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Sample records for biological clocks

  1. 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.

  2. 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

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

    OpenAIRE

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

    2013-01-01

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

  4. Maternal feeding controls fetal biological clock.

    Directory of Open Access Journals (Sweden)

    Hidenobu Ohta

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

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

    OpenAIRE

    Vincent Michael Cassone; David F Westneat

    2012-01-01

    Avian behavior and physiology are embedded in time at many levels of biological organization. Biological clock function in birds is critical for sleep/wake cycles, but may also regulate the acquisition of place memory, learning of song from tutors, social integration and time-compensated navigation. This relationship has two major implications. First, mechanisms of the circadian clock should be linked in some way to the mechanisms of all these behaviors. How is not yet clear, and evidence tha...

  6. The bird of time: cognition and the avian biological clock

    OpenAIRE

    Cassone, Vincent M.; David F Westneat

    2012-01-01

    Avian behavior and physiology are embedded in time at many levels of biological organization. Biological clock function in birds is critical for sleep/wake cycles, but may also regulate the acquisition of place memory, learning of song from tutors, social integration, and time-compensated navigation. This relationship has two major implications. First, mechanisms of the circadian clock should be linked in some way to the mechanisms of all these behaviors. How is not yet clear, and evidence th...

  7. The role of biological clock in glucose homeostasis 

    Directory of Open Access Journals (Sweden)

    Piotr Chrościcki

    2013-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Vincent Michael Cassone

    2012-03-01

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

  9. Telomere biology: cancer firewall or aging clock?

    Science.gov (United States)

    Mitteldorf, J J

    2013-09-01

    It has been a decade since the first surprising discovery that longer telomeres in humans are statistically associated with longer life expectancies. Since then, it has been firmly established that telomere shortening imposes an individual fitness cost in a number of mammalian species, including humans. But telomere shortening is easily avoided by application of telomerase, an enzyme which is coded into nearly every eukaryotic genome, but whose expression is suppressed most of the time. This raises the question how the sequestration of telomerase might have evolved. The predominant assumption is that in higher organisms, shortening telomeres provide a firewall against tumor growth. A more straightforward interpretation is that telomere attrition provides an aging clock, reliably programming lifespans. The latter hypothesis is routinely rejected by most biologists because the benefit of programmed lifespan applies only to the community, and in fact the individual pays a substantial fitness cost. There is a long-standing skepticism that the concept of fitness can be applied on a communal level, and of group selection in general. But the cancer hypothesis is problematic as well. Animal studies indicate that there is a net fitness cost in sequestration of telomerase, even when cancer risk is lowered. The hypothesis of protection against cancer has never been tested in animals that actually limit telomerase expression, but only in mice, whose lifespans are not telomerase-limited. And human medical evidence suggests a net aggravation of cancer risk from the sequestration of telomerase, because cells with short telomeres are at high risk of neoplastic transformation, and they also secrete cytokines that exacerbate inflammation globally. The aging clock hypothesis fits well with what is known about ancestral origins of telomerase sequestration, and the prejudices concerning group selection are without merit. If telomeres are an aging clock, then telomerase makes an

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

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

    2016-01-01

    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...

  12. 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

    2016-01-01

    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. PMID:27128899

  13. 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.

  14. Phase Resetting Light Pulses Induce Per1 and Persistent Spike Activity in a Subpopulation of Biological Clock Neurons

    OpenAIRE

    Kuhlman, Sandra J.; Silver, Rae; Le Sauter, Joseph; Bult-Ito, Abel; McMahon, Douglas G.

    2003-01-01

    The endogenous circadian clock of the mammalian suprachiasmatic nucleus (SCN) can be reset by light to synchronize the biological clock of the brain with the external environment. This process involves induction of immediate-early genes such as the circadian clock gene Period1 (Per1) and results in a stable shift in the timing of behavioral and physiological rhythms on subsequent days. The mechanisms by which gene activation permanently alters the phase of clock neuron activity are unknown. T...

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

    Directory of Open Access Journals (Sweden)

    Shosuke Yamamura

    2001-10-01

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

  16. 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.

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

    NARCIS (Netherlands)

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

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    Kondo, T.; Ishiura, M

    1994-01-01

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

  2. Phase Resetting Light Pulses Induce Per1 and Persistent Spike Activity in a Subpopulation of Biological Clock Neurons

    Science.gov (United States)

    Kuhlman, Sandra J.; Silver, Rae; Le Sauter, Joseph; Bult-Ito, Abel; McMahon, Douglas G.

    2012-01-01

    The endogenous circadian clock of the mammalian suprachiasmatic nucleus (SCN) can be reset by light to synchronize the biological clock of the brain with the external environment. This process involves induction of immediate-early genes such as the circadian clock gene Period1 (Per1) and results in a stable shift in the timing of behavioral and physiological rhythms on subsequent days. The mechanisms by which gene activation permanently alters the phase of clock neuron activity are unknown. To study the relationship between acute gene activation and persistent changes in the neurophysiology of SCN neurons, we recorded from SCN neurons marked with a dynamic green fluorescent protein (GFP) reporter of Per1 gene activity. Phase-resetting light pulses resulted in Per1 induction in a distinct subset of SCN neurons that also exhibited a persistent increase in action potential frequency 3–5 hr after a light pulse. By simultaneously quantifying Per1 gene activation and spike frequency in individual neurons, we found that the degree of Per1 induction was highly correlated with neuronal spike frequency on a cell-by-cell basis. Increased neuronal activity was mediated by membrane potential depolarization as a result of a reduction in outward potassium current. Double-label immunocytochemistry revealed that vasoactive intestinal peptide (VIP)-expressing cells, but not arginine vasopressin (AVP)-expressing cells, exhibited significant Per1 induction by light pulses. Rhythmic GFP expression occurred in both VIP and AVP neurons. Our results indicate that the steps that link acute molecular events to permanent changes in clock phase involve persistent suppression of potassium current, downstream of Per1 gene induction, in a specific subset of Per1-expressing neurons enriched for VIP. PMID:12598633

  3. 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.

  4. Synchronization of Biological Clock Neurons by Light and Peripheral Feedback Systems Promotes Circadian Rhythms and Health

    OpenAIRE

    Ramkisoensing, Ashna; Meijer, Johanna H.

    2015-01-01

    In mammals, the suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-h rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase-synchronization between individual cells have consequences on the amplitude...

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

    Directory of Open Access Journals (Sweden)

    Christy Anna Hipsley

    2014-05-01

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

  6. 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

  7. Synchronization of Biological Clock Neurons by Light and Peripheral Feedback Systems Promotes Circadian Rhythms and Health.

    Science.gov (United States)

    Ramkisoensing, Ashna; Meijer, Johanna H

    2015-01-01

    In mammals, the suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-h rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase-synchronization between individual cells have consequences on the amplitude of the SCN's electrical activity rhythm, and these changes play a major role in the ability to adapt to seasonal changes. Both aging and sleep deprivation negatively affect the circadian amplitude of the SCN, whereas behavioral activity (i.e., exercise) has a positive effect on amplitude. Given that the amplitude of the SCN's electrical activity rhythm is essential for achieving robust rhythmicity in physiology and behavior, the mechanisms that underlie neuronal synchronization warrant further study. A growing body of evidence suggests that the functional integrity of the SCN contributes to health, well-being, cognitive performance, and alertness; in contrast, deterioration of the 24-h rhythm is a risk factor for neurodegenerative disease, cancer, depression, and sleep disorders. PMID:26097465

  8. Synchronization of biological clock neurons by light and peripheral feedback systems promotes circadian rhythms and health

    Directory of Open Access Journals (Sweden)

    Ashna eRamkisoensing

    2015-06-01

    Full Text Available In mammals, the suprachiasmatic nucleus (SCN functions as a circadian clock that drives 24-hour rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase synchronization between individual cells have consequences on the amplitude of the SCN’s electrical activity rhythm, and these changes play a major role in the ability to adapt to seasonal changes. Both aging and sleep deprivation negatively affect the circadian amplitude of the SCN, whereas behavioral activity (i.e., exercise has a positive effect on amplitude. Given that the amplitude of the SCN’s electrical activity rhythm is essential for achieving robust rhythmicity in physiology and behavior, the mechanisms that underlie neuronal synchronization warrant further study. A growing body of evidence suggests that the functional integrity of the SCN contributes to health, well-being, cognitive performance, and alertness; in contrast, deterioration of the 24-hour rhythm is a risk factor for neurodegenerative disease, cancer, depression, and sleep disorders.

  9. 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...

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

  13. Clock Genes in Glia Cells

    Science.gov (United States)

    Chi-Castañeda, Donají

    2016-01-01

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

  14. Network properties of the mammalian circadian clock

    NARCIS (Netherlands)

    Rohling, Johannes Hermanus Theodoor

    2009-01-01

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

  15. "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…

  16. The circadian clock coordinates ribosome biogenesis.

    Directory of Open Access Journals (Sweden)

    Céline Jouffe

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

  17. 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

  18. Lego clocks : building a clock from parts

    NARCIS (Netherlands)

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

    2008-01-01

    A new finding opens up speculation that the molecular mechanism of circadian clocks in Synechococcus elongatus is composed of multiple oscillator systems (Kitayama and colleagues, this issue, pp. 1513-1521), as has been described in many eukaryotic clock model systems. However, an alternative intepr

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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,...

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

    OpenAIRE

    Brand, Karl

    2011-01-01

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

  5. 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.

  6. 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.

  7. An epigenetic clock controls aging.

    Science.gov (United States)

    Mitteldorf, Josh

    2016-02-01

    We are accustomed to treating aging as a set of things that go wrong with the body. But for more than twenty years, there has been accumulating evidence that much of the process takes place under genetic control. We have seen that signaling chemistry can make dramatic differences in life span, and that single molecules can significantly affect longevity. We are frequently confronted with puzzling choices the body makes which benefit neither present health nor fertility nor long-term survival. If we permit ourselves a shift of reference frame and regard aging as a programmed biological function like growth and development, then these observations fall into place and make sense. This perspective suggests that aging proceeds under control of a master clock, or several redundant clocks. If this is so, we may learn to reset the clocks with biochemical interventions and make an old body behave like a young body, including repair of many of the modes of damage that we are accustomed to regard as independent symptoms of the senescent phenotype, and for which we have assumed that the body has no remedy. PMID:26608516

  8. 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...

  9. The Regulation of Segmentation Clock Period in Zebrafish

    OpenAIRE

    Herrgen, Leah

    2008-01-01

    Oscillations are present at many different levels of biological organization. The cell cycle that directs the division of individual cells, the regular depolarization of neurons in the sinu-atrial node which underlies the regular beating of the heart, the circadian rhythms that govern the daily activity cycles of virtually all organisms, and the clocks that make entire populations of fireflies flash on and off in unison feature as prominent examples of biological clocks. During development, b...

  10. 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.

  11. Short-term influence of cataract surgery on circadian biological rhythm and related health outcomes (CLOCK-IOL trial): study protocol for a randomized controlled trial

    OpenAIRE

    Saeki, Keigo; Obayashi, Kenji; Nishi, Tomo; Miyata, Kimie; Maruoka, Shinji; Ueda, Tetsuo; OKAMOTO, Masahiro; Hasegawa, Taiji; Matsuura, Toyoaki; Tone, Nobuhiro; Ogata, Nahoko; Kurumatani, Norio

    2014-01-01

    Background Light information is the most important cue of circadian rhythm which synchronizes biological rhythm with external environment. Circadian misalignment of biological rhythm and external environment is associated with increased risk of depression, insomnia, obesity, diabetes, cardiovascular disease, and cancer. Increased light transmission by cataract surgery may improve circadian misalignment and related health outcomes. Although some observational studies have shown improvement of ...

  12. 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.

  13. Optical atomic clocks

    Science.gov (United States)

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

    2013-12-01

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

  14. 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.

  15. 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.

  16. Clocking in the face of unpredictability beyond quantum uncertainty

    Science.gov (United States)

    Madjid, F. Hadi; Myers, John M.

    2015-05-01

    In earlier papers we showed unpredictability beyond quantum uncertainty in atomic clocks, ensuing from a proven gap between given evidence and explanations of that evidence. Here we reconceive a clock, not as an isolated entity, but as enmeshed in a self-adjusting communications network adapted to one or another particular investigation, in contact with an unpredictable environment. From the practical uses of clocks, we abstract a clock enlivened with the computational capacity of a Turing machine, modified to transmit and to receive numerical communications. Such "live clocks" phase the steps of their computations to mesh with the arrival of transmitted numbers. We lift this phasing, known in digital communications, to a principle of logical synchronization, distinct from the synchronization defined by Einstein in special relativity. Logical synchronization elevates digital communication to a topic in physics, including applications to biology. One explores how feedback loops in clocking affect numerical signaling among entities functioning in the face of unpredictable influences, making the influences themselves into subjects of investigation. The formulation of communications networks in terms of live clocks extends information theory by expressing the need to actively maintain communications channels, and potentially, to create or drop them. We show how networks of live clocks are presupposed by the concept of coordinates in a spacetime. A network serves as an organizing principle, even when the concept of the rigid body that anchors a special-relativistic coordinate system is inapplicable, as is the case, for example, in a generic curved spacetime.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. Conveyor belt clock synchronization

    CERN Document Server

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

    2004-01-01

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

  2. 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

  3. 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.

  4. Synthesising gene clock with toggle switch and oscillator.

    Science.gov (United States)

    Lin, Chun-Liang; Chen, Po-Kuei; Cheng, Young-Yi

    2015-06-01

    The usefulness of a genetic clock lies in its role to stimulate a sequence of logic reactions for sequential biological circuits. A clock signal is a periodic square wave, its amplitude alternates at a steady frequency between fixed minimal and maximal levels. Transition between the minimum and the maximum is instantaneous for an ideal square wave; however, the function is unrealisable in physical bio-systems. This research develops a new genetic clock generator based on a genetic oscillator, in which, a sine wave generator is adopted as a signal oscillator. It is shown that combination of a genetic oscillator with a toggle switch is able to generate clock signals forming an efficient way to generate a near square wave. In silico study confirms the proposed idea.

  5. Optical atomic clocks and metrology

    Science.gov (United States)

    Ludlow, Andrew

    2014-05-01

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

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

    Science.gov (United States)

    Lin, Lin; Yang, Chengfeng; Ma, Maode

    2015-01-01

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

  7. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

  9. 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

  10. '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

  11. The circadian clock in mammals

    OpenAIRE

    Zordan, Mauro; Kyriacou, Charalambos P

    2000-01-01

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

  12. The circadian clock in mammals

    OpenAIRE

    Zordan, M. A.; Kyriacou, C P

    2005-01-01

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

  13. Aging, Rejuvenation, and Epigenetic Reprogramming: Resetting the Aging Clock

    OpenAIRE

    Rando, Thomas A.; Chang, Howard Y.

    2012-01-01

    The underlying cause of aging remains one of the central mysteries of biology. Recent studies in several different systems suggest that not only may the rate of aging be modified by environmental and genetic factors, but also that the aging clock can be reversed, restoring characteristics of youthfulness to aged cells and tissues. This Review focuses on the emerging biology of rejuvenation through the lens of epigenetic reprogramming. By defining youthfulness and senescence as epigenetic stat...

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

    Institute of Scientific and Technical Information of China (English)

    王文栋; 梁辉; 朱晓苏; 陶卉; 徐丽; 司马杨虎; 徐世清

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mark Campanelli

    2010-04-01

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

  16. 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.

  17. 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.

  18. Sr+ single-ion clock

    Science.gov (United States)

    Dubé, P.; Madej, A. A.; Jian, B.

    2016-06-01

    The evaluated uncertainty of the 88Sr+ ion optical clock has decreased by several orders of magnitude during the last 15 years, currently reaching a level of 1.2 x 10-17. In this paper, we review the methods developed to control very effectively the largest frequency shifts that once were the main sources of uncertainty for the 88Sr+ single-ion clock. These shifts are the micromotion shifts, the electric quadrupole shift and the blackbody radiation shift. With further improvements to the evaluation of the systematic shifts, especially the blackbody radiation shift, it is expected that the total uncertainty of the single-ion clock transition frequency will reach the low 10-18 level in the near future.

  19. Circadian molecular clocks and cancer.

    Science.gov (United States)

    Kelleher, Fergal C; Rao, Aparna; Maguire, Anne

    2014-01-01

    Physiological processes such as the sleep-wake cycle, metabolism and hormone secretion are controlled by a circadian rhythm adapted to 24h day-night periodicity. This circadian synchronisation is in part controlled by ambient light decreasing melatonin secretion by the pineal gland and co-ordinated by the suprachiasmatic nucleus of the hypothalamus. Peripheral cell autonomous circadian clocks controlled by the suprachiasmatic nucleus, the master regulator, exist within every cell of the body and are comprised of at least twelve genes. These include the basic helix-loop-helix/PAS domain containing transcription factors; Clock, BMal1 and Npas2 which activate transcription of the periodic genes (Per1 and Per2) and cryptochrome genes (Cry1 and Cry2). Points of coupling exist between the cellular clock and the cell cycle. Cell cycle genes which are affected by the molecular circadian clock include c-Myc, Wee1, cyclin D and p21. Therefore the rhythm of the circadian clock and cancer are interlinked. Molecular examples exist including activation of Per2 leads to c-myc overexpression and an increased tumor incidence. Mice with mutations in Cryptochrome 1 and 2 are arrhythmic (lack a circadian rhythm) and arrhythmic mice have a faster rate of growth of implanted tumors. Epidemiological finding of relevance include 'The Nurses' Health Study' where it was established that women working rotational night shifts have an increased incidence of breast cancer. Compounds that affect circadian rhythm exist with attendant future therapeutic possibilities. These include casein kinase I inhibitors and a candidate small molecule KL001 that affects the degradation of cryptochrome. Theoretically the cell cycle and malignant disease may be targeted vicariously by selective alteration of the cellular molecular clock. PMID:24099911

  20. Circadian clock components in the rat neocortex

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...... 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......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...

  1. 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.

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

    Science.gov (United States)

    Kon, Naohiro; Fukada, Yoshitaka

    2015-02-01

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

  3. 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.

  4. 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

  5. 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.

  6. A generalized gravitomagnetic clock effect

    CERN Document Server

    Hackmann, Eva

    2014-01-01

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

  7. Circadian 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.

  8. 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.

  9. 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.

  10. 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.

  11. Expression conservation within the circadian clock of a monocot: natural variation at barley Ppd-H1 affects circadian expression of flowering time genes, but not clock orthologs

    Directory of Open Access Journals (Sweden)

    Campoli Chiara

    2012-06-01

    Full Text Available Abstract Background The circadian clock is an endogenous mechanism that coordinates biological processes with daily changes in the environment. In plants, circadian rhythms contribute to both agricultural productivity and evolutionary fitness. In barley, the photoperiod response regulator and flowering-time gene Ppd-H1 is orthologous to the Arabidopsis core-clock gene PRR7. However, relatively little is known about the role of Ppd-H1 and other components of the circadian clock in temperate crop species. In this study, we identified barley clock orthologs and tested the effects of natural genetic variation at Ppd-H1 on diurnal and circadian expression of clock and output genes from the photoperiod-response pathway. Results Barley clock orthologs HvCCA1, HvGI, HvPRR1, HvPRR37 (Ppd-H1, HvPRR73, HvPRR59 and HvPRR95 showed a high level of sequence similarity and conservation of diurnal and circadian expression patterns, when compared to Arabidopsis. The natural mutation at Ppd-H1 did not affect diurnal or circadian cycling of barley clock genes. However, the Ppd-H1 mutant was found to be arrhythmic under free-running conditions for the photoperiod-response genes HvCO1, HvCO2, and the MADS-box transcription factor and vernalization responsive gene Vrn-H1. Conclusion We suggest that the described eudicot clock is largely conserved in the monocot barley. However, genetic differentiation within gene families and differences in the function of Ppd-H1 suggest evolutionary modification in the angiosperm clock. Our data indicates that natural variation at Ppd-H1 does not affect the expression level of clock genes, but controls photoperiodic output genes. Circadian control of Vrn-H1 in barley suggests that this vernalization responsive gene is also controlled by the photoperiod-response pathway. Structural and functional characterization of the barley circadian clock will set the basis for future studies of the adaptive significance of the circadian clock in

  12. Hanle detection for optical clocks

    CERN Document Server

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

    2014-01-01

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

  13. Design principles underlying circadian clocks.

    OpenAIRE

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

    2004-01-01

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

  14. Hanle detection for optical clocks.

    Science.gov (United States)

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

    2015-01-01

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

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Yang Ziheng

    2011-09-01

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

  17. Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock.

    Science.gov (United States)

    Rando, Thomas A; Chang, Howard Y

    2012-01-20

    The underlying cause of aging remains one of the central mysteries of biology. Recent studies in several different systems suggest that not only may the rate of aging be modified by environmental and genetic factors, but also that the aging clock can be reversed, restoring characteristics of youthfulness to aged cells and tissues. This Review focuses on the emerging biology of rejuvenation through the lens of epigenetic reprogramming. By defining youthfulness and senescence as epigenetic states, a framework for asking new questions about the aging process emerges. PMID:22265401

  18. 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.

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

    OpenAIRE

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

    2008-01-01

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

  20. 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.

  1. 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.

  2. Tectonic blocks and molecular clocks

    Science.gov (United States)

    2016-01-01

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

  3. Cold atom Clocks and Applications

    CERN Document Server

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

    2005-01-01

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

  4. 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.

  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. 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...

  8. A colorful model of the circadian clock.

    Science.gov (United States)

    Reppert, Steven M

    2006-01-27

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

  9. 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.

  10. A clock synchronization skeleton based on RTAI

    NARCIS (Netherlands)

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

    2006-01-01

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

  11. Fast Clock Recovery for Digital Communications

    Science.gov (United States)

    Tell, R. G.

    1985-01-01

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

  12. 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...

  13. Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle

    Science.gov (United States)

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

    2014-01-01

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

  14. Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle.

    Science.gov (United States)

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

    2014-07-01

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

  15. 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.

  16. The epigenetic clock and telomere length are independently associated with chronological age and mortality

    Science.gov (United States)

    Marioni, Riccardo E; Harris, Sarah E; Shah, Sonia; McRae, Allan F; von Zglinicki, Thomas; Martin-Ruiz, Carmen; Wray, Naomi R; Visscher, Peter M; Deary, Ian J

    2016-01-01

    Background: Telomere length and DNA methylation have been proposed as biological clock measures that track chronological age. Whether they change in tandem, or contribute independently to the prediction of chronological age, is not known. Methods: We address these points using data from two Scottish cohorts: the Lothian Birth Cohorts of 1921 (LBC1921) and 1936 (LBC1936). Telomere length and epigenetic clock estimates from DNA methylation were measured in 920 LBC1936 participants (ages 70, 73 and 76 years) and in 414 LBC1921 participants (ages 79, 87 and 90 years). Results: The epigenetic clock changed over time at roughly the same rate as chronological age in both cohorts. Telomere length decreased at 48–67 base pairs per year on average. Weak, non-significant correlations were found between epigenetic clock estimates and telomere length. Telomere length explained 6.6% of the variance in age in LBC1921, the epigenetic clock explained 10.0%, and combined they explained 17.3% (all P epigenetic age was linked to a 22% increased mortality risk (P = 2.6 × 10−4) whereas, in the same model, a one standard deviation increase in baseline telomere length was independently linked to an 11% decreased mortality risk (P = 0.06). Conclusions: These results suggest that telomere length and epigenetic clock estimates are independent predictors of chronological age and mortality risk. PMID:27075770

  17. 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.

  18. 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...

  19. 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

  20. Time clock requirements for hospital physicians.

    Science.gov (United States)

    Shapira, Chen; Vilnai-Yavetz, Iris; Rafaeli, Anat; Zemel, Moran

    2016-06-01

    An agreement negotiated following a doctors' strike in 2011 introduced a requirement that physicians in Israel's public hospitals clock in and out when starting and leaving work. The press reported strong negative reactions to this policy and predicted doctors deserting hospitals en masse. This study examines physicians' reactions toward the clock-in/clock-out policy 6 months after its implementation, and assesses the relationship between these reactions and aspects of their employment context. 676 physicians in 42 hospitals responded to a survey assessing doctor's reactions toward the clock, hospital policy makers, and aspects of their work. Reactions to the clock were generally negative. Sense of calling correlated positively with negative reactions to the clock, and the latter correlated positively with quit intentions. However, overall, respondents reported a high sense of calling and low quit intentions. We suggest that sense of calling buffers and protects physicians from quit intentions. Differences in reactions to the clock were associated with different employment characteristics, but sense of calling did not vary by hospital size or type or by physicians' specialty. The findings offer insights into how physicians' working environment affects their reactions to regulatory interventions, and highlight medical professionalism as buffering reactions to unpopular regulatory policies. PMID:27142179

  1. How does the body know how old it is? Introducing the epigenetic clock hypothesis.

    Science.gov (United States)

    Mitteldorf, Joshua

    2015-01-01

    Animals and plants have biological clocks that help to regulate circadian cycles, seasonal rhythms, growth, development and sexual maturity. If aging is not a stochastic process of attrition but is centrally orchestrated, it is reasonable to suspect that the timing of senescence is also influenced by one or more biological clocks. Evolutionary reasoning first articulated by G. Williams suggests that multiple, redundant clocks might influence organismal aging. Some aging clocks that have been proposed include the suprachiasmatic nucleus, the hypothalamus, involution of the thymus, and cellular senescence. Cellular senescence, mediated by telomere attrition, is in a class by itself, having recently been validated as a primary regulator of aging. Gene expression is known to change in characteristic ways with age, and in particular DNA methylation changes in age-related ways. Herein, I propose a new candidate for an aging clock, based on epigenetics and the state of chromosome methylation, particularly in stem cells. If validated, this mechanism would present a challenging but not impossible target for medical intervention. PMID:25341512

  2. 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.

  3. 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.

  4. Entrainment Dissociates Transcription and Translation of a Circadian Clock Gene in Neurospora

    NARCIS (Netherlands)

    Tan, Ying; Dragovic, Zdravko; Roenneberg, Till; Merrow, Martha

    2004-01-01

    Circadian systems coordinate the daily sequence of events in cells, tissues, and organisms. In constant conditions, the biological clock oscillates with its endogenous period, whereas it is synchronized to the 24 hr light:dark cycle in nature. Here, we investigate light entrainment of Neurospora cra

  5. 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.

  6. 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...

  7. 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.

  8. 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.

  9. Entrainment of the Neurospora circadian clock

    NARCIS (Netherlands)

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

    2006-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

  11. 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.

  12. Circadian clock proteins in mood regulation

    Directory of Open Access Journals (Sweden)

    Timo ePartonen

    2015-01-01

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

  13. Optical lattice clock with Strontium atoms

    International Nuclear Information System (INIS)

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

  14. 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.

  15. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-06-14

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

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

    Directory of Open Access Journals (Sweden)

    Bordon Alain

    2008-04-01

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

  19. 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

  20. 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.

  1. 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.

  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. 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.

  4. 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.

  5. The Deep Space Atomic Clock Mission

    Science.gov (United States)

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

    2012-01-01

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

  6. Circadian clock: linking epigenetics to aging.

    Science.gov (United States)

    Orozco-Solis, Ricardo; Sassone-Corsi, Paolo

    2014-06-01

    Circadian rhythms are generated by an intrinsic cellular mechanism that controls a large array of physiological and metabolic processes. There is erosion in the robustness of circadian rhythms during aging, and disruption of the clock by genetic ablation of specific genes is associated with aging-related features. Importantly, environmental conditions are thought to modulate the aging process. For example, caloric restriction is a very strong environmental effector capable of delaying aging. Intracellular pathways implicating nutrient sensors, such as SIRTs and mTOR complexes, impinge on cellular and epigenetic mechanisms that control the aging process. Strikingly, accumulating evidences indicate that these pathways are involved in both the modulation of the aging process and the control of the clock. Hence, innovative therapeutic strategies focused at controlling the circadian clock and the nutrient sensing pathways might beneficially influence the negative effects of aging. PMID:25033025

  7. 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.

  8. Clocks, cryptochromes and Monarch migrations

    OpenAIRE

    Kyriacou, Charalambos P.

    2009-01-01

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

  9. Clocks, cryptochromes and Monarch migrations.

    Science.gov (United States)

    Kyriacou, Charalambos P

    2009-01-01

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

  10. Water-Powered Astronomical Clock Tower

    Science.gov (United States)

    Sun, Xiaochun

    The construction of water-powered astronomical instruments was a long tradition of instrument making that started in the second century AD with Zhang Heng's water-powered celestial globe. The technology reached a peak when, in the eleventh century, Su Song and his team constructed the Water-Powered Astronomical Clock Tower which combined the armillary sphere, the celestial globe, and the time-keeping mechanism into a large automatic structure. Su Song's instrument contained a mechanism for controlling the water-powered movements of its wheels that amounts to an "escapement mechanism" for a mechanical clock. A new reconstruction of the mechanism is introduced in this chapter.

  11. 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....

  12. Using GLONASS signal for clock synchronization

    Science.gov (United States)

    Gouzhva, Yuri G.; Gevorkyan, Arvid G.; Bogdanov, Pyotr P.; Ovchinnikov, Vitaly V.

    1994-01-01

    Although in accuracy parameters GLONASS is correlated with GPS, using GLONASS signals for high-precision clock synchronization was, up to the recent time, of limited utility due to the lack of specialized time receivers. In order to improve this situation, in late 1992 the Russian Institute of Radionavigation and Time (RMT) began to develop a GLONASS time receiver using as a basis the airborne ASN-16 receiver. This paper presents results of estimating user clock synchronization accuracy via GLONASS signals using ASN-16 receiver in the direct synchronization and common-view modes.

  13. 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

  14. The Circadian Clock Is a Key Driver of Steroid Hormone Production in Drosophila.

    Science.gov (United States)

    Di Cara, Francesca; King-Jones, Kirst

    2016-09-26

    Biological clocks allow organisms to anticipate daily environmental changes such as temperature fluctuations, abundance of daylight, and nutrient availability. Many circadian-controlled physiological states are coordinated by the release of systemically acting hormones, including steroids and insulin [1-7]. Thus, hormones relay circadian outputs to target tissues, and disrupting these endocrine rhythms impairs human health by affecting sleep patterns, energy homeostasis, and immune functions [8-10]. It is largely unclear, however, whether circadian circuits control hormone levels indirectly via central timekeeping neurons or whether peripheral endocrine clocks can modulate hormone synthesis directly. We show here that perturbing the circadian clock, specifically in the major steroid hormone-producing gland of Drosophila, the prothoracic gland (PG), unexpectedly blocks larval development due to an inability to produce sufficient steroids. This is surprising, because classic circadian null mutants are viable and result in arrhythmic adults [4, 11-14]. We found that Timeless and Period, both core components of the insect clock [15], are required for transcriptional upregulation of steroid hormone-producing enzymes. Timeless couples the circadian machinery directly to the two canonical pathways that regulate steroid synthesis in insects, insulin and PTTH signaling [16], respectively. Activating insulin signaling directly modulates Timeless function, suggesting that the local clock in the PG is normally synced with systemic insulin cues. Because both PTTH and systemic insulin signaling are themselves under circadian control, we conclude that de-synchronization of a local endocrine clock with external circadian cues is the primary cause for steroid production to fail. PMID:27546572

  15. Navstar Global Positioning System (GPS) clock program: Present and future

    Science.gov (United States)

    Tennant, D. M.

    1981-01-01

    Global Positioning System (GPS) program status are discussed and plans for ensuring the long term continuation of the program are presented. Performance of GPS clocks is presented in terms of on orbit data as portrayed by GPS master control station kalman filter processing. The GPS Clock reliability program is reviewed in depth and future plans fo the overall clock program are published.

  16. Vasopressin and the Output of the Hypothalamic Biological Clock

    NARCIS (Netherlands)

    A. Kalsbeek; E. Fliers; M.A. Hofman; D.F. Swaab; R.M. Buijs

    2010-01-01

    The physiological effects of vasopressin as a peripheral hormone were first reported more than 100 years ago. However, it was not until the first immunocytochemical studies were carried out in the early 1970s, using vasopressin antibodies, and the discovery of an extensive distribution of vasopressi

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Quentin eThommen

    2015-02-01

    Full Text Available 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. LOVHK is a blue light photoreceptor under circadian control, that is required for circadian clock function. An involvement of Rhodopsin-HK (RhodHK is also conceivable since rhodopsin photoreceptors mediate blue to green light input in animal circadian clocks.Here, we probe the role of LOVHK and RhodHK 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

  19. 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…

  20. Circadian Clock Regulates Bone Resorption in Mice.

    Science.gov (United States)

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

    2016-07-01

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

  1. An Iodine Fluorescence Quenching Clock Reaction

    Science.gov (United States)

    Weinberg, Richard B.; Muyskens, Mark

    2007-01-01

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

  2. The peripheral clock regulates human pigmentation.

    Science.gov (United States)

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

    2015-04-01

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

  3. Analytic clock frequency selection for global DVFS

    NARCIS (Netherlands)

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

    2014-01-01

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

  4. 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…

  5. On accelerated clocks and the quantum theory

    International Nuclear Information System (INIS)

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

  6. 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.

  7. 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.).

  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. S-Wave Collisional Frequency Shift of a Fermion Clock

    CERN Document Server

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Jiao Chengbo

    2011-08-01

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

  13. 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.

  14. The sympathy of two pendulum clocks: beyond Huygens’ observations

    Science.gov (United States)

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

    2016-01-01

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

  15. Intergeneric complementation of a circadian rhythmicity defect : phylogenetic conservation of structure and function of the clock gene frequency

    NARCIS (Netherlands)

    Merrow, Martha W.; Dunlap, Jay C.; Dover, G.

    1994-01-01

    The Neurospora crassa frequency locus encodes a 989 amino acid protein that is a central component, a state variable, of the circadian biological clock. We have determined the sequence of all or part of this protein and surrounding regulatory regions from additional fungi representing three genera a

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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. PMID:27104983

  2. 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.

  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. Clock drawing performance in cognitively normal elderly

    OpenAIRE

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

    2008-01-01

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

  5. Absolute clock synchronisation and special relativity paradoxes

    OpenAIRE

    Ciborowski, Jacek; Wlodarczyk, Marta

    2012-01-01

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

  6. 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.

  7. 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.

  8. Photoperiodic plasticity in circadian clock neurons in insects

    Directory of Open Access Journals (Sweden)

    Sakiko eShiga

    2013-08-01

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

  9. 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.

  10. 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.

  11. Clock drawing performance in cognitively normal elderly.

    Science.gov (United States)

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

    2008-05-01

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

  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. 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.

  14. Characterization and modeling of intermittent locomotor dynamics in clock gene-deficient mice.

    Directory of Open Access Journals (Sweden)

    Toru Nakamura

    Full Text Available The scale-invariant and intermittent dynamics of animal behavior are attracting scientific interest. Recent findings concerning the statistical laws of behavioral organization shared between healthy humans and wild-type mice (WT and their alterations in human depression patients and circadian clock gene (Period 2; Per2 mutant mice indicate that clock genes play functional roles in intermittent, ultradian locomotor dynamics. They also claim the clinical and biological importance of the laws as objective biobehavioral measures or endophenotypes for psychiatric disorders. In this study, to elucidate the roles of breakdown of the broader circadian regulatory circuit in intermittent behavioral dynamics, we studied the statistical properties and rhythmicity of locomotor activity in Per2 mutants and mice deficient in other clock genes (Bmal1, Clock. We performed wavelet analysis to examine circadian and ultradian rhythms and estimated the cumulative distributions of resting period durations during which locomotor activity levels are continuously lower than a predefined threshold value. The wavelet analysis revealed significant amplification of ultradian rhythms in the BMAL1-deficient mice, and instability in the Per2 mutants. The resting period distributions followed a power-law form in all mice. While the distributions for the BMAL1-deficient and Clock mutant mice were almost identical to those for the WT mice, with no significant differences in their parameter (power-law scaling exponent, only the Per2 mutant mice showed consistently and significantly lower values of the scaling exponent, indicating the increased intermittency in ultradian locomotor dynamics. Furthermore, based on a stochastic priority queuing model, we explained the power-law nature of resting period distributions, as well as its alterations shared with human depressive patients and Per2 mutant mice. Our findings lead to the development of a novel mathematical model for abnormal

  15. 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.

  16. Telomere biology in healthy aging and disease

    NARCIS (Netherlands)

    Oeseburg, Hisko; de Boer, Rudolf A.; van Gilst, Wiek H.; van der Harst, Pim

    2010-01-01

    Aging is a biological process that affects most cells, organisms and species. Telomeres have been postulated as a universal biological clock that shortens in parallel with aging in cells. Telomeres are located at the end of the chromosomes and consist of an evolutionary conserved repetitive nucleoti

  17. 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.

  18. 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.

  19. 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.

  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. 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.

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

    International Nuclear Information System (INIS)

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

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

    CERN Document Server

    Field, J H

    2006-01-01

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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Catalin V Buhusi

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

  6. Clocks and dynamics in quantum models of gravity

    OpenAIRE

    Malkiewicz, Przemyslaw

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena

    2016-01-01

    . The validated chronic mild stress (CMS) animal model of depression was used to investigate rhythmic expression of three clock genes; Per1, Per2 and Bmal1. Brain and liver tissue was collected from 96 animals after 3.5 weeks of CMS (48 control and 48 depression-like rats) at 4 h sampling interval within 24 h. We......: The present results suggest that altered expression of investigated clock genes are likely to associate with the induction of a depression-like state in the CMS model.......Background: Abnormalities in circadian rhythms may be causal factors in development of major depressive disorder. The biology underlying a causal relationship between circadian rhythm disturbances and depression is slowly being unraveled. Although there is no direct evidence of dysregulation...

  9. 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.

  10. 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...

  11. Temperature regulates transcription in the zebrafish circadian clock.

    Directory of Open Access Journals (Sweden)

    2005-11-01

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

  12. Power and Skew Aware Point Diffusion Clock Network

    Science.gov (United States)

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

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

  13. 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.

  14. 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.

  15. 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.

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

    CERN Document Server

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

    2012-01-01

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

  17. Grand-mother clocks and quiet lasers

    OpenAIRE

    Arnaud, Jacques; Chusseau, Laurent; Philippe, Fabrice

    2009-01-01

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

  18. 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.

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

    Science.gov (United States)

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

    2009-01-23

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

  20. 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.

  1. Animal clocks: when science meets nature.

    Science.gov (United States)

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

    2013-08-22

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

  2. The clock ambiguity: Implications and new developments

    CERN Document Server

    Albrecht, Andreas

    2008-01-01

    We consider the ambiguity associated with the choice of clock in time reparameterization invariant theories. This arbitrariness undermines the goal of prescribing a fixed set of physical laws, since a change of time variable can completely alter the predictions of the theory. We review the main features of the clock ambiguity and our earlier work on its implications for the emergence of physical laws in a statistical manner. We also present a number of new results: We show that (contrary to suggestions in our earlier work) time independent Hamiltonians may quite generally be assumed for laws of physics that emerge in this picture. We also further explore the degree to which the observed Universe can be well approximated by a random Hamiltonian. We discuss the possibility of predicting the dimensionality of space, and also relate the 2nd derivative of the density of states to the heat capacity of the Universe. This new work adds to the viability of our proposal that strong predictions for physical laws may eme...

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

    Science.gov (United States)

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

    2016-01-01

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

  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. 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.

  6. Atomic clocks: new prospects in metrology and geodesy

    CERN Document Server

    Delva, Pacôme

    2013-01-01

    We present the latest developments in the field of atomic clocks and their applications in metrology and fundamental physics. In the light of recent advents in the accuracy of optical clocks, we present an introduction to the relativistic modelization of frequency transfer and a detailed review of chronometric geodesy.

  7. 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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Michael F Covington

    2007-08-01

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

  10. An Integrated Architectural Clock Implemented Memory Design Analysis

    Directory of Open Access Journals (Sweden)

    Ravi Khatwal

    2015-07-01

    Full Text Available Recently Low power consumption and Custom Memory design is major issue for embedded designer. Micro wind and Xilinx simulator implements SRAM design architecture and performs efficient simulation. These simulators implements high performances and low power consumption of SRAM design. SRAM efficiency analyzed with 6-T architecture design and row/column based architectural design. We have analyzed clock implemented memory design and simulated with specific application. We have implemented clock based SRAM architecture that improves the internal clock efficiency of SRAM. Architectural Clock implemented memory design reduces the propagation delay and access time. Internal semiconductor material design implemented technique also improves the SRAM data transitions scheme. Semiconductor material and clock implemented design improve simulation performance of SRAM and these design implements for recently developed Application Specific Memory Design Architecture and mobile devices.

  11. 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.

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

    Science.gov (United States)

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

    2015-09-11

    In Einstein's general theory of relativity, time depends locally on gravity; in standard quantum theory, time is global-all clocks "tick" uniformly. We demonstrate a new tool for investigating time in the overlap of these two theories: a self-interfering clock, comprising two atomic spin states. We prepare the clock in a spatial superposition of quantum wave packets, which evolve coherently along two paths into a stable interference pattern. If we make the clock wave packets "tick" at different rates, to simulate a gravitational time lag, the clock time along each path yields "which path" information, degrading the pattern's visibility. In contrast, in standard interferometry, time cannot yield "which path" information. This proof-of-principle experiment may have implications for the study of time and general relativity and their impact on fundamental effects such as decoherence and the emergence of a classical world. PMID:26249229

  13. 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...

  14. 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...

  15. 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.

  16. 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.

  17. 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

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

    Science.gov (United States)

    Preußner, Marco; Heyd, Florian

    2016-06-01

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

  19. 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

  20. 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.

  1. Dynamics and performance of clock pendulums

    CERN Document Server

    Hoyng, Peter

    2015-01-01

    We analyze the dynamics of a driven, damped pendulum as used in mechanical clocks. We derive equations for the amplitude and phase of the oscillation, on time scales longer than the pendulum period. The equations are first order ODEs and permit fast simulations of the joint effects of circular and escapement errors, friction, and other disturbances for long times. The equations contain two averages of the driving torque over a period, so that the results are not very sensitive to the fine structure of the driving. We adopt a constant-torque escapement and study the stationary pendulum rate as a function of driving torque and friction. We also study the reaction of the pendulum to a sudden change in the driving torque, and to stationary noisy driving. The equations for the amplitude and phase are shown to describe the pendulum dynamics quite well on time scales of one period and longer. Our emphasis is on a clear exposition of the physics.

  2. 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.

  3. 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.

  4. 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.

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

    International Nuclear Information System (INIS)

    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. (paper)

  6. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Kadomatsu

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

  9. 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

  10. 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

  11. 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.

  12. Time in the 10,000-Year Clock

    OpenAIRE

    Hillis, Danny; Seaman, Rob; 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 ...

  13. 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.

  14. Relativistic effects for the JUICE on‐board clock

    OpenAIRE

    S. Bauer; Hussmann, H.; J. Mueller; Oberst, J.

    2014-01-01

    We studied relativistic effects on spacecraft clock rates for ESA’s JUICE mission and derived a relationship between dynamical time TDB and on‐board time. We analysed the S/C on‐board clock rate by using the JUICE mission nominal trajectory. We identify significant changes in the rate of the clock due to large changes of the S/C velocity and its distance to the solar system bodies during the various spacecraft operational phases. After ≈ 11.5 years, at the end of the mission, the offset in ti...

  15. Progress Towards a Compact Optical Clock at JPL

    Science.gov (United States)

    Sullivan, Scott; Rellergert, Wade; Grudinin, Ivan; Baumgartel, Lukas; Yu, Nan

    2014-05-01

    The unprecedented stability and accuracy provided by optical clocks allows improved navigation and planetary science in space applications as well as more precise tests of fundamental laws of physics. However, technological advances towards the miniaturization of the physical volume and reduced power consumption of these clocks must be made to suit space-based application. We will describe JPL's effort towards the development of a compact, low-power optical clock based on 171Yb+. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. Partial support from NASA Fundamental Physics Program is acknowledged.

  16. 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.

  17. 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. PMID:26483181

  18. High speed fiber-based clock enhancement of NRZ data

    Institute of Scientific and Technical Information of China (English)

    Tong Wu; Kun Qiu

    2005-01-01

    A scheme for all-fiber clock enhancement of non-return-to-zero (NRZ) data based on cross-phase modulation (XPM) effect in nonlinear fibers is proposed and demonstrated in simulation. The simulation results indicate that the clock-to-data ratio of NRZ signals at 64 Gb/s can be increased to 22.94 dB by using this scheme, and the pattern effect in clock enhanced signals is very weak. The ability of high speed operation up to 140 Gb/s of this scheme is also proved in our simulation.

  19. 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.

  20. 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.

  1. 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...

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

    International Nuclear Information System (INIS)

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

  3. 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...

  4. 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.).

  5. Superradiance on the milliHertz linewidth strontium clock transition

    CERN Document Server

    Norcia, Matthew A; Cline, Julia R K; Thompson, James K

    2016-01-01

    Today's best atomic clocks are limited by frequency noise on the lasers used to interrogate the atoms. A proposed solution to this problem is to create a superradiant laser using an optical clock transition as its gain medium. This laser would act as an active atomic clock, and would be highly immune to the fluctuations in reference cavity length that limit today's best lasers. Here, we demonstrate and characterize superradiant emission from the mHz linewidth clock transition in an ensemble of laser-cooled $^{87}$Sr atoms trapped within a high-finesse optical cavity. We measure a collective enhancement of the emission rate into the cavity mode by a factor of more than 10,000 compared to independently radiating atoms. We also demonstrate a method for seeding superradiant emission and observe interference between two independent transitions lasing simultaneously. We use this interference to characterize the relative spectral properties of the two lasing sub-ensembles.

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

    International Nuclear Information System (INIS)

    It is shown that 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

  7. 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.

  8. 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...

  9. Clocks and dynamics in quantum models of gravity

    CERN Document Server

    Malkiewicz, Przemyslaw

    2016-01-01

    We investigate how the quantum dynamics of gravitational models depend on the clocks employed in quantization procedure. Our previous result demonstrates that almost all physical features of quantum cosmological bounces depend on the choice of clock. The vital question whether all the quantum (or, semiclassical) solutions admit, away from the quantum interaction region in the far past and future, invariant asymptotic limits irrespectively of the clock's choice is addressed herein. We analyze the semiclassical dynamics of the Bianchi Type I model undergoing a quantum bounce. Our result follows from the universal principle of the free choice of clock and thus, it applies to all quantum gravity models based on the concept of the physical Hilbert space and inner dynamics. Then we propose a suitable interpretation of quantum models of gravity. As a by-product of the pursuit of our main goal, we elaborate the semiclassical description of anisotropic singularity resolution.

  10. 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.

  11. An Analysis of the Stationary Operation of Atomic Clocks

    Science.gov (United States)

    Fraas, Martin

    2016-09-01

    We develop an abstract model of atomic clocks that fully describes the dynamics of repeated synchronization between a classical oscillator and a quantum reference. We prove existence of a stationary state of the model and study its dependence on the control scheme, the interrogation time and the stability of the oscillator. For unbiased atomic clocks, we derive a fundamental bound on atomic clocks long time stability for a given local oscillator noise. In particular, we show that for a local oscillator noise with integrated frequency variance scaling as {T^α} for short times T, the optimal clock time variance scales as {F^{-(α +1)/(α +2)}} with respect to the quantum Fisher information, F, associated to the quantum reference. In an attempt to prove the bounds without the unbiasedness assumption, we derive a new Cramer-Rao type inequality.

  12. An atomic clock with $10^{-18}$ instability

    CERN Document Server

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

    2013-01-01

    Atomic clocks have been transformational in science and technology, leading to innovations such as global positioning, advanced communications, and tests of fundamental constant variation. Next-generation optical atomic clocks can extend the capability of these timekeepers, where researchers have long aspired toward measurement precision at 1 part in $\\bm{10^{18}}$. This milestone will enable a second revolution of new timing applications such as relativistic geodesy, enhanced Earth- and space-based navigation and telescopy, and new tests on physics beyond the Standard Model. Here, we describe the development and operation of two optical lattice clocks, both utilizing spin-polarized, ultracold atomic ytterbium. A measurement comparing these systems demonstrates an unprecedented atomic clock instability of $\\bm{1.6\\times 10^{-18}}$ after only $\\bm{7}$ hours of averaging.

  13. Recent progress of neutral mercury lattice clock in SIOM

    Science.gov (United States)

    Zhao, R. C.; Fu, X. H.; Liu, K. K.; Gou, W.; Sun, J. F.; Xu, Z.; Wang, Y. Z.

    2016-06-01

    Neutral mercury atom is one of good candidates of optical lattice clock. Due to its large atomic number, mercury atom is insensitive to black body radiation, which is the severe limitation for the development of optical clocks. However, the challenge of neutral mercury lattice clock is the requirement of high power deep-UV lasers, especially for both the cooling laser and the lattice laser. Here, we report the recent progress of neutral mercury lattice clock in SIOM, including the development for laser cooling of mercury atom and the cooling laser system with fiber laser amplifier. We have realized the magneto-optical trap of mercury atoms and measured the parameters of cold mercury atoms. A home-made external cavity diode laser works as a seed laser for a room temperature 1014.8 nm fiber laser amplifier. A new efficient frequency-doubling cavity from 1015 nm to 507 nm has been developed.

  14. The clock paradox in a static homogeneous gravitational field

    CERN Document Server

    Jones, P; Jones, Preston; Wanex, Lucas F.

    2006-01-01

    The gedanken experiment of the clock paradox is solved exactly using the general relativistic equations for a static homogeneous gravitational field. We demonstrate that the general and special relativistic clock paradox solutions are identical and in particular that they are identical for finite acceleration. Practical expressions are obtained for proper time and coordinate time by using the destination distance as the key observable parameter. This solution provides a formal demonstration of the identity between the special and general relativistic clock paradox with finite acceleration and where proper time is assumed to be the same in both formalisms. By solving the equations of motion for a freely falling clock in a static homogeneous field elapsed times are calculated for realistic journeys to the stars.

  15. Bounds on gravitational wave backgrounds from large distance clock comparisons

    CERN Document Server

    Reynaud, Serge; Duchayne, Loic; Wolf, Peter; Jaekel, Marc-Thierry

    2008-01-01

    Our spacetime is filled with gravitational wave backgrounds that constitute a fluctuating environment created by astrophysical and cosmological sources. Bounds on these backgrounds are obtained from cosmological and astrophysical data but also by analysis of ranging and Doppler signals from distant spacecraft. We propose here a new way to set bounds on those backgrounds by performing clock comparisons between a ground clock and a remote spacecraft equipped with an ultra-stable clock, rather than only ranging to an onboard transponder. This technique can then be optimized as a function of the signal to be measured and the dominant noise sources, leading to significant improvements on present bounds in a promising frequency range where different theoretical models are competing. We illustrate our approach using the SAGAS project which aims to fly an ultra stable optical clock in the outer solar system.

  16. 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.

  17. Clock synchronization of a broadband seismometer through IEEE-1588 protocol

    OpenAIRE

    Pallares, Oriol; Río Fernandez, Joaquín del; Shariat Panahi, Shahram

    2010-01-01

    In seismology, the time of the signal acquisition is highly important in order to know the magnitude and location of the earthquake. This paper presents the tests carried out to synchronize the seismometer clock through the IEEE-1588 protocol.

  18. A Low-jitter 2.5-to-10 GHz Clock Multiplier Unit in CMOS

    OpenAIRE

    Beek, van, P.; Vaucher, C.S.; Leenaerts, D. M. W.; Klumperink, E.A.M.; Nauta, B.

    2003-01-01

    This paper demonstrates a low-jitter clock multiplier unit [1] that generates a 10 GHz output clock from a 2.5 GHz reference clock. An integrated 10 GHz LCoscillator is locked to the input clock, using a simple and fast phase detector circuit. This phase detector overcomes the speed limitation of a conventional tri-state Phase Frequency Detector, by eliminating an internal feedback loop. A frequency detector guarantees PLL locking without degenerating jitter performance. The clock multiplier ...

  19. A clock synchronization method based on IEEE 1588 and its implementation on Ethernet

    Institute of Scientific and Technical Information of China (English)

    XU Wan; CHEN You-ping; CHEN Bing; XIE Jing-ming

    2008-01-01

    We presented a clock synchronization method that contained a clock adjusting algorithm and a frequency compensated clock to achieve precise synchronization among distributed clocks based on IEEE 1588 protocol. Further, we presented its application on Ethernet and implementation of the frequency compensated clock in a field programmable gate array (FPGA) as experiments. The results indicate that this method can support sub-microsecond synchronization with inexpensive standard crystal oscillators.

  20. Improving X10 Program Performances by Clock Removal

    OpenAIRE

    Feautrier, Paul; Violard, Eric; Ketterlin, Alain

    2014-01-01

    X10 is a promising recent parallel language designed specifically to address the challenges of productively programming a wide variety of target platforms. The sequential core of X10 is an object-oriented language in the Java family. This core is augmented by a few parallel constructs that create activities as a generalization of the well known fork/join model. Clocks are a generalization of the familiar barriers. Synchronization on a clock is specified by the advance() method call. Activitie...

  1. 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.

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

    OpenAIRE

    Lindkvist, Joel; Sabín, Carlos; 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...

  3. An Integrated Architectural Clock Implemented Memory Design Analysis

    OpenAIRE

    Ravi Khatwal; Manoj Kumar Jain

    2015-01-01

    Recently Low power consumption and Custom Memory design is major issue for embedded designer. Micro wind and Xilinx simulator implements SRAM design architecture and performs efficient simulation. These simulators implements high performances and low power consumption of SRAM design. SRAM efficiency analyzed with 6-T architecture design and row/column based architectural design. We have analyzed clock implemented memory design and simulated with specific application. We have implemented clock...

  4. Clock Face Drawing Test Performance in Children with ADHD

    Directory of Open Access Journals (Sweden)

    Ahmad Ghanizadeh

    2013-01-01

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

  5. Interpretable Machine Learning Models for the Digital Clock Drawing Test

    OpenAIRE

    Souillard-Mandar, William; Davis, Randall; Rudin, Cynthia; Au, Rhoda; Penney, Dana

    2016-01-01

    The Clock Drawing Test (CDT) is a rapid, inexpensive, and popular neuropsychological screening tool for cognitive conditions. The Digital Clock Drawing Test (dCDT) uses novel software to analyze data from a digitizing ballpoint pen that reports its position with considerable spatial and temporal precision, making possible the analysis of both the drawing process and final product. We developed methodology to analyze pen stroke data from these drawings, and computed a large collection of featu...

  6. The clock ambiguity and the emergence of physical laws

    OpenAIRE

    Albrecht, Andreas; Iglesias, Alberto

    2007-01-01

    The process of identifying a time variable in time reparameterization invariant theories results in great ambiguities about the actual laws of physics described by a given theory. A theory set up to describe one set of physical laws can equally well be interpreted as describing any other laws of physics by making a different choice of time variable or ``clock''. In this article we demonstrate how this ``clock ambiguity'' arises and then discuss how one might still hope to extract specific pre...

  7. Gravitational wave detection with optical lattice atomic clocks

    OpenAIRE

    Kolkowitz, Shimon; Pikovski, Igor; 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 lev...

  8. A mercury optical lattice clock at LNE-SYRTE

    Science.gov (United States)

    De Sarlo, L.; Favier, M.; Tyumenev, R.; Bize, S.

    2016-06-01

    We describe the development of an optical lattice clock based on mercury and the results obtained since the 7 th SFSM. We briefly present a new solution for the cooling laser system and an improved lattice trap that allows us to interrogate a few thousand atoms in parallel. This translates into a fractional short term stability of 1.2 x 10-15 at the clock frequency of 1.129 PHz.

  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. When the circadian clock meets the melanin pigmentary system.

    Science.gov (United States)

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

    2015-04-01

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

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

    OpenAIRE

    Ng, Y. Jack

    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 fluctuati...

  12. Consistency Models in Distributed Systems with Physical Clocks

    OpenAIRE

    Du, Jiaqing

    2014-01-01

    Most existing distributed systems use logical clocks to order events in the implementation of various consistency models. Although logical clocks are straightforward to implement and maintain, they may affect the scalability, availability, and latency of the system when being used to totally order events in strong consistency models. They can also incur considerable overhead when being used to track and check the causal relationships among events in some weak consistency models. In this thesi...

  13. Adrenergic regulation of clock gene expression in mouse liver

    OpenAIRE

    Terazono, Hideyuki; Mutoh, Tatsushi; Yamaguchi, Shun; Kobayashi, Masaki; Akiyama, Masashi; Udo, Rhyuta; Ohdo, Shigehiro; Okamura, Hitoshi; Shibata, Shigenobu

    2003-01-01

    A main oscillator in the suprachiasmatic nucleus (SCN) conveys circadian information to the peripheral clock systems for the regulation of fundamental physiological functions. Although polysynaptic autonomic neural pathways between the SCN and the liver were observed in rats, whether activation of the sympathetic nervous system entrains clock gene expression in the liver has yet to be understood. To assess sympathetic innervation from the SCN to liver tissue, we investigated whether inj...

  14. 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.

  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. 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 ...

  17. 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

    2016-01-01

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

  18. 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.

  19. Serum factors in older individuals change cellular clock properties

    Science.gov (United States)

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

    2011-01-01

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

  20. Mercury Ion Clock for a NASA Technology Demonstration Mission.

    Science.gov (United States)

    Tjoelker, Robert L; Prestage, John D; Burt, Eric A; Chen, Pin; Chong, Yong J; Chung, Sang K; Diener, William; Ely, Todd; Enzer, Daphna G; Mojaradi, Hadi; Okino, Clay; Pauken, Mike; Robison, David; Swenson, Bradford L; Tucker, Blake; Wang, Rabi

    2016-07-01

    There are many different atomic frequency standard technologies but only few meet the demanding performance, reliability, size, mass, and power constraints required for space operation. The Jet Propulsion Laboratory is developing a linear ion-trap-based mercury ion clock, referred to as DSAC (Deep-Space Atomic Clock) under NASA's Technology Demonstration Mission program. This clock is expected to provide a new capability with broad application to space-based navigation and science. A one-year flight demonstration is planned as a hosted payload following an early 2017 launch. This first-generation mercury ion clock for space demonstration has a volume, mass, and power of 17 L, 16 kg, and 47 W, respectively, with further reductions planned for follow-on applications. Clock performance with a signal-to-noise ratio (SNR)*Q limited stability of 1.5E-13/τ(1/2) has been observed and a fractional frequency stability of 2E-15 at one day measured (no drift removed). Such a space-based stability enables autonomous timekeeping of with a technology capable of even higher stability, if desired. To date, the demonstration clock has been successfully subjected to mechanical vibration testing at the 14 grms level, thermal-vacuum operation over a range of 42(°)C, and electromagnetic susceptibility tests. PMID:27019481

  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.

    2015-01-01

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

  2. 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.

  3. 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

  4. 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.

  5. 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 ...

  6. Cardiovascular tissues contain independent circadian clocks

    Science.gov (United States)

    Davidson, A. J.; London, B.; Block, G. D.; Menaker, M.

    2005-01-01

    Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    WANG Yupu

    2016-06-01

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

  9. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-08-16

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

  13. Protecting Clock Synchronization: Adversary Detection through Network Monitoring

    Directory of Open Access Journals (Sweden)

    Elena Lisova

    2016-01-01

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

  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. 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...

  17. 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.

  18. 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.

  19. A high-precision synchronization circuit for clock distribution

    International Nuclear Information System (INIS)

    In this paper, a novel structure of a high-precision synchronization circuit, HPSC, using interleaved delay units and a dynamic compensation circuit is proposed. HPSCs are designed for synchronization of clock distribution networks in large-scale integrated circuits, where high-quality clocks are required. The application of a hybrid structure of a coarse delay line and dynamic compensation circuit performs roughly the alignment of the clock signal in two clock cycles, and finishes the fine tuning in the next three clock cycles with the phase error suppressed under 3.8 ps. The proposed circuit is implemented and fabricated using a SMIC 0.13 μm 1P6M process with a supply voltage at 1.2 V. The allowed operation frequency ranges from 200 to 800 MHz, and the duty cycle ranges between [20%, 80%]. The active area of the core circuits is 245 × 134 μm2, and the power consumption is 1.64 mW at 500 MHz. (paper)

  20. 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.

  1. Tests of local position invariance using continuously running atomic clocks

    CERN Document Server

    Peil, Steven; Hanssen, James L; Swanson, Thomas B; Ekstrom, Christopher R; 10.1103/PhysRevA.87.010102

    2013-01-01

    Tests of local position invariance (LPI) made by comparing the relative redshift of atomic clocks based on different atoms have been carried out for a variety of pairs of atomic species. In most cases, several absolute frequency measurements per year are used to look for an annual signal, resulting in tests that can span on order of a decade. By using the output of continuously running clocks, we carry out LPI tests with comparable or higher precision after less than 1.5 years. These include new measurements of the difference in redshift anomalies \\beta\\ for hyperfine transitions in Rb87 and Cs133 and in H and Cs133 and a measurement comparing Rb87 and H, resulting in a stringent limit on LPI, \\beta(Rb) - \\beta(H)=(-2.7 +/- 4.9) x 10^(-7). The method of making these measurements for continuous clocks is discussed.

  2. 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...

  3. 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.

  4. 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...

  5. ‘Leading clocks lag’ and the de Broglie wavelength

    Science.gov (United States)

    Shuler, Robert L., Jr.

    2016-03-01

    The forgotten history of de Broglie waves as themselves artifacts of a Lorentz transform, not physical lengths and frequencies to be transformed, causes confusion for students and others. In this paper the de Broglie wavelength is derived and dependence of de Broglie frequency on velocity explained in terms of Einstein synchronized reference frame measurements of a single clock (2-on-1) versus measurements of an Einstein reference frame by an observer with a single clock (1-on-2). A new memory aid for the relativity of simultaneity, ‘leading clocks lag,’ is introduced that puts it on a par with the heuristics ‘time dilation’ and ‘length contraction’ for quick and easy problem visualization.

  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. Event-Clock Automata: From Theory to Practice

    CERN Document Server

    Geeraerts, Gilles; Sznajder, Nathalie

    2011-01-01

    Event clock automata (ECA) are a model for timed languages that has been introduced by Alur, Fix and Henzinger as an alternative to timed automata, with better theoretical properties (for instance, ECA are determinizable while timed automata are not). In this paper, we revisit and extend the theory of ECA. We first prove that no finite time abstract language equivalence exists for ECA, thereby disproving a claim in the original work on ECA. This means in particular that regions do not form a time abstract bisimulation. Nevertheless, we show that regions can still be used to build a finite automaton recognizing the untimed language of an ECA. Then, we extend the classical notions of zones and DBMs to let them handle event clocks instead of plain clocks (as in timed automata) by introducing event zones and Event DBMs (EDBMs). We discuss algorithms to handle event zones represented as EDBMs, as well as (semi-) algorithms based on EDBMs to decide language emptiness of ECA.

  8. Fault Secure Encoder and Decoder with Clock Gating

    Directory of Open Access Journals (Sweden)

    N.Kapileswar

    2012-04-01

    Full Text Available This paper presents circuit design for a low power fault secure encoder and decoder system. Memory cells in logic circuits have been protected from soft errors for more than a decade due to increase in soft error rates. In this paper the circuitry around the memory block have been susceptible to soft errors and must be protected from faults. The proposed design uses error correcting codes and ring counter addressing scheme. In the ring counter several new clock gating techniques are proposed to reduce power consumption. A fault secure Encoder and Decoder error free low power logic circuits can be achieved by the proposed design. Simulation results show great improvement in power consumption. Fault secure Encoder and Decoder with clock gated by CG-element consumes approximately half the power of that consumed by the fault free circuit which doesn’t employ clock gating technique

  9. Mapping Out Atom-Wall Interaction with Atomic Clocks

    International Nuclear Information System (INIS)

    We explore the feasibility of probing atom-wall interaction with atomic clocks based on atoms trapped in engineered optical lattices. Optical lattice is normal to the wall. By monitoring the wall-induced clock shift at individual wells of the lattice, one would measure the dependence of the atom-wall interaction on the atom-wall separation. We find that the induced clock shifts are large and observable at already experimentally demonstrated levels of accuracy. We show that this scheme may uniquely probe the long-range atom-wall interaction in all three qualitatively distinct regimes of the interaction: van der Waals (image-charge interaction), Casimir-Polder (QED vacuum fluctuations), and Lifshitz (thermal-bath fluctuations) regimes.

  10. A Movable-Cavity Cold Atom Space Clock

    Institute of Scientific and Technical Information of China (English)

    BIAN Feng-Gang; WEI Rong; JIANG Hai-Feng; WANG Yu-Zhu

    2005-01-01

    @@ We present an experimental scheme of a cold atom space clock with a movable cavity. By using a single microwave cavity, we find that the clock has a significant advantage, i.e. the longitudinal cavity phase shift is eliminated. A theoretical analysis has been carried out in terms of the relation between the atomic transition probability and the velocity of the moving cavity by taking into account the velocity distribution of cold atoms. The requirements for the microwave power and its stability for atomic πr /2 excitation at different moving velocities of the cavity lead to the determination of the proper working parameters of the rubidium clock in frequency accuracy 10-17. Finally,the mechanical stability for the scheme is analysed and the ways of solving the possible mechanical instability of the device are proposed.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  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. Illuminating the circadian clock in monarch butterfly migration.

    Science.gov (United States)

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

    2003-05-23

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

  17. 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.

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

    OpenAIRE

    Peik, Ekkehard; Okhapkin, Maxim

    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 opt...

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Shih, Yanhua (Inventor)

    2010-01-01

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

  5. 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....

  6. 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

    of clock gene expression in depressive patients many studies have reported single-nucleotide polymorphisms in clock genes in these patients. METHODS: In the present study we investigated whether a depression-like state in rats associates with alternations of the diurnal expression of clock genes......: The present results suggest that altered expression of investigated clock genes are likely to associate with the induction of a depression-like state in the CMS model...

  7. Conserved expression profiles of circadian clock-related genes in two Lemna species showing long-day and short-day photoperiodic flowering responses.

    Science.gov (United States)

    Miwa, Kumiko; Serikawa, Masayuki; Suzuki, Sayaka; Kondo, Takao; Oyama, Tokitaka

    2006-05-01

    The Lemna genus is a group of monocotyledonous plants with tiny, floating bodies. Lemna gibba G3 and L. paucicostata 6746 were once intensively analyzed for physiological timing systems of photoperiodic flowering and circadian rhythms since they showed obligatory and sensitive photoperiodic responses of a long-day and a short-day plant, respectively. We attempted to approach the divergence of biological timing systems at the molecular level using these plants. We first employed molecular techniques to study their circadian clock systems. We developed a convenient bioluminescent reporter system to monitor the circadian rhythms of Lemna plants. As in Arabidopsis, the Arabidopsis CCA1 promoter produced circadian expression in Lemna plants, though the phases and the sustainability of bioluminescence rhythms were somewhat diverged between them. Lemna homologs of the Arabidopsis clock-related genes LHY/CCA1, GI, ELF3 and PRRs were then isolated as candidates for clock-related genes in these plants. These genes showed rhythmic expression profiles that were basically similar to those of Arabidopsis under light-dark conditions. Results from co-transfection assays using the bioluminescence reporter and overexpression effectors suggested that the LHY and GI homologs of Lemna can function in the circadian clock system like the counterparts of Arabidopsis. All these results suggested that the frame of the circadian clock appeared to be conserved not only between the two Lemna plants but also between monocotyledons and dicotyledons. However, divergence of gene numbers and expression profiles for LHY/CCA1 homologs were found between Lemna, rice and Arabidopsis, suggesting that some modification of clock-related components occurred through their evolution. PMID:16524874

  8. Telling time from analog and digital clocks: A multiple-route account

    NARCIS (Netherlands)

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

    2007-01-01

    Does the naming of clocks always require conceptual preparation? To examine this question, speakers were presented with analog and digital clocks that had to be named in Dutch using either a relative (e.g., "quarter to four") or an absolute (e.g., "three forty-five") clock time expression format. Na

  9. 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

  10. 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.

  11. 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.

  12. Conceptual Design of a Micron-Scale Atomic Clock

    CERN Document Server

    Hannah, Eric C

    2007-01-01

    A theoretical proposal for reducing an entire atomic clock to micron dimensions. A phosphorus or nitrogen atom is introduced into a fullerene cage. This endohedral fullerene is then coated with an insulating shell and a number of them are deposited as a thin layer on a silicon chip. Next to this layer a GMR sensor is fabricated which is close to the endohedral fullerenes. This GMR sensor measures oscillating magnetic fields on the order of micro-gauss from the nuclear spins varying at the frequency of the hyperfine transition (413 MHz frequency). Given the micron scale and simplicity of this system only a few transistors are needed to control the waveforms and to perform digital clocking. This new form of atomic clock exhibits extremely low power (nano watts), high vibration and shock resistance, stability on the order of 10^{-9}, and is compatible with MEMS fabrication and chip integration. As GMR sensors continue to improve in sensitivity the stability of this form of atomic clock will increase proportionat...

  13. 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 ...

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

    Science.gov (United States)

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

    2016-07-01

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

  15. The hypothalamic clock and its control of glucose homeostasis

    NARCIS (Netherlands)

    A. Kalsbeek; C.X. Yi; S.E. la Fleur; E. Fliers

    2010-01-01

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

  16. 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.

  17. Clock ambiguity and the emergence of physical laws

    International Nuclear Information System (INIS)

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

  18. 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…

  19. Phase resetting of the mammalian circadian clock by DNA damage

    NARCIS (Netherlands)

    Oklejewicz, Malgorzata; Destici, Eugin; Tamanini, Filippo; Hut, Roelof A.; Janssens, Roel; van der Horst, Gijsbertus T. J.

    2008-01-01

    To anticipate the momentum of the day, most organisms have developed an internal clock that drives circadian rhythms in metabolism, physiology, and behavior [1]. Recent studies indicate that cell-cycle progression and DNA-damage-response pathways are under circadian control [2-4]. Because circadian

  20. 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

  1. Mammalian circadian clock and metabolism - the epigenetic link.

    Science.gov (United States)

    Bellet, Marina Maria; Sassone-Corsi, Paolo

    2010-11-15

    Circadian rhythms regulate a wide variety of physiological and metabolic processes. The clock machinery comprises complex transcriptional-translational feedback loops that, through the action of specific transcription factors, modulate the expression of as many as 10% of cellular transcripts. This marked change in gene expression necessarily implicates a global regulation of chromatin remodeling. Indeed, various descriptive studies have indicated that histone modifications occur at promoters of clock-controlled genes (CCGs) in a circadian manner. The finding that CLOCK, a transcription factor crucial for circadian function, has intrinsic histone acetyl transferase (HAT) activity has paved the way to unraveling the molecular mechanisms that govern circadian chromatin remodeling. A search for the histone deacetylase (HDAC) that counterbalances CLOCK activity revealed that SIRT1, a nicotinamide adenin dinucleotide (NAD(+))-dependent HDAC, functions in a circadian manner. Importantly, SIRT1 is a regulator of aging, inflammation and metabolism. As many transcripts that oscillate in mammalian peripheral tissues encode proteins that have central roles in metabolic processes, these findings establish a functional and molecular link between energy balance, chromatin remodeling and circadian physiology. Here we review recent studies that support the existence of this link and discuss their implications for understanding mammalian physiology and pathology. PMID:21048160

  2. 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…

  3. The AGS Ggamma Meter and Calibrating the Gauss Clock

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-31

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

  4. Clock Synchronisation in the Vicinity of the Earth

    OpenAIRE

    Goy, Francois

    1997-01-01

    The transmission time of an electromagnetic signal in the vicinity of the earth is calculated to c-2 and contains an orbital Sagnac term. On earth, the synchronisation of the Barycentric Coordinate Time (TCB) can be realised by atomic clocks, but not the one of Geocentric Coordinate Time (TCG). The principle of equivalence is discussed.

  5. 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…

  6. Metrological characterization of the pulsed Rb clock with optical detection

    CERN Document Server

    Micalizio, Salvatore; Godone, Aldo; Levi, Filippo

    2011-01-01

    We report on the implementation and the metrological characterization of a vapor-cell Rb frequency standard working in pulsed regime. The three main parts that compose the clock, physics package, optics and electronics, are described in detail in the paper. The prototype is designed and optimized to detect the clock transition in the optical domain. Specifically, the reference atomic transition, excited with a Ramsey scheme, is detected by observing the interference pattern on a laser absorption signal. \\ The metrological analysis includes the observation and characterization of the clock signal and the measurement of frequency stability and drift. In terms of Allan deviation, the measured frequency stability results as low as $1.7\\times 10^{-13} \\ \\tau^{-1/2}$, $\\tau$ being the averaging time, and reaches the value of few units of $10^{-15}$ for $\\tau=10^{4}$ s, an unprecedent achievement for a vapor cell clock. We discuss in the paper the physical effects leading to this result with particular care to laser...

  7. Modeling pharmacological clock and memory patterns of interval timing in a striatal beat-frequency model with realistic, noisy neurons

    Directory of Open Access Journals (Sweden)

    Sorinel A. Oprisan

    2011-09-01

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

  8. 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.

  9. 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.

  10. Clock recovering characteristics of adaptive finite-impulse-response filters in digital coherent optical receivers.

    Science.gov (United States)

    Kikuchi, Kazuro

    2011-03-14

    We analyze the clock-recovery process based on adaptive finite-impulse-response (FIR) filtering in digital coherent optical receivers. When the clock frequency is synchronized between the transmitter and the receiver, only five taps in half-symbol-spaced FIR filters can adjust the sampling phase of analog-to-digital conversion optimally, enabling bit-error rate performance independent of the initial sampling phase. Even if the clock frequency is not synchronized between them, the clock-frequency misalignment can be adjusted within an appropriate block interval; thus, we can achieve an asynchronous clock mode of operation of digital coherent receivers with block processing of the symbol sequence. PMID:21445201

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

    Science.gov (United States)

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

    2016-04-15

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

  12. 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 ...

  13. 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.

  14. 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...

  15. 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.

  16. Osmotic stress at the barley root affects expression of circadian clock genes in the shoot.

    Science.gov (United States)

    Habte, Ermias; Müller, Lukas M; Shtaya, Munqez; Davis, Seth J; von Korff, Maria

    2014-06-01

    The circadian clock is an important timing system that controls physiological responses to abiotic stresses in plants. However, there is little information on the effects of the clock on stress adaptation in important crops, like barley. In addition, we do not know how osmotic stress perceived at the roots affect the shoot circadian clock. Barley genotypes, carrying natural variation at the photoperiod response and clock genes Ppd-H1 and HvELF3, were grown under control and osmotic stress conditions to record changes in the diurnal expression of clock and stress-response genes and in physiological traits. Variation at HvELF3 affected the expression phase and shape of clock and stress-response genes, while variation at Ppd-H1 only affected the expression levels of stress genes. Osmotic stress up-regulated expression of clock and stress-response genes and advanced their expression peaks. Clock genes controlled the expression of stress-response genes, but had minor effects on gas exchange and leaf transpiration. This study demonstrated that osmotic stress at the barley root altered clock gene expression in the shoot and acted as a spatial input signal into the clock. Unlike in Arabidopsis, barley primary assimilation was less controlled by the clock and more responsive to environmental perturbations, such as osmotic stress. PMID:24895755

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Guo-Xiang Ruan

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

  20. 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

  1. 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.

  2. Atomic Clock Ensemble in Space: Scientific Objectives and Mission Status

    Energy Technology Data Exchange (ETDEWEB)

    Cacciapuoti, L. [European Space Agency, ESTEC, Keplerlaan 1 - P.O. Box 299, 2200 AG Noordwijk ZH (Netherlands)], E-mail: Luigi.Cacciapuoti@esa.int; Dimarcq, N.; Santarelli, G.; Laurent, P.; Lemonde, P.; Clairon, A. [SYRTE-CNRS UMR8630, Observatoire de Paris, 61, avenue de l' Observatoire 75014 Paris (France); Berthoud, P.; Jornod, A. [Observatoire de Neuchatel, 58, rue de l' Observatoire, CH-2000 Neuchatel (Switzerland); Reina, F.; Feltham, S. [European Space Agency, ESTEC, Keplerlaan 1 - P.O. Box 299, 2200 AG Noordwijk ZH (Netherlands); Salomon, C. [Laboratoire Kastler Brossel, ENS, 24, rue Lhomond, 75005 Paris (France)

    2007-04-15

    Atomic Clock Ensemble in Space (ACES) is a mission in fundamental physics that will operate a new generation of atomic clocks in the microgravity environment of the International Space Station. Fractional frequency instability and inaccuracy at the 10{sup -16} level will be achieved. The on-board time base, distributed on Earth via a microwave link, will be used for space-to-ground as well as ground-to-ground comparisons of atomic frequency standards. Based on these comparisons, ACES will perform fundamental physics tests and develop applications in time and frequency metrology, universal time scales, global positioning and navigation, geodesy, and gravimetry. After a general overview of the mission concept and its scientific objectives, the present status of ACES instruments and sub-systems will be discussed.

  3. PPARs Integrate the Mammalian Clock and Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Lihong Chen

    2014-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential role in various physiological and pathological processes, especially in energy metabolism. It has long been known that metabolism and circadian clocks are tightly intertwined. However, the mechanism of how they influence each other is not fully understood. Recently, all three PPAR isoforms were found to be rhythmically expressed in given mouse tissues. Among them, PPARα and PPARγ are direct regulators of core clock components, Bmal1 and Rev-erbα, and, conversely, PPARα is also a direct Bmal1 target gene. More importantly, recent studies using knockout mice revealed that all PPARs exert given functions in a circadian manner. These findings demonstrated a novel role of PPARs as regulators in correlating circadian rhythm and metabolism. In this review, we summarize advances in our understanding of PPARs in circadian regulation.

  4. 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.

  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. 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.

  7. 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...

  8. 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.

  9. Synchronization of Distant Optical Clocks at the Femtosecond Level

    CERN Document Server

    Deschenes, Jean-Daniel; Giorgetta, Fabrizio R; Swann, William C; Baumann, Esther; Bergeron, Hugo; Cermak, Michael; Coddington, Ian; Newbury, Nathan R

    2015-01-01

    The use of optical clocks/oscillators in future ultra-precise navigation, gravitational sensing, and relativity experiments will require time comparison and synchronization over terrestrial or satellite free-space links. Here we demonstrate full unambiguous synchronization of two optical timescales across a free-space link. The time deviation between synchronized timescales is below 1 fs over durations from 0.1 s to 6500 s, despite atmospheric turbulence and kilometer-scale path length variations. Over several days, the time wander is below +/-20 fs. Our approach relies on the two-way reciprocity of a single-spatial-mode optical link, valid to below 225 attoseconds across a turbulent 4-km path. This femtosecond level of time-frequency transfer should enable optical networks using state-of-the-art optical clocks/oscillators.

  10. 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...

  11. 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.

  12. 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, ...

  13. 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.

  14. Searching for Dark Matter with Atomic Clocks and Laser Interferometry

    Science.gov (United States)

    Stadnik, Yevgeny; Flambaum, Victor

    2016-05-01

    We propose new schemes for the direct detection of low-mass bosonic dark matter, which forms a coherently oscillating classical field and resides in the observed galactic dark matter haloes, using atomic clock, atomic spectroscopy and laser interferometry measurements in the laboratory. We have recently shown that such dark matter can produce both a `slow' cosmological evolution and oscillating variations in the fundamental constants. Using recent atomic dysprosium spectroscopy measurements in, we have derived limits on the quadratic interactions of scalar dark matter with ordinary matter that improve on existing constraints by up to 15 orders of magnitude. We have also proposed the use of laser and maser interferometry as novel high-precision platforms to search for dark matter, with effects due to the variation of the electromagnetic fine-structure constant on alterations in the accumulated phase enhanced by up to 14 orders of magnitude. Other possibilities include the use of highly-charged ions, molecules and nuclear clocks.

  15. 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.

  16. 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.

  17. 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

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

    OpenAIRE

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Harmon Frank G

    2010-06-01

    Full Text Available Abstract Background The plant circadian clock orchestrates 24-hour rhythms in internal physiological processes to coordinate these activities with daily and seasonal changes in the environment. The circadian clock has a profound impact on many aspects of plant growth and development, including biomass accumulation and flowering time. Despite recent advances in understanding the circadian system of the model plant Arabidopsis thaliana, the contribution of the circadian oscillator to important agronomic traits in Zea mays and other cereals remains poorly defined. To address this deficit, this study investigated the transcriptional landscape of the maize circadian system. Results Since transcriptional regulation is a fundamental aspect of circadian systems, genes exhibiting circadian expression were identified in the sequenced maize inbred B73. Of the over 13,000 transcripts examined, approximately 10 percent displayed circadian expression patterns. The majority of cycling genes had peak expression at subjective dawn and dusk, similar to other plant circadian systems. The maize circadian clock organized co-regulation of genes participating in fundamental physiological processes, including photosynthesis, carbohydrate metabolism, cell wall biogenesis, and phytohormone biosynthesis pathways. Conclusions Circadian regulation of the maize genome was widespread and key genes in several major metabolic pathways had circadian expression waveforms. The maize circadian clock coordinated transcription to be coincident with oncoming day or night, which was consistent with the circadian oscillator acting to prepare the plant for these major recurring environmental changes. These findings highlighted the multiple processes in maize plants under circadian regulation and, as a result, provided insight into the important contribution this regulatory system makes to agronomic traits in maize and potentially other C4 plant species.

  20. The cerebellum ages slowly according to the epigenetic clock

    OpenAIRE

    Horvath, Steve; Mah, Vei; Lu, Ake T.; Woo, Jennifer S.; Choi, Oi‐Wa; Jasinska, Anna J.; Riancho Moral, José Antonio; Tung, Spencer; Coles, Natalie S.; Braun, Jonathan; Vinters, Harry V.; Coles, L. Stephen

    2015-01-01

    Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages mo...

  1. 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.

  2. 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.

  3. Estimating metazoan divergence times with a molecular clock

    OpenAIRE

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

    2004-01-01

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

  4. Clock synchronization design and evaluation for trigger-less data acquisition system

    International Nuclear Information System (INIS)

    For modern particle physics experiments, trigger-less data acquisition (DAQ) system has been put into practice because of the need of reaction multiplicity and trigger flexibility. In such new DAQ systems, global synchronized clock plays an important role because it affects the granularity of time slice and precision of reference clock. In this paper, a novel synchronized clock distribution method is proposed. With the help of modulation technique, master clock module distributes system clock to each slave module. To synchronize slave clocks, the propagation delay is adjusted and the clock phase is aligned by an FPGA chip automatically. Furthermore, an ADC- based method is proposed to evaluate the performance of multi-module clock synchronization simultaneously. The experiments of a prototype system show that slave clocks can be synchronized less than 100 ps over 150 m range. The proposed method is simple and flexible, and it can be used in trigger-less DAQ system and other applications of clock distribution preciously. (authors)

  5. 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.

  6. 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

  7. Individual Optical Addressing of Atomic Clock Qubits With Stark Shifts

    Science.gov (United States)

    Lee, Aaron; Smith, Jacob; Richerme, Phillip; Neyenhuis, Brian; Hess, Paul; Zhang, Jiehang; Monroe, Chris

    2016-05-01

    In recent years, trapped ions have proven to be a versatile quantum information platform, enabled by their long lifetimes and high gate fidelities. Some of the most promising trapped ion systems take advantage of groundstate hyperfine ``clock'' qubits, which are insensitive to background fields to first order. This same insensitivity also makes σz manipulations of the qubit impractical, eliminating whole classes of operations. We prove there exists a fourth-order light shift, or four-photon Stark shift, of the clock states derived from two coherent laser beams whose beatnote is close to the qubit splitting. Using a mode-locked source generates a large light shift with only modest laser powers, making it a practical σz operation on a clock qubit. We experimentally verify and measure the four-photon Stark shift and demonstrate its use to coherently individually address qubits in a chain of 10 Yb 171 ions with low crosstalk. We use this individual addressing to prepare arbitrary product states with high fidelity and also to apply independent σz terms transverse to an Ising Hamiltonian. This work is supported by the ARO Atomic Physics Program, the AFOSR MURI on Quantum Measurement and Verification, and the NSF Physics Frontier Center at JQI.

  8. Clock rate comparison in a uniform gravitational field

    CERN Document Server

    Alberici, M

    2004-01-01

    A partially alternative derivation of the expression for the time dilation effect in a uniform static gravitational field is obtained by means of a thought experiment in which rates of clocks at rest at different heights are compared using as reference a clock bound to a free falling reference system (FFRS). Derivations along these lines have already been proposed, but generally introducing some shortcut in order to make the presentation elementary. The treatment is here exact: the clocks whose rates one wishes to compare are let to describe their world lines (Rindler's hyperbolae) with respect to the FFRS, and the result is obtained by comparing their lengths in space-time. The exercise may nonetheless prove pedagogically instructive insofar as it shows that the exact result of General Relativity (GR) can be obtained in terms of physical and geometrical reasoning without having recourse to the general formalism. It also compels to deal with a few subtle points inherent in the very foundations of GR.

  9. 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...

  10. Compact Microwave Mercury Ion Clock for Space Applications

    Science.gov (United States)

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

    2008-01-01

    We have recently completed a breadboard ion-clock physics package based on Hg ions shuttled between a quadrupole and a 16-pole rf trap. With this architecture we have demonstrated short-term stability approximately 1 - 2 x 10(exp -13) at 1 second, averaging to 10(exp -15) at 1 day. This development shows that H-maser quality stabilities can be produced in a small clock package, comparable in size to an ultra-stable quartz oscillator required for holding 1 - 2 x 10(exp -13) at 1 second. This performance was obtained in a sealed vacuum configuration where only a getter pump was used to maintain vacuum. The vacuum tube containing the traps has now been under sealed vacuum conditions for nearly three years with no measurable degradation of ion trapping lifetimes or clock short-term performance. We have fabricated the vacuum tube, ion trap and UV windows from materials that will allow an approximately 400 C bake-out to prepare for tube seal-off. This approach to the vacuum follows the methods used in flight vacuum tube electronics, such as flight TWTA's where tube operation lifetime and shelf life of up to 15 years is achieved.

  11. Progress on Small Mercury Ion Clock for Space Applications

    Science.gov (United States)

    Prestage, John D.; Chung, Sang K.; Thompson, Robert J.; MacNeal, Paul

    2009-01-01

    We have recently completed a breadboard ion-clock physics package based on Hg ions shuttled between a quadrupole and a 16-pole rf trap. With this architecture we have demonstrated short-term stability approx.1-2x10-(sup 1)(sup 3) at 1 second, averaging to 10-(sup 1)? at 1 day. This development shows that H-maser quality stabilities can be produced in a small clock package, comparable in size to an ultra-stable quartz oscillator required for holding 1-2x10-(sup 1)(sup 3) at 1 second. This performance was obtained in a sealed vacuum configuration where only a getter pump was used to maintain vacuum. The vacuum tube containing the traps has now been under sealed vacuum conditions for over three years with no measurable degradation of ion trapping lifetimes or clock short-term performance. We have fabricated the vacuum tube, ion trap and UV windows from materials that will allow approx. 400 deg C bake-out to prepare for tube seal-off. This approach to the vacuum follows the methods used in flight vacuum tube electronics, such as flight TWTA's where tube operation lifetime and shelf life of up to 15 years is achieved.

  12. Using Clocks and Atomic Interferometry for Gravity Field Observations

    Science.gov (United States)

    Müller, Jürgen

    2016-07-01

    New technology developed in the frame of fundamental physics may lead to enhanced capabilities for geodetic applications such as refined observations of the Earth's gravity field. Here, we will present new sensor measurement concepts that apply atomic interferometry for gravimetry and clock measurements for observing potential values. In the first case, gravity anomalies can be determined by observing free-falling atoms (quantum gravimetry). In the second case, highly precise optical clocks can be used to measure differences of the gravity potential over long distances (relativistic geodesy). Principally, also inter-satellite ranging between test masses in space with nanometer accuracy belongs to these novel developments. We will show, how the new measurement concepts are connected to classical geodetic concepts, e.g. geopotential numbers and clock readings. We will illustrate the application of these new methods and their benefit for geodesy, where local and global mass variations can be observed with unforeseen accuracy and resolution, mass variations that reflect processes in the Earth system. We will present a few examples where geodesy will potentially benefit from these developments. Thus, the novel technologies might be applied for defining and realizing height systems in a new way, but also for fast local gravimetric surveys and exploration.

  13. Atomic clocks based on adaptive phase measurements with entangled atoms

    Science.gov (United States)

    Andre, Axel; Sorensen, Anders; Lukin, Mikhail

    2005-05-01

    We show that the frequency stability of atomic clocks limited by local oscillator frequency fluctuations [1] can be greatly improved by using an adaptive measurement strategy with entangled atoms. Our method uses multiple atomic sub-ensembles with various degrees of spin-squeezing and sequential adaptive measurements of the Ramsey phase. With properly optimized degree of squeezing, this method reaches the Heisenberg limit for phase measurements δφ˜1/N, where N is the number of atoms. In addition, we show that multiple interrogation times for these sub-ensembles can be used to improve the long-term stability of the clock. This method allows one to use a very long interrogation time, limited only by environmental fluctuations. The combination of the above two methods leads to an ultimate long-term frequency stability of the clock scaling as σy(τ)=A. Andr'e, A. S. Sørensen, and M. D. Lukin, Phys. Rev. Lett. 92, 230801 (2004).

  14. Suppression of collisional shifts in a strongly interacting lattice clock

    CERN Document Server

    Swallows, Matthew D; Lin, Yige; Blatt, Sebastian; Martin, Michael J; Rey, Ana Maria; Ye, Jun

    2010-01-01

    Atomic clocks based on neutral atoms confined in optical lattices provide a unique opportunity for precise studies of quantum many-body systems. The 87Sr optical lattice clock at JILA has reached an overall fractional frequency uncertainty of 1x10^-16 [1, 2]. This uncertainty is dominated by two contributions: atomic collisions and frequency shifts due to room-temperature blackbody radiation. The density-dependent frequency shift arises from collisions between fermionic atoms that are subject to slightly inhomogeneous optical excitation [3, 4]. Several theories of the underlying frequency shift mechanism have been proposed [5-7]. A three-dimensional optical lattice clock, where each lattice site contains at most one atom, has been reported [8], and its collisional shift has been characterized with an uncertainty of 7x10^-16. Here we present a different and seemingly paradoxical solution to the problem: by strongly confining atoms in an array of quasi-one-dimensional potentials formed by a two-dimensional opti...

  15. 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.

  16. Regulation of clock-controlled genes in mammals.

    Directory of Open Access Journals (Sweden)

    Katarzyna Bozek

    Full Text Available The complexity of tissue- and day time-specific regulation of thousands of clock-controlled genes (CCGs suggests that many regulatory mechanisms contribute to the transcriptional output of the circadian clock. We aim to predict these mechanisms using a large scale promoter analysis of CCGs.Our study is based on a meta-analysis of DNA-array data from rodent tissues. We searched in the promoter regions of 2065 CCGs for highly overrepresented transcription factor binding sites. In order to compensate the relatively high GC-content of CCG promoters, a novel background model to avoid a bias towards GC-rich motifs was employed. We found that many of the transcription factors with overrepresented binding sites in CCG promoters exhibit themselves circadian rhythms. Among the predicted factors are known regulators such as CLOCKratioBMAL1, DBP, HLF, E4BP4, CREB, RORalpha and the recently described regulators HSF1, STAT3, SP1 and HNF-4alpha. As additional promising candidates of circadian transcriptional regulators PAX-4, C/EBP, EVI-1, IRF, E2F, AP-1, HIF-1 and NF-Y were identified. Moreover, GC-rich motifs (SP1, EGR, ZF5, AP-2, WT1, NRF-1 and AT-rich motifs (MEF-2, HMGIY, HNF-1, OCT-1 are significantly overrepresented in promoter regions of CCGs. Putative tissue-specific binding sites such as HNF-3 for liver, NKX2.5 for heart or Myogenin for skeletal muscle were found. The regulation of the erythropoietin (Epo gene was analysed, which exhibits many binding sites for circadian regulators. We provide experimental evidence for its circadian regulated expression in the adult murine kidney. Basing on a comprehensive literature search we integrate our predictions into a regulatory network of core clock and clock-controlled genes. Our large scale analysis of the CCG promoters reveals the complexity and extensiveness of the circadian regulation in mammals. Results of this study point to connections of the circadian clock to other functional systems including

  17. Design and Construction of an Atomic Clock on an Atom Chip

    International Nuclear Information System (INIS)

    We describe the design and construction of an atomic clock on an atom chip, intended as a secondary standard, with a stability in the range of few 10-13 at 1 s. This clock is based on a two-photon transition between the hyperfine states |F = 1; mF = -1> and |2; 1> of the electronic ground state of the 87Rb atom. This transition is interrogated using a Ramsey scheme, operating on either a cloud of thermal atoms or a Bose-Einstein condensate. In contrast to atomic fountain clocks, this clock is magnetically trapped on an atom chip. We describe a theoretical model of the clock stability and the design and construction of a dedicated apparatus. It is able to control the magnetic field at the relative 10-5 level and features a hybrid atom chip, containing DC conductors as well as a microwave transmission line for the clock interrogation. (author)

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. A New Method to Minimize the Clock Skew to Enhance Performance of Digital System

    OpenAIRE

    N. Suresh Kumar,; J. Anitha; M.S.S. Praveen,; N. Asok Kumar,; R. Ajay Suresh Babu

    2010-01-01

    A Pipe line technology is used in any digital system to perform multiple tasks simultaneously and to reduce the data losses in data transactions. But the conventional pipeline system is facing problems due to improper synchronization of clock pulses. This is a universal problem in all the digital systems mostly called jitter or skew. Inmost of the digital systems the propagation of information mainly controlled on the basis of clock pulses. In most of the digital systems the clock skew decrea...

  4. 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.

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

    OpenAIRE

    Z. Yao; Shafer, O.T.

    2014-01-01

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

  6. 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.

  7. Strontium optical lattice clocks for practical realization of the metre and secondary representation of the second

    CERN Document Server

    Bober, M; Cygan, A; Lisak, D; Masłowski, P; Prymaczek, M; Wcisło, P; Ablewski, P; Piwiński, M; Wójtewicz, S; Bielska, K; Bartoszek-Bober, D; Trawiński, R; Zawada, M; Ciuryło, R; Zachorowski, J; Piotrowski, M; Gawlik, W; Ozimek, F; Radzewicz, C

    2015-01-01

    We present a system of two independent strontium optical lattice standards probed with a single shared ultra-narrow laser. The absolute frequency of the clocks can be verified by the use of Er:fiber optical frequency comb with the GPS-disciplined Rb frequency standard. We report hertz-level spectroscopy of the clock line and measurements of frequency stability of the two strontium optical lattice clocks.

  8. 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.

  9. Frequency ratios of optical lattice clocks at the 17th decimal place

    Science.gov (United States)

    Katori, Hidetoshi

    2016-05-01

    Optical lattice clocks benefit from a low quantum-projection noise by simultaneously interrogating a large number of atoms, which are trapped in an optical lattice tuned to the ``magic wavelength'' to largely cancel out light shift perturbation in the clock transition. About a thousand atoms enable the clocks to achieve 10-18 instability in a few hours of operation, allowing intensive investigation and control of systematic uncertainties. As optical lattice clocks have reached inaccuracies approaching 10-18, it is now the uncertainty of the SI second (~ 10-16) itself that restricts the measurement of the absolute frequencies of such optical clocks. Direct comparisons of optical clocks are, therefore, the only way to investigate and utilize their superb performance beyond the SI second. In this presentation, we report on frequency comparisons of optical lattice clocks with neutral strontium (87 Sr), ytterbium (171 Yb) and mercury (199 Hg) atoms. By referencing cryogenic Sr clocks, we determine frequency ratios, νYb/νSr and νHg/νSr, of a cryogenic Yb clock and a Hg clock with uncertainty at the mid 10-17 level. Such ratios provide an access to search for temporal variation of the fundamental constants. We also present remote comparisons between cryogenic Sr clocks located at RIKEN and the University of Tokyo over a 30-km-long phase-stabilized fiber link. The gravitational red shift Δν /ν0 ~ 1.1× 10-18 Δh cm-1 reads out the height difference of Δh ~ 15 m between the two clocks with uncertainty of 5 cm, which demonstrates a step towards relativistic geodesy. ERATO, JST.

  10. Biological Threats

    Science.gov (United States)

    ... Workplace Plans School Emergency Plans Main Content Biological Threats Biological agents are organisms or toxins that can ... for Disease Control and Prevention . Before a Biological Threat Unlike an explosion, a biological attack may or ...

  11. New experiments on the effect of clock shifts on homing in pigeons

    Science.gov (United States)

    Schmidt-Koenig, K.

    1972-01-01

    The effect of clock shifts as an experimental tool for predictably interfering with the homing ability of birds is discussed. Clock shifts introduce specific errors in the birds' sun azimuth compass, resulting in corresponding errors during initial orientation and possibly during orientation enroute. The effects of 6 hour and 12 hour clock shifts resulted in a 90 degree deviation and a 180 degree deviation from the initial orientation, respectively. The method for conducting the clock shift experiments and results obtained from previous experiments are described.

  12. The clock modules in TOF readout system for heavy ion experiments at IMP

    International Nuclear Information System (INIS)

    This paper describes two clock modules in the time-of-flight readout systems, which are applied in the Cold Target Recoil Ion Momentum Spectrometer(COLTRIMS) system and the Cooler Storage Ring (CSRm) at Institute of Modern Physics, Chinese Academy of Sciences.The two clock modules are designed on 3U PXI module and 6U PXI module. With high precision crystal oscillators and clock distribution, these two modules offer clock signal to the TOF readout electronics modules with low jitter less than 11 ps(RMS) and 12 ps(RMS). (authors)

  13. 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.

  14. 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.

  15. Collisional Losses, Decoherence, and Frequency Shifts in Optical Lattice Clocks with Bosons

    International Nuclear Information System (INIS)

    We have quantified collisional losses, decoherence and the collision shift in a one-dimensional optical lattice clock on the highly forbidden transition 1S0-3P0 at 698 nm with bosonic 88Sr. We were able to distinguish two loss channels: inelastic collisions between atoms in the upper and lower clock state and atoms in the upper clock state only. Based on the measured coefficients, we determine the operation parameters at which a 1D-lattice clock with 88Sr shows no degradation due to collisions on the fractional uncertainty level of 10-16.

  16. Time maintenance of user clocks via the tracking and data relay satellite system

    Science.gov (United States)

    Whitworth, G.; Mcintyre, J. W.; Downs, R. E.

    1983-01-01

    A system is described which uses the Tracking and Data Relay Satellite System (TDRSS) itself to compare the user satellite clock with a clock at the White Sands station that is referenced to Universal Time Coordinated (UTC). No command of the spacecraft by the system is required, and actual on-board clock corrections are made by the spacecraft control center at its discretion. Computer models were constructed using basic orbital parameters for user and TDRS satellites. With only first-order corrections and simple averaging techniques for constant clock rates, error measurement precision of better than one microsecond was obtained. More sophisticated computations should allow considerable improvement over this.

  17. 0.75 atoms improve the clock signal of 10,000 atoms

    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 10,000 atoms by 2.05 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 based...

  18. 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.

  19. 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.

  20. The Transcriptional Repressor ID2 Can Interact with the Canonical Clock Components CLOCK and BMAL1 and Mediate Inhibitory Effects on mPer1 Expression*

    OpenAIRE

    Ward, Sarah M.; Fernando, Shanik J.; Hou, Tim Y.; Duffield, Giles E.

    2010-01-01

    ID2 is a rhythmically expressed HLH transcriptional repressor. Deletion of Id2 in mice results in circadian phenotypes, highlighted by disrupted locomotor activity rhythms and an enhanced photoentrainment response. ID2 can suppress the transactivation potential of the positive elements of the clock, CLOCK-BMAL1, on mPer1 and clock-controlled gene (CCG) activity. Misregulation of CCGs is observed in Id2−/− liver, and mutant mice exhibit associated alterations in lipid homeostasis. These data s...

  1. 2.5 Gbps clock data recovery using 1/4th-rate quadricorrelator frequency detector and skew-calibrated multi-phase clock generator

    OpenAIRE

    S. Tontisirin; R. Tielert

    2006-01-01

    A Gb/s clock and data recovery (CDR) circuit using 1/4th-rate digital quadricorrelator frequency detector and skew-calibrated multi-phase voltage-controlled oscillator is presented. With 1/4th-rate clock architecture, the coil-free oscillator can have lower operation frequency providing sufficient low-jitter operation. Moreover, it is an inherent 1-to-4 DEMUX. The skew calibration scheme is applied to reduce phase offset in multi-phase clock generator. The CDR with frequency detector can have...

  2. Laser Cooling of Lanthanides: from Optical Clocks to Quantum Simulators

    Directory of Open Access Journals (Sweden)

    Golovizin A.

    2015-01-01

    Full Text Available We discuss current progress in laser cooling of lanthanides (Er, Yb, Dy, Tm etc. focusing on applications. We describe some important peculiarities taking Thulium atom as an example: Two stage laser cooling, trapping in an optical lattice, anisotropic interactions and spectroscopy of narrow transitions. Specific level structure and presence of magic wavelengths make ultracold Thulium a favorable candidate for optical clock applications. On the other hand, abundance of Feshbach resonances allow to tune interactions in ultracold gases and thus reach quantum degeneracy. It opens intriguing perspectives for novel quantum simulators employing dipole-dipole interactions in an optical lattice.

  3. Prospect for a compact strontium optical lattice clock

    OpenAIRE

    Poli, N.; Drullinger, R. E.; Ferrari, G; Prevedelli, M.; M. G. Tarallo; Tino, G. M.

    2007-01-01

    We report on our progress toward the realization of a compact optical frequency standard referenced to strontium intercombination lines. Our current setup allows the production of ultracold Sr atoms in hundreds of ms. For high resolution spectroscopy of the 1S0-3P0 doubly forbidden transition we have prepared a 698 nm clock laser stabilized on a high finesse, symmetrically suspended cavity and a high power 813 nm light source for the optical lattice trap at the magic wavelength. Due to their ...

  4. Strontium optical lattice clock with all semiconductor sources

    OpenAIRE

    Poli, N.; Drullinger, R. E.; M. G. Tarallo; Tino, G. M.

    2007-01-01

    We report on our progress toward the realization of an optical frequency standard referenced to strontium intercombination lines. Our current setup allows the production of ultracold Sr atoms in hundreds of ms. For high resolution spectroscopy of 1S0-3P0 doubly forbidden transition we have also prepared a 698 nm clock laser stabilized on high finesse symmetrically suspended cavity and a high power 813 nm light source for the optical lattice trap at the magic wavelength. All the laser source e...

  5. 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.

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

    OpenAIRE

    Anafi, Ron C.; Yool Lee; Sato, Trey K.; Anand Venkataraman; Chidambaram Ramanathan; Ibrahim H Kavakli; Hughes, Michael E.; Baggs, Julie E.; Jacqueline Growe; Liu, Andrew C.; Junhyong Kim; Hogenesch, John B.

    2014-01-01

    Machine Learning Helps Identify CHRONO as a Circadian Clock Component Ron C. Anafi1,2.*, Yool Lee3., Trey K. Sato3., Anand Venkataraman3, Chidambaram Ramanathan4, Ibrahim H. Kavakli5, Michael E. Hughes6, Julie E. Baggs7, Jacqueline Growe1,2, Andrew C. Liu4, Junhyong Kim8, John B. Hogenesch2,3* 1 Division of Sleep Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Center for Sleep and Circadian Neurobiology, Univer...

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    James J Hodge

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

  9. CLOCK promotes 3T3-L1 cell proliferation via Wnt signaling.

    Science.gov (United States)

    Zhu, Zhu; Hua, Bingxuan; Xu, Lirong; Yuan, Gongsheng; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Lu, Chao; Qian, Ruizhe

    2016-07-01

    Circadian genes control most of the physiological functions including cell cycle. Cell proliferation is a critical factor in the differentiation of progenitor cells. However, the role of Clock gene in the regulation of cell cycle via wingless-type (Wnt) pathway and the relationship between Clock and adipogenesis are unclear. We found that the circadian locomotor output cycles kaput (Clock) regulated the proliferation and the adipogenesis of 3T3-L1 preadipocytes. We found that Clock attenuation inhibited the viability of 3T3-L1 preadipocytes in the cell counting kit 8. The expression of c-Myc and Cyclin D1 decreased dramatically in 3T3-L1 when Clock was silenced with short interfering RNA and was also decreased in fat tissue and adipose tissue-derived stem cells of Clock(Δ19) mice. Clock directly controls the expression of the components of Wnt signal transduction pathway, which was verified by serum shock, chromatin immunoprecipitation, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, IWR-1, a Wnt signal pathway inhibitor, inhibited the cell cycle promotion by CLOCK, which was detected by cell viability assay, flow cytometry, and qRT-PCR. Therefore, CLOCK transcription control of Wnt signaling promotes cell cycle progression in 3T3-L1 preadipocytes. Clock inhibited the adipogenesis on day 2 in 3T3-L1 cells via Oil Red O staining and qRT-PCR detection and probably related to cellular differentiation. These data provide evidence that the circadian gene Clock regulates the proliferation of preadipocytes and affects adipogenesis. © 2016 IUBMB Life, 68(7):557-568, 2016. PMID:27194636

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

    Directory of Open Access Journals (Sweden)

    Carlo C Lazado

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

  11. Stability of a trapped atom clock on a chip

    CERN Document Server

    Szmuk, Ramon; Maineult, Wilfried; Reichel, Jakob; Rosenbusch, Peter

    2015-01-01

    We present a compact atomic clock interrogating ultracold 87Rb magnetically trapped on an atom chip. Very long coherence times sustained by spin self-rephasing allow us to interrogate the atomic transition with 85% contrast at 5 s Ramsey time. The clock exhibits a fractional frequency stability of $5.8\\times 10^{-13}$ at 1 s and is likely to integrate into the $1\\times10^{-15}$ range in less than a day. A detailed analysis of 7 noise sources explains the measured frequency stability. Fluctuations in the atom temperature (0.4 nK shot-to-shot) and in the offset magnetic field ($5\\times10^{-6}$ relative fluctuations shot-to-shot) are the main noise sources together with the local oscillator, which is degraded by the 30% duty cycle. The analysis suggests technical improvements to be implemented in a future second generation set-up. The results demonstrate the remarkable degree of technical control that can be reached in an atom chip experiment.

  12. Toward a detailed computational model for the mammalian circadian clock

    Science.gov (United States)

    Leloup, Jean-Christophe; Goldbeter, Albert

    2003-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Alun R Barnard

    2008-05-01

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

  14. Microwave interrogation cavity for the rubidium space cold atom clock

    Science.gov (United States)

    Wei, Ren; Yuan-Ci, Gao; Tang, Li; De-Sheng, Lü; Liang, Liu

    2016-06-01

    The performance of space cold atom clocks (SCACs) should be improved thanks to the microgravity environment in space. The microwave interrogation cavity is a key element in a SCAC. In this paper, we develop a microwave interrogation cavity especially for the rubidium SCAC. The interrogation cavity has two microwave interaction zones with a single feed-in source, which is located at the center of the cavity for symmetric coupling excitation and to ensure that the two interaction zones are in phase. The interrogation cavity has a measured resonance frequency of 6.835056471 GHz with a loaded quality factor of nearly 4200, which shows good agreement with simulation results. We measure the Rabi frequency of the clock transition of the rubidium atom in each microwave interaction zone, and subsequently demonstrate that the distributions of the magnetic field in the two interaction zones are the same and meet all requirements of the rubidium SCAC. Project supported by the National Natural Science Foundation of China (Grant No. 11034008), the Fund from the Ministry of Science and Technology of China (Grant No. 2013YQ09094304), and the Youth Innovation Promotion Association, Chinese Academy of Sciences.

  15. Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila

    Directory of Open Access Journals (Sweden)

    Simonetta Andreazza

    2015-05-01

    Full Text Available In the Drosophila circadian oscillator, the CLOCK/CYCLE complex activates transcription of period (per and timeless (tim in the evening. PER and TIM proteins then repress CLOCK (CLK activity during the night. The pace of the oscillator depends upon post-translational regulation that affects both positive and negative components of the transcriptional loop. CLK protein is highly phosphorylated and inactive in the morning, whereas hypophosphorylated active forms are present in the evening. How this critical dephosphorylation step is mediated is unclear. We show here that two components of the STRIPAK complex, the CKA regulatory subunit of the PP2A phosphatase and its interacting protein STRIP, promote CLK dephosphorylation during the daytime. In contrast, the WDB regulatory PP2A subunit stabilizes CLK without affecting its phosphorylation state. Inhibition of the PP2A catalytic subunit and CKA downregulation affect daytime CLK similarly, suggesting that STRIPAK complexes are the main PP2A players in producing transcriptionally active hypophosphorylated CLK.

  16. Synthetic Frequency Protocol in the Ramsey Spectroscopy of Clock Transitions

    CERN Document Server

    Yudin, V I; Basalaev, M Yu

    2016-01-01

    We develop an universal method to significantly suppress probe-induced shifts in any types of atomic clocks using the Ramsey spectroscopy. Our approach is based on adaptation of the synthetic frequency concept [V. I. Yudin, et al., Phys. Rev. Lett. 107, 030801 (2011)] (previously developed for BBR shift suppression) to the Ramsey spectroscopy with the use of interrogations for different dark time intervals. Universality of the method consists in arbitrariness of the possible Ramsey schemes. However, most extremal results are obtained in combination with so-called hyper-Ramsey spectroscopy [V. I. Yudin, et al., Phys. Rev. A 82, 011804(R) (2010)]. In the latter case, the probe-induced frequency shifts can be suppressed considerably below a fractional level of 10$^{-18}$ practically for any optical atomic clocks, where this shift previously was metrologically significant. The main advantage of our method in comparison with other radical hyper-Ramsey approaches [R. Hobson, et al., Phys. Rev. A 93, 010501(R) (2016...

  17. Compact Microwave Mercury Ion Clock for Deep-Space Applications

    Science.gov (United States)

    Prestage, John D.; Chung, Sang K.; Lim, Lawrence; Matevosian, Annond

    2007-01-01

    We have recently completed a breadboard ion-dock physics package based on Kg ions shuttled between a quadrupole and a 16-pole rf trap. With this architecture we have demonstrated short-term stability -1-2xl0-13 at 1 second, averaging to 10-15 at 1 day. This development shows that 8- maser quality stabilities can be produced in a small clock package, comparable in size to an oItra-stable quartz oscillator required for holding 1-2xl0-13 at 1 second. This performance was obtained in a sealed vacuum configuration where only agetter pump was used to maintain vacuum. The vacuum tube containing the traps has now been onder sealed vacuum conditions for nearly two years with no measurable degradation of ion trapping lifetimes or clock short-term performance. We have fabricated the vacuum tube, ion trap and UV windows from materials that will allow a - 400 C tube bake-out to prepare for tube sealoff. This approach to the vacuum follows the methods used in mght vacuum tube electronics, such as flight TWTA's where tube operation lifetime and shelf life of up to 15 years is achieved. We use neon as a buffer gas with 2-3 times less pressure induced frequency pulling than helium and, being heavier, negligable diffusion losses will occur over the operation lifetime.

  18. 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.

  19. Al+ Optical Clocks for Fundamental Physics and Geodesy

    Energy Technology Data Exchange (ETDEWEB)

    Chou, James Chin-wen (Ion Storage Group, NIST)

    2011-07-13

    Laser-cooled trapped atoms have long been recognized as potentially very accurate frequency standards for clocks. Ultimate accuracies of 10-18 to 10-19 appear possible, limited by the time-dilation of trapped ions that move at laser-cooled velocities. The Al+ ion is an attractive candidate for high accuracy, owing to its narrow electronic transition in the optical regime and low sensitivity to ambient field perturbations. Precision spectroscopy on Al+ is enabled by quantum information techniques. With Al+ “quantum-logic” clocks, the current accuracy of 8.6×10-18 has enabled a geo-potential-difference measurement that detected a height change of 37±17 cm due to the gravitational red-shift. We have also observed quantum coherence between two Al+ ions with a record Q-factor of 3.4×1016, and compared the Al+ resonance frequency to that of a single Hg+ ion to place limits on the temporal variation of the fine-structure constant.

  20. 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...

  1. 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...

  2. 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...

  3. 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.

  4. Effects of temperature on circadian clock and chronotype: an experimental study in a passerine bird

    NARCIS (Netherlands)

    Lehmann, M.; Spoelstra, K.; Visser, M.E.; Helm, B.

    2012-01-01

    Daily schedules of many organisms, including birds, are thought to affect fitness. Timing in birds is based on circadian clocks that have a heritable period length, but fitness consequences for individuals in natural environments depend on the scheduling of entrained clocks. This chronotype, i.e., t

  5. Effects of Temperature on Circadian Clock and Chronotype : An Experimental Study on a Passerine Bird

    NARCIS (Netherlands)

    Lehmann, Marina; Spoelstra, Kamiel; Visser, Marcel E.; Helm, Barbara

    2012-01-01

    Daily schedules of many organisms, including birds, are thought to affect fitness. Timing in birds is based on circadian clocks that have a heritable period length, but fitness consequences for individuals in natural environments depend on the scheduling of entrained clocks. This chronotype, i.e., t

  6. 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...

  7. Temporal dynamics of mouse hippocampal clock gene expression support memory processing.

    Science.gov (United States)

    Jilg, Antje; Lesny, Sandra; Peruzki, Natalie; Schwegler, Herbert; Selbach, Oliver; Dehghani, Faramarz; Stehle, Jörg H

    2010-03-01

    Hippocampal plasticity and mnemonic processing exhibit a striking time-of-day dependence and likely implicate a temporally structured replay of memory traces. Molecular mechanisms fulfilling the requirements of sensing time and capturing time-related information are coded in dynamics of so-called clock genes and their protein products, first discovered and described in the hypothalamic suprachiasmatic nucleus. Using real-time PCR and immunohistochemical analyses, we show that in wildtype mice core clock components (mPer1/PER1, mPer2/PER2, mCry1/CRY1, mCry2/CRY2, mClock/CLOCK, mBmal1/BMAL1) are expressed in neurons of all subregions of the hippocampus in a time-locked fashion over a 24-h (diurnal) day/night cycle. Temporal profiling of these transcriptional regulators reveals distinct and parallel peaks, at times when memory traces are usually formed and/or consolidated. The coordinated rhythmic expression of hippocampal clock gene expression is greatly disordered in mice deficient for the clock gene mPer1, a key player implicated in both, maintenance and adaptative plasticity of circadian clocks. Moreover, Per1-knockout animals are severely handicapped in a hippocampus-dependent long-term spatial learning paradigm. We propose that the dynamics of hippocampal clock gene expression imprint a temporal structure on memory processing and shape at the same time the efficacy of behavioral learning. PMID:19437502

  8. 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 investigates...

  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. Method and apparatus to debug an integrated circuit chip via synchronous clock stop and scan

    Science.gov (United States)

    Bellofatto, Ralph E.; Ellavsky, Matthew R.; Gara, Alan G.; Giampapa, Mark E.; Gooding, Thomas M.; Haring, Rudolf A.; Hehenberger, Lance G.; Ohmacht, Martin

    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.

  11. 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.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    , recent studies have shown the presence of extrahypothalamic oscillators in other areas of the brain including the cerebellum. In the present study, the authors unravel the cerebellar molecular clock by analyzing clock gene expression in the cerebellum of the rat by use of radiochemical in situ...

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

    Science.gov (United States)

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

    2012-12-01

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

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

    Science.gov (United States)

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

  15. 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

  16. 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.

  17. Influence Factors of an All-Optical Recovered Clock from Two-Section DFB Lasers

    Institute of Scientific and Technical Information of China (English)

    KONG Duan-Hua; ZHU Hong-Liang; LIANG Song; WANG Bao-Jun; BIAN Jing; MA Li; YU Wen-Ke; LOU Cai-Yun

    2011-01-01

    @@ All-optical clock recovery by a two-section DFB laser with different injection wavelengths is demonstrated exper-imentally at 38.5GHz.An optical clock with a root-mean-square timing jitter of 250fs and an extinction ratio of 12.1 dB is obtained with 1551 run injection.The timing jitter of the recovered clock is further investigated for various intensity ratios of the two DFB emission modes.%All-optical clock recovery by a Iwu-wcliuii DFIS laser v, Uh different ijijcciiuii wavnk'U^lhs is dt-iwm^.ttnind experimentally af 3H.5GBz. An optical clock with a root-mean-square timing jitter of 2.50& and an extinction ratio of !2.idB is obtained with 1551 nm injection. The timing jitter of the recovered duck is Further invesUgui id fo: various intensity ratios of [Jit two DFB emission modes.

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

    Science.gov (United States)

    Chen, Wantong

    2016-09-01

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

  19. A New Generation of Atomic Clocks: Accuracy and Stability at the 10^{-18} Level

    CERN Document Server

    Bloom, B J; Williams, J R; Campbell, S L; Bishof, M; Zhang, X; Zhang, W; Bromley, S L; Ye, J

    2013-01-01

    The exquisite control exhibited over quantum states of individual particles has revolutionized the field of precision measurement, as exemplified by the most accurate atomic clock realized in single trapped ions. Whereas many-atom lattice clocks have shown advantages in measurement precision over trapped-ion clocks, their accuracy has remained 20 times worse. Here we demonstrate, for the first time, that a many-atom system achieves accuracy (6x10^{-18}) better than a single ion-based clock, with vastly reduced averaging times (3000 s). This is the first time a single clock has achieved the best performance in all three key ingredients necessary for consideration as a primary standard - stability, reproducibility, and accuracy. This work paves the way for future experiments to integrate many-body quantum state engineering into the frontiers of quantum metrology, creating exciting opportunities to advance precision beyond the standard quantum limit. Improved frequency standards will have impact to a wide range ...

  20. Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila.

    Science.gov (United States)

    Katewa, Subhash D; Akagi, Kazutaka; Bose, Neelanjan; Rakshit, Kuntol; Camarella, Timothy; Zheng, Xiangzhong; Hall, David; Davis, Sonnet; Nelson, Christopher S; Brem, Rachel B; Ramanathan, Arvind; Sehgal, Amita; Giebultowicz, Jadwiga M; Kapahi, Pankaj

    2016-01-12

    Endogenous circadian clocks orchestrate several metabolic and signaling pathways that are known to modulate lifespan, suggesting clocks as potential targets for manipulation of metabolism and lifespan. We report here that the core circadian clock genes, timeless (tim) and period (per), are required for the metabolic and lifespan responses to DR in Drosophila. Consistent with the involvement of a circadian mechanism, DR enhances the amplitude of cycling of most circadian clock genes, including tim, in peripheral tissues. Mass-spectrometry-based lipidomic analysis suggests a role of tim in cycling of specific medium chain triglycerides under DR. Furthermore, overexpression of tim in peripheral tissues improves its oscillatory amplitude and extends lifespan under ad libitum conditions. Importantly, effects of tim on lifespan appear to be mediated through enhanced fat turnover. These findings identify a critical role for specific clock genes in modulating the effects of nutrient manipulation on fat metabolism and aging. PMID:26626459

  1. Time and Frequency Injection into a Stabilized Fiber Link for Multi-clock Dissemination Network

    CERN Document Server

    Chen, Wei; Liu, Qin; Cheng, Nan; Feng, Zitong; Yang, Fei; Gui, Youzhen; Cai, Haiwen

    2016-01-01

    Owing to the characteristics of ultra-low loss and anti-electromagnetic interference, using optical fiber to deliver time and frequency signal has been a preferred choice for high precise clock dissemination and comparison. As a brilliant idea, one has been able to reproduce ultra-stable signals from one local station to multiple users. In this paper, we take a step further. A concept of multi-clock (in different locations) dissemination for multi-terminals is presented. By injecting frequency signals into one stabilized ring-like fiber network, the relative stabilities of 3.4e-14@1s for a master clock dissemination and 5.1e-14@1s for a slave clock dissemination have been achieved. The proposed scheme can greatly simplify the future 'N' to 'N' time and frequency dissemination network, especially facing a multi-clock comparison situation.

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

    Science.gov (United States)

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

    2015-08-13

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

  3. High accuracy measure of atomic polarizability in an optical lattice clock

    CERN Document Server

    Sherman, J A; 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 (such as blackbody radiation) as the differential static polarizability of the ground and excited clock levels: 36.2612(7) kHz (kV/cm)^{-2}. The clock's fractional uncertainty due to room temperature blackbody radiation is reduced an order of magnitude to 3 \\times 10^{-17}.

  4. Estrogen-related receptor α, the molecular clock, and transcriptional control of metabolic outputs.

    Science.gov (United States)

    Giguère, V; Dufour, C R; Eichner, L J; Deblois, G; Cermakian, N

    2011-01-01

    Metabolism and circadian rhythms must be closely integrated to support the energetic needs of the organism linked to the daily timing of physiological and behavioral processes. Although components of the molecular clock can directly target some metabolic genes, the control of metabolic clock output is believed to be mediated mostly through the action of transcription factors whose patterns of expression are rhythmic in metabolic tissues. Our recent work has identified the orphan nuclear receptor estrogen-related receptor α (ERRα), a potent effector of metabolic gene networks, as a direct regulator of the molecular clock. Thus, by acting both upstream of and downstream from the molecular clock, ERRα serves as a key transcription factor linking the clock with metabolic control.

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

    Directory of Open Access Journals (Sweden)

    Jonathan A Hardman

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mitsunori Miyazaki

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

  8. Freezing the biological clock: a viable fertility preservation option for young Singapore women?

    Science.gov (United States)

    Blyth, Eric; Yee, Samantha; Lee, Geok Ling

    2013-09-01

    In March 2012, an article in The Straits Times entitled 'Freezing eggs could reverse falling birth rate' suggested that employing the latest oocyte cryopreservation techniques could both foster individual women's reproductive autonomy and impact Singapore's fertility rate, which in recent years has consistently been among the world's lowest. The article cited both local and international fertility specialists' approval of elective oocyte cryopreservation for young women wishing to protect their reproductive potential against ageing and as a potential antidote to the contemporary 'delay and defer' model of family-building. Later in 2012, the Ministry of Health announced a review of oocyte cryopreservation policy taking into account related medical, scientific and ethical issues, while the Singapore College of Obstetricians and Gynaecologists endorsed oocyte cryopreservation as an "important, safe and efficient technology". This paper outlines and analyses the arguments and empirical evidence used both to support and oppose offering elective oocyte cryopreservation as a routine fertility service, before concluding that this remains unjustifiable on the basis of insufficient evidence of its clinical efficacy and safety as regards either pregnancy rates or birth outcomes. If it is to be made available at all for these reasons in Singapore, it should be subjected to rigorous clinic-specific evaluation in accordance with accepted clinical and ethical norms.

  9. The biological clock keeps ticking, but exercise may turn it back

    Directory of Open Access Journals (Sweden)

    Andrea Deslandes

    2013-02-01

    Full Text Available Aging is an inevitable process that is associated to loss of functional capacities in several body systems, like the cardiovascular, the skeletal muscle mass, the osteoarticular and the neuro-immune-endocrine systems. Changes appear due to interactions between genetic factors and way of life, such as diet and sedentary life style. This review shows evidence from the past twenty years concerning the importance of physical exercise to reduce the deleterious effects of aging, regarding the improvement in functional performance, the prevention of diseases and increased longevity. Moreover, physical exercise improves the cognitive function and the mood. Aerobic and strength training collaborate with the prevention and treatment of mental diseases, which are mostly prevalent in older adults, like major depression, dementia and Parkinson’s disease. Several mechanisms of neurobiological action are proposed to explain how exercise can actually reduce the effects of aging.

  10. The Circadian Clock Gene Period1 Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus.

    Science.gov (United States)

    Kudo, Takashi; Block, Gene D; Colwell, Christopher S

    2015-01-01

    The neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and yet the mechanisms by which the molecular clockwork drives changes in the membrane are not well understood. In this study, we sought to examine how the clock gene Period1 (Per1) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca(2+)]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium currents were altered by the treatment. These recordings revealed that the large conductance [Ca(2+)]i-activated potassium currents were reduced in antisense-treated neurons and that blocking this current mimicked the effects of the anti-sense on SCN firing rate. These results indicate that the circadian clock gene Per1 alters firing rate in SCN neurons and raise the possibility that the large conductance [Ca(2+)]i-activated channel is one of the targets.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Circadian oscillations of KaiA-KaiC and KaiB-KaiC complex formations in an in vitro reconstituted KaiABC clock oscillator.

    Science.gov (United States)

    Murakami, Reiko; Mutoh, Risa; Ishii, Ketaro; Ishiura, Masahiro

    2016-08-01

    The circadian clock is an endogenous biological mechanism that generates autonomous daily cycles in physiological activities. The phosphorylation levels of KaiC oscillated with a period of 24 h in an ATP-dependent clock oscillator reconstituted in vitro from KaiA, KaiB and KaiC. We examined the complex formations of KaiA and KaiB with KaiC in the KaiABC clock oscillator by fluorescence correlation spectrometry (FCS) analysis. The formation of KaiB-containing protein complex(es) oscillated in a circadian manner, with a single peak at 12 h and single trough at 24 h in the circadian cycle, whereas that of KaiA-containing protein complex(es) oscillated with two peaks at 12 and 24 h. FCS and surface plasmon resonance analyses showed that the binding affinity of KaiA for a mutant KaiC with Ala substitutions at the two phosphorylation sites considered to mimic the nonphosphorylated form of KaiC (np-KaiC) was higher than that for a mutant KaiC with Asp substitutions at the two phosphorylation sites considered to mimic the completely phosphorylated form of KaiC (cp-KaiC). The results from the study suggest that a KaiA-KaiB-cp-KaiC ternary complex and a KaiA-np-KaiC complex were formed at 12 and 24 h, respectively.

  13. A survey of genomic studies supports association of circadian clock genes with bipolar disorder spectrum illnesses and lithium response.

    Directory of Open Access Journals (Sweden)

    Michael J McCarthy

    Full Text Available Circadian rhythm abnormalities in bipolar disorder (BD have led to a search for genetic abnormalities in circadian "clock genes" associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies (GWAS. At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at three levels: essential "core" clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD (major depression, schizophrenia, attention deficit/hyperactivity. Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies.

  14. Modeling of regulatory networks: theory and applications in the study of the Drosophila circadian clock.

    Science.gov (United States)

    Scribner, Elizabeth Y; Fathallah-Shaykh, Hassan M

    2011-01-01

    Biological networks can be very complex. Mathematical modeling and simulation of regulatory networks can assist in resolving unanswered questions about these complex systems, which are often impossible to explore experimentally. The network regulating the Drosophila circadian clock is particularly amenable to such modeling given its complexity and what we call the clockwork orange (CWO) anomaly. CWO is a protein whose function in the network as an indirect activator of genes per, tim, vri, and pdp1 is counterintuitive--in isolated experiments, CWO inhibits transcription of these genes. Although many different types of modeling frameworks have recently been applied to the Drosophila circadian network, this chapter focuses on the application of continuous deterministic dynamic modeling to this network. In particular, we present three unique systems of ordinary differential equations that have been used to successfully model different aspects of the circadian network. The last model incorporates the newly identified protein CWO, and we explain how this model's unique mathematical equations can be used to explore and resolve the CWO anomaly. Finally, analysis of these equations gives rise to a new network regulatory rule, which clarifies the unusual role of CWO in this dynamical system.

  15. Relaxing the Molecular Clock to Different Degrees for Different Substitution Types.

    Science.gov (United States)

    Lee, Hui-Jie; Rodrigue, Nicolas; Thorne, Jeffrey L

    2015-08-01

    Rates of molecular evolution can vary over time. Diverse statistical techniques for divergence time estimation have been developed to accommodate this variation. These typically require that all sequence (or codon) positions at a locus change independently of one another. They also generally assume that the rates of different types of nucleotide substitutions vary across a phylogeny in the same way. This permits divergence time estimation procedures to employ an instantaneous rate matrix with relative rates that do not differ among branches. However, previous studies have suggested that some substitution types (e.g., CpG to TpG changes in mammals) are more clock-like than others. As has been previously noted, this is biologically plausible given the mutational mechanism of CpG to TpG changes. Through stochastic mapping of sequence histories from context-independent substitution models, our approach allows for context-dependent nucleotide substitutions to change their relative rates over time. We apply our approach to the analysis of a 0.15 Mb intergenic region from eight primates. In accord with previous findings, we find comparatively little rate variation over time for CpG to TpG substitutions but we find more for other substitution types. We conclude by discussing the limitations and prospects of our approach.

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

    Indian Academy of Sciences (India)

    Yuuichi Seki; Teiichi Tanimura

    2014-09-01

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

  17. Low Power Reduced Instruction Set Architecture Using Clock Gating Technique

    Directory of Open Access Journals (Sweden)

    M.Kamaraju

    2013-10-01

    Full Text Available Today, all the portable device’s in electronics nee ds to be realized with low power architectures beca use of power consumption is a main consideration along wit h other performance parameters. Low power consumption helps to reduce heat dissipation, incre ases battery life and also reliability. In this pap er a 16- bit Reduced Instruction set Architecture (RISA pre sented. This architecture can handle multiple inter rupts and performing serial communication effectively. It can supported RISC (Reduced Instruction Set Computer concepts. A popular technique of Clock ga ting is applied to the proposed architecture and th en reduces the power. This entire architecture capture d using VerilogHDL and implemented on FPGA using Xilinx tools .

  18. A low jitter PLL clock used for phase change memory

    Institute of Scientific and Technical Information of China (English)

    Hong Xiao; Chen Houpeng; Song Zhitang; Cai Daolin; Li Xi

    2013-01-01

    A fully integrated low-jitter,precise frequency CMOS phase-locked loop (PLL) clock for the phase change memory (PCM) drive circuit is presented.The design consists of a dynamic dual-reset phase frequency detector (PFD) with high frequency acquisition,a novel low jitter charge pump,a CMOS ring oscillator based voltage-controlled oscillator (VCO),a 2nd order passive loop filter,and a digital frequency divider.The design is fabricated in 0.35μm CMOS technology and consumes 20 mW from a supply voltage of 5 V.In terms of the PCM's program operation requirement,the output frequency range is from 1 to 140 MHz.For the 140 MHz output frequency,the circuit features a cycle-to-cycle jitter of 28 ps RMS and 250 ps peak-to-peak.

  19. Resolved atomic interaction sidebands in an optical clock transition

    CERN Document Server

    Bishof, Michael; Swallows, Matthew D; Gorshkov, Alexey V; Ye, Jun; Rey, Ana Maria

    2011-01-01

    We report the observation of resolved atomic interaction sidebands (ISB) in the ${}^{87}$Sr optical clock transition when atoms at microkelvin temperatures are confined in a two-dimensional (2D) optical lattice. The ISB are a manifestation of the strong interactions that occur between atoms confined in a quasi-one-dimensional geometry and disappear when the confinement is relaxed along one dimension. The emergence of ISB is linked to the recently observed suppression of collisional frequency shifts in [1]. At the current temperatures, the ISB can be resolved but are broad. At lower temperatures, ISB are predicted to be substantially narrower and usable as powerful spectroscopic tools in strongly interacting alkaline-earth gases.

  20. A magnetoplasmonic electrical-to-optical clock multiplier

    Science.gov (United States)

    Firby, C. J.; Elezzabi, A. Y.

    2016-02-01

    We propose and investigate an electrical-to-optical clock multiplier, based on a bismuth-substituted yttrium iron garnet (Bi:YIG) magnetoplasmonic Mach-Zehnder interferometer (MZI). Transient magnetic fields induce a precession of the magnetization vector of the Bi:YIG, which in turn modulates the nonreciprocal phase shift in the MZI arms, and hence the intensity at the output port. We show that the device is capable of modulation depth of 16.26 dB and has a tunable output frequency between 279.9 MHz and 5.6 GHz. Correspondingly, the input electrical modulation frequency can be multiplied by factors of up to 2.1 × 10 3 in the optical signal. Such a device is envisioned as a critical component in the development of hybrid electrical-optical circuitry.