, without any reference to thermodynamical potentials, order parameters, or response functions. Finally, we show that the roughness exponent {alpha} is insensitive to geometric critical phenomena.« less
An atomic clock with 10(-18) instability.

PubMed

Hinkley, N; Sherman, J A; Phillips, N B; Schioppo, M; Lemke, N D; Beloy, K; Pizzocaro, M; Oates, C W; Ludlow, A D

2013-09-13

Atomic clocks have been instrumental in science and technology, leading to innovations such as global positioning, advanced communications, and tests of fundamental constant variation. Timekeeping precision at 1 part in 10(18) enables new timing applications in relativistic geodesy, enhanced Earth- and space-based navigation and telescopy, and new tests of physics beyond the standard model. Here, we describe the development and operation of two optical lattice clocks, both using spin-polarized, ultracold atomic ytterbium. A measurement comparing these systems demonstrates an unprecedented atomic clock instability of 1.6 × 10(-18) after only 7 hours of averaging.
Reciprocity Between Robustness of Period and Plasticity of Phase in Biological Clocks

NASA Astrophysics Data System (ADS)

Hatakeyama, Tetsuhiro S.; Kaneko, Kunihiko

2015-11-01

Circadian clocks exhibit the robustness of period and plasticity of phase against environmental changes such as temperature and nutrient conditions. Thus far, however, it is unclear how both are simultaneously achieved. By investigating distinct models of circadian clocks, we demonstrate reciprocity between robustness and plasticity: higher robustness in the period implies higher plasticity in the phase, where changes in period and in phase follow a linear relationship with a negative coefficient. The robustness of period is achieved by the adaptation on the limit cycle via a concentration change of a buffer molecule, whose temporal change leads to a phase shift following a shift of the limit-cycle orbit in phase space. Generality of reciprocity in clocks with the adaptation mechanism is confirmed with theoretical analysis of simple models, while biological significance is discussed.
Satellite clock corrections estimation to accomplish real time ppp: experiments for brazilian real time network

NASA Astrophysics Data System (ADS)

Marques, Haroldo; Monico, João; Aquino, Marcio; Melo, Weyller

2014-05-01

The real time PPP method requires the availability of real time precise orbits and satellites clocks corrections. Currently, it is possible to apply the solutions of clocks and orbits available by BKG within the context of IGS Pilot project or by using the operational predicted IGU ephemeris. The accuracy of the satellite position available in the IGU is enough for several applications requiring good quality. However, the satellites clocks corrections do not provide enough accuracy (3 ns ~ 0.9 m) to accomplish real time PPP with the same level of accuracy. Therefore, for real time PPP application it is necessary to further research and develop appropriated methodologies for estimating the satellite clock corrections in real time with better accuracy. Currently, it is possible to apply the real time solutions of clocks and orbits available by Federal Agency for Cartography and Geodesy (BKG) within the context of IGS Pilot project. The BKG corrections are disseminated by a new proposed format of the RTCM 3.x and can be applied in the broadcasted orbits and clocks. Some investigations have been proposed for the estimation of the satellite clock corrections using GNSS code and phase observable at the double difference level between satellites and epochs (MERVAT, DOUSA, 2007). Another possibility consists of applying a Kalman Filter in the PPP network mode (HAUSCHILD, 2010) and it is also possible the integration of both methods, using network PPP and observables at double difference level in specific time intervals (ZHANG; LI; GUO, 2010). For this work the methodology adopted consists in the estimation of the satellite clock corrections based on the data adjustment in the PPP mode, but for a network of GNSS stations. The clock solution can be solved by using two types of observables: code smoothed by carrier phase or undifferenced code together with carrier phase. In the former, we estimate receiver clock error; satellite clock correction and troposphere, considering that the phase ambiguities are eliminated when applying differences between consecutive epochs. However, when using undifferenced code and phase, the ambiguities may be estimated together with receiver clock errors, satellite clock corrections and troposphere parameters. In both strategies it is also possible to correct the troposphere delay from a Numerical Weather Forecast Model instead of estimating it. The prediction of the satellite clock correction can be performed using a straight line or a second degree polynomial using the time series of the estimated satellites clocks. To estimate satellite clock correction and to accomplish real time PPP two pieces of software have been developed, respectively, "RT_PPP" and "RT_SAT_CLOCK". The system (RT_PPP) is able to process GNSS code and phase data using precise ephemeris and precise satellites clocks corrections together with several corrections required for PPP. In the software RT_SAT_CLOCK we apply a Kalman filter algorithm to estimate satellite clock correction in the network PPP mode. In this case, all PPP corrections must be applied for each station. The experiments were generated in real time and post-processed mode (simulating real time) considering data from the Brazilian continuous GPS network and also from the IGS network in a global satellite clock solution. We have used IGU ephemeris for satellite position and estimated the satellite clock corrections, performing the updates as soon as new ephemeris files were available. Experiments were accomplished in order to assess the accuracy of the estimated clocks when using the Brazilian Numerical Weather Forecast Model (BNWFM) from CPTEC/INPE and also using the ZTD from European Centre for Medium-Range Weather Forecasts (ECMWF) together with Vienna Mapping Function VMF or estimating troposphere with clocks and ambiguities in the Kalman Filter. The daily precision of the estimated satellite clock corrections reached the order of 0.15 nanoseconds. The clocks were applied in the Real Time PPP for Brazilian network stations and also for flight test of the Brazilian airplanes and the results show that it is possible to accomplish real time PPP in the static and kinematic modes with accuracy of the order of 10 to 20 cm, respectively.
Redox rhythm reinforces the circadian clock to gate immune response.

PubMed

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.
Transcriptional Control of Antioxidant Defense by the Circadian Clock

PubMed Central

Patel, Sonal A.; Velingkaar, Nikkhil S.

2014-01-01

Abstract Significance: The circadian clock, an internal timekeeping system, is implicated in the regulation of metabolism and physiology, and circadian dysfunctions are associated with pathological changes in model organisms and increased risk of some diseases in humans. Recent Advances: Data obtained in different organisms, including humans, have established a tight connection between the clock and cellular redox signaling making it among the major candidates for a link between the circadian system and physiological processes. Critical Issues: In spite of the recent progress in understanding the importance of the circadian clock in the regulation of reactive oxygen species homeostasis, molecular mechanisms and key regulators are mostly unknown. Future Directions: Here we review, with an emphasis on transcriptional control, the circadian-clock-dependent control of oxidative stress response system as a potential mechanism in age-associated diseases. We will discuss the roles of the core clock components such as brain and muscle ARNT-like 1, Circadian Locomotor Output Cycles Kaput, the circadian-clock-controlled transcriptional factors such as nuclear factor erythroid-2-related factor, and peroxisome proliferator-activated receptor and circadian clock control chromatin modifying enzymes from sirtuin family in the regulation of cellular and organism antioxidant defense. Antioxid. Redox Signal. 20, 2997–3006. PMID:24111970
Investigations of the CLOCK and BMAL1 Proteins Binding to DNA: A Molecular Dynamics Simulation Study.

PubMed

Xue, Tuo; Song, Chunnian; Wang, Qing; Wang, Yan; Chen, Guangju

2016-01-01

The circadian locomotor output cycles kaput (CLOCK), and brain and muscle ARNT-like 1 (BMAL1) proteins are important transcriptional factors of the endogenous circadian clock. The CLOCK and BMAL1 proteins can regulate the transcription-translation activities of the clock-related genes through the DNA binding. The hetero-/homo-dimerization and DNA combination of the CLOCK and BMAL1 proteins play a key role in the positive and negative transcriptional feedback processes. In the present work, we constructed a series of binary and ternary models for the bHLH/bHLH-PAS domains of the CLOCK and BMAL1 proteins, and the DNA molecule, and carried out molecular dynamics simulations, free energy calculations and conformational analysis to explore the interaction properties of the CLOCK and BMAL1 proteins with DNA. The results show that the bHLH domains of CLOCK and BMAL1 can favorably form the heterodimer of the bHLH domains of CLOCK and BMAL1 and the homodimer of the bHLH domains of BMAL1. And both dimers could respectively bind to DNA at its H1-H1 interface. The DNA bindings of the H1 helices in the hetero- and homo-bHLH dimers present the rectangular and diagonal binding modes, respectively. Due to the function of the α-helical forceps in these dimers, the tight gripping of the H1 helices to the major groove of DNA would cause the decrease of interactions at the H1-H2 interfaces in the CLOCK and BMAL1 proteins. The additional PAS domains in the CLOCK and BMAL1 proteins affect insignificantly the interactions of the CLOCK and BMAL1 proteins with the DNA molecule due to the flexible and long loop linkers located at the middle of the PAS and bHLH domains. The present work theoretically explains the interaction mechanisms of the bHLH domains of the CLOCK and BMAL1 proteins with DNA.
Sound Clocks and Sonic Relativity

NASA Astrophysics Data System (ADS)

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

PubMed Central

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
The circadian clock regulates cisplatin-induced toxicity and tumor regression in melanoma mouse and human models

PubMed Central

Dakup, Panshak P.; Porter, Kenneth I.; Little, Alexander A.; Gajula, Rajendra P.; Zhang, Hui; Skornyakov, Elena; Kemp, Michael G.; Van Dongen, Hans P.A; Gaddameedhi, Shobhan

2018-01-01

Cisplatin is one of the most commonly used chemotherapeutic drugs; however, toxicity and tumor resistance limit its use. Studies using murine models and human subjects have shown that the time of day of cisplatin treatment influences renal and blood toxicities. We hypothesized that the mechanisms responsible for these outcomes are driven by the circadian clock. We conducted experiments using wild-type and circadian disrupted Per1/2−/− mice treated with cisplatin at selected morning (AM) and evening (PM) times. Wild-type mice treated in the evening showed an enhanced rate of removal of cisplatin-DNA adducts and less toxicity than the morning-treated mice. This temporal variation in toxicity was lost in the Per1/2−/− clock-disrupted mice, suggesting that the time-of-day effect is linked to the circadian clock. Observations in blood cells from humans subjected to simulated day and night shift schedules corroborated this view. Per1/2−/− mice also exhibited a more robust immune response and slower tumor growth rate, indicating that the circadian clock also influences the immune response to melanoma tumors. Our findings indicate that cisplatin chronopharmacology involves the circadian clock control of DNA repair as well as immune responses, and thus affects both cisplatin toxicity and tumor growth. This has important implications for chronochemotherapy in cancer patients, and also suggests that influencing the circadian clock (e.g., through bright light treatment) may be explored as a tool to improve patient outcomes. PMID:29581861
Astronomical Calendar and Restoration Design of Clepsydra in the Silla era

NASA Astrophysics Data System (ADS)

Lee, Yong Sam; Jeong, Jang Hae; Sang, Hyuk Kim; Lee, Yong Bok

2008-09-01

We study on the astronomical calendars that was used in the Silla era. The calendars are deduced from the records in Samguksagi. They were influenced from calendaric system of Tang Dynasty, which are Lin duk calendar(?), Ta yen calendar(?) and Sun myung calendar(?). We analyse them in detail according to the time and duration of use. Water clock system of Unified Silla was used four water vessels for supplying water. We found the model from documents on ancient water clock that are appeared in the old Korean, Chinese and Japanese historical records. We have assumed the model of Unified Silla clepsydra is similar type with Chinese records during Tang dynasty and with Japanese reconstructed water clock in Temple Asoka. After fluid dynamic experiment, we decide the suitable diameter of supplying pipe and volume of the vessels used in the clepsydra. We introduce the experimental instruments and methods for accomplishing the clock. We designed and reconstructed the water clock of Unified Silla and float rods for measuring time, that is based on the Silla's calendaric system.
The Navstar GPS master control station's Kalman filter experience

NASA Technical Reports Server (NTRS)

Scardera, Michael P.

1990-01-01

The Navstar Global Positioning System (GPS) is a highly accurate space based navigation system providing all weather, 24 hour a day service to both military and civilian users. The system provides a Gaussian position solution with four satellites, each providing its ephemeris and clock offset with respect to GPS time. The GPS Master Clock Station (MCS) is charged with tracking each Navstar spacecraft and precisely defining the ephemeris and clock parameters for upload into the vehicle's navigation message. Briefly described here are the Navstar system and the Kalman filter estimation process used by MCS to determine, predict, and ensure quality control for each of the satellite's ephemeris and clock states. Routine performance is shown. Kalman filter reaction and response is discussed for anomalous clock behavior and trajectory perturbations. Particular attention is given to MCS efforts to improve orbital adjust modeling. The satellite out of service time due to orbital maneuvering has been reduced in the past year from four days to under twelve hours. The planning, reference trajectory model, and Kalman filter management improvements are explained.
On the Modeling of the Residual Effects of the Clock Behavior and the Atmosphere Effects in the Analysis of VLBI Data

NASA Astrophysics Data System (ADS)

Bo, Zhang; Li, Jin-Ling; Wang, Guan-Gli

2002-01-01

We checked the dependence of the estimation of parameters on the choice of piecewise interval in the continuous piecewise linear modeling of the residual clock and atmosphere effects by single analysis of 27 VLBI experiments involving Shanghai station (Seshan 25m). The following are tentatively shown: (1) Different choices of the piecewise interval lead to differences in the estimation of station coordinates and in the weighted root mean squares ( wrms ) of the delay residuals, which can be of the order of centimeters or dozens of picoseconds respectively. So the choice of piecewise interval should not be arbitrary . (2) The piecewise interval should not be too long, otherwise the short - term variations in the residual clock and atmospheric effects can not be properly modeled. While in order to maintain enough degrees of freedom in parameter estimation, the interval can not be too short, otherwise the normal equation may become near or solely singular and the noises can not be constrained as well. Therefore the choice of the interval should be within some reasonable range. (3) Since the conditions of clock and atmosphere are different from experiment to experiment and from station to station, the reasonable range of the piecewise interval should be tested and chosen separately for each experiment as well as for each station by real data analysis. This is really arduous work in routine data analysis. (4) Generally speaking, with the default interval for clock as 60min, the reasonable range of piecewise interval for residual atmospheric effect modeling is between 10min to 40min, while with the default interval for atmosphere as 20min, that for residual clock behavior is between 20min to 100min.

Evidence Suggesting that the Cardiomyocyte Circadian Clock Modulates Responsiveness of the Heart to Hypertrophic Stimuli in Mice

PubMed Central

Durgan, David J.; Tsai, Ju-Yun; Grenett, Maximiliano H.; Pat, Betty M.; Ratcliffe, William F.; Villegas-Montoya, Carolina; Garvey, Merissa E.; Nagendran, Jeevan; Dyck, Jason R.B.; Bray, Molly S.; Gamble, Karen L.; Gimble, Jeffrey M.; Young, Martin E.

2011-01-01

Circadian dyssynchrony of an organism (at the whole body level) with its environment, either through light/dark cycle or genetic manipulation of clock genes, augments various cardiometabolic diseases. The cardiomyocyte circadian clock has recently been shown to influence multiple myocardial processes, ranging from transcriptional regulation and energy metabolism, to contractile function. We therefore reasoned that chronic dyssychrony of the cardiomyocyte circadian clock with its environment would precipitate myocardial maladaptation to a circadian challenge (simulated shift work; SSW). To test this hypothesis, 2 and 20 month old wild-type and CCM (Cardiomyocyte Clock Mutant; a model with genetic temporal suspension of the cardiomyocyte circadian clock at the active-to-sleep phase transition) mice were subjected to chronic (16-wks) bi-weekly 12-hr phase shifts in the light/dark cycle (i.e., SSW). Assessment of adaptation/maladaptation at whole body homeostatic, gravimetric, humoral, histological, transcriptional, and cardiac contractile function levels revealed essentially identical responses between wild-type and CCM littermates. However, CCM hearts exhibit increased bi-ventricular weight, cardiomyocyte size, and molecular markers of hypertrophy (anf, mcip1) independent of aging and/or SSW. Similarly, a second genetic model of selective temporal suspension of the cardiomyocyte circadian clock (Cardiomyocyte-specific BMAL1 Knockout [CBK] mice) exhibits increased bi-ventricular weight and mcip1 expression. Wild-type mice exhibit 5-fold greater cardiac hypertrophic growth (and 6-fold greater anf mRNA induction) when challenged with the hypertrophic agonist isoproterenol at the active-to-sleep phase transition, relative to isoproterenol administration at the sleep-to-active phase transition. This diurnal variation was absent in CCM mice. Collectively, these data suggest that the cardiomyocyte circadian clock likely influences responsiveness of the heart to hypertrophic stimuli. PMID:21452915
Temperature compensation and temperature sensation in the circadian clock

PubMed Central

Kidd, Philip B.; Young, Michael W.; Siggia, Eric D.

2015-01-01

All known circadian clocks have an endogenous period that is remarkably insensitive to temperature, a property known as temperature compensation, while at the same time being readily entrained by a diurnal temperature oscillation. Although temperature compensation and entrainment are defining features of circadian clocks, their mechanisms remain poorly understood. Most models presume that multiple steps in the circadian cycle are temperature-dependent, thus facilitating temperature entrainment, but then insist that the effect of changes around the cycle sums to zero to enforce temperature compensation. An alternative theory proposes that the circadian oscillator evolved from an adaptive temperature sensor: a gene circuit that responds only to temperature changes. This theory implies that temperature changes should linearly rescale the amplitudes of clock component oscillations but leave phase relationships and shapes unchanged. We show using timeless luciferase reporter measurements and Western blots against TIMELESS protein that this prediction is satisfied by the Drosophila circadian clock. We also review evidence for pathways that couple temperature to the circadian clock, and show previously unidentified evidence for coupling between the Drosophila clock and the heat-shock pathway. PMID:26578788
Two Clock Transitions in Neutral Yb for the Highest Sensitivity to Variations of the Fine-Structure Constant.

PubMed

Safronova, Marianna S; Porsev, Sergey G; Sanner, Christian; Ye, Jun

2018-04-27

We propose a new frequency standard based on a 4f^{14}6s6p ^{3}P_{0}-4f^{13}6s^{2}5d (J=2) transition in neutral Yb. This transition has a potential for high stability and accuracy and the advantage of the highest sensitivity among atomic clocks to variation of the fine-structure constant α. We find its dimensionless α-variation enhancement factor to be K=-15, in comparison to the most sensitive current clock (Yb^{+} E3, K=-6), and it is 18 times larger than in any neutral-atomic clocks (Hg, K=0.8). Combined with the unprecedented stability of an optical lattice clock for neutral atoms, this high sensitivity opens new perspectives for searches for ultralight dark matter and for tests of theories beyond the standard model of elementary particles. Moreover, together with the well-established ^{1}S_{0}-^{3}P_{0} transition, one will have two clock transitions operating in neutral Yb, whose interleaved interrogations may further reduce systematic uncertainties of such clock-comparison experiments.
Two Clock Transitions in Neutral Yb for the Highest Sensitivity to Variations of the Fine-Structure Constant

NASA Astrophysics Data System (ADS)

Safronova, Marianna S.; Porsev, Sergey G.; Sanner, Christian; Ye, Jun

2018-04-01

We propose a new frequency standard based on a 4 f146 s 6 p P0 3 -4 f136 s25 d (J =2 ) transition in neutral Yb. This transition has a potential for high stability and accuracy and the advantage of the highest sensitivity among atomic clocks to variation of the fine-structure constant α . We find its dimensionless α -variation enhancement factor to be K =-15 , in comparison to the most sensitive current clock (Yb+ E 3 , K =-6 ), and it is 18 times larger than in any neutral-atomic clocks (Hg, K =0.8 ). Combined with the unprecedented stability of an optical lattice clock for neutral atoms, this high sensitivity opens new perspectives for searches for ultralight dark matter and for tests of theories beyond the standard model of elementary particles. Moreover, together with the well-established 1S0-3P0 transition, one will have two clock transitions operating in neutral Yb, whose interleaved interrogations may further reduce systematic uncertainties of such clock-comparison experiments.
Population specific biomarkers of human aging: a big data study using South Korean, Canadian and Eastern European patient populations.

PubMed

Mamoshina, Polina; Kochetov, Kirill; Putin, Evgeny; Cortese, Franco; Aliper, Alexander; Lee, Won-Suk; Ahn, Sung-Min; Uhn, Lee; Skjodt, Neil; Kovalchuk, Olga; Scheibye-Knudsen, Morten; Zhavoronkov, Alex

2018-01-11

Accurate and physiologically meaningful biomarkers for human aging are key to assessing anti-aging therapies. Given ethnic differences in health, diet, lifestyle, behaviour, environmental exposures and even average rate of biological aging, it stands to reason that aging clocks trained on datasets obtained from specific ethnic populations are more likely to account for these potential confounding factors, resulting in an enhanced capacity to predict chronological age and quantify biological age. Here we present a deep learning-based hematological aging clock modeled using the large combined dataset of Canadian, South Korean and Eastern European population blood samples that show increased predictive accuracy in individual populations compared to population-specific hematologic aging clocks. The performance of models was also evaluated on publicly-available samples of the American population from the National Health and Nutrition Examination Survey (NHANES). In addition, we explored the association between age predicted by both population-specific and combined hematological clocks and all-cause mortality. Overall, this study suggests a) the population-specificity of aging patterns and b) hematologic clocks predicts all-cause mortality. Proposed models added to the freely available Aging.AI system allowing improved ability to assess human aging. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America.
Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution.

PubMed

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.
Topology and Dynamics of the Zebrafish Segmentation Clock Core Circuit

PubMed Central

Schröter, Christian; Isakova, Alina; Hens, Korneel; Soroldoni, Daniele; Gajewski, Martin; Jülicher, Frank; Maerkl, Sebastian J.; Deplancke, Bart; Oates, Andrew C.

2012-01-01

During vertebrate embryogenesis, the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock. We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation of the network's topology and precise measurements of somitogenesis dynamics in novel genetic mutants. We show that the core pace-making circuit consists of two distinct negative feedback loops, one with Her1 homodimers and the other with Her7:Hes6 heterodimers, operating in parallel. To explain the observed single and double mutant phenotypes of her1, her7, and hes6 mutant embryos in our dynamic model, we postulate that the availability and effective stability of the dimers with DNA binding activity is controlled in a “dimer cloud” that contains all possible dimeric combinations between the three factors. This feature of our model predicts that Hes6 protein levels should oscillate despite constant hes6 mRNA production, which we confirm experimentally using novel Hes6 antibodies. The control of the circuit's dynamics by a population of dimers with and without DNA binding activity is a new principle for the segmentation clock and may be relevant to other biological clocks and transcriptional regulatory networks. PMID:22911291
Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks.

PubMed

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.
Light directs zebrafish period2 expression via conserved D and E boxes.

PubMed

Vatine, Gad; Vallone, Daniela; Appelbaum, Lior; Mracek, Philipp; Ben-Moshe, Zohar; Lahiri, Kajori; Gothilf, Yoav; Foulkes, Nicholas S

2009-10-01

For most species, light represents the principal environmental signal for entraining the endogenous circadian clock. The zebrafish is a fascinating vertebrate model for studying this process since unlike mammals, direct exposure of most of its tissues to light leads to local clock entrainment. Importantly, light induces the expression of a set of genes including certain clock genes in most zebrafish cell types in vivo and in vitro. However, the mechanism linking light to gene expression remains poorly understood. To elucidate this key mechanism, here we focus on how light regulates transcription of the zebrafish period2 (per2) gene. Using transgenic fish and stably transfected cell line-based assays, we define a Light Responsive Module (LRM) within the per2 promoter. The LRM lies proximal to the transcription start site and is both necessary and sufficient for light-driven gene expression and also for a light-dependent circadian clock regulation. Curiously, the LRM sequence is strongly conserved in other vertebrate per2 genes, even in species lacking directly light-sensitive peripheral clocks. Furthermore, we reveal that the human LRM can substitute for the zebrafish LRM to confer light-regulated transcription in zebrafish cells. The LRM contains E- and D-box elements that are critical for its function. While the E-box directs circadian clock regulation by mediating BMAL/CLOCK activity, the D-box confers light-driven expression. The zebrafish homolog of the thyrotroph embryonic factor binds efficiently to the LRM D-box and transactivates expression. We demonstrate that tef mRNA levels are light inducible and that knock-down of tef expression attenuates light-driven transcription from the per2 promoter in vivo. Together, our results support a model where a light-dependent crosstalk between E- and D-box binding factors is a central determinant of per2 expression. These findings extend the general understanding of the mechanism whereby the clock is entrained by light and how the regulation of clock gene expression by light has evolved in vertebrates.
Integrated Formal Analysis of Timed-Triggered Ethernet

NASA Technical Reports Server (NTRS)

Dutertre, Bruno; Shankar, Nstarajan; Owre, Sam

2012-01-01

We present new results related to the verification of the Timed-Triggered Ethernet (TTE) clock synchronization protocol. This work extends previous verification of TTE based on model checking. We identify a suboptimal design choice in a compression function used in clock synchronization, and propose an improvement. We compare the original design and the improved definition using the SAL model checker.
Method and apparatus for autonomous, in-receiver prediction of GNSS ephemerides

NASA Technical Reports Server (NTRS)

Bar-Sever, Yoaz E. (Inventor); Bertiger, William I. (Inventor)

2012-01-01

Methods and apparatus for autonomous in-receiver prediction of orbit and clock states of Global Navigation Satellite Systems (GNSS) are described. Only the GNSS broadcast message is used, without need for periodic externally-communicated information. Earth orientation information is extracted from the GNSS broadcast ephemeris. With the accurate estimation of the Earth orientation parameters it is possible to propagate the best-fit GNSS orbits forward in time in an inertial reference frame. Using the estimated Earth orientation parameters, the predicted orbits are then transformed into Earth-Centered-Earth-Fixed (ECEF) coordinates to be used to assist the GNSS receiver in the acquisition of the signals. GNSS satellite clock states are also extracted from the broadcast ephemeris and a parameterized model of clock behavior is fit to that data. The estimated modeled clocks are then propagated forward in time to enable, together with the predicted orbits, quicker GNSS signal acquisition.
GNSS global real-time augmentation positioning: Real-time precise satellite clock estimation, prototype system construction and performance analysis

NASA Astrophysics Data System (ADS)

Chen, Liang; Zhao, Qile; Hu, Zhigang; Jiang, Xinyuan; Geng, Changjiang; Ge, Maorong; Shi, Chuang

2018-01-01

Lots of ambiguities in un-differenced (UD) model lead to lower calculation efficiency, which isn't appropriate for the high-frequency real-time GNSS clock estimation, like 1 Hz. Mixed differenced model fusing UD pseudo-range and epoch-differenced (ED) phase observations has been introduced into real-time clock estimation. In this contribution, we extend the mixed differenced model for realizing multi-GNSS real-time clock high-frequency updating and a rigorous comparison and analysis on same conditions are performed to achieve the best real-time clock estimation performance taking the efficiency, accuracy, consistency and reliability into consideration. Based on the multi-GNSS real-time data streams provided by multi-GNSS Experiment (MGEX) and Wuhan University, GPS + BeiDou + Galileo global real-time augmentation positioning prototype system is designed and constructed, including real-time precise orbit determination, real-time precise clock estimation, real-time Precise Point Positioning (RT-PPP) and real-time Standard Point Positioning (RT-SPP). The statistical analysis of the 6 h-predicted real-time orbits shows that the root mean square (RMS) in radial direction is about 1-5 cm for GPS, Beidou MEO and Galileo satellites and about 10 cm for Beidou GEO and IGSO satellites. Using the mixed differenced estimation model, the prototype system can realize high-efficient real-time satellite absolute clock estimation with no constant clock-bias and can be used for high-frequency augmentation message updating (such as 1 Hz). The real-time augmentation message signal-in-space ranging error (SISRE), a comprehensive accuracy of orbit and clock and effecting the users' actual positioning performance, is introduced to evaluate and analyze the performance of GPS + BeiDou + Galileo global real-time augmentation positioning system. The statistical analysis of real-time augmentation message SISRE is about 4-7 cm for GPS, whlile 10 cm for Beidou IGSO/MEO, Galileo and about 30 cm for BeiDou GEO satellites. The real-time positioning results prove that the GPS + BeiDou + Galileo RT-PPP comparing to GPS-only can effectively accelerate convergence time by about 60%, improve the positioning accuracy by about 30% and obtain averaged RMS 4 cm in horizontal and 6 cm in vertical; additionally RT-SPP accuracy in the prototype system can realize positioning accuracy with about averaged RMS 1 m in horizontal and 1.5-2 m in vertical, which are improved by 60% and 70% to SPP based on broadcast ephemeris, respectively.
DLRS: gene tree evolution in light of a species tree.

PubMed

Sjöstrand, Joel; Sennblad, Bengt; Arvestad, Lars; Lagergren, Jens

2012-11-15

PrIME-DLRS (or colloquially: 'Delirious') is a phylogenetic software tool to simultaneously infer and reconcile a gene tree given a species tree. It accounts for duplication and loss events, a relaxed molecular clock and is intended for the study of homologous gene families, for example in a comparative genomics setting involving multiple species. PrIME-DLRS uses a Bayesian MCMC framework, where the input is a known species tree with divergence times and a multiple sequence alignment, and the output is a posterior distribution over gene trees and model parameters. PrIME-DLRS is available for Java SE 6+ under the New BSD License, and JAR files and source code can be downloaded from http://code.google.com/p/jprime/. There is also a slightly older C++ version available as a binary package for Ubuntu, with download instructions at http://prime.sbc.su.se. The C++ source code is available upon request. joel.sjostrand@scilifelab.se or jens.lagergren@scilifelab.se. PrIME-DLRS is based on a sound probabilistic model (Åkerborg et al., 2009) and has been thoroughly validated on synthetic and biological datasets (Supplementary Material online).
Punctual Transcriptional Regulation by the Rice Circadian Clock under Fluctuating Field Conditions[OPEN

PubMed Central

Matsuzaki, Jun; Kawahara, Yoshihiro; Izawa, Takeshi

2015-01-01

Plant circadian clocks that oscillate autonomously with a roughly 24-h period are entrained by fluctuating light and temperature and globally regulate downstream genes in the field. However, it remains unknown how punctual internal time produced by the circadian clock in the field is and how it is affected by environmental fluctuations due to weather or daylength. Using hundreds of samples of field-grown rice (Oryza sativa) leaves, we developed a statistical model for the expression of circadian clock-related genes integrating diurnally entrained circadian clock with phase setting by light, both responses to light and temperature gated by the circadian clock. We show that expression of individual genes was strongly affected by temperature. However, internal time estimated from expression of multiple genes, which may reflect transcriptional regulation of downstream genes, is punctual to 22 min and not affected by weather, daylength, or plant developmental age in the field. We also revealed perturbed progression of internal time under controlled environment or in a mutant of the circadian clock gene GIGANTEA. Thus, we demonstrated that the circadian clock is a regulatory network of multiple genes that retains accurate physical time of day by integrating the perturbations on individual genes under fluctuating environments in the field. PMID:25757473
Discrete gene replication events drive coupling between the cell cycle and circadian clocks

PubMed Central

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

2016-01-01

Many organisms possess both a cell cycle to control DNA replication and a circadian clock to anticipate changes between day and night. In some cases, these two rhythmic systems are known to be coupled by specific, cross-regulatory interactions. Here, we use mathematical modeling to show that, additionally, the cell cycle generically influences circadian clocks in a nonspecific fashion: The regular, discrete jumps in gene-copy number arising from DNA replication during the cell cycle cause a periodic driving of the circadian clock, which can dramatically alter its behavior and impair its function. A clock built on negative transcriptional feedback either phase-locks to the cell cycle, so that the clock period tracks the cell division time, or exhibits erratic behavior. We argue that the cyanobacterium Synechococcus elongatus has evolved two features that protect its clock from such disturbances, both of which are needed to fully insulate it from the cell cycle and give it its observed robustness: a phosphorylation-based protein modification oscillator, together with its accompanying push–pull read-out circuit that responds primarily to the ratios of different phosphoform concentrations, makes the clock less susceptible to perturbations in protein synthesis; the presence of multiple, asynchronously replicating copies of the same chromosome diminishes the effect of replicating any single copy of a gene. PMID:27035936
Discrete gene replication events drive coupling between the cell cycle and circadian clocks.

PubMed

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

2016-04-12

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

PubMed

McTaggart, Alistair R; Shivas, Roger G; van der Nest, Magriet A; Roux, Jolanda; Wingfield, Brenda D; Wingfield, Michael J

2016-02-01

The aim of this study was to determine the evolutionary time line for rust fungi and date key speciation events using a molecular clock. Evidence is provided that supports a contemporary view for a recent origin of rust fungi, with a common ancestor on a flowering plant. Divergence times for > 20 genera of rust fungi were studied with Bayesian evolutionary analyses. A relaxed molecular clock was applied to ribosomal and mitochondrial genes, calibrated against estimated divergence times for the hosts of rust fungi, such as Acacia (Fabaceae), angiosperms and the cupressophytes. Results showed that rust fungi shared a most recent common ancestor with a mean age between 113 and 115 million yr. This dates rust fungi to the Cretaceous period, which is much younger than previous estimations. Host jumps, whether taxonomically large or between host genera in the same family, most probably shaped the diversity of rust genera. Likewise, species diversified by host shifts (through coevolution) or via subsequent host jumps. This is in contrast to strict coevolution with their hosts. Puccinia psidii was recovered in Sphaerophragmiaceae, a family distinct from Raveneliaceae, which were regarded as confamilial in previous studies. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.

PubMed

Corella, Dolores; Asensio, Eva M; Coltell, Oscar; Sorlí, José V; Estruch, Ramón; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Castañer, Olga; Arós, Fernando; Lapetra, José; Serra-Majem, Lluís; Gómez-Gracia, Enrique; Ortega-Azorín, Carolina; Fiol, Miquel; Espino, Javier Díez; Díaz-López, Andrés; Fitó, Montserrat; Ros, Emilio; Ordovás, José M

2016-01-07

Circadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes. We analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations. We observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model. In agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.
A study on predicting network corrections in PPP-RTK processing

NASA Astrophysics Data System (ADS)

Wang, Kan; Khodabandeh, Amir; Teunissen, Peter

2017-10-01

In PPP-RTK processing, the network corrections including the satellite clocks, the satellite phase biases and the ionospheric delays are provided to the users to enable fast single-receiver integer ambiguity resolution. To solve the rank deficiencies in the undifferenced observation equations, the estimable parameters are formed to generate full-rank design matrix. In this contribution, we firstly discuss the interpretation of the estimable parameters without and with a dynamic satellite clock model incorporated in a Kalman filter during the network processing. The functionality of the dynamic satellite clock model is tested in the PPP-RTK processing. Due to the latency generated by the network processing and data transfer, the network corrections are delayed for the real-time user processing. To bridge the latencies, we discuss and compare two prediction approaches making use of the network corrections without and with the dynamic satellite clock model, respectively. The first prediction approach is based on the polynomial fitting of the estimated network parameters, while the second approach directly follows the dynamic model in the Kalman filter of the network processing and utilises the satellite clock drifts estimated in the network processing. Using 1 Hz data from two networks in Australia, the influences of the two prediction approaches on the user positioning results are analysed and compared for latencies ranging from 3 to 10 s. The accuracy of the positioning results decreases with the increasing latency of the network products. For a latency of 3 s, the RMS of the horizontal and the vertical coordinates (with respect to the ground truth) do not show large differences applying both prediction approaches. For a latency of 10 s, the prediction approach making use of the satellite clock model has generated slightly better positioning results with the differences of the RMS at mm-level. Further advantages and disadvantages of both prediction approaches are also discussed in this contribution.
Genetic architecture of the circadian clock and flowering time in Brassica rapa.

PubMed

Lou, P; Xie, Q; Xu, X; Edwards, C E; Brock, M T; Weinig, C; McClung, C R

2011-08-01

The circadian clock serves to coordinate physiology and behavior with the diurnal cycles derived from the daily rotation of the earth. In plants, circadian rhythms contribute to growth and yield and, hence, to both agricultural productivity and evolutionary fitness. Arabidopsis thaliana has served as a tractable model species in which to dissect clock mechanism and function, but it now becomes important to define the extent to which the Arabidopsis model can be extrapolated to other species, including crops. Accordingly, we have extended our studies to the close Arabidopsis relative and crop species, Brassica rapa. We have investigated natural variation in circadian function and flowering time among multiple B. rapa collections. There is wide variation in clock function, based on a robust rhythm in cotyledon movement, within a collection of B. rapa accessions, wild populations and recombinant inbred lines (RILs) derived from a cross between parents from two distinct subspecies, a rapid cycling Chinese cabbage (ssp. pekinensis) and a Yellow Sarson oilseed (ssp. trilocularis). We further analyzed the RILs to identify the quantitative trait loci (QTL) responsible for this natural variation in clock period and temperature compensation, as well as for flowering time under different temperature and day length settings. Most clock and flowering-time QTL mapped to overlapping chromosomal loci. We have exploited micro-synteny between the Arabidopsis and B. rapa genomes to identify candidate genes for these QTL.

Machine Learning Helps Identify CHRONO as a Circadian Clock Component

PubMed Central

Venkataraman, Anand; Ramanathan, Chidambaram; Kavakli, Ibrahim H.; Hughes, Michael E.; Baggs, Julie E.; Growe, Jacqueline; Liu, Andrew C.; Kim, Junhyong; Hogenesch, John B.

2014-01-01

Over the last decades, researchers have characterized a set of “clock genes” that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components. We used a simple form of probabilistic machine learning to integrate biologically relevant, genome-scale data and ranked genes on their similarity to known clock components. We then used a secondary experimental screen to characterize the top candidates. We found that several physically interact with known clock components in a mammalian two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse fibroblast line (NIH 3T3). One candidate, Gene Model 129, interacts with BMAL1 and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK transcriptional complex. Given these results, we have renamed the gene CHRONO (computationally highlighted repressor of the network oscillator). Bi-molecular fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO represses by abrogating the binding of BMAL1 to its transcriptional co-activator CBP. Most importantly, CHRONO knockout mice display a prolonged free-running circadian period similar to, or more drastic than, six other clock components. We conclude that CHRONO is a functional clock component providing a new layer of control on circadian molecular dynamics. PMID:24737000
Modelling Delta-Notch perturbations during zebrafish somitogenesis.

PubMed

Murray, Philip J; Maini, Philip K; Baker, Ruth E

2013-01-15

The discovery over the last 15 years of molecular clocks and gradients in the pre-somitic mesoderm of numerous vertebrate species has added significant weight to Cooke and Zeeman's 'clock and wavefront' model of somitogenesis, in which a travelling wavefront determines the spatial position of somite formation and the somitogenesis clock controls periodicity (Cooke and Zeeman, 1976). However, recent high-throughput measurements of spatiotemporal patterns of gene expression in different zebrafish mutant backgrounds allow further quantitative evaluation of the clock and wavefront hypothesis. In this study we describe how our recently proposed model, in which oscillator coupling drives the propagation of an emergent wavefront, can be used to provide mechanistic and testable explanations for the following observed phenomena in zebrafish embryos: (a) the variation in somite measurements across a number of zebrafish mutants; (b) the delayed formation of somites and the formation of 'salt and pepper' patterns of gene expression upon disruption of oscillator coupling; and (c) spatial correlations in the 'salt and pepper' patterns in Delta-Notch mutants. In light of our results, we propose a number of plausible experiments that could be used to further test the model. Copyright © 2012 Elsevier Inc. All rights reserved.
Fine-structure constant constraints on dark energy. II. Extending the parameter space

NASA Astrophysics Data System (ADS)

Martins, C. J. A. P.; Pinho, A. M. M.; Carreira, P.; Gusart, A.; López, J.; Rocha, C. I. S. A.

2016-01-01

Astrophysical tests of the stability of fundamental couplings, such as the fine-structure constant α , are a powerful probe of new physics. Recently these measurements, combined with local atomic clock tests and Type Ia supernova and Hubble parameter data, were used to constrain the simplest class of dynamical dark energy models where the same degree of freedom is assumed to provide both the dark energy and (through a dimensionless coupling, ζ , to the electromagnetic sector) the α variation. One caveat of these analyses was that it was based on fiducial models where the dark energy equation of state was described by a single parameter (effectively its present day value, w0). Here we relax this assumption and study broader dark energy model classes, including the Chevallier-Polarski-Linder and early dark energy parametrizations. Even in these extended cases we find that the current data constrains the coupling ζ at the 1 0-6 level and w0 to a few percent (marginalizing over other parameters), thus confirming the robustness of earlier analyses. On the other hand, the additional parameters are typically not well constrained. We also highlight the implications of our results for constraints on violations of the weak equivalence principle and improvements to be expected from forthcoming measurements with high-resolution ultrastable spectrographs.
Identification of the Molecular Clockwork of the Oyster Crassostrea gigas

PubMed Central

Perrigault, Mickael; Tran, Damien

2017-01-01

Molecular clock system constitutes the origin of biological rhythms that allow organisms to anticipate cyclic environmental changes and adapt their behavior and physiology. Components of the molecular clock are largely conserved across a broad range of species but appreciable diversity in clock structure and function is also present especially in invertebrates. The present work aimed at identify and characterize molecular clockwork components in relationship with the monitoring of valve activity behavior in the oyster Crassostrea gigas. Results provided the characterization of most of canonical clock gene including clock, bmal/cycle, period, timeless, vertebrate-type cry, rev-erb, ror as well as other members of the cryptochrome/photolyase family (plant-like cry, 6–4 photolyase). Analyses of transcriptional variations of clock candidates in oysters exposed to light / dark regime and to constant darkness led to the generation of a putative and original clockwork model in C. gigas, intermediate of described systems in vertebrates and insects. This study is the first characterization of a mollusk clockwork. It constitutes essential bases to understand interactions of the different components of the molecular clock in C. gigas as well as the global mechanisms associated to the generation and the synchronization of biological rhythms in oysters. PMID:28072861
Dynamic modelling and estimation of the error due to asynchronism in a redundant asynchronous multiprocessor system

NASA Technical Reports Server (NTRS)

Huynh, Loc C.; Duval, R. W.

1986-01-01

The use of Redundant Asynchronous Multiprocessor System to achieve ultrareliable Fault Tolerant Control Systems shows great promise. The development has been hampered by the inability to determine whether differences in the outputs of redundant CPU's are due to failures or to accrued error built up by slight differences in CPU clock intervals. This study derives an analytical dynamic model of the difference between redundant CPU's due to differences in their clock intervals and uses this model with on-line parameter identification to idenitify the differences in the clock intervals. The ability of this methodology to accurately track errors due to asynchronisity generate an error signal with the effect of asynchronisity removed and this signal may be used to detect and isolate actual system failures.
Circadian Rhythms in Cyanobacteria

PubMed Central

Golden, Susan S.

2015-01-01

SUMMARY Life on earth is subject to daily and predictable fluctuations in light intensity, temperature, and humidity created by rotation of the earth. Circadian rhythms, generated by a circadian clock, control temporal programs of cellular physiology to facilitate adaptation to daily environmental changes. Circadian rhythms are nearly ubiquitous and are found in both prokaryotic and eukaryotic organisms. Here we introduce the molecular mechanism of the circadian clock in the model cyanobacterium Synechococcus elongatus PCC 7942. We review the current understanding of the cyanobacterial clock, emphasizing recent work that has generated a more comprehensive understanding of how the circadian oscillator becomes synchronized with the external environment and how information from the oscillator is transmitted to generate rhythms of biological activity. These results have changed how we think about the clock, shifting away from a linear model to one in which the clock is viewed as an interactive network of multifunctional components that are integrated into the context of the cell in order to pace and reset the oscillator. We conclude with a discussion of how this basic timekeeping mechanism differs in other cyanobacterial species and how information gleaned from work in cyanobacteria can be translated to understanding rhythmic phenomena in other prokaryotic systems. PMID:26335718
Genetic variation in the CLOCK gene is associated with idiopathic recurrent spontaneous abortion.

PubMed

Hodžić, Alenka; Lavtar, Polona; Ristanović, Momčilo; Novaković, Ivana; Dotlić, Jelena; Peterlin, Borut

2018-01-01

Physiological studies in animals and human support an important role of circadian system in reproduction. The aim of this study was to investigate the potential association of CLOCK gene polymorphisms with idiopathic recurrent spontaneous abortion (IRSA). We performed a case-control study. The study group consisted of 268 women with a history of three or more idiopathic recurrent spontaneous abortions and 284 women with at least two live births and no history of pathologic pregnancies all from Slovenia and Serbia. Two SNPs in the CLOCK gene were chosen and genotyped. The results showed a statistically significant difference in genotype distribution between the two groups in the CLOCK gene for rs6850524 and rs11932595. Our analysis showed that G allele under dominant model (GG+GC/CC) for rs6850524 (p = 2∙10-4, OR = 2.28, 95%CI = 1.46-3.56) as well as G allele under dominant model (GA+AA/AA) for rs11932595 (p = 0.04, OR = 1.47, 95%CI = 1.01-2.04) might be risk factors against IRSA. Our data suggest that genetic variability in the CLOCK gene is associated with IRSA warranting further confirmation and mechanistic investigations.
Genetic variation in the CLOCK gene is associated with idiopathic recurrent spontaneous abortion

PubMed Central

Hodžić, Alenka; Lavtar, Polona; Ristanović, Momčilo; Novaković, Ivana; Dotlić, Jelena; Peterlin, Borut

2018-01-01

Physiological studies in animals and human support an important role of circadian system in reproduction. The aim of this study was to investigate the potential association of CLOCK gene polymorphisms with idiopathic recurrent spontaneous abortion (IRSA). We performed a case-control study. The study group consisted of 268 women with a history of three or more idiopathic recurrent spontaneous abortions and 284 women with at least two live births and no history of pathologic pregnancies all from Slovenia and Serbia. Two SNPs in the CLOCK gene were chosen and genotyped. The results showed a statistically significant difference in genotype distribution between the two groups in the CLOCK gene for rs6850524 and rs11932595. Our analysis showed that G allele under dominant model (GG+GC/CC) for rs6850524 (p = 2∙10−4, OR = 2.28, 95%CI = 1.46–3.56) as well as G allele under dominant model (GA+AA/AA) for rs11932595 (p = 0.04, OR = 1.47, 95%CI = 1.01–2.04) might be risk factors against IRSA. Our data suggest that genetic variability in the CLOCK gene is associated with IRSA warranting further confirmation and mechanistic investigations. PMID:29768442
Studying the Evolution of the Vertebrate Circadian Clock: The Power of Fish as Comparative Models.

PubMed

Foulkes, N S; Whitmore, D; Vallone, D; Bertolucci, C

2016-01-01

The utility of any model species cannot be judged solely in terms of the tools and approaches it provides for genetic analysis. A fundamental consideration is also how its biology has been shaped by the environment and the ecological niche which it occupies. By comparing different species occupying very different habitats we can learn how molecular and cellular mechanisms change during evolution in order to optimally adapt to their environment. Such knowledge is as important as understanding how these mechanisms work. This is illustrated by the use of fish models for studying the function and evolution of the circadian clock. In this review we outline our current understanding of how fish clocks sense and respond to light and explain how this differs fundamentally from the situation with mammalian clocks. In addition, we present results from comparative studies involving two species of blind cavefish, Astyanax mexicanus and Phreatichthys andruzzii. This work reveals the consequences of evolution in perpetual darkness for the circadian clock and its regulation by light as well as for other mechanisms such as DNA repair, sleep, and metabolism which directly or indirectly are affected by regular exposure to sunlight. Major differences in the cave habitats inhabited by these two cavefish species have a clear impact on shaping the molecular and cellular adaptations to life in complete darkness. Copyright © 2016 Elsevier Inc. All rights reserved.
Accelerating recovery from jet lag: prediction from a multi-oscillator model and its experimental confirmation in model animals

NASA Astrophysics Data System (ADS)

Kori, Hiroshi; Yamaguchi, Yoshiaki; Okamura, Hitoshi

2017-04-01

The endogenous circadian clock drives oscillations that are completely synchronized with the environmental day-night rhythms with a period of approximately 24 hours. Temporal misalignment between one’s internal circadian clock and the external solar time often occurs in shift workers and long-distance travelers; such misalignments are accompanied by sleep disturbances and gastrointestinal distress. Repeated exposure to jet lag and rotating shift work increases the risk of lifestyle-related diseases, such as cardiovascular complaints and metabolic insufficiencies. However, the mechanism behind the disruption of one’s internal clock is not well understood. In this paper, we therefore present a new theoretical concept called “jet lag separatrix” to understand circadian clock disruption and slow recovery from jet lag based on the mathematical model describing the hierarchical structure of the circadian clock. To demonstrate the utility of our theoretical study, we applied it to predict that re-entrainment via a two-step jet lag in which a four-hour shift of the light-dark cycle is given in the span of two successive days requires fewer days than when given as a single eight-hour shift. We experimentally verified the feasibility of our theory in C57BL/6 strain mice, with results indicating that this pre-exposure of jet lag is indeed beneficial.
Equivalent Relaxations of Optimal Power Flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bose, S; Low, SH; Teeraratkul, T

2015-03-01

Several convex relaxations of the optimal power flow (OPF) problem have recently been developed using both bus injection models and branch flow models. In this paper, we prove relations among three convex relaxations: a semidefinite relaxation that computes a full matrix, a chordal relaxation based on a chordal extension of the network graph, and a second-order cone relaxation that computes the smallest partial matrix. We prove a bijection between the feasible sets of the OPF in the bus injection model and the branch flow model, establishing the equivalence of these two models and their second-order cone relaxations. Our results implymore » that, for radial networks, all these relaxations are equivalent and one should always solve the second-order cone relaxation. For mesh networks, the semidefinite relaxation and the chordal relaxation are equally tight and both are strictly tighter than the second-order cone relaxation. Therefore, for mesh networks, one should either solve the chordal relaxation or the SOCP relaxation, trading off tightness and the required computational effort. Simulations are used to illustrate these results.« less
Genomic clocks and evolutionary timescales

NASA Technical Reports Server (NTRS)

Blair Hedges, S.; Kumar, Sudhir

2003-01-01

For decades, molecular clocks have helped to illuminate the evolutionary timescale of life, but now genomic data pose a challenge for time estimation methods. It is unclear how to integrate data from many genes, each potentially evolving under a different model of substitution and at a different rate. Current methods can be grouped by the way the data are handled (genes considered separately or combined into a 'supergene') and the way gene-specific rate models are applied (global versus local clock). There are advantages and disadvantages to each of these approaches, and the optimal method has not yet emerged. Fortunately, time estimates inferred using many genes or proteins have greater precision and appear to be robust to different approaches.
The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer's disease.

PubMed

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.
Compact Microwave Mercury Ion Clock for Space Applications

NASA Technical Reports Server (NTRS)

Prestage, John D.; Tu, Meirong; Chung, Sang K.; MacNeal, Paul

2007-01-01

We review progress in developing a small Hg ion clock for space operation based on breadboard ion-clock physics package where Hg ions are shuttled between a quadrupole and a 16-pole rf trap. With this architecture we have demonstrated short-term stability approx.1-2x10(exp -13) at 1 second, averaging to 10-15 at 1 day. This development shows that H-maser quality stabilities can be produced in a small clock package, comparable in size to an ultra-stable quartz oscillator required or holding 1-2x10(exp -13) at 1 second. We have completed an ion clock physics package designed to withstand vibration of launch and are currently building a approx. 1 kg engineering model for test. We also discuss frequency steering software algorithms that simultaneously measure ion signal size and lamp light output, useful for long term operation and self-optimization of microwave power and return engineering data.
The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer’s disease

PubMed Central

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

2014-01-01

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. PMID:24574361
Clock measurements to improve the geopotential determination

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

PubMed

Marcolino-Gomes, Juliana; Rodrigues, Fabiana Aparecida; Fuganti-Pagliarini, Renata; Bendix, Claire; Nakayama, Thiago Jonas; Celaya, Brandon; Molinari, Hugo Bruno Correa; de Oliveira, Maria Cristina Neves; Harmon, Frank G; Nepomuceno, Alexandre

2014-01-01

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.
The Circadian Clock in Cancer Development and Therapy

PubMed Central

Fu, Loning; Kettner, Nicole M.

2014-01-01

Most aspects of mammalian function display circadian rhythms driven by an endogenous clock. The circadian clock is operated by genes and comprises a central clock in the brain that responds to environmental cues and controls subordinate clocks in peripheral tissues via circadian output pathways. The central and peripheral clocks coordinately generate rhythmic gene expression in a tissue-specific manner in vivo to couple diverse physiological and behavioral processes to periodic changes in the environment. However, as the world industrialized, activities that disrupt endogenous homeostasis with external circadian cues have increased. This change in lifestyle has been linked to increased risk of diseases in all aspects of human health, including cancer. Studies in humans and animal models have revealed that cancer development in vivo is closely associated with the loss of circadian homeostasis in energy balance, immune function and aging that are supported by cellular functions important for tumor suppression including cell proliferation, senescence, metabolism and DNA damage response. The clock controls these cellular functions both locally in cells of peripheral tissues and at the organismal level via extracellular signaling. Thus, the hierarchical mammalian circadian clock provides a unique system to study carcinogenesis as a deregulated physiological process in vivo. The asynchrony between host and malignant tissues in cell proliferation and metabolism also provides new and exciting options for novel anti-cancer therapies. PMID:23899600
Diurnal Oscillations of Soybean Circadian Clock and Drought Responsive Genes

PubMed Central

Marcolino-Gomes, Juliana; Rodrigues, Fabiana Aparecida; Fuganti-Pagliarini, Renata; Bendix, Claire; Nakayama, Thiago Jonas; Celaya, Brandon; Molinari, Hugo Bruno Correa; de Oliveira, Maria Cristina Neves; Harmon, Frank G.; Nepomuceno, Alexandre

2014-01-01

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. PMID:24475115
Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture.

PubMed

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 circuit to generate robust 24-h rhythms.

Real Time GPS- Satellite Clock Estimation Development of a RTIGS Web Service

NASA Astrophysics Data System (ADS)

Opitz, M.; Weber, R.; Caissy, M.

2006-12-01

Since 3 years the IGS (International GNSS Service) Real-Time Working Group disseminates via Internet raw observation data of a subset of stations of the IGS network. This observation data can be used to establish a real-time integrity monitoring of the IGS predicted orbits (Ultra Rapid (IGU-) Orbits) and clocks, according to the recommendations of the IGS Workshop 2004 in Bern. The Institute for "Geodesy and Geophysics" of the TU-Vienna develops in cooperation with the IGS Real-Time Working Group the software "RTR- Control", which currently provides a real-time integrity monitoring of predicted IGU Clock Corrections to GPS Time. Our poster presents the results of a prototype version which is in operation since August this year. Besides RTR-Control allows for the comparison of pseudoranges measured at any permanent station in the global network with theoretical pseudoranges calculated on basis of the IGU- orbits. Thus, the programme can diagnose incorrectly predicted satellite orbits and clocks as well as detect multi-path distorted pseudoranges in real- time. RTR- Control calculates every 15 seconds Satellite Clock Corrections with respect to the most recent IGU- clocks (updated in a 6 hours interval). The clock estimations are referenced to a stable station clock (H-maser) with a small offset to GPS- time. This real-time Satellite Clocks are corrected for individual outliers and modelling errors. The most recent GPS- Satellite Clock Corrections (updated every 60 seconds) are published in Real Time via the Internet. The user group interested in a rigorous integrity monitoring comprises on the one hand the components of IGS itself to qualify the issued orbital data and on the other hand all users of the IGS Ultra Rapid Products (e.g. for PPP in Real Time).
Epigenetic and Posttranslational Modifications in Light Signal Transduction and the Circadian Clock in Neurospora crassa

PubMed Central

Proietto, Marco; Bianchi, Michele Maria; Ballario, Paola; Brenna, Andrea

2015-01-01

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. PMID:26198228
Multiple PAR and E4BP4 bZIP transcription factors in zebrafish: diverse spatial and temporal expression patterns.

PubMed

Ben-Moshe, Zohar; Vatine, Gad; Alon, Shahar; Tovin, Adi; Mracek, Philipp; Foulkes, Nicholas S; Gothilf, Yoav

2010-09-01

Circadian rhythms of physiology and behavior are generated by an autonomous circadian oscillator that is synchronized daily with the environment, mainly by light input. The PAR subfamily of transcriptional activators and the related E4BP4 repressor belonging to the basic leucine zipper (bZIP) family are clock-controlled genes that are suggested to mediate downstream circadian clock processes and to feedback onto the core oscillator. Here, the authors report the characterization of these genes in the zebrafish, an increasingly important model in the field of chronobiology. Five novel PAR and six novel e4bp4 zebrafish homolog genes were identified using bioinformatic tools and their coding sequences were cloned. Based on their evolutionary relationships, these genes were annotated as ztef2, zhlf1 and zhlf2, zdbp1 and zdbp2, and ze4bp4-1 to -6. The spatial and temporal mRNA expression pattern of each of these factors was characterized in zebrafish embryos in the context of a functional circadian clock and regulation by light. Nine of the factors exhibited augmented and rhythmic expression in the pineal gland, a central clock organ in zebrafish. Moreover, these genes were found to be regulated, to variable extents, by the circadian clock and/or by light. Differential expression patterns of multiple paralogs in zebrafish suggest multiple roles for these factors within the vertebrate circadian clock. This study, in the genetically accessible zebrafish model, lays the foundation for further research regarding the involvement and specific roles of PAR and E4BP4 transcription factors in the vertebrate circadian clock mechanism.
Modeling Pharmacological Clock and Memory Patterns of Interval Timing in a Striatal Beat-Frequency Model with Realistic, Noisy Neurons

PubMed Central

Oprisan, Sorinel A.; Buhusi, Catalin V.

2011-01-01

In most species, the capability of perceiving and using the passage of time in the seconds-to-minutes range (interval timing) is not only accurate but also scalar: errors in time estimation are linearly related to the estimated duration. The ubiquity of scalar timing extends over behavioral, lesion, and pharmacological manipulations. For example, in mammals, dopaminergic drugs induce an immediate, scalar change in the perceived time (clock pattern), whereas cholinergic drugs induce a gradual, scalar change in perceived time (memory pattern). How do these properties emerge from unreliable, noisy neurons firing in the milliseconds range? Neurobiological information relative to the brain circuits involved in interval timing provide support for an striatal beat frequency (SBF) model, in which time is coded by the coincidental activation of striatal spiny neurons by cortical neural oscillators. While biologically plausible, the impracticality of perfect oscillators, or their lack thereof, questions this mechanism in a brain with noisy neurons. We explored the computational mechanisms required for the clock and memory patterns in an SBF model with biophysically realistic and noisy Morris–Lecar neurons (SBF–ML). Under the assumption that dopaminergic drugs modulate the firing frequency of cortical oscillators, and that cholinergic drugs modulate the memory representation of the criterion time, we show that our SBF–ML model can reproduce the pharmacological clock and memory patterns observed in the literature. Numerical results also indicate that parameter variability (noise) – which is ubiquitous in the form of small fluctuations in the intrinsic frequencies of neural oscillators within and between trials, and in the errors in recording/retrieving stored information related to criterion time – seems to be critical for the time-scale invariance of the clock and memory patterns. PMID:21977014
Modeling the emergence of circadian rhythms in a clock neuron network.

PubMed

Diambra, Luis; Malta, Coraci P

2012-01-01

Circadian rhythms in pacemaker cells persist for weeks in constant darkness, while in other types of cells the molecular oscillations that underlie circadian rhythms damp rapidly under the same conditions. Although much progress has been made in understanding the biochemical and cellular basis of circadian rhythms, the mechanisms leading to damped or self-sustained oscillations remain largely unknown. There exist many mathematical models that reproduce the circadian rhythms in the case of a single cell of the Drosophila fly. However, not much is known about the mechanisms leading to coherent circadian oscillation in clock neuron networks. In this work we have implemented a model for a network of interacting clock neurons to describe the emergence (or damping) of circadian rhythms in Drosophila fly, in the absence of zeitgebers. Our model consists of an array of pacemakers that interact through the modulation of some parameters by a network feedback. The individual pacemakers are described by a well-known biochemical model for circadian oscillation, to which we have added degradation of PER protein by light and multiplicative noise. The network feedback is the PER protein level averaged over the whole network. In particular, we have investigated the effect of modulation of the parameters associated with (i) the control of net entrance of PER into the nucleus and (ii) the non-photic degradation of PER. Our results indicate that the modulation of PER entrance into the nucleus allows the synchronization of clock neurons, leading to coherent circadian oscillations under constant dark condition. On the other hand, the modulation of non-photic degradation cannot reset the phases of individual clocks subjected to intrinsic biochemical noise.
Optical Lattice Clocks with Weakly Bound Molecules.

PubMed

Borkowski, Mateusz

2018-02-23

Optical molecular clocks promise unparalleled sensitivity to the temporal variation of the electron-to-proton mass ratio and insight into possible new physics beyond the standard model. We propose to realize a molecular clock with bosonic ^{174}Yb_{2} molecules, where the forbidden ^{1}S_{0}→^{3}P_{0} clock transition would be induced magnetically. The use of a bosonic species avoids possible complications due to the hyperfine structure present in fermionic species. While direct clock line photoassociation would be challenging, weakly bound ground state molecules could be produced by stimulated Raman adiabatic passage and used instead. The recent scattering measurements [L. Franchi, et al. New J. Phys. 19, 103037 (2017)NJOPFM1367-263010.1088/1367-2630/aa8fb4] enable us to determine the positions of target ^{1}S_{0}+^{3}P_{0} vibrational levels and calculate the Franck-Condon factors for clock transitions between ground and excited molecular states. The resulting magnetically induced Rabi frequencies are similar to those for atoms hinting that an experimental realization is feasible. A successful observation could pave the way towards Hz-level molecular spectroscopy.
Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Zhiqiang; Su, Lijing; Pei, Jimin

In the canonical clock model, CLOCK:BMAL1-mediated transcriptional activation is feedback regulated by its repressors CRY and PER and, in association with other coregulators, ultimately generates oscillatory gene expression patterns. How CLOCK:BMAL1 interacts with coregulator(s) is not well understood. Here we report the crystal structures of the mouse CLOCK transactivating domain Exon19 in complex with CIPC, a potent circadian repressor that functions independently of CRY and PER. The Exon19:CIPC complex adopts a three-helical coiled-coil bundle conformation containing two Exon19 helices and one CIPC. Unique to Exon19:CIPC, three highly conserved polar residues, Asn341 of CIPC and Gln544 of the two Exon19 helices,more » are located at the mid-section of the coiled-coil bundle interior and form hydrogen bonds with each other. Combining results from protein database search, sequence analysis, and mutagenesis studies, we discovered for the first time that CLOCK Exon19:CIPC interaction is a conserved transcription regulatory mechanism among mammals, fish, flies, and other invertebrates.« less
The Plant Circadian Clock: From a Simple Timekeeper to a Complex Developmental Manager.

PubMed

Sanchez, Sabrina E; Kay, Steve A

2016-12-01

The plant circadian clock allows organisms to anticipate the predictable changes in the environment by adjusting their developmental and physiological traits. In the last few years, it was determined that responses known to be regulated by the oscillator are also able to modulate clock performance. These feedback loops and their multilayer communications create a complex web, and confer on the clock network a role that exceeds the measurement of time. In this article, we discuss the current knowledge of the wiring of the clock, including the interplay with metabolism, hormone, and stress pathways in the model species Arabidopsis thaliana We outline the importance of this system in crop agricultural traits, highlighting the identification of natural alleles that alter the pace of the timekeeper. We report evidence supporting the understanding of the circadian clock as a master regulator of plant life, and we hypothesize on its relevant role in the adaptability to the environment and the impact on the fitness of most organisms. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.
Optical Lattice Clocks with Weakly Bound Molecules

NASA Astrophysics Data System (ADS)

Borkowski, Mateusz

2018-02-01

Optical molecular clocks promise unparalleled sensitivity to the temporal variation of the electron-to-proton mass ratio and insight into possible new physics beyond the standard model. We propose to realize a molecular clock with bosonic 174Yb2 molecules, where the forbidden 1S0 →3P0 clock transition would be induced magnetically. The use of a bosonic species avoids possible complications due to the hyperfine structure present in fermionic species. While direct clock line photoassociation would be challenging, weakly bound ground state molecules could be produced by stimulated Raman adiabatic passage and used instead. The recent scattering measurements [L. Franchi, et al. New J. Phys. 19, 103037 (2017), 10.1088/1367-2630/aa8fb4] enable us to determine the positions of target 1S0 +3P0 vibrational levels and calculate the Franck-Condon factors for clock transitions between ground and excited molecular states. The resulting magnetically induced Rabi frequencies are similar to those for atoms hinting that an experimental realization is feasible. A successful observation could pave the way towards Hz-level molecular spectroscopy.
So many genes, so little time: A practical approach to divergence-time estimation in the genomic era

PubMed Central

2018-01-01

Phylogenomic datasets have been successfully used to address questions involving evolutionary relationships, patterns of genome structure, signatures of selection, and gene and genome duplications. However, despite the recent explosion in genomic and transcriptomic data, the utility of these data sources for efficient divergence-time inference remains unexamined. Phylogenomic datasets pose two distinct problems for divergence-time estimation: (i) the volume of data makes inference of the entire dataset intractable, and (ii) the extent of underlying topological and rate heterogeneity across genes makes model mis-specification a real concern. “Gene shopping”, wherein a phylogenomic dataset is winnowed to a set of genes with desirable properties, represents an alternative approach that holds promise in alleviating these issues. We implemented an approach for phylogenomic datasets (available in SortaDate) that filters genes by three criteria: (i) clock-likeness, (ii) reasonable tree length (i.e., discernible information content), and (iii) least topological conflict with a focal species tree (presumed to have already been inferred). Such a winnowing procedure ensures that errors associated with model (both clock and topology) mis-specification are minimized, therefore reducing error in divergence-time estimation. We demonstrated the efficacy of this approach through simulation and applied it to published animal (Aves, Diplopoda, and Hymenoptera) and plant (carnivorous Caryophyllales, broad Caryophyllales, and Vitales) phylogenomic datasets. By quantifying rate heterogeneity across both genes and lineages we found that every empirical dataset examined included genes with clock-like, or nearly clock-like, behavior. Moreover, many datasets had genes that were clock-like, exhibited reasonable evolutionary rates, and were mostly compatible with the species tree. We identified overlap in age estimates when analyzing these filtered genes under strict clock and uncorrelated lognormal (UCLN) models. However, this overlap was often due to imprecise estimates from the UCLN model. We find that “gene shopping” can be an efficient approach to divergence-time inference for phylogenomic datasets that may otherwise be characterized by extensive gene tree heterogeneity. PMID:29772020
So many genes, so little time: A practical approach to divergence-time estimation in the genomic era.

PubMed

Smith, Stephen A; Brown, Joseph W; Walker, Joseph F

2018-01-01

Phylogenomic datasets have been successfully used to address questions involving evolutionary relationships, patterns of genome structure, signatures of selection, and gene and genome duplications. However, despite the recent explosion in genomic and transcriptomic data, the utility of these data sources for efficient divergence-time inference remains unexamined. Phylogenomic datasets pose two distinct problems for divergence-time estimation: (i) the volume of data makes inference of the entire dataset intractable, and (ii) the extent of underlying topological and rate heterogeneity across genes makes model mis-specification a real concern. "Gene shopping", wherein a phylogenomic dataset is winnowed to a set of genes with desirable properties, represents an alternative approach that holds promise in alleviating these issues. We implemented an approach for phylogenomic datasets (available in SortaDate) that filters genes by three criteria: (i) clock-likeness, (ii) reasonable tree length (i.e., discernible information content), and (iii) least topological conflict with a focal species tree (presumed to have already been inferred). Such a winnowing procedure ensures that errors associated with model (both clock and topology) mis-specification are minimized, therefore reducing error in divergence-time estimation. We demonstrated the efficacy of this approach through simulation and applied it to published animal (Aves, Diplopoda, and Hymenoptera) and plant (carnivorous Caryophyllales, broad Caryophyllales, and Vitales) phylogenomic datasets. By quantifying rate heterogeneity across both genes and lineages we found that every empirical dataset examined included genes with clock-like, or nearly clock-like, behavior. Moreover, many datasets had genes that were clock-like, exhibited reasonable evolutionary rates, and were mostly compatible with the species tree. We identified overlap in age estimates when analyzing these filtered genes under strict clock and uncorrelated lognormal (UCLN) models. However, this overlap was often due to imprecise estimates from the UCLN model. We find that "gene shopping" can be an efficient approach to divergence-time inference for phylogenomic datasets that may otherwise be characterized by extensive gene tree heterogeneity.
Nanomagnet Logic: Architectures, design, and benchmarking

NASA Astrophysics Data System (ADS)

Kurtz, Steven J.

Nanomagnet Logic (NML) is an emerging technology being studied as a possible replacement or supplementary device for Complimentary Metal-Oxide-Semiconductor (CMOS) Field-Effect Transistors (FET) by the year 2020. NML devices offer numerous potential advantages including: low energy operation, steady state non-volatility, radiation hardness and a clear path to fabrication and integration with CMOS. However, maintaining both low-energy operation and non-volatility while scaling from the device to the architectural level is non-trivial as (i) nearest neighbor interactions within NML circuits complicate the modeling of ensemble nanomagnet behavior and (ii) the energy intensive clock structures required for re-evaluation and NML's relatively high latency challenge its ability to offer system-level performance wins against other emerging nanotechnologies. Thus, further research efforts are required to model more complex circuits while also identifying circuit design techniques that balance low-energy operation with steady state non-volatility. In addition, further work is needed to design and model low-power on-chip clocks while simultaneously identifying application spaces where NML systems (including clock overhead) offer sufficient energy savings to merit their inclusion in future processors. This dissertation presents research advancing the understanding and modeling of NML at all levels including devices, circuits, and line clock structures while also benchmarking NML against both scaled CMOS and tunneling FETs (TFET) devices. This is accomplished through the development of design tools and methodologies for (i) quantifying both energy and stability in NML circuits and (ii) evaluating line-clocked NML system performance. The application of these newly developed tools improves the understanding of ideal design criteria (i.e., magnet size, clock wire geometry, etc.) for NML architectures. Finally, the system-level performance evaluation tool offers the ability to project what advancements are required for NML to realize performance improvements over scaled-CMOS hardware equivalents at the functional unit and/or application-level.
Role of Bacopa monnieri in the temporal regulation of oxidative stress in clock mutant (cryb) of Drosophila melanogaster.

PubMed

Subramanian, Perumal; Prasanna, Vinoth; Jayapalan, Jaime Jacqueline; Abdul Rahman, Puteri Shafinaz; Hashim, Onn Haji

2014-06-01

Accruing evidences imply that circadian organization of biochemical, endocrinological, cellular and physiological processes contribute to wellness of organisms and in the development of pathologies such as malignancy, sleep and endocrine disorders. Oxidative stress is known to mediate a number of diseases and it is notable to comprehend the orchestration of circadian clock of a model organism of circadian biology, Drosophila melanogaster, under oxidative stress. We investigated the nexus between circadian clock and oxidative stress susceptibility by exposing D. melanogaster to hydrogen peroxide (H2O2) or rotenone; the reversibility of rhythms following exposure to Bacopa monnieri extract (ayurvedic medicine rich in antioxidants) was also investigated. Abolishment of 24h rhythms in physiological response (negative geotaxis), oxidative stress markers (protein carbonyl and thiobarbituric acid reactive substances) and antioxidants (superoxide dismutase, catalase, glutathione-S-transferase and reduced glutathione) were observed under oxidative stress. Furthermore, abolishment of per mRNA rhythm in H2O2 treated wild type flies and augmented susceptibility to oxidative stress in clock mutant (cry(b)) flies connotes the role of circadian clock in reactive oxygen species (ROS) homeostasis. Significant reversibility of rhythms was noted following B. monnieri treatment in wild type flies than cry(b) flies. Our experimental approach revealed a relationship involving oxidative stress and circadian clock in fruit fly and the utility of Drosophila model in screening putative antioxidative phytomedicines prior to their use in mammalian systems. Copyright © 2014 Elsevier Ltd. All rights reserved.
Cultural and climatic changes shape the evolutionary history of the Uralic languages.

PubMed

Honkola, T; Vesakoski, O; Korhonen, K; Lehtinen, J; Syrjänen, K; Wahlberg, N

2013-06-01

Quantitative phylogenetic methods have been used to study the evolutionary relationships and divergence times of biological species, and recently, these have also been applied to linguistic data to elucidate the evolutionary history of language families. In biology, the factors driving macroevolutionary processes are assumed to be either mainly biotic (the Red Queen model) or mainly abiotic (the Court Jester model) or a combination of both. The applicability of these models is assumed to depend on the temporal and spatial scale observed as biotic factors act on species divergence faster and in smaller spatial scale than the abiotic factors. Here, we used the Uralic language family to investigate whether both 'biotic' interactions (i.e. cultural interactions) and abiotic changes (i.e. climatic fluctuations) are also connected to language diversification. We estimated the times of divergence using Bayesian phylogenetics with a relaxed-clock method and related our results to climatic, historical and archaeological information. Our timing results paralleled the previous linguistic studies but suggested a later divergence of Finno-Ugric, Finnic and Saami languages. Some of the divergences co-occurred with climatic fluctuation and some with cultural interaction and migrations of populations. Thus, we suggest that both 'biotic' and abiotic factors contribute either directly or indirectly to the diversification of languages and that both models can be applied when studying language evolution. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.
SimPhy: Phylogenomic Simulation of Gene, Locus, and Species Trees

PubMed Central

Mallo, Diego; De Oliveira Martins, Leonardo; Posada, David

2016-01-01

We present a fast and flexible software package—SimPhy—for the simulation of multiple gene families evolving under incomplete lineage sorting, gene duplication and loss, horizontal gene transfer—all three potentially leading to species tree/gene tree discordance—and gene conversion. SimPhy implements a hierarchical phylogenetic model in which the evolution of species, locus, and gene trees is governed by global and local parameters (e.g., genome-wide, species-specific, locus-specific), that can be fixed or be sampled from a priori statistical distributions. SimPhy also incorporates comprehensive models of substitution rate variation among lineages (uncorrelated relaxed clocks) and the capability of simulating partitioned nucleotide, codon, and protein multilocus sequence alignments under a plethora of substitution models using the program INDELible. We validate SimPhy's output using theoretical expectations and other programs, and show that it scales extremely well with complex models and/or large trees, being an order of magnitude faster than the most similar program (DLCoal-Sim). In addition, we demonstrate how SimPhy can be useful to understand interactions among different evolutionary processes, conducting a simulation study to characterize the systematic overestimation of the duplication time when using standard reconciliation methods. SimPhy is available at https://github.com/adamallo/SimPhy, where users can find the source code, precompiled executables, a detailed manual and example cases. PMID:26526427
Ground-based optical atomic clocks as a tool to monitor vertical surface motion

NASA Astrophysics Data System (ADS)

Bondarescu, Ruxandra; Schärer, Andreas; Lundgren, Andrew; Hetényi, György; Houlié, Nicolas; Jetzer, Philippe; Bondarescu, Mihai

2015-09-01

According to general relativity, a clock experiencing a shift in the gravitational potential ΔU will measure a frequency change given by Δf/f ≈ ΔU/c2. The best clocks are optical clocks. After about 7 hr of integration they reach stabilities of Δf/f ˜ 10-18 and can be used to detect changes in the gravitational potential that correspond to vertical displacements of the centimetre level. At this level of performance, ground-based atomic clock networks emerge as a tool that is complementary to existing technology for monitoring a wide range of geophysical processes by directly measuring changes in the gravitational potential. Vertical changes of the clock's position due to magmatic, post-seismic or tidal deformations can result in measurable variations in the clock tick rate. We illustrate the geopotential change arising due to an inflating magma chamber using the Mogi model and apply it to the Etna volcano. Its effect on an observer on the Earth's surface can be divided into two different terms: one purely due to uplift (free-air gradient) and one due to the redistribution of matter. Thus, with the centimetre-level precision of current clocks it is already possible to monitor volcanoes. The matter redistribution term is estimated to be 3 orders of magnitude smaller than the uplift term. Additionally, clocks can be compared over distances of thousands of kilometres over short periods of time, which improves our ability to monitor periodic effects with long wavelength like the solid Earth tide.
Effects of continuous white light and 12h white-12h blue light-cycles on the expression of clock genes in diencephalon, liver, and skeletal muscle in chicks.

PubMed

Honda, Kazuhisa; Kondo, Makoto; Hiramoto, Daichi; Saneyasu, Takaoki; Kamisoyama, Hiroshi

2017-05-01

The core circadian clock mechanism relies on a feedback loop comprised of clock genes, such as the brain and muscle Arnt-like 1 (Bmal1), chriptochrome 1 (Cry1), and period 3 (Per3). Exposure to the light-dark cycle synchronizes the master circadian clock in the brain, and which then synchronizes circadian clocks in peripheral tissues. Birds have long been used as a model for the investigation of circadian rhythm in human neurobiology. In the present study, we examined the effects of continuous light and the combination of white and blue light on the expression of clock genes (Bmal1, Cry1, and Per3) in the central and peripheral tissues in chicks. Seventy two day-old male chicks were weighed, allocated to three groups and maintained under three light schedules: 12h white light-12h dark-cycles group (control); 24h white light group (WW group); 12h white light-12h blue light-cycles group (WB group). The mRNA levels of clock genes in the diencephalon were significantly different between the control and WW groups. On the other hand, the alteration in the mRNA levels of clock genes was similar between the control and WB groups. Similar phenomena were observed in the liver and skeletal muscle (biceps femoris). These results suggest that 12h white-12h blue light-cycles did not disrupt the circadian rhythm of clock gene expression in chicks. Copyright © 2017 Elsevier Inc. All rights reserved.
Developmental stage-specific regulation of the circadian clock by temperature in zebrafish.

PubMed

Lahiri, Kajori; Froehlich, Nadine; Heyd, Andreas; Foulkes, Nicholas S; Vallone, Daniela

2014-01-01

The circadian clock enables animals to adapt their physiology and behaviour in anticipation of the day-night cycle. Light and temperature represent two key environmental timing cues (zeitgebers) able to reset this mechanism and so maintain its synchronization with the environmental cycle. One key challenge is to unravel how the regulation of the clock by zeitgebers matures during early development. The zebrafish is an ideal model for studying circadian clock ontogeny since the process of development occurs ex utero in an optically transparent chorion and many tools are available for genetic analysis. However, the role played by temperature in regulating the clock during zebrafish development is poorly understood. Here, we have established a clock-regulated luciferase reporter transgenic zebrafish line (Tg (-3.1) per1b::luc) to study the effects of temperature on clock entrainment. We reveal that under complete darkness, from an early developmental stage onwards (48 to 72 hpf), exposure to temperature cycles is a prerequisite for the establishment of self-sustaining rhythms of zfper1b, zfaanat2, and zfirbp expression and also for circadian cell cycle rhythms. Furthermore, we show that following the 5-9 somite stage, the expression of zfper1b is regulated by acute temperature shifts.
Automatic Clock and Time Signal System of the Astronomical Agency in East Asia Area

NASA Astrophysics Data System (ADS)

Lee, Yong Sam

2009-09-01

We analysed the old automatic clock and time signal system that was used by the national astronomical agency in East Asian Area. Jagyeongnu is a kind of water clock that was operated by the flowing water in Joseon Dynasty. Seowoongwan managed the water clock so as to keep the standard time system in the dynasty from the 16th year (1434) of King Sejong's reign. In 1438 the Okru that was invented in the period. Such kind of clock system already was used in China, which was Shui yun i hsiang t'ai (?) in 1092. During the period Joseon Dynasty, China and Japan had been kept the time system that one day is divided into 12 shin (?2?) or 100 gak (?). However detailed part of the system had a little difference among the three countries. Though the whole system of water clock in Joseon had manufactured on the basis of Chinese, it had been gradually developed by own method and idea. In this study we show the historical records of the standard time keeping system in East Asian history. And then we can inform materials on the structure and functional devises for the purpose of new restoration models about the automatic clock and time system.
Circadian clocks in the cnidaria: environmental entrainment, molecular regulation, and organismal outputs.

PubMed

Reitzel, Adam M; Tarrant, Ann M; Levy, Oren

2013-07-01

The circadian clock is a molecular network that translates predictable environmental signals, such as light levels, into organismal responses, including behavior and physiology. Regular oscillations of the molecular components of the clock enable individuals to anticipate regularly fluctuating environmental conditions. Cnidarians play important roles in benthic and pelagic marine environments and also occupy a key evolutionary position as the likely sister group to the bilaterians. Together, these attributes make members of this phylum attractive as models for testing hypotheses on roles for circadian clocks in regulating behavior, physiology, and reproduction as well as those regarding the deep evolutionary conservation of circadian regulatory pathways in animal evolution. Here, we review and synthesize the field of cnidarian circadian biology by discussing the diverse effects of daily light cycles on cnidarians, summarizing the molecular evidence for the conservation of a bilaterian-like circadian clock in anthozoan cnidarians, and presenting new empirical data supporting the presence of a conserved feed-forward loop in the starlet sea anemone, Nematostella vectensis. Furthermore, we discuss critical gaps in our current knowledge about the cnidarian clock, including the functions directly regulated by the clock and the precise molecular interactions that drive the oscillating gene-expression patterns. We conclude that the field of cnidarian circadian biology is moving rapidly toward linking molecular mechanisms with physiology and behavior.

Search for transient ultralight dark matter signatures with networks of precision measurement devices using a Bayesian statistics method

NASA Astrophysics Data System (ADS)

Roberts, B. M.; Blewitt, G.; Dailey, C.; Derevianko, A.

2018-04-01

We analyze the prospects of employing a distributed global network of precision measurement devices as a dark matter and exotic physics observatory. In particular, we consider the atomic clocks of the global positioning system (GPS), consisting of a constellation of 32 medium-Earth orbit satellites equipped with either Cs or Rb microwave clocks and a number of Earth-based receiver stations, some of which employ highly-stable H-maser atomic clocks. High-accuracy timing data is available for almost two decades. By analyzing the satellite and terrestrial atomic clock data, it is possible to search for transient signatures of exotic physics, such as "clumpy" dark matter and dark energy, effectively transforming the GPS constellation into a 50 000 km aperture sensor array. Here we characterize the noise of the GPS satellite atomic clocks, describe the search method based on Bayesian statistics, and test the method using simulated clock data. We present the projected discovery reach using our method, and demonstrate that it can surpass the existing constrains by several order of magnitude for certain models. Our method is not limited in scope to GPS or atomic clock networks, and can also be applied to other networks of precision measurement devices.
Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle

PubMed Central

Feillet, Céline; Krusche, Peter; Tamanini, Filippo; Janssens, Roel C.; Downey, Mike J.; Martin, Patrick; Teboul, Michèle; Saito, Shoko; Lévi, Francis A.; Bretschneider, Till; van der Horst, Gijsbertus T. J.; Delaunay, Franck; Rand, David A.

2014-01-01

Daily synchronous rhythms of cell division at the tissue or organism level are observed in many species and suggest that the circadian clock and cell cycle oscillators are coupled. For mammals, despite known mechanistic interactions, the effect of such coupling on clock and cell cycle progression, and hence its biological relevance, is not understood. In particular, we do not know how the temporal organization of cell division at the single-cell level produces this daily rhythm at the tissue level. Here we use multispectral imaging of single live cells, computational methods, and mathematical modeling to address this question in proliferating mouse fibroblasts. We show that in unsynchronized cells the cell cycle and circadian clock robustly phase lock each other in a 1:1 fashion so that in an expanding cell population the two oscillators oscillate in a synchronized way with a common frequency. Dexamethasone-induced synchronization reveals additional clock states. As well as the low-period phase-locked state there are distinct coexisting states with a significantly higher period clock. Cells transition to these states after dexamethasone synchronization. The temporal coordination of cell division by phase locking to the clock at a single-cell level has significant implications because disordered circadian function is increasingly being linked to the pathogenesis of many diseases, including cancer. PMID:24958884
Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle.

PubMed

Feillet, Céline; Krusche, Peter; Tamanini, Filippo; Janssens, Roel C; Downey, Mike J; Martin, Patrick; Teboul, Michèle; Saito, Shoko; Lévi, Francis A; Bretschneider, Till; van der Horst, Gijsbertus T J; Delaunay, Franck; Rand, David A

2014-07-08

Daily synchronous rhythms of cell division at the tissue or organism level are observed in many species and suggest that the circadian clock and cell cycle oscillators are coupled. For mammals, despite known mechanistic interactions, the effect of such coupling on clock and cell cycle progression, and hence its biological relevance, is not understood. In particular, we do not know how the temporal organization of cell division at the single-cell level produces this daily rhythm at the tissue level. Here we use multispectral imaging of single live cells, computational methods, and mathematical modeling to address this question in proliferating mouse fibroblasts. We show that in unsynchronized cells the cell cycle and circadian clock robustly phase lock each other in a 1:1 fashion so that in an expanding cell population the two oscillators oscillate in a synchronized way with a common frequency. Dexamethasone-induced synchronization reveals additional clock states. As well as the low-period phase-locked state there are distinct coexisting states with a significantly higher period clock. Cells transition to these states after dexamethasone synchronization. The temporal coordination of cell division by phase locking to the clock at a single-cell level has significant implications because disordered circadian function is increasingly being linked to the pathogenesis of many diseases, including cancer.
Slow secondary relaxation in a free-energy landscape model for relaxation in glass-forming liquids

NASA Astrophysics Data System (ADS)

Diezemann, Gregor; Mohanty, Udayan; Oppenheim, Irwin

1999-02-01

Within the framework of a free-energy landscape model for the relaxation in supercooled liquids the primary (α) relaxation is modeled by transitions among different free-energy minima. The secondary (β) relaxation then corresponds to intraminima relaxation. We consider a simple model for the reorientational motions of the molecules associated with both processes and calculate the dielectric susceptibility as well as the spin-lattice relaxation times. The parameters of the model can be chosen in a way that both quantities show a behavior similar to that observed in experimental studies on supercooled liquids. In particular we find that it is not possible to obtain a crossing of the time scales associated with α and β relaxation. In our model these processes always merge at high temperatures and the α process remains above the merging temperature. The relation to other models is discussed.
Population clocks: motor timing with neural dynamics

PubMed Central

Buonomano, Dean V.; Laje, Rodrigo

2010-01-01

An understanding of sensory and motor processing will require elucidation of the mechanisms by which the brain tells time. Open questions relate to whether timing relies on dedicated or intrinsic mechanisms and whether distinct mechanisms underlie timing across scales and modalities. Although experimental and theoretical studies support the notion that neural circuits are intrinsically capable of sensory timing on short scales, few general models of motor timing have been proposed. For one class of models, population clocks, it is proposed that time is encoded in the time-varying patterns of activity of a population of neurons. We argue that population clocks emerge from the internal dynamics of recurrently connected networks, are biologically realistic and account for many aspects of motor timing. PMID:20889368
Phylogenetic relationships and timing of diversification in gonorynchiform fishes inferred using nuclear gene DNA sequences (Teleostei: Ostariophysi).

PubMed

Near, Thomas J; Dornburg, Alex; Friedman, Matt

2014-11-01

The Gonorynchiformes are the sister lineage of the species-rich Otophysi and provide important insights into the diversification of ostariophysan fishes. Phylogenies of gonorynchiforms inferred using morphological characters and mtDNA gene sequences provide differing resolutions with regard to the sister lineage of all other gonorynchiforms (Chanos vs. Gonorynchus) and support for monophyly of the two miniaturized lineages Cromeria and Grasseichthys. In this study the phylogeny and divergence times of gonorynchiforms are investigated with DNA sequences sampled from nine nuclear genes and a published morphological character matrix. Bayesian phylogenetic analyses reveal substantial congruence among individual gene trees with inferences from eight genes placing Gonorynchus as the sister lineage to all other gonorynchiforms. Seven gene trees resolve Cromeria and Grasseichthys as a clade, supporting previous inferences using morphological characters. Phylogenies resulting from either concatenating the nuclear genes, performing a multispecies coalescent species tree analysis, or combining the morphological and nuclear gene DNA sequences resolve Gonorynchus as the living sister lineage of all other gonorynchiforms, strongly support the monophyly of Cromeria and Grasseichthys, and resolve a clade containing Parakneria, Cromeria, and Grasseichthys. The morphological dataset, which includes 13 gonorynchiform fossil taxa that range in age from Early Cretaceous to Eocene, was analyzed in combination with DNA sequences from the nine nuclear genes and a relaxed molecular clock to estimate times of evolutionary divergence. This "tip dating" strategy accommodates uncertainty in the phylogenetic resolution of fossil taxa that provide calibration information in the relaxed molecular clock analysis. The estimated age of the most recent common ancestor (MRCA) of living gonorynchiforms is slightly older than estimates from previous node dating efforts, but the molecular tip dating estimated ages of Kneriinae (Kneria, Parakneria, Cromeria, and Grasseichthys) and the two paedomorphic lineages, Cromeria and Grasseichthys, are considerably younger. Copyright © 2014 Elsevier Inc. All rights reserved.
A fluorescence spotlight on the clockwork development and metabolism of bone.

PubMed

Iimura, Tadahiro; Nakane, Ayako; Sugiyama, Mayu; Sato, Hiroki; Makino, Yuji; Watanabe, Takashi; Takagi, Yuzo; Numano, Rika; Yamaguchi, Akira

2012-05-01

Biological phenomena that exhibit periodic activity are often referred as biorhythms or biological clocks. Among these, circadian rhythms, cyclic patterns reflecting a 24-h cycle, are the most obvious in many physiological activities including bone growth and metabolism. In the late 1990s, several clock genes were isolated and their primary structures and functions were identified. The feedback loop model of transcriptional factors was proposed to work as a circadian core oscillator not only in the suprachiasmatic nuclei of the anterior hypothalamus, which is recognized as the mammalian central clock, but also in various peripheral tissues including cartilage and bone. Looking back to embryonic development, the fundamental architecture of skeletal patterning is regulated by ultradian clocks that are defined as biorhythms that cycle more than once every 24 h. As post-genomic approaches, transcriptome analysis by micro-array and bioimaging assays to detect luminescent and fluorescent signals have been exploited to uncover a more comprehensive set of genes and spatio-temporal regulation of the clockwork machinery in animal models. In this review paper, we provide an overview of topics related to these molecular clocks in skeletal biology and medicine, and discuss how fluorescence imaging approaches can contribute to widening our views of this realm of biomedical science.
An improved grey model for the prediction of real-time GPS satellite clock bias

NASA Astrophysics Data System (ADS)

Zheng, Z. Y.; Chen, Y. Q.; Lu, X. S.

2008-07-01

In real-time GPS precise point positioning (PPP), real-time and reliable satellite clock bias (SCB) prediction is a key to implement real-time GPS PPP. It is difficult to hold the nuisance and inenarrable performance of space-borne GPS satellite atomic clock because of its high-frequency, sensitivity and impressionable, it accords with the property of grey model (GM) theory, i. e. we can look on the variable process of SCB as grey system. Firstly, based on limits of quadratic polynomial (QP) and traditional GM to predict SCB, a modified GM (1,1) is put forward to predict GPS SCB in this paper; and then, taking GPS SCB data for example, we analyzed clock bias prediction with different sample interval, the relationship between GM exponent and prediction accuracy, precision comparison of GM to QP, and concluded the general rule of different type SCB and GM exponent; finally, to test the reliability and validation of the modified GM what we put forward, taking IGS clock bias ephemeris product as reference, we analyzed the prediction precision with the modified GM, It is showed that the modified GM is reliable and validation to predict GPS SCB and can offer high precise SCB prediction for real-time GPS PPP.
Spatial gradients of protein-level time delays set the pace of the traveling segmentation clock waves

PubMed Central

Ay, Ahmet; Holland, Jack; Sperlea, Adriana; Devakanmalai, Gnanapackiam Sheela; Knierer, Stephan; Sangervasi, Sebastian; Stevenson, Angel; Özbudak, Ertuğrul M.

2014-01-01

The vertebrate segmentation clock is a gene expression oscillator controlling rhythmic segmentation of the vertebral column during embryonic development. The period of oscillations becomes longer as cells are displaced along the posterior to anterior axis, which results in traveling waves of clock gene expression sweeping in the unsegmented tissue. Although various hypotheses necessitating the inclusion of additional regulatory genes into the core clock network at different spatial locations have been proposed, the mechanism underlying traveling waves has remained elusive. Here, we combined molecular-level computational modeling and quantitative experimentation to solve this puzzle. Our model predicts the existence of an increasing gradient of gene expression time delays along the posterior to anterior direction to recapitulate spatiotemporal profiles of the traveling segmentation clock waves in different genetic backgrounds in zebrafish. We validated this prediction by measuring an increased time delay of oscillatory Her1 protein production along the unsegmented tissue. Our results refuted the need for spatial expansion of the core feedback loop to explain the occurrence of traveling waves. Spatial regulation of gene expression time delays is a novel way of creating dynamic patterns; this is the first report demonstrating such a control mechanism in any tissue and future investigations will explore the presence of analogous examples in other biological systems. PMID:25336742
Bayesian Modeling of NMR Data: Quantifying Longitudinal Relaxation in Vivo, and in Vitro with a Tissue-Water-Relaxation Mimic (Crosslinked Bovine Serum Albumin).

PubMed

Meinerz, Kelsey; Beeman, Scott C; Duan, Chong; Bretthorst, G Larry; Garbow, Joel R; Ackerman, Joseph J H

2018-01-01

Recently, a number of MRI protocols have been reported that seek to exploit the effect of dissolved oxygen (O 2 , paramagnetic) on the longitudinal 1 H relaxation of tissue water, thus providing image contrast related to tissue oxygen content. However, tissue water relaxation is dependent on a number of mechanisms, and this raises the issue of how best to model the relaxation data. This problem, the model selection problem, occurs in many branches of science and is optimally addressed by Bayesian probability theory. High signal-to-noise, densely sampled, longitudinal 1 H relaxation data were acquired from rat brain in vivo and from a cross-linked bovine serum albumin (xBSA) phantom, a sample that recapitulates the relaxation characteristics of tissue water in vivo . Bayesian-based model selection was applied to a cohort of five competing relaxation models: (i) monoexponential, (ii) stretched-exponential, (iii) biexponential, (iv) Gaussian (normal) R 1 -distribution, and (v) gamma R 1 -distribution. Bayesian joint analysis of multiple replicate datasets revealed that water relaxation of both the xBSA phantom and in vivo rat brain was best described by a biexponential model, while xBSA relaxation datasets truncated to remove evidence of the fast relaxation component were best modeled as a stretched exponential. In all cases, estimated model parameters were compared to the commonly used monoexponential model. Reducing the sampling density of the relaxation data and adding Gaussian-distributed noise served to simulate cases in which the data are acquisition-time or signal-to-noise restricted, respectively. As expected, reducing either the number of data points or the signal-to-noise increases the uncertainty in estimated parameters and, ultimately, reduces support for more complex relaxation models.
Brain clock driven by neuropeptides and second messengers

NASA Astrophysics Data System (ADS)

Miro-Bueno, Jesus; Sosík, Petr

2014-09-01

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

PubMed

Miro-Bueno, Jesus; Sosík, Petr

2014-09-01

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

NASA Astrophysics Data System (ADS)

Nikolova, A.; Brennen, G. K.; Osborne, T. J.; Milburn, G. J.; Stace, T. M.

2018-03-01

In a seminal paper [Phys. Rev. D 27, 2885 (1983), 10.1103/PhysRevD.27.2885], Page and Wootters suggest that time evolution could be described solely in terms of correlations between systems and clocks, as a means of dealing with the "problem of time" stemming from vanishing Hamiltonian dynamics in many theories of quantum gravity. Their approach seeks to identify relational dynamics given a Hamiltonian constraint on the physical states. Here we present a "state-centric" reformulation of the Page and Wootters model better suited to cases where the Hamiltonian constraint is satisfied, such as anyons emerging in Chern-Simons theories. We describe relational time by encoding logical "clock" qubits into topologically protected anyonic degrees of freedom. The minimum temporal increment of such anyonic clocks is determined by the universality of the anyonic braid group, with nonuniversal models naturally exhibiting discrete time. We exemplify this approach by using SU (2) 2 anyons and discuss generalizations to other states and models.
Cycling of clock genes entrained to the solar rhythm enables plants to tell time: data from Arabidopsis.

PubMed

Yeang, Hoong-Yeet

2015-07-01

An endogenous rhythm synchronized to dawn cannot time photosynthesis-linked genes to peak consistently at noon since the interval between sunrise and noon changes seasonally. In this study, a solar clock model that circumvents this limitation is proposed using two daily timing references synchronized to noon and midnight. Other rhythmic genes that are not directly linked to photosynthesis, and which peak at other times, also find an adaptive advantage in entrainment to the solar rhythm. Fourteen datasets extracted from three published papers were used in a meta-analysis to examine the cyclic behaviour of the Arabidopsis thaliana photosynthesis-related gene CAB2 and the clock oscillator genes TOC1 and LHY in T cycles and N-H cycles. Changes in the rhythms of CAB2, TOC1 and LHY in plants subjected to non-24-h light:dark cycles matched the hypothesized changes in their behaviour as predicted by the solar clock model, thus validating it. The analysis further showed that TOC1 expression peaked ∼5·5 h after mid-day, CAB2 peaked close to noon, while LHY peaked ∼7·5 h after midnight, regardless of the cycle period, the photoperiod or the light:dark period ratio. The solar clock model correctly predicted the zeitgeber timing of these genes under 11 different lighting regimes comprising combinations of seven light periods, nine dark periods, four cycle periods and four light:dark period ratios. In short cycles that terminated before LHY could be expressed, the solar clock correctly predicted zeitgeber timing of its expression in the following cycle. Regulation of gene phases by the solar clock enables the plant to tell the time, by which means a large number of genes are regulated. This facilitates the initiation of gene expression even before the arrival of sunrise, sunset or noon, thus allowing the plant to 'anticipate' dawn, dusk or mid-day respectively, independently of the photoperiod. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Geometrical Model of Solar Radiation Pressure Based on High-Performing Galileo Clocks - First Geometrical Mapping of the Yarkowsky effect

NASA Astrophysics Data System (ADS)

Svehla, Drazen; Rothacher, Markus; Hugentobler, Urs; Steigenberger, Peter; Ziebart, Marek

2014-05-01

Solar radiation pressure is the main source of errors in the precise orbit determination of GNSS satellites. All deficiencies in the modeling of Solar radiation pressure map into estimated terrestrial reference frame parameters as well as into derived gravity field coefficients and altimetry results when LEO orbits are determined using GPS. Here we introduce a new approach to geometrically map radial orbit perturbations of GNSS satellites using highly-performing clocks on board the first Galileo satellites. Only a linear model (time bias and time drift) needs to be removed from the estimated clock parameters and the remaining clock residuals map all radial orbit perturbations along the orbit. With the independent SLR measurements, we show that a Galileo clock is stable enough to map radial orbit perturbations continuously along the orbit with a negative sign in comparison to SLR residuals. Agreement between the SLR residuals and the clock residuals is at the 1 cm RMS for an orbit arc of 24 h. Looking at the clock parameters determined along one orbit revolution over a period of one year, we show that the so-called SLR bias in Galileo and GPS orbits can be explained by the translation of the determined orbit in the orbital plane towards the Sun. This orbit translation is due to thermal re-radiation and not accounting for the Sun elevation in the parameterization of the estimated Solar radiation pressure parameters. SLR ranging to GNSS satellites takes place typically at night, e.g. between 6 pm and 6 am local time when the Sun is in opposition to the satellite. Therefore, SLR observes only one part of the GNSS orbit with a negative radial orbit error that is mapped as an artificial bias in SLR observables. The Galileo clocks clearly show orbit translation for all Sun elevations: the radial orbit error is positive when the Sun is in conjuction (orbit noon) and negative when the Sun is in opposition (orbit midnight). The magnitude of this artificial negative SLR bias depends on the orbit quality and should rather be called GNSS orbit bias instead of SLR bias. When LEO satellite orbits are estimated using GPS, this GPS orbit bias is mapped into the antenna phase center. All LEO satellites, such as CHAMP, GRACE and JASON-1/2, need an adjustment of the radial antenna phase center offset. GNSS orbit translations towards the Sun in the orbital plane do not only propagate into the estimated LEO orbits, but also into derived gravity field and altimetry products. Geometrical mapping of orbit perturbations using an on board GNSS clock is a new technique to monitor orbit perturbations along the orbit and was successfully applied in the modeling of Solar radiation pressure. We show that CODE Solar radiation pressure parameterization lacks dependency with the Sun's elevation, i.e. elongation angle (rotation of Solar arrays), especially at low Sun elevations (eclipses). Parameterisation with the Sun elongation angle is used in the so-called T30 model (ROCK-model) that includes thermal re-radiation. A preliminary version of Solar radiation pressure for the first five Galileo and the GPS-36 satellite is based on 2×180 days of the MGEX Campaign. We show that Galileo clocks map the Yarkowsky effect along the orbit, i.e. the lag between the Sun's illumination and thermal re-radiation. We present the first geometrical mapping of anisotropic thermal emission of absorbed sunlight of an illuminated satellite. In this way, the effects of Solar radiation pressure can be modelled with only two paramaters for all Sun elevations.
Time determination for spacecraft users of the Navstar Global Positioning System /GPS/

NASA Technical Reports Server (NTRS)

Grenchik, T. J.; Fang, B. T.

1977-01-01

Global Positioning System (GPS) navigation is performed by time measurements. A description is presented of a two body model of spacecraft motion. Orbit determination is the process of inferring the position, velocity, and clock offset of the user from measurements made of the user motion in the Newtonian coordinate system. To illustrate the effect of clock errors and the accuracy with which the user spacecraft time and orbit may be determined, a low-earth-orbit spacecraft (Seasat) as tracked by six Phase I GPS space vehicles is considered. The obtained results indicate that in the absence of unmodeled dynamic parameter errors clock biases may be determined to the nanosecond level. There is, however, a high correlation between the clock bias and the uncertainty in the gravitational parameter GM, i.e., the product of the universal gravitational constant and the total mass of the earth. It is, therefore, not possible to determine clock bias to better than 25 nanosecond accuracy in the presence of a gravitational error of one part per million.
ROS signaling pathways and biological rhythms: perspectives in crustaceans.

PubMed

Fanjul-Moles, Maria Luisa

2013-01-01

This work reviews concepts regarding the endogenous circadian clock and the relationship between oxidative stress (OS), light and entrainment in different organisms including crustaceans, particularly crayfish. In the first section, the molecular control of circadian rhythms in invertebrates, particularly in Drosophila, is reviewed, and this model is contrasted with recent reports on the circadian genes and proteins in crayfish. Second, the redox mechanisms and signaling pathways that participate in the entrainment of the circadian clock in different organisms are reviewed. Finally, the light signals and transduction pathways involved in the entrainment of the circadian clock, specifically in relation to cryptochromes (CRYs) and their dual role in the circadian clock of different animal groups and their possible relationship to the circadian clock and redox mechanisms in crustaceans is discussed. The relationship between metabolism, ROS signals and transcription factors, such as HIF-1 alpha in crayfish, as well as the possibility that HIF-1 alpha participates in the regulation of circadian control genes (ccgs) in crustaceans is discussed.
Conservation and Divergence of Circadian Clock Operation in a Stress-Inducible Crassulacean Acid Metabolism Species Reveals Clock Compensation against Stress1

PubMed Central

Boxall, Susanna F.; Foster, Jonathan M.; Bohnert, Hans J.; Cushman, John C.; Nimmo, Hugh G.; Hartwell, James

2005-01-01

One of the best-characterized physiological rhythms in plants is the circadian rhythm of CO2 metabolism in Crassulacean acid metabolism (CAM) plants, which is the focus here. The central components of the plant circadian clock have been studied in detail only in Arabidopsis (Arabidopsis thaliana). Full-length cDNAs have been obtained encoding orthologs of CIRCADIAN CLOCK-ASSOCIATED1 (CCA1)/LATE ELONGATED HYPOCOTYL (LHY), TIMING OF CAB EXPRESSION1 (TOC1), EARLY FLOWERING4 (ELF4), ZEITLUPE (ZTL), FLAVIN-BINDING KELCH REPEAT F-BOX1 (FKF1), EARLY FLOWERING3 (ELF3), and a partial cDNA encoding GIGANTEA in the model stress-inducible CAM plant, Mesembryanthemum crystallinum (Common Ice Plant). TOC1 and LHY/CCA1 are under reciprocal circadian control in a manner similar to their regulation in Arabidopsis. ELF4, FKF1, ZTL, GIGANTEA, and ELF3 are under circadian control in C3 and CAM leaves. ELF4 transcripts peak in the evening and are unaffected by CAM induction. FKF1 shows an abrupt transcript peak 3 h before subjective dusk. ELF3 transcripts appear in the evening, consistent with their role in gating light input to the circadian clock. Intriguingly, ZTL transcripts do not oscillate in Arabidopsis, but do in M. crystallinum. The transcript abundance of the clock-associated genes in M. crystallinum is largely unaffected by development and salt stress, revealing compensation of the central circadian clock against development and abiotic stress in addition to the well-known temperature compensation. Importantly, the clock in M. crystallinum is very similar to that in Arabidopsis, indicating that such a clock could control CAM without requiring additional components of the central oscillator or a novel CAM oscillator. PMID:15734916
Immersed boundary lattice Boltzmann model based on multiple relaxation times

NASA Astrophysics Data System (ADS)

Lu, Jianhua; Han, Haifeng; Shi, Baochang; Guo, Zhaoli

2012-01-01

As an alterative version of the lattice Boltzmann models, the multiple relaxation time (MRT) lattice Boltzmann model introduces much less numerical boundary slip than the single relaxation time (SRT) lattice Boltzmann model if some special relationship between the relaxation time parameters is chosen. On the other hand, most current versions of the immersed boundary lattice Boltzmann method, which was first introduced by Feng and improved by many other authors, suffer from numerical boundary slip as has been investigated by Le and Zhang. To reduce such a numerical boundary slip, an immerse boundary lattice Boltzmann model based on multiple relaxation times is proposed in this paper. A special formula is given between two relaxation time parameters in the model. A rigorous analysis and the numerical experiments carried out show that the numerical boundary slip reduces dramatically by using the present model compared to the single-relaxation-time-based model.
Atomic clocks for geodesy.

PubMed

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.

Code-Phase Clock Bias and Frequency Offset in PPP Clock Solutions.

PubMed

Defraigne, Pascale; Sleewaegen, Jean-Marie

2016-07-01

Precise point positioning (PPP) is a zero-difference single-station technique that has proved to be very effective for time and frequency transfer, enabling the comparison of atomic clocks with a precision of a hundred picoseconds and a one-day stability below the 1e-15 level. It was, however, noted that for some receivers, a frequency difference is observed between the clock solution based on the code measurements and the clock solution based on the carrier-phase measurements. These observations reveal some inconsistency either between the code and carrier phases measured by the receiver or between the data analysis strategy of codes and carrier phases. One explanation for this discrepancy is the time offset that can exist for some receivers between the code and the carrier-phase latching. This paper explains how a code-phase bias in the receiver hardware can induce a frequency difference between the code and the carrier-phase clock solutions. The impact on PPP is then quantified. Finally, the possibility to determine this code-phase bias in the PPP modeling is investigated, and the first results are shown to be inappropriate due to the high level of code noise.
Atomic clocks for geodesy

NASA Astrophysics Data System (ADS)

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

PubMed

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.
Extracting Zero-Gravity Surface Figure of a Mirror

NASA Technical Reports Server (NTRS)

Bloemhof, Eric E.; Lam, Jonathan C.; Feria, Alfonso; Chang, Zensheu

2011-01-01

The technical innovation involves refinement of the classic optical technique of averaging surface measurements made in different orientations with respect to gravity, so the effects of gravity cancel in the averaged image. Particularly for large, thin mirrors subject to substantial deformation, the further requirement is that mount forces must also cancel when averaged over measurement orientations. The zerogravity surface figure of a mirror in a hexapod mount is obtained by analyzing the summation of mount forces in the frame of the optic as surface metrology is averaged over multiple clockings. This is illustrated with measurements taken from the Space Interferometry Mission (SIM) PT-Ml mirror for both twofold and threefold clocking. The positive results of these measurements and analyses indicate that, from this perspective, a lighter mirror could be used; that is, one might place less reliance on the damping effects of the elliptic partial differential equations that describe the propagation of forces through glass. The advantage over prior art is relaxing the need for an otherwise substantial thickness of glass that might be needed to ensure accurate metrology in the absence of a detailed understanding and analysis of the mount forces. The general insights developed here are new, and provide the basic design principles on which mirror mount geometry may be chosen.
State resolved vibrational relaxation modeling for strongly nonequilibrium flows

NASA Astrophysics Data System (ADS)

Boyd, Iain D.; Josyula, Eswar

2011-05-01

Vibrational relaxation is an important physical process in hypersonic flows. Activation of the vibrational mode affects the fundamental thermodynamic properties and finite rate relaxation can reduce the degree of dissociation of a gas. Low fidelity models of vibrational activation employ a relaxation time to capture the process at a macroscopic level. High fidelity, state-resolved models have been developed for use in continuum gas dynamics simulations based on computational fluid dynamics (CFD). By comparison, such models are not as common for use with the direct simulation Monte Carlo (DSMC) method. In this study, a high fidelity, state-resolved vibrational relaxation model is developed for the DSMC technique. The model is based on the forced harmonic oscillator approach in which multi-quantum transitions may become dominant at high temperature. Results obtained for integrated rate coefficients from the DSMC model are consistent with the corresponding CFD model. Comparison of relaxation results obtained with the high-fidelity DSMC model shows significantly less excitation of upper vibrational levels in comparison to the standard, lower fidelity DSMC vibrational relaxation model. Application of the new DSMC model to a Mach 7 normal shock wave in carbon monoxide provides better agreement with experimental measurements than the standard DSMC relaxation model.
Modelling and Analysis of the Feeding Regimen Induced Entrainment of Hepatocyte Circadian Oscillators Using Petri Nets

PubMed Central

Tareen, Samar Hayat Khan; Ahmad, Jamil

2015-01-01

Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system. PMID:25789928
The Logic of Circadian Organization in Drosophila

PubMed Central

Dissel, Stephane; Hansen, Celia N.; Özkaya, Özge; Hemsley, Matthew; Kyriacou, Charalambos P.; Rosato, Ezio

2014-01-01

Summary Background In the fruit fly Drosophila melanogaster, interlocked negative transcription/translation feedback loops provide the core of the circadian clock that generates rhythmic phenotypes. Although the current molecular model portrays the oscillator as cell autonomous, cross-talk among clock neurons is essential for robust cycling behavior. Nevertheless, the functional organization of the neuronal network remains obscure. Results Here we show that shortening or lengthening of the circadian period of locomotor activity can be obtained either by targeting different groups of clock cells with the same genetic manipulation or by challenging the same group of cells with activators and repressors of neuronal excitability. Conclusions Based on these observations we interpret circadian rhythmicity as an emerging property of the circadian network and we propose an initial model for its architectural design. PMID:25220056
Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

PubMed Central

Sundar, Isaac K.; Ahmad, Tanveer; Yao, Hongwei; Hwang, Jae-woong; Gerloff, Janice; Lawrence, B. Paige; Sellix, Michael T.; Rahman, Irfan

2015-01-01

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations. PMID:25923474
Influence of temperature on the liver circadian clock in the ruin lizard Podarcis sicula.

PubMed

Malatesta, Manuela; Frigato, Elena; Baldelli, Beatrice; Battistelli, Serafina; Foà, Augusto; Bertolucci, Cristiano

2007-07-01

Reptiles represent an interesting animal model to investigate the influence of temperature on molecular circadian clocks. The ruin lizard Podarcis sicula lives in a continental climate and it is subjected to wide range of environmental temperatures during the course of the year. As consequence, ruin lizard daily activity pattern includes either the hibernation or periods of inactivity determined by hypothermia. Here we showed the rhythmic expression of two clock genes, lPer2 and lClock, in the liver of active lizards exposed to summer photo-thermoperiodic conditions. Interestingly, the exposition of lizards to hypothermic conditions, typical of winter season, induced a strong dampening of clock genes mRNA rhythmicity with a coincident decrease of levels. We also examined the qualitative and quantitative distribution of lPER2 and lCLOCK protein in different cellular compartments during the 24-h cycle. In the liver of active lizards both proteins showed a rhythmic expression profile in all cellular compartments. After 3 days at 6 degrees C, some temporal fluctuations of the lCLOCK and lPER2 are still detectable, although, with some marked modifications in respect to the values detected in the liver of active lizards. Besides demonstrating the influence of low temperature on the lizard liver circadian oscillators, present results could provide new essential information for comparative studies on the influence of temperature on the circadian system across vertebrate classes.
Circadian Clocks in the Cnidaria: Environmental Entrainment, Molecular Regulation, and Organismal Outputs

PubMed Central

Reitzel, Adam M.; Tarrant, Ann M.; Levy, Oren

2013-01-01

The circadian clock is a molecular network that translates predictable environmental signals, such as light levels, into organismal responses, including behavior and physiology. Regular oscillations of the molecular components of the clock enable individuals to anticipate regularly fluctuating environmental conditions. Cnidarians play important roles in benthic and pelagic marine environments and also occupy a key evolutionary position as the likely sister group to the bilaterians. Together, these attributes make members of this phylum attractive as models for testing hypotheses on roles for circadian clocks in regulating behavior, physiology, and reproduction as well as those regarding the deep evolutionary conservation of circadian regulatory pathways in animal evolution. Here, we review and synthesize the field of cnidarian circadian biology by discussing the diverse effects of daily light cycles on cnidarians, summarizing the molecular evidence for the conservation of a bilaterian-like circadian clock in anthozoan cnidarians, and presenting new empirical data supporting the presence of a conserved feed-forward loop in the starlet sea anemone, Nematostella vectensis. Furthermore, we discuss critical gaps in our current knowledge about the cnidarian clock, including the functions directly regulated by the clock and the precise molecular interactions that drive the oscillating gene-expression patterns. We conclude that the field of cnidarian circadian biology is moving rapidly toward linking molecular mechanisms with physiology and behavior. PMID:23620252
Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

PubMed Central

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 circuit to generate robust 24-h rhythms. PMID:29075180
Using a transportable optical clock for chronometric levelling

NASA Astrophysics Data System (ADS)

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

2016-07-01

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

PubMed Central

Hinze, Thomas; Schumann, Mathias; Bodenstein, Christian; Heiland, Ines; Schuster, Stefan

2011-01-01

Exploration of chronobiological systems emerges as a growing research field within bioinformatics focusing on various applications in medicine, agriculture, and material sciences. From a systems biological perspective, the question arises whether biological control systems for regulation of oscillatory signals and their technical counterparts utilise similar mechanisms. If so, modelling approaches and parameterisation adopted from building blocks can help to identify general components for frequency control in circadian clocks along with gaining insight into mechanisms of clock synchronisation to external stimuli like the daily rhythm of sunlight and darkness. Phase-locked loops could be an interesting candidate in this context. Both, biology and engineering, can benefit from a unified view resulting from systems modularisation. In a first experimental study, we analyse a model of coupled repressilators. We demonstrate its ability to synchronise clock signals in a monofrequential manner. Several oscillators initially deviate in phase difference and frequency with respect to explicit reaction and diffusion rates. Accordingly, the duration of the synchronisation process depends on dedicated reaction and diffusion parameters whose settings still lack to be sufficiently captured analytically. PMID:22046179
Isoform switching facilitates period control in the Neurospora crassa circadian clock.

PubMed

Akman, Ozgur E; Locke, James C W; Tang, Sanyi; Carré, Isabelle; Millar, Andrew J; Rand, David A

2008-01-01

A striking and defining feature of circadian clocks is the small variation in period over a physiological range of temperatures. This is referred to as temperature compensation, although recent work has suggested that the variation observed is a specific, adaptive control of period. Moreover, given that many biological rate constants have a Q(10) of around 2, it is remarkable that such clocks remain rhythmic under significant temperature changes. We introduce a new mathematical model for the Neurospora crassa circadian network incorporating experimental work showing that temperature alters the balance of translation between a short and long form of the FREQUENCY (FRQ) protein. This is used to discuss period control and functionality for the Neurospora system. The model reproduces a broad range of key experimental data on temperature dependence and rhythmicity, both in wild-type and mutant strains. We present a simple mechanism utilising the presence of the FRQ isoforms (isoform switching) by which period control could have evolved, and argue that this regulatory structure may also increase the temperature range where the clock is robustly rhythmic.
Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish.

PubMed

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.
Applying the relaxation model of interfacial heat transfer to calculate the liquid outflow with supercritical initial parameters

NASA Astrophysics Data System (ADS)

Alekseev, M. V.; Vozhakov, I. S.; Lezhnin, S. I.; Pribaturin, N. A.

2017-09-01

A comparative numerical simulation of the supercritical fluid outflow on the thermodynamic equilibrium and non-equilibrium relaxation models of phase transition for different times of relaxation has been performed. The model for the fixed relaxation time based on the experimentally determined radius of liquid droplets was compared with the model of dynamically changing relaxation time, calculated by the formula (7) and depending on local parameters. It is shown that the relaxation time varies significantly depending on the thermodynamic conditions of the two-phase medium in the course of outflowing. The application of the proposed model with dynamic relaxation time leads to qualitatively correct results. The model can be used for both vaporization and condensation processes. It is shown that the model can be improved on the basis of processing experimental data on the distribution of the droplet sizes formed during the breaking up of the liquid jet.
Modeling and Analysis of Asynchronous Systems Using SAL and Hybrid SAL

NASA Technical Reports Server (NTRS)

Tiwari, Ashish; Dutertre, Bruno

2013-01-01

We present formal models and results of formal analysis of two different asynchronous systems. We first examine a mid-value select module that merges the signals coming from three different sensors that are each asynchronously sampling the same input signal. We then consider the phase locking protocol proposed by Daly, Hopkins, and McKenna. This protocol is designed to keep a set of non-faulty (asynchronous) clocks phase locked even in the presence of Byzantine-faulty clocks on the network. All models and verifications have been developed using the SAL model checking tools and the Hybrid SAL abstractor.
Phylogeography of the Western Lyresnake (Trimorphodon biscutatus): testing aridland biogeographical hypotheses across the Nearctic-Neotropical transition.

PubMed

Devitt, Thomas J

2006-12-01

The Western Lyresnake (Trimorphodon biscutatus) is a widespread, polytypic taxon inhabiting arid regions from the warm deserts of the southwestern United States southward along the Pacific versant of Mexico to the tropical deciduous forests of Mesoamerica. This broadly distributed species provides a unique opportunity to evaluate a priori biogeographical hypotheses spanning two major distinct biogeographical realms (the Nearctic and Neotropical) that are usually treated separately in phylogeographical analyses. I investigated the phylogeography of T. biscutatus using maximum likelihood and Bayesian phylogenetic analysis of mitochondrial DNA (mtDNA) from across this species' range. Phylogenetic analyses recovered five well-supported clades whose boundaries are concordant with existing geographical barriers, a pattern consistent with a model of vicariant allopatric divergence. Assuming a vicariance model, divergence times between mitochondrial lineages were estimated using Bayesian relaxed molecular clock methods calibrated using geological information from putative vicariant events. Divergence time point estimates were bounded by broad confidence intervals, and thus these highly conservative estimates should be considered tentative hypotheses at best. Comparison of mtDNA lineages and taxa traditionally recognized as subspecies based on morphology suggest this taxon is comprised of multiple independent lineages at various stages of divergence, ranging from putative secondary contact and hybridization to sympatry of 'subspecies'.
The young age of Earth

NASA Astrophysics Data System (ADS)

Zhang, Youxue

1998-09-01

Patterson (1956) established that the age of Earth is close to that of meteorites. Over the last 20 years, workers argued for younger age for core differentiation based on Pb-Pb model ages and tungsten isotopic data and for gas retention based on I-Xe modeling. However, disagreement is abundant, and the young age of Earth has not been widely accepted. In this work, I examine all radiogenic noble gases in the atmosphere and use a model-independent approach and total inversion to show that (1) the Xe-closure age of Earth is 109 ± 23 million years younger than the formation of meteorite Bjurbole (˜4560 Ma) and (2) all radiogenic components of noble gases in the atmosphere can be quantitatively accounted for by production and degassing ˜60% of the bulk silicate earth. The agreement between the 129I- 129Xe clock and 244Pu- 238U- 136Xe- 134Xe- 132Xe- 131Xe clock suggests that the volatility of iodine does not affect the 129I- 129Xe clock. Earth's Xe-closure age is 4.45 ± 0.02 Ga, consistent with the model age of Pb and the 146Sm- 142Nd, 147Sm- 143Nd and 182Hf- 182W systematics. On the basis of the consistency of these ages, 4.45 ± 0.02 Ga probably represents the time when the last Martian-sized planetesimal hit Earth and reinitialized the global clocks.
Modulation of learning and memory by the targeted deletion of the circadian clock gene Bmal1 in forebrain circuits

PubMed Central

Snider, Kaitlin H.; Dziema, Heather; Aten, Sydney; Loeser, Jacob; Norona, Frances E.; Hoyt, Kari; Obrietan, Karl

2017-01-01

A large body of literature has shown that the disruption of circadian clock timing has profound effects on mood, memory and complex thinking. Central to this time keeping process is the master circadian pacemaker located within the suprachiasmatic nucleus (SCN). Of note, within the central nervous system, clock timing is not exclusive to the SCN, but rather, ancillary oscillatory capacity has been detected in a wide range of cell types and brain regions, including forebrain circuits that underlie complex cognitive processes. These observations raise questions about the hierarchical and functional relationship between the SCN and forebrain oscillators, and, relatedly, about the underlying clock-gated synaptic circuitry that modulates cognition. Here, we utilized a clock knockout strategy in which the essential circadian timing gene Bmal1 was selectively deleted from excitatory forebrain neurons, whilst the SCN clock remained intact, to test the role of forebrain clock timing in learning, memory, anxiety, and behavioral despair. With this model system, we observed numerous effects on hippocampus-dependent measures of cognition. Mice lacking forebrain Bmal1 exhibited deficits in both acquisition and recall on the Barnes maze. Notably, loss of forebrain Bmal1 abrogated time-of-day dependent novel object location memory. However, the loss of Bmal1 did not alter performance on the elevated plus maze, open field assay, and tail suspension test, indicating that this phenotype specifically impairs cognition but not affect. Together, these data suggest that forebrain clock timing plays a critical role in shaping the efficiency of learning and memory retrieval over the circadian day. PMID:27091299

Clock genes and their genomic distributions in three species of salmonid fishes: Associations with genes regulating sexual maturation and cell cycling

PubMed Central

2010-01-01

Background Clock family genes encode transcription factors that regulate clock-controlled genes and thus regulate many physiological mechanisms/processes in a circadian fashion. Clock1 duplicates and copies of Clock3 and NPAS2-like genes were partially characterized (genomic sequencing) and mapped using family-based indels/SNPs in rainbow trout (RT)(Oncorhynchus mykiss), Arctic charr (AC)(Salvelinus alpinus), and Atlantic salmon (AS)(Salmo salar) mapping panels. Results Clock1 duplicates mapped to linkage groups RT-8/-24, AC-16/-13 and AS-2/-18. Clock3/NPAS2-like genes mapped to RT-9/-20, AC-20/-43, and AS-5. Most of these linkage group regions containing the Clock gene duplicates were derived from the most recent 4R whole genome duplication event specific to the salmonids. These linkage groups contain quantitative trait loci (QTL) for life history and growth traits (i.e., reproduction and cell cycling). Comparative synteny analyses with other model teleost species reveal a high degree of conservation for genes in these chromosomal regions suggesting that functionally related or co-regulated genes are clustered in syntenic blocks. For example, anti-müllerian hormone (amh), regulating sexual maturation, and ornithine decarboxylase antizymes (oaz1 and oaz2), regulating cell cycling, are contained within these syntenic blocks. Conclusions Synteny analyses indicate that regions homologous to major life-history QTL regions in salmonids contain many candidate genes that are likely to influence reproduction and cell cycling. The order of these genes is highly conserved across the vertebrate species examined, and as such, these genes may make up a functional cluster of genes that are likely co-regulated. CLOCK, as a transcription factor, is found within this block and therefore has the potential to cis-regulate the processes influenced by these genes. Additionally, clock-controlled genes (CCGs) are located in other life-history QTL regions within salmonids suggesting that at least in part, trans-regulation of these QTL regions may also occur via Clock expression. PMID:20670436
The Satellite Clock Bias Prediction Method Based on Takagi-Sugeno Fuzzy Neural Network

NASA Astrophysics Data System (ADS)

Cai, C. L.; Yu, H. G.; Wei, Z. C.; Pan, J. D.

2017-05-01

The continuous improvement of the prediction accuracy of Satellite Clock Bias (SCB) is the key problem of precision navigation. In order to improve the precision of SCB prediction and better reflect the change characteristics of SCB, this paper proposes an SCB prediction method based on the Takagi-Sugeno fuzzy neural network. Firstly, the SCB values are pre-treated based on their characteristics. Then, an accurate Takagi-Sugeno fuzzy neural network model is established based on the preprocessed data to predict SCB. This paper uses the precise SCB data with different sampling intervals provided by IGS (International Global Navigation Satellite System Service) to realize the short-time prediction experiment, and the results are compared with the ARIMA (Auto-Regressive Integrated Moving Average) model, GM(1,1) model, and the quadratic polynomial model. The results show that the Takagi-Sugeno fuzzy neural network model is feasible and effective for the SCB short-time prediction experiment, and performs well for different types of clocks. The prediction results for the proposed method are better than the conventional methods obviously.
A formal model of asynchronous communication and its use in mechanically verifying a biphase mark protocol

NASA Technical Reports Server (NTRS)

Moore, J. Strother

1992-01-01

In this paper we present a formal model of asynchronous communication as a function in the Boyer-Moore logic. The function transforms the signal stream generated by one processor into the signal stream consumed by an independently clocked processor. This transformation 'blurs' edges and 'dilates' time due to differences in the phases and rates of the two clocks and the communications delay. The model can be used quantitatively to derive concrete performance bounds on asynchronous communications at ISO protocol level 1 (physical level). We develop part of the reusable formal theory that permits the convenient application of the model. We use the theory to show that a biphase mark protocol can be used to send messages of arbitrary length between two asynchronous processors. We study two versions of the protocol, a conventional one which uses cells of size 32 cycles and an unconventional one which uses cells of size 18. We conjecture that the protocol can be proved to work under our model for smaller cell sizes and more divergent clock rates but the proofs would be harder.
A thermodynamically consistent model of the post-translational Kai circadian clock

PubMed Central

Lubensky, David K.; ten Wolde, Pieter Rein

2017-01-01

The principal pacemaker of the circadian clock of the cyanobacterium S. elongatus is a protein phosphorylation cycle consisting of three proteins, KaiA, KaiB and KaiC. KaiC forms a homohexamer, with each monomer consisting of two domains, CI and CII. Both domains can bind and hydrolyze ATP, but only the CII domain can be phosphorylated, at two residues, in a well-defined sequence. While this system has been studied extensively, how the clock is driven thermodynamically has remained elusive. Inspired by recent experimental observations and building on ideas from previous mathematical models, we present a new, thermodynamically consistent, statistical-mechanical model of the clock. At its heart are two main ideas: i) ATP hydrolysis in the CI domain provides the thermodynamic driving force for the clock, switching KaiC between an active conformational state in which its phosphorylation level tends to rise and an inactive one in which it tends to fall; ii) phosphorylation of the CII domain provides the timer for the hydrolysis in the CI domain. The model also naturally explains how KaiA, by acting as a nucleotide exchange factor, can stimulate phosphorylation of KaiC, and how the differential affinity of KaiA for the different KaiC phosphoforms generates the characteristic temporal order of KaiC phosphorylation. As the phosphorylation level in the CII domain rises, the release of ADP from CI slows down, making the inactive conformational state of KaiC more stable. In the inactive state, KaiC binds KaiB, which not only stabilizes this state further, but also leads to the sequestration of KaiA, and hence to KaiC dephosphorylation. Using a dedicated kinetic Monte Carlo algorithm, which makes it possible to efficiently simulate this system consisting of more than a billion reactions, we show that the model can describe a wealth of experimental data. PMID:28296888
Identification of Small Molecule Activators of Cryptochrome

PubMed Central

Hirota, Tsuyoshi; Lee, Jae Wook; St. John, Peter C.; Sawa, Mariko; Iwaisako, Keiko; Noguchi, Takako; Pongsawakul, Pagkapol Y.; Sonntag, Tim; Welsh, David K.; Brenner, David A.; Doyle, Francis J.; Schultz, Peter G.; Kay, Steve A.

2013-01-01

Impairment of the circadian clock has been associated with numerous disorders, including metabolic disease. Although small molecules that modulate clock function might offer therapeutic approaches to such diseases, only a few compound have been identified that selectively target core clock proteins. From an unbiased cell-based circadian screen, we identified KL001, a small molecule that specifically interacts with cryptochrome (CRY). KL001 prevented ubiquitin-dependent degradation of CRY, resulting in lengthening of the circadian period. In combination with mathematical modeling, KL001 revealed that CRY1 and CRY2 share a similar functional role in the period regulation. Furthermore, KL001- mediated CRY stabilization inhibited glucagon-induced gluconeogenesis in primary hepatocytes. KL001 thus provides a tool to study the regulation of CRY-dependent physiology and aid development of clock-based therapeutics of diabetes. PMID:22798407
Multi-Model Validation of Currents in the Chesapeake Bay Region in June 2010

DTIC Science & Technology

2012-01-01

host “ DaVinci ” at the Naval Oceanographic Office (NAVOCEANO). The same model configuration also took approximately 1 hr of wall clock time for a 72-hr...comparable to the performance Navy DSRC host DaVinci . Products of water level and horizontal current maps as well as station time series, identical to...DSRC host DaVinci and required approximately 5 hrs of wall-clock time for 72-hr forecasts, including data Figure 10. The Chesapeake Bay Delft3D
Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice.

PubMed

Landgraf, Dominic; Long, Jaimie E; Proulx, Christophe D; Barandas, Rita; Malinow, Roberto; Welsh, David K

2016-12-01

Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.
Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice

PubMed Central

Landgraf, Dominic; Long, Jaimie E.; Proulx, Christophe D.; Barandas, Rita; Malinow, Roberto; Welsh, David K.

2016-01-01

Background Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. Methods We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). Results In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Conclusions Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. PMID:27113500
Diurnal expression of clock genes in pineal gland and brain and plasma levels of melatonin and cortisol in Atlantic salmon parr and smolts.

PubMed

Huang, Tien-sheng; Ruoff, Peter; Fjelldal, Per G

2010-10-01

In Atlantic salmon, the preadaptation to a marine life, i.e., parr-smolt transformation, and melatonin production in the pineal gland are regulated by the photoperiod. However, the clock genes have never been studied in the pineal gland of this species. The aim of the present study was to describe the diurnal expression of clock genes (Per1-like, Cry2, and Clock) in the pineal gland and brain of Atlantic salmon parr and smolts in freshwater, as well as plasma levels of melatonin and cortisol. By employing an out-of-season smolt production model, the parr-smolt transformation was induced by subjecting triplicate groups of parr to 6 wks (wks 0 to 6) under a 12 h:12 h light-dark (LD) regime followed by 6 wks (wks 6 to 12) of continuous light (LL). The measured clock genes in both pineal gland and brain and the plasma levels of melatonin and cortisol showed significant daily variations in parr under LD in wk 6, whereas these rhythms were abolished in smolts under LL in wk 12. In parr, the pineal Per1-like and Cry2 expression peaked in the dark phase, whereas the pineal Clock expression was elevated during the light phase. Although this study presents novel findings on the clock gene system in the teleost pineal gland, the role of this system in the regulation of smoltification needs to be studied in more detail.
Circadian Clock Regulates Response to Pesticides in Drosophila via Conserved Pdp1 Pathway

PubMed Central

Beaver, Laura Michelle; Hooven, Louisa Ada; Butcher, Shawn Michael; Krishnan, Natraj; Sherman, Katherine Alice; Chow, Eileen Shin-Yeu; Giebultowicz, Jadwiga Maria

2010-01-01

Daily rhythms generated by the circadian clock regulate many life functions, including responses to xenobiotic compounds. In Drosophila melanogaster, the circadian clock consists of positive elements encoded by cycle (cyc) and Clock (Clk) and negative elements encoded by period (per) and timeless (tim) genes. The ϵ-isoform of the PAR-domain protein 1 (Pdp1ε) transcription factor is controlled by positive clock elements and regulates daily locomotor activity rhythms. Pdp1 target genes have not been identified, and its involvement in other clock output pathways is not known. Mammalian orthologs of Pdp1 have been implicated in the regulation of xenobiotic metabolism; therefore, we asked whether Pdp1 has a similar role in the fly. Using pesticides as model toxicants, we determined that disruption of Pdp1ε increased pesticide-induced mortality in flies. Flies deficient for cyc also showed increased mortality, while disruption of per and tim had no effect. Day/night and Pdp1-dependent differences in the expression of xenobiotic-metabolizing enzymes Cyp6a2, Cyp6g1, and α-Esterase-7 were observed and likely contribute to impaired detoxification. DHR96, a homolog of constitutive androstane receptor and pregnane X receptor, is involved in pesticide response, and DHR96 expression decreased when Pdp1 was suppressed. Taken together, our data uncover a pathway from the positive arm of the circadian clock through Pdp1 to detoxification effector genes, demonstrating a conserved role of the circadian system in modulating xenobiotic toxicity. PMID:20348229
Atomic clock ensemble in space (ACES) data analysis

NASA Astrophysics Data System (ADS)

Meynadier, F.; Delva, P.; le Poncin-Lafitte, C.; Guerlin, C.; Wolf, P.

2018-02-01

The Atomic Clocks Ensemble in Space (ACES/PHARAO mission, ESA & CNES) will be installed on board the International Space Station (ISS) next year. A crucial part of this experiment is its two-way microwave link (MWL), which will compare the timescale generated on board with those provided by several ground stations disseminated on the Earth. A dedicated data analysis center is being implemented at SYRTE—Observatoire de Paris, where our team currently develops theoretical modelling, numerical simulations and the data analysis software itself. In this paper, we present some key aspects of the MWL measurement method and the associated algorithms for simulations and data analysis. We show the results of tests using simulated data with fully realistic effects such as fundamental measurement noise, Doppler, atmospheric delays, or cycle ambiguities. We demonstrate satisfactory performance of the software with respect to the specifications of the ACES mission. The main scientific product of our analysis is the clock desynchronisation between ground and space clocks, i.e. the difference of proper times between the space clocks and ground clocks at participating institutes. While in flight, this measurement will allow for tests of general relativity and Lorentz invariance at unprecedented levels, e.g. measurement of the gravitational redshift at the 3×10-6 level. As a specific example, we use real ISS orbit data with estimated errors at the 10 m level to study the effect of such errors on the clock desynchronisation obtained from MWL data. We demonstrate that the resulting effects are totally negligible.
Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis.

PubMed

Nicholas, B; Rudrasingham, V; Nash, S; Kirov, G; Owen, M J; Wimpory, D C

2007-06-01

Clock gene anomalies have been suggested as causative factors in autism. We screened eleven clock/clock-related genes in a predominantly high-functioning Autism Genetic Resource Exchange sample of strictly diagnosed autistic disorder progeny and their parents (110 trios) for association of clock gene variants with autistic disorder. We found significant association (P<0.05) for two single-nucleotide polymorphisms in per1 and two in npas2. Analysis of all possible combinations of two-marker haplotypes for each gene showed that in npas2 40 out of the 136 possible two-marker combinations were significant at the P<0.05 level, with the best result between markers rs1811399 and rs2117714, P=0.001. Haplotype analysis within per1 gave a single significant result: a global P=0.027 for the markers rs2253820-rs885747. No two-marker haplotype was significant in any of the other genes, despite the large number of tests performed. Our findings support the hypothesis that these epistatic clock genes may be involved in the etiology of autistic disorder. Problems in sleep, memory and timing are all characteristics of autistic disorder and aspects of sleep, memory and timing are each clock-gene-regulated in other species. We identify how our findings may be relevant to theories of autism that focus on the amygdala, cerebellum, memory and temporal deficits. We outline possible implications of these findings for developmental models of autism involving temporal synchrony/social timing.
An Autonomous Satellite Time Synchronization System Using Remotely Disciplined VC-OCXOs.

PubMed

Gu, Xiaobo; Chang, Qing; Glennon, Eamonn P; Xu, Baoda; Dempseter, Andrew G; Wang, Dun; Wu, Jiapeng

2015-07-23

An autonomous remote clock control system is proposed to provide time synchronization and frequency syntonization for satellite to satellite or ground to satellite time transfer, with the system comprising on-board voltage controlled oven controlled crystal oscillators (VC-OCXOs) that are disciplined to a remote master atomic clock or oscillator. The synchronization loop aims to provide autonomous operation over extended periods, be widely applicable to a variety of scenarios and robust. A new architecture comprising the use of frequency division duplex (FDD), synchronous time division (STDD) duplex and code division multiple access (CDMA) with a centralized topology is employed. This new design utilizes dual one-way ranging methods to precisely measure the clock error, adopts least square (LS) methods to predict the clock error and employs a third-order phase lock loop (PLL) to generate the voltage control signal. A general functional model for this system is proposed and the error sources and delays that affect the time synchronization are discussed. Related algorithms for estimating and correcting these errors are also proposed. The performance of the proposed system is simulated and guidance for selecting the clock is provided.
Rhythm and mood: relationships between the circadian clock and mood-related behavior.

PubMed

Schnell, Anna; Albrecht, Urs; Sandrelli, Federica

2014-06-01

Mood disorders are multifactorial and heterogeneous diseases caused by the interplay of several genetic and environmental factors. In humans, mood disorders are often accompanied by abnormalities in the organization of the circadian system, which normally synchronizes activities and functions of cells and tissues. Studies on animal models suggest that the basic circadian clock mechanism, which runs in essentially all cells, is implicated in the modulation of biological phenomena regulating affective behaviors. In particular, recent findings highlight the importance of the circadian clock mechanisms in neurological pathways involved in mood, such as monoaminergic neurotransmission, hypothalamus-pituitary-adrenal axis regulation, suprachiasmatic nucleus and olfactory bulb activities, and neurogenesis. Defects at the level of both, the circadian clock mechanism and system, may contribute to the etiology of mood disorders. Modification of the circadian system using chronotherapy appears to be an effective treatment for mood disorders. Additionally, understanding the role of circadian clock mechanisms, which affect the regulation of different mood pathways, will open up the possibility for targeted pharmacological treatments. PsycINFO Database Record (c) 2014 APA, all rights reserved.
The circadian molecular clock regulates adult hippocampal neurogenesis by controlling the timing of cell-cycle entry and exit.

PubMed

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.
Fish Oil Accelerates Diet-Induced Entrainment of the Mouse Peripheral Clock via GPR120

PubMed Central

Itokawa, Misa; Nagahama, Hiroki; Ohtsu, Teiji; Furutani, Naoki; Kamagata, Mayo; Yang, Zhi-Hong; Hirasawa, Akira; Tahara, Yu; Shibata, Shigenobu

2015-01-01

The circadian peripheral clock is entrained by restricted feeding (RF) at a fixed time of day, and　insulin secretion regulates RF-induced entrainment of the peripheral clock in mice. Thus, carbohydrate-rich food may be ideal for facilitating RF-induced entrainment, although the role of dietary oils in insulin secretion and RF-induced entrainment has not been described. The soybean oil component of standard mouse chow was substituted with fish or soybean oil containing docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). Tuna oil (high DHA/EPA), menhaden oil (standard), and DHA/EPA dissolved in soybean oil increased insulin secretion and facilitated RF-induced phase shifts of the liver clock as represented by the bioluminescence rhythms of PER2::LUCIFERASE knock-in mice. In this model, insulin depletion blocked the effect of tuna oil and fish oil had no effect on mice deficient for GPR120, a polyunsaturated fatty acid receptor. These results suggest food containing fish oil or DHA/EPA is ideal for adjusting the peripheral clock. PMID:26161796
On the feasibility of phase only PPP for kinematic LEO orbits

NASA Astrophysics Data System (ADS)

Wallat, Christoph; Schön, Steffen

2016-04-01

Low Earth Orbiters (LEO) are satellites in altitudes up to 1000 kilometers. From the sensor data collected on board the Earth's gravity field can be recovered. Over the last 15 years several satellite missions were brought into space and the orbit determination improved over the years. To process the sensor data, precise positioning and timing of the satellite is mandatory. There are two approaches for precise orbit determination (POD) of LEO satellites. Kinematic orbits are based on GNSS observations and star camera data measured on board of the LEO. With a Precise Point Positioning (PPP) known from the terrestrial case, using ionospheric-free linear combinations P3 and L3 three-dimensional coordinates of the LEO can be estimated for every observation epoch. To counteract the challenges in kinematic orbit determination our approach is based on a technique called GNSS receiver clock modeling (RCM). Here the frequency stability of an external oscillator is used to model the behavior of the GNSS receiver clock with piecewise linear polynomials instead of estimating epoch-wise the receiver clock time offset as an unknown parameter. When using RCM the observation geometry is stabilized and the orbit coordinates and the receiver clock error can be estimated with a better precision. The satellites of the Gravity Recovery And Climate Experiment (GRACE) mission are equipped with Ultra Stable quartz Oscillators (USO). The USO frequency stability is used to correct the GRACE GPS receiver clock. Therefore, receiver clock modeling is feasible for polynomials with a length up to 60 seconds, leading to improved mean PDOP values of 30 % and smaller formal mean standard deviations of the coordinates between 6 and 33 %. We developed a new approach for GRACE orbits using kinematic PPP with clock modeling and tested our approach with simulated and real GPS data. The idea to use only carrier phase observations in the final processing and no code measurements leads to a reduced number of observations and changes in parameter correlation in the adjustment. Canceling the code observations out of the normal equation system is possible due to a technique named parameter lumping, which will be explained in detail. The estimated coordinates of our phase only approach are comparable to the conventional PPP solution concerning standard deviations and RMS values. We will point out the advantages of our approach for the kinematic orbit determination of the GRACE satellites also for improvements in computing phase ambiguities.
General anesthesia alters time perception by phase shifting the circadian clock.

PubMed

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.
Loss of circadian rhythm of circulating insulin concentration induced by high-fat diet intake is associated with disrupted rhythmic expression of circadian clock genes in the liver.

PubMed

Honma, Kazue; Hikosaka, Maki; Mochizuki, Kazuki; Goda, Toshinao

2016-04-01

Peripheral clock genes show a circadian rhythm is correlated with the timing of feeding in peripheral tissues. It was reported that these clock genes are strongly regulated by insulin action and that a high-fat diet (HFD) intake in C57BL/6J mice for 21days induced insulin secretion during the dark phase and reduced the circadian rhythm of clock genes. In this study, we examined the circadian expression patterns of these clock genes in insulin-resistant animal models with excess secretion of insulin during the day. We examined whether insulin resistance induced by a HFD intake for 80days altered blood parameters (glucose and insulin concentrations) and expression of mRNA and proteins encoded by clock and functional genes in the liver using male ICR mice. Serum insulin concentrations were continuously higher during the day in mice fed a HFD than control mice. Expression of lipogenesis-related genes (Fas and Accβ) and the transcription factor Chrebp peaked at zeitgeber time (ZT)24 in the liver of control mice. A HFD intake reduced the expression of these genes at ZT24 and disrupted the circadian rhythm. Expression of Bmal1 and Clock, transcription factors that compose the core feedback loop, showed circadian variation and were synchronously associated with Fas gene expression in control mice, but not in those fed a HFD. These results indicate that the disruption of the circadian rhythm of insulin secretion by HFD intake is closely associated with the disappearance of circadian expression of lipogenic and clock genes in the liver of mice. Copyright © 2016 Elsevier Inc. All rights reserved.
Hypothalamic expression and moonlight-independent changes of Cry3 and Per4 implicate their roles in lunar clock oscillators of the lunar-responsive Goldlined spinefoot.

PubMed

Toda, Riko; Okano, Keiko; Takeuchi, Yuki; Yamauchi, Chihiro; Fukushiro, Masato; Takemura, Akihiro; Okano, Toshiyuki

2014-01-01

Lunar cycle-associated physiology has been found in a wide variety of organisms. Studies suggest the presence of a circalunar clock in some animals, but the location of the lunar clock is unclear. We previously found lunar-associated expression of transcripts for Cryptochrome3 gene (SgCry3) in the brain of a lunar phase-responsive fish, the Goldlined spinefoot (Siganus guttatus). Then we proposed a photoperiodic model for the lunar phase response, in which SgCry3 might function as a phase-specific light response gene and/or an oscillatory factor in unidentified circalunar clock. In this study, we have developed an anti-SgCRY3 antibody to identify SgCRY3-immunoreactive cells in the brain. We found immunoreactions in the subependymal cells located in the mediobasal region of the diencephalon, a crucial site for photoperiodic seasonal responses in birds. For further assessment of the lunar-responding mechanism and the circalunar clock, we investigated mRNA levels of Cry3 as well as those of the other clock(-related) genes, Period (Per2 and Per4), in S. guttatus reared under nocturnal moonlight interruption or natural conditions. Not only SgCry3 but SgPer4 mRNA levels showed lunar phase-dependent variations in the diencephalon without depending on light condition during the night. These results suggest that the expressions of SgCry3 and SgPer4 are not directly regulated by moonlight stimulation but endogenously mediated in the brain, and implicate that circadian clock(-related) genes may be involved in the circalunar clock locating within the mediobasal region of the diencephalon.

Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line.

PubMed

Chappell, Patrick E; White, Rachel S; Mellon, Pamela L

2003-12-03

Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse hypothalamic cell line as a model for GnRH secretion, because these cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1-7 cells by transient expression of the dominant-negative Clock-Delta19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.
Modulation of learning and memory by the targeted deletion of the circadian clock gene Bmal1 in forebrain circuits.

PubMed

Snider, Kaitlin H; Dziema, Heather; Aten, Sydney; Loeser, Jacob; Norona, Frances E; Hoyt, Kari; Obrietan, Karl

2016-07-15

A large body of literature has shown that the disruption of circadian clock timing has profound effects on mood, memory and complex thinking. Central to this time keeping process is the master circadian pacemaker located within the suprachiasmatic nucleus (SCN). Of note, within the central nervous system, clock timing is not exclusive to the SCN, but rather, ancillary oscillatory capacity has been detected in a wide range of cell types and brain regions, including forebrain circuits that underlie complex cognitive processes. These observations raise questions about the hierarchical and functional relationship between the SCN and forebrain oscillators, and, relatedly, about the underlying clock-gated synaptic circuitry that modulates cognition. Here, we utilized a clock knockout strategy in which the essential circadian timing gene Bmal1 was selectively deleted from excitatory forebrain neurons, whilst the SCN clock remained intact, to test the role of forebrain clock timing in learning, memory, anxiety, and behavioral despair. With this model system, we observed numerous effects on hippocampus-dependent measures of cognition. Mice lacking forebrain Bmal1 exhibited deficits in both acquisition and recall on the Barnes maze. Notably, loss of forebrain Bmal1 abrogated time-of-day dependent novel object location memory. However, the loss of Bmal1 did not alter performance on the elevated plus maze, open field assay, and tail suspension test, indicating that this phenotype specifically impairs cognition but not affect. Together, these data suggest that forebrain clock timing plays a critical role in shaping the efficiency of learning and memory retrieval over the circadian day. Copyright © 2016 Elsevier B.V. All rights reserved.
Mechanical relaxation in a Zr-based bulk metallic glass: Analysis based on physical models

NASA Astrophysics Data System (ADS)

Qiao, J. C.; Pelletier, J. M.

2012-08-01

The mechanical relaxation behavior in a Zr55Cu30Ni5Al10 bulk metallic glass is investigated by dynamic mechanical analysis in both temperature and frequency domains. Master curves can be obtained for the storage modulus G' and for the loss modulus G'', confirming the validity of the time-temperature superposition principle. Different models are discussed to describe the main (α) relaxation, e.g., Debye model, Havriliak-Negami (HN) model, Kohlrausch-Williams-Watt (KWW) model, and quasi-point defects (QPDs) model. The main relaxation in bulk metallic glass cannot be described using a single relaxation time. The HN model, the KWW model, and the QPD theory can be used to fit the data of mechanical spectroscopy experiments. However, unlike the HN model and the KWW model, some physical parameters are introduced in QPD model, i.e., atomic mobility and correlation factor, giving, therefore, a new physical approach to understand the mechanical relaxation in bulk metallic glasses.
Prevalence of Cam Deformity with Associated Femoroacetabular Impingement Syndrome in Hip Joint Computed Tomography of Asymptomatic Adults

PubMed Central

Han, Jun; Won, Seok-Hyung; Kim, Jung-Taek; Hahn, Myung-Hoon

2018-01-01

Purpose Femoroacetabular impingement (FAI) is considered an important cause of early degenerative arthritis development. Although three-dimensional (3D) imaging such as computed tomography (CT) and magnetic resonance imaging are considered precise imaging modalities for 3D morphology of FAI, they are associated with several limitations when used in out-patient clinics. The paucity of FAI morphologic data in Koreans makes it difficult to select the most effective radiographical method when screening for general orthopedic problems. We postulate that there might be an individual variation in the distribution of cam deformity in the asymptomatic Korean population. Materials and Methods From January 2011 to December 2015, CT images of the hips of 100 subjects without any history of hip joint ailments were evaluated. A computer program which generates 3D models from CT scans was used to provide sectional images which cross the central axis of the femoral head and neck. Alpha angles were measured in each sectional images. Alpha angles above 55° were regarded as cam deformity. Results The mean alpha angle was 43.5°, range 34.7–56.1°(3 o'clock); 51.24°, range 39.5–58.8°(2 o'clock); 52.45°, range 43.3–65.5°(1 o'clock); 44.09°, range 36.8–49.8°(12 o'clock); 40.71, range 33.5–45.8°(11 o'clock); and 39.21°, range 34.1–44.6°(10 o'clock). Alpha angle in 1 and 2 o'clock was significantly larger than other locations (P<0.01). The prevalence of cam deformity was 18.0% and 19.0% in 1 and 2 o'clock, respectively. Conclusion Cam deformity of FAI was observed in 31% of asymptomatic hips. The most common region of cam deformity was antero-superior area of femoral head-neck junction (1 and 2 o'clock). PMID:29564291
Adaptive evolution during the establishment of European avian-like H1N1 influenza A virus in swine.

PubMed

Joseph, Udayan; Vijaykrishna, Dhanasekaran; Smith, Gavin J D; Su, Yvonne C F

2018-04-01

An H1N1 subtype influenza A virus with all eight gene segments derived from wild birds (including mallards), ducks and chickens, caused severe disease outbreaks in swine populations in Europe beginning in 1979 and successfully adapted to form the European avian-like swine (EA-swine) influenza lineage. Genes of the EA-swine lineage that are clearly segregated from its closest avian relatives continue to circulate in swine populations globally and represent a unique opportunity to study the adaptive process of an avian-to-mammalian cross-species transmission. Here, we used a relaxed molecular clock model to test whether the EA-swine virus originated through the introduction of a single avian ancestor as an entire genome, followed by an analysis of host-specific selection pressures among different gene segments. Our data indicated independent introduction of gene segments via transmission of avian viruses into swine followed by reassortment events that occurred at least 1-4 years prior to the EA-swine outbreak. All EA-swine gene segments exhibit greater selection pressure than avian viruses, reflecting both adaptive pressures and relaxed selective constraints that are associated with host switching. Notably, we identified key amino acid mutations in the viral surface proteins (H1 and N1) that play a role in adaptation to new hosts. Following the establishment of EA-swine lineage, we observed an increased frequency of intrasubtype reassortment of segments compared to the earlier strains that has been associated with adaptive amino acid replacements, disease severity and vaccine escape. Taken together, our study provides key insights into the adaptive changes in viral genomes following the transmission of avian influenza viruses to swine and the early establishment of the EA-swine lineage.
Natural changes in light interact with circadian regulation at promoters to control gene expression in cyanobacteria

PubMed Central

2017-01-01

The circadian clock interacts with other regulatory pathways to tune physiology to predictable daily changes and unexpected environmental fluctuations. However, the complexity of circadian clocks in higher organisms has prevented a clear understanding of how natural environmental conditions affect circadian clocks and their physiological outputs. Here, we dissect the interaction between circadian regulation and responses to fluctuating light in the cyanobacterium Synechococcus elongatus. We demonstrate that natural changes in light intensity substantially affect the expression of hundreds of circadian-clock-controlled genes, many of which are involved in key steps of metabolism. These changes in expression arise from circadian and light-responsive control of RNA polymerase recruitment to promoters by a network of transcription factors including RpaA and RpaB. Using phenomenological modeling constrained by our data, we reveal simple principles that underlie the small number of stereotyped responses of dusk circadian genes to changes in light. PMID:29239721
Suppressing the Neurospora crassa circadian clock while maintaining light responsiveness in continuous stirred tank reactors

PubMed Central

Cockrell, Allison L.; Pirlo, Russell K.; Babson, David M.; Cusick, Kathleen D.; Soto, Carissa M.; Petersen, Emily R.; Davis, Miah J.; Hong, Christian I.; Lee, Kwangwon; Fitzgerald, Lisa A.; Biffinger, Justin C.

2015-01-01

Neurospora crassa has been utilized as a model organism for studying biological, regulatory, and circadian rhythms for over 50 years. These circadian cycles are driven at the molecular level by gene transcription events to prepare for environmental changes. N. crassa is typically found on woody biomass and is commonly studied on agar-containing medium which mimics its natural environment. We report a novel method for disrupting circadian gene transcription while maintaining light responsiveness in N. crassa when held in a steady metabolic state using bioreactors. The arrhythmic transcription of core circadian genes and downstream clock-controlled genes was observed in constant darkness (DD) as determined by reverse transcription-quantitative PCR (RT-qPCR). Nearly all core circadian clock genes were up-regulated upon exposure to light during 11hr light/dark cycle experiments under identical conditions. Our results demonstrate that the natural timing of the robust circadian clock in N. crassa can be disrupted in the dark when maintained in a consistent metabolic state. Thus, these data lead to a path for the production of industrial scale enzymes in the model system, N. crassa, by removing the endogenous negative feedback regulation by the circadian oscillator. PMID:26031221
A Computational Method to Quantify Fly Circadian Activity.

PubMed

Lazopulo, Andrey; Syed, Sheyum

2017-10-28

In most animals and plants, circadian clocks orchestrate behavioral and molecular processes and synchronize them to the daily light-dark cycle. Fundamental mechanisms that underlie this temporal control are widely studied using the fruit fly Drosophila melanogaster as a model organism. In flies, the clock is typically studied by analyzing multiday locomotor recording. Such a recording shows a complex bimodal pattern with two peaks of activity: a morning peak that happens around dawn, and an evening peak that happens around dusk. These two peaks together form a waveform that is very different from sinusoidal oscillations observed in clock genes, suggesting that mechanisms in addition to the clock have profound effects in producing the observed patterns in behavioral data. Here we provide instructions on using a recently developed computational method that mathematically describes temporal patterns in fly activity. The method fits activity data with a model waveform that consists of four exponential terms and nine independent parameters that fully describe the shape and size of the morning and evening peaks of activity. The extracted parameters can help elucidate the kinetic mechanisms of substrates that underlie the commonly observed bimodal activity patterns in fly locomotor rhythms.
On the possible onset of the Pioneer anomaly

NASA Astrophysics Data System (ADS)

Feldman, Michael R.; Anderson, John D.

2015-06-01

We explore the possibility that the observed onset of the Pioneer anomaly after Saturn encounter by Pioneer 11 is not necessarily due to mismodeling of solar radiation pressure but instead reflects a physically relevant characteristic of the anomaly itself. We employ the principles of a recently proposed cosmological model termed "the theory of inertial centers" along with an understanding of the fundamental assumptions taken by the Deep Space Network (DSN) to attempt to model this sudden onset. Due to an ambiguity that arises from the difference in the DSN definition of expected light-time with light-time according to the theory of inertial centers, we are forced to adopt a seemingly arbitrary convention to relate DSN-assumed clock-rates to physical clock-rates for this model. We offer a possible reason for adopting the convention employed in our analysis; however, we remain skeptical. Nevertheless, with this convention, one finds that this theory is able to replicate the previously reported Hubble-like behavior of the "clock acceleration" for the Pioneer anomaly as well as the sudden onset of the anomalous acceleration after Pioneer 11 Saturn encounter. While oscillatory behavior with a yearly period is also predicted for the anomalous clock accelerations of both Pioneer 10 and Pioneer 11, the predicted amplitude is an order of magnitude too small when compared with that reported for Pioneer 10.
Fossil record of stem groups employed in evaluating the chronogram of insects (Arthropoda: Hexapoda)

PubMed Central

Wang, Yan-hui; Engel, Michael S.; Rafael, José A.; Wu, Hao-yang; Rédei, Dávid; Xie, Qiang; Wang, Gang; Liu, Xiao-guang; Bu, Wen-jun

2016-01-01

Insecta s. str. (=Ectognatha), comprise the largest and most diversified group of living organisms, accounting for roughly half of the biodiversity on Earth. Understanding insect relationships and the specific time intervals for their episodes of radiation and extinction are critical to any comprehensive perspective on evolutionary events. Although some deeper nodes have been resolved congruently, the complete evolution of insects has remained obscure due to the lack of direct fossil evidence. Besides, various evolutionary phases of insects and the corresponding driving forces of diversification remain to be recognized. In this study, a comprehensive sample of all insect orders was used to reconstruct their phylogenetic relationships and estimate deep divergences. The phylogenetic relationships of insect orders were congruently recovered by Bayesian inference and maximum likelihood analyses. A complete timescale of divergences based on an uncorrelated log-normal relaxed clock model was established among all lineages of winged insects. The inferred timescale for various nodes are congruent with major historical events including the increase of atmospheric oxygen in the Late Silurian and earliest Devonian, the radiation of vascular plants in the Devonian, and with the available fossil record of the stem groups to various insect lineages in the Devonian and Carboniferous. PMID:27958352
Comprehensive evolutionary and phylogenetic analysis of Hepacivirus N (HNV).

PubMed

da Silva, M S; Junqueira, D M; Baumbach, L F; Cibulski, S P; Mósena, A C S; Weber, M N; Silveira, S; de Moraes, G M; Maia, R D; Coimbra, V C S; Canal, C W

2018-05-24

Hepaciviruses (HVs) have been detected in several domestic and wild animals and present high genetic diversity. The actual classification divides the genus Hepacivirus into 14 species (A-N), according to their phylogenetic relationships, including the bovine hepacivirus [Hepacivirus N (HNV)]. In this study, we confirmed HNV circulation in Brazil and sequenced the whole genome of two strains. Based on the current classification of HCV, which is divided into genotypes and subtypes, we analysed all available bovine hepacivirus sequences in the GenBank database and proposed an HNV classification. All of the sequences were grouped into a single genotype, putatively named 'genotype 1'. This genotype can be clearly divided into four subtypes: A and D containing sequences from Germany and Brazil, respectively, and B and C containing Ghanaian sequences. In addition, the NS3-coding region was used to estimate the time to the most recent common ancestor (TMRCA) of each subtype, using a Bayesian approach and a relaxed molecular clock model. The analyses indicated a common origin of the virus circulating in Germany and Brazil. Ghanaian sequences seemed to have an older TMRCA, indicating a long time of circulation of these viruses in the African continent.
Metabolism and the Circadian Clock Converge

PubMed Central

Eckel-Mahan, Kristin

2013-01-01

Circadian rhythms occur in almost all species and control vital aspects of our physiology, from sleeping and waking to neurotransmitter secretion and cellular metabolism. Epidemiological studies from recent decades have supported a unique role for circadian rhythm in metabolism. As evidenced by individuals working night or rotating shifts, but also by rodent models of circadian arrhythmia, disruption of the circadian cycle is strongly associated with metabolic imbalance. Some genetically engineered mouse models of circadian rhythmicity are obese and show hallmark signs of the metabolic syndrome. Whether these phenotypes are due to the loss of distinct circadian clock genes within a specific tissue versus the disruption of rhythmic physiological activities (such as eating and sleeping) remains a cynosure within the fields of chronobiology and metabolism. Becoming more apparent is that from metabolites to transcription factors, the circadian clock interfaces with metabolism in numerous ways that are essential for maintaining metabolic homeostasis. PMID:23303907
The circadian clock controls toll-like receptor 9-mediated innate and adaptive immunity

PubMed Central

Silver, Adam C.; Arjona, Alvaro; Walker, Wendy E.; Fikrig, Erol

2012-01-01

Circadian rhythms refer to biologic processes that oscillate with a period of approximately 24 hours. These rhythms are sustained by a molecular clock and provide a temporal matrix that ensures the coordination of homeostatic processes with the periodicity of environmental challenges. We demonstrate the circadian molecular clock controls the expression and function of toll like receptor 9 (TLR9). In a vaccination model using TLR9 ligand as adjuvant, mice immunized at the time of enhanced TLR9 responsiveness presented weeks later with an improved adaptive immune response. In a TLR9-dependent mouse model of sepsis, we found that disease severity was dependent on the timing of sepsis induction, coinciding with the daily changes in TLR9 expression and function. These findings unveil a direct molecular link between the circadian and innate immune systems with important implications for immunoprophylaxis and immunotherapy. PMID:22342842
Clique Relaxations in Biological and Social Network Analysis Foundations and Algorithms

DTIC Science & Technology

2015-10-26

study of clique relaxation models arising in biological and social networks. This project examines the elementary clique-defining properties... elementary clique-defining properties inherently exploited in the available clique relaxation models and pro- poses a taxonomic framework that not...analyzes the elementary clique-defining properties implicitly exploited in the available clique relaxation models and proposes a taxonomic framework that
Development of the Astyanax mexicanus circadian clock and non-visual light responses.

PubMed

Frøland Steindal, Inga A; Beale, Andrew D; Yamamoto, Yoshiyuki; Whitmore, David

2018-06-23

Most animals and plants live on the planet exposed to periods of rhythmic light and dark. As such, they have evolved endogenous circadian clocks to regulate their physiology rhythmically, and non-visual light detection mechanisms to set the clock to the environmental light-dark cycle. In the case of fish, circadian pacemakers are not only present in the majority of tissues and cells, but these tissues are themselves directly light-sensitive, expressing a wide range of opsin photopigments. This broad non-visual light sensitivity exists to set the clock, but also impacts a wide range of fundamental cell biological processes, such as DNA repair regulation. In this context, Astyanax mexicanus is a very intriguing model system with which to explore non-visual light detection and circadian clock function. Previous work has shown that surface fish possess the same directly light entrainable circadian clocks, described above. The same is true for cave strains of Astyanax in the laboratory, though no daily rhythms have been observed under natural dark conditions in Mexico. There are, however, clear alterations in the cave strain light response and changes to the circadian clock, with a difference in phase of peak gene expression and a reduction in amplitude. In this study, we expand these early observations by exploring the development of non-visual light sensitivity and clock function between surface and cave populations. When does the circadian pacemaker begin to oscillate during development, and are there differences between the various strains? Is the difference in acute light sensitivity, seen in adults, apparent from the earliest stages of development? Our results show that both cave and surface populations must experience daily light exposure to establish a larval gene expression rhythm. These oscillations begin early, around the third day of development in all strains, but gene expression rhythms show a significantly higher amplitude in surface fish larvae. In addition, the light induction of clock genes is developmentally delayed in cave populations. Zebrafish embryonic light sensitivity has been shown to be critical not only for clock entrainment, but also for transcriptional activation of DNA repair processes. Similar downstream transcriptional responses to light also occur in Astyanax. Interestingly, the establishment of the adult timing profile of clock gene expression takes several days to become apparent. This fact may provide mechanistic insight into the key differences between the cave and surface fish clock mechanisms. Copyright © 2018. Published by Elsevier Inc.
Impacts of Satellite Orbit and Clock on Real-Time GPS Point and Relative Positioning.

PubMed

Shi, Junbo; Wang, Gaojing; Han, Xianquan; Guo, Jiming

2017-06-12

Satellite orbit and clock corrections are always treated as known quantities in GPS positioning models. Therefore, any error in the satellite orbit and clock products will probably cause significant consequences for GPS positioning, especially for real-time applications. Currently three types of satellite products have been made available for real-time positioning, including the broadcast ephemeris, the International GNSS Service (IGS) predicted ultra-rapid product, and the real-time product. In this study, these three predicted/real-time satellite orbit and clock products are first evaluated with respect to the post-mission IGS final product, which demonstrates cm to m level orbit accuracies and sub-ns to ns level clock accuracies. Impacts of real-time satellite orbit and clock products on GPS point and relative positioning are then investigated using the P3 and GAMIT software packages, respectively. Numerical results show that the real-time satellite clock corrections affect the point positioning more significantly than the orbit corrections. On the contrary, only the real-time orbit corrections impact the relative positioning. Compared with the positioning solution using the IGS final product with the nominal orbit accuracy of ~2.5 cm, the real-time broadcast ephemeris with ~2 m orbit accuracy provided <2 cm relative positioning error for baselines no longer than 216 km. As for the baselines ranging from 574 to 2982 km, the cm-dm level positioning error was identified for the relative positioning solution using the broadcast ephemeris. The real-time product could result in <5 mm relative positioning accuracy for baselines within 2982 km, slightly better than the predicted ultra-rapid product.
Characterisation of circadian rhythms of various duckweeds.

PubMed

Muranaka, T; Okada, M; Yomo, J; Kubota, S; Oyama, T

2015-01-01

The plant circadian clock controls various physiological phenomena that are important for adaptation to natural day-night cycles. Many components of the circadian clock have been identified in Arabidopsis thaliana, the model plant for molecular genetic studies. Recent studies revealed evolutionary conservation of clock components in green plants. Homologues of clock-related genes have been isolated from Lemna gibba and Lemna aequinoctialis, and it has been demonstrated that these homologues function in the clock system in a manner similar to their functioning in Arabidopsis. While clock components are widely conserved, circadian phenomena display diversity even within the Lemna genus. In order to survey the full extent of diversity in circadian rhythms among duckweed plants, we characterised the circadian rhythms of duckweed by employing a semi-transient bioluminescent reporter system. Using a particle bombardment method, circadian bioluminescent reporters were introduced into nine strains representing five duckweed species: Spirodela polyrhiza, Landoltia punctata, Lemna gibba, L. aequinoctialis and Wolffia columbiana. We then monitored luciferase (luc+) reporter activities driven by AtCCA1, ZmUBQ1 or CaMV35S promoters under entrainment and free-running conditions. Under entrainment, AtCCA1::luc+ showed similar diurnal rhythms in all strains. This suggests that the mechanism of biological timing under day-night cycles is conserved throughout the evolution of duckweeds. Under free-running conditions, we observed circadian rhythms of AtCCA1::luc+, ZmUBQ1::luc+ and CaMV35S::luc+. These circadian rhythms showed diversity in period length and sustainability, suggesting that circadian clock mechanisms are somewhat diversified among duckweeds. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.
Transvaginal Pelvic Floor Muscle Injection Technique: A Cadaver Study.

PubMed

Gupta, Priyanka; Ehlert, Michael; Sirls, Larry T; Peters, Kenneth

Women with pelvic floor dysfunction can have tender areas on vaginal examination, which can be treated with trigger-point injections. There are no publications to evaluate the accuracy of pelvic floor muscle injections. Trigger-point injections were performed on 2 fresh cadaveric pelvises using a curved nasal cannula guide and 7-in spinal needle. This was performed using our standard template of 2 sets of injections at the 1-, 3-, and 5-o'clock positions distally and proximally. The first pelvis was dissected to examine dye penetration. Based on these results, we modified our technique and repeated the injections on the second cadaver. We dissected the second pelvis and compared our findings. The 1-o'clock proximal and distal injections stained the obturator internus and externus near the insertion at the ischiopubic ramus. The 3-o'clock injections stained the midbody of the pubococcygeus and puborectalis. The distal 5-o'clock position was too deep and stained the fat of the ischiorectal space. The proximal 5-o'clock injection stained the area of the pudendal nerve. Our goal at the distal 5-o'clock position was to infuse the iliococcygeus muscle, so we shortened the needle depth from 2 to 1 cm beyond the cannula tip. In our second dissection, the distal 5-o'clock injection again stained only the fat of the ischiorectal space. This is the first study to characterize the distribution of pelvic floor muscle injections in a cadaver model and confirms the ability to deliver medications effectively to the pelvic floor muscles.
Gaussian signal relaxation around spin echoes: Implications for precise reversible transverse relaxation quantification of pulmonary tissue at 1.5 and 3 Tesla.

PubMed

Zapp, Jascha; Domsch, Sebastian; Weingärtner, Sebastian; Schad, Lothar R

2017-05-01

To characterize the reversible transverse relaxation in pulmonary tissue and to study the benefit of a quadratic exponential (Gaussian) model over the commonly used linear exponential model for increased quantification precision. A point-resolved spectroscopy sequence was used for comprehensive sampling of the relaxation around spin echoes. Measurements were performed in an ex vivo tissue sample and in healthy volunteers at 1.5 Tesla (T) and 3 T. The goodness of fit using χred2 and the precision of the fitted relaxation time by means of its confidence interval were compared between the two relaxation models. The Gaussian model provides enhanced descriptions of pulmonary relaxation with lower χred2 by average factors of 4 ex vivo and 3 in volunteers. The Gaussian model indicates higher sensitivity to tissue structure alteration with increased precision of reversible transverse relaxation time measurements also by average factors of 4 ex vivo and 3 in volunteers. The mean relaxation times of the Gaussian model in volunteers are T2,G' = (1.97 ± 0.27) msec at 1.5 T and T2,G' = (0.83 ± 0.21) msec at 3 T. Pulmonary signal relaxation was found to be accurately modeled as Gaussian, providing a potential biomarker T2,G' with high sensitivity. Magn Reson Med 77:1938-1945, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.
The Hubble Space Telescope UV Legacy Survey of Galactic Globular Clusters. XV. The Dynamical Clock: Reading Cluster Dynamical Evolution from the Segregation Level of Blue Straggler Stars

NASA Astrophysics Data System (ADS)

Ferraro, F. R.; Lanzoni, B.; Raso, S.; Nardiello, D.; Dalessandro, E.; Vesperini, E.; Piotto, G.; Pallanca, C.; Beccari, G.; Bellini, A.; Libralato, M.; Anderson, J.; Aparicio, A.; Bedin, L. R.; Cassisi, S.; Milone, A. P.; Ortolani, S.; Renzini, A.; Salaris, M.; van der Marel, R. P.

2018-06-01

The parameter A +, defined as the area enclosed between the cumulative radial distribution of blue straggler stars (BSSs) and that of a reference population, is a powerful indicator of the level of BSS central segregation. As part of the Hubble Space Telescope UV Legacy Survey of Galactic globular clusters (GCs), here we present the BSS population and the determination of A + in 27 GCs observed out to about one half-mass radius. In combination with 21 additional clusters discussed in a previous paper, this provides us with a global sample of 48 systems (corresponding to ∼32% of the Milky Way GC population), for which we find a strong correlation between A + and the ratio of cluster age to the current central relaxation time. Tight relations have also been found with the core radius and the central luminosity density, which are expected to change with the long-term cluster dynamical evolution. An interesting relation is emerging between A + and the ratio of the BSS velocity dispersion relative to that of main sequence turn-off stars, which measures the degree of energy equipartition experienced by BSSs in the cluster. These results provide further confirmation that BSSs are invaluable probes of GC internal dynamics and that A + is a powerful dynamical clock.

A 9-Bit 50 MSPS Quadrature Parallel Pipeline ADC for Communication Receiver Application

NASA Astrophysics Data System (ADS)

Roy, Sounak; Banerjee, Swapna

2018-03-01

This paper presents the design and implementation of a pipeline Analog-to-Digital Converter (ADC) for superheterodyne receiver application. Several enhancement techniques have been applied in implementing the ADC, in order to relax the target specifications of its building blocks. The concepts of time interleaving and double sampling have been used simultaneously to enhance the sampling speed and to reduce the number of amplifiers used in the ADC. Removal of a front end sample-and-hold amplifier is possible by employing dynamic comparators with switched capacitor based comparison of input signal and reference voltage. Each module of the ADC comprises two 2.5-bit stages followed by two 1.5-bit stages and a 3-bit flash stage. Four such pipeline ADC modules are time interleaved using two pairs of non-overlapping clock signals. These two pairs of clock signals are in phase quadrature with each other. Hence the term quadrature parallel pipeline ADC has been used. These configurations ensure that the entire ADC contains only eight operational-trans-conductance amplifiers. The ADC is implemented in a 0.18-μm CMOS process and supply voltage of 1.8 V. The proto-type is tested at sampling frequencies of 50 and 75 MSPS producing an Effective Number of Bits (ENOB) of 6.86- and 6.11-bits respectively. At peak sampling speed, the core ADC consumes only 65 mW of power.
A 9-Bit 50 MSPS Quadrature Parallel Pipeline ADC for Communication Receiver Application

NASA Astrophysics Data System (ADS)

Roy, Sounak; Banerjee, Swapna

2018-06-01

This paper presents the design and implementation of a pipeline Analog-to-Digital Converter (ADC) for superheterodyne receiver application. Several enhancement techniques have been applied in implementing the ADC, in order to relax the target specifications of its building blocks. The concepts of time interleaving and double sampling have been used simultaneously to enhance the sampling speed and to reduce the number of amplifiers used in the ADC. Removal of a front end sample-and-hold amplifier is possible by employing dynamic comparators with switched capacitor based comparison of input signal and reference voltage. Each module of the ADC comprises two 2.5-bit stages followed by two 1.5-bit stages and a 3-bit flash stage. Four such pipeline ADC modules are time interleaved using two pairs of non-overlapping clock signals. These two pairs of clock signals are in phase quadrature with each other. Hence the term quadrature parallel pipeline ADC has been used. These configurations ensure that the entire ADC contains only eight operational-trans-conductance amplifiers. The ADC is implemented in a 0.18-μm CMOS process and supply voltage of 1.8 V. The proto-type is tested at sampling frequencies of 50 and 75 MSPS producing an Effective Number of Bits (ENOB) of 6.86- and 6.11-bits respectively. At peak sampling speed, the core ADC consumes only 65 mW of power.
Evolution of subterranean diving beetles (Coleoptera: Dytiscidae: Hydroporini, Bidessini) in the arid zone of Australia.

PubMed

Leys, Remko; Watts, Chris H S; Cooper, Steve J B; Humphreys, William F

2003-12-01

Calcrete aquifers in arid inland Australia have recently been found to contain the world's most diverse assemblage of subterranean diving beetles (Coleoptera: Dytiscidae). In this study we test whether the adaptive shift hypothesis (ASH) or the climatic relict hypothesis (CRH) is the most likely mode of evolution for the Australian subterranean diving beetles by using a phylogeny based on two sequenced fragments of mitochondrial genes (CO1 and 16S-tRNA-ND1) and linearized using a relaxed molecular clock method. Most individual calcrete aquifers contain an assemblage of diving beetle species of distantly related lineages and/or a single pair of sister species that significantly differ in size and morphology. Evolutionary transitions from surface to subterranean life took place in a relatively small time frame between nine and four million years ago. Most of the variation in divergence times of the sympatric sister species is explained by the variation in latitude of the localities, which correlates with the onset of aridity from the north to the south and with an aridity maximum in the Early Pliocene (five mya). We conclude that individual calcrete aquifers were colonized by several distantly related diving beetle lineages. Several lines of evidence from molecular clock analyses support the CRH, indicating that all evolutionary transitions took place during the Late Miocene and Early Pliocene as a result of aridification.
Anatomy of the anterior cruciate ligament with regard to its two bundles.

PubMed

Petersen, Wolf; Zantop, Thore

2007-01-01

The anterior cruciate ligament (ACL) consists of two major fiber bundles, namely the anteromedial and posterolateral bundle. When the knee is extended, the posterolateral bundle (PL) is tight and the anteromedial (AM) bundle is moderately lax. As the knee is flexed, the femoral attachment of the ACL becomes a more horizontal orientation; causing the AM bundle to tighten and the PL bundle to relax. There is some degree of variability for the femoral origin of the anterome-dial and posterolateral bundle. The anteromedial bundle is located proximal and anterior in the femoral ACL origin (high and deep in the notch when the knee is flexed at 90 degrees ); the posterolateral bundle starts in the distal and posterior aspect of the femoral ACL origin (shallow and low when the knee is flexed at 90 degrees ). In the frontal plane the anteromedial bundle origin is in the 10:30 clock position and the postero-lateral bundle origin in the 9:30 clock position. At the tibial insertion the ACL fans out to form the foot region. The anteromedial bundle insertion is in the anterior part of the tibial ACL footprint, the posterolateral bundle in the posterior part. While the anteromedial bundle is the primary restraint against anterior tibial translation, the posterolateral bundle tends to stabilize the knee near full extension, particularly against rotatory loads.
Circadian rhythmicity of active GSK3 isoforms modulates molecular clock gene rhythms in the suprachiasmatic nucleus.

PubMed

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).
The Circadian Oscillator of the Cerebral Cortex: Molecular, Biochemical and Behavioral Effects of Deleting the Arntl Clock Gene in Cortical Neurons.

PubMed

Bering, Tenna; Carstensen, Mikkel Bloss; Wörtwein, Gitta; Weikop, Pia; Rath, Martin Fredensborg

2018-02-01

A molecular circadian oscillator resides in neurons of the cerebral cortex, but its role is unknown. Using the Cre-LoxP method, we have here abolished the core clock gene Arntl in those neurons. This mouse represents the first model carrying a deletion of a circadian clock component specifically in an extrahypothalamic cell type of the brain. Molecular analyses of clock gene expression in the cerebral cortex of the Arntl conditional knockout mouse revealed disrupted circadian expression profiles, whereas clock gene expression in the suprachiasmatic nucleus was still rhythmic, thus showing that Arntl is required 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. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Critical role for CCA1 and LHY in maintaining circadian rhythmicity in Arabidopsis.

PubMed

Alabadí, David; Yanovsky, Marcelo J; Más, Paloma; Harmer, Stacey L; Kay, Steve A

2002-04-30

Circadian clocks are autoregulatory, endogenous mechanisms that allow organisms, from bacteria to humans, to advantageously time a wide range of activities within 24-hr environmental cycles. CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) are thought to be important components of the circadian clock in the model plant Arabidopsis. The similar circadian phenotypes of lines overexpressing either CCA1 or LHY have suggested that the functions of these two transcription factors are largely overlapping. cca1-1 plants, which lack CCA1 protein, show a short-period phenotype for the expression of several genes when assayed under constant light conditions. This suggests that LHY function is able to only partially compensate for the lack of CCA1 protein, resulting in a clock with a faster pace in cca1-1 plants. We have obtained plants lacking CCA1 and with LHY function strongly reduced, cca1-1 lhy-R, and show that these plants are unable to maintain sustained oscillations in both constant light and constant darkness. However, these plants exhibit some circadian function in light/dark cycles, showing that the Arabidopsis circadian clock is not entirely dependent on CCA1 and LHY activities.
An Autonomous Satellite Time Synchronization System Using Remotely Disciplined VC-OCXOs

PubMed Central

Gu, Xiaobo; Chang, Qing; Glennon, Eamonn P.; Xu, Baoda; Dempseter, Andrew G.; Wang, Dun; Wu, Jiapeng

2015-01-01

An autonomous remote clock control system is proposed to provide time synchronization and frequency syntonization for satellite to satellite or ground to satellite time transfer, with the system comprising on-board voltage controlled oven controlled crystal oscillators (VC-OCXOs) that are disciplined to a remote master atomic clock or oscillator. The synchronization loop aims to provide autonomous operation over extended periods, be widely applicable to a variety of scenarios and robust. A new architecture comprising the use of frequency division duplex (FDD), synchronous time division (STDD) duplex and code division multiple access (CDMA) with a centralized topology is employed. This new design utilizes dual one-way ranging methods to precisely measure the clock error, adopts least square (LS) methods to predict the clock error and employs a third-order phase lock loop (PLL) to generate the voltage control signal. A general functional model for this system is proposed and the error sources and delays that affect the time synchronization are discussed. Related algorithms for estimating and correcting these errors are also proposed. The performance of the proposed system is simulated and guidance for selecting the clock is provided. PMID:26213929
Altered Stra13 and Dec2 circadian gene expression in hypoxic cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guillaumond, Fabienne; Lacoche, Samuel; Dulong, Sandrine

2008-05-16

The circadian system regulates rhythmically most of the mammalian physiology in synchrony with the environmental light/dark cycle. Alteration of circadian clock gene expression has been associated with tumour progression but the molecular links between the two mechanisms remain poorly defined. Here we show that Stra13 and Dec2, two circadian transcriptional regulators which play a crucial role in cell proliferation and apoptosis are overexpressed and no longer rhythmic in serum shocked fibroblasts treated with CoCl{sub 2,} a substitute of hypoxia. This effect is associated with a loss of circadian expression of the clock genes Rev-erb{alpha} and Bmal1, and the clock-controlled genemore » Dbp. Consistently, cotransfection assays demonstrate that STRA13 and DEC2 both antagonize CLOCK:BMAL1 dependent transactivation of the Rev-erb{alpha} and Dbp promoters. Using a transplantable osteosarcoma tumour model, we show that hypoxia is associated with altered circadian expression of Stra13, Dec2, Rev-erb{alpha}, Bmal1 and Dbp in vivo. These observations collectively support the notion that overexpression of Stra13 and Dec2 links hypoxia signalling to altered circadian clock gene expression.« less
Reconfigurable radio receiver with fractional sample rate converter and multi-rate ADC based on LO-derived sampling clock

NASA Astrophysics Data System (ADS)

Park, Sungkyung; Park, Chester Sungchung

2018-03-01

A composite radio receiver back-end and digital front-end, made up of a delta-sigma analogue-to-digital converter (ADC) with a high-speed low-noise sampling clock generator, and a fractional sample rate converter (FSRC), is proposed and designed for a multi-mode reconfigurable radio. The proposed radio receiver architecture contributes to saving the chip area and thus lowering the design cost. To enable inter-radio access technology handover and ultimately software-defined radio reception, a reconfigurable radio receiver consisting of a multi-rate ADC with its sampling clock derived from a local oscillator, followed by a rate-adjustable FSRC for decimation, is designed. Clock phase noise and timing jitter are examined to support the effectiveness of the proposed radio receiver. A FSRC is modelled and simulated with a cubic polynomial interpolator based on Lagrange method, and its spectral-domain view is examined in order to verify its effect on aliasing, nonlinearity and signal-to-noise ratio, giving insight into the design of the decimation chain. The sampling clock path and the radio receiver back-end data path are designed in a 90-nm CMOS process technology with 1.2V supply.
Common features in diverse insect clocks.

PubMed

Numata, Hideharu; Miyazaki, Yosuke; Ikeno, Tomoko

2015-01-01

This review describes common features among diverse biological clocks in insects, including circadian, circatidal, circalunar/circasemilunar, and circannual clocks. These clocks control various behaviors, physiological functions, and developmental events, enabling adaptation to periodic environmental changes. Circadian clocks also function in time-compensation for celestial navigation and in the measurement of day or night length for photoperiodism. Phase response curves for such clocks reported thus far exhibit close similarities; specifically, the circannual clock in Anthrenus verbasci shows striking similarity to circadian clocks in its phase response. It is suggested that diverse biological clocks share physiological properties in their phase responses irrespective of period length. Molecular and physiological mechanisms are best understood for the optic-lobe and mid-brain circadian clocks, although there is no direct evidence that these clocks are involved in rhythmic phenomena other than circadian rhythms in daily events. Circadian clocks have also been localized in peripheral tissues, and research on their role in various rhythmic phenomena has been started. Although clock genes have been identified as controllers of circadian rhythms in daily events, some of these genes have also been shown to be involved in photoperiodism and possibly in time-compensated celestial navigation. In contrast, there is no experimental evidence indicating that any known clock gene is involved in biological clocks other than circadian clocks.
Flying with the birds? Recent large-area dispersal of four Australian Limnadopsis species (Crustacea: Branchiopoda: Spinicaudata)

PubMed Central

Schwentner, Martin; Timms, Brian V; Richter, Stefan

2012-01-01

Temporary water bodies are important freshwater habitats in the arid zone of Australia. They harbor a distinct fauna and provide important feeding and breeding grounds for water birds. This paper assesses, on the basis of haplotype networks, analyses of molecular variation and relaxed molecular clock divergence time estimates, the phylogeographic history, and population structure of four common temporary water species of the Australian endemic clam shrimp taxon Limnadopsis in eastern and central Australia (an area of >1,350,000 km2). Mitochondrial cytochrome c oxidase subunit I sequences of 413 individuals and a subset of 63 nuclear internal transcribed spacer 2 sequences were analyzed. Genetic differentiation was observed between populations inhabiting southeastern and central Australia and those inhabiting the northern Lake Eyre Basin and Western Australia. However, over large parts of the study area and across river drainage systems in southeastern and central Australia (the Murray–Darling Basin, Bulloo River, and southern Lake Eyre Basin), no evidence of population subdivision was observed in any of the four Limnadopsis species. This indicates recent gene flow across an area of ∼800,000 km2. This finding contrasts with patterns observed in other Australian arid zone taxa, particularly freshwater species, whose populations are often structured according to drainage systems. The lack of genetic differentiation within the area in question may be linked to the huge number of highly nomadic water birds that potentially disperse the resting eggs of Limnadopsis among temporary water bodies. Genetically undifferentiated populations on a large geographic scale contrast starkly with findings for many other large branchiopods in other parts of the world, where pronounced genetic structure is often observed even in populations inhabiting pools separated by a few kilometers. Due to its divergent genetic lineages (up to 5.6% uncorrected p-distance) and the relaxed molecular clock divergence time estimates obtained, Limnadopsis parvispinus is assumed to have inhabited the Murray–Darling Basin continuously since the mid-Pliocene (∼4 million years ago). This means that suitable temporary water bodies would have existed in this area throughout the wet–dry cycles of the Pleistocene. PMID:22957166
Formal Uncertainty and Dispersion of Single and Double Difference Models for GNSS-Based Attitude Determination.

PubMed

Chen, Wen; Yu, Chao; Dong, Danan; Cai, Miaomiao; Zhou, Feng; Wang, Zhiren; Zhang, Lei; Zheng, Zhengqi

2017-02-20

With multi-antenna synchronized global navigation satellite system (GNSS) receivers, the single difference (SD) between two antennas is able to eliminate both satellite and receiver clock error, thus it becomes necessary to reconsider the equivalency problem between the SD and double difference (DD) models. In this paper, we quantitatively compared the formal uncertainties and dispersions between multiple SD models and the DD model, and also carried out static and kinematic short baseline experiments. The theoretical and experimental results show that under a non-common clock scheme the SD and DD model are equivalent. Under a common clock scheme, if we estimate stochastic uncalibrated phase delay (UPD) parameters every epoch, this SD model is still equivalent to the DD model, but if we estimate only one UPD parameter for all epochs or take it as a known constant, the SD (here called SD2) and DD models are no longer equivalent. For the vertical component of baseline solutions, the formal uncertainties of the SD2 model are two times smaller than those of the DD model, and the dispersions of the SD2 model are even more than twice smaller than those of the DD model. In addition, to obtain baseline solutions, the SD2 model requires a minimum of three satellites, while the DD model requires a minimum of four satellites, which makes the SD2 more advantageous in attitude determination under sheltered environments.
Formal Uncertainty and Dispersion of Single and Double Difference Models for GNSS-Based Attitude Determination

PubMed Central

Chen, Wen; Yu, Chao; Dong, Danan; Cai, Miaomiao; Zhou, Feng; Wang, Zhiren; Zhang, Lei; Zheng, Zhengqi

2017-01-01

With multi-antenna synchronized global navigation satellite system (GNSS) receivers, the single difference (SD) between two antennas is able to eliminate both satellite and receiver clock error, thus it becomes necessary to reconsider the equivalency problem between the SD and double difference (DD) models. In this paper, we quantitatively compared the formal uncertainties and dispersions between multiple SD models and the DD model, and also carried out static and kinematic short baseline experiments. The theoretical and experimental results show that under a non-common clock scheme the SD and DD model are equivalent. Under a common clock scheme, if we estimate stochastic uncalibrated phase delay (UPD) parameters every epoch, this SD model is still equivalent to the DD model, but if we estimate only one UPD parameter for all epochs or take it as a known constant, the SD (here called SD2) and DD models are no longer equivalent. For the vertical component of baseline solutions, the formal uncertainties of the SD2 model are two times smaller than those of the DD model, and the dispersions of the SD2 model are even more than twice smaller than those of the DD model. In addition, to obtain baseline solutions, the SD2 model requires a minimum of three satellites, while the DD model requires a minimum of four satellites, which makes the SD2 more advantageous in attitude determination under sheltered environments. PMID:28230753
Modeling and Predicting the Stress Relaxation of Composites with Short and Randomly Oriented Fibers

PubMed Central

Obaid, Numaira; Sain, Mohini

2017-01-01

The addition of short fibers has been experimentally observed to slow the stress relaxation of viscoelastic polymers, producing a change in the relaxation time constant. Our recent study attributed this effect of fibers on stress relaxation behavior to the interfacial shear stress transfer at the fiber-matrix interface. This model explained the effect of fiber addition on stress relaxation without the need to postulate structural changes at the interface. In our previous study, we developed an analytical model for the effect of fully aligned short fibers, and the model predictions were successfully compared to finite element simulations. However, in most industrial applications of short-fiber composites, fibers are not aligned, and hence it is necessary to examine the time dependence of viscoelastic polymers containing randomly oriented short fibers. In this study, we propose an analytical model to predict the stress relaxation behavior of short-fiber composites where the fibers are randomly oriented. The model predictions were compared to results obtained from Monte Carlo finite element simulations, and good agreement between the two was observed. The analytical model provides an excellent tool to accurately predict the stress relaxation behavior of randomly oriented short-fiber composites. PMID:29053601
Global synchronization of parallel processors using clock pulse width modulation

DOEpatents

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.
The kinetic activation-relaxation technique: an off-lattice, self-learning kinetic Monte Carlo algorithm with on-the-fly event search

NASA Astrophysics Data System (ADS)

Mousseau, Nomand

2012-02-01

While kinetic Monte Carlo algorithm has been proposed almost 40 years ago, its application in materials science has been mostly limited to lattice-based motion due to the difficulties associated with identifying new events and building usable catalogs when atoms moved into off-lattice position. Here, I present the kinetic activation-relaxation technique (kinetic ART) is an off-lattice, self-learning kinetic Monte Carlo algorithm with on-the-fly event search [1]. It combines ART nouveau [2], a very efficient unbiased open-ended activated method for finding transition states, with a topological classification [3] that allows a discrete cataloguing of local environments in complex systems, including disordered materials. In kinetic ART, local topologies are first identified for all atoms in a system. ART nouveau event searches are then launched for new topologies, building an extensive catalog of barriers and events. Next, all low energy events are fully reconstructed and relaxed, allowing to take complete account of elastic effects in the system's kinetics. Using standard kinetic Monte Carlo, the clock is brought forward and an event is then selected and applied before a new search for topologies is launched. In addition to presenting the various elements of the algorithm, I will discuss three recent applications to ion-bombarded silicon, defect diffusion in Fe and structural relaxation in amorphous silicon.[4pt] This work was done in collaboration with Laurent Karim B'eland, Peter Brommer, Fedwa El-Mellouhi, Jean-Francois Joly and Laurent Lewis.[4pt] [1] F. El-Mellouhi, N. Mousseau and L.J. Lewis, Phys. Rev. B. 78, 153202 (2008); L.K. B'eland et al., Phys. Rev. E 84, 046704 (2011).[2] G.T. Barkema and N. Mousseau, Phys. Rev. Lett. 77, 4358 (1996); E. Machado-Charry et al., J. Chem Phys. 135, 034102, (2011).[3] B.D. McKay, Congressus Numerantium 30, 45 (1981).
Model of an Injection Semiconductor Quantum-Dot Laser

NASA Astrophysics Data System (ADS)

Koryukin, I. V.

2018-05-01

We propose an asymmetric electron-hole model of an injection semiconductor quantum-dot laser, which correctly allows for relaxation at transitions between the electron and hole levels. Steady-state solutions of the proposed model, conditions for the simultaneous operation at transitions between the ground and first excited state levels, and relaxation oscillations in the two-wave lasing regime are studied. It is shown that the model can be simplified when the relaxation between hole levels is much faster than the relaxation between electron levels.
Solution of non-continuum flows using BGK-type model with enforced relaxation of moments

NASA Astrophysics Data System (ADS)

Alekseenko, Alexander; Gimelshein, Sergey; Nguyen, Truong; Vedula, Prakash

2016-11-01

A BGK-type model with velocity dependent collision frequency and enforced relaxation rates for selected moments is applied to simulation of one- and two-dimensional super sonic flows. Relaxation rates of the moments are estimated by evaluating the full Boltzmann collision integral several times during the simulation. The solutions show improvements in velocity and temperature profiles as compared to the classical ES-BGK model. However, enforcement of relaxation rates for high order moments increases stiffness of the model.
A periodic DFT study of ammonia adsorption on the V2O5 (001), V2O5 (010) and V2O5 (100) surfaces: Lewis versus Brönsted acid sites

NASA Astrophysics Data System (ADS)

Yao, Huichao; Chen, Yu; Wei, Yuechang; Zhao, Zhen; Liu, Zhichang; Xu, Chunming

2012-11-01

The adsorption of ammonia at Brönsted and Lewis acid sites on three low-index (001), (010) and (100) surfaces of V2O5 catalyst was investigated using density functional theory (DFT) method. Three levels of surface relaxation periodic models including top single layer relaxation (S-model), moderately deeper relaxation (M-model) and full relaxation model (F-model) were applied to examine the effect of the surface relaxation on the binding structures and adsorption energies. The results of calculations showed that on the saturated basal plane V2O5 (001), ammonia adsorption at the Brönsted acid sites (VOH) is energetically more favorable. On unsaturated (010) and (100) surfaces, ammonia is adsorbed strongly on both Brönsted (VOH) and Lewis acid sites (V). Surface relaxations have no influence on ammonia adsorption on saturated (001) surface, while a strong dependence on the relaxation models is observed for NH3-adsorption energies on (010) and (100) surfaces, especially at the Lewis acid sites of both side planes. When complete relaxation considered (F-model), ammonia adsorption on the Lewis acid sites (V) dominates for side planes (010) and (100). In the presence of VOH as neighbor, the ammonia adsorption at V sites is however weakened significantly due to steric hindrance. Hydrogen bonds may play a role, although not determining one, in the respect of the adsorption of ammonia on (010) and (100) surfaces. Moderate relaxation and full relaxation are absolutely necessary for the description of both H and NH3 adsorption on unsaturated (100) and (010) surfaces, respectively.

Central and peripheral clocks are coupled by a neuropeptide pathway in Drosophila

PubMed Central

Selcho, Mareike; Millán, Carola; Palacios-Muñoz, Angelina; Ruf, Franziska; Ubillo, Lilian; Chen, Jiangtian; Bergmann, Gregor; Ito, Chihiro; Silva, Valeria; Wegener, Christian; Ewer, John

2017-01-01

Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour. Despite its importance for optimal performance and health, the mechanism of clock coordination is poorly understood. Here we dissect the pathway through which the circadian clock of Drosophila imposes daily rhythmicity to the pattern of adult emergence. Rhythmicity depends on the coupling between the brain clock and a peripheral clock in the prothoracic gland (PG), which produces the steroid hormone, ecdysone. Time information from the central clock is transmitted via the neuropeptide, sNPF, to non-clock neurons that produce the neuropeptide, PTTH. These secretory neurons then forward time information to the PG clock. We also show that the central clock exerts a dominant role on the peripheral clock. This use of two coupled clocks could serve as a paradigm to understand how daily steroid hormone rhythms are generated in animals. PMID:28555616
The Drosophila Clock Neuron Network Features Diverse Coupling Modes and Requires Network-wide Coherence for Robust Circadian Rhythms.

PubMed

Yao, Zepeng; Bennett, Amelia J; Clem, Jenna L; Shafer, Orie T

2016-12-13

In animals, networks of clock neurons containing molecular clocks orchestrate daily rhythms in physiology and behavior. However, how various types of clock neurons communicate and coordinate with one another to produce coherent circadian rhythms is not well understood. Here, we investigate clock neuron coupling in the brain of Drosophila and demonstrate that the fly's various groups of clock neurons display unique and complex coupling relationships to core pacemaker neurons. Furthermore, we find that coordinated free-running rhythms require molecular clock synchrony not only within the well-characterized lateral clock neuron classes but also between lateral clock neurons and dorsal clock neurons. These results uncover unexpected patterns of coupling in the clock neuron network and reveal that robust free-running behavioral rhythms require a coherence of molecular oscillations across most of the fly's clock neuron network. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Genomic evidence reveals a radiation of placental mammals uninterrupted by the KPg boundary

PubMed Central

Liu, Liang; Zhang, Jin; Rheindt, Frank E.; Lei, Fumin; Qu, Yanhua; Wang, Yu; Zhang, Yu; Sullivan, Corwin; Nie, Wenhui; Wang, Jinhuan; Yang, Fengtang; Chen, Jinping; Edwards, Scott V.; Meng, Jin; Wu, Shaoyuan

2017-01-01

The timing of the diversification of placental mammals relative to the Cretaceous–Paleogene (KPg) boundary mass extinction remains highly controversial. In particular, there have been seemingly irreconcilable differences in the dating of the early placental radiation not only between fossil-based and molecular datasets but also among molecular datasets. To help resolve this discrepancy, we performed genome-scale analyses using 4,388 loci from 90 taxa, including representatives of all extant placental orders and transcriptome data from flying lemurs (Dermoptera) and pangolins (Pholidota). Depending on the gene partitioning scheme, molecular clock model, and genic deviation from molecular clock assumptions, extensive sensitivity analyses recovered widely varying diversification scenarios for placental mammals from a given gene set, ranging from a deep Cretaceous origin and diversification to a scenario spanning the KPg boundary, suggesting that the use of suboptimal molecular clock markers and methodologies is a major cause of controversies regarding placental diversification timing. We demonstrate that reconciliation between molecular and paleontological estimates of placental divergence times can be achieved using the appropriate clock model and gene partitioning scheme while accounting for the degree to which individual genes violate molecular clock assumptions. A birth-death-shift analysis suggests that placental mammals underwent a continuous radiation across the KPg boundary without apparent interruption by the mass extinction, paralleling a genus-level radiation of multituberculates and ecomorphological diversification of both multituberculates and therians. These findings suggest that the KPg catastrophe evidently played a limited role in placental diversification, which, instead, was likely a delayed response to the slightly earlier radiation of angiosperms. PMID:28808022
Genomic evidence reveals a radiation of placental mammals uninterrupted by the KPg boundary.

PubMed

Liu, Liang; Zhang, Jin; Rheindt, Frank E; Lei, Fumin; Qu, Yanhua; Wang, Yu; Zhang, Yu; Sullivan, Corwin; Nie, Wenhui; Wang, Jinhuan; Yang, Fengtang; Chen, Jinping; Edwards, Scott V; Meng, Jin; Wu, Shaoyuan

2017-08-29

The timing of the diversification of placental mammals relative to the Cretaceous-Paleogene (KPg) boundary mass extinction remains highly controversial. In particular, there have been seemingly irreconcilable differences in the dating of the early placental radiation not only between fossil-based and molecular datasets but also among molecular datasets. To help resolve this discrepancy, we performed genome-scale analyses using 4,388 loci from 90 taxa, including representatives of all extant placental orders and transcriptome data from flying lemurs (Dermoptera) and pangolins (Pholidota). Depending on the gene partitioning scheme, molecular clock model, and genic deviation from molecular clock assumptions, extensive sensitivity analyses recovered widely varying diversification scenarios for placental mammals from a given gene set, ranging from a deep Cretaceous origin and diversification to a scenario spanning the KPg boundary, suggesting that the use of suboptimal molecular clock markers and methodologies is a major cause of controversies regarding placental diversification timing. We demonstrate that reconciliation between molecular and paleontological estimates of placental divergence times can be achieved using the appropriate clock model and gene partitioning scheme while accounting for the degree to which individual genes violate molecular clock assumptions. A birth-death-shift analysis suggests that placental mammals underwent a continuous radiation across the KPg boundary without apparent interruption by the mass extinction, paralleling a genus-level radiation of multituberculates and ecomorphological diversification of both multituberculates and therians. These findings suggest that the KPg catastrophe evidently played a limited role in placental diversification, which, instead, was likely a delayed response to the slightly earlier radiation of angiosperms.
USNO Master Clock - Naval Oceanography Portal

Science.gov Websites

section Advanced Search... Sections Home Time Earth Orientation Astronomy Meteorology Oceanography Ice You are here: Home âº USNO âº Precise Time âº Master Clock USNO Logo USNO Navigation Master Clock GPS Display Clocks TWSTT Telephone Time NTP Info USNO Master Clock clock vault The USNO Master Clock is the
Drosophila: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse

PubMed Central

De Nobrega, Aliza K.

2017-01-01

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. PMID:29391952
A Study on the Operation Mechanism of Ongnu, the Astronomical Clock in Sejong Era

NASA Astrophysics Data System (ADS)

Kim, Sang Hyuk; Lee, Yong Sam; Lee, Min Soo

2011-03-01

Ongnu (Jade Clepsydra; also called Heumgyeonggaknu) is a water clock was made by Jang Yeong-sil in 1438. It is not only an automatic water clock that makes the sound at every hour on the hour by striking bell, drum and gong, but also an astronomical clock that shows the sun's movement over time. Ongnu's power mechanism used is a water-hammering method applied to automatic time-signal device. The appearance of Ongnu is modeled by Gasan (pasted-paper imitation mountain) and Binpungdo (landscape of farming work scene) is drawn at the foot of the mountain. The structure of Ongnu is divided into the top of the mountain, the foot of the mountain and the flatland. There located are sunmovement device, Ongnyeo (jade female immortal; I) and Four gods (shaped of animal-like immortals) at the top of the mountain, Sasin (jack hour) and Musa (warrior) at the foot of the mountain, and Twelve gods, Ongnyeo (II) and Gwanin on the flatland. In this study, we clearly and systematically understood the time-announcing mechanism of each puppet.Also, we showed the working mechanism of the sun-movement device. Finally, we completely established the 3D model of Ongnu based on this study.
Distinguishing Between Convergent Evolution and Violation of the Molecular Clock for Three Taxa.

PubMed

Mitchell, Jonathan D; Sumner, Jeremy G; Holland, Barbara R

2018-05-18

We give a non-technical introduction to convergence-divergence models, a new modeling approach for phylogenetic data that allows for the usual divergence of lineages after lineage-splitting but also allows for taxa to converge, i.e. become more similar over time. By examining the 3-taxon case in some detail we illustrate that phylogeneticists have been "spoiled" in the sense of not having to think about the structural parameters in their models by virtue of the strong assumption that evolution is tree-like. We show that there are not always good statistical reasons to prefer the usual class of tree-like models over more general convergence-divergence models. Specifically we show many 3-taxon data sets can be equally well explained by supposing violation of the molecular clock due to change in the rate of evolution along different edges, or by keeping the assumption of a constant rate of evolution but instead assuming that evolution is not a purely divergent process. Given the abundance of evidence that evolution is not strictly tree-like, our discussion is an illustration that as phylogeneticists we need to think clearly about the structural form of the models we use. For cases with four taxa we show that there will be far greater ability to distinguish models with convergence from non-clock-like tree models.
Alterations of Clock Gene RNA Expression in Brain Regions of a Triple Transgenic Model of Alzheimer’s Disease

PubMed Central

Bellanti, Francesco; Iannelli, Giuseppina; Blonda, Maria; Tamborra, Rosanna; Villani, Rosanna; Romano, Adele; Calcagnini, Silvio; Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Gaetani, Silvana; Giudetti, Anna Maria; Vendemiale, Gianluigi; Cassano, Tommaso; Serviddio, Gaetano

2017-01-01

A disruption to circadian rhythmicity and the sleep/wake cycle constitutes a major feature of Alzheimer’s disease (AD). The maintenance of circadian rhythmicity is regulated by endogenous clock genes and a number of external Zeitgebers, including light. This study investigated the light induced changes in the expression of clock genes in a triple transgenic model of AD (3×Tg-AD) and their wild type littermates (Non-Tg). Changes in gene expression were evaluated in four brain areas¾suprachiasmatic nucleus (SCN), hippocampus, frontal cortex and brainstem¾of 6- and 18-month-old Non-Tg and 3×Tg-AD mice after 12 h exposure to light or darkness. Light exposure exerted significant effects on clock gene expression in the SCN, the site of the major circadian pacemaker. These patterns of expression were disrupted in 3×Tg-AD and in 18-month-old compared with 6-month-old Non-Tg mice. In other brain areas, age rather than genotype affected gene expression; the effect of genotype was observed on hippocampal Sirt1 expression, while it modified the expression of genes regulating the negative feedback loop as well as Rorα, Csnk1ɛ and Sirt1 in the brainstem. In conclusion, during the early development of AD, there is a disruption to the normal expression of genes regulating circadian function after exposure to light, particularly in the SCN but also in extra-hypothalamic brain areas supporting circadian regulation, suggesting a severe impairment of functioning of the clock gene pathway. Even though this study did not demonstrate a direct association between these alterations in clock gene expression among brain areas with the cognitive impairments and chrono-disruption that characterize the early onset of AD, our novel results encourage further investigation aimed at testing this hypothesis. PMID:28671110
A transportable optical clock for chronometric levelling

NASA Astrophysics Data System (ADS)

Lisdat, C.; Koller, S. B.; Grotti, J.; Vogt, S.; Al-Masoudi, A.; Dörscher, S.; Herbers, S.; Häfner, S.; Sterr, U.

2016-12-01

With their supreme accuracy and precision, optical clocks in combination with new methods of long-distance frequency transfer can be used to determine height differences by measuring the gravitational red shift between two clocks without accumulation of measurement errors, as in classical levelling. We are developing transportable optical clocks for this purpose that will also serve for the technology development regarding optical clocks in Space and for international comparisons between optical clocks that cannot be linked with sufficient accuracy otherwise.In this talk we will focus on the transportable strontium lattice clock that we are developing and its first evaluation. Presently, we achieve a fractional frequency instability of 3×10-17 after 1000 s averaging time, which is equivalent to a height resolution of 30 cm. The first uncertainty evaluation of the system yielded 7×10-17. We expect rapid improvements to an uncertainty of a few parts in 1017.The clock then placed within a car trailer, which requires compact and rugged lasers systems and physics package. Special care has been taken in the design of the ultra-frequency stable interrogation laser that has to achieve fractional frequency instabilities of considerably below 10-15. Typical laboratory constructions of the reference resonator system used to pre-stabilize the laser frequency are not compatible with the requirement of transportability.In an actual levelling campaign, this clock will be connected e.g. via a stabilized optical fibre link with another, stationary frequency standard. The measured gravitational red shift can be compared to the ones calculated from potential differences derived with state of the art geodetic data and models. A first campaign has been completed in cooperation with colleagues from the Italian and UK metrology institutes INRIM and NPL, respectively, and the Institut für Erdmessung (IfE), Leibniz University Hannover. We will discuss the status of the evaluation and give an outlook on our next steps.This work is supported by QUEST, DFG (CRC 1128, 1227), EU-FP7 (FACT) and EMRP (ITOC). The EMRP is jointly funded by the EMRP participating countries within EURAMET and the European Union.
Testing general relativity and alternative theories of gravity with space-based atomic clocks and atom interferometers

NASA Astrophysics Data System (ADS)

Bondarescu, Ruxandra; Schärer, Andreas; Jetzer, Philippe; Angélil, Raymond; Saha, Prasenjit; Lundgren, Andrew

2015-05-01

The successful miniaturisation of extremely accurate atomic clocks and atom interferometers invites prospects for satellite missions to perform precision experiments. We discuss the effects predicted by general relativity and alternative theories of gravity that can be detected by a clock, which orbits the Earth. Our experiment relies on the precise tracking of the spacecraft using its observed tick-rate. The spacecraft's reconstructed four-dimensional trajectory will reveal the nature of gravitational perturbations in Earth's gravitational field, potentially differentiating between different theories of gravity. This mission can measure multiple relativistic effects all during the course of a single experiment, and constrain the Parametrized Post-Newtonian Parameters around the Earth. A satellite carrying a clock of fractional timing inaccuracy of Δ f / f ˜ 10-16 in an elliptic orbit around the Earth would constrain the PPN parameters |β - 1|, |γ - 1| ≲ 10-6. We also briefly review potential constraints by atom interferometers on scalar tensor theories and in particular on Chameleon and dilaton models.
Robust and tunable circadian rhythms from differentially sensitive catalytic domains

PubMed Central

Phong, Connie; Markson, Joseph S.; Wilhoite, Crystal M.; Rust, Michael J.

2013-01-01

Circadian clocks are ubiquitous biological oscillators that coordinate an organism’s behavior with the daily cycling of the external environment. To ensure synchronization with the environment, the period of the clock must be maintained near 24 h even as amplitude and phase are altered by input signaling. We show that, in a reconstituted circadian system from cyanobacteria, these conflicting requirements are satisfied by distinct functions for two domains of the central clock protein KaiC: the C-terminal autokinase domain integrates input signals through the ATP/ADP ratio, and the slow N-terminal ATPase acts as an input-independent timer. We find that phosphorylation in the C-terminal domain followed by an ATPase cycle in the N-terminal domain is required to form the inhibitory KaiB•KaiC complexes that drive the dynamics of the clock. We present a mathematical model in which this ATPase-mediated delay in negative feedback gives rise to a compensatory mechanism that allows a tunable phase and amplitude while ensuring a robust circadian period. PMID:23277568
A Self-Stabilizing Distributed Clock Synchronization Protocol for Arbitrary Digraphs

NASA Technical Reports Server (NTRS)

Malekpour, Mahyar R.

2011-01-01

This report presents a self-stabilizing distributed clock synchronization protocol in the absence of faults in the system. It is focused on the distributed clock synchronization of an arbitrary, non-partitioned digraph ranging from fully connected to 1-connected networks of nodes while allowing for differences in the network elements. This protocol does not rely on assumptions about the initial state of the system, other than the presence of at least one node, and no central clock or a centrally generated signal, pulse, or message is used. Nodes are anonymous, i.e., they do not have unique identities. There is no theoretical limit on the maximum number of participating nodes. The only constraint on the behavior of the node is that the interactions with other nodes are restricted to defined links and interfaces. We present an outline of a deductive proof of the correctness of the protocol. A model of the protocol was mechanically verified using the Symbolic Model Verifier (SMV) for a variety of topologies. Results of the mechanical proof of the correctness of the protocol are provided. The model checking results have verified the correctness of the protocol as they apply to the networks with unidirectional and bidirectional links. In addition, the results confirm the claims of determinism and linear convergence. As a result, we conjecture that the protocol solves the general case of this problem. We also present several variations of the protocol and discuss that this synchronization protocol is indeed an emergent system.
Broadband spectral analysis of non-Debye dielectric relaxation in percolating heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tuncer, Enis; Bellatar, J; Achour, M E

2011-01-01

In this study, the main features of dielectric relaxation in carbon black epoxy composites are discussed using several types of complementary modelling (i.e., the Cole-Cole phenomenological equation, Jonscher s universal dielectric response, and an approach that relies on a continuous distribution of relaxation times). These methods of characterizing the relaxation were conducted below Tg. Through the numerical model we can obtain the characteristic effective relaxation time and exponents straightforwardly. However, the true relaxation spectrum can be obtained from the distribution of relaxation times calculated from the complex dielectric permittivity. Over the compositional range explored, relaxation occurs by a Vogel-Tammam-Fulcher-like temperaturemore » dependence within the limits of experimental accuracy.« less
Identification, Characterization, and Diel Pattern of Expression of Canonical Clock Genes in Nephrops norvegicus (Crustacea: Decapoda) Eyestalk

PubMed Central

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

2015-01-01

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

NASA Astrophysics Data System (ADS)

Salloum, Ahmed

Constraint relaxation by definition means that certain security, operational, or financial constraints are allowed to be violated in the energy market model for a predetermined penalty price. System operators utilize this mechanism in an effort to impose a price-cap on shadow prices throughout the market. In addition, constraint relaxations can serve as corrective approximations that help in reducing the occurrence of infeasible or extreme solutions in the day-ahead markets. This work aims to capture the impact constraint relaxations have on system operational security. Moreover, this analysis also provides a better understanding of the correlation between DC market models and AC real-time systems and analyzes how relaxations in market models propagate to real-time systems. This information can be used not only to assess the criticality of constraint relaxations, but also as a basis for determining penalty prices more accurately. Constraint relaxations practice was replicated in this work using a test case and a real-life large-scale system, while capturing both energy market aspects and AC real-time system performance. System performance investigation included static and dynamic security analysis for base-case and post-contingency operating conditions. PJM peak hour loads were dynamically modeled in order to capture delayed voltage recovery and sustained depressed voltage profiles as a result of reactive power deficiency caused by constraint relaxations. Moreover, impacts of constraint relaxations on operational system security were investigated when risk based penalty prices are used. Transmission lines in the PJM system were categorized according to their risk index and each category was as-signed a different penalty price accordingly in order to avoid real-time overloads on high risk lines. This work also extends the investigation of constraint relaxations to post-contingency relaxations, where emergency limits are allowed to be relaxed in energy market models. Various scenarios were investigated to capture and compare between the impacts of base-case and post-contingency relaxations on real-time system performance, including the presence of both relaxations simultaneously. The effect of penalty prices on the number and magnitude of relaxations was investigated as well.
[Elevated expression of CLOCK is associated with poor prognosis in hepatocellular carcinoma].

PubMed

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.
Joint CPT and N resonance in compact atomic time standards

NASA Astrophysics Data System (ADS)

Crescimanno, Michael; Hohensee, Michael; Xiao, Yanhong; Phillips, David; Walsworth, Ron

2008-05-01

Currently development efforts towards small, low power atomic time standards use current-modulated VCSELs to generate phase-coherent optical sidebands that interrogate the hyperfine structure of alkali atoms such as rubidium. We describe and use a modified four-level quantum optics model to study the optimal operating regime of the joint CPT- and N-resonance clock. Resonant and non-resonant light shifts as well as modulation comb detuning effects play a key role in determining the optimal operating point of such clocks. We further show that our model is in good agreement with experimental tests performed using Rb-87 vapor cells.
Hysteresis prediction inside magnetic shields and application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morić, Igor; CNES, Edouard Belin 18, 31400 Toulouse; De Graeve, Charles-Marie

2014-07-15

We have developed a simple model that is able to describe and predict hysteresis behavior inside Mumetal magnetic shields, when the shields are submitted to ultra-low frequency (<0.01 Hz) magnetic perturbations with amplitudes lower than 60 μT. This predictive model has been implemented in a software to perform an active compensation system. With this compensation the attenuation of longitudinal magnetic fields is increased by two orders of magnitude. The system is now integrated in the cold atom space clock called PHARAO. The clock will fly onboard the International Space Station in the frame of the ACES space mission.
Multi-tissue DNA methylation age predictor in mouse.

PubMed

Stubbs, Thomas M; Bonder, Marc Jan; Stark, Anne-Katrien; Krueger, Felix; von Meyenn, Ferdinand; Stegle, Oliver; Reik, Wolf

2017-04-11

DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. We have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations with age which allowed us to develop a multi-tissue predictor of age in the mouse. Our model, which estimates age based on DNA methylation at 329 unique CpG sites, has a median absolute error of 3.33 weeks and has similar properties to the recently described human epigenetic clock. Using publicly available datasets, we find that the mouse clock is accurate enough to measure effects on biological age, including in the context of interventions. While females and males show no significant differences in predicted DNA methylation age, ovariectomy results in significant age acceleration in females. Furthermore, we identify significant differences in age-acceleration dependent on the lipid content of the diet. Here we identify and characterise an epigenetic predictor of age in mice, the mouse epigenetic clock. This clock will be instrumental for understanding the biology of ageing and will allow modulation of its ticking rate and resetting the clock in vivo to study the impact on biological age.

Relaxation model for extended magnetohydrodynamics: Comparison to magnetohydrodynamics for dense Z-pinches

DOE PAGES

Seyler, C. E.; Martin, M. R.

2011-01-14

In this study, it is shown that the two-fluid model under a generalized Ohm’s law formulation and the resistive magnetohydrodynamics (MHD) can both be described as relaxation systems. In the relaxation model, the under-resolved stiff source terms constrain the dynamics of a set of hyperbolic equations to give the correct asymptotic solution. When applied to the collisional two-fluid model, the relaxation of fast time scales associated with displacement current and finite electron mass allows for a natural transition from a system where Ohm’s law determines the current density to a system where Ohm’s law determines the electric field. This resultmore » is used to derive novel algorithms, which allow for multiscale simulation of low and high frequency extended-MHD physics. This relaxation formulation offers an efficient way to implicitly advance the Hall term and naturally simulate a plasma-vacuum interface without invoking phenomenological models. The relaxation model is implemented as an extended-MHD code, which is used to analyze pulsed power loads such as wire arrays and ablating foils. Two-dimensional simulations of pulsed power loads are compared for extended-MHD and MHD. For these simulations, it is also shown that the relaxation model properly recovers the resistive-MHD limit.« less
Testing relativity with orbiting clocks

NASA Astrophysics Data System (ADS)

Nissen, J. A.; Lipa, J. A.; Wang, S.; Avaloff, D.; Stricker, D. A.

2011-02-01

We describe the background and status of a superconducting microwave clock suitable for relativity experiments in earth orbit. The project has the capability of performing improved tests of Lorentz invariance via a Michelson-Morley type experiment, and setting new limits on nine parameters in the Standard Model Extension. If flown with a high stability atomic clock, a Kennedy-Thorndike experiment along with additional tests in general relativity could be performed.In orbit, unwanted cavity frequency variations are expected to be caused mainly by acceleration effects due to residual drag and vibration, temperature variations, and fluctuations in the energy stored in the cavity. A cavity support system has been designed to reduce acceleration effects and a high resolution thermometer has been implemented to improve temperature control.
A discrete spectral analysis for determining quasi-linear viscoelastic properties of biological materials

PubMed Central

Babaei, Behzad; Abramowitch, Steven D.; Elson, Elliot L.; Thomopoulos, Stavros; Genin, Guy M.

2015-01-01

The viscoelastic behaviour of a biological material is central to its functioning and is an indicator of its health. The Fung quasi-linear viscoelastic (QLV) model, a standard tool for characterizing biological materials, provides excellent fits to most stress–relaxation data by imposing a simple form upon a material's temporal relaxation spectrum. However, model identification is challenging because the Fung QLV model's ‘box’-shaped relaxation spectrum, predominant in biomechanics applications, can provide an excellent fit even when it is not a reasonable representation of a material's relaxation spectrum. Here, we present a robust and simple discrete approach for identifying a material's temporal relaxation spectrum from stress–relaxation data in an unbiased way. Our ‘discrete QLV’ (DQLV) approach identifies ranges of time constants over which the Fung QLV model's typical box spectrum provides an accurate representation of a particular material's temporal relaxation spectrum, and is effective at providing a fit to this model. The DQLV spectrum also reveals when other forms or discrete time constants are more suitable than a box spectrum. After validating the approach against idealized and noisy data, we applied the methods to analyse medial collateral ligament stress–relaxation data and identify the strengths and weaknesses of an optimal Fung QLV fit. PMID:26609064
A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock.

PubMed

Boyd, Joseph S; Cheng, Ryan R; Paddock, Mark L; Sancar, Cigdem; Morcos, Faruck; Golden, Susan S

2016-09-15

Two-component systems (TCS) that employ histidine kinases (HK) and response regulators (RR) are critical mediators of cellular signaling in bacteria. In the model cyanobacterium Synechococcus elongatus PCC 7942, TCSs control global rhythms of transcription that reflect an integration of time information from the circadian clock with a variety of cellular and environmental inputs. The HK CikA and the SasA/RpaA TCS transduce time information from the circadian oscillator to modulate downstream cellular processes. Despite immense progress in understanding of the circadian clock itself, many of the connections between the clock and other cellular signaling systems have remained enigmatic. To narrow the search for additional TCS components that connect to the clock, we utilized direct-coupling analysis (DCA), a statistical analysis of covariant residues among related amino acid sequences, to infer coevolution of new and known clock TCS components. DCA revealed a high degree of interaction specificity between SasA and CikA with RpaA, as expected, but also with the phosphate-responsive response regulator SphR. Coevolutionary analysis also predicted strong specificity between RpaA and a previously undescribed kinase, HK0480 (herein CikB). A knockout of the gene for CikB (cikB) in a sasA cikA null background eliminated the RpaA phosphorylation and RpaA-controlled transcription that is otherwise present in that background and suppressed cell elongation, supporting the notion that CikB is an interactor with RpaA and the clock network. This study demonstrates the power of DCA to identify subnetworks and key interactions in signaling pathways and of combinatorial mutagenesis to explore the phenotypic consequences. Such a combined strategy is broadly applicable to other prokaryotic systems. Signaling networks are complex and extensive, comprising multiple integrated pathways that respond to cellular and environmental cues. A TCS interaction model, based on DCA, independently confirmed known interactions and revealed a core set of subnetworks within the larger HK-RR set. We validated high-scoring candidate proteins via combinatorial genetics, demonstrating that DCA can be utilized to reduce the search space of complex protein networks and to infer undiscovered specific interactions for signaling proteins in vivo Significantly, new interactions that link circadian response to cell division and fitness in a light/dark cycle were uncovered. The combined analysis also uncovered a more basic core clock, illustrating the synergy and applicability of a combined computational and genetic approach for investigating prokaryotic signaling networks. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Automated analysis of long-term grooming behavior in Drosophila using a k-nearest neighbors classifier

PubMed Central

Allen, Victoria W; Shirasu-Hiza, Mimi

2018-01-01

Despite being pervasive, the control of programmed grooming is poorly understood. We addressed this gap by developing a high-throughput platform that allows long-term detection of grooming in Drosophila melanogaster. In our method, a k-nearest neighbors algorithm automatically classifies fly behavior and finds grooming events with over 90% accuracy in diverse genotypes. Our data show that flies spend ~13% of their waking time grooming, driven largely by two major internal programs. One of these programs regulates the timing of grooming and involves the core circadian clock components cycle, clock, and period. The second program regulates the duration of grooming and, while dependent on cycle and clock, appears to be independent of period. This emerging dual control model in which one program controls timing and another controls duration, resembles the two-process regulatory model of sleep. Together, our quantitative approach presents the opportunity for further dissection of mechanisms controlling long-term grooming in Drosophila. PMID:29485401
Quantum clocks and the foundations of relativity

NASA Astrophysics Data System (ADS)

Davies, Paul C. W.

2004-05-01

The conceptual foundations of the special and general theories of relativity differ greatly from those of quantum mechanics. Yet in all cases investigated so far, quantum mechanics seems to be consistent with the principles of relativity theory, when interpreted carefully. In this paper I report on a new investigation of this consistency using a model of a quantum clock to measure time intervals; a topic central to all metric theories of gravitation, and to cosmology. Results are presented for two important scenarios related to the foundations of relativity theory: the speed of light as a limiting velocity and the weak equivalence principle (WEP). These topics are investigated in the light of claims of superluminal propagation in quantum tunnelling and possible violations of WEP. Special attention is given to the role of highly non-classical states. I find that by using a definition of time intervals based on a precise model of a quantum clock, ambiguities are avoided and, at least in the scenarios investigated, there is consistency with the theory of relativity, albeit with some subtleties.
Curved backgrounds in emergent gravity

NASA Astrophysics Data System (ADS)

Chaurasia, Shikha; Erlich, Joshua; Zhou, Yiyu

2018-06-01

Field theories that are generally covariant but nongravitational at tree level typically give rise to an emergent gravitational interaction whose strength depends on a physical regulator. We consider emergent gravity models in which scalar fields assume the role of clock and rulers, addressing the problem of time in quantum gravity. We discuss the possibility of nontrivial dynamics for clock and ruler fields, and describe some of the consequences of those dynamics for the emergent gravitational theory.
Dynamic Data Driven Applications Systems (DDDAS)

DTIC Science & Technology

2013-03-06

INS •  Chip-scale atomic clocks •  Ad hoc networks •  Polymorphic networks •  Agile networks •  Laser communications •  Frequency-agile RF...atomi clocks •  Ad hoc networks •  Polymorphic networks •  Agile networks •  Laser co munications •  Frequency-agile RF systems...Real-Time Doppler Wind Wind field Sensor observations Energy Estimation Atmospheric Models for On-line Planning Planning and Control
Deterministic Execution of Ptides Programs

DTIC Science & Technology

2013-05-15

at a time no later than 30+1+5 = 36. Assume the maximum clock synchronization error is . Therefore, the AddSubtract adder must delay processing the...the synchronization of the platform real- time clock to its peers in other system platforms. The portions of PtidyOS code that implement access to the...interesting opportunities for future research. References [1] Y. Zhao, E. A. Lee, and J. Liu, “A programming model for time - synchronized distributed real
CLOCK regulates mammary epithelial cell growth and differentiation

PubMed Central

Crodian, Jennifer; Suárez-Trujillo, Aridany; Erickson, Emily; Weldon, Bethany; Crow, Kristi; Cummings, Shelby; Chen, Yulu; Shamay, Avi; Mabjeesh, Sameer J.; Plaut, Karen

2016-01-01

Circadian clocks influence virtually all physiological processes, including lactation. Here, we investigate the role of the CLOCK gene in regulation of mammary epithelial cell growth and differentiation. Comparison of mammary morphology in late-pregnant wild-type and ClockΔ19 mice, showed that gland development was negatively impacted by genetic loss of a functional timing system. To understand whether these effects were due, in part, to loss of CLOCK function in the gland, the mouse mammary epithelial cell line, HC11, was transfected with short hairpin RNA that targeted Clock (shClock). Cells transfected with shClock expressed 70% less Clock mRNA than wild-type (WT) HC11 cultures, which resulted in significantly depressed levels of CLOCK protein (P < 0.05). HC11 lines carrying shClock had four-fold higher growth rates (P < 0.05), and the percentage of cells in G1 phase was significantly higher (90.1 ± 1.1% of shClock vs. 71.3 ± 3.6% of WT-HC11) following serum starvation. Quantitative-PCR (qPCR) analysis showed shClock had significant effects (P < 0.0001) on relative expression levels of Ccnd1, Wee1, and Tp63. qPCR analysis of the effect of shClock on Fasn and Cdh1 expression in undifferentiated cultures and cultures treated 96 h with dexamethasone, insulin, and prolactin (differentiated) found levels were reduced by twofold and threefold, respectively (P < 0.05), in shClock line relative to WT cultures. Abundance of CDH1 and TP63 proteins were significantly reduced in cultures transfected with shClock. These data support how CLOCK plays a role in regulation of epithelial cell growth and differentiation in the mammary gland. PMID:27707717
Characterization of anomalous relaxation using the time-fractional Bloch equation and multiple echo T2 *-weighted magnetic resonance imaging at 7 T.

PubMed

Qin, Shanlin; Liu, Fawang; Turner, Ian W; Yu, Qiang; Yang, Qianqian; Vegh, Viktor

2017-04-01

To study the utility of fractional calculus in modeling gradient-recalled echo MRI signal decay in the normal human brain. We solved analytically the extended time-fractional Bloch equations resulting in five model parameters, namely, the amplitude, relaxation rate, order of the time-fractional derivative, frequency shift, and constant offset. Voxel-level temporal fitting of the MRI signal was performed using the classical monoexponential model, a previously developed anomalous relaxation model, and using our extended time-fractional relaxation model. Nine brain regions segmented from multiple echo gradient-recalled echo 7 Tesla MRI data acquired from five participants were then used to investigate the characteristics of the extended time-fractional model parameters. We found that the extended time-fractional model is able to fit the experimental data with smaller mean squared error than the classical monoexponential relaxation model and the anomalous relaxation model, which do not account for frequency shift. We were able to fit multiple echo time MRI data with high accuracy using the developed model. Parameters of the model likely capture information on microstructural and susceptibility-induced changes in the human brain. Magn Reson Med 77:1485-1494, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.
PPARalpha is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders.

PubMed

Shirai, Hidenori; Oishi, Katsutaka; Kudo, Takashi; Shibata, Shigenobu; Ishida, Norio

2007-06-08

Recent progress at the molecular level has revealed that nuclear receptors play an important role in the generation of mammalian circadian rhythms. To examine whether peroxisome proliferator-activated receptor alpha (PPARalpha) is involved in the regulation of circadian behavioral rhythms in mammals, we evaluated the locomotor activity of mice administered with the hypolipidemic PPARalpha ligand, bezafibrate. Circadian locomotor activity was phase-advanced about 3h in mice given bezafibrate under light-dark (LD) conditions. Transfer from LD to constant darkness did not change the onset of activity in these mice, suggesting that bezafibrate advanced the phase of the endogenous clock. Surprisingly, bezafibrate also advanced the phase in mice with lesions of the suprachiasmatic nucleus (SCN; the central clock in mammals). The circadian expression of clock genes such as period2, BMAL1, and Rev-erbalpha was also phase-advanced in various tissues (cortex, liver, and fat) without affecting the SCN. Bezafibrate also phase-advanced the activity phase that is delayed in model mice with delayed sleep phase syndrome (DSPS) due to a Clock gene mutation. Our results indicated that PPARalpha is involved in circadian clock control independently of the SCN and that PPARalpha could be a potent target of drugs to treat circadian rhythm sleep disorders including DSPS.
Barley (Hordeum vulgare) circadian clock genes can respond rapidly to temperature in an EARLY FLOWERING 3-dependent manner

PubMed Central

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
Resynchronization of circadian oscillators and the east-west asymmetry of jet-lag

NASA Astrophysics Data System (ADS)

Lu, Zhixin; Klein-Cardeña, Kevin; Lee, Steven; Antonsen, Thomas M.; Girvan, Michelle; Ott, Edward

2016-09-01

Cells in the brain's Suprachiasmatic Nucleus (SCN) are known to regulate circadian rhythms in mammals. We model synchronization of SCN cells using the forced Kuramoto model, which consists of a large population of coupled phase oscillators (modeling individual SCN cells) with heterogeneous intrinsic frequencies and external periodic forcing. Here, the periodic forcing models diurnally varying external inputs such as sunrise, sunset, and alarm clocks. We reduce the dimensionality of the system using the ansatz of Ott and Antonsen and then study the effect of a sudden change of clock phase to simulate cross-time-zone travel. We estimate model parameters from previous biological experiments. By examining the phase space dynamics of the model, we study the mechanism leading to the difference typically experienced in the severity of jet-lag resulting from eastward and westward travel.
A Circadian Clock-Regulated Toggle Switch Explains AtGRP7 and AtGRP8 Oscillations in Arabidopsis thaliana

PubMed Central

Schmal, Christoph; Reimann, Peter; Staiger, Dorothee

2013-01-01

The circadian clock controls many physiological processes in higher plants and causes a large fraction of the genome to be expressed with a 24h rhythm. The transcripts encoding the RNA-binding proteins AtGRP7 (Arabidopsis thaliana Glycine Rich Protein 7) and AtGRP8 oscillate with evening peaks. The circadian clock components CCA1 and LHY negatively affect AtGRP7 expression at the level of transcription. AtGRP7 and AtGRP8, in turn, negatively auto-regulate and reciprocally cross-regulate post-transcriptionally: high protein levels promote the generation of an alternative splice form that is rapidly degraded. This clock-regulated feedback loop has been proposed to act as a molecular slave oscillator in clock output. While mathematical models describing the circadian core oscillator in Arabidopsis thaliana were introduced recently, we propose here the first model of a circadian slave oscillator. We define the slave oscillator in terms of ordinary differential equations and identify the model's parameters by an optimization procedure based on experimental results. The model successfully reproduces the pertinent experimental findings such as waveforms, phases, and half-lives of the time-dependent concentrations. Furthermore, we obtain insights into possible mechanisms underlying the observed experimental dynamics: the negative auto-regulation and reciprocal cross-regulation via alternative splicing could be responsible for the sharply peaking waveforms of the AtGRP7 and AtGRP8 mRNA. Moreover, our results suggest that the AtGRP8 transcript oscillations are subordinated to those of AtGRP7 due to a higher impact of AtGRP7 protein on alternative splicing of its own and of the AtGRP8 pre-mRNA compared to the impact of AtGRP8 protein. Importantly, a bifurcation analysis provides theoretical evidence that the slave oscillator could be a toggle switch, arising from the reciprocal cross-regulation at the post-transcriptional level. In view of this, transcriptional repression of AtGRP7 and AtGRP8 by LHY and CCA1 induces oscillations of the toggle switch, leading to the observed high-amplitude oscillations of AtGRP7 mRNA. PMID:23555221
Variable frequency microprocessor clock generator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Branson, C.N.

A microprocessor-based system is described comprising: a digital central microprocessor provided with a clock input and having a rate of operation determined by the frequency of a clock signal input thereto; memory means operably coupled to the central microprocessor for storing programs respectively including a plurality of instructions and addressable by the central microprocessor; peripheral device operably connected to the central microprocessor, the first peripheral device being addressable by the central microprocessor for control thereby; a system clock generator for generating a digital reference clock signal having a reference frequency rate; and frequency rate reduction circuit means connected between themore » clock generator and the clock input of the central microprocessor for selectively dividing the reference clock signal to generate a microprocessor clock signal as an input to the central microprocessor for clocking the central microprocessor.« less
Molecular targets for small-molecule modulators of circadian clocks

PubMed Central

He, Baokun; Chen, Zheng

2016-01-01

Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111
Entanglement of quantum clocks through gravity

NASA Astrophysics Data System (ADS)

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

2017-03-01

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.
Entanglement of quantum clocks through gravity.

PubMed

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.
Geopotential measurements with synchronously linked optical lattice clocks

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Oscillator networks with tissue-specific circadian clocks in plants.

PubMed

Inoue, Keisuke; Araki, Takashi; Endo, Motomu

2017-09-08

Many organisms rely on circadian clocks to synchronize their biological processes with the 24-h rotation of the earth. In mammals, the circadian clock consists of a central clock in the suprachiasmatic nucleus and peripheral clocks in other tissues. The central clock is tightly coupled to synchronize rhythmicity and can organize peripheral clocks through neural and hormonal signals. In contrast to mammals, it has long been assumed that the circadian clocks in each plant cell is able to be entrained by external light, and they are only weakly coupled to each other. Recently, however, several reports have demonstrated that plants have unique oscillator networks with tissue-specific circadian clocks. Here, we introduce our current view regarding tissue-specific properties and oscillator networks of plant circadian clocks. Accumulating evidence suggests that plants have multiple oscillators, which show distinct properties and reside in different tissues. A direct tissue-isolation technique and micrografting have clearly demonstrated that plants have hierarchical oscillator networks consisting of multiple tissue-specific clocks. Copyright © 2017. Published by Elsevier Ltd.
Entanglement of quantum clocks through gravity

PubMed Central

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

2017-01-01

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. PMID:28270623
The poro-viscoelastic properties of trabecular bone: a micro computed tomography-based finite element study.

PubMed

Sandino, Clara; McErlain, David D; Schipilow, John; Boyd, Steven K

2015-04-01

Bone is a porous structure with a solid phase that contains hydroxyapatite and collagen. Due to its composition, bone is often represented either as a poroelastic or as a viscoelastic material; however, the poro-viscoelastic formulation that allows integrating the effect of both the fluid flow and the collagen on the mechanical response of the tissue, has not been applied yet. The objective of this study was to develop a micro computed tomography (µCT)-based finite element (FE) model of trabecular bone that includes both the poroelastic and the viscoelastic nature of the tissue. Cubes of trabecular bone (N=25) from human distal tibia were scanned with µCT and stress relaxation experiments were conducted. The µCT images were the basis for sample specific FE models, and the stress relaxation experiments were simulated applying a poro-viscoelastic formulation. The model considers two scales of the tissue: the intertrabecular pore and the lacunar-canalicular pore scales. Independent viscoelastic and poroelastic models were also developed to determine their contribution to the poro-viscoelastic model. All the experiments exhibited a similar relaxation trend. The average reaction force before relaxation was 9.28 × 10(2)N (SD ± 5.11 × 10(2)N), and after relaxation was 4.69 × 10(2)N (SD ± 2.88 × 10(2)N). The slope of the regression line between the force before and after relaxation was 1.92 (R(2)=0.96). The poro-viscoelastic models captured 49% of the variability of the experimental data before relaxation and 33% after relaxation. The relaxation predicted with viscoelastic models was similar to the poro-viscoelastic ones; however, the poroelastic formulation underestimated the reaction force before relaxation. These data suggest that the contribution of viscoelasticity (fluid flow-independent mechanism) to the mechanical response of the tissue is significantly greater than the contribution of the poroelasticity (fluid flow-dependent mechanism). Copyright © 2015 Elsevier Ltd. All rights reserved.
Circadian rhythms synchronize mitosis in Neurospora crassa.

PubMed

Hong, Christian I; Zámborszky, Judit; Baek, Mokryun; Labiscsak, Laszlo; Ju, Kyungsu; Lee, Hyeyeong; Larrondo, Luis F; Goity, Alejandra; Chong, Hin Siong; Belden, William J; Csikász-Nagy, Attila

2014-01-28

The cell cycle and the circadian clock communicate with each other, resulting in circadian-gated cell division cycles. Alterations in this network may lead to diseases such as cancer. Therefore, it is critical to identify molecular components that connect these two oscillators. However, molecular mechanisms between the clock and the cell cycle remain largely unknown. A model filamentous fungus, Neurospora crassa, is a multinucleate system used to elucidate molecular mechanisms of circadian rhythms, but not used to investigate the molecular coupling between these two oscillators. In this report, we show that a conserved coupling between the circadian clock and the cell cycle exists via serine/threonine protein kinase-29 (STK-29), the Neurospora homolog of mammalian WEE1 kinase. Based on this finding, we established a mathematical model that predicts circadian oscillations of cell cycle components and circadian clock-dependent synchronized nuclear divisions. We experimentally demonstrate that G1 and G2 cyclins, CLN-1 and CLB-1, respectively, oscillate in a circadian manner with bioluminescence reporters. The oscillations of clb-1 and stk-29 gene expression are abolished in a circadian arrhythmic frq(ko) mutant. Additionally, we show the light-induced phase shifts of a core circadian component, frq, as well as the gene expression of the cell cycle components clb-1 and stk-29, which may alter the timing of divisions. We then used a histone hH1-GFP reporter to observe nuclear divisions over time, and show that a large number of nuclear divisions occur in the evening. Our findings demonstrate the circadian clock-dependent molecular dynamics of cell cycle components that result in synchronized nuclear divisions in Neurospora.
Clock Genes Explain a Large Proportion of Phenotypic Variance in Systolic Blood Pressure and This Control Is Not Modified by Environmental Temperature.

PubMed

Dashti, Hassan S; Aslibekyan, Stella; Scheer, Frank A J L; Smith, Caren E; Lamon-Fava, Stefania; Jacques, Paul; Lai, Chao-Qiang; Tucker, Katherine L; Arnett, Donna K; Ordovás, José M

2016-01-01

Diurnal variation in blood pressure (BP) is regulated, in part, by an endogenous circadian clock; however, few human studies have identified associations between clock genes and BP. Accounting for environmental temperature may be necessary to correct for seasonal bias. We examined whether environmental temperature on the day of participants' assessment was associated with BP, using adjusted linear regression models in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (n = 819) and the Boston Puerto Rican Health Study (BPRHS) (n = 1,248) cohorts. We estimated phenotypic variance in BP by 18 clock genes and examined individual single-nucleotide polymorphism (SNP) associations with BP using an additive genetic model, with further consideration of environmental temperature. In GOLDN, each additional 1 °C increase in environmental temperature was associated with 0.18 mm Hg lower systolic BP [SBP; β ± SE = -0.18 ± 0.05 mm Hg; P = 0.0001] and 0.10mm Hg lower diastolic BP [DBP; -0.10 ± 0.03 mm Hg; P = 0.001]. Similar results were seen in the BPRHS for SBP only. Clock genes explained a statistically significant proportion of the variance in SBP [V G/V P ± SE = 0.071 ± 0.03; P = 0.001] in GOLDN, but not in the BPRHS, and we did not observe associations between individual SNPs and BP. Environmental temperature did not influence the identified genetic associations. We identified clock genes that explained a statistically significant proportion of the phenotypic variance in SBP, supporting the importance of the circadian pathway underlying cardiac physiology. Although temperature was associated with BP, it did not affect results with genetic markers in either study. Therefore, it does not appear that temperature measures are necessary for interpreting associations between clock genes and BP. Trials related to this study were registered at clinicaltrials.gov as NCT00083369 (Genetic and Environmental Determinants of Triglycerides) and NCT01231958 (Boston Puerto Rican Health Study). © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2015. This work is written by (a) US Government employees(s) and is in the public domain in the US.
Electromagnetic synchronisation of clocks with finite separation in a rotating system

NASA Astrophysics Data System (ADS)

Cohen, J. M.; Moses, H. E.; Rosenblum, A.

1984-11-01

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 synchronization error as a closely spaced band of clocks along the same light path. In addition, the above result is generalized to n equally spaced clocks.
SPARTAN: An Instructional High Resolution Land Combat Model

DTIC Science & Technology

1992-03-01

being: Next Event Time Advance - this method initializes the time clock at zero and updates the clock to the time of the next most imminent event and...whenever the soldier’s movement attribute switch is on and his speed is greater than zero . When startmove is called, it begins by performing several...status attribute goes to zero , his movement goes to zero , and his posture goes to prone. Lastly, the "killsoldier" subprogram is called which removes
High-Performance Clock Synchronization Algorithms for Distributed Wireless Airborne Computer Networks with Applications to Localization and Tracking of Targets

DTIC Science & Technology

2010-06-01

GMKPF represents a better and more flexible alternative to the Gaussian Maximum Likelihood (GML), and Exponential Maximum Likelihood ( EML ...accurate results relative to GML and EML when the network delays are modeled in terms of a single non-Gaussian/non-exponential distribution or as a...to the Gaussian Maximum Likelihood (GML), and Exponential Maximum Likelihood ( EML ) estimators for clock offset estimation in non-Gaussian or non
Computer Aided Wirewrap Interconnect.

DTIC Science & Technology

1980-11-01

ECLI (180 MHz System Clock Generated via Ring Oscillator) Clock Waveform: Synchronous Phase 0 Output Binary Counter: Power Plane Noie: (Loaded) LSB...LOGIC (ECL) (185 MHz System Clock Generated via Ring Oscillator) Clock Woveform Synchronous Phase 0 Output Binary Counter- Power Plane Voise (Loaded...High Speed .. ......... . 98 Clock Signals Into Logic Panels in a Multiboard System On-Eoard Clock Distribution Via Fanout .... ......... 102 Through
Circadian clock gene plays a key role on ovarian cycle and spontaneous abortion.

PubMed

Li, Ruiwen; Cheng, Shuting; Wang, Zhengrong

2015-01-01

Circadian locomotor output cycles protein kaput (CLOCK) plays a key role in maintaining circadian rhythms and activation of downstream elements. However, its function on human female reproductive system remains unknown. To investigate the potential role of CLOCK, CLOCK-shRNAs were transfected into mouse 129 ES cells or injected into the ovaries of adult female mice. Western blotting was utilized to analyze the protein interactions and flow cytometry was used to assess apoptosis. The expression of CLOCK peaked at the 6th week in the healthy fetuses. However, an abnormal expression of CLOCK was detected in fetuses from spontaneous miscarriage. To determine the effect of CLOCK on female fertility, a small hairpin RNA (shRNA) strategy was used to specifically knockdown the CLOCK gene expression in vitro and in vivo. Knockdown of CLOCK induced apoptosis in mouse embryonic stem (mES) cells and inhibited the proliferation in mES cells in vitro. CLOCK knockdown also led to decreased release of oocytes and smaller litter size compared with control in vivo. Collectively, theses findings indicate that CLOCK plays an important role in fertility and that the CLOCK knockdown leads to reduction in reproduction and increased miscarriage risk. © 2015 S. Karger AG, Basel.
Relaxation Dynamics of a Granular Pile on a Vertically Vibrating Plate

NASA Astrophysics Data System (ADS)

Tsuji, Daisuke; Otsuki, Michio; Katsuragi, Hiroaki

2018-03-01

Nonlinear relaxation dynamics of a vertically vibrated granular pile is experimentally studied. In the experiment, the flux and slope on the relaxing pile are measured by using a high-speed laser profiler. The relation of these quantities can be modeled by the nonlinear transport law assuming the uniform vibrofluidization of an entire pile. The fitting parameter in this model is only the relaxation efficiency, which characterizes the energy conversion rate from vertical vibration into horizontal transport. We demonstrate that this value is a constant independent of experimental conditions. The actual relaxation is successfully reproduced by the continuity equation with the proposed model. Finally, its specific applicability toward an astrophysical phenomenon is shown.
Combining fossil and molecular data to date the diversification of New World Primates.

PubMed

Schrago, C G; Mello, B; Soares, A E R

2013-11-01

Recent methodological advances in molecular dating associated with the growing availability of sequence data have prompted the study of the evolution of New World Anthropoidea in recent years. Motivated by questions regarding historical biogeography or the mode of evolution, these works aimed to obtain a clearer scenario of Platyrrhini origins and diversification. Although some consensus was found, disputed issues, especially those relating to the evolutionary affinities of fossil taxa, remain. The use of fossil taxa for divergence time analysis is traditionally restricted to the provision of calibration priors. However, new analytical approaches have been developed that incorporate fossils as terminals and, thus, directly assign ages to the fossil tips. In this study, we conducted a combined analysis of molecular and morphological data, including fossils, to derive the timescale of New World anthropoids. Differently from previous studies that conducted total-evidence analysis of molecules and morphology, our approach investigated the morphological clock alone. Our results corroborate the hypothesis that living platyrrhines diversified in the last 20 Ma and that Miocene Patagonian fossils compose an independent evolutionary radiation that diversified in the late Oligocene. When compared to the node ages inferred from the molecular timescale, the inclusion of fossils augmented the precision of the estimates for nodes constrained by the fossil tips. We show that morphological data can be analysed using the same methodological framework applied in relaxed molecular clock studies. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.
Accurate Sample Time Reconstruction of Inertial FIFO Data.

PubMed

Stieber, Sebastian; Dorsch, Rainer; Haubelt, Christian

2017-12-13

In the context of modern cyber-physical systems, the accuracy of underlying sensor data plays an increasingly important role in sensor data fusion and feature extraction. The raw events of multiple sensors have to be aligned in time to enable high quality sensor fusion results. However, the growing number of simultaneously connected sensor devices make the energy saving data acquisition and processing more and more difficult. Hence, most of the modern sensors offer a first-in-first-out (FIFO) interface to store multiple data samples and to relax timing constraints, when handling multiple sensor devices. However, using the FIFO interface increases the negative influence of individual clock drifts-introduced by fabrication inaccuracies, temperature changes and wear-out effects-onto the sampling data reconstruction. Furthermore, additional timing offset errors due to communication and software latencies increases with a growing number of sensor devices. In this article, we present an approach for an accurate sample time reconstruction independent of the actual clock drift with the help of an internal sensor timer. Such timers are already available in modern sensors, manufactured in micro-electromechanical systems (MEMS) technology. The presented approach focuses on calculating accurate time stamps using the sensor FIFO interface in a forward-only processing manner as a robust and energy saving solution. The proposed algorithm is able to lower the overall standard deviation of reconstructed sampling periods below 40 μ s, while run-time savings of up to 42% are achieved, compared to single sample acquisition.
Single-Copy Nuclear Genes Place Haustorial Hydnoraceae within Piperales and Reveal a Cretaceous Origin of Multiple Parasitic Angiosperm Lineages

PubMed Central

Naumann, Julia; Salomo, Karsten; Der, Joshua P.; Wafula, Eric K.; Bolin, Jay F.; Maass, Erika; Frenzke, Lena; Samain, Marie-Stéphanie; Neinhuis, Christoph

2013-01-01

Extreme haustorial parasites have long captured the interest of naturalists and scientists with their greatly reduced and highly specialized morphology. Along with the reduction or loss of photosynthesis, the plastid genome often decays as photosynthetic genes are released from selective constraint. This makes it challenging to use traditional plastid genes for parasitic plant phylogenetics, and has driven the search for alternative phylogenetic and molecular evolutionary markers. Thus, evolutionary studies, such as molecular clock-based age estimates, are not yet available for all parasitic lineages. In the present study, we extracted 14 nuclear single copy genes (nSCG) from Illumina transcriptome data from one of the “strangest plants in the world”, Hydnora visseri (Hydnoraceae). A ∼15,000 character molecular dataset, based on all three genomic compartments, shows the utility of nSCG for reconstructing phylogenetic relationships in parasitic lineages. A relaxed molecular clock approach with the same multi-locus dataset, revealed an ancient age of ∼91 MYA for Hydnoraceae. We then estimated the stem ages of all independently originated parasitic angiosperm lineages using a published dataset, which also revealed a Cretaceous origin for Balanophoraceae, Cynomoriaceae and Apodanthaceae. With the exception of Santalales, older parasite lineages tend to be more specialized with respect to trophic level and have lower species diversity. We thus propose the “temporal specialization hypothesis” (TSH) implementing multiple independent specialization processes over time during parasitic angiosperm evolution. PMID:24265760
An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock.

PubMed

Agrawal, Parul; Hardin, Paul E

2016-12-07

Circadian clocks in eukaryotes keep time via cell-autonomous transcriptional feedback loops. A well-characterized example of such a transcriptional feedback loop is in Drosophila, where CLOCK-CYCLE (CLK-CYC) complexes activate transcription of period (per) and timeless (tim) genes, rising levels of PER-TIM complexes feed-back to repress CLK-CYC activity, and degradation of PER and TIM permits the next cycle of CLK-CYC transcription. The timing of CLK-CYC activation and PER-TIM repression is regulated posttranslationally, in part through rhythmic phosphorylation of CLK, PER, and TIM. Previous behavioral screens identified several kinases that control CLK, PER, and TIM levels, subcellular localization, and/or activity, but two phosphatases that function within the clock were identified through the analysis of candidate genes from other pathways or model systems. To identify phosphatases that play a role in the clock, we screened clock cell-specific RNA interference (RNAi) knockdowns of all annotated protein phosphatases and protein phosphatase regulators in Drosophila for altered activity rhythms. This screen identified 19 protein phosphatases that lengthened or shortened the circadian period by ≥1 hr (p ≤ 0.05 compared to controls) or were arrhythmic. Additional RNAi lines, transposon inserts, overexpression, and loss-of-function mutants were tested to independently confirm these RNAi phenotypes. Based on genetic validation and molecular analysis, 15 viable protein phosphatases remain for future studies. These candidates are expected to reveal novel features of the circadian timekeeping mechanism in Drosophila that are likely to be conserved in all animals including humans. Copyright © 2016 Agrawal and Hardin.
Aging studies on micro-fabricated alkali buffer-gas cells for miniature atomic clocks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdullah, S.; Affolderbach, C.; Gruet, F.

2015-04-20

We report an aging study on micro-fabricated alkali vapor cells using neon as a buffer gas. An experimental atomic clock setup is used to measure the cell's intrinsic frequency, by recording the clock frequency shift at different light intensities and extrapolating to zero intensity. We find a drift of the cell's intrinsic frequency of (−5.2 ± 0.6) × 10{sup −11}/day and quantify deterministic variations in sources of clock frequency shifts due to the major physical effects to identify the most probable cause of the drift. The measured drift is one order of magnitude stronger than the total frequency variations expected from clock parameter variationsmore » and corresponds to a slow reduction of buffer gas pressure inside the cell, which is compatible with the hypothesis of loss of Ne gas from the cell due to its permeation through the cell windows. A negative drift on the intrinsic cell frequency is reproducible for another cell of the same type. Based on the Ne permeation model and the measured cell frequency drift, we determine the permeation constant of Ne through borosilicate glass as (5.7 ± 0.7) × 10{sup −22} m{sup 2} s{sup −1 }Pa{sup −1} at 81 °C. We propose this method based on frequency metrology in an alkali vapor cell atomic clock setup based on coherent population trapping for measuring permeation constants of inert gases.« less
Neuroanatomical details of the lateral neurons of Drosophila melanogaster support their functional role in the circadian system

PubMed Central

Schubert, Frank K.; Hagedorn, Nicolas; Yoshii, Taishi; Helfrich‐Förster, Charlotte

2018-01-01

Abstract Drosophila melanogaster is a long‐standing model organism in the circadian clock research. A major advantage is the relative small number of about 150 neurons, which built the circadian clock in Drosophila. In our recent work, we focused on the neuroanatomical properties of the lateral neurons of the clock network. By applying the multicolor‐labeling technique Flybow we were able to identify the anatomical similarity of the previously described E2 subunit of the evening oscillator of the clock, which is built by the 5th small ventrolateral neuron (5th s‐LNv) and one ITP positive dorsolateral neuron (LNd). These two clock neurons share the same spatial and functional properties. We found both neurons innervating the same brain areas with similar pre‐ and postsynaptic sites in the brain. Here the anatomical findings support their shared function as a main evening oscillator in the clock network like also found in previous studies. A second quite surprising finding addresses the large lateral ventral PDF‐neurons (l‐LNvs). We could show that the four hardly distinguishable l‐LNvs consist of two subgroups with different innervation patterns. While three of the neurons reflect the well‐known branching pattern reproduced by PDF immunohistochemistry, one neuron per brain hemisphere has a distinguished innervation profile and is restricted only to the proximal part of the medulla‐surface. We named this neuron “extra” l‐LNv (l‐LNvx). We suggest the anatomical findings reflect different functional properties of the two l‐LNv subgroups. PMID:29424420
Drosophila TIM binds importin α1, and acts as an adapter to transport PER to the nucleus.

PubMed

Jang, A Reum; Moravcevic, Katarina; Saez, Lino; Young, Michael W; Sehgal, Amita

2015-02-01

Regulated nuclear entry of clock proteins is a conserved feature of eukaryotic circadian clocks and serves to separate the phase of mRNA activation from mRNA repression in the molecular feedback loop. In Drosophila, nuclear entry of the clock proteins, PERIOD (PER) and TIMELESS (TIM), is tightly controlled, and impairments of this process produce profound behavioral phenotypes. We report here that nuclear entry of PER-TIM in clock cells, and consequently behavioral rhythms, require a specific member of a classic nuclear import pathway, Importin α1 (IMPα1). In addition to IMPα1, rhythmic behavior and nuclear expression of PER-TIM require a specific nuclear pore protein, Nup153, and Ran-GTPase. IMPα1 can also drive rapid and efficient nuclear expression of TIM and PER in cultured cells, although the effect on PER is mediated by TIM. Mapping of interaction domains between IMPα1 and TIM/PER suggests that TIM is the primary cargo for the importin machinery. This is supported by attenuated interaction of IMPα1 with TIM carrying a mutation previously shown to prevent nuclear entry of TIM and PER. TIM is detected at the nuclear envelope, and computational modeling suggests that it contains HEAT-ARM repeats typically found in karyopherins, consistent with its role as a co-transporter for PER. These findings suggest that although PER is the major timekeeper of the clock, TIM is the primary target of nuclear import mechanisms. Thus, the circadian clock uses specific components of the importin pathway with a novel twist in that TIM serves a karyopherin-like role for PER.
Depression-like behaviour in mice is associated with disrupted circadian rhythms in nucleus accumbens and periaqueductal grey.

PubMed

Landgraf, Dominic; Long, Jaimie E; Welsh, David K

2016-05-01

An association between circadian rhythms and mood regulation is well established, and disturbed circadian clocks are believed to contribute to the development of mood disorders, including major depressive disorder. The circadian system is coordinated by the suprachiasmatic nucleus (SCN), the master pacemaker in the hypothalamus that receives light input from the retina and synchronizes circadian oscillators in other brain regions and peripheral tissues. Lacking the tight neuronal network that couples single-cell oscillators in the SCN, circadian clocks outside the SCN may be less stable and more susceptible to disturbances, for example by clock gene mutations or uncontrollable stress. However, non-SCN circadian clocks have not been studied extensively in rodent models of mood disorders. In the present study, it was hypothesized that disturbances of local circadian clocks in mood-regulating brain areas are associated with depression-like behaviour in mice. Using the learned helplessness procedure, depression-like behaviour was evoked in mice bearing the PER2::LUC circadian reporter, and then circadian rhythms of PER2 expression were examined in brain slices from these mice using luminometry and bioluminescence imaging. It was found that helplessness is associated with absence of circadian rhythms in the nucleus accumbens and the periaqueductal grey, two of the most critical brain regions within the reward circuit. The current study provides evidence that susceptibility of mice to depression-like behaviour is associated with disturbed local circadian clocks in a subset of mood-regulating brain areas, but the direction of causality remains to be determined. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Regulation of circadian clock transcriptional output by CLOCK:BMAL1

PubMed Central

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

The role of sleep problems and circadian clock genes in attention-deficit hyperactivity disorder and mood disorders during childhood and adolescence: an update.

PubMed

Dueck, Alexander; Berger, Christoph; Wunsch, Katharina; Thome, Johannes; Cohrs, Stefan; Reis, Olaf; Haessler, Frank

2017-02-01

A more recent branch of research describes the importance of sleep problems in the development and treatment of mental disorders in children and adolescents, such as attention-deficit hyperactivity disorder (ADHD) and mood disorders (MD). Research about clock genes has continued since 2012 with a focus on metabolic processes within all parts of the mammalian body, but particularly within different cerebral regions. Research has focused on complex regulatory circuits involving clock genes themselves and their influence on circadian rhythms of diverse body functions. Current publications on basic research in human and animal models indicate directions for the treatment of mental disorders targeting circadian rhythms and mechanisms. The most significant lines of research are described in this paper.
Organization of the Drosophila circadian control circuit.

PubMed

Nitabach, Michael N; Taghert, Paul H

2008-01-22

Molecular genetics has revealed the identities of several components of the fundamental circadian molecular oscillator - an evolutionarily conserved molecular mechanism of transcription and translation that can operate in a cell-autonomous manner. Therefore, it was surprising when studies of circadian rhythmic behavior in the fruit fly Drosophila suggested that the normal operations of circadian clock cells, which house the molecular oscillator, in fact depend on non-cell-autonomous effects - interactions between the clock cells themselves. Here we review several genetic analyses that broadly extend that viewpoint. They support a model whereby the approximately 150 circadian clock cells in the brain of the fly are sub-divided into functionally discrete rhythmic centers. These centers alternatively cooperate or compete to control the different episodes of rhythmic behavior that define the fly's daily activity profile.
Anomalous NMR Relaxation in Cartilage Matrix Components and Native Cartilage: Fractional-Order Models

PubMed Central

Magin, Richard L.; Li, Weiguo; Velasco, M. Pilar; Trujillo, Juan; Reiter, David A.; Morgenstern, Ashley; Spencer, Richard G.

2011-01-01

We present a fractional-order extension of the Bloch equations to describe anomalous NMR relaxation phenomena (T1 and T2). The model has solutions in the form of Mittag-Leffler and stretched exponential functions that generalize conventional exponential relaxation. Such functions have been shown by others to be useful for describing dielectric and viscoelastic relaxation in complex, heterogeneous materials. Here, we apply these fractional-order T1 and T2 relaxation models to experiments performed at 9.4 and 11.7 Tesla on type I collagen gels, chondroitin sulfate mixtures, and to bovine nasal cartilage (BNC), a largely isotropic and homogeneous form of cartilage. The results show that the fractional-order analysis captures important features of NMR relaxation that are typically described by multi-exponential decay models. We find that the T2 relaxation of BNC can be described in a unique way by a single fractional-order parameter (α), in contrast to the lack of uniqueness of multi-exponential fits in the realistic setting of a finite signal-to-noise ratio. No anomalous behavior of T1 was observed in BNC. In the single-component gels, for T2 measurements, increasing the concentration of the largest components of cartilage matrix, collagen and chondroitin sulfate, results in a decrease in α, reflecting a more restricted aqueous environment. The quality of the curve fits obtained using Mittag-Leffler and stretched exponential functions are in some cases superior to those obtained using mono- and bi-exponential models. In both gels and BNC, α appears to account for microstructural complexity in the setting of an altered distribution of relaxation times. This work suggests the utility of fractional-order models to describe T2 NMR relaxation processes in biological tissues. PMID:21498095
Anomalous NMR relaxation in cartilage matrix components and native cartilage: Fractional-order models

NASA Astrophysics Data System (ADS)

Magin, Richard L.; Li, Weiguo; Pilar Velasco, M.; Trujillo, Juan; Reiter, David A.; Morgenstern, Ashley; Spencer, Richard G.

2011-06-01

We present a fractional-order extension of the Bloch equations to describe anomalous NMR relaxation phenomena ( T1 and T2). The model has solutions in the form of Mittag-Leffler and stretched exponential functions that generalize conventional exponential relaxation. Such functions have been shown by others to be useful for describing dielectric and viscoelastic relaxation in complex, heterogeneous materials. Here, we apply these fractional-order T1 and T2 relaxation models to experiments performed at 9.4 and 11.7 Tesla on type I collagen gels, chondroitin sulfate mixtures, and to bovine nasal cartilage (BNC), a largely isotropic and homogeneous form of cartilage. The results show that the fractional-order analysis captures important features of NMR relaxation that are typically described by multi-exponential decay models. We find that the T2 relaxation of BNC can be described in a unique way by a single fractional-order parameter ( α), in contrast to the lack of uniqueness of multi-exponential fits in the realistic setting of a finite signal-to-noise ratio. No anomalous behavior of T1 was observed in BNC. In the single-component gels, for T2 measurements, increasing the concentration of the largest components of cartilage matrix, collagen and chondroitin sulfate, results in a decrease in α, reflecting a more restricted aqueous environment. The quality of the curve fits obtained using Mittag-Leffler and stretched exponential functions are in some cases superior to those obtained using mono- and bi-exponential models. In both gels and BNC, α appears to account for micro-structural complexity in the setting of an altered distribution of relaxation times. This work suggests the utility of fractional-order models to describe T2 NMR relaxation processes in biological tissues.
A dynamical study of Galactic globular clusters under different relaxation conditions

NASA Astrophysics Data System (ADS)

Zocchi, A.; Bertin, G.; Varri, A. L.

2012-03-01

Aims: We perform a systematic combined photometric and kinematic analysis of a sample of globular clusters under different relaxation conditions, based on their core relaxation time (as listed in available catalogs), by means of two well-known families of spherical stellar dynamical models. Systems characterized by shorter relaxation time scales are expected to be better described by isotropic King models, while less relaxed systems might be interpreted by means of non-truncated, radially-biased anisotropic f(ν) models, originally designed to represent stellar systems produced by a violent relaxation formation process and applied here for the first time to the study of globular clusters. Methods: The comparison between dynamical models and observations is performed by fitting simultaneously surface brightness and velocity dispersion profiles. For each globular cluster, the best-fit model in each family is identified, along with a full error analysis on the relevant parameters. Detailed structural properties and mass-to-light ratios are also explicitly derived. Results: We find that King models usually offer a good representation of the observed photometric profiles, but often lead to less satisfactory fits to the kinematic profiles, independently of the relaxation condition of the systems. For some less relaxed clusters, f(ν) models provide a good description of both observed profiles. Some derived structural characteristics, such as the total mass or the half-mass radius, turn out to be significantly model-dependent. The analysis confirms that, to answer some important dynamical questions that bear on the formation and evolution of globular clusters, it would be highly desirable to acquire larger numbers of accurate kinematic data-points, well distributed over the cluster field. Appendices are available in electronic form at http://www.aanda.org
Stress and strain relaxation in magnesium AZ31 rolled plate: In-situ neutron measurement and elastic viscoplastic polycrystal modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Huamiao; Clausen, Bjorn; Capolungo, Laurent

Continuous mechanical tests with strain holds (stress relaxation) and with stress holds (strain relaxation) are performed simultaneously with in-situ neutron measurements to analyze the mechanisms of stress and strain relaxation in Mg AZ31 rolled plate. A dislocation activity based constitutive model, accounting for internal stress statistical distributions, is proposed and implemented into an elastic viscoplastic self-consistent (EVPSC) framework to simultaneously describe both stress and strain relaxation. The model captures the experimental data in terms of macroscopic stress strain curves, evolution of stress and strain during holding, as well as evolution of the internal elastic strains. Model results indicate that themore » magnitude of the stress relaxed during strain holding is dependent on both, the magnitude of the flow stress and the spread of the resolved shear stress distribution. The magnitude of strain accumulated during stress holding is, on the other hand, dependent on the magnitude of the hardening rate and on the spread of the resolved shear stress distribution. Furthermore, the internal elastic strains are directly correlated with the stress state, and hence the stress relaxation during strain holds has a greater influence on the lattice strains than strain relaxation during stress holds.« less
Stress and strain relaxation in magnesium AZ31 rolled plate: In-situ neutron measurement and elastic viscoplastic polycrystal modeling

DOE PAGES

Wang, Huamiao; Clausen, Bjorn; Capolungo, Laurent; ...

2015-07-16

Continuous mechanical tests with strain holds (stress relaxation) and with stress holds (strain relaxation) are performed simultaneously with in-situ neutron measurements to analyze the mechanisms of stress and strain relaxation in Mg AZ31 rolled plate. A dislocation activity based constitutive model, accounting for internal stress statistical distributions, is proposed and implemented into an elastic viscoplastic self-consistent (EVPSC) framework to simultaneously describe both stress and strain relaxation. The model captures the experimental data in terms of macroscopic stress strain curves, evolution of stress and strain during holding, as well as evolution of the internal elastic strains. Model results indicate that themore » magnitude of the stress relaxed during strain holding is dependent on both, the magnitude of the flow stress and the spread of the resolved shear stress distribution. The magnitude of strain accumulated during stress holding is, on the other hand, dependent on the magnitude of the hardening rate and on the spread of the resolved shear stress distribution. Furthermore, the internal elastic strains are directly correlated with the stress state, and hence the stress relaxation during strain holds has a greater influence on the lattice strains than strain relaxation during stress holds.« less
RH1020 Single Event Clock Upset Summary Report

NASA Technical Reports Server (NTRS)

Katz, Richard B.; Wang, J. J.

1998-01-01

This report summarizes the testing and analysis of "single event clock upset' in the RH1020. Also included are SEU-rate predictions and design recommendations for risk analysis and reduction. The subject of "upsets" in the RH1020 is best understood by using a model consisting of a global clock buffer and a D-type flip-flop as the basic memory unit. The RH1020 is built on the ACT 1 family architecture. As such, it has one low-skew global clock buffer with a TTL-level input threshold that is accessed via a single dedicated pin. The clock signal is driven to full CMOS levels, buffered, and sent to individual row buffers with one buffer per channel. For low-skew performance, the outputs of all of the RH1020 row buffers are shorted together via metal lines, as is done in the A1020B. All storage in the RH1020 consists of routed flip-flops, constructed with multiplexors and feedback through the routing segments. A simple latch can be constructed from a single (combinatorial or C) module; an edge-triggered flip-flop is constructed using two concatenated latches. There is no storage in the I/O modules. The front end of the clock buffering circuitry, at a common point relative to the row buffer, is a sub-circuit that was determined to be the most susceptible to heavy ions. This is due, in part, to its smaller transistors compared to the rest of the circuitry. This conclusion is also supported by SPICE simulations and an analysis of the heavy ion data, described in this report. The edge triggered D flip-flop has two single-event-upset modes. Mode one, called C-module upset, is caused by a heavy ion striking the C-module's sensitive area on the silicon and produces a soft single bit error at the output of the flip-flop. Mode two, called clock upset, is caused by a heavy ion strike on the clock buffer, generating a runt pulse interpreted as a false clock signal and consequently producing errors at the flip-flop outputs. C-module upset sensitivity in the RH1020 is essentially the same as that of its ACT 1 siblings (A1020, A1020A and A1020B), which were well tested, analyzed, and documented in the literature.
Phenomenological description of depoling current in Pb0.99Nb0.02(Zr0.95Ti0.05)0.98O3 ferroelectric ceramics under shock wave compression: Relaxation model

NASA Astrophysics Data System (ADS)

Jiang, Dongdong; Du, Jinmei; Gu, Yan; Feng, Yujun

2012-05-01

By assuming a relaxation process for depolarization associated with the ferroelectric (FE) to antiferroelectric (AFE) phase transition in Pb0.99Nb0.02(Zr0.95Ti0.05)0.98O3 ferroelectric ceramics under shock wave compression, we build a new model for the depoling current, which is different from both the traditional constant current source (CCS) model and the phase transition kinetics (PTK) model. The characteristic relaxation time and new-equilibrated polarization are dependent on both the shock pressure and electric field. After incorporating a Maxwell s equation, the relaxation model developed applies to all the depoling currents under short-circuit condition and high-impedance condition. Influences of shock pressure, load resistance, dielectric property, and electrical conductivity on the depoling current are also discussed. The relaxation model gives a good description about the suppressing effect of the self-generated electric field on the FE-to-AFE phase transition at low shock pressures, which cannot be described by the traditional models. After incorporating a time- and electric-field-dependent repolarization, this model predicts that the high-impedance current eventually becomes higher than the short-circuit current, which is consistent with the experimental results in the literature. Finally, we make the comparison between our relaxation model and the traditional CCS model and PTK model.
Slow relaxation of cascade-induced defects in Fe

DOE PAGES

Béland, Laurent Karim; Osetsky, Yuri N.; Stoller, Roger E.; ...

2015-02-17

On-the-fly kinetic Monte Carlo (KMC) simulations are performed to investigate slow relaxation of non-equilibrium systems. Point defects induced by 25 keV cascades in α -Fe are shown to lead to a characteristic time-evolution, described by the replenish and relax mechanism. Then, we produce an atomistically-based assessment of models proposed to explain the slow structural relaxation by focusing on the aggregation of 50 vacancies and 25 self-interstital atoms (SIA) in 10-lattice-parameter α-Fe boxes, two processes that are closely related to cascade annealing and exhibit similar time signature. Four atomistic effects explain the timescales involved in the evolution: defect concentration heterogeneities, concentration-enhancedmore » mobility, cluster-size dependent bond energies and defect-induced pressure. In conclusion, these findings suggest that the two main classes of models to explain slow structural relaxation, the Eyring model and the Gibbs model, both play a role to limit the rate of relaxation of these simple point-defect systems.« less
Defect-phase-dynamics approach to statistical domain-growth problem of clock models

NASA Technical Reports Server (NTRS)

Kawasaki, K.

1985-01-01

The growth of statistical domains in quenched Ising-like p-state clock models with p = 3 or more is investigated theoretically, reformulating the analysis of Ohta et al. (1982) in terms of a phase variable and studying the dynamics of defects introduced into the phase field when the phase variable becomes multivalued. The resulting defect/phase domain-growth equation is applied to the interpretation of Monte Carlo simulations in two dimensions (Kaski and Gunton, 1983; Grest and Srolovitz, 1984), and problems encountered in the analysis of related Potts models are discussed. In the two-dimensional case, the problem is essentially that of a purely dissipative Coulomb gas, with a sq rt t growth law complicated by vertex-pinning effects at small t.
Susceptibility of Redundant Versus Singular Clock Domains Implemented in SRAM-Based FPGA TMR Designs

NASA Technical Reports Server (NTRS)

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.
Hunting for dark matter with ultra-stable fibre as frequency delay system.

PubMed

Yang, Wanpeng; Li, Dawei; Zhang, Shuangyou; Zhao, Jianye

2015-07-10

Many cosmological observations point towards the existence of dark-matter(DM) particles and consider them as the main component of the matter content of the universe. The goal of revealing the nature of dark-matter has triggered the development of new, extremely sensitive detectors. It has been demonstrated that the frequencies and phases of optical clock have a transient shift during the DMs' arrival due to the DM-SM(Standard Model) coupling. A simple, reliable and feasible experimental scheme is firstly proposed in this paper, based on "frequency-delay system" to search dark-matter by "self-frequency comparison" of an optical clock. During the arrival of a dark-matter, frequency discrepancy is expected between two signals with a short time difference(~ms) of the same optical clock to exhibit the interaction between atoms and dark-matter. Furthermore, this process can determine the exact position of dark-matter when it is crossing the optical clocks, therefore a network of detecting stations located in different places is recommended to reduce the misjudgment risk to an acceptable level.
Hunting for dark matter with ultra-stable fibre as frequency delay system

PubMed Central

Yang, Wanpeng; Li, Dawei; Zhang, Shuangyou; Zhao, Jianye

2015-01-01

Many cosmological observations point towards the existence of dark-matter(DM) particles and consider them as the main component of the matter content of the universe. The goal of revealing the nature of dark-matter has triggered the development of new, extremely sensitive detectors. It has been demonstrated that the frequencies and phases of optical clock have a transient shift during the DMs’ arrival due to the DM-SM(Standard Model) coupling. A simple, reliable and feasible experimental scheme is firstly proposed in this paper, based on “frequency-delay system” to search dark-matter by “self-frequency comparison” of an optical clock. During the arrival of a dark-matter, frequency discrepancy is expected between two signals with a short time difference(~ms) of the same optical clock to exhibit the interaction between atoms and dark-matter. Furthermore, this process can determine the exact position of dark-matter when it is crossing the optical clocks, therefore a network of detecting stations located in different places is recommended to reduce the misjudgment risk to an acceptable level. PMID:26159113
Specific role of VTA dopamine neuronal firing rates and morphology in the reversal of anxiety-related, but not depression-related behavior in the ClockΔ19 mouse model of mania.

PubMed

Coque, Laurent; Mukherjee, Shibani; Cao, Jun-Li; Spencer, Sade; Marvin, Marian; Falcon, Edgardo; Sidor, Michelle M; Birnbaum, Shari G; Graham, Ami; Neve, Rachael L; Gordon, Elizabeth; Ozburn, Angela R; Goldberg, Matthew S; Han, Ming-Hu; Cooper, Donald C; McClung, Colleen A

2011-06-01

Lithium has been used extensively for mood stabilization, and it is particularly efficacious in the treatment of bipolar mania. Like other drugs used in the treatment of psychiatric diseases, it has little effect on the mood of healthy individuals. Our previous studies found that mice with a mutation in the Clock gene (ClockΔ19) have a complete behavioral profile that is very similar to human mania, which can be reversed with chronic lithium treatment. However, the cellular and physiological effects that underlie its targeted therapeutic efficacy remain unknown. Here we find that ClockΔ19 mice have an increase in dopaminergic activity in the ventral tegmental area (VTA), and that lithium treatment selectively reduces the firing rate in the mutant mice with no effect on activity in wild-type mice. Furthermore, lithium treatment reduces nucleus accumbens (NAc) dopamine levels selectively in the mutant mice. The increased dopaminergic activity in the Clock mutants is associated with cell volume changes in dopamine neurons, which are also rescued by lithium treatment. To determine the role of dopaminergic activity and morphological changes in dopamine neurons in manic-like behavior, we manipulated the excitability of these neurons by overexpressing an inwardly rectifying potassium channel subunit (Kir2.1) selectively in the VTA of ClockΔ19 mice and wild-type mice using viral-mediated gene transfer. Introduction of this channel mimics the effects of lithium treatment on the firing rate of dopamine neurons in ClockΔ19 mice and leads to a similar change in dopamine cell volume. Furthermore, reduction of dopaminergic firing rates in ClockΔ19 animals results in a normalization of locomotor- and anxiety-related behavior that is very similar to lithium treatment; however, it is not sufficient to reverse depression-related behavior. These results suggest that abnormalities in dopamine cell firing and associated morphology underlie alterations in anxiety-related behavior in bipolar mania, and that the therapeutic effects of lithium come from a reversal of these abnormal phenotypes.
Toward a detailed computational model for the mammalian circadian clock

NASA Astrophysics Data System (ADS)

Leloup, Jean-Christophe; Goldbeter, Albert

2003-06-01

We present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, Clock, and Rev-Erb genes. In agreement with experimental observations, the model can give rise to sustained circadian oscillations in continuous darkness, characterized by an antiphase relationship between Per/Cry/Rev-Erb and Bmal1 mRNAs. Sustained oscillations correspond to the rhythms autonomously generated by suprachiasmatic nuclei. For other parameter values, damped oscillations can also be obtained in the model. These oscillations, which transform into sustained oscillations when coupled to a periodic signal, correspond to rhythms produced by peripheral tissues. When incorporating the light-induced expression of the Per gene, the model accounts for entrainment of the oscillations by light-dark cycles. Simulations show that the phase of the oscillations can then vary by several hours with relatively minor changes in parameter values. Such a lability of the phase could account for physiological disorders related to circadian rhythms in humans, such as advanced or delayed sleep phase syndrome, whereas the lack of entrainment by light-dark cycles can be related to the non-24h sleep-wake syndrome. The model uncovers the possible existence of multiple sources of oscillatory behavior. Thus, in conditions where the indirect negative autoregulation of Per and Cry expression is inoperative, the model indicates the possibility that sustained oscillations might still arise from the negative autoregulation of Bmal1 expression.
Amazonian Amphibian Diversity Is Primarily Derived from Late Miocene Andean Lineages

PubMed Central

Santos, Juan C; Coloma, Luis A; Summers, Kyle; Caldwell, Janalee P; Ree, Richard; Cannatella, David C

2009-01-01

The Neotropics contains half of remaining rainforests and Earth's largest reservoir of amphibian biodiversity. However, determinants of Neotropical biodiversity (i.e., vicariance, dispersals, extinctions, and radiations) earlier than the Quaternary are largely unstudied. Using a novel method of ancestral area reconstruction and relaxed Bayesian clock analyses, we reconstructed the biogeography of the poison frog clade (Dendrobatidae). We rejected an Amazonian center-of-origin in favor of a complex connectivity model expanding over the Neotropics. We inferred 14 dispersals into and 18 out of Amazonia to adjacent regions; the Andes were the major source of dispersals into Amazonia. We found three episodes of lineage dispersal with two interleaved periods of vicariant events between South and Central America. During the late Miocene, Amazonian, and Central American-Chocoan lineages significantly increased their diversity compared to the Andean and Guianan-Venezuelan-Brazilian Shield counterparts. Significant percentage of dendrobatid diversity in Amazonia and Chocó resulted from repeated immigrations, with radiations at <10.0 million years ago (MYA), rather than in situ diversification. In contrast, the Andes, Venezuelan Highlands, and Guiana Shield have undergone extended in situ diversification at near constant rate since the Oligocene. The effects of Miocene paleogeographic events on Neotropical diversification dynamics provided the framework under which Quaternary patterns of endemism evolved. PMID:19278298
Archaeobatrachian paraphyly and pangaean diversification of crown-group frogs.

PubMed

Roelants, Kim; Bossuyt, Franky

2005-02-01

Current models for the early diversification of living frogs inferred from morphological, ontogenetic, or DNA sequence data invoke very different scenarios of character evolution and biogeography. To explore central controversies on the phylogeny of Anura, we analyzed nearly 4000 base pairs of mitochondrial and nuclear DNA for the major frog lineages. Likelihood-based analyses of this data set are congruent with morphological evidence in supporting a paraphyletic arrangement of archaeobatrachian frogs, with an (Ascaphus + Leiopelma) clade as the sister-group of all other living anurans. The stability of this outcome is reinforced by screening for phylogenetic bias resulting from site-specific rate variation, homoplasy, or the obligatory use of distantly related outgroups. Twenty-one alternative branching and rooting hypotheses were evaluated using a nonparametric multicomparison test and parametric bootstrapping. Relaxed molecular clock estimates situate the emergence of crown-group anurans in the Triassic, approximately 55 million years prior to their first appearance in the fossil record. The existence of at least four extant frog lineages on the supercontinent Pangaea before its breakup gains support from the estimation that three early splits between Laurasia- and Gondwana-associated families coincide with the initial rifting of these landmasses. This observation outlines the potential significance of this breakup event in the formation of separate Mesozoic faunal assemblages in both hemispheres.
The circadian clock in cancer development and therapy

USDA-ARS?s Scientific Manuscript database

Most aspects of mammalian function display circadian rhythms driven by an endogenous clock. The circadian clock is operated by genes and comprises a central clock in the brain that responds to environmental cues and controls subordinate clocks in peripheral tissues via circadian output pathways. The...
Dual-Mode Operation of an Optical Lattice Clock Using Strontium and Ytterbium Atoms.

PubMed

Akamatsu, Daisuke; Kobayashi, Takumi; Hisai, Yusuke; Tanabe, Takehiko; Hosaka, Kazumoto; Yasuda, Masami; Hong, Feng-Lei

2018-06-01

We have developed an optical lattice clock that can operate in dual modes: a strontium (Sr) clock mode and an ytterbium (Yb) clock mode. Dual-mode operation of the Sr-Yb optical lattice clock is achieved by alternately cooling and trapping 87 Sr and 171 Yb atoms inside the vacuum chamber of the clock. Optical lattices for Sr and Yb atoms were arranged with horizontal and vertical configurations, respectively, resulting in a small distance of the order of between the trapped Sr and Yb atoms. The 1 S 0 - 3 P 0 clock transitions in the trapped atoms were interrogated in turn and the clock lasers were stabilized to the transitions. We demonstrated the frequency ratio measurement of the Sr and Yb clock transitions by using the dual-mode operation of the Sr-Yb optical lattice clock. The dual-mode operation can reduce the uncertainty of the blackbody radiation shift in the frequency ratio measurement, because both Sr and Yb atoms share the same blackbody radiation.

Derivation and experimental verification of clock synchronization theory

NASA Technical Reports Server (NTRS)

Palumbo, Daniel L.

1994-01-01

The objective of this work is to validate mathematically derived clock synchronization theories and their associated algorithms through experiment. Two theories are considered, the Interactive Convergence Clock Synchronization Algorithm and the Mid-Point Algorithm. Special clock circuitry was designed and built so that several operating conditions and failure modes (including malicious failures) could be tested. Both theories are shown to predict conservative upper bounds (i.e., measured values of clock skew were always less than the theory prediction). Insight gained during experimentation led to alternative derivations of the theories. These new theories accurately predict the clock system's behavior. It is found that a 100% penalty is paid to tolerate worst case failures. It is also shown that under optimal conditions (with minimum error and no failures) the clock skew can be as much as 3 clock ticks. Clock skew grows to 6 clock ticks when failures are present. Finally, it is concluded that one cannot rely solely on test procedures or theoretical analysis to predict worst case conditions. conditions.
Experimental validation of clock synchronization algorithms

NASA Technical Reports Server (NTRS)

Palumbo, Daniel L.; Graham, R. Lynn

1992-01-01

The objective of this work is to validate mathematically derived clock synchronization theories and their associated algorithms through experiment. Two theories are considered, the Interactive Convergence Clock Synchronization Algorithm and the Midpoint Algorithm. Special clock circuitry was designed and built so that several operating conditions and failure modes (including malicious failures) could be tested. Both theories are shown to predict conservative upper bounds (i.e., measured values of clock skew were always less than the theory prediction). Insight gained during experimentation led to alternative derivations of the theories. These new theories accurately predict the behavior of the clock system. It is found that a 100 percent penalty is paid to tolerate worst-case failures. It is also shown that under optimal conditions (with minimum error and no failures) the clock skew can be as much as three clock ticks. Clock skew grows to six clock ticks when failures are present. Finally, it is concluded that one cannot rely solely on test procedures or theoretical analysis to predict worst-case conditions.
A numerical study of the South China Sea Warm Current during winter monsoon relaxation

NASA Astrophysics Data System (ADS)

Zhang, Cong; Ding, Yang; Bao, Xianwen; Bi, Congcong; Li, Ruixiang; Zhang, Cunjie; Shen, Biao; Wan, Kai

2018-03-01

Using a Finite-Volume Community Ocean Model, we investigated the dynamic mechanism of the South China Sea Warm Current (SCSWC) in the northern South China Sea (NSCS) during winter monsoon relaxation. The model reproduces the mean surface circulation of the NSCS during winter, while model-simulated subtidal currents generally capture its current pattern. The model shows that the current over the continental shelf is generally southwestward, under a strong winter monsoon condition, but a northeastward counter-wind current usually develops between 50-and 100-m isobaths, when the monsoon relaxes. Model experiments, focusing on the wind relaxation process, show that sea level is elevated in the northwestern South China Sea (SCS), related to the persistent northeasterly monsoon. Following wind relaxation, a high sea level band builds up along the mid-shelf, and a northeastward current develops, having an obvious vertical barotropic structure. Momentum balance analysis indicates that an along-shelf pressure gradient provides the initial driving force for the SCSWC during the first few days following wind relaxation. The SCSWC subsequently reaches a steady quasi-geostrophic balance in the cross-shelf direction, mainly linked to sea level adjustment over the shelf. Lagrangian particle tracking experiments show that both the southwestward coastal current and slope current contribute to the northeastward movement of the SCSWC during winter monsoon relaxation.
Clock Drawing in Spatial Neglect: A Comprehensive Analysis of Clock Perimeter, Placement, and Accuracy

PubMed Central

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
Critical thickness and strain relaxation in high-misfit heteroepitaxial systems: PbTe1-xSex on PbSe (001)

NASA Astrophysics Data System (ADS)

Wiesauer, Karin; Springholz, G.

2004-06-01

Strain relaxation and misfit dislocation formation is investigated for the high-misfit PbTe1-xSex/PbSe (001) heteroepitaxial system in which the lattice mismatch varies from 0% to 5.5%. Because a two-dimensional (2D) layer growth prevails for all PbTe1-xSex ternary compositions, the lattice mismatch is relaxed purely by misfit dislocations. In addition, it is found that strain relaxation is not hindered by dislocation kinetics. Therefore, this material combination is an ideal model system for testing the equilibrium Frank van der Merwe and Matthews Blakeslee strain relaxation models. In our experiments, we find significantly lower values of the critical layer thickness as compared to the model predictions. This discrepancy is caused by the inappropriate description of the dislocation self-energies when the layer thickness becomes comparable to the dislocation core radius. To resolve this problem, a modified expression for the dislocation self-energy is proposed. The resulting theoretical critical thicknesses are in excellent agreement with the experimental data. In addition, a remarkable universal scaling behavior is found for the strain relaxation data. This underlines the breakdown of the current strain relaxation models.
Mission Assignment Model and Simulation Tool for Different Types of Unmanned Aerial Vehicles

DTIC Science & Technology

2008-09-01

TABLE OF ABBREVIATIONS AND ACRONYMS AAA Anti Aircraft Artillery ATO Air Tasking Order BDA Battle Damage Assessment DES Discrete Event Simulation...clock is advanced in small, fixed time steps. Since the value of simulated time is important in DES , an internal variable, called as simulation clock...VEHICLES Yücel Alver Captain, Turkish Air Force B.S., Turkish Air Force Academy, 2000 Murat Özdoğan 1st Lieutenant, Turkish Air Force B.S., Turkish
Shuttle Global Positioning System (GPS) system design study

NASA Technical Reports Server (NTRS)

Nilsen, P. W.

1979-01-01

The various integration problems in the Shuttle GPS system were investigated. The analysis of the Shuttle GPS link was studied. A preamplifier was designed since the Shuttle GPS antennas must be located remotely from the receiver. Several GPS receiver architecture trade-offs were discussed. The Shuttle RF harmonics and intermode that fall within the GPS receiver bandwidth were analyzed. The GPS PN code acquisition was examined. Since the receiver clock strongly affects both GPS carrier and code acquisition performance, a clock model was developed.
A Neural Network Underlying Circadian Entrainment and Photoperiodic Adjustment of Sleep and Activity in Drosophila.

PubMed

Schlichting, Matthias; Menegazzi, Pamela; Lelito, Katharine R; Yao, Zepeng; Buhl, Edgar; Dalla Benetta, Elena; Bahle, Andrew; Denike, Jennifer; Hodge, James John; Helfrich-Förster, Charlotte; Shafer, Orie Thomas

2016-08-31

A sensitivity of the circadian clock to light/dark cycles ensures that biological rhythms maintain optimal phase relationships with the external day. In animals, the circadian clock neuron network (CCNN) driving sleep/activity rhythms receives light input from multiple photoreceptors, but how these photoreceptors modulate CCNN components is not well understood. Here we show that the Hofbauer-Buchner eyelets differentially modulate two classes of ventral lateral neurons (LNvs) within the Drosophila CCNN. The eyelets antagonize Cryptochrome (CRY)- and compound-eye-based photoreception in the large LNvs while synergizing CRY-mediated photoreception in the small LNvs. Furthermore, we show that the large LNvs interact with subsets of "evening cells" to adjust the timing of the evening peak of activity in a day length-dependent manner. Our work identifies a peptidergic connection between the large LNvs and a group of evening cells that is critical for the seasonal adjustment of circadian rhythms. In animals, circadian clocks have evolved to orchestrate the timing of behavior and metabolism. Consistent timing requires the entrainment these clocks to the solar day, a process that is critical for an organism's health. Light cycles are the most important external cue for the entrainment of circadian clocks, and the circadian system uses multiple photoreceptors to link timekeeping to the light/dark cycle. How light information from these photorecptors is integrated into the circadian clock neuron network to support entrainment is not understood. Our results establish that input from the HB eyelets differentially impacts the physiology of neuronal subgroups. This input pathway, together with input from the compound eyes, precisely times the activity of flies under long summer days. Our results provide a mechanistic model of light transduction and integration into the circadian system, identifying new and unexpected network motifs within the circadian clock neuron network. Copyright © 2016 the authors 0270-6474/16/369084-13$15.00/0.
Laser Ranging to the Lunar Reconnaissance Orbiter: improved timing and orbits

NASA Astrophysics Data System (ADS)

Mao, D.; Mcgarry, J.; Sun, X.; Torrence, M. H.; Skillman, D.; Hoffman, E.; Mazarico, E.; Rowlands, D. D.; Golder, J.; Barker, M. K.; Neumann, G. A.; Smith, D. E.; Zuber, M. T.

2013-12-01

The Laser ranging (LR) experiment to the Lunar Reconnaissance Orbiter (LRO) has been under operation for more than 4 years, since the launch of the spacecraft in June 2009. Led by NASA's Next Generation Satellite Laser Ranging(NGSLR) station at Greenbelt, Maryland, ten laser ranging stations over the world have been participating in the experiment and have collected over 3,200 hours of ranging data. These range measurements are used to monitor the behavior of the LRO clock and to generate orbital solutions for LRO. To achieve high-quality results in range, ground stations like NGSLR are using H-maser clocks to obtain a stable and continuous time baseline for the orbit solutions. An All-View GPS receiver was included at NGSLR since January 2013 which monitors the H-maser time against the master clock at the United State Naval Observatory (USNO) via the GPS satellites. NGSLR has successfully established nano-second level epoch time accuracy and 10-15 clock stability since then. Time transfer experiments using LRO as a common receiver have been verified in ground testing between NGSLR and MOBLAS7 via a ground terminal with a Lunar Orbiter Laser Altimeter (LOLA)-like receiver at Greenbelt, Maryland. Two hour-long ground tests using a LOLA-like detector and two different ground targets yielded results consistent with each other, and those from the previous 10-minute test completed one year ago. Time transfer tests between NGSLR and MOBLAS7 via LRO are ongoing. More time transfer tests are being planned from NGSLR to McDonald Laser Ranging Station (MLRS) in Texas and later from NGSLR to European satellite laser ranging (SLR) stations. Upon the completion of these time transfer experiments, nanosecond-level epoch time accuracy will be brought to stations besides NGSLR, and such high precision of the ground time can contribute to the LRO precision orbit determination (POD) process. Presently, by using the high-resolution GRAIL gravity models, the LRO orbits determined from LR data alone have a total position error of 10 meters in average, and show the same quality as those generated using conventional radiometric tracking data. In these LR orbital solutions, a bias was adjusted to compensate both the ground and spacecraft clock characteristics. By taking advantage of the knowledge we have gained through LR of the long-term stability of the LRO clock, the spacecraft clock behavior is separated from the ground station clocks and modeled over a 10-month time span in our current POD process. Here we present the results from this new approach, and further improvements in the quality of the orbital reconstruction.
Dating of the human-ape splitting by a molecular clock of mitochondrial DNA.

PubMed

Hasegawa, M; Kishino, H; Yano, T

1985-01-01

A new statistical method for estimating divergence dates of species from DNA sequence data by a molecular clock approach is developed. This method takes into account effectively the information contained in a set of DNA sequence data. The molecular clock of mitochondrial DNA (mtDNA) was calibrated by setting the date of divergence between primates and ungulates at the Cretaceous-Tertiary boundary (65 million years ago), when the extinction of dinosaurs occurred. A generalized least-squares method was applied in fitting a model to mtDNA sequence data, and the clock gave dates of 92.3 +/- 11.7, 13.3 +/- 1.5, 10.9 +/- 1.2, 3.7 +/- 0.6, and 2.7 +/- 0.6 million years ago (where the second of each pair of numbers is the standard deviation) for the separation of mouse, gibbon, orangutan, gorilla, and chimpanzee, respectively, from the line leading to humans. Although there is some uncertainty in the clock, this dating may pose a problem for the widely believed hypothesis that the pipedal creature Australopithecus afarensis, which lived some 3.7 million years ago at Laetoli in Tanzania and at Hadar in Ethiopia, was ancestral to man and evolved after the human-ape splitting. Another likelier possibility is that mtDNA was transferred through hybridization between a proto-human and a proto-chimpanzee after the former had developed bipedalism.
PPAR{alpha} is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirai, Hidenori; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8502; Oishi, Katsutaka

Recent progress at the molecular level has revealed that nuclear receptors play an important role in the generation of mammalian circadian rhythms. To examine whether peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is involved in the regulation of circadian behavioral rhythms in mammals, we evaluated the locomotor activity of mice administered with the hypolipidemic PPAR{alpha} ligand, bezafibrate. Circadian locomotor activity was phase-advanced about 3 h in mice given bezafibrate under light-dark (LD) conditions. Transfer from LD to constant darkness did not change the onset of activity in these mice, suggesting that bezafibrate advanced the phase of the endogenous clock. Surprisingly, bezafibrate alsomore » advanced the phase in mice with lesions of the suprachiasmatic nucleus (SCN; the central clock in mammals). The circadian expression of clock genes such as period2, BMAL1, and Rev-erb{alpha} was also phase-advanced in various tissues (cortex, liver, and fat) without affecting the SCN. Bezafibrate also phase-advanced the activity phase that is delayed in model mice with delayed sleep phase syndrome (DSPS) due to a Clock gene mutation. Our results indicated that PPAR{alpha} is involved in circadian clock control independently of the SCN and that PPAR{alpha} could be a potent target of drugs to treat circadian rhythm sleep disorders including DSPS.« less
The Effects of Race Conditions when Implementing Single-Source Redundant Clock Trees in Triple Modular Redundant Synchronous Architectures

NASA Technical Reports Server (NTRS)

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. Heavy-ion radiation data show that a singular clock domain (DTMR) provides an improved TMR methodology for SRAM-based FPGAs over redundant clocks.
Real-time simulation clock

NASA Technical Reports Server (NTRS)

Bennington, Donald R. (Inventor); Crawford, Daniel J. (Inventor)

1990-01-01

The invention is a clock for synchronizing operations within a high-speed, distributed data processing network. The clock is actually a distributed system comprising a central clock and multiple site clock interface units (SCIUs) which are connected by means of a fiber optic star network and which operate under control of separate clock software. The presently preferred embodiment is a part of the flight simulation system now in current use at the NASA Langley Research Center.
The mammalian circadian clock and its entrainment by stress and exercise.

PubMed

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.
Noninvasive method for assessing the human circadian clock using hair follicle cells

PubMed Central

Akashi, Makoto; Soma, Haruhiko; Yamamoto, Takuro; Tsugitomi, Asuka; Yamashita, Shiko; Yamamoto, Takuya; Nishida, Eisuke; Yasuda, Akio; Liao, James K.; Node, Koichi

2010-01-01

A thorough understanding of the circadian clock requires qualitative evaluation of circadian clock gene expression. Thus far, no simple and effective method for detecting human clock gene expression has become available. This limitation has greatly hampered our understanding of human circadian rhythm. Here we report a convenient, reliable, and less invasive method for detecting human clock gene expression using biopsy samples of hair follicle cells from the head or chin. We show that the circadian phase of clock gene expression in hair follicle cells accurately reflects that of individual behavioral rhythms, demonstrating that this strategy is appropriate for evaluating the human peripheral circadian clock. Furthermore, using this method, we indicate that rotating shift workers suffer from a serious time lag between circadian gene expression rhythms and lifestyle. Qualitative evaluation of clock gene expression in hair follicle cells, therefore, may be an effective approach for studying the human circadian clock in the clinical setting. PMID:20798039
Novel transcriptional networks regulated by CLOCK in human neurons.

PubMed

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.
Generating clock signals for a cycle accurate, cycle reproducible FPGA based hardware accelerator

DOEpatents

Asaad, Sameth W.; Kapur, Mohit

2016-01-05

A method, system and computer program product are disclosed for generating clock signals for a cycle accurate FPGA based hardware accelerator used to simulate operations of a device-under-test (DUT). In one embodiment, the DUT includes multiple device clocks generating multiple device clock signals at multiple frequencies and at a defined frequency ratio; and the FPG hardware accelerator includes multiple accelerator clocks generating multiple accelerator clock signals to operate the FPGA hardware accelerator to simulate the operations of the DUT. In one embodiment, operations of the DUT are mapped to the FPGA hardware accelerator, and the accelerator clock signals are generated at multiple frequencies and at the defined frequency ratio of the frequencies of the multiple device clocks, to maintain cycle accuracy between the DUT and the FPGA hardware accelerator. In an embodiment, the FPGA hardware accelerator may be used to control the frequencies of the multiple device clocks.
Light signaling to the zebrafish circadian clock by Cryptochrome 1a

PubMed Central

Tamai, T. Katherine; Young, Lucy C.; Whitmore, David

2007-01-01

Zebrafish tissues and cells have the unusual feature of not only containing a circadian clock, but also being directly light-responsive. Several zebrafish genes are induced by light, but little is known about their role in clock resetting or the mechanism by which this might occur. Here we show that Cryptochrome 1a (Cry1a) plays a key role in light entrainment of the zebrafish clock. Intensity and phase response curves reveal a strong correlation between light induction of Cry1a and clock resetting. Overexpression studies show that Cry1a acts as a potent repressor of clock function and mimics the effect of constant light to “stop” the circadian oscillator. Yeast two-hybrid analysis demonstrates that the Cry1a protein interacts directly with specific regions of core clock components, CLOCK and BMAL, blocking their ability to fully dimerize and transactivate downstream targets, providing a likely mechanism for clock resetting. A comparison of entrainment of zebrafish cells to complete versus skeleton photoperiods reveals that clock phase is identical under these two conditions. However, the amplitude of the core clock oscillation is much higher on a complete photoperiod, as are the levels of light-induced Cry1a. We believe that Cry1a acts on the core clock machinery in both a continuous and discrete fashion, leading not only to entrainment, but also to the establishment of a high-amplitude rhythm and even stopping of the clock under long photoperiods. PMID:17785416
CLOCK phosphorylation by AKT regulates its nuclear accumulation and circadian gene expression in peripheral tissues.

PubMed

Luciano, Amelia K; Zhou, Wenping; Santana, Jeans M; Kyriakides, Cleo; Velazquez, Heino; Sessa, William C

2018-06-08

C ircadian l ocomotor o utput c ycles k aput (CLOCK) is a transcription factor that activates transcription of clock-controlled genes by heterodimerizing with BMAL1 and binding to E-box elements on DNA. Although several phosphorylation sites on CLOCK have already been identified, this study characterizes a novel phosphorylation site at serine 845 (Ser-836 in humans). Here, we show that CLOCK is a novel AKT substrate in vitro and in cells, and this phosphorylation site is a negative regulator of CLOCK nuclear localization by acting as a binding site for 14-3-3 proteins. To examine the role of CLOCK phosphorylation in vivo , Clock S845A knockin mice were generated using CRISPR/Cas9 technology. Clock S845A mice are essentially normal with normal central circadian rhythms and hemodynamics. However, examination of core circadian gene expression from peripheral tissues demonstrated that Clock S845A mice have diminished expression of Per2, Reverba, Dbp, and Npas2 in skeletal muscle and Per2, Reverba, Dbp, Per1 , Rora, and Npas2 in the liver during the circadian cycle. The reduction in Dbp levels is associated with reduced H3K9ac at E-boxes where CLOCK binds despite no change in total CLOCK levels. Thus, CLOCK phosphorylation by AKT on Ser-845 regulates its nuclear translocation and the expression levels of certain core circadian genes in insulin-sensitive tissues.
The circadian clock network in the brain of different Drosophila species.

PubMed

Hermann, Christiane; Saccon, Rachele; Senthilan, Pingkalai R; Domnik, Lilith; Dircksen, Heinrich; Yoshii, Taishi; Helfrich-Förster, Charlotte

2013-02-01

Comparative studies on cellular and molecular clock mechanisms have revealed striking similarities in the organization of the clocks among different animal groups. To gain evolutionary insight into the properties of the clock network within the Drosophila genus, we analyzed sequence identities and similarities of clock protein homologues and immunostained brains of 10 different Drosophila species using antibodies against vrille (VRI), PAR-protein domain1 (PDP1), and cryptochrome (CRY). We found that the clock network of both subgenera Sophophora and Drosophila consists of all lateral and dorsal clock neuron clusters that were previously described in Drosophila melanogaster. Immunostaining against CRY and the neuropeptide pigment-dispersing factor (PDF), however, revealed species-specific differences. All species of the Drosophila subgenus and D. pseudoobscura of the Sophophora subgenus completely lacked CRY in the large ventrolateral clock neurons (lLN(v) s) and showed reduced PDF immunostaining in the small ventrolateral clock neurons (sLN(v) s). In contrast, we found the expression of the ion transport peptide (ITP) to be consistent within the fifth sLN(v) and one dorsolateral clock neuron (LN(d) ) in all investigated species, suggesting a conserved putative function of this neuropeptide in the clock. We conclude that the general anatomy of the clock network is highly conserved throughout the Drosophila genus, although there is variation in PDF and CRY expression. Our comparative study is a first step toward understanding the organization of the circadian clock in Drosophila species adapted to different habitats. Copyright © 2012 Wiley Periodicals, Inc.

A Riemann solver for single-phase and two-phase shallow flow models based on relaxation. Relations with Roe and VFRoe solvers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pelanti, Marica, E-mail: Marica.Pelanti@ens.f; Bouchut, Francois, E-mail: francois.bouchut@univ-mlv.f; Mangeney, Anne, E-mail: mangeney@ipgp.jussieu.f

2011-02-01

We present a Riemann solver derived by a relaxation technique for classical single-phase shallow flow equations and for a two-phase shallow flow model describing a mixture of solid granular material and fluid. Our primary interest is the numerical approximation of this two-phase solid/fluid model, whose complexity poses numerical difficulties that cannot be efficiently addressed by existing solvers. In particular, we are concerned with ensuring a robust treatment of dry bed states. The relaxation system used by the proposed solver is formulated by introducing auxiliary variables that replace the momenta in the spatial gradients of the original model systems. The resultingmore » relaxation solver is related to Roe solver in that its Riemann solution for the flow height and relaxation variables is formally computed as Roe's Riemann solution. The relaxation solver has the advantage of a certain degree of freedom in the specification of the wave structure through the choice of the relaxation parameters. This flexibility can be exploited to handle robustly vacuum states, which is a well known difficulty of standard Roe's method, while maintaining Roe's low diffusivity. For the single-phase model positivity of flow height is rigorously preserved. For the two-phase model positivity of volume fractions in general is not ensured, and a suitable restriction on the CFL number might be needed. Nonetheless, numerical experiments suggest that the proposed two-phase flow solver efficiently models wet/dry fronts and vacuum formation for a large range of flow conditions. As a corollary of our study, we show that for single-phase shallow flow equations the relaxation solver is formally equivalent to the VFRoe solver with conservative variables of Gallouet and Masella [T. Gallouet, J.-M. Masella, Un schema de Godunov approche C.R. Acad. Sci. Paris, Serie I, 323 (1996) 77-84]. The relaxation interpretation allows establishing positivity conditions for this VFRoe method.« less
Z n clock models and chains of so(n)2 non-Abelian anyons: symmetries, integrable points and low energy properties

NASA Astrophysics Data System (ADS)

Finch, Peter E.; Flohr, Michael; Frahm, Holger

2018-02-01

We study two families of quantum models which have been used previously to investigate the effect of topological symmetries in one-dimensional correlated matter. Various striking similarities are observed between certain {Z}n quantum clock models, spin chains generalizing the Ising model, and chains of non-Abelian anyons constructed from the so(n)2 fusion category for odd n, both subject to periodic boundary conditions. In spite of the differences between these two types of quantum chains, e.g. their Hilbert spaces being spanned by tensor products of local spin states or fusion paths of anyons, the symmetries of the lattice models are shown to be closely related. Furthermore, under a suitable mapping between the parameters describing the interaction between spins and anyons the respective Hamiltonians share part of their energy spectrum (although their degeneracies may differ). This spin-anyon correspondence can be extended by fine-tuning of the coupling constants leading to exactly solvable models. We show that the algebraic structures underlying the integrability of the clock models and the anyon chain are the same. For n = 3,5,7 we perform an extensive finite size study—both numerical and based on the exact solution—of these models to map out their ground state phase diagram and to identify the effective field theories describing their low energy behaviour. We observe that the continuum limit at the integrable points can be described by rational conformal field theories with extended symmetry algebras which can be related to the discrete ones of the lattice models.
EPAs Virtual Embryo: Modeling Developmental Toxicity

EPA Science Inventory

Embryogenesis is regulated by concurrent activities of signaling pathways organized into networks that control spatial patterning, molecular clocks, morphogenetic rearrangements and cell differentiation. Quantitative mathematical and computational models are needed to better unde...
Light effects in the atomic-motion-induced Ramsey narrowing of dark resonances in wall-coated cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breschi, E.; Schori, C.; Di Domenico, G.

2010-12-15

We report on light shift and broadening in the atomic-motion-induced Ramsey narrowing of dark resonances prepared in alkali-metal vapors contained in wall-coated cells without buffer gas. The atomic-motion-induced Ramsey narrowing is due to the free motion of the polarized atomic spins in and out of the optical interaction region before spin relaxation. As a consequence of this effect, we observe a narrowing of the dark resonance linewidth as well as a reduction of the ground states' light shift when the volume of the interaction region decreases at constant optical intensity. The results can be intuitively interpreted as a dilution ofmore » the intensity effect similar to a pulsed interrogation due to the atomic motion. Finally the influence of this effect on the performance of compact atomic clocks is discussed.« less
Phylogenetic Status and Timescale for the Diversification of Steno and Sotalia Dolphins

PubMed Central

Cunha, Haydée A.; Moraes, Lucas C.; Medeiros, Bruna V.; Lailson-Brito, José; da Silva, Vera M. F.; Solé-Cava, Antonio M.; Schrago, Carlos G.

2011-01-01

Molecular data have provided many insights into cetacean evolution but some unsettled issues still remain. We estimated the topology and timing of cetacean evolutionary relationships using Bayesian and maximum likelihood analyses of complete mitochondrial genomes. In order to clarify the phylogenetic placement of Sotalia and Steno within the Delphinidae, we sequenced three new delphinid mitogenomes. Our analyses support three delphinid clades: one joining Steno and Sotalia (supporting the revised subfamily Stenoninae); another placing Sousa within the Delphininae; and a third, the Globicephalinae, which includes Globicephala, Feresa, Pseudorca, Peponocephala and Grampus. We also conclude that Orcinus does not belong in the Globicephalinae, but Orcaella may be part of that subfamily. Divergence dates were estimated using the relaxed molecular clock calibrated with fossil data. We hypothesise that the timing of separation of the marine and Amazonian Sotalia species (2.3 Ma) coincided with the establishment of the modern Amazon River basin. PMID:22163290
Phylogenetic status and timescale for the diversification of Steno and Sotalia dolphins.

PubMed

Cunha, Haydée A; Moraes, Lucas C; Medeiros, Bruna V; Lailson-Brito, José; da Silva, Vera M F; Solé-Cava, Antonio M; Schrago, Carlos G

2011-01-01

Molecular data have provided many insights into cetacean evolution but some unsettled issues still remain. We estimated the topology and timing of cetacean evolutionary relationships using bayesian and maximum likelihood analyses of complete mitochondrial genomes. In order to clarify the phylogenetic placement of Sotalia and Steno within the Delphinidae, we sequenced three new delphinid mitogenomes. Our analyses support three delphinid clades: one joining Steno and Sotalia (supporting the revised subfamily Stenoninae); another placing Sousa within the Delphininae; and a third, the Globicephalinae, which includes Globicephala, Feresa, Pseudorca, Peponocephala and Grampus. We also conclude that Orcinus does not belong in the Globicephalinae, but Orcaella may be part of that subfamily. Divergence dates were estimated using the relaxed molecular clock calibrated with fossil data. We hypothesise that the timing of separation of the marine and Amazonian Sotalia species (2.3 Ma) coincided with the establishment of the modern Amazon River basin.
Synchronization sampling method based on delta-sigma analog-digital converter for underwater towed array system.

PubMed

Jiang, Jia-Jia; Duan, Fa-Jie; Li, Yan-Chao; Hua, Xiang-Ning

2014-03-01

Synchronization sampling is very important in underwater towed array system where every acquisition node (AN) samples analog signals by its own analog-digital converter (ADC). In this paper, a simple and effective synchronization sampling method is proposed to ensure synchronized operation among different ANs of the underwater towed array system. We first present a master-slave synchronization sampling model, and then design a high accuracy phase-locked loop to synchronize all delta-sigma ADCs to a reference clock. However, when the master-slave synchronization sampling model is used, both the time-delay (TD) of messages traveling along the wired transmission medium and the jitter of the clocks will bring out synchronization sampling error (SSE). Therefore, a simple method is proposed to estimate and compensate the TD of the messages transmission, and then another effective method is presented to overcome the SSE caused by the jitter of the clocks. An experimental system with three ANs is set up, and the related experimental results verify the validity of the synchronization sampling method proposed in this paper.
Synchronization sampling method based on delta-sigma analog-digital converter for underwater towed array system

NASA Astrophysics Data System (ADS)

Jiang, Jia-Jia; Duan, Fa-Jie; Li, Yan-Chao; Hua, Xiang-Ning

2014-03-01

Synchronization sampling is very important in underwater towed array system where every acquisition node (AN) samples analog signals by its own analog-digital converter (ADC). In this paper, a simple and effective synchronization sampling method is proposed to ensure synchronized operation among different ANs of the underwater towed array system. We first present a master-slave synchronization sampling model, and then design a high accuracy phase-locked loop to synchronize all delta-sigma ADCs to a reference clock. However, when the master-slave synchronization sampling model is used, both the time-delay (TD) of messages traveling along the wired transmission medium and the jitter of the clocks will bring out synchronization sampling error (SSE). Therefore, a simple method is proposed to estimate and compensate the TD of the messages transmission, and then another effective method is presented to overcome the SSE caused by the jitter of the clocks. An experimental system with three ANs is set up, and the related experimental results verify the validity of the synchronization sampling method proposed in this paper.
Low Variation in the Polymorphic Clock Gene Poly-Q Region Despite Population Genetic Structure across Barn Swallow (Hirundo rustica) Populations

PubMed Central

Dor, Roi; Lovette, Irby J.; Safran, Rebecca J.; Billerman, Shawn M.; Huber, Gernot H.; Vortman, Yoni; Lotem, Arnon; McGowan, Andrew; Evans, Matthew R.; Cooper, Caren B.; Winkler, David W.

2011-01-01

Recent studies of several species have reported a latitudinal cline in the circadian clock gene, Clock, which influences rhythms in both physiology and behavior. Latitudinal variation in this gene may hence reflect local adaptation to seasonal variation. In some bird populations, there is also an among-individual association between Clock poly-Q genotype and clutch initiation date and incubation period. We examined Clock poly-Q allele variation in the Barn Swallow (Hirundo rustica), a species with a cosmopolitan geographic distribution and considerable variation in life-history traits that may be influenced by the circadian clock. We genotyped Barn Swallows from five populations (from three subspecies) and compared variation at the Clock locus to that at microsatellite loci and mitochondrial DNA (mtDNA). We found very low variation in the Clock poly-Q region, as >96% of individuals were homozygous, and the two other alleles at this locus were globally rare. Genetic differentiation based on the Clock poly-Q locus was not correlated with genetic differentiation based on either microsatellite loci or mtDNA sequences. Our results show that high diversity in Clock poly-Q is not general across avian species. The low Clock variation in the background of heterogeneity in microsatellite and mtDNA loci in Barn Swallows may be an outcome of stabilizing selection on the Clock locus. PMID:22216124
Lessons from (triggered) tremor

USGS Publications Warehouse

Gomberg, Joan

2010-01-01

I test a “clock-advance” model that implies triggered tremor is ambient tremor that occurs at a sped-up rate as a result of loading from passing seismic waves. This proposed model predicts that triggering probability is proportional to the product of the ambient tremor rate and a function describing the efficacy of the triggering wave to initiate a tremor event. Using data mostly from Cascadia, I have compared qualitatively a suite of teleseismic waves that did and did not trigger tremor with ambient tremor rates. Many of the observations are consistent with the model if the efficacy of the triggering wave depends on wave amplitude. One triggered tremor observation clearly violates the clock-advance model. The model prediction that larger triggering waves result in larger triggered tremor signals also appears inconsistent with the measurements. I conclude that the tremor source process is a more complex system than that described by the clock-advance model predictions tested. Results of this and previous studies also demonstrate that (1) conditions suitable for tremor generation exist in many tectonic environments, but, within each, only occur at particular spots whose locations change with time; (2) any fluid flow must be restricted to less than a meter; (3) the degree to which delayed failure and secondary triggering occurs is likely insignificant; and 4) both shear and dilatational deformations may trigger tremor. Triggered and ambient tremor rates correlate more strongly with stress than stressing rate, suggesting tremor sources result from time-dependent weakening processes rather than simple Coulomb failure.
Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis

PubMed Central

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 and environmental stress adaptation in plants. It is also envisioned that alternative splicing of the clock genes plays more complex roles than previously expected. PMID:24885185
Internal friction and mode relaxation in a simple chain model.

PubMed

Fugmann, S; Sokolov, I M

2009-12-21

We consider the equilibrium relaxation properties of the end-to-end distance and of the principal components in a one-dimensional polymer chain model with nonlinear interaction between the beads. While for the single-well potentials these properties are similar to the ones of a Rouse chain, for the double-well interaction potentials, modeling internal friction, they differ vastly from the ones of the harmonic chain at intermediate times and intermediate temperatures. This minimal description within a one-dimensional model mimics the relaxation properties found in much more complex polymer systems. Thus, the relaxation time of the end-to-end distance may grow by orders of magnitude at intermediate temperatures. The principal components (whose directions are shown to coincide with the normal modes of the harmonic chain, whatever interaction potential is assumed) not only display larger relaxation times but also subdiffusive scaling.
Biogeographical Consequences of Cenozoic Tectonic Events within East Asian Margins: A Case Study of Hynobius Biogeography

PubMed Central

Li, Jun; Fu, Cuizhang; Lei, Guangchun

2011-01-01

Few studies have explored the role of Cenozoic tectonic evolution in shaping patterns and processes of extant animal distributions within East Asian margins. We select Hynobius salamanders (Amphibia: Hynobiidae) as a model to examine biogeographical consequences of Cenozoic tectonic events within East Asian margins. First, we use GenBank molecular data to reconstruct phylogenetic interrelationships of Hynobius by Bayesian and maximum likelihood analyses. Second, we estimate the divergence time using the Bayesian relaxed clock approach and infer dispersal/vicariance histories under the ‘dispersal–extinction–cladogenesis’ model. Finally, we test whether evolutionary history and biogeographical processes of Hynobius should coincide with the predictions of two major hypotheses (the ‘vicariance’/‘out of southwestern Japan’ hypothesis). The resulting phylogeny confirmed Hynobius as a monophyletic group, which could be divided into nine major clades associated with six geographical areas. Our results show that: (1) the most recent common ancestor of Hynobius was distributed in southwestern Japan and Hokkaido Island, (2) a sister taxon relationship between Hynobius retardatus and all remaining species was the results of a vicariance event between Hokkaido Island and southwestern Japan in the Middle Eocene, (3) ancestral Hynobius in southwestern Japan dispersed into the Taiwan Island, central China, ‘Korean Peninsula and northeastern China’ as well as northeastern Honshu during the Late Eocene–Late Miocene. Our findings suggest that Cenozoic tectonic evolution plays an important role in shaping disjunctive distributions of extant Hynobius within East Asian margins. PMID:21738684
Evolution of the trypanorhynch tapeworms: parasite phylogeny supports independent lineages of sharks and rays.

PubMed

Olson, Peter D; Caira, Janine N; Jensen, Kirsten; Overstreet, Robin M; Palm, Harry W; Beveridge, Ian

2010-02-01

Trypanorhynch tapeworms (Platyhelminthes: Cestoda) are among the most diverse and abundant groups of metazoan parasites of elasmobranchs and are a ubiquitous part of the marine food webs that include these apex predators. Here we present a comprehensive analysis of their phylogeny, character evolution and host associations based on 10years of sampling effort, including representatives of 12 of 15 and 44 of 66 currently recognized trypanorhynch families and genera, respectively. Using a combination of ssrDNA and lsrDNA (Domains 1-3) for 79 and 80 taxa, respectively, we maintain one-to-one correspondence between molecules and morphology by scoring 45 characters from the same specimens used for sequencing, and provide museum vouchers for this material. Host associations are examined through likelihood-based ancestral character state reconstructions (ACSRs) and by estimating dates of divergence using strict and relaxed molecular clock models in a Bayesian context. Maximum parsimony and Bayesian inference analyses of rDNA produced well-resolved and strongly supported trees in which the trypanorhynchs formed two primary lineages and were monophyletic with respect to the diphyllidean outgroup taxa. These lineages showed marked differences in their rates of divergence which in turn resulted in differing support and stability characteristics within the lineages. Mapping of morphological characters onto the tree resulting from combined analysis of rDNA showed most traits to be highly plastic, including some previously considered of key taxonomic importance such as underlying symmetries in tentacular armature. The resulting tree was found to be congruent with the most recent morphologically based superfamily designations in the order, providing support for four proposed superfamilies, but not for the Tentacularioidea and Eutetrarhynchoidea. ACSRs based on the combined analysis of rDNA estimated the original hosts of the two primary parasite lineages to be alternatively rajiform batoids and carcharhiniform sharks. This fundamental split provides independent support for rejecting the notion that rays are derived sharks, and thus supports the most recent molecular phylogenies of the Neoselachii. Beyond the basal split between shark- and ray-inhabiting lineages, no pattern was found to suggest that the trypanorhynchs have closely tracked the evolutionary histories of these host lineages, but instead, it appears that host-switching has been common and that the subsequent evolution of the parasites has been ecologically driven primarily through overlap in the niches of their shark and ray hosts. Using a relaxed molecular clock model calibrated by means of host fossil data, the ray-inhabiting lineage is estimated to have diversified around the Jurassic-Cretaceous boundary, whereas the shark-inhabiting lineage is estimated to have diversified later, in the Middle Cretaceous. Although the large error associated with the estimated divergence dates prevents robust conclusions from being drawn, the dates are nevertheless found to be consistent in a relative sense with the origins of their major hosts groups. The erection and definition of the suborders Trypanobatoida and Trypanoselachoida, for the major clades of trypanorhynchs parasitizing primarily rays and sharks, respectively, is proposed for the two primary lineages recovered here. 2009. Published by Elsevier Ltd. All rights reserved.
Polymorphism in the CLOCK gene may influence the effect of fat intake reduction on weight loss.

PubMed

Loria-Kohen, Viviana; Espinosa-Salinas, Isabel; Marcos-Pasero, Helena; Lourenço-Nogueira, Thais; Herranz, Jesús; Molina, Susana; Reglero, Guillermo; Ramirez de Molina, Ana

2016-04-01

The aim of this study was to assess the effect of a weight loss treatment on obesity- associated variables with respect to the CLOCK and FTO genotypes. In all, 179 volunteers (78% female) participated in a 12-week calorie-restriction program; hypocaloric diets of between 5442 and 10048 kJ/d were individually prescribed to all participants. Dietetic, anthropometric, and biochemical data were collected at baseline and at the end of the intervention. When treatment was over, five single nucleotide polymorphisms (SNPs) were sought in CLOCK and FTO in all participants who provided consent. Bonferroni-corrected linear regression models were used to examine the influence of interactions of the type genotype × dietetic change on obesity-associated variables. Variation in the CLOCK and FTO genotypes had no significant influence on the change in obesity-associated variables. The interaction genotype × percentage intake of dietary fat had a significant influence on body mass index (BMI; adjusted P = 0.03). Participants carrying CLOCK rs3749474 (TT + CT) showed a positive association between the change in percentage intake of dietary fat and change in BMI (β = 0.044; 95% confidence interval [CI], 0.0119-0.0769; P = 0.008), whereas participants homozygous for the wild-type allele (CC) showed a negative, although nonsignificant association (β = -0.032; 95% CI, -0.0694 to 0.036; P = 0.077). The possession of CLOCK rs3749474 may influence the effect of reducing the percentage intake of dietary fat on obesity-associated variables. Participants carrying this SNP might benefit more than others from weight loss treatment involving dietary fat restriction. The treatment of obesity might therefore be customized, depending on the alleles carried. Copyright © 2016 Elsevier Inc. All rights reserved.
Obesity Disrupts Rhythmic Clock Gene Expression in Maternal Adipose Tissue during Rat Pregnancy.

PubMed

Crew, Rachael C; Mark, Peter J; Waddell, Brendan J

2018-06-01

Obesity during pregnancy causes numerous maternal and fetal health complications, but the underlying mechanisms remain unclear. Adipose tissue dysfunction in obesity has previously been linked to disruption of the intrinsic adipose clock gene network that is crucial for normal metabolic function. This adipose clock also undergoes major change as part of the maternal metabolic adaptation to pregnancy, but whether this is affected by maternal obesity is unknown. Consequently, in this study we tested the hypothesis that obesity disturbs rhythmic gene expression in maternal adipose tissue across pregnancy. A rat model of maternal obesity was established by cafeteria (CAF) feeding, and adipose expression of clock genes and associated nuclear receptors ( Ppars and Pgc1α) was measured across days 15-16 and 21-22 of gestation (term = 23 days). CAF feeding suppressed the mesor and/or amplitude of adipose tissue clock genes (most notably Bmal1, Per2, and Rev-erbα) relative to chow-fed controls (CON) across both days of gestation. On day 15, the CAF diet also induced adipose Pparα, Pparδ, and Pgc1α rhythmicity but repressed that of Pparγ, while expression of Pparα, Pparδ, and Pgc1α was reduced at select time points. CAF mothers were hyperleptinemic at both stages of gestation, and at day 21 this effect was time-of-day dependent. Fetal plasma leptin exhibited clear rhythmicity, albeit with low amplitude, but interestingly these levels were unaffected by CAF feeding. Our data show that maternal obesity disrupts rhythmic expression of clock and metabolic genes in maternal adipose tissue and leads to maternal but not fetal hyperleptinemia.
Drosophila TIM Binds Importin α1, and Acts as an Adapter to Transport PER to the Nucleus

PubMed Central

Jang, A. Reum; Moravcevic, Katarina; Saez, Lino; Young, Michael W.; Sehgal, Amita

2015-01-01

Regulated nuclear entry of clock proteins is a conserved feature of eukaryotic circadian clocks and serves to separate the phase of mRNA activation from mRNA repression in the molecular feedback loop. In Drosophila, nuclear entry of the clock proteins, PERIOD (PER) and TIMELESS (TIM), is tightly controlled, and impairments of this process produce profound behavioral phenotypes. We report here that nuclear entry of PER-TIM in clock cells, and consequently behavioral rhythms, require a specific member of a classic nuclear import pathway, Importin α1 (IMPα1). In addition to IMPα1, rhythmic behavior and nuclear expression of PER-TIM require a specific nuclear pore protein, Nup153, and Ran-GTPase. IMPα1 can also drive rapid and efficient nuclear expression of TIM and PER in cultured cells, although the effect on PER is mediated by TIM. Mapping of interaction domains between IMPα1 and TIM/PER suggests that TIM is the primary cargo for the importin machinery. This is supported by attenuated interaction of IMPα1 with TIM carrying a mutation previously shown to prevent nuclear entry of TIM and PER. TIM is detected at the nuclear envelope, and computational modeling suggests that it contains HEAT-ARM repeats typically found in karyopherins, consistent with its role as a co-transporter for PER. These findings suggest that although PER is the major timekeeper of the clock, TIM is the primary target of nuclear import mechanisms. Thus, the circadian clock uses specific components of the importin pathway with a novel twist in that TIM serves a karyopherin-like role for PER. PMID:25674790
Direct simulation Monte Carlo modeling of relaxation processes in polyatomic gases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pfeiffer, M., E-mail: mpfeiffer@irs.uni-stuttgart.de; Nizenkov, P., E-mail: nizenkov@irs.uni-stuttgart.de; Mirza, A., E-mail: mirza@irs.uni-stuttgart.de

2016-02-15

Relaxation processes of polyatomic molecules are modeled and implemented in an in-house Direct Simulation Monte Carlo code in order to enable the simulation of atmospheric entry maneuvers at Mars and Saturn’s Titan. The description of rotational and vibrational relaxation processes is derived from basic quantum-mechanics using a rigid rotator and a simple harmonic oscillator, respectively. Strategies regarding the vibrational relaxation process are investigated, where good agreement for the relaxation time according to the Landau-Teller expression is found for both methods, the established prohibiting double relaxation method and the new proposed multi-mode relaxation. Differences and applications areas of these two methodsmore » are discussed. Consequently, two numerical methods used for sampling of energy values from multi-dimensional distribution functions are compared. The proposed random-walk Metropolis algorithm enables the efficient treatment of multiple vibrational modes within a time step with reasonable computational effort. The implemented model is verified and validated by means of simple reservoir simulations and the comparison to experimental measurements of a hypersonic, carbon-dioxide flow around a flat-faced cylinder.« less
Direct simulation Monte Carlo modeling of relaxation processes in polyatomic gases

NASA Astrophysics Data System (ADS)

Pfeiffer, M.; Nizenkov, P.; Mirza, A.; Fasoulas, S.

2016-02-01

Relaxation processes of polyatomic molecules are modeled and implemented in an in-house Direct Simulation Monte Carlo code in order to enable the simulation of atmospheric entry maneuvers at Mars and Saturn's Titan. The description of rotational and vibrational relaxation processes is derived from basic quantum-mechanics using a rigid rotator and a simple harmonic oscillator, respectively. Strategies regarding the vibrational relaxation process are investigated, where good agreement for the relaxation time according to the Landau-Teller expression is found for both methods, the established prohibiting double relaxation method and the new proposed multi-mode relaxation. Differences and applications areas of these two methods are discussed. Consequently, two numerical methods used for sampling of energy values from multi-dimensional distribution functions are compared. The proposed random-walk Metropolis algorithm enables the efficient treatment of multiple vibrational modes within a time step with reasonable computational effort. The implemented model is verified and validated by means of simple reservoir simulations and the comparison to experimental measurements of a hypersonic, carbon-dioxide flow around a flat-faced cylinder.
Skeletal muscle tensile strain dependence: hyperviscoelastic nonlinearity

PubMed Central

Wheatley, Benjamin B; Morrow, Duane A; Odegard, Gregory M; Kaufman, Kenton R; Donahue, Tammy L Haut

2015-01-01

Introduction Computational modeling of skeletal muscle requires characterization at the tissue level. While most skeletal muscle studies focus on hyperelasticity, the goal of this study was to examine and model the nonlinear behavior of both time-independent and time-dependent properties of skeletal muscle as a function of strain. Materials and Methods Nine tibialis anterior muscles from New Zealand White rabbits were subject to five consecutive stress relaxation cycles of roughly 3% strain. Individual relaxation steps were fit with a three-term linear Prony series. Prony series coefficients and relaxation ratio were assessed for strain dependence using a general linear statistical model. A fully nonlinear constitutive model was employed to capture the strain dependence of both the viscoelastic and instantaneous components. Results Instantaneous modulus (p<0.0005) and mid-range relaxation (p<0.0005) increased significantly with strain level, while relaxation at longer time periods decreased with strain (p<0.0005). Time constants and overall relaxation ratio did not change with strain level (p>0.1). Additionally, the fully nonlinear hyperviscoelastic constitutive model provided an excellent fit to experimental data, while other models which included linear components failed to capture muscle function as accurately. Conclusions Material properties of skeletal muscle are strain-dependent at the tissue level. This strain dependence can be included in computational models of skeletal muscle performance with a fully nonlinear hyperviscoelastic model. PMID:26409235

Flexible programmable logic module

DOEpatents

Robertson, Perry J.; Hutchinson, Robert L.; Pierson, Lyndon G.

2001-01-01

The circuit module of this invention is a VME board containing a plurality of programmable logic devices (PLDs), a controlled impedance clock tree, and interconnecting buses. The PLDs are arranged to permit systolic processing of a problem by offering wide data buses and a plurality of processing nodes. The board contains a clock reference and clock distribution tree that can drive each of the PLDs with two critically timed clock references. External clock references can be used to drive additional circuit modules all operating from the same synchronous clock reference.
Extended MHD Modeling of Tearing-Driven Magnetic Relaxation

NASA Astrophysics Data System (ADS)

Sauppe, Joshua

2016-10-01

Driven plasma pinch configurations are characterized by the gradual accumulation and episodic release of free energy in discrete relaxation events. The hallmark of this relaxation in a reversed-field pinch (RFP) plasma is flattening of the parallel current density profile effected by a fluctuation-induced dynamo emf in Ohm's law. Nonlinear two-fluid modeling of macroscopic RFP dynamics has shown appreciable coupling of magnetic relaxation and the evolution of plasma flow. Accurate modeling of RFP dynamics requires the Hall effect in Ohm's law as well as first order ion finite Larmor radius (FLR) effects, represented by the Braginskii ion gyroviscous stress tensor. New results find that the Hall dynamo effect from < J × B > / ne can counter the MHD effect from - < V × B > in some of the relaxation events. The MHD effect dominates these events and relaxes the current profile toward the Taylor state, but the opposition of the two dynamos generates plasma flow in the direction of equilibrium current density, consistent with experimental measurements. Detailed experimental measurements of the MHD and Hall emf terms are compared to these extended MHD predictions. Tracking the evolution of magnetic energy, helicity, and hybrid helicity during relaxation identifies the most important contributions in single-fluid and two-fluid models. Magnetic helicity is well conserved relative to the magnetic energy during relaxation. The hybrid helicity is dominated by magnetic helicity in realistic low-beta pinch conditions and is also well conserved. Differences of less than 1 % between magnetic helicity and hybrid helicity are observed with two-fluid modeling and result from cross helicity evolution through ion FLR effects, which have not been included in contemporary relaxation theories. The kinetic energy driven by relaxation in the computations is dominated by velocity components perpendicular to the magnetic field, an effect that had not been predicted. Work performed at University of Wisconsin-Madison. LA-UR-16-24727.
Pharmacological targeting of the mammalian clock reveals a novel analgesic for osteoarthritis-induced pain.

PubMed

Das, Vaskar; Kc, Ranjan; Li, Xin; Varma, Disha; Qiu, Sujun; Kroin, Jeffrey S; Forsyth, Christopher B; Keshavarzian, Ali; van Wijnen, Andre J; Park, Thomas J; Stein, Gary S; O-Sullivan, Insug; Burris, Thomas P; Im, Hee-Jeong

2018-05-20

Environmental disruption of the circadian rhythm is linked with increased pain due to osteoarthritis (OA). We aimed to characterize the role of the clock gene in OA-induced pain more systemically using both genetic and pharmacological approaches. Genetically modified mice, (bmal1f/fNav1.8CreERT mice), generated by deleting the critical clock gene, bmal1, from Nav1.8 sensory neurons, were resistant to the development of mechanical hyperalgesia associated with OA induced by partial medial meniscectomy (PMM) of the knee. In wild-type mice, induction of OA by PMM surgery led to a substantial increase in BMAL1 expression in DRG neurons. Interestingly, pharmacological activation of the REV-ERB (a negative regulator of bmal1 transcription) with SR9009 resulted in reduction of BMAL1 expression, and a significant decrease in mechanical hyperalgesia associated with OA. Cartilage degeneration was also significantly reduced in mice treated with the REV-ERB agonist SR9009. Based on these data, we also assessed the effect of pharmacological activation of REV-ERB using a model of environmental circadian disruption with its associated mechanical hyperalgesia, and noted that SR9009 was an effective analgesic in this model as well. Our data clearly demonstrate that genetic disruption of the molecular clock, via deletion of bmal1 in the sensory neurons of the DRG, decreases pain in a model of OA. Furthermore, pharmacological activation of REV-ERB leading to suppression of BMAL1 expression may be an effective method for treating OA-related pain, as well as to reduce joint damage associated with this disease. Copyright © 2018. Published by Elsevier B.V.
Predicted Role of NAD Utilization in the Control of Circadian Rhythms during DNA Damage Response

PubMed Central

Luna, Augustin; McFadden, Geoffrey B.; Aladjem, Mirit I.; Kohn, Kurt W.

2015-01-01

The circadian clock is a set of regulatory steps that oscillate with a period of approximately 24 hours influencing many biological processes. These oscillations are robust to external stresses, and in the case of genotoxic stress (i.e. DNA damage), the circadian clock responds through phase shifting with primarily phase advancements. The effect of DNA damage on the circadian clock and the mechanism through which this effect operates remains to be thoroughly investigated. Here we build an in silico model to examine damage-induced circadian phase shifts by investigating a possible mechanism linking circadian rhythms to metabolism. The proposed model involves two DNA damage response proteins, SIRT1 and PARP1, that are each consumers of nicotinamide adenine dinucleotide (NAD), a metabolite involved in oxidation-reduction reactions and in ATP synthesis. This model builds on two key findings: 1) that SIRT1 (a protein deacetylase) is involved in both the positive (i.e. transcriptional activation) and negative (i.e. transcriptional repression) arms of the circadian regulation and 2) that PARP1 is a major consumer of NAD during the DNA damage response. In our simulations, we observe that increased PARP1 activity may be able to trigger SIRT1-induced circadian phase advancements by decreasing SIRT1 activity through competition for NAD supplies. We show how this competitive inhibition may operate through protein acetylation in conjunction with phosphorylation, consistent with reported observations. These findings suggest a possible mechanism through which multiple perturbations, each dominant during different points of the circadian cycle, may result in the phase advancement of the circadian clock seen during DNA damage. PMID:26020938
Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

PubMed Central

Musiek, Erik S.; Lim, Miranda M.; Yang, Guangrui; Bauer, Adam Q.; Qi, Laura; Lee, Yool; Roh, Jee Hoon; Ortiz-Gonzalez, Xilma; Dearborn, Joshua T.; Culver, Joseph P.; Herzog, Erik D.; Hogenesch, John B.; Wozniak, David F.; Dikranian, Krikor; Giasson, Benoit I.; Weaver, David R.; Holtzman, David M.; FitzGerald, Garret A.

2013-01-01

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator–like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration. PMID:24270424
High Performance Clocks and Gravity Field Determination

NASA Astrophysics Data System (ADS)

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 closely-related deficiencies of this method like an extra-ordinary knowledge of the spacecraft velocity, etc. For all these applications besides the near-future prospects, we also discuss the challenges that are related to using those novel clock data in geodesy.
Advances in Time Estimation Methods for Molecular Data.

PubMed

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 sets. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Limited, episodic diversification and contrasting phylogeography in a New Zealand cicada radiation.

PubMed

Marshall, David C; Hill, Kathy B R; Marske, Katharine A; Chambers, Colleen; Buckley, Thomas R; Simon, Chris

2012-09-11

The New Zealand (NZ) cicada fauna contains two co-distributed lineages that independently colonized the isolated continental fragment in the Miocene. One extensively studied lineage includes 90% of the extant species (Kikihia + Maoricicada + Rhodopsalta; ca 51 spp.), while the other contains just four extant species (Amphipsalta - 3 spp. + Notopsalta - 1 sp.) and has been little studied. We examined mitochondrial and nuclear-gene phylogenies and phylogeography, Bayesian relaxed-clock divergence timing (incorporating literature-based uncertainty of molecular clock estimates) and ecological niche models of the species from the smaller radiation. Mitochondrial and nuclear-gene trees supported the monophyly of Amphipsalta. Most interspecific diversification within Amphipsalta-Notopsalta occurred from the mid-Miocene to the Pliocene. However, interspecific divergence time estimates had large confidence intervals and were highly dependent on the assumed tree prior, and comparisons of uncorrected and patristic distances suggested difficulty in estimation of branch lengths. In contrast, intraspecific divergence times varied little across analyses, and all appear to have occurred during the Pleistocene. Two large-bodied forest taxa (A. cingulata, A. zelandica) showed minimal phylogeographic structure, with intraspecific diversification dating to ca. 0.16 and 0.37 Ma, respectively. Mid-Pleistocene-age phylogeographic structure was found within two smaller-bodied species (A. strepitans - 1.16 Ma, N. sericea - 1.36 Ma] inhabiting dry open habitats. Branches separating independently evolving species were long compared to intraspecific branches. Ecological niche models hindcast to the Last Glacial Maximum (LGM) matched expectations from the genetic datasets for A. zelandica and A. strepitans, suggesting that the range of A. zelandica was greatly reduced while A. strepitans refugia were more extensive. However, no LGM habitat could be reconstructed for A. cingulata and N. sericea, suggesting survival in microhabitats not detectable with our downscaled climate data. Unlike the large and continuous diversification exhibited by the Kikihia-Maoricicada-Rhodopsalta clade, the contemporaneous Amphipsalta-Notopsalta lineage contains four comparatively old (early branching) species that show only recent diversification. This indicates either a long period of stasis with no speciation, or one or more bouts of extinction that have pruned the radiation. Within Amphipsalta-Notopsalta, greater population structure is found in dry-open-habitat species versus forest specialists. We attribute this difference to the fact that NZ lowland forests were repeatedly reduced in extent during glacial periods, while steep, open habitats likely became more available during late Pleistocene uplift.
Estimation of primate speciation dates using local molecular clocks.

PubMed

Yoder, A D; Yang, Z

2000-07-01

Protein-coding genes of the mitochondrial genomes from 31 mammalian species were analyzed to estimate the speciation dates within primates and also between rats and mice. Three calibration points were used based on paleontological data: one at 20-25 MYA for the hominoid/cercopithecoid divergence, one at 53-57 MYA for the cetacean/artiodactyl divergence, and the third at 110-130 MYA for the metatherian/eutherian divergence. Both the nucleotide and the amino acid sequences were analyzed, producing conflicting results. The global molecular clock was clearly violated for both the nucleotide and the amino acid data. Models of local clocks were implemented using maximum likelihood, allowing different evolutionary rates for some lineages while assuming rate constancy in others. Surprisingly, the highly divergent third codon positions appeared to contain phylogenetic information and produced more sensible estimates of primate divergence dates than did the amino acid sequences. Estimated dates varied considerably depending on the data type, the calibration point, and the substitution model but differed little among the four tree topologies used. We conclude that the calibration derived from the primate fossil record is too recent to be reliable; we also point out a number of problems in date estimation when the molecular clock does not hold. Despite these obstacles, we derived estimates of primate divergence dates that were well supported by the data and were generally consistent with the paleontological record. Estimation of the mouse-rat divergence date, however, was problematic.
Oxyntomodulin regulates resetting of the liver circadian clock by food

PubMed Central

Landgraf, Dominic; Tsang, Anthony H; Leliavski, Alexei; Koch, Christiane E; Barclay, Johanna L; Drucker, Daniel J; Oster, Henrik

2015-01-01

Circadian clocks coordinate 24-hr rhythms of behavior and physiology. In mammals, a master clock residing in the suprachiasmatic nucleus (SCN) is reset by the light–dark cycle, while timed food intake is a potent synchronizer of peripheral clocks such as the liver. Alterations in food intake rhythms can uncouple peripheral clocks from the SCN, resulting in internal desynchrony, which promotes obesity and metabolic disorders. Pancreas-derived hormones such as insulin and glucagon have been implicated in signaling mealtime to peripheral clocks. In this study, we identify a novel, more direct pathway of food-driven liver clock resetting involving oxyntomodulin (OXM). In mice, food intake stimulates OXM secretion from the gut, which resets liver transcription rhythms via induction of the core clock genes Per1 and 2. Inhibition of OXM signaling blocks food-mediated resetting of hepatocyte clocks. These data reveal a direct link between gastric filling with food and circadian rhythm phasing in metabolic tissues. DOI: http://dx.doi.org/10.7554/eLife.06253.001 PMID:25821984
The metabolic sensor AKIN10 modulates the Arabidopsis circadian clock in a light-dependent manner.

PubMed

Shin, Jieun; Sánchez-Villarreal, Alfredo; Davis, Amanda M; Du, Shen-Xiu; Berendzen, Kenneth W; Koncz, Csaba; Ding, Zhaojun; Li, Cuiling; Davis, Seth J

2017-07-01

Plants generate rhythmic metabolism during the repetitive day/night cycle. The circadian clock produces internal biological rhythms to synchronize numerous metabolic processes such that they occur at the required time of day. Metabolism conversely influences clock function by controlling circadian period and phase and the expression of core-clock genes. Here, we show that AKIN10, a catalytic subunit of the evolutionarily conserved key energy sensor sucrose non-fermenting 1 (Snf1)-related kinase 1 (SnRK1) complex, plays an important role in the circadian clock. Elevated AKIN10 expression led to delayed peak expression of the circadian clock evening-element GIGANTEA (GI) under diurnal conditions. Moreover, it lengthened clock period specifically under light conditions. Genetic analysis showed that the clock regulator TIME FOR COFFEE (TIC) is required for this effect of AKIN10. Taken together, we propose that AKIN10 conditionally works in a circadian clock input pathway to the circadian oscillator. © 2017 John Wiley & Sons Ltd.
Escape time, relaxation, and sticky states of a softened Henon-Heiles model: Low-frequency vibrational mode effects and glass relaxation

NASA Astrophysics Data System (ADS)

Toledo-Marín, J. Quetzalcóatl; Naumis, Gerardo G.

2018-04-01

Here we study the relaxation of a chain consisting of three masses joined by nonlinear springs and periodic conditions when the stiffness is weakened. This system, when expressed in their normal coordinates, yields a softened Henon-Heiles system. By reducing the stiffness of one low-frequency vibrational mode, a faster relaxation is enabled. This is due to a reduction of the energy barrier heights along the softened normal mode as well as for a widening of the opening channels of the energy landscape in configurational space. The relaxation is for the most part exponential, and can be explained by a simple flux equation. Yet, for some initial conditions the relaxation follows as a power law, and in many cases there is a regime change from exponential to power-law decay. We pinpoint the initial conditions for the power-law decay, finding two regions of sticky states. For such states, quasiperiodic orbits are found since almost for all components of the initial momentum orientation, the system is trapped inside two pockets of configurational space. The softened Henon-Heiles model presented here is intended as the simplest model in order to understand the interplay of rigidity, nonlinear interactions and relaxation for nonequilibrium systems such as glass-forming melts or soft matter. Our softened system can be applied to model β relaxation in glasses and suggest that local reorientational jumps can have an exponential and a nonexponential contribution for relaxation, the latter due to asymmetric molecules sticking in cages for certain orientations.
The time dependence of rock healing as a universal relaxation process, a tutorial

NASA Astrophysics Data System (ADS)

Snieder, Roel; Sens-Schönfelder, Christoph; Wu, Renjie

2017-01-01

The material properties of earth materials often change after the material has been perturbed (slow dynamics). For example, the seismic velocity of subsurface materials changes after earthquakes, and granular materials compact after being shaken. Such relaxation processes are associated by observables that change logarithmically with time. Since the logarithm diverges for short and long times, the relaxation can, strictly speaking, not have a log-time dependence. We present a self-contained description of a relaxation function that consists of a superposition of decaying exponentials that has log-time behaviour for intermediate times, but converges to zero for long times, and is finite for t = 0. The relaxation function depends on two parameters, the minimum and maximum relaxation time. These parameters can, in principle, be extracted from the observed relaxation. As an example, we present a crude model of a fracture that is closing under an external stress. Although the fracture model violates some of the assumptions on which the relaxation function is based, it follows the relaxation function well. We provide qualitative arguments that the relaxation process, just like the Gutenberg-Richter law, is applicable to a wide range of systems and has universal properties.
Vibrational relaxation of I2 in complexing solvents: The role of solvent-solute attractive forces

NASA Astrophysics Data System (ADS)

Shiang, Joseph J.; Liu, Hongjun; Sension, Roseanne J.

1998-12-01

Femtosecond transient absorption studies of I2-arene complexes, with arene=hexamethylbenzene (HMB), mesitylene (MST), or m-xylene (mX), are used to investigate the effect of solvent-solute attractive forces upon the rate of vibrational relaxation in solution. Comparison of measurements on I2-MST complexes in neat mesitylene and I2-MST complexes diluted in carbontetrachloride demonstrate that binary solvent-solute attractive forces control the rate of vibrational relaxation in this prototypical model of diatomic vibrational relaxation. The data obtained for different arenes demonstrate that the rate of I2 relaxation increases with the magnitude of the I2-arene attractive interaction. I2-HMB relaxes much faster than I2 in MST or mX. The results of these experiments are discussed in terms of both isolated binary collision and instantaneous normal mode models for vibrational relaxation.
Relaxation-phenomena in LiAl/FeS-cells

NASA Astrophysics Data System (ADS)

Borger, W.; Kappus, W.; Panesar, H. S.

A theoretical model of the capacity of strongly relaxing electrochemical systems is applied to the LiAl/FeS system. Relaxation phenomena in LiAl and FeS electrodes can be described by this model. Experimental relaxation data indicate that lithium transport through the alpha-LiAl layer to the particle surface is the capacity limiting process at high discharge current density in the LiAl electrode in LiCl-KCl and LiF-LiCl-LiBr mixtures. Strong relaxation is observed in the FeS electrode with LiCl-KCl electrolyte caused by lithium concentration gradients and precipitation of KCl in the pores.
Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina.

PubMed

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.
MYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation.

PubMed

Shostak, Anton; Ruppert, Bianca; Ha, Nati; Bruns, Philipp; Toprak, Umut H; Eils, Roland; Schlesner, Matthias; Diernfellner, Axel; Brunner, Michael

2016-06-24

The circadian clock and the cell cycle are major cellular systems that organize global physiology in temporal fashion. It seems conceivable that the potentially conflicting programs are coordinated. We show here that overexpression of MYC in U2OS cells attenuates the clock and conversely promotes cell proliferation while downregulation of MYC strengthens the clock and reduces proliferation. Inhibition of the circadian clock is crucially dependent on the formation of repressive complexes of MYC with MIZ1 and subsequent downregulation of the core clock genes BMAL1 (ARNTL), CLOCK and NPAS2. We show furthermore that BMAL1 expression levels correlate inversely with MYC levels in 102 human lymphomas. Our data suggest that MYC acts as a master coordinator that inversely modulates the impact of cell cycle and circadian clock on gene expression.
A precise clock distribution network for MRPC-based experiments

NASA Astrophysics Data System (ADS)

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

2016-06-01

In high energy physics experiments, the MRPC (Multi-Gap Resistive Plate Chamber) detectors are widely used recently which can provide higher-resolution measurement for particle identification. However, the application of MRPC detectors leads to a series of challenges in electronics design with large number of front-end electronic channels, especially for distributing clock precisely. To deal with these challenges, this paper presents a universal scheme of clock transmission network for MRPC-based experiments with advantages of both precise clock distribution and global command synchronization. For precise clock distributing, the clock network is designed into a tree architecture with two stages: the first one has a point-to-multipoint long range bidirectional distribution with optical channels and the second one has a fan-out structure with copper link inside readout crates. To guarantee the precision of clock frequency or phase, the r-PTP (reduced Precision Time Protocol) and the DDMTD (digital Dual Mixer Time Difference) methods are used for frequency synthesis, phase measurement and adjustment, which is implemented by FPGA (Field Programmable Gate Array) in real-time. In addition, to synchronize global command execution, based upon this clock distribution network, synchronous signals are coded with clock for transmission. With technique of encoding/decoding and clock data recovery, signals such as global triggers or system control commands, can be distributed to all front-end channels synchronously, which greatly simplifies the system design. The experimental results show that both the clock jitter (RMS) and the clock skew can be less than 100 ps.
Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimizu, Takashi, E-mail: shimizut@obihiro.ac.jp; Hirai, Yuko; Murayama, Chiaki

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 ofmore » 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.« less
Clock Controller For Ac Self-Timing Analysis Of Logic System

DOEpatents

Lo, Tinchee; Flanagan, John D.

2004-05-18

A clock controller and clock generating method are provided for AC self-test timing analysis of a logic system. The controller includes latch circuitry which receives a DC input signal at a data input, and a pair of continuous out-of-phase clock signals at capture and launch clock inputs thereof. The latch circuitry outputs two overlapping pulses responsive to the DC input signal going high. The two overlapping pulses are provided to waveform shaper circuitry which produces therefrom two non-overlapping pulses at clock speed of the logic system to be tested. The two non-overlapping pulses are a single pair of clock pulses which facilitate AC self-test timing analysis of the logic system.

Phylogeny and divergence of the pinnipeds (Carnivora: Mammalia) assessed using a multigene dataset

PubMed Central

Higdon, Jeff W; Bininda-Emonds, Olaf RP; Beck, Robin MD; Ferguson, Steven H

2007-01-01

Background Phylogenetic comparative methods are often improved by complete phylogenies with meaningful branch lengths (e.g., divergence dates). This study presents a dated molecular supertree for all 34 world pinniped species derived from a weighted matrix representation with parsimony (MRP) supertree analysis of 50 gene trees, each determined under a maximum likelihood (ML) framework. Divergence times were determined by mapping the same sequence data (plus two additional genes) on to the supertree topology and calibrating the ML branch lengths against a range of fossil calibrations. We assessed the sensitivity of our supertree topology in two ways: 1) a second supertree with all mtDNA genes combined into a single source tree, and 2) likelihood-based supermatrix analyses. Divergence dates were also calculated using a Bayesian relaxed molecular clock with rate autocorrelation to test the sensitivity of our supertree results further. Results The resulting phylogenies all agreed broadly with recent molecular studies, in particular supporting the monophyly of Phocidae, Otariidae, and the two phocid subfamilies, as well as an Odobenidae + Otariidae sister relationship; areas of disagreement were limited to four more poorly supported regions. Neither the supertree nor supermatrix analyses supported the monophyly of the two traditional otariid subfamilies, supporting suggestions for the need for taxonomic revision in this group. Phocid relationships were similar to other recent studies and deeper branches were generally well-resolved. Halichoerus grypus was nested within a paraphyletic Pusa, although relationships within Phocina tend to be poorly supported. Divergence date estimates for the supertree were in good agreement with other studies and the available fossil record; however, the Bayesian relaxed molecular clock divergence date estimates were significantly older. Conclusion Our results join other recent studies and highlight the need for a re-evaluation of pinniped taxonomy, especially as regards the subfamilial classification of otariids and the generic nomenclature of Phocina. Even with the recent publication of new sequence data, the available genetic sequence information for several species, particularly those in Arctocephalus, remains very limited, especially for nuclear markers. However, resolution of parts of the tree will probably remain difficult, even with additional data, due to apparent rapid radiations. Our study addresses the lack of a recent pinniped phylogeny that includes all species and robust divergence dates for all nodes, and will therefore prove indispensable to comparative and macroevolutionary studies of this group of carnivores. PMID:17996107
An analysis of clock-shift experiments: is scatter increased and deflection reduced in clock-shifted homing pigeons?

PubMed

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).
Normal vision can compensate for the loss of the circadian clock

PubMed Central

Schlichting, Matthias; Menegazzi, Pamela; Helfrich-Förster, Charlotte

2015-01-01

Circadian clocks are thought to be essential for timing the daily activity of animals, and consequently increase fitness. This view was recently challenged for clock-less fruit flies and mice that exhibited astonishingly normal activity rhythms under outdoor conditions. Compensatory mechanisms appear to enable even clock mutants to live a normal life in nature. Here, we show that gradual daily increases/decreases of light in the laboratory suffice to provoke normally timed sharp morning (M) and evening (E) activity peaks in clock-less flies. We also show that the compound eyes, but not Cryptochrome (CRY), mediate the precise timing of M and E peaks under natural-like conditions, as CRY-less flies do and eyeless flies do not show these sharp peaks independently of a functional clock. Nevertheless, the circadian clock appears critical for anticipating dusk, as well as for inhibiting sharp activity peaks during midnight. Clock-less flies only increase E activity after dusk and not before the beginning of dusk, and respond strongly to twilight exposure in the middle of the night. Furthermore, the circadian clock responds to natural-like light cycles, by slightly broadening Timeless (TIM) abundance in the clock neurons, and this effect is mediated by CRY. PMID:26378222
Effect of Resveratrol, a SIRT1 Activator, on the Interactions of the CLOCK/BMAL1 Complex

PubMed Central

Park, Insung; Lee, Yool; Kim, Hee-Dae

2014-01-01

Background In mammals, the CLOCK/BMAL1 heterodimer is a key transcription factor complex that drives the cyclic expression of clock-controlled genes involved in various physiological functions and behavioral consequences. Recently, a growing number of studies have reported a molecular link between the circadian clock and metabolism. In the present study, we explored the regulatory effects of SIRTUIN1 (SIRT1), an NAD+-dependent deacetylase, on CLOCK/BMAL1-mediated clock gene expression. Methods To investigate the interaction between SIRT1 and CLOCK/BMAL1, we conducted bimolecular fluorescence complementation (BiFC) analyses supplemented with immunocytochemistry assays. BiFC experiments employing deletion-specific mutants of BMAL1 were used to elucidate the specific domains that are necessary for the SIRT1-BMAL1 interaction. Additionally, luciferase reporter assays were used to delineate the effects of SIRT1 on circadian gene expression. Results BiFC analysis revealed that SIRT1 interacted with both CLOCK and BMAL1 in most cell nuclei. As revealed by BiFC assays using various BMAL1 deletion mutants, the PAS-B domain of BMAL1 was essential for interaction with SIRT1. Activation of SIRT1 with resveratrol did not exert any significant change on the interaction with the CLOCK/BMAL1 complex. However, promoter analysis using Per1-Luc and Ebox-Luc reporters showed that SIRT1 significantly downregulated both promoter activities. This inhibitory effect was intensified by treatment with resveratrol, indicating a role for SIRT1 and its activator in CLOCK/BMAL1-mediated transcription of clock genes. Conclusion These results suggest that SIRT1 may form a regulatory complex with CLOCK/BMAL1 that represses clock gene expression, probably via deacetylase activity. PMID:25309798
Clock is not a component of Z-bands.

PubMed

Wang, Jushuo; Dube, Dipak K; White, Jennifer; Fan, Yingli; Sanger, Jean M; Sanger, Joseph W

2012-12-01

The process of Z-band assembly begins with the formation of small Z-bodies composed of a complex of proteins rich in alpha-actinin. As additional proteins are added to nascent myofibrils, Z-bodies are transformed into continuous bands that form coherent discs of interacting proteins at the boundaries of sarcomeres. The steps controlling the transition of Z-bodies to Z-bands are not known. The report that a circadian protein, Clock, was localized in the Z-bands of neonatal rat cardiomyocytes raised the question whether this transcription factor could be involved in Z-band assembly. We found that the anti-Clock antibody used in the reported study also stained the Z-bands and Z-bodies of mouse and avian cardiac and skeletal muscle cells. YFP constructs of Clock that were assembled, however, did not localize to the Z-bands of muscle cells. Controls of Clock's activity showed that cotransfection of muscle cells with pYFP-Clock and pCeFP-BMAL1 led to the expected nuclear localization of YFP-Clock with its binding partner CeFP-BMAL1. Neither CeFP-BMAL1 nor antibodies directed against BMAL1 localized to Z-bands. A bimolecular fluorescence complementation assay (VC-BMAL1 and VN-Clock) confirmed the absence of Clock and BMAL1 from Z-bands, and their nuclear colocalization. A second anti-Clock antibody stained nuclei, but not Z-bands, of cells cotransfected with Clock and BMAL1 plasmids. Western blots of reactions of muscle extracts and purified alpha-actinins with the two anti-Clock antibodies showed that the original antibody cross-reacted with alpha-actinin and the second did not. These results cannot confirm Clock as an active component of Z-bands. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.
A Novel Photonic Clock and Carrier Recovery Device

NASA Technical Reports Server (NTRS)

Yao, X. Steve; Lutes, George; Maleki, Lute

1996-01-01

As data communication rates climb toward ten Gb/s, clock recovery and synchronization become more difficult, if not impossible, using conventional electronic circuits. We present in this article experimental results of a high speed clock and carrier recovery using a novel device called a photonic oscillator that we recently developed in our laboratory. This device is capable of recovering clock signals up to 70 GHz. To recover the clock, the incoming data is injected into the photonic oscillator either through the optical injection port or the electrical injection port. The free running photonic oscillator is tuned to oscillate at a nominal frequency equal to the clock frequency of the incoming data. With the injection of the data, the photonic oscillator will be quickly locked to clock frequency of the data stream while rejecting other frequency components associated with the data. Consequently, the output of the locked photonic oscillator is a continuous periodical wave synchronized with the incoming data or simply the recovered clock. We have demonstrated a clock to spur ratio of more than 60 dB of the recovered clock using this technique. Similar to the clock recovery, the photonic oscillator can be used to recover a high frequency carrier degraded by noise and an improvement of about 50 dB in signal-to-noise ratio was demonstrated. The photonic oscillator has both electrical and optical inputs and outputs and can be directly interfaced with a photonic system without signal conversion. In addition to clock and carrier recovery, the photonic oscillator can also be used for (1) stable high frequency clock signal generation, (2) frequency multiplication, (3) square wave and comb frequency generation, and (4) photonic phase locked loop.
Chronic consumption of dietary proanthocyanidins modulates peripheral clocks in healthy and obese rats.

PubMed

Ribas-Latre, A; Baselga-Escudero, L; Casanova, E; Arola-Arnal, A; Salvadó, M J; Arola, L; Bladé, C

2015-02-01

Circadian rhythm plays an important role in maintaining homeostasis, and its disruption increases the risk of developing metabolic syndrome. Circadian rhythm is maintained by a central clock in the hypothalamus that is entrained by light, but circadian clocks are also present in peripheral tissues. These peripheral clocks are trained by other cues, such as diet. The aim of this study was to determine whether proanthocyanidins, the most abundant polyphenols in the human diet, modulate the expression of clock and clock-controlled genes in the liver, gut and mesenteric white adipose tissue (mWAT) in healthy and obese rats. Grape seed proanthocyanidin extracts (GSPEs) were administered for 21 days at 5, 25 or 50 mg GSPE/kg body weight in healthy rats and 25 mg GSPE/kg body weight in rats with diet-induced obesity. In healthy animals, GSPE administration led to the overexpression of core clock genes in a positive dose-dependent manner. Moreover, the acetylated BMAL1 protein ratio increased with the same pattern in the liver and mWAT. With regards to clock-controlled genes, Per2 was also overexpressed, whereas Rev-erbα and RORα were repressed in a negative dose-dependent manner. Diet-induced obesity always resulted in the overexpression of some core clock and clock-related genes, although the particular gene affected was tissue specific. GSPE administration counteracted disturbances in the clock genes in the liver and gut but was less effective in normalizing the clock gene disruption in WAT. In conclusion, proanthocyanidins have the capacity to modulate peripheral molecular clocks in both healthy and obese states. Copyright © 2015 Elsevier Inc. All rights reserved.
Room 103, transom woodwork and original clock. All clocks are ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Room 103, transom woodwork and original clock. All clocks are driven by a common signal. - San Bernardino Valley College, Life Science Building, 701 South Mount Vernon Avenue, San Bernardino, San Bernardino County, CA
Musings on cosmological relaxation and the hierarchy problem

NASA Astrophysics Data System (ADS)

Jaeckel, Joerg; Mehta, Viraf M.; Witkowski, Lukas T.

2016-03-01

Recently Graham, Kaplan and Rajendran proposed cosmological relaxation as a mechanism for generating a hierarchically small Higgs vacuum expectation value. Inspired by this we collect some thoughts on steps towards a solution to the electroweak hierarchy problem and apply them to the original model of cosmological relaxation [Phys. Rev. Lett. 115, 221801 (2015)]. To do so, we study the dynamics of the model and determine the relation between the fundamental input parameters and the electroweak vacuum expectation value. Depending on the input parameters the model exhibits three qualitatively different regimes, two of which allow for hierarchically small Higgs vacuum expectation values. One leads to standard electroweak symmetry breaking whereas in the other regime electroweak symmetry is mainly broken by a Higgs source term. While the latter is not acceptable in a model based on the QCD axion, in non-QCD models this may lead to new and interesting signatures in Higgs observables. Overall, we confirm that cosmological relaxation can successfully give rise to a hierarchically small Higgs vacuum expectation value if (at least) one model parameter is chosen sufficiently small. However, we find that the required level of tuning for achieving this hierarchy in relaxation models can be much more severe than in the Standard Model.
Nonequilibrium Nonideal Nanoplasma Generated by a Fast Single Ion in Condensed Matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faenov, A. Ya.; Kansai Photon Science Institut, Japan Atomic Energy Agency; Lankin, A. V.

A plasma model of relaxation of a medium in heavy ion tracks in condensed matter is proposed. The model is based on three assumptions: the Maxwell distribution of plasma electrons, localization of plasma inside the track nanochannel and constant values of the plasma electron density and temperature during the X-ray irradiation. It is demonstrated that the plasma relaxation model adequately describes the X-ray spectra observed upon interaction of a fast ion with condensed target. Preassumptions of plasma relaxation model are validated by the molecular dynamics modeling and simulation.
Next Generation JPL Ultra-Stable Trapped Ion Atomic Clocks

NASA Technical Reports Server (NTRS)

Burt, Eric; Tucker, Blake; Larsen, Kameron; Hamell, Robert; Tjoelker, Robert

2013-01-01

Over the past decade, trapped ion atomic clock development at the Jet Propulsion Laboratory (JPL) has focused on two directions: 1) new atomic clock technology for space flight applications that require strict adherence to size, weight, and power requirements, and 2) ultra-stable atomic clocks, usually for terrestrial applications emphasizing ultimate performance. In this paper we present a new ultra-stable trapped ion clock designed, built, and tested in the second category. The first new standard, L10, will be delivered to the Naval Research Laboratory for use in characterizing DoD space clocks.
Transcriptional oscillation of canonical clock genes in mouse peripheral tissues

PubMed Central

Yamamoto, Takuro; Nakahata, Yasukazu; Soma, Haruhiko; Akashi, Makoto; Mamine, Takayoshi; Takumi, Toru

2004-01-01

Background The circadian rhythm of about 24 hours is a fundamental physiological function observed in almost all organisms from prokaryotes to humans. Identification of clock genes has allowed us to study the molecular bases for circadian behaviors and temporal physiological processes such as hormonal secretion, and has prompted the idea that molecular clocks reside not only in a central pacemaker, the suprachiasmatic nuclei (SCN) of hypothalamus in mammals, but also in peripheral tissues, even in immortalized cells. Furthermore, previous molecular dissection revealed that the mechanism of circadian oscillation at a molecular level is based on transcriptional regulation of clock and clock-controlled genes. Results We systematically analyzed the mRNA expression of clock and clock-controlled genes in mouse peripheral tissues. Eight genes (mBmal1, mNpas2, mRev-erbα, mDbp, mRev-erbβ, mPer3, mPer1 and mPer2; given in the temporal order of the rhythm peak) showed robust circadian expressions of mRNAs in all tissues except testis, suggesting that these genes are core molecules of the molecular biological clock. The bioinformatics analysis revealed that these genes have one or a combination of 3 transcriptional elements (RORE, DBPE, and E-box), which are conserved among human, mouse, and rat genome sequences, and indicated that these 3 elements may be responsible for the biological timing of expression of canonical clock genes. Conclusions The observation of oscillatory profiles of canonical clock genes is not only useful for physiological and pathological examination of the circadian clock in various organs but also important for systematic understanding of transcriptional regulation on a genome-wide basis. Our finding of the oscillatory expression of canonical clock genes with a temporal order provides us an interesting hypothesis, that cyclic timing of all clock and clock-controlled genes may be dependent on several transcriptional elements including 3 known elements, E-box, RORE, and DBPE. PMID:15473909
Generating a fault-tolerant global clock using high-speed control signals for the MetaNet architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ofek, Y.

1994-05-01

This work describes a new technique, based on exchanging control signals between neighboring nodes, for constructing a stable and fault-tolerant global clock in a distributed system with an arbitrary topology. It is shown that it is possible to construct a global clock reference with time step that is much smaller than the propagation delay over the network's links. The synchronization algorithm ensures that the global clock tick' has a stable periodicity, and therefore, it is possible to tolerate failures of links and clocks that operate faster and/or slower than nominally specified, as well as hard failures. The approach taken inmore » this work is to generate a global clock from the ensemble of the local transmission clocks and not to directly synchronize these high-speed clocks. The steady-state algorithm, which generates the global clock, is executed in hardware by the network interface of each node. At the network interface, it is possible to measure accurately the propagation delay between neighboring nodes with a small error or uncertainty and thereby to achieve global synchronization that is proportional to these error measurements. It is shown that the local clock drift (or rate uncertainty) has only a secondary effect on the maximum global clock rate. The synchronization algorithm can tolerate any physical failure. 18 refs.« less
Neuronal oscillations on an ultra-slow timescale: daily rhythms in electrical activity and gene expression in the mammalian master circadian clockwork.

PubMed

Belle, Mino D C; Diekman, Casey O

2018-02-03

Neuronal oscillations of the brain, such as those observed in the cortices and hippocampi of behaving animals and humans, span across wide frequency bands, from slow delta waves (0.1 Hz) to ultra-fast ripples (600 Hz). Here, we focus on ultra-slow neuronal oscillators in the hypothalamic suprachiasmatic nuclei (SCN), the master daily clock that operates on interlocking transcription-translation feedback loops to produce circadian rhythms in clock gene expression with a period of near 24 h (< 0.001 Hz). This intracellular molecular clock interacts with the cell's membrane through poorly understood mechanisms to drive the daily pattern in the electrical excitability of SCN neurons, exhibiting an up-state during the day and a down-state at night. In turn, the membrane activity feeds back to regulate the oscillatory activity of clock gene programs. In this review, we emphasise the circadian processes that drive daily electrical oscillations in SCN neurons, and highlight how mathematical modelling contributes to our increasing understanding of circadian rhythm generation, synchronisation and communication within this hypothalamic region and across other brain circuits. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Analysis of the Precision of Pulsar Time Clock Modeltwo

NASA Astrophysics Data System (ADS)

Zhao, Cheng-shi; Tong, Ming-lei; Gao, Yu-ping; Yang, Ting-gao

2018-04-01

Millisecond pulsars have a very high rotation stability, which can be applied to many research fields, such as the establishment of the pulsar time standard, the detection of gravitational wave, the spacecraft navigation by using X-ray pulsars and so on. In this paper, we employ two millisecond pulsars PSR J0437-4715 and J1713+0743, which are observed by the International Pulsar Timing Array (IPTA), to analyze the precision of pulsar clock parameter and the prediction accuracy of pulse time of arrival (TOA). It is found that the uncertainty of spin frequency is 10-15 Hz, the uncertainty of the first derivative of spin frequency is 10-23 s-2, and the precision of measured rotational parameters increases by one order of magnitude with the accumulated observational data every 4∼5 years. In addition, the errors of TOAs within 4.8 yr which are predicted by the clock model established by the 10 yr data of J0437-4715 are less than 1 μs. Therefore, one can use the pulsar time standard to calibrate the atomic clock, and make the atomic time deviate from the TT (Terrestrial Time) less than 1 μs within 4.8 yr.
Enhancing Kondo coupling in alkaline-earth-metal atomic gases with confinement-induced resonances in mixed dimensions

NASA Astrophysics Data System (ADS)

Cheng, Yanting; Zhang, Ren; Zhang, Peng; Zhai, Hui

2017-12-01

The Kondo effect describes the spin-exchange interaction between localized impurities and itinerant fermions. The ultracold alkaline-earth atomic gas provides a natural platform for quantum simulation of the Kondo model, utilizing its long-lived clock state and the nuclear-spin exchange interaction between clock state and ground state. One of the key issue now is whether the Kondo temperature can be high enough to be reached in current experiments, for which we have proposed to use transverse confinement to confine atoms into a one-dimensional tube and to use the confinement-induced resonance to enhance Kondo coupling. In this work, we further consider the (1 +0 ) -dimensional scattering problem when the clock state is further confined by an axial harmonic confinement. We show that this axial confinement for the clock-state atoms not only plays a role for localizing them, but can also act as an additional control knob to reach the confinement-induced resonance. We show that, in the presence of both the transverse and the axial confinements, the confinement-induced resonance can be reached in the practical conditions and the Kondo effect can be attainable in this system.
From two competing oscillators to one coupled-clock pacemaker cell system

PubMed Central

Yaniv, Yael; Lakatta, Edward G.; Maltsev, Victor A.

2015-01-01

At the beginning of this century, debates regarding “what are the main control mechanisms that ignite the action potential (AP) in heart pacemaker cells” dominated the electrophysiology field. The original theory which prevailed for over 50 years had advocated that the ensemble of surface membrane ion channels (i.e., “M-clock”) is sufficient to ignite rhythmic APs. However, more recent experimental evidence in a variety of mammals has shown that the sarcoplasmic reticulum (SR) acts as a “Ca2+-clock” rhythmically discharges diastolic local Ca2+ releases (LCRs) beneath the cell surface membrane. LCRs activate an inward current (likely that of the Na+/Ca2+ exchanger) that prompts the surface membrane “M-clock” to ignite an AP. Theoretical and experimental evidence has mounted to indicate that this clock “crosstalk” operates on a beat-to-beat basis and determines both the AP firing rate and rhythm. Our review is focused on the evolution of experimental definition and numerical modeling of the coupled-clock concept, on how mechanisms intrinsic to pacemaker cell determine both the heart rate and rhythm, and on future directions to develop further the coupled-clock pacemaker cell concept. PMID:25741284
Dynamics of interacting fermions under spin-orbit coupling in an optical lattice clock

NASA Astrophysics Data System (ADS)

Bromley, S. L.; Kolkowitz, S.; Bothwell, T.; Kedar, D.; Safavi-Naini, A.; Wall, M. L.; Salomon, C.; Rey, A. M.; Ye, J.

2018-04-01

Quantum statistics and symmetrization dictate that identical fermions do not interact via s-wave collisions. However, in the presence of spin-orbit coupling (SOC), fermions prepared in identical internal states with distinct momenta become distinguishable. The resulting strongly interacting system can exhibit exotic topological and pairing behaviours, many of which are yet to be observed in condensed matter systems. Ultracold atomic gases offer a promising pathway for simulating these rich phenomena, but until recently have been hindered by heating and losses. Here we enter a new regime of many-body interacting SOC in a fermionic optical lattice clock (OLC), where the long-lived electronic clock states mitigate unwanted dissipation. Using clock spectroscopy, we observe the precession of the collective magnetization and the emergence of spin-locking effects arising from an interplay between p-wave and SOC-induced exchange interactions. The many-body dynamics are well captured by a collective XXZ spin model, which describes a broad class of condensed matter systems ranging from superconductors to quantum magnets. Furthermore, our work will aid in the design of next-generation OLCs by offering a route for avoiding the observed large density shifts caused by SOC-induced exchange interactions.
Tight real-time synchronization of a microwave clock to an optical clock across a turbulent air path

PubMed Central

Bergeron, Hugo; Sinclair, Laura C.; Swann, William C.; Nelson, Craig W.; Deschênes, Jean-Daniel; Baumann, Esther; Giorgetta, Fabrizio R.; Coddington, Ian; Newbury, Nathan R.

2018-01-01

The ability to distribute the precise time and frequency from an optical clock to remote platforms could enable future precise navigation and sensing systems. Here we demonstrate tight, real-time synchronization of a remote microwave clock to a master optical clock over a turbulent 4-km open air path via optical two-way time-frequency transfer. Once synchronized, the 10-GHz frequency signals generated at each site agree to 10−14 at one second and below 10−17 at 1000 seconds. In addition, the two clock times are synchronized to ±13 fs over an 8-hour period. The ability to phase-synchronize 10-GHz signals across platforms supports future distributed coherent sensing, while the ability to time-synchronize multiple microwave-based clocks to a high-performance master optical clock supports future precision navigation/timing systems. PMID:29607352
Orthogonally referenced integrated ensemble for navigation and timing

DOEpatents

Smith, Stephen Fulton; Moore, James Anthony

2013-02-26

An orthogonally referenced integrated ensemble for navigation and timing includes a dual-polyhedral oscillator array, including an outer sensing array of oscillators and an inner clock array of oscillators situated inside the outer sensing array. The outer sensing array includes a first pair of sensing oscillators situated along a first axis of the outer sensing array, a second pair of sensing oscillators situated along a second axis of the outer sensing array, and a third pair of sensing oscillators situated along a third axis of the outer sensing array. The inner clock array of oscillators includes a first pair of clock oscillators situated along a first axis of the inner clock array, a second pair of clock oscillators situated along a second axis of the inner clock array, and a third pair of clock oscillators situated along a third axis of the inner clock array.

Fault-Tolerant Self-Stabilizing Distributed Clock Synchronization Protocol for Arbitrary Digraphs

NASA Technical Reports Server (NTRS)

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

NASA Astrophysics Data System (ADS)

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.
Automatic control of clock duty cycle

NASA Technical Reports Server (NTRS)

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.
Geodesy and metrology with a transportable optical clock

NASA Astrophysics Data System (ADS)

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.
Tight real-time synchronization of a microwave clock to an optical clock across a turbulent air path.

PubMed

Bergeron, Hugo; Sinclair, Laura C; Swann, William C; Nelson, Craig W; Deschênes, Jean-Daniel; Baumann, Esther; Giorgetta, Fabrizio R; Coddington, Ian; Newbury, Nathan R

2016-04-01

The ability to distribute the precise time and frequency from an optical clock to remote platforms could enable future precise navigation and sensing systems. Here we demonstrate tight, real-time synchronization of a remote microwave clock to a master optical clock over a turbulent 4-km open air path via optical two-way time-frequency transfer. Once synchronized, the 10-GHz frequency signals generated at each site agree to 10 -14 at one second and below 10 -17 at 1000 seconds. In addition, the two clock times are synchronized to ±13 fs over an 8-hour period. The ability to phase-synchronize 10-GHz signals across platforms supports future distributed coherent sensing, while the ability to time-synchronize multiple microwave-based clocks to a high-performance master optical clock supports future precision navigation/timing systems.
Closing the gap between rocks and clocks using total-evidence dating.

PubMed

Ronquist, Fredrik; Lartillot, Nicolas; Phillips, Matthew J

2016-07-19

Total-evidence dating (TED) allows evolutionary biologists to incorporate a wide range of dating information into a unified statistical analysis. One might expect this to improve the agreement between rocks and clocks but this is not necessarily the case. We explore the reasons for such discordance using a mammalian dataset with rich molecular, morphological and fossil information. There is strong conflict in this dataset between morphology and molecules under standard stochastic models. This causes TED to push divergence events back in time when using inadequate models or vague priors, a phenomenon we term 'deep root attraction' (DRA). We identify several causes of DRA. Failure to account for diversified sampling results in dramatic DRA, but this can be addressed using existing techniques. Inadequate morphological models also appear to be a major contributor to DRA. The major reason seems to be that current models do not account for dependencies among morphological characters, causing distorted topology and branch length estimates. This is particularly problematic for huge morphological datasets, which may contain large numbers of correlated characters. Finally, diversification and fossil sampling priors that do not incorporate all the available background information can contribute to DRA, but these priors can also be used to compensate for DRA. Specifically, we show that DRA in the mammalian dataset can be addressed by introducing a modest extra penalty for ghost lineages that are unobserved in the fossil record, for instance by assuming rapid diversification, rare extinction or high fossil sampling rate; any of these assumptions produces highly congruent divergence time estimates with a minimal gap between rocks and clocks. Under these conditions, fossils have a stabilizing influence on divergence time estimates and significantly increase the precision of those estimates, which are generally close to the dates suggested by palaeontologists.This article is part of the themed issue 'Dating species divergences using rocks and clocks'. © 2016 The Authors.
Single-transistor-clocked flip-flop

DOEpatents

Zhao, Peiyi; Darwish, Tarek; Bayoumi, Magdy

2005-08-30

The invention provides a low power, high performance flip-flop. The flip-flop uses only one clocked transistor. The single clocked transistor is shared by the first and second branches of the device. A pulse generator produces a clock pulse to trigger the flip-flop. In one preferred embodiment the device can be made as a static explicit pulsed flip-flop which employs only two clocked transistors.
Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex.

PubMed

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

PubMed Central

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. PMID:22039518
Robust determination of surface relaxivity from nuclear magnetic resonance DT2 measurements

NASA Astrophysics Data System (ADS)

Luo, Zhi-Xiang; Paulsen, Jeffrey; Song, Yi-Qiao

2015-10-01

Nuclear magnetic resonance (NMR) is a powerful tool to probe into geological materials such as hydrocarbon reservoir rocks and groundwater aquifers. It is unique in its ability to obtain in situ the fluid type and the pore size distributions (PSD). The T1 and T2 relaxation times are closely related to the pore geometry through the parameter called surface relaxivity. This parameter is critical for converting the relaxation time distribution into the PSD and so is key to accurately predicting permeability. The conventional way to determine the surface relaxivity ρ2 had required independent laboratory measurements of the pore size. Recently Zielinski et al. proposed a restricted diffusion model to extract the surface relaxivity from the NMR diffusion-T2 relaxation (DT2) measurement. Although this method significantly improved the ability to directly extract surface relaxivity from a pure NMR measurement, there are inconsistencies with their model and it relies on a number of preset parameters. Here we propose an improved signal model to incorporate a scalable LT and extend their method to extract the surface relaxivity based on analyzing multiple DT2 maps with varied diffusion observation time. With multiple diffusion observation times, the apparent diffusion coefficient correctly describes the restricted diffusion behavior in samples with wide PSDs, and the new method does not require predetermined parameters, such as the bulk diffusion coefficient and tortuosity. Laboratory experiments on glass beads packs with the beads diameter ranging from 50 μm to 500 μm are used to validate the new method. The extracted diffusion parameters are consistent with their known values and the determined surface relaxivity ρ2 agrees with the expected value within ±7%. This method is further successfully applied on a Berea sandstone core and yields surface relaxivity ρ2 consistent with the literature.
Reprocessing the Elliptical Orbiting Galileo Satellites E14 and E18: Preliminary Results

NASA Astrophysics Data System (ADS)

Männel, Benjamin

2017-04-01

In August 2014, the two Galileo satellites FOC-1 (E18) and FOC-2 (E14) were - due to a technical problem - launched into a wrong, elliptic orbit. In a recovery mission a series of orbit maneuvers were performed to raise the perigee to an altitude where both spacecrafts could be introduced to the Galileo navigation service. After this period of orbit maintenance both satellites started to transmit navigation signals at November 29, 2014 (E18) and March 17, 2015 (E14). However, as it was not possible to recover the nominal orbits due to propellant limitations, both spacecrafts orbit the Earth with a numerical eccentricity of 0.16 and an inclination of 50.2°. Very soon, it was assumed that both satellites could be highly useful for studies on general relativity, especially as the Galileo spacecrafts are equipped with very stable passive hydrogen masers. A prerequisite for dedicated studies in this field are highly accurate satellite orbits and clock corrections. Preliminary results for orbit and satellite clock determination will be presented based on an initial reprocessing over the past 2.5 years. The presentation focuses firstly on orbit modeling aspects with respect to the elliptically orbits. Secondly the derived clock corrections for the on-board passive clocks are assessed with respect to the reference clock at ground stations. The results will be discussed also with respect to the proposed Galileo-based studies on the gravitational redshift.
Regulation of molecular clock oscillations and phagocytic activity via muscarinic Ca2+ signaling in human retinal pigment epithelial cells

PubMed Central

Ikarashi, Rina; Akechi, Honami; Kanda, Yuzuki; Ahmad, Alsawaf; Takeuchi, Kouhei; Morioka, Eri; Sugiyama, Takashi; Ebisawa, Takashi; Ikeda, Masaaki; Ikeda, Masayuki

2017-01-01

Vertebrate eyes are known to contain circadian clocks, however, the intracellular mechanisms regulating the retinal clockwork remain largely unknown. To address this, we generated a cell line (hRPE-YC) from human retinal pigmental epithelium, which stably co-expressed reporters for molecular clock oscillations (Bmal1-luciferase) and intracellular Ca2+ concentrations (YC3.6). The hRPE-YC cells demonstrated circadian rhythms in Bmal1 transcription. Also, these cells represented circadian rhythms in Ca2+-spiking frequencies, which were canceled by dominant-negative Bmal1 transfections. The muscarinic agonist carbachol, but not photic stimulation, phase-shifted Bmal1 transcriptional rhythms with a type-1 phase response curve. This is consistent with significant M3 muscarinic receptor expression and little photo-sensor (Cry2 and Opn4) expression in these cells. Moreover, forskolin phase-shifted Bmal1 transcriptional rhythm with a type-0 phase response curve, in accordance with long-lasting CREB phosphorylation levels after forskolin exposure. Interestingly, the hRPE-YC cells demonstrated apparent circadian rhythms in phagocytic activities, which were abolished by carbachol or dominant-negative Bmal1 transfection. Because phagocytosis in RPE cells determines photoreceptor disc shedding, molecular clock oscillations and cytosolic Ca2+ signaling may be the driving forces for disc-shedding rhythms known in various vertebrates. In conclusion, the present study provides a cellular model to understand molecular and intracellular signaling mechanisms underlying human retinal circadian clocks. PMID:28276525
Unraveling the complexities of circadian and sleep interactions with memory formation through invertebrate research

PubMed Central

Michel, Maximilian; Lyons, Lisa C.

2014-01-01

Across phylogeny, the endogenous biological clock has been recognized as providing adaptive advantages to organisms through coordination of physiological and behavioral processes. Recent research has emphasized the role of circadian modulation of memory in generating peaks and troughs in cognitive performance. The circadian clock along with homeostatic processes also regulates sleep, which itself impacts the formation and consolidation of memory. Thus, the circadian clock, sleep and memory form a triad with ongoing dynamic interactions. With technological advances and the development of a global 24/7 society, understanding the mechanisms underlying these connections becomes pivotal for development of therapeutic treatments for memory disorders and to address issues in cognitive performance arising from non-traditional work schedules. Invertebrate models, such as Drosophila melanogaster and the mollusks Aplysia and Lymnaea, have proven invaluable tools for identification of highly conserved molecular processes in memory. Recent research from invertebrate systems has outlined the influence of sleep and the circadian clock upon synaptic plasticity. In this review, we discuss the effects of the circadian clock and sleep on memory formation in invertebrates drawing attention to the potential of in vivo and in vitro approaches that harness the power of simple invertebrate systems to correlate individual cellular processes with complex behaviors. In conclusion, this review highlights how studies in invertebrates with relatively simple nervous systems can provide mechanistic insights into corresponding behaviors in higher organisms and can be used to outline possible therapeutic options to guide further targeted inquiry. PMID:25136297
A (201)Hg+ Comagnetometer for (199)Hg+ Trapped Ion Space Atomic Clocks

NASA Technical Reports Server (NTRS)

Burt, Eric A.; Taghavi, Shervin; Tjoelker, Robert L.

2011-01-01

A method has been developed for unambiguously measuring the exact magnetic field experienced by trapped mercury ions contained within an atomic clock intended for space applications. In general, atomic clocks are insensitive to external perturbations that would change the frequency at which the clocks operate. On a space platform, these perturbative effects can be much larger than they would be on the ground, especially in dealing with the magnetic field environment. The solution is to use a different isotope of mercury held within the same trap as the clock isotope. The magnetic field can be very accurately measured with a magnetic-field-sensitive atomic transition in the added isotope. Further, this measurement can be made simultaneously with normal clock operation, thereby not degrading clock performance. Instead of using a conventional magnetometer to measure ambient fields, which would necessarily be placed some distance away from the clock atoms, first order field-sensitive atomic transition frequency changes in the atoms themselves determine the variations in the magnetic field. As a result, all ambiguity over the exact field value experienced by the atoms is removed. Atoms used in atomic clocks always have an atomic transition (often referred to as the clock transition) that is sensitive to magnetic fields only in second order, and usually have one or more transitions that are first-order field sensitive. For operating parameters used in the (199)Hg(+) clock, the latter can be five orders of magnitude or more sensitive to field fluctuations than the clock transition, thereby providing an unambiguous probe of the magnetic field strength.
Circadian molecular clock in lung pathophysiology

PubMed Central

Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.

2015-01-01

Disrupted daily or circadian rhythms of lung function and inflammatory responses are common features of chronic airway diseases. At the molecular level these circadian rhythms depend on the activity of an autoregulatory feedback loop oscillator of clock gene transcription factors, including the BMAL1:CLOCK activator complex and the repressors PERIOD and CRYPTOCHROME. The key nuclear receptors and transcription factors REV-ERBα and RORα regulate Bmal1 expression and provide stability to the oscillator. Circadian clock dysfunction is implicated in both immune and inflammatory responses to environmental, inflammatory, and infectious agents. Molecular clock function is altered by exposomes, tobacco smoke, lipopolysaccharide, hyperoxia, allergens, bleomycin, as well as bacterial and viral infections. The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors. Environmental agents and redox modulation may alter the levels of REV-ERBα and RORα in lung tissue in association with a heightened DNA damage response, cellular senescence, and inflammation. A reciprocal relationship exists between the molecular clock and immune/inflammatory responses in the lungs. Molecular clock function in lung cells may be used as a biomarker of disease severity and exacerbations or for assessing the efficacy of chronotherapy for disease management. Here, we provide a comprehensive overview of clock-controlled cellular and molecular functions in the lungs and highlight the repercussions of clock disruption on the pathophysiology of chronic airway diseases and their exacerbations. Furthermore, we highlight the potential for the molecular clock as a novel chronopharmacological target for the management of lung pathophysiology. PMID:26361874
Space-based augmentation for global navigation satellite systems.

PubMed

Grewal, Mohinder S

2012-03-01

This paper describes space-based augmentation for global navigation satellite systems (GNSS). Space-based augmentations increase the accuracy and integrity of the GNSS, thereby enhancing users' safety. The corrections for ephemeris, ionospheric delay, and clocks are calculated from reference station measurements of GNSS data in wide-area master stations and broadcast via geostationary earth orbit (GEO) satellites. This paper discusses the clock models, satellite orbit determination, ionospheric delay estimation, multipath mitigation, and GEO uplink subsystem (GUS) as used in the Wide Area Augmentation System developed by the FAA.
Pigment-Dispersing Factor Signaling and Circadian Rhythms in Insect Locomotor Activity

PubMed Central

Shafer, Orie T.; Yao, Zepeng

2014-01-01

Though expressed in relatively few neurons in insect nervous systems, pigment-dispersing factor (PDF) plays many roles in the control of behavior and physiology. PDF’s role in circadian timekeeping is its best-understood function and the focus of this review. Here we recount the isolation and characterization of insect PDFs, review the evidence that PDF acts as a circadian clock output factor, and discuss emerging models of how PDF functions within circadian clock neuron network of Drosophila, the species in which this peptide’s circadian roles are best understood. PMID:25386391
Design of high-speed burst mode clock and data recovery IC for passive optical network

NASA Astrophysics Data System (ADS)

Yan, Minhui; Hong, Xiaobin; Huang, Wei-Ping; Hong, Jin

2005-09-01

Design of a high bit rate burst mode clock and data recovery (BMCDR) circuit for gigabit passive optical networks (GPON) is described. A top-down design flow is established and some of the key issues related to the behavioural level modeling are addressed in consideration for the complexity of the BMCDR integrated circuit (IC). Precise implementation of Simulink behavioural model accounting for the saturation of frequency control voltage is therefore developed for the BMCDR, and the parameters of the circuit blocks can be readily adjusted and optimized based on the behavioural model. The newly designed BMCDR utilizes the 0.18um standard CMOS technology and is shown to be capable of operating at bit rate of 2.5Gbps, as well as the recovery time of one bit period in our simulation. The developed behaviour model is verified by comparing with the detailed circuit simulation.
PHARAO laser source flight model: Design and performances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lévèque, T., E-mail: thomas.leveque@cnes.fr; Faure, B.; Esnault, F. X.

2015-03-15

In this paper, we describe the design and the main performances of the PHARAO laser source flight model. PHARAO is a laser cooled cesium clock specially designed for operation in space and the laser source is one of the main sub-systems. The flight model presented in this work is the first remote-controlled laser system designed for spaceborne cold atom manipulation. The main challenges arise from mechanical compatibility with space constraints, which impose a high level of compactness, a low electric power consumption, a wide range of operating temperature, and a vacuum environment. We describe the main functions of the lasermore » source and give an overview of the main technologies developed for this instrument. We present some results of the qualification process. The characteristics of the laser source flight model, and their impact on the clock performances, have been verified in operational conditions.« less
Covariance and Quantum Cosmology: A Comparison of Two Matter Clocks

NASA Astrophysics Data System (ADS)

Halnon, Theodore; Bojowald, Martin

2017-01-01

In relativity, time is relative between reference frames. However, quantum mechanics requires a specific time coordinate in order to write an evolution equation for wave functions. This difference between the two theories leads to the problem of time in quantum gravity. One method to study quantum relativity is to interpret the dynamics of a matter field as a clock. In order to test the relationship between different reference frames, an isotropic cosmological model with two matter ingredients is introduced. One is given by a scalar field and one by vacuum energy or a cosmological constant. There are two matter fields, and thus two different Hamiltonians are derived from the respective clock rates. Semi-classical solutions are found for these equations and a comparison is made of the physical predictions that they imply. Partial funding from the Ronald E. McNair Postbaccalaureate Achievement Program.

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