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Sample records for bayesian molecular clock

  1. Variable molecular clocks in hominoids

    OpenAIRE

    Elango, Navin; Thomas, James W.; Yi, Soojin V.

    2006-01-01

    Generation time is an important determinant of a neutral molecular clock. There are several human-specific life history traits that led to a substantially longer generation time in humans than in other hominoids. Indeed, a long generation time is considered an important trait that distinguishes humans from their closest relatives. Therefore, humans may exhibit a significantly slower molecular clock as compared to other hominoids. To investigate this hypothesis, we performed a large-scale anal...

  2. Tectonic blocks and molecular clocks

    Science.gov (United States)

    2016-01-01

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

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

    Science.gov (United States)

    Wares, John P.

    2008-01-01

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

  4. Molecular clock in neutral protein evolution

    Directory of Open Access Journals (Sweden)

    Wilke Claus O

    2004-08-01

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

  5. Finding Clocks in Genes: A Bayesian Approach to Estimate Periodicity

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    Yan Ren

    2016-01-01

    Full Text Available Identification of rhythmic gene expression from metabolic cycles to circadian rhythms is crucial for understanding the gene regulatory networks and functions of these biological processes. Recently, two algorithms, JTK_CYCLE and ARSER, have been developed to estimate periodicity of rhythmic gene expression. JTK_CYCLE performs well for long or less noisy time series, while ARSER performs well for detecting a single rhythmic category. However, observing gene expression at high temporal resolution is not always feasible, and many scientists are interested in exploring both ultradian and circadian rhythmic categories simultaneously. In this paper, a new algorithm, named autoregressive Bayesian spectral regression (ABSR, is proposed. It estimates the period of time-course experimental data and classifies gene expression profiles into multiple rhythmic categories simultaneously. Through the simulation studies, it is shown that ABSR substantially improves the accuracy of periodicity estimation and clustering of rhythmic categories as compared to JTK_CYCLE and ARSER for the data with low temporal resolution. Moreover, ABSR is insensitive to rhythmic patterns. This new scheme is applied to existing time-course mouse liver data to estimate period of rhythms and classify the genes into ultradian, circadian, and arrhythmic categories. It is observed that 49.2% of the circadian profiles detected by JTK_CYCLE with 1-hour resolution are also detected by ABSR with only 4-hour resolution.

  6. The molecular clock may be an episodic clock.

    OpenAIRE

    Gillespie, J. H.

    1984-01-01

    It is argued that the apparent constancy of the rate of molecular evolution may be an artifact due to the very slow rate of evolution of individual amino acids. A statistical analysis of protein evolution using a stationary point process as the null hypothesis leads to the conclusion that molecular evolution is episodic, with short bursts of rapid evolution followed by long periods of slow evolution. Such dynamics are incompatible with the neutral allele theory and require a revision of the s...

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

    Science.gov (United States)

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

    2016-01-01

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

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

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    Tsuyoshi Kadomatsu

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

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

    Science.gov (United States)

    Udoh, Uduak S.; Valcin, Jennifer A.; Gamble, Karen L.; Bailey, Shannon M.

    2015-01-01

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases. PMID:26473939

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

    Directory of Open Access Journals (Sweden)

    Uduak S. Udoh

    2015-10-01

    Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  11. Estimation of divergence times in litostomatean ciliates (Ciliophora: Intramacronucleata), using Bayesian relaxed clock and 18S rRNA gene.

    Science.gov (United States)

    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. PMID:26204556

  12. Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

    OpenAIRE

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

    2011-01-01

    Almost all organisms ranging from single cell bacteria to humans exhibit a variety of behavioral, physiological, and biochemical rhythms. In mammals, circadian rhythms control the timing of many physiological processes over a 24-h period, including sleep-wake cycles, body temperature, feeding, and hormone production. This body of research has led to defined characteristics of circadian rhythms based on period length, phase, and amplitude. Underlying circadian behaviors is a molecular clock me...

  13. Estimating metazoan divergence times with a molecular clock

    OpenAIRE

    Peterson, Kevin J.; Lyons, Jessica B.; Nowak, Kristin S.; Takacs, Carter M.; Wargo, Matthew J.; McPeek, Mark A.

    2004-01-01

    Accurately dating when the first bilaterally symmetrical animals arose is crucial to our understanding of early animal evolution. The earliest unequivocally bilaterian fossils are ≈555 million years old. In contrast, molecular-clock analyses calibrated by using the fossil record of vertebrates estimate that vertebrates split from dipterans (Drosophila) ≈900 million years ago (Ma). Nonetheless, comparative genomic analyses suggest that a significant rate difference exists between vertebrates a...

  14. Applications of Bayesian filtering in wireless networks: Clock synchronization, localization, and RF tomography

    Science.gov (United States)

    Hamilton, Benjamin Russell

    In this work, we investigate the application of Bayesian filtering techniques such as Kalman Filtering and Particle filtering to the problems of network time synchronization, self-localization and radio-frequency (RF) tomography in wireless networks. Networks of large numbers of small, cheap, mobile wireless devices have shown enormous potential in applications ranging from intrusion detection to environmental monitoring. These applications require the devices to have accurate time and position estimates, however traditional techniques may not be available. Additionally RF tomography offers a new paradigm to sense the network environment and could greatly enhance existing network capabilities. While there are some existing works addressing these problems, they all suffer from limitations. Current time synchronization methods are not energy efficient on small wireless devices with low quality oscillators. Existing localization methods do not consider additional sources of information available to nodes in the network such as measurements from accelerometers or models of the shadowing environment in the network. RF tomography has only been examined briefly in such networks, and current algorithms can not handle node mobility and rely on shadowing models that have not been experimentally verified. We address the time synchronization problem by analyzing the characteristics of the clocks in small wireless devices, developing a model for it, and then applying a Kalman filter to track both clock offset and skew. In our investigation into RF tomography, we present a method using a Kalman filter which jointly estimates and tracks static and dynamic objects in the environment. We also use channel measurements collected from a field test of our RF tomography testbed to compare RF shadowing models. For the localization problem, we present two algorithms incorporating additional information for improved localization: one based on a distributed extended Kalman filter that

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

    Directory of Open Access Journals (Sweden)

    Eva-Liis Loogväli

    Full Text Available The molecular clock of mitochondrial DNA has been extensively used to date various genetic events. However, its substitution rate among humans appears to be higher than rates inferred from human-chimpanzee comparisons, limiting the potential of interspecies clock calibrations for intraspecific dating. It is not well understood how and why the substitution rate accelerates. We have analyzed a phylogenetic tree of 3057 publicly available human mitochondrial DNA coding region sequences for changes in the ratios of mutations belonging to different functional classes. The proportion of non-synonymous and RNA genes substitutions has reduced over hundreds of thousands of years. The highest mutation ratios corresponding to fast acceleration in the apparent substitution rate of the coding sequence have occurred after the end of the Last Ice Age. We recalibrate the molecular clock of human mtDNA as 7990 years per synonymous mutation over the mitochondrial genome. However, the distribution of substitutions at synonymous sites in human data significantly departs from a model assuming a single rate parameter and implies at least 3 different subclasses of sites. Neutral model with 3 synonymous substitution rates can explain most, if not all, of the apparent molecular clock difference between the intra- and interspecies levels. Our findings imply the sluggishness of purifying selection in removing the slightly deleterious mutations from the human as well as the Neandertal and chimpanzee populations. However, for humans, the weakness of purifying selection has been further exacerbated by the population expansions associated with the out-of Africa migration and the end of the Last Ice Age.

  16. Pacemaker-neuron-dependent disturbance of the molecular clockwork by a Drosophila CLOCK mutant homologous to the mouse Clock mutation.

    Science.gov (United States)

    Lee, Euna; Cho, Eunjoo; Kang, Doo Hyun; Jeong, Eun Hee; Chen, Zheng; Yoo, Seung-Hee; Kim, Eun Young

    2016-08-16

    Circadian clocks are composed of transcriptional/translational feedback loops (TTFLs) at the cellular level. In Drosophila TTFLs, the transcription factor dCLOCK (dCLK)/CYCLE (CYC) activates clock target gene expression, which is repressed by the physical interaction with PERIOD (PER). Here, we show that amino acids (AA) 657-707 of dCLK, a region that is homologous to the mouse Clock exon 19-encoded region, is crucial for PER binding and E-box-dependent transactivation in S2 cells. Consistently, in transgenic flies expressing dCLK with an AA657-707 deletion in the Clock (Clk(out)) genetic background (p{dClk-Δ};Clk(out)), oscillation of core clock genes' mRNAs displayed diminished amplitude compared with control flies, and the highly abundant dCLKΔ657-707 showed significantly decreased binding to PER. Behaviorally, the p{dClk-Δ};Clk(out) flies exhibited arrhythmic locomotor behavior in the photic entrainment condition but showed anticipatory activities of temperature transition and improved free-running rhythms in the temperature entrainment condition. Surprisingly, p{dClk-Δ};Clk(out) flies showed pacemaker-neuron-dependent alterations in molecular rhythms; the abundance of dCLK target clock proteins was reduced in ventral lateral neurons (LNvs) but not in dorsal neurons (DNs) in both entrainment conditions. In p{dClk-Δ};Clk(out) flies, however, strong but delayed molecular oscillations in temperature cycle-sensitive pacemaker neurons, such as DN1s and DN2s, were correlated with delayed anticipatory activities of temperature transition. Taken together, our study reveals that the LNv molecular clockwork is more sensitive than the clockwork of DNs to dysregulation of dCLK by AA657-707 deletion. Therefore, we propose that the dCLK/CYC-controlled TTFL operates differently in subsets of pacemaker neurons, which may contribute to their specific functions. PMID:27489346

  17. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy.

    Science.gov (United States)

    Scotton, Chiara; Bovolenta, Matteo; Schwartz, Elena; Falzarano, Maria Sofia; Martoni, Elena; Passarelli, Chiara; Armaroli, Annarita; Osman, Hana; Rodolico, Carmelo; Messina, Sonia; Pegoraro, Elena; D'Amico, Adele; Bertini, Enrico; Gualandi, Francesca; Neri, Marcella; Selvatici, Rita; Boffi, Patrizia; Maioli, Maria Antonietta; Lochmüller, Hanns; Straub, Volker; Bushby, Katherine; Castrignanò, Tiziana; Pesole, Graziano; Sabatelli, Patrizia; Merlini, Luciano; Braghetta, Paola; Bonaldo, Paolo; Bernardi, Paolo; Foley, Reghan; Cirak, Sebahattin; Zaharieva, Irina; Muntoni, Francesco; Capitanio, Daniele; Gelfi, Cecilia; Kotelnikova, Ekaterina; Yuryev, Anton; Lebowitz, Michael; Zhang, Xiping; Hodge, Brian A; Esser, Karyn A; Ferlini, Alessandra

    2016-04-15

    Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in bothCol6a1(-/-)mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly,Bmal1(-/-)(also known asArntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis. PMID:26945058

  18. Enhancing coherence in molecular spin qubits via atomic clock transitions

    Science.gov (United States)

    Shiddiq, Muhandis; Komijani, Dorsa; Duan, Yan; Gaita-Ariño, Alejandro; Coronado, Eugenio; Hill, Stephen

    2016-03-01

    Quantum computing is an emerging area within the information sciences revolving around the concept of quantum bits (qubits). A major obstacle is the extreme fragility of these qubits due to interactions with their environment that destroy their quantumness. This phenomenon, known as decoherence, is of fundamental interest. There are many competing candidates for qubits, including superconducting circuits, quantum optical cavities, ultracold atoms and spin qubits, and each has its strengths and weaknesses. When dealing with spin qubits, the strongest source of decoherence is the magnetic dipolar interaction. To minimize it, spins are typically diluted in a diamagnetic matrix. For example, this dilution can be taken to the extreme of a single phosphorus atom in silicon, whereas in molecular matrices a typical ratio is one magnetic molecule per 10,000 matrix molecules. However, there is a fundamental contradiction between reducing decoherence by dilution and allowing quantum operations via the interaction between spin qubits. To resolve this contradiction, the design and engineering of quantum hardware can benefit from a ‘bottom-up’ approach whereby the electronic structure of magnetic molecules is chemically tailored to give the desired physical behaviour. Here we present a way of enhancing coherence in solid-state molecular spin qubits without resorting to extreme dilution. It is based on the design of molecular structures with crystal field ground states possessing large tunnelling gaps that give rise to optimal operating points, or atomic clock transitions, at which the quantum spin dynamics become protected against dipolar decoherence. This approach is illustrated with a holmium molecular nanomagnet in which long coherence times (up to 8.4 microseconds at 5 kelvin) are obtained at unusually high concentrations. This finding opens new avenues for quantum computing based on molecular spin qubits.

  19. Enhancing coherence in molecular spin qubits via atomic clock transitions.

    Science.gov (United States)

    Shiddiq, Muhandis; Komijani, Dorsa; Duan, Yan; Gaita-Ariño, Alejandro; Coronado, Eugenio; Hill, Stephen

    2016-03-17

    Quantum computing is an emerging area within the information sciences revolving around the concept of quantum bits (qubits). A major obstacle is the extreme fragility of these qubits due to interactions with their environment that destroy their quantumness. This phenomenon, known as decoherence, is of fundamental interest. There are many competing candidates for qubits, including superconducting circuits, quantum optical cavities, ultracold atoms and spin qubits, and each has its strengths and weaknesses. When dealing with spin qubits, the strongest source of decoherence is the magnetic dipolar interaction. To minimize it, spins are typically diluted in a diamagnetic matrix. For example, this dilution can be taken to the extreme of a single phosphorus atom in silicon, whereas in molecular matrices a typical ratio is one magnetic molecule per 10,000 matrix molecules. However, there is a fundamental contradiction between reducing decoherence by dilution and allowing quantum operations via the interaction between spin qubits. To resolve this contradiction, the design and engineering of quantum hardware can benefit from a 'bottom-up' approach whereby the electronic structure of magnetic molecules is chemically tailored to give the desired physical behaviour. Here we present a way of enhancing coherence in solid-state molecular spin qubits without resorting to extreme dilution. It is based on the design of molecular structures with crystal field ground states possessing large tunnelling gaps that give rise to optimal operating points, or atomic clock transitions, at which the quantum spin dynamics become protected against dipolar decoherence. This approach is illustrated with a holmium molecular nanomagnet in which long coherence times (up to 8.4 microseconds at 5 kelvin) are obtained at unusually high concentrations. This finding opens new avenues for quantum computing based on molecular spin qubits. PMID:26983539

  20. Circadian Clocks in the Cnidaria: Environmental Entrainment, Molecular Regulation, and Organismal Outputs

    OpenAIRE

    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, ...

  1. Nucleotide sequences of immunoglobulin epsilon genes of chimpanzee and orangutan: DNA molecular clock and hominoid evolution.

    OpenAIRE

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

    1987-01-01

    To determine the phylogenetic relationships among hominoids and the dates of their divergence, the complete nucleotide sequences of the constant region of the immunoglobulin epsilon-chain (C epsilon 1) genes from chimpanzee and orangutan have been determined. These sequences were compared with the human epsilon-chain constant-region sequence. A molecular clock (silent molecular clock), measured by the degree of sequence divergence at the synonymous (silent) positions of protein-encoding regio...

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

    Directory of Open Access Journals (Sweden)

    Mitsunori Miyazaki

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

  3. Photoperiodic entrainment of the circadian molecular clock in the mice

    Czech Academy of Sciences Publication Activity Database

    Sosniyenko, Serhiy; Hut, R.; Matějů, Kristýna; Sládek, Martin; Illnerová, Helena; Sumová, Alena

    Praha : The Czech Neuroscience Society, 2007. s. 92-92. [Conference of the Czech Neuroscience Society /6./. 19.11.2007-20.11.2007, Praha] Grant ostatní: 6th Framework project EUCLOCK(XE) 18741 Institutional research plan: CEZ:AV0Z50110509 Keywords : spo2 * photoperiod * clock genes * mice Subject RIV: FH - Neurology

  4. Photoperiodic entrainment of the circadian molecular clock in the mice

    Czech Academy of Sciences Publication Activity Database

    Sosniyenko, Serhiy; Laurinová, Kristýna; Sládek, Martin; Sumová, Alena

    Brno : Fyziologický ústav LF MU, 2007. [Fyziologické dny /83./. 06.02.2007-08.02.2007, Brno] Grant ostatní: 6th Framework project EUCLOCK(XE) 18741 Institutional research plan: CEZ:AV0Z50110509 Keywords : spo2 * photoperiod * clock genes * mice Subject RIV: FH - Neurology

  5. Investigations of the CLOCK and BMAL1 Proteins Binding to DNA: A Molecular Dynamics Simulation Study

    Science.gov (United States)

    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. PMID:27153104

  6. Molecular clocks in reptiles: life history influences rate of molecular evolution.

    Science.gov (United States)

    Bromham, Lindell

    2002-03-01

    Life history has been implicated as a determinant of variation in rate of molecular evolution amongst vertebrate species because of a negative correlation between body size and substitution rate for many molecular data sets. Both the generality and the cause of the negative body size trend have been debated, and the validity of key studies has been questioned (particularly concerning the failure to account for phylogenetic bias). In this study, a comparative method has been used to test for an association between a range of life-history variables-such as body size, age at maturity, and clutch size-and DNA substitution rate for three genes (NADH4, cytochrome b, and c-mos). A negative relationship between body size and rate of molecular evolution was found for phylogenetically independent pairs of reptile species spanning turtles, lizards, snakes, crocodile, and tuatara. Although this study was limited by the number of comparisons for which both sequence and life-history data were available, the results suggest that a negative body size trend in rate of molecular evolution may be a general feature of reptile molecular evolution, consistent with similar studies of mammals and birds. This observation has important implications for uncovering the mechanisms of molecular evolution and warns against assuming that related lineages will share the same substitution rate (a local molecular clock) in order to date evolutionary divergences from DNA sequences. PMID:11861889

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    , recent studies have shown the presence of extrahypothalamic oscillators in other areas of the brain including the cerebellum. In the present study, the authors unravel the cerebellar molecular clock by analyzing clock gene expression in the cerebellum of the rat by use of radiochemical in situ...... hybridization and quantitative real-time polymerase chain reaction. The authors here show that all core clock genes, i.e., Per1, Per2, Per3, Cry1, Cry2, Clock, Arntl, and Nr1d1, as well as the clock-controlled gene Dbp, are expressed in the granular and Purkinje cell layers of the cerebellar cortex. Among these...... genes, Per1, Per2, Per3, Cry1, Arntl, Nr1d1, and Dbp were found to exhibit circadian rhythms in a sequential temporal manner similar to that of the SCN, but with several hours of delay. The results of lesion studies indicate that the molecular oscillatory profiles of Per1, Per2, and Cry1 in the...

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

    International Nuclear Information System (INIS)

    To determine the phylogenetic relationships among hominoids and the dates of their divergence, the complete nucleotide sequences of the constant region of the immunoglobulin eta-chain (C/sub eta1/) genes from chimpanzee and orangutan have been determined. These sequences were compared with the human eta-chain constant-region sequence. A molecular clock (silent molecular clock), measured by the degree of sequence divergence at the synonymous (silent) positions of protein-encoding regions, was introduced for the present study. From the comparison of nucleotide sequences of α1-antitrypsin and β- and δ-globulin genes between humans and Old World monkeys, the silent molecular clock was calibrated: the mean evolutionary rate of silent substitution was determined to be 1.56 x 10-9 substitutions per site per year. Using the silent molecular clock, the mean divergence dates of chimpanzee and orangutan from the human lineage were estimated as 6.4 +/- 2.6 million years and 17.3 +/- 4.5 million years, respectively. It was also shown that the evolutionary rate of primate genes is considerably slower than those of other mammalian genes

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

    OpenAIRE

    Wendy Mok; Kelly Seto; Jon Stone

    2007-01-01

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

  10. Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks.

    Science.gov (United States)

    Wolff, Gretchen; Duncan, Marilyn J; Esser, Karyn A

    2013-08-01

    Shifting the onset of light, acutely or chronically, can profoundly affect responses to infection, tumor progression, development of metabolic disease, and mortality in mammals. To date, the majority of phase-shifting studies have focused on acute exposure to a shift in the timing of the light cycle, whereas the consequences of chronic phase shifts alone on molecular rhythms in peripheral tissues such as skeletal muscle have not been studied. In this study, we tested the effect of chronic phase advance on the molecular clock mechanism in two phenotypically different skeletal muscles. The phase advance protocol (CPA) involved 6-h phase advances (earlier light onset) every 4 days for 8 wk. Analysis of the molecular clock, via bioluminescence recording, in the soleus and flexor digitorum brevis (FDB) muscles and lung demonstrated that CPA advanced the phase of the rhythm when studied immediately after CPA. However, if the mice were placed into free-running conditions (DD) for 2 wk after CPA, the molecular clock was not phase shifted in the two muscles but was still shifted in the lung. Wheel running behavior remained rhythmic in CPA mice; however, the endogenous period length of the free-running rhythm was significantly shorter than that of control mice. Core body temperature, cage activity, and heart rate remained rhythmic throughout the experiment, although the onset of the rhythms was significantly delayed with CPA. These results provide clues that lifestyles associated with chronic environmental desynchrony, such as shift work, can have disruptive effects on the molecular clock mechanism in peripheral tissues, including both types of skeletal muscle. Whether this can contribute, long term, to increased incidence of insulin resistance/metabolic disease requires further study. PMID:23703115

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

    Science.gov (United States)

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

    2004-12-01

    Criticism of molecular clock studies often centres on inadequate calibration and a perceived lack of correlation between reproductive isolation and recognisable morphological evolution. Since many major groups (e.g. birds, mammals, reptiles) have a poor fossil record, it is often difficult to test and refute these limitations. Planktic foraminifera represent an exception to this rule. Deep-sea sediments are super-abundant in foraminifera, and large numbers of specimens and occurrences are easily garnered from Ocean Drilling Programme cores. Planktic foraminifera therefore represent an ideal model group with which to test and refine molecular clock studies. Since the 1990AƒAøAøâ_sA¬Aøâ_zAøs, genetic sequences (principally 18S r-RNA) have been extracted from living planktic foraminifera, and a large genetic library has developed. Our study attempts to contextualise and test molecular data, particularly AƒAøAøâ_sA¬Aecologies and longevities, which in Recent and sub-Recent sediments can be distinguished either on the basis of pore ultrastructure (Gl. siphonifera) or test colouration (Gs. ruber). In both cases, molecular clock estimates are indicative of ancient (7-11 Ma) intra-species cryptic divergences, which seem to be considerably older than fossil dates. In particular, the calculated molecular split between the two forms of Gs. ruber (AƒAøAøâ_sA¬Asmall amount of morphological evolution observed within the plexus. We have used morphometric methods on a large (over 2000 pooled specimens) dataset in an effort to independently test the molecular clock, using SEM-based measurement of pore metrics (for Gl. siphonifera) and a multivariate analysis of whole-test characteristics (for Gs. ruber). Comparison of results for the two species suggests interesting patterns; whilst the two cryptic sub-types of Gl. siphonifera seemingly can be traced through time and seem to respond to external oceanographic forcing, the sub-types of Gs. ruber appear to be truly

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

    Directory of Open Access Journals (Sweden)

    Benjamin Allen

    2015-02-01

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

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

    Science.gov (United States)

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

    2015-09-01

    Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function. PMID:26332979

  14. Identification of the molecular components of a Tigriopus californicus (Crustacea, Copepoda) circadian clock.

    Science.gov (United States)

    Nesbit, Katherine T; Christie, Andrew E

    2014-12-01

    Copepods of the genus Tigriopus have been proposed as marine models for investigations of environmental perturbation. One rapidly increasing anthropogenic stressor for intertidal organisms is light pollution. Given the sensitivity of circadian rhythms to exogenous light, the genes/proteins of a Tigriopus circadian pacemaker represent a potential system for investigating the influences of artificial light sources on circadian behavior in an intertidal species. Here, the molecular components of a putative Tigriopus californicus circadian clock were identified using publicly accessible transcriptome data; the recently deduced circadian proteins of the copepod Calanus finmarchicus were used as a reference. Transcripts encoding homologs of all commonly recognized ancestral arthropod core clock proteins were identified (i.e. CLOCK, CRYPTOCHROME 2, CYCLE, PERIOD and TIMELESS), as were ones encoding proteins likely to modulate the core clock (i.e. CASEIN KINASE II, CLOCKWORK ORANGE, DOUBLETIME, PROTEIN PHOSPHATASE 1, PROTEIN PHOSPHATASE 2A, SHAGGY, SUPERNUMERARY LIMBS and VRILLE) or to act as inputs to it (i.e. CRYPTOCHROME 1). PAR DOMAIN PROTEIN 1 was the only circadian-associated protein not identified in Tigriopus; it appears absent in Calanus too. These data represent just the third full set of molecular components for a crustacean circadian pacemaker (Daphnia pulex and C. finmarchicus previously), and only the second obtained from transcribed sequences (C. finmarchicus previously). Given Tigriopus' proposed status as a model for investigating the influences of anthropogenic stressors in the marine environment, these data provide the first suite of gene/protein targets for understanding how light pollution may influence circadian physiology and behavior in an intertidal organism. PMID:25310881

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

    Directory of Open Access Journals (Sweden)

    Ochman Howard

    2009-09-01

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

  16. Bayesian molecular phylogenetics: estimation of divergence dates and hypothesis testing

    OpenAIRE

    Aris-Brosou, S.

    2002-01-01

    With the advent of automated sequencing, sequence data are now available to help us understand the functioning of our genome, as well as its history. To date,powerful methods such as maximum likelihood have been used to estimate its mode and tempo of evolution and its branching pattern. However, these methods appear to have some limitations. The purpose of this thesis is to examine these issues in light of Bayesian modelling, taking advantage of some recent advances in Bayesian compu...

  17. Molecular clocks

    OpenAIRE

    Robinson, Noah E; Robinson, Arthur B.

    2001-01-01

    A convenient and precise mass spectrometric method for measurement of the deamidation rates of glutaminyl and asparaginyl residues in peptides and proteins has been developed; the rates of deamidation of 306 asparaginyl sequences in model peptides at pH 7.4, 37.0°C, 0.15 M Tris⋅HCl buffer have been determined; a library of 913 amide-containing peptides for use by other investigators in similar studies has been established; and, by means of simultaneous deamidation ...

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

    Directory of Open Access Journals (Sweden)

    Christy Anna Hipsley

    2014-05-01

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

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

    Indian Academy of Sciences (India)

    G V R Prasad

    2009-11-01

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

  20. Relaxed Molecular Clock Provides Evidence for Long-Distance Dispersal of Nothofagus (Southern Beech

    Directory of Open Access Journals (Sweden)

    Knapp Michael

    2005-01-01

    Full Text Available Nothofagus (southern beech, with an 80-million-year-old fossil record, has become iconic as a plant genus whose ancient Gondwanan relationships reach back into the Cretaceous era. Closely associated with Wegener's theory of "Kontinentaldrift", Nothofagus has been regarded as the "key genus in plant biogeography". This paradigm has the New Zealand species as passengers on a Moa's Ark that rafted away from other landmasses following the breakup of Gondwana. An alternative explanation for the current transoceanic distribution of species seems almost inconceivable given that Nothofagus seeds are generally thought to be poorly suited for dispersal across large distances or oceans. Here we test the Moa's Ark hypothesis using relaxed molecular clock methods in the analysis of a 7.2-kb fragment of the chloroplast genome. Our analyses provide the first unequivocal molecular clock evidence that, whilst some Nothofagus transoceanic distributions are consistent with vicariance, trans-Tasman Sea distributions can only be explained by long-distance dispersal. Thus, our analyses support the interpretation of an absence of Lophozonia and Fuscospora pollen types in the New Zealand Cretaceous fossil record as evidence for Tertiary dispersals of Nothofagus to New Zealand. Our findings contradict those from recent cladistic analyses of biogeographic data that have concluded transoceanic Nothofagus distributions can only be explained by vicariance events and subsequent extinction. They indicate that the biogeographic history of Nothofagus is more complex than envisaged under opposing polarised views expressed in the ongoing controversy over the relevance of dispersal and vicariance for explaining plant biodiversity. They provide motivation and justification for developing more complex hypotheses that seek to explain the origins of Southern Hemisphere biota.

  1. Relaxed molecular clock provides evidence for long-distance dispersal of Nothofagus (southern beech.

    Directory of Open Access Journals (Sweden)

    Michael Knapp

    2005-01-01

    Full Text Available Nothofagus (southern beech, with an 80-million-year-old fossil record, has become iconic as a plant genus whose ancient Gondwanan relationships reach back into the Cretaceous era. Closely associated with Wegener's theory of "Kontinentaldrift", Nothofagus has been regarded as the "key genus in plant biogeography". This paradigm has the New Zealand species as passengers on a Moa's Ark that rafted away from other landmasses following the breakup of Gondwana. An alternative explanation for the current transoceanic distribution of species seems almost inconceivable given that Nothofagus seeds are generally thought to be poorly suited for dispersal across large distances or oceans. Here we test the Moa's Ark hypothesis using relaxed molecular clock methods in the analysis of a 7.2-kb fragment of the chloroplast genome. Our analyses provide the first unequivocal molecular clock evidence that, whilst some Nothofagus transoceanic distributions are consistent with vicariance, trans-Tasman Sea distributions can only be explained by long-distance dispersal. Thus, our analyses support the interpretation of an absence of Lophozonia and Fuscospora pollen types in the New Zealand Cretaceous fossil record as evidence for Tertiary dispersals of Nothofagus to New Zealand. Our findings contradict those from recent cladistic analyses of biogeographic data that have concluded transoceanic Nothofagus distributions can only be explained by vicariance events and subsequent extinction. They indicate that the biogeographic history of Nothofagus is more complex than envisaged under opposing polarised views expressed in the ongoing controversy over the relevance of dispersal and vicariance for explaining plant biodiversity. They provide motivation and justification for developing more complex hypotheses that seek to explain the origins of Southern Hemisphere biota.

  2. Lego clocks : building a clock from parts

    NARCIS (Netherlands)

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

    2008-01-01

    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 intepr

  3. Age-Associated Disruption of Molecular Clock Expression in Skeletal Muscle of the Spontaneously Hypertensive Rat

    OpenAIRE

    Miyazaki, Mitsunori; Schroder, Elizabeth; Stephanie E Edelmann; Michael E Hughes; Kornacker, Karl; Balke, C. William; Esser, Karyn A.

    2011-01-01

    It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart ...

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

    Directory of Open Access Journals (Sweden)

    Ko-Fan Chen

    2014-04-01

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

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

    Science.gov (United States)

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

    2014-01-01

    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

  6. Molecular Approach to the Nyctinastic Movement of the Plant Controlled by a Biological Clock

    Directory of Open Access Journals (Sweden)

    Shosuke Yamamura

    2001-10-01

    Full Text Available Most leguminous plants close their leaves in the evening, as if to sleep, and open them early in the morning. This circadian rhythm is known to be controlled by the biological clock of such plants. Extensive studies on other nyctinastic plants led to the isolation of a variety of leaf-closing and leaf-opening substances. And, we found that the circadian rhythmic leaf-movement of these plants is controlled by a biological clock that regulates the balance of concentration between leaf-opening and -closing substances.

  7. Molecular mechanism of temperature sensing by the circadian clock of Neurospora crassa

    NARCIS (Netherlands)

    Diernfellner, ACR; Schafmeier, T; Merrow, MW; Brunner, M; Diernfellner, Axel C.R.

    2005-01-01

    Expression levels and ratios of the long (1) and short (s) isoforms of the Neurospora circadian clock protein FREQUENCY (FRQ) are crucial for temperature compensation of circadian rhythms. We show that the ratio of 1-FRQ versus s-FRQ is regulated by thermosensitive splicing of intron 6 of frq, a pro

  8. Circadian clock components in the rat neocortex

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  9. Chronic ethanol consumption disrupts the core molecular clock and diurnal rhythms of metabolic genes in the liver without affecting the suprachiasmatic nucleus.

    Directory of Open Access Journals (Sweden)

    Ashley N Filiano

    Full Text Available Chronic ethanol consumption disrupts several metabolic pathways including β-oxidation and lipid biosynthesis, facilitating the development of alcoholic fatty liver disease. Many of these same metabolic pathways are directly regulated by cell autonomous circadian clocks, and recent studies suggest that disruption of daily rhythms in metabolism contributes to multiple common cardiometabolic diseases (including non-alcoholic fatty liver disease. However, it is not known whether ethanol disrupts the core molecular clock in the liver, nor whether this, in turn, alters rhythms in lipid metabolism. Herein, we tested the hypothesis that chronic ethanol consumption disrupts the molecular circadian clock in the liver and potentially changes the diurnal expression patterns of lipid metabolism genes. Consistent with previous studies, male C57BL/6J mice fed an ethanol-containing diet exhibited higher levels of liver triglycerides compared to control mice, indicating hepatic steatosis. Further, the diurnal oscillations of core clock genes (Bmal1, Clock, Cry1, Cry2, Per1, and Per2 and clock-controlled genes (Dbp, Hlf, Nocturnin, Npas2, Rev-erbα, and Tef were altered in livers from ethanol-fed mice. In contrast, ethanol had only minor effects on the expression of core clock genes in the suprachiasmatic nucleus (SCN. These results were confirmed in Per2(Luciferase knock-in mice, in which ethanol induced a phase advance in PER2::LUC bioluminescence oscillations in liver, but not SCN. Further, there was greater variability in the phase of PER2::LUC oscillations in livers from ethanol-fed mice. Ethanol consumption also affected the diurnal oscillations of metabolic genes, including Adh1, Cpt1a, Cyp2e1, Pck1, Pdk4, Ppargc1a, Ppargc1b and Srebp1c, in the livers of C57BL/6J mice. In summary, chronic ethanol consumption alters the function of the circadian clock in liver. Importantly, these results suggest that chronic ethanol consumption, at levels sufficient to

  10. A bayesian mixed regression based prediction of quantitative traits from molecular marker and gene expression data.

    Directory of Open Access Journals (Sweden)

    Madhuchhanda Bhattacharjee

    Full Text Available Both molecular marker and gene expression data were considered alone as well as jointly to serve as additive predictors for two pathogen-activity-phenotypes in real recombinant inbred lines of soybean. For unobserved phenotype prediction, we used a bayesian hierarchical regression modeling, where the number of possible predictors in the model was controlled by different selection strategies tested. Our initial findings were submitted for DREAM5 (the 5th Dialogue on Reverse Engineering Assessment and Methods challenge and were judged to be the best in sub-challenge B3 wherein both functional genomic and genetic data were used to predict the phenotypes. In this work we further improve upon this previous work by considering various predictor selection strategies and cross-validation was used to measure accuracy of in-data and out-data predictions. The results from various model choices indicate that for this data use of both data types (namely functional genomic and genetic simultaneously improves out-data prediction accuracy. Adequate goodness-of-fit can be easily achieved with more complex models for both phenotypes, since the number of potential predictors is large and the sample size is not small. We also further studied gene-set enrichment (for continuous phenotype in the biological process in question and chromosomal enrichment of the gene set. The methodological contribution of this paper is in exploration of variable selection techniques to alleviate the problem of over-fitting. Different strategies based on the nature of covariates were explored and all methods were implemented under the bayesian hierarchical modeling framework with indicator-based covariate selection. All the models based in careful variable selection procedure were found to produce significant results based on permutation test.

  11. Introduction: Finding new clock components; past and future

    OpenAIRE

    Takahashi, Joseph S.

    2004-01-01

    The molecular mechanism of circadian clocks has been unraveled primarily by the use of phenotype-driven (forward) genetic analysis in a number of model systems. We are now in a position to consider what constitutes a clock component, whether we can establish criteria for clock components, and whether we have found most of the primary clock components? This perspective discusses clock genes and how genetics, molecular biology and biochemistry have been used to find clock gene...

  12. CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock

    OpenAIRE

    DeBruyne, Jason P.; Weaver, David R.; Reppert, Steven M.

    2007-01-01

    Heterodimers of CLOCK and BMAL1, bHLH-PAS transcription factors, are believed to be the major transcriptional regulators of the circadian clock mechanism in mammals. However, a recent study shows that CLOCK-deficient mice continue to exhibit robust behavioral and molecular rhythms. Here we report that the transcription factor NPAS2 (MOP4) is able to functionally substitute for CLOCK in the master brain clock in mice to regulate circadian rhythmicity.

  13. Working around the clock: circadian rhythms and skeletal muscle

    OpenAIRE

    ZHANG, XIPING; Dube, Thomas J.; Esser, Karyn A.

    2009-01-01

    The study of the circadian molecular clock in skeletal muscle is in the very early stages. Initial research has demonstrated the presence of the molecular clock in skeletal muscle and that skeletal muscle of a clock-compromised mouse, Clock mutant, exhibits significant disruption in normal expression of many genes required for adult muscle structure and metabolism. In light of the growing association between the molecular clock, metabolism, and metabolic disease, it will also be important to ...

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

    Directory of Open Access Journals (Sweden)

    Flávia Cal Sabino

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

  15. Three-Dimensional Phylogeny Explorer: Distinguishing paralogs, lateral transfer, and violation of "molecular clock" assumption with 3D visualization

    Directory of Open Access Journals (Sweden)

    Lee Christopher

    2007-06-01

    Full Text Available Abstract Background Construction and interpretation of phylogenetic trees has been a major research topic for understanding the evolution of genes. Increases in sequence data and complexity are creating a need for more powerful and insightful tree visualization tools. Results We have developed 3D Phylogeny Explorer (3DPE, a novel phylogeny tree viewer that maps trees onto three spatial axes (species on the X-axis; paralogs on Z; evolutionary distance on Y, enabling one to distinguish at a glance evolutionary features such as speciation; gene duplication and paralog evolution; lateral gene transfer; and violation of the "molecular clock" assumption. Users can input any tree on the online 3DPE, then rotate, scroll, rescale, and explore it interactively as "live" 3D views. All objects in 3DPE are clickable to display subtrees, connectivity path highlighting, sequence alignments, and gene summary views, and etc. To illustrate the value of this visualization approach for microbial genomes, we also generated 3D phylogeny analyses for all clusters from the public COG database. We constructed tree views using well-established methods and graph algorithms. We used Scientific Python to generate VRML2 3D views viewable in any web browser. Conclusion 3DPE provides a novel phylogenetic tree projection method into 3D space and its web-based implementation with live 3D features for reconstruction of phylogenetic trees of COG database.

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

    Czech Academy of Sciences Publication Activity Database

    Kobelková, Alena; Bajgar, Adam; Doležel, David

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    The disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) emerged independently and almost simultaneously in Europe (1990) and North America (1987). The original reservoir of the virus and the date it entered the pig populations is not known. In this study, we demonstrate...... an accurate molecular clock for the European PRRSV ORF 3 gene, place the root in the genealogy, estimate the rate of nucleotide substitution, and date the most recent common viral ancestor of the data set to 1979; more than 10 years before the onset of the European epidemic. Based on these findings, we...

  18. The circadian clock in mammals

    OpenAIRE

    Zordan, Mauro; Kyriacou, Charalambos P

    2000-01-01

    The basic physiological and anatomical basis for circadian rhythms in mammalian behaviour and physiology is introduced. The pathways involved in photic entrainment of the circadian clock are discussed in relation of new findings that identify the molecules that are involved in signalling between the environment and the clock. The molecular basis of endogenous cycles is described in the mouse, and compared to the mechanism that is present in the fly. Finally we speculate on the relationship be...

  19. The circadian clock in mammals

    OpenAIRE

    Zordan, M. A.; Kyriacou, C P

    2005-01-01

    The basic physiological and anatomical basis for circadian rhythms in mammalian behaviour and physiology is introduced. The pathways involved in photic entrainment of the circadian clock are discussed in relation of new findings that identify the molecules that are involved in signalling between the environment and the clock. The molecular basis of endogenous cycles is described in the mouse, and compared to the mechanism that is present in the fly. Finally we speculate on the relationship be...

  20. Molecular convergence of clock and photosensory pathways through PIF3-TOC1 interaction and co-occupancy of target promoters.

    Science.gov (United States)

    Soy, Judit; Leivar, Pablo; González-Schain, Nahuel; Martín, Guiomar; Diaz, Céline; Sentandreu, Maria; Al-Sady, Bassem; Quail, Peter H; Monte, Elena

    2016-04-26

    A mechanism for integrating light perception and the endogenous circadian clock is central to a plant's capacity to coordinate its growth and development with the prevailing daily light/dark cycles. Under short-day (SD) photocycles, hypocotyl elongation is maximal at dawn, being promoted by the collective activity of a quartet of transcription factors, called PIF1, PIF3, PIF4, and PIF5 (phytochrome-interacting factors). PIF protein abundance in SDs oscillates as a balance between synthesis and photoactivated-phytochrome-imposed degradation, with maximum levels accumulating at the end of the long night. Previous evidence shows that elongation under diurnal conditions (as well as in shade) is also subjected to circadian gating. However, the mechanism underlying these phenomena is incompletely understood. Here we show that the PIFs and the core clock component Timing of CAB expression 1 (TOC1) display coincident cobinding to the promoters of predawn-phased, growth-related genes under SD conditions. TOC1 interacts with the PIFs and represses their transcriptional activation activity, antagonizing PIF-induced growth. Given the dynamics of TOC1 abundance (displaying high postdusk levels that progressively decline during the long night), our data suggest that TOC1 functions to provide a direct output from the core clock that transiently constrains the growth-promoting activity of the accumulating PIFs early postdusk, thereby gating growth to predawn, when conditions for cell elongation are optimal. These findings unveil a previously unrecognized mechanism whereby a core circadian clock output signal converges immediately with the phytochrome photosensory pathway to coregulate directly the activity of the PIF transcription factors positioned at the apex of a transcriptional network that regulates a diversity of downstream morphogenic responses. PMID:27071129

  1. Body Clock

    Institute of Scientific and Technical Information of China (English)

    刘洪毓

    2000-01-01

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

  2. 鸭科部分类群分子钟的标定%Calibration of Partial Anatidae Molecular Clocks

    Institute of Scientific and Technical Information of China (English)

    孟冬梅; 王继丈

    2011-01-01

    [Objective] The divergence times of Anatidae were estimated in order to investigate their genetic background. [Method] The mitochondrial cytochrome b (Cyt b) gene sequences of 44 individuals in Chinese domestic geese (15 breeds) and European domestic geese (2 breeds) were sequenced. The consensus sequence of Cyt b was obtained from the Anser anser and Anser cygnoides, respectively, together with 13 partial sequences of Cyt b gene in other birds (4 sequences form Galliformes, 9 from Anseriformes ) provided at NCBI, were totally constructed a 15 sequences database for the next step analysis. And the divergence time between Anseriformes and Galliformes was chosen as an anchor point to calibrate the Anatidae molecular clocks using a sequence calibration method. [Result] The results show that the estimation of the divergence time between Phasianidae and Anatidae is 101.798 MYA (Poisson Model) and 129.461 MYA (Gamma Model). The estimation of divergence time between Anser and Anatinae is 55.1225 MYA (Poisson Model) and 62.5223 MYA (Gamma Model). [Conclusion] The divergence of the two basal groups {Phasianidae/Anatidae, Arisen/Anatinae) took place in the Cretaceous period( 146-65 MYA). These results are consistent with the view that avian was originated in the Cretaceous period.%[目的]估计鸭科鸟类间的分歧时间,了解鸭科不同鸟类的遗传背景.[方法]测定鸿雁家鹅15个品种、灰雁家鹅2个品种共44个个体的细胞色素b基因的全序列.将获得的鸿雁家鹅和灰雁家鹅的一致序列(2条)与GenBank中已知的鸟类细胞色素b基因部分序列(共1 3条;其中,鸡形目4条、鸭科鸟类9条)一起组成共15条序列作为本研究的数据集,并以鸡形目与雁形目(鸡/绿头鸭)的分歧时间( 89.8 MYA)为锚定点,对鸭科的分子钟进行顺序标定.[结果]雉科(Gallus gallus和Coturnix japonical、Coturnix japonica4、Coturnix chinensis)与鸭科(Anas platyrhynchos、Anas poecilorhyncha; Bucephala clangula

  3. Circadian Clocks, Stress, and Immunity

    Science.gov (United States)

    Dumbell, Rebecca; Matveeva, Olga; Oster, Henrik

    2016-01-01

    In mammals, molecular circadian clocks are present in most cells of the body, and this circadian network plays an important role in synchronizing physiological processes and behaviors to the appropriate time of day. The hypothalamic–pituitary–adrenal endocrine axis regulates the response to acute and chronic stress, acting through its final effectors – glucocorticoids – released from the adrenal cortex. Glucocorticoid secretion, characterized by its circadian rhythm, has an important role in synchronizing peripheral clocks and rhythms downstream of the master circadian pacemaker in the suprachiasmatic nucleus. Finally, glucocorticoids are powerfully anti-inflammatory, and recent work has implicated the circadian clock in various aspects and cells of the immune system, suggesting a tight interplay of stress and circadian systems in the regulation of immunity. This mini-review summarizes our current understanding of the role of the circadian clock network in both the HPA axis and the immune system, and discusses their interactions. PMID:27199894

  4. Atomic Clocks

    Science.gov (United States)

    Wynands, Robert

    Time is a strange thing. On the one hand it is arguably the most inaccessible physical phenomenon of all: both in that it is impossible to manipulate or modify—for all we know—and in that even after thousands of years mankind's philosophers still have not found a fully satisfying way to understand it. On the other hand, no other quantity can be measured with greater precision. Today's atomic clocks allow us to reproduce the length of the second as the SI unit of time with an uncertainty of a few parts in 1016—orders of magnitude better than any other quantity. In a sense, one can say [1

  5. A colorful model of the circadian clock.

    Science.gov (United States)

    Reppert, Steven M

    2006-01-27

    The migration of the colorful monarch butterfly provides biologists with a unique model system with which to study the cellular and molecular mechanisms underlying a sophisticated circadian clock. The monarch circadian clock is involved in the induction of the migratory state and navigation over long distances, using the sun as a compass. PMID:16439193

  6. The circadian clock coordinates ribosome biogenesis.

    Directory of Open Access Journals (Sweden)

    Céline Jouffe

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

  7. Avian Circadian Organization: A Chorus of Clocks

    OpenAIRE

    Cassone, Vincent M.

    2013-01-01

    In birds, biological clock function pervades all aspects of biology, controlling daily changes in sleep: wake, visual function, song, migratory patterns and orientation, as well as seasonal patterns of reproduction, song and migration. The molecular bases for circadian clocks are highly conserved, and it is likely the avian molecular mechanisms are similar to those expressed in mammals, including humans. The central pacemakers in the avian pineal gland, retinae and SCN dynamically interact to...

  8. Circadian clocks, epigenetics, and cancer

    KAUST Repository

    Masri, Selma

    2015-01-01

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

  9. Multiphoton Ionization as a clock to Reveal Molecular Dynamics with Intense Short X-ray Free Electron Laser Pulses

    OpenAIRE

    L. FANG; Osipov, T.; Murphy, B.; Tarantelli, F.; Kukk, E.; Cryan, J. P.; Glownia, M.; Bucksbaum, P. H.; Coffee, R. N.; M. Chen; Buth, C.; Berrah, N.

    2013-01-01

    We investigate molecular dynamics of multiple ionization in N2 through multiple core-level photoabsorption and subsequent Auger decay processes induced by intense, short X-ray free electron laser pulses. The timing dynamics of the photoabsorption and dissociation processes is mapped onto the kinetic energy of the fragments. Measurements of the latter allow us to map out the average internuclear separation for every molecular photoionization sequence step and obtain the average time interval b...

  10. Accelerating molecular simulations of proteins using Bayesian inference on weak information

    Science.gov (United States)

    Perez, Alberto; MacCallum, Justin L.; Dill, Ken A.

    2015-01-01

    Atomistic molecular dynamics (MD) simulations of protein molecules are too computationally expensive to predict most native structures from amino acid sequences. Here, we integrate “weak” external knowledge into folding simulations to predict protein structures, given their sequence. For example, we instruct the computer “to form a hydrophobic core,” “to form good secondary structures,” or “to seek a compact state.” This kind of information has been too combinatoric, nonspecific, and vague to help guide MD simulations before. Within atomistic replica-exchange molecular dynamics (REMD), we develop a statistical mechanical framework, modeling using limited data with coarse physical insight(s) (MELD + CPI), for harnessing weak information. As a test, we apply MELD + CPI to predict the native structures of 20 small proteins. MELD + CPI samples to within less than 3.2 Å from native for all 20 and correctly chooses the native structures (<4 Å) for 15 of them, including ubiquitin, a millisecond folder. MELD + CPI is up to five orders of magnitude faster than brute-force MD, satisfies detailed balance, and should scale well to larger proteins. MELD + CPI may be useful where physics-based simulations are needed to study protein mechanisms and populations and where we have some heuristic or coarse physical knowledge about states of interest. PMID:26351667

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

    DEFF Research Database (Denmark)

    Yang, Yaoming; Duguay, David; Bédard, Nathalie;

    2012-01-01

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

  12. BEAST: Bayesian evolutionary analysis by sampling trees

    Directory of Open Access Journals (Sweden)

    Drummond Alexei J

    2007-11-01

    Full Text Available Abstract Background The evolutionary analysis of molecular sequence variation is a statistical enterprise. This is reflected in the increased use of probabilistic models for phylogenetic inference, multiple sequence alignment, and molecular population genetics. Here we present BEAST: a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree. A large number of popular stochastic models of sequence evolution are provided and tree-based models suitable for both within- and between-species sequence data are implemented. Results BEAST version 1.4.6 consists of 81000 lines of Java source code, 779 classes and 81 packages. It provides models for DNA and protein sequence evolution, highly parametric coalescent analysis, relaxed clock phylogenetics, non-contemporaneous sequence data, statistical alignment and a wide range of options for prior distributions. BEAST source code is object-oriented, modular in design and freely available at http://beast-mcmc.googlecode.com/ under the GNU LGPL license. Conclusion BEAST is a powerful and flexible evolutionary analysis package for molecular sequence variation. It also provides a resource for the further development of new models and statistical methods of evolutionary analysis.

  13. Multiphoton Ionization as a clock to Reveal Molecular Dynamics with Intense Short X-ray Free Electron Laser Pulses

    CERN Document Server

    Fang, L; Murphy, B; Tarantelli, F; Kukk, E; Cryan, J P; Glownia, M; Bucksbaum, P H; Coffee, R N; Chen, M; Buth, C; Berrah, N

    2013-01-01

    We investigate molecular dynamics of multiple ionization in N2 through multiple core-level photoabsorption and subsequent Auger decay processes induced by intense, short X-ray free electron laser pulses. The timing dynamics of the photoabsorption and dissociation processes is mapped onto the kinetic energy of the fragments. Measurements of the latter allow us to map out the average internuclear separation for every molecular photoionization sequence step and obtain the average time interval between the photoabsorption events. Using multiphoton ionization as a tool of multiple-pulse pump-probe scheme, we demonstrate the modi?cation of the ionization dynamics as we vary the x-ray laser pulse duration.

  14. Optical Clocks in Space

    CERN Document Server

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

    2007-01-01

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

  15. Sticking to (first) principles: quantum molecular dynamics and Bayesian probabilistic methods to simulate aquatic pollutant absorption spectra.

    Science.gov (United States)

    Trerayapiwat, Kasidet; Ricke, Nathan; Cohen, Peter; Poblete, Alex; Rudel, Holly; Eustis, Soren N

    2016-08-10

    This work explores the relationship between theoretically predicted excitation energies and experimental molar absorption spectra as they pertain to environmental aquatic photochemistry. An overview of pertinent Quantum Chemical descriptions of sunlight-driven electronic transitions in organic pollutants is presented. Second, a combined molecular dynamics (MD), time-dependent density functional theory (TD-DFT) analysis of the ultraviolet to visible (UV-Vis) absorption spectra of six model organic compounds is presented alongside accurate experimental data. The functional relationship between the experimentally observed molar absorption spectrum and the discrete quantum transitions is examined. A rigorous comparison of the accuracy of the theoretical transition energies (ΔES0→Sn) and oscillator strength (fS0→Sn) is afforded by the probabilistic convolution and deconvolution procedure described. This method of deconvolution of experimental spectra using a Gaussian Mixture Model combined with Bayesian Information Criteria (BIC) to determine the mean (μ) and standard deviation (σ) as well as the number of observed singlet to singlet transition energy state distributions. This procedure allows a direct comparison of the one-electron (quantum) transitions that are the result of quantum chemical calculations and the ensemble of non-adiabatic quantum states that produce the macroscopic effect of a molar absorption spectrum. Poor agreement between the vertical excitation energies produced from TD-DFT calculations with five different functionals (CAM-B3LYP, PBE0, M06-2X, BP86, and LC-BLYP) suggest a failure of the theory to capture the low energy, environmentally important, electronic transitions in our model organic pollutants. However, the method of explicit-solvation of the organic solute using the quantum Effective Fragment Potential (EFP) in a density functional molecular dynamics trajectory simulation shows promise as a robust model of the hydrated organic

  16. The Glyoxal Clock Reaction

    Science.gov (United States)

    Ealy, Julie B.; Negron, Alexandra Rodriguez; Stephens, Jessica; Stauffer, Rebecca; Furrow, Stanley D.

    2007-01-01

    Research on the glyoxal clock reaction has led to adaptation of the clock reaction to a general chemistry experiment. This particular reaction is just one of many that used formaldehyde in the past. The kinetics of the glyoxal clock makes the reaction suitable as a general chemistry lab using a Calculator Based Laboratory (CBL) or a LabPro. The…

  17. Inferring Genotype of DNA Molecular Marker by Bayesian Theorem%应用贝叶斯理论推断DNA分子标记基因型

    Institute of Scientific and Technical Information of China (English)

    莫惠栋; 姜长鉴

    2002-01-01

    引入贝叶斯理论用以从DNA分子标记的表现型(电泳谱带)推断其基因型(DNA来源).结果表明,根据标记座位独立假定而确定的遗传信息不完全标记的基因型概率,与根据邻近的遗传信息完全标记的基因型和有关重组率算得的相应贝叶斯概率,通常都有很大的差异.所以在进行数量性状基因定位和标记辅助选择等工作之前,应当计算每一个体基因组上所有遗传信息不完全座位的有关基因型的贝叶斯概率.文中列出计算未知基因型的贝叶斯概率的详细过程,也讨论了贝叶斯概率的若干推广应用.%Bayesian theorem is applied to infer the DNA molecular marker genotype(DNA chain type) from its phenotype (electrophoresis band type). The results indicated that large differences often present in the genotype probability of a molecular marker with incomplete genetic information when it is obtained from the assumption of independence among markers as compared with that inferred from the genotypes of the flanking markers with the complete genetic information and the recombination fractions among them based on the Bayesian theorem. Therefore, before utilizing the marker information, such as in mapping quantitative trait loci (QTL), marker assisted selection (MAS) etc., Bayesian probability of the genotype for all markers with incomplete genetic information must be calculated over the whole genome for every individual. This study provides detailed procedure for the calculation of the Bayesian probability of the unknown genotype. Several extensions were also discussed for the application of the Bayesian theorem.

  18. The intrinsic circadian clock within the cardiomyocyte directly regulates myocardial gene expression, metabolism, and contractile function

    Science.gov (United States)

    Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology remains unknown. We hypothesized that circadian clock within the cardiomyocyte plays a role in regulating myocardia...

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

    Directory of Open Access Journals (Sweden)

    Tammy M. Joska

    2014-09-01

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

  20. Bayesian biostatistics

    CERN Document Server

    Lesaffre, Emmanuel

    2012-01-01

    The growth of biostatistics has been phenomenal in recent years and has been marked by considerable technical innovation in both methodology and computational practicality. One area that has experienced significant growth is Bayesian methods. The growing use of Bayesian methodology has taken place partly due to an increasing number of practitioners valuing the Bayesian paradigm as matching that of scientific discovery. In addition, computational advances have allowed for more complex models to be fitted routinely to realistic data sets. Through examples, exercises and a combination of introd

  1. The historical biogeography of Pteroglossus aracaris (Aves, Piciformes, Ramphastidae based on Bayesian analysis of mitochondrial DNA sequences

    Directory of Open Access Journals (Sweden)

    Sérgio L. Pereira

    2008-01-01

    Full Text Available Most Neotropical birds, including Pteroglossus aracaris, do not have an adequate fossil record to be used as time constraints in molecular dating. Hence, the evolutionary timeframe of the avian biota can only be inferred using alternative time constraints. We applied a Bayesian relaxed clock approach to propose an alternative interpretation for the historical biogeography of Pteroglossus based on mitochondrial DNA sequences, using different combinations of outgroups and time constraints obtained from outgroup fossils, vicariant barriers and molecular time estimates. The results indicated that outgroup choice has little effect on the Bayesian posterior distribution of divergence times within Pteroglossus , that geological and molecular time constraints seem equally suitable to estimate the Bayesian posterior distribution of divergence times for Pteroglossus , and that the fossil record alone overestimates divergence times within the fossil-lacking ingroup. The Bayesian estimates of divergence times suggest that the radiation of Pteroglossus occurred from the Late Miocene to the Pliocene (three times older than estimated by the “standard” mitochondrial rate of 2% sequence divergence per million years, likely triggered by Andean uplift, multiple episodes of marine transgressions in South America, and formation of present-day river basins. The time estimates are in agreement with other Neotropical taxa with similar geographic distributions.

  2. Precision Clock Evaluation Facility

    Data.gov (United States)

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

  3. Bayesian statistics

    OpenAIRE

    Draper, D.

    2001-01-01

    © 2012 Springer Science+Business Media, LLC. All rights reserved. Article Outline: Glossary Definition of the Subject and Introduction The Bayesian Statistical Paradigm Three Examples Comparison with the Frequentist Statistical Paradigm Future Directions Bibliography

  4. Placing confidence limits on the molecular age of the human–chimpanzee divergence

    OpenAIRE

    Kumar, Sudhir; Filipski, Alan; Swarna, Vinod; Walker, Alan; Hedges, S. Blair

    2005-01-01

    Molecular clocks have been used to date the divergence of humans and chimpanzees for nearly four decades. Nonetheless, this date and its confidence interval remain to be firmly established. In an effort to generate a genomic view of the human–chimpanzee divergence, we have analyzed 167 nuclear protein-coding genes and built a reliable confidence interval around the calculated time by applying a multifactor bootstrap-resampling approach. Bayesian and maximum likelihood analyses of neutral DNA ...

  5. Biological Clocks & Circadian Rhythms

    Science.gov (United States)

    Robertson, Laura; Jones, M. Gail

    2009-01-01

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

  6. Design of Alarm Clock

    OpenAIRE

    Budík, Marek

    2015-01-01

    The goal of this thesis is to create alarm clock, which respect the functional, technical and aesthetic requirements of this device and attain an attractive design of this product. The final draft should be innovative, original and user attractive alarm clock.

  7. Active optical clock

    Institute of Scientific and Technical Information of China (English)

    CHEN JingBiao

    2009-01-01

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

  8. Photoperiodic plasticity in circadian clock neurons in insects

    Directory of Open Access Journals (Sweden)

    Sakiko eShiga

    2013-08-01

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

  9. Progress in the Molecular Mechanism of Circadian Clock in Cyanobacterium%蓝藻生物节律性分子调控机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    李青雁; 庞羽彤; 李小龙; 周飞飞; 张芳; 霍宇鹏; 赵宇玮

    2013-01-01

    Circadian clocks are endogenous time-keeping mechanisms which are ubiquitous in a variety of o rganisms from bacteria to mammals. In order to coordinate with and adapt to the daily environmental changes which are driven by the self-rolling of the earth, the circadian clock controls various metabolic and biological activities with a circle period of 24 h. One of the cyanobacterial species, Synechococcus elongatus PCC7942 is a model organism for the circadian clock system. Three proteins encoded by the kaiA/B/C gene cluster, which is functional basis for the circadian rhythm, generate the basic timing loop of the circadian clock in Synechococcus. Circadian time clue is transmitted from the KaiABC-based central oscillator to the clock-controlled transcription factors. KaiC, an autokinase and autophosphatase, is the central component of the cyanobacterial circadian clock. The daily auto-phosphorylation and auto-dephosphorylation cycle of KaiC and the post-translational modification of the proteins, which consisted the inputing and output pathways of the circadian clock, have composed the transcriptional and translational feed-back loop (TTFL). In traditional theory of circadian clock model in cyanobacteria, TTFL regulation of clock genes are thought to be essential for sustaining and outputing of the basic circadian timing loop in Synechococcus. But surprisingly, KaiABC-based central oscillators are only found in cyanobacteria and very few prokaryotic species. It seems that this Kai-based clock is not an ubiquitous time-keeping mechanism that has been selected by organisms during natural evolution. Recently, some circadian clock research groups have demonstrated that non-transcriptional and translational oscillators could be the driving force of the generating and sustaining of biological circadian rhythm. The peroxiredoxins (PRX) are reported to be conserved markers of circadian rhythms, which are also thought to be a new focus of the researches on the molecular

  10. On-chip clock error characterization for clock distribution system

    OpenAIRE

    Shan, Chuan; Galayko, Dimitri; Anceau, François

    2013-01-01

    In this paper, we investigate a test strategy for characterization of clock error statistics between two clock domains in high-speed clocking systems (gigahertz and more). The method allows an indirect measurement (not based on time interval measurement) of clock error distribution by observing the integrity of a periodic sequence transmitted between two clocking domains. The method is compatible with fully on-chip implementation, and the readout of result to off-chip signals is cadenced at l...

  11. Stable clocks and general relativity

    CERN Document Server

    Will, C M

    1995-01-01

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

  12. Functional Implications of the CLOCK 3111T/C Single-Nucleotide Polymorphism.

    Science.gov (United States)

    Ozburn, Angela R; Purohit, Kush; Parekh, Puja K; Kaplan, Gabrielle N; Falcon, Edgardo; Mukherjee, Shibani; Cates, Hannah M; McClung, Colleen A

    2016-01-01

    Circadian rhythm disruptions are prominently associated with bipolar disorder (BD). Circadian rhythms are regulated by the molecular clock, a family of proteins that function together in a transcriptional-translational feedback loop. The CLOCK protein is a key transcription factor of this feedback loop, and previous studies have found that manipulations of the Clock gene are sufficient to produce manic-like behavior in mice (1). The CLOCK 3111T/C single-nucleotide polymorphism (SNP; rs1801260) is a genetic variation of the human CLOCK gene that is significantly associated with increased frequency of manic episodes in BD patients (2). The 3111T/C SNP is located in the 3'-untranslated region of the CLOCK gene. In this study, we sought to examine the functional implications of the human CLOCK 3111T/C SNP by transfecting a mammalian cell line (mouse embryonic fibroblasts isolated from Clock(-/-) knockout mice) with pcDNA plasmids containing the human CLOCK gene with either the T or C SNP at position 3111. We then measured circadian gene expression over a 24-h time period. We found that the CLOCK3111C SNP resulted in higher mRNA levels than the CLOCK 3111T SNP. Furthermore, we found that Per2, a transcriptional target of CLOCK, was also more highly expressed with CLOCK 3111C expression, indicating that the 3'-UTR SNP affects the expression, function, and stability of CLOCK mRNA. PMID:27148095

  13. Subtleties of the clock retardation

    OpenAIRE

    Redzic, D. V.

    2015-01-01

    For a simple electromagnetic model of a clock introduced by Jefimenko (clock $\\#$ 1 in 1996 {\\it Am. J. Phys.} {\\bf 64} 812), a change of the rate of the clock when it is set in uniform motion is calculated exactly, employing the correct equation of motion of a charged particle in the electromagnetic field and the universal boostability assumption. Thus, for the clock under consideration, a dynamical content of the clock retardation is demonstrated. Somewhat surprisingly, the analysis present...

  14. Temperature regulates transcription in the zebrafish circadian clock.

    Directory of Open Access Journals (Sweden)

    2005-11-01

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

  15. Circadian clocks are designed optimally

    CERN Document Server

    Hasegawa, Yoshihiko

    2014-01-01

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

  16. Bayesian Monitoring.

    OpenAIRE

    Kirstein, Roland

    2005-01-01

    This paper presents a modification of the inspection game: The ?Bayesian Monitoring? model rests on the assumption that judges are interested in enforcing compliant behavior and making correct decisions. They may base their judgements on an informative but imperfect signal which can be generated costlessly. In the original inspection game, monitoring is costly and generates a perfectly informative signal. While the inspection game has only one mixed strategy equilibrium, three Perfect Bayesia...

  17. Circadian clock and the onset of cardiovascular events.

    Science.gov (United States)

    Takeda, Norihiko; Maemura, Koji

    2016-06-01

    The onset of cardiovascular diseases often shows time-of-day variation. Acute myocardial infarction or ventricular arrhythmia such as ventricular tachycardia occurs mainly in the early morning. Multiple biochemical and physiological parameters show circadian rhythm, which may account for the diurnal variation of cardiovascular events. These include the variations in blood pressure, activity of the autonomic nervous system and renin-angiotensin axis, coagulation cascade, vascular tone and the intracellular metabolism of cardiomyocytes. Importantly, the molecular clock system seems to underlie the circadian variation of these parameters. The center of the biological clock, also known as the central clock, exists in the suprachiasmatic nucleus. In contrast, the molecular clock system is also activated in each cell of the peripheral organs and constitute the peripheral clock. The biological clock system is currently considered to have a beneficial role in maintaining the homeostasis of each organ. Discoordination, however, between the peripheral clock and external environment could potentially underlie the development of cardiovascular events. Therefore, understanding the molecular and cellular pathways by which cardiovascular events occur in a diurnal oscillatory pattern will help the establishment of a novel therapeutic approach to the management of cardiovascular disorders. PMID:26888119

  18. On clocks and clouds

    Directory of Open Access Journals (Sweden)

    M. K. Witte

    2013-09-01

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

  19. Inferring Population Size History from Large Samples of Genome-Wide Molecular Data - An Approximate Bayesian Computation Approach.

    Directory of Open Access Journals (Sweden)

    Simon Boitard

    2016-03-01

    Full Text Available Inferring the ancestral dynamics of effective population size is a long-standing question in population genetics, which can now be tackled much more accurately thanks to the massive genomic data available in many species. Several promising methods that take advantage of whole-genome sequences have been recently developed in this context. However, they can only be applied to rather small samples, which limits their ability to estimate recent population size history. Besides, they can be very sensitive to sequencing or phasing errors. Here we introduce a new approximate Bayesian computation approach named PopSizeABC that allows estimating the evolution of the effective population size through time, using a large sample of complete genomes. This sample is summarized using the folded allele frequency spectrum and the average zygotic linkage disequilibrium at different bins of physical distance, two classes of statistics that are widely used in population genetics and can be easily computed from unphased and unpolarized SNP data. Our approach provides accurate estimations of past population sizes, from the very first generations before present back to the expected time to the most recent common ancestor of the sample, as shown by simulations under a wide range of demographic scenarios. When applied to samples of 15 or 25 complete genomes in four cattle breeds (Angus, Fleckvieh, Holstein and Jersey, PopSizeABC revealed a series of population declines, related to historical events such as domestication or modern breed creation. We further highlight that our approach is robust to sequencing errors, provided summary statistics are computed from SNPs with common alleles.

  20. Optical atomic clocks

    International Nuclear Information System (INIS)

    In the last ten years extraordinary results in time and frequency metrology have been demonstrated. Frequency-stabilization techniques for continuous-wave lasers and femtosecond optical frequency combs have enabled a rapid development of frequency standards based on optical transitions in ultra-cold neutral atoms and trapped ions. As a result, today’s best performing atomic clocks tick at an optical rate and allow scientists to perform high-resolution measurements with a precision approaching a few parts in 1018. This paper reviews the history and the state of the art in optical-clock research and addresses the implementation of optical clocks in a possible future redefinition of the SI second as well as in tests of fundamental physics.

  1. Optical atomic clocks

    CERN Document Server

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

    2014-01-01

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

  2. Optical atomic clocks

    Science.gov (United States)

    Poli, N.; Oates, C. W.; Gill, P.; Tino, G. M.

    2013-12-01

    In the last ten years extraordinary results in time and frequency metrology have been demonstrated. Frequency-stabilization techniques for continuous-wave lasers and femtosecond optical frequency combs have enabled a rapid development of frequency standards based on optical transitions in ultra-cold neutral atoms and trapped ions. As a result, today's best performing atomic clocks tick at an optical rate and allow scientists to perform high-resolution measurements with a precision approaching a few parts in 1018. This paper reviews the history and the state of the art in optical-clock research and addresses the implementation of optical clocks in a possible future redefinition of the SI second as well as in tests of fundamental physics.

  3. The circadian clock goes genomic

    OpenAIRE

    Staiger, D; Shin, J; Johansson, M; Davis, S

    2013-01-01

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

  4. Bayesian programming

    CERN Document Server

    Bessiere, Pierre; Ahuactzin, Juan Manuel; Mekhnacha, Kamel

    2013-01-01

    Probability as an Alternative to Boolean LogicWhile logic is the mathematical foundation of rational reasoning and the fundamental principle of computing, it is restricted to problems where information is both complete and certain. However, many real-world problems, from financial investments to email filtering, are incomplete or uncertain in nature. Probability theory and Bayesian computing together provide an alternative framework to deal with incomplete and uncertain data. Decision-Making Tools and Methods for Incomplete and Uncertain DataEmphasizing probability as an alternative to Boolean

  5. Decamp Clock Board Firmware

    International Nuclear Information System (INIS)

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

  6. Clock Reaction: Outreach Attraction

    Science.gov (United States)

    Carpenter, Yuen-ying; Phillips, Heather A.; Jakubinek, Michael B.

    2010-01-01

    Chemistry students are often introduced to the concept of reaction rates through demonstrations or laboratory activities involving the well-known iodine clock reaction. For example, a laboratory experiment involving thiosulfate as an iodine scavenger is part of the first-year general chemistry laboratory curriculum at Dalhousie University. With…

  7. Decamp Clock Board Firmware

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-27

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

  8. Magic Wavelength of an Optical Clock Transition of Barium

    International Nuclear Information System (INIS)

    Similar to most of the other alkaline earth elements, barium atoms can be candidates for optical clocks, thus the magic wavelength for an optical lattice is important for the clock transition. We calculate the magic wavelength of a possible clock transition between 6s21S0 and 6s5d3 D2 states of barium atoms. Our theoretical result shows that there are three magic wavelengths 615.9nm, 641.2nm and 678.8nm for a linearly polarized optical lattice laser for barium. (atomic and molecular physics)

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

    Directory of Open Access Journals (Sweden)

    Yaoming Yang

    2012-06-01

    Endogenous 24-hour rhythms are generated by circadian clocks located in most tissues. The molecular clock mechanism is based on feedback loops involving clock genes and their protein products. Post-translational modifications, including ubiquitination, are important for regulating the clock feedback mechanism. Previous work has focused on the role of ubiquitin ligases in the clock mechanism. Here we show a role for the rhythmically-expressed deubiquitinating enzyme ubiquitin specific peptidase 2 (USP2 in clock function. Mice with a deletion of the Usp2 gene (Usp2 KO display a longer free-running period of locomotor activity rhythms and altered responses of the clock to light. This was associated with altered expression of clock genes in synchronized Usp2 KO mouse embryonic fibroblasts and increased levels of clock protein PERIOD1 (PER1. USP2 can be coimmunoprecipitated with several clock proteins but directly interacts specifically with PER1 and deubiquitinates it. Interestingly, this deubiquitination does not alter PER1 stability. Taken together, our results identify USP2 as a new core component of the clock machinery and demonstrate a role for deubiquitination in the regulation of the circadian clock, both at the level of the core pacemaker and its response to external cues.

  10. A Blind Circadian Clock in Cavefish Reveals that Opsins Mediate Peripheral Clock Photoreception

    OpenAIRE

    Cavallari, N; E.Frigato; Vallone, D.; N.Fröhlich; J.F. Lopez-Olmeda; A.Foà; R.De Berti; Sánchez-Vázquez, F. J.; C.Bertolucci; Foulkes, N S

    2011-01-01

    The circadian clock is a physiological timing mechanism that allows organisms to anticipate and adapt to the day-night cycle. Since it ticks with a period that is not precisely 24 h, it is vital that it is reset on a daily basis by signals such as light to ensure that it remains synchronized with the day-night cycle. The molecular mechanisms whereby light regulates the clock remain incompletely understood. Here we have studied a cavefish that has evolved for millions of years in the perpetual...

  11. Maximum-Likelihood Estimator of Clock Offset between Nanomachines in Bionanosensor Networks

    Directory of Open Access Journals (Sweden)

    Lin Lin

    2015-12-01

    Full Text Available Recent advances in nanotechnology, electronic technology and biology have enabled the development of bio-inspired nanoscale sensors. The cooperation among the bionanosensors in a network is envisioned to perform complex tasks. Clock synchronization is essential to establish diffusion-based distributed cooperation in the bionanosensor networks. This paper proposes a maximum-likelihood estimator of the clock offset for the clock synchronization among molecular bionanosensors. The unique properties of diffusion-based molecular communication are described. Based on the inverse Gaussian distribution of the molecular propagation delay, a two-way message exchange mechanism for clock synchronization is proposed. The maximum-likelihood estimator of the clock offset is derived. The convergence and the bias of the estimator are analyzed. The simulation results show that the proposed estimator is effective for the offset compensation required for clock synchronization. This work paves the way for the cooperation of nanomachines in diffusion-based bionanosensor networks.

  12. Maximum-Likelihood Estimator of Clock Offset between Nanomachines in Bionanosensor Networks

    Science.gov (United States)

    Lin, Lin; Yang, Chengfeng; Ma, Maode

    2015-01-01

    Recent advances in nanotechnology, electronic technology and biology have enabled the development of bio-inspired nanoscale sensors. The cooperation among the bionanosensors in a network is envisioned to perform complex tasks. Clock synchronization is essential to establish diffusion-based distributed cooperation in the bionanosensor networks. This paper proposes a maximum-likelihood estimator of the clock offset for the clock synchronization among molecular bionanosensors. The unique properties of diffusion-based molecular communication are described. Based on the inverse Gaussian distribution of the molecular propagation delay, a two-way message exchange mechanism for clock synchronization is proposed. The maximum-likelihood estimator of the clock offset is derived. The convergence and the bias of the estimator are analyzed. The simulation results show that the proposed estimator is effective for the offset compensation required for clock synchronization. This work paves the way for the cooperation of nanomachines in diffusion-based bionanosensor networks. PMID:26690173

  13. When the circadian clock meets the melanin pigmentary system.

    Science.gov (United States)

    Slominski, Andrzej T; Hardeland, Rüdiger; Reiter, Russel J

    2015-04-01

    Silencing of BMAL1 and PER1 stimulates melanogenic activity of follicular and epidermal melanocytes, indicating a novel role for peripheral circadian clock processes in the regulation of melanin pigmentation. Linking the expression levels of BMAL1/PER1 with changes in melanogenesis opens exciting opportunities to study the role of the local molecular clock in modulation of melanocyte functions in the hair follicle and the epidermis with attendant effects on epidermal barrier functions in general. PMID:25785947

  14. The peripheral clock regulates human pigmentation.

    Science.gov (United States)

    Hardman, Jonathan A; Tobin, Desmond J; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Al-Nuaimi, Yusur; Grimaldi, Benedetto; Paus, Ralf

    2015-04-01

    Although the regulation of pigmentation is well characterized, it remains unclear whether cell-autonomous controls regulate the cyclic on-off switching of pigmentation in the hair follicle (HF). As human HFs and epidermal melanocytes express clock genes and proteins, and given that core clock genes (PER1, BMAL1) modulate human HF cycling, we investigated whether peripheral clock activity influences human HF pigmentation. We found that silencing BMAL1 or PER1 in human HFs increased HF melanin content. Furthermore, tyrosinase expression and activity, as well as TYRP1 and TYRP2 mRNA levels, gp100 protein expression, melanocyte dendricity, and the number gp100+ HF melanocytes, were all significantly increased in BMAL1 and/or PER1-silenced HFs. BMAL1 or PER1 silencing also increased epidermal melanin content, gp100 protein expression, and tyrosinase activity in human skin. These effects reflect direct modulation of melanocytes, as BMAL1 and/or PER1 silencing in isolated melanocytes increased tyrosinase activity and TYRP1/2 expression. Mechanistically, BMAL1 knockdown reduces PER1 transcription, and PER1 silencing induces phosphorylation of the master regulator of melanogenesis, microphthalmia-associated transcription factor, thus stimulating human melanogenesis and melanocyte activity in situ and in vitro. Therefore, the molecular clock operates as a cell-autonomous modulator of human pigmentation and may be targeted for future therapeutic strategies. PMID:25310406

  15. Circadian Clock Regulates Bone Resorption in Mice.

    Science.gov (United States)

    Xu, Cheng; Ochi, Hiroki; Fukuda, Toru; Sato, Shingo; Sunamura, Satoko; Takarada, Takeshi; Hinoi, Eiichi; Okawa, Atsushi; Takeda, Shu

    2016-07-01

    The circadian clock controls many behavioral and physiological processes beyond daily rhythms. Circadian dysfunction increases the risk of cancer, obesity, and cardiovascular and metabolic diseases. Although clinical studies have shown that bone resorption is controlled by circadian rhythm, as indicated by diurnal variations in bone resorption, the molecular mechanism of circadian clock-dependent bone resorption remains unknown. To clarify the role of circadian rhythm in bone resorption, aryl hydrocarbon receptor nuclear translocator-like (Bmal1), a prototype circadian gene, was knocked out specifically in osteoclasts. Osteoclast-specific Bmal1-knockout mice showed a high bone mass phenotype due to reduced osteoclast differentiation. A cell-based assay revealed that BMAL1 upregulated nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (Nfatc1) transcription through its binding to an E-box element located on the Nfatc1 promoter in cooperation with circadian locomotor output cycles kaput (CLOCK), a heterodimer partner of BMAL1. Moreover, steroid receptor coactivator (SRC) family members were shown to interact with and upregulate BMAL1:CLOCK transcriptional activity. Collectively, these data suggest that bone resorption is controlled by osteoclastic BMAL1 through interactions with the SRC family and binding to the Nfatc1 promoter. © 2016 American Society for Bone and Mineral Research. PMID:26841172

  16. The Bird of Time: Cognition and the Avian Biological Clock

    Directory of Open Access Journals (Sweden)

    Vincent Michael Cassone

    2012-03-01

    Full Text Available Avian behavior and physiology are embedded in time at many levels of biological organization. Biological clock function in birds is critical for sleep/wake cycles, but may also regulate the acquisition of place memory, learning of song from tutors, social integration and time-compensated navigation. This relationship has two major implications. First, mechanisms of the circadian clock should be linked in some way to the mechanisms of all these behaviors. How is not yet clear, and evidence that the central clock has effects is piecemeal. Second, selection acting on characters that are linked to the circadian clock should influence aspects of the clock mechanism itself. Little evidence exists for this in birds, but there have been few attempts to assess this idea. At its core, the avian circadian clock is a multi-oscillator system comprising the pineal gland, the retinae and the avian homologues of the suprachiasmatic nuclei, whose mutual interactions ensure coordinated physiological functions, which are in turn synchronized to ambient light cycles via encephalic, pineal and retinal photoreceptors. At the molecular level, avian biological clocks comprise a genetic network of positive elements clock and bmal1 whose interactions with the negative elements period2, period3 and the cryptochromes form an oscillatory feedback loop that circumnavigates the 24 hrs of the day. We assess the possibilities for dual integration of the clock with time-dependent cognitive processes. Closer examination of the molecular, physiological, and behavioral elements of the circadian system would place birds at a very interesting fulcrum in the neurobiology of time in learning, memory and navigation. 

  17. Conveyor belt clock synchronization

    CERN Document Server

    Giovannetti, V; Maccone, L; Shapiro, J H; Wong, F N C; Giovannetti, Vittorio; Lloyd, Seth; Maccone, Lorenzo; Shapiro, Jeffrey H.; Wong, Franco N. C.

    2004-01-01

    A protocol for synchronizing distant clocks is proposed that does not rely on the arrival times of the signals which are exchanged, and an optical implementation based on coherent-state pulses is described. This protocol is not limited by any dispersion that may be present in the propagation medium through which the light signals are exchanged. Possible improvements deriving from the use of quantum-mechanical effects are also addressed.

  18. Divergent roles of clock genes in retinal and suprachiasmatic nucleus circadian oscillators.

    Directory of Open Access Journals (Sweden)

    Guo-Xiang Ruan

    Full Text Available The retina is both a sensory organ and a self-sustained circadian clock. Gene targeting studies have revealed that mammalian circadian clocks generate molecular circadian rhythms through coupled transcription/translation feedback loops which involve 6 core clock genes, namely Period (Per 1 and 2, Cryptochrome (Cry 1 and 2, Clock, and Bmal1 and that the roles of individual clock genes in rhythms generation are tissue-specific. However, the mechanisms of molecular circadian rhythms in the mammalian retina are incompletely understood and the extent to which retinal neural clocks share mechanisms with the suprachiasmatic nucleus (SCN, the central neural clock, is unclear. In the present study, we examined the rhythmic amplitude and period of real-time bioluminescence rhythms in explants of retina from Per1-, Per2-, Per3-, Cry1-, Cry2-, and Clock-deficient mice that carried transgenic PERIOD2::LUCIFERASE (PER2::LUC or Period1::luciferase (Per1::luc circadian reporters. Per1-, Cry1- and Clock-deficient retinal and SCN explants showed weakened or disrupted rhythms, with stronger effects in retina compared to SCN. Per2, Per3, and Cry2 were individually dispensable for sustained rhythms in both tissues. Retinal and SCN explants from double knockouts of Cry1 and Cry2 were arrhythmic. Gene effects on period were divergent with reduction in the number of Per1 alleles shortening circadian period in retina, but lengthening it in SCN, and knockout of Per3 substantially shortening retinal clock period, but leaving SCN unaffected. Thus, the retinal neural clock has a unique pattern of clock gene dependence at the tissue level that it is similar in pattern, but more severe in degree, than the SCN neural clock, with divergent clock gene regulation of rhythmic period.

  19. Evolutionary Analysis of Dengue Serotype 2 Viruses Using Phylogenetic and Bayesian Methods from New Delhi, India.

    Science.gov (United States)

    Afreen, Nazia; Naqvi, Irshad H; Broor, Shobha; Ahmed, Anwar; Kazim, Syed Naqui; Dohare, Ravins; Kumar, Manoj; Parveen, Shama

    2016-03-01

    Dengue fever is the most important arboviral disease in the tropical and sub-tropical countries of the world. Delhi, the metropolitan capital state of India, has reported many dengue outbreaks, with the last outbreak occurring in 2013. We have recently reported predominance of dengue virus serotype 2 during 2011-2014 in Delhi. In the present study, we report molecular characterization and evolutionary analysis of dengue serotype 2 viruses which were detected in 2011-2014 in Delhi. Envelope genes of 42 DENV-2 strains were sequenced in the study. All DENV-2 strains grouped within the Cosmopolitan genotype and further clustered into three lineages; Lineage I, II and III. Lineage III replaced lineage I during dengue fever outbreak of 2013. Further, a novel mutation Thr404Ile was detected in the stem region of the envelope protein of a single DENV-2 strain in 2014. Nucleotide substitution rate and time to the most recent common ancestor were determined by molecular clock analysis using Bayesian methods. A change in effective population size of Indian DENV-2 viruses was investigated through Bayesian skyline plot. The study will be a vital road map for investigation of epidemiology and evolutionary pattern of dengue viruses in India. PMID:26977703

  20. Evolutionary Analysis of Dengue Serotype 2 Viruses Using Phylogenetic and Bayesian Methods from New Delhi, India.

    Directory of Open Access Journals (Sweden)

    Nazia Afreen

    2016-03-01

    Full Text Available Dengue fever is the most important arboviral disease in the tropical and sub-tropical countries of the world. Delhi, the metropolitan capital state of India, has reported many dengue outbreaks, with the last outbreak occurring in 2013. We have recently reported predominance of dengue virus serotype 2 during 2011-2014 in Delhi. In the present study, we report molecular characterization and evolutionary analysis of dengue serotype 2 viruses which were detected in 2011-2014 in Delhi. Envelope genes of 42 DENV-2 strains were sequenced in the study. All DENV-2 strains grouped within the Cosmopolitan genotype and further clustered into three lineages; Lineage I, II and III. Lineage III replaced lineage I during dengue fever outbreak of 2013. Further, a novel mutation Thr404Ile was detected in the stem region of the envelope protein of a single DENV-2 strain in 2014. Nucleotide substitution rate and time to the most recent common ancestor were determined by molecular clock analysis using Bayesian methods. A change in effective population size of Indian DENV-2 viruses was investigated through Bayesian skyline plot. The study will be a vital road map for investigation of epidemiology and evolutionary pattern of dengue viruses in India.

  1. Synchronization of clocks

    International Nuclear Information System (INIS)

    In this report we recall the famous Huygens’ experiment which gave the first evidence of the synchronization phenomenon. We consider the synchronization of two clocks which are accurate (show the same time) but have pendula with different masses. It has been shown that such clocks hanging on the same beam can show the almost complete (in-phase) and almost antiphase synchronizations. By almost complete and almost antiphase synchronization we defined the periodic motion of the pendula in which the phase shift between the displacements of the pendula is respectively close (but not equal) to 0 or π. We give evidence that almost antiphase synchronization was the phenomenon observed by Huygens in XVII century. We support our numerical studies by considering the energy balance in the system and showing how the energy is transferred between the pendula via oscillating beam allowing the pendula’s synchronization. Additionally we discuss the synchronization of a number of different pendulum clocks hanging from a horizontal beam which can roll on the parallel surface. It has been shown that after a transient, different types of synchronization between pendula can be observed; (i) the complete synchronization in which all pendula behave identically, (ii) pendula create three or five clusters of synchronized pendula. We derive the equations for the estimation of the phase differences between phase synchronized clusters. The evidence, why other configurations with a different number of clusters are not observed, is given.

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

    Directory of Open Access Journals (Sweden)

    Dominic Landgraf

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    MichaelTSellix

    2013-07-01

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

  4. Prediction of GNSS satellite clocks

    International Nuclear Information System (INIS)

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

  5. Microchip-Based Trapped-Atom Clocks

    OpenAIRE

    Vuletic, Vladan; Leroux, Ian D.; Schleier-Smith, Monika H.

    2011-01-01

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

  6. Serum factors in older individuals change cellular clock properties

    Science.gov (United States)

    Pagani, Lucia; Schmitt, Karen; Meier, Fides; Izakovic, Jan; Roemer, Konstanze; Viola, Antoine; Cajochen, Christian; Wirz-Justice, Anna; Brown, Steven A.; Eckert, Anne

    2011-01-01

    Human aging is accompanied by dramatic changes in daily sleep–wake behavior: Activity shifts to an earlier phase, and the consolidation of sleep and wake is disturbed. Although this daily circadian rhythm is brain-controlled, its mechanism is encoded by cell-autonomous circadian clocks functioning in nearly every cell of the body. In fact, human clock properties measured in peripheral cells such as fibroblasts closely mimic those measured physiologically and behaviorally in the same subjects. To understand better the molecular mechanisms by which human aging affects circadian clocks, we characterized the clock properties of fibroblasts cultivated from dermal biopsies of young and older subjects. Fibroblast period length, amplitude, and phase were identical in the two groups even though behavior was not, thereby suggesting that basic clock properties of peripheral cells do not change during aging. Interestingly, measurement of the same cells in the presence of human serum from older donors shortened period length and advanced the phase of cellular circadian rhythms compared with treatment with serum from young subjects, indicating that a circulating factor might alter human chronotype. Further experiments demonstrated that this effect is caused by a thermolabile factor present in serum of older individuals. Thus, even though the molecular machinery of peripheral circadian clocks does not change with age, some age-related circadian dysfunction observed in vivo might be of hormonal origin and therefore might be pharmacologically remediable. PMID:21482780

  7. The Drosophila circadian clock is a variably coupled network of multiple peptidergic units

    OpenAIRE

    Z. Yao; Shafer, O.T.

    2014-01-01

    Daily rhythms in behavior emerge from networks of neurons that express molecular clocks. Drosophila’s clock neuron network consists of a diversity of cell types, yet is modeled as two hierarchically organized groups, one of which serves as a master pacemaker. Here we establish that the fly’s clock neuron network consists of multiple units of independent neuronal oscillators, each unified by its neuropeptide transmitter and mode of coupling to other units. Our work reveals that the circadian c...

  8. Bayesian artificial intelligence

    CERN Document Server

    Korb, Kevin B

    2010-01-01

    Updated and expanded, Bayesian Artificial Intelligence, Second Edition provides a practical and accessible introduction to the main concepts, foundation, and applications of Bayesian networks. It focuses on both the causal discovery of networks and Bayesian inference procedures. Adopting a causal interpretation of Bayesian networks, the authors discuss the use of Bayesian networks for causal modeling. They also draw on their own applied research to illustrate various applications of the technology.New to the Second EditionNew chapter on Bayesian network classifiersNew section on object-oriente

  9. Bayesian Graphical Models

    DEFF Research Database (Denmark)

    Jensen, Finn Verner; Nielsen, Thomas Dyhre

    2016-01-01

    Mathematically, a Bayesian graphical model is a compact representation of the joint probability distribution for a set of variables. The most frequently used type of Bayesian graphical models are Bayesian networks. The structural part of a Bayesian graphical model is a graph consisting of nodes and...... largely due to the availability of efficient inference algorithms for answering probabilistic queries about the states of the variables in the network. Furthermore, to support the construction of Bayesian network models, learning algorithms are also available. We give an overview of the Bayesian network...

  10. Optical atomic clocks and metrology

    Science.gov (United States)

    Ludlow, Andrew

    2014-05-01

    The atomic clock has long demonstrated the capability to measure time or frequency with very high precision. Consequently, these clocks are used extensively in technological applications such as advanced synchronization or communication and navigation networks. Optical atomic clocks are next- generation timekeepers which reference narrowband optical transitions between suitable atomic states. Many optical time/frequency standards utilize state-of-the-art quantum control and precision measurement. Combined with the ultrahigh quality factors of the atomic resonances at their heart, optical atomic clocks have promised new levels of timekeeping precision, orders of magnitude higher than conventional atomic clocks based on microwave transitions. Such measurement capability enables and/or enhances many of the most exciting applications of these clocks, including the study of fundamental laws of physics through the measurement of time evolution. Here, I will highlight optical atomic clocks and their utility, as well as review recent advances in their development and performance. In particular, I will describe in detail the optical lattice clock and the realization of frequency measurement at the level of one part in 1018. To push the performance of these atomic timekeepers to such a level and beyond, several key advances are being explored worldwide. These will be discussed generally, with particular emphasis on our recent efforts at NIST in developing the optical lattice clock based on atomic ytterbium.

  11. Optimal implementations for reliable circadian clocks.

    Science.gov (United States)

    Hasegawa, Yoshihiko; Arita, Masanori

    2014-09-01

    Circadian rhythms are acquired through evolution to increase the chances for survival through synchronizing with the daylight cycle. Reliable synchronization is realized through two trade-off properties: regularity to keep time precisely, and entrainability to synchronize the internal time with daylight. We find by using a phase model with multiple inputs that achieving the maximal limit of regularity and entrainability entails many inherent features of the circadian mechanism. At the molecular level, we demonstrate the role sharing of two light inputs, phase advance and delay, as is well observed in mammals. At the behavioral level, the optimal phase-response curve inevitably contains a dead zone, a time during which light pulses neither advance nor delay the clock. We reproduce the results of phase-controlling experiments entrained by two types of periodic light pulses. Our results indicate that circadian clocks are designed optimally for reliable clockwork through evolution. PMID:25238386

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

    Science.gov (United States)

    West, Joseph

    2007-01-01

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

  13. Bayesian quantum frequency estimation in presence of collective dephasing

    International Nuclear Information System (INIS)

    We advocate a Bayesian approach to optimal quantum frequency estimation—an important issue for future quantum enhanced atomic clock operation. The approach provides a clear insight into the interplay between decoherence and the extent of prior knowledge in determining the optimal interrogation times and optimal estimation strategies. We propose a general framework capable of describing local oscillator noise as well as additional collective atomic dephasing effects. For a Gaussian noise, the average Bayesian cost can be expressed using the quantum Fisher information. Thus we establish a direct link between the two, often competing, approaches to quantum estimation theory. (paper)

  14. Bayesian data analysis

    CERN Document Server

    Gelman, Andrew; Stern, Hal S; Dunson, David B; Vehtari, Aki; Rubin, Donald B

    2013-01-01

    FUNDAMENTALS OF BAYESIAN INFERENCEProbability and InferenceSingle-Parameter Models Introduction to Multiparameter Models Asymptotics and Connections to Non-Bayesian ApproachesHierarchical ModelsFUNDAMENTALS OF BAYESIAN DATA ANALYSISModel Checking Evaluating, Comparing, and Expanding ModelsModeling Accounting for Data Collection Decision AnalysisADVANCED COMPUTATION Introduction to Bayesian Computation Basics of Markov Chain Simulation Computationally Efficient Markov Chain Simulation Modal and Distributional ApproximationsREGRESSION MODELS Introduction to Regression Models Hierarchical Linear

  15. Bayesian Mediation Analysis

    OpenAIRE

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian mediation analysis, inference is straightforward and exact, which makes it appealing for studies with small samples. Third, the Bayesian approach is conceptua...

  16. Bayesian Games with Intentions

    OpenAIRE

    Bjorndahl, Adam; Halpern, Joseph Y.; Pass, Rafael

    2016-01-01

    We show that standard Bayesian games cannot represent the full spectrum of belief-dependent preferences. However, by introducing a fundamental distinction between intended and actual strategies, we remove this limitation. We define Bayesian games with intentions, generalizing both Bayesian games and psychological games, and prove that Nash equilibria in psychological games correspond to a special class of equilibria as defined in our setting.

  17. The adipocyte clock controls brown adipogenesis through the TGF-Beta and BMP signaling pathways

    Science.gov (United States)

    The molecular clock is intimately linked to metabolic regulation, and brown adipose tissue plays a key role in energy homeostasis. However, whether the cell-intrinsic clock machinery participates in brown adipocyte development is unknown. Here, we show that Bmal1 (also known as ARNTL), the essential...

  18. The Evolution of the Cyanobacterial Posttranslational Clock from a Primitive "Phoscillator"

    NARCIS (Netherlands)

    Simons, Mirre J. P.

    2009-01-01

    Cyanobacteria were among the 1st organisms to evolve on earth. The molecular circadian clock proteins of cyanobacteria and their phylogenetics have recently been elucidated. This allows for a conjecture on the evolution of 1 of the 1st circadian clocks. A scenario has now been created by combining k

  19. Where's the glass? Biomarkers, molecular clocks, and microRNAs suggest a 200-Myr missing Precambrian fossil record of siliceous sponge spicules

    Science.gov (United States)

    Sperling, E. A.; Robinson, J.; Pisani, D.; Peterson, K.

    2010-12-01

    The earliest evidence for animal life comes from the fossil record of 24-isopropylcholestane, a sterane found in Cryogenian deposits, and whose precursors are found in modern demosponges, but not choanoflagellates, calcareans, hexactinellids, or eumetazoans. However, many modern demosponges are also characterized by the presence of siliceous spicules, and there are no convincing demosponge spicules in strata older than the Cambrian. This temporal disparity highlights a problem with our understanding of the Precambrian fossil record - either these supposed demosponge-specific biomarkers were derived from the sterols of some other organism and are simply retained in modern demosponges, or spicules do not primitively characterize crown-group demosponges. Resolving this issue requires resolving the phylogenetic placement of another group of sponges, the hexactinellids, which not only make a spicule thought to be homologous to the spicules of demosponges, but also make their first appearance near the Precambrian/Cambrian boundary. Using two independent analytical approaches and data sets - traditional molecular phylogenetic analyses and the presence or absence of specific microRNA genes - we show that demosponges are monophyletic, and that hexactinellids are their sister group (together forming the Silicea). Thus, spicules must have evolved before the last common ancestor of all living siliceans, suggesting the presence of a significant gap in the silicean spicule fossil record. Molecular divergence estimates date the origin of this last common ancestor well within the Cryogenian, consistent with the biomarker record, and strongly suggests that siliceous spicules were present during the Precambrian but were not preserved.

  20. Bayesian quantum frequency estimation in presence of collective dephasing

    OpenAIRE

    Macieszczak, Katarzyna; Fraas, Martin; Demkowicz-Dobrzanski, Rafal

    2013-01-01

    We advocate a Bayesian approach to optimal quantum frequency estimation - an important issue for future quantum enhanced atomic clock operation. The approach provides a clear insight into the interplay between decoherence and the extent of the prior knowledge in determining the optimal interrogation times and optimal estimation strategies. We propose a general framework capable of describing local oscillator noise as well as additional collective atomic dephasing effects. For a Gaussian noise...

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

    Science.gov (United States)

    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.

  2. Controllable clock circuit design in PEM system

    International Nuclear Information System (INIS)

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

  3. BEAST: Bayesian evolutionary analysis by sampling trees

    OpenAIRE

    Drummond Alexei J; Rambaut Andrew

    2007-01-01

    Abstract Background The evolutionary analysis of molecular sequence variation is a statistical enterprise. This is reflected in the increased use of probabilistic models for phylogenetic inference, multiple sequence alignment, and molecular population genetics. Here we present BEAST: a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree. A large number of popular stochastic models of sequence evolution are provided and tree-based m...

  4. BEAST: Bayesian evolutionary analysis by sampling trees

    OpenAIRE

    Drummond, Alexei J.; Rambaut, Andrew

    2007-01-01

    Background: The evolutionary analysis of molecular sequence variation is a statistical enterprise. This is reflected in the increased use of probabilistic models for phylogenetic inference, multiple sequence alignment, and molecular population genetics. Here we present BEAST: a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree. A large number of popular stochastic models of sequence evolution are provided and tree-based models su...

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

    Directory of Open Access Journals (Sweden)

    Yang Ziheng

    2011-09-01

    Full Text Available Abstract Background 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. Results 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

  6. Circadian clock, cell cycle and cancer

    OpenAIRE

    Cansu Özbayer; İrfan Değirmenci

    2011-01-01

    There are a few rhythms of our daily lives that we are under the influence. One of them is characterized by predictable changes over a 24-hour timescale called circadian clock. This cellular clock is coordinated by the suprachiasmatic nucleus in the anterior hypothalamus. The clock consist of an autoregulatory transcription-translation feedback loop compose of four genes/proteins; BMAL1, Clock, Cyrptochrome, and Period. BMAL 1 and Clock are transcriptional factors and Period and Cyrptochrome ...

  7. Gravitomagnetism and Relative Observer Clock Effects

    OpenAIRE

    Bini, Donato; Jantzen, Robert T; Mashhoon, Bahram

    2000-01-01

    The gravitomagnetic clock effect and the Sagnac effect for circularly rotating orbits in stationary axisymmetric spacetimes are studied from a relative observer point of view, clarifying their relationships and the roles played by special observer families. In particular Semer\\'ak's recent characterization of extremely accelerated observers in terms of the two-clock clock effect is shown to be complemented by a similarly special property of the single-clock clock effect.

  8. Illuminating the circadian clock in monarch butterfly migration.

    Science.gov (United States)

    Froy, Oren; Gotter, Anthony L; Casselman, Amy L; Reppert, Steven M

    2003-05-23

    Migratory monarch butterflies use a time-compensated Sun compass to navigate to their overwintering grounds in Mexico. Here, we report that constant light, which disrupts circadian clock function at both the behavioral and molecular levels in monarchs, also disrupts the time-compensated component of flight navigation. We further show that ultraviolet light is important for flight navigation but is not required for photic entrainment of circadian rhythms. Tracing these distinct light-input pathways into the brain should aid our understanding of the clock-compass mechanisms necessary for successful migration. PMID:12764200

  9. The Bayesian Bootstrap

    OpenAIRE

    Rubin, Donald B.

    1981-01-01

    The Bayesian bootstrap is the Bayesian analogue of the bootstrap. Instead of simulating the sampling distribution of a statistic estimating a parameter, the Bayesian bootstrap simulates the posterior distribution of the parameter; operationally and inferentially the methods are quite similar. Because both methods of drawing inferences are based on somewhat peculiar model assumptions and the resulting inferences are generally sensitive to these assumptions, neither method should be applied wit...

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

    Directory of Open Access Journals (Sweden)

    Carlo C Lazado

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

  11. Function of the Shaw potassium channel within the Drosophila circadian clock.

    Directory of Open Access Journals (Sweden)

    James J Hodge

    Full Text Available BACKGROUND: In addition to the molecular feedback loops, electrical activity has been shown to be important for the function of networks of clock neurons in generating rhythmic behavior. Most studies have used over-expression of foreign channels or pharmacological manipulations that alter membrane excitability. In order to determine the cellular mechanisms that regulate resting membrane potential (RMP in the native clock of Drosophila we modulated the function of Shaw, a widely expressed neuronal potassium (K(+ channel known to regulate RMP in Drosophila central neurons. METHODOLOGY/PRINCIPAL FINDINGS: We show that Shaw is endogenously expressed in clock neurons. Differential use of clock gene promoters was employed to express a range of transgenes that either increase or decrease Shaw function in different clusters of clock neurons. Under LD conditions, increasing Shaw levels in all clock neurons (LNv, LNd, DN(1, DN(2 and DN(3, or in subsets of clock neurons (LNd and DNs or DNs alone increases locomotor activity at night. In free-running conditions these manipulations result in arrhythmic locomotor activity without disruption of the molecular clock. Reducing Shaw in the DN alone caused a dramatic lengthening of the behavioral period. Changing Shaw levels in all clock neurons also disrupts the rhythmic accumulation and levels of Pigment Dispersing Factor (PDF in the dorsal projections of LNv neurons. However, changing Shaw levels solely in LNv neurons had little effect on locomotor activity or rhythmic accumulation of PDF. CONCLUSIONS/SIGNIFICANCE: Based on our results it is likely that Shaw modulates pacemaker and output neuronal electrical activity that controls circadian locomotor behavior by affecting rhythmic release of PDF. The results support an important role of the DN clock neurons in Shaw-mediated control of circadian behavior. In conclusion, we have demonstrated a central role of Shaw for coordinated and rhythmic output from clock

  12. Bayesian statistics an introduction

    CERN Document Server

    Lee, Peter M

    2012-01-01

    Bayesian Statistics is the school of thought that combines prior beliefs with the likelihood of a hypothesis to arrive at posterior beliefs. The first edition of Peter Lee’s book appeared in 1989, but the subject has moved ever onwards, with increasing emphasis on Monte Carlo based techniques. This new fourth edition looks at recent techniques such as variational methods, Bayesian importance sampling, approximate Bayesian computation and Reversible Jump Markov Chain Monte Carlo (RJMCMC), providing a concise account of the way in which the Bayesian approach to statistics develops as wel

  13. Understanding Computational Bayesian Statistics

    CERN Document Server

    Bolstad, William M

    2011-01-01

    A hands-on introduction to computational statistics from a Bayesian point of view Providing a solid grounding in statistics while uniquely covering the topics from a Bayesian perspective, Understanding Computational Bayesian Statistics successfully guides readers through this new, cutting-edge approach. With its hands-on treatment of the topic, the book shows how samples can be drawn from the posterior distribution when the formula giving its shape is all that is known, and how Bayesian inferences can be based on these samples from the posterior. These ideas are illustrated on common statistic

  14. Animal clocks: when science meets nature.

    Science.gov (United States)

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

    2013-08-22

    Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian 'clock'), with the alternation of environmental light and darkness synchronizing (entraining) these rhythms to the natural day-night cycle. Our knowledge of the circadian system of animals at the molecular, cellular, tissue and organismal levels is remarkable, and we are beginning to understand how each of these levels contributes to the emergent properties and increased complexity of the system as a whole. For the most part, these analyses have been carried out using model organisms in standard laboratory housing, but to begin to understand the adaptive significance of the clock, we must expand our scope to study diverse animal species from different taxonomic groups, showing diverse activity patterns, in their natural environments. The seven papers in this Special Feature of Proceedings of the Royal Society B take on this challenge, reviewing the influences of moonlight, latitudinal clines, evolutionary history, social interactions, specialized temporal niches, annual variation and recently appreciated post-transcriptional molecular mechanisms. The papers emphasize that the complexity and diversity of the natural world represent a powerful experimental resource. PMID:23825215

  15. [Cognitive Function and Calcium. Ca2+-dependent regulatory mechanism of circadian clock oscillation and its relevance to neuronal function].

    Science.gov (United States)

    Kon, Naohiro; Fukada, Yoshitaka

    2015-02-01

    Circadian clock generates a variety of biological rhythms such as sleep/wake cycles and blood hormone rhythms. The circadian clock also bolsters daily mental activities. In fact, abnormalities of the circadian rhythms are found in several neurological disorders. The circadian clock has two important functions: (i) a cell-autonomous oscillatory function and (ii) a phase-adjusting function that synchronizes the clock oscillation with environmental cycling conditions such as light/dark cycle. Behavioral rhythms are controlled by the central clock in hypothalamic suprachiasmatic nucleus (SCN). The central clock orchestrates peripheral clocks in the other tissues via neuronal connection and/or actions of humoral factors. The molecular mechanism of the cell-autonomous clock is based on transcriptional feedback regulation of clock genes by their encoded products. Ca2+ is essential for not only the light response of the clock but also the cell autonomous oscillation mechanism. This article provides an overview of recent progress in studies of Ca2+-dependent regulatory mechanism of the molecular clockwork. PMID:25634045

  16. A fossil-calibrated relaxed clock for Ephedra indicates an Oligocene age for the divergence of Asian and New World clades and Miocene dispersal into South America

    Institute of Scientific and Technical Information of China (English)

    Stefanie M. ICKERT-BOND; Catarina RYDIN; Susanne S. RENNER

    2009-01-01

    Ephedra comprises approximately 50 species, which are roughly equally distributed between the Old and New World deserts, but not in the intervening regions (amphitropical range). Great heterogeneity in the substitution rates of Gnetales (Ephedra, Gnetum, and Welwitschia) has made it difficult to infer the ages of the major divergence events in Ephedra, such as the timing of the Beringian disjunction in the genus and the entry into South America. Here, we use data from as many Gnetales species and genes as available from GenBank and from a recent study to investigate the timing of the major divergence events. Because of the tradeoff between the amount of missing data and taxon/gene sampling, we reduced the initial matrix of 265 accessions and 12 loci to 95 accessions and 10 loci, and further to 42 species (and 7736 aligned nucleotides) to achieve stationary distributions in the Bayesian molecular clock runs. Results from a relaxed clock with an uncorrelated rates model and fossil-based calibration reveal that New World species are monophyletic and diverged from their mostly Asian sister clade some 30 mya, fitting with many other Beringian disjunctions. The split between the single North American and the single South American clade occurred approximately 25 mya, well before the closure of the Panamanian Isthmus. Overall, the biogeographic history of Ephedra appears dominated by long-distance dispersal, but finer-scale studies are needed to test this hypothesis.

  17. Molecular cloning and bioinformatic analysis of biological clock genes Bmcry1 and Bmcry2 in Bombyx mori%家蚕生物钟基因Bmcryl与Bmcry2的克隆及生物信息学分析

    Institute of Scientific and Technical Information of China (English)

    王文栋; 梁辉; 朱晓苏; 陶卉; 徐丽; 司马杨虎; 徐世清

    2011-01-01

    隐花色素基因(cryptochrome gene,Cry)是已确认的主要生物钟基因之一,它广泛分布于细菌和真核生物中.昆虫Cry基因分为Cry1,和Cry2两类,果蝇只有Cry1,蜜蜂等膜翅目昆虫只有Cry2.为了研究鳞翅目模式昆虫家蚕Bombyx mori的昼夜生物钟分子调控机制和昆虫CRY蛋白的进化,本研究克隆了家蚕Bmcry1与Bmcry2基因的全长cDNA序列,长度分别为2 166 bp和2 389 bp(GenBank登录号分别为HM747059和HM747060),拼接了全基因序列(GenBank 登录号分别为HM747057和HM747058).Bmcry1基因具有12个外显子和11个内含子,Bmcry2具有9个外显子,8个内含子.染色体定位表明Bmcry1和8mcry2分别位于第17号和15号染色体.通过同源建模获得了Bmcry1和Bmcry2蛋白的三维结构,其FAD入口大而深,这与CRY不与嘧啶二聚体结合相符;Bmcry1和Bmcry2表面多为负电荷,只在FAD人口位置有正电荷富集.多序列比对、蛋白质基序和功能域分析、聚类分析等结果显示,Bmcry1和Bmcry2分属昆虫的CRY1和CRY2,与柞蚕Antheraea pernyi等鳞翅目昆虫中CRY蛋白的亲缘关系最近.家蚕的两类CRY与其他昆虫CRY相似,也都具有DNA光解酶和FAD结合功能域,但保守位点和蛋白基序位点不同.本实验为进一步研究家蚕CRY1和CRY2的分子进化机制和功能创造了条件.%Cryptochrome gene (Cry) is one of the major biological clock genes which were widely distributed in bacteria and eukaryotes. Cry genes of insect species are clearly divided into two types, Cry1 and Cry2. Only Cry1 is expressed in Drosophila, while only Cry2 was expressed in bees and other hymenopteran insects. In order to explore the molecular mechanism of circadian clock in lepidopteran model insect Bombyx mori and the evolution of CRY proteins in insect species, we cloned the eDNA sequences of Bmcryl (2 166 bp, GenBank accession no. HM747059) and Bmcry2 (2 389 bp, GenBank accession no.HM747060), and obtained their gene sequences (Gen

  18. On Fuzzy Bayesian Inference

    OpenAIRE

    Frühwirth-Schnatter, Sylvia

    1990-01-01

    In the paper at hand we apply it to Bayesian statistics to obtain "Fuzzy Bayesian Inference". In the subsequent sections we will discuss a fuzzy valued likelihood function, Bayes' theorem for both fuzzy data and fuzzy priors, a fuzzy Bayes' estimator, fuzzy predictive densities and distributions, and fuzzy H.P.D .-Regions. (author's abstract)

  19. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  20. Atomic clock ensemble in space

    International Nuclear Information System (INIS)

    Atomic Clock Ensemble in Space (ACES) is a mission using high-performance clocks and links to test fundamental laws of physics in space. Operated in the microgravity environment of the International Space Station, the ACES clocks, PHARAO and SHM, will generate a frequency reference reaching instability and inaccuracy at the 1 · 10−16 level. A link in the microwave domain (MWL) and an optical link (ELT) will make the ACES clock signal available to ground laboratories equipped with atomic clocks. Space-to-ground and ground-to-ground comparisons of atomic frequency standards will be used to test Einstein's theory of general relativity including a precision measurement of the gravitational red-shift, a search for time variations of fundamental constants, and Lorentz Invariance tests. Applications in geodesy, optical time transfer, and ranging will also be supported. ACES has now reached an advanced technology maturity, with engineering models completed and successfully tested and flight hardware under development. This paper presents the ACES mission concept and the status of its main instruments.

  1. A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability.

    Science.gov (United States)

    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

    2015-08-13

    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

  2. Altered circadian clock gene expression in patients with schizophrenia.

    Science.gov (United States)

    Johansson, Anne-Sofie; Owe-Larsson, Björn; Hetta, Jerker; Lundkvist, Gabriella B

    2016-07-01

    Impaired circadian rhythmicity has been reported in several psychiatric disorders. Schizophrenia is commonly associated with aberrant sleep-wake cycles and insomnia. It is not known if schizophrenia is associated with disturbances in molecular rhythmicity. We cultured fibroblasts from skin samples obtained from patients with chronic schizophrenia and from healthy controls, respectively, and analyzed the circadian expression during 48h of the clock genes CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBα and DBP. In fibroblasts obtained from patients with chronic schizophrenia, we found a loss of rhythmic expression of CRY1 and PER2 compared to cells from healthy controls. We also estimated the sleep quality in these patients and found that most of them suffered from poor sleep in comparison with the healthy controls. In another patient sample, we analyzed mononuclear blood cells from patients with schizophrenia experiencing their first episode of psychosis, and found decreased expression of CLOCK, PER2 and CRY1 compared to blood cells from healthy controls. These novel findings show disturbances in the molecular clock in schizophrenia and have important implications in our understanding of the aberrant rhythms reported in this disease. PMID:27132483

  3. Colloquium: Physics of optical lattice clocks

    International Nuclear Information System (INIS)

    Recently invented and demonstrated optical lattice clocks hold great promise for improving the precision of modern time keeping. These clocks aim at the 10-18 fractional accuracy, which translates into a clock that would neither lose nor gain a fraction of a second over an estimated age of the Universe. In these clocks, millions of atoms are trapped and interrogated simultaneously, dramatically improving clock stability. Here the principles of operation of these clocks are discussed and, in particular, a novel concept of magic trapping of atoms in optical lattices. Recently proposed microwave lattice clocks are also highlights and several applications that employ the optical lattice clocks as a platform for precision measurements and quantum information processing.

  4. Acting with the Clock: Clocking Practices in Early Childhood

    Science.gov (United States)

    Pacini-Ketchabaw, Veronica

    2012-01-01

    In this article, the author addresses intra-actions that take place among humans and non-human others--the physical world, the materials--in early childhood education's everyday practices. Her object of study is the clock. Specifically, she provides an example of what it might mean to account for the intra-activity of the material-discursive…

  5. Identifying Nonstationary Clock Noises in Navigation Systems

    OpenAIRE

    Patrizia Tavella; Lorenzo Galleani

    2008-01-01

    The stability of the atomic clocks on board the satellites of a navigation system should remain constant with time. In reality there are numerous physical phenomena that make the behavior of the clocks a function of time, and for this reason we have recently introduced the dynamic Allan variance (DAVAR), a measure of the time-varying stability of an atomic clock. In this paper we discuss the dynamic Allan variance for phase and frequency jumps, two common nonstationarities of atomic clocks. T...

  6. Single-transistor-clocked flip-flop

    Science.gov (United States)

    Zhao, Peiyi; Darwish, Tarek; Bayoumi, Magdy

    2005-08-30

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

  7. 47 CFR 80.935 - Station clock.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Station clock. 80.935 Section 80.935... MARITIME SERVICES Compulsory Radiotelephone Installations for Small Passenger Boats § 80.935 Station clock. Each station subject to this subpart must have a working clock or timepiece readily available to...

  8. Collisionally induced atomic clock shifts and correlations

    International Nuclear Information System (INIS)

    We develop a formalism to incorporate exchange symmetry considerations into the calculation of collisional frequency shifts for atomic clocks using a density-matrix formalism. The formalism is developed for both fermionic and bosonic atomic clocks. Numerical results for a finite-temperature 87Sr 1S0 (F=9/2) atomic clock in a magic wavelength optical lattice are presented.

  9. Clock Drawing in Developmental Dyslexia.

    Science.gov (United States)

    Eden, Guinevere F.; Wood, Frank B.; Stein, John F.

    2003-01-01

    A study involving 93 children (ages 10-12), 295 with poor reading skills, found many children with dyslexia and some garden-variety poor readers showed significant left neglect on the Clock Drawing Test. In poor readers with dyslexia, spatial construction deficits were observed like those of parents with acquired right-hemisphere lesions.…

  10. A quantum network of clocks

    Science.gov (United States)

    Komar, Peter; Kessler, Eric; Bishof, Michael; Jiang, Liang; Sorensen, Anders; Ye, Jun; Lukin, Mikhail

    2014-05-01

    Shared timing information constitutes a key resource for positioning and navigation with a direct correspondence between timing accuracy and precision in applications such as the Global Positioning System (GPS). By combining precision metrology and quantum networks, we propose here a quantum, cooperative protocol for the operation of a network consisting of geographically remote optical atomic clocks. Using non-local entangled states, we demonstrate an optimal utilization of the global network resources, and show that such a network can be operated near the fundamental limit set by quantum theory yielding an ultra-precise clock signal. Furthermore, the internal structure of the network, combined with basic techniques from quantum communication, guarantees security both from internal and external threats. Realization of such a global quantum network of clocks may allow construction of a real-time single international time scale (world clock) with unprecedented stability and accuracy. See also: Komar et al. arXiv:1310.6045 (2013) and Kessler et al. arXiv:1310.6043 (2013).

  11. Clock gene expression during development

    Czech Academy of Sciences Publication Activity Database

    Sumová, Alena; Bendová, Zdeňka; Sládek, Martin; Kováčiková, Zuzana; El-Hennamy, Rehab; Laurinová, Kristýna; Illnerová, Helena

    2007-01-01

    Roč. 191, Suppl.658 (2007), s. 18-18. ISSN 1748-1708. [Joint meeting of The Slovak Physiological Society, The Physiological Society and The Federation of European Physiological Societies. 11.09.2007-14.09.2007, Bratislava] Institutional research plan: CEZ:AV0Z50110509 Keywords : cpr1 * clock genes * suprachiasmatic nucleus * rat Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  12. Interaction of MAGED1 with nuclear receptors affects circadian clock function

    OpenAIRE

    Wang, Xiaohan; Tang, Jing; Xing, Lijuan; Shi, Guangsen; Ruan, Haibin; Gu, Xiwen; Liu, Zhiwei; Wu, Xi; Gao, Xiang; Xu, Ying

    2010-01-01

    The circadian clock has a central role in physiological adaption and anticipation of day/night changes. In a genetic screen for novel regulators of circadian rhythms, we found that mice lacking MAGED1 (Melanoma Antigen Family D1) exhibit a shortened period and altered rest–activity bouts. These circadian phenotypes are proposed to be caused by a direct effect on the core molecular clock network that reduces the robustness of the circadian clock. We provide in vitro and in vivo evidence indica...

  13. The Mouse Clock Locus: Sequence and Comparative Analysis of 204 Kb from Mouse Chromosome 5

    OpenAIRE

    Wilsbacher, Lisa D.; Sangoram, Ashvin M.; Antoch, Marina P.; Takahashi, Joseph S.

    2000-01-01

    The Clock gene encodes a basic helix-loop-helix (bHLH)–PAS transcription factor that regulates circadian rhythms in mice. We previously cloned Clock in mouse and human using a battery of behavioral and molecular techniques, including shotgun sequencing of two bacterial artificial chromosome (BAC) clones. Here we report the finished sequence of a 204-kb region from mouse chromosome 5. This region contains the complete loci for the Clock and Tpardl (pFT27) genes, as well as the 3′ partial locus...

  14. Practical Bayesian Tomography

    CERN Document Server

    Granade, Christopher; Cory, D G

    2015-01-01

    In recent years, Bayesian methods have been proposed as a solution to a wide range of issues in quantum state and process tomography. State-of- the-art Bayesian tomography solutions suffer from three problems: numerical intractability, a lack of informative prior distributions, and an inability to track time-dependent processes. Here, we solve all three problems. First, we use modern statistical methods, as pioneered by Husz\\'ar and Houlsby and by Ferrie, to make Bayesian tomography numerically tractable. Our approach allows for practical computation of Bayesian point and region estimators for quantum states and channels. Second, we propose the first informative priors on quantum states and channels. Finally, we develop a method that allows online tracking of time-dependent states and estimates the drift and diffusion processes affecting a state. We provide source code and animated visual examples for our methods.

  15. Bayesian exploratory factor analysis

    OpenAIRE

    Gabriella Conti; Sylvia Frühwirth-Schnatter; James Heckman; Rémi Piatek

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identifi cation criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study c...

  16. Bayesian Exploratory Factor Analysis

    OpenAIRE

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.; Piatek, Rémi

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study co...

  17. Bayesian Exploratory Factor Analysis

    OpenAIRE

    Gabriella Conti; Sylvia Fruehwirth-Schnatter; Heckman, James J.; Remi Piatek

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on \\emph{ad hoc} classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo s...

  18. Bayesian exploratory factor analysis

    OpenAIRE

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.; Piatek, Rémi

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo st...

  19. Bayesian exploratory factor analysis

    OpenAIRE

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James; Piatek, Rémi

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study co...

  20. Nonparametric Bayesian Logic

    OpenAIRE

    Carbonetto, Peter; Kisynski, Jacek; De Freitas, Nando; Poole, David L

    2012-01-01

    The Bayesian Logic (BLOG) language was recently developed for defining first-order probability models over worlds with unknown numbers of objects. It handles important problems in AI, including data association and population estimation. This paper extends BLOG by adopting generative processes over function spaces - known as nonparametrics in the Bayesian literature. We introduce syntax for reasoning about arbitrary collections of objects, and their properties, in an intuitive manner. By expl...

  1. Bayesian default probability models

    OpenAIRE

    Andrlíková, Petra

    2014-01-01

    This paper proposes a methodology for default probability estimation for low default portfolios, where the statistical inference may become troublesome. The author suggests using logistic regression models with the Bayesian estimation of parameters. The piecewise logistic regression model and Box-Cox transformation of credit risk score is used to derive the estimates of probability of default, which extends the work by Neagu et al. (2009). The paper shows that the Bayesian models are more acc...

  2. A wheel of time: the circadian clock, nuclear receptors, and physiology

    OpenAIRE

    Yang, Xiaoyong

    2010-01-01

    It is a long-standing view that the circadian clock functions to proactively align internal physiology with the 24-h rotation of the earth. Recent studies, including one by Schmutz and colleagues (pp. 345–357) in the February 15, 2010, issue of Genes & Development, delineate strikingly complex connections between molecular clocks and nuclear receptor signaling pathways, implying the existence of a large-scale circadian regulatory network coordinating a diverse array of physiological processes...

  3. Interactions between circadian clocks and photosynthesis for the temporal and spatial coordination of metabolism

    OpenAIRE

    Dodd, Antony N; Belbin, Fiona E.; Frank, Alexander; Webb, Alex A. R.

    2015-01-01

    All plant productivity, including the food that we eat, arises from the capture of solar energy by plants. At most latitudes sunlight is available for only part of the 24 h day due to the rotation of the planet. This rhythmic and predictable alteration in the environment has driven the evolution of the circadian clock, which has an extremely pervasive influence upon plant molecular biology, physiology and phenology. A number of recent studies have demonstrated that the circadian clock is inte...

  4. Regulation of Fatty Acid Metabolism by Cell Autonomous Circadian Clocks: Time to Fatten up on Information?*

    OpenAIRE

    Bray, Molly S; Young, Martin E.

    2011-01-01

    Molecular, cellular, and animal-based studies have recently exposed circadian clocks as critical regulators of energy balance. Invariably, mouse models of genetically manipulated circadian clock components display features indicative of altered lipid/fatty acid metabolism, including differential adiposity and circulating lipids. The purpose of this minireview is to provide a comprehensive summary of current knowledge regarding the regulation of fatty acid metabolism by distinct cell autonomou...

  5. Circadian rhythms of cyanobacteria: monitoring the biological clocks of individual colonies by bioluminescence.

    OpenAIRE

    Kondo, T.; Ishiura, M

    1994-01-01

    Reproducible circadian rhythms of bioluminescence from individual colonies of cyanobacteria (Synechococcus sp. strain PCC 7942) has been observed. Phenotypic monitoring of colonies on agar plates will enable us to genetically analyze the molecular mechanism of the circadian clock of cyanobacteria by screening for clock mutants. By the introduction of a bacterial luciferase gene, we previously developed a transformed cyanobacterial strain (AMC149) that expresses luciferase as a bioluminescent ...

  6. Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

    OpenAIRE

    Zohar Ben-Moshe; Foulkes, Nicholas S.; Yoav Gothilf

    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 pine...

  7. Automatic control of clock duty cycle

    Science.gov (United States)

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

    2010-01-01

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

  8. Circadian clock, cell cycle and cancer

    Directory of Open Access Journals (Sweden)

    Cansu Özbayer

    2011-12-01

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

  9. Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle.

    Directory of Open Access Journals (Sweden)

    Jonathan A Hardman

    Full Text Available The human hair follicle (HF exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1 prolonging active hair growth (anagen and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4 also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2 were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease.

  10. Bayesian phylogeography finds its roots.

    Directory of Open Access Journals (Sweden)

    Philippe Lemey

    2009-09-01

    Full Text Available As a key factor in endemic and epidemic dynamics, the geographical distribution of viruses has been frequently interpreted in the light of their genetic histories. Unfortunately, inference of historical dispersal or migration patterns of viruses has mainly been restricted to model-free heuristic approaches that provide little insight into the temporal setting of the spatial dynamics. The introduction of probabilistic models of evolution, however, offers unique opportunities to engage in this statistical endeavor. Here we introduce a Bayesian framework for inference, visualization and hypothesis testing of phylogeographic history. By implementing character mapping in a Bayesian software that samples time-scaled phylogenies, we enable the reconstruction of timed viral dispersal patterns while accommodating phylogenetic uncertainty. Standard Markov model inference is extended with a stochastic search variable selection procedure that identifies the parsimonious descriptions of the diffusion process. In addition, we propose priors that can incorporate geographical sampling distributions or characterize alternative hypotheses about the spatial dynamics. To visualize the spatial and temporal information, we summarize inferences using virtual globe software. We describe how Bayesian phylogeography compares with previous parsimony analysis in the investigation of the influenza A H5N1 origin and H5N1 epidemiological linkage among sampling localities. Analysis of rabies in West African dog populations reveals how virus diffusion may enable endemic maintenance through continuous epidemic cycles. From these analyses, we conclude that our phylogeographic framework will make an important asset in molecular epidemiology that can be easily generalized to infer biogeogeography from genetic data for many organisms.

  11. An In Vitro ES Cell-Based Clock Recapitulation Assay Model Identifies CK2α as an Endogenous Clock Regulator

    OpenAIRE

    Umemura, Yasuhiro; Yoshida, Junko; Wada, Masashi; Tsuchiya, Yoshiki; Minami, Yoichi; Watanabe, Hitomi; Kondoh, Gen; Takeda, Junji; Inokawa, Hitoshi; Horie, Kyoji; Yagita, Kazuhiro

    2013-01-01

    We previously reported emergence and disappearance of circadian molecular oscillations during differentiation of mouse embryonic stem (ES) cells and reprogramming of differentiated cells, respectively. Here we present a robust and stringent in vitro circadian clock formation assay that recapitulates in vivo circadian phenotypes. This assay system first confirmed that a mutant ES cell line lacking Casein Kinase I delta (CKIδ) induced ∼3 hours longer period-length of circadian rhythm than the w...

  12. Bayesian ensemble refinement by replica simulations and reweighting

    Science.gov (United States)

    Hummer, Gerhard; Köfinger, Jürgen

    2015-12-01

    We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be characterized by integrating a wide range of experimental data, including measurements of ensemble-averaged observables. We start from a Bayesian formulation in which the posterior is a functional that ranks different configuration space distributions. By maximizing this posterior, we derive an optimal Bayesian ensemble distribution. For discrete configurations, this optimal distribution is identical to that obtained by the maximum entropy "ensemble refinement of SAXS" (EROS) formulation. Bayesian replica ensemble refinement enhances the sampling of relevant configurations by imposing restraints on averages of observables in coupled replica molecular dynamics simulations. We show that the strength of the restraints should scale linearly with the number of replicas to ensure convergence to the optimal Bayesian result in the limit of infinitely many replicas. In the "Bayesian inference of ensembles" method, we combine the replica and EROS approaches to accelerate the convergence. An adaptive algorithm can be used to sample directly from the optimal ensemble, without replicas. We discuss the incorporation of single-molecule measurements and dynamic observables such as relaxation parameters. The theoretical analysis of different Bayesian ensemble refinement approaches provides a basis for practical applications and a starting point for further investigations.

  13. Bayesian ensemble refinement by replica simulations and reweighting

    CERN Document Server

    Hummer, Gerhard

    2015-01-01

    We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be characterized by integrating a wide range of experimental data, including measurements of ensemble-averaged observables. We start from a Bayesian formulation in which the posterior is a functional that ranks different configuration space distributions. By maximizing this posterior, we derive an optimal Bayesian ensemble distribution. For discrete configurations, this optimal distribution is identical to that obtained by the maximum entropy "ensemble refinement of SAXS" (EROS) formulation. Bayesian replica ensemble refinement enhances the sampling of relevant configurations by imposing restraints on averages of observables in coupled replica molecular dynamics simulations. We find that the strength of the restraint scales with the number of replicas and we show that this sca...

  14. Mitigating aliasing in atomic clocks

    Science.gov (United States)

    Uys, Hermann; Akhalwaya, Ismail; Sastrawan, Jarrah; Biercuk, Michael

    2015-05-01

    Passive atomic clocks periodically calibrate a classical local oscillator against an atomic quantum reference through feedback. The periodic nature of this correction leads to undesirable aliasing noise. The Dick Effect, is a special case of aliasing noise consisting of the down-conversion of clock noise at harmonics of the correction frequency to a frequency of zero. To combat the Dick effect and aliasing noise in general, we suggest an extension to the usual feedback protocol, in which we incorporate information from multiple past measurements into the correction after the most recent measurement, approximating a crude low pass anti-aliasing filter of the noise. An analytical frequency domain analysis of the approach is presented and supported by numerical time domain simulations.

  15. Hanle detection for optical clocks

    CERN Document Server

    Zhang, Xiaogang; Pan, Duo; Chen, Peipei; Xue, Xiaobo; Zhuang, Wei; Chen, Jingbiao

    2014-01-01

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

  16. Circadian clocks and the regulation of virulence in fungi: Getting up to speed.

    Science.gov (United States)

    Hevia, Montserrat A; Canessa, Paulo; Larrondo, Luis F

    2016-09-01

    You cannot escape time. Therefore, it seems wise to learn how to keep track of it and use it to your advantage. Circadian clocks are molecular circuits that allow organisms to temporally coordinate a plethora of processes, including gene expression, with a close to 24h rhythm, optimizing cellular function in synchrony with daily environmental cycles. The molecular bases of these clocks have been extensively studied in the fungus Neurospora crassa, providing a detailed molecular description. Surprisingly, there is scarce molecular information of clocks in fungi other than Neurospora, despite the existence of rhythmic phenomena in many fungal species, including pathogenic ones. This review will comment on the overall importance of clocks, what is known in Neurospora and what has been described in other fungi including new insights on the evolution of fungal clock components. The molecular description of the circadian system of the phytopathogenic fungus Botrytis cinerea will be revisited, as well as time-of-the-day variation in host-pathogen interaction dynamics, utilizing an Arabidopsis-Botrytis system, including also what is known regarding circadian regulation of defense mechanisms in the Arabidopsis thaliana plant model. Finally, this review will mention how little is known about circadian regulation of human pathogenic fungi, commenting on potential future directions and the overall perspective of fungal circadian studies. PMID:27039027

  17. Signal processing in cellular clocks

    OpenAIRE

    Forger, Daniel B.

    2011-01-01

    Many biochemical events within a cell need to be timed properly to occur at specific times of day, after other events have happened within the cell or in response to environmental signals. The cellular biochemical feedback loops that time these events have already received much recent attention in the experimental and modeling communities. Here, we show how ideas from signal processing can be applied to understand the function of these clocks. Consider two signals from the network s(t) and r(...

  18. Gaming in Combinatorial Clock Auctions

    OpenAIRE

    Janssen, Maarten; Karamychev, Vladimir

    2013-01-01

    textabstractIn recent years, Combinatorial Clock Auctions (CCAs) have been used around the world to allocate frequency spectrum for mobile telecom licenses. CCAs are claimed to significantly reduce the scope for gaming or strategic bidding. In this paper, we show, however, that CCAs significantly enhance the possibilities for strategic bidding. Real bidders in telecom markets are not only interested in the spectrum they win themselves and the price they pay for that, but also in the price com...

  19. Design principles underlying circadian clocks.

    OpenAIRE

    Rand, D.A.; Shulgin, B. V.; D. Salazar; Millar, A. J.

    2004-01-01

    A fundamental problem for regulatory networks is to understand the relation between form and function: to uncover the underlying design principles of the network. Circadian clocks present a particularly interesting instance, as recent work has shown that they have complex structures involving multiple interconnected feedback loops with both positive and negative feedback. While several authors have speculated on the reasons for this, a convincing explanation is still lacking.We analyse both t...

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

    Directory of Open Access Journals (Sweden)

    Hirokazu Yamada

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

  1. The Potorous CPD photolyase rescues a cryptochrome-deficient mammalian circadian clock.

    Directory of Open Access Journals (Sweden)

    Inês Chaves

    Full Text Available Despite the sequence and structural conservation between cryptochromes and photolyases, members of the cryptochrome/photolyase (flavoprotein family, their functions are divergent. Whereas photolyases are DNA repair enzymes that use visible light to lesion-specifically remove UV-induced DNA damage, cryptochromes act as photoreceptors and circadian clock proteins. To address the functional diversity of cryptochromes and photolyases, we investigated the effect of ectopically expressed Arabidopsis thaliana (6-4PP photolyase and Potorous tridactylus CPD-photolyase (close and distant relatives of mammalian cryptochromes, respectively, on the performance of the mammalian cryptochromes in the mammalian circadian clock. Using photolyase transgenic mice, we show that Potorous CPD-photolyase affects the clock by shortening the period of behavioral rhythms. Furthermore, constitutively expressed CPD-photolyase is shown to reduce the amplitude of circadian oscillations in cultured cells and to inhibit CLOCK/BMAL1 driven transcription by interacting with CLOCK. Importantly, we show that Potorous CPD-photolyase can restore the molecular oscillator in the liver of (clock-deficient Cry1/Cry2 double knockout mice. These data demonstrate that a photolyase can act as a true cryptochrome. These findings shed new light on the importance of the core structure of mammalian cryptochromes in relation to its function in the circadian clock and contribute to our further understanding of the evolution of the cryptochrome/photolyase protein family.

  2. Hanle Detection for Optical Clocks

    Directory of Open Access Journals (Sweden)

    Xiaogang Zhang

    2015-01-01

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

  3. Hanle detection for optical clocks.

    Science.gov (United States)

    Zhang, Xiaogang; Zhang, Shengnan; Pan, Duo; Chen, Peipei; Xue, Xiaobo; Zhuang, Wei; Chen, Jingbiao

    2015-01-01

    Considering the strong inhomogeneous spatial polarization and intensity distribution of spontaneous decay fluorescence due to the Hanle effect, we propose and demonstrate a universe Hanle detection configuration of electron-shelving method for optical clocks. Experimental results from Ca atomic beam optical frequency standard with electron-shelving method show that a designed Hanle detection geometry with optimized magnetic field direction, detection laser beam propagation and polarization direction, and detector position can improve the fluorescence collection rate by more than one order of magnitude comparing with that of inefficient geometry. With the fixed 423 nm fluorescence, the improved 657 nm optical frequency standard signal intensity is presented. The potential application of the Hanle detection geometry designed for facilitating the fluorescence collection for optical lattice clock with a limited solid angle of the fluorescence collection has been discussed. The Hanle detection geometry is also effective for ion detection in ion optical clock and quantum information experiments. Besides, a cylinder fluorescence collection structure is designed to increase the solid angle of the fluorescence collection in Ca atomic beam optical frequency standard. PMID:25734183

  4. Bayesian least squares deconvolution

    Science.gov (United States)

    Asensio Ramos, A.; Petit, P.

    2015-11-01

    Aims: We develop a fully Bayesian least squares deconvolution (LSD) that can be applied to the reliable detection of magnetic signals in noise-limited stellar spectropolarimetric observations using multiline techniques. Methods: We consider LSD under the Bayesian framework and we introduce a flexible Gaussian process (GP) prior for the LSD profile. This prior allows the result to automatically adapt to the presence of signal. We exploit several linear algebra identities to accelerate the calculations. The final algorithm can deal with thousands of spectral lines in a few seconds. Results: We demonstrate the reliability of the method with synthetic experiments and we apply it to real spectropolarimetric observations of magnetic stars. We are able to recover the magnetic signals using a small number of spectral lines, together with the uncertainty at each velocity bin. This allows the user to consider if the detected signal is reliable. The code to compute the Bayesian LSD profile is freely available.

  5. Bayesian least squares deconvolution

    CERN Document Server

    Ramos, A Asensio

    2015-01-01

    Aims. To develop a fully Bayesian least squares deconvolution (LSD) that can be applied to the reliable detection of magnetic signals in noise-limited stellar spectropolarimetric observations using multiline techniques. Methods. We consider LSD under the Bayesian framework and we introduce a flexible Gaussian Process (GP) prior for the LSD profile. This prior allows the result to automatically adapt to the presence of signal. We exploit several linear algebra identities to accelerate the calculations. The final algorithm can deal with thousands of spectral lines in a few seconds. Results. We demonstrate the reliability of the method with synthetic experiments and we apply it to real spectropolarimetric observations of magnetic stars. We are able to recover the magnetic signals using a small number of spectral lines, together with the uncertainty at each velocity bin. This allows the user to consider if the detected signal is reliable. The code to compute the Bayesian LSD profile is freely available.

  6. Bayesian Adaptive Exploration

    CERN Document Server

    Loredo, T J

    2004-01-01

    I describe a framework for adaptive scientific exploration based on iterating an Observation--Inference--Design cycle that allows adjustment of hypotheses and observing protocols in response to the results of observation on-the-fly, as data are gathered. The framework uses a unified Bayesian methodology for the inference and design stages: Bayesian inference to quantify what we have learned from the available data and predict future data, and Bayesian decision theory to identify which new observations would teach us the most. When the goal of the experiment is simply to make inferences, the framework identifies a computationally efficient iterative ``maximum entropy sampling'' strategy as the optimal strategy in settings where the noise statistics are independent of signal properties. Results of applying the method to two ``toy'' problems with simulated data--measuring the orbit of an extrasolar planet, and locating a hidden one-dimensional object--show the approach can significantly improve observational eff...

  7. Bayesian and frequentist inequality tests

    OpenAIRE

    David M. Kaplan; Zhuo, Longhao

    2016-01-01

    Bayesian and frequentist criteria are fundamentally different, but often posterior and sampling distributions are asymptotically equivalent (and normal). We compare Bayesian and frequentist hypothesis tests of inequality restrictions in such cases. For finite-dimensional parameters, if the null hypothesis is that the parameter vector lies in a certain half-space, then the Bayesian test has (frequentist) size $\\alpha$; if the null hypothesis is any other convex subspace, then the Bayesian test...

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

    CERN Document Server

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

    2016-01-01

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

  9. PI3K regulates BMAL1/CLOCK-mediated circadian transcription from the Dbp promoter.

    Science.gov (United States)

    Morishita, Yoshikazu; Miura, Daiki; Kida, Satoshi

    2016-06-01

    The circadian rhythm generated by circadian clock underlies a molecular mechanism of rhythmic transcriptional regulation by transcription factor BMAL1/CLOCK. Importantly, the circadian clock is coordinated by exogenous cues to accommodate to changes in the external environment. However, the molecular mechanisms by which intracellular-signaling pathways mediate the adjustments of the circadian transcriptional rhythms remain unclear. In this study, we found that pharmacological inhibition or shRNA-mediated knockdown of phosphatidylinositol 3-kinase (PI3K) blocked upregulation of Dbp mRNA induced by serum shock in NIH 3T3 cells. Moreover, the inhibition of PI3K significantly reduced the promoter activity of the Dbp gene, as well as decreased the recruitment of BMAL1/CLOCK to the E-box in the Dbp promoter. Interestingly, the inhibition of PI3K blocked heterodimerization of BMAL1 and CLOCK. Our findings suggest that PI3K signaling plays a modulatory role in the regulation of the transcriptional rhythm of the Dbp gene by targeting BMAL1 and CLOCK. PMID:27022680

  10. Bayesian multiple target tracking

    CERN Document Server

    Streit, Roy L

    2013-01-01

    This second edition has undergone substantial revision from the 1999 first edition, recognizing that a lot has changed in the multiple target tracking field. One of the most dramatic changes is in the widespread use of particle filters to implement nonlinear, non-Gaussian Bayesian trackers. This book views multiple target tracking as a Bayesian inference problem. Within this framework it develops the theory of single target tracking, multiple target tracking, and likelihood ratio detection and tracking. In addition to providing a detailed description of a basic particle filter that implements

  11. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.;

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the...... corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  12. Atomic clocks: A mathematical physics perspective

    International Nuclear Information System (INIS)

    Full text: Accuracy of atomic clocks (since their introduction in 50's) is increasing by roughly one order per decade. A natural theoretical problem posed by this development is to seek the ultimate accuracy of atomic clocks and means to achieve it. This problem was indeed extensively studied and various bounds on the accuracy are well understood, e.g. shot noise limit. I would present a mathematical minded (but simple) model of atomic clocks and discuss accuracy bounds within the model. (author)

  13. The Square Light Clock and Special Relativity

    Science.gov (United States)

    Galli, J. Ronald; Amiri, Farhang

    2012-01-01

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

  14. Unraveling the circadian clock in Arabidopsis

    OpenAIRE

    Wang, Xiaoxue; Ma, Ligeng

    2012-01-01

    The circadian clock is an endogenous timing system responsible for coordinating an organism’s biological processes with its environment. Interlocked transcriptional feedback loops constitute the fundamental architecture of the circadian clock. In Arabidopsis, three feedback loops, the core loop, morning loop and evening loop, comprise a network that is the basis of the circadian clock. The components of these three loops are regulated in distinct ways, including transcriptional, post-transcri...

  15. Performance Evaluation of Clock Synchronization Algorithms

    OpenAIRE

    Anceaume, Emmanuelle; Puaut, Isabelle

    1998-01-01

    Clock synchronization algorithms ensure that physically dispersed processors have a common knowledge of time. This report proposes a survey of software fault-tolerant clock synchronization algorithms: deterministic, probabilistic and statistical ; internal and external ; and resilient from crash to Byzantine failures. Our survey is based on a classification of clock synchronization algorithms (according to their internal structure and to three orthogonal and independent basic building blocks ...

  16. CLOCK and BMAL1 Regulate Muscle Insulin Sensitivity via SIRT1 in Male Mice.

    Science.gov (United States)

    Liu, Jun; Zhou, Ben; Yan, Menghong; Huang, Rui; Wang, Yuangao; He, Zhishui; Yang, Yonggang; Dai, Changgui; Wang, Yiqian; Zhang, Fang; Zhai, Qiwei

    2016-06-01

    Circadian misalignment induces insulin resistance in both human and animal models, and skeletal muscle is the largest organ response to insulin. However, how circadian clock regulates muscle insulin sensitivity and the underlying molecular mechanisms are still largely unknown. Here we show circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1, two core circadian transcription factors, are down-regulated in insulin-resistant C2C12 myotubes and mouse skeletal muscle. Furthermore, insulin signaling is attenuated in the skeletal muscle of Clock(Δ19/Δ19) mice, and knockdown of CLOCK or BMAL1 by small interfering RNAs induces insulin resistance in C2C12 myotubes. Consistently, ectopic expression of CLOCK and BMAL1 improves insulin sensitivity in C2C12 myotubes. Moreover, CLOCK and BMAL1 regulate the expression of sirtuin 1 (SIRT1), an important regulator of insulin sensitivity, in C2C12 myotubes and mouse skeletal muscle, and two E-box elements in Sirt1 promoter are responsible for its CLOCK- and BMAL1-dependent transcription in muscle cells. Further studies show that CLOCK and BMAL1 regulate muscle insulin sensitivity through SIRT1. In addition, we find that BMAL1 and SIRT1 are decreased in the muscle of mice maintained in constant darkness, and resveratrol supplementation activates SIRT1 and improves insulin sensitivity. All these data demonstrate that CLOCK and BMAL1 regulate muscle insulin sensitivity via SIRT1, and activation of SIRT1 might be a potential valuable strategy to attenuate muscle insulin resistance related to circadian misalignment. PMID:27035655

  17. Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK

    OpenAIRE

    Bordon Alain; Tallone Tiziano; Langmesser Sonja; Rusconi Sandro; Albrecht Urs

    2008-01-01

    Abstract Background Circadian oscillation of clock-controlled gene expression is mainly regulated at the transcriptional level. Heterodimers of CLOCK and BMAL1 act as activators of target gene transcription; however, interactions of PER and CRY proteins with the heterodimer abolish its transcriptional activation capacity. PER and CRY are therefore referred to as negative regulators of the circadian clock. To further elucidate the mechanism how positive and negative components of the clock int...

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

    Directory of Open Access Journals (Sweden)

    Paula S Nieto

    Full Text Available 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.

  19. A molecular palaeobiological hypothesis for the origin of aplacophoran molluscs and their derivation from chiton-like ancestors.

    Science.gov (United States)

    Vinther, Jakob; Sperling, Erik A; Briggs, Derek E G; Peterson, Kevin J

    2012-04-01

    Aplacophorans have long been argued to be basal molluscs. We present a molecular phylogeny, including the aplacophorans Neomeniomorpha (Solenogastres) and Chaetodermomorpha (Caudofoveata), which recovered instead the clade Aculifera (Aplacophora + Polyplacophora). Our relaxed Bayesian molecular clock estimates an Early Ordovician appearance of the aculiferan crown group consistent with the presence of chiton-like molluscs with seven or eight dorsal shell plates by the Late Cambrian (approx. 501-490 Ma). Molecular, embryological and palaeontological data indicate that aplacophorans, as well as chitons, evolved from a paraphyletic assemblage of chiton-like ancestors. The recovery of cephalopods as a sister group to aculiferans suggests that the plesiomorphic condition in molluscs might be a morphology similar to that found in monoplacophorans. PMID:21976685

  20. Visualizing and Quantifying Intracellular Behavior and Abundance of the Core Circadian Clock Protein PERIOD2.

    Science.gov (United States)

    Smyllie, Nicola J; Pilorz, Violetta; Boyd, James; Meng, Qing-Jun; Saer, Ben; Chesham, Johanna E; Maywood, Elizabeth S; Krogager, Toke P; Spiller, David G; Boot-Handford, Raymond; White, Michael R H; Hastings, Michael H; Loudon, Andrew S I

    2016-07-25

    Transcriptional-translational feedback loops (TTFLs) are a conserved molecular motif of circadian clocks. The principal clock in mammals is the suprachiasmatic nucleus (SCN) of the hypothalamus. In SCN neurons, auto-regulatory feedback on core clock genes Period (Per) and Cryptochrome (Cry) following nuclear entry of their protein products is the basis of circadian oscillation [1, 2]. In Drosophila clock neurons, the movement of dPer into the nucleus is subject to a circadian gate that generates a delay in the TTFL, and this delay is thought to be critical for oscillation [3, 4]. Analysis of the Drosophila clock has strongly influenced models of the mammalian clock, and such models typically infer complex spatiotemporal, intracellular behaviors of mammalian clock proteins. There are, however, no direct measures of the intracellular behavior of endogenous circadian proteins to support this: dynamic analyses have been limited and often have no circadian dimension [5-7]. We therefore generated a knockin mouse expressing a fluorescent fusion of native PER2 protein (PER2::VENUS) for live imaging. PER2::VENUS recapitulates the circadian functions of wild-type PER2 and, importantly, the behavior of PER2::VENUS runs counter to the Drosophila model: it does not exhibit circadian gating of nuclear entry. Using fluorescent imaging of PER2::VENUS, we acquired the first measures of mobility, molecular concentration, and localization of an endogenous circadian protein in individual mammalian cells, and we showed how the mobility and nuclear translocation of PER2 are regulated by casein kinase. These results provide new qualitative and quantitative insights into the cellular mechanism of the mammalian circadian clock. PMID:27374340

  1. Bayesian Geostatistical Design

    DEFF Research Database (Denmark)

    Diggle, Peter; Lophaven, Søren Nymand

    2006-01-01

    locations to, or deletion of locations from, an existing design, and prospective design, which consists of choosing positions for a new set of sampling locations. We propose a Bayesian design criterion which focuses on the goal of efficient spatial prediction whilst allowing for the fact that model...

  2. Bayesian Filters in Practice

    Czech Academy of Sciences Publication Activity Database

    Krejsa, Jiří; Věchet, S.

    Bratislava: Slovak University of Technology in Bratislava, 2010, s. 217-222. ISBN 978-80-227-3353-3. [Robotics in Education . Bratislava (SK), 16.09.2010-17.09.2010] Institutional research plan: CEZ:AV0Z20760514 Keywords : mobile robot localization * bearing only beacons * Bayesian filters Subject RIV: JD - Computer Applications, Robotics

  3. Subjective Bayesian Beliefs

    DEFF Research Database (Denmark)

    Antoniou, Constantinos; Harrison, Glenn W.; Lau, Morten I.;

    2015-01-01

    A large literature suggests that many individuals do not apply Bayes’ Rule when making decisions that depend on them correctly pooling prior information and sample data. We replicate and extend a classic experimental study of Bayesian updating from psychology, employing the methods of experimenta...

  4. Bayesian Independent Component Analysis

    DEFF Research Database (Denmark)

    Winther, Ole; Petersen, Kaare Brandt

    2007-01-01

    In this paper we present an empirical Bayesian framework for independent component analysis. The framework provides estimates of the sources, the mixing matrix and the noise parameters, and is flexible with respect to choice of source prior and the number of sources and sensors. Inside the engine...

  5. Noncausal Bayesian Vector Autoregression

    DEFF Research Database (Denmark)

    Lanne, Markku; Luoto, Jani

    We propose a Bayesian inferential procedure for the noncausal vector autoregressive (VAR) model that is capable of capturing nonlinearities and incorporating effects of missing variables. In particular, we devise a fast and reliable posterior simulator that yields the predictive distribution as a...

  6. Bayesian Adaptive Exploration

    Science.gov (United States)

    Loredo, Thomas J.

    2004-04-01

    I describe a framework for adaptive scientific exploration based on iterating an Observation-Inference-Design cycle that allows adjustment of hypotheses and observing protocols in response to the results of observation on-the-fly, as data are gathered. The framework uses a unified Bayesian methodology for the inference and design stages: Bayesian inference to quantify what we have learned from the available data and predict future data, and Bayesian decision theory to identify which new observations would teach us the most. When the goal of the experiment is simply to make inferences, the framework identifies a computationally efficient iterative ``maximum entropy sampling'' strategy as the optimal strategy in settings where the noise statistics are independent of signal properties. Results of applying the method to two ``toy'' problems with simulated data-measuring the orbit of an extrasolar planet, and locating a hidden one-dimensional object-show the approach can significantly improve observational efficiency in settings that have well-defined nonlinear models. I conclude with a list of open issues that must be addressed to make Bayesian adaptive exploration a practical and reliable tool for optimizing scientific exploration.

  7. Bayesian logistic regression analysis

    NARCIS (Netherlands)

    Van Erp, H.R.N.; Van Gelder, P.H.A.J.M.

    2012-01-01

    In this paper we present a Bayesian logistic regression analysis. It is found that if one wishes to derive the posterior distribution of the probability of some event, then, together with the traditional Bayes Theorem and the integrating out of nuissance parameters, the Jacobian transformation is an

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  10. Could Atomic clocks be affected by neutrinos?

    CERN Document Server

    Hanafi, Hanaa

    2016-01-01

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

  11. Fast Clock Recovery for Digital Communications

    Science.gov (United States)

    Tell, R. G.

    1985-01-01

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

  12. Temperature influences in receiver clock modelling

    Science.gov (United States)

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

    2016-04-01

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

  13. Progress of the 87Rb Fountain Clock

    International Nuclear Information System (INIS)

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

  14. Network properties of the mammalian circadian clock

    NARCIS (Netherlands)

    Rohling, Johannes Hermanus Theodoor

    2009-01-01

    The biological clock regulates daily and seasonal rhythms in mammals. This clock is located in the suprachiasmatic nuclei (SCN), which are two small nuclei each consisting of 10,000 neurons. The neurons of the SCN endogenously generate a rhythm of approximately 24 hours. Under the influence of the l

  15. Internal Clock Drift Estimation in Computer Clusters

    Directory of Open Access Journals (Sweden)

    Hicham Marouani

    2008-01-01

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

  16. Cold atom Clocks and Applications

    CERN Document Server

    Bize, S; Abgrall, M; Marion, H; Maksimovic, I; Cacciapuoti, L; Gruenert, J; Vian, C; Dos Santos, F P; Rosenbusch, P; Lemonde, P; Santarelli, G; Wolf, P; Clairon, A; Luiten, A; Tobar, M; Salomon, C

    2005-01-01

    This paper describes advances in microwave frequency standards using laser-cooled atoms at BNM-SYRTE. First, recent improvements of the $^{133}$Cs and $^{87}$Rb atomic fountains are described. Thanks to the routine use of a cryogenic sapphire oscillator as an ultra-stable local frequency reference, a fountain frequency instability of $1.6\\times 10^{-14}\\tau^{-1/2}$ where $\\tau $ is the measurement time in seconds is measured. The second advance is a powerful method to control the frequency shift due to cold collisions. These two advances lead to a frequency stability of $2\\times 10^{-16}$ at $50,000s for the first time for primary standards. In addition, these clocks realize the SI second with an accuracy of $7\\times 10^{-16}$, one order of magnitude below that of uncooled devices. In a second part, we describe tests of possible variations of fundamental constants using $^{87}$Rb and $^{133}$Cs fountains. Finally we give an update on the cold atom space clock PHARAO developed in collaboration with CNES. This ...

  17. Single electron relativistic clock interferometer

    CERN Document Server

    Bushev, Pavel; Sholokhov, Dmitry; Kukharchyk, Nadezhda; Zych, Magdalena

    2016-01-01

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

  18. Induction of the CLOCK Gene by E2-ERα Signaling Promotes the Proliferation of Breast Cancer Cells

    Science.gov (United States)

    Bi, Hailian; Li, Shujing; Wang, Miao; Xing, Xinrong; Wu, Huijian

    2014-01-01

    Growing genetic and epidemiological evidence suggests a direct connection between the disruption of circadian rhythm and breast cancer. Moreover, the expression of several molecular components constituting the circadian clock machinery has been found to be modulated by estrogen-estrogen receptor α (E2-ERα) signaling in ERα-positive breast cancer cells. In this study, we investigated the regulation of CLOCK expression by ERα and its roles in cell proliferation. Immunohistochemical analysis of human breast tumor samples revealed high expression of CLOCK in ERα-positive breast tumor samples. Subsequent experiments using ERα-positive human breast cancer cell lines showed that both protein and mRNA levels of CLOCK were up-regulated by E2 and ERα. In these cells, E2 promoted the binding of ERα to the EREs (estrogen-response elements) of CLOCK promoter, thereby up-regulating the transcription of CLOCK. Knockdown of CLOCK attenuated cell proliferation in ERα-positive breast cancer cells. Taken together, these results demonstrated that CLOCK could be an important gene that mediates cell proliferation in breast cancer cells. PMID:24789043

  19. Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Liyun Xiao

    Full Text Available Growing genetic and epidemiological evidence suggests a direct connection between the disruption of circadian rhythm and breast cancer. Moreover, the expression of several molecular components constituting the circadian clock machinery has been found to be modulated by estrogen-estrogen receptor α (E2-ERα signaling in ERα-positive breast cancer cells. In this study, we investigated the regulation of CLOCK expression by ERα and its roles in cell proliferation. Immunohistochemical analysis of human breast tumor samples revealed high expression of CLOCK in ERα-positive breast tumor samples. Subsequent experiments using ERα-positive human breast cancer cell lines showed that both protein and mRNA levels of CLOCK were up-regulated by E2 and ERα. In these cells, E2 promoted the binding of ERα to the EREs (estrogen-response elements of CLOCK promoter, thereby up-regulating the transcription of CLOCK. Knockdown of CLOCK attenuated cell proliferation in ERα-positive breast cancer cells. Taken together, these results demonstrated that CLOCK could be an important gene that mediates cell proliferation in breast cancer cells.

  20. Circadian proteins CLOCK and BMAL1 in the chromatoid body, a RNA processing granule of male germ cells.

    Directory of Open Access Journals (Sweden)

    Rita L Peruquetti

    Full Text Available Spermatogenesis is a complex differentiation process that involves genetic and epigenetic regulation, sophisticated hormonal control, and extensive structural changes in male germ cells. RNA nuclear and cytoplasmic bodies appear to be critical for the progress of spermatogenesis. The chromatoid body (CB is a cytoplasmic organelle playing an important role in RNA post-transcriptional and translation regulation during the late steps of germ cell differentiation. The CB is also important for fertility determination since mutations of genes encoding its components cause infertility by spermatogenesis arrest. Targeted ablation of the Bmal1 and Clock genes, which encode central regulators of the circadian clock also result in fertility defects caused by problems other than spermatogenesis alterations. We show that the circadian proteins CLOCK and BMAL1 are localized in the CB in a stage-specific manner of germ cells. Both BMAL1 and CLOCK proteins physically interact with the ATP-dependent DEAD-box RNA helicase MVH (mouse VASA homolog, a hallmark component of the CB. BMAL1 is differentially expressed during the spermatogenic cycle of seminiferous tubules, and Bmal1 and Clock deficient mice display significant CB morphological alterations due to BMAL1 ablation or low expression. These findings suggest that both BMAL1 and CLOCK contribute to CB assembly and physiology, raising questions on the role of the circadian clock in reproduction and on the molecular function that CLOCK and BMAL1 could potentially have in the CB assembly and physiology.

  1. A low maintenance Sr optical lattice clock

    CERN Document Server

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

    2016-01-01

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

  2. The Molecular Clockwork of the Fire Ant Solenopsis invicta

    OpenAIRE

    Ingram, Krista K.; Alexander Kutowoi; Yannick Wurm; Dewayne Shoemaker; Rudolf Meier; Guy Bloch

    2012-01-01

    The circadian clock is a core molecular mechanism that allows organisms to anticipate daily environmental changes and adapt the timing of behaviors to maximize efficiency. In social insects, the ability to maintain the appropriate temporal order is thought to improve colony efficiency and fitness. We used the newly sequenced fire ant (Solenopsis invicta) genome to characterize the first ant circadian clock. Our results reveal that the fire ant clock is similar to the clock of the honeybee, a ...

  3. Diurnal rhythmicity of the canonical clock genes Per1, per2 and Bmal1 in the rat adrenal gland is unaltered after hypophysectomy

    DEFF Research Database (Denmark)

    Fahrenkrug, J.; Hannibal, J.; Georg, B.

    2008-01-01

    Circadian rhythms are generated by endogenous clocks in the central brain oscillator, the suprachiasmatic nucleus (SCN), and peripheral tissues. The molecular basis for the circadian clock consists of a number of genes and proteins that form transcriptional/translational feedback loops. Rhythmic...... expression of clock genes in the adrenal glands has previously been reported. Since the central clock in the SCN communicates with the adrenal glands via circadian release of adrenocorticotrophic hormone, we quantified the mRNAs for the canonical clock genes, Per1, Per2 and Bmal1 in the adrenal glands by...... real-time reverse transcription-polymerase chain reaction during a 24-h-cycle in normal and hypophysectomised rats. The mRNAs for all the three clock genes disclosed rhythmic oscillations with a period of 24 h and the phase did not differ between the hypophysectomised and intact rats. The expression...

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

    Directory of Open Access Journals (Sweden)

    Casey O Diekman

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

  5. Temporal Regulation of Cytokines by the Circadian Clock

    Directory of Open Access Journals (Sweden)

    Atsuhito Nakao

    2014-01-01

    Full Text Available Several parameters of the immune system exhibit oscillations with a period of approximately 24 hours that refers to “circadian rhythms.” Such daily variations in host immune system status might evolve to maximize immune reactions at times when encounters with pathogens are most likely to occur. However, the mechanisms behind circadian immunity have not been fully understood. Recent studies reveal that the internal time keeping system “circadian clock” plays a key role in driving the daily rhythms evident in the immune system. Importantly, several studies unveil molecular mechanisms of how certain clock proteins (e.g., BMAL1 and CLOCK temporally regulate expression of cytokines. Since cytokines are crucial mediators for shaping immune responses, this review mainly summarizes the new knowledge that highlights an emerging role of the circadian clock as a novel regulator of cytokines. A greater understanding of circadian regulation of cytokines will be important to exploit new strategies to protect host against infection by efficient cytokine induction or to treat autoimmunity and allergy by ameliorating excessive activity of cytokines.

  6. Probability and Bayesian statistics

    CERN Document Server

    1987-01-01

    This book contains selected and refereed contributions to the "Inter­ national Symposium on Probability and Bayesian Statistics" which was orga­ nized to celebrate the 80th birthday of Professor Bruno de Finetti at his birthplace Innsbruck in Austria. Since Professor de Finetti died in 1985 the symposium was dedicated to the memory of Bruno de Finetti and took place at Igls near Innsbruck from 23 to 26 September 1986. Some of the pa­ pers are published especially by the relationship to Bruno de Finetti's scientific work. The evolution of stochastics shows growing importance of probability as coherent assessment of numerical values as degrees of believe in certain events. This is the basis for Bayesian inference in the sense of modern statistics. The contributions in this volume cover a broad spectrum ranging from foundations of probability across psychological aspects of formulating sub­ jective probability statements, abstract measure theoretical considerations, contributions to theoretical statistics an...

  7. Bayesian Magic in Asteroseismology

    Science.gov (United States)

    Kallinger, T.

    2015-09-01

    Only a few years ago asteroseismic observations were so rare that scientists had plenty of time to work on individual data sets. They could tune their algorithms in any possible way to squeeze out the last bit of information. Nowadays this is impossible. With missions like MOST, CoRoT, and Kepler we basically drown in new data every day. To handle this in a sufficient way statistical methods become more and more important. This is why Bayesian techniques started their triumph march across asteroseismology. I will go with you on a journey through Bayesian Magic Land, that brings us to the sea of granulation background, the forest of peakbagging, and the stony alley of model comparison.

  8. Bayesian Nonparametric Graph Clustering

    OpenAIRE

    Banerjee, Sayantan; Akbani, Rehan; Baladandayuthapani, Veerabhadran

    2015-01-01

    We present clustering methods for multivariate data exploiting the underlying geometry of the graphical structure between variables. As opposed to standard approaches that assume known graph structures, we first estimate the edge structure of the unknown graph using Bayesian neighborhood selection approaches, wherein we account for the uncertainty of graphical structure learning through model-averaged estimates of the suitable parameters. Subsequently, we develop a nonparametric graph cluster...

  9. Approximate Bayesian recursive estimation

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav

    2014-01-01

    Roč. 285, č. 1 (2014), s. 100-111. ISSN 0020-0255 R&D Projects: GA ČR GA13-13502S Institutional support: RVO:67985556 Keywords : Approximate parameter estimation * Bayesian recursive estimation * Kullback–Leibler divergence * Forgetting Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 4.038, year: 2014 http://library.utia.cas.cz/separaty/2014/AS/karny-0425539.pdf

  10. Bayesian Benchmark Dose Analysis

    OpenAIRE

    Fang, Qijun; Piegorsch, Walter W.; Barnes, Katherine Y.

    2014-01-01

    An important objective in environmental risk assessment is estimation of minimum exposure levels, called Benchmark Doses (BMDs) that induce a pre-specified Benchmark Response (BMR) in a target population. Established inferential approaches for BMD analysis typically involve one-sided, frequentist confidence limits, leading in practice to what are called Benchmark Dose Lower Limits (BMDLs). Appeal to Bayesian modeling and credible limits for building BMDLs is far less developed, however. Indee...

  11. Bayesian Generalized Rating Curves

    OpenAIRE

    Helgi Sigurðarson 1985

    2014-01-01

    A rating curve is a curve or a model that describes the relationship between water elevation, or stage, and discharge in an observation site in a river. The rating curve is fit from paired observations of stage and discharge. The rating curve then predicts discharge given observations of stage and this methodology is applied as stage is substantially easier to directly observe than discharge. In this thesis a statistical rating curve model is proposed working within the framework of Bayesian...

  12. Heteroscedastic Treed Bayesian Optimisation

    OpenAIRE

    Assael, John-Alexander M.; Wang, Ziyu; Shahriari, Bobak; De Freitas, Nando

    2014-01-01

    Optimising black-box functions is important in many disciplines, such as tuning machine learning models, robotics, finance and mining exploration. Bayesian optimisation is a state-of-the-art technique for the global optimisation of black-box functions which are expensive to evaluate. At the core of this approach is a Gaussian process prior that captures our belief about the distribution over functions. However, in many cases a single Gaussian process is not flexible enough to capture non-stat...

  13. Efficient Bayesian Phase Estimation

    Science.gov (United States)

    Wiebe, Nathan; Granade, Chris

    2016-07-01

    We introduce a new method called rejection filtering that we use to perform adaptive Bayesian phase estimation. Our approach has several advantages: it is classically efficient, easy to implement, achieves Heisenberg limited scaling, resists depolarizing noise, tracks time-dependent eigenstates, recovers from failures, and can be run on a field programmable gate array. It also outperforms existing iterative phase estimation algorithms such as Kitaev's method.

  14. Bayesian Word Sense Induction

    OpenAIRE

    Brody, Samuel; Lapata, Mirella

    2009-01-01

    Sense induction seeks to automatically identify word senses directly from a corpus. A key assumption underlying previous work is that the context surrounding an ambiguous word is indicative of its meaning. Sense induction is thus typically viewed as an unsupervised clustering problem where the aim is to partition a word’s contexts into different classes, each representing a word sense. Our work places sense induction in a Bayesian context by modeling the contexts of the ambiguous word as samp...

  15. Bayesian Neural Word Embedding

    OpenAIRE

    Barkan, Oren

    2016-01-01

    Recently, several works in the domain of natural language processing presented successful methods for word embedding. Among them, the Skip-gram (SG) with negative sampling, known also as Word2Vec, advanced the state-of-the-art of various linguistics tasks. In this paper, we propose a scalable Bayesian neural word embedding algorithm that can be beneficial to general item similarity tasks as well. The algorithm relies on a Variational Bayes solution for the SG objective and a detailed step by ...

  16. Bayesian Attractor Learning

    Science.gov (United States)

    Wiegerinck, Wim; Schoenaker, Christiaan; Duane, Gregory

    2016-04-01

    Recently, methods for model fusion by dynamically combining model components in an interactive ensemble have been proposed. In these proposals, fusion parameters have to be learned from data. One can view these systems as parametrized dynamical systems. We address the question of learnability of dynamical systems with respect to both short term (vector field) and long term (attractor) behavior. In particular we are interested in learning in the imperfect model class setting, in which the ground truth has a higher complexity than the models, e.g. due to unresolved scales. We take a Bayesian point of view and we define a joint log-likelihood that consists of two terms, one is the vector field error and the other is the attractor error, for which we take the L1 distance between the stationary distributions of the model and the assumed ground truth. In the context of linear models (like so-called weighted supermodels), and assuming a Gaussian error model in the vector fields, vector field learning leads to a tractable Gaussian solution. This solution can then be used as a prior for the next step, Bayesian attractor learning, in which the attractor error is used as a log-likelihood term. Bayesian attractor learning is implemented by elliptical slice sampling, a sampling method for systems with a Gaussian prior and a non Gaussian likelihood. Simulations with a partially observed driven Lorenz 63 system illustrate the approach.

  17. Bayesian theory and applications

    CERN Document Server

    Dellaportas, Petros; Polson, Nicholas G; Stephens, David A

    2013-01-01

    The development of hierarchical models and Markov chain Monte Carlo (MCMC) techniques forms one of the most profound advances in Bayesian analysis since the 1970s and provides the basis for advances in virtually all areas of applied and theoretical Bayesian statistics. This volume guides the reader along a statistical journey that begins with the basic structure of Bayesian theory, and then provides details on most of the past and present advances in this field. The book has a unique format. There is an explanatory chapter devoted to each conceptual advance followed by journal-style chapters that provide applications or further advances on the concept. Thus, the volume is both a textbook and a compendium of papers covering a vast range of topics. It is appropriate for a well-informed novice interested in understanding the basic approach, methods and recent applications. Because of its advanced chapters and recent work, it is also appropriate for a more mature reader interested in recent applications and devel...

  18. Clock and clock-controlled genes are differently expressed in the retina, lamina and in selected cells of the visual system of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Milena eDamulewicz

    2015-09-01

    Full Text Available The retina and the first optic neuropil (lamina of Drosophila show circadian rhythms in various processes. To learn about the regulation of circadian rhythms in the retina and lamina and in two cell types, glial and the lamina L2 interneurons, we examined expression of the following clock genes; per, tim, clk, and cry and clock-controlled genes; Atp, nrv2, brp, Pdfr. We found that the expression of gene studied is specific for the retina and lamina. The rhythms of per and tim expression in the retina and glial cells are similar to that observed in the whole head and in clock neurons, while they differ in the lamina and L2 cells. In both the retina and lamina, CRY seems to be a repressor of clk expression. In L2 interneurons per expression is not cyclic indicating the other function of PER in those cells than in the circadian molecular clock. In contrast to per and tim, the pattern of clk and cry expression is similar in both the retina and lamina. The retina holds the autonomous oscillators but the expression of cry and clock-controlled genes, Atp and nrv2, is also regulated by inputs from the pacemaker transmitted by PDF and ITP neuropeptides.

  19. An in vitro ES cell-based clock recapitulation assay model identifies CK2α as an endogenous clock regulator.

    Science.gov (United States)

    Umemura, Yasuhiro; Yoshida, Junko; Wada, Masashi; Tsuchiya, Yoshiki; Minami, Yoichi; Watanabe, Hitomi; Kondoh, Gen; Takeda, Junji; Inokawa, Hitoshi; Horie, Kyoji; Yagita, Kazuhiro

    2013-01-01

    We previously reported emergence and disappearance of circadian molecular oscillations during differentiation of mouse embryonic stem (ES) cells and reprogramming of differentiated cells, respectively. Here we present a robust and stringent in vitro circadian clock formation assay that recapitulates in vivo circadian phenotypes. This assay system first confirmed that a mutant ES cell line lacking Casein Kinase I delta (CKIδ) induced ∼3 hours longer period-length of circadian rhythm than the wild type, which was compatible with recently reported results using CKIδ null mice. In addition, this assay system also revealed that a Casein Kinase 2 alpha subunit (CK2α) homozygous mutant ES cell line developed significantly longer (about 2.5 hours) periods of circadian clock oscillations after in vitro or in vivo differentiation. Moreover, revertant ES cell lines in which mutagenic vector sequences were deleted showed nearly wild type periods after differentiation, indicating that the abnormal circadian period of the mutant ES cell line originated from the mutation in the CK2α gene. Since CK2α deficient mice are embryonic lethal, this in vitro assay system represents the genetic evidence showing an essential role of CK2α in the mammalian circadian clock. This assay was successfully applied for the phenotype analysis of homozygous mutant ES cells, demonstrating that an ES cell-based in vitro assay is available for circadian genetic screening. PMID:23840637

  20. Dilatation effect of ''quantum clocks''

    International Nuclear Information System (INIS)

    The relativistic dilatation effect of the life-time of unstable microparticles combined with quantum symmetry of their description results in the ''quantum-dilatation'' dilemma. It is due to the classical character of the relativity theory which here reveals itself in the classical world-line of the clock necessary in order to deduce the dilatation effect from the Lorentz transformation. It is shown how to solve this dilemma, basing on the relation continuum C4. Two types of measurements of time intervals, the direct and indirect one, are analyzed. The former type corresponds to the external space-time continuum, where any direct measurement takes place, and the latter, to the internal relation continuum C4, where the internal structures of isolated micro-systems are sunk. (author)

  1. Unbounded Bayesian Optimization via Regularization

    OpenAIRE

    Shahriari, Bobak; Bouchard-Côté, Alexandre; De Freitas, Nando

    2015-01-01

    Bayesian optimization has recently emerged as a popular and efficient tool for global optimization and hyperparameter tuning. Currently, the established Bayesian optimization practice requires a user-defined bounding box which is assumed to contain the optimizer. However, when little is known about the probed objective function, it can be difficult to prescribe such bounds. In this work we modify the standard Bayesian optimization framework in a principled way to allow automatic resizing of t...

  2. Bayesian optimization for materials design

    OpenAIRE

    Frazier, Peter I.; Wang, Jialei

    2015-01-01

    We introduce Bayesian optimization, a technique developed for optimizing time-consuming engineering simulations and for fitting machine learning models on large datasets. Bayesian optimization guides the choice of experiments during materials design and discovery to find good material designs in as few experiments as possible. We focus on the case when materials designs are parameterized by a low-dimensional vector. Bayesian optimization is built on a statistical technique called Gaussian pro...

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

    Science.gov (United States)

    Lent, Craig S.; Liu, Mo; Lu, Yuhui

    2006-08-01

    We examine power dissipation in different clocking schemes for molecular quantum-dot cellular automata (QCA) circuits. 'Landauer clocking' involves the adiabatic transition of a molecular cell from the null state to an active state carrying data. Cell layout creates devices which allow data in cells to interact and thereby perform useful computation. We perform direct solutions of the equation of motion for the system in contact with the thermal environment and see that Landauer's Principle applies: one must dissipate an energy of at least kBT per bit only when the information is erased. The ideas of Bennett can be applied to keep copies of the bit information by echoing inputs to outputs, thus embedding any logically irreversible circuit in a logically reversible circuit, at the cost of added circuit complexity. A promising alternative which we term 'Bennett clocking' requires only altering the timing of the clocking signals so that bit information is simply held in place by the clock until a computational block is complete, then erased in the reverse order of computation. This approach results in ultralow power dissipation without additional circuit complexity. These results offer a concrete example in which to consider recent claims regarding the fundamental limits of binary logic scaling.

  4. When clocks go bad: neurobehavioural consequences of disrupted circadian timing.

    Directory of Open Access Journals (Sweden)

    Alun R Barnard

    2008-05-01

    Full Text Available Progress in unravelling the cellular and molecular basis of mammalian circadian regulation over the past decade has provided us with new avenues through which we can explore central nervous system disease. Deteriorations in measurable circadian output parameters, such as sleep/wake deficits and dysregulation of circulating hormone levels, are common features of most central nervous system disorders. At the core of the mammalian circadian system is a complex of molecular oscillations within the hypothalamic suprachiasmatic nucleus. These oscillations are modifiable by afferent signals from the environment, and integrated signals are subsequently conveyed to remote central neural circuits where specific output rhythms are regulated. Mutations in circadian genes in mice can disturb both molecular oscillations and measurable output rhythms. Moreover, systematic analysis of these mutants indicates that they can express an array of abnormal behavioural phenotypes that are intermediate signatures of central nervous system disorders. Furthermore, the response of these mutants to psychoactive drugs suggests that clock genes can modify a number of the brain's critical neurotransmitter systems. This evidence has led to promising investigations into clock gene polymorphisms in psychiatric disease. Preliminary indications favour the systematic investigation of the contribution of circadian genes to central nervous system disease.

  5. Iterative quantum algorithm for distributed clock synchronization

    International Nuclear Information System (INIS)

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

  6. Using Atomic Clocks to Detect Gravitational Waves

    CERN Document Server

    Loeb, Abraham

    2015-01-01

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

  7. The circadian clock in cancer development and therapy

    Science.gov (United States)

    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...

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

    NARCIS (Netherlands)

    K. Brand (Karl)

    2011-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2009-01-01

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

  11. Advances in Study on Molecular Mechanism of Circadian Clock in Pineal Gland%松果体昼夜节律生物钟分子机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    王国卿; 童建

    2003-01-01

    在下丘脑视交叉上核(SCN)的调控下,哺乳类松果体通过合成褪黑素(MEL)而表达输出效应.松果体作为一个神经内分泌器官,也在各种非哺乳类脊椎动物中起着中枢昼夜节律振荡器的作用.在多数情况下,松果体振荡器均保持与光信号输入通路和内分泌输出通路的密切联系.近来,在鸟类松果体中相继发现了几种钟基因,如Per 、Cry、Clock和Bmal等,其表达的时间变化规律与哺乳类SCN的非常相似.钟的振荡由其自身调控反馈环路的转录和翻译组成,鸟类松果体和哺乳类SCN似乎具有共同的钟振荡基本分子构架;若干钟基因产物作为正向(CLOCK/BMAL)或负向(PER/CRY)调节子影响钟的振荡;昼夜性的控时机制同时也需要翻译后事件的参与,包括蛋白移位、降解和磷酸化等过程.这些过程对钟振荡器稳定的24小时周期和/或钟导引的光输入通路有着重要的调控作用.

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

    Science.gov (United States)

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

    1996-12-01

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

  13. Draper Clock-Synchronization Protocol in SAL

    Data.gov (United States)

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

  14. The Mechanics of Mechanical Watches and Clocks

    CERN Document Server

    Du, Ruxu

    2013-01-01

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

  15. Entrainment of the Neurospora circadian clock

    NARCIS (Netherlands)

    Merrow, M; Boesl, C; Ricken, J; Messerschmitt, M; Goedel, M; Roenneberg, T

    2006-01-01

    Neurospora crassa has been systematically investigated for circadian entrainment behavior. Many aspects of synchronization can be investigated in this simple, cellular system, ranging from systematic entrainment and drivenness to masking. Clock gene expression during entrainment and entrainment with

  16. Programmable Clock Waveform Generation for CCD Readout

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-01

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

  17. Micro Mercury Ion Clock (MMIC) Project

    Data.gov (United States)

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

  18. High-Accuracy Microwave Atomic Clock via Magic Optical Lattice

    OpenAIRE

    Zhou, Xiaoji; Chen, Xuzong; Chen, Jingbiao

    2005-01-01

    A microwave atomic clock scheme based on Rb and Cs atoms trapped in optical lattice with magic wavelength for clock transition is proposed. The ac Stark shift of clock transition due to trapping laser can be canceled at some specific laser wavelengths. Comparing with in fountain clock, the cavity related shifts, the collision shift, and the Doppler effect are eliminated or suppressed dramatically in atomic clock when the magic optical lattice is exploited. By carefully analyzing various sourc...

  19. Automated Synthesis of Skew-Based Clock Distribution Networks

    OpenAIRE

    José Luis Neves; Eby G. Friedman

    1998-01-01

    In this paper a top-down methodology is presented for synthesizing clock distribution networks based on application-dependent localized clock skew. The methodology is divided into four phases: 1) determination of an optimal clock skew schedule for improving circuit performance and reliability; 2) design of the topology of the clock tree based on the circuit hierarchy and minimum clock path delays; 3) design of circuit structures to implement the delay values associated with the branches of th...

  20. The impact of ancestral population size and incomplete lineage sorting on Bayesian estimation of species divergence times

    Institute of Scientific and Technical Information of China (English)

    Konstantinos ANGELIS; Mario DOS REIS

    2015-01-01

    Although the effects of the coalescent process on sequence divergence and genealogies are well understood, the vir-tual majority of studies that use molecular sequences to estimate times of divergence among species have failed to account for the coalescent process. Here we study the impact of ancestral population size and incomplete lineage sorting on Bayesian estimates of species divergence times under the molecular clock when the inference model ignores the coalescent process. Using a combi-nation of mathematical analysis, computer simulations and analysis of real data, we find that the errors on estimates of times and the molecular rate can be substantial when ancestral populations are large and when there is substantial incomplete lineage sort-ing. For example, in a simple three-species case, we find that if the most precise fossil calibration is placed on the root of the phylogeny, the age of the internal node is overestimated, while if the most precise calibration is placed on the internal node, then the age of the root is underestimated. In both cases, the molecular rate is overestimated. Using simulations on a phylogeny of nine species, we show that substantial errors in time and rate estimates can be obtained even when dating ancient divergence events. We analyse the hominoid phylogeny and show that estimates of the neutral mutation rate obtained while ignoring the coalescent are too high. Using a coalescent-based technique to obtain geological times of divergence, we obtain estimates of the mutation rate that are within experimental estimates and we also obtain substantially older divergence times within the phylogeny [Current Zoology 61 (5): 874–885, 2015].

  1. Bayesian nonparametric data analysis

    CERN Document Server

    Müller, Peter; Jara, Alejandro; Hanson, Tim

    2015-01-01

    This book reviews nonparametric Bayesian methods and models that have proven useful in the context of data analysis. Rather than providing an encyclopedic review of probability models, the book’s structure follows a data analysis perspective. As such, the chapters are organized by traditional data analysis problems. In selecting specific nonparametric models, simpler and more traditional models are favored over specialized ones. The discussed methods are illustrated with a wealth of examples, including applications ranging from stylized examples to case studies from recent literature. The book also includes an extensive discussion of computational methods and details on their implementation. R code for many examples is included in on-line software pages.

  2. Decentralized Distributed Bayesian Estimation

    Czech Academy of Sciences Publication Activity Database

    Dedecius, Kamil; Sečkárová, Vladimíra

    Praha: ÚTIA AVČR, v.v.i, 2011 - (Janžura, M.; Ivánek, J.). s. 16-16 [7th International Workshop on Data–Algorithms–Decision Making. 27.11.2011-29.11.2011, Mariánská] R&D Projects: GA ČR 102/08/0567; GA ČR GA102/08/0567 Institutional research plan: CEZ:AV0Z10750506 Keywords : estimation * distributed estimation * model Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2011/AS/dedecius-decentralized distributed bayesian estimation.pdf

  3. Applied Bayesian modelling

    CERN Document Server

    Congdon, Peter

    2014-01-01

    This book provides an accessible approach to Bayesian computing and data analysis, with an emphasis on the interpretation of real data sets. Following in the tradition of the successful first edition, this book aims to make a wide range of statistical modeling applications accessible using tested code that can be readily adapted to the reader's own applications. The second edition has been thoroughly reworked and updated to take account of advances in the field. A new set of worked examples is included. The novel aspect of the first edition was the coverage of statistical modeling using WinBU

  4. Computationally efficient Bayesian tracking

    Science.gov (United States)

    Aughenbaugh, Jason; La Cour, Brian

    2012-06-01

    In this paper, we describe the progress we have achieved in developing a computationally efficient, grid-based Bayesian fusion tracking system. In our approach, the probability surface is represented by a collection of multidimensional polynomials, each computed adaptively on a grid of cells representing state space. Time evolution is performed using a hybrid particle/grid approach and knowledge of the grid structure, while sensor updates use a measurement-based sampling method with a Delaunay triangulation. We present an application of this system to the problem of tracking a submarine target using a field of active and passive sonar buoys.

  5. Improved iterative Bayesian unfolding

    CERN Document Server

    D'Agostini, G

    2010-01-01

    This paper reviews the basic ideas behind a Bayesian unfolding published some years ago and improves their implementation. In particular, uncertainties are now treated at all levels by probability density functions and their propagation is performed by Monte Carlo integration. Thus, small numbers are better handled and the final uncertainty does not rely on the assumption of normality. Theoretical and practical issues concerning the iterative use of the algorithm are also discussed. The new program, implemented in the R language, is freely available, together with sample scripts to play with toy models.

  6. Clock genes, hair growth and aging

    OpenAIRE

    Geyfman, Mikhail; Andersen, Bogi

    2010-01-01

    Hair follicles undergo continuous cycles of growth, involution and rest. This process, referred to as the hair growth cycle, has a periodicity of weeks to months. At the same time, skin and hair follicles harbor a functional circadian clock that regulates gene expression with a periodicity of approximately twenty four hours. In our recent study we found that circadian clock genes play a role in regulation of the hair growth cycle during synchronized hair follicle cycling, uncovering an unexpe...

  7. Expression of Clock Proteins in Developing Tooth

    OpenAIRE

    Zheng, Li; Papagerakis, Silvana; Schnell, Santiago D.; Hoogerwerf, Willemijntje A; Papagerakis, Petros

    2010-01-01

    Morphological and functional changes during ameloblast and odontoblast differentiation suggest that enamel and dentin formation is under circadian control. Circadian rhythms are endogenous self-sustained oscillations with periods of 24 hours that control diverse physiological and metabolic processes. Mammalian clock genes play a key role in synchronizing circadian functions in many organs. However, close to nothing is known on clock genes expression during tooth development. In this work, we ...

  8. Circadian Clock Proteins in Mood Regulation

    OpenAIRE

    Partonen, Timo

    2015-01-01

    Mood regulation is known to be affected by the change of seasons. Recent research findings have suggested that mood regulation may be influenced by the function of circadian clocks. In addition, the activity of brown adipocytes has been hypothesized to contribute to mood regulation. Here, the overarching link to mood disorders might be the circadian clock protein nuclear receptor subfamily 1, group D, member 1.

  9. Circadian clock proteins in mood regulation

    Directory of Open Access Journals (Sweden)

    Timo ePartonen

    2015-01-01

    Full Text Available Mood regulation is known to be affected by the change of seasons. Recent research findings have suggested that mood regulation may be influenced by the function of circadian clocks. In addition, the activity of brown adipocytes has been hypothesized to contribute to mood regulation. Here, the overarching link to mood disorders might be the circadian clock protein NR1D1 (nuclear receptor subfamily 1, group D, member 1.

  10. Reduced Kalman Filters for Clock Ensembles

    Science.gov (United States)

    Greenhall, Charles A.

    2011-01-01

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

  11. Optical lattice clock with Strontium atoms

    International Nuclear Information System (INIS)

    This thesis presents the latest achievements regarding the optical lattice clock with Strontium atoms developed at LNE-SYRTE. After a review of the different types of optical clocks that are currently under development, we stress on the concept of optical lattice clock which was first imagined for Sr87 using the 1S0 → 3P0 transition. We exhibit the features of this atom, in particular the concept of magic wavelength for the trap, and the achievable performances for this kind of clock. The second part presents the experimental aspects, insisting particularly on the ultra-stable laser used for the interrogation of the atoms which is a central part of the experiment. Among the latest improvements, an optical pumping phase and an interrogation phase using a magnetic field have been added in order to refine the evaluation of the Zeeman effect. Finally, the last part presents the experimental results. The last evaluation of the clock using Sr87 atoms allowed us to reach a frequency accuracy of 2.6*10-15 and a measurement in agreement with the one made at JILA (Tokyo university) at the 10-15 level. On another hand, thanks to recent theoretical proposals, we made a measurement using the bosonic isotope Sr88 by adapting the experimental setup. This measurement represents the first evaluation for this type of clock, with a frequency accuracy of 7*10-14. (author)

  12. Bayesian Inference on Gravitational Waves

    Directory of Open Access Journals (Sweden)

    Asad Ali

    2015-12-01

    Full Text Available The Bayesian approach is increasingly becoming popular among the astrophysics data analysis communities. However, the Pakistan statistics communities are unaware of this fertile interaction between the two disciplines. Bayesian methods have been in use to address astronomical problems since the very birth of the Bayes probability in eighteenth century. Today the Bayesian methods for the detection and parameter estimation of gravitational waves have solid theoretical grounds with a strong promise for the realistic applications. This article aims to introduce the Pakistan statistics communities to the applications of Bayesian Monte Carlo methods in the analysis of gravitational wave data with an  overview of the Bayesian signal detection and estimation methods and demonstration by a couple of simplified examples.

  13. Adaptive Dynamic Bayesian Networks

    Energy Technology Data Exchange (ETDEWEB)

    Ng, B M

    2007-10-26

    A discrete-time Markov process can be compactly modeled as a dynamic Bayesian network (DBN)--a graphical model with nodes representing random variables and directed edges indicating causality between variables. Each node has a probability distribution, conditional on the variables represented by the parent nodes. A DBN's graphical structure encodes fixed conditional dependencies between variables. But in real-world systems, conditional dependencies between variables may be unknown a priori or may vary over time. Model errors can result if the DBN fails to capture all possible interactions between variables. Thus, we explore the representational framework of adaptive DBNs, whose structure and parameters can change from one time step to the next: a distribution's parameters and its set of conditional variables are dynamic. This work builds on recent work in nonparametric Bayesian modeling, such as hierarchical Dirichlet processes, infinite-state hidden Markov networks and structured priors for Bayes net learning. In this paper, we will explain the motivation for our interest in adaptive DBNs, show how popular nonparametric methods are combined to formulate the foundations for adaptive DBNs, and present preliminary results.

  14. Bayesian analysis toolkit - BAT

    International Nuclear Information System (INIS)

    Statistical treatment of data is an essential part of any data analysis and interpretation. Different statistical methods and approaches can be used, however the implementation of these approaches is complicated and at times inefficient. The Bayesian analysis toolkit (BAT) is a software package developed in C++ framework that facilitates the statistical analysis of the data using Bayesian theorem. The tool evaluates the posterior probability distributions for models and their parameters using Markov Chain Monte Carlo which in turn provide straightforward parameter estimation, limit setting and uncertainty propagation. Additional algorithms, such as simulated annealing, allow extraction of the global mode of the posterior. BAT sets a well-tested environment for flexible model definition and also includes a set of predefined models for standard statistical problems. The package is interfaced to other software packages commonly used in high energy physics, such as ROOT, Minuit, RooStats and CUBA. We present a general overview of BAT and its algorithms. A few physics examples are shown to introduce the spectrum of its applications. In addition, new developments and features are summarized.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-01-01

    Chemical clocks are often used as exciting classroom experiments, where an induction time is followed by rapidly changing colours that expose oscillating concentration patterns. This type of reaction belongs to a class of nonlinear chemical kinetics also linked to chaos, wave propagation and Turing patterns. Despite its vastness in occurrence and applicability, the clock reaction is only well understood for liquid-state processes. Here we report a chemical clock reaction, in which a solidifying entity, metal-organic framework UiO-66, displays oscillations in crystal dimension and number, as shown by X-ray scattering. In rationalizing this result, we introduce a computational approach, the metal-organic molecular orbital methodology, to pinpoint interaction between the tectonic building blocks that construct the metal-organic framework material. In this way, we show that hydrochloric acid plays the role of autocatalyst, bridging separate processes of condensation and crystallization. PMID:27282410

  17. Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK

    Directory of Open Access Journals (Sweden)

    Bordon Alain

    2008-04-01

    Full Text Available Abstract Background Circadian oscillation of clock-controlled gene expression is mainly regulated at the transcriptional level. Heterodimers of CLOCK and BMAL1 act as activators of target gene transcription; however, interactions of PER and CRY proteins with the heterodimer abolish its transcriptional activation capacity. PER and CRY are therefore referred to as negative regulators of the circadian clock. To further elucidate the mechanism how positive and negative components of the clock interplay, we characterized the interactions of PER2, CRY1 and CRY2 with BMAL1 and CLOCK using a mammalian two-hybrid system and co-immunoprecipitation assays. Results Both PER2 and the CRY proteins were found to interact with BMAL1 whereas only PER2 interacts with CLOCK. CRY proteins seem to have a higher affinity to BMAL1 than PER2. Moreover, we provide evidence that PER2, CRY1 and CRY2 bind to different domains in the BMAL1 protein. Conclusion The regulators of clock-controlled transcription PER2, CRY1 and CRY2 differ in their capacity to interact with each single component of the BMAL1-CLOCK heterodimer and, in the case of BMAL1, also in their interaction sites. Our data supports the hypothesis that CRY proteins, especially CRY1, are stronger repressors than PER proteins.

  18. Molecular systematics of the Cape Parrot (Poicephalus robustus: implications for taxonomy and conservation.

    Directory of Open Access Journals (Sweden)

    Willem G Coetzer

    Full Text Available The taxonomic position of the Cape Parrot (Poicephalus robustus robustus has been the focus of much debate. A number of authors suggest that the Cape Parrot should be viewed as a distinct species separate from the other two P. robustus subspecies (P. r. fuscicollis and P. r. suahelicus. These recommendations were based on morphological, ecological, and behavioural assessments. In this study we investigated the validity of these recommendations using multilocus DNA analyses. We genotyped 138 specimens from five Poicephalus species (P. cryptoxanthus, P. gulielmi, P. meyeri, P. robustus, and P. rueppellii using 11 microsatellite loci. Additionally, two mitochondrial (cytochrome oxidase I gene and 16S ribosomal RNA and one nuclear intron (intron 7 of the β-fibrinogen gene markers were amplified and sequenced. Bayesian clustering analysis and pairwise FST analysis of microsatellite data identified P. r. robustus as genetically distinct from the other P. robustus subspecies. Phylogenetic and molecular clock analyses on sequence data also supported the microsatellite analyses, placing P. r. robustus in a distinct clade separate from the other P. robustus subspecies. Molecular clock analysis places the most recent common ancestor between P. r. robustus and P. r. fuscicollis / P. r. suahelicus at 2.13 to 2.67 million years ago. Our results all support previous recommendations to elevate the Cape Parrot to species level. This will facilitate better planning and implementation of international and local conservation management strategies for the Cape Parrot.

  19. Interaction of MAGED1 with nuclear receptors affects circadian clock function

    Science.gov (United States)

    Wang, Xiaohan; Tang, Jing; Xing, Lijuan; Shi, Guangsen; Ruan, Haibin; Gu, Xiwen; Liu, Zhiwei; Wu, Xi; Gao, Xiang; Xu, Ying

    2010-01-01

    The circadian clock has a central role in physiological adaption and anticipation of day/night changes. In a genetic screen for novel regulators of circadian rhythms, we found that mice lacking MAGED1 (Melanoma Antigen Family D1) exhibit a shortened period and altered rest–activity bouts. These circadian phenotypes are proposed to be caused by a direct effect on the core molecular clock network that reduces the robustness of the circadian clock. We provide in vitro and in vivo evidence indicating that MAGED1 binds to RORα to bring about positive and negative effects on core clock genes of Bmal1, Rev-erbα and E4bp4 expression through the Rev-Erbα/ROR responsive elements (RORE). Maged1 is a non-rhythmic gene that, by binding RORα in non-circadian way, enhances rhythmic input and buffers the circadian system from irrelevant, perturbing stimuli or noise. We have thus identified and defined a novel circadian regulator, Maged1, which is indispensable for the robustness of the circadian clock to better serve the organism. PMID:20300063

  20. Protein sequestration versus Hill-type repression in circadian clock models.

    Science.gov (United States)

    Kim, Jae Kyoung

    2016-08-01

    Circadian (∼24 h) clocks are self-sustained endogenous oscillators with which organisms keep track of daily and seasonal time. Circadian clocks frequently rely on interlocked transcriptional-translational feedback loops to generate rhythms that are robust against intrinsic and extrinsic perturbations. To investigate the dynamics and mechanisms of the intracellular feedback loops in circadian clocks, a number of mathematical models have been developed. The majority of the models use Hill functions to describe transcriptional repression in a way that is similar to the Goodwin model. Recently, a new class of models with protein sequestration-based repression has been introduced. Here, the author discusses how this new class of models differs dramatically from those based on Hill-type repression in several fundamental aspects: conditions for rhythm generation, robust network designs and the periods of coupled oscillators. Consistently, these fundamental properties of circadian clocks also differ among Neurospora, Drosophila, and mammals depending on their key transcriptional repression mechanisms (Hill-type repression or protein sequestration). Based on both theoretical and experimental studies, this review highlights the importance of careful modelling of transcriptional repression mechanisms in molecular circadian clocks. PMID:27444022

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

    Science.gov (United States)

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

    2015-01-01

    Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic, or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumor growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer. PMID:26029155

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

    Directory of Open Access Journals (Sweden)

    Celine eFeillet

    2015-05-01

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

  3. Defence responses of Arabidopsis thaliana to infection by Pseudomonas syringae are regulated by the circadian clock.

    Directory of Open Access Journals (Sweden)

    Vaibhav Bhardwaj

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

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

    KAUST Repository

    Bhardwaj, Vaibhav

    2011-10-31

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

  5. Mass spectrometry-based absolute quantification reveals rhythmic variation of mouse circadian clock proteins.

    Science.gov (United States)

    Narumi, Ryohei; Shimizu, Yoshihiro; Ukai-Tadenuma, Maki; Ode, Koji L; Kanda, Genki N; Shinohara, Yuta; Sato, Aya; Matsumoto, Katsuhiko; Ueda, Hiroki R

    2016-06-14

    Absolute values of protein expression levels in cells are crucial information for understanding cellular biological systems. Precise quantification of proteins can be achieved by liquid chromatography (LC)-mass spectrometry (MS) analysis of enzymatic digests of proteins in the presence of isotope-labeled internal standards. Thus, development of a simple and easy way for the preparation of internal standards is advantageous for the analyses of multiple target proteins, which will allow systems-level studies. Here we describe a method, termed MS-based Quantification By isotope-labeled Cell-free products (MS-QBiC), which provides the simple and high-throughput preparation of internal standards by using a reconstituted cell-free protein synthesis system, and thereby facilitates both multiplexed and sensitive quantification of absolute amounts of target proteins. This method was applied to a systems-level dynamic analysis of mammalian circadian clock proteins, which consist of transcription factors and protein kinases that govern central and peripheral circadian clocks in mammals. Sixteen proteins from 20 selected circadian clock proteins were successfully quantified from mouse liver over a 24-h time series, and 14 proteins had circadian variations. Quantified values were applied to detect internal body time using a previously developed molecular timetable method. The analyses showed that single time-point data from wild-type mice can predict the endogenous state of the circadian clock, whereas data from clock mutant mice are not applicable because of the disappearance of circadian variation. PMID:27247408

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

    Institute of Scientific and Technical Information of China (English)

    Wang Pengjun; Yu Junjun

    2007-01-01

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

  7. Book review: Bayesian analysis for population ecology

    Science.gov (United States)

    Link, William A.

    2011-01-01

    Brian Dennis described the field of ecology as “fertile, uncolonized ground for Bayesian ideas.” He continued: “The Bayesian propagule has arrived at the shore. Ecologists need to think long and hard about the consequences of a Bayesian ecology. The Bayesian outlook is a successful competitor, but is it a weed? I think so.” (Dennis 2004)

  8. Bayesian grid matching

    DEFF Research Database (Denmark)

    Hartelius, Karsten; Carstensen, Jens Michael

    2003-01-01

    A method for locating distorted grid structures in images is presented. The method is based on the theories of template matching and Bayesian image restoration. The grid is modeled as a deformable template. Prior knowledge of the grid is described through a Markov random field (MRF) model which...... represents the spatial coordinates of the grid nodes. Knowledge of how grid nodes are depicted in the observed image is described through the observation model. The prior consists of a node prior and an arc (edge) prior, both modeled as Gaussian MRFs. The node prior models variations in the positions of grid...... nodes and the arc prior models variations in row and column spacing across the grid. Grid matching is done by placing an initial rough grid over the image and applying an ensemble annealing scheme to maximize the posterior distribution of the grid. The method can be applied to noisy images with missing...

  9. Microwave Atomic Clock in the Optical Lattice with Specific Frequency

    International Nuclear Information System (INIS)

    A scheme for a microwave atomic clock is proposed for Cs or Rb atoms trapped in a blue detuned optical lattice. The ac Stark shift of the clock transition due to a trapping laser is calculated. We analyze it at some specific laser wavelength. Compared with the case of the fountain clock, the cavity related shifts, the collision shift and the Doppler effect are eliminated or suppressed dramatically in an atomic lattice clock. By analyzing various sources of clock uncertainty, a microwave atomic lattice clock with a high accuracy and small volume is feasible

  10. Compact, Highly Stable Ion Atomic Clock

    Science.gov (United States)

    Prestage, John

    2008-01-01

    A mercury-ion clock now at the breadboard stage of development (see figure) has a stability comparable to that of a hydrogen-maser clock: In tests, the clock exhibited an Allan deviation of between 2 x 10(exp -13) and 3 x 10(exp -13) at a measurement time of 1 second, averaging to about 10(exp -15) at 1 day. However, the clock occupies a volume of only about 2 liters . about a hundredth of the volume of a hydrogen-maser clock. The ion-handling parts of the apparatus are housed in a sealed vacuum tube, wherein only a getter pump is used to maintain the vacuum. Hence, this apparatus is a prototype of a generation of small, potentially portable high-precision clocks for diverse ground- and space-based navigation and radio science applications. Furthermore, this new ion-clock technology is about 100 times more stable and precise than the rubidium atomic clocks currently in use in the NAV STAR GPS Earth-orbiting satellites. In this clock, mercury ions are shuttled between a quadrupole and a 16-pole linear radio-frequency trap. In the quadrupole trap, the ions are tightly confined and optical state selection from a Hg-202 radio-frequency-discharge ultraviolet lamp is carried out. In the 16-pole trap, the ions are more loosely confined and atomic transitions resonant at frequency of about 40.507 GHz are interrogated by use of a microwave beam at that frequency. The trapping of ions effectively eliminates the frequency pulling caused by wall collisions inherent to gas-cell clocks. The shuttling of the ions between the two traps enables separation of the state-selection process from the clock microwave- resonance process, so that each of these processes can be optimized independently of the other. The basic ion-shuttling, two-trap scheme as described thus far is not new: it has been the basis of designs of prior larger clocks. The novelty of the present development lies in major redesigns of its physics package (the ion traps and the vacuum and optical subsystems) to effect

  11. A Bayesian variable selection procedure for ranking overlapping gene sets

    DEFF Research Database (Denmark)

    Skarman, Axel; Mahdi Shariati, Mohammad; Janss, Luc;

    2012-01-01

    data to study how the variable selection method was affected by overlaps among the pathways. In addition, we compared our approach to another that ignores the overlaps, and studied the differences in the prioritization. The variable selection method was robust to a change in prior probability...... described. In many cases, these methods test one gene set at a time, and therefore do not consider overlaps among the pathways. Here, we present a Bayesian variable selection method to prioritize gene sets that overcomes this limitation by considering all gene sets simultaneously. We applied Bayesian...... variable selection to differential expression to prioritize the molecular and genetic pathways involved in the responses to Escherichia coli infection in Danish Holstein cows. Results We used a Bayesian variable selection method to prioritize Kyoto Encyclopedia of Genes and Genomes pathways. We used our...

  12. Dual-wavelength active optical clock

    CERN Document Server

    Xu, Zhichao; Zhuang, Wei; Chen, Jingbiao

    2014-01-01

    We experimentally realize the dual-wavelength active optical clock for the first time. As the Cs cell temperature is kept between 118 $^{\\circ }C$ and 144 $^{\\circ }C$, both the 1359 nm and the 1470 nm stimulated emission output of Cs four-level active optical clock are detected. The 1470 nm output linewidth of each experimental setup of Cs four-level active optical clock is measured to be 590 Hz with the main cavity length unstabilized. To stabilize the cavity length of active optical clock, the experimental scheme of 633 nm and 1359 nm good-bad cavity dual-wavelength active optical clock is proposed, where 633 nm and 1359 nm stimulated emission is working at good-cavity and bad-cavity regime respectively. The cavity length is stabilized by locking the 633 nm output frequency to a super-cavity with the Pound-Drever-Hall (PDH) technique. The frequency stability of 1359 nm bad-cavity stimulated emission output is then expected to be further improved by at least 1 order of magnitude than the 633 nm PDH system d...

  13. Circadian Clock Control of Liver Metabolic Functions.

    Science.gov (United States)

    Reinke, Hans; Asher, Gad

    2016-03-01

    The circadian clock is an endogenous biological timekeeping system that synchronizes physiology and behavior to day/night cycles. A wide variety of processes throughout the entire gastrointestinal tract and notably the liver appear to be under circadian control. These include various metabolic functions such as nutrient uptake, processing, and detoxification, which align organ function to cycle with nutrient supply and demand. Remarkably, genetic or environmental disruption of the circadian clock can cause metabolic diseases or exacerbate pathological states. In addition, modern lifestyles force more and more people worldwide into asynchrony between the external time and their circadian clock, resulting in a constant state of social jetlag. Recent evidence indicates that interactions between altered energy metabolism and disruptions in the circadian clock create a downward spiral that can lead to diabetes and other metabolic diseases. In this review, we provide an overview of rhythmic processes in the liver and highlight the functions of circadian clock genes under physiological and pathological conditions; we focus on their roles in regulation of hepatic glucose as well as lipid and bile acid metabolism and detoxification and their potential effects on the development of fatty liver and nonalcoholic steatohepatitis. PMID:26657326

  14. Direct laser cooling Al+ ions optical clocks

    CERN Document Server

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

    2016-01-01

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

  15. Current trends in Bayesian methodology with applications

    CERN Document Server

    Upadhyay, Satyanshu K; Dey, Dipak K; Loganathan, Appaia

    2015-01-01

    Collecting Bayesian material scattered throughout the literature, Current Trends in Bayesian Methodology with Applications examines the latest methodological and applied aspects of Bayesian statistics. The book covers biostatistics, econometrics, reliability and risk analysis, spatial statistics, image analysis, shape analysis, Bayesian computation, clustering, uncertainty assessment, high-energy astrophysics, neural networking, fuzzy information, objective Bayesian methodologies, empirical Bayes methods, small area estimation, and many more topics.Each chapter is self-contained and focuses on

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Quantum clock: A critical discussion on spacetime

    Science.gov (United States)

    Burderi, Luciano; Di Salvo, Tiziana; Iaria, Rosario

    2016-03-01

    We critically discuss the measure of very short time intervals. By means of a Gedankenexperiment, we describe an ideal clock based on the occurrence of completely random events. Many previous thought experiments have suggested fundamental Planck-scale limits on measurements of distance and time. Here we present a new type of thought experiment, based on a different type of clock, that provide further support for the existence of such limits. We show that the minimum time interval Δ t that this clock can measure scales as the inverse of its size Δ r . This implies an uncertainty relation between space and time: Δ r Δ t >G ℏ/c4, where G , ℏ, and c are the gravitational constant, the reduced Planck constant, and the speed of light, respectively. We outline and briefly discuss the implications of this uncertainty conjecture.

  18. Which came first, spacetime or clocks?

    International Nuclear Information System (INIS)

    Emergent quantum mechanics seeks a deeper level theory, anticipating that such a theory will provide a clearer picture of the relation between the quantum and classical worlds. In this work we show that the quantum-classical divide is a manifestation of the transition from Newton's absolute time to relativity's path-dependent time. The prior theory in this case is that particles are intrinsic clocks. The emergence of separate classical and quantum behaviour is seen by considering different continuum limits in a single digital clock model. A continuum limit that constructs a continuous worldline provides a simple basis for Minkowski spacetime. An alternative limit in which the clock itself contains boost information leads to the Dirac equation.

  19. Quantum clock: A critical discussion on spacetime

    CERN Document Server

    Burderi, Luciano; Iaria, Rosario

    2016-01-01

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

  20. Models of the Primordial Standard Clock

    CERN Document Server

    Chen, Xingang; Wang, Yi

    2014-01-01

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

  1. The Deep Space Atomic Clock Mission

    Science.gov (United States)

    Ely, Todd A.; Koch, Timothy; Kuang, Da; Lee, Karen; Murphy, David; Prestage, John; Tjoelker, Robert; Seubert, Jill

    2012-01-01

    The Deep Space Atomic Clock (DSAC) mission will demonstrate the space flight performance of a small, low-mass, high-stability mercury-ion atomic clock with long term stability and accuracy on par with that of the Deep Space Network. The timing stability introduced by DSAC allows for a 1-Way radiometric tracking paradigm for deep space navigation, with benefits including increased tracking via utilization of the DSN's Multiple Spacecraft Per Aperture (MSPA) capability and full ground station-spacecraft view periods, more accurate radio occultation signals, decreased single-frequency measurement noise, and the possibility for fully autonomous on-board navigation. Specific examples of navigation and radio science benefits to deep space missions are highlighted through simulations of Mars orbiter and Europa flyby missions. Additionally, this paper provides an overview of the mercury-ion trap technology behind DSAC, details of and options for the upcoming 2015/2016 space demonstration, and expected on-orbit clock performance.

  2. Bayesian Methods and Universal Darwinism

    OpenAIRE

    Campbell, John

    2010-01-01

    Bayesian methods since the time of Laplace have been understood by their practitioners as closely aligned to the scientific method. Indeed a recent champion of Bayesian methods, E. T. Jaynes, titled his textbook on the subject Probability Theory: the Logic of Science. Many philosophers of science including Karl Popper and Donald Campbell have interpreted the evolution of Science as a Darwinian process consisting of a 'copy with selective retention' algorithm abstracted from Darwin's theory of...

  3. Portfolio Allocation for Bayesian Optimization

    OpenAIRE

    Brochu, Eric; Hoffman, Matthew W.; De Freitas, Nando

    2010-01-01

    Bayesian optimization with Gaussian processes has become an increasingly popular tool in the machine learning community. It is efficient and can be used when very little is known about the objective function, making it popular in expensive black-box optimization scenarios. It uses Bayesian methods to sample the objective efficiently using an acquisition function which incorporates the model's estimate of the objective and the uncertainty at any given point. However, there are several differen...

  4. Neuronanatomy, neurology and Bayesian networks

    OpenAIRE

    Bielza Lozoya, Maria Concepcion

    2014-01-01

    Bayesian networks are data mining models with clear semantics and a sound theoretical foundation. In this keynote talk we will pinpoint a number of neuroscience problems that can be addressed using Bayesian networks. In neuroanatomy, we will show computer simulation models of dendritic trees and classification of neuron types, both based on morphological features. In neurology, we will present the search for genetic biomarkers in Alzheimer's disease and the prediction of health-related qualit...

  5. Bayesian Networks and Influence Diagrams

    DEFF Research Database (Denmark)

    Kjærulff, Uffe Bro; Madsen, Anders Læsø

     Probabilistic networks, also known as Bayesian networks and influence diagrams, have become one of the most promising technologies in the area of applied artificial intelligence, offering intuitive, efficient, and reliable methods for diagnosis, prediction, decision making, classification......, troubleshooting, and data mining under uncertainty. Bayesian Networks and Influence Diagrams: A Guide to Construction and Analysis provides a comprehensive guide for practitioners who wish to understand, construct, and analyze intelligent systems for decision support based on probabilistic networks. Intended...

  6. Sample-Clock Phase-Control Feedback

    Science.gov (United States)

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

    2012-01-01

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

  7. The development of clocks into the eighteenth century

    OpenAIRE

    Dugan, David

    2004-01-01

    The advantages of clocks with escapements over water clocks, that they can be miniaturized. The superb chronometers of the seventeenth century onwards, Harrison and others. The emergence of clockmakers and precise engineering. Superb luxury goods. Simon Schaffer explains.

  8. Clocking Scheme for Switched-Capacitor Circuits

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

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

  9. Caring around the Clock: rounding in practice.

    Science.gov (United States)

    Hutchings, Marie

    A large acute trust in the East Midlands looked to the US to inform its implementation of hourly rounding, otherwise known as intentional rounding. A combination of transformational leadership and meaningful interactions form the basis of a new approach to rounding--Caring around the Clock. The trust piloted the concept on 10 wards with results showing a 32% reduction in call lights. The successful change in practice required an investment in staff education to equip staff with the necessary skills. The trust is currently rolling out Caring around Hourly rounding can reducethe Clock to 79 inpatient wards. PMID:23342834

  10. Clocking Scheme for Switched-Capacitor Circuits

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    1998-01-01

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

  11. Bayesian Interpretations of Heteroskedastic Consistent Covariance Estimators Using the Informed Bayesian Bootstrap

    OpenAIRE

    Dale Poirier

    2008-01-01

    This paper provides Bayesian rationalizations for White’s heteroskedastic consistent (HC) covariance estimator and various modifications of it. An informed Bayesian bootstrap provides the statistical framework.

  12. Robustness from flexibility in the fungal circadian clock

    Directory of Open Access Journals (Sweden)

    Akman Ozgur E

    2010-06-01

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

  13. On the Evolution of Memory: A Time for Clocks

    Directory of Open Access Journals (Sweden)

    Jason Robert Gerstner

    2012-02-01

    Full Text Available What was the earliest engram? Biology has evolved to encode representations of past events, and in neuroscience, we are attempting to link experience-dependent changes in molecular signaling with cellular processes that ultimately lead to behavioral output. The theory of evolution has guided biological research for decades, and since phylogenetically conserved mechanisms drive circadian rhythms, these processes may serve as common predecessors underlying more complex behavioral phenotypes. For example, the cAMP/MAPK/CREB cascade is interwoven with the clock to trigger circadian output, and is also known to affect memory formation. Time-of-day dependent changes have been observed in long-term potentiation (LTP within the mammalian suprachiasmatic nucleus and hippocampus, along with light-induced circadian phase resetting and fear conditioning behaviors. Together this suggests during evolution, similar processes underlying metaplasticity in more simple circuits may have been redeployed in higher-order brain regions. Therefore, this notion predicts a model that LTP and metaplasticity may exist in clock-forming circuits of lower-order species, through phylogenetically conserved pathways, leading to several testable hypotheses.

  14. Clocking Surface Reaction by In-Plane Product Rotation.

    Science.gov (United States)

    Anggara, Kelvin; Huang, Kai; Leung, Lydie; Chatterjee, Avisek; Cheng, Fang; Polanyi, John C

    2016-06-15

    Electron-induced reaction of physisorbed meta-diiodobenzene (mDIB) on Cu(110) at 4.6 K was studied by Scanning Tunneling Microscopy and molecular dynamics theory. Single-electron dissociation of the first C-I bond led to in-plane rotation of an iodophenyl (IPh) intermediate, whose motion could be treated as a "clock" of the reaction dynamics. Alternative reaction mechanisms, successive and concerted, were observed giving different product distributions. In the successive mechanism, two electrons successively broke single C-I bonds; the first C-I bond breaking yielded IPh that rotated directionally by three different angles, with the second C-I bond breaking giving chemisorbed I atoms (#2) at three preferred locations corresponding to the C-I bond alignments in the prior rotated IPh configurations. In the concerted mechanism a single electron broke two C-I bonds, giving two chemisorbed I atoms; significantly these were found at angles corresponding to the C-I bond direction for unrotated mDIB. Molecular dynamics accounted for the difference in reaction outcomes between the successive and the concerted mechanisms in terms of the time required for the IPh to rotate in-plane; in successive reaction the time delay between first and second C-I bond-breaking events allowed the IPh to rotate, whereas in concerted reaction the computed delay between excitation and reaction (∼1 ps) was too short for molecular rotation before the second C-I bond broke. The dependence of the extent of motion at a surface on the delay between first and second bond breaking suggested a novel means to "clock" sub-picosecond dynamics by imaging the products arising from varying time delays between impacting pairs of electrons. PMID:27191189

  15. Clocks, cryptochromes and Monarch migrations

    OpenAIRE

    Kyriacou, Charalambos P.

    2009-01-01

    The annual migration of the Monarch butterfly (Danaus plexippus) from eastern North America to central Mexico is one of nature's most inspiring spectacles. Recent studies including one in BMC Biology, have begun to dissect the molecular and neurogenetic basis for this most complex behavior.

  16. Clocks, cryptochromes and Monarch migrations.

    Science.gov (United States)

    Kyriacou, Charalambos P

    2009-01-01

    The annual migration of the Monarch butterfly (Danaus plexippus) from eastern North America to central Mexico is one of nature's most inspiring spectacles. Recent studies including one in BMC Biology, have begun to dissect the molecular and neurogenetic basis for this most complex behavior. PMID:19591650

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

    OpenAIRE

    Weinstein, Jonathan D.; Beloy, Kyle; Derevianko, Andrei

    2009-01-01

    We present a scheme for entangling the atoms of an optical lattice to reduce the quantum projection noise of a clock measurement. The divalent clock atoms are held in a lattice at a ``magic'' wavelength that does not perturb the clock frequency -- to maintain clock accuracy -- while an open-shell J=1/2 ``head'' atom is coherently transported between lattice sites via the lattice polarization. This polarization-dependent ``Archimedes' screw'' transport at magic wavelength takes advantage of th...

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

    DEFF Research Database (Denmark)

    Fahrenkrug, Jan; Georg, Birgitte; Hannibal, Jens;

    2012-01-01

    The circadian time-keeping system consists of clocks in the suprachiasmatic nucleus (SCN) and in peripheral organs including an adrenal clock linked to the rhythmic corticosteroid production by regulating steroidogenic acute regulatory protein (StAR). Clock cells contain an autonomous molecular...... oscillator based on a group of clock genes and their protein products. Mice lacking the VPAC2 receptor display disrupted circadian rhythm of physiology and behaviour, and therefore, we using real-time RT-PCR quantified (1) the mRNAs for the clock genes Per1 and Bmal1 in the adrenal gland and SCN, (2) the...... a 24-h rhythmic expression in the adrenal of WT mice under L/D and dark conditions. During a L/D cycle, the adrenal clock gene rhythm in VPAC2-KO mice was phase-advanced by approximately 6 h compared to WT mice and became arrhythmic in constant darkness. A significant 24-h rhythmic variation in the...

  19. 47 CFR 80.865 - Radiotelephone station clock.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Radiotelephone station clock. 80.865 Section 80.865 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES... W § 80.865 Radiotelephone station clock. A clock having a face of at least 12.7 cm (5 in.)...

  20. On synchronization of clocks in general space-times

    Directory of Open Access Journals (Sweden)

    M. R. H Khajehpour

    2005-09-01

    Full Text Available   Einstein and transport synchronizations of infinitesimally spaced and distant clocks are considered in a general Riemannian space-time. It is shown that infinitesimally spaced clocks can always be synchronized. In general one can not find observers for whom distant clock are Einstein synchronized but transport synchronized observers do always exit. Whenever both procedures are possible, they are equivalent.

  1. Nonparametric Bayesian Classification

    CERN Document Server

    Coram, M A

    2002-01-01

    A Bayesian approach to the classification problem is proposed in which random partitions play a central role. It is argued that the partitioning approach has the capacity to take advantage of a variety of large-scale spatial structures, if they are present in the unknown regression function $f_0$. An idealized one-dimensional problem is considered in detail. The proposed nonparametric prior uses random split points to partition the unit interval into a random number of pieces. This prior is found to provide a consistent estimate of the regression function in the $\\L^p$ topology, for any $1 \\leq p < \\infty$, and for arbitrary measurable $f_0:[0,1] \\rightarrow [0,1]$. A Markov chain Monte Carlo (MCMC) implementation is outlined and analyzed. Simulation experiments are conducted to show that the proposed estimate compares favorably with a variety of conventional estimators. A striking resemblance between the posterior mean estimate and the bagged CART estimate is noted and discussed. For higher dimensions, a ...

  2. BAT - Bayesian Analysis Toolkit

    International Nuclear Information System (INIS)

    One of the most vital steps in any data analysis is the statistical analysis and comparison with the prediction of a theoretical model. The many uncertainties associated with the theoretical model and the observed data require a robust statistical analysis tool. The Bayesian Analysis Toolkit (BAT) is a powerful statistical analysis software package based on Bayes' Theorem, developed to evaluate the posterior probability distribution for models and their parameters. It implements Markov Chain Monte Carlo to get the full posterior probability distribution that in turn provides a straightforward parameter estimation, limit setting and uncertainty propagation. Additional algorithms, such as Simulated Annealing, allow to evaluate the global mode of the posterior. BAT is developed in C++ and allows for a flexible definition of models. A set of predefined models covering standard statistical cases are also included in BAT. It has been interfaced to other commonly used software packages such as ROOT, Minuit, RooStats and CUBA. An overview of the software and its algorithms is provided along with several physics examples to cover a range of applications of this statistical tool. Future plans, new features and recent developments are briefly discussed.

  3. Analytic clock frequency selection for global DVFS

    NARCIS (Netherlands)

    Gerards, Marco E.T.; Hurink, Johann L.; Hölzenspies, Philip K.F.; Kuper, Jan; Smit, Gerard J.M.

    2014-01-01

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

  4. The salient features of the clock

    DEFF Research Database (Denmark)

    Ebbesen, Toke Riis

    2005-01-01

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

  5. An Iodine Fluorescence Quenching Clock Reaction

    Science.gov (United States)

    Weinberg, Richard B.; Muyskens, Mark

    2007-01-01

    Clock reactions based upon competing oxidation and reduction reactions of iodine and starch as the most popular type of chemistry example is presented to illustrate the redox phenomena, reaction kinetics, and principles of chemical titration. The examination of the photophysical principles underlying the iodine fluorescence quenching clock…

  6. On accelerated clocks and the quantum theory

    International Nuclear Information System (INIS)

    It is shown that the locality hypothesis of relativity breaks down for large proper accelerations which are relevant to semiclassical phenomena. A general modification for the rate of accelerated clocks incorporating the effect of proper acceleration is thus proposed. Connection is made with Caianiello's quantum line element

  7. Clock Synchronization for Multihop Wireless Sensor Networks

    Science.gov (United States)

    Solis Robles, Roberto

    2009-01-01

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

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

    Indian Academy of Sciences (India)

    Yuuichi Seki; Teiichi Tanimura

    2014-09-01

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

  9. Suppression of clock shifts at field-insensitive transitions

    CERN Document Server

    Arnold, Kyle J

    2016-01-01

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

  10. Atomic clocks: the atoms as primary time and frequency standards

    International Nuclear Information System (INIS)

    In this article, we present the atomic clock as time and frequency standard and as one of the peaceful uses of atoms for development. In the first part, we present the general principles of time and frequency metrology and the key role of the caesium atom in this field as well as the main applications of atomic clocks. In the second part we introduce the different clock technologies based on Ramsey method, with a focus on atomic beam clocks and atomic fountain clocks. (author)

  11. Next Generation JPL Ultra-Stable Trapped Ion Atomic Clocks

    Science.gov (United States)

    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.

  12. S-Wave Collisional Frequency Shift of a Fermion Clock

    CERN Document Server

    Hazlett, Eric L; Stites, Ronald W; Gibble, Kurt; O'Hara, Kenneth M

    2012-01-01

    We report an s-wave collisional frequency shift of an atomic clock based on fermions. In contrast to bosons, the fermion clock shift is insensitive to the population difference of the clock states, set by the first pulse area in Ramsey spectroscopy, \\theta_1. The fermion shift instead depends strongly on the second pulse area \\theta_2. It allows the shift to be canceled, nominally at \\theta_2 = \\pi/2, but correlations shift the null to slightly larger \\theta_2. The shift applies to optical lattice clocks and increases with the spatial inhomogeneity of the clock excitation field, naturally large at optical frequencies.

  13. Bayesian seismic AVO inversion

    Energy Technology Data Exchange (ETDEWEB)

    Buland, Arild

    2002-07-01

    A new linearized AVO inversion technique is developed in a Bayesian framework. The objective is to obtain posterior distributions for P-wave velocity, S-wave velocity and density. Distributions for other elastic parameters can also be assessed, for example acoustic impedance, shear impedance and P-wave to S-wave velocity ratio. The inversion algorithm is based on the convolutional model and a linearized weak contrast approximation of the Zoeppritz equation. The solution is represented by a Gaussian posterior distribution with explicit expressions for the posterior expectation and covariance, hence exact prediction intervals for the inverted parameters can be computed under the specified model. The explicit analytical form of the posterior distribution provides a computationally fast inversion method. Tests on synthetic data show that all inverted parameters were almost perfectly retrieved when the noise approached zero. With realistic noise levels, acoustic impedance was the best determined parameter, while the inversion provided practically no information about the density. The inversion algorithm has also been tested on a real 3-D dataset from the Sleipner Field. The results show good agreement with well logs but the uncertainty is high. The stochastic model includes uncertainties of both the elastic parameters, the wavelet and the seismic and well log data. The posterior distribution is explored by Markov chain Monte Carlo simulation using the Gibbs sampler algorithm. The inversion algorithm has been tested on a seismic line from the Heidrun Field with two wells located on the line. The uncertainty of the estimated wavelet is low. In the Heidrun examples the effect of including uncertainty of the wavelet and the noise level was marginal with respect to the AVO inversion results. We have developed a 3-D linearized AVO inversion method with spatially coupled model parameters where the objective is to obtain posterior distributions for P-wave velocity, S

  14. Study on the Distribution of Networked Devices’ Clock Skew

    Directory of Open Access Journals (Sweden)

    Jiao Chengbo

    2011-08-01

    Full Text Available Clock skews of devices on the Internet are viewed as one way delay noise, but their distribution is unknown. We explore the distribution of clock skews to see the conflict probability. In this paper, we introduce an accurate clock skew estimation algorithm to filter inaccurate clock skew estimation by comparing the results between linear programming method and least square fitting. Delay jitter and other noises affect the estimation result. When the difference of two methods is large, the estimation result is unstable and inaccurate, so the estimation result should be dropped. Based on this algorithm, we use traces of real Internet measurements to collect 1825 accurate clock skews of different devices to establish a fingerprint database. Furthermore, we show the distribution of clock skews and comparing conflict probability with different number of devices. The distribution shows that clock skews are diverse, and most of clock skews are in the region of [-100, 100] PPM. The results indicate that when the number of devices is small (<5, clock skews won’t be conflict with each other, so clock skews are good tools to detect faked devices or NAT; When the number of devices increases, the conflict probability increases linearly, so clock skews of different devices can not distinguish each devices effectively.

  15. Clock distribution system for large high altitude air shower observatory

    International Nuclear Information System (INIS)

    In this paper, we report a clock distribution system for Water Cherenkov Detector Arrays (WCDAs) in Large High Altitude Air Shower Observatory (LHAASO) project. The designed electronics system is of high performance in implementing the clock distribution among detectors of a large scale of dimension. Based on Serializer/Deserializer (SerDes) and fiber transmission, the clock distribution system is the modules of central back end to distributed front end. The clock distribution system has been evaluated with a two modules system. While all the four SerDes candidates for clock transmission with jitters below 17 ps, the DS92LV16 has a fixed phase relationship between transmission clock and recovered clock, hence its use in LHAASO WCDAs. (authors)

  16. Satellite virtual atomic clock with pseudorange difference function

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

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

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

    CERN Document Server

    Weinstein, Jonathan D; Derevianko, Andrei

    2009-01-01

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

  18. Circadian rhythms of clock gene expression in Nile tilapia (Oreochromis niloticus) central and peripheral tissues: influence of different lighting and feeding conditions.

    Science.gov (United States)

    Costa, Leandro S; Serrano, Ignacio; Sánchez-Vázquez, Francisco J; López-Olmeda, Jose F

    2016-08-01

    The present research aimed to investigate the existence of clock gene expression rhythms in tilapia, their endogenous origin, and how light and feeding cycles synchronize these rhythms. In the first experiment, two groups of fish were kept under an LD cycle and fed at two different time points: in the middle of the light (ML) or in the middle of the dark (MD) phase. In the second experiment, fish fed at ML was fasted and kept under constant lighting (LL) conditions for 1 day. In both experiments, the samples from central (optic tectum and hypothalamus) and peripheral (liver) tissues were collected every 3 h throughout a 24 h cycle. The expression levels of clock genes bmal1a, clock1, per1b, cry2a, and cry5 were analyzed by quantitative PCR. All the clock genes analyzed in brain regions showed daily rhythms: clock1, bmal1a, and cry2a showed the acrophase approximately at the end of the light phase (ZT 8:43-11:22 h), whereas per1b and cry5 did so between the end of the dark phase and the beginning of the light phase, respectively (ZT 21:16-4:00 h). These rhythms persisted under constant conditions. No effect of the feeding time was observed in the brain. In the liver, however, the rhythms of clock1 and cry5 were influenced by feeding, and a shift was observed in the MD fish group (ZT 3:58 h for clock1 and 11:20 h for cry5). This study provides the first insights into the molecular clock of tilapia, a very important fish species for aquaculture. It also reveals the endogenous origin of clock gene rhythms and the ability of feeding time to shift the phase in some clock genes in the peripheral, but not the central, oscillator. PMID:27085855

  19. Bayesian modeling using WinBUGS

    CERN Document Server

    Ntzoufras, Ioannis

    2009-01-01

    A hands-on introduction to the principles of Bayesian modeling using WinBUGS Bayesian Modeling Using WinBUGS provides an easily accessible introduction to the use of WinBUGS programming techniques in a variety of Bayesian modeling settings. The author provides an accessible treatment of the topic, offering readers a smooth introduction to the principles of Bayesian modeling with detailed guidance on the practical implementation of key principles. The book begins with a basic introduction to Bayesian inference and the WinBUGS software and goes on to cover key topics, including: Markov Chain Monte Carlo algorithms in Bayesian inference Generalized linear models Bayesian hierarchical models Predictive distribution and model checking Bayesian model and variable evaluation Computational notes and screen captures illustrate the use of both WinBUGS as well as R software to apply the discussed techniques. Exercises at the end of each chapter allow readers to test their understanding of the presented concepts and all ...

  20. Probability biases as Bayesian inference

    Directory of Open Access Journals (Sweden)

    Andre; C. R. Martins

    2006-11-01

    Full Text Available In this article, I will show how several observed biases in human probabilistic reasoning can be partially explained as good heuristics for making inferences in an environment where probabilities have uncertainties associated to them. Previous results show that the weight functions and the observed violations of coalescing and stochastic dominance can be understood from a Bayesian point of view. We will review those results and see that Bayesian methods should also be used as part of the explanation behind other known biases. That means that, although the observed errors are still errors under the be understood as adaptations to the solution of real life problems. Heuristics that allow fast evaluations and mimic a Bayesian inference would be an evolutionary advantage, since they would give us an efficient way of making decisions. %XX In that sense, it should be no surprise that humans reason with % probability as it has been observed.

  1. Bayesian Methods and Universal Darwinism

    CERN Document Server

    Campbell, John

    2010-01-01

    Bayesian methods since the time of Laplace have been understood by their practitioners as closely aligned to the scientific method. Indeed a recent champion of Bayesian methods, E. T. Jaynes, titled his textbook on the subject Probability Theory: the Logic of Science. Many philosophers of science including Karl Popper and Donald Campbell have interpreted the evolution of Science as a Darwinian process consisting of a 'copy with selective retention' algorithm abstracted from Darwin's theory of Natural Selection. Arguments are presented for an isomorphism between Bayesian Methods and Darwinian processes. Universal Darwinism, as the term has been developed by Richard Dawkins, Daniel Dennett and Susan Blackmore, is the collection of scientific theories which explain the creation and evolution of their subject matter as due to the operation of Darwinian processes. These subject matters span the fields of atomic physics, chemistry, biology and the social sciences. The principle of Maximum Entropy states that system...

  2. Hyperfine Clock Transitions of Bismuth Donors in Silicon Detected by Spin Dependent Recombination

    OpenAIRE

    Mortemousque, Pierre-André; Berger, Simon; Sekiguchi, Takeharu; Culan, Christophe; Elliman, Robert G.; Kohei M. Itoh

    2014-01-01

    Bismuth donors ion-implanted in $^{28}$Si and $^\\text{nat}$Si are studied using magnetic resonance spectroscopy based on spin dependent recombination. The hyperfine clock transition, at which the linewidth is significantly narrowed, is observed for the bismuth donors. The experimental results are modeled quantitatively by molecular orbital theory for a coupled pair consisting of a bismuth donor and a spin dependent recombination readout center, including the effect of hyperfine and Zeeman int...

  3. Improved limits on interactions of low-mass spin-0 dark matter from atomic clock spectroscopy

    OpenAIRE

    Stadnik, Y. V.; Flambaum, V. V.

    2016-01-01

    Low-mass (sub-eV) spin-0 dark matter particles, which form a coherently oscillating classical field $\\phi = \\phi_0 \\cos(m_\\phi t)$, can induce oscillating variations in the fundamental constants through their interactions with the Standard Model sector. We calculate the effects of such possible interactions, which may include the linear interaction of $\\phi$ with the Higgs boson, on atomic and molecular transitions. Using recent atomic clock spectroscopy measurements, we derive new limits on ...

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

    OpenAIRE

    Foulkes, Nicholas S.; Yoav Gothilf; Lior Appelbaum

    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 manipul...

  5. Bayesian methods for proteomic biomarker development

    Directory of Open Access Journals (Sweden)

    Belinda Hernández

    2015-12-01

    In this review we provide an introduction to Bayesian inference and demonstrate some of the advantages of using a Bayesian framework. We summarize how Bayesian methods have been used previously in proteomics and other areas of bioinformatics. Finally, we describe some popular and emerging Bayesian models from the statistical literature and provide a worked tutorial including code snippets to show how these methods may be applied for the evaluation of proteomic biomarkers.

  6. Bayesian variable selection and data integration for biological regulatory networks

    OpenAIRE

    Jensen, Shane T; Chen, Guang; Stoeckert, Jr, Christian J.

    2007-01-01

    A substantial focus of research in molecular biology are gene regulatory networks: the set of transcription factors and target genes which control the involvement of different biological processes in living cells. Previous statistical approaches for identifying gene regulatory networks have used gene expression data, ChIP binding data or promoter sequence data, but each of these resources provides only partial information. We present a Bayesian hierarchical model that integrates all three dat...

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

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

    Roč. 30, č. 2 (2015), s. 104-116. ISSN 0748-7304 R&D Projects: GA ČR GC14-32654J Institutional support: RVO:60077344 Keywords : circadian clock * activity rhythms * eclosion rhythm Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.774, year: 2014

  8. Mammalian TIMELESS Is Involved in Period Determination and DNA Damage-Dependent Phase Advancing of the Circadian Clock

    NARCIS (Netherlands)

    M.P. Engelen (Erik); R. Janssens (Roel); K. Yagita (Kazuhiro); V.A.J. Smits (Veronique); G.T.J. van der Horst (Gijsbertus); F. Tamanini (Filippo)

    2013-01-01

    textabstractThe transcription/translation feedback loop-based molecular oscillator underlying the generation of circadian gene expression is preserved in almost all organisms. Interestingly, the animal circadian clock proteins CRYPTOCHROME (CRY), PERIOD (PER) and TIMELESS (TIM) are strongly conserve

  9. Bayesian test and Kuhn's paradigm

    Institute of Scientific and Technical Information of China (English)

    Chen Xiaoping

    2006-01-01

    Kuhn's theory of paradigm reveals a pattern of scientific progress,in which normal science alternates with scientific revolution.But Kuhn underrated too much the function of scientific test in his pattern,because he focuses all his attention on the hypothetico-deductive schema instead of Bayesian schema.This paper employs Bayesian schema to re-examine Kuhn's theory of paradigm,to uncover its logical and rational components,and to illustrate the tensional structure of logic and belief,rationality and irrationality,in the process of scientific revolution.

  10. 3D Bayesian contextual classifiers

    DEFF Research Database (Denmark)

    Larsen, Rasmus

    2000-01-01

    We extend a series of multivariate Bayesian 2-D contextual classifiers to 3-D by specifying a simultaneous Gaussian distribution for the feature vectors as well as a prior distribution of the class variables of a pixel and its 6 nearest 3-D neighbours.......We extend a series of multivariate Bayesian 2-D contextual classifiers to 3-D by specifying a simultaneous Gaussian distribution for the feature vectors as well as a prior distribution of the class variables of a pixel and its 6 nearest 3-D neighbours....

  11. Bayesian Model Averaging for Propensity Score Analysis

    Science.gov (United States)

    Kaplan, David; Chen, Jianshen

    2013-01-01

    The purpose of this study is to explore Bayesian model averaging in the propensity score context. Previous research on Bayesian propensity score analysis does not take into account model uncertainty. In this regard, an internally consistent Bayesian framework for model building and estimation must also account for model uncertainty. The…

  12. Bayesian networks and food security - An introduction

    NARCIS (Netherlands)

    Stein, A.

    2004-01-01

    This paper gives an introduction to Bayesian networks. Networks are defined and put into a Bayesian context. Directed acyclical graphs play a crucial role here. Two simple examples from food security are addressed. Possible uses of Bayesian networks for implementation and further use in decision sup

  13. Molecular systematics of the wolf spider genus Lycosa (Araneae: Lycosidae) in the Western Mediterranean Basin.

    Science.gov (United States)

    Planas, Enric; Fernández-Montraveta, Carmen; Ribera, Carles

    2013-05-01

    In this study, we present the first molecular phylogeny of the wolf spider genus Lycosa Latreille, 1804 in the Western Mediterranean Basin. With a wide geographic sampling comprising 90 localities and including more than 180 individuals, we conducted species delimitation analyses with a Maximum Likelihood approach that uses a mixed Yule-coalescent model to detect species boundaries. We estimated molecular phylogenetic relationships employing Maximum Likelihood and Bayesian Inference methods using mitochondrial and nuclear sequences. We conducted divergence time analyses using a relaxed clock model implemented in BEAST. Our results recovered 12 species that form four groups: Lycosa tarantula group comprising L. tarantula the type species of the genus, L. hispanica and L. bedeli; Lycosa oculata group composed of L.oculata, L. suboculata and three putative new species; Lycosa baulnyi group formed by the maghrebian L. baulnyi and L. vachoni and Lycosa fasciiventris group that includes two widespread species, L. fasciiventris and L. munieri. We found that each group of species shows a characteristic burrowing behavior and molecular and morphological diagnostic characters. Molecular clock analyses support the hypothesis of a relatively recent evolutionary origin of diversification of the group (4.96 Mya (3.53-6.45 Mya)). The establishment of the Mediterranean-like climate and the Pleistocenic glacial cycles seem to have been the main factors that promoted the diversification within the group. Finally, the results obtained in this study together with the revision of museum specimens, descriptions, redescriptions and illustrations, lead us to propose 18 nomenclatural changes (synonymies, generic transfers and nomina dubia) concerning the genera Lycosa, Allocosa and Hogna in the Western Mediterranean. PMID:23416758

  14. Bayesian variable order Markov models: Towards Bayesian predictive state representations

    NARCIS (Netherlands)

    C. Dimitrakakis

    2009-01-01

    We present a Bayesian variable order Markov model that shares many similarities with predictive state representations. The resulting models are compact and much easier to specify and learn than classical predictive state representations. Moreover, we show that they significantly outperform a more st

  15. Divergence date estimation and a comprehensive molecular tree of extant cetaceans.

    Science.gov (United States)

    McGowen, Michael R; Spaulding, Michelle; Gatesy, John

    2009-12-01

    Cetaceans are remarkable among mammals for their numerous adaptations to an entirely aquatic existence, yet many aspects of their phylogeny remain unresolved. Here we merged 37 new sequences from the nuclear genes RAG1 and PRM1 with most published molecular data for the group (45 nuclear loci, transposons, mitochondrial genomes), and generated a supermatrix consisting of 42,335 characters. The great majority of these data have never been combined. Model-based analyses of the supermatrix produced a solid, consistent phylogenetic hypothesis for 87 cetacean species. Bayesian analyses corroborated odontocete (toothed whale) monophyly, stabilized basal odontocete relationships, and completely resolved branching events within Mysticeti (baleen whales) as well as the problematic speciose clade Delphinidae (oceanic dolphins). Only limited conflicts relative to maximum likelihood results were recorded, and discrepancies found in parsimony trees were very weakly supported. We utilized the Bayesian supermatrix tree to estimate divergence dates among lineages using relaxed-clock methods. Divergence estimates revealed rapid branching of basal odontocete lineages near the Eocene-Oligocene boundary, the antiquity of river dolphin lineages, a Late Miocene radiation of balaenopteroid mysticetes, and a recent rapid radiation of Delphinidae beginning approximately 10 million years ago. Our comprehensive, time-calibrated tree provides a powerful evolutionary tool for broad-scale comparative studies of Cetacea. PMID:19699809

  16. Supporting Family Awareness with the Whereabouts Clock

    Science.gov (United States)

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

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

  17. The suprachiasmatic nuclei as a seasonal clock.

    Science.gov (United States)

    Coomans, Claudia P; Ramkisoensing, Ashna; Meijer, Johanna H

    2015-04-01

    In mammals, the suprachiasmatic nucleus (SCN) contains a central clock that synchronizes daily (i.e., 24-h) rhythms in physiology and behavior. SCN neurons are cell-autonomous oscillators that act synchronously to produce a coherent circadian rhythm. In addition, the SCN helps regulate seasonal rhythmicity. Photic information is perceived by the SCN and transmitted to the pineal gland, where it regulates melatonin production. Within the SCN, adaptations to changing photoperiod are reflected in changes in neurotransmitters and clock gene expression, resulting in waveform changes in rhythmic electrical activity, a major output of the SCN. Efferent pathways regulate the seasonal timing of breeding and hibernation. In humans, seasonal physiology and behavioral rhythms are also present, and the human SCN has seasonally rhythmic neurotransmitter levels and morphology. In summary, the SCN perceives and encodes changes in day length and drives seasonal changes in downstream pathways and structures in order to adapt to the changing seasons. PMID:25451984

  18. The Large Built Water Clock Of Amphiaraeion.

    Science.gov (United States)

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

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

  19. Clock drawing performance in cognitively normal elderly

    OpenAIRE

    Hubbard, E J; Santini, V; Blankevoort, C.G.; Volkers, K.M.; Barrup, M.S.; Byerly, L; Chaisson, C.; Jefferson, A.L.; Kaplan, E; Green, R.C.; Stern, R. A.

    2008-01-01

    The Clock Drawing Test (CDT) is a common neuropsychological measure sensitive to cognitive changes and functional skills (e.g., driving test performance) among older adults. However, normative data have not been adequately developed. We report the distribution of CDT scores using three common scoring systems (Mendez, Ala, and Underwood, 1992; Freund, Gravenstein, Ferris, Burke, & Shaheen, 2005; and Cahn, Salmon, Monsch, Butters, Wiederholt, & Corey-Bloom, 1996), among 207 cognitively normal e...

  20. The circadian clock, reward and memory

    OpenAIRE

    Urs eAlbrecht

    2011-01-01

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

  1. Absolute clock synchronisation and special relativity paradoxes

    OpenAIRE

    Ciborowski, Jacek; Wlodarczyk, Marta

    2012-01-01

    Solving special relativity paradoxes requires rigorous analysis of event timing, due to relative simultaneity in consequence of the Lorentz transformation. Since clock synchronisation is a convention in special theory of relativity, instead of the Einstein's procedure one may choose such that offers absolute simultaneity. We present in short the corresponding formalism in one spatial dimension. We show that paradoxes do not arise with this choice of synchronisation and descriptions of these i...

  2. Clock drawing performance in cognitively normal elderly.

    Science.gov (United States)

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

    2008-05-01

    The Clock Drawing Test (CDT) is a common neuropsychological measure sensitive to cognitive changes and functional skills (e.g., driving test performance) among older adults. However, normative data have not been adequately developed. We report the distribution of CDT scores using three common scoring systems [Mendez, M. F., Ala, T., & Underwood, K. L. (1992). Development of scoring criteria for the Clock Drawing Task in Alzheimer's Disease. Journal of the American Geriatrics Society, 40, 1095-1099; Cahn, D. A., Salmon, D. P., Monsch, A. U., Butters, N., Wiederholt, W. C., & Corey-Bloom, J. (1996). Screening for dementia of the Alzheimer type in the community: The utility of the Clock Drawing Test. Archives of Clinical Neuropsychology, 11(6), 529-539], among 207 cognitively normal elderly. The systems were well correlated, took little time to use, and had high inter-rater reliability. We found statistically significant differences in CDT scores based on age and WRAT-3 Reading score, a marker of education quality. We present means, standard deviations, and t- and z-scores based on these subgroups. We found that "normal" CDT performance includes a wider distribution of scores than previously reported. Our results may serve as useful comparisons for clinicians wishing to know whether their patients perform in the general range of cognitively normal elderly. PMID:18243644

  3. A microresonator frequency comb optical clock

    CERN Document Server

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

    2013-01-01

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

  4. Quantum mechanics, matter waves, and moving clocks

    CERN Document Server

    Mueller, Holger

    2013-01-01

    This paper is divided into three parts. In the first (section 1), we demonstrate that all of quantum mechanics can be derived from the fundamental property that the propagation of a matter wave packet is described by the same gravitational and kinematic time dilation that applies to a clock. We will do so in several steps, first deriving the Schroedinger equation for a nonrelativistic particle without spin in a weak gravitational potential, and eventually the Dirac equation in curved space-time describing the propagation of a relativistic particle with spin in strong gravity. In the second part (sections 2-4), we present interesting consequences of the above quantum mechanics: that it is possible to use wave packets as a reference for a clock, to test general relativity, and to realize a mass standard based on a proposed redefinition of the international system of units, wherein the Planck constant would be assigned a fixed value. The clock achieved an absolute accuracy of 4 parts per billion (ppb). The exper...

  5. Atomic Clocks with Suppressed Blackbody Radiation Shift

    International Nuclear Information System (INIS)

    We develop a concept of atomic clocks where the blackbody radiation shift and its fluctuations can be suppressed by 1-3 orders of magnitude independent of the environmental temperature. The suppression is based on the fact that in a system with two accessible clock transitions (with frequencies ν1 and ν2) which are exposed to the same thermal environment, there exists a 'synthetic' frequency νsyn ∝ (ν1-ε12ν2) largely immune to the blackbody radiation shift. For example, in the case of 171Yb+ it is possible to create a synthetic-frequency-based clock in which the fractional blackbody radiation shift can be suppressed to the level of 10-18 in a broad interval near room temperature (300±15 K). We also propose a realization of our method with the use of an optical frequency comb generator stabilized to both frequencies ν1 and ν2, where the frequency νsyn is generated as one of the components of the comb spectrum.

  6. Bayesian Analysis of Experimental Data

    Directory of Open Access Journals (Sweden)

    Lalmohan Bhar

    2013-10-01

    Full Text Available Analysis of experimental data from Bayesian point of view has been considered. Appropriate methodology has been developed for application into designed experiments. Normal-Gamma distribution has been considered for prior distribution. Developed methodology has been applied to real experimental data taken from long term fertilizer experiments.

  7. Bayesian image restoration, using configurations

    DEFF Research Database (Denmark)

    Thorarinsdottir, Thordis Linda

    2006-01-01

    configurations are expressed in terms of the mean normal measure of the random set. These probabilities are used as prior probabilities in a Bayesian image restoration approach. Estimation of the remaining parameters in the model is outlined for the salt and pepper noise. The inference in the model is discussed...

  8. Bayesian image restoration, using configurations

    DEFF Research Database (Denmark)

    Thorarinsdottir, Thordis

    configurations are expressed in terms of the mean normal measure of the random set. These probabilities are used as prior probabilities in a Bayesian image restoration approach. Estimation of the remaining parameters in the model is outlined for salt and pepper noise. The inference in the model is discussed in...

  9. ANALYSIS OF BAYESIAN CLASSIFIER ACCURACY

    Directory of Open Access Journals (Sweden)

    Felipe Schneider Costa

    2013-01-01

    Full Text Available The naïve Bayes classifier is considered one of the most effective classification algorithms today, competing with more modern and sophisticated classifiers. Despite being based on unrealistic (naïve assumption that all variables are independent, given the output class, the classifier provides proper results. However, depending on the scenario utilized (network structure, number of samples or training cases, number of variables, the network may not provide appropriate results. This study uses a process variable selection, using the chi-squared test to verify the existence of dependence between variables in the data model in order to identify the reasons which prevent a Bayesian network to provide good performance. A detailed analysis of the data is also proposed, unlike other existing work, as well as adjustments in case of limit values between two adjacent classes. Furthermore, variable weights are used in the calculation of a posteriori probabilities, calculated with mutual information function. Tests were applied in both a naïve Bayesian network and a hierarchical Bayesian network. After testing, a significant reduction in error rate has been observed. The naïve Bayesian network presented a drop in error rates from twenty five percent to five percent, considering the initial results of the classification process. In the hierarchical network, there was not only a drop in fifteen percent error rate, but also the final result came to zero.

  10. Bayesian Agglomerative Clustering with Coalescents

    OpenAIRE

    Teh, Yee Whye; Daumé III, Hal; Roy, Daniel

    2009-01-01

    We introduce a new Bayesian model for hierarchical clustering based on a prior over trees called Kingman's coalescent. We develop novel greedy and sequential Monte Carlo inferences which operate in a bottom-up agglomerative fashion. We show experimentally the superiority of our algorithms over others, and demonstrate our approach in document clustering and phylolinguistics.

  11. Bayesian Networks and Influence Diagrams

    DEFF Research Database (Denmark)

    Kjærulff, Uffe Bro; Madsen, Anders Læsø

    Bayesian Networks and Influence Diagrams: A Guide to Construction and Analysis, Second Edition, provides a comprehensive guide for practitioners who wish to understand, construct, and analyze intelligent systems for decision support based on probabilistic networks. This new edition contains six new...

  12. Topics in Bayesian statistics and maximum entropy

    International Nuclear Information System (INIS)

    Notions of Bayesian decision theory and maximum entropy methods are reviewed with particular emphasis on probabilistic inference and Bayesian modeling. The axiomatic approach is considered as the best justification of Bayesian analysis and maximum entropy principle applied in natural sciences. Particular emphasis is put on solving the inverse problem in digital image restoration and Bayesian modeling of neural networks. Further topics addressed briefly include language modeling, neutron scattering, multiuser detection and channel equalization in digital communications, genetic information, and Bayesian court decision-making. (author)

  13. Bayesian analysis of rare events

    Science.gov (United States)

    Straub, Daniel; Papaioannou, Iason; Betz, Wolfgang

    2016-06-01

    In many areas of engineering and science there is an interest in predicting the probability of rare events, in particular in applications related to safety and security. Increasingly, such predictions are made through computer models of physical systems in an uncertainty quantification framework. Additionally, with advances in IT, monitoring and sensor technology, an increasing amount of data on the performance of the systems is collected. This data can be used to reduce uncertainty, improve the probability estimates and consequently enhance the management of rare events and associated risks. Bayesian analysis is the ideal method to include the data into the probabilistic model. It ensures a consistent probabilistic treatment of uncertainty, which is central in the prediction of rare events, where extrapolation from the domain of observation is common. We present a framework for performing Bayesian updating of rare event probabilities, termed BUS. It is based on a reinterpretation of the classical rejection-sampling approach to Bayesian analysis, which enables the use of established methods for estimating probabilities of rare events. By drawing upon these methods, the framework makes use of their computational efficiency. These methods include the First-Order Reliability Method (FORM), tailored importance sampling (IS) methods and Subset Simulation (SuS). In this contribution, we briefly review these methods in the context of the BUS framework and investigate their applicability to Bayesian analysis of rare events in different settings. We find that, for some applications, FORM can be highly efficient and is surprisingly accurate, enabling Bayesian analysis of rare events with just a few model evaluations. In a general setting, BUS implemented through IS and SuS is more robust and flexible.

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

    Directory of Open Access Journals (Sweden)

    Guo-Xiang Ruan

    2008-10-01

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

  15. Bayesian methods for measures of agreement

    CERN Document Server

    Broemeling, Lyle D

    2009-01-01

    Using WinBUGS to implement Bayesian inferences of estimation and testing hypotheses, Bayesian Methods for Measures of Agreement presents useful methods for the design and analysis of agreement studies. It focuses on agreement among the various players in the diagnostic process.The author employs a Bayesian approach to provide statistical inferences based on various models of intra- and interrater agreement. He presents many examples that illustrate the Bayesian mode of reasoning and explains elements of a Bayesian application, including prior information, experimental information, the likelihood function, posterior distribution, and predictive distribution. The appendices provide the necessary theoretical foundation to understand Bayesian methods as well as introduce the fundamentals of programming and executing the WinBUGS software.Taking a Bayesian approach to inference, this hands-on book explores numerous measures of agreement, including the Kappa coefficient, the G coefficient, and intraclass correlation...

  16. Plug & Play object oriented Bayesian networks

    DEFF Research Database (Denmark)

    Bangsø, Olav; Flores, J.; Jensen, Finn Verner

    2003-01-01

    Object oriented Bayesian networks have proven themselves useful in recent years. The idea of applying an object oriented approach to Bayesian networks has extended their scope to larger domains that can be divided into autonomous but interrelated entities. Object oriented Bayesian networks have...... been shown to be quite suitable for dynamic domains as well. However, processing object oriented Bayesian networks in practice does not take advantage of their modular structure. Normally the object oriented Bayesian network is transformed into a Bayesian network and, inference is performed...... by constructing a junction tree from this network. In this paper we propose a method for translating directly from object oriented Bayesian networks to junction trees, avoiding the intermediate translation. We pursue two main purposes: firstly, to maintain the original structure organized in an instance tree...

  17. Using Playing Cards to Simulate a Molecular Clock

    Science.gov (United States)

    Westerling, Karin E.

    2008-01-01

    Changes in DNA base-repair may serve as an indicator of the time elapsed since divergence from a common ancestor. DNA sequences can now be analyzed. The simulation presented in this article allows students to observe the accumulation of changes in a randomly mutating sequence of playing cards. The cards are analogous to DNA nucleotide or protein…

  18. Glutamine synthetase gene evolution: A good molecular clock

    International Nuclear Information System (INIS)

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

  19. On the clock paradox in the case of circular motion of the moving clock

    International Nuclear Information System (INIS)

    Very often in many textbooks the formalism of the general theory of relativity is applied to gravitational problems. We think that it would be didactically useful to show how it can be adopted also for describing physical situations in accelerated frames of reference by working out in detail a particular case. This choice will also offer an opportunity to discuss a classical topic of relativistic physics. Indeed, we deal analytically with a version of the so-called clock paradox in which the moving clock performs a circular motion. The rest clock is denoted as (1), the rotating clock is (2), the inertial frame in which (1) is at rest and (2) moves is I and, finally, the accelerated frame in which (2) is at rest and (1) rotates is A. By using the general theory of relativity in order to describe the motion of (1) as seen in A we will show the following features. (I) A differential ageing between (1) and (2) occurs at their reunion and it has an absolute character, i.e. the proper time interval measured by a given clock is the same both in I and in A. (II) From a quantitative point of view, the magnitude of the differential ageing between (1) and (2) does depend on the kind of rotational motion performed by A. Indeed, if it is uniform there is no tangential force in the direction of motion of (2) but only normal to it. In this case, the proper time interval reckoned by (2) does depend only on its constant velocity v = rω. In contrast, if the rotational motion is uniformly accelerated, i.e. a constant force acts tangentially along the direction of motion, the proper time intervals do depend on the angular acceleration α. (III) Finally, in regard to the sign of the ageing, the moving clock (2) always measures a shorter interval of proper time with respect to (1)

  20. The Effects of Clock Drift on the Mars Exploration Rovers

    Science.gov (United States)

    Ali, Khaled S.; Vanelli, C. Anthony

    2012-01-01

    All clocks drift by some amount, and the mission clock on the Mars Exploration Rovers (MER) is no exception. The mission clock on both MER rovers drifted significantly since the rovers were launched, and it is still drifting on the Opportunity rover. The drift rate is temperature dependent. Clock drift causes problems for onboard behaviors and spacecraft operations, such as attitude estimation, driving, operation of the robotic arm, pointing for imaging, power analysis, and telecom analysis. The MER operations team has techniques to deal with some of these problems. There are a few techniques for reducing and eliminating the clock drift, but each has drawbacks. This paper presents an explanation of what is meant by clock drift on the rovers, its relationship to temperature, how we measure it, what problems it causes, how we deal with those problems, and techniques for reducing the drift.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    CERN Document Server

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

    2015-01-01

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

  3. Clock Auto-synchronizing Method for BES III ETOF Upgrade

    CERN Document Server

    Si-Yu, Wang; Shu-Bin, Liu; Qi, An

    2015-01-01

    An automatic clock synchronizing method implemented in field programmable gate array (FPGA) is proposed in this paper. It is developed for the clock system which will be applied in the end-cap time of flight (ETOF) upgrade of the Beijing Spectrometer (BESIII). In this design, an FPGA is used to automatically monitor the synchronization circuit and deal with signals coming from external clock synchronization circuit. By testing different delay time of the detection signal and analyzing state signals returned, the synchronization windows will be found automatically in FPGA. The new clock system not only retains low clock jitter which is less than 20ps root mean square (RMS), but also demonstrates automatic synchronization to the beam bunches. So far, the clock auto-synchronizing function has been working successfully under a series of tests. It will greatly simplify the system initialization and maintenance in the future.

  4. A clock network for geodesy and fundamental science

    CERN Document Server

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

  6. Clock rates, clock settings and the physics of the space-time Lorentz transformation

    CERN Document Server

    Field, J H

    2006-01-01

    A careful study is made of the operational meaning of the time symbols appearing in the space-time Lorentz transformation. Four distinct symbols, with different physical meanings, are needed to describe reciprocal measurements involving stationary and uniformly-moving clocks. Physical predictions concern only the observed rate of a clock as a function of its relative speed, not its setting. How the failure to make this distinction leads to the conventional predictions of spurious `relativity of simultaneity' and `length contraction' effects in special relativity is explained.

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

    Directory of Open Access Journals (Sweden)

    Takao Hirai

    2015-11-01

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

  8. The circadian clock and cell cycle: Interconnected biological circuits

    OpenAIRE

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

    2013-01-01

    The circadian clock governs biological timekeeping on a systemic level, helping to regulate and maintain physiological processes, including endocrine and metabolic pathways with a periodicity of 24-hours. Disruption within the circadian clock machinery has been linked to numerous pathological conditions, including cancer, suggesting that clock-dependent regulation of the cell cycle is an essential control mechanism. This review will highlight recent advances on the ‘gating’ controls of the ci...

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

    CERN Document Server

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

    2015-01-01

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

  10. Clocks and dynamics in quantum models of gravity

    OpenAIRE

    Malkiewicz, Przemyslaw

    2016-01-01

    We investigate how the quantum dynamics of gravitational models depend on the clocks employed in quantization procedure. Our previous result demonstrates that almost all physical features of quantum cosmological bounces depend on the choice of clock. The vital question whether all the quantum (or, semiclassical) solutions admit, away from the quantum interaction region in the far past and future, invariant asymptotic limits irrespectively of the clock's choice is addressed herein. We analyze ...

  11. The Clock-Proxy Auction: A Practical Combinatorial Auction Design

    OpenAIRE

    Lawrence M. Ausubel; Peter Cramton; Paul Milgrom

    2004-01-01

    We propose the clock-proxy auction as a practical means for auctioning many related items. A clock auction phase is followed by a last-and-final proxy round. The approach combines the simple and transparent price discovery of the clock auction with the efficiency of the proxy auction. Linear pricing is maintained as long as possible, but then is abandoned in the proxy round to improve efficiency and enhance seller revenues. The approach has many advantages over the simultaneous ascending auct...

  12. Gated Clock Implementation of Arithmetic Logic Unit (ALU)

    OpenAIRE

    Dr. Neelam R. Prakash; Akash

    2013-01-01

    Low power design has emerged as one of the challenging area in today’s ASIC (Application specific integrated circuit) design. With continuous decrease in transistor size, power density is increasing and there is an urgent need for reduction in total power consumption. Clock gating is one most effective technique for low power synchronous circuit design. Clock gating technique in low power design is used to reduce the dynamic power consumption. Clock signal in a synchronous circuit is used for...

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

    Directory of Open Access Journals (Sweden)

    Catalin V Buhusi

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  14. AMPK at the crossroads of circadian clocks and metabolism

    OpenAIRE

    Jordan, Sabine D.; Lamia, Katja A.

    2012-01-01

    Circadian clocks coordinate behavior and physiology with daily environmental cycles and thereby optimize the timing of metabolic processes such as glucose production and insulin secretion. Such circadian regulation of metabolism provides an adaptive advantage in diverse organisms. Mammalian clocks are primarily based on a transcription and translation feedback loop in which a heterodimeric complex of the transcription factors CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain an...

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

    Science.gov (United States)

    Preußner, Marco; Heyd, Florian

    2016-06-01

    Many aspects of human physiology and behavior display rhythmicity with a period of approximately 24 h. Rhythmic changes are controlled by an endogenous time keeper, the circadian clock, and include sleep-wake cycles, physical and mental performance capability, blood pressure, and body temperature. Consequently, many diseases, such as metabolic, sleep, autoimmune and mental disorders and cancer, are connected to the circadian rhythm. The development of therapies that take circadian biology into account is thus a promising strategy to improve treatments of diverse disorders, ranging from allergic syndromes to cancer. Circadian alteration of body functions and behavior are, at the molecular level, controlled and mediated by widespread changes in gene expression that happen in anticipation of predictably changing requirements during the day. At the core of the molecular clockwork is a well-studied transcription-translation negative feedback loop. However, evidence is emerging that additional post-transcriptional, RNA-based mechanisms are required to maintain proper clock function. Here, we will discuss recent work implicating regulated mRNA stability, translation and alternative splicing in the control of the mammalian circadian clock, and its role in health and disease. PMID:27108448

  16. Flexible Bayesian Nonparametric Priors and Bayesian Computational Methods

    OpenAIRE

    Zhu, Weixuan

    2016-01-01

    The definition of vectors of dependent random probability measures is a topic of interest in Bayesian nonparametrics. They represent dependent nonparametric prior distributions that are useful for modelling observables for which specific covariate values are known. Our first contribution is the introduction of novel multivariate vectors of two-parameter Poisson-Dirichlet process. The dependence is induced by applying a L´evy copula to the marginal L´evy intensities. Our attenti...

  17. Power and Skew Aware Point Diffusion Clock Network

    Science.gov (United States)

    Jung, Gunok; Kim, Chunghee; Chae, Kyoungkuk; Park, Giho; Park, Sung Bae

    This letter presents point diffusion clock network (PDCN) with local clock tree synthesis (CTS) scheme. The clock network is implemented with ten times wider metal line space than typical mesh networks for low power and utilized to nine times smaller area CTS execution for minimized clock skew amount. The measurement results show that skew amount of PDCN with local CTS is reduced to 36% and latency is shrunk to 45% of the amount in a 4.81mm2 CortexA-8 core with 65nm Samsung process.

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

    OpenAIRE

    Brand, Karl

    2011-01-01

    textabstractWe all know it when we wake mere moments before an alarm clock is scheduled to wake us: our body clock made the alarm clock redundant. This phenomenon is driven by an endogenous timer known as the biological, or circadian clock. Each revolution of the Earth about its own axis produces periods of light and dark which define what we all experience as a ‘day’. This profound cyclic variation in solar energy is responsible for driving the evolution of adaptive responses as early as 3.8...

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

    CERN Document Server

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

    2016-01-01

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

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

    Science.gov (United States)

    Álvarez, Víctor Pérez

    2015-03-01

    The invention and spread of the mechanical clock is a complex and multifaceted historical phenomenon. Some of these facets, such as its social impact, have been widely studied, but their scientific dimensions have often been dismissed. The mechanical clock was probably born as a scientific instrument for driving a model of the universe, and not only natural philosophers but also kings, nobles and other members of the social elites showed an interest in clocks as scientific instruments. Public clocks later spread a new way of telling time based on equal hours, laying the foundations for changes in time consciousness that would accelerate scientific thinking. PMID:25802023

  1. Late Glacial Demographic Expansion Motivates a Clock Overhaul for Population Genetics.

    Science.gov (United States)

    Hoareau, Thierry B

    2016-05-01

    The molecular clock hypothesis is fundamental in evolutionary biology as by assuming constancy of the molecular rate it provides a timeframe for evolution. However, increasing evidence shows time dependence of inferred molecular rates with inflated values obtained using recent calibrations. As recent demographic calibrations are virtually non-existent in most species, older phylogenetic calibration points (>1 Ma) are commonly used, which overestimate demographic parameters. To obtain more reliable rates of molecular evolution for population studies, I propose the calibration of demographic transition (CDT) method, which uses the timing of climatic changes over the late glacial warming period to calibrate expansions in various species. Simulation approaches and empirical data sets from a diversity of species (from mollusk to humans) confirm that, when compared with other genealogy-based calibration methods, the CDT provides a robust and broadly applicable clock for population genetics. The resulting CDT rates of molecular evolution also confirm rate heterogeneity over time and among taxa. Comparisons of expansion dates with ecological evidence confirm the inaccuracy of phylogenetically derived divergence rates when dating population-level events. The CDT method opens opportunities for addressing issues such as demographic responses to past climate change and the origin of rate heterogeneity related to taxa, genes, time, and genetic information content. PMID:26683588

  2. Bayesian approach to rough set

    CERN Document Server

    Marwala, Tshilidzi

    2007-01-01

    This paper proposes an approach to training rough set models using Bayesian framework trained using Markov Chain Monte Carlo (MCMC) method. The prior probabilities are constructed from the prior knowledge that good rough set models have fewer rules. Markov Chain Monte Carlo sampling is conducted through sampling in the rough set granule space and Metropolis algorithm is used as an acceptance criteria. The proposed method is tested to estimate the risk of HIV given demographic data. The results obtained shows that the proposed approach is able to achieve an average accuracy of 58% with the accuracy varying up to 66%. In addition the Bayesian rough set give the probabilities of the estimated HIV status as well as the linguistic rules describing how the demographic parameters drive the risk of HIV.

  3. Attention in a bayesian framework

    DEFF Research Database (Denmark)

    Whiteley, Louise Emma; Sahani, Maneesh

    2012-01-01

    include both selective phenomena, where attention is invoked by cues that point to particular stimuli, and integrative phenomena, where attention is invoked dynamically by endogenous processing. However, most previous Bayesian accounts of attention have focused on describing relatively simple experimental...... settings, where cues shape expectations about a small number of upcoming stimuli and thus convey "prior" information about clearly defined objects. While operationally consistent with the experiments it seeks to describe, this view of attention as prior seems to miss many essential elements of both its......The behavioral phenomena of sensory attention are thought to reflect the allocation of a limited processing resource, but there is little consensus on the nature of the resource or why it should be limited. Here we argue that a fundamental bottleneck emerges naturally within Bayesian models of...

  4. Bayesian Sampling using Condition Indicators

    DEFF Research Database (Denmark)

    Faber, Michael H.; Sørensen, John Dalsgaard

    2002-01-01

    allows for a Bayesian formulation of the indicators whereby the experience and expertise of the inspection personnel may be fully utilized and consistently updated as frequentistic information is collected. The approach is illustrated on an example considering a concrete structure subject to corrosion......The problem of control quality of components is considered for the special case where the acceptable failure rate is low, the test costs are high and where it may be difficult or impossible to test the condition of interest directly. Based on the classical control theory and the concept of...... condition indicators introduced by Benjamin and Cornell (1970) a Bayesian approach to quality control is formulated. The formulation is then extended to the case where the quality control is based on sampling of indirect information about the condition of the components, i.e. condition indicators. This...

  5. BAYESIAN IMAGE RESTORATION, USING CONFIGURATIONS

    Directory of Open Access Journals (Sweden)

    Thordis Linda Thorarinsdottir

    2011-05-01

    Full Text Available In this paper, we develop a Bayesian procedure for removing noise from images that can be viewed as noisy realisations of random sets in the plane. The procedure utilises recent advances in configuration theory for noise free random sets, where the probabilities of observing the different boundary configurations are expressed in terms of the mean normal measure of the random set. These probabilities are used as prior probabilities in a Bayesian image restoration approach. Estimation of the remaining parameters in the model is outlined for salt and pepper noise. The inference in the model is discussed in detail for 3 X 3 and 5 X 5 configurations and examples of the performance of the procedure are given.

  6. Bayesian Seismology of the Sun

    CERN Document Server

    Gruberbauer, Michael

    2013-01-01

    We perform a Bayesian grid-based analysis of the solar l=0,1,2 and 3 p modes obtained via BiSON in order to deliver the first Bayesian asteroseismic analysis of the solar composition problem. We do not find decisive evidence to prefer either of the contending chemical compositions, although the revised solar abundances (AGSS09) are more probable in general. We do find indications for systematic problems in standard stellar evolution models, unrelated to the consequences of inadequate modelling of the outer layers on the higher-order modes. The seismic observables are best fit by solar models that are several hundred million years older than the meteoritic age of the Sun. Similarly, meteoritic age calibrated models do not adequately reproduce the observed seismic observables. Our results suggest that these problems will affect any asteroseismic inference that relies on a calibration to the Sun.

  7. Bayesian priors for transiting planets

    CERN Document Server

    Kipping, David M

    2016-01-01

    As astronomers push towards discovering ever-smaller transiting planets, it is increasingly common to deal with low signal-to-noise ratio (SNR) events, where the choice of priors plays an influential role in Bayesian inference. In the analysis of exoplanet data, the selection of priors is often treated as a nuisance, with observers typically defaulting to uninformative distributions. Such treatments miss a key strength of the Bayesian framework, especially in the low SNR regime, where even weak a priori information is valuable. When estimating the parameters of a low-SNR transit, two key pieces of information are known: (i) the planet has the correct geometric alignment to transit and (ii) the transit event exhibits sufficient signal-to-noise to have been detected. These represent two forms of observational bias. Accordingly, when fitting transits, the model parameter priors should not follow the intrinsic distributions of said terms, but rather those of both the intrinsic distributions and the observational ...

  8. Bayesian Inference for Radio Observations

    CERN Document Server

    Lochner, Michelle; Zwart, Jonathan T L; Smirnov, Oleg; Bassett, Bruce A; Oozeer, Nadeem; Kunz, Martin

    2015-01-01

    (Abridged) New telescopes like the Square Kilometre Array (SKA) will push into a new sensitivity regime and expose systematics, such as direction-dependent effects, that could previously be ignored. Current methods for handling such systematics rely on alternating best estimates of instrumental calibration and models of the underlying sky, which can lead to inaccurate uncertainty estimates and biased results because such methods ignore any correlations between parameters. These deconvolution algorithms produce a single image that is assumed to be a true representation of the sky, when in fact it is just one realisation of an infinite ensemble of images compatible with the noise in the data. In contrast, here we report a Bayesian formalism that simultaneously infers both systematics and science. Our technique, Bayesian Inference for Radio Observations (BIRO), determines all parameters directly from the raw data, bypassing image-making entirely, by sampling from the joint posterior probability distribution. Thi...

  9. Bayesian inference on proportional elections.

    Science.gov (United States)

    Brunello, Gabriel Hideki Vatanabe; Nakano, Eduardo Yoshio

    2015-01-01

    Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software. PMID:25786259

  10. The Space Optical Clocks Project: Development of high-performance transportable and breadboard optical clocks and advanced subsystems

    CERN Document Server

    Schiller, S; Nevsky, A; Alighanbari, S; Vasilyev, S; Abou-Jaoudeh, C; Mura, G; Franzen, T; Sterr, U; Falke, S; Lisdat, Ch; Rasel, E; Kulosa, A; Bize, S; Lodewyck, J; Tino, G M; Poli, N; Schioppo, M; Bongs, K; Singh, Y; Gill, P; Barwood, G; Ovchinnikov, Y; Stuhler, J; Kaenders, W; Braxmaier, C; Holzwarth, R; Donati, A; Lecomte, S; Calonico, D; Levi, F

    2012-01-01

    The use of ultra-precise optical clocks in space ("master clocks") will allow for a range of new applications in the fields of fundamental physics (tests of Einstein's theory of General Relativity, time and frequency metrology by means of the comparison of distant terrestrial clocks), geophysics (mapping of the gravitational potential of Earth), and astronomy (providing local oscillators for radio ranging and interferometry in space). Within the ELIPS-3 program of ESA, the "Space Optical Clocks" (SOC) project aims to install and to operate an optical lattice clock on the ISS towards the end of this decade, as a natural follow-on to the ACES mission, improving its performance by at least one order of magnitude. The payload is planned to include an optical lattice clock, as well as a frequency comb, a microwave link, and an optical link for comparisons of the ISS clock with ground clocks located in several countries and continents. Undertaking a necessary step towards optical clocks in space, the EU-FP7-SPACE-2...

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

  12. A Bayesian Nonparametric IRT Model

    OpenAIRE

    Karabatsos, George

    2015-01-01

    This paper introduces a flexible Bayesian nonparametric Item Response Theory (IRT) model, which applies to dichotomous or polytomous item responses, and which can apply to either unidimensional or multidimensional scaling. This is an infinite-mixture IRT model, with person ability and item difficulty parameters, and with a random intercept parameter that is assigned a mixing distribution, with mixing weights a probit function of other person and item parameters. As a result of its flexibility...

  13. Bayesian segmentation of hyperspectral images

    CERN Document Server

    Mohammadpour, Adel; Mohammad-Djafari, Ali

    2007-01-01

    In this paper we consider the problem of joint segmentation of hyperspectral images in the Bayesian framework. The proposed approach is based on a Hidden Markov Modeling (HMM) of the images with common segmentation, or equivalently with common hidden classification label variables which is modeled by a Potts Markov Random Field. We introduce an appropriate Markov Chain Monte Carlo (MCMC) algorithm to implement the method and show some simulation results.

  14. Bayesian segmentation of hyperspectral images

    Science.gov (United States)

    Mohammadpour, Adel; Féron, Olivier; Mohammad-Djafari, Ali

    2004-11-01

    In this paper we consider the problem of joint segmentation of hyperspectral images in the Bayesian framework. The proposed approach is based on a Hidden Markov Modeling (HMM) of the images with common segmentation, or equivalently with common hidden classification label variables which is modeled by a Potts Markov Random Field. We introduce an appropriate Markov Chain Monte Carlo (MCMC) algorithm to implement the method and show some simulation results.

  15. Bayesian Stable Isotope Mixing Models

    OpenAIRE

    Parnell, Andrew C.; Phillips, Donald L.; Bearhop, Stuart; Semmens, Brice X.; Ward, Eric J.; Moore, Jonathan W.; Andrew L Jackson; Inger, Richard

    2012-01-01

    In this paper we review recent advances in Stable Isotope Mixing Models (SIMMs) and place them into an over-arching Bayesian statistical framework which allows for several useful extensions. SIMMs are used to quantify the proportional contributions of various sources to a mixture. The most widely used application is quantifying the diet of organisms based on the food sources they have been observed to consume. At the centre of the multivariate statistical model we propose is a compositional m...

  16. Bayesian Network--Response Regression

    OpenAIRE

    WANG, LU; Durante, Daniele; Dunson, David B.

    2016-01-01

    There is an increasing interest in learning how human brain networks vary with continuous traits (e.g., personality, cognitive abilities, neurological disorders), but flexible procedures to accomplish this goal are limited. We develop a Bayesian semiparametric model, which combines low-rank factorizations and Gaussian process priors to allow flexible shifts of the conditional expectation for a network-valued random variable across the feature space, while including subject-specific random eff...

  17. Bayesian estimation of turbulent motion

    OpenAIRE

    Héas, P.; Herzet, C.; Mémin, E.; Heitz, D.; P. D. Mininni

    2013-01-01

    International audience Based on physical laws describing the multi-scale structure of turbulent flows, this article proposes a regularizer for fluid motion estimation from an image sequence. Regularization is achieved by imposing some scale invariance property between histograms of motion increments computed at different scales. By reformulating this problem from a Bayesian perspective, an algorithm is proposed to jointly estimate motion, regularization hyper-parameters, and to select the ...

  18. Elements of Bayesian experimental design

    Energy Technology Data Exchange (ETDEWEB)

    Sivia, D.S. [Rutherford Appleton Lab., Oxon (United Kingdom)

    1997-09-01

    We consider some elements of the Bayesian approach that are important for optimal experimental design. While the underlying principles used are very general, and are explained in detail in a recent tutorial text, they are applied here to the specific case of characterising the inferential value of different resolution peakshapes. This particular issue was considered earlier by Silver, Sivia and Pynn (1989, 1990a, 1990b), and the following presentation confirms and extends the conclusions of their analysis.

  19. Skill Rating by Bayesian Inference

    OpenAIRE

    Di Fatta, Giuseppe; Haworth, Guy McCrossan; Regan, Kenneth W.

    2009-01-01

    Systems Engineering often involves computer modelling the behaviour of proposed systems and their components. Where a component is human, fallibility must be modelled by a stochastic agent. The identification of a model of decision-making over quantifiable options is investigated using the game-domain of Chess. Bayesian methods are used to infer the distribution of players’ skill levels from the moves they play rather than from their competitive results. The approach is used on large sets of ...

  20. Topics in Nonparametric Bayesian Statistics

    OpenAIRE

    2003-01-01

    The intersection set of Bayesian and nonparametric statistics was almost empty until about 1973, but now seems to be growing at a healthy rate. This chapter gives an overview of various theoretical and applied research themes inside this field, partly complementing and extending recent reviews of Dey, Müller and Sinha (1998) and Walker, Damien, Laud and Smith (1999). The intention is not to be complete or exhaustive, but rather to touch on research areas of interest, partly by example.

  1. Cover Tree Bayesian Reinforcement Learning

    OpenAIRE

    Tziortziotis, Nikolaos; Dimitrakakis, Christos; Blekas, Konstantinos

    2013-01-01

    This paper proposes an online tree-based Bayesian approach for reinforcement learning. For inference, we employ a generalised context tree model. This defines a distribution on multivariate Gaussian piecewise-linear models, which can be updated in closed form. The tree structure itself is constructed using the cover tree method, which remains efficient in high dimensional spaces. We combine the model with Thompson sampling and approximate dynamic programming to obtain effective exploration po...

  2. Bayesian kinematic earthquake source models

    Science.gov (United States)

    Minson, S. E.; Simons, M.; Beck, J. L.; Genrich, J. F.; Galetzka, J. E.; Chowdhury, F.; Owen, S. E.; Webb, F.; Comte, D.; Glass, B.; Leiva, C.; Ortega, F. H.

    2009-12-01

    Most coseismic, postseismic, and interseismic slip models are based on highly regularized optimizations which yield one solution which satisfies the data given a particular set of regularizing constraints. This regularization hampers our ability to answer basic questions such as whether seismic and aseismic slip overlap or instead rupture separate portions of the fault zone. We present a Bayesian methodology for generating kinematic earthquake source models with a focus on large subduction zone earthquakes. Unlike classical optimization approaches, Bayesian techniques sample the ensemble of all acceptable models presented as an a posteriori probability density function (PDF), and thus we can explore the entire solution space to determine, for example, which model parameters are well determined and which are not, or what is the likelihood that two slip distributions overlap in space. Bayesian sampling also has the advantage that all a priori knowledge of the source process can be used to mold the a posteriori ensemble of models. Although very powerful, Bayesian methods have up to now been of limited use in geophysical modeling because they are only computationally feasible for problems with a small number of free parameters due to what is called the "curse of dimensionality." However, our methodology can successfully sample solution spaces of many hundreds of parameters, which is sufficient to produce finite fault kinematic earthquake models. Our algorithm is a modification of the tempered Markov chain Monte Carlo (tempered MCMC or TMCMC) method. In our algorithm, we sample a "tempered" a posteriori PDF using many MCMC simulations running in parallel and evolutionary computation in which models which fit the data poorly are preferentially eliminated in favor of models which better predict the data. We present results for both synthetic test problems as well as for the 2007 Mw 7.8 Tocopilla, Chile earthquake, the latter of which is constrained by InSAR, local high

  3. Bayesian Kernel Mixtures for Counts

    OpenAIRE

    Canale, Antonio; David B Dunson

    2011-01-01

    Although Bayesian nonparametric mixture models for continuous data are well developed, there is a limited literature on related approaches for count data. A common strategy is to use a mixture of Poissons, which unfortunately is quite restrictive in not accounting for distributions having variance less than the mean. Other approaches include mixing multinomials, which requires finite support, and using a Dirichlet process prior with a Poisson base measure, which does not allow smooth deviatio...

  4. Bayesian Optimization for Adaptive MCMC

    OpenAIRE

    Mahendran, Nimalan; Wang, Ziyu; Hamze, Firas; De Freitas, Nando

    2011-01-01

    This paper proposes a new randomized strategy for adaptive MCMC using Bayesian optimization. This approach applies to non-differentiable objective functions and trades off exploration and exploitation to reduce the number of potentially costly objective function evaluations. We demonstrate the strategy in the complex setting of sampling from constrained, discrete and densely connected probabilistic graphical models where, for each variation of the problem, one needs to adjust the parameters o...

  5. Inference in hybrid Bayesian networks

    DEFF Research Database (Denmark)

    Lanseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael;

    2009-01-01

    and reliability block diagrams). However, limitations in the BNs' calculation engine have prevented BNs from becoming equally popular for domains containing mixtures of both discrete and continuous variables (so-called hybrid domains). In this paper we focus on these difficulties, and summarize some of the last...... decade's research on inference in hybrid Bayesian networks. The discussions are linked to an example model for estimating human reliability....

  6. Quantile pyramids for Bayesian nonparametrics

    OpenAIRE

    2009-01-01

    P\\'{o}lya trees fix partitions and use random probabilities in order to construct random probability measures. With quantile pyramids we instead fix probabilities and use random partitions. For nonparametric Bayesian inference we use a prior which supports piecewise linear quantile functions, based on the need to work with a finite set of partitions, yet we show that the limiting version of the prior exists. We also discuss and investigate an alternative model based on the so-called substitut...

  7. Space Shuttle RTOS Bayesian Network

    Science.gov (United States)

    Morris, A. Terry; Beling, Peter A.

    2001-01-01

    With shrinking budgets and the requirements to increase reliability and operational life of the existing orbiter fleet, NASA has proposed various upgrades for the Space Shuttle that are consistent with national space policy. The cockpit avionics upgrade (CAU), a high priority item, has been selected as the next major upgrade. The primary functions of cockpit avionics include flight control, guidance and navigation, communication, and orbiter landing support. Secondary functions include the provision of operational services for non-avionics systems such as data handling for the payloads and caution and warning alerts to the crew. Recently, a process to selection the optimal commercial-off-the-shelf (COTS) real-time operating system (RTOS) for the CAU was conducted by United Space Alliance (USA) Corporation, which is a joint venture between Boeing and Lockheed Martin, the prime contractor for space shuttle operations. In order to independently assess the RTOS selection, NASA has used the Bayesian network-based scoring methodology described in this paper. Our two-stage methodology addresses the issue of RTOS acceptability by incorporating functional, performance and non-functional software measures related to reliability, interoperability, certifiability, efficiency, correctness, business, legal, product history, cost and life cycle. The first stage of the methodology involves obtaining scores for the various measures using a Bayesian network. The Bayesian network incorporates the causal relationships between the various and often competing measures of interest while also assisting the inherently complex decision analysis process with its ability to reason under uncertainty. The structure and selection of prior probabilities for the network is extracted from experts in the field of real-time operating systems. Scores for the various measures are computed using Bayesian probability. In the second stage, multi-criteria trade-off analyses are performed between the scores

  8. Bayesian analysis of contingency tables

    OpenAIRE

    Gómez Villegas, Miguel A.; González Pérez, Beatriz

    2005-01-01

    The display of the data by means of contingency tables is used in different approaches to statistical inference, for example, to broach the test of homogeneity of independent multinomial distributions. We develop a Bayesian procedure to test simple null hypotheses versus bilateral alternatives in contingency tables. Given independent samples of two binomial distributions and taking a mixed prior distribution, we calculate the posterior probability that the proportion of successes in the first...

  9. Bayesian Credit Ratings (new version)

    OpenAIRE

    Paola Cerchiello; Paolo Giudici

    2013-01-01

    In this contribution we aim at improving ordinal variable selection in the context of causal models. In this regard, we propose an approach that provides a formal inferential tool to compare the explanatory power of each covariate, and, therefore, to select an effective model for classification purposes. Our proposed model is Bayesian nonparametric, and, thus, keeps the amount of model specification to a minimum. We consider the case in which information from the covariates is at the ordinal ...

  10. Polarizabilities of the beryllium clock transition

    International Nuclear Information System (INIS)

    The polarizabilities of the three lowest states of the beryllium atom are determined from a large basis configuration interaction calculation. The polarizabilities of the 2s21Se ground state (37.73a03) and the 2s2p 3P0o metastable state (39.04a03) are found to be very similar in size and magnitude. This leads to an anomalously small blackbody radiation shift at 300 K of -0.018(4) Hz for the 2s21Se-2s2p 3P0o clock transition. Magic wavelengths for simultaneous trapping of the ground and metastable states are also computed.

  11. Grand-mother clocks and quiet lasers

    OpenAIRE

    Arnaud, Jacques; Chusseau, Laurent; Philippe, Fabrice

    2009-01-01

    7 pages Galileo noted in the 16th century that the period of oscillation of a pendulum is almost independent of the amplitude. However, such a pendulum is damped by air friction. The latter may be viewed as resulting from air molecules getting in contact with the pendulum. It follows that air friction, not only damps the oscillation, but also introduces randomness. In the so-called ``grand-mother'' clock, discovered by Huygens in the 18th century, damping is compensated for, on the average...

  12. Bayesian second law of thermodynamics

    Science.gov (United States)

    Bartolotta, Anthony; Carroll, Sean M.; Leichenauer, Stefan; Pollack, Jason

    2016-08-01

    We derive a generalization of the second law of thermodynamics that uses Bayesian updates to explicitly incorporate the effects of a measurement of a system at some point in its evolution. By allowing an experimenter's knowledge to be updated by the measurement process, this formulation resolves a tension between the fact that the entropy of a statistical system can sometimes fluctuate downward and the information-theoretic idea that knowledge of a stochastically evolving system degrades over time. The Bayesian second law can be written as Δ H (ρm,ρ ) + F |m≥0 , where Δ H (ρm,ρ ) is the change in the cross entropy between the original phase-space probability distribution ρ and the measurement-updated distribution ρm and F |m is the expectation value of a generalized heat flow out of the system. We also derive refined versions of the second law that bound the entropy increase from below by a non-negative number, as well as Bayesian versions of integral fluctuation theorems. We demonstrate the formalism using simple analytical and numerical examples.

  13. Quantum Inference on Bayesian Networks

    Science.gov (United States)

    Yoder, Theodore; Low, Guang Hao; Chuang, Isaac

    2014-03-01

    Because quantum physics is naturally probabilistic, it seems reasonable to expect physical systems to describe probabilities and their evolution in a natural fashion. Here, we use quantum computation to speedup sampling from a graphical probability model, the Bayesian network. A specialization of this sampling problem is approximate Bayesian inference, where the distribution on query variables is sampled given the values e of evidence variables. Inference is a key part of modern machine learning and artificial intelligence tasks, but is known to be NP-hard. Classically, a single unbiased sample is obtained from a Bayesian network on n variables with at most m parents per node in time (nmP(e) - 1 / 2) , depending critically on P(e) , the probability the evidence might occur in the first place. However, by implementing a quantum version of rejection sampling, we obtain a square-root speedup, taking (n2m P(e) -1/2) time per sample. The speedup is the result of amplitude amplification, which is proving to be broadly applicable in sampling and machine learning tasks. In particular, we provide an explicit and efficient circuit construction that implements the algorithm without the need for oracle access.

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

    Science.gov (United States)

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

    2016-06-01

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

  15. Dopamine receptor-mediated regulation of neuronal "clock" gene expression.

    Science.gov (United States)

    Imbesi, M; Yildiz, S; Dirim Arslan, A; Sharma, R; Manev, H; Uz, T

    2009-01-23

    Using a transgenic mice model (i.e. "clock" knockouts), clock transcription factors have been suggested as critical regulators of dopaminergic behaviors induced by drugs of abuse. Moreover, it has been shown that systemic administration of psychostimulants, such as cocaine and methamphetamine regulates the striatal expression of clock genes. However, it is not known whether dopamine receptors mediate these regulatory effects of psychostimulants at the cellular level. Primary striatal neurons in culture express dopamine receptors as well as clock genes and have been successfully used in studying dopamine receptor functioning. Therefore, we investigated the role of dopamine receptors on neuronal clock gene expression in this model using specific receptor agonists. We found an inhibitory effect on the expression of mClock and mPer1 genes with the D2-class (i.e. D2/D3) receptor agonist quinpirole. We also found a generalized stimulatory effect on the expression of clock genes mPer1, mClock, mNPAS2 (neuronal PAS domain protein 2), and mBmal1 with the D1-class (i.e. D1) receptor agonist SKF38393. Further, we tested whether systemic administration of dopamine receptor agonists causes similar changes in striatal clock gene expression in vivo. We found quinpirole-induced alterations in mPER1 protein levels in the mouse striatum (i.e. rhythm shift). Collectively, our results indicate that the dopamine receptor system may mediate psychostimulant-induced changes in clock gene expression. Using striatal neurons in culture as a model, further research is needed to better understand how dopamine signaling modulates the expression dynamics of clock genes (i.e. intracellular signaling pathways) and thereby influences neuronal gene expression, neuronal transmission, and brain functioning. PMID:19017537

  16. 12th Brazilian Meeting on Bayesian Statistics

    CERN Document Server

    Louzada, Francisco; Rifo, Laura; Stern, Julio; Lauretto, Marcelo

    2015-01-01

    Through refereed papers, this volume focuses on the foundations of the Bayesian paradigm; their comparison to objectivistic or frequentist Statistics counterparts; and the appropriate application of Bayesian foundations. This research in Bayesian Statistics is applicable to data analysis in biostatistics, clinical trials, law, engineering, and the social sciences. EBEB, the Brazilian Meeting on Bayesian Statistics, is held every two years by the ISBrA, the International Society for Bayesian Analysis, one of the most active chapters of the ISBA. The 12th meeting took place March 10-14, 2014 in Atibaia. Interest in foundations of inductive Statistics has grown recently in accordance with the increasing availability of Bayesian methodological alternatives. Scientists need to deal with the ever more difficult choice of the optimal method to apply to their problem. This volume shows how Bayes can be the answer. The examination and discussion on the foundations work towards the goal of proper application of Bayesia...

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

    OpenAIRE

    Landgraf, Dominic; Wang, Lexie L.; Diemer, Tanja; Welsh, David K.

    2016-01-01

    Heterodimers of CLOCK and BMAL1 are the major transcriptional activators of the mammalian circadian clock. Because the paralog NPAS2 can substitute for CLOCK in the suprachiasmatic nucleus (SCN), the master circadian pacemaker, CLOCK-deficient mice maintain circadian rhythms in behavior and in tissues in vivo. However, when isolated from the SCN, CLOCK-deficient peripheral tissues are reportedly arrhythmic, suggesting a fundamental difference in circadian clock function between SCN and periph...

  18. Bayesian Posterior Distributions Without Markov Chains

    OpenAIRE

    Cole, Stephen R.; Chu, Haitao; Greenland, Sander; Hamra, Ghassan; Richardson, David B.

    2012-01-01

    Bayesian posterior parameter distributions are often simulated using Markov chain Monte Carlo (MCMC) methods. However, MCMC methods are not always necessary and do not help the uninitiated understand Bayesian inference. As a bridge to understanding Bayesian inference, the authors illustrate a transparent rejection sampling method. In example 1, they illustrate rejection sampling using 36 cases and 198 controls from a case-control study (1976–1983) assessing the relation between residential ex...

  19. Oscillation of Clock and Clock Controlled Genes Induced by Serum Shock in Human Breast Epithelial and Breast Cancer Cells: Regulation by Melatonin

    OpenAIRE

    S. Xiang; Mao, L; T. Duplessis; Yuan, L.; R. Dauchy; Dauchy, E.; D.E. Blask,; T. Frasch; Hill, S M

    2012-01-01

    This study investigates differences in expression of clock and clock-controlled genes (CCGs) between human breast epithelial and breast cancer cells and breast tumor xenografts in circadian intact rats and examines if the pineal hormone melatonin influences clock gene and CCG expression. Oscillation of clock gene expression was not observed under standard growth conditions in vitro, however, serum shock (50% horse serum for 2 h) induced oscillation of clock gene and CCG expression in MCF-10A ...

  20. Real-time estimation of satellite clock offset using adaptively robust Kalman filter with classified adaptive factors

    OpenAIRE

    G Huang; Q. Zhang;  

    2012-01-01

    In order to estimate the satellite clock offset in a real-time mode, a new algorithm of adaptively robust Kalman filter with classified adaptive factors for clock offset estimation is proposed. Compared with standard Kalman filter clock offset model, the new method can detect and control outliers and clock jumps automatically in real-time. Moreover, the clock model parameters, which contain the clock offset, clock speed and clock shift, are classified to decide the adaptive factors in the new...

  1. Limits to clock synchronization induced by completely dephasing communication channels

    International Nuclear Information System (INIS)

    Clock synchronization procedures are analyzed in the presence of imperfect communications. In this context we show that there are physical limitations, which prevent one from synchronizing distant clocks when the intervening medium is completely dephasing, as in the case of a rapidly varying dispersive medium

  2. Atomic clocks: new prospects in metrology and geodesy

    CERN Document Server

    Delva, Pacôme

    2013-01-01

    We present the latest developments in the field of atomic clocks and their applications in metrology and fundamental physics. In the light of recent advents in the accuracy of optical clocks, we present an introduction to the relativistic modelization of frequency transfer and a detailed review of chronometric geodesy.

  3. Clocking in the face of unpredictability beyond quantum uncertainty

    Science.gov (United States)

    Madjid, F. Hadi; Myers, John M.

    2015-05-01

    In earlier papers we showed unpredictability beyond quantum uncertainty in atomic clocks, ensuing from a proven gap between given evidence and explanations of that evidence. Here we reconceive a clock, not as an isolated entity, but as enmeshed in a self-adjusting communications network adapted to one or another particular investigation, in contact with an unpredictable environment. From the practical uses of clocks, we abstract a clock enlivened with the computational capacity of a Turing machine, modified to transmit and to receive numerical communications. Such "live clocks" phase the steps of their computations to mesh with the arrival of transmitted numbers. We lift this phasing, known in digital communications, to a principle of logical synchronization, distinct from the synchronization defined by Einstein in special relativity. Logical synchronization elevates digital communication to a topic in physics, including applications to biology. One explores how feedback loops in clocking affect numerical signaling among entities functioning in the face of unpredictable influences, making the influences themselves into subjects of investigation. The formulation of communications networks in terms of live clocks extends information theory by expressing the need to actively maintain communications channels, and potentially, to create or drop them. We show how networks of live clocks are presupposed by the concept of coordinates in a spacetime. A network serves as an organizing principle, even when the concept of the rigid body that anchors a special-relativistic coordinate system is inapplicable, as is the case, for example, in a generic curved spacetime.

  4. The Circadian Clock-Controlled Transcriptome of Developing Soybean Seeds.

    Science.gov (United States)

    A number of metabolic and physiological processes in plants are controlled by the circadian clock, which enables the plant to anticipate daily changes in the environment. Microarray expression profiling was used to identify circadian clock controlled genes expressed in developing soybean seeds. 1.8...

  5. Optimal Infinite Runs in One-Clock Priced Timed Automata

    DEFF Research Database (Denmark)

    David, Alexandre; Ejsing-Duun, Daniel; Fontani, Lisa; Larsen, Kim Guldstrand; Popescu, Vasile; Haubach Smedegård, Jacob

    We address the problem of finding an infinite run with the optimal cost-time ratio in a one-clock priced timed automaton and pro- vide an algorithmic solution. Through refinements of the quotient graph obtained by strong time-abstracting bisimulation partitioning, we con- struct a graph with time...... of the one-clock priced timed automaton....

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

    Science.gov (United States)

    Denny, Mark

    2010-01-01

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

  7. Circadian clock genes universally control key agricultural traits

    Science.gov (United States)

    Circadian clocks are endogenous timers that enable plants to synchronize biological processes with daily and seasonal environmental conditions in order to allocate resources during the most beneficial times of day and year. The circadian clock regulates a number of central plant activities, includin...

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Michael F Covington

    2007-08-01

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

  10. The role of biological clock in glucose homeostasis 

    Directory of Open Access Journals (Sweden)

    Piotr Chrościcki

    2013-06-01

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

  11. A Novel Method of Clock Synchronization in Distributed System

    Science.gov (United States)

    Li, G.; Niu, M. J.; Cai, Y. S.; Chen, X.; Ren, Y. Q.

    2016-03-01

    Time synchronization plays an important role in application of aircraft flying formation and constellation autonomous navigation, etc. In application of clock synchronization in the network system, it is not always true that each observed node may be interconnected, therefore, it is difficult to achieve time synchronization of network system with high precision in the condition that a certain node can only obtain the measurement information of clock from one of its corresponding neighbors, and cannot obtain from other nodes. According to this special problem, a novel method of high precision time synchronization of network system has been proposed. In this paper, we regard each clock as a node in the network system, and based on different distributed topology definition, the following three control algorithms of time synchronization under three circumstances have been designed: without a master clock (reference clock), with a master clock (reference clock), and with a fixed communication delay in the network system. The validity of the designed clock synchronization protocol has been proved both theoretically and through numerical simulation.

  12. From atomic clocks to coordinate times

    Science.gov (United States)

    Petit, G.

    2006-08-01

    The IAU'1991 Resolution A4, complemented by IAU'2000 Resolution B1.3-4, provide rigorous definitions for barycentric and geocentric reference systems in a relativistic framework and define the coordinate times of these systems as TCB and TCG, respectively. Other coordinate times in use are TT, defined from TCG through IAU'2000 Resolution B1.9, and TDB, whose rigorous definition from TCB is now proposed. For practical use, these coordinate times must be realized and the proper time provided by atomic clocks (Atomic time AT) is used to generate all coordinate times. The present sequence is AT => TT ||> TCG -> TCB ||> TDB, where the sign => indicates the complex series of operations involved in generating International atomic time TAI and where ||> is an exact transformation. The paper examines the uncertainty of realization of TAI and the uncertainty brought by the transformation TCG -> TCB. On-going and future evolutions of atomic clocks are reviewed along with their impact on the diagram of time transformations.

  13. The clock ambiguity: Implications and new developments

    CERN Document Server

    Albrecht, Andreas

    2008-01-01

    We consider the ambiguity associated with the choice of clock in time reparameterization invariant theories. This arbitrariness undermines the goal of prescribing a fixed set of physical laws, since a change of time variable can completely alter the predictions of the theory. We review the main features of the clock ambiguity and our earlier work on its implications for the emergence of physical laws in a statistical manner. We also present a number of new results: We show that (contrary to suggestions in our earlier work) time independent Hamiltonians may quite generally be assumed for laws of physics that emerge in this picture. We also further explore the degree to which the observed Universe can be well approximated by a random Hamiltonian. We discuss the possibility of predicting the dimensionality of space, and also relate the 2nd derivative of the density of states to the heat capacity of the Universe. This new work adds to the viability of our proposal that strong predictions for physical laws may eme...

  14. Bayesian networks with applications in reliability analysis

    OpenAIRE

    Langseth, Helge

    2002-01-01

    A common goal of the papers in this thesis is to propose, formalize and exemplify the use of Bayesian networks as a modelling tool in reliability analysis. The papers span work in which Bayesian networks are merely used as a modelling tool (Paper I), work where models are specially designed to utilize the inference algorithms of Bayesian networks (Paper II and Paper III), and work where the focus has been on extending the applicability of Bayesian networks to very large domains (Paper IV and ...

  15. An Integrated Architectural Clock Implemented Memory Design Analysis

    Directory of Open Access Journals (Sweden)

    Ravi Khatwal

    2015-07-01

    Full Text Available Recently Low power consumption and Custom Memory design is major issue for embedded designer. Micro wind and Xilinx simulator implements SRAM design architecture and performs efficient simulation. These simulators implements high performances and low power consumption of SRAM design. SRAM efficiency analyzed with 6-T architecture design and row/column based architectural design. We have analyzed clock implemented memory design and simulated with specific application. We have implemented clock based SRAM architecture that improves the internal clock efficiency of SRAM. Architectural Clock implemented memory design reduces the propagation delay and access time. Internal semiconductor material design implemented technique also improves the SRAM data transitions scheme. Semiconductor material and clock implemented design improve simulation performance of SRAM and these design implements for recently developed Application Specific Memory Design Architecture and mobile devices.

  16. The quantum beat principles and applications of atomic clocks

    CERN Document Server

    Major, F

    2007-01-01

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

  17. Multiple-bit-rate clock recovery circuit: theory

    International Nuclear Information System (INIS)

    The multiple-bit-rate clock recovery circuit has been recently proposed as a part of the communications packet switch. All packets must be the same length and be preceded by the frequency header, which is a number of consecutive ones (return-to-zero mode). The header is compared with the internal clock, and the result is used to set output clock frequency. The clock rate is defined by a number of fluxons propagating in ring oscillator, which is a close circular Josephson transmission line. The theory gives a bit rate bandwidth as a function of internal clock frequency, header length and silence time (maximum number of consecutive zeros in the packet). (author)

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

    International Nuclear Information System (INIS)

    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

  19. Clock-turning gait synthesis for humanoid robots

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2015-09-11

    In Einstein's general theory of relativity, time depends locally on gravity; in standard quantum theory, time is global-all clocks "tick" uniformly. We demonstrate a new tool for investigating time in the overlap of these two theories: a self-interfering clock, comprising two atomic spin states. We prepare the clock in a spatial superposition of quantum wave packets, which evolve coherently along two paths into a stable interference pattern. If we make the clock wave packets "tick" at different rates, to simulate a gravitational time lag, the clock time along each path yields "which path" information, degrading the pattern's visibility. In contrast, in standard interferometry, time cannot yield "which path" information. This proof-of-principle experiment may have implications for the study of time and general relativity and their impact on fundamental effects such as decoherence and the emergence of a classical world. PMID:26249229

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

    CERN Document Server

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

    2012-01-01

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

  2. The Retina and Other Light-sensitive Ocular Clocks.

    Science.gov (United States)

    Besharse, Joseph C; McMahon, Douglas G

    2016-06-01

    Ocular clocks, first identified in the retina, are also found in the retinal pigment epithelium (RPE), cornea, and ciliary body. The retina is a complex tissue of many cell types and considerable effort has gone into determining which cell types exhibit clock properties. Current data suggest that photoreceptors as well as inner retinal neurons exhibit clock properties with photoreceptors dominating in nonmammalian vertebrates and inner retinal neurons dominating in mice. However, these differences may in part reflect the choice of circadian output, and it is likely that clock properties are widely dispersed among many retinal cell types. The phase of the retinal clock can be set directly by light. In nonmammalian vertebrates, direct light sensitivity is commonplace among body clocks, but in mice only the retina and cornea retain direct light-dependent phase regulation. This distinguishes the retina and possibly other ocular clocks from peripheral oscillators whose phase depends on the pace-making properties of the hypothalamic central brain clock, the suprachiasmatic nuclei (SCN). However, in mice, retinal circadian oscillations dampen quickly in isolation due to weak coupling of its individual cell-autonomous oscillators, and there is no evidence that retinal clocks are directly controlled through input from other oscillators. Retinal circadian regulation in both mammals and nonmammalian vertebrates uses melatonin and dopamine as dark- and light-adaptive neuromodulators, respectively, and light can regulate circadian phase indirectly through dopamine signaling. The melatonin/dopamine system appears to have evolved among nonmammalian vertebrates and retained with modification in mammals. Circadian clocks in the eye are critical for optimum visual function where they play a role fine tuning visual sensitivity, and their disruption can affect diseases such as glaucoma or retinal degeneration syndromes. PMID:27095816

  3. The eCDR-PLL, a radiation-tolerant ASIC for clock and data recovery and deterministic phase clock synthesis

    International Nuclear Information System (INIS)

    A radiation-tolerant CDR/PLL ASIC has been developed for the upcoming LHC upgrades, featuring clock Frequency Multiplication (FM) and Clock and Data Recovery (CDR), showing deterministic phase and low jitter. Two FM modes have been implemented: either generating 40, 60, 120 and 240 MHz clock outputs for GBT-FPGA applications or providing 40, 80, 160 and 320 MHz clocks for TTC and e-link applications. The CDR operates with 40, 80, 160 or 320 Mbit/s data rates while always generating clocks at 40, 80, 160 and 320 MHz, regardless of the data rate. All the outputs are phase programmable with a resolution of 195 ps or 260 ps, depending on the selected mode. The ASIC has been designed using radiation-tolerant techniques in a 130 nm CMOS technology and operates at a 1.2 V supply voltage

  4. Bayesian Methods and Universal Darwinism

    Science.gov (United States)

    Campbell, John

    2009-12-01

    Bayesian methods since the time of Laplace have been understood by their practitioners as closely aligned to the scientific method. Indeed a recent Champion of Bayesian methods, E. T. Jaynes, titled his textbook on the subject Probability Theory: the Logic of Science. Many philosophers of science including Karl Popper and Donald Campbell have interpreted the evolution of Science as a Darwinian process consisting of a `copy with selective retention' algorithm abstracted from Darwin's theory of Natural Selection. Arguments are presented for an isomorphism between Bayesian Methods and Darwinian processes. Universal Darwinism, as the term has been developed by Richard Dawkins, Daniel Dennett and Susan Blackmore, is the collection of scientific theories which explain the creation and evolution of their subject matter as due to the Operation of Darwinian processes. These subject matters span the fields of atomic physics, chemistry, biology and the social sciences. The principle of Maximum Entropy states that Systems will evolve to states of highest entropy subject to the constraints of scientific law. This principle may be inverted to provide illumination as to the nature of scientific law. Our best cosmological theories suggest the universe contained much less complexity during the period shortly after the Big Bang than it does at present. The scientific subject matter of atomic physics, chemistry, biology and the social sciences has been created since that time. An explanation is proposed for the existence of this subject matter as due to the evolution of constraints in the form of adaptations imposed on Maximum Entropy. It is argued these adaptations were discovered and instantiated through the Operations of a succession of Darwinian processes.

  5. Bayesian Query-Focused Summarization

    CERN Document Server

    Daumé, Hal

    2009-01-01

    We present BayeSum (for ``Bayesian summarization''), a model for sentence extraction in query-focused summarization. BayeSum leverages the common case in which multiple documents are relevant to a single query. Using these documents as reinforcement for query terms, BayeSum is not afflicted by the paucity of information in short queries. We show that approximate inference in BayeSum is possible on large data sets and results in a state-of-the-art summarization system. Furthermore, we show how BayeSum can be understood as a justified query expansion technique in the language modeling for IR framework.

  6. Numeracy, frequency, and Bayesian reasoning

    Directory of Open Access Journals (Sweden)

    Gretchen B. Chapman

    2009-02-01

    Full Text Available Previous research has demonstrated that Bayesian reasoning performance is improved if uncertainty information is presented as natural frequencies rather than single-event probabilities. A questionnaire study of 342 college students replicated this effect but also found that the performance-boosting benefits of the natural frequency presentation occurred primarily for participants who scored high in numeracy. This finding suggests that even comprehension and manipulation of natural frequencies requires a certain threshold of numeracy abilities, and that the beneficial effects of natural frequency presentation may not be as general as previously believed.

  7. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...... intensity function, while the second approach is based on an underlying clustering and branching structure in the Hawkes process. For practical use, MCMC (Markov chain Monte Carlo) methods are employed. The two approaches are compared numerically using three examples of the Hawkes process....

  8. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    2013-01-01

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...... intensity function, while the second approach is based on an underlying clustering and branching structure in the Hawkes process. For practical use, MCMC (Markov chain Monte Carlo) methods are employed. The two approaches are compared numerically using three examples of the Hawkes process....

  9. Collaborative Kalman Filtration: Bayesian Perspective

    Czech Academy of Sciences Publication Activity Database

    Dedecius, Kamil

    Lisabon, Portugalsko: Institute for Systems and Technologies of Information, Control and Communication (INSTICC), 2014, s. 468-474. ISBN 978-989-758-039-0. [11th International Conference on Informatics in Control, Automation and Robotics - ICINCO 2014. Vien (AT), 01.09.2014-03.09.2014] R&D Projects: GA ČR(CZ) GP14-06678P Institutional support: RVO:67985556 Keywords : Bayesian analysis * Kalman filter * distributed estimation Subject RIV: BB - Applied Statistics, Operational Research http://library.utia.cas.cz/separaty/2014/AS/dedecius-0431324.pdf

  10. Modeling the emergence of circadian rhythms in a clock neuron network.

    Directory of Open Access Journals (Sweden)

    Luis Diambra

    Full Text Available 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.

  11. Sleep disturbances and circadian CLOCK genes in borderline personality disorder.

    Science.gov (United States)

    Fleischer, Monika; Schäfer, Michael; Coogan, Andrew; Häßler, Frank; Thome, Johannes

    2012-10-01

    Borderline personality disorder (BPD) is characterised by a deep-reaching pattern of affective instability, incoherent identity, self-injury, suicide attempts, and disturbed interpersonal relations and lifestyle. The daily activities of BPD patients are often chaotic and disorganized, with patients often staying up late while sleeping during the day. These behavioural patterns suggest that altered circadian rhythms may be associated with BPD. Furthermore, BPD patients frequently report suffering from sleep disturbances. In this review, we overview the evidence that circadian rhythms and sleep are disturbed in BPD, and we explore the possibility that personality traits that are pertinent for BPD may be associated with circadian typology, and perhaps to circadian genotypes. With regards to sleep architecture, we review the evidence that BPD patients display altered non-REM and REM sleep. A possible cue to a deeper understanding of this temporal dysregulation might be an analysis of the circadian clock at the molecular and cellular level, as well as behavioural studies using actigraphy and we suggest avenues for further exploration of these factors. PMID:22806005

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

    Science.gov (United States)

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

    2016-01-19

    Circadian rhythms with an endogenous period close to or equal to the natural light-dark cycle are considered evolutionarily adaptive ("circadian resonance hypothesis"). Despite remarkable insight into the molecular mechanisms driving circadian cycles, this hypothesis has not been tested under natural conditions for any eukaryotic organism. We tested this hypothesis in mice bearing a short-period mutation in the enzyme casein kinase 1ε (tau mutation), which accelerates free-running circadian cycles. We compared daily activity (feeding) rhythms, survivorship, and reproduction in six replicate populations in outdoor experimental enclosures, established with wild-type, heterozygous, and homozygous mice in a Mendelian ratio. In the release cohort, survival was reduced in the homozygote mutant mice, revealing strong selection against short-period genotypes. Over the course of 14 mo, the relative frequency of the tau allele dropped from initial parity to 20%. Adult survival and recruitment of juveniles into the population contributed approximately equally to the selection for wild-type alleles. The expression of activity during daytime varied throughout the experiment and was significantly increased by the tau mutation. The strong selection against the short-period tau allele observed here contrasts with earlier studies showing absence of selection against a Period 2 (Per2) mutation, which disrupts internal clock function, but does not change period length. These findings are consistent with, and predicted by the theory that resonance of the circadian system plays an important role in individual fitness. PMID:26715747

  13. Bayesian credible interval construction for Poisson statistics

    Institute of Scientific and Technical Information of China (English)

    ZHU Yong-Sheng

    2008-01-01

    The construction of the Bayesian credible (confidence) interval for a Poisson observable including both the signal and background with and without systematic uncertainties is presented.Introducing the conditional probability satisfying the requirement of the background not larger than the observed events to construct the Bayesian credible interval is also discussed.A Fortran routine,BPOCI,has been developed to implement the calculation.

  14. Bayesian Decision Theoretical Framework for Clustering

    Science.gov (United States)

    Chen, Mo

    2011-01-01

    In this thesis, we establish a novel probabilistic framework for the data clustering problem from the perspective of Bayesian decision theory. The Bayesian decision theory view justifies the important questions: what is a cluster and what a clustering algorithm should optimize. We prove that the spectral clustering (to be specific, the…

  15. Bayesian Statistics for Biological Data: Pedigree Analysis

    Science.gov (United States)

    Stanfield, William D.; Carlton, Matthew A.

    2004-01-01

    The use of Bayes' formula is applied to the biological problem of pedigree analysis to show that the Bayes' formula and non-Bayesian or "classical" methods of probability calculation give different answers. First year college students of biology can be introduced to the Bayesian statistics.

  16. Using Bayesian Networks to Improve Knowledge Assessment

    Science.gov (United States)

    Millan, Eva; Descalco, Luis; Castillo, Gladys; Oliveira, Paula; Diogo, Sandra

    2013-01-01

    In this paper, we describe the integration and evaluation of an existing generic Bayesian student model (GBSM) into an existing computerized testing system within the Mathematics Education Project (PmatE--Projecto Matematica Ensino) of the University of Aveiro. This generic Bayesian student model had been previously evaluated with simulated…

  17. Nonparametric Bayesian Modeling of Complex Networks

    DEFF Research Database (Denmark)

    Schmidt, Mikkel Nørgaard; Mørup, Morten

    2013-01-01

    Modeling structure in complex networks using Bayesian nonparametrics makes it possible to specify flexible model structures and infer the adequate model complexity from the observed data. This article provides a gentle introduction to nonparametric Bayesian modeling of complex networks: Using...... for complex networks can be derived and point out relevant literature....

  18. Compiling Relational Bayesian Networks for Exact Inference

    DEFF Research Database (Denmark)

    Jaeger, Manfred; Chavira, Mark; Darwiche, Adnan

    2004-01-01

    We describe a system for exact inference with relational Bayesian networks as defined in the publicly available \\primula\\ tool. The system is based on compiling propositional instances of relational Bayesian networks into arithmetic circuits and then performing online inference by evaluating and ...

  19. Compiling Relational Bayesian Networks for Exact Inference

    DEFF Research Database (Denmark)

    Jaeger, Manfred; Darwiche, Adnan; Chavira, Mark

    We describe in this paper a system for exact inference with relational Bayesian networks as defined in the publicly available PRIMULA tool. The system is based on compiling propositional instances of relational Bayesian networks into arithmetic circuits and then performing online inference by eva...

  20. Bayesian analysis of exoplanet and binary orbits

    CERN Document Server

    Schulze-Hartung, Tim; Henning, Thomas

    2012-01-01

    We introduce BASE (Bayesian astrometric and spectroscopic exoplanet detection and characterisation tool), a novel program for the combined or separate Bayesian analysis of astrometric and radial-velocity measurements of potential exoplanet hosts and binary stars. The capabilities of BASE are demonstrated using all publicly available data of the binary Mizar A.