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Sample records for biological clocks

  1. Resetting Biological Clocks

    Science.gov (United States)

    Winfree, Arthur T.

    1975-01-01

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

  2. Biological clocks: riding the tides.

    Science.gov (United States)

    de la Iglesia, Horacio O; Johnson, Carl Hirschie

    2013-10-21

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

  3. Researchers Discover Plants Biological Clock

    Institute of Scientific and Technical Information of China (English)

    王全良

    1996-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  5. Maternal feeding controls fetal biological clock.

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    Hidenobu Ohta

    Full Text Available BACKGROUND: It is widely accepted that circadian physiological rhythms of the fetus are affected by oscillators in the maternal brain that are coupled to the environmental light-dark (LD cycle. METHODOLOGY/PRINCIPAL FINDINGS: To study the link between fetal and maternal biological clocks, we investigated the effects of cycles of maternal food availability on the rhythms of Per1 gene expression in the fetal suprachiasmatic nucleus (SCN and liver using a transgenic rat model whose tissues express luciferase in vitro. Although the maternal SCN remained phase-locked to the LD cycle, maternal restricted feeding phase-advanced the fetal SCN and liver by 5 and 7 hours respectively within the 22-day pregnancy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that maternal feeding entrains the fetal SCN and liver independently of both the maternal SCN and the LD cycle. This indicates that maternal-feeding signals can be more influential for the fetal SCN and particular organ oscillators than hormonal signals controlled by the maternal SCN, suggesting the importance of a regular maternal feeding schedule for appropriate fetal molecular clockwork during pregnancy.

  6. The role of biological clock in glucose homeostasis 

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    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

  7. Putative melatonin receptors in a human biological clock

    Energy Technology Data Exchange (ETDEWEB)

    Reppert, S.M.; Weaver, D.R.; Rivkees, S.A.; Stopa, E.G.

    1988-10-07

    In vitro autoradiography with /sup 125/I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific /sup 125/I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific /sup 125/I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific /sup 125/I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.

  8. Chronobiology: biological clocks and rhythms of the skin.

    Science.gov (United States)

    Mehling, A; Fluhr, J W

    2006-01-01

    The cyclicity of time affects virtually all aspects of our being and is the basis of the underlying rhythmicity which is typical of our lives. To 'tell time', most living organisms use internal timing mechanisms known as 'biological clocks'. These 'clocks' coordinate our physiological and behavioral functions and interactions with our environment. One of the strongest influences on rhythmicity is the solar day. The study of these temporal rhythms in biological systems has been coined chronobiology. With the present article we aim to give an overview on chronobiology. Examples of chronobiological effects on skin will be described. Particular emphasis will be placed on circadian rhythms (including rhythms that take place within a 24-hour period, including so-called infradian and/or diurnal rhythms) but also on seasonal variations (circaannual rhythms).

  9. Positive temporal dependence of the biological clock implies hyperbolic discounting

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    Debajyoti eRay

    2011-01-01

    Full Text Available Temporal preferences of animals and humans often exhibit inconsistencies, whereby an earlier, smaller reward may be preferred when it occurs immediately but not when it is delayed. Such choices reflect hyperbolic discounting of future rewards, rather than the exponential discounting required for temporal consistency. Simultaneously, however, evidence has emerged that suggests that animals and humans have an internal representation of time that often differs from the calendar time used in detection of temporal inconsistencies. Here, we prove that temporal inconsistencies emerge if fixed durations in calendar time are experienced as positively related (positive quadrant dependent. Hence, what are time-consistent choices within the time framework of the decision maker appear as time-inconsistent to an outsider who analyzes choices in calendar time. As the biological clock becomes more variable, the fit of the hyperbolic discounting model improves. A recent alternative explanation for temporal choice inconsistencies builds on persistent under-estimation of the length of distant time intervals. By increasing the expected speed of our stochastic biological clock for time farther into the future, we can emulate this explanation. Ours is therefore an encompassing theoretical framework that predicts context-dependent degrees of intertemporal choice inconsistencies, to the extent that context can generate changes in autocorrelation, variability, and expected speed of the biological clock. Our finding should lead to novel experiments that will clarify the role of time perception in impulsivity, with critical implications for, among others, our understanding of aging, drug abuse and pathological gambling.

  10. Peripheral Skin Temperature and Circadian Biological Clock in Shift Nurses after a Day off.

    Science.gov (United States)

    Bracci, Massimo; Ciarapica, Veronica; Copertaro, Alfredo; Barbaresi, Mariella; Manzella, Nicola; Tomasetti, Marco; Gaetani, Simona; Monaco, Federica; Amati, Monica; Valentino, Matteo; Rapisarda, Venerando; Santarelli, Lory

    2016-04-26

    The circadian biological clock is essentially based on the light/dark cycle. Some people working with shift schedules cannot adjust their sleep/wake cycle to the light/dark cycle, and this may result in alterations of the circadian biological clock. This study explored the circadian biological clock of shift and daytime nurses using non-invasive methods. Peripheral skin temperature, cortisol and melatonin levels in saliva, and Per2 expression in pubic hair follicle cells were investigated for 24 h after a day off. Significant differences were observed in peripheral skin temperature and cortisol levels between shift and daytime nurses. No differences in melatonin levels were obtained. Per2 maximum values were significantly different between the two groups. Shift nurses exhibited lower circadian variations compared to daytime nurses, and this may indicate an adjustment of the circadian biological clock to continuous shift schedules. Non-invasive procedures, such as peripheral skin temperature measurement, determination of cortisol and melatonin in saliva, and analysis of clock genes in hair follicle cells, may be effective approaches to extensively study the circadian clock in shift workers.

  11. Peripheral Skin Temperature and Circadian Biological Clock in Shift Nurses after a Day off

    Directory of Open Access Journals (Sweden)

    Massimo Bracci

    2016-04-01

    Full Text Available The circadian biological clock is essentially based on the light/dark cycle. Some people working with shift schedules cannot adjust their sleep/wake cycle to the light/dark cycle, and this may result in alterations of the circadian biological clock. This study explored the circadian biological clock of shift and daytime nurses using non-invasive methods. Peripheral skin temperature, cortisol and melatonin levels in saliva, and Per2 expression in pubic hair follicle cells were investigated for 24 h after a day off. Significant differences were observed in peripheral skin temperature and cortisol levels between shift and daytime nurses. No differences in melatonin levels were obtained. Per2 maximum values were significantly different between the two groups. Shift nurses exhibited lower circadian variations compared to daytime nurses, and this may indicate an adjustment of the circadian biological clock to continuous shift schedules. Non-invasive procedures, such as peripheral skin temperature measurement, determination of cortisol and melatonin in saliva, and analysis of clock genes in hair follicle cells, may be effective approaches to extensively study the circadian clock in shift workers.

  12. Biological clocks and regulation of seasonal reproduction and migration in birds.

    Science.gov (United States)

    Kumar, Vinod; Wingfield, John C; Dawson, Alistair; Ramenofsky, Marilyn; Rani, Sangeeta; Bartell, Paul

    2010-01-01

    Timekeeping is important at two levels: to time changes in physiology and behavior within each day and within each year. For the former, birds have a system of at least three independent circadian clocks present in the retina of the eyes, the pineal gland, and the hypothalamus. This differs from the situation in mammals in which the input, pacemaker, and output are localized in different structures. Each bird clock interacts with at least one other clock, and together, they appear to form a centralized clock system that keeps daily time. These clocks have a powerful endogenous component, and the daily light-dark cycle entrains them to 24 h. The timing and duration of life history stages that make up annual cycle of an individual must also be controlled by some form of timekeeping. However, evidence for the existence of an equivalent endogenous circannual clock is less clear. Environmental cues, particularly photoperiod, appear to have a more direct role than simply entraining the clock to calendar time. For example, the timing of migration is probably greatly influenced by photoperiod, but its manifestation each day, as Zugunruhe, appears to be under circadian control. Migration involves marked changes in physiology to cope with the energetic demands. There is still much that we do not know about how organisms' timekeeping systems respond to their natural environment, particularly how salient signals from the environment are perceived and then transduced into appropriately timed biological functions. However, given that changes in environmental input affects the clock, increasing human disturbance of the environment is likely to adversely affect these systems.

  13. Extreme violation of sleep hygiene: sleeping against the biological clock during a multiday relay event

    NARCIS (Netherlands)

    van Maanen, A.; Roest, B.; Moen, M.; Oort, F.; Vergouwen, P.; Paul, I; Groenenboom, P.; Smits, M.

    2015-01-01

    Background: Sleep hygiene is important for sleep quality and optimal performance during the day. However, it is not always possible to follow sleep hygiene requirements. In multiday relay events, athletes have to sleep immediately after physical exertion and sometimes against their biological clock.

  14. The male biological clock is ticking: a review of the literature.

    Science.gov (United States)

    Pasqualotto, Fabio Firmbach; Borges Júnior, Edson; Pasqualotto, Eleonora Bedin

    2008-05-01

    The term biological clock is usually used by physicians and psychologists to refer to the declining fertility, increasing risk of fetal birth defects and alterations to hormone levels experienced by women as they age. Female fecundity declines slowly after the age of 30 years and more rapidly after 40 and is considered the main limiting factor in treating infertility. However, there are several scientific reports, chapters in books and review articles suggesting that men may also have a biological clock. The aim of our study was to conduct a review of the literature, based on the Medical Literature Analysis and Retrieval System Online (Medline), to evaluate the male biological clock. After adjustments for other factors, the data demonstrate that the likelihood that a fertile couple will take more than 12 months to conceive nearly doubles from 8% when the man is 35 years old. Thus, paternal age is a further factor to be taken into account when deciding on the prognosis for infertile couples. Also, increasing male age is associated with a significant decline in fertility (five times longer to achieve pregnancy at the age of 45 years). Patients and their physicians therefore need to understand the effects of the male biological clock on sexual and reproductive health, in that it leads to erectile dysfunction and male infertility, as well as its potential implications for important medical conditions such as diabetes and cardiovascular diseases.

  15. The biological clock is regulated by adrenergic signaling in brown fat but is dispensable for cold-induced thermogenesis.

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    Siming Li

    Full Text Available The biological clock plays an important role in integrating nutrient and energy metabolism with other cellular processes. Previous studies have demonstrated that core clock genes are rhythmically expressed in peripheral tissues, including the liver, skeletal muscle, pancreatic islets, and white and brown adipose tissues. These peripheral clocks are entrained by physiological cues, thereby aligning the circadian pacemaker to tissue functions. The mechanisms that regulate brown adipose tissue clock in response to physiological signals remain poorly understood. Here we found that the expression of core clock genes is highly responsive to cold exposure in brown fat, but not in white fat. This cold-inducible regulation of the clock network is mediated by adrenergic receptor activation and the transcriptional coactivator PGC-1α. Brown adipocytes in mice lacking a functional clock contain large lipid droplets accompanied by dysregulation of genes involved in lipid metabolism and adaptive thermogenesis. Paradoxically, the "clockless" mice were competent in maintaining core body temperature during cold exposure. These studies elucidated the presence of adrenergic receptor/clock crosstalk that appears to be required for normal thermogenic gene expression in brown fat.

  16. Diurnal rhythms in neurexins transcripts and inhibitory/excitatory synapse scaffold proteins in the biological clock.

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    Mika Shapiro-Reznik

    Full Text Available The neurexin genes (NRXN1/2/3 encode two families (α and β of highly polymorphic presynaptic proteins that are involved in excitatory/inhibitory synaptic balance. Recent studies indicate that neuronal activation and memory formation affect NRXN1/2/3α expression and alternative splicing at splice sites 3 and 4 (SS#3/SS#4. Neurons in the biological clock residing in the suprachiasmatic nuclei of the hypothalamus (SCN act as self-sustained oscillators, generating rhythms in gene expression and electrical activity, to entrain circadian bodily rhythms to the 24 hours day/night cycles. Cell autonomous oscillations in NRXN1/2/3α expression and SS#3/SS#4 exons splicing and their links to rhythms in excitatory/inhibitory synaptic balance in the circadian clock were explored. NRXN1/2/3α expression and SS#3/SS#4 splicing, levels of neurexin-2α and the synaptic scaffolding proteins PSD-95 and gephyrin (representing excitatory and inhibitory synapses, respectively were studied in mRNA and protein extracts obtained from SCN of C3H/J mice at different times of the 24 hours day/night cycle. Further studies explored the circadian oscillations in these components and causality relationships in immortalized rat SCN2.2 cells. Diurnal rhythms in mNRXN1α and mNRXN2α transcription, SS#3/SS#4 exon-inclusion and PSD-95 gephyrin and neurexin-2α levels were found in the SCN in vivo. No such rhythms were found with mNRXN3α. SCN2.2 cells also exhibited autonomous circadian rhythms in rNRXN1/2 expression SS#3/SS#4 exon inclusion and PSD-95, gephyrin and neurexin-2α levels. rNRXN3α and rNRXN1/2β were not expressed. Causal relationships were demonstrated, by use of specific siRNAs, between rNRXN2α SS#3 exon included transcripts and gephyrin levels in the SCN2.2 cells. These results show for the first time dynamic, cell autonomous, diurnal rhythms in expression and splicing of NRXN1/2 and subsequent effects on the expression of neurexin-2α and postsynaptic

  17. Extreme Violation of Sleep Hygiene: Sleeping Against the Biological Clock During a Multiday Relay Event

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    van Maanen

    2015-12-01

    Full Text Available Background Sleep hygiene is important for sleep quality and optimal performance during the day. However, it is not always possible to follow sleep hygiene requirements. In multiday relay events, athletes have to sleep immediately after physical exertion and sometimes against their biological clock. Objectives In this pilot study we investigated the effect of having to sleep at an abnormal circadian time on sleep duration. Patients and Methods Eight runners and two cyclists performing a 500 km relay race were followed. They were divided into two groups that took turns in running and resting. Each group ran four times for approximately five hours while the other group slept. As a result, sleep times varied between normal and abnormal times. All athletes wore actigraphs to record the duration and onset of sleep. Results Linear mixed model analyses showed that athletes slept on average 43 minutes longer when they slept during usual (night times than during abnormal (day times. In general, sleep duration decreased during the race with on average 18 minutes per period. Conclusions This pilot study shows that, even under extreme violation of sleep hygiene rules, there still is an apparent effect of circadian rhythm on sleep duration in relay race athletes.

  18. Watch the clock-engineering biological systems to be on time.

    Science.gov (United States)

    Aubel, Dominique; Fussenegger, Martin

    2010-12-01

    Inspired by natural time-keeping devices controlling the circadian clock, managing information processing in the brain and coordinating physiological activities on a daily (feeding and sleeping) or seasonal timescale (reproductive activity or hibernation), synthetic biologists have successfully assembled functional synthetic clocks from cataloged genetic components with standardized activities and arranging them in transcription circuits containing positive and negative feedback loops with integrated time-delay dynamics. While the positive feedback loop drives the clock like the (balance) spring in a mechanical watch the negative time-delay circuit represents the pulse generator defining a minimal time unit and precision of the clock like the pendulum fallback or the movement of the balance wheel in a classical mechanic watch. This basic design principle enabled the construction of a variety of synthetic oscillators whose design details are concisely covered in this review.

  19. 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.

  20. The biological clock modulates the human cortisol response in a multiplicative fashion

    NARCIS (Netherlands)

    van de Werken, Maan; Booij, Sanne H.; van der Zwan, J Esi; Simons, Mirre J. P.; Gordijn, Marijke C. M.; Beersma, Domien G. M.

    2014-01-01

    Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol resp

  1. Biological clocks in the duodenum and the diurnal regulation of duodenal and plasma serotonin.

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    Elizabeth Ebert-Zavos

    Full Text Available Serotonin in blood plasma is primarily synthesized in the duodenum, as brain derived serotonin does not cross the blood-brain barrier. Because serotonin in the brain and retina is synthesized under the control of a circadian clock, we sought to determine if a circadian clock in the duodenum regulates serotonin synthesis and release in blood. We examined gene expression in the duodenum of chickens at different times of the day and found that the duodenum rhythmically expresses molecular circadian clock genes and genes controlling serotonin biosynthesis, specifically tryptophan hydroxylase, in a light dark cycle (LD. Analysis of the duodenum and blood plasma showed that the amount of serotonin in the duodenum varies across the day and that serotonin profiles in blood plasma are also rhythmic in LD, but were not rhythmic in constant darkness. Because serotonin in the gut affects duodenal nutrient absorption and gut motility, the control of serotonin production in the duodenum by LD cycles could provide an additional mechanism by which the external environment controls nutrient uptake and digestive function. The diurnal regulation of plasma serotonin may also serve as an additional biochemical signal in the blood encoding time and could be used by target tissues to indicate the status of nutrient absorption.

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

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    Christy Anna Hipsley

    2014-05-01

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

  3. Beyond fossil calibrations: realities of molecular clock practices in evolutionary biology.

    Science.gov (United States)

    Hipsley, Christy A; Müller, Johannes

    2014-01-01

    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 in 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 in methodological evaluations. 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

  4. 生物钟基因研究进展%Progress in the Studies of Biological Clocks Genes

    Institute of Scientific and Technical Information of China (English)

    徐军; 童建

    2001-01-01

    Circadian rhythms describe biological phenomena that oscillate with an 24 hour cycle. These rhythms include blood pressure, body temperature, hormone level, the number of immune cells in blood, and the sleep-wake cycle. The aim is to introduce common genes between species that are responsible for determining the circadian behavior, especially some transcription factor s that serve to regulate many circadian rhythm genes. And the common molecular mechanism of biological clocks between fly and human will be in troduced.%昼夜节律是以大约24 h为周期波动的生物现象.这些节律包括血压、体温 、激素水平、血中免疫细胞的数量、睡眠觉醒周期循环等.基因水平上的昼夜节律研究还只 是刚起步,介绍不同物种控制昼夜行为的共同基因(如period 、timless 、clock基因 等)的研究进展,特别是一些有关调控昼夜节律基因的转录因子的研究.同时讨论果蝇和人 类生物钟调节的共同分子机制.

  5. Circadian clocks and breast cancer

    OpenAIRE

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

    2016-01-01

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

  6. cGMP-phosphodiesterase inhibition enhances photic responses and synchronization of the biological circadian clock in rodents.

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    Santiago A Plano

    Full Text Available The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN and is synchronized by several environmental stimuli, mainly the light-dark (LD cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2. The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC, cGMP and its related protein kinase (PKG. Pharmacological manipulation of cGMP by phosphodiesterase (PDE inhibition (e.g., sildenafil increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions.

  7. 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

  8. A circadian clock in Saccharomyces cerevisiae

    NARCIS (Netherlands)

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

    2010-01-01

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

  9. Clock Genes in Glia Cells

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    Chi-Castañeda, Donají

    2016-01-01

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

  10. Einstein's Clocks and Langevin's Twins

    CERN Document Server

    Weinstein, Galina

    2012-01-01

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

  11. "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…

  12. The circadian clock coordinates ribosome biogenesis.

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    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.

  13. Clocks and cardiovascular function

    Science.gov (United States)

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

    2016-01-01

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

  14. Metabolic regulation of circadian clocks.

    Science.gov (United States)

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

    2013-05-01

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

  15. Lego clocks: building a clock from parts.

    Science.gov (United States)

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

    2008-06-01

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

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

    OpenAIRE

    Johnson, Carl Hirschie

    2010-01-01

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

  17. 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.

  18. Changes of biological clock protein in neonatal rats with hypoxic-ischemic brain damage%缺氧缺血性脑损伤新生大鼠松果体钟基因表达的变化

    Institute of Scientific and Technical Information of China (English)

    李永富; 金美芳; 孙斌; 冯星

    2013-01-01

    Objective To study the effects of biological clock protein on circadian disorders in hypoxic-ischemic brain damage ( HIBD) by examining levels of CLOCK and BMAL1 proteins in the pineal gland of neonatal rats. Methods Seventy-two 7-day-old Sprague-Dawley (SD) rats were randomly divided into sham-operated and HIBD groups. HIBD model was prepared according to the modified Levine method. Western blot analysis was used to measure the levels of CLOCK and BMAL1 in the pineal gland at 0, 2, 12, 24, 36 and 48 hours after operation. Results Both CLOCK and BMAL levels in the pineal gland increased significantly 48 hours after HIBD compared with the sham-operated group ( P 0. 05 ) . Conclusions Levels of CLOCK and BMAL1 proteins in the pineal gland of rats increase significantly 48 hours after HIBD, suggesting that both CLOCK and BMAL1 may be involved the regulatory mechanism of circadian disorders in rats with HIBD.%目的 观察缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)新生大鼠松果体中CLOCK、BMAL1蛋白表达的变化,探讨钟基因表达异常在HIBD导致的昼夜节律紊乱中的作用.方法 72只7日龄新生Sprague-Dawley大鼠随机分为假手术组与HIBD模型组,每组36只.采用改良Levine法建立HIBD模型,用Western blot方法测定两组新生大鼠术后0、2、12、24、36、48 h松果体中CLOCK、BMAL1蛋白水平.结果 HIBD模型组松果体的CLOCK及BMAL1蛋白表达水平在HIBD后48 h高于假手术组(P<0.05),在0、2、12、24、36 h CLOCK及BMAL1蛋白表达水平与假手术组相比差异均无统计学意义(P>0.05).结论 HIBD新生大鼠松果体中CLOCK和BMAL1蛋白在损伤48 h后有显著升高,提示两者可能共同参与缺氧缺血时昼夜节律紊乱的发生.

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Optimizing passive quantum clocks

    Science.gov (United States)

    Mullan, Michael; Knill, Emanuel

    2014-10-01

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

  1. Optical clock networks

    Science.gov (United States)

    Riehle, Fritz

    2017-01-01

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

  2. The molecular clock as a metabolic rheostat.

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

    Ho, Simon Y W; Duchêne, Sebastián

    2014-12-01

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

  4. Circadian clock circuitry in colorectal cancer.

    Science.gov (United States)

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

    2014-04-21

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

  5. Transcriptional repressor PRR5 directly regulates clock-output pathways

    OpenAIRE

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

    2012-01-01

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

  6. Precision Clock Evaluation Facility

    Data.gov (United States)

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

  7. Clocked combustor can array

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-17

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

  8. 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.

  9. Zebrafish circadian clocks: cells that see light.

    Science.gov (United States)

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

    2005-11-01

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

  10. Adipose Clocks: Burning the Midnight Oil.

    Science.gov (United States)

    Henriksson, Emma; Lamia, Katja A

    2015-10-01

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

  11. Optical Lattice Clocks

    Science.gov (United States)

    Oates, Chris

    2012-06-01

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

  12. Clock genes, chronotypes and diseases

    Directory of Open Access Journals (Sweden)

    Bogdan I. Voinescu

    2009-08-01

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

  13. Optical Clocks and Relativity

    Science.gov (United States)

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

    2010-09-01

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

  14. Circadian clocks - from genes to complex behaviour

    NARCIS (Netherlands)

    Roenneberg, Till; Merrow, Martha

    1999-01-01

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

  15. 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...

  16. Biogeographic calibrations for the molecular clock.

    Science.gov (United States)

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

    2015-09-01

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

  17. 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.

  18. 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.

  19. Relativistic quantum clocks

    CERN Document Server

    Lock, Maximilian P E

    2016-01-01

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

  20. SRC: Smart Reminder Clock

    Science.gov (United States)

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

    2016-11-01

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

  1. 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.

  2. Cyclotomic quantum clock

    CERN Document Server

    Rosu, H C

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nakahata Yasukazu

    2004-10-01

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

  4. Postnatal ontogenesis of molecular clock in mouse striatum.

    Science.gov (United States)

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

    2009-04-01

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

  5. Relativity and Al^+ Optical Clocks

    Science.gov (United States)

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

    2010-03-01

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

  6. Round the clock librarianship

    OpenAIRE

    1995-01-01

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

  7. Living by the clock: the circadian pacemaker in older people.

    NARCIS (Netherlands)

    Hofman, M.A.; Swaab, D.F.

    2006-01-01

    The suprachiasmatic nucleus (SCN) of the hypothalamus is considered to be a critical component of a neural oscillator system implicated in the timing of a wide variety of biological processes. The circadian cycles established by this biological clock occur throughout nature and have a period of appr

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

    Directory of Open Access Journals (Sweden)

    Taishi Yoshii

    2009-04-01

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

  9. Microchip-Based Trapped-Atom Clocks

    CERN Document Server

    Vuletic, Vladan; Schleier-Smith, Monika H

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ron C Anafi

    2014-04-01

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

  11. 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…

  12. A mixed relaxed clock model

    Science.gov (United States)

    2016-01-01

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

  13. Comparison of Circadian Expression of Biological Clock Gene,Clock and Bmal 1 ,in Peripheral Blood Lymphocytes of Chinese Antarctic Wintering Team Members before and after Antarctic Expedition%中国南极越冬队员外周血生物钟基因Clock和Bmal1昼夜性节律表达赴南极前后对比

    Institute of Scientific and Technical Information of China (English)

    余万霰; 陈绍平; 夏艳芝; 王国卿; 王洁; 张永虹

    2012-01-01

    目的 观察中国南极考察队越冬队员外周血淋巴细胞钟基因Clock和Bmal 1表达昼夜节律性变化.方法 在中国第25次南极考察队越冬队员中选择8名队员,平均年龄38岁,均为男性,在1个昼夜周期内设立6个时点(ZT):02:00、06:00、10:00、14:00、18:00和22:00,每一时点采集外周静脉血6 mL,采集赴南极前后2组血样.用实时定量RT-PCR方法,测定不同昼夜时点(ZT)样品中核心钟基因Clock和Bmal 1的mRNA表达量,通过余弦法和Clock Lab软件获取节律参数,进行赴南极前后对比.结果 赴南极前,8个样本Clock和Bmal的mRNA表达均有显著昼夜节律特征(P<0.05),Clock的峰值相位位于-335.85士13.80,Bmal 1的峰值相位位于-307.12±8.17.赴南极后,仅2例Clock和3例Bmal1表达还存在显著昼夜节律变化.Clock的峰值相位移位到-42.28±5.27,Bmal 1的同峰值相位移位到-184.58±29.58.结论 南极特殊周期环境对人体生物钟基因表达的昼夜节律会产生影响.%Objective To investigate the circadian expression of core clock gene, Clock and Bmal 1 ,in the peripheral blood lymphocytes of Chinese scientific expeditioners during the Antarctic winter. Methods Peripheral blood (6 mL) were collected in 8 healthy male volunteers (mean age 38 years) from wintering team of the 25th Chinese Antarctic Research Expedition at 6 time points in the day-night cycle (02: 00,06:00,10; 00,14:00,18:00 and 22:00). In addition, blood samples were collected before and after Antarctic expedition. The expression of Clock and Bmal 1 at different Zeitgeber times (ZT) was detected by RT-PCR. The circadian parameters were obtained and analyzed by the cosine function,Clock Lab software and amplitude F test for comparison before and after Antarctic expedition. Results Before Antarctic expedition,the expression of Clock and Bmal 1 mRNA showed a significant circadian feature(P<0. 05). The Peak phase of Clock at -335. 85±13. 80. The Peak phase of Bmal 1 at -307. 12

  14. Protein phosphatase 1 (PP1 is a post-translational regulator of the mammalian circadian clock.

    Directory of Open Access Journals (Sweden)

    Isabelle Schmutz

    Full Text Available Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set of clock genes generate and maintain these rhythms with a period of about 24 hours. Many clock proteins undergo circadian cycles of post-translational modifications. Among these modifications, protein phosphorylation plays an important role in regulating activity, stability and intracellular localization of clock components. Several protein kinases were characterized as regulators of the circadian clock. However, the function of protein phosphatases, which balance phosphorylation events, in the mammalian clock mechanism is less well understood. Here, we identify protein phosphatase 1 (PP1 as regulator of period and light-induced resetting of the mammalian circadian clock. Down-regulation of PP1 activity in cells by RNA interference and in vivo by expression of a specific inhibitor in the brain of mice tended to lengthen circadian period. Moreover, reduction of PP1 activity in the brain altered light-mediated clock resetting behavior in mice, enhancing the phase shifts in either direction. At the molecular level, diminished PP1 activity increased nuclear accumulation of the clock component PER2 in neurons. Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock.

  15. Rethinking transcriptional activation in the Arabidopsis circadian clock.

    Directory of Open Access Journals (Sweden)

    Karl Fogelmark

    2014-07-01

    Full Text Available Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops.

  16. Rethinking transcriptional activation in the Arabidopsis circadian clock.

    Science.gov (United States)

    Fogelmark, Karl; Troein, Carl

    2014-07-01

    Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops.

  17. Clocks around Sgr A*

    CERN Document Server

    Angélil, Raymond

    2014-01-01

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

  18. Enhanced Phenotyping of Complex Traits with a Circadian Clock Model

    NARCIS (Netherlands)

    Merrow, Martha; Roenneberg, Till

    2005-01-01

    Models of biological systems are increasingly used to generate and test predictions in silico. This article explores the basic workings of a multifeedback network model of a circadian clock. In a series of in silico experiments, we investigated the influence of the number of feedbacks by adding and

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

    Science.gov (United States)

    2010-11-01

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

  20. 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...

  1. 'The clocks that time us'-circadian rhythms in neurodegenerative disorders

    NARCIS (Netherlands)

    Videnovic, A.; Lazar, A.S.; Barker, R.A.; Overeem, S.

    2014-01-01

    Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep-wake homeostasis. Impaired sleep and alertness are common symptoms of neurodeg

  2. Role of circadian gene Clock during differentiation of mouse pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Chao Lu

    2016-09-01

    Full Text Available Abstract Biological rhythms controlled by the circadian clock are absent in embryonic stem cells (ESCs. However, they start to develop during the differentiation of pluripotent ESCs to downstream cells. Conversely, biological rhythms in adult somatic cells disappear when they are reprogrammed into induced pluripotent stem cells (iPSCs. These studies indicated that the development of biological rhythms in ESCs might be closely associated with the maintenance and differentiation of ESCs. The core circadian gene Clock is essential for regulation of biological rhythms. Its role in the development of biological rhythms of ESCs is totally unknown. Here, we used CRISPR/CAS9-mediated genetic editing techniques, to completely knock out the Clock expression in mouse ESCs. By AP, teratoma formation, quantitative real-time PCR and Immunofluorescent staining, we did not find any difference between Clock knockout mESCs and wild type mESCs in morphology and pluripotent capability under the pluripotent state. In brief, these data indicated Clock did not influence the maintaining of pluripotent state. However, they exhibited decreased proliferation and increased apoptosis. Furthermore, the biological rhythms failed to develop in Clock knockout mESCs after spontaneous differentiation, which indicated that there was no compensational factor in most peripheral tissues as described in mice models before (DeBruyne et al., 2007b. After spontaneous differentiation, loss of CLOCK protein due to Clock gene silencing induced spontaneous differentiation of mESCs, indicating an exit from the pluripotent state, or its differentiating ability. Our findings indicate that the core circadian gene Clock may be essential during normal mESCs differentiation by regulating mESCs proliferation, apoptosis and activity.

  3. A quantum network of clocks

    Science.gov (United States)

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

    2014-08-01

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

  4. Stochastic models for atomic clocks

    Science.gov (United States)

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

    1983-01-01

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

  5. Simulation of the clock framework of Gaia

    CERN Document Server

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

    2005-01-01

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

  6. 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.

  7. Types for X10 Clocks

    Directory of Open Access Journals (Sweden)

    Francisco Martins

    2011-10-01

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

  8. Synchronous clock stopper for microprocessor

    Science.gov (United States)

    Kitchin, David A. (Inventor)

    1985-01-01

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

  9. The Tibetan medicine Zuotai influences clock gene expression in the liver of mice

    Directory of Open Access Journals (Sweden)

    Huan Li

    2016-01-01

    Full Text Available Background. The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and “detoxification,” and is mainly composed of metacinnabar (β-HgS. The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice. Materials and methods. Mice were orally given Zuotai (10 mg/kg, 1.5-fold of clinical dose daily for 7 days, and livers were collected every 4 h during the 24 h period. Total RNA was extracted and subjected to real-time RT-PCR analysis of circadian clock gene expression. Results. Zuotai decreased the oscillation amplitude of the clock core gene Clock, neuronal PAS domain protein 2 (Npas2, Brain and muscle Arnt-like protein-1 (Bmal1 at 10:00. For the clock feedback negative control genes, Zuotai had no effect on the oscillation of the clock gene Cryptochrome (Cry1 and Period genes (Per1–3. For the clock-driven target genes, Zuotai increased the oscillation amplitude of the PAR-bZip family member D-box-binding protein (Dbp, decreased nuclear factor interleukin 3 (Nfil3 at 10:00, but had no effect on thyrotroph embryonic factor (Tef; Zuotai increased the expression of nuclear receptor Rev-Erbα (Nr1d1 at 18:00, but had little influence on the nuclear receptor Rev-Erbβ (Nr1d2 and RORα. Conclusion. The Tibetan medicine Zuotai could influence the expression of clock genes, which could contribute to pharmacological and/or toxicological effects of Zuotai.

  10. Clock gene modulates roles of OXTR and AVPR1b genes in prosociality.

    Directory of Open Access Journals (Sweden)

    Haipeng Ci

    Full Text Available BACKGROUND: The arginine vasopressin receptor (AVPR and oxytocin receptor (OXTR genes have been demonstrated to contribute to prosocial behavior. Recent research has focused on the manner by which these simple receptor genes influence prosociality, particularly with regard to the AVP system, which is modulated by the clock gene. The clock gene is responsible for regulating the human biological clock, affecting sleep, emotion and behavior. The current study examined in detail whether the influences of the OXTR and AVPR1b genes on prosociality are dependent on the clock gene. METHODOLOGY/PRINCIPAL FINDINGS: This study assessed interactions between the clock gene (rs1801260, rs6832769 and the OXTR (rs1042778, rs237887 and AVPR1b (rs28373064 genes in association with individual differences in prosociality in healthy male Chinese subjects (n = 436. The Prosocial Tendencies Measure (PTM-R was used to assess prosociality. Participants carrying both the GG/GA variant of AVPR1b rs28373064 and the AA variant of clock rs6832769 showed the highest scores on the Emotional PTM. Carriers of both the T allele of OXTR rs1042778 and the C allele of clock rs1801260 showed the lowest total PTM scores compared with the other groups. CONCLUSIONS: The observed interaction effects provide converging evidence that the clock gene and OXT/AVP systems are intertwined and contribute to human prosociality.

  11. Effect of light on expression of clock genes in Xenopus laevis melanophores.

    Science.gov (United States)

    Magalhães Moraes, Maria Nathália de Carvalho; de Oliveira Poletini, Maristela; Ribeiro Ramos, Bruno Cesar; de Lima, Leonardo Henrique Ribeiro Graciani; de Lauro Castrucci, Ana Maria

    2014-01-01

    Light-dark cycles are considered important cues to entrain biological clocks. A feedback loop of clock gene transcription and translation is the molecular basis underlying the mechanism of both central and peripheral clocks. Xenopus laevis embryonic melanophores respond to light with melanin granule dispersion, response possibly mediated by the photopigment melanopsin. To test whether light modulates clock gene expression in Xenopus melanophores, we used qPCR to evaluate the relative mRNA levels of Per1, Per2, Clock and Bmal1 in cultured melanophores exposed to light-dark (LD) cycle or constant darkness (DD). LD cycles elicited temporal changes in the expression of Per1, Per2 and Bmal1. A 10-min pulse of blue light was able to increases the expression of Per1 and Per2. Red light had no effect on the expression of these clock genes. These data suggest the participation of a blue-wavelength sensitive pigment in the light-dark cycle-mediated oscillation of the endogenous clock. Our results add an important contribution to the emerging field of peripheral clocks, which in nonmammalian vertebrates have been mostly studied in Drosophila and Danio rerio. Within this context, we show that X. laevis melanophores, which have already led to melanopsin discovery, represent an ideal model to understanding circadian rhythms.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    R Daniel Rudic

    2004-11-01

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

  14. Light and the human circadian clock

    NARCIS (Netherlands)

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

    2013-01-01

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

  15. A generalized gravitomagnetic clock effect

    CERN Document Server

    Hackmann, Eva

    2014-01-01

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

  16. Bayesian molecular clock dating of species divergences in the genomics era.

    Science.gov (United States)

    dos Reis, Mario; Donoghue, Philip C J; Yang, Ziheng

    2016-02-01

    Five decades have passed since the proposal of the molecular clock hypothesis, which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics and studying the macroevolutionary process of speciation and extinction to estimating a timescale for life on Earth.

  17. 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.

  18. Disruption of the somitic molecular clock causes abnormal vertebral segmentation.

    Science.gov (United States)

    Sparrow, Duncan B; Chapman, Gavin; Turnpenny, Peter D; Dunwoodie, Sally L

    2007-06-01

    Somites are the precursors of the vertebral column. They segment from the presomitic mesoderm (PSM) that is caudally located and newly generated from the tailbud. Somites form in synchrony on either side of the embryonic midline in a reiterative manner. A molecular clock that operates in the PSM drives this reiterative process. Genetic manipulation in mouse, chick and zebrafish has revealed that the molecular clock controls the activity of the Notch and WNT signaling pathways in the PSM. Disruption of the molecular clock impacts on somite formation causing abnormal vertebral segmentation (AVS). A number of dysmorphic syndromes manifest AVS defects. Interaction between developmental biologists and clinicians has lead to groundbreaking research in this area with the identification that spondylocostal dysostosis (SCD) is caused by mutation in Delta-like 3 (DLL3), Mesoderm posterior 2 (MESP2), and Lunatic fringe (LFNG); three genes that are components of the Notch signaling pathway. This review describes our current understanding of the somitic molecular clock and highlights how key findings in developmental biology can impact on clinical practice.

  19. Chronopharmacological strategies: Intra- and inter-individual variability of molecular clock.

    Science.gov (United States)

    Ohdo, Shigehiro; Koyanagi, Satoru; Matsunaga, Naoya

    2010-07-31

    In all living organisms, one of the most indispensable biological functions is the circadian clock (suprachiasmatic nuclei; SCN), which acts like a multifunction timer to regulate homeostatic systems such as sleep and activity, hormone levels, appetite, and other bodily functions with 24h cycles. Circadian rhythms regulate diverse physiologic processes, including homeostatic functions of steroid hormones and their receptors. Perturbations of these rhythms are associated with pathogenic conditions such as depression, diabetes and cancer. Clock genes are identified as the genes that ultimately control a vast array of circadian rhythms in physiology and behavior. Clock gene regulates several diseases such as cancer, metabolic syndrome and sleep etc. CLOCK mutation affects the expression of rhythmic genes in wild-type (WT) tissue, but also affects that of non-rhythmic genes. On the other hand, the change of the drug pharmacodynamic and pharmacokinetic (PK/PD) parameters are influenced by not only inter-individual variability but also intra-individual variabilities of medications. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. The mechanisms underlying chronopharmacological findings should be clarified from viewpoint of clock genes. On the other hand, several drugs have an effect on molecular clock. Thus, the knowledge of intra- and inter-individual variability of molecular clock should be applied for the clinical practice. Therefore, we introduce the regulatory system of biological rhythm from viewpoints of clock genes and the possibility of pharmacotherapy based on the intra- and inter-individual variability of clock genes.

  20. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  1. Physical Layer Ethernet Clock Synchronization

    Science.gov (United States)

    2010-11-01

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

  2. Entanglement of quantum clocks through gravity.

    Science.gov (United States)

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

    2017-03-21

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

  3. Cellular circadian clocks in mood disorders.

    Science.gov (United States)

    McCarthy, Michael J; Welsh, David K

    2012-10-01

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

  4. 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.

  5. Reciprocal Control of the Circadian Clock and Cellular Redox State - a Critical Appraisal.

    Science.gov (United States)

    Putker, Marrit; O'Neill, John Stuart

    2016-01-01

    Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redox-sensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian time-keeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological time-keeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping.

  6. 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.

  7. Exploitation of host clock gene machinery by hepatitis viruses B and C.

    Science.gov (United States)

    Vinciguerra, Manlio; Mazzoccoli, Gianluigi; Piccoli, Claudia; Tataranni, Tiziana; Andriulli, Angelo; Pazienza, Valerio

    2013-12-21

    Many aspects of cellular physiology display circadian (approximately 24-h) rhythms. Dysfunction of the circadian clock molecular circuitry is associated with human health derangements, including neurodegeneration, increased risk of cancer, cardiovascular diseases and the metabolic syndrome. Viruses triggering hepatitis depend tightly on the host cell synthesis machinery for their own replication, survival and spreading. Recent evidences support a link between the circadian clock circuitry and viruses' biological cycle within host cells. Currently, in vitro models for chronobiological studies of cells infected with viruses need to be implemented. The establishment of such in vitro models would be helpful to better understand the link between the clock gene machinery and viral replication/viral persistence in order to develop specifically targeted therapeutic regimens. Here we review the recent literature dealing with the interplay between hepatitis B and C viruses and clock genes.

  8. 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…

  9. Collisionally induced atomic clock shifts and correlations

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Saito Shigeru

    2010-05-01

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

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

    Science.gov (United States)

    Smarandache, Florentin

    2013-03-01

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

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

    OpenAIRE

    Aurore Woller; Hélène Duez; Bart Staels; Marc Lefranc

    2016-01-01

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

  13. Clock genes, pancreatic function, and diabetes.

    Science.gov (United States)

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

    2014-12-01

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

  14. Daily rhythm and regulation of clock gene expression in the rat pineal gland.

    Science.gov (United States)

    Simonneaux, V; Poirel, V-J; Garidou, M-L; Nguyen, D; Diaz-Rodriguez, E; Pévet, P

    2004-01-05

    Rhythms in pineal melatonin synthesis are controlled by the biological clock located in the suprachiasmatic nuclei. The endogenous clock oscillations rely upon genetic mechanisms involving clock genes coding for transcription factors working in negative and positive feedback loops. Most of these clock genes are expressed rhythmically in other tissues. Because of the peculiar role of the pineal gland in the photoneuroendocrine axis regulating biological rhythms, we studied whether clock genes are expressed in the rat pineal gland and how their expression is regulated.Per1, Per3, Cry2 and Cry1 clock genes are expressed in the pineal gland and their transcription is increased during the night. Analysis of the regulation of these pineal clock genes indicates that they may be categorized into two groups. Expression of Per1 and Cry2 genes shows the following features: (1) the 24 h rhythm persists, although damped, in constant darkness; (2) the nocturnal increase is abolished following light exposure or injection with a beta-adrenergic antagonist; and (3) the expression during daytime is stimulated by an injection with a beta-adrenergic agonist. In contrast, Per3 and Cry1 day and night mRNA levels are not responsive to adrenergic ligands (as previously reported for Per2) and daily expression of Per3 and Cry1 appears strongly damped or abolished in constant darkness. These data show that the expression of Per1 and Cry2 in the rat pineal gland is regulated by the clock-driven changes in norepinephrine, in a similar manner to the melatonin rhythm-generating enzyme arylalkylamine N-acetyltransferase. The expression of Per3 and Cry1 displays a daily rhythm not regulated by norepinephrine, suggesting the involvement of another day/night regulated transmitter(s).

  15. Uncertainty principle in larmor clock

    Institute of Scientific and Technical Information of China (English)

    QIAO Chuan; REN Zhong-Zhou

    2011-01-01

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

  16. Circadian molecular clock in lung pathophysiology.

    Science.gov (United States)

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

    2015-11-15

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

  17. Rhythmic profiles of cell cycle and circadian clock gene transcripts in mice: a possible association between two periodic systems.

    Science.gov (United States)

    Weigl, Yuval; Ashkenazi, Israel E; Peleg, Leah

    2013-06-15

    The circadian system shapes the rhythms of most biological functions. The regulation of the cell cycle by a circadian clock was suggested to operate via stages S, G2 and G2/M. This study investigated a possible time link at stages G1 and G1/S as well. The daily expression profiles of cell cycle markers (Ccnd1, Ccne1 and Pcna) and circadian clock genes (Per2 and Clock) were monitored in liver and esophagus (low and high proliferation index, respectively) of BALB/c mice. Locomotor activity displayed a 24 h rhythm, establishing the circadian organization of the suprachiasmatic nucleus. In the liver, the mRNA level of Per2 and Clock fitted the circadian rhythm with a 7.5 h shift. This temporal pattern suggests that the liver harbors a functional circadian clock. The rhythm of the analyzed cell cycle genes, however, was of low significance fitness and showed an opposite peak time between Pcna and Clock. These results indicate a weak regulatory role of the circadian clock. In the esophagus, the rhythms of Clock and Per2 mRNA had a similar peak time and non-circadian periods. These results suggest either that the esophagus does not harbor a functional circadian apparatus or that the phenotypes stem from differences in phase and amplitude of the rhythms of its various cell types. The similarity in the rhythm parameters of Clock, Ccne1 and Pcna transcripts questions the control of the circadian clock on the cell cycle along the G1 and G1/S stages. Yet the G1/S transition may play a role in modulating the local clock of proliferating tissues.

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

    Directory of Open Access Journals (Sweden)

    Quentin Thommen

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

  19. 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

  20. Single electron relativistic clock interferometer

    Science.gov (United States)

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

    2016-09-01

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

  1. 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).

  2. 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...

  3. Atomic clocks with suppressed blackbody radiation shift

    CERN Document Server

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

    2011-01-01

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

  4. Internal Clock Drift Estimation in Computer Clusters

    Directory of Open Access Journals (Sweden)

    Hicham Marouani

    2008-01-01

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

  5. Temperature influences in receiver clock modelling

    Science.gov (United States)

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

    2016-04-01

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

  6. 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.

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

    Science.gov (United States)

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

    2013-04-02

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

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

    Directory of Open Access Journals (Sweden)

    Aurore Woller

    2016-10-01

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

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

    Science.gov (United States)

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

    2016-10-18

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

  10. Laser controlled atom source for optical clocks

    Science.gov (United States)

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

    2016-11-01

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

  11. Cost and Precision of Brownian Clocks

    CERN Document Server

    Barato, Andre C

    2016-01-01

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

  12. Circadian clock genes contribute to the regulation of hair follicle cycling.

    Directory of Open Access Journals (Sweden)

    Kevin K Lin

    2009-07-01

    Full Text Available Hair follicles undergo recurrent cycling of controlled growth (anagen, regression (catagen, and relative quiescence (telogen with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes.

  13. 肠道菌群失调与生物钟紊乱的相关性%Relationship between intestinal dysbacteriosis and circadian clock disturbance

    Institute of Scientific and Technical Information of China (English)

    黄文雅; 陆付耳; 董慧

    2015-01-01

    The human gut harbours a certain quantity and variety of microbes called intestinal flora, which is in a state of balance under normal circumstances, and dysbacteriosis occurs when the balance of the intestinal flora is dis-turbed by the host and the changes of the external environment.Circadian clock is the biological regulation system to adapt to natural circadian rhythm, including central clock and peripheral clock.Circadian clock disturbance, particularly rotating shift-workers with irregular light-night schedules, is associated with an increased risk of immune-related diseases.The de-velopment of these diseases is closely related to intestinal dysbacteriosis.Therefore, the correlation between intestinal dys-bacteriosis and circadian clock disturbance has attracted much attention.This review aims to explore the pathophysiological basis of the development in some immune-related diseases based on the latest scientific findings about the relationship be-tween intestinal microbial flora and circadian clock.

  14. 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...

  15. Best practices for fluorescence microscopy of the cyanobacterial circadian clock

    Science.gov (United States)

    Cohen, Susan E.; Erb, Marcella L.; Pogliano, Joe; Golden, Susan S.

    2015-01-01

    Summary This chapter deals with methods of monitoring the subcellular localization of proteins in single cells in the circadian model system Synechococcus elongatus PCC 7942. While genetic, biochemical and structural insights into the cyanobacterial circadian oscillator have flourished, difficulties in achieving informative subcellular imaging in cyanobacterial cells have delayed progress of the cell biology aspects of the clock. Here, we describe best practices for using fluorescent protein tags to monitor localization. Specifically we address how to vet fusion proteins and overcome challenges in microscopic imaging of very small autofluorescent cells. PMID:25662459

  16. Entrainment of the human circadian clock to the natural light-dark cycle.

    Science.gov (United States)

    Wright, Kenneth P; McHill, Andrew W; Birks, Brian R; Griffin, Brandon R; Rusterholz, Thomas; Chinoy, Evan D

    2013-08-19

    The electric light is one of the most important human inventions. Sleep and other daily rhythms in physiology and behavior, however, evolved in the natural light-dark cycle [1], and electrical lighting is thought to have disrupted these rhythms. Yet how much the age of electrical lighting has altered the human circadian clock is unknown. Here we show that electrical lighting and the constructed environment is associated with reduced exposure to sunlight during the day, increased light exposure after sunset, and a delayed timing of the circadian clock as compared to a summer natural 14 hr 40 min:9 hr 20 min light-dark cycle camping. Furthermore, we find that after exposure to only natural light, the internal circadian clock synchronizes to solar time such that the beginning of the internal biological night occurs at sunset and the end of the internal biological night occurs before wake time just after sunrise. In addition, we find that later chronotypes show larger circadian advances when exposed to only natural light, making the timing of their internal clocks in relation to the light-dark cycle more similar to earlier chronotypes. These findings have important implications for understanding how modern light exposure patterns contribute to late sleep schedules and may disrupt sleep and circadian clocks.

  17. Iterative quantum algorithm for distributed clock synchronization

    Institute of Scientific and Technical Information of China (English)

    Wang Hong-Fu; Zhang Shou

    2012-01-01

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

  18. 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.

  19. CMOS Law-jitter Clock Driver Design

    OpenAIRE

    2012-01-01

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

  20. Light clocks in strong gravitational fields

    CERN Document Server

    Punzi, Raffaele; Wohlfarth, Mattias N R

    2009-01-01

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

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

    Science.gov (United States)

    Galleani, Lorenzo; Tavella, Patrizia

    2015-05-01

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

  2. Circadian and Circalunar Clock Interactions in a Marine Annelid

    Directory of Open Access Journals (Sweden)

    Juliane Zantke

    2013-10-01

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

  3. 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.

  4. A New Design of Clock Synchronization Algorithm

    Directory of Open Access Journals (Sweden)

    Jingmeng Liu

    2014-05-01

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

  5. 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.

  6. Turning Back the Aging Clock -- in Mice

    Science.gov (United States)

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

  7. 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...

  8. 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...

  9. Magic Wavelengths for Terahertz Clock Transitions

    OpenAIRE

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

    2010-01-01

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

  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. Cesium Atomic Fountain Clocks at NMIJ

    Science.gov (United States)

    2010-11-01

    shift in caesium fountain clocks,” Physical Review Letters, 98, 153002. [10] A. Takamizawa, Y. Shirakawa, S. Yanagimachi et al., 2010, “Proposal of a...beam of laser-cooled cesium atoms,” Physical Review, A 60, R4241-R4244. [13] V. Gerginov, N. Nemitz, S. Weyers, et al., 2010, “Uncertainty evaluation of the caesium fountain clock PTB-CSF2,” Metrologia, 47, 65-79.

  12. The PRR family of transcriptional regulators reflects the complexity and evolution of plant circadian clocks.

    Science.gov (United States)

    Farré, Eva M; Liu, Tiffany

    2013-10-01

    Circadian clocks are internal time-keeping mechanisms that provide an adaptive advantage by enabling organisms to anticipate daily changes and orchestrate biological processes accordingly. Circadian regulated pseudo-response regulators are key components of transcription/translation circadian networks in green alga and plants. Recent studies in Arabidopsis thaliana have shown that most of them act as transcriptional repressors and directly regulate output pathways suggesting a close relationship between the central oscillator and circadian regulated processes. Moreover, phylogenetic studies on this small gene family have shed light on the evolution of circadian clocks in the green lineage.

  13. Short-term GNSS satellite clock stability

    Science.gov (United States)

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

    2015-08-01

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

  14. Cross-talk between Circadian clocks, Sleep-wake Cycles and Metabolic Networks: Dispelling the Darkness

    OpenAIRE

    Ray, Sandipan; Reddy, Akhilesh B.

    2016-01-01

    This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/bies.201500056 Integration of knowledge concerning circadian rhythms, metabolic networks, and sleep-wake cycles is imperative for unraveling the mysteries of biological cycles and their underlying mechanisms. During the last decade, enormous progress in circadian biology research has provided a plethora of new insights into the molecular architecture of circadian clocks. However, the recent i...

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Gated Clock Implementation of Arithmetic Logic Unit (ALU

    Directory of Open Access Journals (Sweden)

    Dr. Neelam R. Prakash

    2013-05-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Wang Pengjun; Yu Junjun

    2007-01-01

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

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

    Science.gov (United States)

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

    2009-05-01

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

  2. 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 ...

  3. Orbitography for next generation space clocks

    CERN Document Server

    Duchayne, Loïc; Wolf, Peter

    2007-01-01

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

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

    Science.gov (United States)

    Meuti, Megan E; Denlinger, David L

    2013-07-01

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

  5. 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.

  6. 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.

  7. Sugars, the clock and transition to flowering

    Directory of Open Access Journals (Sweden)

    Mohammad Reza eBolouri Moghaddam

    2013-02-01

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

  8. 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.

  9. 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.

  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. The Large Water-Clock of Amphiaraeion

    Science.gov (United States)

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

    2010-07-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    OpenAIRE

    Early, James O.; Curtis, Anne M.

    2016-01-01

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

  14. Circadian clocks - the fall and rise of physiology

    NARCIS (Netherlands)

    Roenneberg, Till; Merrow, Martha

    2005-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  16. Effects of nocturnal light on (clock gene expression in peripheral organs: a role for the autonomic innervation of the liver.

    Directory of Open Access Journals (Sweden)

    Cathy Cailotto

    Full Text Available BACKGROUND: The biological clock, located in the hypothalamic suprachiasmatic nucleus (SCN, controls the daily rhythms in physiology and behavior. Early studies demonstrated that light exposure not only affects the phase of the SCN but also the functional activity of peripheral organs. More recently it was shown that the same light stimulus induces immediate changes in clock gene expression in the pineal and adrenal, suggesting a role of peripheral clocks in the organ-specific output. In the present study, we further investigated the immediate effect of nocturnal light exposure on clock genes and metabolism-related genes in different organs of the rat. In addition, we investigated the role of the autonomic nervous system as a possible output pathway of the SCN to modify the activity of the liver after light exposure. METHODOLOGY AND PRINCIPAL FINDINGS: First, we demonstrated that light, applied at different circadian times, affects clock gene expression in a different manner, depending on the time of day and the organ. However, the changes in clock gene expression did not correlate in a consistent manner with those of the output genes (i.e., genes involved in the functional output of an organ. Then, by selectively removing the autonomic innervation to the liver, we demonstrated that light affects liver gene expression not only via the hormonal pathway but also via the autonomic input. CONCLUSION: Nocturnal light immediately affects peripheral clock gene expression but without a clear correlation with organ-specific output genes, raising the question whether the peripheral clock plays a "decisive" role in the immediate (functional response of an organ to nocturnal light exposure. Interestingly, the autonomic innervation of the liver is essential to transmit the light information from the SCN, indicating that the autonomic nervous system is an important gateway for the SCN to cause an immediate resetting of peripheral physiology after phase

  17. The mammalian retina as a clock

    Science.gov (United States)

    Tosini, Gianluca; Fukuhara, Chiaki

    2002-01-01

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

  18. Circadian clock proteins in prokaryotes: hidden rhythms?

    Directory of Open Access Journals (Sweden)

    Maria eLoza-Correa

    2010-12-01

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

  19. Circadian clocks: Omnes viae Romam ducunt.

    Science.gov (United States)

    Roenneberg, T; Merrow, M

    2000-10-19

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

  20. Using circadian entrainment to find cryptic clocks

    NARCIS (Netherlands)

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

    2015-01-01

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

  1. The Rubidium Atomic Clock and Basic Research

    Science.gov (United States)

    2007-12-10

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

  2. Current Status of the Molecular Clock Hypothesis

    Science.gov (United States)

    Hermann, Gilbert

    2003-01-01

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

  3. Circadian Clocks in the Immune System.

    Science.gov (United States)

    Labrecque, Nathalie; Cermakian, Nicolas

    2015-08-01

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

  4. 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…

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  6. Maximum likelihood molecular clock comb: analytic solutions.

    Science.gov (United States)

    Chor, Benny; Khetan, Amit; Snir, Sagi

    2006-04-01

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

  7. Light at night alters daily patterns of cortisol and clock proteins in female Siberian hamsters.

    Science.gov (United States)

    Bedrosian, T A; Galan, A; Vaughn, C A; Weil, Z M; Nelson, R J

    2013-06-01

    Humans and other organisms have adapted to a 24-h solar cycle in response to life on Earth. The rotation of the planet on its axis and its revolution around the sun cause predictable daily and seasonal patterns in day length. To successfully anticipate and adapt to these patterns in the environment, a variety of biological processes oscillate with a daily rhythm of approximately 24 h in length. These rhythms arise from hierarchally-coupled cellular clocks generated by positive and negative transcription factors of core circadian clock gene expression. From these endogenous cellular clocks, overt rhythms in activity and patterns in hormone secretion and other homeostatic processes emerge. These circadian rhythms in physiology and behaviour can be organised by a variety of cues, although they are most potently entrained by light. In recent history, there has been a major change from naturally-occurring light cycles set by the sun, to artificial and sometimes erratic light cycles determined by the use of electric lighting. Virtually every individual living in an industrialised country experiences light at night (LAN) but, despite its prevalence, the biological effects of such unnatural lighting have not been fully considered. Using female Siberian hamsters (Phodopus sungorus), we investigated the effects of chronic nightly exposure to dim light on daily rhythms in locomotor activity, serum cortisol concentrations and brain expression of circadian clock proteins (i.e. PER1, PER2, BMAL1). Although locomotor activity remained entrained to the light cycle, the diurnal fluctuation of cortisol concentrations was blunted and the expression patterns of clock proteins in the suprachiasmatic nucleus and hippocampus were altered. These results demonstrate that chronic exposure to dim LAN can dramatically affect fundamental cellular function and emergent physiology.

  8. Monitoring cell-autonomous circadian clock rhythms of gene expression using luciferase bioluminescence reporters.

    Science.gov (United States)

    Ramanathan, Chidambaram; Khan, Sanjoy K; Kathale, Nimish D; Xu, Haiyan; Liu, Andrew C

    2012-09-27

    genome of both dividing and non-dividing cells. Once a reporter cell line is established, the dynamics of clock function can be examined through bioluminescence recording. We first describe the generation of P(Per2)-dLuc reporter lines, and then present data from this and other circadian reporters. In these assays, 3T3 mouse fibroblasts and U2OS human osteosarcoma cells are used as cellular models. We also discuss various ways of using these clock models in circadian studies. Methods described here can be applied to a great variety of cell types to study the cellular and molecular basis of circadian clocks, and may prove useful in tackling problems in other biological systems.

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

    Science.gov (United States)

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

    2016-10-01

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

  10. 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.

  11. True logarithmic amplification of frequency clock in SS-OCT for calibration

    OpenAIRE

    2011-01-01

    With swept source optical coherence tomography (SS-OCT), imprecise signal calibration prevents optimal imaging of biological tissues such as coronary artery. This work demonstrates an approach using a true logarithmic amplifier to precondition the clock signal, with the effort to minimize the noises and phase errors for optimal calibration. This method was validated and tested with a high-speed SS-OCT. The experimental results manifest its superior ability on optimization of the calibration a...

  12. 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.

  13. 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.

  14. Casein kinase 1 proteomics reveal prohibitin 2 function in molecular clock.

    Directory of Open Access Journals (Sweden)

    Lorna S Kategaya

    Full Text Available Throughout the day, clock proteins synchronize changes in animal physiology (e.g., wakefulness and appetite with external cues (e.g., daylight and food. In vertebrates, both casein kinase 1 delta and epsilon (CK1δ and CK1ε regulate these circadian changes by phosphorylating other core clock proteins. In addition, CK1 can regulate circadian-dependent transcription in a non-catalytic manner, however, the mechanism is unknown. Furthermore, the extent of functional redundancy between these closely related kinases is debated. To further advance knowledge about CK1δ and CK1ε mechanisms of action in the biological clock, we first carried out proteomic analysis of both kinases in human cells. Next, we tested interesting candidates in a cell-based circadian readout which resulted in the discovery of PROHIBITIN 2 (PHB2 as a modulator of period length. Decreasing the expression of PHB2 increases circadian-driven transcription, thus revealing PHB2 acts as an inhibitor in the molecular clock. While stable binding of PHB2 to either kinase was not detected, knocking down CK1ε expression increases PHB2 protein levels and, unexpectedly, knocking down CK1δ decreases PHB2 transcript levels. Thus, isolating CK1 protein complexes led to the identification of PHB2 as an inhibitor of circadian transcription. Furthermore, we show that CK1δ and CK1ε differentially regulate the expression of PHB2.

  15. Modeling light adaptation in circadian clock: prediction of the response that stabilizes entrainment.

    Science.gov (United States)

    Tsumoto, Kunichika; Kurosawa, Gen; Yoshinaga, Tetsuya; Aihara, Kazuyuki

    2011-01-01

    Periods of biological clocks are close to but often different from the rotation period of the earth. Thus, the clocks of organisms must be adjusted to synchronize with day-night cycles. The primary signal that adjusts the clocks is light. In Neurospora, light transiently up-regulates the expression of specific clock genes. This molecular response to light is called light adaptation. Does light adaptation occur in other organisms? Using published experimental data, we first estimated the time course of the up-regulation rate of gene expression by light. Intriguingly, the estimated up-regulation rate was transient during light period in mice as well as Neurospora. Next, we constructed a computational model to consider how light adaptation had an effect on the entrainment of circadian oscillation to 24-h light-dark cycles. We found that cellular oscillations are more likely to be destabilized without light adaption especially when light intensity is very high. From the present results, we predict that the instability of circadian oscillations under 24-h light-dark cycles can be experimentally observed if light adaptation is altered. We conclude that the functional consequence of light adaptation is to increase the adjustability to 24-h light-dark cycles and then adapt to fluctuating environments in nature.

  16. Modeling light adaptation in circadian clock: prediction of the response that stabilizes entrainment.

    Directory of Open Access Journals (Sweden)

    Kunichika Tsumoto

    Full Text Available Periods of biological clocks are close to but often different from the rotation period of the earth. Thus, the clocks of organisms must be adjusted to synchronize with day-night cycles. The primary signal that adjusts the clocks is light. In Neurospora, light transiently up-regulates the expression of specific clock genes. This molecular response to light is called light adaptation. Does light adaptation occur in other organisms? Using published experimental data, we first estimated the time course of the up-regulation rate of gene expression by light. Intriguingly, the estimated up-regulation rate was transient during light period in mice as well as Neurospora. Next, we constructed a computational model to consider how light adaptation had an effect on the entrainment of circadian oscillation to 24-h light-dark cycles. We found that cellular oscillations are more likely to be destabilized without light adaption especially when light intensity is very high. From the present results, we predict that the instability of circadian oscillations under 24-h light-dark cycles can be experimentally observed if light adaptation is altered. We conclude that the functional consequence of light adaptation is to increase the adjustability to 24-h light-dark cycles and then adapt to fluctuating environments in nature.

  17. Casein kinase 1 proteomics reveal prohibitin 2 function in molecular clock.

    Science.gov (United States)

    Kategaya, Lorna S; Hilliard, Aisha; Zhang, Louying; Asara, John M; Ptáček, Louis J; Fu, Ying-Hui

    2012-01-01

    Throughout the day, clock proteins synchronize changes in animal physiology (e.g., wakefulness and appetite) with external cues (e.g., daylight and food). In vertebrates, both casein kinase 1 delta and epsilon (CK1δ and CK1ε) regulate these circadian changes by phosphorylating other core clock proteins. In addition, CK1 can regulate circadian-dependent transcription in a non-catalytic manner, however, the mechanism is unknown. Furthermore, the extent of functional redundancy between these closely related kinases is debated. To further advance knowledge about CK1δ and CK1ε mechanisms of action in the biological clock, we first carried out proteomic analysis of both kinases in human cells. Next, we tested interesting candidates in a cell-based circadian readout which resulted in the discovery of PROHIBITIN 2 (PHB2) as a modulator of period length. Decreasing the expression of PHB2 increases circadian-driven transcription, thus revealing PHB2 acts as an inhibitor in the molecular clock. While stable binding of PHB2 to either kinase was not detected, knocking down CK1ε expression increases PHB2 protein levels and, unexpectedly, knocking down CK1δ decreases PHB2 transcript levels. Thus, isolating CK1 protein complexes led to the identification of PHB2 as an inhibitor of circadian transcription. Furthermore, we show that CK1δ and CK1ε differentially regulate the expression of PHB2.

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

    Science.gov (United States)

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

    2014-11-14

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

  19. Epigenetic drift, epigenetic clocks and cancer risk.

    Science.gov (United States)

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

    2016-05-01

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

  20. 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.

  1. 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.

  2. Sagnac interferometry with a single atomic clock

    CERN Document Server

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

    2015-01-01

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

  3. Molecular clock on a neutral network.

    Science.gov (United States)

    Raval, Alpan

    2007-09-28

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

  4. 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.

  5. The circadian clock, reward and memory

    Directory of Open Access Journals (Sweden)

    Urs eAlbrecht

    2011-11-01

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

  6. 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.

  7. 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.

  8. Geopotential measurements with synchronously linked optical lattice clocks

    Science.gov (United States)

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

    2016-10-01

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

  9. 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.

  10. Incremental Placement-Based Clock Network Minimization Methodology

    Institute of Scientific and Technical Information of China (English)

    ZHOU Oiang; CAI Yici; HUANG Liang; HONG Xianlong

    2008-01-01

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

  11. A compact model for the complex plant circadian clock

    Directory of Open Access Journals (Sweden)

    Didier eGonze

    2016-02-01

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

  12. 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.

  13. 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.

  14. Radium single-ion optical clock

    CERN Document Server

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

    2011-01-01

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

  15. Phosphoproteome Profiling Reveals Circadian Clock Regulation of Posttranslational Modifications in the Murine Hippocampus

    Science.gov (United States)

    Chiang, Cheng-Kang; Xu, Bo; Mehta, Neel; Mayne, Janice; Sun, Warren Y. L.; Cheng, Kai; Ning, Zhibin; Dong, Jing; Zou, Hanfa; Cheng, Hai-Ying Mary; Figeys, Daniel

    2017-01-01

    The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior, and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve oscillatory expression of core clock genes that is driven by interconnecting transcription–translation feedback loops (TTFLs). Circadian clock TTFLs are further regulated by posttranslational modifications, in particular, phosphorylation. The hippocampus plays an important role in spatial memory and the conversion of short- to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus and have highlighted the importance of circadian regulation in memory formation. Given the general importance of phosphorylation in circadian clock regulation, we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry (MS). Of the 3,052 proteins and 2,868 phosphosites on 1,368 proteins that were accurately quantified, 1.7% of proteins and 5.2% of phosphorylation events exhibited time-of-day-dependent expression profiles. The majority of circadian phosphopeptides displayed abrupt fluctuations at mid-to-late day without underlying rhythms of protein abundance. Bioinformatic analysis of cyclic phosphorylation events revealed their diverse distribution in different biological pathways, most notably, cytoskeletal organization and neuronal morphogenesis. This study provides the first large-scale, quantitative MS analysis of the circadian phosphoproteome and proteome of the murine hippocampus and highlights the significance of rhythmic regulation at the posttranslational level in this peripheral oscillator. In addition to providing molecular insights into the hippocampal circadian clock, our results will assist in the understanding of genetic factors that underlie rhythms-associated pathological states of

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

    Science.gov (United States)

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

    2012-09-01

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

  17. MiR-206-mediated dynamic mechanism of the mammalian circadian clock

    Directory of Open Access Journals (Sweden)

    Wu Lianqi

    2011-09-01

    Full Text Available Abstract Background As a group of highly conserved small non-coding RNAs with a length of 21~23 nucleotides, microRNAs (miRNAs regulate the gene expression post-transcriptionally by base pairing with the partial or full complementary sequences in target mRNAs, thus resulting in the repression of mRNA translation and the acceleration of mRNA degradation. Recent work has revealed that miRNAs are essential for the development and functioning of the skeletal muscles where they are. In particular, miR-206 has not only been identified as the only miRNA expressed in skeletal muscles, but also exhibited crucial roles in regulation of the muscle development. Although miRNAs are known to regulate various biological processes ranging from development to cancer, much less is known about their role in the dynamic regulation of the mammalian circadian clock. Results A detailed dynamic model of miR-206-mediated mammalian circadian clock system was developed presently by using Hill-type terms, Michaelis-Menten type and mass action kinetics. Based on a system-theoretic approach, the model accurately predicts both the periodicity and the entrainment of the circadian clock. It also explores the dynamics properties of the oscillations mediated by miR-206 by means of sensitivity analysis and alterations of parameters. Our results show that miR-206 is an important regulator of the circadian clock in skeletal muscle, and thus by study of miR-206 the main features of its mediation on the clock may be captured. Simulations of these processes display that the amplitude and frequency of the oscillation can be significantly altered through the miR-206-mediated control. Conclusions MiR-206 has a profound effect on the dynamic mechanism of the mammalian circadian clock, both by control of the amplitude and control or alteration of the frequency to affect the level of the gene expression and to interfere with the temporal sequence of the gene production or delivery. This

  18. The functional interplay between protein kinase CK2 and CCA1 transcriptional activity is essential for clock temperature compensation in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Sergi Portolés

    2010-11-01

    Full Text Available Circadian rhythms are daily biological oscillations driven by an endogenous mechanism known as circadian clock. The protein kinase CK2 is one of the few clock components that is evolutionary conserved among different taxonomic groups. CK2 regulates the stability and nuclear localization of essential clock proteins in mammals, fungi, and insects. Two CK2 regulatory subunits, CKB3 and CKB4, have been also linked with the Arabidopsis thaliana circadian system. However, the biological relevance and the precise mechanisms of CK2 function within the plant clockwork are not known. By using ChIP and Double-ChIP experiments together with in vivo luminescence assays at different temperatures, we were able to identify a temperature-dependent function for CK2 modulating circadian period length. Our study uncovers a previously unpredicted mechanism for CK2 antagonizing the key clock regulator CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1. CK2 activity does not alter protein accumulation or subcellular localization but interferes with CCA1 binding affinity to the promoters of the oscillator genes. High temperatures enhance the CCA1 binding activity, which is precisely counterbalanced by the CK2 opposing function. Altering this balance by over-expression, mutation, or pharmacological inhibition affects the temperature compensation profile, providing a mechanism by which plants regulate circadian period at changing temperatures. Therefore, our study establishes a new model demonstrating that two opposing and temperature-dependent activities (CCA1-CK2 are essential for clock temperature compensation in Arabidopsis.

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

    Science.gov (United States)

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

    2014-10-01

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

  20. 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...

  1. 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.

  2. Self-Adaptive Clock Synchronization for Computational Grid

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

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

    Science.gov (United States)

    Early, James O; Curtis, Anne M

    2016-10-01

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

  4. 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.

  5. 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.

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

    Science.gov (United States)

    1977-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-19

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

  8. 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.

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

    OpenAIRE

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

    2013-01-01

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

  10. 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.

  11. Experiments with a New 201Hg+ Ion Clock

    Science.gov (United States)

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

    2009-04-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  13. 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...

  14. Temperature regulates transcription in the zebrafish circadian clock.

    Directory of Open Access Journals (Sweden)

    Kajori Lahiri

    2005-11-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Science.gov (United States)

    Oishi, Katsutaka; Koyanagi, Satoru; Ohkura, Naoki

    2013-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Michael T Sellix

    2013-07-01

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

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

    CERN Document Server

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

    2012-01-01

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

  19. Miniaturized optical system for atomic fountain clock

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  20. Improved master clock reference system at USNO

    Science.gov (United States)

    Winkler, G. M. R.

    1985-04-01

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

  1. 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.

  2. The Renaissance or the cuckoo clock.

    Science.gov (United States)

    Pines, Jonathon; Hagan, Iain

    2011-12-27

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

  3. 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.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Science.gov (United States)

    Takamoto, Masao; Takano, Tetsushi; Katori, Hidetoshi

    2011-05-01

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

  7. 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…

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

    NARCIS (Netherlands)

    Merrow, Martha; Brunner, Michael; Roenneberg, Till

    1999-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    CERN Document Server

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

    2013-01-01

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

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

    CERN Document Server

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2009-03-15

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

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

    Science.gov (United States)

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

    2010-02-01

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

  14. Hunting for topological dark matter with atomic clocks

    CERN Document Server

    Derevianko, A

    2013-01-01

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

  15. Remote atomic clock synchronization via satellites and optical fibers

    CERN Document Server

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

    2011-01-01

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

  16. 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...

  17. 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...

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

    Science.gov (United States)

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

    2005-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Valerio Sbragaglia

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

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Screening of Clock Gene Polymorphisms Demonstrates Association of a PER3 Polymorphism with Morningness–Eveningness Preference and Circadian Rhythm Sleep Disorder

    Science.gov (United States)

    Hida, Akiko; Kitamura, Shingo; Katayose, Yasuko; Kato, Mie; Ono, Hiroko; Kadotani, Hiroshi; Uchiyama, Makoto; Ebisawa, Takashi; Inoue, Yuichi; Kamei, Yuichi; Okawa, Masako; Takahashi, Kiyohisa; Mishima, Kazuo

    2014-01-01

    A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep–wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness–eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes. PMID:25201053

  3. Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder.

    Science.gov (United States)

    Hida, Akiko; Kitamura, Shingo; Katayose, Yasuko; Kato, Mie; Ono, Hiroko; Kadotani, Hiroshi; Uchiyama, Makoto; Ebisawa, Takashi; Inoue, Yuichi; Kamei, Yuichi; Okawa, Masako; Takahashi, Kiyohisa; Mishima, Kazuo

    2014-09-09

    A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes.

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

    Directory of Open Access Journals (Sweden)

    Galuh Boy Hertantyo

    2014-11-01

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

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

    NARCIS (Netherlands)

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

    1995-01-01

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

  6. Circadian Clock Genes Modulate Human Bone Marrow Mesenchymal Stem Cell Differentiation, Migration and Cell Cycle.

    Science.gov (United States)

    Boucher, Helene; Vanneaux, Valerie; Domet, Thomas; Parouchev, Alexandre; Larghero, Jerome

    2016-01-01

    Many of the components that regulate the circadian clock have been identified in organisms and humans. The influence of circadian rhythm (CR) on the regulation of stem cells biology began to be evaluated. However, little is known on the role of CR on human mesenchymal stem cell (hMSCs) properties. The objective of this study was to investigate the influence of CR on the differentiation capacities of bone marrow hMSCs, as well as the regulation of cell cycle and migration capabilities. To that, we used both a chemical approach with a GSK-3β specific inhibitor (2'E,3'Z-6-bromoindirubin-3'-oxime, BIO) and a knockdown of CLOCK and PER2, two of the main genes involved in CR regulation. In these experimental conditions, a dramatic inhibition of adipocyte differentiation was observed, while osteoblastic differentiation capacities were not modified. In addition, cell migration was decreased in PER2-/- cells. Lastly, downregulation of circadian clock genes induced a modification of the hMSCs cell cycle phase distribution, which was shown to be related to a change of the cyclin expression profile. Taken together, these data showed that CR plays a role in the regulation of hMSCs differentiation and division, and likely represent key factor in maintaining hMSCs properties.

  7. The Circadian Clock Modulates Global Daily Cycles of mRNA Ribosome Loading.

    Science.gov (United States)

    Missra, Anamika; Ernest, Ben; Lohoff, Tim; Jia, Qidong; Satterlee, James; Ke, Kenneth; von Arnim, Albrecht G

    2015-09-01

    Circadian control of gene expression is well characterized at the transcriptional level, but little is known about diel or circadian control of translation. Genome-wide translation state profiling of mRNAs in Arabidopsis thaliana seedlings grown in long day was performed to estimate ribosome loading per mRNA. The experiments revealed extensive translational regulation of key biological processes. Notably, translation of mRNAs for ribosomal proteins and mitochondrial respiration peaked at night. Central clock mRNAs are among those subject to fluctuations in ribosome loading. There was no consistent phase relationship between peak translation states and peak transcript levels. The overlay of distinct transcriptional and translational cycles can be expected to alter the waveform of the protein synthesis rate. Plants that constitutively overexpress the clock gene CCA1 showed phase shifts in peak translation, with a 6-h delay from midnight to dawn or from noon to evening being particularly common. Moreover, cycles of ribosome loading that were detected under continuous light in the wild type collapsed in the CCA1 overexpressor. Finally, at the transcript level, the CCA1-ox strain adopted a global pattern of transcript abundance that was broadly correlated with the light-dark environment. Altogether, these data demonstrate that gene-specific diel cycles of ribosome loading are controlled in part by the circadian clock.

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

    Science.gov (United States)

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

    2013-05-22

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

  9. Modes Of The Spiral Clock Gong

    Science.gov (United States)

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

    1993-03-01

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

  10. Clock comparison based on laser ranging technologies

    Science.gov (United States)

    Samain, Etienne

    2015-06-01

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

  11. True logarithmic amplification of frequency clock in SS-OCT for calibration.

    Science.gov (United States)

    Liu, Bin; Azimi, Ehsan; Brezinski, Mark E

    2011-06-01

    With swept source optical coherence tomography (SS-OCT), imprecise signal calibration prevents optimal imaging of biological tissues such as coronary artery. This work demonstrates an approach using a true logarithmic amplifier to precondition the clock signal, with the effort to minimize the noises and phase errors for optimal calibration. This method was validated and tested with a high-speed SS-OCT. The experimental results manifest its superior ability on optimization of the calibration and improvement of the imaging performance. Particularly, this hardware-based approach is suitable for real-time calibration in a high-speed system where computation time is constrained.

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

    Science.gov (United States)

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

    2015-07-01

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

  13. Hunting for dark matter with GPS and atomic clocks

    Science.gov (United States)

    Derevianko, Andrei

    2015-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Juliana Marcolino-Gomes

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

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

    Science.gov (United States)

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

    2010-12-01

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

  16. Crosstalk of clock gene expression and autophagy in aging

    Science.gov (United States)

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

    2016-01-01

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

  17. Use of Very Stable Clocks in Satellite Geodesy

    Science.gov (United States)

    Hugentobler, Urs; Romanyuk, Tetyana

    2016-07-01

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

  18. Ultrastable optical clock with two cold-atom ensembles

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Kadomatsu

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

  1. Molecular clocks, molecular profiles, and optimum diets: three approaches to the problem of aging.

    Science.gov (United States)

    Robinson, A B

    1979-02-01

    It has been hypothesized that the deamidation of glutaminyl and asparaginyl residues serves as a molecular clock for many biological processes including protein turnover, development, and aging. At present, this hypothesis has passed some experimental tests which are necessary but not sufficient for its acceptance. The current state of evidence about deamidation as a molecular clock is discussed. In addition, since the molecular biology of aging, especially in humans, is only partly understood, it is of value to develop quantitative, empirical measures of physiological human age and to use these measures to evaluate alternative human living conditions, especially easily adopted alternatives like variations in diet. This may allow some decrease in the suffering and loss from human aging until such time as molecular biology provides superior and more intellectually satisfying answers. An empirical system which consists of quantitative measurement of several hundred human chemical constituents followed by computerized pattern recognition is described. It is hoped that this system will eventually become an aid in the minimization of the rate of human aging through changes in diet and other factors.

  2. Using a transportable optical clock for chronometric levelling

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  4. Differential clock comparisons with phase-locked local oscillators

    CERN Document Server

    Hume, David B

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

    Huang, Xinming; Gong, Hang; Ou, Gang

    2014-05-01

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

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

    CERN Document Server

    Chen, Xingang

    2014-01-01

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

  8. Spatial gradients of protein-level time delays set the pace of the traveling segmentation clock waves.

    Science.gov (United States)

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

    2014-11-01

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

  9. The genetic equidistance result: misreading by the molecular clock and neutral theory and reinterpretation nearly half of a century later.

    Science.gov (United States)

    Hu, Taobo; Long, Mengping; Yuan, Dejian; Zhu, Zhubing; Huang, Yimin; Huang, Shi

    2013-03-01

    In 1963, Margoliash discovered the unexpected genetic equidistance result after comparing cytochrome c sequences from different species. This finding, together with the hemoglobin analyses of Zuckerkandl and Pauling in 1962, directly inspired the ad hoc molecular clock hypothesis. Unfortunately, however, many biologists have since mistakenly viewed the molecular clock as a genuine reality, which in turn inspired Kimura, King, and Jukes to propose the neutral theory of molecular evolution. Many years of studies have found numerous contradictions to the theory, and few today believe in a universal constant clock. What is being neglected, however, is that the failure of the molecular clock hypothesis has left the original equidistance result an unsolved mystery. In recent years, we fortuitously rediscovered the equidistance result, which remains unknown to nearly all researchers. Incorporating the proven virtues of existing evolutionary theories and introducing the novel concept of maximum genetic diversity, we proposed a more complete hypothesis of evolutionary genetics and reinterpreted the equidistance result and other major evolutionary phenomena. The hypothesis may rewrite molecular phylogeny and population genetics and solve major biomedical problems that challenge the existing framework of evolutionary biology.

  10. 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...

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

    Science.gov (United States)

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

    2007-01-01

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

  12. Atomic Clocks and Variations of the FIne Structure Constant

    Science.gov (United States)

    Prestage, John D.; Tjoelker, Robert L.; Maleki, Lute

    1995-01-01

    We describe a new test for possible variations of the fine structure constant alpha by comparisons of rates between clocks based on hyperfine transitions in alkali atoms with different atomic number Z. H-maser, Cs, and Hg(+) clocks have a different dependence on alpha via relativistic contributions of order (Z-alpha)(sup 2). Recent H-maser vs Hg(+) clock comparison data improve laboratory limits on a time variation by 100-fold to give dot-alpha less than or equal to 3.7 x 10(exp -14)/yr. Future laser cooled clocks (Be(+), Rb, Cs, Hg(+), etc.), when compared, will yield the most sensitive of all tests for dot-alpha/alpha.

  13. Two-photon assisted clock comparison to picosecond precision

    CERN Document Server

    Zhang, Shi-Wei; Yao, Yin-Ping; Wan, Ren-Gang; Zhang, Tong-Yi

    2015-01-01

    We have experimentally demonstrated a clock comparison scheme utilizing time-correlated photon pairs generated from the spontaneous parametric down conversion process of a laser pumped beta-barium borate crystal. The coincidence of two-photon events are analyzed by the cross correlation of the two time stamp sequences. Combining the coarse and fine part of the time differences at different resolutions, a 64 ps precision for clock synchronization has been realized. We also investigate the effects of hardware devices used in the system on the precision of clock comparison. The results indicate that the detector's time jitter and the background noise will degrade the system performance. With this method, comparison and synchronization of two remote clocks could be implemented with a precision at the level of a few tens of picoseconds.

  14. Clocked, fast electronics trigger for high energy physics

    Energy Technology Data Exchange (ETDEWEB)

    Gray, R.; Rutherfoord, J.P.

    1986-04-01

    For a Fermilab experiment we have designed and built gated-pulse-stretcher modules which allow us to clock all of the fast electronics with the accelerator rf, thus simplifying the trigger design. (orig.).

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

    Science.gov (United States)

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

    1977-01-01

    Despite the recent criticism within the special theory of relativity, there exists an arrangement of stable clocks rotating with the earth which predicts diurnal variations of the one-way speed of light, as suggested previously.

  16. Improvement of an Atomic Clock using Squeezed Vacuum

    DEFF Research Database (Denmark)

    Kruse, I.; Lange, K; Peise, Jan;

    2016-01-01

    , the vacuum noise restricts the precision of the interferometer to the standard quantum limit (SQL). Here, we propose and experimentally demonstrate a novel clock configuration that surpasses the SQL by squeezing the vacuum in the empty input state. We create a squeezed vacuum state containing an average of 0.......75 atoms to improve the clock sensitivity of 10000 atoms by 2.05+0.34−0.37  dB. The SQL poses a significant limitation for today’s microwave fountain clocks, which serve as the main time reference. We evaluate the major technical limitations and challenges for devising a next generation of fountain clocks......Since the pioneering work of Ramsey, atom interferometers are employed for precision metrology, in particular to measure time and to realize the second. In a classical interferometer, an ensemble of atoms is prepared in one of the two input states, whereas the second one is left empty. In this case...

  17. Novel putative mechanisms to link circadian clocks to healthy aging.

    Science.gov (United States)

    Popa-Wagner, Aurel; Catalin, Bogdan; Buga, Ana-Maria

    2015-08-01

    The circadian clock coordinates the internal physiology to increase the homeostatic capacity thereby providing both a survival advantage to the system and an optimization of energy budgeting. Multiple-oscillator circadian mechanisms are likely to play a role in regulating human health and may contribute to the aging process. Our aim is to give an overview of how the central clock in the hypothalamus and peripheral clocks relate to aging and metabolic disorders, including hyperlipidemia and hyperglycemia. In particular, we unravel novel putative mechanisms to link circadian clocks to healthy aging. This review may lead to the design of large-scale interventions to help people stay healthy as they age by adjusting daily activities, such as feeding behavior, and or adaptation to age-related changes in individual circadian rhythms.

  18. Open Core Protocol (OCP) Clock Domain Crossing Interfaces

    DEFF Research Database (Denmark)

    Herlev, Mathias; Poulsen, Christian Keis; Sparsø, Jens

    2014-01-01

    The open core protocol (OCP) is an openly licensed configurable and scalable interface protocol for on-chip subsystem communications. The protocol defines read and write transactions from a master towards a slave across a point-to-point connection and the protocol assumes a single common clock....... This paper presents the design of two OCP clock domain crossing interface modules that can be used to construct systems with multiple clock domains. An OCP interface typically has control signals related to both the master issuing a read or write request and the slave producing a response. If all...... these control signals are passed across the clock-domain boundary and synchronized it may add significant latency to the duration of a transaction. Our interface designs avoid this and synchronize only a single signal transition in each direction during a read or a write transaction. While the problem...

  19. Complementary approaches to understanding the plant circadian clock

    CERN Document Server

    Akman, Ozgur E; Loewe, Laurence; Troein, Carl; 10.4204/EPTCS.19.1

    2010-01-01

    Circadian clocks are oscillatory genetic networks that help organisms adapt to the 24-hour day/night cycle. The clock of the green alga Ostreococcus tauri is the simplest plant clock discovered so far. Its many advantages as an experimental system facilitate the testing of computational predictions. We present a model of the Ostreococcus clock in the stochastic process algebra Bio-PEPA and exploit its mapping to different analysis techniques, such as ordinary differential equations, stochastic simulation algorithms and model-checking. The small number of molecules reported for this system tests the limits of the continuous approximation underlying differential equations. We investigate the difference between continuous-deterministic and discrete-stochastic approaches. Stochastic simulation and model-checking allow us to formulate new hypotheses on the system behaviour, such as the presence of self-sustained oscillations in single cells under constant light conditions. We investigate how to model the timing of...

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

    NARCIS (Netherlands)

    Merrow, Martha; Roenneberg, Till

    2004-01-01

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

  1. Time in motion: the molecular clock meets the microbiome.

    Science.gov (United States)

    Liang, Xue; Bushman, Frederic D; FitzGerald, Garret A

    2014-10-23

    Thaiss et al. report that the intestinal microbiota undergoes diurnal oscillation, which is controlled by host feeding time. Disruption of the host circadian clock induces dysbiosis, which is associated with host metabolic disorders.

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

    Science.gov (United States)

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

    2011-10-11

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

  3. CSAC Characterization and Its Impact on GNSS Clock Augmentation Performance

    Directory of Open Access Journals (Sweden)

    Enric Fernández

    2017-02-01

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

  4. Quantum Clock Synchronization a Multi-Party Protocol

    CERN Document Server

    Krco, M; Krco, Marko; Paul, Prabasaj

    2001-01-01

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

  5. Clock reading: an underestimated topic in children with mathematics difficulties

    OpenAIRE

    2012-01-01

    Recent studies have shown that children with mathematics difficulties (MD) have weaknesses in multiple areas of mathematics. Andersson (2008), for example, recently found that children with MD perform significantly worse than other children on clock reading tasks. The present study builds on this recent finding and aims at a more profound understanding of the difficulties that children with MD experience with telling time. Therefore, clock reading abilities of 154 children with MD were compar...

  6. A control theory approach to clock steering techniques.

    Science.gov (United States)

    Farina, Marcello; Galleani, Lorenzo; Tavella, Patrizia; Bittanti, Sergio

    2010-10-01

    Several clock and time scale steering methods have been developed according to different viewpoints by various time laboratories. By resorting to control theory ideas, we propose a common theoretical framework encompassing these methods. A comparison of the most common steering methodologies, namely, the classical steering approach, the GPS bang-bang method, and the linear quadratic Gaussian technique, is carried out. We believe that the use of control theory methods can potentially lead to a better understanding of clock steering algorithms.

  7. A model of guarded recursion with clock synchronisation

    DEFF Research Database (Denmark)

    Bizjak, Aleš; Møgelberg, Rasmus Ejlers

    2015-01-01

    productivity to be captured in types. The calculus uses clocks representing time streams and clock quantifiers which allow limited and controlled elimination of modalities. The calculus has since been extended to dependent types by Møgelberg. Both works give denotational semantics but no rewrite semantics...... by removing freshness restrictions from typing rules, and is a necessary step towards defining rewrite semantics, and ultimately implementing the calculus....

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

    OpenAIRE

    2015-01-01

    Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in...

  9. General relativistic effects in quantum interference of "clocks"

    CERN Document Server

    Zych, Magdalena; Costa, Fabio; Brukner, Časlav

    2016-01-01

    Quantum mechanics and general relativity have been each successfully tested in numerous experiments. However, the regime where both theories are jointly required to explain physical phenomena remains untested by laboratory experiments, and is also not fully understood by theory. This contribution reviews recent ideas for a new type of experiments: quantum interference of "clocks", which aim to test novel quantum effects that arise from time dilation. "Clock" interference experiments could be realised with atoms or photons in near future laboratory experiments.

  10. CSAC Characterization and Its Impact on GNSS Clock Augmentation Performance

    Science.gov (United States)

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

    2017-01-01

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

  11. Clocking In Turbines: Remarks On Physical Nature And Geometric Requirements

    Directory of Open Access Journals (Sweden)

    Swirydczuk Jerzy

    2015-04-01

    Full Text Available The article discusses two issues relating to the clocking phenomenon in turbines, which are the physical course of stator wake deformation in rotor passages and its further interaction with downstream stator blades, and turbine geometry parameters which are believed to be most favourable for clocking. In both cases, the results presented in the article have made it possible to verify and reformulate the previously accepted opinions.

  12. Expanding circadian input, output, and the clock through genomic screens

    OpenAIRE

    2011-01-01

    Many aspects of mammalian physiology display circadian--or once daily--rhythms, such as heart rate, blood pressure, activity levels, metabolism, and liver regeneration. These rhythms are regulated by an entrainable, self-sustaining, cell-autonomous mechanism found in nearly every cell of the body: the circadian clock. The circadian clock itself represents a regulatory network, composed of interlocking negative feedback loops, that in turn is influenced by two other types of regulatory network...

  13. Low-cost on-chip clock jitter measurement scheme

    OpenAIRE

    Omana, Martin; Rossi, Daniele; Giaffreda, Daniele; Metra, Cecilia; Mak, T.M.; Raman, Asifur; Tam, Simon

    2014-01-01

    In this paper, we present a low-cost, on-chip clock jitter digital measurement scheme for high performance microprocessors. It enables in situ jitter measurement during the test or debug phase. It provides very high measurement resolution and accuracy, despite the possible presence of power supply noise (representing a major source of clock jitter), at low area and power costs. The achieved resolution is scalable with technology node and can in principle be increased as much as desired, at lo...

  14. Amyloid-β–Induced Changes in Molecular Clock Properties and Cellular Bioenergetics

    Science.gov (United States)

    Schmitt, Karen; Grimm, Amandine; Eckert, Anne

    2017-01-01

    Ageing is an inevitable biological process that results in a progressive structural and functional decline, as well as biochemical alterations that altogether lead to reduced ability to adapt to environmental changes. As clock oscillations and clock-controlled rhythms are not resilient to the aging process, aging of the circadian system may also increase susceptibility to age-related pathologies such as Alzheimer's disease (AD). Besides the amyloid-beta protein (Aβ)-induced metabolic decline and neuronal toxicity in AD, numerous studies have demonstrated that the disruption of sleep and circadian rhythms is one of the common and earliest signs of the disease. In this study, we addressed the questions of whether Aβ contributes to an abnormal molecular circadian clock leading to a bioenergetic imbalance. For this purpose, we used different oscillator cellular models: human skin fibroblasts, human glioma cells, as well as mouse primary cortical and hippocampal neurons. We first evaluated the circadian period length, a molecular clock property, in the presence of different Aβ species. We report here that physiologically relevant Aβ1–42 concentrations ranging from 10 to 500 nM induced an increase of the period length in human skin fibroblasts, human A172 glioma cells as well as in mouse primary neurons whereas the reverse control peptide Aβ42-1, which is devoid of toxic action, did not influence the circadian period length within the same concentration range. To better understand the underlying mechanisms that are involved in the Aβ-related alterations of the circadian clock, we examined the cellular metabolic state in the human primary skin fibroblast model. Notably, under normal conditions, ATP levels displayed circadian oscillations, which correspond to the respective circadian pattern of mitochondrial respiration. In contrast, Aβ1–42 treatment provoked a strong dampening in the metabolic oscillations of ATP levels as well as mitochondrial respiration and

  15. A Clock Enhanced Loop for Simultaneous Error-Free Demultiplexing and Clock Recovery of 160 Gb/s OTDM Signal Single-Channel Transmission over 100 km

    Institute of Scientific and Technical Information of China (English)

    JIA Nan; LI Tang-Jun; ZHONG Kang-Ping; WANG Mu-Guang; CHEN Ming; LI Jing; CHI Jian-Feng

    2010-01-01

    @@ A simple clock enhanced loop of cascaded electro-absorption modulators(EAMs)and 10GHz clock recovery modules is presented.The intensity of harmonic of clock-frequency component is analyzed theoretically and verified experimentally in a 160Gb/s OTDM 100km transmission system.The 10GHz clock component is enhanced obviously before launching into the clock recovery module and the recovered clock signal exhibits low rms jitter of < 400 fs.Moreover,completely error-free(10-12)transmission is observed for more than two hours without using forward error correction technology.The power penalty is about 3.6dB.The proposed loop has merits of enhancing base clock component,simultaneously de-multiplexing and clock recovery,which make the performance of this loop more stable and high suppression of non-target channels.

  16. Register Clustering Methodology for Low Power Clock Tree Synthesis

    Institute of Scientific and Technical Information of China (English)

    邓超; 蔡懿慈; 周强

    2015-01-01

    Clock networks dissipate a significant fraction of the entire chip power budget. Therefore, the optimization for power consumption of clock networks has become one of the most important objectives in high performance IC designs. In contrast to most of the traditional studies that handle this problem with clock routing or buffer insertion strategy, this paper proposes a novel register clustering methodology in generating the leaf level topology of the clock tree to reduce the power consumption. Three register clustering algorithms called KMR, KSR and GSR are developed and a comprehensive study of them is discussed in this paper. Meanwhile, a buffer allocation algorithm is proposed to satisfy the slew constraint within the clusters at a minimum cost of power consumption. We integrate our algorithms into a classical clock tree synthesis (CTS) flow to test the register clustering methodology on ISPD 2010 benchmark circuits. Experimental results show that all the three register clustering algorithms achieve more than 20% reduction in power consumption without affecting the skew and the maximum latency of the clock tree. As the most effective method among the three algorithms, GSR algorithm achieves a 31%reduction in power consumption as well as a 4%reduction in skew and a 5%reduction in maximum latency. Moreover, the total runtime of the CTS flow with our register clustering algorithms is significantly reduced by almost an order of magnitude.

  17. Experimental constraint on dark matter detection with optical atomic clocks

    Science.gov (United States)

    Wcisło, P.; Morzyński, P.; Bober, M.; Cygan, A.; Lisak, D.; Ciuryło, R.; Zawada, M.

    2016-12-01

    The total mass density of the Universe appears to be dominated by dark matter. However, beyond its gravitational interactions at the galactic scale, little is known about its nature1. Several proposals have been advanced in recent years for the detection of dark matter2-4. In particular, a network of atomic clocks could be used to search for transient indicators of hypothetical dark matter5 in the form of stable topological defects; for example, monopoles, strings or domain walls6. The clocks become desynchronized when a dark-matter object sweeps through the network. This pioneering approach5 requires a comparison between at least two distant optical atomic clocks7-9. Here, by exploiting differences in the susceptibilities of the atoms and the cavity to the fine-structure constant10,11, we show that a single optical atomic clock12 is already sensitive to dark-matter events. This implies that existing optical atomic clocks13,14 can serve as a global topological-defect dark-matter observatory, without any further developments in experimental apparatus or the need for long phase-noise-compensated optical-fibre links15. Using optical atomic clocks, we explored a new dimension of astrophysical observations by constraining the strength of atomic coupling to hypothetical dark-matter cosmic objects. Under the conditions of our experiments, the degree of constraint was found to exceed the previously reported limits16 by more than three orders of magnitude.

  18. A clock network for geodesy and fundamental science

    Science.gov (United States)

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

    2016-08-01

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

  19. Time in the 10,000-Year Clock

    CERN Document Server

    Hillis, Danny; Allen, Steve; Giorgini, Jon

    2011-01-01

    The Long Now Foundation is building a mechanical clock that is designed to keep time for the next 10,000 years. The clock maintains its long-term accuracy by synchronizing to the Sun. The 10,000-Year Clock keeps track of five different types of time: Pendulum Time, Uncorrected Solar Time, Corrected Solar Time, Displayed Solar Time and Orrery Time. Pendulum Time is generated from the mechanical pendulum and adjusted according to the equation of time to produce Uncorrected Solar Time, which is in turn mechanically corrected by the Sun to create Corrected Solar Time. Displayed Solar Time advances each time the clock is wound, at which point it catches up with Corrected Solar Time. The clock uses Displayed Solar Time to compute various time indicators to be displayed, including the positions of the Sun, and Gregorian calendar date. Orrery Time is a better approximation of Dynamical Time, used to compute positions of the Moon, planets and stars and the phase of the Moon. This paper describes how the clock reckons ...

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-10-14

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

  2. Electronics for the pulsed rubidium clock: design and characterization.

    Science.gov (United States)

    Calosso, Claudio E; Micalizio, Salvatore; Godone, Aldo; Bertacco, Elio K; Levi, Filippo

    2007-09-01

    Pulsing the different operation phases of a vapor-cell clock (optical pumping, interrogation, and detection) has been recognized as one of the most effective techniques to reduce light shift and then to improve the stability perspectives of vapor cell clocks. However, in order to take full advantage of the pulsed scheme, a fast-gated electronics is required, the times involved being of the order of milliseconds. In this paper we describe the design and the implementation of the electronics that synchronizes the different phases of the clock operation, as well as of the electronics that is mainly devoted to the thermal stabilization of the clock physics package. We also report some characterization measurements, including a measurement of the clock frequency stability. In particular, in terms of Allan deviation, we measured a frequency stability of 1.2 x 10(-12) tao(-1/2) for averaging times up to tao = 10(5) s, a very interesting result by itself and also for a possible space application of such a clock.

  3. The 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.

  4. In vitro and ex vivo models indicate that the molecular clock in fast skeletal muscle of Atlantic cod is not autonomous.

    Science.gov (United States)

    Lazado, Carlo C; Kumaratunga, Hiruni P S; Nagasawa, Kazue; Babiak, Igor; Caipang, Christopher Marlowe A; Fernandes, Jorge M O

    2014-10-01

    The notion that the circadian rhythm is exclusively regulated by a central clock has been challenged by the discovery of peripheral oscillators. These peripheral clocks are known to have a direct influence on the biological processes in a tissue or cell. In fish, several peripheral clocks respond directly to light, thus raising the hypothesis of autonomous regulation. Several clock genes are expressed with daily rhythmicity in Atlantic cod (Gadus morhua) fast skeletal muscle. In the present study, myosatellite cell culture and short-term cultured fast skeletal muscle explant models were developed and characterized, in order to investigate the autonomy of the clock system in skeletal muscle of Atlantic cod. Myosatellite cells proliferated and differentiated in vitro, as shown by the changes in cellular and myogenic gene markers. The high expression of myogenic differentiation 1 during the early days post-isolation implied the commitment to myogenic lineage and the increasing mRNA levels of proliferating cell nuclear antigen (pcna) indicated the proliferation of the cells in vitro. Transcript levels of myogenic marker genes such as pcna and myogenin increased during 5 days in culture of skeletal muscle explants, indicating that the muscle cells were proliferating and differentiating under ex vivo conditions. Transcript levels of the clock gene aryl hydrocarbon receptor nuclear translocator-like 2 (arntl2) in myosatellite cells showed no daily oscillation regardless of photoperiod manipulation. On the other hand, mRNA levels of the clock gene circadian locomotor output cycles kaput (clock) showed circadian rhythmicity in 5-day-old skeletal muscle explant under different photoperiod regimes. The expression of arntl2, cryptochrome2 (cry2), period 2a (per2a) and nuclear receptor subfamily 1, group D, member 1 was not rhythmic in muscle explants but photoperiod manipulation had a significant effect on mRNA levels of cry2 and per2a. Taken together, the lack of rhythmicity

  5. Reduced Voltage Scaling in Clock Distribution Networks

    Directory of Open Access Journals (Sweden)

    Khader Mohammad

    2009-01-01

    Full Text Available We propose a novel circuit technique to generate a reduced voltage swing (RVS signals for active power reduction on main buses and clocks. This is achieved without performance degradation, without extra power supply requirement, and with minimum area overhead. The technique stops the discharge path on the net that is swinging low at a certain voltage value. It reduces active power on the target net by as much as 33% compared to traditional full swing signaling. The logic 0 voltage value is programmable through control bits. If desired, the reduced-swing mode can also be disabled. The approach assumes that the logic 0 voltage value is always less than the threshold voltage of the nMOS receivers, which eliminate the need of the low to high voltage translation. The reduced noise margin and the increased leakage on the receiver transistors using this approach have been addressed through the selective usage of multithreshold voltage (MTV devices and the programmability of the low voltage value.

  6. Chemical clocks for early-type galaxies

    CERN Document Server

    Carretero, C; Beckman, J E

    2007-01-01

    We present a detailed stellar population analysis of 27 massive elliptical galaxies within 4 very rich clusters at redshift z~0.2. We obtained accurate estimates of the mean luminosity-weighted ages and relative abundances of CN, Mg and Fe as functions of the galaxy velocity dispersion, sigma. Our results are compatible with a scenario in which the stellar populations of massive elliptical galaxies, independently of their environment and mass, had formation timescales shorter than ~1 Gyr. This result implies that massive elliptical galaxies have evolved passively since, at least, as long ago as z~2. For a given galaxy mass the duration of star formation is shorter in those galaxies belonging to more dense environments. Finally, we show that the abundance ratios [CN/Fe] and [Mg/Fe] are the key "chemical clocks" to infer the star formation history timescales in ellipticals. In particular, [Mg/Fe] provides an upper limit for those formation timescales, while [CN/Fe] apperars to be the most suitable parameter to ...

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

    Science.gov (United States)

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

    2013-08-01

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

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

    Science.gov (United States)

    Singh, Yeshpal

    2016-07-01

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

  9. Cross-talk between circadian clocks, sleep-wake cycles, and metabolic networks: Dispelling the darkness.

    Science.gov (United States)

    Ray, Sandipan; Reddy, Akhilesh B

    2016-04-01

    Integration of knowledge concerning circadian rhythms, metabolic networks, and sleep-wake cycles is imperative for unraveling the mysteries of biological cycles and their underlying mechanisms. During the last decade, enormous progress in circadian biology research has provided a plethora of new insights into the molecular architecture of circadian clocks. However, the recent identification of autonomous redox oscillations in cells has expanded our view of the clockwork beyond conventional transcription/translation feedback loop models, which have been dominant since the first circadian period mutants were identified in fruit fly. Consequently, non-transcriptional timekeeping mechanisms have been proposed, and the antioxidant peroxiredoxin proteins have been identified as conserved markers for 24-hour rhythms. Here, we review recent advances in our understanding of interdependencies amongst circadian rhythms, sleep homeostasis, redox cycles, and other cellular metabolic networks. We speculate that systems-level investigations implementing integrated multi-omics approaches could provide novel mechanistic insights into the connectivity between daily cycles and metabolic systems.

  10. British domestic synchronous clocks 1930-1980 the rise and fall of a technology

    CERN Document Server

    Pook, Leslie Philip

    2015-01-01

    This book complements available one-make books on domestic synchronous clocks. It is also a history of science book that sets British domestic synchronous clocks, their manufacturers and technology in their social context. Part I covers the historical background, British domestic synchronous clock manufacturers and brands, how synchronous clocks work, domestic synchronous clock cases, practical advice on the servicing of domestic synchronous clocks, and analysis of the marketing and reliability of British domestic synchronous clocks. This analysis provides an explanation of the rise and eventual fall of their technology. Part II contains galleries of a selection of British domestic synchronous clocks, and of the movements with which they are fitted. There is a front and back view of each clock, together with a brief description. Views of each movement include views with the movement partly dismantled, together with a brief technical description of the movement. This profusely illustrated book is primarily fo...

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

    Science.gov (United States)

    Maltsev, Victor A; Lakatta, Edward G

    2009-03-01

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

  12. Differentially timed extracellular signals synchronize pacemaker neuron clocks.

    Directory of Open Access Journals (Sweden)

    Ben Collins

    2014-09-01

    Full Text Available Synchronized neuronal activity is vital for complex processes like behavior. Circadian pacemaker neurons offer an unusual opportunity to study synchrony as their molecular clocks oscillate in phase over an extended timeframe (24 h. To identify where, when, and how synchronizing signals are perceived, we first studied the minimal clock neural circuit in Drosophila larvae, manipulating either the four master pacemaker neurons (LNvs or two dorsal clock neurons (DN1s. Unexpectedly, we found that the PDF Receptor (PdfR is required in both LNvs and DN1s to maintain synchronized LNv clocks. We also found that glutamate is a second synchronizing signal that is released from DN1s and perceived in LNvs via the metabotropic glutamate receptor (mGluRA. Because simultaneously reducing Pdfr and mGluRA expression in LNvs severely dampened Timeless clock protein oscillations, we conclude that the master pacemaker LNvs require extracellular signals to function normally. These two synchronizing signals are released at opposite times of day and drive cAMP oscillations in LNvs. Finally we found that PdfR and mGluRA also help synchronize Timeless oscillations in adult s-LNvs. We propose that differentially timed signals that drive cAMP oscillations and synchronize pacemaker neurons in circadian neural circuits will be conserved across species.

  13. Buffer Gas Experiments in Mercury (Hg+) Ion Clock

    Science.gov (United States)

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

    2004-01-01

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

  14. Energy Efficient Global Clock Synchronization for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Vinod Namboodiri

    2010-05-01

    Full Text Available Clock synchronization is critical to many sensor networks for the success of the application as well as energyefficiency. Achieving a global time frame through localized averaging of clock values for multiple rounds till convergenceis a promising approach to clock synchronization due to the decentralized nature of computation coupled withscalability. However, it is not clear what power levels for all nodes would make the synchronization process energyefficient.Large power levels lead to faster convergence but consume a lot of energy per round of synchronization.On the other hand, smaller powers consume little energy per round, but convergence is very slow requiring a lotof rounds to achieve synchronization. In this paper we look at the problem of finding a power assignment thatachieves global clock synchronization in the most energy-efficient manner possible. We look at the problem throughtwo dimensions; rate of convergence and energy consumed per round of synchronization. A centralized algorithm ispresented that uses the path congestion of the induced communication graph to estimate which power assignmentshave good convergence properties and find one that minimizes the total energy to achieve clock synchronization.Our evaluation demonstrates that the power assignment derived from this algorithm is very energy-efficient and isapplicable for wireless communication environments with various distance-power gradients. Further, we present asimple distributed algorithm which nodes can execute locally to derive energy-efficient power levels for global clocksynchronization, and is especially useful in large-scale deployments.

  15. Atomic clocks as a tool to monitor vertical surface motion

    CERN Document Server

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

    2015-01-01

    Atomic clock technology is advancing rapidly, now reaching stabilities of $\\Delta f/f \\sim 10^{-18}$, which corresponds to resolving $1$ cm in equivalent geoid height over an integration timescale of about 7 hours. At this level of performance, ground-based atomic clock networks emerge as a tool for monitoring a variety of geophysical processes by directly measuring changes in the gravitational potential. Vertical changes of the clock's position due to magmatic, volcanic, post-seismic or tidal deformations can result in measurable variations in the clock tick rate. As an example, we discuss the geopotential change arising due to an inflating point source (Mogi model), and apply it to the Etna volcano. Its effect on an observer on the Earth's surface can be divided into two different terms: one purely due to uplift and one due to the redistribution of matter. Thus, with the centimetre-level precision of current clocks it is already possible to monitor volcanoes. The matter redistribution term is estimated to b...

  16. Synchronization of the Drosophila circadian clock by temperature cycles.

    Science.gov (United States)

    Glaser, F T; Stanewsky, R

    2007-01-01

    The natural light/dark and temperature cycles are considered to be the most prominent factors that synchronize circadian clocks with the environment. Understanding the principles of temperature entrainment significantly lags behind our current knowledge of light entrainment in any organism subject to circadian research. Nevertheless, several effects of temperature on circadian clocks are well understood, and similarities as well as differences to the light-entrainment pathways start to emerge. This chapter provides an overview of the temperature effects on the Drosophila circadian clock with special emphasis on synchronization by temperature cycles. As in other organisms, such temperature cycles can serve as powerful time cues to synchronize the clock. Mutants that specifically interfere with aspects of temperature entrainment have been isolated and will likely help to reveal the underlying mechanisms. These mechanisms involve transcriptional and posttranscriptional regulation of clock genes. For synchronization of fly behavior by temperature cycles, the generation of a whole organism or systemic signal seems to be required, even though individual fly tissues can be synchronized under isolated culture conditions. If true, the requirement for such a signal would reveal a fundamental difference to the light-entrainment mechanism.

  17. The circadian molecular clock creates epidermal stem cell heterogeneity.

    Science.gov (United States)

    Janich, Peggy; Pascual, Gloria; Merlos-Suárez, Anna; Batlle, Eduard; Ripperger, Jürgen; Albrecht, Urs; Cheng, Hai-Ying M; Obrietan, Karl; Di Croce, Luciano; Benitah, Salvador Aznar

    2011-11-09

    Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.

  18. 2e-18 total uncertainty in an atomic clock

    CERN Document Server

    Nicholson, T L; Hutson, R B; Marti, G E; Bloom, B J; McNally, R L; Zhang, W; Barrett, M D; Safronova, M S; Strouse, G F; Tew, W L; Ye, J

    2014-01-01

    The pursuit of better atomic clocks has advanced many research areas, providing better quantum state control, new insights in quantum science, tighter limits on fundamental constant variation, and improved tests of relativity. The record for the best stability and accuracy is currently held by optical lattice clocks. This work takes an important step towards realizing the full potential of a many-particle clock with a state-of-the-art stable laser. Here, we achieve fractional stability of 2.2e-16 at 1 s by using seconds-long coherent interrogations of our clock transition in a low-density system not limited by atomic interactions. With this better stability, we perform a new accuracy evaluation of our clock, improving many systematic uncertainties that limited our previous measurements, such as the lattice ac Stark and blackbody radiation (BBR) shifts. For the lattice ac Stark systematic, we identify the lattice laser frequency where the scalar and tensor components of the shift cancel, allowing for state ind...

  19. Circadian rhythms in biologically closed electrical circuits of plants.

    Science.gov (United States)

    Volkov, Alexander; Waite, Astian J; Wooten, Joseph D; Markin, Vladislav S

    2012-02-01

    The circadian clock regulates a wide range of electrophysiological and developmental processes in plants. Here, we discuss the direct influence of a circadian clock on biologically closed electrochemical circuits in vivo. The biologically closed electrochemical circuits in the leaves of C. miniata (Kaffir lily), Aloe vera and Mimosa pudica, which regulate their physiology, were analyzed using the charge stimulation method. Plants are able to memorize daytime and nighttime. Even at continuous light or darkness, plants recognize nighttime or daytime and change the input resistance. The circadian clock can be maintained endogenously and has electrochemical oscillators, which can activate ion channels in biologically closed electrochemical circuits. The activation of voltage gated channels depends on the applied voltage, electrical charge, and the speed of transmission of electrical energy from the electrostimulator to plants.

  20. Evaluating and Minimizing Distributed Cavity Phase Errors in Atomic Clocks

    CERN Document Server

    Li, Ruoxin

    2010-01-01

    We perform 3D finite element calculations of the fields in microwave cavities and analyze the distributed cavity phase errors of atomic clocks that they produce. The fields of cylindrical cavities are treated as an azimuthal Fourier series. Each of the lowest components produces clock errors with unique characteristics that must be assessed to establish a clock's accuracy. We describe the errors and how to evaluate them. We prove that sharp structures in the cavity do not produce large frequency errors, even at moderately high powers, provided the atomic density varies slowly. We model the amplitude and phase imbalances of the feeds. For larger couplings, these can lead to increased phase errors. We show that phase imbalances produce a novel distributed cavity phase error that depends on the cavity detuning. We also design improved cavities by optimizing the geometry and tuning the mode spectrum so that there are negligible phase variations, allowing this source of systematic error to be dramatically reduced.

  1. Revisiting a Classic Study of the Molecular Clock.

    Science.gov (United States)

    Robinson, Lauren M; Boland, Joseph R; Braverman, John M

    2016-03-01

    A constant rate of molecular evolution among homologous proteins and across lineages is known as the molecular clock. This concept has been useful for estimating divergence times. Here, we revisit a study by Richard Dickerson (J Mol Evol 1:26-45, 1971), wherein he provided striking visual evidence for a constant rate of amino acid changes among various evolutionary branch points. Dickerson's study is commonly cited as support of the molecular clock and a figure from it is often reproduced in textbooks. Since its publication, however, there have been updates made to dates of common ancestors based on the fossil record that should be considered. Additionally, collecting the accession numbers and carefully outlining Dickerson's methods serves as a resource to students of the molecular clock hypothesis.

  2. Heisenberg-limited atom clocks based on entangled qubits.

    Science.gov (United States)

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

    2014-05-16

    We present a quantum-enhanced atomic clock protocol based on groups of sequentially larger Greenberger-Horne-Zeilinger (GHZ) states that achieves the best clock stability allowed by quantum theory up to a logarithmic correction. Importantly the protocol is designed to work under realistic conditions where the drift of the phase of the laser interrogating the atoms is the main source of decoherence. The simultaneous interrogation of the laser phase with a cascade of GHZ states realizes an incoherent version of the phase estimation algorithm that enables Heisenberg-limited operation while extending the coherent interrogation time beyond the laser noise limit. We compare and merge the new protocol with existing state of the art interrogation schemes, and identify the precise conditions under which entanglement provides an advantage for clock stabilization: it allows a significant gain in the stability for short averaging time.

  3. Clock Synchronization and Navigation in the Vicinity of the Earth

    CERN Document Server

    Bahder, T B

    2004-01-01

    Clock synchronization is the backbone of applications such as high-accuracy satellite navigation, geolocation, space-based interferometry, and cryptographic communication systems. The high accuracy of synchronization needed over satellite-to-ground and satellite-to-satellite distances requires the use of general relativistic concepts. The role of geometrical optics and antenna phase center approximations are discussed in high accuracy work. The clock synchronization problem is explored from a general relativistic point of view, with emphasis on the local measurement process and the use of the tetrad formalism as the correct model of relativistic measurements. The treatment makes use of J. L. Synge's world function of space-time as a basic coordinate independent geometric concept. A metric is used for space-time in the vicinity of the Earth, where coordinate time is proper time on the geoid. The problem of satellite clock syntonization is analyzed by numerically integrating the geodesic equations of motion for...

  4. Searching for dark matter with optical atomic clocks

    CERN Document Server

    Wcislo, Piotr; Bober, Marcin; Cygan, Agata; Lisak, Daniel; Ciurylo, Roman; Zawada, Michal

    2016-01-01

    One of the most fundamental questions of modern physics is the existence of yet unknown forms of matter and interactions. The total mass density of the Universe appears to be dominated by some hypothetical dark matter (DM). However, beyond its gravitational interaction at galactic scale, little is known about the DM nature and properties. One possibility is that it has a form of stable topological defects built from light scalar fields which, for nonzero DM-SM coupling, would result in transient variations of fundamental constants. Optical atomic clocks, highly sensitive to variations of the fine-structure constant, seem to be natural candidates for such searches. Here we demonstrate the first experimental constraint on the strength of transient DM-SM coupling determined with optical atomic clocks. Instead of measuring the phase difference between two distant clocks we determine a common component of their readouts. We show that our constraint, even for one-day measurement, greatly exceeds previous laboratory...

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

    Science.gov (United States)

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

    1987-01-01

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

  6. The twin paradox with macroscopic clocks in superconducting circuits

    CERN Document Server

    Lindkvist, Joel; Fuentes, Ivette; Dragan, Andrzej; Svensson, Ida-Maria; Delsing, Per; Johansson, Göran

    2014-01-01

    Time dilation, a striking prediction of Einstein's relativity, plays an important role in applications such as the Global Positioning System. One of the most compelling consequences of time dilation is known as the twin paradox, where a twin at rest ages more than her sibling travelling at relativistic speeds. In this paper, we propose an implementation of the twin paradox in superconducting circuits with velocities as large as a few percent of the speed of light. Ultrafast modulation of the boundary conditions for the electromagnetic field in a microwave cavity simulates a clock moving at relativistic speeds. While previous demonstrations of this effect involve point-like clocks, our superconducting cavity has a finite length, allowing us to investigate the role of clock size as well as interesting quantum effects on time dilation. In particular, our theoretical results show that the travelling twin ages slower for larger cavity lengths and that quantum particle creation, known in this context as the dynamic...

  7. Circadian clocks optimally adapt to sunlight for reliable synchronization

    CERN Document Server

    Hasegawa, Yoshihiko

    2014-01-01

    Circadian oscillation provides selection advantages through synchronization to the daylight cycle. However, a reliable clock must be designed through two conflicting properties: entrainability to properly respond to external stimuli such as sunlight, and regularity to oscillate with a precise period. These two aspects do not easily coexist because better entrainability favors higher sensitivity, which may sacrifice the regularity. To investigate conditions for satisfying the two properties, we analytically calculated the optimal phase-response curve with a variational method. Our result indicates an existence of a dead zone, i.e., a time during which external stimuli neither advance nor delay the clock. This result is independent of model details and a dead zone appears only when the input stimuli obey the time course of actual insolation. Our calculation demonstrates that every circadian clock with a dead zone is optimally adapted to the daylight cycle. Our result also explains the lack of a dead zone in osc...

  8. Multi-GNSS Orbit and Clock Combination: Preliminary Results

    Science.gov (United States)

    Fritsche, Mathias

    2016-04-01

    In the framework of the Multi-GNSS Experiment (MGEX) a number of Analysis Centers (ACs) extended their software capabilities to process signals from the BeiDou, Galileo, and QZSS systems in addition to the well established systems GPS and GLONASS. Currently, the MGEX product portfolio covers precise satellite orbits and clocks, receiver clocks, signal biases, and Earth rotation parameters generated by the individual ACs. This presentation will provide an overview on the available AC-specific MGEX products. In addition, an introduction to a multi-GNSS orbit and clock combination procedure will be given. Finally, preliminary results from that multi-GNSS combination including a comparison with corresponding operational IGS products will be reported along with a discussion of the results.

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

    Science.gov (United States)

    Maltsev, Victor A; Lakatta, Edward G

    2013-06-01

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

  10. Reference clock parameters for digital communications systems applications

    Science.gov (United States)

    Kartaschoff, P.

    1981-01-01

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

  11. Methods to study the mechanism of the Neurospora Circadian Clock

    Science.gov (United States)

    Cha, Joonseok; Zhou, Mian; Liu, Yi

    2015-01-01

    Eukaryotic circadian clocks are comprised of interlocked auto-regulatory feedback loops that control gene expression at the levels of transcription and translation. The filamentous fungus Neurospora crassa is an excellent model for the complex molecular network of regulatory mechanisms that are common to all eukaryotes. In the heart of the network, post-translational regulations and functions of the core clock elements are of major interest. This chapter will discuss the methods that were recently used to study the Neurospora circadian oscillator mechanisms at the molecular level. PMID:25662455

  12. General flat four-dimensional world pictures and clock systems

    Science.gov (United States)

    Hsu, J. P.; Underwood, J. A.

    1978-01-01

    We explore the mathematical structure and the physical implications of a general four-dimensional symmetry framework which is consistent with the Poincare-Einstein principle of relativity for physical laws and with experiments. In particular, we discuss a four-dimensional framework in which all observers in different frames use one and the same grid of clocks. The general framework includes special relativity and a recently proposed new four-dimensional symmetry with a nonuniversal light speed as two special simple cases. The connection between the properties of light propagation and the convention concerning clock systems is also discussed, and is seen to be nonunique within the four-dimensional framework.

  13. The absolute frequency of the 87Sr optical clock transition

    DEFF Research Database (Denmark)

    Campbell, Gretchen K.; Ludlow, Andrew D.; Blatt, Sebastian;

    2008-01-01

    The absolute frequency of the 1S0–3P0 clock transition of 87Sr has been measured to be 429 228 004 229 873.65 (37) Hz using lattice-confined atoms, where the fractional uncertainty of 8.6 × 10-16 represents one of the most accurate measurements of an atomic transition frequency to date. After a d...... is made possible using a femtosecond laser based optical frequency comb to phase coherently connect the optical and microwave spectral regions and by a 3.5 km fibre transfer scheme to compare the remotely located clock signals....

  14. Probing beyond the laser coherence time in optical clock comparisons

    Science.gov (United States)

    Hume, David B.; Leibrandt, David R.

    2016-03-01

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

  15. THE STOCHASTIC ESTIMATION OF SATELLITE CLOCK CORRECTION INFORMATION IN WADGPS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Using autocorrelation information of the pseudorange errors generated by se lective availability (SA) frequency dithering, we have constructed a simple first order stochas tic model for SA effects. This model has been used in a Kalman filter to account for the stochastic behavior of SA dithering in estimating satellite clock information in wide area dif ferential GPS. We have obtained fifteen percent improvement in the user positioning using the correlation information on the satellite clock information in a Kalman filter, when comparing the results obtained using a regular least square estimation.

  16. Nuclear clocks based on resonant excitation of gamma-transitions

    CERN Document Server

    Peik, Ekkehard

    2015-01-01

    We review the ideas and concepts for a clock that is based on a radiative transition in the nucleus rather than in the electron shell. This type of clock offers advantages like an insensitivity against field-induced systematic frequency shifts and the opportunity to obtain high stability from interrogating many nuclei in the solid state. Experimental work concentrates on the low-energy (about 8 eV) isomeric transition in Th-229. We review the status of the experiments that aim at a direct optical observation of this transition and outline the plans for high-resolution laser spectroscopy experiments.

  17. Stability improvements for the NIST Yb optical lattice clock

    Science.gov (United States)

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

    2016-05-01

    To reach the fundamental limit given by quantum projection noise, optical lattice clocks require advanced laser stabilization techniques. The NIST ytterbium clock has benefited from several generations of extremely high finesse optical cavities, with cavity linewidths below 1 kHz. Characterization of the cavity drift rate has allowed compensation to the mHz/s level, improving the medium-term stability of the cavity. Based on recent measurements using Ramsey spectroscopy with synchronous interrogation, we report a fractional instability σy(1s) thermal noise floor, which will improve our Dick-limited fractional instability at 1 s to below 10-16. Also at University of Colorado.

  18. Clocks, computers, black holes, spacetime foam, and holographic principle

    CERN Document Server

    Ng, Y J

    2000-01-01

    What do simple clocks, simple computers, black holes, space-time foam, and holographic principle have in common? I will show that the physics behind them is inter-related, linking together our concepts of information, gravity, and quantum uncertainty. Thus, the physics that sets the limits to computation and clock precision also yields Hawking radiation of black holes and the holographic principle. Moreover, the latter two strongly imply that space-time undergoes much larger quantum fluctuations than what the folklore suggests --- large enough to be detected with modern gravitational-wave interferometers through future refinements.

  19. Dopamine in the Turkey retina-an impact of environmental light, circadian clock, and melatonin.

    Science.gov (United States)

    Lorenc-Duda, Anna; Berezińska, Małgorzata; Urbańska, Anna; Gołembiowska, Krystyna; Zawilska, Jolanta B

    2009-05-01

    Substantial evidence suggests that dopamine and melatonin are mutually inhibitory factors that act in the retina as chemical analogs of day and night. Here, we show an impact of environmental light, biological clock, and melatonin on retinal levels of dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the turkey. In turkeys held under different light (L) to dark (D) cycles (16L:8D, 12L:12D, 8L:16D), retinal levels of dopamine and DOPAC fluctuated with daily rhythms. High levels of dopamine and DOPAC were observed during light hours and low during dark hours. Under the three photoperiodic regimes, rhythms of dopamine and DOPAC were out of phase with daily oscillation in retinal melatonin content. In constant darkness, dopamine and DOPAC levels oscillated in circadian rhythms. Light deprivation resulted, however, in a significant decline in amplitudes of both rhythms. Injections of melatonin (0.1-1 mumol/eye) during daytime significantly reduced retinal levels of DOPAC. This suppressive effect of melatonin was more pronounced in the dark-adapted than light-exposed turkeys. Quinpirole (a D(2)/D(4)-dopamine receptor agonist; 0.1-10 nmol/eye) injected to dark-adapted turkeys significantly decreased retinal melatonin. Our results indicate that in the turkey retina: (1) environmental light is the major factor regulating dopamine synthesis and metabolism; (2) dopaminergic neurones are controlled, in part, by intrinsic circadian clock; and (3) dopamine and melatonin are components of the mutually inhibitory loop.

  20. Altered expression pattern of clock genes in a rat model of depression

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Bouzinova, Elena; Fahrenkrug, Jan;

    2016-01-01

    quantified expression of clock genes on brain sections in the prefrontal cortex, nucleus accumbens, pineal gland, suprachiasmatic nucleus, substantia nigra, amygdala, ventral tegmental area, subfields of the hippocampus, and the lateral habenula using in situ hybridization histochemistry. Expression of clock...

  1. The E3 ubiquitin ligase CTRIP controls CLOCK levels and PERIOD oscillations in Drosophila.

    Science.gov (United States)

    Lamaze, Angélique; Lamouroux, Annie; Vias, Carine; Hung, Hsiu-Cheng; Weber, Frank; Rouyer, François

    2011-06-01

    In the Drosophila circadian clock, the CLOCK/CYCLE complex activates the period and timeless genes that negatively feedback on CLOCK/CYCLE activity. The 24-h pace of this cycle depends on the stability of the clock proteins. RING-domain E3 ubiquitin ligases have been shown to destabilize PERIOD or TIMELESS. Here we identify a clock function for the circadian trip (ctrip) gene, which encodes a HECT-domain E3 ubiquitin ligase. ctrip expression in the brain is mostly restricted to clock neurons and its downregulation leads to long-period activity rhythms in constant darkness. This altered behaviour is associated with high CLOCK levels and persistence of phosphorylated PERIOD during the subjective day. The control of CLOCK protein levels does not require PERIOD. Thus, CTRIP seems to regulate the pace of the oscillator by controlling the stability of both the activator and the repressor of the feedback loop.

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

    Science.gov (United States)

    Asaad, Sameth W.; Kapur, Mohit

    2016-01-05

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-19

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  5. Oscillating perceptions: the ups and downs of the CLOCK protein in the mouse circadian system

    Indian Academy of Sciences (India)

    Jason P. Debruyne

    2008-12-01

    A functional mouse CLOCK protein has long been thought to be essential for mammalian circadian clockwork function, based mainly on studies of mice bearing a dominant negative, antimorphic mutation in the Clock gene. However, new discoveries using recently developed Clock-null mutant mice have shaken up this view. In this review, I discuss how this recent work impacts and alters the previous view of the role of CLOCK in the mouse circadian clockwork.

  6. Nonvisual Opsins and the Regulation of Peripheral Clocks by Light and Hormones.

    Science.gov (United States)

    Poletini, Maristela O; Ramos, Bruno C; Moraes, Maria Nathalia; Castrucci, Ana Maria L

    2015-01-01

    The molecular clock machinery is conserved throughout evolution. However, how environmental cues are perceived has evolved in such a way that peripheral clocks in mammals require a variety of signals, including hormones. On the other hand, in nonmammalian cells able to directly detect light, light seems to play a major role in the synchronization of the clock. The interaction between perception of circadian light by nonvisual opsins and hormones will be discussed under the perspective of clock synchronization at the molecular level.

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

    DEFF Research Database (Denmark)

    Peucheret, Christophe; Seoane, Jorge; Ji, Hua

    2009-01-01

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

  8. The Long-term Performance Analysis for On-board Atomic Clocks of BDS

    OpenAIRE

    WANG Yupu; LÜ Zhiping; Wang, Ning

    2017-01-01

    BeiDou Navigation Satellite System (BDS) has begun to provide regional services since the end of 2012. It plays an important role in analyzing the long-term performance of BDS satellite clocks in evaluating the performance of the whole system, determining and predicting satellite clock bias (SCB) etc. Precise satellite clock data products derived from multi-satellite orbit determination are used to conduct the performance analysis of BDS satellite clocks. Specifically, the characteristics of ...

  9. The research progress of circadian clock and related diseases%生物钟紊乱与相关疾病关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    王春燕

    2015-01-01

    Circadian clock, which is also known as circadian rhythm is the cyclical fluctuation of biological behavior and physiological phenomena in organism. Recently, studies on the molecular mechanism of circadian clock generation and synchronization were increasing. Results showed some diseases (e.g., insomnia, cancer, depression, Alzheimer's disease etc.) are related to the periodic variations of circadian clock. Therefore, the studies on the relationship between the periodic variations of circadian clock and some related diseases have important implication. In this article, the studies on the physiological mechanism of circadian clock and related diseases were summarized, which could provide theoretical basis for the researches on circadian clock and the controls of related diseases.%生物钟又称生物节律,是生物体内周期性波动的行为和生理现象,近年来对生物钟产生和同步的分子机制的研究日益深入.研究表明,生物钟的周期性变化与生物体的某些疾病(如失眠、癌症、抑郁症、阿尔茨海默氏病等)息息相关.所以,对生物钟与相关疾病的关系的研究有重要的意义.本文就国内外有关生物钟的生理机制及生物钟相关疾病的研究综述如下,以期为更好地研究生物钟的生理机制及防治相关疾病提供理论依据.

  10. Frequency Ratio of ${}^{199}$Hg and ${}^{87}$Sr Optical Lattice Clocks beyond the SI Limit

    CERN Document Server

    Yamanaka, Kazuhiro; Ushijima, Ichiro; Takamoto, Masao; Katori, Hidetoshi

    2015-01-01

    We report on a frequency ratio measurement of a ${}^{199}$Hg-based optical lattice clock referencing a ${}^{87}$Sr-based clock. Evaluations of lattice light shift, including atomic-motion-dependent shift, enable us to achieve a total systematic uncertainty of $7.2 \\times 10^{-17}$ for the Hg clock. The frequency ratio is measured to be $\

  11. CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock

    NARCIS (Netherlands)

    T. Tamaru (Teruya); M. Hattori (Mitsuru); K. Honda (Kousuke); Y. Nakahata (Yasukazu); P. Sassone-Corsi (Paolo); G.T.J. van der Horst (Gijsbertus); T. Ozawa (Takeaki); K. Takamatsu (Ken)

    2015-01-01

    textabstractIntracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we establi

  12. Using Integer Clocks to Verify the Timing-Sync Sensor Network Protocol

    Science.gov (United States)

    Huang, Xiaowan; Singh, Anu; Smolka, Scott A.

    2010-01-01

    We use the UPPAAL model checker for Timed Automata to verify the Timing-Sync time-synchronization protocol for sensor networks (TPSN). The TPSN protocol seeks to provide network-wide synchronization of the distributed clocks in a sensor network. Clock-synchronization algorithms for sensor networks such as TPSN must be able to perform arithmetic on clock values to calculate clock drift and network propagation delays. They must be able to read the value of a local clock and assign it to another local clock. Such operations are not directly supported by the theory of Timed Automata. To overcome this formal-modeling obstacle, we augment the UPPAAL specification language with the integer clock derived type. Integer clocks, which are essentially integer variables that are periodically incremented by a global pulse generator, greatly facilitate the encoding of the operations required to synchronize clocks as in the TPSN protocol. With this integer-clock-based model of TPSN in hand, we use UPPAAL to verify that the protocol achieves network-wide time synchronization and is devoid of deadlock. We also use the UPPAAL Tracer tool to illustrate how integer clocks can be used to capture clock drift and resynchronization during protocol execution

  13. Noise in state of the art clocks and their impact for fundamental physics

    Science.gov (United States)

    Maleki, L.

    2001-01-01

    In this paper a review of the use of advanced atomic clocks in testing the fundamental physical laws will be presented. Noise sources of clocks will be discussed, together with an outline their characterization based on current models. The paper will conclude with a discussion of recent attempts to reduce the fundamental, as well as technical noise in atomic clocks.

  14. Curriculum Sequencing and the Acquisition of Clock-Reading Skills among Chinese and Flemish Children

    Science.gov (United States)

    Burny, Elise; Valcke, Martin; Desoete, Annemie; Van Luit, Johannes E. Hans

    2013-01-01

    The present study addresses the impact of the curriculum on primary school children's acquisition of clock-reading knowledge from analog and digital clocks. Focusing on Chinese and Flemish children's clock-reading knowledge, the study is about whether the differences in sequencing of learning and instruction opportunities--as defined by the…

  15. 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.

  16. Representing the object of controversy: the case of the molecular clock.

    Science.gov (United States)

    Dietrich, Michael R

    2007-01-01

    Through a case study of the controversies surrounding the molecular clock, this paper examines the role of visual representation in the dynamics of scientific controversies. Representations of the molecular clock themselves became objects of controversy and so were not a means for closure. Instead visual representations of the molecular clock became tools for the further articulation of an ongoing controversy.

  17. Analysis of Random Jitter in a Clock Multiplying DLL Architecture

    NARCIS (Netherlands)

    Beek, van de R.C.H; Klumperink, E.A.M.; Vaucher, C.S.; Nauta, B.

    2001-01-01

    In this paper, a thorough analysis of the jitter behavior of a Delay Locked Loop (DLL) based clock multiplying architecture is presented. The noise sources that are included in the analysis are the noise of the delay elements, the reference jitter and the noise of the Phase Frequency Detector and Ch

  18. Special Relativity in Week One: 2) All Clocks Run Slow

    Science.gov (United States)

    Huggins, Elisha

    2011-01-01

    In our initial article on teaching special relativity in the first week of an introductory physics course, we used the principle of relativity and Maxwell's theory of light to derive Einstein's second postulate (that the speed of light is the same to all observers). In this paper we study thought experiments involving a light pulse clock moving…

  19. The AGS Ggamma Meter and Calibrating the Gauss Clock

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-31

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

  20. NAVEX - A Space Shuttle Experiment with Atomic Clocks

    Science.gov (United States)

    1982-12-01

    for synchronization will be clock transportations. In cooperation with our national time institute ’ Physikalisch -Technische Bundesanstalt’ (FTB...Einwegentfernungsrnessung" Nachrichtentechniskh Zeitschrift 29 (1976) H. 9, S. 673-677. [41 Tschiesche, H, : Experiment zur "Syllchronisation und Ein

  1. Clock Reading: An Underestimated Topic in Children with Mathematics Difficulties

    Science.gov (United States)

    Burny, Elise; Valcke, Martin; Desoete, Annemie

    2012-01-01

    Recent studies have shown that children with mathematics difficulties (MD) have weaknesses in multiple areas of mathematics. Andersson, for example, recently found that children with MD perform significantly worse than other children on clock reading tasks. The present study builds on this recent finding and aims at a more profound understanding…

  2. Experimental Progress on the NIST ^27Al^+ Optical Clock

    Science.gov (United States)

    Chou, Chin-Wen; Hume, David B.; Koelemeij, Jeroen C. J.; Rosenband, Till; Bergquist, James C.; Wineland, Dave J.

    2009-05-01

    A recent measurement of the frequency ratio between single-ion optical clocks based on ^27Al^+ and ^199Hg^+ at NIST showed a combined statistical and systematic uncertainty of 5.2 x 10-17[1]. Here we report progress on improving both the accuracy and stability of the ^27Al^+ optical clock. We have developed a new trap and laser systems that enable the use of ^25Mg^+ for sympathetic cooling and clock-state detection of ^27Al^+. These developments should reduce time-dilation shifts caused by harmonic motion of the ions and thus lower the dominant systematic uncertainty below 10-17. In the new clock apparatus we have demonstrated spectroscopy of the ^27Al^+ ^1S0 to ^3P0 transition with a quality factor of Q = 3.5 x 10^14 and simultaneously a contrast approaching unity. In addition, we have developed techniques for the sympathetic laser cooling and quantum logic spectroscopy of multiple aluminum ions with the goal of further improving measurement stability [2]. *supported by ONR and NIST [1] T. Rosenband et al., Science 319, 1808 (2008) [2] D. B. Hume et al., Phys. Rev. Lett. 99, 120502 (2007)

  3. A Medieval Clock Made out of Simple Materials

    Science.gov (United States)

    Danese, B.; Oss, S.

    2008-01-01

    A cheap replica of the verge-and-foliot clock has been built from simple materials. It is a didactic tool of great power for physics teaching at every stage of schooling, in particular at university level. An account is given of its construction and its working principles, together with motivated examples of a few activities. (Contains 3 tables…

  4. Signaling to the circadian clock: plasticity by chromatin remodeling.

    Science.gov (United States)

    Nakahata, Yasukazu; Grimaldi, Benedetto; Sahar, Saurabh; Hirayama, Jun; Sassone-Corsi, Paolo

    2007-04-01

    Circadian rhythms govern several fundamental physiological functions in almost all organisms, from prokaryotes to humans. The circadian clocks are intrinsic time-tracking systems with which organisms can anticipate environmental changes and adapt to the appropriate time of day. In mammals, circadian rhythms are generated in pacemaker neurons within the suprachiasmatic nuclei (SCN), a small area of the hypothalamus, and are entrained by environmental cues, principally light. Disruption of these rhythms can profoundly influence human health, being linked to depression, insomnia, jet lag, coronary heart disease and a variety of neurodegenerative disorders. It is now well established that circadian clocks operate via transcriptional feedback autoregulatory loops that involve the products of circadian clock genes. Furthermore, peripheral tissues also contain independent clocks, whose oscillatory function is orchestrated by the SCN. The complex program of gene expression that characterizes circadian physiology involves dynamic changes in chromatin transitions. These remodeling events are therefore of great importance to ensure the proper timing and extent of circadian regulation. How signaling influences chromatin remodeling through histone modifications is therefore highly relevant in the context of circadian oscillation. Recent advances in the field have revealed unexpected links between circadian regulators, chromatin remodeling and cellular metabolism.

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

    Science.gov (United States)

    Kelter, Paul B.; And Others

    1996-01-01

    Describes the recent history, chemistry, and educational uses of the Orange Juice Clock demonstration in which a galvanic cell is made from the combination of a magnesium strip, a copper strip, and juice in a beaker. Discusses the chemistry basics, extensions for more advanced students, questions for student/teacher workshop participants, and…

  6. The Cell Cycle & Circadian Clock: a tale of two cycles

    NARCIS (Netherlands)

    E. Destici (Eugin)

    2010-01-01

    textabstractMost organisms have evolved an internal timekeeper to anticipate and coordinate internal processes with the external 24-h environment imposed upon all living creatures due to rotation of the Earth around its axis. At the cellular level, the circadian clock is generated by a genetic progr

  7. The circadian clock mutation alters sleep homeostasis in the mouse.

    Science.gov (United States)

    Naylor, E; Bergmann, B M; Krauski, K; Zee, P C; Takahashi, J S; Vitaterna, M H; Turek, F W

    2000-11-01

    The onset and duration of sleep are thought to be primarily under the control of a homeostatic mechanism affected by previous periods of wake and sleep and a circadian timing mechanism that partitions wake and sleep into different portions of the day and night. The mouse Clock mutation induces pronounced changes in overall circadian organization. We sought to determine whether this genetic disruption of circadian timing would affect sleep homeostasis. The Clock mutation affected a number of sleep parameters during entrainment to a 12 hr light/dark (LD 12:12) cycle, when animals were free-running in constant darkness (DD), and during recovery from 6 hr of sleep deprivation in LD 12:12. In particular, in LD 12:12, heterozygous and homozygous Clock mutants slept, respectively, approximately 1 and approximately 2 hr less than wild-type mice, and they had 25 and 51% smaller increases in rapid eye movement (REM) sleep during 24 hr recovery, respectively, than wild-type mice. The effects of the mutation on sleep are not readily attributable to differential entrainment to LD 12:12 because the baseline sleep differences between genotypes were also present when animals were free-running in DD. These results indicate that genetic alterations of the circadian clock system and/or its regulatory genes are likely to have widespread effects on a variety of sleep and wake parameters, including the homeostatic regulation of sleep.

  8. The NIST 27 Al+ quantum-logic clock

    Science.gov (United States)

    Leibrandt, David; Brewer, Samuel; Chen, Jwo-Sy; Hume, David; Hankin, Aaron; Huang, Yao; Chou, Chin-Wen; Rosenband, Till; Wineland, David

    2016-05-01

    Optical atomic clocks based on quantum-logic spectroscopy of the 1 S0 3 P0 transition in 27 Al+ have reached a systematic fractional frequency uncertainty of 8 . 0 ×10-18 , enabling table-top tests of fundamental physics as well as measurements of gravitational potential differences. Currently, the largest limitations to the accuracy are second order time dilation shifts due to the driven motion (i.e., micromotion) and thermal motion of the trapped ions. In order to suppress these shifts, we have designed and built new ion traps based on gold-plated, laser-machined diamond wafers with differential RF drive, and we have operated one of our clocks with the ions laser cooled to near the six mode motional ground state. We present a characterization of the time dilation shifts in the new traps with uncertainties near 1 ×10-18 . Furthermore, we describe a new protocol for clock comparison measurements based on synchronous probing of the two clocks using phase-locked local oscillators, which allows for probe times longer than the laser coherence time and avoids the Dick effect. This work is supported by ARO, DARPA, and ONR.

  9. High-performance coherent population trapping clock with polarization modulation

    CERN Document Server

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

    2016-01-01

    We demonstrate a vapor cell atomic clock prototype based on continuous-wave (CW) interrogation and double-modulation coherent population trapping (DM-CPT) technique. The DM-CPT technique uses a synchronous modulation of polarization and relative phase of a bi-chromatic laser beam in order to increase the number of atoms trapped in a dark state, i.e. a non-absorbing state. The narrow resonance, observed in transmission of a Cs vapor cell, is used as a narrow frequency discriminator in an atomic clock. A detailed characterization of the CPT resonance versus numerous parameters is reported. A short-term frequency stability of $3.2 \\times 10^{-13} \\tau^{-1/2}$ up to 100 s averaging time is measured. These performances are more than one order of magnitude better than industrial Rb clocks and comparable to those of best laboratory-prototype vapor cell clocks. The noise budget analysis shows that the short and mid-term frequency stability is mainly limited by the power fluctuations of the microwave used to generate ...

  10. Nanomagnetic logic with non-uniform states of clocking

    Science.gov (United States)

    Puliafito, Vito; Giordano, Anna; Azzerboni, Bruno; Finocchio, Giovanni

    2016-04-01

    Nanomagnetic logic transmits information along a path of nanomagnets. The basic mechanism to drive such a transmission, known as clocking, can be achieved by exploiting the spin-Hall effect (SHE), as recently observed in experiments on Ta/CoFeB/MgO multilayers (Bhowmik et al 2014 Nat. Nano 9 59). This paper shows the fundamental mechanism of the spin-Hall driven clocking by using a full micromagnetic framework and considering two different devices, Ta/CoFeB/MgO and Pt/CoFeB/MgO. The former is used for a direct comparison of the numerical results with the experiments while the latter permits the effect of the Dzyaloshinskii-Moriya interaction (DMI) in the clocking mechanism to be predicted. Results show that the clocking state is non-uniform and it is characterized by the presence of domains separated by Bloch (Néel) domain walls depending on the absence (presence) of the DMI. Our findings point out that for the design of nanomagnetic logic a full micromagnetic approach is necessary.

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

    Science.gov (United States)

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

    2015-04-04

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

  12. The effect of white light on normal and malignant murine melanocytes: A link between opsins, clock genes, and melanogenesis.

    Science.gov (United States)

    de Assis, L V M; Moraes, M N; da Silveira Cruz-Machado, S; Castrucci, A M L

    2016-06-01

    The skin possesses a photosensitive system comprised of opsins whose function is not fully understood, and clock genes which exert an important regulatory role in skin biology. Here, we evaluated the presence of opsins in normal (Melan-a cells) and malignant (B16-F10 cells) murine melanocytes. Both cell lines express Opn2, Opn4--for the first time reported in these cell types--as well as S-opsin. OPN4 protein was found in a small area capping the cell nuclei of B16-F10 cells kept in constant dark (DD); twenty-four hours after the white light pulse (WLP), OPN4 was found in the cell membrane. Despite the fact that B16-F10 cells expressed less Opn2 and Opn4 than Melan-a cells, our data indicate that the malignant melanocytes exhibited increased photoresponsiveness. The clock gene machinery is also severely downregulated in B16-F10 cells as compared to Melan-a cells. Per1, Per2, and Bmal1 expression increased in B16-F10 cells in response to WLP. Although no response in clock gene expression to WLP was observed in Melan-a cells, gene correlational data suggest a minor effect of WLP. In contrast to opsins and clock genes, melanogenesis is significantly upregulated in malignant melanocytes in comparison to Melan-a cells. Tyrosinase expression increased after WLP only in B16-F10 cells; however no increase in melanin content after WLP was seen in either cell line. Our findings may prove useful in the treatment and the development of new pharmacological approaches of depigmentation diseases and skin cancer.

  13. Firefly Clock Synchronization in an 802.15.4 Wireless Network

    Directory of Open Access Journals (Sweden)

    Elmenreich Wilfried

    2009-01-01

    Full Text Available This paper describes the design and implementation of a distributed self-stabilizing clock synchronization algorithm based on the biological example of Asian Fireflies. Huge swarms of these fireflies use the principle of pulse coupled oscillators in order to synchronously emit light flashes to attract mating partners. When applying this algorithm to real sensor networks, typically, nodes cannot receive messages while transmitting, which prevents the networked nodes from reaching synchronization. In order to counteract this deafness problem, we adopt a variant of the Reachback Firefly Algorithm to distribute the timing of light flashes in a given time window without affecting the quality of the synchronization. A case study implemented on 802.15.4 Zigbee nodes presents the application of this approach for a time-triggered communication scheduling and coordinated duty cycling in order to enhance the battery lifetime of the nodes.

  14. CULLIN-3 controls TIMELESS oscillations in the Drosophila circadian clock.

    Directory of Open Access Journals (Sweden)

    Brigitte Grima

    Full Text Available Eukaryotic circadian clocks rely on transcriptional feedback loops. In Drosophila, the PERIOD (PER and TIMELESS (TIM proteins accumulate during the night, inhibit the activity of the CLOCK (CLK/CYCLE (CYC transcriptional complex, and are degraded in the early morning. The control of PER and TIM oscillations largely depends on post-translational mechanisms. They involve both light-dependent and light-independent pathways that rely on the phosphorylation, ubiquitination, and proteasomal degradation of the clock proteins. SLMB, which is part of a CULLIN-1-based E3 ubiquitin ligase complex, is required for the circadian degradation of phosphorylated PER. We show here that CULLIN-3 (CUL-3 is required for the circadian control of PER and TIM oscillations. Expression of either Cul-3 RNAi or dominant negative forms of CUL-3 in the clock neurons alters locomotor behavior and dampens PER and TIM oscillations in light-dark cycles. In constant conditions, CUL-3 deregulation induces behavioral arrhythmicity and rapidly abolishes TIM cycling, with slower effects on PER. CUL-3 affects TIM accumulation more strongly in the absence of PER and forms protein complexes with hypo-phosphorylated TIM. In contrast, SLMB affects TIM more strongly in the presence of PER and preferentially associates with phosphorylated TIM. CUL-3 and SLMB show additive effects on TIM and PER, suggesting different roles for the two ubiquitination complexes on PER and TIM cycling. This work thus shows that CUL-3 is a new component of the Drosophila clock, which plays an important role in the control of TIM oscillations.

  15. Time-of-day- and light-dependent expression of ubiquitin protein ligase E3 component N-recognin 4 (UBR4 in the suprachiasmatic nucleus circadian clock.

    Directory of Open Access Journals (Sweden)

    Harrod H Ling

    Full Text Available Circadian rhythms of behavior and physiology are driven by the biological clock that operates endogenously but can also be entrained to the light-dark cycle of the environment. In mammals, the master circadian pacemaker is located in the suprachiasmatic nucleus (SCN, which is composed of individual cellular oscillators that are driven by a set of core clock genes interacting in transcriptional/translational feedback loops. Light signals can trigger molecular events in the SCN that ultimately impact on the phase of expression of core clock genes to reset the master pacemaker. While transcriptional regulation has received much attention in the field of circadian biology in the past, other mechanisms including targeted protein degradation likely contribute to the clock timing and entrainment process. In the present study, proteome-wide screens of the murine SCN led to the identification of ubiquitin protein ligase E3 component N-recognin 4 (UBR4, a novel E3 ubiquitin ligase component of the N-end rule pathway, as a time-of-day-dependent and light-inducible protein. The spatial and temporal expression pattern of UBR4 in the SCN was subsequently characterized by immunofluorescence microscopy. UBR4 is expressed across the entire rostrocaudal extent of the SCN in a time-of-day-dependent fashion. UBR4 is localized exclusively to arginine vasopressin (AVP-expressing neurons of the SCN shell. Upon photic stimulation in the early subjective night, the number of UBR4-expressing cells within the SCN increases. This study is the first to identify a novel E3 ubiquitin ligase component, UBR4, in the murine SCN and to implicate the N-end rule degradation pathway as a potential player in regulating core clock mechanisms and photic entrainment.

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

    CERN Document Server

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

    2009-01-01

    We present the results from an optical and near-infrared spectroscopic study of the ultraviolet-luminous z = 2.73 galaxy, the 8 o'clock arc. Due to gravitational lensing, this galaxy is magnified by a factor of > 10, allowing in-depth measurements which are usually unfeasible at such redshifts. In the optical spectra, we measured the systemic redshift of the galaxy, z = 2.7322 +/- 0.0012, using stellar photospheric lines. This differs from the redshift of absorption lines in the interstellar medium, z = 2.7302 +/- 0.0006, implying gas outflows on the order of 160 km/s. With H and K-band near-infrared spectra, we have measured nebular emission lines of Halpha, Hbeta, Hgamma, [N II] and [O III], which have a redshift z = 2.7333 +/- 0.0001, consistent with the derived systemic redshift. From the Balmer decrement, we measured the dust extinction to be A_5500 = 0.53 +/- 0.16 mag. Correcting Halpha for dust extinction and the assumed lensing factor, we measure a star-formation rate of ~ 90 Msol/yr, which is higher ...

  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 both Col6a1(-/-)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 as Arntl) 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.

  18. Byzantine-fault tolerant self-stabilizing protocol for distributed clock synchronization systems

    Science.gov (United States)

    Malekpour, Mahyar R. (Inventor)

    2010-01-01

    A rapid Byzantine self-stabilizing clock synchronization protocol that self-stabilizes from any state, tolerates bursts of transient failures, and deterministically converges within a linear convergence time with respect to the self-stabilization period. Upon self-stabilization, all good clocks proceed synchronously. The Byzantine self-stabilizing clock synchronization protocol does not rely on any assumptions about the initial state of the clocks. Furthermore, there is neither a central clock nor an externally generated pulse system. The protocol converges deterministically, is scalable, and self-stabilizes in a short amount of time. The convergence time is linear with respect to the self-stabilization period.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect...... that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry....

  20. Circadian Clock Gene Plays a Key Role on Ovarian Cycle and Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    Ruiwen Li

    2015-09-01

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

  1. 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.

  2. Design and Analysis of Sequential Elements for Low Power Clocking System with Low Power Techniques

    Directory of Open Access Journals (Sweden)

    S.Sasidhar Reddy

    2014-09-01

    Full Text Available This paper proposed the design of sequential elements for low power clocking system with low low power techniques for saving the power. Power consumption is a major bottleneck of system performance and is listed as one of the top three challenges in International Technology Roadmap for Semiconductor 2008. In practice, a large portion of the on chip power is consumed by the clock system which is made of the clock distribution network and flop-flops. In this paper, various design techniques for a low power clocking system are surveyed. Among them is an effective way to reduce capacity of the clock load by minimizing number of clocked transistors. To approach this, proposed a novel clocked pair shared flip-flop which reduces the number of local clocked transistors by approximately 40%. A 24% reduction of clock driving power is achieved. In addition, low swing and double edge clocking, can be easily incorporated into the new flip-flop to build clocking systems. As the feature size becomes smaller, shorter channel lengths result in increased sub-threshold leakage current through a transistor when it is off. Dual sleep and sleepy stack methods are proposed to avoid static power consumption; the flip flops are simulated using HSPICE.

  3. Circadian regulation of cell cycle: Molecular connections between aging and the circadian clock.

    Science.gov (United States)

    Khapre, Rohini V; Samsa, William E; Kondratov, Roman V

    2010-09-01

    The circadian clock generates oscillations in physiology and behavior, known as circadian rhythms. Links between the circadian clock genes Periods, Bmal1, and Cryptochromes and aging and cancer are emerging. Circadian clock gene expression is changed in human pathologies, and transgenic mice with mutations in clock genes develop cancer and premature aging. Control of genome integrity and cell proliferation play key roles in the development of age-associated pathologies and carcinogenesis. Here, we review recent data on the connection between the circadian clock and control of the cell cycle. The circadian clock regulates the activity and expression of several critical cell cycle and cell cycle check-point-related proteins, and in turn cell cycle-associated proteins regulate circadian clock proteins. DNA damage can reset the circadian clock, which provides a molecular mechanism for reciprocal regulation between the circadian clock and the cell cycle. This circadian clock-dependent control of cell proliferation, together with other known physiological functions of the circadian clock such as the control of metabolism, oxidative and genotoxic stress response, and DNA repair, opens new horizons for understanding the mechanisms behind aging and carcinogenesis.

  4. Frequency ratios of Sr, Yb and Hg based optical lattice clocks and their applications

    CERN Document Server

    Takamoto, Masao; Das, Manoj; Nemitz, Nils; Ohkubo, Takuya; Yamanaka, Kazuhiro; Ohmae, Noriaki; Takano, Tetsushi; Akatsuka, Tomoya; Yamaguchi, Atsushi; Katori, Hidetoshi

    2015-01-01

    This article describes the recent progress of optical lattice clocks with neutral strontium ($^{87}$Sr), ytterbium ($^{171}$Yb) and mercury ($^{199}$Hg) atoms. In particular, we present frequency comparison between the clocks locally via an optical frequency comb and between two Sr clocks at remote sites using a phase-stabilized fibre link. We first review cryogenic Sr optical lattice clocks that reduce the room-temperature blackbody radiation shift by two orders of magnitude and serve as a reference in the following clock comparisons. Similar physical properties of Sr and Yb atoms, such as transition wavelengths and vapour pressure, have allowed our development of a compatible clock for both species. A cryogenic Yb clock is evaluated by referencing a Sr clock. We also report on a Hg clock, which shows one order of magnitude less sensitivity to blackbody radiation, while its large nuclear charge makes the clock sensitive to the variation of fine-structure constant. Connecting all three types of clocks by an o...

  5. Differential maturation of rhythmic clock gene expression during early development in medaka (Oryzias latipes).

    Science.gov (United States)

    Cuesta, Ines H; Lahiri, Kajori; Lopez-Olmeda, Jose Fernando; Loosli, Felix; Foulkes, Nicholas S; Vallone, Daniela

    2014-05-01

    One key challenge for the field of chronobiology is to identify how circadian clock function emerges during early embryonic development. Teleosts such as the zebrafish are ideal models for studying circadian clock ontogeny since the entire process of development occurs ex utero in an optically transparent chorion. Medaka (Oryzias latipes) represents another powerful fish model for exploring early clock function with, like the zebrafish, many tools available for detailed genetic analysis. However, to date there have been no reports documenting circadian clock gene expression during medaka development. Here we have characterized the expression of key clock genes in various developmental stages and in adult tissues of medaka. As previously reported for other fish, light dark cycles are required for the emergence of clock gene expression rhythms in this species. While rhythmic expression of per and cry genes is detected very early during development and seems to be light driven, rhythmic clock and bmal expression appears much later around hatching time. Furthermore, the maturation of clock function seems to correlate with the appearance of rhythmic expression of these positive elements of the clock feedback loop. By accelerating development through elevated temperatures or by artificially removing the chorion, we show an earlier onset of rhythmicity in clock and bmal expression. Thus, differential maturation of key elements of the medaka clock mechanism depends on the developmental stage and the presence of the chorion.

  6. Interactions between the circadian clock and metabolism: there are good times and bad times

    Institute of Scientific and Technical Information of China (English)

    Mi Shi; Xiangzhong Zheng

    2013-01-01

    An endogenous circadian (~24 h) clock regulates rhythmic processes of physiology,metabolism and behavior in most living organisms.While able to free-run under constant conditions,the circadian clock is coupled to day:night cycles to increase its amplitude and align the phase of circadian rhythms to the right time of the day.Disruptions of the circadian clock are correlated with brain dysfunctions,cardiovascular diseases and metabolic disorders.In this review,we focus on the interactions between the circadian clock and metabolism.We discuss recent findings on circadian clock regulation of feeding behavior and rhythmic expression of metabolic genes,and present evidence of metabolic input to the circadian clock.We emphasize how misalignment of circadian clocks within the body and with environmental cycles or daily schedules leads to the increasing prevalence of metabolic syndromes in modern society.

  7. Photoperiod sensitivity of the Arabidopsis circadian clock is tissue-specific.

    Science.gov (United States)

    Shimizu, Hanako; Araki, Takashi; Endo, Motomu

    2015-01-01

    Tissue-specific functions of the circadian clock in Arabidopsis have recently been revealed. The vasculature clock shows distinctive gene expression profiles compared to the clock in other tissues under light-dark cycles. However, it has not yet been established whether the vasculature clock also shows unique gene expression patterns that correlate with temperature cycles, another important environmental cue. Here, we detected diel phase of TIMING OF CAB EXPRESSION 1 (TOC1) expression in the vasculature and whole leaf under long-day light-dark cycles and temperature cycles. We found that the vasculature clock had advanced TOC1 phase under light-dark cycles but not under temperature cycles, suggesting that the vasculature clock has lower sensitivity against temperature signals. Furthermore, the phase advancement of TOC1 was seen only under long-day condition but not under short-day condition. These results support our previous conclusion that the circadian clock in vasculature preferentially senses photoperiodic signals.

  8. Making optical atomic clocks more stable with $10^{-16}$ level laser stabilization

    CERN Document Server

    Jiang, Y Y; Lemke, N D; Fox, R W; Sherman, J A; Ma, L -S; Oates, C W

    2011-01-01

    The superb precision of an atomic clock is derived from its stability. Atomic clocks based on optical (rather than microwave) frequencies are attractive because of their potential for high stability, which scales with operational frequency. Nevertheless, optical clocks have not yet realized this vast potential, due in large part to limitations of the laser used to excite the atomic resonance. To address this problem, we demonstrate a cavity-stabilized laser system with a reduced thermal noise floor, exhibiting a fractional frequency instability of $2 \\times 10^{-16}$. We use this laser as a stable optical source in a Yb optical lattice clock to resolve an ultranarrow 1 Hz transition linewidth. With the stable laser source and the signal to noise ratio (S/N) afforded by the Yb optical clock, we dramatically reduce key stability limitations of the clock, and make measurements consistent with a clock instability of $5 \\times 10^{-16} / \\sqrt{\\tau}$.

  9. Biological rhythms and fertility: the hypothalamus–pituitary–ovary axis

    Directory of Open Access Journals (Sweden)

    Toffol E

    2016-03-01

    Full Text Available Elena Toffol,1 Oskari Heikinheimo,2,3 Timo Partonen1 1Department of Health, National Institute for Health and Welfare (THL, 2Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, 3Kätilöopisto Hospital, Helsinki University Hospital, Helsinki, Finland Abstract: In addition to normal physiological processes, a number of pathological conditions exhibit diurnal and seasonal fluctuations in their incidence. These biological rhythms are generated by the circadian clocks that adjust their functions and adapt to the habitat. Misalignment of biological rhythms and disrupted functions of the circadian clocks may eventually have a negative impact on reproduction, which is the focus of this review. A large body of literature from animal studies has demonstrated the role of core clock genes and clock-controlled genes in regulation of reproductive events. In contrast, only a few studies, mostly epidemiological ones, suggest that perturbations of the circadian clock functions, eg, due to shift work or jet lag, compromise human reproduction. Keywords: animal, circadian, diurnal, human, reproduction

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

    Science.gov (United States)

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

    1996-12-01

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

  11. Genome increase as a clock for the origin and evolution of life

    Directory of Open Access Journals (Sweden)

    Sharov Alexei A

    2006-06-01

    Full Text Available Abstract Background The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution. Results I propose a hypothesis that biological complexity increased exponentially during evolution. Regression of the logarithm of functional non-redundant genome size versus time of origin in major groups of organisms showed a 7.8-fold increase per 1 billion years, and hence the increase of complexity can be viewed as a clock of macro-evolution. A strong version of the exponential hypothesis is that the rate of complexity increase in early (pre-prokaryotic evolution of life was at most the same (or even slower than observed in the evolution of prokaryotes and eukaryotes. Conclusion The increase of functional non-redundant genome size in macro-evolution was consistent with the exponential hypothesis. If the strong exponential hypothesis is true, then the origin of life should be dated 10 billion years ago. Thus, the possibility of panspermia as a source of life on earth should be discussed on equal basis with alternative hypotheses of de-novo life origin. Panspermia may be proven if bacteria similar to terrestrial ones are found on other planets or satellites in the solar system. Reviewers This article was reviewed by Eugene V. Koonin, Chris Adami and Arcady Mushegian.

  12. Genome increase as a clock for the origin and evolution of life

    Science.gov (United States)

    Sharov, Alexei A

    2006-01-01

    Background The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution. Results I propose a hypothesis that biological complexity increased exponentially during evolution. Regression of the logarithm of functional non-redundant genome size versus time of origin in major groups of organisms showed a 7.8-fold increase per 1 billion years, and hence the increase of complexity can be viewed as a clock of macro-evolution. A strong version of the exponential hypothesis is that the rate of complexity increase in early (pre-prokaryotic) evolution of life was at most the same (or even slower) than observed in the evolution of prokaryotes and eukaryotes. Conclusion The increase of functional non-redundant genome size in macro-evolution was consistent with the exponential hypothesis. If the strong exponential hypothesis is true, then the origin of life should be dated 10 billion years ago. Thus, the possibility of panspermia as a source of life on earth should be discussed on equal basis with alternative hypotheses of de-novo life origin. Panspermia may be proven if bacteria similar to terrestrial ones are found on other planets or satellites in the solar system. Reviewers This article was reviewed by Eugene V. Koonin, Chris Adami and Arcady Mushegian. PMID:16768805

  13. Circadian clocks are resounding in peripheral tissues.

    Directory of Open Access Journals (Sweden)

    Andrey A Ptitsyn

    2006-03-01

    Full Text Available Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%-10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity.

  14. Timing of Photoperiodic Flowering:Light Perception and Circadian Clock

    Institute of Scientific and Technical Information of China (English)

    Yun Zhou; Xiao-Dong Sun; Min Ni

    2007-01-01

    Flowering symbolizes the transition of a plant from vegetative phase to reproductive phase and is controlled by fairly complex and highly coordinated regulatory pathways. Over the last decade, genetic studies in Arabidopsis have aided the discovery of many signaling components involved in these pathways. In this review, we discuss how the timing of flowering is regulated by photoperiod and the involvement of light perception and the circadian clock in this process. The specific regulatory mechanisms on CONSTANS expression and CONSTANS stability by the circadian clock and photoreceptors are described in detail. In addition, the roles of CONSTANS, FLOWERING LOCUS T, and several other light signaling and circadiandependent components in photoperiodic flowering are also highlighted.

  15. Phase locking a clock oscillator to a coherent atomic ensemble

    CERN Document Server

    Kohlhaas, R; Cantin, E; Aspect, A; Landragin, A; Bouyer, P

    2015-01-01

    The sensitivity of an atomic interferometer increases when the phase evolution of its quantum superposition state is measured over a longer interrogation interval. In practice, a limit is set by the measurement process, which returns not the phase, but its projection in terms of population difference on two energetic levels. The phase interval over which the relation can be inverted is thus limited to the interval $[-\\pi/2,\\pi/2]$; going beyond it introduces an ambiguity in the read out, hence a sensitivity loss. Here, we extend the unambiguous interval to probe the phase evolution of an atomic ensemble using coherence preserving measurements and phase corrections, and demonstrate the phase lock of the clock oscillator to an atomic superposition state. We propose a protocol based on the phase lock to improve atomic clocks under local oscillator noise, and foresee the application to other atomic interferometers such as inertial sensors.

  16. Covariance and Quantum Cosmology: A Comparison of Two Matter Clocks

    Science.gov (United States)

    Halnon, Theodore; Bojowald, Martin

    2017-01-01

    In relativity, time is relative between reference frames. However, quantum mechanics requires a specific time coordinate in order to write an evolution equation for wave functions. This difference between the two theories leads to the problem of time in quantum gravity. One method to study quantum relativity is to interpret the dynamics of a matter field as a clock. In order to test the relationship between different reference frames, an isotropic cosmological model with two matter ingredients is introduced. One is given by a scalar field and one by vacuum energy or a cosmological constant. There are two matter fields, and thus two different Hamiltonians are derived from the respective clock rates. Semi-classical solutions are found for these equations and a comparison is made of the physical predictions that they imply. Partial funding from the Ronald E. McNair Postbaccalaureate Achievement Program.

  17. Spin-orbit coupled fermions in an optical lattice clock

    CERN Document Server

    Kolkowitz, S; Bothwell, T; Wall, M L; Marti, G E; Koller, A P; Zhang, X; Rey, A M; Ye, J

    2016-01-01

    Engineered spin-orbit coupling (SOC) in cold atom systems can aid in the study of novel synthetic materials and complex condensed matter phenomena. Despite great advances, alkali atom SOC systems are hindered by heating from spontaneous emission, which limits the observation of many-body effects. Here we demonstrate the use of optical lattice clocks (OLCs) to engineer and study SOC with metrological precision and negligible heating. We show that clock spectroscopy of the ultra-narrow transition in fermionic 87Sr represents a momentum- and spin-resolved in situ probe of the SOC band structure and eigenstates, providing direct access to the SOC dynamics and control over lattice band populations, internal electronic states, and quasimomenta. We utilize these capabilities to study Bloch oscillations, spin-momentum locking, and van Hove singularities in the transition density of states. Our results lay the groundwork for the use of OLCs to probe novel SOC phases including magnetic crystals, helical liquids, and to...

  18. Gravitational wave detection with optical lattice atomic clocks

    CERN Document Server

    Kolkowitz, Shimon; Langellier, Nicholas; Lukin, Mikhail D; Walsworth, Ronald L; Ye, Jun

    2016-01-01

    We propose a space-based gravitational wave detector consisting of two spatially separated, drag-free satellites sharing ultra-stable optical laser light over a single baseline. Each satellite contains an optical lattice atomic clock, which serves as a sensitive, narrowband detector of the local frequency of the shared laser light. A synchronized two-clock comparison between the satellites will be sensitive to the effective Doppler shifts induced by incident gravitational waves (GWs) at a level competitive with other proposed space-based GW detectors, while providing complementary features. The detected signal is a differential frequency shift of the shared laser light due to the relative velocity of the satellites, rather than a phase shift arising from the relative satellite positions, and the detection window can be tuned through the control sequence applied to the atoms' internal states. This scheme enables the detection of GWs from continuous, spectrally narrow sources, such as compact binary inspirals, ...

  19. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice.

    Science.gov (United States)

    Peek, Clara Bien; Affinati, Alison H; Ramsey, Kathryn Moynihan; Kuo, Hsin-Yu; Yu, Wei; Sena, Laura A; Ilkayeva, Olga; Marcheva, Biliana; Kobayashi, Yumiko; Omura, Chiaki; Levine, Daniel C; Bacsik, David J; Gius, David; Newgard, Christopher B; Goetzman, Eric; Chandel, Navdeep S; Denu, John M; Mrksich, Milan; Bass, Joseph

    2013-11-01

    Circadian clocks are self-sustained cellular oscillators that synchronize oxidative and reductive cycles in anticipation of the solar cycle. We found that the clock transcription feedback loop produces cycles of nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, adenosine triphosphate production, and mitochondrial respiration through modulation of mitochondrial protein acetylation to synchronize oxidative metabolic pathways with the 24-hour fasting and feeding cycle. Circadian control of the activity of the NAD(+)-dependent deacetylase sirtuin 3 (SIRT3) generated rhythms in the acetylation and activity of oxidative enzymes and respiration in isolated mitochondria, and NAD(+) supplementation restored protein deacetylation and enhanced oxygen consumption in circadian mutant mice. Thus, circadian control of NAD(+) bioavailability modulates mitochondrial oxidative function and organismal metabolism across the daily cycles of fasting and feeding.

  20. Regulation of intestinal lipid absorption by clock genes.

    Science.gov (United States)

    Hussain, M Mahmood

    2014-01-01

    Plasma levels of triacylglycerols and diacylglycerols, the lipoproteins that transport them, and proteins involved in their absorption from the intestinal lumen fluctuate in a circadian manner. These changes are likely controlled by clock genes expressed in the intestine that are probably synchronized by neuronal and humoral signals from the suprachiasmatic nuclei, which constitute a master clock entrained by light signals from the eyes and from the environment, e.g., food availability. Acute changes in circadian rhythms--e.g., due to nonsynchronous work schedules or a transcontinental flight--may trigger intestinal discomfort. Chronic disruptions in circadian control mechanisms may predispose the individual to irritable bowel syndrome, gastroesophageal reflux disease, and peptic ulcer disease. A more detailed understanding of the molecular mechanisms underlying temporal changes in intestinal activity might allow us to identify novel targets for developing therapeutic approaches to these disorders.

  1. Synchronous Droplet Microfluidics: One "Clock" to rule them all

    CERN Document Server

    Katsikis, Georgios

    2013-01-01

    Controlling fluid droplets efficiently in the microscale is of great interest both from a basic science and a technology perspective. We have designed and developed a general-purpose, highly scalable microfluidic control strategy through a single global clock signal that enables synchronous control of arbitrary number of droplets in a planar geometry. A rotating precessive magnetic field provides a global clock signal, enabling simultaneous control of droplet position, velocity and trajectories. Here, in this fluid dynamics video, we explain the main physics of this new microfluidic concept. Video data from droplets moving in sync in different fluidic circuits are included. The experimental setup is described and video data is analyzed to provide a detailed view of the time-dynamics of propagating droplets. Finally, we explore the operational limits of this concept, scaling and phase diagram with physical regime diagram.

  2. Optical Stabilization of a Microwave Oscillator for Fountain Clock Interrogation

    CERN Document Server

    Lipphardt, Burghard; Weyers, Stefan

    2016-01-01

    We describe an optical frequency stabilization scheme of a microwave oscillator that is used for the interrogation of primary caesium fountain clocks. Because of its superior phase noise properties, the new scheme, which is based on an ultrastable laser and a femtosecond laser frequency comb, overcomes the fountain clock frequency instability limitations given by the previously utilized quartz oscillator based frequency synthesis. The presented scheme combines the transfer of the short-term frequency instability of an optical cavity and the long-term frequency instability of a hydrogen maser to the microwave oscillator and is designed to provide continuous long-term operation for extended measurement periods of weeks. The utilization of the twofold stabilization scheme on the one hand ensures referencing of the fountain frequency to the hydrogen maser frequency and on the other hand results in a phase noise level of the fountain interrogation signal, which enables quantum projection noise limited fountain fre...

  3. The Pentose Phosphate Pathway Regulates the Circadian Clock.

    Science.gov (United States)

    Rey, Guillaume; Valekunja, Utham K; Feeney, Kevin A; Wulund, Lisa; Milev, Nikolay B; Stangherlin, Alessandra; Ansel-Bollepalli, Laura; Velagapudi, Vidya; O'Neill, John S; Reddy, Akhilesh B

    2016-09-13

    The circadian clock is a ubiquitous timekeeping system that organizes the behavior and physiology of organisms over the day and night. Current models rely on transcriptional networks that coordinate circadian gene expression of thousands of transcripts. However, recent studies have uncovered phylogenetically conserved redox rhythms that can occur independently of transcriptional cycles. Here we identify the pentose phosphate pathway (PPP), a critical source of the redox cofactor NADPH, as an important regulator of redox and transcriptional oscillations. Our results show that genetic and pharmacological inhibition of the PPP prolongs the period of circadian rhythms in human cells, mouse tissues, and fruit flies. These metabolic manipulations also cause a remodeling of circadian gene expression programs that involves the circadian transcription factors BMAL1 and CLOCK, and the redox-sensitive transcription factor NRF2. Thus, the PPP regulates circadian rhythms via NADPH metabolism, suggesting a pivotal role for NADPH availability in circadian timekeeping.

  4. Brain clock driven by neuropeptides and second messengers

    Science.gov (United States)

    Miro-Bueno, Jesus; Sosík, Petr

    2014-09-01

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

  5. Motion and gravity effects in the precision of quantum clocks

    CERN Document Server

    Lindkvist, Joel; Johansson, Göran; Fuentes, Ivette

    2014-01-01

    We show that motion and gravity affect the precision of quantum clocks. We consider a localised quantum field as a fundamental model of a quantum clock moving in spacetime and show that its state is modified due to changes in acceleration. By computing the quantum Fisher information we determine how relativistic motion modifies the ultimate bound in the precision of the measurement of time. While in the absence of motion the squeezed vacuum is the ideal state for time estimation, we find that it is highly sensitive to the motion-induced degradation of the quantum Fisher information. We show that coherent states are generally more resilient to this degradation and that in the case of very low initial number of photons, the optimal precision can be even increased by motion. These results can be tested with current technology by using superconducting resonators with tunable boundary conditions.

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

    CERN Document Server

    Gauvin, Laetitia; Cattuto, Ciro; Barrat, Alain

    2013-01-01

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

  7. C-terminal binding protein (CtBP activates the expression of E-box clock genes with CLOCK/CYCLE in Drosophila.

    Directory of Open Access Journals (Sweden)

    Taichi Q Itoh

    Full Text Available In Drosophila, CLOCK/CYCLE heterodimer (CLK/CYC is the primary activator of circadian clock genes that contain the E-box sequence in their promoter regions (hereafter referred to as "E-box clock genes". Although extensive studies have investigated the feedback regulation of clock genes, little is known regarding other factors acting with CLK/CYC. Here we show that Drosophila C-terminal binding protein (dCtBP, a transcriptional co-factor, is involved in the regulation of the E-box clock genes. In vivo overexpression of dCtBP in clock cells lengthened or abolished circadian locomotor rhythm with up-regulation of a subset of the E-box clock genes, period (per, vrille (vri, and PAR domain protein 1ε (Pdp1ε. Co-expression of dCtBP with CLK in vitro also increased the promoter activity of per, vri, Pdp1ε and cwo depending on the amount of dCtBP expression, whereas no effect was observed without CLK. The activation of these clock genes in vitro was not observed when we used mutated dCtBP which carries amino acid substitutions in NAD+ domain. These results suggest that dCtBP generally acts as a putative co-activator of CLK/CYC through the E-box sequence.

  8. NONO couples the circadian clock to the cell cycle

    OpenAIRE

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

    2013-01-01

    Mammalian circadian clocks restrict cell proliferation to defined time windows, but the mechanism and consequences of this interrelationship are not fully understood. Previously we identified the multifunctional nuclear protein NONO as a partner of circadian PERIOD (PER) proteins. Here we show that it also conveys circadian gating to the cell cycle, a connection surprisingly important for wound healing in mice. Specifically, although fibroblasts from NONO-deficient mice showed approximately n...

  9. 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.

  10. Correcting for purifying selection: an improved human mitochondrial molecular clock.

    Science.gov (United States)

    Soares, Pedro; Ermini, Luca; Thomson, Noel; Mormina, Maru; Rito, Teresa; Röhl, Arne; Salas, Antonio; Oppenheimer, Stephen; Macaulay, Vincent; Richards, Martin B

    2009-06-01

    There is currently no calibration available for the whole human mtDNA genome, incorporating both coding and control regions. Furthermore, as several authors have pointed out recently, linear molecular clocks that incorporate selectable characters are in any case problematic. We here confirm a modest effect of purifying selection on the mtDNA coding region and propose an improved molecular clock for dating human mtDNA, based on a worldwide phylogeny of > 2000 complete mtDNA genomes and calibrating against recent evidence for the divergence time of humans and chimpanzees. We focus on a time-dependent mutation rate based on the entire mtDNA genome and supported by a neutral clock based on synonymous mutations alone. We show that the corrected rate is further corroborated by archaeological dating for the settlement of the Canary Islands and Remote Oceania and also, given certain phylogeographic assumptions, by the timing of the first modern human settlement of Europe and resettlement after the Last Glacial Maximum. The corrected rate yields an age of modern human expansion in the Americas at approximately 15 kya that-unlike the uncorrected clock-matches the archaeological evidence, but continues to indicate an out-of-Africa dispersal at around 55-70 kya, 5-20 ky before any clear archaeological record, suggesting the need for archaeological research efforts focusing on this time window. We also present improved rates for the mtDNA control region, and the first comprehensive estimates of positional mutation rates for human mtDNA, which are essential for defining mutation models in phylogenetic analyses.

  11. Ultra-stable clock laser system development towards space applications

    Science.gov (United States)

    Świerad, Dariusz; Häfner, Sebastian; Vogt, Stefan; Venon, Bertrand; Holleville, David; Bize, Sébastien; Kulosa, André; Bode, Sebastian; Singh, Yeshpal; Bongs, Kai; Rasel, Ernst Maria; Lodewyck, Jérôme; Le Targat, Rodolphe; Lisdat, Christian; Sterr, Uwe

    2016-09-01

    The increasing performance of optical lattice clocks has made them attractive for scientific applications in space and thus has pushed the development of their components including the interrogation lasers of the clock transitions towards being suitable for space, which amongst others requires making them more power efficient, radiation hardened, smaller, lighter as well as more mechanically stable. Here we present the development towards a space-compatible interrogation laser system for a strontium lattice clock constructed within the Space Optical Clock (SOC2) project where we have concentrated on mechanical rigidity and size. The laser reaches a fractional frequency instability of 7.9 × 10-16 at 300 ms averaging time. The laser system uses a single extended cavity diode laser that gives enough power for interrogating the atoms, frequency comparison by a frequency comb and diagnostics. It includes fibre link stabilisation to the atomic package and to the comb. The optics module containing the laser has dimensions 60 × 45 × 8 cm3 and the ultra-stable reference cavity used for frequency stabilisation with its vacuum system takes 30 × 30 × 30 cm3. The acceleration sensitivities in three orthogonal directions of the cavity are 3.6 × 10-10/g, 5.8 × 10-10/g and 3.1 × 10-10/g, where g ≈ 9.8 m/s2 is the standard gravitational acceleration.

  12. The fission time scale measured with an atomic clock

    NARCIS (Netherlands)

    Kravchuk, VL; Wilschut, HW; Hunyadi, M; Kopecky, S; Lohner, H; Rogachevskiy, A; Siemssen, RH; Krasznahorkay, A; Hamilton, JH; Ramayya, AV; Carter, HK

    2003-01-01

    We present a new direct method of measuring the fission absolute time scale using an atomic clock based on the lifetime of a vacancy in the atomic K-shell. We studied the reaction Ne-20 + Th-232 -> O-16 + U-236* at 30 MeV/u. The excitation energy of about 115 MeV in such a reaction is in the range w

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

    Science.gov (United States)

    Loogväli, Eva-Liis; Kivisild, Toomas; Margus, Tõnu; Villems, Richard

    2009-12-29

    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.

  14. Molecular clock fork phylogenies: closed form analytic maximum likelihood solutions.

    Science.gov (United States)

    Chor, Benny; Snir, Sagi

    2004-12-01

    Maximum likelihood (ML) is increasingly used as an optimality criterion for selecting evolutionary trees, but finding the global optimum is a hard computational task. Because no general analytic solution is known, numeric techniques such as hill climbing or expectation maximization (EM) are used in order to find optimal parameters for a given tree. So far, analytic solutions were derived only for the simplest model-three-taxa, two-state characters, under a molecular clock. Quoting Ziheng Yang, who initiated the analytic approach,"this seems to be the simplest case, but has many of the conceptual and statistical complexities involved in phylogenetic estimation."In this work, we give general analytic solutions for a family of trees with four-taxa, two-state characters, under a molecular clock. The change from three to four taxa incurs a major increase in the complexity of the underlying algebraic system, and requires novel techniques and approaches. We start by presenting the general maximum likelihood problem on phylogenetic trees as a constrained optimization problem, and the resulting system of polynomial equations. In full generality, it is infeasible to solve this system, therefore specialized tools for the molecular clock case are developed. Four-taxa rooted trees have two topologies-the fork (two subtrees with two leaves each) and the comb (one subtree with three leaves, the other with a single leaf). We combine the ultrametric properties of molecular clock fork trees with the Hadamard conjugation to derive a number of topology dependent identities. Employing these identities, we substantially simplify the system of polynomial equations for the fork. We finally employ symbolic algebra software to obtain closed formanalytic solutions (expressed parametrically in the input data). In general, four-taxa trees can have multiple ML points. In contrast, we can now prove that each fork topology has a unique(local and global) ML point.

  15. Newly Described Components and Regulatory Mechanisms of Circadian Clock Function in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Manuel Adrián Troncoso-Ponce; Paloma Mas

    2012-01-01

    The circadian clock temporally coordinates plant growth and metabolism in close synchronization with the diurnal and seasonal environmental changes.Research over the last decade has identified a number of clock components and a variety of regulatory mechanisms responsible for the rhythmic oscillations in metabolic and physiological activities.At the core of the clock,transcriptional/translational feedback loops modulate the expression of a significant proportion of the genome.In this article,we briefly describe some of the very recent advances that have improved our understanding of clock organization and function in Arabidopsis thaliana.The new studies illustrate the role of clock protein complex formation on circadian gating of plant growth and identify alternative splicing as a new regulatory mechanism for clock function.Examination of key clock properties such as temperature compensation has also opened new avenues for functional research within the plant clockwork.The emerging connections between the circadian clock and metabolism,hormone signaling and response to biotic and abiotic stress also add new layers of complexity to the clock network and underscore the significance of the circadian clock regulating the daily life of plants.

  16. Circadian clock components in the rat neocortex: daily dynamics, localization and regulation.

    Science.gov (United States)

    Rath, Martin F; Rohde, Kristian; Fahrenkrug, Jan; Møller, Morten

    2013-03-01

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

  17. The Long-term Performance Analysis for On-board Atomic Clocks of BDS

    Directory of Open Access Journals (Sweden)

    WANG Yupu

    2017-02-01

    Full Text Available BeiDou Navigation Satellite System (BDS has begun to provide regional services since the end of 2012. It plays an important role in analyzing the long-term performance of BDS satellite clocks in evaluating the performance of the whole system, determining and predicting satellite clock bias (SCB etc. Precise satellite clock data products derived from multi-satellite orbit determination are used to conduct the performance analysis of BDS satellite clocks. Specifically, the characteristics of SCB data are discussed by using a proposed modified median absolute deviation (MAD to preprocess original SCB data. Long-term variations of satellite clocks' phase, frequency, frequency drift and model noise level are analyzed based on the quadratic polynomial SCB model. Frequency stability of BDS satellite clocks is calculated and discussed based on Overlapping Hadamard Variance. Periodicity of BDS SCB is analyzed by using spectral analysis method. Integrating the above mentioned discussions and corresponding experiment results, the long-term performance of BDS satellite clocks is relatively comprehensively evaluated and analyzed. In addition, some valuable conclusions are obtained. For example, in the aspects of noise characteristics and clock drift, the performance of MEO satellite clocks is the best, followed by the IGSO satellite clocks, and the GEO satellite clocks' performance is the worst. The average values of noise level and frequency drift of BDS satellite clocks are respectively 0.677 ns and 1.922×10-18. There are also obvious periodic terms in BDS SCB data derived from multi-satellite orbit determination and their primary periods are approximate equal or one-half to the corresponding satellite orbit periods. The average value of frequency stability of BDS satellite clocks is 1.484×10-13.

  18. 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.

  19. Synchronization of Active Atomic Clocks via Quantum and Classical Channels

    CERN Document Server

    Roth, Alexander

    2016-01-01

    Superradiant lasers based on atomic ensembles exhibiting ultra-narrow optical transitions can emit light of unprecedented spectral purity and may serve as active atomic clocks. We consider two frequency-detuned active atomic clocks, which are coupled in a cascaded setup, i.e. as master & slave lasers, and study the synchronization of the slave to the master clock. In a setup where both atomic ensembles are coupled to a common cavity mode such synchronization phenomena have been predicted by Xu et al. [Phys. Rev. Lett. 113, 154101 (2014)] and experimentally observed by Weiner et al. [arXiv:1503.06464 (2015)]. Here we demonstrate that synchronization still occurs in cascaded setups but exhibits distinctly different phase diagrams. We study the characteristics of synchronization in comparison to the case of coupling through a common cavity. We also consider synchronization through a classical channel where light of the master laser is measured phase sensitively and the slave laser is injection locked by feed...

  20. Compact atomic clock prototype based on coherent population trapping

    Directory of Open Access Journals (Sweden)

    Danet Jean-Marie

    2014-01-01

    Full Text Available Toward the next generations of compact atomic clocks, clocks based on coherent population trapping (CPT offer a very interesting alternative. Thanks to CPT, a quantum interfering process, this technology has made a decisive step in the miniaturization direction. Fractional frequency stability of 1.5x10-10 at 1 s has been demonstrated in commercial devices of a few cm3. The laboratory prototype presented here intends to explore what could be the ultimate stability of a CPT based device. To do so, an original double-Λ optical scheme and a pulsed interrogation have been implemented in order to get a good compromise between contrast and linewidth. A study of two main sources of noise, the relative intensity and the local oscillator (LO noise, has been performed. By designing simple solutions, it led to a new fractional frequency limitation lower than 4x10-13 at 1 s integration. Such a performance proves that such a technology could rival with classical ones as double resonance clocks.

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

    Science.gov (United States)

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

    2013-01-29

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

  2. GRK2: putting the brakes on the circadian clock

    Science.gov (United States)

    Mendoza-Viveros, Lucia; Cheng, Arthur H.

    2016-01-01

    G protein-coupled receptor kinases (GRKs) are a family of serine/threonine protein kinases that terminate G protein-coupled receptor (GPCR) signaling by phosphorylating the receptor and inducing its internalization. In addition to their canonical function, some GRKs can phosphorylate non-GPCR substrates and regulate GPCR signaling in a kinase-independent manner. GPCRs are abundantly expressed in the suprachiasmatic nucleus (SCN), a structure in the mammalian brain that serves as the central circadian pacemaker. Various facets of circadian timekeeping are under the influence of GPCR signaling, and thus are potential targets for GRK regulation. Despite this, little attention has been given to the role of GRKs in circadian rhythms. In this research highlight, we discuss our latest findings on the functional involvement of GRK2 in mammalian circadian timekeeping in the SCN. Using grk2 knockout mice, we demonstrate that GRK2 is critical for maintaining proper clock speed and ensuring that the clock is appropriately synchronized to environmental light cycles. Although grk2 deficiency expectedly alters the expression of a key GPCR in the SCN, our study also reveals that GRK2 has a more direct function that touches the heart of the circadian clock. PMID:27088110

  3. Experimenting an optical second with strontium lattice clocks

    CERN Document Server

    Targat, R Le; Coq, Y Le; Zawada, M; Guéna, J; Abgrall, M; Gurov, M; Rosenbusch, P; Rovera, D G; Nagórny, B; Gartman, R; Westergaard, P G; Tobar, M E; Lours, M; Santarelli, G; Clairon, A; Bize, S; Laurent, P; Lemonde, P; Lodewyck, J

    2013-01-01

    Progress in realizing the SI second had multiple technological impacts and enabled to further constraint theoretical models in fundamental physics. Caesium microwave fountains, realizing best the second according to its current definition with a relative uncertainty of 2-4x10^(-16), have already been superseded by atomic clocks referenced to an optical transition, both more stable and more accurate. Are we ready for a new definition of the second? Here we present an important step in this direction: our system of five clocks connects with an unprecedented consistency the optical and the microwave worlds. For the first time, two state-of-the-art strontium optical lattice clocks are proven to agree within their accuracy budget, with a total uncertainty of 1.6x10^(-16). Their comparison with three independent caesium fountains shows a degree of reproducibility henceforth solely limited at the level of 3.1x10^(-16) by the best realizations of the microwave-defined second.

  4. Synchronization of active atomic clocks via quantum and classical channels

    Science.gov (United States)

    Roth, Alexander; Hammerer, Klemens

    2016-10-01

    Superradiant lasers based on atomic ensembles exhibiting ultranarrow optical transitions can emit light of unprecedented spectral purity and may serve as active atomic clocks. We consider two frequency-detuned active atomic clocks, which are coupled in a cascaded setup, i.e., as master and slave lasers, and study the synchronization of the slave to the master clock. In a setup where both atomic ensembles are coupled to a common cavity mode, such synchronization phenomena have been predicted by Xu et al. [M. Xu, D. A. Tieri, E. C. Fine, J. K. Thompson, and M. J. Holland, Phys. Rev. Lett. 113, 154101 (2014)., 10.1103/PhysRevLett.113.154101] and experimentally observed by Weiner et al. (J. M. Weiner et al., arXiv:1503.06464). Here we demonstrate that synchronization still occurs in cascaded setups but exhibits distinctly different phase diagrams. We study the characteristics of synchronization in comparison to the case of coupling through a common cavity. We also consider synchronization through a classical channel where light of the master laser is measured phase sensitively and the slave laser is injection locked by feedback and compare to the results achievable by coupling through quantum channels.

  5. Carbonic anhydrase activity in the vas deferens of the cotton leafworm - Spodoptera littoralis (Lepidoptera: Noctuidae) controlled by circadian clock.

    Science.gov (United States)

    Kotwica, J; Ciuk, M A; Joachimiak, E; Rowinski, S; Cymborowski, B; Bebas, P

    2006-11-01

    The male reproductive tract of Lepidoptera is an ideal model for the study of the physiological role of peripheral clocks in insects. The latter are significant in the generation and coordination of rhythmic phenomena which facilitate the initial stages of sperm capacitation. This process requires the maintenance of pH in the upper vas deferens (UVD) aided by, among others, H+-ATPase. Our aim was to determine the potential involvement of carbonic anhydrase (CA) in this process, an enzyme tasked with generating protons subsequently utilized by H+-ATPase to acidify the UVD milieu in S. littoralis, during the time when the lumen of this organ is filled with sperm. We attempted to answer the question whether CA activity can be controlled by the biological oscillator present in the male reproductive tract of the cotton leafworm. Using PAGE zymography, the presence of CA was demonstrated in the UVD wall, but not in the luminal fluid nor in the sperm. Using histochemistry, it was shown that CA is active in the UVD epithelium, and that this activity varies throughout the day and is most likely controlled by an endogenous biological clock. Conversely, the application of CA inhibitors, acetazolamide and sodium thiocyanate, in conjunction with an analysis of H+-ATPase activity in the acidification the UVD environment shows that CA most likely does not play a direct role in the regulation of the pH in this organ.

  6. Estradiol differently affects melanin synthesis of malignant and normal melanocytes: a relationship with clock and clock-controlled genes.

    Science.gov (United States)

    Poletini, Maristela Oliveira; de Assis, Leonardo Vinicius Monteiro; Moraes, Maria Nathalia; Castrucci, Ana Maria de Lauro

    2016-10-01

    Melanin production within melanocytes is regulated, among others, by estradiol, whose effects on melanogenesis are still not completely elucidated. Here we show that although 10(-7) M 17β-estradiol (E2) increased tyrosinase mRNA levels in B16-F10 malignant melanocytes, there was a transient decrease and abolishment of the temporal variation of melanin content. Both parameters were much higher in the malignant than in normal Melan-a cells. Considering that silencing clock machinery in human melanocytes increases melanogenesis, we investigated clock gene expression in those cell lines. Except for Melan-a Bmal1 and B16-F10 Per2 expression of control cells, Per1, Per2, and Bmal1 expression increased independently of cell type or E2 treatment after 24 h. However, melanoma cells showed a marked increase in Per1 and Bma11 expression in response to E2 at the same time points, what may rule out E2 as a synchronizer agent since the expression of those genes were not in antiphase. Next, we investigated the expression of Xpa, a clock-controlled gene, which in Melan-a cells, peaked at 18 h, and E2 treatment shifted this peak to 24 h, whereas B16-F10 Xpa expression peaked at 24 h in both control and E2 group, and it was higher compared to Melan-a cells in both groups. Therefore, malignant and normal melanocytes display profound differences on core elements of the local clock, and how they respond to E2, what is most probably determinant of the differences seen on melanin synthesis and Tyrosinase and Xpa expression. Understanding these processes at the molecular level could bring new strategies to treat melanoma.

  7. Detecting gravitational decoherence with clocks: Limits on temporal resolution from a classical channel model of gravity

    CERN Document Server

    Khosla, Kiran

    2016-01-01

    The notion of time is given a different footing in Quantum Mechanics and General Relativity, treated as a parameter in the former and being an observer dependent property in the later. From a operational point of view time is simply the correlation between a system and a clock, where an idealized clock can be modelled as a two level systems. We investigate the dynamics of clocks interacting gravitationally by treating the gravitational interaction as a classical information channel. In particular, we focus on the decoherence rates and temporal resolution of arrays of $N$ clocks showing how the minimum dephasing rate scales with $N$, and the spatial configuration. Furthermore, we consider the gravitational redshift between a clock and massive particle and show that a classical channel model of gravity predicts a finite dephasing rate from the non-local interaction. In our model we obtain a fundamental limitation in time accuracy that is intrinsic to each clock.

  8. Entrainment of the mouse circadian clock by sub-acute physical and psychological stress.

    Science.gov (United States)

    Tahara, Yu; Shiraishi, Takuya; Kikuchi, Yosuke; Haraguchi, Atsushi; Kuriki, Daisuke; Sasaki, Hiroyuki; Motohashi, Hiroaki; Sakai, Tomoko; Shibata, Shigenobu

    2015-01-01

    The effects of acute stress on the peripheral circadian system are not well understood in vivo. Here, we show that sub-acute stress caused by restraint or social defeat potently altered clock gene expression in the peripheral tissues of mice. In these peripheral tissues, as well as the hippocampus and cortex, stressful stimuli induced time-of-day-dependent phase-advances or -delays in rhythmic clock gene expression patterns; however, such changes were not observed in the suprachiasmatic nucleus, i.e. the central circadian clock. Moreover, several days of stress exposure at the beginning of the light period abolished circadian oscillations and caused internal desynchronisation of peripheral clocks. Stress-induced changes in circadian rhythmicity showed habituation and disappeared with long-term exposure to repeated stress. These findings suggest that sub-acute physical/psychological stress potently entrains peripheral clocks and causes transient dysregulation of circadian clocks in vivo.

  9. Towards a Re-definition of the Second Based on Optical Atomic Clocks

    CERN Document Server

    Riehle, Fritz

    2015-01-01

    The rapid increase in accuracy and stability of optical atomic clocks compared to the caesium atomic clock as primary standard of time and frequency asks for a future re-definition of the second in the International System of Units (SI). The status of the optical clocks based on either single ions in radio-frequency traps or on neutral atoms stored in an optical lattice is described with special emphasis of the current work at the Physikalisch-Technische Bundesanstalt (PTB). Besides the development and operation of different optical clocks with estimated fractional uncertainties in the 10^-18 range, the supporting work on ultra-stable lasers as core elements and the means to compare remote optical clocks via transportable standards, optical fibers, or transportable clocks is reported. Finally, the conditions, methods and next steps are discussed that are the prerequisites for a future re-definition of the second.

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

    CERN Document Server

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

    2016-01-01

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

  11. Frequency Stability of Atomic Clocks Based on Coherent Population Trapping Resonance in 85Rb

    Institute of Scientific and Technical Information of China (English)

    LIU Lu; GUO Tao; DENG Ke; LIU Xin-Yuan; CHEN Xu-Zong; WANG Zhong

    2007-01-01

    An atomic clock system based on coherent population trapping (CPT) resonance in 85Rb is reported, while most past works about the CPT clock are in 87Rb. A new modulation method (full-hyperfine-frequency-splitting modulation) is presented to reduce the effect of light shift to improve the frequency stability of the CPT clock in 85Rb. The experimental results show that the short-term frequency stability of the CPT clock in 85Rb is in the order of 10-10/s and the long-term frequency stability can achieve 1.5 × 10-11 /80000s, which performs as well as 87Rb in CPT resonance. This very good frequency stability performance associated with the low-cost and low-power properties of 85Rb indicates that an atomic clock based on CPT in 85 Rb should be a promising candidate for making the chip scale atomic clock.

  12. Variation in candidate genes CLOCK and ADCYAP1 does not consistently predict differences in migratory behavior in the songbird genus Junco [v1; ref status: indexed, http://f1000r.es/11p

    Directory of Open Access Journals (Sweden)

    Mark P Peterson

    2013-04-01

    Full Text Available Recent studies exploring the molecular genetic basis for migratory variation in animals have identified polymorphisms in two genes (CLOCK and ADCYAP1 that are linked to circadian rhythms and correlate with migratory propensity and phenology among individuals and populations. Results from these initial studies are mixed, however, and additional data are needed to assess the generality and diversity of the molecular mechanisms that regulate the biology of migration. We sequenced CLOCK and ADCYAP1 in 15 populations across the two species of the avian genus Junco, a North American lineage in which multiple recently diverged subspecies and populations range from sedentary to long-distance migrants. We found no consistent associations between allele length and migratory status across the genus for either CLOCK or ADCYAP1. However, within two subspecies groups, populations that migrate longer distances have longer CLOCK alleles on average. Additionally, there was a positive relationship between ADCYAP1 allele length and migratory restlessness (zugunruhe among individuals within one of two captive populations studied—a result similar to those reported previously within captive blackcaps (Sylvia atricapilla. We conclude that, while both ADCYAP1 and CLOCK may correlate with migratory propensity within or among certain populations or species, previously identified relationships between migratory behavior and sequence variants cannot be easily generalized across taxa.

  13. High accuracy measure of atomic polarizability in an optical lattice clock

    OpenAIRE

    Sherman, J. A.; Lemke, N. D.; Hinkley, N.; Pizzocaro, M.; Fox, R. W.; Ludlow, A. D.; Oates, C. W.

    2011-01-01

    Despite being a canonical example of quantum mechanical perturbation theory, as well as one of the earliest observed spectroscopic shifts, the Stark effect contributes the largest source of uncertainty in a modern optical atomic clock through blackbody radiation. By employing an ultracold, trapped atomic ensemble and high stability optical clock, we characterize the quadratic Stark effect with unprecedented precision. We report the ytterbium optical clock's sensitivity to electric fields (suc...

  14. Interfacing Of PIC 18F252 Microcontroller with Real Time Clock via I2C Protocol

    Directory of Open Access Journals (Sweden)

    Arnab G. Samanta

    2014-09-01

    Full Text Available This paper describes a microcontroller based digital clock which can be used in real time systems. The system is constructed using PIC18F252 (microcontroller, DS1307 (real time clock IC and its software program is written with C programming language. A 3v battery backup is provided to real time clock IC. Communication between PIC microcontroller and DS1307 takes place through I²C Bus protocol.

  15. Novel approach to reduce the pattern effect in 10-Gb/s clock recovery

    Institute of Scientific and Technical Information of China (English)

    Tong Wang(王桐); Caiyun Lou(娄采云); Li Huo(霍力); Yizhi Gao(高以智)

    2004-01-01

    @@ A Fabry-Perot(F-P)etalon and a semiconductor optical amplifier(SOA)were combined to preprocess thedata signals before clock recovery.With this technology in the 10-Gb/s clock recovery utilizing injectionmode-locked laser(IMLL)based on SOA,the amplitude fluctuation and timing jitters caused by thepattern effect in recovered clock pulses were greatly reduced,experimentally.It also demonstrated thatclock could be recovered from the very degraded signals.

  16. Feeding cues and injected nutrients induce acute expression of multiple clock genes in the mouse liver.

    Directory of Open Access Journals (Sweden)

    Hideaki Oike

    Full Text Available The circadian clock is closely associated with energy metabolism. The liver clock can rapidly adapt to a new feeding cycle within a few days, whereas the lung clock is gradually entrained over one week. However, the mechanism underlying tissue-specific clock resetting is not fully understood. To characterize the rapid response to feeding cues in the liver clock, we examined the effects of a single time-delayed feeding on circadian rhythms in the liver and lungs of Per2::Luc reporter knockin mice. After adapting to a night-time restricted feeding schedule, the mice were fed according to a 4, 8, or 13 h delayed schedule on the last day. The phase of the liver clock was delayed in all groups with delayed feeding, whereas the lung clock remained unaffected. We then examined the acute response of clock and metabolism-related genes in the liver using focused DNA-microarrays. Clock mutant mice were bred under constant light to attenuate the endogenous circadian rhythm, and gene expression profiles were determined during 24 h of fasting followed by 8 h of feeding. Per2 and Dec1 were significantly increased within 1 h of feeding. Real-time RT-PCR analysis revealed a similarly acute response in hepatic clock gene expression caused by feeding wild type mice after an overnight fast. In addition to Per2 and Dec1, the expression of Per1 increased, and that of Rev-erbα decreased in the liver within 1 h of feeding after fasting, whereas none of these clock genes were affected in the lung. Moreover, an intraperitoneal injection of glucose combined with amino acids, but not either alone, reproduced a similar hepatic response. Our findings show that multiple clock genes respond to nutritional cues within 1 h in the liver but not in the lung.

  17. Onboard clock correction for SS/TDMA and baseband processing satellites

    Science.gov (United States)

    Inukai, T.; Campanella, S. J.

    1981-05-01

    A clock correction scheme is presented that employs a predictor to achieve stability. A linear discrete model is used to analyze the worst-case timing error, clock correction rate, and buffer size requirements for traffic stations. The effects of secondary factors such as Doppler shift, range measurement error, quantization error of correction data, and delay incurred in transferring correction data to the satellite are also discussed. Special consideration is given to a sidereal day clock correction.

  18. Design and implementation of a clock recovery circuit for fast Ethernet applications

    Institute of Scientific and Technical Information of China (English)

    朱全庆; 邹雪城; 沈绪榜

    2004-01-01

    A circuit architechure to realize clock recovery for fast Ethernet applications is presented, whick includies system architecture, modified Mueller Muller algorithm for 100BASE-TX, phase detector for 100BASE-TX and multiple output charge pump PLL. The clock recovery circuit is verified by TSMC 0.35um 1P5M CMOS process. The results show that this clock recovery circuit exactly extracts the timing information. It has advantages over others for simple and easy implementation.

  19. The expression of melanopsin and clock genes in Xenopus laevis melanophores and their modulation by melatonin

    Energy Technology Data Exchange (ETDEWEB)

    Bluhm, A.P.C.; Obeid, N.N.; Castrucci, A.M.L.; Visconti, M.A. [Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-05-25

    Vertebrates have a central clock and also several peripheral clocks. Light responses might result from the integration of light signals by these clocks. The dermal melanophores of Xenopus laevis have a photoreceptor molecule denominated melanopsin (OPN4x). The mechanisms of the circadian clock involve positive and negative feedback. We hypothesize that these dermal melanophores also present peripheral clock characteristics. Using quantitative PCR, we analyzed the pattern of temporal expression of Opn4x and the clock genes Per1, Per2, Bmal1, and Clock in these cells subjected to a 14-h light:10-h dark (14L:10D) regime or constant darkness (DD). Also, in view of the physiological role of melatonin in the dermal melanophores of X. laevis, we determined whether melatonin modulates the expression of these clock genes. These genes show a time-dependent expression pattern when these cells are exposed to 14L:10D, which differs from the pattern observed under DD. Cells kept in DD for 5 days exhibited overall increased mRNA expression for Opn4x and Clock, and a lower expression for Per1, Per2, and Bmal1. When the cells were kept in DD for 5 days and treated with melatonin for 1 h, 24 h before extraction, the mRNA levels tended to decrease for Opn4x and Clock, did not change for Bmal1, and increased for Per1 and Per2 at different Zeitgeber times (ZT). Although these data are limited to one-day data collection, and therefore preliminary, we suggest that the dermal melanophores of X. laevis might have some characteristics of a peripheral clock, and that melatonin modulates, to a certain extent, melanopsin and clock gene expression.

  20. Clock is important for food and circadian regulation of macronutrient absorption in mice.

    Science.gov (United States)

    Pan, Xiaoyue; Hussain, M Mahmood

    2009-09-01

    Clock genes respond to external stimuli and exhibit circadian rhythms. This study investigated the expression of clock genes in the small intestine and their contribution in the regulation of nutrient absorption by enterocytes. We examined expression of clock genes and macronutrient transport proteins in the small intestines of wild-type and Clock mutant (Clk(mt/mt)) mice with free or limited access to food. In addition, we studied absorption of macronutrients in these mice. Intestinal clock genes show circadian expression and respond to food entrainment in wild-type mice. Dominant negative Clock in Clk(mt/mt) mice disrupts circadian expression and food entrainment of clock genes. The absorption of lipids and monosaccharides was high in Clk(mt/mt) mice whereas peptide absorption was reduced. Molecular studies revealed that Clock regulates several transport proteins involved in nutrient absorption. Clock plays an important role in light and food entrainment of intestinal functions by regulating nutrient transport proteins. Disruptions in intestinal circadian activity may contribute to hyperlipidemia and hyperglycemia.

  1. Atomic clocks: A brief history and current status of research in India

    Indian Academy of Sciences (India)

    Poonam Arora; Amrita Awasthi; Vattikonda Bharath; Aishik Acharya; Suchi Yadav; Aashish Agarwal; Amitava Sen Gupta

    2014-02-01

    Frequency corresponding to the energy difference between designated levels of an atom provides precise reference for making a universally accurate clock. Since the middle of the 20th century till now, there have been tremendous efforts in the field of atomic clocks making time the most accurately measured physical quantity. National Physical Laboratory India (NPLI) is the nation’s timekeeper and is developing an atomic fountain clock which will be a primary frequency standard. The fountain is currently operational and is at the stage of complete frequency evaluation. In this paper, a brief review on atomic time along with some of the recent results from the fountain clock will be discussed.

  2. Parallel analysis of Arabidopsis circadian clock mutants reveals different scales of transcriptome and proteome regulation

    Science.gov (United States)

    Graf, Alexander; Coman, Diana; Walsh, Sean; Flis, Anna; Stitt, Mark; Gruissem, Wilhelm

    2017-01-01

    The circadian clock regulates physiological processes central to growth and survival. To date, most plant circadian clock studies have relied on diurnal transcriptome changes to elucidate molecular connections between the circadian clock and observable phenotypes in wild-type plants. Here, we have integrated RNA-sequencing and protein mass spectrometry data to comparatively analyse the lhycca1, prr7prr9, gi and toc1 circadian clock mutant rosette at the end of day and end of night. Each mutant affects specific sets of genes and proteins, suggesting that the circadian clock regulation is modular. Furthermore, each circadian clock mutant maintains its own dynamically fluctuating transcriptome and proteome profile specific to subcellular compartments. Most of the measured protein levels do not correlate with changes in their corresponding transcripts. Transcripts and proteins that have coordinated changes in abundance are enriched for carbohydrate- and cold-responsive genes. Transcriptome changes in all four circadian clock mutants also affect genes encoding starch degradation enzymes, transcription factors and protein kinases. The comprehensive transcriptome and proteome datasets demonstrate that future system-driven research of the circadian clock requires multi-level experimental approaches. Our work also shows that further work is needed to elucidate the roles of post-translational modifications and protein degradation in the regulation of clock-related processes. PMID:28250106

  3. Ultrafast all-optical clock recovery based on phase-only linear optical filtering

    DEFF Research Database (Denmark)

    Maram, Reza; Kong, Deming; Galili, Michael;

    2014-01-01

    We report on a novel technique for all-optical clock recovery from RZ OOK data based on phase-only filtering, significantly enhancing the recovered clock quality and energy-efficiency compared to the use of a Fabry-Perot filter.......We report on a novel technique for all-optical clock recovery from RZ OOK data based on phase-only filtering, significantly enhancing the recovered clock quality and energy-efficiency compared to the use of a Fabry-Perot filter....

  4. Design of On—Chip Clock Generation with 50/50 Duty Cycle Correction

    Institute of Scientific and Technical Information of China (English)

    HANYueqiu; CUIWei; CHENHe

    2003-01-01

    A circuit design of on-chip clock generation which improves the duty cycle performance and prevents latch-up effect is described.The circuity provides onchip clock with automatic duty cycle correction so as to overcome the shortcoming of clock duty cycle dependence on technology parameters of the traditional on-chip clock generation circuit.It is extremely important that the dynamic power consumption equals approximately the one of its predecessor.The effective performance of the proposed circuit is confirmed by SPICE simulation.

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

    Science.gov (United States)

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

    2003-02-01

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

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

    Science.gov (United States)

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

    2015-09-22

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

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

    Science.gov (United States)

    Maltsev, Victor A; Lakatta, Edward G

    2008-01-15

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

  8. The molecular clock in terms of quantum information processing of coherent states, entanglement and replication of evolutionarily selected decohered isomers.

    Science.gov (United States)

    Cooper, W Grant

    2011-06-01

    Evolutionary pressures have selected quantum uncertainty limits -ΔxΔp ( x ) ≥ 1/2ħ-to operate on metastable amino DNA protons. This introduces a probability of molecular clock arrangement, keto-amino → enol-imine, where product protons are entangled and participate in coupled quantum oscillation at frequencies of ∼ 10(13) s(-1). The ket "seen by" the transcriptase, reading a coherent enol-imine G'-state, is |φ >= α| + + > +β|+- > +γ|-+ > +δ|-->. The transcriptase implements its measurement and generates an output qubit of observable genetic specificity information in an interval Δt ≪ 10(-13) s. These quantum measurements can specify the relative distribution of coherent G'-C' states at time of measurement. The ensuing quantum entanglement between coherent protons and transcriptase units is utilized as a resource to generate proper decoherence and introduce selected time-dependent substitutions, ts, and deletions, td. Topal-Fresco ts are G'202 → T, G'002 → C, *G020(0) → A and *C202(2) → T, whereas td are exhibited at coherent *A-*T sites. Variation in clock 'tic-rate' is a consequence of clock introduction of initiation codons - UUG, CUG, AUG, GUG - and stop codons, UAA, UAG, UGA. Using approximate quantum methods for times t < ∼ 100 y, the probability, P(t), of keto-amino → enolimine arrangement is P ( ρ )(t) = 1/2(γ ( ρ )/ħ)(2) t (2) where γ ( ρ ) is the energy shift. This introduces a quantum Darwinian evolution model which provides insight into biological consequences of coherent states populating human genes, including inherited (CAG)( n ) repeat tracts.

  9. Generating and probing entangled states for optical atomic clocks

    Science.gov (United States)

    Braverman, Boris; Kawasaki, Akio; Vuletic, Vladan

    2016-05-01

    The precision of quantum measurements is inherently limited by projection noise caused by the measurement process itself. Spin squeezing and more complex forms of entanglement have been proposed as ways of surpassing this limitation. In our system, a high-finesse asymmetric micromirror-based optical cavity can mediate the atom-atom interaction necessary for generating entanglement in an 171 Yb optical lattice clock. I will discuss approaches for creating, characterizing, and optimally utilizing these nonclassical states for precision measurement, as well as recent progress toward their realization. This research is supported by DARPA QuASAR, NSF, and NSERC.

  10. Designing Zeeman slower for strontium atoms - towards optical atomic clock

    CERN Document Server

    Bober, Marcin; Gawlik, Wojciech

    2010-01-01

    We report on design and construction of a Zeeman slower for strontium atoms which will be used in an optical atomic clock experiment. The paper describes briefly required specifications of the device, possible solutions, and concentrates on the chosen design. The magnetic field produced by the built Zeeman slower has been measured and compared with the simulations. The system consisting of an oven and Zeeman slower are designed to produce an atomic beam of 10-12 s-1 flux and final velocity of ~30 m/s.

  11. Designing Zeeman slower for strontium atoms - towards optical atomic clock

    OpenAIRE

    Bober, Marcin; Zachorowski, Jerzy; Gawlik, Wojciech

    2010-01-01

    We report on design and construction of a Zeeman slower for strontium atoms which will be used in an optical atomic clock experiment. The paper describes briefly required specifications of the device, possible solutions, and concentrates on the chosen design. The magnetic field produced by the built Zeeman slower has been measured and compared with the simulations. The system consisting of an oven and Zeeman slower are designed to produce an atomic beam of 10-12 s-1 flux and final velocity of...

  12. Hardware-assisted software clock synchronization for homogeneous distributed systems

    Science.gov (United States)

    Ramanathan, P.; Kandlur, Dilip D.; Shin, Kang G.

    1990-01-01

    A clock synchronization scheme that strikes a balance between hardware and software solutions is proposed. The proposed is a software algorithm that uses minimal additional hardware to achieve reasonably tight synchronization. Unlike other software solutions, the guaranteed worst-case skews can be made insensitive to the maximum variation of message transit delay in the system. The scheme is particularly suitable for large partially connected distributed systems with topologies that support simple point-to-point broadcast algorithms. Examples of such topologies include the hypercube and the mesh interconnection structures.

  13. Circadian clock disruption in neurodegenerative diseases: Cause and effect?

    Directory of Open Access Journals (Sweden)

    Erik Steven Musiek

    2015-02-01

    Full Text Available Disturbance of the circadian system, manifested as disrupted daily rhythms of physiologic parameters such as sleep, activity, and hormone secretion, has long been observed as a symptom of several neurodegenerative diseases, including Alzheimer Disease. Circadian abnormalities have generally been considered consequences of the neurodegeneration. Recent evidence suggests, however, that circadian disruption might actually contribute to the neurodegenerative process, and thus might be a modifiable cause of neural injury. Herein we will review the evidence implicating circadian rhythms disturbances and clock gene dysfunction in neurodegeneration, with an emphasis on future research directions and potential therapeutic implications for neurodegenerative diseases.

  14. Measurement of phase synchrony of coupled segmentation clocks.

    Science.gov (United States)

    Alam, Md Jahoor; Bhayana, Latika; Devi, Gurumayum Reenaroy; Singh, Heisnam Dinachandra; Singh, R K Brojen; Sharma, B Indrajit

    2011-10-01

    The temporal behavior of segmentation clock oscillations shows phase synchrony via mean field like coupling of delta protein restricting to nearest neighbors only, in a configuration of cells arranged in a regular three dimensional array. We found the increase of amplitudes of oscillating dynamical variables of the cells as the activation rate of delta-notch signaling is increased, however, the frequencies of oscillations are decreased correspondingly. Our results show the phase transition from desynchronized to synchronized behavior by identifying three regimes, namely, desynchronized, transition and synchronized regimes supported by various qualitative and quantitative measurements.

  15. A Clock Fingerprints-Based Approach for Wireless Transmitter Identification

    Science.gov (United States)

    Zhao, Caidan; Xie, Liang; Huang, Lianfen; Yao, Yan

    Cognitive radio (CR) was proposed as one of the promising solutions for low spectrum utilization. However, security problems such as the primary user emulation (PUE) attack severely limit its applications. In this paper, we propose a clock fingerprints-based authentication approach to prevent PUE attacks in CR networks with the help of curve fitting and classifier. An experimental setup was constructed using the WLAN cards and software radio devices, and the corresponding results show that satisfied identification can be achieved for wireless transmitters.

  16. Atomic clock with nuclear transition: current status in TU Wien

    OpenAIRE

    Kazakov, G. A.; Schreitl, M.; Winkler, G.; Sterba, J. H.; Steinhauser, G; Schumm, T.

    2011-01-01

    The nucleus of 229Thorium presents a unique isomer state of very low energy and long lifetime, current estimates are around 7.8 eV and seconds to hours respectively. This nuclear transitions therefore is a promising candidate for a novel type of frequency standard and several groups worldwide have set out to investigate this system. Our aim is to construct a "solid state nuclear clock", i.e. a frequency standard where Thorium ions are implanted into Calciumfluoride crystals transparent in vac...

  17. Insulin-FOXO3 signaling modulates circadian rhythms via regulation of clock transcription.

    Science.gov (United States)

    Chaves, Inês; van der Horst, Gijsbertus T J; Schellevis, Raymond; Nijman, Romana M; Koerkamp, Marian Groot; Holstege, Frank C P; Smidt, Marten P; Hoekman, Marco F M

    2014-06-02

    Circadian rhythms are responsive to external and internal cues, light and metabolism being among the most important. In mammals, the light signal is sensed by the retina and transmitted to the suprachiasmatic nucleus (SCN) master clock [1], where it is integrated into the molecular oscillator via regulation of clock gene transcription. The SCN synchronizes peripheral oscillators, an effect that can be overruled by incoming metabolic signals [2]. As a consequence, peripheral oscillators can be uncoupled from the master clock when light and metabolic signals are not in phase. The signaling pathways responsible for coupling metabolic cues to the molecular clock are being rapidly uncovered [3-5]. Here we show that insulin-phosphatidylinositol 3-kinase (PI3K)-Forkhead box class O3 (FOXO3) signaling is required for circadian rhythmicity in the liver via regulation of Clock. Knockdown of FoxO3 dampens circadian amplitude, an effect that is rescued by overexpression of Clock. Subsequently, we show binding of FOXO3 to two Daf-binding elements (DBEs) located in the Clock promoter area, implicating Clock as a transcriptional target of FOXO3. Transcriptional oscillation of both core clock and output genes in the liver of FOXO3-deficient mice is affected, indicating a disrupted hepatic circadian rhythmicity. Finally, we show that insulin, a major regulator of FOXO activity [6-9], regulates Clock levels in a PI3K- and FOXO3-dependent manner. Our data point to a key role of the insulin-FOXO3-Clock signaling pathway in the modulation of circadian rhythms.

  18. 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.

  19. Critical behavior of the random-bond clock model

    Science.gov (United States)

    Wu, Raymond P. H.; Lo, Veng-cheong; Huang, Haitao

    2012-09-01

    The critical behavior of the clock model in two-dimensional square lattice is studied numerically using Monte Carlo method with Wolff algorithm. The Kosterlitz-Thouless (KT) transition is observed in the 8-state clock model, where an intermediate phase exists between the low-temperature ordered phase and the high-temperature disordered phase. The bond randomness is introduced to the system by assuming a Gaussian distribution for the coupling coefficients with the mean μ = 1 and different values of variance: from σ2 = 0.1 to σ2 = 3.0. An abrupt jump in the helicity modulus at the transition, which is the key characteristic of the KT transition, is verified with a stability argument. Our results show that, a small amount of disorder (small σ) reduces the critical temperature of the system, without altering the nature of transition. However, a larger amount of disorder changes the transition from the KT-type into that of non-KT-type.

  20. A Low Power Single Phase Clock Distribution Multiband Network

    Directory of Open Access Journals (Sweden)

    Dr.A.Muruganandham#1,

    2014-02-01

    Full Text Available Frequency synthesizer is one of the important elements for wireless communication application. The speed of VCO and prescaler determines how fast the frequency synthesizer is. A dual modulus prescaler contains logic gates and flip-flops. This project aim for developing a low power single clock multiband network which will supply for the multi clock domain network. The multiband divider consists of a proposed wideband multi modulus 32/33/47/48 prescaler and an improved bitcell for swallow (S counter and can divide the frequencies in the three bands of 2.4–2.484 GHz, 5.15–5.35 GHz, and 5.725– 5.825 GHz with a resolution selectable from 1 to 25 MHz The proposed multiband flexible divider is silicon verified and consumes power of 0.96 and 2.2 mW in 2.4- and 5-GHz bands, respectively, when operated at 1.8-V power supply.

  1. Elite Athletes Refine Their Internal Clocks: A Bayesian Analysis.

    Science.gov (United States)

    Chen, Yin-Hua; Verdinelli, Isabella; Cesari, Paola

    2016-07-01

    This paper carries out a full Bayesian analysis for a data set examined in Chen & Cesari (2015). These data were collected for assessing people's ability in evaluating short intervals of time. Chen & Cesari (2015) showed evidence of the existence of two independent internal clocks for evaluating time intervals below and above the second. We reexamine here, the same question by performing a complete statistical Bayesian analysis of the data. The Bayesian approach can be used to analyze these data thanks to the specific trial design. Data were obtained from evaluation of time ranges from two groups of individuals. More specifically, information gathered from a nontrained group (considered as baseline) allowed us to build a prior distribution for the parameter(s) of interest, and data from the trained group determined the likelihood function. This paper's main goals are (i) showing how the Bayesian inferential method can be used in statistical analyses and (ii) showing that the Bayesian methodology gives additional support to the findings presented in Chen & Cesari (2015) regarding the existence of two internal clocks in assessing duration of time intervals.

  2. H2+ and HD+: candidates for a molecular clock

    CERN Document Server

    Karr, Jean-Philippe

    2014-01-01

    We investigate the leading systematic effects in ro-vibrational spectroscopy of the molecular hydrogen ions H2+ and HD+, in order to assess their potential for the realization of optical clocks that would be sensitive to possible variations of the proton-to-electron mass ratio. Both two-photon (2E1) and quadrupole (E2) transitions are considered. In view of the weakness of these transitions, most attention is devoted to the light shift induced by the probe laser, which we express as a function of the transition amplitude, differential dynamic polarizability and clock interrogation times. Transition amplitudes and dynamic polarizabilites including the effect of hyperfine structure are then calculated in a full three-body approach to get a precise evaluation of the light shift. Together with the quadrupole and Zeeman shifts that are obtained from previous works, these results provide a realistic estimate of the achievable accuracy. We show that the lightshift is the main limiting factor in the case of two-photo...

  3. Searching for dilaton dark matter with atomic clocks

    CERN Document Server

    Arvanitaki, Asimina; Van Tilburg, Ken

    2014-01-01

    We propose an experiment to search for ultralight scalar dark matter (DM) with dilatonic interactions. Such couplings can arise for the dilaton as well as for moduli and axion-like particles in the presence of CP violation. Ultralight dilaton DM acts as a background field that can cause tiny but coherent oscillations in Standard Model parameters such as the fine structure constant and the proton-electron mass ratio. These minute variations can be detected through precise frequency comparisons of atomic clocks. Our experiment extends current searches for drifts in fundamental constants to the well-motivated high-frequency regime. Our proposed setups can probe scalars lighter than 10^-15 eV with discovery potential of dilatonic couplings as weak as 10^-11 times the strength of gravity, improving current equivalence principle bounds by up to 8 orders of magnitude. We point out potential 10^4 sensitivity enhancements with future optical and nuclear clocks, as well as possible signatures in gravitational wave dete...

  4. Raman transitions between hyperfine clock states in a magnetic trap

    CERN Document Server

    Naber, J B; Hubert, T; Spreeuw, R J C

    2016-01-01

    We present our experimental investigation of an optical Raman transition between the magnetic clock states of $^{87}$Rb in an atom chip magnetic trap. The transfer of atomic population is induced by a pair of diode lasers which couple the two clock states off-resonantly to an intermediate state manifold. This transition is subject to destructive interference of two excitation paths, which leads to a reduction of the effective two-photon Rabi-frequency. Furthermore, we find that the transition frequency is highly sensitive to the intensity ratio of the diode lasers. Our results are well described in terms of light shifts in the multi-level structure of $^{87}$Rb. The differential light shifts vanish at an optimal intensity ratio, which we observe as a narrowing of the transition linewidth. We also observe the temporal dynamics of the population transfer and find good agreement with a model based on the system's master equation and a Gaussian laser beam profile. Finally, we identify several sources of decoheren...

  5. Relative clock demonstrates the endogenous heterogeneity of human dynamics

    CERN Document Server

    Zhou, Tao; Yang, Zimo; Zhou, Changsong

    2011-01-01

    The heavy-tailed inter-event time distributions are widely observed in many human-activated systems, which may result from both endogenous mechanisms like the highest-priority-first protocol and exogenous factors like the varying global activity versus time. To distinguish the effects on temporal statistics from different mechanisms is this of theoretical significance. In this Letter, we propose a new timing method by using a relative clock, where the time length between two consecutive events of an individual is counted as the number of other individuals' events appeared during this interval. We propose a model, in which agents act either in a constant rate or with a power-law inter-event time distribution, and the global activity either keeps unchanged or varies periodically versus time. Our analysis shows that the heavy tails caused by the heterogeneity of global activity can be eliminated by setting the relative clock, yet the heterogeneity due to real individual behaviors still exists. We perform extensi...

  6. The human circadian clock's seasonal adjustment is disrupted by daylight saving time

    NARCIS (Netherlands)

    Kantermann, Thomas; Juda, Myriam; Merrow, Martha; Roenneberg, Till

    2007-01-01

    A quarter of the world's population is subjected to a 1 hr time change twice a year (daylight saving time, DST). This reflects a change in social clocks, not environmental ones (e.g., dawn). The impact of DST is poorly understood. Circadian clocks use daylight to synchronize (entrain) to the organis

  7. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    DEFF Research Database (Denmark)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.;

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-s...

  8. A Simple Electromagnetic Model for the Light Clock of Special Relativity

    Science.gov (United States)

    Smith, Glenn S.

    2011-01-01

    Thought experiments involving a light clock are common in introductory treatments of special relativity, because they provide a simple way of demonstrating the non-intuitive phenomenon of time dilation. The properties of the ray or pulse of light that is continuously reflected between the parallel mirrors of the clock are often stated vaguely and…

  9. 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

  10. Reduction of Timing Jitter by Clock Recovery based on an Optical Phase-Locked Loop

    DEFF Research Database (Denmark)

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

    2006-01-01

    We numerically investigate the phase noise requirements for combined electrical/optical local oscillators in a PLL-based clock recovery. Suggestions for reducing the timing jitter are given.......We numerically investigate the phase noise requirements for combined electrical/optical local oscillators in a PLL-based clock recovery. Suggestions for reducing the timing jitter are given....

  11. A Method for Estimating BeiDou Inter-frequency Satellite Clock Bias

    Directory of Open Access Journals (Sweden)

    LI Haojun

    2016-02-01

    Full Text Available A new method for estimating the BeiDou inter-frequency satellite clock bias is proposed, considering the shortage of the current methods. The constant and variable parts of the inter-frequency satellite clock bias are considered in the new method. The data from 10 observation stations are processed to validate the new method. The characterizations of the BeiDou inter-frequency satellite clock bias are also analyzed using the computed results. The results of the BeiDou inter-frequency satellite clock bias indicate that it is stable in the short term. The estimated BeiDou inter-frequency satellite clock bias results are molded. The model results show that the 10 parameters of model for each satellite can express the BeiDou inter-frequency satellite clock bias well and the accuracy reaches cm level. When the model parameters of the first day are used to compute the BeiDou inter-frequency satellite clock bias of the second day, the accuracy also reaches cm level. Based on the stability and modeling, a strategy for the BeiDou satellite clock service is presented to provide the reference of our BeiDou.

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

    CERN Document Server

    Origlia, S; Pramod, M S; Smith, L; Singh, Y; He, W; Viswam, S; Świerad, D; Hughes, J; Bongs, K; Sterr, U; Lisdat, Ch; Vogt, S; Bize, S; Lodewyck, J; Targat, R Le; Holleville, D; Venon, B; Gill, P; Barwood, G; Hill, I R; Ovchinnikov, Y; Kulosa, A; Ertmer, W; Rasel, E -M; Stuhler, J; Kaenders, W

    2016-01-01

    The ESA mission "Space Optical Clock" project aims at operating an optical lattice clock on the ISS in approximately 2023. The scientific goals of the mission are to perform tests of fundamental physics, to enable space-assisted relativistic geodesy and to intercompare optical clocks on the ground using microwave and optical links. The performance goal of the space clock is less than $1 \\times 10^{-17}$ uncertainty and $1 \\times 10^{-15} {\\tau}^{-1/2}$ instability. Within an EU-FP7-funded project, a strontium optical lattice clock demonstrator has been developed. Goal performances are instability below $1 \\times 10^{-15} {\\tau}^{-1/2}$ and fractional inaccuracy $5 \\times 10^{-17}$. For the design of the clock, techniques and approaches suitable for later space application are used, such as modular design, diode lasers, low power consumption subunits, and compact dimensions. The Sr clock apparatus is fully operational, and the clock transition in $^{88}$Sr was observed with linewidth as small as 9 Hz.

  13. 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

    The central circadian clock of the mammalian brain resides in the suprachiasmatic nucleus (SCN) of the hypothalamus. At the molecular level, the circadian clockwork of the SCN constitutes a self-sustained autoregulatory feedback mechanism reflected by the rhythmic expression of clock genes. Howev...

  14. Prototype of the DLR Operational Composite Clock: Methods and Test Cases

    Science.gov (United States)

    2009-11-01

    Study of Time Scale Algorithms,” Metrologia , 28, 57-63. [2] R. Jones and P. Tryon, 1983, “Estimating Time From Atomic Clocks,” Journal of Research of...L. Galleani and P. Tavella, 2008, “Detection and identification of atomic clock anomalies,” Metrologia , 45, 127-133. [16] C. Zucca and P

  15. User-Defined Clocks in the Real-Time Specification for Java

    DEFF Research Database (Denmark)

    Wellings, Andy; Schoeberl, Martin

    2011-01-01

    This paper analyses the new user-defined clock model that is to be supported in Version 1.1 of the Real-Time Specification for Java (RTSJ). The model is a compromise between the current position, where there is no support for user-defined clocks, and a fully integrated model. The paper investigat...

  16. Flip-Flops for accurate multiphase clocking: transmission gate versus current mode logic

    NARCIS (Netherlands)

    Dutta, R.; Klumperink, E.A.M.; Gao, X.; Ru, Z.; Zee, van der R.A.R.; Nauta, B.

    2013-01-01

    Dynamic transmission gate (DTG) flip-flops (FFs) (DTG-FFs) and current mode logic (CML) FFs (CML-FFs) are compared targeting power efficient multiphase clock generation with low phase error. The effect of component mismatches on multiphase clock timing inaccuracies is modeled and compared, using the

  17. Atomic clock using coherent population trapping in a cesium cell: frequency stability and limitations

    Science.gov (United States)

    Mejri, Sinda; Tricot, Francois; Danet, Jean-Marie; Yun, Peter; De Clercq, Emeric; Guerandel, Stephane

    2016-06-01

    Toward the next generation of compact devices, atomic clocks based on coherent population trapping (CPT) offer a very interesting alternative. We present a review of our studies on the short and mid term stability of a compact high performance atomic clock based on CPT in view of portable applications.

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

    Science.gov (United States)

    Origlia, S.; Schiller, S.; Pramod, M. S.; Smith, L.; Singh, Y.; He, W.; Viswam, S.; Świerad, D.; Hughes, J.; Bongs, K.; Sterr, U.; Lisdat, Ch.; Vogt, S.; Bize, S.; Lodewyck, J.; Le Targat, R.; Holleville, D.; Venon, B.; Gill, P.; Barwood, G.; Hill, I. R.; Ovchinnikov, Y.; Kulosa, A.; Ertmer, W.; Rasel, E.-M.; Stuhler, J.; Kaenders, W.

    2016-04-01

    The ESA mission "Space Optical Clock" project aims at operating an optical lattice clock on the ISS in approximately 2023. The scientific goals of the mission are to perform tests of fundamental physics, to enable space-assisted relativistic geodesy and to intercompare optical clocks on the ground using microwave and optical links. The performance goal of the space clock is less than 1 × 10-17 uncertainty and 1 × 10-15 τ-1/2 instability. Within an EU-FP7-funded project, a strontium optical lattice clock demonstrator has been developed. Goal performances are instability below 1 × 10-15 τ-1/2 and fractional inaccuracy 5 × 10-17. For the design of the clock, techniques and approaches suitable for later space application are used, such as modular design, diode lasers, low power consumption subunits, and compact dimensions. The Sr clock apparatus is fully operational, and the clock transition in 88Sr was observed with linewidth as small as 9 Hz.

  19. Method and apparatus to debug an integrated circuit chip via synchronous clock stop and scan

    Science.gov (United States)

    Bellofatto, Ralph E [Ridgefield, CT; Ellavsky, Matthew R [Rochester, MN; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Gooding, Thomas M [Rochester, MN; Haring, Rudolf A [Cortlandt Manor, NY; Hehenberger, Lance G [Leander, TX; Ohmacht, Martin [Yorktown Heights, NY

    2012-03-20

    An apparatus and method for evaluating a state of an electronic or integrated circuit (IC), each IC including one or more processor elements for controlling operations of IC sub-units, and each the IC supporting multiple frequency clock domains. The method comprises: generating a synchronized set of enable signals in correspondence with one or more IC sub-units for starting operation of one or more IC sub-units according to a determined timing configuration; counting, in response to one signal of the synchronized set of enable signals, a number of main processor IC clock cycles; and, upon attaining a desired clock cycle number, generating a stop signal for each unique frequency clock domain to synchronously stop a functional clock for each respective frequency clock domain; and, upon synchronously stopping all on-chip functional clocks on all frequency clock domains in a deterministic fashion, scanning out data values at a desired IC chip state. The apparatus and methodology enables construction of a cycle-by-cycle view of any part of the state of a running IC chip, using a combination of on-chip circuitry and software.

  20. On the Stable Limit Cycle of a Weight-Driven Pendulum Clock

    Science.gov (United States)

    Llibre, J; Teixeira, M. A.

    2010-01-01

    In a recent paper (Denny 2002 Eur. J. Phys. 23 449-58), entitled "The pendulum clock: a venerable dynamical system", Denny showed that in a first approximation the steady-state motion of a weight-driven pendulum clock is shown to be a stable limit cycle. He placed the problem in a historical context and obtained an approximate solution using the…