Computer Aided Wirewrap Interconnect.

DTIC Science & Technology

1980-11-01

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

Molecular cogs of the insect circadian clock.

PubMed

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

2003-08-01

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

Circadian clock gene plays a key role on ovarian cycle and spontaneous abortion.

PubMed

Li, Ruiwen; Cheng, Shuting; Wang, Zhengrong

2015-01-01

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

The sympathy of two pendulum clocks: beyond Huygens' observations.

PubMed

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

2016-03-29

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

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

PubMed Central

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

2011-01-01

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

Regulation of circadian clock transcriptional output by CLOCK:BMAL1

PubMed Central

Trott, Alexandra J.

2018-01-01

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

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

NASA Technical Reports Server (NTRS)

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

2016-01-01

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

The circadian clock in cancer development and therapy

USDA-ARS?s Scientific Manuscript database

Most aspects of mammalian function display circadian rhythms driven by an endogenous clock. The circadian clock is operated by genes and comprises a central clock in the brain that responds to environmental cues and controls subordinate clocks in peripheral tissues via circadian output pathways. The...

Dual-Mode Operation of an Optical Lattice Clock Using Strontium and Ytterbium Atoms.

PubMed

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

2018-06-01

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

Derivation and experimental verification of clock synchronization theory

NASA Technical Reports Server (NTRS)

Palumbo, Daniel L.

1994-01-01

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

Experimental validation of clock synchronization algorithms

NASA Technical Reports Server (NTRS)

Palumbo, Daniel L.; Graham, R. Lynn

1992-01-01

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

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

PubMed Central

Chen, Peii; Goedert, Kelly M.

2012-01-01

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

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

NASA Technical Reports Server (NTRS)

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

2016-01-01

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

Real-time simulation clock

NASA Technical Reports Server (NTRS)

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

1990-01-01

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

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

PubMed

Tahara, Yu; Aoyama, Shinya; Shibata, Shigenobu

2017-01-01

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

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

PubMed Central

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

2010-01-01

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

Novel transcriptional networks regulated by CLOCK in human neurons.

PubMed

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

2017-11-01

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

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

DOEpatents

Asaad, Sameth W.; Kapur, Mohit

2016-01-05

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

A new stochastic model considering satellite clock interpolation errors in precise point positioning

NASA Astrophysics Data System (ADS)

Wang, Shengli; Yang, Fanlin; Gao, Wang; Yan, Lizi; Ge, Yulong

2018-03-01

Precise clock products are typically interpolated based on the sampling interval of the observational data when they are used for in precise point positioning. However, due to the occurrence of white noise in atomic clocks, a residual component of such noise will inevitable reside within the observations when clock errors are interpolated, and such noise will affect the resolution of the positioning results. In this paper, which is based on a twenty-one-week analysis of the atomic clock noise characteristics of numerous satellites, a new stochastic observation model that considers satellite clock interpolation errors is proposed. First, the systematic error of each satellite in the IGR clock product was extracted using a wavelet de-noising method to obtain the empirical characteristics of atomic clock noise within each clock product. Then, based on those empirical characteristics, a stochastic observation model was structured that considered the satellite clock interpolation errors. Subsequently, the IGR and IGS clock products at different time intervals were used for experimental validation. A verification using 179 stations worldwide from the IGS showed that, compared with the conventional model, the convergence times using the stochastic model proposed in this study were respectively shortened by 4.8% and 4.0% when the IGR and IGS 300-s-interval clock products were used and by 19.1% and 19.4% when the 900-s-interval clock products were used. Furthermore, the disturbances during the initial phase of the calculation were also effectively improved.

Light signaling to the zebrafish circadian clock by Cryptochrome 1a

PubMed Central

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

2007-01-01

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

CLOCK phosphorylation by AKT regulates its nuclear accumulation and circadian gene expression in peripheral tissues.

PubMed

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

2018-06-08

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

The circadian clock network in the brain of different Drosophila species.

PubMed

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

2013-02-01

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

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

PubMed

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

2014-05-01

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

Low Variation in the Polymorphic Clock Gene Poly-Q Region Despite Population Genetic Structure across Barn Swallow (Hirundo rustica) Populations

PubMed Central

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

2011-01-01

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

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

PubMed Central

2014-01-01

Background The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. Results We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5′ splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Conclusion Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock and environmental stress adaptation in plants. It is also envisioned that alternative splicing of the clock genes plays more complex roles than previously expected. PMID:24885185

Flexible programmable logic module

DOEpatents

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

2001-01-01

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

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

NASA Technical Reports Server (NTRS)

Seidel, Dave; Thompson, R. J.; Klipstein, W. M.; Kohel, J.; Maleki, L.

2000-01-01

This paper presents the Laser Cooling and Atomic Physics (LCAP) program. It focuses on clock technology development. The topics include: 1) Overview of LCAP Flight Projects; 2) Space Clock 101; 3) Physics with Clocks in microgravity; 4) Space Clock Challenges; 5) LCAP Timeline; 6) International Space Station (ISS) Science Platforms; 7) ISS Express Rack; 8) Space Qualification of Components; 9) Laser Configuration; 10) Clock Rate Comparisons: GPS Carrier Phase Frequency Transfer; and 11) ISS Model Views. This paper is presented in viewgraph form.

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

PubMed Central

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

2013-01-01

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

High Performance Clocks and Gravity Field Determination

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Oxyntomodulin regulates resetting of the liver circadian clock by food

PubMed Central

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

2015-01-01

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

The metabolic sensor AKIN10 modulates the Arabidopsis circadian clock in a light-dependent manner.

PubMed

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

2017-07-01

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

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

PubMed

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

1999-08-13

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

The sympathy of two pendulum clocks: beyond Huygens’ observations

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-06-24

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

A precise clock distribution network for MRPC-based experiments

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

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

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

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

2011-08-19

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

Mercury Atomic Frequency Standards for Space Based Navigation and Timekeeping

NASA Technical Reports Server (NTRS)

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

2012-01-01

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

Clock Controller For Ac Self-Timing Analysis Of Logic System

DOEpatents

Lo, Tinchee; Flanagan, John D.

2004-05-18

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

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

PubMed

Chappell

1997-01-01

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

Normal vision can compensate for the loss of the circadian clock

PubMed Central

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

2015-01-01

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

Meta-analysis of stratus OCT glaucoma diagnostic accuracy.

PubMed

Chen, Hsin-Yi; Chang, Yue-Cune

2014-09-01

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

Effect of Resveratrol, a SIRT1 Activator, on the Interactions of the CLOCK/BMAL1 Complex

PubMed Central

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

2014-01-01

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

Relativity theory and time perception: single or multiple clocks?

PubMed

Buhusi, Catalin V; Meck, Warren H

2009-07-22

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

Clock is not a component of Z-bands.

PubMed

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

2012-12-01

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

A Novel Photonic Clock and Carrier Recovery Device

NASA Technical Reports Server (NTRS)

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

1996-01-01

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

Chronic consumption of dietary proanthocyanidins modulates peripheral clocks in healthy and obese rats.

PubMed

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

2015-02-01

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

Room 103, transom woodwork and original clock. All clocks are ...

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

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

Next Generation JPL Ultra-Stable Trapped Ion Atomic Clocks

NASA Technical Reports Server (NTRS)

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

2013-01-01

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

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

PubMed

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

2016-01-01

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

Transcriptional oscillation of canonical clock genes in mouse peripheral tissues

PubMed Central

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

2004-01-01

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

Generating a fault-tolerant global clock using high-speed control signals for the MetaNet architecture

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

Ofek, Y.

1994-05-01

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

Organ specificity in the plant circadian system is explained by different light inputs to the shoot and root clocks.

PubMed

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

2016-10-01

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

Satellite clock corrections estimation to accomplish real time ppp: experiments for brazilian real time network

NASA Astrophysics Data System (ADS)

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

2014-05-01

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

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

PubMed Central

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

2018-01-01

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

Orthogonally referenced integrated ensemble for navigation and timing

DOEpatents

Smith, Stephen Fulton; Moore, James Anthony

2013-02-26

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

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

NASA Technical Reports Server (NTRS)

Malekpour, Mahyar R. (Inventor)

2014-01-01

A self-stabilizing network in the form of an arbitrary, non-partitioned digraph includes K nodes having a synchronizer executing a protocol. K-1 monitors of each node may receive a Sync message transmitted from a directly connected node. When the Sync message is received, the logical clock value for the receiving node is set to between 0 and a communication latency value (gamma) if the clock value is less than a minimum event-response delay (D). A new Sync message is also transmitted to any directly connected nodes if the clock value is greater than or equal to both D and a graph threshold (T(sub S)). When the Sync message is not received the synchronizer increments the clock value if the clock value is less than a resynchronization period (P), and resets the clock value and transmits a new Sync message to all directly connected nodes when the clock value equals or exceeds P.

The Clock gene clone and its circadian rhythms in Pelteobagrus vachelli

NASA Astrophysics Data System (ADS)

Qin, Chuanjie; Shao, Ting

2015-05-01

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

Automatic control of clock duty cycle

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Geodesy and metrology with a transportable optical clock

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

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

PubMed

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

2016-04-01

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

Lego clocks: building a clock from parts.

PubMed

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

2008-06-01

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

Single-transistor-clocked flip-flop

DOEpatents

Zhao, Peiyi; Darwish, Tarek; Bayoumi, Magdy

2005-08-30

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

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

PubMed

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

2011-01-01

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

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

PubMed Central

Curie, Thomas; Franken, Paul

2011-01-01

We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), −6, −12, and −18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and −6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven. PMID:22039518

A (201)Hg+ Comagnetometer for (199)Hg+ Trapped Ion Space Atomic Clocks

NASA Technical Reports Server (NTRS)

Burt, Eric A.; Taghavi, Shervin; Tjoelker, Robert L.

2011-01-01

A method has been developed for unambiguously measuring the exact magnetic field experienced by trapped mercury ions contained within an atomic clock intended for space applications. In general, atomic clocks are insensitive to external perturbations that would change the frequency at which the clocks operate. On a space platform, these perturbative effects can be much larger than they would be on the ground, especially in dealing with the magnetic field environment. The solution is to use a different isotope of mercury held within the same trap as the clock isotope. The magnetic field can be very accurately measured with a magnetic-field-sensitive atomic transition in the added isotope. Further, this measurement can be made simultaneously with normal clock operation, thereby not degrading clock performance. Instead of using a conventional magnetometer to measure ambient fields, which would necessarily be placed some distance away from the clock atoms, first order field-sensitive atomic transition frequency changes in the atoms themselves determine the variations in the magnetic field. As a result, all ambiguity over the exact field value experienced by the atoms is removed. Atoms used in atomic clocks always have an atomic transition (often referred to as the clock transition) that is sensitive to magnetic fields only in second order, and usually have one or more transitions that are first-order field sensitive. For operating parameters used in the (199)Hg(+) clock, the latter can be five orders of magnitude or more sensitive to field fluctuations than the clock transition, thereby providing an unambiguous probe of the magnetic field strength.

Circadian molecular clock in lung pathophysiology

PubMed Central

Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.

2015-01-01

Disrupted daily or circadian rhythms of lung function and inflammatory responses are common features of chronic airway diseases. At the molecular level these circadian rhythms depend on the activity of an autoregulatory feedback loop oscillator of clock gene transcription factors, including the BMAL1:CLOCK activator complex and the repressors PERIOD and CRYPTOCHROME. The key nuclear receptors and transcription factors REV-ERBα and RORα regulate Bmal1 expression and provide stability to the oscillator. Circadian clock dysfunction is implicated in both immune and inflammatory responses to environmental, inflammatory, and infectious agents. Molecular clock function is altered by exposomes, tobacco smoke, lipopolysaccharide, hyperoxia, allergens, bleomycin, as well as bacterial and viral infections. The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors. Environmental agents and redox modulation may alter the levels of REV-ERBα and RORα in lung tissue in association with a heightened DNA damage response, cellular senescence, and inflammation. A reciprocal relationship exists between the molecular clock and immune/inflammatory responses in the lungs. Molecular clock function in lung cells may be used as a biomarker of disease severity and exacerbations or for assessing the efficacy of chronotherapy for disease management. Here, we provide a comprehensive overview of clock-controlled cellular and molecular functions in the lungs and highlight the repercussions of clock disruption on the pathophysiology of chronic airway diseases and their exacerbations. Furthermore, we highlight the potential for the molecular clock as a novel chronopharmacological target for the management of lung pathophysiology. PMID:26361874

Search for Effects of an Electrostatic Potential on Clocks in the Frame of Reference of a Charged Particle

NASA Technical Reports Server (NTRS)

Ringermacher, Harry I.; Conradi, Mark S.; Cassenti, Brice

2005-01-01

Results of experiments to confirm a theory that links classical electromagnetism with the geometry of spacetime are described. The theory, based on the introduction of a Torsion tensor into Einstein s equations and following the approach of Schroedinger, predicts effects on clocks attached to charged particles, subject to intense electric fields, analogous to the effects on clocks in a gravitational field. We show that in order to interpret this theory, one must re-interpret all clock changes, both gravitational and electromagnetic, as arising from changes in potential energy and not merely potential. The clock is provided naturally by proton spins in hydrogen atoms subject to Nuclear Magnetic Resonance trials. No frequency change of clocks was observed to a resolution of 6310(exp -9). A new "Clock Principle" was postulated to explain the null result. There are two possible implications of the experiments: (a) The Clock Principle is invalid and, in fact, no metric theory incorporating electromagnetism is possible; (b) The Clock Principle is valid and it follows that a negative rest mass cannot exist.

Crosstalk between the Circadian Clock and Innate Immunity in Arabidopsis

PubMed Central

Zhang, Chong; Xie, Qiguang; Anderson, Ryan G.; Ng, Gina; Seitz, Nicholas C.; Peterson, Thomas; McClung, C. Robertson; McDowell, John M.; Kong, Dongdong; Kwak, June M.; Lu, Hua

2013-01-01

The circadian clock integrates temporal information with environmental cues in regulating plant development and physiology. Recently, the circadian clock has been shown to affect plant responses to biotic cues. To further examine this role of the circadian clock, we tested disease resistance in mutants disrupted in CCA1 and LHY, which act synergistically to regulate clock activity. We found that cca1 and lhy mutants also synergistically affect basal and resistance gene-mediated defense against Pseudomonas syringae and Hyaloperonospora arabidopsidis. Disrupting the circadian clock caused by overexpression of CCA1 or LHY also resulted in severe susceptibility to P. syringae. We identified a downstream target of CCA1 and LHY, GRP7, a key constituent of a slave oscillator regulated by the circadian clock and previously shown to influence plant defense and stomatal activity. We show that the defense role of CCA1 and LHY against P. syringae is at least partially through circadian control of stomatal aperture but is independent of defense mediated by salicylic acid. Furthermore, we found defense activation by P. syringae infection and treatment with the elicitor flg22 can feedback-regulate clock activity. Together this data strongly supports a direct role of the circadian clock in defense control and reveal for the first time crosstalk between the circadian clock and plant innate immunity. PMID:23754942

Relativistic theory for syntonization of clocks in the vicinity of the Earth

NASA Technical Reports Server (NTRS)

Wolf, Peter; Petit, G.

1995-01-01

A well known prediction of Einstein's general theory of relativity states that two ideal clocks that move with a relative velocity, and are submitted to different gravitational fields will, in general, be observed to run at different rates. Similarly the rate of a clock with respect to the coordinate time of some spacetime reference system is dependent on the velocity of the clock in that reference system and on the gravitational fields it is submitted to. For the syntonization of clocks and the realization of coordinate times (like TAI) this rate shift has to be taken into account at an accuracy level which should be below the frequency stability of the clocks in question, i.e. all terms that are larger than the instability of the clocks should be corrected for. We present a theory for the calculation of the relativistic rate shift for clocks in the vicinity of the Earth, including all terms larger than one part in 10(exp 18). This, together with previous work on clock synchronization (Petit & Wolf 1993, 1994), amounts to a complete relativistic theory for the realization of coordinate time scales at picosecond synchronization and 10(exp -18) syntonization accuracy, which should be sufficient to accommodate future developments in time transfer and clock technology.

Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1

DOE PAGES

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

2017-01-31

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

Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature.

PubMed

Chen, Chenghao; Buhl, Edgar; Xu, Min; Croset, Vincent; Rees, Johanna S; Lilley, Kathryn S; Benton, Richard; Hodge, James J L; Stanewsky, Ralf

2015-11-26

Circadian clocks are endogenous timers adjusting behaviour and physiology with the solar day. Synchronized circadian clocks improve fitness and are crucial for our physical and mental well-being. Visual and non-visual photoreceptors are responsible for synchronizing circadian clocks to light, but clock-resetting is also achieved by alternating day and night temperatures with only 2-4 °C difference. This temperature sensitivity is remarkable considering that the circadian clock period (~24 h) is largely independent of surrounding ambient temperatures. Here we show that Drosophila Ionotropic Receptor 25a (IR25a) is required for behavioural synchronization to low-amplitude temperature cycles. This channel is expressed in sensory neurons of internal stretch receptors previously implicated in temperature synchronization of the circadian clock. IR25a is required for temperature-synchronized clock protein oscillations in subsets of central clock neurons. Extracellular leg nerve recordings reveal temperature- and IR25a-dependent sensory responses, and IR25a misexpression confers temperature-dependent firing of heterologous neurons. We propose that IR25a is part of an input pathway to the circadian clock that detects small temperature differences. This pathway operates in the absence of known 'hot' and 'cold' sensors in the Drosophila antenna, revealing the existence of novel periphery-to-brain temperature signalling channels.

Inexpensive programmable clock for a 12-bit computer

NASA Technical Reports Server (NTRS)

Vrancik, J. E.

1972-01-01

An inexpensive programmable clock was built for a digital PDP-12 computer. The instruction list includes skip on flag; clear the flag, clear the clock, and stop the clock; and preset the counter with the contents of the accumulator and start the clock. The clock counts at a rate determined by an external oscillator and causes an interrupt and sets a flag when a 12-bit overflow occurs. An overflow can occur after 1 to 4096 counts. The clock can be built for a total parts cost of less than $100 including power supply and I/O connector. Slight modification can be made to permit its use on larger machines (16 bit, 24 bit, etc.) and logic level shifting can be made to make it compatible with any computer.

The Circadian Clock Coordinates Ribosome Biogenesis

PubMed Central

Symul, Laura; Martin, Eva; Atger, Florian; Naef, Felix; Gachon, Frédéric

2013-01-01

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. PMID:23300384

Dynamics of statistical distance: Quantum limits for two-level clocks

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

Braunstein, S.L.; Milburn, G.J.

1995-03-01

We study the evolution of statistical distance on the Bloch sphere under unitary and nonunitary dynamics. This corresponds to studying the limits to clock precision for a clock constructed from a two-state system. We find that the initial motion away from pure states under nonunitary dynamics yields the greatest accuracy for a one-tick'' clock; in this case the clock's precision is not limited by the largest frequency of the system.

Ground control system for the midcourse space experiment UTC clock

NASA Technical Reports Server (NTRS)

Dragonette, Richard

1994-01-01

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

Identification and temporal expression of putative circadian clock transcripts in the amphipod crustacean Talitrus saltator

PubMed Central

O’Grady, Joseph F.; Hoelters, Laura S.; Swain, Martin T.

2016-01-01

Background Talitrus saltator is an amphipod crustacean that inhabits the supralittoral zone on sandy beaches in the Northeast Atlantic and Mediterranean. T. saltator exhibits endogenous locomotor activity rhythms and time-compensated sun and moon orientation, both of which necessitate at least one chronometric mechanism. Whilst their behaviour is well studied, currently there are no descriptions of the underlying molecular components of a biological clock in this animal, and very few in other crustacean species. Methods We harvested brain tissue from animals expressing robust circadian activity rhythms and used homology cloning and Illumina RNAseq approaches to sequence and identify the core circadian clock and clock-related genes in these samples. We assessed the temporal expression of these genes in time-course samples from rhythmic animals using RNAseq. Results We identified a comprehensive suite of circadian clock gene homologues in T. saltator including the ‘core’ clock genes period (Talper), cryptochrome 2 (Talcry2), timeless (Taltim), clock (Talclk), and bmal1 (Talbmal1). In addition we describe the sequence and putative structures of 23 clock-associated genes including two unusual, extended isoforms of pigment dispersing hormone (Talpdh). We examined time-course RNAseq expression data, derived from tissues harvested from behaviourally rhythmic animals, to reveal rhythmic expression of these genes with approximately circadian period in Talper and Talbmal1. Of the clock-related genes, casein kinase IIβ (TalckIIβ), ebony (Talebony), jetlag (Taljetlag), pigment dispensing hormone (Talpdh), protein phosphatase 1 (Talpp1), shaggy (Talshaggy), sirt1 (Talsirt1), sirt7 (Talsirt7) and supernumerary limbs (Talslimb) show temporal changes in expression. Discussion We report the sequences of principle genes that comprise the circadian clock of T. saltator and highlight the conserved structural and functional domains of their deduced cognate proteins. Our sequencing data contribute to the growing inventory of described comparative clocks. Expression profiling of the identified clock genes illuminates tantalising targets for experimental manipulation to elucidate the molecular and cellular control of clock-driven phenotypes in this crustacean. PMID:27761341

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

NASA Technical Reports Server (NTRS)

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

2016-01-01

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

Real Time Distributed Embedded Oscillator Operating Frequency Monitoring

NASA Technical Reports Server (NTRS)

Pollock, Julie (Inventor); Oliver, Brett D. (Inventor); Brickner, Christopher (Inventor)

2013-01-01

A method for clock monitoring in a network is provided. The method comprises receiving a first network clock signal at a network device and comparing the first network clock signal to a local clock signal from a primary oscillator coupled to the network device.

Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk between the PPARs/RXRα-Regulated and CLOCK/BMAL1-Regulated Systems

PubMed Central

Nakamura, Koh-ichi; Inoue, Ikuo; Takahashi, Seiichiro; Komoda, Tsugikazu; Katayama, Shigehiro

2008-01-01

Feeding and the circadian system regulate lipid absorption and metabolism, and the expression of enzymes involved in lipid metabolism is believed to be directly controlled by the clock system. To investigate the interaction between the lipid metabolism system and the circadian system, we analyzed the effect of a CLOCK/BMAL1 heterodimer on the transcriptional regulation of PPAR-controlled genes through PPAR response elements (PPREs). Transcription of acyl-CoA oxidase, cellular retinol binding protein II (CRBPII), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was altered by CLOCK/BMAL1, and transcriptional activity via PPRE by PPARs/RXRα was enhanced by CLOCK/BMAL1 and/or by PPARs ligand/activators. We also found that CLOCK/BMAL1-mediated transcription of period (PER) and cryptochrome (CRY) was modulated by PPARα/RXRα. These results suggest that there may be crosstalk between the PPARs/RXRα-regulated system and the CLOCK/BMAL1-regulated system. PMID:18317514

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

PubMed

McClung, C Robertson; Gutiérrez, Rodrigo A

2010-12-01

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

A clocking discipline for two-phase digital integrated circuits

NASA Astrophysics Data System (ADS)

Noice, D. C.

1983-09-01

Sooner or later a designer of digital circuits must face the problem of timing verification so he can avoid errors caused by clock skew, critical races, and hazards. Unlike previous verification methods, such as timing simulation and timing analysis, the approach presented here guarantees correct operation despite uncertainty about delays in the circuit. The result is a clocking discipline that deals with timing abstractions only. It is not based on delay calculations; it is only concerned with the correct, synchronous operation at some clock rate. Accordingly, it may be used earlier in the design cycle, which is particularly important to integrated circuit designs. The clocking discipline consists of a notation of clocking types, and composition rules for using the types. Together, the notation and rules define a formal theory of two phase clocking. The notation defines the names and exact characteristics for different signals that are used in a two phase digital system. The notation makes it possible to develop rules for propagating the clocking types through particular circuits.

The space optical clocks project

NASA Astrophysics Data System (ADS)

Schiller, S.; Tino, G. M.; Lemonde, P.; Sterr, U.; Lisdat, Ch.; Görlitz, A.; Poli, N.; Nevsky, A.; Salomon, C.

2017-11-01

The Space Optical Clocks project aims at operating lattice clocks on the ISS for tests of fundamental physics and for providing high-accuracy comparisons of future terrestrial optical clocks. A pre-phase-A study (2007- 10), funded partially by ESA and DLR, included the implementation of several optical lattice clock systems using Strontium and Ytterbium as atomic species and their characterization. Subcomponents of clock demonstrators with the added specification of transportability and using techniques suitable for later space use, such as all-solid-state lasers, low power consumption, and compact dimensions, have been developed and have been validated. This included demonstration of laser-cooling and magneto-optical trapping of Sr atoms in a compact breadboard apparatus and demonstration of a transportable clock laser with 1 Hz linewidth. With two laboratory Sr lattice clock systems a number of fundamental results were obtained, such as observing atomic resonances with linewidths as low as 3 Hz, non-destructive detection of atom excitation, determination of decoherence effects and reaching a frequency instability of 1×10-16.

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

PubMed Central

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

2009-01-01

Since 1960, magnetic fields have been discussed as Zeitgebers for circadian clocks, but the mechanism by which clocks perceive and process magnetic information has remained unknown. Recently, the radical-pair model involving light-activated photoreceptors as magnetic field sensors has gained considerable support, and the blue-light photoreceptor cryptochrome (CRY) has been proposed as a suitable molecule to mediate such magnetosensitivity. Since CRY is expressed in the circadian clock neurons and acts as a critical photoreceptor of Drosophila's clock, we aimed to test the role of CRY in magnetosensitivity of the circadian clock. In response to light, CRY causes slowing of the clock, ultimately leading to arrhythmic behavior. We expected that in the presence of applied magnetic fields, the impact of CRY on clock rhythmicity should be altered. Furthermore, according to the radical-pair hypothesis this response should be dependent on wavelength and on the field strength applied. We tested the effect of applied static magnetic fields on the circadian clock and found that flies exposed to these fields indeed showed enhanced slowing of clock rhythms. This effect was maximal at 300 μT, and reduced at both higher and lower field strengths. Clock response to magnetic fields was present in blue light, but absent under red-light illumination, which does not activate CRY. Furthermore, cryb and cryOUT mutants did not show any response, and flies overexpressing CRY in the clock neurons exhibited an enhanced response to the field. We conclude that Drosophila's circadian clock is sensitive to magnetic fields and that this sensitivity depends on light activation of CRY and on the applied field strength, consistent with the radical pair mechanism. CRY is widespread throughout biological systems and has been suggested as receptor for magnetic compass orientation in migratory birds. The present data establish the circadian clock of Drosophila as a model system for CRY-dependent magnetic sensitivity. Furthermore, given that CRY occurs in multiple tissues of Drosophila, including those potentially implicated in fly orientation, future studies may yield insights that could be applicable to the magnetic compass of migratory birds and even to potential magnetic field effects in humans. PMID:19355790

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.

PubMed

Campoli, Chiara; Shtaya, Munqez; Davis, Seth J; von Korff, Maria

2012-06-21

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. 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. 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 Triticeae species.

Ultrahigh-speed clock recovery with optical phase lock loop based on four-wave-mixing in a semiconductor optical amplifier

NASA Astrophysics Data System (ADS)

Kim, Dong Hwan; Kim, Sang Hyuck; Jo, Jae Cheol; Choi, Sang Sam

2000-08-01

A new phase lock loop (PLL) is proposed and demonstrated for clock recovery from 40 Gbps time-division-multiplexed (TDM) optical signal using simple optical phase lock loop circuit. The proposed clock recovery scheme improves the jitter effect in PLL circuit from the clock pulse laser of harmonically-mode locked fiber laser. The cross-correlation component between the optical signal and an optical clock pulse train is detected as a four-wave-mixing (FWM) signal generated in SOA. The lock-in frequency range of the clock recovery is found to be within 10 KHz.

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

NASA Technical Reports Server (NTRS)

Malekpour, Mahyar R. (Inventor)

2010-01-01

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

Processing circuit with asymmetry corrector and convolutional encoder for digital data

NASA Technical Reports Server (NTRS)

Pfiffner, Harold J. (Inventor)

1987-01-01

A processing circuit is provided for correcting for input parameter variations, such as data and clock signal symmetry, phase offset and jitter, noise and signal amplitude, in incoming data signals. An asymmetry corrector circuit performs the correcting function and furnishes the corrected data signals to a convolutional encoder circuit. The corrector circuit further forms a regenerated clock signal from clock pulses in the incoming data signals and another clock signal at a multiple of the incoming clock signal. These clock signals are furnished to the encoder circuit so that encoded data may be furnished to a modulator at a high data rate for transmission.

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

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

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

Asynchronous oscillations of two zebrafish CLOCK partners reveal differential clock control and function

PubMed Central

Cermakian, Nicolas; Whitmore, David; Foulkes, Nicholas S.; Sassone-Corsi, Paolo

2000-01-01

Most clock genes encode transcription factors that interact to elicit cooperative control of clock function. Using a two-hybrid system approach, we have isolated two different partners of zebrafish (zf) CLOCK, which are similar to the mammalian BMAL1 (brain and muscle arylhydrocarbon receptor nuclear translocator-like protein 1). The two homologs, zfBMAL1 and zfBMAL2, contain conserved basic helix–loop–helix-PAS (Period-Arylhydrocarbon receptor-Singleminded) domains but diverge in the carboxyl termini, thus bearing different transcriptional activation potential. As for zfClock, the expression of both zfBmals oscillates in most tissues in the animal. However, in many tissues, the peak, levels, and kinetics of expression are different between the two genes and for the same gene from tissue to tissue. These results support the existence of independent peripheral oscillators and suggest that zfBMAL1 and zfBMAL2 may exert distinct circadian functions, interacting differentially with zfCLOCK at various times in different tissues. Our findings also indicate that multiple controls may be exerted by the central clock and/or that peripheral oscillators can differentially interpret central clock signals. PMID:10760301

Localization and expression of putative circadian clock transcripts in the brain of the nudibranch Melibe leonina.

PubMed

Duback, Victoria E; Sabrina Pankey, M; Thomas, Rachel I; Huyck, Taylor L; Mbarani, Izhar M; Bernier, Kyle R; Cook, Geoffrey M; O'Dowd, Colleen A; Newcomb, James M; Watson, Winsor H

2018-09-01

The nudibranch, Melibe leonina, expresses a circadian rhythm of locomotion, and we recently determined the sequences of multiple circadian clock transcripts that may play a role in controlling these daily patterns of behavior. In this study, we used these genomic data to help us: 1) identify putative clock neurons using fluorescent in situ hybridization (FISH); and 2) determine if there is a daily rhythm of expression of clock transcripts in the M. leonina brain, using quantitative PCR. FISH indicated the presence of the clock-related transcripts clock, period, and photoreceptive and non-photoreceptive cryptochrome (pcry and npcry, respectively) in two bilateral neurons in each cerebropleural ganglion and a group of <10 neurons in the anterolateral region of each pedal ganglion. Double-label experiments confirmed colocalization of all four clock transcripts with each other. Quantitative PCR demonstrated that the genes clock, period, pcry and npcry exhibited significant differences in expression levels over 24 h. These data suggest that the putative circadian clock network in M. leonina consists of a small number of identifiable neurons that express circadian genes with a daily rhythm. Copyright © 2018 Elsevier Inc. All rights reserved.

Single-ion, transportable optical atomic clocks

NASA Astrophysics Data System (ADS)

Delehaye, Marion; Lacroûte, Clément

2018-03-01

For the past 15 years, tremendous progress within the fields of laser stabilization, optical frequency combs and atom cooling and trapping have allowed the realization of optical atomic clocks with unrivaled performances. These instruments can perform frequency comparisons with fractional uncertainties well below ?, finding applications in fundamental physics tests, relativistic geodesy and time and frequency metrology. Even though most optical clocks are currently laboratory setups, several proposals for using these clocks for field measurements or within an optical clock network have been published, and most of time and frequency metrology institutes have started to develop transportable optical clocks. For the purpose of this special issue, we chose to focus on trapped-ion optical clocks. Even though their short-term fractional frequency stability is impaired by a lower signal-to-noise ratio, they offer a high potential for compactness: trapped ions demand low optical powers and simple loading schemes, and can be trapped in small vacuum chambers. We review recent advances on the clock key components, including ion trap and ultra-stable optical cavity, as well as existing projects and experiments which draw the picture of what future transportable, single-ion optical clocks may resemble.

Circadian organization in hemimetabolous insects.

PubMed

Tomioka, Kenji; Abdelsalam, Salaheldin

2004-12-01

The circadian system of hemimetabolous insects is reviewed in respect to the locus of the circadian clock and multioscillatory organization. Because of relatively easy access to the nervous system, the neuronal organization of the clock system in hemimetabolous insects has been studied, yielding identification of the compound eye as the major photoreceptor for entrainment and the optic lobe for the circadian clock locus. The clock site within the optic lobe is inconsistent among reported species; in cockroaches the lobula was previously thought to be a most likely clock locus but accessory medulla is recently stressed to be a clock center, while more distal part of the optic lobe including the lamina and the outer medulla area for the cricket. Identification of the clock cells needs further critical studies. Although each optic lobe clock seems functionally identical, in respect to photic entrainment and generation of the rhythm, the bilaterally paired clocks form a functional unit. They interact to produce a stable time structure within individual insects by exchanging photic and temporal information through neural pathways, in which serotonin and pigment-dispersing factor (PDF) are involved as chemical messengers. The mutual interaction also plays an important role in seasonal adaptation of the rhythm.

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

DOEpatents

Bellofatto, Ralph E [Ridgefield, CT; Ellavsky, Matthew R [Rochester, MN; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Gooding, Thomas M [Rochester, MN; Haring, Rudolf A [Cortlandt Manor, NY; Hehenberger, Lance G [Leander, TX; Ohmacht, Martin [Yorktown Heights, NY

2012-03-20

An apparatus and method for evaluating a state of an electronic or integrated circuit (IC), each IC including one or more processor elements for controlling operations of IC sub-units, and each the IC supporting multiple frequency clock domains. The method comprises: generating a synchronized set of enable signals in correspondence with one or more IC sub-units for starting operation of one or more IC sub-units according to a determined timing configuration; counting, in response to one signal of the synchronized set of enable signals, a number of main processor IC clock cycles; and, upon attaining a desired clock cycle number, generating a stop signal for each unique frequency clock domain to synchronously stop a functional clock for each respective frequency clock domain; and, upon synchronously stopping all on-chip functional clocks on all frequency clock domains in a deterministic fashion, scanning out data values at a desired IC chip state. The apparatus and methodology enables construction of a cycle-by-cycle view of any part of the state of a running IC chip, using a combination of on-chip circuitry and software.

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

NASA Technical Reports Server (NTRS)

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.

Practical security analysis of continuous-variable quantum key distribution with jitter in clock synchronization

NASA Astrophysics Data System (ADS)

Xie, Cailang; Guo, Ying; Liao, Qin; Zhao, Wei; Huang, Duan; Zhang, Ling; Zeng, Guihua

2018-03-01

How to narrow the gap of security between theory and practice has been a notoriously urgent problem in quantum cryptography. Here, we analyze and provide experimental evidence of the clock jitter effect on the practical continuous-variable quantum key distribution (CV-QKD) system. The clock jitter is a random noise which exists permanently in the clock synchronization in the practical CV-QKD system, it may compromise the system security because of its impact on data sampling and parameters estimation. In particular, the practical security of CV-QKD with different clock jitter against collective attack is analyzed theoretically based on different repetition frequencies, the numerical simulations indicate that the clock jitter has more impact on a high-speed scenario. Furthermore, a simplified experiment is designed to investigate the influence of the clock jitter.

BDS Precise Point Positioning for Seismic Displacements Monitoring: Benefit from the High-Rate Satellite Clock Corrections

PubMed Central

Geng, Tao; Su, Xing; Fang, Rongxin; Xie, Xin; Zhao, Qile; Liu, Jingnan

2016-01-01

In order to satisfy the requirement of high-rate high-precision applications, 1 Hz BeiDou Navigation Satellite System (BDS) satellite clock corrections are generated based on precise orbit products, and the quality of the generated clock products is assessed by comparing with those from the other analysis centers. The comparisons show that the root mean square (RMS) of clock errors of geostationary Earth orbits (GEO) is about 0.63 ns, whereas those of inclined geosynchronous orbits (IGSO) and medium Earth orbits (MEO) are about 0.2–0.3 ns and 0.1 ns, respectively. Then, the 1 Hz clock products are used for BDS precise point positioning (PPP) to retrieve seismic displacements of the 2015 Mw 7.8 Gorkha, Nepal, earthquake. The derived seismic displacements from BDS PPP are consistent with those from the Global Positioning System (GPS) PPP, with RMS of 0.29, 0.38, and 1.08 cm in east, north, and vertical components, respectively. In addition, the BDS PPP solutions with different clock intervals of 1 s, 5 s, 30 s, and 300 s are processed and compared with each other. The results demonstrate that PPP with 300 s clock intervals is the worst and that with 1 s clock interval is the best. For the scenario of 5 s clock intervals, the precision of PPP solutions is almost the same to 1 s results. Considering the time consumption of clock estimates, we suggest that 5 s clock interval is competent for high-rate BDS solutions. PMID:27999384

An optical lattice clock with accuracy and stability at the 10(-18) level.

PubMed

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

2014-02-06

Progress in atomic, optical and quantum science has led to rapid improvements in atomic clocks. At the same time, atomic clock research has helped to advance the frontiers of science, affecting both fundamental and applied research. The ability to control quantum states of individual atoms and photons is central to quantum information science and precision measurement, and optical clocks based on single ions have achieved the lowest systematic uncertainty of any frequency standard. Although many-atom lattice clocks have shown advantages in measurement precision over trapped-ion clocks, their accuracy has remained 16 times worse. Here we demonstrate a many-atom system that achieves an accuracy of 6.4 × 10(-18), which is not only better than a single-ion-based clock, but also reduces the required measurement time by two orders of magnitude. By systematically evaluating all known sources of uncertainty, including in situ monitoring of the blackbody radiation environment, we improve the accuracy of optical lattice clocks by a factor of 22. This single clock has simultaneously achieved the best known performance in the key characteristics necessary for consideration as a primary standard-stability and accuracy. More stable and accurate atomic clocks will benefit a wide range of fields, such as the realization and distribution of SI units, the search for time variation of fundamental constants, clock-based geodesy and other precision tests of the fundamental laws of nature. This work also connects to the development of quantum sensors and many-body quantum state engineering (such as spin squeezing) to advance measurement precision beyond the standard quantum limit.

BDS Precise Point Positioning for Seismic Displacements Monitoring: Benefit from the High-Rate Satellite Clock Corrections.

PubMed

Geng, Tao; Su, Xing; Fang, Rongxin; Xie, Xin; Zhao, Qile; Liu, Jingnan

2016-12-20

In order to satisfy the requirement of high-rate high-precision applications, 1 Hz BeiDou Navigation Satellite System (BDS) satellite clock corrections are generated based on precise orbit products, and the quality of the generated clock products is assessed by comparing with those from the other analysis centers. The comparisons show that the root mean square (RMS) of clock errors of geostationary Earth orbits (GEO) is about 0.63 ns, whereas those of inclined geosynchronous orbits (IGSO) and medium Earth orbits (MEO) are about 0.2-0.3 ns and 0.1 ns, respectively. Then, the 1 Hz clock products are used for BDS precise point positioning (PPP) to retrieve seismic displacements of the 2015 Mw 7.8 Gorkha, Nepal, earthquake. The derived seismic displacements from BDS PPP are consistent with those from the Global Positioning System (GPS) PPP, with RMS of 0.29, 0.38, and 1.08 cm in east, north, and vertical components, respectively. In addition, the BDS PPP solutions with different clock intervals of 1 s, 5 s, 30 s, and 300 s are processed and compared with each other. The results demonstrate that PPP with 300 s clock intervals is the worst and that with 1 s clock interval is the best. For the scenario of 5 s clock intervals, the precision of PPP solutions is almost the same to 1 s results. Considering the time consumption of clock estimates, we suggest that 5 s clock interval is competent for high-rate BDS solutions.

Simulating Future GPS Clock Scenarios with Two Composite Clock Algorithms

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Dynamics of the slowing segmentation clock reveal alternating two-segment periodicity

PubMed Central

Shih, Nathan P.; François, Paul; Delaune, Emilie A.; Amacher, Sharon L.

2015-01-01

The formation of reiterated somites along the vertebrate body axis is controlled by the segmentation clock, a molecular oscillator expressed within presomitic mesoderm (PSM) cells. Although PSM cells oscillate autonomously, they coordinate with neighboring cells to generate a sweeping wave of cyclic gene expression through the PSM that has a periodicity equal to that of somite formation. The velocity of each wave slows as it moves anteriorly through the PSM, although the dynamics of clock slowing have not been well characterized. Here, we investigate segmentation clock dynamics in the anterior PSM in developing zebrafish embryos using an in vivo clock reporter, her1:her1-venus. The her1:her1-venus reporter has single-cell resolution, allowing us to follow segmentation clock oscillations in individual cells in real-time. By retrospectively tracking oscillations of future somite boundary cells, we find that clock reporter signal increases in anterior PSM cells and that the periodicity of reporter oscillations slows to about ∼1.5 times the periodicity in posterior PSM cells. This gradual slowing of the clock in the anterior PSM creates peaks of clock expression that are separated at a two-segment periodicity both spatially and temporally, a phenomenon we observe in single cells and in tissue-wide analyses. These results differ from previous predictions that clock oscillations stop or are stabilized in the anterior PSM. Instead, PSM cells oscillate until they incorporate into somites. Our findings suggest that the segmentation clock may signal somite formation using a phase gradient with a two-somite periodicity. PMID:25968314

Comparison of the clock test and a questionnaire-based test for screening for cognitive impairment in Nigerians.

PubMed

VanderJagt, D J; Ganga, S; Obadofin, M O; Stanley, P; Zimmerman, M; Skipper, B J; Glew, R H

2006-01-01

Since it is projected that by 2020 seventy percent of the elderly will reside in developing countries, a reliable screening method for dementia and cognitive impairment in general in populations with diverse languages, culture, education and literacy will be needed. We sought to determine if the Clock Test, a screening test for dementia, was suitable for use in a Nigerian population. Cross-sectional survey of 54 men and 12 women from Northern Nigeria. Researchers administered two dementia screening tools: a questionnaire-based test adapted for use in a Nigerian population and the Clock Test. Overall, 53.0% of the subjects had an abnormal Clock Test whereas 10.6% of the subjects had an abnormal questionnaire score. Only 9.1% of the subjects had abnormal scores on both tests. Subjects with more schooling had a greater probability of having a positive clock concept (understanding that a circle represented a clock). Of those with more than 6 years of schooling, 91.0% had a positive clock concept. Subjects with a negative clock concept were more likely to have an abnormal Clock Test (93.3%) than a questionnaire (26.6%). The main finding of our study was the discrepancy between the results of the Clock Test and the questionnaire. Performance on the Clock Test appeared to have been heavily influenced by education level, indicating the test is not universally applicable across cultures. The questionnaire-based test appears to reduce the effects of illiteracy on assessing dementia in a Nigerian population. Larger studies should be done to control for how education affects the assessment of dementia.

Submillimeter Schottky Diodes with Electron Beam Lithography.

DTIC Science & Technology

1979-12-01

Timer 2: external clock, oneshot , 0’ sixteen bit counting modes are .,selected, no data is entered; interrupts are disabled. Timer 3: external clock and...CLOCK, ONESHOT MODE, NO INTERRUPTS, 00031* 16 BIT COUNTING MODE, OUTPUT IS EN- 00032 * ABLED; NO DATA IS ENTERED, 00033 00034 * TIMER3: EXT CLOCK

Sex Differences in Patients With CAM Deformities With Femoroacetabular Impingement: 3-Dimensional Computed Tomographic Quantification.

PubMed

Yanke, Adam B; Khair, M Michael; Stanley, Robert; Walton, David; Lee, Simon; Bush-Joseph, Charles A; Espinoza Orías, Alejandro; Espinosa Orias, Alejandro A; Inoue, Nozomu; Nho, Shane J

2015-12-01

To determine if significant differences exist between male and female CAM deformities using quantitative 3-dimensional (3D) volume and location analysis. Retrospective analysis of preoperative computed tomographic (CT) scans for 138 femurs (69 from male patients and 69 from female patients) diagnosed with impingement from November 2009 to November 2011 was completed. Those patients who presented with hip complaints and had a history, physical examination (limited range of motion, positive impingement signs), plain radiographs (anteroposterior pelvis, 90° Dunn view, false profile view), and magnetic resonance images consistent with femoroacetabular impingement (FAI) and in whom a minimum of 6 months of conservative therapy (oral anti-inflammatory agents, physical therapy, and activity modification) had failed were indicated for arthroscopic surgery and had a preoperative CT scan. Scans were segmented, converted to point cloud data, and analyzed with a custom-written computer program. Analysis included mean CAM height and volume, head radius, and femoral version. Differences were analyzed using an unpaired t test with significance set at P < .05. Female patients had greater femoral anteversion compared with male patients (female patients, 15.5° ± 8.3°; male patients, 11.3° ± 9.0°; P = .06). Male femoral head radii were significantly larger than female femoral heads (female patients, 22.0 ± 1.3 mm; male patients, 25.4 ± 1.3 mm; P < .001). Male CAM height was significantly larger than that in female patients (female patients, 0.66 ± 0.61 mm; male patients, 1.51 ± 0.75 mm; P < .001). Male CAM volume was significantly larger as well (male patients, 433 ± 471 mm(3); female patients, 89 ± 124 mm(3); P < .001). These differences persisted after normalizing height (P < .001) and volume (P < .001) to femoral head radius. Average clock face distribution was from the 1:09 o'clock position ± the 2:51 o'clock position to the 3:28 o'clock position ± the 1:59 o'clock position, with an average span from the 3:06 o'clock position ± the 1:29 o'clock position (male patients, the 11:23 o'clock position ± the 0:46 o'clock position to the 3:05 o'clock position ± the 1:20 o'clock position; female patients, the 11:33 o'clock position ± the 0:37 o'clock position to the 2:27 o'clock position ± the 0:45 o'clock position). There were no differences in the posterior (P = .60) or anterior (P = .14) extent of CAM deformities. However, the span on the clock face of the CAM deformities varied when comparing men with women (male patients, the 3:43 o'clock position ± the 1:29 o'clock position; female patients, the 2:54 o'clock position ± the 1:09 o'clock position; P = .02). Our data show that female CAM deformities are shallower and of smaller volume than male lesions. Further studies will allow further characterization of the 3D geometry of the proximal femur and provide more precise guidance for femoral osteochondroplasty for the treatment of CAM deformities. Female CAM deformities may not be detectable using current 2D nonquantitative methods. These findings should raise the clinician's index of suspicion when diagnosing a symptomatic CAM lesion in female patients. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Countdown Clock Ribbon Cutting

NASA Image and Video Library

2016-03-01

Confetti is launched as the spaceport's historic countdown clock is dedicated as the newest display at the Kennedy Space Center Visitor Complex. Now located at the entrance to the visitor complex, the spaceport's historic countdown clock was used starting with the launch of Apollo 12 on Nov. 14, 1969. Originally set up at the space center's Press Site, the clock operated through the final space shuttle mission, STS-135, launched on July 8, 2011. The old countdown clock was replaced in 2014 with a modern light emitting diode, or LED, display.

The Space Optical Clock project: status and perspectives

NASA Astrophysics Data System (ADS)

Schiller, Stephan; Tino, Guglielmo M.; Sterr, Uwe; Lemonde, Pierre; Görlitz, Axel; Salomon, Christophe

The Space Optical Clocks project aims at operating lattice clocks on the ISS for tests of funda-mental physics and for providing high-accuracy comparisons of future terrestrial optical clocks. A pre-phase-A study (2007-10), funded partially by ESA and DLR, includes the implementa-tion of several optical lattice clock systems using Strontium and Ytterbium as atomic systems and their characterization. Subcomponents of clock demonstrators with the added specification of transportability and using techniques that are suitable for later space use, such as all-solid-state lasers, low power consumption, and compact dimensions, have been developed and are being validated. The talk will give a brief overview over the achieved results and outline future developments.

A Genome-Wide RNAi Screen for Modifiers of the Circadian Clock in Human Cells

PubMed Central

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

2009-01-01

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

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

NASA Astrophysics Data System (ADS)

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

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

Orthogonally referenced integrated ensemble for navigation and timing

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

Smith, Stephen Fulton; Moore, James Anthony

2014-04-01

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

Precise time dissemination via portable atomic clocks

NASA Technical Reports Server (NTRS)

Putkovich, K.

1982-01-01

The most precise operational method of time dissemination over long distances presently available to the Precise Time and Time Interval (PTTI) community of users is by means of portable atomic clocks. The Global Positioning System (GPS), the latest system showing promise of replacing portable clocks for global PTTI dissemination, was evaluated. Although GPS has the technical capability of providing superior world-wide dissemination, the question of present cost and future accessibility may require a continued reliance on portable clocks for a number of years. For these reasons a study of portable clock operations as they are carried out today was made. The portable clock system that was utilized by the U.S. Naval Observatory (NAVOBSY) in the global synchronization of clocks over the past 17 years is described and the concepts on which it is based are explained. Some of its capabilities and limitations are also discussed.

The Effects of Clock Drift on the Mars Exploration Rovers

NASA Technical Reports Server (NTRS)

Ali, Khaled S.; Vanelli, C. Anthony

2012-01-01

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

Clock-drawing test and unilateral spatial neglect.

PubMed

Ishiai, S; Sugishita, M; Ichikawa, T; Gono, S; Watabiki, S

1993-01-01

We investigated the ability of 25 patients with left unilateral spatial neglect to make a clock face by putting numbers inside a printed circle. Impairment seen in this clock-drawing test did not parallel neglect severity as judged by results of the line-cancellation and line-bisection tests, as well as the copying of a daisy. The score for clock drawing correlated highly with the verbal WAIS score. Most neglect patients with a verbal IQ of 87 or more could draw a clock face fairly well and used planning in placing the numbers 12, 3, 6, and 9 before the others. In clock drawing, verbal intelligence may compensate for left unilateral spatial neglect. We therefore recommend use of the line-cancellation and line-bisection tests, as well as the copying test, but do not recommend use of the clock-drawing test in the diagnosis of left unilateral spatial neglect.

Apparatus and method for compensating for clock drift in downhole drilling components

DOEpatents

Hall, David R [Provo, UT; Pixton, David S [Lehi, UT; Johnson, Monte L [Orem, UT; Bartholomew, David B [Springville, UT; Hall, Jr., H. Tracy

2007-08-07

A precise downhole clock that compensates for drift includes a prescaler configured to receive electrical pulses from an oscillator. The prescaler is configured to output a series of clock pulses. The prescaler outputs each clock pulse after counting a preloaded number of electrical pulses from the oscillator. The prescaler is operably connected to a compensator module for adjusting the number loaded into the prescaler. By adjusting the number that is loaded into the prescaler, the timing may be advanced or retarded to more accurately synchronize the clock pulses with a reference time source. The compensator module is controlled by a counter-based trigger module configured to trigger the compensator module to load a value into the prescaler. Finally, a time-base logic module is configured to calculate the drift of the downhole clock by comparing the time of the downhole clock with a reference time source.

A Light Clock Satisfying the Clock Hypothesis of Special Relativity

ERIC Educational Resources Information Center

West, Joseph

2007-01-01

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

Crosstalk of clock gene expression and autophagy in aging

PubMed Central

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

2016-01-01

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

Crosstalk of clock gene expression and autophagy in aging.

PubMed

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

2016-08-28

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

On-orbit frequency stability analysis of the GPS NAVSTAR-1 quartz clock and the NAVSTARs-6 and -8 rubidium clocks

NASA Technical Reports Server (NTRS)

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

1984-01-01

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

Genetic differences in human circadian clock genes among worldwide populations.

PubMed

Ciarleglio, Christopher M; Ryckman, Kelli K; Servick, Stein V; Hida, Akiko; Robbins, Sam; Wells, Nancy; Hicks, Jennifer; Larson, Sydney A; Wiedermann, Joshua P; Carver, Krista; Hamilton, Nalo; Kidd, Kenneth K; Kidd, Judith R; Smith, Jeffrey R; Friedlaender, Jonathan; McMahon, Douglas G; Williams, Scott M; Summar, Marshall L; Johnson, Carl Hirschie

2008-08-01

The daily biological clock regulates the timing of sleep and physiological processes that are of fundamental importance to human health, performance, and well-being. Environmental parameters of relevance to biological clocks include (1) daily fluctuations in light intensity and temperature, and (2) seasonal changes in photoperiod (day length) and temperature; these parameters vary dramatically as a function of latitude and locale. In wide-ranging species other than humans, natural selection has genetically optimized adaptiveness along latitudinal clines. Is there evidence for selection of clock gene alleles along latitudinal/photoperiod clines in humans? A number of polymorphisms in the human clock genes Per2, Per3, Clock, and AANAT have been reported as alleles that could be subject to selection. In addition, this investigation discovered several novel polymorphisms in the human Arntl and Arntl2 genes that may have functional impact upon the expression of these clock transcriptional factors. The frequency distribution of these clock gene polymorphisms is reported for diverse populations of African Americans, European Americans, Ghanaians, Han Chinese, and Papua New Guineans (including 5 subpopulations within Papua New Guinea). There are significant differences in the frequency distribution of clock gene alleles among these populations. Population genetic analyses indicate that these differences are likely to arise from genetic drift rather than from natural selection.

Molecular clock integration of brown adipose tissue formation and function

PubMed Central

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. PMID:27385482

Assessing the short-term clock drift of early broadband stations with burst events of the 26 s persistent and localized microseism

NASA Astrophysics Data System (ADS)

Xie, J.; Ni, S.; Chu, R.; Xia, Y.

2017-12-01

Accurate seismometer clock plays an important role in seismological studies including earthquake location and tomography. However, some seismic stations may have clock drift larger than 1 second, especially in early days of global seismic network. The 26 s Persistent Localized (PL) microseism event in the Gulf of Guinea sometime excites strong and coherent signals, and can be used as repeating source for assessing stability of seismometer clocks. Taking station GSC/TS in southern California, USA as an example, the 26 s PL signal can be easily observed in the ambient Noise Cross-correlation Function (NCF) between GSC/TS and a remote station. The variation of travel-time of this 26 s signal in the NCF is used to infer clock error. A drastic clock error is detected during June, 1992. This short-term clock error is confirmed by both teleseismic and local earthquake records with a magnitude of ±25 s. Using 26 s PL source, the clock can be validated for historical records of sparsely distributed stations, where usual NCF of short period microseism (<20 s) might be less effective due to its attenuation over long interstation distances. However, this method suffers from cycling problem, and should be verified by teleseismic/local P waves. The location change of the 26 s PL source may influence the measured clock drift, using regional stations with stable clock, we estimate the possible location change of the source.

Synthesizing genetic sequential logic circuit with clock pulse generator.

PubMed

Chuang, Chia-Hua; Lin, Chun-Liang

2014-05-28

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

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

PubMed

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

2018-04-03

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

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

PubMed

Hardman, Jonathan A; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Paus, Ralf

2015-01-01

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.

Extra-hypothalamic brain clocks in songbirds: Photoperiodic state dependent clock gene oscillations in night-migratory blackheaded buntings, Emberiza melanocephala.

PubMed

Singh, Devraj; Kumar, Vinod

2017-04-01

The avian circadian pacemaker system is comprised of independent clocks in the retina, pineal and hypothalamus, as shown by daily and circadian oscillations of core clock genes (Per2, Cry1, Bmal1 and Clock) in several birds including migratory blackheaded buntings (Emberiza melanocephala). This study investigated the extra-hypothalamic brain circadian clocks in blackheaded buntings, and measured Per2, Cry1, Cry2, Bmal1 and Clock mRNA expressions at 4h intervals over 24h beginning 1h after light-on in the left and right telencephalon, optic tectum and cerebellum, the brain regions involved in several physiological and cognitive functions. Because of seasonal alterations in the circadian clock dependent brain functions, we measured daily clock gene oscillations in buntings photoperiod-induced with the non-migratory state under short days (SDnM), and the pre-migratory (LDpM), migratory (LDM) and post-migratory (refractory, LDR) states under long days. Daily Per2 oscillations were not altered with changes in the photoperiodic states, except for about 2-3h phase difference in the optic tectum between the SDnM and LDpM states. However, there were about 3-5h differences in the phase and 2 to 4 fold change in the amplitude of daily Bmal1 and Cry1 mRNA oscillations between the photoperiod-induced states. Further, Cry2 and Clock genes lacked a significant oscillation, except in Cb (Cry2) and TeO and Rt (Clock) under LDR state. Overall, these results show the presence of circadian clocks in extra-hypothalamic brain regions of blackheaded buntings, and suggest tissue-dependent alterations in the waveforms of mRNA oscillations with transitions in the photoperiod-induced seasonal states in a long-day species. Copyright © 2017 Elsevier B.V. All rights reserved.

Gigabit Ethernet Asynchronous Clock Compensation FIFO

NASA Technical Reports Server (NTRS)

Duhachek, Jeff

2012-01-01

Clock compensation for Gigabit Ethernet is necessary because the clock recovered from the 1.25 Gb/s serial data stream has the potential to be 200 ppm slower or faster than the system clock. The serial data is converted to 10-bit parallel data at a 125 MHz rate on a clock recovered from the serial data stream. This recovered data needs to be processed by a system clock that is also running at a nominal rate of 125 MHz, but not synchronous to the recovered clock. To cross clock domains, an asynchronous FIFO (first-in-first-out) is used, with the write pointer (wprt) in the recovered clock domain and the read pointer (rptr) in the system clock domain. Because the clocks are generated from separate sources, there is potential for FIFO overflow or underflow. Clock compensation in Gigabit Ethernet is possible by taking advantage of the protocol data stream features. There are two distinct data streams that occur in Gigabit Ethernet where identical data is transmitted for a period of time. The first is configuration, which happens during auto-negotiation. The second is idle, which occurs at the end of auto-negotiation and between every packet. The identical data in the FIFO can be repeated by decrementing the read pointer, thus compensating for a FIFO that is draining too fast. The identical data in the FIFO can also be skipped by incrementing the read pointer, which compensates for a FIFO draining too slowly. The unique and novel features of this FIFO are that it works in both the idle stream and the configuration streams. The increment or decrement of the read pointer is different in the idle and compensation streams to preserve disparity. Another unique feature is that the read pointer to write pointer difference range changes between compensation and idle to minimize FIFO latency during packet transmission.

Role of monochromatic light on daily variation of clock gene expression in the pineal gland of chick.

PubMed

Jiang, Nan; Wang, Zixu; Cao, Jing; Dong, Yulan; Chen, Yaoxing

2016-11-01

The avian pineal gland is a master clock that can receive external photic cues and translate them into output rhythms. To clarify whether a shift in light wavelength can influence the circadian expression in chick pineal gland, a total of 240 Arbor Acre male broilers were exposed to white light (WL), red light (RL), green light (GL) or blue light (BL). After 2weeks light illumination, circadian expressions of seven core clock genes in pineal gland and the level of melatonin in plasma were examined. The results showed after illumination with monochromatic light, 24h profiles of all clock gene mRNAs retained circadian oscillation, except that RL tended to disrupt the rhythm of cCry2. Compared to WL, BL advanced the acrophases of the negative elements (cCry1, cCry2, cPer2 and cPer3) by 0.1-1.5h and delayed those of positive elements (cClock, cBmal1 and cBmal2) by 0.2-0.8h. And, RL advanced all clock genes except cClock and cPer2 by 0.3-2.1h, while GL delayed all clock genes by 0.5-1.5h except cBmal2. Meanwhile, GL increased the amplitude and mesor of positive and reduced both parameters of negative clock genes, but RL showed the opposite pattern. Although the acrophase of plasma melatonin was advanced by both GL and RL, the melatonin level was significantly increased in GL and decreased in RL. This tendency was consistent with the variations in the positive clock gene mRNA levels under monochromatic light and contrasted with those of negative clock genes. Therefore, we speculate that GL may enhance positive clock genes expression, leading to melatonin synthesis, whereas RL may enhance negative genes expression, suppressing melatonin synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Guo, Jiang; Geng, Jianghui

2017-12-01

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

A closer look at the concept of regional clocks for Precise Point Positioning

NASA Astrophysics Data System (ADS)

Weber, Robert; Karabatic, Ana; Thaler, Gottfried; Abart, Christoph; Huber, Katrin

2010-05-01

Under the precondition of at least two successfully tracked signals at different carrier frequencies we may obtain their ionosphere free linear combination. By introducing approximate values for geometric effects like orbits and tropospheric delay as well as an initial bias parameter N per individual satellite we can solve for the satellite clock with respect to the receiver clock. Noting, that residual effects like orbit errors, remaining tropospheric delays and a residual bias parameter map into these parameters, this procedure leaves us with a kind of virtual clock differences. These clocks cover regional effects and are therefore clearly correlated with clocks at nearby station. Therefore we call these clock differences, which are clearly different from clock solutions provided for instance by IGS, the "regional clocks". When introducing the regional clocks obtained from real-time data of a GNSS reference station network we are able to process the coordinates of a nearby isolated station via a PPP .In terms of PPP-convergence time which will be reduced down to 30 minutes or less, this procedure is clearly favorable. The accuracy is quite comparable with state of the art PPP procedures. Nevertheless, this approach cannot compete in fixing times with double-difference approaches but the correlation holds over hundreds of kilometers distance to our master station and the clock differences can easily by obtained, even in real-time. This presentation provides preliminary results of the project RA-PPP. RA-PPP is a research project financed by the Federal Ministry for Transport, Innovation and Technology, managed by the Austrian Research Promotion Agency (FFG) in the course of the 6th call of the Austrian Space Application Program (ASAP). RA-PPP stands for Rapid Precise Point Positioning, which denotes the wish for faster and more accurate algorithms for PPP. The concept of regional clocks which will be demonstrated in detail in this presentation is one out of 4 concepts to be evaluated in this project.

Improved Short-Term Clock Prediction Method for Real-Time Positioning.

PubMed

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

2017-06-06

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

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

PubMed

Brown, Richard P; Yang, Ziheng

2011-09-26

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

Clock recovery for high-speed optical communication

NASA Astrophysics Data System (ADS)

Pedrotti, Kenneth D.

1996-01-01

This paper reviews recent results for clock recovery circuits operating at speeds in excess of 1 Gbit/sec or realized as multichannel arrays. The emphasis is on synchronous optical network (SONET) type systems, their requirements, and the effect of the clock recovery circuits on system performance. Clock recovery approaches include filter based, phase-locked-loops, and all-optical methods.

Clock recovery for high-speed optical communication

NASA Astrophysics Data System (ADS)

Pedrotti, Ken

1996-01-01

This paper reviews recent results for clock recovery circuits operating at speeds in excess of 1 Gbit/sec or realized as multichannel arrays. The emphasis is on Synchronous Optical NETwork (SONET) type systems, their requirements, and the effect of the clock recovery circuits on system performance. Clock recovery approaches include filter based, phase-lockcd-loops, and all-optical methods.

Sound Affects the Speed of Visual Processing

ERIC Educational Resources Information Center

Keetels, Mirjam; Vroomen, Jean

2011-01-01

The authors examined the effects of a task-irrelevant sound on visual processing. Participants were presented with revolving clocks at or around central fixation and reported the hand position of a target clock at the time an exogenous cue (1 clock turning red) or an endogenous cue (a line pointing toward 1 of the clocks) was presented. A…

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

ERIC Educational Resources Information Center

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

2013-01-01

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

High-speed clock recovery with phase-locked-loop-based on LiNbO3 modulators

NASA Astrophysics Data System (ADS)

Zhu, Guanghao; Chen, Hongmin; Wang, Qiang; Dutta, Niloy K.

2003-08-01

In this paper, we present a scheme for recovering 10 GHz clock from 40 Gb/s and 80 Gb/s time division multiplexed (TDM) return to zero (RZ) data stream. The proposed clock recovery is successfully demonstrated using an electrical phase locked loop (PLL). The jitter of the recovered clock is estimated to be around 50 fs. The key part in the proposed clock recovery circuit is a LiNbO3 Mach-Zehnder modulator which is shown to be highly effective in optical to electrical down conversion.

A novel approach for clock recovery without pattern effect from degraded signal

NASA Astrophysics Data System (ADS)

Wang, Zhaoxin; Wang, Tong; Lou, Caiyun; Huo, Li; Gao, Yizhi

2003-04-01

A novel clock recovery scheme using two-ring injection mode-locked fiber ring laser based on all 10 GHz bandwidth components was demonstrated. With this scheme, the clock with low timing jitter was obtained from a degraded 10 Gb/s optical data stream. Optical clock recovery was also achieved from a degraded 20 Gb/s optical data train when the clock division technique in the opto-electronic oscillator (OEO) and the rational harmonic mode-locking technique in the fiber ring laser were applied. No pattern effect was observed in the experiments.

Precise time transfer using MKIII VLBI technology

NASA Technical Reports Server (NTRS)

Johnston, K. J.; Buisson, J. A.; Lister, M. J.; Oaks, O. J.; Spencer, J. H.; Waltman, W. B.; Elgered, G.; Lundqvist, G.; Rogers, A. E. E.; Clark, T. A.

1984-01-01

It is well known that Very Long Baseline Interferometry (VLBI) is capable of precise time synchronization at subnanosecond levels. This paper deals with a demonstration of clock synchronization using the MKIII VBLI system. The results are compared with clock synchronization by traveling cesium clocks and GPS. The comparison agrees within the errors of the portable clocks (+ 5 ns) and GPS(+ or - 30 ns) systems. The MKIII technology appears to be capable of clock synchronization at subnanosecond levels and appears to be very good benchmark system against which future time synchronization systems can be evaluated.

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

NASA Technical Reports Server (NTRS)

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.

Advancing the state-of-the-art of the optical atomic clock

NASA Astrophysics Data System (ADS)

Ye, Jun

2014-05-01

The continued advance in laser phase coherence has permitted an improvement of the stability of optical lattice clocks by a factor of 10. This measurement precision has facilitated characterization of systematic effects, allowing us to improve the lattice clock accuracy by a factor of 20. The accuracy and stability of the JILA Sr clock now reach the 10-18 level. Owing to these advances, the lattice clock has also emerged as an effective laboratory to study many-body spin correlations. NIST, NSF, DARPA-QuASAR.

METAS New Time Scale Generation System - A Progress Report

DTIC Science & Technology

2007-01-01

and a TWSTFT station are used for remote T&F comparisons. The GPS TAI link is driven by one of the atomic clocks defined as the REF clock...UTC(CH.P) paper clock TA(CH.P) paper clock TWSTFT link GPS link CH00 WAB1 H-maser 1-PPS H-maser 1-PPS REF 1-PPS 5-MHz from all clocks UTC(CH.R) 1-PPS...lost, the only consequence would be a transient of UTC (CH.P), which can be corrected by a subsequent steering. The GPS and TWSTFT links can be

Feedback repression is required for mammalian circadian clock function.

PubMed

Sato, Trey K; Yamada, Rikuhiro G; Ukai, Hideki; Baggs, Julie E; Miraglia, Loren J; Kobayashi, Tetsuya J; Welsh, David K; Kay, Steve A; Ueda, Hiroki R; Hogenesch, John B

2006-03-01

Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive. Here, we developed a molecular genetic screen in mammalian cells to identify mutants of the circadian transcriptional activators CLOCK and BMAL1, which were uncoupled from CRYPTOCHROME (CRY)-mediated transcriptional repression. Notably, mutations in the PER-ARNT-SIM domain of CLOCK and the C terminus of BMAL1 resulted in synergistic insensitivity through reduced physical interactions with CRY. Coexpression of these mutant proteins in cultured fibroblasts caused arrhythmic phenotypes in population and single-cell assays. These data demonstrate that CRY-mediated repression of the CLOCK/BMAL1 complex activity is required for maintenance of circadian rhythmicity and provide formal proof that transcriptional feedback is required for mammalian clock function.

Initial atomic coherences and Ramsey frequency pulling in fountain clocks

NASA Astrophysics Data System (ADS)

Gerginov, Vladislav; Nemitz, Nils; Weyers, Stefan

2014-09-01

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

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

NASA Astrophysics Data System (ADS)

Chen, Wantong

2016-09-01

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

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

PubMed Central

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

2015-01-01

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

A proportional integral estimator-based clock synchronization protocol for wireless sensor networks.

PubMed

Yang, Wenlun; Fu, Minyue

2017-11-01

Clock synchronization is an issue of vital importance in applications of WSNs. This paper proposes a proportional integral estimator-based protocol (EBP) to achieve clock synchronization for wireless sensor networks. As each local clock skew gradually drifts, synchronization accuracy will decline over time. Compared with existing consensus-based approaches, the proposed synchronization protocol improves synchronization accuracy under time-varying clock skews. Moreover, by restricting synchronization error of clock skew into a relative small quantity, it could reduce periodic re-synchronization frequencies. At last, a pseudo-synchronous implementation for skew compensation is introduced as synchronous protocol is unrealistic in practice. Numerical simulations are shown to illustrate the performance of the proposed protocol. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Regulation of the Rhythmic Emission of Plant Volatiles by the Circadian Clock.

PubMed

Zeng, Lanting; Wang, Xiaoqin; Kang, Ming; Dong, Fang; Yang, Ziyin

2017-11-13

Like other organisms, plants have endogenous biological clocks that enable them to organize their metabolic, physiological, and developmental processes. The representative biological clock is the circadian system that regulates daily (24-h) rhythms. Circadian-regulated changes in growth have been observed in numerous plants. Evidence from many recent studies indicates that the circadian clock regulates a multitude of factors that affect plant metabolites, especially emitted volatiles that have important ecological functions. Here, we review recent progress in research on plant volatiles showing rhythmic emission under the regulation of the circadian clock, and on how the circadian clock controls the rhythmic emission of plant volatiles. We also discuss the potential impact of other factors on the circadian rhythmic emission of plant volatiles.

An expanding universe of circadian networks in higher plants.

PubMed

Pruneda-Paz, Jose L; Kay, Steve A

2010-05-01

Extensive circadian clock networks regulate almost every biological process in plants. Clock-controlled physiological responses are coupled with daily oscillations in environmental conditions resulting in enhanced fitness and growth vigor. Identification of core clock components and their associated molecular interactions has established the basic network architecture of plant clocks, which consists of multiple interlocked feedback loops. A hierarchical structure of transcriptional feedback overlaid with regulated protein turnover sets the pace of the clock and ultimately drives all clock-controlled processes. Although originally described as linear entities, increasing evidence suggests that many signaling pathways can act as both inputs and outputs within the overall network. Future studies will determine the molecular mechanisms involved in these complex regulatory loops. 2010 Elsevier Ltd. All rights reserved.

High-speed clock recovery unit based on a phase aligner

NASA Astrophysics Data System (ADS)

Tejera, Efrain; Esper-Chain, Roberto; Tobajas, Felix; De Armas, Valentin; Sarmiento, Roberto

2003-04-01

Nowadays clock recovery units are key elements in high speed digital communication systems. For an efficient operation, this units should generate a low jitter clock based on the NRZ received data, and be tolerant to long absence of transitions. Architectures based on Hogge phase detectors have been widely used, nevertheless, they are very sensitive to jitter of the received data and they have a limited tolerance to the absence of transitions. This paper shows a novel high speed clock recovery unit based on a phase aligner. The system allows a very fast clock recovery with a low jitter, moreover, it is very resistant to absence of transitions. The design is based on eight phases obtained from a reference clock running at the nominal frequency of the received signal. This high speed reference clock is generated using a crystal and a clock multiplier unit. The phase alignment system chooses, as starting point, the two phases closest to the data phase. This allows a maximum error of 45 degrees between the clock and data signal phases. Furthermore, the system includes a feed-back loop that interpolates the chosen phases to reduce the phase error to zero. Due to the high stability and reduced tolerance of the local reference clock, the jitter obtained is highly reduced and the system becomes able to operate under long absence of transitions. This performances make this design suitable for systems such as high speed serial link technologies. This system has been designed for CMOS 0.25μm at 1.25GHz and has been verified through HSpice simulations.

nocte Is Required for Integrating Light and Temperature Inputs in Circadian Clock Neurons of Drosophila.

PubMed

Chen, Chenghao; Xu, Min; Anantaprakorn, Yuto; Rosing, Mechthild; Stanewsky, Ralf

2018-05-21

Circadian clocks organize biological processes to occur at optimized times of day and thereby contribute to overall fitness. While the regular daily changes of environmental light and temperature synchronize circadian clocks, extreme external conditions can bypass the temporal constraints dictated by the clock. Despite advanced knowledge about how the daily light-dark changes synchronize the clock, relatively little is known with regard to how the daily temperature changes influence daily timing and how temperature and light signals are integrated. In Drosophila, a network of ∼150 brain clock neurons exhibit 24-hr oscillations of clock gene expression to regulate daily activity and sleep. We show here that a temperature input pathway from peripheral sensory organs, which depends on the gene nocte, targets specific subsets of these clock neurons to synchronize molecular and behavioral rhythms to temperature cycles. Strikingly, while nocte 1 mutant flies synchronize normally to light-dark cycles at constant temperatures, the combined presence of light-dark and temperature cycles inhibits synchronization. nocte 1 flies exhibit altered siesta sleep, suggesting that the sleep-regulating clock neurons are an important target for nocte-dependent temperature input, which dominates a parallel light input into these cells. In conclusion, we reveal a nocte-dependent temperature input pathway to central clock neurons and show that this pathway and its target neurons are important for the integration of sensory light and temperature information in order to temporally regulate activity and sleep during daily light and temperature cycles. Copyright © 2018 Elsevier Ltd. All rights reserved.

Machine Learning Helps Identify CHRONO as a Circadian Clock Component

PubMed Central

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

2014-01-01

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

Synthesizing genetic sequential logic circuit with clock pulse generator

PubMed Central

2014-01-01

Background Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. Results This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. Conclusions A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal. PMID:24884665

Stable Kalman filters for processing clock measurement data

NASA Technical Reports Server (NTRS)

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

1989-01-01

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

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

PubMed

Ci, Haipeng; Wu, Nan; Su, Yanjie

2014-01-01

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

Master/slave clock arrangement for providing reliable clock signal

NASA Technical Reports Server (NTRS)

Abbey, Duane L. (Inventor)

1977-01-01

The outputs of two like frequency oscillators are combined to form a single reliable clock signal, with one oscillator functioning as a slave under the control of the other to achieve phase coincidence when the master is operative and in a free-running mode when the master is inoperative so that failure of either oscillator produces no effect on the clock signal.

CLOCKΔ19 mutation modifies the manner of synchrony among oscillation neurons in the suprachiasmatic nucleus.

PubMed

Sujino, Mitsugu; Asakawa, Takeshi; Nagano, Mamoru; Koinuma, Satoshi; Masumoto, Koh-Hei; Shigeyoshi, Yasufumi

2018-01-16

In mammals, the principal circadian oscillator exists in the hypothalamic suprachiasmatic nucleus (SCN). In the SCN, CLOCK works as an essential component of molecular circadian oscillation, and ClockΔ19 mutant mice show unique characteristics of circadian rhythms such as extended free running periods, amplitude attenuation, and high-magnitude phase-resetting responses. Here we investigated what modifications occur in the spatiotemporal organization of clock gene expression in the SCN of ClockΔ19 mutants. The cultured SCN, sampled from neonatal homozygous ClockΔ19 mice on an ICR strain comprising PERIOD2::LUCIFERASE, demonstrated that the Clock gene mutation not only extends the circadian period, but also affects the spatial phase and period distribution of circadian oscillations in the SCN. In addition, disruption of the synchronization among neurons markedly attenuated the amplitude of the circadian rhythm of individual oscillating neurons in the mutant SCN. Further, with numerical simulations based on the present studies, the findings suggested that, in the SCN of the ClockΔ19 mutant mice, stable oscillation was preserved by the interaction among oscillating neurons, and that the orderly phase and period distribution that makes a phase wave are dependent on the functionality of CLOCK.

Redox rhythm reinforces the circadian clock to gate immune response.

PubMed

Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E; Dong, Xinnian

2015-07-23

Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism's metabolic activities. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant's redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism.

Noninertial coordinate time: A new concept affecting time standards, time transfers, and clock synchronization

NASA Technical Reports Server (NTRS)

Deines, Steven D.

1992-01-01

Relativity compensations must be made in precise and accurate measurements whenever an observer is accelerated. Although many believe the Earth-centered frame is sufficiently inertial, accelerations of the Earth, as evidenced by the tides, prove that it is technically a noninertial system for even an Earth-based observer. Using the constant speed of light, a set of fixed remote clocks in an inertial frame can be synchronized to a fixed master clock transmitting its time in that frame. The time on the remote clock defines the coordinate time at that coordinate position. However, the synchronization procedure for an accelerated frame is affected, because the distance between the master and remote clocks is altered due to the acceleration of the remote clock toward or away from the master clock during the transmission interval. An exact metric that converts observations from noninertial frames to inertial frames was recently derived. Using this metric with other physical relationships, a new concept of noninertial coordinate time is defined. This noninertial coordinate time includes all relativity compensations. This new issue raises several timekeeping issues, such as proper time standards, time transfer process, and clock synchronization, all in a noninertial frame such as Earth.

Transcriptional Control of Antioxidant Defense by the Circadian Clock

PubMed Central

Patel, Sonal A.; Velingkaar, Nikkhil S.

2014-01-01

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

High speed imager test station

DOEpatents

Yates, George J.; Albright, Kevin L.; Turko, Bojan T.

1995-01-01

A test station enables the performance of a solid state imager (herein called a focal plane array or FPA) to be determined at high image frame rates. A programmable waveform generator is adapted to generate clock pulses at determinable rates for clock light-induced charges from a FPA. The FPA is mounted on an imager header board for placing the imager in operable proximity to level shifters for receiving the clock pulses and outputting pulses effective to clock charge from the pixels forming the FPA. Each of the clock level shifters is driven by leading and trailing edge portions of the clock pulses to reduce power dissipation in the FPA. Analog circuits receive output charge pulses clocked from the FPA pixels. The analog circuits condition the charge pulses to cancel noise in the pulses and to determine and hold a peak value of the charge for digitizing. A high speed digitizer receives the peak signal value and outputs a digital representation of each one of the charge pulses. A video system then displays an image associated with the digital representation of the output charge pulses clocked from the FPA. In one embodiment, the FPA image is formatted to a standard video format for display on conventional video equipment.

High speed imager test station

DOEpatents

Yates, G.J.; Albright, K.L.; Turko, B.T.

1995-11-14

A test station enables the performance of a solid state imager (herein called a focal plane array or FPA) to be determined at high image frame rates. A programmable waveform generator is adapted to generate clock pulses at determinable rates for clock light-induced charges from a FPA. The FPA is mounted on an imager header board for placing the imager in operable proximity to level shifters for receiving the clock pulses and outputting pulses effective to clock charge from the pixels forming the FPA. Each of the clock level shifters is driven by leading and trailing edge portions of the clock pulses to reduce power dissipation in the FPA. Analog circuits receive output charge pulses clocked from the FPA pixels. The analog circuits condition the charge pulses to cancel noise in the pulses and to determine and hold a peak value of the charge for digitizing. A high speed digitizer receives the peak signal value and outputs a digital representation of each one of the charge pulses. A video system then displays an image associated with the digital representation of the output charge pulses clocked from the FPA. In one embodiment, the FPA image is formatted to a standard video format for display on conventional video equipment. 12 figs.

Association between genetic variants of the clock gene and obesity and sleep duration.

PubMed

Valladares, Macarena; Obregón, Ana María; Chaput, Jean-Philippe

2015-12-01

Obesity is a multifactorial disease caused by the interaction of genetic and environmental factors related to lifestyle aspects. It has been shown that reduced sleep is associated with increased body mass index (BMI). Circadian Locomotor Output Cycles Kaput (CLOCK) gene variants have also been associated with obesity. The objective of this mini-review was to discuss the available literature related to CLOCK gene variants associated with adiposity and sleep duration in humans. In total, 16 articles complied with the terms of the search that reported CLOCK variants associated with sleep duration, energy intake, and BMI. Overall, six CLOCK single nucleotide polymorphisms (SNPs) have been associated with sleep duration, and three variants have been associated with energy intake variables. Overall, the most studied area has been the association of CLOCK gene with obesity; close to eight common variants have been associated with obesity. The most studied CLOCK SNP in different populations is rs1801260, and most of these populations correspond to European populations. Collectively, identifying at risk CLOCK genotypes is a new area of research that may help identify individuals who are more susceptible to overeating and gaining weight when exposed to short sleep durations.

A Role for Timely Nuclear Translocation of Clock Repressor Proteins in Setting Circadian Clock Speed

PubMed Central

Lee, Euna

2014-01-01

By means of a circadian clock system, all the living organisms on earth including human beings can anticipate the environmental rhythmic changes such as light/dark and warm/cold periods in a daily as well as in a yearly manner. Anticipating such environmental changes provide organisms with survival benefits via manifesting behavior and physiology at an advantageous time of the day and year. Cell-autonomous circadian oscillators, governed by transcriptional feedback loop composed of positive and negative elements, are organized into a hierarchical system throughout the organisms and generate an oscillatory expression of a clock gene by itself as well as clock controlled genes (ccgs) with a 24 hr periodicity. In the feedback loop, hetero-dimeric transcription factor complex induces the expression of negative regulatory proteins, which in turn represses the activity of transcription factors to inhibit their own transcription. Thus, for robust oscillatory rhythms of the expression of clock genes as well as ccgs, the precise control of subcellular localization and/or timely translocation of core clock protein are crucial. Here, we discuss how sub-cellular localization and nuclear translocation are controlled in a time-specific manner focusing on the negative regulatory clock proteins. PMID:25258565

The impact of routine cognitive screening by using the clock drawing task in the evaluation of elderly patients in the emergency department.

PubMed

Salen, Philip; Heller, Michael; Oller, Carlo; Reed, James

2009-07-01

The prevalence of cognitive impairment, as reflected by failure to correctly perform a clock drawing task, in elderly Emergency Department (ED) patients was assessed. Additionally, we evaluated whether primary care provider notification of cognitive impairment spurred further cognitive evaluation. The clock drawing task was administered to a convenience sample of 100 elderly, English-speaking subjects presenting for reasons other than altered mentation at a community hospital ED. Primary care providers were contacted regarding abnormal clock drawing task results immediately and again after 2 months to determine if there was further evaluation of cognition. Of the 100 subjects enrolled, 30% were unable to correctly complete the clock drawing task, but only 8 had further evaluation of their cognitive abilities, resulting in four new diagnoses of dementia. Subjects who drew incorrect clocks (54%; 16/30) were more likely to be reevaluated in the ED within 2 months than those who drew correct clocks (29%; 20/70; p < 0.02). Cognitive screening of elderly ED patients with the clock drawing task identified a substantial number with unsuspected abnormal cognition. Further evaluation by their primary care physicians in follow-up was disappointing.

Frequency stability of on-orbit GPS Block-I and Block-II Navstar clocks

NASA Astrophysics Data System (ADS)

McCaskill, Thomas B.; Reid, Wilson G.; Buisson, James A.

On-orbit analysis of the Global Positioning System (GPS) Block-I and Block-II Navstar clocks has been performed by the Naval Research Laboratory using a multi-year database. The Navstar clock phase-offset measurements were computed from pseudorange measurements made by the five GPS monitor sites and from the U.S. Naval Observatory precise-time site using single or dual frequency GPS receivers. Orbital data was obtained from the Navstar broadcast ephemeris and from the best-fit, postprocessed orbital ephemerides supplied by the Naval Surface Weapons Center or by the Defense Mapping Agency. Clock performance in the time domain is characterized using frequency-stability profiles with sample times that vary from 1 to 100 days. Composite plots of Navstar frequency stability and time-prediction uncertainty are included as a summary of clock analysis results. The analysis includes plots of the clock phase offset and frequency offset histories with the eclipse seasons superimposed on selected plots to demonstrate the temperature sensitivity of one of the Block-I Navstar rubidium clocks. The potential impact on navigation and on transferring precise time of the degradation in the long-term frequency stability of the rubidium clocks is discussed.

Applications of Clocks to Space Navigation & "Planetary GPS"

NASA Technical Reports Server (NTRS)

Lichten, Stephen M.

2004-01-01

The ability to fly atomic clocks on GPS satellites has profoundly defined the capabilities and limitations of GPS in near-Earth applications. It is likely that future infrastructure for Lunar and Mars applications will be constrained by financial factors. The development of a low cost, small, high performance space clock -- or ultrahigh performance space clocks -- could revolutionize and drive the entire approach to GPS-like systems at the Moon (or Mars), and possibly even change the future of GPS at Earth. Many system trade studies are required. The performance of future GPS-like tracking systems at the Moon or Mars will depend critically on clock performance, availability of inertial sensors, and constellation coverage. Example: present-day GPS carry 10(exp -13) clocks and require several updates per day. With 10(exp -15) clocks, a constellation at Mars could operate autonomously with updates just once per month. Use of GPS tracking at the Moon should be evaluated in a technical study.

Public health assessment for public health implications of radiation contamination at former clock factories located in Bristo (Hartford County), New Haven, (New Haven County), Thomaston (Litchfield County), and Waterbury (New Haven County), Connecticut, Region 1. Final report

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

NONE

This public health assessment was developed (1) to evaluate the radiation data collected by the Connecticut Department of Environmental Protection (CT DEP) at structures that once housed clock factories in four Connecticut municipalities, and (2) to determine whether a public health hazard exists at any of these sites from the contamination. Contamination was detected at levels that may pose a health risk to current occupants at the former Waterbury Clock Factory, the former Lux Clock Factory, and the former Benrus Clock Company buildings in Waterbury; the former Sessions Clock Company in Bristol; and the former Seth Thomas Clock Company inmore » Thomaston. However, none of the radiation levels detected pose an immediate health problem. The Connecticut Department of Public Health recommends that individuals be disassociated from areas with radiation at levels exceeding 15 mRem/year.« less

Inexpensive Clock for Displaying Planetary or Sidereal Time

NASA Technical Reports Server (NTRS)

Lux, James

2007-01-01

An inexpensive wall clock has been devised for displaying solar time or sidereal time as it would be perceived on a planet other than the Earth, or for displaying sidereal time on the Earth. The concept of a wall clock synchronized to a period other than the terrestrial mean solar day is not new in itself. What is new here is that the clock is realized through a relatively simple electronic modification of a common battery-powered, quartz-crystal-oscillator-driven wall clock. The essence of the modification is to shut off the internal oscillator of the clock and replace the internal-oscillator output signal with a signal of the required frequency generated by an external oscillator. The unmodified clock electronic circuitry includes a quartz crystal connected to an integrated circuit (IC) that includes, among other parts, a buffer amplifier that conditions the oscillator output. The modification is effected by removing the quartz crystal and connecting the output terminal of the external oscillator, via a capacitor, to the input terminal of the buffer amplifier

Clock Drawing as a Screen for Impaired Driving in Aging and Dementia: Is It Worth the Time?

PubMed Central

Manning, Kevin J.; Davis, Jennifer D.; Papandonatos, George D.; Ott, Brian R.

2014-01-01

Clock drawing is recommended by medical and transportation authorities as a screening test for unsafe drivers. The objective of the present study was to assess the usefulness of different clock drawing systems as screening measures of driving performance in 122 healthy and cognitively impaired older drivers. Clock drawing was measured using four different scoring systems. Driving outcomes included global ratings of safety and the error rate on a standardized on-road test. Findings revealed that clock drawing was significantly correlated with the driving score on the road test for each of the scoring systems. However, receiver operator curve analyses showed limited clinical utility for clock drawing as a screening instrument for impaired on-road driving performance with the area under the curve ranging from 0.53 to 0.61. Results from this study indicate that clock drawing has limited utility as a solitary screening measure of on-road driving, even when considering a variety of scoring approaches. PMID:24296110

Clock drawing as a screen for impaired driving in aging and dementia: is it worth the time?

PubMed

Manning, Kevin J; Davis, Jennifer D; Papandonatos, George D; Ott, Brian R

2014-02-01

Clock drawing is recommended by medical and transportation authorities as a screening test for unsafe drivers. The objective of the present study was to assess the usefulness of different clock drawing systems as screening measures of driving performance in 122 healthy and cognitively impaired older drivers. Clock drawing was measured using four different scoring systems. Driving outcomes included global ratings of safety and the error rate on a standardized on-road test. Findings revealed that clock drawing was significantly correlated with the driving score on the road test for each of the scoring systems. However, receiver operator curve analyses showed limited clinical utility for clock drawing as a screening instrument for impaired on-road driving performance with the area under the curve ranging from 0.53 to 0.61. Results from this study indicate that clock drawing has limited utility as a solitary screening measure of on-road driving, even when considering a variety of scoring approaches.

A clock network for geodesy and fundamental science

PubMed Central

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

2016-01-01

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

Systematic evaluation of an atomic clock at 2 × 10−18 total uncertainty

PubMed Central

Nicholson, T.L.; Campbell, S.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.

2015-01-01

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. Here we take an important step towards realizing the full potential of a many-particle clock with a state-of-the-art stable laser. Our 87Sr optical lattice clock now achieves fractional stability of 2.2 × 10−16 at 1 s. With this improved stability, we perform a new accuracy evaluation of our clock, reducing many systematic uncertainties that limited our previous measurements, such as those in the lattice ac Stark shift, the atoms' thermal environment and the atomic response to room-temperature blackbody radiation. Our combined measurements have reduced the total uncertainty of the JILA Sr clock to 2.1 × 10−18 in fractional frequency units. PMID:25898253

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

PubMed

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

2017-07-20

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

Towards Self-Clocked Gated OCDMA Receiver

NASA Astrophysics Data System (ADS)

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

2013-02-01

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

A clock network for geodesy and fundamental science.

PubMed

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

2016-08-09

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

Circadian expression profiles of chromatin remodeling factor genes in Arabidopsis.

PubMed

Lee, Hong Gil; Lee, Kyounghee; Jang, Kiyoung; Seo, Pil Joon

2015-01-01

The circadian clock is a biological time keeper mechanism that regulates biological rhythms to a period of approximately 24 h. The circadian clock enables organisms to anticipate environmental cycles and coordinates internal cellular physiology with external environmental cues. In plants, correct matching of the clock with the environment confers fitness advantages to plant survival and reproduction. Therefore, circadian clock components are regulated at multiple layers to fine-tune the circadian oscillation. Epigenetic regulation provides an additional layer of circadian control. However, little is known about which chromatin remodeling factors are responsible for circadian control. In this work, we analyzed circadian expression of 109 chromatin remodeling factor genes and identified 17 genes that display circadian oscillation. In addition, we also found that a candidate interacts with a core clock component, supporting that clock activity is regulated in part by chromatin modification. As an initial attempt to elucidate the relationship between chromatin modification and circadian oscillation, we identified novel regulatory candidates that provide a platform for future investigations of chromatin regulation of the circadian clock.

Science Goals of the Primary Atomic Reference Clock in Space (PARCS) Experiment

NASA Technical Reports Server (NTRS)

Ashby, N.

2003-01-01

The PARCS (Primary Atomic Reference Clock in Space) experiment will use a laser-cooled Cesium atomic clock operating in the microgravity environment aboard the International Space Station (ISS) to provide both advanced tests of gravitational theory and to demonstrate a new cold-atom clock technology for space. PARCS is a joint project of the National Institute of Standards and Technology (NIST), NASA's Jet Propulsion Laboratory (JPL), and the University of Colorado (CU). This paper concentrates on the scientific goals of the PARCS mission. The microgravity space environment allows laser-cooled Cs atoms to have Ramsey times in excess of those feasible on Earth, resulting in improved clock performance. Clock stabilities of 5x10(exp -14) at one second, and accuracies better than 10(exp -16) are projected.

All-polarization-maintaining, single-port Er:fiber comb for high-stability comparison of optical lattice clocks

NASA Astrophysics Data System (ADS)

Ohmae, Noriaki; Kuse, Naoya; Fermann, Martin E.; Katori, Hidetoshi

2017-06-01

All-polarization-maintaining, single-port Er:fiber combs offer long-term robust operation as well as high stability. We have built two such combs and evaluated the transfer noise for linking optical clocks. A uniformly broadened spectrum over 135-285 THz with a high signal-to-noise ratio enables the optical frequency measurement of the subharmonics of strontium, ytterbium, and mercury optical lattice clocks with the fractional frequency-noise power spectral density of (1-2) × 10-17 Hz-1/2 at 1 Hz. By applying a synchronous clock comparison, the comb enables clock ratio measurements with 10-17 instability at 1 s, which is one order of magnitude smaller than the best instability of the frequency ratio of optical lattice clocks.

Molecular Mechanisms Regulating Temperature Compensation of the Circadian Clock.

PubMed

Narasimamurthy, Rajesh; Virshup, David M

2017-01-01

An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep-wake cycle, feeding-fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks. But, unlike other chemical reactions, the output of the clock system remains nearly constant with fluctuations in ambient temperature, a phenomenon known as temperature compensation. In this brief review, we focus on recent advances in our understanding of the posttranslational modifications, especially a phosphoswitch mechanism controlling the stability of PER2 and its implications for the regulation of temperature compensation.

Synthesis of energy-efficient FSMs implemented in PLD circuits

NASA Astrophysics Data System (ADS)

Nawrot, Radosław; Kulisz, Józef; Kania, Dariusz

2017-11-01

The paper presents an outline of a simple synthesis method of energy-efficient FSMs. The idea consists in using local clock gating to selectively block the clock signal, if no transition of a state of a memory element is required. The research was dedicated to logic circuits using Programmable Logic Devices as the implementation platform, but the conclusions can be applied to any synchronous circuit. The experimental section reports a comparison of three methods of implementing sequential circuits in PLDs with respect to clock distribution: the classical fully synchronous structure, the structure exploiting the Enable Clock inputs of memory elements, and the structure using clock gating. The results show that the approach based on clock gating is the most efficient one, and it leads to significant reduction of dynamic power consumed by the FSM.

Quantum Algorithmic Readout in Multi-Ion Clocks.

PubMed

Schulte, M; Lörch, N; Leroux, I D; Schmidt, P O; Hammerer, K

2016-01-08

Optical clocks based on ensembles of trapped ions promise record frequency accuracy with good short-term stability. Most suitable ion species lack closed transitions, so the clock signal must be read out indirectly by transferring the quantum state of the clock ions to cotrapped logic ions of a different species. Existing methods of quantum logic readout require a linear overhead in either time or the number of logic ions. Here we describe a quantum algorithmic readout whose overhead scales logarithmically with the number of clock ions in both of these respects. The scheme allows a quantum nondemolition readout of the number of excited clock ions using a single multispecies gate operation which can also be used in other areas of ion trap technology such as quantum information processing, quantum simulations, metrology, and precision spectroscopy.

A polarization converting device for an interfering enhanced CPT atomic clock.

PubMed

Wang, Kewei; Tian, Yuan; Yin, Yi; Wang, Yuanchao; Gu, Sihong

2017-11-01

With interfering enhanced coherent population trapping (CPT) signals, a CPT atomic clock with improved frequency stability performance can be realized. We explore an optical device that converts single-polarized bichromatic light to left and right circularly polarized superposed bichromatic light to generate interfering enhanced CPT resonance with atoms. We have experimentally studied a tabletop CPT atomic clock apparatus with a microfabricated 87 Rb atomic chip-scale cell, and the study results show that it is promising to realize a compact CPT atomic clock, even a chip-scale CPT atomic clock through microfabrication, with improved frequency stability performance.

The New Countdown Clock is Turned on for the First Time

NASA Image and Video Library

2014-12-01

At NASA's Kennedy Space Center in Florida, the new countdown clock at the spaceport's Press Site is being tested. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex.

The Shroud is Put Over the New Countdown Clock

NASA Image and Video Library

2014-12-09

At NASA's Kennedy Space Center in Florida, a shade is placed around the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen is nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has acquired the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex.

Countdown Clock Ribbon Cutting

NASA Image and Video Library

2016-03-01

Kennedy Space Center Director Bob Cabana, left, and Therrin Protze, chief operating officer of Kennedy's Visitor Complex, celebrate the dedication of the spaceport's historic countdown clock as the newest display at the center's visitor complex. Now located at the entrance to the visitor complex, the spaceport's historic countdown clock was used starting with the launch of Apollo 12 on Nov. 14, 1969. Originally set up at the space center's Press Site, the clock operated through the final space shuttle mission, STS-135, launched on July 8, 2011. The old countdown clock was replaced in 2014 with a modern light emitting diode, or LED, display.

Countdown Clock Ribbon Cutting

NASA Image and Video Library

2016-03-01

Therrin Protze, chief operating officer of the Kennedy Space Center Visitor Complex, speaks at the dedication of the center's historic countdown clock. To the right is space center director Bob Cabana. Now located at the entrance to the visitor complex, the spaceport's historic countdown clock was used starting with the launch of Apollo 12 on Nov. 14, 1969. Originally set up at the space center's Press Site, the clock was used through the final space shuttle mission, STS-135, launched on July 8, 2011. The old countdown clock was replaced in 2014 with a modern light emitting diode, or LED, display.

Countdown Clock Ribbon Cutting

NASA Image and Video Library

2016-03-01

Therrin Protze, chief operating officer of the Kennedy Space Center Visitor Complex, left, and center director Bob Cabana watch as confetti was launched as the spaceport's historic countdown clock is dedicated as the newest display at the entrance to Kennedy's visitor complex. The spaceport's historic countdown clock was used beginning with the launch of Apollo 12 on Nov. 14, 1969. Originally set up at the space center's Press Site, the clock was used through the final space shuttle mission, STS-135, launched on July 8, 2011. The old countdown clock was replaced in 2014 with a modern light emitting diode, or LED, display.

A polarization converting device for an interfering enhanced CPT atomic clock

NASA Astrophysics Data System (ADS)

Wang, Kewei; Tian, Yuan; Yin, Yi; Wang, Yuanchao; Gu, Sihong

2017-11-01

With interfering enhanced coherent population trapping (CPT) signals, a CPT atomic clock with improved frequency stability performance can be realized. We explore an optical device that converts single-polarized bichromatic light to left and right circularly polarized superposed bichromatic light to generate interfering enhanced CPT resonance with atoms. We have experimentally studied a tabletop CPT atomic clock apparatus with a microfabricated 87Rb atomic chip-scale cell, and the study results show that it is promising to realize a compact CPT atomic clock, even a chip-scale CPT atomic clock through microfabrication, with improved frequency stability performance.

Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health.

PubMed

Ribas-Latre, Aleix; Eckel-Mahan, Kristin

2016-03-01

While additional research is needed, a number of large epidemiological studies show an association between circadian disruption and metabolic disorders. Specifically, obesity, insulin resistance, cardiovascular disease, and other signs of metabolic syndrome all have been linked to circadian disruption in humans. Studies in other species support this association and generally reveal that feeding that is not in phase with the external light/dark cycle, as often occurs with night or rotating shift workers, is disadvantageous in terms of energy balance. As food is a strong driver of circadian rhythms in the periphery, understanding how nutrient metabolism drives clocks across the body is important for dissecting out why circadian misalignment may produce such metabolic effects. A number of circadian clock proteins as well as their accessory proteins (such as nuclear receptors) are highly sensitive to nutrient metabolism. Macronutrients and micronutrients can function as zeitgebers for the clock in a tissue-specific way and can thus impair synchrony between clocks across the body, or potentially restore synchrony in the case of circadian misalignment. Circadian nuclear receptors are particularly sensitive to nutrient metabolism and can alter tissue-specific rhythms in response to changes in the diet. Finally, SNPs in human clock genes appear to be correlated with diet-specific responses and along with chronotype eventually may provide valuable information from a clinical perspective on how to use diet and nutrition to treat metabolic disorders. This article presents a background of the circadian clock components and their interrelated metabolic and transcriptional feedback loops, followed by a review of some recent studies in humans and rodents that address the effects of nutrient metabolism on the circadian clock and vice versa. We focus on studies in which results suggest that nutrients provide an opportunity to restore or, alternatively, can destroy synchrony between peripheral clocks and the central pacemaker in the brain as well as between peripheral clocks themselves. In addition, we review several studies looking at clock gene SNPs in humans and the metabolic phenotypes or tendencies associated with particular clock gene mutations. Targeted use of specific nutrients based on chronotype has the potential for immense clinical utility in the future. Macronutrients and micronutrients have the ability to function as zeitgebers for the clock by activating or modulating specific clock proteins or accessory proteins (such as nuclear receptors). Circadian clock control by nutrients can be tissue-specific. With a better understanding of the mechanisms that support nutrient-induced circadian control in specific tissues, human chronotype and SNP information might eventually be used to tailor nutritional regimens for metabolic disease treatment and thus be an important part of personalized medicine's future.

Eight-Channel Continuous Timer

NASA Technical Reports Server (NTRS)

Cole, Steven

2004-01-01

A custom laboratory electronic timer circuit measures the durations of successive cycles of nominally highly stable input clock signals in as many as eight channels, for the purpose of statistically quantifying the small instabilities of these signals. The measurement data generated by this timer are sent to a personal computer running software that integrates the measurements to form a phase residual for each channel and uses the phase residuals to compute Allan variances for each channel. (The Allan variance is a standard statistical measure of instability of a clock signal.) Like other laboratory clock-cycle-measuring circuits, this timer utilizes an externally generated reference clock signal having a known frequency (100 MHz) much higher than the frequencies of the input clock signals (between 100 and 120 Hz). It counts the number of reference-clock cycles that occur between successive rising edges of each input clock signal of interest, thereby affording a measurement of the input clock-signal period to within the duration (10 ns) of one reference clock cycle. Unlike typical prior laboratory clock-cycle-measuring circuits, this timer does not skip some cycles of the input clock signals. The non-cycle-skipping feature is an important advantage because in applications that involve integration of measurements over long times for characterizing nominally highly stable clock signals, skipping cycles can degrade accuracy. The timer includes a field-programmable gate array that functions as a 20-bit counter running at the reference clock rate of 100 MHz. The timer also includes eight 20-bit latching circuits - one for each channel - at the output terminals of the counter. Each transition of an input signal from low to high causes the corresponding latching circuit to latch the count at that instant. Each such transition also sets a status flip-flop circuit to indicate the presence of the latched count. A microcontroller reads the values of all eight status flipflops and then reads the latched count for each channel for which the flip-flop indicates the presence of a count. Reading the count for each channel automatically causes the flipflop of that channel to be reset. The microcontroller places the counts in time order, identifies the channel number for each count, and transmits these data to the personal computer.

Investigating the detection of multi-homed devices independent of operating systems

DTIC Science & Technology

2017-09-01

timestamp data was used to estimate clock skews using linear regression and linear optimization methods. Analysis revealed that detection depends on...the consistency of the estimated clock skew. Through vertical testing, it was also shown that clock skew consistency depends on the installed...optimization methods. Analysis revealed that detection depends on the consistency of the estimated clock skew. Through vertical testing, it was also

The Square Light Clock and Special Relativity

ERIC Educational Resources Information Center

Galli, J. Ronald; Amiri, Farhang

2012-01-01

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

Estimation of accuracy of time synchronization obtained by means of clock transportation

NASA Astrophysics Data System (ADS)

Zhang, Yuzhen; Ma, Dekang; Jin, Wenjing; Zhao, Gang; Huang, Peicheng

A portable clock experiment was carried out in October 1985 between Shanghai Observatory and Beijing Observatory using a small quartz clock made in Switzerland. The accuracy of time synchronization in 5 days is 70.18 microsec and the accuracy of determining the transmission time of short wave is satisfactory for reduction of the astronomical observations to the same master clock.

Segregation of Clock and Non-Clock Regulatory Functions of REV-ERB.

PubMed

Butler, Andrew A; Burris, Thomas P

2015-08-04

The molecular clock is a master controller of circadian cellular processes that affect growth, metabolic homeostasis, and behavior. A report in Science by Zhang et al. (2015) redefines our understanding of how Rev-erba acts as an internal feedback inhibitor that modulates activity of the core clock while simultaneously regulating tissue-specific metabolic processes. Copyright © 2015 Elsevier Inc. All rights reserved.

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

NASA Technical Reports Server (NTRS)

Maleki, L.

2001-01-01

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

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

NASA Technical Reports Server (NTRS)

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.

Circadian signaling in Homarus americanus: Region-specific de novo assembled transcriptomes show that both the brain and eyestalk ganglia possess the molecular components of a putative clock system.

PubMed

Christie, Andrew E; Yu, Andy; Pascual, Micah G; Roncalli, Vittoria; Cieslak, Matthew C; Warner, Amanda N; Lameyer, Tess J; Stanhope, Meredith E; Dickinson, Patsy S; Joe Hull, J

2018-04-11

Essentially all organisms exhibit recurring patterns of physiology/behavior that oscillate with a period of ~24-h and are synchronized to the solar day. Crustaceans are no exception, with robust circadian rhythms having been documented in many members of this arthropod subphylum. However, little is known about the molecular underpinnings of their circadian rhythmicity. Moreover, the location of the crustacean central clock has not been firmly established, although both the brain and eyestalk ganglia have been hypothesized as loci. The American lobster, Homarus americanus, is known to exhibit multiple circadian rhythms, and immunodetection data suggest that its central clock is located within the eyestalk ganglia rather than in the brain. Here, brain- and eyestalk ganglia-specific transcriptomes were generated and used to assess the presence/absence of transcripts encoding the commonly recognized protein components of arthropod circadian signaling systems in these two regions of the lobster central nervous system. Transcripts encoding putative homologs of the core clock proteins clock, cryptochrome 2, cycle, period and timeless were found in both the brain and eyestalk ganglia assemblies, as were transcripts encoding similar complements of putative clock-associated, clock input pathway and clock output pathway proteins. The presence and identity of transcripts encoding core clock proteins in both regions were confirmed using PCR. These findings suggest that both the brain and eyestalk ganglia possess all of the molecular components needed for the establishment of a circadian signaling system. Whether the brain and eyestalk clocks are independent of one another or represent a single timekeeping system remains to be determined. Interestingly, while most of the proteins deduced from the identified transcripts are shared by both the brain and eyestalk ganglia, assembly-specific isoforms were also identified, e.g., several period variants, suggesting the possibility of region-specific variation in clock function, especially if the brain and eyestalk clocks represent independent oscillators. Copyright © 2018 Elsevier B.V. All rights reserved.

Light Stimulates the Mouse Adrenal through a Retinohypothalamic Pathway Independent of an Effect on the Clock in the Suprachiasmatic Nucleus

PubMed Central

Kiessling, Silke; Sollars, Patricia J.; Pickard, Gary E.

2014-01-01

The brain's master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed to peripheral organs: 1) via retinal input to SCN clock neurons; 2) via retinal input to non-clock neurons in the SCN; or 3) via retinal input to hypothalamic regions neighboring the SCN. It is very well documented that light-induced responses of the SCN clock (i.e., clock gene expression, neural activity, and behavioral phase shifts) occur primarily during the subjective night. Thus to determine the role of the SCN clock in transmitting photic signals to descending autonomic circuits, we compared the phase dependency of light-evoked responses in the SCN and a peripheral oscillator, the adrenal gland. We observed light-evoked clock gene expression in the mouse adrenal throughout the subjective day and subjective night. Light also induced adrenal corticosterone secretion during both the subjective day and subjective night. The irradiance threshold for light-evoked adrenal responses was greater during the subjective day compared to the subjective night. These results suggest that retinohypothalamic signals may be relayed to the adrenal clock during the subjective day by a retinal pathway or cellular mechanism that is independent of an effect of light on the SCN neural clock network and thus may be important for the temporal integration of physiology and metabolism. PMID:24658072

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

PubMed

Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

2017-01-01

Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian circuit to generate robust 24-h rhythms.

A review of atomic clock technology, the performance capability of present spaceborne and terrestrial atomic clocks, and a look toward the future

NASA Technical Reports Server (NTRS)

Vessot, Robert F. C.

1989-01-01

Clocks have played a strong role in the development of general relativity. The concept of the proper clock is presently best realized by atomic clocks, whose development as precision instruments has evolved very rapidly in the last decades. To put a historical prospective on this progress since the year AD 1000, the time stability of various clocks expressed in terms of seconds of time error over one day of operation is shown. This stability of operation must not be confused with accuracy. Stability refers to the constancy of a clock operation as compared to that of some other clocks that serve as time references. Accuracy, on the other hand, is the ability to reproduce a previously defined frequency. The issues are outlined that must be considered when accuracy and stability of clocks and oscillators are studied. In general, the most widely used resonances result from the hyperfine interaction of the nuclear magnetic dipole moment and that of the outermost electron, which is characteristic of hydrogen and the alkali atoms. During the past decade hyperfine resonances of ions have also been used. The principal reason for both the accuracy and the stability of atomic clocks is the ability of obtaining very narrow hyperfine transition resonances by isolating the atom in some way so that only the applied stimulating microwave magnetic field is a significant source of perturbation. It is also important to make resonance transitions among hyperfine magnetic sublevels where separation is independent, at least to first order, of the magnetic field. In the case of ions stored in traps operating at high magnetic fields, one selects the trapping field to be consistent with a field-independent transition of the trapped atoms.

Glucocorticoids Affect 24 h Clock Genes Expression in Human Adipose Tissue Explant Cultures

PubMed Central

Gómez-Abellán, Purificación; Díez-Noguera, Antoni; Madrid, Juan A.; Luján, Juan A.; Ordovás, José M.; Garaulet, Marta

2012-01-01

Aims to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression. Subjects and Methods VAT and SAT biopsies were obtained from morbid obese women (body mass index≥40 kg/m2) (n = 6). In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX) and AT explants treated with DEX (2 hours) were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR. Results CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element) was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements) in the SAT (situation not present in VAT). A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues. Conclusions 24 h patterns in CLOCK and BMAL1 (positive clock elements) and PER2 (negative element) mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure. PMID:23251369

Bayesian random local clocks, or one rate to rule them all

PubMed Central

2010-01-01

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

An out-of-lab trial: a case example for the effect of intensive exercise on rhythms of human clock gene expression

PubMed Central

2013-01-01

Background Although out-of-lab investigation of the human circadian clock at the clock gene expression level remains difficult, a recent method using hair follicle cells might be useful. While exercise may function as an entrainment cue for circadian rhythms, it remains unclear whether exercise affects human circadian clock gene expression. Methods Efforts to observe apparent effects of exercise on clock gene expression require that several specific conditions be met: intense exercise should be habitually performed at a relatively uncommon time of day over an extended period; and any relative phase shift thereby observed should be validated by comparison of exercise and no-exercise periods. Wake-up and meal times should be kept almost constant over the experimental period. The present study was conducted using a professional fighter who met these strict criteria as subject. Facial hair samples were collected at 4-h intervals around the clock to ascertain rhythms of clock gene expression. Results During a period in which nighttime training (from 20:00 to 22:00) was habitually performed, circadian clock gene expression was phase-delayed by 2 to 4 h compared with that during a no-exercise period. Maximum level and circadian amplitude of clock gene expression were not affected by the nighttime training. Conclusion Our trial observations illustrate the possibility that heavy physical exercise might strongly affect the circadian phase of clock gene expression. Exercise might be therefore effective for the clinical care of circadian disorders. The results also suggest that athletes may require careful scheduling of heavy physical exercise to maintain normal circadian phase and ensure optimal athletic performance. PMID:24004634

Circadian Rhythms, the Molecular Clock, and Skeletal Muscle

PubMed Central

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

2015-01-01

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 ClockΔ19 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. PMID:21621073

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

NASA Astrophysics Data System (ADS)

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

2006-12-01

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

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

PubMed Central

Zordan, Mauro Agostino; Sandrelli, Federica

2015-01-01

There is evidence of a link between the circadian system and psychiatric diseases. Studies in humans and mammals suggest that environmental and/or genetic disruption of the circadian system leads to an increased liability to psychiatric disease. Disruption of clock genes and/or the clock network might be related to the etiology of these pathologies; also, some genes, known for their circadian clock functions, might be associated to mental illnesses through clock-independent pleiotropy. Here, we examine the features which we believe make Drosophila melanogaster a model apt to study the role of the circadian clock in psychiatric disease. Despite differences in the organization of the clock system, the molecular architecture of the Drosophila and mammalian circadian oscillators are comparable and many components are evolutionarily related. In addition, Drosophila has a rather complex nervous system, which shares much at the cell and neurobiological level with humans, i.e., a tripartite brain, the main neurotransmitter systems, and behavioral traits: circadian behavior, learning and memory, motivation, addiction, social behavior. There is evidence that the Drosophila brain shares some homologies with the vertebrate cerebellum, basal ganglia, and hypothalamus-pituitary-adrenal axis, the dysfunctions of which have been tied to mental illness. We discuss Drosophila in comparison to mammals with reference to the: organization of the brain and neurotransmitter systems; architecture of the circadian clock; clock-controlled behaviors. We sum up current knowledge on behavioral endophenotypes, which are amenable to modeling in flies, such as defects involving sleep, cognition, or social interactions, and discuss the relationship of the circadian system to these traits. Finally, we consider if Drosophila could be a valuable asset to understand the relationship between circadian clock malfunction and psychiatric disease. PMID:25941512

Hyperpolarizability and Operational Magic Wavelength in an Optical Lattice Clock

NASA Astrophysics Data System (ADS)

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

2017-12-01

Optical clocks benefit from tight atomic confinement enabling extended interrogation times as well as Doppler- and recoil-free operation. However, these benefits come at the cost of frequency shifts that, if not properly controlled, may degrade clock accuracy. Numerous theoretical studies have predicted optical lattice clock frequency shifts that scale nonlinearly with trap depth. To experimentally observe and constrain these shifts in an 171Yb optical lattice clock, we construct a lattice enhancement cavity that exaggerates the light shifts. We observe an atomic temperature that is proportional to the optical trap depth, fundamentally altering the scaling of trap-induced light shifts and simplifying their parametrization. We identify an "operational" magic wavelength where frequency shifts are insensitive to changes in trap depth. These measurements and scaling analysis constitute an essential systematic characterization for clock operation at the 10-18 level and beyond.

Kruppel-like factor KLF10 is a link between the circadian clock and metabolism in liver.

PubMed

Guillaumond, Fabienne; Gréchez-Cassiau, Aline; Subramaniam, Malayannan; Brangolo, Sophie; Peteri-Brünback, Brigitta; Staels, Bart; Fiévet, Catherine; Spelsberg, Thomas C; Delaunay, Franck; Teboul, Michèle

2010-06-01

The circadian timing system coordinates many aspects of mammalian physiology and behavior in synchrony with the external light/dark cycle. These rhythms are driven by endogenous molecular clocks present in most body cells. Many clock outputs are transcriptional regulators, suggesting that clock genes primarily control physiology through indirect pathways. Here, we show that Krüppel-like factor 10 (KLF10) displays a robust circadian expression pattern in wild-type mouse liver but not in clock-deficient Bmal1 knockout mice. Consistently, the Klf10 promoter recruited the BMAL1 core clock protein and was transactivated by the CLOCK-BMAL1 heterodimer through a conserved E-box response element. Profiling the liver transcriptome from Klf10(-/-) mice identified 158 regulated genes with significant enrichment for transcripts involved in lipid and carbohydrate metabolism. Importantly, approximately 56% of these metabolic genes are clock controlled. Male Klf10(-/-) mice displayed postprandial and fasting hyperglycemia, a phenotype accompanied by a significant time-of-day-dependent upregulation of the gluconeogenic gene Pepck and increased hepatic glucose production. Consistently, functional data showed that the proximal Pepck promoter is repressed directly by KLF10. Klf10(-/-) females were normoglycemic but displayed higher plasma triglycerides. Correspondingly, rhythmic gene expression of components of the lipogenic pathway, including Srebp1c, Fas, and Elovl6, was altered in females. Collectively, these data establish KLF10 as a required circadian transcriptional regulator that links the molecular clock to energy metabolism in the liver.

Time maintenance system for the BMDO MSX spacecraft

NASA Technical Reports Server (NTRS)

Hermes, Martin J.

1994-01-01

The Johns Hopkins University Applied Physics Laboratory (APL) is responsible for designing and implementing a clock maintenance system for the Ballistic Missile Defense Organizations (BMDO) Midcourse Space Experiment (MSX) spacecraft. The MSX spacecraft has an on-board clock that will be used to control execution of time-dependent commands and to time tag all science and housekeeping data received from the spacecraft. MSX mission objectives have dictated that this spacecraft time, UTC(MSX), maintain a required accuracy with respect to UTC(USNO) of +/- 10 ms with a +/- 1 ms desired accuracy. APL's atomic time standards and the downlinked spacecraft time were used to develop a time maintenance system that will estimate the current MSX clock time offset during an APL pass and make estimates of the clock's drift and aging using the offset estimates from many passes. Using this information, the clock's accuracy will be maintained by uplinking periodic clock correction commands. The resulting time maintenance system is a combination of offset measurement, command/telemetry, and mission planning hardware and computing assets. All assets provide necessary inputs for deciding when corrections to the MSX spacecraft clock must be made to maintain its required accuracy without inhibiting other mission objectives. The MSX time maintenance system is described as a whole and the clock offset measurement subsystem, a unique combination of precision time maintenance and measurement hardware controlled by a Macintosh computer, is detailed. Simulations show that the system estimates the MSX clock offset to less than+/- 33 microseconds.

Subnanosecond GPS-based clock synchronization and precision deep-space tracking

NASA Technical Reports Server (NTRS)

Dunn, C. E.; Lichten, S. M.; Jefferson, D. C.; Border, J. S.

1992-01-01

Interferometric spacecraft tracking is accomplished by the Deep Space Network (DSN) by comparing the arrival time of electromagnetic spacecraft signals at ground antennas separated by baselines on the order of 8000 km. Clock synchronization errors within and between DSN stations directly impact the attainable tracking accuracy, with a 0.3-nsec error in clock synchronization resulting in an 11-nrad angular position error. This level of synchronization is currently achieved by observing a quasar which is angularly close to the spacecraft just after the spacecraft observations. By determining the differential arrival times of the random quasar signal at the stations, clock offsets and propagation delays within the atmosphere and within the DSN stations are calibrated. Recent developments in time transfer techniques may allow medium accuracy (50-100 nrad) spacecraft tracking without near-simultaneous quasar-based calibrations. Solutions are presented for a worldwide network of Global Positioning System (GPS) receivers in which the formal errors for DSN clock offset parameters are less than 0.5 nsec. Comparisons of clock rate offsets derived from GPS measurements and from very long baseline interferometry (VLBI), as well as the examination of clock closure, suggest that these formal errors are a realistic measure of GPS-based clock offset precision and accuracy. Incorporating GPS-based clock synchronization measurements into a spacecraft differential ranging system would allow tracking without near-simultaneous quasar observations. The impact on individual spacecraft navigation-error sources due to elimination of quasar-based calibrations is presented. System implementation, including calibration of station electronic delays, is discussed.

Sub-nanosecond clock synchronization and precision deep space tracking

NASA Technical Reports Server (NTRS)

Dunn, Charles; Lichten, Stephen; Jefferson, David; Border, James S.

1992-01-01

Interferometric spacecraft tracking is accomplished at the NASA Deep Space Network (DSN) by comparing the arrival time of electromagnetic spacecraft signals to ground antennas separated by baselines on the order of 8000 km. Clock synchronization errors within and between DSN stations directly impact the attainable tracking accuracy, with a 0.3 ns error in clock synchronization resulting in an 11 nrad angular position error. This level of synchronization is currently achieved by observing a quasar which is angularly close to the spacecraft just after the spacecraft observations. By determining the differential arrival times of the random quasar signal at the stations, clock synchronization and propagation delays within the atmosphere and within the DSN stations are calibrated. Recent developments in time transfer techniques may allow medium accuracy (50-100 nrad) spacecraft observations without near-simultaneous quasar-based calibrations. Solutions are presented for a global network of GPS receivers in which the formal errors in clock offset parameters are less than 0.5 ns. Comparisons of clock rate offsets derived from GPS measurements and from very long baseline interferometry and the examination of clock closure suggest that these formal errors are a realistic measure of GPS-based clock offset precision and accuracy. Incorporating GPS-based clock synchronization measurements into a spacecraft differential ranging system would allow tracking without near-simultaneous quasar observations. The impact on individual spacecraft navigation error sources due to elimination of quasar-based calibrations is presented. System implementation, including calibration of station electronic delays, is discussed.

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

PubMed Central

Kim, Min-Ho; Rao, Neethi Varadaraja; Bonilla, Gloribel; Wijnen, Herman

2011-01-01

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex. PMID:21750685

Frequency Standards and Metrology

NASA Astrophysics Data System (ADS)

Maleki, Lute

2009-04-01

Preface / Lute Maleki -- Symposium history / Jacques Vanier -- Symposium photos -- pt. I. Fundamental physics. Variation of fundamental constants from the big bang to atomic clocks: theory and observations (Invited) / V. V. Flambaum and J. C. Berengut. Alpha-dot or not: comparison of two single atom optical clocks (Invited) / T. Rosenband ... [et al.]. Variation of the fine-structure constant and laser cooling of atomic dysprosium (Invited) / N. A. Leefer ... [et al.]. Measurement of short range forces using cold atoms (Invited) / F. Pereira Dos Santos ... [et al.]. Atom interferometry experiments in fundamental physics (Invited) / S. W. Chiow ... [et al.]. Space science applications of frequency standards and metrology (Invited) / M. Tinto -- pt. II. Frequency & metrology. Quantum metrology with lattice-confined ultracold Sr atoms (Invited) / A. D. Ludlow ... [et al.]. LNE-SYRTE clock ensemble: new [symbol]Rb hyperfine frequency measurement - spectroscopy of [symbol]Hg optical clock transition (Invited) / M. Petersen ... [et al.]. Precise measurements of S-wave scattering phase shifts with a juggling atomic clock (Invited) / S. Gensemer ... [et al.]. Absolute frequency measurement of the [symbol] clock transition (Invited) / M. Chwalla ... [et al.]. The semiclassical stochastic-field/atom interaction problem (Invited) / J. Camparo. Phase and frequency noise metrology (Invited) / E. Rubiola ... [et al.]. Optical spectroscopy of atomic hydrogen for an improved determination of the Rydberg constant / J. L. Flowers ... [et al.] -- pt. III. Clock applications in space. Recent progress on the ACES mission (Invited) / L. Cacciapuoti and C. Salomon. The SAGAS mission (Invited) / P. Wolf. Small mercury microwave ion clock for navigation and radioScience (Invited) / J. D. Prestage ... [et al.]. Astro-comb: revolutionizing precision spectroscopy in astrophysics (Invited) / C. E. Kramer ... [et al.]. High frequency very long baseline interferometry: frequency standards and imaging an event horizon (Invited) / S. Doeleman. Optically-pumped space cesium clock for Galileo: results of the breadboard / R. Ruffieux ... [et al.] -- pt. IV. Optical clocks I: lattice clocks. Optical lattice clock: seven years of progress and next steps (Invited) / H. Katori, M. Takamoto and T. Akatsuka. The Yb optical lattice clock (Invited) / N. D. Demke ... [et al.]. Optical Lattice clock with Sr atoms (Invited) / P. G. Westergaard ... [et al.]. Development of an optical clock based on neutral strontium atoms held in a lattice trap / E. A. Curtis ... [et al.]. Decoherence and losses by collisions in a [symbol]Sr lattice clock / J. S. R. Vellore Winfred ... [et al.]. Lattice Yb optical clock and cryogenic Cs fountain at INRIM / F. Levi ... [et al.] -- pt. V. Optical clocks II: ion clocks. [Symbol]Yb+ single-ion optical frequency standards (Invited) / Chr. Tamm ... [et al.]. An optical clock based on a single trapped [symbol]Sr+ ion (Invited) / H. S. Margolis ... [et al.]. A trapped [symbol]Yb+ ion optical frequency standard based on the [symbol] transition (Invited) / P. Gill ... [et al.]. Overview of highly accurate RF and optical frequency standards at the National Research Council of Canada (Invited) / A. A. Madej ... [et al.] -- pt. VI. Optical frequency combs. Extreme ultraviolet frequency combs for spectroscopy (Invited) / A. Ozawa ... [et al.]. Development of an optical clockwork for the single trapped strontium ion standard at 445 THz / J. E. Bernard ... [et al.]. A phase-coherent link between the visible and infrared spectral ranges using a combination of CW OPO and femtosecond laser frequency comb / E. V. Kovalchuk and A. Peters. Improvements to the robustness of a TI: sapphire-based femtosecond comb at NPL / V. Tsatourian ... [et al.] -- pt. VII. Atomic microwave standards. NIST FI and F2 (Invited) / T. P. Heavner ... [et al.]. Atomic fountains for the USNO master clock (Invited) / C. Ekstrom ... [et al.]. The transportable cesium fountain clock NIM5: its construction and performance (Invited) / T. Li ... [et al.].Compensated multi-pole mercury trapped ion frequency standard and stability evaluation of systematic effects (Invited) / E. A. Burt ... [et al.]. Research of frequency standards in SIOM - atomic frequency standards based on coherent storage (Invited) / B. Yan ... [et al.]. The PTB fountain clock ensemble preliminary characterization of the new fountain CSF2 / N. Nemitz ... [et al.]. The pulsed optically pumped clock: microwave and optical detection / S. Micalizio ... [et al.]. Research on characteristics of pulsed optically pumped rubidium frequency standard / J. Deng ... [et al.]. Status of the continuous cold fountain clocks at METAS-LTF / A. Joyet ... [et al.]. Experiments with a new [symbol]Hg+ ion clock / E. A. Burt ... [et al.]. Optimising a high-stability CW laser-pumped rubidium gas-cell frequency standard / C. Affolderbach ... [et al.]. Raman-Ramsey Cs cell atomic clock / R. Boudot ... [et al.] -- pt. VIII. Microwave resonators & oscillators. Solutions and ultimate limits in temperature compensation of metallic cylindrical microwave resonators (Invited) / A. De Marchi. Cryogenic sapphire oscillators (Invited) / J. G. Hartnett, E. N. Ivanov and M. E. Tobar. Ultra-stable optical cavity: design and experiments / J. Millo ... [et al.]. New results for whispering gallery mode cryogenic sapphire maser oscillators / K. Benmessai ... [et al.] -- pt. IX. Advanced techniques. Fundamental noise-limited optical phase locking at Femtowatt light levels (Invited) / J. Dick ... [et al.]. Microwave and optical frequency transfer via optical fibre / G. Marra ... [et al.]. Ultra-stable laser source for the [symbol]Sr+ single-ion optical frequency standard at NRC / P. Dubé, A. A. Madej and J. E. Bernard. Clock laser system for a strontium lattice clock / T. Legero ... [et al.]. Measurement noise floor for a long-distance optical carrier transmission via fiber / G. Grosche ... [et al.]. Optical frequency transfer over 172 KM of installed fiber / S. Crane -- pt. X. Miniature systems. Chip-scale atomic devices: precision atomic instruments based on MEMS (Invited) / J. Kitching ... [et al.]. CSAC - the chip-scale atomic clock (Invited) / R. Lutwak ... [et al.]. Reaching a few 10[symbol] stability level with a compact cold atom clock / F. X. Esnault ... [et al.]. Evaluation of Lin||Lin CPT for compact and high performance frequency standard / E. Breschi ... [et al.] -- pt. XI. Time scales. Atomic time scales TAI and TI(BIPM): present status and prospects (Invited) / G. Petit. Weight functions for biases in atomic frequency standards / J. H. Shirley -- pt. XII. Interferometers. Definition and construction of noise budget in atom interferometry (Invited) / E. D'Ambriosio. Characterization of a cold atom gyroscope (Invited) / A. Landragin ... [et al.]. A mobile atom interferometer for high precision measurements of local gravity / M. Schmidt ... [et al.]. Demonstration of atom interferometer comprised of geometric beam splitters / Hiromitsu Imai and Atsuo Morinaga -- pt. XIII. New directions. Active optical clocks (Invited) / J. Chen. Prospects for a nuclear optical frequency standard based on Thorium-229 (Invited) / E. Peik ... [et al.]. Whispering gallery mode oscillators and optical comb generators (Invited) / A. B. Matsko ... [et al.]. Frequency comparison using energy-time entangled photons / A. Stefanov -- List of participants.

Array Receivers and Sound Sources for Three Dimensional Shallow Water Acoustic Field Experiments

DTIC Science & Technology

2016-12-06

upgrade included improving the SHRU clocks by utilizing chip- scale atomic clocks (CSAC), enlarging battery packs to extend the operation duration, and...instrument upgrade included improving the SHRU clocks by utilizing chip-scale atomic clocks (CSAC), enlarging battery packs to extend the operation...Changing the deployment configuration to use dual pressure housings to augment the alkaline primary battery payload to achieve the one-year duration

An Adaptive Method for Reducing Clock Skew in an Accumulative Z-Axis Interconnect System

NASA Technical Reports Server (NTRS)

Bolotin, Gary; Boyce, Lee

1997-01-01

This paper will present several methods for adjusting clock skew variations that occur in a n accumulative z-axis interconnect system. In such a system, delay between modules in a function of their distance from one another. Clock distribution in a high-speed system, where clock skew must be kept to a minimum, becomes more challenging when module order is variable before design.

PARCS-Primary Atomic Reference Clock in Space

NASA Astrophysics Data System (ADS)

Ashby, Neil

2000-04-01

The purpose of the PARCS project is to place an advanced Cesium clock on the International Space Station (ISS). The project has been approved by NASA at the level of Science Concept Review. Groups at the National Institute of Standards and Technology, Jet Propulsion Laboratory, University of Colorado, and Harvard-Smithsonian Astrophysical Observatory, University of Torino are collaborating on clock design and construction. The microgravity space environment allows laser-cooled Cs atoms to spend longer times in the beam, resulting in improved clock performance. Clock stabilities of 3 × 10-14 at one second and accuracies of 1 × 10-16 are projected. With improved clock performance, significant improvements in several fundamental special and general relativity experiments are expected. For an ISS orbit at 400 km altitude and eccentricity 0.02, the gravitational frequency shift should be measureable about 35 times better than the previous best, Gravity Probe A. Improvements in testing Local Position Invariance and in a Kennedy-Thorndike experiment are expected. Areas of technology such as world-wide timing and time transfer and navigation will also directly benefit from such a high-performance clock in space. This paper will briefly describe the PARCS clock. The principal limitations on performance of relativity experiments, scientific objectives and benefits, and projected outcomes, will be discussed.

Diurnal Variation in Vascular and Metabolic Function in Diet-Induced Obesity

PubMed Central

Prasai, Madhu J.; Mughal, Romana S.; Wheatcroft, Stephen B.; Kearney, Mark T.; Grant, Peter J.; Scott, Eleanor M.

2013-01-01

Circadian rhythms are integral to the normal functioning of numerous physiological processes. Evidence from human and mouse studies suggests that loss of rhythm occurs in obesity and cardiovascular disease and may be a neglected contributor to pathophysiology. Obesity has been shown to impair the circadian clock mechanism in liver and adipose tissue but its effect on cardiovascular tissues is unknown. We investigated the effect of diet-induced obesity in C57BL6J mice upon rhythmic transcription of clock genes and diurnal variation in vascular and metabolic systems. In obesity, clock gene function and physiological rhythms were preserved in the vasculature but clock gene transcription in metabolic tissues and rhythms of glucose tolerance and insulin sensitivity were blunted. The most pronounced attenuation of clock rhythm occurred in adipose tissue, where there was also impairment of clock-controlled master metabolic genes and both AMPK mRNA and protein. Across tissues, clock gene disruption was associated with local inflammation but diverged from impairment of insulin signaling. We conclude that vascular tissues are less sensitive to pathological disruption of diurnal rhythms during obesity than metabolic tissues and suggest that cellular disruption of clock gene rhythmicity may occur by mechanisms shared with inflammation but distinct from those leading to insulin resistance. PMID:23382450

Visuoconstructional Impairment in Subtypes of Mild Cognitive Impairment

PubMed Central

Ahmed, Samrah; Brennan, Laura; Eppig, Joel; Price, Catherine C.; Lamar, Melissa; Delano-Wood, Lisa; Bangen, Katherine J.; Edmonds, Emily C.; Clark, Lindsey; Nation, Daniel A.; Jak, Amy; Au, Rhoda; Swenson, Rodney; Bondi, Mark W.; Libon, David J.

2018-01-01

Clock Drawing Test performance was examined alongside other neuropsychological tests in mild cognitive impairment (MCI). We tested the hypothesis that clock-drawing errors are related to executive impairment. The current research examined 86 patients with MCI for whom, in prior research, cluster analysis was used to sort patients into dysexecutive (dMCI, n=22), amnestic (aMCI, n=13), and multi-domain (mMCI, n=51) subtypes. First, principal components analysis (PCA) and linear regression examined relations between clock-drawing errors and neuropsychological test performance independent of MCI subtype. Second, between-group differences were assessed with analysis of variance (ANOVA) where MCI subgroups were compared to normal controls (NC). PCA yielded a 3-group solution. Contrary to expectations, clock-drawing errors loaded with lower performance on naming/lexical retrieval, rather than with executive tests. Regression analyses found increasing clock-drawing errors to command were associated with worse performance only on naming/lexical retrieval tests. ANOVAs revealed no differences in clock-drawing errors between dMCI versus mMCI or aMCI versus NCs. Both the dMCI and mMCI groups generated more clock-drawing errors than the aMCI and NC groups in the command condition. In MCI, language-related skills contribute to clock-drawing impairment. PMID:26397732

Punctual Transcriptional Regulation by the Rice Circadian Clock under Fluctuating Field Conditions[OPEN

PubMed Central

Matsuzaki, Jun; Kawahara, Yoshihiro; Izawa, Takeshi

2015-01-01

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

GNSS Clock Error Impacts on Radio Occultation Retrievals

NASA Astrophysics Data System (ADS)

Weiss, Jan; Sokolovskiy, Sergey; Schreiner, Bill; Yoon, Yoke

2017-04-01

We assess the impacts of GPS and GLONASS clock errors on radio occultation retrieval of bending angle, refractivity, and temperature from low Earth orbit. The major contributing factor is the interpretation of GNSS clock offsets sampled at 30 sec or longer intervals. Using 1 Hz GNSS clock estimates as truth we apply several interpolation and fitting schemes to evaluate how they affect the accuracy of atmospheric retrieval products. The results are organized by GPS and GLONASS space vehicle and the GNSS clock interpolation/fitting scheme. We find that bending angle error is roughly similar for all current GPS transmitters (about 0.7 mcrad) but note some differences related to the type of atomic oscillator onboard the transmitter satellite. GLONASS bending angle errors show more variation over the constellation and are approximately two times larger than GPS. An investigation of the transmitter clock spectra reveals this is due to more power in periods between 2-10 sec. Retrieved refractivity and temperature products show clear differences between GNSS satellite generations, and indicate that GNSS clocks sampled at intervals smaller than 5 sec significantly improve accuracy, particularly for GLONASS. We conclude by summarizing the tested GNSS clock estimation and application strategies in the context of current and future radio occultation missions.

Proceedings of the Workshop on the Scientific Applications of Clocks in Space

NASA Technical Reports Server (NTRS)

Maleki, Lute (Editor)

1997-01-01

The Workshop on Scientific Applications of Clocks in space was held to bring together scientists and technologists interested in applications of ultrastable clocks for test of fundamental theories, and for other science investigations. Time and frequency are the most precisely determined of all physical parameters, and thus are the required tools for performing the most sensitive tests of physical theories. Space affords the opportunity to make measurement, parameters inaccessible on Earth, and enables some of the most original and sensitive tests of fundamental theories. In the past few years, new developments in clock technologies have pointed to the opportunity for flying ultrastable clocks in support of science investigations of space missions. This development coincides with the new NASA paradigm for space flights, which relies on frequent, low-cost missions in place of the traditional infrequent and high-cost missions. The heightened interest in clocks in space is further advanced by new theoretical developments in various fields. For example, recent developments in certain Grand Unified Theory formalisms have vastly increased interest in fundamental tests of gravitation physics with clocks. The workshop included sessions on all related science including relativity and gravitational physics, cosmology, orbital dynamics, radio science, geodynamics, and GPS science and others, as well as a session on advanced clock technology.

Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood.

PubMed

Hampp, Gabriele; Ripperger, Jürgen A; Houben, Thijs; Schmutz, Isabelle; Blex, Christian; Perreau-Lenz, Stéphanie; Brunk, Irene; Spanagel, Rainer; Ahnert-Hilger, Gudrun; Meijer, Johanna H; Albrecht, Urs

2008-05-06

The circadian clock has been implicated in addiction and several forms of depression [1, 2], indicating interactions between the circadian and the reward systems in the brain [3-5]. Rewards such as food, sex, and drugs influence this system in part by modulating dopamine neurotransmission in the mesolimbic dopamine reward circuit, including the ventral tegmental area (VTA) and the ventral striatum (NAc). Hence, changes in dopamine levels in these brain areas are proposed to influence mood in humans and mice [6-10]. To establish a molecular link between the circadian-clock mechanism and dopamine metabolism, we analyzed the murine promoters of genes encoding key enzymes important in dopamine metabolism. We find that transcription of the monoamine oxidase A (Maoa) promoter is regulated by the clock components BMAL1, NPAS2, and PER2. A mutation in the clock gene Per2 in mice leads to reduced expression and activity of MAOA in the mesolimbic dopaminergic system. Furthermore, we observe increased levels of dopamine and altered neuronal activity in the striatum, and these results probably lead to behavioral alterations observed in Per2 mutant mice in despair-based tests. These findings suggest a role of circadian-clock components in dopamine metabolism highlighting a role of the clock in regulating mood-related behaviors.

Agile Blocker and Clock Jitter Tolerant Low-Power Frequency Selective Receiver with Energy Harvesting Capability.

PubMed

Hasan, Abul; Helaoui, Mohamed; Ghannouchi, Fadhel M

2017-08-29

In this article, a novel tunable, blocker and clock jitter tolerant, low power, quadrature phase shift frequency selective (QPS-FS) receiver with energy harvesting capability is proposed. The receiver's design embraces and integrates (i) the baseband to radio frequency (RF) impedance translation concept to improve selectivity over that of conventional homodyne receiver topologies and (ii) broadband quadrature phase shift circuitry in the RF path to remove an active multi-phase clock generation circuit in passive mixer (PM) receivers. The use of a single local oscillator clock signal with a passive clock division network improves the receiver's robustness against clock jitter and reduces the source clock frequency by a factor of N, compared to PM receivers using N switches (N≥4). As a consequence, the frequency coverage of the QPS-FS receiver is improved by a factor of N, given a clock source of maximum frequency; and, the power consumption of the whole receiver system can eventually be reduced. The tunable QPS-FS receiver separates the wanted RF band signal from the unwanted blockers/interferers. The desired RF signal is frequency down-converted to baseband, while the undesired blocker/interferer signals are reflected by the receiver, collected and could be energy recycled using an auxiliary energy harvesting device.

Discrete gene replication events drive coupling between the cell cycle and circadian clocks

PubMed Central

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

2016-01-01

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

Discrete gene replication events drive coupling between the cell cycle and circadian clocks.

PubMed

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

2016-04-12

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

The New Countdown Clock is Turned on for the First Time

NASA Image and Video Library

2014-12-01

At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex.

The Last Panels are Installed on the New Countdown Clock

NASA Image and Video Library

2014-11-26

At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex.

Work Continues on Installing New Countdown Clock

NASA Image and Video Library

2014-11-26

At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex.

Atomic Clocks and Variations of the FIne Structure Constant

NASA Technical Reports Server (NTRS)

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.

Expression of Clock genes in the pineal glands of newborn rats with hypoxic-ischemic encephalopathy☆

PubMed Central

Sun, Bin; Feng, Xing; Ding, Xin; Bao, Li; Li, Yongfu; He, Jun; Jin, Meifang

2012-01-01

Clock genes are involved in circadian rhythm regulation, and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal. This study aimed to determine the expression of the clock genes Clock and Bmal1, in the pineal gland of rats with hypoxic-ischemic brain damage. Results showed that levels of Clock mRNA were not significantly changed within 48 hours after cerebral hypoxia and ischemia. Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours. The levels of Bmal1 mRNA reached a peak at 36 hours, but were significantly reduced at 48 hours. Experimental findings indicate that Clock and Bmal1 genes were indeed expressed in the pineal glands of neonatal rats. At the initial stage (within 36 hours) of hypoxic-ischemic brain damage, only slight changes in the expression levels of these two genes were detected, followed by significant changes at 36–48 hours. These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage. PMID:25538743

The Central Clock Neurons Regulate Lipid Storage in Drosophila

PubMed Central

DiAngelo, Justin R.; Erion, Renske; Crocker, Amanda; Sehgal, Amita

2011-01-01

A proper balance of lipid breakdown and synthesis is essential for achieving energy homeostasis as alterations in either of these processes can lead to pathological states such as obesity. The regulation of lipid metabolism is quite complex with multiple signals integrated to control overall triglyceride levels in metabolic tissues. Based upon studies demonstrating effects of the circadian clock on metabolism, we sought to determine if the central clock cells in the Drosophila brain contribute to lipid levels in the fat body, the main nutrient storage organ of the fly. Here, we show that altering the function of the Drosophila central clock neurons leads to an increase in fat body triglycerides. We also show that although triglyceride levels are not affected by age, they are increased by expression of the amyloid-beta protein in central clock neurons. The effect on lipid storage seems to be independent of circadian clock output as changes in triglycerides are not always observed in genetic manipulations that result in altered locomotor rhythms. These data demonstrate that the activity of the central clock neurons is necessary for proper lipid storage. PMID:21625640

Temperature compensation and temperature sensation in the circadian clock

PubMed Central

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

2015-01-01

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

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

NASA Astrophysics Data System (ADS)

Khosla, Kiran E.; Altamirano, Natacha

2017-05-01

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

Cost and Precision of Brownian Clocks

NASA Astrophysics Data System (ADS)

Barato, Andre C.; Seifert, Udo

2016-10-01

Brownian clocks are biomolecular networks that can count time. A paradigmatic example are proteins that go through a cycle, thus regulating some oscillatory behavior 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 the nonequilibrium steady state of the resulting bipartite Markov process, the uncertainty of the clock can be deduced from the calculable dispersion of a corresponding current.

The circadian clock stops ticking during deep hibernation in the European hamster

PubMed Central

Revel, Florent G.; Herwig, Annika; Garidou, Marie-Laure; Dardente, Hugues; Menet, Jérôme S.; Masson-Pévet, Mireille; Simonneaux, Valérie; Saboureau, Michel; Pévet, Paul

2007-01-01

Hibernation is a fascinating, yet enigmatic, physiological phenomenon during which body temperature and metabolism are reduced to save energy. During the harsh season, this strategy allows substantial energy saving by reducing body temperature and metabolism. Accordingly, biological processes are considerably slowed down and reduced to a minimum. However, the persistence of a temperature-compensated, functional biological clock in hibernating mammals has long been debated. Here, we show that the master circadian clock no longer displays 24-h molecular oscillations in hibernating European hamsters. The clock genes Per1, Per2, and Bmal1 and the clock-controlled gene arginine vasopressin were constantly expressed in the suprachiasmatic nucleus during deep torpor, as assessed by radioactive in situ hybridization. Finally, the melatonin rhythm-generating enzyme, arylalkylamine N-acetyltransferase, whose rhythmic expression in the pineal gland is controlled by the master circadian clock, no longer exhibits day/night changes of expression but constantly elevated mRNA levels over 24 h. Overall, these data provide strong evidence that in the European hamster the molecular circadian clock is arrested during hibernation and stops delivering rhythmic output signals. PMID:17715068

The Clock Mission Optis

NASA Astrophysics Data System (ADS)

Dittus, Hansjörg; Lämmerzahl, Claus

Clocks are an almost universal tool for exploring the fundamental structure of theories related to relativity. For future clock experiments, it is important for them to be performed in space. One mission which has the capability to perform and improve all relativity tests based on clocks by several orders of magnitude is OPTIS. These tests consist of (i) tests of the isotropy of light propagation (from which information about the matter sector which the optical resonators are made of can also be drawn), (ii) tests of the constancy of the speed of light, (iii) tests of the universality of the gravitational redshift by comparing clocks based on light propagation, like light clocks and various atomic clocks, (iv) time dilation based on the Doppler effect, (v) measuring the absolute gravitational redshift, (vi) measuring the perihelion advance of the satellite's orbit by using very precise tracking techniques, (vii) measuring the Lense-Thirring effect, and (viii) testing Newton's gravitational potential law on the scale of Earth-bound satellites. The corresponding tests are not only important for fundamental physics but also indispensable for practical purposes like navigation, Earth sciences, metrology, etc.

A Byzantine-Fault Tolerant Self-Stabilizing Protocol for Distributed Clock Synchronization Systems

NASA Technical Reports Server (NTRS)

Malekpour, Mahyar R.

2006-01-01

Embedded distributed systems have become an integral part of safety-critical computing applications, necessitating system designs that incorporate fault tolerant clock synchronization in order to achieve ultra-reliable assurance levels. Many efficient clock synchronization protocols do not, however, address Byzantine failures, and most protocols that do tolerate Byzantine failures do not self-stabilize. Of the Byzantine self-stabilizing clock synchronization algorithms that exist in the literature, they are based on either unjustifiably strong assumptions about initial synchrony of the nodes or on the existence of a common pulse at the nodes. The Byzantine self-stabilizing clock synchronization protocol presented here does not rely on any assumptions about the initial state of the clocks. Furthermore, there is neither a central clock nor an externally generated pulse system. The proposed protocol converges deterministically, is scalable, and self-stabilizes in a short amount of time. The convergence time is linear with respect to the self-stabilization period. Proofs of the correctness of the protocol as well as the results of formal verification efforts are reported.

Two Clock Transitions in Neutral Yb for the Highest Sensitivity to Variations of the Fine-Structure Constant.

PubMed

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

2018-04-27

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

Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

PubMed Central

Ben-Moshe, Zohar; Foulkes, Nicholas S.

2014-01-01

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

Two Clock Transitions in Neutral Yb for the Highest Sensitivity to Variations of the Fine-Structure Constant

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Trojan Horse Strategy for Non-invasive Interference of Clock Gene in the Oyster Crassostrea gigas.

PubMed

Payton, Laura; Perrigault, Mickael; Bourdineaud, Jean-Paul; Marcel, Anjara; Massabuau, Jean-Charles; Tran, Damien

2017-08-01

RNA interference is a powerful method to inhibit specific gene expression. Recently, silencing target genes by feeding has been successfully carried out in nematodes, insects, and small aquatic organisms. A non-invasive feeding-based RNA interference is reported here for the first time in a mollusk bivalve, the pacific oyster Crassostrea gigas. In this Trojan horse strategy, the unicellular alga Heterocapsa triquetra is the food supply used as a vector to feed oysters with Escherichia coli strain HT115 engineered to express the double-stranded RNA targeting gene. To test the efficacy of the method, the Clock gene, a central gene of the circadian clock, was targeted for knockout. Results demonstrated specific and systemic efficiency of the Trojan horse strategy in reducing Clock mRNA abundance. Consequences of Clock disruption were observed in Clock-related genes (Bmal, Tim1, Per, Cry1, Cry2, Rev.-erb, and Ror) and triploid oysters were more sensitive than diploid to the interference. This non-invasive approach shows an involvement of the circadian clock in oyster bioaccumulation of toxins produced by the harmful alga Alexandrium minutum.

What is dynamics in quantum gravity?

NASA Astrophysics Data System (ADS)

Małkiewicz, Przemysław

2017-10-01

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

One O'Clock, Two O'Clock, Three O'Clock Rock!

ERIC Educational Resources Information Center

Koontz, Elizabeth Duncan

1975-01-01

Considered the long period identified with the movement to bring women into full citizenship and participation at all social levels and the new effort to pass legislation that will grant women equal rights. (Author/RK)

Tick Tock: Your Body Clocks: Understanding Your Daily Rhythms

MedlinePlus

... has its own internal network of clocks? These biological clocks help you feel alert during the day, ... NIH’s Dr. Michael Sesma, an expert in circadian biology. “They affect almost every part of your physiology ...

The ferroin-catalyzed Belousov-Zhabotinskii system with a "clock" behaviour

NASA Astrophysics Data System (ADS)

Melicherčík, Milan; Treindl, L̆udovít

1991-07-01

The ferroin-catalyzed Belousov-Zhabotinskii oscillatory system with methyl-, ethyl-, or isopropyl-ester of 3-oxobutanoic acid exhibits a "clock" behaviour and subsequent two-frequency oscillations. The influence of oxygen on the "clock" behaviour is assumed to be caused by an interaction of oxygen as a scavenger with intermediary radicals. A mechanism of the "clock" behaviour together with two-frequency oscillations of the Belousov-Zhabotinskii type will be developed later.

Molecular clock of HIV-1 envelope genes under early immune selection

DOE PAGES

Park, Sung Yong; Love, Tanzy M. T.; Perelson, Alan S.; ...

2016-06-01

Here, the molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.

Molecular clock of HIV-1 envelope genes under early immune selection

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

Park, Sung Yong; Love, Tanzy M. T.; Perelson, Alan S.

Here, the molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.

Processing of visually presented clock times.

PubMed

Goolkasian, P; Park, D C

1980-11-01

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

A self-interfering clock as a “which path” witness

NASA Astrophysics Data System (ADS)

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

2015-09-01

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.

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

PubMed

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

2015-09-11

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

Systematic evaluation of a 171Yb optical clock by synchronous comparison between two lattice systems.

PubMed

Gao, Qi; Zhou, Min; Han, Chengyin; Li, Shangyan; Zhang, Shuang; Yao, Yuan; Li, Bo; Qiao, Hao; Ai, Di; Lou, Ge; Zhang, Mengya; Jiang, Yanyi; Bi, Zhiyi; Ma, Longsheng; Xu, Xinye

2018-05-22

Optical clocks are the most precise measurement devices. Here we experimentally characterize one such clock based on the 1 S 0 - 3 P 0 transition of neutral 171 Yb atoms confined in an optical lattice. Given that the systematic evaluation using an interleaved stabilization scheme is unable to avoid noise from the clock laser, synchronous comparisons against a second 171 Yb lattice system were implemented to accelerate the evaluation. The fractional instability of one clock falls below 4 × 10 -17 after an averaging over a time of 5,000 seconds. The systematic frequency shifts were corrected with a total uncertainty of 1.7 × 10 -16 . The lattice polarizability shift currently contributes the largest source. This work paves the way to measuring the absolute clock transition frequency relative to the primary Cs standard or against the International System of Units (SI) second.

Physiological links of circadian clock and biological clock of aging.

PubMed

Liu, Fang; Chang, Hung-Chun

2017-07-01

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

Central and peripheral regulation of feeding and nutrition by the mammalian circadian clock: implications for nutrition during manned space flight

NASA Technical Reports Server (NTRS)

Cassone, Vincent M.; Stephan, Friedrich K.

2002-01-01

Circadian clocks have evolved to predict and coordinate physiologic processes with the rhythmic environment on Earth. Space studies in non-human primates and humans have suggested that this clock persists in its rhythmicity in space but that its function is altered significantly in long-term space flight. Under normal circumstances, the clock is synchronized by the light-dark cycle via the retinohypothalamic tract and the suprachiasmatic nucleus. It is also entrained by restricted feeding regimes via a suprachiasmatic nucleus-independent circadian oscillator. The site of this suboscillator (or oscillators) is not known, but new evidence has suggested that peripheral tissues in the liver and viscera may express circadian clock function when forced to do so by restricted feeding schedules or other homeostatic disruptions. New research on the role of the circadian clock in the control of feeding on Earth and in space is warranted.

Early sex-specific modulation of the molecular clock in trauma.

PubMed

Mehraj, Vikram; Wiramus, Sandrine; Capo, Christian; Leone, Marc; Mege, Jean-Louis; Textoris, Julien

2014-01-01

Immune system biology and most physiologic functions are tightly linked to circadian rhythms. Time of day-dependent variations in many biologic parameters also play a fundamental role in the disease process. We previously showed that the genes encoding the peripheral molecular clock were modulated in a sex-dependent manner in Q fever. Here, we examined severe trauma patients at admission to the intensive care unit. Using quantitative real-time polymerase chain reaction, the whole-blood expression of the molecular clock components ARNTL, CLOCK, and PER2 was assessed in male and female trauma patients. Healthy volunteers of both sexes were used as controls. We observed a significant overexpression of both ARNTL and CLOCK in male trauma patients. We report, for the first time, the sex-related modulation of the molecular clock genes in the blood following severe trauma. These results emphasize the role of circadian rhythms in the immune response in trauma patients. Epidemiologic study, level IV.

A VLBI experiment using a remote atomic clock via a coherent fibre link

PubMed Central

Clivati, Cecilia; Ambrosini, Roberto; Artz, Thomas; Bertarini, Alessandra; Bortolotti, Claudio; Frittelli, Matteo; Levi, Filippo; Mura, Alberto; Maccaferri, Giuseppe; Nanni, Mauro; Negusini, Monia; Perini, Federico; Roma, Mauro; Stagni, Matteo; Zucco, Massimo; Calonico, Davide

2017-01-01

We describe a VLBI experiment in which, for the first time, the clock reference is delivered from a National Metrology Institute to a radio telescope using a coherent fibre link 550 km long. The experiment consisted of a 24-hours long geodetic campaign, performed by a network of European telescopes; in one of those (Medicina, Italy) the local clock was alternated with a signal generated from an optical comb slaved to a fibre-disseminated optical signal. The quality of the results obtained with this facility and with the local clock is similar: interferometric fringes were detected throughout the whole 24-hours period and it was possible to obtain a solution whose residuals are comparable to those obtained with the local clock. These results encourage further investigation of the ultimate VLBI performances achievable using fibre dissemination at the highest precision of state-of-the-art atomic clocks. PMID:28145451

Vasculature on the clock: Circadian rhythm and vascular dysfunction.

PubMed

Crnko, Sandra; Cour, Martin; Van Laake, Linda W; Lecour, Sandrine

2018-05-17

The master mammalian circadian clock (i.e. central clock), located in the suprachiasmatic nucleus of the hypothalamus, orchestrates the synchronization of the daily behavioural and physiological rhythms to better adapt the organism to the external environment in an anticipatory manner. This central clock is entrained by a variety of signals, the best established being light and food. However, circadian cycles are not simply the consequences of these two cues but are generated by endogenous circadian clocks. Indeed, clock machinery is found in mainly all tissues and cell types, including cells of the vascular system such as endothelial cells, fibroblasts, smooth muscle cells and stem cells. This machinery physiologically contributes to modulate the daily vascular function, and its disturbance therefore plays a major role in the pathophysiology of vascular dysfunction. Therapies targeting the circadian rhythm may therefore be of benefit against vascular disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Potential Role for Peripheral Circadian Clock Dyssynchrony in the Pathogenesis of Cardiovascular Dysfunction

PubMed Central

Young, Martin E.; Bray, Molly S.

2007-01-01

Circadian clocks are intracellular molecular mechanisms designed to allow the cell, organ, and organism to prepare for an anticipated stimulus prior to its onset. In order for circadian clocks to maintain their selective advantage, they must be entrained to the environment. Light, sound, temperature, physical activity (including sleep/wake transitions), and food intake are among the strongest environmental factors influencing mammalian circadian clocks. Normal circadian rhythmicities in these environmental factors have become severely disrupted in our modern day society, concomitant with increased incidence of type 2 diabetes mellitus, obesity, and cardiovascular disease. Here, we review our current knowledge regarding the roles of peripheral circadian clocks, concentrating on those found within tissues directly involved in metabolic homeostasis and cardiovascular function. We propose that both inter- and intra- organ dyssynchronization, through alteration/impairment of peripheral circadian clocks, accelerates the development of cardiovascular disease risk factors associated with cardiometabolic syndrome. PMID:17387040

A Group Neighborhood Average Clock Synchronization Protocol for Wireless Sensor Networks

PubMed Central

Lin, Lin; Ma, Shiwei; Ma, Maode

2014-01-01

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

Test of an orbiting hydrogen maser clock system using laser time transfer

NASA Technical Reports Server (NTRS)

Vessot, Robert F. C.; Mattison, Edward M.; Nystrom, G. U.; Decher, Rudolph

1992-01-01

We describe a joint Smithsonian Astrophysical Laboratory/National Aeronautics and Space Administration (SAO/NASA) program for flight testing a atomic hydrogen maser clock system designed for long-term operation in space. The clock system will be carried by a shuttle-launched EURECA spacecraft. Comparisons with earth clocks to measure the clock's long-term frequency stability (tau = 10(exp 4) seconds) will be made using laser time transfer from existing NASA laser tracking stations. We describe the design of the maser clock and its control systems, and the laser timing technique. We describe the precision of station time synchronization and the limitations in the comparison between the earth and space time scales owing to gravitational and relativistic effects. We will explore the implications of determining the spacecraft's location by an on-board Global Position System (GPS) receiver, and of using microwave techniques for time and frequency transfer.

Laser controlled atom source for optical clocks.

PubMed

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

2016-11-18

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

Compensation for intracellular environment in expression levels of mammalian circadian clock genes

PubMed Central

Matsumura, Ritsuko; Okamoto, Akihiko; Node, Koichi; Akashi, Makoto

2014-01-01

The circadian clock is driven by transcriptional oscillation of clock genes in almost all body cells. To investigate the effect of cell type-specific intracellular environment on the circadian machinery, we examined gene expression profiles in five peripheral tissues. As expected, the phase relationship between expression rhythms of nine clock genes was similar in all tissues examined. We also compared relative expression levels of clock genes among tissues, and unexpectedly found that quantitative variation remained within an approximately three-fold range, which was substantially smaller than that of metabolic housekeeping genes. Interestingly, circadian gene expression was little affected even when fibroblasts were cultured with different concentrations of serum. Together, these findings support a hypothesis that expression levels of clock genes are quantitatively compensated for the intracellular environment, such as redox potential and metabolite composition. However, more comprehensive studies are required to reach definitive conclusions. PMID:24504324

Rb vapor-cell clock demonstration with a frequency-doubled telecom laser.

PubMed

Almat, Nil; Pellaton, Matthieu; Moreno, William; Gruet, Florian; Affolderbach, Christoph; Mileti, Gaetano

2018-06-01

We employ a recently developed laser system, based on a low-noise telecom laser emitting around 1.56 μm, to evaluate its impact on the performance of an Rb vapor-cell clock in a continuous-wave double-resonance scheme. The achieved short-term clock instability below 2.5·10 -13 ·τ -1/2 demonstrates, for the first time, the suitability of a frequency-doubled telecom laser for this specific application. We measure and study quantitatively the impact of laser amplitude and frequency noises and of the ac Stark shift, which limit the clock frequency stability on short timescales. We also report on the detailed noise budgets and demonstrate experimentally that, under certain conditions, the short-term stability of the clock operated with the low-noise telecom laser is improved by a factor of three compared to clock operation using the direct 780-nm laser.

Realistic clocks, universal decoherence, and the black hole information paradox.

PubMed

Gambini, Rodolfo; Porto, Rafael A; Pullin, Jorge

2004-12-10

Ordinary quantum mechanics is formulated on the basis of the existence of an ideal classical clock external to the system under study. This is clearly an idealization. As emphasized originally by Salecker and Wigner and more recently by others, there exist limits in nature to how "classical" even the best possible clock can be. With realistic clocks, quantum mechanics ceases to be unitary and a fundamental mechanism of decoherence of quantum states arises. We estimate the rate of the universal loss of unitarity using optimal realistic clocks. In particular, we observe that the rate is rapid enough to eliminate the black hole information puzzle: all information is lost through the fundamental decoherence before the black hole can evaporate. This improves on a previous calculation we presented with a suboptimal clock in which only part of the information was lost by the time of evaporation.

A VLBI experiment using a remote atomic clock via a coherent fibre link.

PubMed

Clivati, Cecilia; Ambrosini, Roberto; Artz, Thomas; Bertarini, Alessandra; Bortolotti, Claudio; Frittelli, Matteo; Levi, Filippo; Mura, Alberto; Maccaferri, Giuseppe; Nanni, Mauro; Negusini, Monia; Perini, Federico; Roma, Mauro; Stagni, Matteo; Zucco, Massimo; Calonico, Davide

2017-02-01

We describe a VLBI experiment in which, for the first time, the clock reference is delivered from a National Metrology Institute to a radio telescope using a coherent fibre link 550 km long. The experiment consisted of a 24-hours long geodetic campaign, performed by a network of European telescopes; in one of those (Medicina, Italy) the local clock was alternated with a signal generated from an optical comb slaved to a fibre-disseminated optical signal. The quality of the results obtained with this facility and with the local clock is similar: interferometric fringes were detected throughout the whole 24-hours period and it was possible to obtain a solution whose residuals are comparable to those obtained with the local clock. These results encourage further investigation of the ultimate VLBI performances achievable using fibre dissemination at the highest precision of state-of-the-art atomic clocks.

Astrocyte deletion of Bmal1 alters daily locomotor activity and cognitive functions via GABA signalling

PubMed Central

Barca-Mayo, Olga; Pons-Espinal, Meritxell; Follert, Philipp; Armirotti, Andrea; Berdondini, Luca; De Pietri Tonelli, Davide

2017-01-01

Circadian rhythms are controlled by a network of clock neurons in the central pacemaker, the suprachiasmatic nucleus (SCN). Core clock genes, such as Bmal1, are expressed in SCN neurons and in other brain cells, such as astrocytes. However, the role of astrocytic clock genes in controlling rhythmic behaviour is unknown. Here we show that ablation of Bmal1 in GLAST-positive astrocytes alters circadian locomotor behaviour and cognition in mice. Specifically, deletion of astrocytic Bmal1 has an impact on the neuronal clock through GABA signalling. Importantly, pharmacological modulation of GABAA-receptor signalling completely rescues the behavioural phenotypes. Our results reveal a crucial role of astrocytic Bmal1 for the coordination of neuronal clocks and propose a new cellular target, astrocytes, for neuropharmacology of transient or chronic perturbation of circadian rhythms, where alteration of astrocytic clock genes might contribute to the impairment of the neurobehavioural outputs such as cognition. PMID:28186121

Standard Clock in primordial density perturbations and cosmic microwave background

NASA Astrophysics Data System (ADS)

Chen, Xingang; Namjoo, Mohammad Hossein

2014-12-01

Standard Clocks in the primordial epoch leave a special type of features in the primordial perturbations, which can be used to directly measure the scale factor of the primordial universe as a function of time a (t), thus discriminating between inflation and alternatives. We have started to search for such signals in the Planck 2013 data using the key predictions of the Standard Clock. In this Letter, we summarize the key predictions of the Standard Clock and present an interesting candidate example in Planck 2013 data. Motivated by this candidate, we construct and compute full Standard Clock models and use the more complete prediction to make more extensive comparison with data. Although this candidate is not yet statistically significant, we use it to illustrate how Standard Clocks appear in Cosmic Microwave Background (CMB) and how they can be further tested by future data. We also use it to motivate more detailed theoretical model building.

A VLBI experiment using a remote atomic clock via a coherent fibre link

NASA Astrophysics Data System (ADS)

Clivati, Cecilia; Ambrosini, Roberto; Artz, Thomas; Bertarini, Alessandra; Bortolotti, Claudio; Frittelli, Matteo; Levi, Filippo; Mura, Alberto; Maccaferri, Giuseppe; Nanni, Mauro; Negusini, Monia; Perini, Federico; Roma, Mauro; Stagni, Matteo; Zucco, Massimo; Calonico, Davide

2017-02-01

We describe a VLBI experiment in which, for the first time, the clock reference is delivered from a National Metrology Institute to a radio telescope using a coherent fibre link 550 km long. The experiment consisted of a 24-hours long geodetic campaign, performed by a network of European telescopes; in one of those (Medicina, Italy) the local clock was alternated with a signal generated from an optical comb slaved to a fibre-disseminated optical signal. The quality of the results obtained with this facility and with the local clock is similar: interferometric fringes were detected throughout the whole 24-hours period and it was possible to obtain a solution whose residuals are comparable to those obtained with the local clock. These results encourage further investigation of the ultimate VLBI performances achievable using fibre dissemination at the highest precision of state-of-the-art atomic clocks.

Laser controlled atom source for optical clocks

PubMed Central

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

2016-01-01

Precision timekeeping has been a driving force in innovation, from defining agricultural seasons to atomic clocks enabling satellite navigation, broadband communication and high-speed trading. We are on the verge of a revolution in atomic timekeeping, where optical clocks promise an over thousand-fold improvement in stability and accuracy. However, complex setups and sensitivity to thermal radiation pose limitations to progress. Here we report on an atom source for a strontium optical lattice clock which circumvents these limitations. We demonstrate fast (sub 100 ms), cold and controlled emission of strontium atomic vapours from bulk strontium oxide irradiated by a simple low power diode laser. Our results demonstrate that millions of strontium atoms from the vapour can be captured in a magneto-optical trap (MOT). Our method enables over an order of magnitude reduction in scale of the apparatus. Future applications range from satellite clocks testing general relativity to portable clocks for inertial navigation systems and relativistic geodesy. PMID:27857214

Clock distribution for BaF2 readout electronics at CSNS-WNS

NASA Astrophysics Data System (ADS)

He, Bing; Cao, Ping; Zhang, De-Liang; Wang, Qi; Zhang, Ya-Xi; Qi, Xin-Cheng; An, Qi

2017-01-01

A BaF2 (Barium Fluoride) detector array is designed to precisely measure the (n, γ) cross section at the CSNS-WNS (white neutron source at China Spallation Neutron Source). It is a 4π solid angle-shaped detector array consisting of 92 BaF2 crystal elements. To discriminate signals from the BaF2 detector, a pulse shape discrimination method is used, supported by a waveform digitization technique. There are 92 channels for digitizing. The precision and synchronization of clock distribution restricts the performance of waveform digitizing. In this paper, a clock prototype for the BaF2 readout electronics at CSNS-WNS is introduced. It is based on the PXIe platform and has a twin-stage tree topology. In the first stage, clock is synchronously distributed from the tree root to each PXIe crate through a coaxial cable over a long distance, while in the second stage, the clock is further distributed to each electronic module through a PXIe dedicated differential star bus. With the help of this topology, each tree node can fan out up to 20 clocks with 3U size. Test results show the clock jitter is less than 20 ps, which meets the requirements of the BaF2 readout electronics. Besides, this clock system has the advantages of high density, simplicity, scalability and cost saving, so it can be useful for other clock distribution applications. Supported by National Research and Development plan (2016 YFA0401602) NSAF (U1530111) and National Natural Science Foundation of China (11005107)

Sensitivity to Pigment-Dispersing Factor (PDF) Is Cell-Type Specific among PDF-Expressing Circadian Clock Neurons in the Madeira Cockroach.

PubMed

Gestrich, Julia; Giese, Maria; Shen, Wen; Zhang, Yi; Voss, Alexandra; Popov, Cyril; Stengl, Monika; Wei, HongYing

2018-02-01

Transplantation studies have pinpointed the circadian clock of the Madeira cockroach to the accessory medulla (AME) of the brain's optic lobes. The AME is innervated by approximately 240 adjacent neuropeptidergic neurons, including 12 pigment-dispersing factor (PDF)-expressing neurons anterior to the AME (aPDFMEs). Four of the aPDFMEs project contralaterally, controlling locomotor activity rhythms of the night-active cockroach. The present in vitro Ca 2+ imaging analysis focuses on contralaterally projecting AME neurons and their responses to PDF, GABA, and acetylcholine (ACh). First, rhodamine-dextran backfills from the contralateral optic stalk identified contralaterally projecting AME neurons, which were then dispersed in primary cell cultures. After characterization of PDF, GABA, and ACh responses, PDF immunocytochemistry identified ipsilaterally and contralaterally projecting PDFMEs. All PDF-sensitive clock neurons, PDF-immunoreactive clock neurons, and the majority of ipsilaterally and contralaterally projecting cells were excited by ACh. GABA inhibited all PDF-expressing clock neurons, and about half of other ipsilaterally projecting and most contralaterally projecting clock neurons. For the first time, we identified PDF autoreceptors in PDF-secreting cockroach circadian pacemakers. The medium-sized aPDFMEs and all other contralaterally projecting PDF-sensitive clock cells were inhibited by PDF. The ipsilaterally remaining small PDF-sensitive clock cells were activated by PDF. Only the largest aPDFME did not express PDF autoreceptors. We hypothesize that opposing PDF signaling generates 2 different ensembles of clock cells with antiphasic activity, regulating and maintaining a constant phase relationship between rest and activity cycles of the night-active cockroach.

Ground-based optical atomic clocks as a tool to monitor vertical surface motion

NASA Astrophysics Data System (ADS)

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

2015-09-01

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

Clock face drawing test performance in children with ADHD.

PubMed

Ghanizadeh, Ahmad; Safavi, Salar; Berk, Michael

2013-01-01

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

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

Keith, Dove; Finlay, Liam; Butler, Judy

Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve thesemore » results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.« less

Clock gene variation in Tachycineta swallows

PubMed Central

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

2012-01-01

Many animals use photoperiod cues to synchronize reproduction with environmental conditions and thereby improve their reproductive success. The circadian clock, which creates endogenous behavioral and physiological rhythms typically entrained to photoperiod, is well characterized at the molecular level. Recent work provided evidence for an association between Clock poly-Q length polymorphism and latitude and, within a population, an association with the date of laying and the length of the incubation period. Despite relatively high overall breeding synchrony, the timing of clutch initiation has a large impact on the fitness of swallows in the genus Tachycineta. We compared length polymorphism in the Clock poly-Q region among five populations from five different Tachycineta species that breed across a hemisphere-wide latitudinal gradient (Fig. 1). Clock poly-Q variation was not associated with latitude; however, there was an association between Clock poly-Q allele diversity and the degree of clutch size decline within breeding seasons. We did not find evidence for an association between Clock poly-Q variation and date of clutch initiation in for any of the five Tachycineta species, nor did we found a relationship between incubation duration and Clock genotype. Thus, there is no general association between latitude, breeding phenology, and Clock polymorphism in this clade of closely related birds. Figure 1 Photos of Tachycineta swallows that were used in this study: A) T. bicolor from Ithaca, New York, B) T. leucorrhoa from Chascomús, Argentina, C) T. albilinea from Hill Bank, Belize, D) T. meyeni from Puerto Varas, Chile, and E) T. thalassina from Mono Lake, California, Photographers: B: Valentina Ferretti; A, C-E: David Winkler. PMID:22408729

Solving of Clock Problems Using An Algebraic Approach And Developing An Application For Automatic Conversion

NASA Astrophysics Data System (ADS)

Lakshmi Devaraj, Shanmuga

2018-04-01

The recent trend in learning Mathematics is through android apps like Byju’s. The clock problems asked in aptitude tests could be learnt using such computer applications. The Clock problems are of four categories namely: 1. What is the angle between the hands of a clock at a particular time 2. When the hands of a clock will meet after a particular time 3. When the hands of a clock will be at right angle after a particular time 4. When the hands of a clock will be in a straight line but not together after a particular time The aim of this article is to convert the clock problems which were solved using the traditional approach to algebraic equations and solve them. Shortcuts are arrived which help in solving the questions in just a few seconds. Any aptitude problem could be converted to an algebraic equation by tracing the way the problem proceeds by applying our analytical skills. Solving of equations would be the easiest part in coming up with the solution. Also a computer application could be developed by using the equations that were arrived at in the analysis part. The computer application aims at solving the four different problems in Clocks. The application helps the learners of aptitude for CAT and other competitive exams to know the approach of the problem. Learning Mathematics with a gaming tool like this would be interesting to the learners. This paper provides a path to creating gaming apps to learn Mathematics.

Effects of continuous white light and 12h white-12h blue light-cycles on the expression of clock genes in diencephalon, liver, and skeletal muscle in chicks.

PubMed

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

2017-05-01

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

Role of cardiomyocyte circadian clock in myocardial metabolic adaptation

USDA-ARS?s Scientific Manuscript database

Marked circadian rhythmicities in cardiovascular physiology and pathophysiology exist. The cardiomyocyte circadian clock has recently been linked to circadian rhythms in myocardial gene expression, metabolism, and contractile function. For instance, the cardiomyocyte circadian clock is essential f...

Teaching How to Tell Time.

ERIC Educational Resources Information Center

Britton, Richard Aquinas

1981-01-01

An approach to teaching time telling to learning disabled children begins with the child drawing a clock, then designating 5-minute marks, using old alarm or play clocks to manipulate the hands, and drawing clock hands to represent specific times. (CL)

An optical clock to go

NASA Astrophysics Data System (ADS)

Ludlow, Andrew D.

2018-05-01

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

Circadian expression of clock and putative clock-controlled genes in skeletal muscle of the zebrafish.

PubMed

Amaral, Ian P G; Johnston, Ian A

2012-01-01

To identify circadian patterns of gene expression in skeletal muscle, adult male zebrafish were acclimated for 2 wk to a 12:12-h light-dark photoperiod and then exposed to continuous darkness for 86 h with ad libitum feeding. The increase in gut food content associated with the subjective light period was much diminished by the third cycle, enabling feeding and circadian rhythms to be distinguished. Expression of zebrafish paralogs of mammalian transcriptional activators of the circadian mechanism (bmal1, clock1, and rora) followed a rhythmic pattern with a ∼24-h periodicity. Peak expression of rora paralogs occurred at the beginning of the subjective light period [Zeitgeber time (ZT)07 and ZT02 for roraa and rorab], whereas the highest expression of bmal1 and clock paralogs occurred 12 h later (ZT13-15 and ZT16 for bmal and clock paralogs). Expression of the transcriptional repressors cry1a, per1a/1b, per2, per3, nr1d2a/2b, and nr1d1 also followed a circadian pattern with peak expression at ZT0-02. Expression of the two paralogs of cry2 occurred in phase with clock1a/1b. Duplicated genes had a high correlation of expression except for paralogs of clock1, nr1d2, and per1, with cry1b showing no circadian pattern. The highest expression difference was 9.2-fold for the activator bmal1b and 51.7-fold for the repressor per1a. Out of 32 candidate clock-controlled genes, only myf6, igfbp3, igfbp5b, and hsf2 showed circadian expression patterns. Igfbp3, igfbp5b, and myf6 were expressed in phase with clock1a/1b and had an average of twofold change in expression from peak to trough, whereas hsf2 transcripts were expressed in phase with cry1a and had a 7.2-fold-change in expression. The changes in expression of clock and clock-controlled genes observed during continuous darkness were also observed at similar ZTs in fish exposed to a normal photoperiod in a separate control experiment. The role of circadian clocks in regulating muscle maintenance and growth are discussed.

The contribution of Multi-GNSS Experiment (MGEX) to precise point positioning

NASA Astrophysics Data System (ADS)

Guo, Fei; Li, Xingxing; Zhang, Xiaohong; Wang, Jinling

2017-06-01

In response to the changing world of GNSS, the International GNSS Service (IGS) has initiated the Multi-GNSS Experiment (MGEX). As part of the MGEX project, initial precise orbit and clock products have been released for public use, which are the key prerequisites for multi-GNSS precise point positioning (PPP). In particular, precise orbits and clocks at intervals of 5 min and 30 s are presently available for the new emerging systems. This paper investigates the benefits of multi-GNSS for PPP. Firstly, orbit and clock consistency tests (between different providers) were performed for GPS, GLONASS, Galileo and BeiDou. In general, the differences of GPS are, respectively, 1.0-1.5 cm for orbit and 0.1 ns for clock. The consistency of GLONASS is worse than GPS by a factor of 2-3, i.e. 2-4 cm for orbit and 0.2 ns for clock. However, the corresponding differences of Galileo and BeiDou are significantly larger than those of GPS and GLONASS, particularly for the BeiDou GEO satellites. Galileo as well as BeiDou IGSO/MEO products have a consistency of 0.1-0.2 m for orbit, and 0.2-0.3 ns for clock. As to BeiDou GEO satellites, the difference of their orbits reaches 3-4 m in along-track, 0.5-0.6 m in cross-track, and 0.2-0.3 m in the radial directions, together with an average RMS of 0.6 ns for clock. Furthermore, the short-term stability of multi-GNSS clocks was analyzed by Allan deviation. Results show that clock stability of the onboard GNSS is highly dependent on the satellites generations, operational lifetime, orbit types, and frequency standards. Finally, kinematic PPP tests were conducted to investigate the contribution of multi-GNSS and higher rate clock corrections. As expected, the positioning accuracy as well as convergence speed benefit from the fusion of multi-GNSS and higher rate of precise clock corrections. The multi-GNSS PPP improves the positioning accuracy by 10-20%, 40-60%, and 60-80% relative to the GPS-, GLONASS-, and BeiDou-only PPP. The usage of 30 s interval clock products decreases interpolation errors, and the positioning accuracy is improved by an average of 30-50% for the all the cases except for the BeiDou-only PPP.

Potential Conservation of Circadian Clock Proteins in the phylum Nematoda as Revealed by Bioinformatic Searches

PubMed Central

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

2014-01-01

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

First of 24 LED Panels Installed in New Countdown Clock

NASA Image and Video Library

2014-11-25

At NASA's Kennedy Space Center in Florida, assembly has begun on the first of 24 light emitting diode LED panels for installation in the new countdown clock at the spaceport's Press Site. The new modern, multimedia display will be similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex.

First of 24 LED Panels Installed in New Countdown Clock

NASA Image and Video Library

2014-11-25

At NASA's Kennedy Space Center in Florida, the first of 24 light emitting diode LED panels have arrived for installation in the new countdown clock at the spaceport's Press Site. A new modern, multimedia display soon will be installed, similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex.

The development of a Kalman filter clock predictor

NASA Technical Reports Server (NTRS)

Davis, John A.; Greenhall, Charles A.; Boudjemaa, Redoane

2005-01-01

A Kalman filter based clock predictor is developed, and its performance evaluated using both simulated and real data. The clock predictor is shown to possess a neat to optimal Prediction Error Variance (PEV) when the underlying noise consists of one of the power law noise processes commonly encountered in time and frequency measurements. The predictor's performance is the presence of multiple noise processes is also examined. The relationship between the PEV obtained in the presence of multiple noise processes and those obtained for the individual component noise processes is examined. Comparisons are made with a simple linear clock predictor. The clock predictor is used to predict future values of the time offset between pairs of NPL's active hydrogen masers.

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches.

PubMed

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

2014-01-01

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

The role of the mechanical clock in medieval science.

PubMed

Álvarez, Víctor Pérez

2015-03-01

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

Selected highly charged ions as prospective candidates for optical clocks with quality factors larger than 1015

NASA Astrophysics Data System (ADS)

Yu, Yan-mei; Sahoo, B. K.

2018-04-01

The Ni12 +, Cu13 +, Pd12 +, and Ag13 + highly charged ions (HCIs) are proposed for making very accurate optical clocks with the fractional uncertainties below 10-19 level. These HCIs have simple atomic energy levels, clock transitions with quality factors larger than 1015, and optical magnetic-dipole (M 1 ) transitions that can be used for laser cooling and detecting quantum jumps on the clock transitions by the shelving method. To demonstrate the projected fractional uncertainties, we estimate orders of magnitude of the Zeeman, Stark, blackbody radiation, and electric quadrupole shifts of the clock transitions by performing calculations of the relevant atomic properties in the above HCIs.

Countdown Clock Ribbon Cutting

NASA Image and Video Library

2016-03-01

The newest display at the Kennedy Space Center Visitor Complex is the spaceport's historic countdown clock. It is now located at the entrance to the visitor complex. The clock was set up at the space center's Press Site and used from the launch of Apollo 12 on Nov. 14, 1969 to the final space shuttle mission, STS-135, launched on July 8, 2011. The old countdown clock was replaced in 2014 with a modern light emitting diode, or LED, display.

Strong resetting of the mammalian clock by constant light followed by constant darkness

PubMed Central

Chen, Rongmin; Seo, Dong-oh; Bell, Elijah; von Gall, Charlotte; Lee, Choogon

2008-01-01

The mammalian molecular circadian clock in the suprachiasmatic nuclei (SCN) regulates locomotor activity rhythms as well as clocks in peripheral tissues (Reppert and Weaver, 2002; Ko and Takahashi, 2006). Constant light (LL) can induce behavioral and physiological arrhythmicity, by desynchronizing clock cells in the SCN (Ohta et al., 2005). We examined how the disordered clock cells resynchronize by probing the molecular clock and measuring behavior in mice transferred from LL to constant darkness (DD). The circadian locomotor activity rhythms disrupted in LL become robustly rhythmic again from the beginning of DD, and the starting phase of the rhythm in DD is specific, not random, suggesting that the desynchronized clock cells are quickly reset in an unconventional manner by the L:D transition. By measuring mPERIOD protein rhythms, we showed that the SCN and peripheral tissue clocks quickly become rhythmic again in phase with the behavioral rhythms. We propose that this resetting mechanism may be different from conventional phase shifting, which involves light-induction of Period genes (Albrecht et al., 1997; Shearman et al., 1997; Shigeyoshi et al., 1997). Using our functional insights, we could shift the circadian phase of locomotor activity rhythms by 12 hours using a 15-hour LL treatment: essentially producing phase reversal by a single light pulse, a feat that has not been reported previously in wild-type mice and that has potential clinical utility. PMID:19005049

Rapid resetting of human peripheral clocks by phototherapy during simulated night shift work.

PubMed

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

2017-11-24

A majority of night shift workers have their circadian rhythms misaligned to their atypical schedule. While bright light exposure at night is known to reset the human central circadian clock, the behavior of peripheral clocks under conditions of shift work is more elusive. The aim of the present study was to quantify the resetting effects of bright light exposure on both central (plasma cortisol and melatonin) and peripheral clocks markers (clock gene expression in peripheral blood mononuclear cells, PBMCs) in subjects living at night. Eighteen healthy subjects were enrolled to either a control (dim light) or a bright light group. Blood was sampled at baseline and on the 4 th day of simulated night shift. In response to a night-oriented schedule, the phase of PER1 and BMAL1 rhythms in PBMCs was delayed by ~2.5-3 h (P < 0.05), while no shift was observed for the other clock genes and the central markers. Three cycles of 8-h bright light induced significant phase delays (P < 0.05) of ~7-9 h for central and peripheral markers, except BMAL1 (advanced by +5h29; P < 0.05). Here, we demonstrate in humans a lack of peripheral clock adaptation under a night-oriented schedule and a rapid resetting effect of nocturnal bright light exposure on peripheral clocks.

Diurnal oscillations of soybean circadian clock and drought responsive genes.

PubMed

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

2014-01-01

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

Biomedical ultrasonoscope

NASA Technical Reports Server (NTRS)

Lee, R. D. (Inventor)

1979-01-01

The combination of a "C" mode scan electronics in a portable, battery powered biomedical ultrasonoscope having "A" and "M" mode scan electronics, the latter including a clock generator for generating clock pulses, a cathode ray tube having X, Y and Z axis inputs, a sweep generator connected between the clock generator and the X axis input of the cathode ray tube for generating a cathode ray sweep signal synchronized by the clock pulses, and a receiver adapted to be connected to the Z axis input of the cathode ray tube. The "C" mode scan electronics comprises a plurality of transducer elements arranged in a row and adapted to be positioned on the skin of the patient's body for converting a pulsed electrical signal to a pulsed ultrasonic signal, radiating the ultrasonic signal into the patient's body, picking up the echoes reflected from interfaces in the patient's body and converting the echoes to electrical signals; a plurality of transmitters, each transmitter being coupled to a respective transducer for transmitting a pulsed electrical signal thereto and for transmitting the converted electrical echo signals directly to the receiver, a sequencer connected between the clock generator and the plurality of transmitters and responsive to the clock pulses for firing the transmitters in cyclic order; and a staircase voltage generator connected between the clock generator and the Y axis input of the cathode ray tube for generating a staircase voltage having steps synchronized by the clock pulses.

The Circadian Clock in Cancer Development and Therapy

PubMed Central

Fu, Loning; Kettner, Nicole M.

2014-01-01

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

TNF-alpha suppresses the expression of clock genes by interfering with E-box-mediated transcription.

PubMed

Cavadini, Gionata; Petrzilka, Saskia; Kohler, Philipp; Jud, Corinne; Tobler, Irene; Birchler, Thomas; Fontana, Adriano

2007-07-31

Production of TNF-alpha and IL-1 in infectious and autoimmune diseases is associated with fever, fatigue, and sleep disturbances, which are collectively referred to as sickness behavior syndrome. In mice TNF-alpha and IL-1 increase nonrapid eye movement sleep. Because clock genes regulate the circadian rhythm and thereby locomotor activity and may alter sleep architecture we assessed the influence of TNF-alpha on the circadian timing system. TNF-alpha is shown here to suppress the expression of the PAR bZip clock-controlled genes Dbp, Tef, and Hlf and of the period genes Per1, Per2, and Per3 in fibroblasts in vitro and in vivo in the liver of mice infused with the cytokine. The effect of TNF-alpha on clock genes is shared by IL-1beta, but not by IFN-alpha, and IL-6. Furthermore, TNF-alpha interferes with the expression of Dbp in the suprachiasmatic nucleus and causes prolonged rest periods in the dark when mice show spontaneous locomotor activity. Using clock reporter genes TNF-alpha is found here to inhibit CLOCK-BMAL1-induced activation of E-box regulatory elements-dependent clock gene promoters. We suggest that the increase of TNF-alpha and IL-1beta, as seen in infectious and autoimmune diseases, impairs clock gene functions and causes fatigue.

Diurnal Oscillations of Soybean Circadian Clock and Drought Responsive Genes

PubMed Central

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

2014-01-01

Rhythms produced by the endogenous circadian clock play a critical role in allowing plants to respond and adapt to the environment. While there is a well-established regulatory link between the circadian clock and responses to abiotic stress in model plants, little is known of the circadian system in crop species like soybean. This study examines how drought impacts diurnal oscillation of both drought responsive and circadian clock genes in soybean. Drought stress induced marked changes in gene expression of several circadian clock-like components, such as LCL1-, GmELF4- and PRR-like genes, which had reduced expression in stressed plants. The same conditions produced a phase advance of expression for the GmTOC1-like, GmLUX-like and GmPRR7-like genes. Similarly, the rhythmic expression pattern of the soybean drought-responsive genes DREB-, bZIP-, GOLS-, RAB18- and Remorin-like changed significantly after plant exposure to drought. In silico analysis of promoter regions of these genes revealed the presence of cis-elements associated both with stress and circadian clock regulation. Furthermore, some soybean genes with upstream ABRE elements were responsive to abscisic acid treatment. Our results indicate that some connection between the drought response and the circadian clock may exist in soybean since (i) drought stress affects gene expression of circadian clock components and (ii) several stress responsive genes display diurnal oscillation in soybeans. PMID:24475115

Upset due to a single particle caused propagated transients in a bulk CMOS microprocessor

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

Leavy, J.F.; Hoffmann, L.F.; Shoran, R.W.

1991-12-01

This paper reports on data pattern advances observed in preset, single event upset (SEU) hardened clocked flip-flops, during static Cf-252 exposures on a bulk CMOS microprocessor, that were attributable to particle caused anomalous clock signals, or propagated transients. SPICE simulations established that particle strikes in the output nodes of a clock control logic flip-flop could produce transients of sufficient amplitude and duration to be accepted as legitimate pulses by clock buffers fed by the flip-flop's output nodes. The buffers would then output false clock pulses, thereby advancing the state of the present flip-flops. Masking the clock logic on one ofmore » the test chips made the flip-flop data advance cease, confirming the clock logic as the source of the SEU. By introducing N{sub 2} gas, at reduced pressures, into the SEU test chamber to attenuate Cf-252 particle LET's, a 24-26 MeV-cm{sup 2}/mg LET threshold was deduced. Subsequent tests, at the 88-inch cyclotron at Berkeley, established an LET threshold of 30 MeV-cm{sup 2}/mg (283 MeV Cu at 0{degrees}) for the generation of false clocks. Cyclotron SEU tests are considered definitive, while Cf-252 data usually is not. However, in this instance Cf-252 tests proved analytically useful, providing SEU characterization data that was both timely and inexpensive.« less

Circadian factor BMAL1 in histaminergic neurons regulates sleep architecture.

PubMed

Yu, Xiao; Zecharia, Anna; Zhang, Zhe; Yang, Qianzi; Yustos, Raquel; Jager, Polona; Vyssotski, Alexei L; Maywood, Elizabeth S; Chesham, Johanna E; Ma, Ying; Brickley, Stephen G; Hastings, Michael H; Franks, Nicholas P; Wisden, William

2014-12-01

Circadian clocks allow anticipation of daily environmental changes. The suprachiasmatic nucleus (SCN) houses the master clock, but clocks are also widely expressed elsewhere in the body. Although some peripheral clocks have established roles, it is unclear what local brain clocks do. We tested the contribution of one putative local clock in mouse histaminergic neurons in the tuberomamillary nucleus to the regulation of the sleep-wake cycle. Histaminergic neurons are silent during sleep, and start firing after wake onset; the released histamine, made by the enzyme histidine decarboxylase (HDC), enhances wakefulness. We found that hdc gene expression varies with time of day. Selectively deleting the Bmal1 (also known as Arntl or Mop3) clock gene from histaminergic cells removes this variation, producing higher HDC expression and brain histamine levels during the day. The consequences include more fragmented sleep, prolonged wake at night, shallower sleep depth (lower nonrapid eye movement [NREM] δ power), increased NREM-to-REM transitions, hindered recovery sleep after sleep deprivation, and impaired memory. Removing BMAL1 from histaminergic neurons does not, however, affect circadian rhythms. We propose that for mammals with polyphasic/nonwake consolidating sleep, the local BMAL1-dependent clock directs appropriately timed declines and increases in histamine biosynthesis to produce an appropriate balance of wake and sleep within the overall daily cycle of rest and activity specified by the SCN. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Enhanced extinction of contextual fear conditioning in ClockΔ19 mutant mice.

PubMed

Bernardi, Rick E; Spanagel, Rainer

2014-08-01

Clock genes have been implicated in several disorders, such as schizophrenia, bipolar disorder, autism spectrum disorders, and drug dependence. However, few studies to date have examined the role of clock genes in fear-related behaviors. The authors used mice with the ClockΔ19 mutation to assess the involvement of this gene in contextual fear conditioning. Male wild-type (WT) and ClockΔ19 mutant mice underwent a single session of contextual fear conditioning (12 min, 4 unsignaled shocks), followed by daily 12-min retention trials. There were no differences between mutant and WT mice in the acquisition of contextual fear, and WT and mutant mice demonstrated similar freezing during the first retention session. However, extinction of contextual fear was accelerated in mutant mice across the remaining retention sessions, as compared to WT mice, suggesting a role for Clock in extinction following aversive learning. Because the ClockΔ19 mutation has previously been demonstrated to result in an increase in dopamine signaling, the authors confirmed the role of dopamine in extinction learning using preretention session administration of a low dose of the dopamine transport reuptake inhibitor modafinil (0.75 mg/kg), which resulted in decreased freezing across retention sessions. These findings are consistent with an emerging portrayal of the importance of Clock genes in noncircadian functions, as well as the important role of dopamine in extinction learning.

Consequences of Exposure to Light at Night on the Pancreatic Islet Circadian Clock and Function in Rats

PubMed Central

Qian, Jingyi; Block, Gene D.; Colwell, Christopher S.; Matveyenko, Aleksey V.

2013-01-01

There is a correlation between circadian disruption, type 2 diabetes mellitus (T2DM), and islet failure. However, the mechanisms underlying this association are largely unknown. Pancreatic islets express self-sustained circadian clocks essential for proper β-cell function and survival. We hypothesized that exposure to environmental conditions associated with disruption of circadian rhythms and susceptibility to T2DM in humans disrupts islet clock and β-cell function. To address this hypothesis, we validated the use of Per-1:LUC transgenic rats for continuous longitudinal assessment of islet circadian clock function ex vivo. Using this methodology, we subsequently examined effects of the continuous exposure to light at night (LL) on islet circadian clock and insulin secretion in vitro in rat islets. Our data show that changes in the light–dark cycle in vivo entrain the phase of islet clock transcriptional oscillations, whereas prolonged exposure (10 weeks) to LL disrupts islet circadian clock function through impairment in the amplitude, phase, and interislet synchrony of clock transcriptional oscillations. We also report that exposure to LL leads to diminished glucose-stimulated insulin secretion due to a decrease in insulin secretory pulse mass. Our studies identify potential mechanisms by which disturbances in circadian rhythms common to modern life can predispose to islet failure in T2DM. PMID:23775768

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

PubMed Central

2010-01-01

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

Development of a strontium optical lattice clock for space applications

NASA Astrophysics Data System (ADS)

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 advanced subsystems" on "Let's embrace space, volume II" 45, 452-463 (2012). ISBN 978-92-79-22207-8. [3] www.soc2.eu

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

NASA Astrophysics Data System (ADS)

Zhou, Jiguang; Li, Yongan

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

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

PubMed Central

Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

2017-01-01

Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian circuit to drive behavioral rhythms. However, whether this principle is universal to circadian systems in animals remains unanswered. Here, we examined the autonomy of the Drosophila circadian clock by monitoring transcriptional and post-transcriptional rhythms of individual clock neurons in dispersed culture with time-lapse microscopy. Expression patterns of the transcriptional reporter show that CLOCK/CYCLE (CLK/CYC)-mediated transcription is constantly active in dissociated clock neurons. In contrast, the expression profile of the post-transcriptional reporter indicates that PERIOD (PER) protein levels fluctuate and ~10% of cells display rhythms in PER levels with periods in the circadian range. Nevertheless, PER and TIM are enriched in the cytoplasm and no periodic PER nuclear accumulation was observed. These results suggest that repression of CLK/CYC-mediated transcription by nuclear PER is impaired, and thus the negative feedback loop of the molecular clock is incomplete in isolated clock neurons. We further demonstrate that, by pharmacological assays using the non-amidated form of neuropeptide pigment-dispersing factor (PDF), which could be specifically secreted from larval LNvs and adult s-LNvs, downstream events of the PDF signaling are partly impaired in dissociated larval clock neurons. Although non-amidated PDF is likely to be less active than the amidated one, these results point out the possibility that alteration in PDF downstream signaling may play a role in dampening of molecular rhythms in isolated clock neurons. Taken together, our results suggest that Drosophila clocks are weak oscillators that need to be in the intact circadian circuit to generate robust 24-h rhythms. PMID:29075180

Dual PDF signaling pathways reset clocks via TIMELESS and acutely excite target neurons to control circadian behavior.

PubMed

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-03-01

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(-) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(-) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per⁰¹ mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per⁰¹ flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output.

Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior

PubMed Central

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-01-01

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(−) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(−) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per01 mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per01 flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output. PMID:24643294

Using a transportable optical clock for chronometric levelling

NASA Astrophysics Data System (ADS)

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

2016-07-01

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

GPS/GLONASS Combined Precise Point Positioning with Receiver Clock Modeling

PubMed Central

Wang, Fuhong; Chen, Xinghan; Guo, Fei

2015-01-01

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

The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity

PubMed Central

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

2015-01-01

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

Immediate Effects of Clock-Turn Strategy on the Pattern and Performance of Narrow Turning in Persons With Parkinson Disease.

PubMed

Yang, Wen-Chieh; Hsu, Wei-Li; Wu, Ruey-Meei; Lin, Kwan-Hwa

2016-10-01

Turning difficulty is common in people with Parkinson disease (PD). The clock-turn strategy is a cognitive movement strategy to improve turning performance in people with PD despite its effects are unverified. Therefore, this study aimed to investigate the effects of the clock-turn strategy on the pattern of turning steps, turning performance, and freezing of gait during a narrow turning, and how these effects were influenced by concurrent performance of a cognitive task (dual task). Twenty-five people with PD were randomly assigned to the clock-turn or usual-turn group. Participants performed the Timed Up and Go test with and without concurrent cognitive task during the medication OFF period. The clock-turn group performed the Timed Up and Go test using the clock-turn strategy, whereas participants in the usual-turn group performed in their usual manner. Measurements were taken during the 180° turn of the Timed Up and Go test. The pattern of turning steps was evaluated by step time variability and step time asymmetry. Turning performance was evaluated by turning time and number of turning steps. The number and duration of freezing of gait were calculated by video review. The clock-turn group had lower step time variability and step time asymmetry than the usual-turn group. Furthermore, the clock-turn group turned faster with fewer freezing of gait episodes than the usual-turn group. Dual task increased the step time variability and step time asymmetry in both groups but did not affect turning performance and freezing severity. The clock-turn strategy reduces turning time and freezing of gait during turning, probably by lowering step time variability and asymmetry. Dual task compromises the effects of the clock-turn strategy, suggesting a competition for attentional resources.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A141).

Factors reducing the expected deflection in initial orientation in clock-shifted homing pigeons.

PubMed

Gagliardo, Anna; Odetti, Francesca; Ioalè, Paolo

2005-02-01

To orient from familiar sites, homing pigeons can rely on both an olfactory map and visual familiar landmarks. The latter can in principle be used in two different ways: either within a topographical map exploited for piloting or in a so-called mosaic map associated with a compass bearing. One way to investigate the matter is to put the compass and the topographical information in conflict by releasing clock-shifted pigeons from familiar locations. Although the compass orientation is in general dominant over a piloting strategy, a stronger or weaker tendency to correct towards the home direction by clock-shifted pigeons released from very familiar sites has often been observed. To investigate which factors are involved in the reduction of the deviation due to clock-shift, we performed a series of releases with intact and anosmic pigeons from familiar sites in unshifted and clock-shifted conditions and a series of releases from the same sites with naive clock-shifted birds. Our data suggest that the following factors have a role in reducing deviation due to the clock-shift: familiarity with the release site, the lack of olfactory information and some unknown site-dependent features.

Silencing Nicotiana attenuata LHY and ZTL alters circadian rhythms in flowers

PubMed Central

Yon, Felipe; Joo, Youngsung; Cortés Llorca, Lucas; Rothe, Eva; Baldwin, Ian T.; Kim, Sang-Gyu

2016-01-01

Summary The rhythmic opening/closing and volatile emissions of flowers is known to attract pollinators at specific times. That these rhythms are maintained under constant light or dark conditions suggests a circadian clock involvement. Although a forward and reverse genetic approach led to the identification of core circadian clock components in Arabidopsis thaliana, involvement of these clock components for floral rhythms remained untested likely due to weak diurnal rhythms in A. thaliana flowers.Here we addressed the role of these core clock components in the flowers of the wild tobacco Nicotiana attenuata, whose flowers open at night, emit benzyl acetone (BA) scents, and move vertically through a 140° arc.We first measured N. attenuata floral rhythms under constant light conditions. The results suggest that the circadian clock controls flower opening, BA emission, and pedicel movement, but not flower closing.We generated transgenic N. attenuata lines silenced in the homologous genes of Arabidopsis LATE ELONGATED HYPOCOTYL (LHY) and ZEITLUPE (ZTL), which are known as a core clock component. Silencing NaLHY and NaZTL strongly altered floral rhythms in different ways, indicating that conserved clock components in N. attenuata coordinate these floral rhythms. PMID:26439540

Atomic clocks and the continuous-time random-walk

NASA Astrophysics Data System (ADS)

Formichella, Valerio; Camparo, James; Tavella, Patrizia

2017-11-01

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

Verification of fault-tolerant clock synchronization systems. M.S. Thesis - College of William and Mary, 1992

NASA Technical Reports Server (NTRS)

Miner, Paul S.

1993-01-01

A critical function in a fault-tolerant computer architecture is the synchronization of the redundant computing elements. The synchronization algorithm must include safeguards to ensure that failed components do not corrupt the behavior of good clocks. Reasoning about fault-tolerant clock synchronization is difficult because of the possibility of subtle interactions involving failed components. Therefore, mechanical proof systems are used to ensure that the verification of the synchronization system is correct. In 1987, Schneider presented a general proof of correctness for several fault-tolerant clock synchronization algorithms. Subsequently, Shankar verified Schneider's proof by using the mechanical proof system EHDM. This proof ensures that any system satisfying its underlying assumptions will provide Byzantine fault-tolerant clock synchronization. The utility of Shankar's mechanization of Schneider's theory for the verification of clock synchronization systems is explored. Some limitations of Shankar's mechanically verified theory were encountered. With minor modifications to the theory, a mechanically checked proof is provided that removes these limitations. The revised theory also allows for proven recovery from transient faults. Use of the revised theory is illustrated with the verification of an abstract design of a clock synchronization system.

Experimental verification of clock noise transfer and components for space based gravitational wave detectors.

PubMed

Sweeney, Dylan; Mueller, Guido

2012-11-05

The Laser Interferometer Space Antenna (LISA) and other space based gravitational wave detector designs require a laser communication subsystem to, among other things, transfer clock signals between spacecraft (SC) in order to cancel clock noise in post-processing. The original LISA baseline design requires frequency synthesizers to convert each SC clock into a 2 GHz signal, and electro-optic modulators (EOMs) to modulate this 2 GHz clock signal onto the laser light. Both the frequency synthesizers and the EOMs must operate with a phase fidelity of 2×10(-4)cycles/√Hz. In this paper we present measurements of the phase fidelity of frequency synthesizers and EOMs. We found that both the frequency synthesizers and the EOMs meet the requirement when tested independently and together. We also performed an electronic test of the clock noise transfer using frequency synthesizers and the University of Florida LISA Interferometry (UFLIS) phasemeter. We found that by applying a time varying fractional delay filter we could suppress the clock noise to a level below our measurement limit, which is currently determined by timing jitter and is less than an order of magnitude above the LISA requirement for phase measurements.

An algorithm for the Italian atomic time scale

NASA Technical Reports Server (NTRS)

Cordara, F.; Vizio, G.; Tavella, P.; Pettiti, V.

1994-01-01

During the past twenty years, the time scale at the IEN has been realized by a commercial cesium clock, selected from an ensemble of five, whose rate has been continuously steered towards UTC to maintain a long term agreement within 3 x 10(exp -13). A time scale algorithm, suitable for a small clock ensemble and capable of improving the medium and long term stability of the IEN time scale, has been recently designed taking care of reducing the effects of the seasonal variations and the sudden frequency anomalies of the single cesium clocks. The new time scale, TA(IEN), is obtained as a weighted average of the clock ensemble computed once a day from the time comparisons between the local reference UTC(IEN) and the single clocks. It is foreseen to include in the computation also ten cesium clocks maintained in other Italian laboratories to further improve its reliability and its long term stability. To implement this algorithm, a personal computer program in Quick Basic has been prepared and it has been tested at the IEN time and frequency laboratory. Results obtained using this algorithm on the real clocks data relative to a period of about two years are presented.

Effects of Light and Temperature on Daily Activity and Clock Gene Expression in Two Mosquito Disease Vectors.

PubMed

Rivas, Gustavo B S; Teles-de-Freitas, Rayane; Pavan, Márcio G; Lima, José B P; Peixoto, Alexandre A; Bruno, Rafaela Vieira

2018-06-01

Most organisms feature an endogenous circadian clock capable of synchronization with their environment. The most well-known synchronizing agents are light and temperature. The circadian clock of mosquitoes, vectors of many pathogens, drives important behaviors related to vectoral capacity, including oviposition, host seeking, and hematophagy. Main clock gene expression, as well as locomotor activity patterns, has been identified in Aedes aegypti and Culex quinquefasciatus under artificial light-dark cycles. Given that these mosquito species thrive in tropical areas, it is reasonable to speculate that temperature plays an important role in the circadian clock. Here, we provide data supporting a different hierarchy of light and temperature as zeitgebers of two mosquito species. We recorded their locomotor activity and quantified mRNA expression of the main clock genes in several combinations of light and temperature cycles. We observed that A. aegypti is more sensitive to temperature, while C. quinquefasciatus is more responsive to light. These variations in clock gene expression and locomotor activity may have affected the mosquito species' metabolism, energy expenditure, fitness cost, and pathogen transmission efficiency. Our findings are relevant to chronobiology studies and also have epidemiological implications.

Chronobiology of crickets: a review.

PubMed

Tomioka, Kenji

2014-10-01

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

Identification of the Molecular Clockwork of the Oyster Crassostrea gigas

PubMed Central

Perrigault, Mickael; Tran, Damien

2017-01-01

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

The Chip-Scale Atomic Clock - Recent Development Progress

DTIC Science & Technology

2004-09-01

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

Technology development for laser-cooled clocks on the International Space Station

NASA Technical Reports Server (NTRS)

Klipstein, W. M.

2003-01-01

The PARCS experiment will use a laser-cooled cesium atomic clock operating in the microgravity environment aboard the International Space Station to provide both advanced tests of gravitational theory to demonstrate a new cold-atom clock technology for space.

A novel simultaneous demultiplexing and clock recovery unit for high speed OTDM system

NASA Astrophysics Data System (ADS)

Zhong, Kangping; Jia, Nan; Li, Tangjun; Wang, Muguang; Chi, Jianfeng; Sun, Jian; Wang, Jingtian

2010-11-01

In this letter, a novel simultaneous demultiplexing and clock recovery unit based on EAMs and clock recovery module is presented and experimentally demonstrated for a high speed OTDM system. The 10GHz clock signal with low jitter is extracted from 80Gbit/s and 160Gbit/s OTDM signal, and every channel of the OTDM signal is successfully demultiplexed using this unit. The power penalty is lower than 3dB at BER of 10-9.

Analyses of conversion efficiency in high-speed clock recovery based on Mach-Zehnder modulator

NASA Astrophysics Data System (ADS)

Dong, H.; Sun, H.; Zhu, G.; Dutta, N. K.

2006-09-01

In this paper, detailed analyses of the conversion efficiency in high-speed clock recovery based on Mach-Zehnder (MZ) modulator has been carried out. The theoretical results show the conversion efficiency changes with RF driving power and the mixing order. For high order clock recovery, the cascaded MZ modulator provides higher conversion efficiency. A study of clock recovery at 160 Gb/s using the cascaded MZ modulator has been carried out. The experimental results agree with the results of the analysis.

System-wide power management control via clock distribution network

DOEpatents

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

2015-05-19

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

System and method for adaptively deskewing parallel data signals relative to a clock

DOEpatents

Jenkins, Philip Nord [Eau Claire, WI; Cornett, Frank N [Chippewa Falls, WI

2008-10-07

A system and method of reducing skew between a plurality of signals transmitted with a transmit clock is described. Skew is detected between the received transmit clock and each of received data signals. Delay is added to the clock or to one or more of the plurality of data signals to compensate for the detected skew. The delay added to each of the plurality of delayed signals is updated to adapt to changes in detected skew.

System and method for adaptively deskewing parallel data signals relative to a clock

DOEpatents

Jenkins, Philip Nord [Redwood Shores, CA; Cornett, Frank N [Chippewa Falls, WI

2011-10-04

A system and method of reducing skew between a plurality of signals transmitted with a transmit clock is described. Skew is detected between the received transmit clock and each of received data signals. Delay is added to the clock or to one or more of the plurality of data signals to compensate for the detected skew. The delay added to each of the plurality of delayed signals is updated to adapt to changes in detected skew.

Non-canonical Phototransduction Mediates Synchronization of the Drosophila melanogaster Circadian Clock and Retinal Light Responses.

PubMed

Ogueta, Maite; Hardie, Roger C; Stanewsky, Ralf

2018-06-04

The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical visual Rhodopsin phototransduction. Here, we show that at least three of the seven Drosophila rhodopsins can utilize an alternative transduction mechanism involving the same α-subunit of the heterotrimeric G protein operating in canonical visual phototransduction (Gq). Surprisingly, in mutants lacking the canonical phospholipase C-β (PLC-β) encoded by the no receptor potential A (norpA) gene, we uncovered a novel transduction pathway using a different PLC-β encoded by the Plc21C gene. This novel pathway is important for behavioral clock resetting to semi-natural light-dark cycles and mediates light-dependent molecular synchronization within the s-LNv clock neurons. The same pathway appears to be responsible for norpA-independent light responses in the compound eye. We show that Rhodopsin 5 (Rh5) and Rh6, present in the R8 subset of retinal photoreceptor cells, drive both the long-term circadian and rapid light responses in the eye. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evolution of circadian rhythms in Drosophila melanogaster populations reared in constant light and dark regimes for over 330 generations.

PubMed

Shindey, Radhika; Varma, Vishwanath; Nikhil, K L; Sharma, Vijay Kumar

2017-01-01

Organisms are believed to have evolved circadian clocks as adaptations to deal with cyclic environmental changes, and therefore it has been hypothesized that evolution in constant environments would lead to regression of such clocks. However, previous studies have yielded mixed results, and evolution of circadian clocks under constant conditions has remained an unsettled topic of debate in circadian biology. In continuation of our previous studies, which reported persistence of circadian rhythms in Drosophila melanogaster populations evolving under constant light, here we intended to examine whether circadian clocks and the associated properties evolve differently under constant light and constant darkness. In this regard, we assayed activity-rest, adult emergence and oviposition rhythms of D. melanogaster populations which have been maintained for over 19 years (~330 generations) under three different light regimes - constant light (LL), light-dark cycles of 12:12 h (LD) and constant darkness (DD). We observed that while circadian rhythms in all the three behaviors persist in both LL and DD stocks with no differences in circadian period, they differed in certain aspects of the entrained rhythms when compared to controls reared in rhythmic environment (LD). Interestingly, we also observed that DD stocks have evolved significantly higher robustness or power of free-running activity-rest and adult emergence rhythms compared to LL stocks. Thus, our study, in addition to corroborating previous results of circadian clock evolution in constant light, also highlights that, contrary to the expected regression of circadian clocks, rearing in constant darkness leads to the evolution of more robust circadian clocks which may be attributed to an intrinsic adaptive advantage of circadian clocks and/or pleiotropic functions of clock genes in other traits.

Conservation and Divergence of Circadian Clock Operation in a Stress-Inducible Crassulacean Acid Metabolism Species Reveals Clock Compensation against Stress1

PubMed Central

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

2005-01-01

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

Advances in time-scale algorithms

NASA Technical Reports Server (NTRS)

Stein, S. R.

1993-01-01

The term clock is usually used to refer to a device that counts a nearly periodic signal. A group of clocks, called an ensemble, is often used for time keeping in mission critical applications that cannot tolerate loss of time due to the failure of a single clock. The time generated by the ensemble of clocks is called a time scale. The question arises how to combine the times of the individual clocks to form the time scale. One might naively be tempted to suggest the expedient of averaging the times of the individual clocks, but a simple thought experiment demonstrates the inadequacy of this approach. Suppose a time scale is composed of two noiseless clocks having equal and opposite frequencies. The mean time scale has zero frequency. However if either clock fails, the time-scale frequency immediately changes to the frequency of the remaining clock. This performance is generally unacceptable and simple mean time scales are not used. First, previous time-scale developments are reviewed and then some new methods that result in enhanced performance are presented. The historical perspective is based upon several time scales: the AT1 and TA time scales of the National Institute of Standards and Technology (NIST), the A.1(MEAN) time scale of the US Naval observatory (USNO), the TAI time scale of the Bureau International des Poids et Measures (BIPM), and the KAS-1 time scale of the Naval Research laboratory (NRL). The new method was incorporated in the KAS-2 time scale recently developed by Timing Solutions Corporation. The goal is to present time-scale concepts in a nonmathematical form with as few equations as possible. Many other papers and texts discuss the details of the optimal estimation techniques that may be used to implement these concepts.

Manipulating the circadian and sleep cycles to protect against metabolic disease.

PubMed

Nohara, Kazunari; Yoo, Seung-Hee; Chen, Zheng Jake

2015-01-01

Modernization of human society parallels an epidemic of metabolic disorders including obesity. Apart from excess caloric intake, a 24/7 lifestyle poses another important challenge to our metabolic health. Recent research under both laboratory and epidemiological settings has indicated that abnormal temporal organization of sleep and wakeful activities including food intake is a significant risk factor for metabolic disease. The circadian clock system is our intrinsic biological timer that regulates internal rhythms such as the sleep/wake cycle and also responses to external stimuli including light and food. Initially thought to be mainly involved in the timing of sleep, the clock, and/or clock genes may also play a role in sleep architecture and homeostasis. Importantly, an extensive body of evidence has firmly established a master regulatory role of the clock in energy balance. Together, a close relationship between well-timed circadian/sleep cycles and metabolic health is emerging. Exploiting this functional connection, an important holistic strategy toward curbing the epidemic of metabolic disorders (e.g., obesity) involves corrective measures on the circadian clock and sleep. In addition to behavioral and environmental interventions including meal timing and light control, pharmacological agents targeting sleep and circadian clocks promise convenient and effective applications. Recent studies, for example, have reported small molecules targeting specific clock components and displaying robust beneficial effects on sleep and metabolism. Furthermore, a group of clock-amplitude-enhancing small molecules (CEMs) identified via high-throughput chemical screens are of particular interest for future in vivo studies of their metabolic and sleep efficacies. Elucidating the functional relationship between clock, sleep, and metabolism will also have far-reaching implications for various chronic human diseases and aging.

Assessing the short-term clock drift of early broadband stations with burst events of the 26 s persistent and localized microseism

NASA Astrophysics Data System (ADS)

Xie, Jun; Ni, Sidao; Chu, Risheng; Xia, Yingjie

2018-01-01

Accurate seismometer clock plays an important role in seismological studies including earthquake location and tomography. However, some seismic stations may have clock drift larger than 1 s (e.g. GSC in 1992), especially in early days of global seismic networks. The 26 s Persistent Localized (PL) microseism event in the Gulf of Guinea sometime excites strong and coherent signals, and can be used as repeating source for assessing stability of seismometer clocks. Taking station GSC, PAS and PFO in the TERRAscope network as an example, the 26 s PL signal can be easily observed in the ambient noise cross-correlation function between these stations and a remote station OBN with interstation distance about 9700 km. The travel-time variation of this 26 s signal in the ambient noise cross-correlation function is used to infer clock error. A drastic clock error is detected during June 1992 for station GSC, but not found for station PAS and PFO. This short-term clock error is confirmed by both teleseismic and local earthquake records with a magnitude of 25 s. Averaged over the three stations, the accuracy of the ambient noise cross-correlation function method with the 26 s source is about 0.3-0.5 s. Using this PL source, the clock can be validated for historical records of sparsely distributed stations, where the usual ambient noise cross-correlation function of short-period (<20 s) ambient noise might be less effective due to its attenuation over long interstation distances. However, this method suffers from cycling problem, and should be verified by teleseismic/local P waves. Further studies are also needed to investigate whether the 26 s source moves spatially and its effects on clock drift detection.

Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study.

PubMed

Riestra, Pia; Gebreab, Samson Y; Xu, Ruihua; Khan, Rumana J; Gaye, Amadou; Correa, Adolfo; Min, Nancy; Sims, Mario; Davis, Sharon K

2017-06-23

Circadian rhythms regulate key biological processes and the dysregulation of the intrinsic clock mechanism affects sleep patterns and obesity onset. The CLOCK (circadian locomotor output cycles protein kaput) gene encodes a core transcription factor of the molecular circadian clock influencing diverse metabolic pathways, including glucose and lipid homeostasis. The primary objective of this study was to evaluate the associations between CLOCK single nucleotide polymorphisms (SNPs) and body mass index (BMI). We also evaluated the association of SNPs with BMI related factors such as sleep duration and quality, adiponectin and leptin, in 2962 participants (1116 men and 1810 women) from the Jackson Heart Study. Genotype data for the selected 23 CLOCK gene SNPS was obtained by imputation with IMPUTE2 software and reference phase data from the 1000 genome project. Genetic analyses were conducted with PLINK RESULTS: We found a significant association between the CLOCK SNP rs2070062 and sleep duration, participants carriers of the T allele showed significantly shorter sleep duration compared to non-carriers after the adjustment for individual proportions of European ancestry (PEA), socio economic status (SES), body mass index (BMI), alcohol consumption and smoking status that reach the significance threshold after multiple testing correction. In addition, we found nominal associations of the CLOCK SNP rs6853192 with longer sleep duration and the rs6820823, rs3792603 and rs11726609 with BMI. However, these associations did not reach the significance threshold after correction for multiple testing. In this work, CLOCK gene variants were associated with sleep duration and BMI suggesting that the effects of these polymorphisms on circadian rhythmicity may affect sleep duration and body weight regulation in Africans Americans.

BMAL1 and CLOCK proteins in regulating UVB-induced apoptosis and DNA damage responses in human keratinocytes.

PubMed

Sun, Yang; Wang, Peiling; Li, Hongyu; Dai, Jun

2018-06-26

A diverse array of biological processes are under circadian controls. In mouse skin, ultraviolet ray (UVR)-induced apoptosis and DNA damage responses are time-of-day dependent, which are controlled by core clock proteins. This study investigates the roles of clock proteins in regulating UVB responses in human keratinocytes (HKCs). We found that the messenger RNA expression of brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) genes is altered by low doses (5 mJ/cm 2 ) of UVB in the immortalized HaCat HKCs cell line. Although depletion of BMAL1 or CLOCK has no effect on the activation of Rad3-related protein kinases-checkpoint kinase 1-p53 mediated DNA damage checkpoints, it leads to suppression of UVB-stimulated apoptotic responses, and downregulation of UVB-elevated expression of DNA damage marker γ-H2AX and cell cycle inhibitor p21. Diminished apoptotic responses are also observed in primary HKCs depleted of BMAL1 or CLOCK after UVB irradiation. While CLOCK depletion shows a suppressive effect on UVB-induced p53 protein accumulation, depletion of either clock gene triggers early keratinocyte differentiation of HKCs at their steady state. These results suggest that UVB-induced apoptosis and DNA damage responses are controlled by clock proteins, but via different mechanisms in the immortalized human adult low calcium temperature and primary HKCs. Given the implication of UVB in photoaging and photocarcinogenesis, mechanistic elucidation of circadian controls on UVB effects in human skin will be critical and beneficial for prevention and treatment of skin cancers and other skin-related diseases. © 2018 Wiley Periodicals, Inc.

Effect of monochromatic light on circadian rhythmic expression of clock genes in the hypothalamus of chick.

PubMed

Jiang, Nan; Wang, Zixu; Cao, Jing; Dong, Yulan; Chen, Yaoxing

2017-08-01

To clarify the effect of monochromatic light on circadian clock gene expression in chick hypothalamus, a total 240 newly hatched chickens were reared under blue light (BL), green light (GL), red light (RL) and white light (WL), respectively. On the post-hatched day 14, 24-h profiles of seven core clock genes (cClock, cBmal1, cBmal2, cCry1, cCry2, cPer2 and cPer3) were measured at six time points (CT 0, CT 4, CT 8, CT 12, CT 16, CT 20, circadian time). We found all these clock genes expressed with a significant rhythmicity in different light wavelength groups. Meanwhile, cClock and cBmal1 showed a high level under GL, and followed a corresponding high expression of cCry1. However, RL decreased the expression levels of these genes. Be consistent with the mRNA level, CLOCK and BMAL1 proteins also showed a high level under GL. The CLOCK-like immunoreactive neurons were observed not only in the SCN, but also in the non-SCN brain region such as the nucleus anterior medialis hypothalami, the periventricularis nucleus, the paraventricular nucleus and the median eminence. All these results are consistent with the auto-regulatory circadian feedback loop, and indicate that GL may play an important role on the circadian time generation and development in the chick hypothalamus. Our results also suggest that the circadian clock in the chick hypothalamus such as non-SCN brain region were involved in the regulation of photo information. Copyright © 2017 Elsevier B.V. All rights reserved.

Restoration of labral anatomy and biomechanics after superior labral anterior-posterior repair: comparison of mattress versus simple technique.

PubMed

Boddula, Madhav R; Adamson, Gregory J; Gupta, Akash; McGarry, Michelle H; Lee, Thay Q

2012-04-01

Both simple and mattress repair techniques have been utilized with success for type II superior labral anterior-posterior (SLAP) lesions; however, direct anatomic and biomechanical comparisons of these techniques have yet to be clearly demonstrated. For type II SLAP lesions, the mattress suture repair technique will result in greater labral height and better position on the glenoid face and exhibit stronger biomechanical characteristics, when cyclically loaded and loaded to failure through the biceps, compared with the simple suture repair technique. Controlled laboratory study. Six matched pairs of cadaveric shoulders were dissected, and a clock face was created on the glenoid from 9 o'clock (posterior) to 3 o'clock (anterior). For the intact specimen, labral height and labral distance from the glenoid edge were measured using a MicroScribe. A SLAP lesion was then created from 10 o'clock to 2 o'clock. Lesions were repaired with two 3.0-mm BioSuture-Tak anchors placed at 11 o'clock and 1 o'clock. For each pair, a mattress repair was used for one shoulder, and a simple repair was used for the contralateral shoulder. After repair, labral height and labral distance from the glenoid edge were again measured. The specimens were then cyclically loaded and loaded to failure through the biceps using an Instron machine. A paired t test was used for statistical analysis. After mattress repair, a significant increase in labral height occurred compared with intact from 2.5 ± 0.3 mm to 4.3 ± 0.3 mm at 11 o'clock (P = .013), 2.7 ± 0.5 mm to 4.2 ± 0.7 mm at 12:30 o'clock (P = .007), 3.1 ± 0.5 mm to 4.2 ± 0.7 mm at 1 o'clock (P = .006), and 2.8 ± 0.7 mm to 3.7 ± 0.8 mm at 1:30 o'clock (P = .037). There was no significant difference in labral height between the intact condition and after simple repair at any clock face position. Labral height was significantly increased in the mattress repairs compared with simple repairs at 11 o'clock (mean difference, 2.0 mm; P = .008) and 12:30 o'clock (mean difference, 1.3 mm; P = .044). Labral distance from the glenoid edge was not significantly different between techniques. No difference was observed between the mattress and simple repair techniques for all biomechanical parameters, except the simple technique had a higher load and energy absorbed at 2-mm displacement. The mattress technique created a greater labral height while maintaining similar biomechanical characteristics compared with the simple repair, with the exception of load and energy absorbed at 2-mm displacement, which was increased for the simple technique. Mattress repair for type II SLAP lesions creates a higher labral bumper compared with simple repairs, while both techniques resulted in similar biomechanical characteristics.

Autobalanced Ramsey Spectroscopy

NASA Astrophysics Data System (ADS)

Sanner, Christian; Huntemann, Nils; Lange, Richard; Tamm, Christian; Peik, Ekkehard

2018-01-01

We devise a perturbation-immune version of Ramsey's method of separated oscillatory fields. Spectroscopy of an atomic clock transition without compromising the clock's accuracy is accomplished by actively balancing the spectroscopic responses from phase-congruent Ramsey probe cycles of unequal durations. Our simple and universal approach eliminates a wide variety of interrogation-induced line shifts often encountered in high precision spectroscopy, among them, in particular, light shifts, phase chirps, and transient Zeeman shifts. We experimentally demonstrate autobalanced Ramsey spectroscopy on the light shift prone Yb+ 171 electric octupole optical clock transition and show that interrogation defects are not turned into clock errors. This opens up frequency accuracy perspectives below the 10-18 level for the Yb+ system and for other types of optical clocks.

Direct regulation of myocardial triglyceride metabolism by the cardiomyocyte circadian clock

USDA-ARS?s Scientific Manuscript database

Maintenance of circadian alignment between an organism and its environment is essential to ensure metabolic homeostasis. Synchrony is achieved by cell autonomous circadian clocks. Despite a growing appreciation of the integral relation between clocks and metabolism, little is known regarding the dir...

Disruption of the circadian clock within the cardiomyocyte influences mycardial contractile function, metabolism, and gene expression

USDA-ARS?s Scientific Manuscript database

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variatio...

Development of an optically-pumped cesium standard at the Aerospace Corporation

NASA Technical Reports Server (NTRS)

Chan, Yat C.

1992-01-01

We have initiated a research program to study the performance of compact optically-pumped cesium (Cs) frequency standards, which have potential for future timekeeping applications in space. A Cs beam clock apparatus has been assembled. Basic functions of the frequency standard have been demonstrated. Clock signals are observed with optical pumping schemes using one or two lasers. With two laser pumping, we are able to selectively place up to 80 percent of the atomic population into one of the clock transition states. The observed pattern of clock signal indicates that the velocity distribution of the Cs atoms contributing to the microwave signal is beam-Maxwellian. Thus, in the optically-pumped Cs frequency standards, the entire Cs population in the atomic beam could be utilized to generate the clock signals. This is in contrast to the conventional Cs beam standards where only approx. 1 percent of the atoms in the beam are used. More efficient Cs consumption can lead to improved reliability and increased useful lifetime of the clock.

The role of feeding rhythm, adrenal hormones and neuronal inputs in synchronizing daily clock gene rhythms in the liver.

PubMed

Su, Yan; Cailotto, Cathy; Foppen, Ewout; Jansen, Remi; Zhang, Zhi; Buijs, Ruud; Fliers, Eric; Kalsbeek, Andries

2016-02-15

The master clock in the hypothalamic suprachiasmatic nucleus (SCN) is assumed to distribute rhythmic information to the periphery via neural, humoral and/or behavioral connections. Until now, feeding, corticosterone and neural inputs are considered important signals for synchronizing daily rhythms in the liver. In this study, we investigated the necessity of neural inputs as well as of the feeding and adrenal hormone rhythms for maintaining daily hepatic clock gene rhythms. Clock genes kept their daily rhythm when only one of these three signals was disrupted, or when we disrupted hepatic neuronal inputs together with the adrenal hormone rhythm or with the daily feeding rhythm. However, all clock genes studied lost their daily expression rhythm after simultaneous disruption of the feeding and adrenal hormone rhythm. These data indicate that either a daily rhythm of feeding or adrenal hormones should be present to synchronize clock gene rhythms in the liver with the SCN. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Circadian clock proteins and immunity.

PubMed

Curtis, Anne M; Bellet, Marina M; Sassone-Corsi, Paolo; O'Neill, Luke A J

2014-02-20

Immune parameters change with time of day and disruption of circadian rhythms has been linked to inflammatory pathologies. A circadian-clock-controlled immune system might allow an organism to anticipate daily changes in activity and feeding and the associated risk of infection or tissue damage to the host. Responses to bacteria have been shown to vary depending on time of infection, with mice being more at risk of sepsis when challenged ahead of their activity phase. Studies highlight the extent to which the molecular clock, most notably the core clock proteins BMAL1, CLOCK, and REV-ERBα, control fundamental aspects of the immune response. Examples include the BMAL1:CLOCK heterodimer regulating toll-like receptor 9 (TLR9) expression and repressing expression of the inflammatory monocyte chemokine ligand (CCL2) as well as REV-ERBα suppressing the induction of interleukin-6. Understanding the daily rhythm of the immune system could have implications for vaccinations and how we manage infectious and inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

RNA-seq analysis of Drosophila clock and non-clock neurons reveals neuron-specific cycling and novel candidate neuropeptides.

PubMed

Abruzzi, Katharine C; Zadina, Abigail; Luo, Weifei; Wiyanto, Evelyn; Rahman, Reazur; Guo, Fang; Shafer, Orie; Rosbash, Michael

2017-02-01

Locomotor activity rhythms are controlled by a network of ~150 circadian neurons within the adult Drosophila brain. They are subdivided based on their anatomical locations and properties. We profiled transcripts "around the clock" from three key groups of circadian neurons with different functions. We also profiled a non-circadian outgroup, dopaminergic (TH) neurons. They have cycling transcripts but fewer than clock neurons as well as low expression and poor cycling of clock gene transcripts. This suggests that TH neurons do not have a canonical circadian clock and that their gene expression cycling is driven by brain systemic cues. The three circadian groups are surprisingly diverse in their cycling transcripts and overall gene expression patterns, which include known and putative novel neuropeptides. Even the overall phase distributions of cycling transcripts are distinct, indicating that different regulatory principles govern transcript oscillations. This surprising cell-type diversity parallels the functional heterogeneity of the different neurons.

Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging.

PubMed

Shafer, Orie T; Kim, Dong Jo; Dunbar-Yaffe, Richard; Nikolaev, Viacheslav O; Lohse, Martin J; Taghert, Paul H

2008-04-24

The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of approximately 150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of approximately 150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network.

CK1/Doubletime activity delays transcription activation in the circadian clock

PubMed Central

O'Neil, Jenna L; Merz, Gregory E; Dusad, Kritika; Crane, Brian R; Young, Michael W

2018-01-01

In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex. Our results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence. The role of DBT in regulating PER activity, stabilization and degradation ensures that these events are chronologically and biochemically linked, and contributes to the timing of an essential delay that influences the period of the circadian clock. PMID:29611807

RighTime: A real time clock correcting program for MS-DOS-based computer systems

NASA Technical Reports Server (NTRS)

Becker, G. Thomas

1993-01-01

A computer program is described which effectively eliminates the misgivings of the DOS system clock in PC/AT-class computers. RighTime is a small, sophisticated memory-resident program that automatically corrects both the DOS system clock and the hardware 'CMOS' real time clock (RTC) in real time. RighTime learns what corrections are required without operator interaction beyond the occasional accurate time set. Both warm (power on) and cool (power off) errors are corrected, usually yielding better than one part per million accuracy in the typical desktop computer with no additional hardware, and RighTime increases the system clock resolution from approximately 0.0549 second to 0.01 second. Program tools are also available which allow visualization of RighTime's actions, verification of its performance, display of its history log, and which provide data for graphing of the system clock behavior. The program has found application in a wide variety of industries, including astronomy, satellite tracking, communications, broadcasting, transportation, public utilities, manufacturing, medicine, and the military.

Realistic Clocks for a Universe Without Time

NASA Astrophysics Data System (ADS)

Bryan, K. L. H.; Medved, A. J. M.

2018-01-01

There are a number of problematic features within the current treatment of time in physical theories, including the "timelessness" of the Universe as encapsulated by the Wheeler-DeWitt equation. This paper considers one particular investigation into resolving this issue; a conditional probability interpretation that was first proposed by Page and Wooters. Those authors addressed the apparent timelessness by subdividing a faux Universe into two entangled parts, "the clock" and "the remainder of the Universe", and then synchronizing the effective dynamics of the two subsystems by way of conditional probabilities. The current treatment focuses on the possibility of using a (somewhat) realistic clock system; namely, a coherent-state description of a damped harmonic oscillator. This clock proves to be consistent with the conditional probability interpretation; in particular, a standard evolution operator is identified with the position of the clock playing the role of time for the rest of the Universe. Restrictions on the damping factor are determined and, perhaps contrary to expectations, the optimal choice of clock is not necessarily one of minimal damping.

Placement of clock gates in time-of-flight optoelectronic circuits

NASA Astrophysics Data System (ADS)

Feehrer, John R.; Jordan, Harry F.

1995-12-01

Time-of-flight synchronized optoelectronic circuits capitalize on the highly controllable delays of optical waveguides. Circuits have no latches; synchronization is achieved by adjustment of the lengths of waveguides that connect circuit elements. Clock gating and pulse stretching are used to restore timing and power. A functional circuit requires that every feedback loop contain at least one clock gate to prevent cumulative timing drift and power loss. A designer specifies an ideal circuit, which contains no or very few clock gates. To make the circuit functional, we must identify locations in which to place clock gates. Because clock gates are expensive, add area, and increase delay, a minimal set of locations is desired. We cast this problem in graph-theoretical form as the minimum feedback edge set problem and solve it by using an adaptation of an algorithm proposed in 1966 [IEEE Trans. Circuit Theory CT-13, 399 (1966)]. We discuss a computer-aided-design implementation of the algorithm that reduces computational complexity and demonstrate it on a set of circuits.

Circadian Amplitude Regulation via FBXW7-Targeted REV-ERBα Degradation.

PubMed

Zhao, Xuan; Hirota, Tsuyoshi; Han, Xuemei; Cho, Han; Chong, Ling-Wa; Lamia, Katja; Liu, Sihao; Atkins, Annette R; Banayo, Ester; Liddle, Christopher; Yu, Ruth T; Yates, John R; Kay, Steve A; Downes, Michael; Evans, Ronald M

2016-06-16

Defects in circadian rhythm influence physiology and behavior with implications for the treatment of sleep disorders, metabolic disease, and cancer. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms underpinning amplitude is limited. Here, we show that REV-ERBα, a core inhibitory component of clock transcription, is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7. By relieving REV-ERBα-dependent repression, FBXW7 provides an unrecognized mechanism for enhancing the amplitude of clock gene transcription. Cyclin-dependent kinase 1 (CDK1)-mediated phosphorylation of REV-ERBα is necessary for FBXW7 recognition. Moreover, targeted hepatic disruption of FBXW7 alters circadian expression of core clock genes and perturbs whole-body lipid and glucose levels. This CDK1-FBXW7 pathway controlling REV-ERBα repression defines an unexpected molecular mechanism for re-engaging the positive transcriptional arm of the clock, as well as a potential route to manipulate clock amplitude via small molecule CDK1 inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

Test of Special Relativity Using a Fiber Network of Optical Clocks.

PubMed

Delva, P; Lodewyck, J; Bilicki, S; Bookjans, E; Vallet, G; Le Targat, R; Pottie, P-E; Guerlin, C; Meynadier, F; Le Poncin-Lafitte, C; Lopez, O; Amy-Klein, A; Lee, W-K; Quintin, N; Lisdat, C; Al-Masoudi, A; Dörscher, S; Grebing, C; Grosche, G; Kuhl, A; Raupach, S; Sterr, U; Hill, I R; Hobson, R; Bowden, W; Kronjäger, J; Marra, G; Rolland, A; Baynes, F N; Margolis, H S; Gill, P

2017-06-02

Phase compensated optical fiber links enable high accuracy atomic clocks separated by thousands of kilometers to be compared with unprecedented statistical resolution. By searching for a daily variation of the frequency difference between four strontium optical lattice clocks in different locations throughout Europe connected by such links, we improve upon previous tests of time dilation predicted by special relativity. We obtain a constraint on the Robertson-Mansouri-Sexl parameter |α|≲1.1×10^{-8}, quantifying a violation of time dilation, thus improving by a factor of around 2 the best known constraint obtained with Ives-Stilwell type experiments, and by 2 orders of magnitude the best constraint obtained by comparing atomic clocks. This work is the first of a new generation of tests of fundamental physics using optical clocks and fiber links. As clocks improve, and as fiber links are routinely operated, we expect that the tests initiated in this Letter will improve by orders of magnitude in the near future.

Circadian clock-deficient mice as a tool for exploring disease etiology.

PubMed

Doi, Masao

2012-01-01

One of the most significant conceptual changes brought about by the analysis of circadian clock-deficient mice is that abnormalities in the circadian clock are linked not only to sleep arousal disorder but also to a wide variety of common diseases, including hypertension, diabetes, obesity, and cancer. It has recently been shown that the disruption of the two cryptochrome genes Cry1 and Cry2-core elements of the circadian clock-induces salt-dependent hypertension due to abnormally high synthesis of the mineralocorticoid aldosterone by the adrenal gland. This adrenal disorder occurs as a result of increased expression of Hsd3b6, a newly identified steroidogenic enzyme that regulates aldosterone production within the adrenal zona glomerular cells. Importantly, this enzyme is functionally conserved in humans, and the pathophysiologic condition of human idiopathic hyperaldosteronism resembles that of Cry1/2-deficient mice. This review highlights the potential utility of circadian clock-deficient mice as a tool for exploring hitherto unknown disease etiology linked to the circadian clock.

The melatonin-sensitive circadian clock of the enteric bacterium Enterobacter aerogenes.

PubMed

Paulose, Jiffin K; Cassone, Vincent M

2016-09-02

Circadian clocks are fundamental properties of all eukaryotic organisms and at least some prokaryotic organisms. Recent studies in our laboratory have shown that the gastrointestinal system contains a circadian clock that controls many, if not all, aspects of gastrointestinal function. We now report that at least one species of intestinal bacteria, Enterobacter aerogenes, responds to the pineal and gastrointestinal hormone melatonin by an increase in swarming activity. This swarming behavior is expressed rhythmically, with a period of approximately 24 hrs. Transformation of E. aerogenes to express luciferase with a MotA promoter reveals circadian patterns of bioluminescence that are synchronized by melatonin and whose periods are temperature compensated from 26°C to 40°C. Bioinformatics suggest similarities between the E. aerogenes and cyanobacterial clocks, suggesting the circadian clock may have evolved very early in the evolution of life. They also point to a coordination of host circadian clocks with those residing in the microbiota themselves.

The cyanobacterial circadian clock follows midday in vivo and in vitro

PubMed Central

Leypunskiy, Eugene; Lin, Jenny; Yoo, Haneul; Lee, UnJin; Dinner, Aaron R; Rust, Michael J

2017-01-01

Circadian rhythms are biological oscillations that schedule daily changes in physiology. Outside the laboratory, circadian clocks do not generally free-run but are driven by daily cues whose timing varies with the seasons. The principles that determine how circadian clocks align to these external cycles are not well understood. Here, we report experimental platforms for driving the cyanobacterial circadian clock both in vivo and in vitro. We find that the phase of the circadian rhythm follows a simple scaling law in light-dark cycles, tracking midday across conditions with variable day length. The core biochemical oscillator comprised of the Kai proteins behaves similarly when driven by metabolic pulses in vitro, indicating that such dynamics are intrinsic to these proteins. We develop a general mathematical framework based on instantaneous transformation of the clock cycle by external cues, which successfully predicts clock behavior under many cycling environments. DOI: http://dx.doi.org/10.7554/eLife.23539.001 PMID:28686160

Forced rather than voluntary exercise entrains peripheral clocks via a corticosterone/noradrenaline increase in PER2::LUC mice

PubMed Central

Sasaki, Hiroyuki; Hattori, Yuta; Ikeda, Yuko; Kamagata, Mayo; Iwami, Shiho; Yasuda, Shinnosuke; Tahara, Yu; Shibata, Shigenobu

2016-01-01

Exercise during the inactive period can entrain locomotor activity and peripheral circadian clock rhythm in mice; however, mechanisms underlying this entrainment are yet to be elucidated. Here, we showed that the bioluminescence rhythm of peripheral clocks in PER2::LUC mice was strongly entrained by forced treadmill and forced wheel-running exercise rather than by voluntary wheel-running exercise at middle time during the inactivity period. Exercise-induced entrainment was accompanied by increased levels of serum corticosterone and norepinephrine in peripheral tissues, similar to the physical stress-induced response. Adrenalectomy with norepinephrine receptor blockers completely blocked the treadmill exercise-induced entrainment. The entrainment of the peripheral clock by exercise is independent of the suprachiasmatic nucleus clock, the main oscillator in mammals. The present results suggest that the response of forced exercise, but not voluntary exercise, may be similar to that of stress, and possesses the entrainment ability of peripheral clocks through the activation of the adrenal gland and the sympathetic nervous system. PMID:27271267

Power efficient, clock gated multiplexer based full adder cell using 28 nm technology

NASA Astrophysics Data System (ADS)

Gupta, Ashutosh; Murgai, Shruti; Gulati, Anmol; Kumar, Pradeep

2016-03-01

Clock gating is a leading technique used for power saving. Full adders is one of the basic circuit that can be found in maximum VLSI circuits. In this paper clock gated multiplexer based full adder cell is implemented on 28 nm technology. We have designed a full adder cell using a multiplexer with a gated clock without degrading its performance of the cell. We have negative latch circuit for generating gated clock. This gated clock is used to control the multiplexer based full adder cell. The circuit has been synthesized on kintex FPGA through Xilinx ISE Design Suite 14.7 using 28 nm technology in Verilog HDL. The circuit has been simulated on Modelsim 10.3c. The design is verified using System Verilog on QuestaSim in UVM environment. The total power of the circuit has been reduced by 7.41% without degrading the performance of original circuit. The power has been calculated using XPower Analyzer tool of XILINX ISE DESIGN SUITE 14.3.

FAD Regulates CRYPTOCHROME Protein Stability and Circadian Clock in Mice.

PubMed

Hirano, Arisa; Braas, Daniel; Fu, Ying-Hui; Ptáček, Louis J

2017-04-11

The circadian clock generates biological rhythms of metabolic and physiological processes, including the sleep-wake cycle. We previously identified a missense mutation in the flavin adenine dinucleotide (FAD) binding pocket of CRYPTOCHROME2 (CRY2), a clock protein that causes human advanced sleep phase. This prompted us to examine the role of FAD as a mediator of the clock and metabolism. FAD stabilized CRY proteins, leading to increased protein levels. In contrast, knockdown of Riboflavin kinase (Rfk), an FAD biosynthetic enzyme, enhanced CRY degradation. RFK protein levels and FAD concentrations oscillate in the nucleus, suggesting that they are subject to circadian control. Knockdown of Rfk combined with a riboflavin-deficient diet altered the CRY levels in mouse liver and the expression profiles of clock and clock-controlled genes (especially those related to metabolism including glucose homeostasis). We conclude that light-independent mechanisms of FAD regulate CRY and contribute to proper circadian oscillation of metabolic genes in mammals. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

APOLLO clock performance and normal point corrections

NASA Astrophysics Data System (ADS)

Liang, Y.; Murphy, T. W., Jr.; Colmenares, N. R.; Battat, J. B. R.

2017-12-01

The Apache point observatory lunar laser-ranging operation (APOLLO) has produced a large volume of high-quality lunar laser ranging (LLR) data since it began operating in 2006. For most of this period, APOLLO has relied on a GPS-disciplined, high-stability quartz oscillator as its frequency and time standard. The recent addition of a cesium clock as part of a timing calibration system initiated a comparison campaign between the two clocks. This has allowed correction of APOLLO range measurements—called normal points—during the overlap period, but also revealed a mechanism to correct for systematic range offsets due to clock errors in historical APOLLO data. Drift of the GPS clock on  ∼1000 s timescales contributed typically 2.5 mm of range error to APOLLO measurements, and we find that this may be reduced to  ∼1.6 mm on average. We present here a characterization of APOLLO clock errors, the method by which we correct historical data, and the resulting statistics.

Natural Variation of the Circadian Clock in Neurospora.

PubMed

Koritala, Bala S C; Lee, Kwangwon

2017-01-01

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

Effects of circadian clock genes and environmental factors on cognitive aging in old adults in a Taiwanese population.

PubMed

Lin, Eugene; Kuo, Po-Hsiu; Liu, Yu-Li; Yang, Albert C; Kao, Chung-Feng; Tsai, Shih-Jen

2017-04-11

Previous animal studies have indicated associations between circadian clock genes and cognitive impairment . In this study, we assessed whether 11 circadian clockgenes are associated with cognitive aging independently and/or through complex interactions in an old Taiwanese population. We also analyzed the interactions between environmental factors and these genes in influencing cognitive aging. A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to evaluate cognitive function. Our data showed associations between cognitive aging and single nucleotide polymorphisms (SNPs) in 4 key circadian clock genes, CLOCK rs3749473 (p = 0.0017), NPAS2 rs17655330 (p = 0.0013), RORA rs13329238 (p = 0.0009), and RORB rs10781247 (p = 7.9 x 10-5). We also found that interactions between CLOCK rs3749473, NPAS2 rs17655330, RORA rs13329238, and RORB rs10781247 affected cognitive aging (p = 0.007). Finally, we investigated the influence of interactions between CLOCK rs3749473, RORA rs13329238, and RORB rs10781247 with environmental factors such as alcohol consumption, smoking status, physical activity, and social support on cognitive aging (p = 0.002 ~ 0.01). Our study indicates that circadian clock genes such as the CLOCK, NPAS2, RORA, and RORB genes may contribute to the risk of cognitive aging independently as well as through gene-gene and gene-environment interactions.

Circadian clock regulation of the cell cycle in the zebrafish intestine.

PubMed

Peyric, Elodie; Moore, Helen A; Whitmore, David

2013-01-01

The circadian clock controls cell proliferation in a number of healthy tissues where cell renewal and regeneration are critical for normal physiological function. The intestine is an organ that typically undergoes regular cycles of cell division, differentiation and apoptosis as part of its role in digestion and nutrient absorption. The aim of this study was to explore circadian clock regulation of cell proliferation and cell cycle gene expression in the zebrafish intestine. Here we show that the zebrafish gut contains a directly light-entrainable circadian pacemaker, which regulates the daily timing of mitosis. Furthermore, this intestinal clock controls the expression of key cell cycle regulators, such as cdc2, wee1, p21, PCNA and cdk2, but only weakly influences cyclin B1, cyclin B2 and cyclin E1 expression. Interestingly, food deprivation has little impact on circadian clock function in the gut, but dramatically reduces cell proliferation, as well as cell cycle gene expression in this tissue. Timed feeding under constant dark conditions is able to drive rhythmic expression not only of circadian clock genes, but also of several cell cycle genes, suggesting that food can entrain the clock, as well as the cell cycle in the intestine. Rather surprisingly, we found that timed feeding is critical for high amplitude rhythms in cell cycle gene expression, even when zebrafish are maintained on a light-dark cycle. Together these results suggest that the intestinal clock integrates multiple rhythmic cues, including light and food, to function optimally.

Circadian Clock Regulation of the Cell Cycle in the Zebrafish Intestine

PubMed Central

Peyric, Elodie; Moore, Helen A.; Whitmore, David

2013-01-01

The circadian clock controls cell proliferation in a number of healthy tissues where cell renewal and regeneration are critical for normal physiological function. The intestine is an organ that typically undergoes regular cycles of cell division, differentiation and apoptosis as part of its role in digestion and nutrient absorption. The aim of this study was to explore circadian clock regulation of cell proliferation and cell cycle gene expression in the zebrafish intestine. Here we show that the zebrafish gut contains a directly light-entrainable circadian pacemaker, which regulates the daily timing of mitosis. Furthermore, this intestinal clock controls the expression of key cell cycle regulators, such as cdc2, wee1, p21, PCNA and cdk2, but only weakly influences cyclin B1, cyclin B2 and cyclin E1 expression. Interestingly, food deprivation has little impact on circadian clock function in the gut, but dramatically reduces cell proliferation, as well as cell cycle gene expression in this tissue. Timed feeding under constant dark conditions is able to drive rhythmic expression not only of circadian clock genes, but also of several cell cycle genes, suggesting that food can entrain the clock, as well as the cell cycle in the intestine. Rather surprisingly, we found that timed feeding is critical for high amplitude rhythms in cell cycle gene expression, even when zebrafish are maintained on a light-dark cycle. Together these results suggest that the intestinal clock integrates multiple rhythmic cues, including light and food, to function optimally. PMID:24013905

SKIP Is a Component of the Spliceosome Linking Alternative Splicing and the Circadian Clock in Arabidopsis[W

PubMed Central

Wang, Xiaoxue; Wu, Fangming; Xie, Qiguang; Wang, Huamei; Wang, Ying; Yue, Yanling; Gahura, Ondrej; Ma, Shuangshuang; Liu, Lei; Cao, Ying; Jiao, Yuling; Puta, Frantisek; McClung, C. Robertson; Xu, Xiaodong; Ma, Ligeng

2012-01-01

Circadian clocks generate endogenous rhythms in most organisms from cyanobacteria to humans and facilitate entrainment to environmental diurnal cycles, thus conferring a fitness advantage. Both transcriptional and posttranslational mechanisms are prominent in the basic network architecture of circadian systems. Posttranscriptional regulation, including mRNA processing, is emerging as a critical step for clock function. However, little is known about the molecular mechanisms linking RNA metabolism to the circadian clock network. Here, we report that a conserved SNW/Ski-interacting protein (SKIP) domain protein, SKIP, a splicing factor and component of the spliceosome, is involved in posttranscriptional regulation of circadian clock genes in Arabidopsis thaliana. Mutation in SKIP lengthens the circadian period in a temperature-sensitive manner and affects light input and the sensitivity of the clock to light resetting. SKIP physically interacts with the spliceosomal splicing factor Ser/Arg-rich protein45 and associates with the pre-mRNA of clock genes, such as PSEUDORESPONSE REGULATOR7 (PRR7) and PRR9, and is necessary for the regulation of their alternative splicing and mRNA maturation. Genome-wide investigations reveal that SKIP functions in regulating alternative splicing of many genes, presumably through modulating recognition or cleavage of 5′ and 3′ splice donor and acceptor sites. Our study addresses a fundamental question on how the mRNA splicing machinery contributes to circadian clock function at a posttranscriptional level. PMID:22942380

Simple Sequence Repeats Provide a Substrate for Phenotypic Variation in the Neurospora crassa Circadian Clock

PubMed Central

Michael, Todd P.; Park, Sohyun; Kim, Tae-Sung; Booth, Jim; Byer, Amanda; Sun, Qi; Chory, Joanne; Lee, Kwangwon

2007-01-01

Background WHITE COLLAR-1 (WC-1) mediates interactions between the circadian clock and the environment by acting as both a core clock component and as a blue light photoreceptor in Neurospora crassa. Loss of the amino-terminal polyglutamine (NpolyQ) domain in WC-1 results in an arrhythmic circadian clock; this data is consistent with this simple sequence repeat (SSR) being essential for clock function. Methodology/Principal Findings Since SSRs are often polymorphic in length across natural populations, we reasoned that investigating natural variation of the WC-1 NpolyQ may provide insight into its role in the circadian clock. We observed significant phenotypic variation in the period, phase and temperature compensation of circadian regulated asexual conidiation across 143 N. crassa accessions. In addition to the NpolyQ, we identified two other simple sequence repeats in WC-1. The sizes of all three WC-1 SSRs correlated with polymorphisms in other clock genes, latitude and circadian period length. Furthermore, in a cross between two N. crassa accessions, the WC-1 NpolyQ co-segregated with period length. Conclusions/Significance Natural variation of the WC-1 NpolyQ suggests a mechanism by which period length can be varied and selected for by the local environment that does not deleteriously affect WC-1 activity. Understanding natural variation in the N. crassa circadian clock will facilitate an understanding of how fungi exploit their environments. PMID:17726525

47 CFR 80.865 - Radiotelephone station clock.

Code of Federal Regulations, 2010 CFR

2010-10-01

....865 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Technical Equipment Requirements for Cargo Vessels Not Subject to Subpart W § 80.865 Radiotelephone station clock. A clock having a face of at least 12.7 cm (5 in.) in...

Biological Clocks & Circadian Rhythms

ERIC Educational Resources Information Center

Robertson, Laura; Jones, M. Gail

2009-01-01

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

The Vitamin C Clock Reaction.

ERIC Educational Resources Information Center

Wright, Stephen W.

2002-01-01

Describes an iodine clock reaction that produces an effect similar to the Landolt clock reaction. This reaction uses supermarket chemicals and avoids iodate, bisulfite, and mercury compounds. Ascorbic acid and tincture of iodine are the main reactants with alternate procedures provided for vitamin C tablets and orange juice. (DDR)

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

USDA-ARS?s Scientific Manuscript database

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

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

USDA-ARS?s Scientific Manuscript database

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

Fast Clock Recovery for Digital Communications

NASA Technical Reports Server (NTRS)

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).

Development of the Astyanax mexicanus circadian clock and non-visual light responses.

PubMed

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

2018-06-23

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

Correction of clock errors in seismic data using noise cross-correlations

NASA Astrophysics Data System (ADS)

Hable, Sarah; Sigloch, Karin; Barruol, Guilhem; Hadziioannou, Céline

2017-04-01

Correct and verifiable timing of seismic records is crucial for most seismological applications. For seismic land stations, frequent synchronization of the internal station clock with a GPS signal should ensure accurate timing, but loss of GPS synchronization is a common occurrence, especially for remote, temporary stations. In such cases, retrieval of clock timing has been a long-standing problem. The same timing problem applies to Ocean Bottom Seismometers (OBS), where no GPS signal can be received during deployment and only two GPS synchronizations can be attempted upon deployment and recovery. If successful, a skew correction is usually applied, where the final timing deviation is interpolated linearly across the entire operation period. If GPS synchronization upon recovery fails, then even this simple and unverified, first-order correction is not possible. In recent years, the usage of cross-correlation functions (CCFs) of ambient seismic noise has been demonstrated as a clock-correction method for certain network geometries. We demonstrate the great potential of this technique for island stations and OBS that were installed in the course of the Réunion Hotspot and Upper Mantle - Réunions Unterer Mantel (RHUM-RUM) project in the western Indian Ocean. Four stations on the island La Réunion were affected by clock errors of up to several minutes due to a missing GPS signal. CCFs are calculated for each day and compared with a reference cross-correlation function (RCF), which is usually the average of all CCFs. The clock error of each day is then determined from the measured shift between the daily CCFs and the RCF. To improve the accuracy of the method, CCFs are computed for several land stations and all three seismic components. Averaging over these station pairs and their 9 component pairs reduces the standard deviation of the clock errors by a factor of 4 (from 80 ms to 20 ms). This procedure permits a continuous monitoring of clock errors where small clock drifts (1 ms/day) as well as large clock jumps (6 min) are identified. The same method is applied to records of five OBS stations deployed within a radius of 150 km around La Réunion. The assumption of a linear clock drift is verified by correlating OBS for which GPS-based skew corrections were available with land stations. For two OBS stations without skew estimates, we find clock drifts of 0.9 ms/day and 0.4 ms/day. This study salvages expensive seismic records from remote regions that would be otherwise lost for seismicity or tomography studies.

"Molecular Clock" Analogs: A Relative Rates Exercise

ERIC Educational Resources Information Center

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…

Rapid attenuation of circadian clock gene oscillations in the rat heart following ischemia-reperfusion

USDA-ARS?s Scientific Manuscript database

The intracellular circadian clock consists of a series of transcriptional modulators that together allow the cell to perceive the time of day. Circadian clocks have been identified within various components of the cardiovascular system (e.g., cardiomyocytes, vascular smooth muscle cells) and possess...

77 FR 66911 - Requested Administrative Waiver of the Coastwise Trade Laws: Vessel FIVE O'CLOCK HERE; Invitation...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-07

... DEPARTMENT OF TRANSPORTATION Maritime Administration [Docket No. MARAD-2012-0102] Requested Administrative Waiver of the Coastwise Trade Laws: Vessel FIVE O'CLOCK HERE; Invitation for Public Comments... O'CLOCK HERE is: Intended Commercial Use of Vessel: ``Day and overnight charters in California...

High-precision multi-node clock network distribution.

PubMed

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

2017-10-01

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

International time and frequency comparison using very long baseline interferometer

NASA Astrophysics Data System (ADS)

Hama, Shinichi; Yoshino, Taizoh; Kiuchi, Hitoshi; Morikawa, Takao; Sato, Tokuo

VLBI time comparison experiments using the Kashima station of the Radio Research Laboratory and the Richmond and Maryland Point stations of the U.S. Naval Observatory have been performed since April 1985. A precision of 0.2 ns for the clock offset and 0.2 ps/s for the clock rate have been achieved, and good agreement has been found with GPS results for clock offset. Much higher precision has been found for VLBI time and frequency comparison than that possible with conventional portable clock or Loran-C methods.

New Tests for Variations of the Fine Structure Constant

NASA Technical Reports Server (NTRS)

Prestage, John D.

1995-01-01

We describe a new test for possible variations of the fine structure constant, by comparisons of rates between clocks based on hyperfine transitions in alkali atomos with different atomic number Z. H- maser, Cs and Hg+ clocks have a different dependence on ia relativistic contributions of order (Z. Recent H-maser vs Hg+ clock comparison data improves laboratory limits on a time variation by 100-fold to giveFuture laser cooled clocks (Be+, Rb, Cs, Hg+, etc.), when compared, will yield the most senstive of all tests for.

Method and system for downhole clock synchronization

DOEpatents

Hall, David R.; Bartholomew, David B.; Johnson, Monte; Moon, Justin; Koehler, Roger O.

2006-11-28

A method and system for use in synchronizing at least two clocks in a downhole network are disclosed. The method comprises determining a total signal latency between a controlling processing element and at least one downhole processing element in a downhole network and sending a synchronizing time over the downhole network to the at least one downhole processing element adjusted for the signal latency. Electronic time stamps may be used to measure latency between processing elements. A system for electrically synchronizing at least two clocks connected to a downhole network comprises a controlling processing element connected to a synchronizing clock in communication over a downhole network with at least one downhole processing element comprising at least one downhole clock. Preferably, the downhole network is integrated into a downhole tool string.

KSC-2014-4592

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Ben Smegelsky

KSC-2014-4594

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Ben Smegelsky

KSC-2014-4603

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Jim Grossman

KSC-2014-4600

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Jim Grossman

KSC-2014-4595

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Ben Smegelsky

KSC-2014-4589

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Cory Huston

KSC-2014-4602

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Jim Grossman

KSC-2014-4588

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Cory Huston

KSC-2014-4591

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Cory Huston

KSC-2014-4593

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Ben Smegelsky

KSC-2014-4590

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Cory Huston

KSC-2014-4601

NASA Image and Video Library

2014-11-26

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, work continues to install 24 light emitting diode LED panels in the new countdown clock at the spaceport's Press Site. The modern, multimedia display is similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Jim Grossman

Bayesian view of single-qubit clocks, and an energy versus accuracy tradeoff

NASA Astrophysics Data System (ADS)

Gopalkrishnan, Manoj; Kandula, Varshith; Sriram, Praveen; Deshpande, Abhishek; Muralidharan, Bhaskaran

2017-09-01

We bring a Bayesian approach to the analysis of clocks. Using exponential distributions as priors for clocks, we analyze how well one can keep time with a single qubit freely precessing under a magnetic field. We find that, at least with a single qubit, quantum mechanics does not allow exact timekeeping, in contrast to classical mechanics, which does. We find the design of the single-qubit clock that leads to maximum accuracy. Further, we find an energy versus accuracy tradeoff—the energy cost is at least kBT times the improvement in accuracy as measured by the entropy reduction in going from the prior distribution to the posterior distribution. We propose a physical realization of the single-qubit clock using charge transport across a capacitively coupled quantum dot.

On-Chip AC self-test controller

DOEpatents

Flanagan, John D [Rhinebeck, NY; Herring, Jay R [Poughkeepsie, NY; Lo, Tin-Chee [Fishkill, NY

2009-09-29

A system for performing AC self-test on an integrated circuit that includes a system clock for normal operation is provided. The system includes the system clock, self-test circuitry, a first and second test register to capture and launch test data in response to a sequence of data pulses, and a logic circuit to be tested. The self-test circuitry includes an AC self-test controller and a clock splitter. The clock splitter generates the sequence of data pulses including a long data capture pulse followed by an at speed data launch pulse and an at speed data capture pulse followed by a long data launch pulse. The at speed data launch pulse and the at speed data capture pulse are generated for a common cycle of the system clock.

Note: Pulsed optically pumped atomic clock based on a paraffin-coated cell

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

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

Shepard, Kenneth L.; Sturcken, Noah Andrew

Power controller includes an output terminal having an output voltage, at least one clock generator to generate a plurality of clock signals and a plurality of hardware phases. Each hardware phase is coupled to the at least one clock generator and the output terminal and includes a comparator. Each hardware phase is configured to receive a corresponding one of the plurality of clock signals and a reference voltage, combine the corresponding clock signal and the reference voltage to produce a reference input, generate a feedback voltage based on the output voltage, compare the reference input and the feedback voltage usingmore » the comparator and provide a comparator output to the output terminal, whereby the comparator output determines a duty cycle of the power controller. An integrated circuit including the power controller is also provided.« less

Developmental stage-specific regulation of the circadian clock by temperature in zebrafish.

PubMed

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

2014-01-01

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

PDF as a coupling mediator between the light-entrainable and temperature-entrainable clocks in Drosophila melanogaster.

PubMed

Tomioka, K; Miyasako, Y; Umezaki, Y

2008-01-01

Drosophila shows bimodal circadian locomotor rhythms with peaks around light-on (morning peak) and before light-off (evening peak). The rhythm synchronizes to light and temperature cycles and the synchronization is achieved by two sets of clocks: one entrains to light cycles and the other to temperature cycles. The light-entrainable clock consists of the clock neurons located in the lateral protocerebrum (LNs) and the temperature-entrainable clock involves those located in the dorsal protocerebrum (DNs) and the cells located in the posterior lateral protocerebrum (LPNs). To understand the interaction between the light-entrainable and the temperature-entrainable clock neurons, locomotor rhythms of the mutant flies lacking PDF or PDF-positive clock neurons were examined. Under the light cycles, they showed altered phase of the evening peak. When exposed to temperature cycles of lower temperature levels, the onset of evening peak showed larger advance in contrast to those of wild-type flies. The termination of the peak also advanced while that of wild-type flies remained almost at the same phase as in the constant temperature. These results support our hypothesis that the PDF-positive light entrainable cells regulate the phase of the temperature entrainable cells to be synchronized to their own phase using PDF as a coupling mediator.

Silencing Nicotiana attenuata LHY and ZTL alters circadian rhythms in flowers.

PubMed

Yon, Felipe; Joo, Youngsung; Cortés Llorca, Lucas; Rothe, Eva; Baldwin, Ian T; Kim, Sang-Gyu

2016-02-01

The rhythmic opening/closing and volatile emissions of flowers are known to attract pollinators at specific times. That these rhythms are maintained under constant light or dark conditions suggests a circadian clock involvement. Although a forward and reverse genetic approach has led to the identification of core circadian clock components in Arabidopsis thaliana, the involvement of these clock components in floral rhythms has remained untested, probably because of the weak diurnal rhythms in A. thaliana flowers. Here, we addressed the role of these core clock components in the flowers of the wild tobacco Nicotiana attenuata, whose flowers open at night, emit benzyl acetone (BA) scents and move vertically through a 140° arc. We first measured N. attenuata floral rhythms under constant light conditions. The results suggest that the circadian clock controls flower opening, BA emission and pedicel movement, but not flower closing. We generated transgenic N. attenuata lines silenced in the homologous genes of Arabidopsis LATE ELONGATED HYPOCOTYL (LHY) and ZEITLUPE (ZTL), which are known to be core clock components. Silencing NaLHY and NaZTL strongly altered floral rhythms in different ways, indicating that conserved clock components in N. attenuata coordinate these floral rhythms. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior.

PubMed

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

2016-11-01

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

Automatic Clock and Time Signal System of the Astronomical Agency in East Asia Area

NASA Astrophysics Data System (ADS)

Lee, Yong Sam

2009-09-01

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

Mercury Ion Clock for a NASA Technology Demonstration Mission.

PubMed

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.

A novel power-efficient high-speed clock management unit using quantum-dot cellular automata

NASA Astrophysics Data System (ADS)

Abutaleb, M. M.

2017-04-01

Quantum-dot cellular automata (QCA) is one of the most attractive alternatives for complementary metal-oxide semiconductor technology. The QCA widely supports a new paradigm in the field of nanotechnology that has the potential for high density, low power, and high speed. The clock manager is an essential building block in the new microwave and radio frequency integrated circuits. This paper describes a novel QCA-based clock management unit (CMU) that provides innovative clocking capabilities. The proposed CMU is achieved by utilizing edge-triggered D-type flip-flops (D-FFs) in the design of frequency synthesizer and phase splitter. Edge-triggered D-FF structures proposed in this paper have the successful QCA implementation and simulation with the least complexity and power dissipation as compared to earlier structures. The frequency synthesizer is used to generate new clock frequencies from the reference clock frequency based on a combination of power-of-two frequency dividers. The phase splitter is integrated with the frequency synthesizer to generate four clock signals that are 90o out of phase with each other. This paper demonstrates that the proposed QCA CMU structure has a superior performance. Furthermore, the proposed CMU is straightforwardly scalable due to the use of modular component architecture.

The Trade-Off Mechanism in Mammalian Circadian Clock Model with Two Time Delays

NASA Astrophysics Data System (ADS)

Yan, Jie; Kang, Xiaxia; Yang, Ling

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

Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior

PubMed Central

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

2016-01-01

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

A Fermi-degenerate three-dimentional optical lattice clock

NASA Astrophysics Data System (ADS)

Goban, Akihisa; Campbell, Sara; Hutson, Ross; Marti, G. Edward; Sonderhouse, Lindsay; Robinson, John; Zhang, Wei; Ye, Jun

2017-04-01

The pursuit of better atomic clocks has advanced many research areas, providing better quantum state control, tighter limits on fundamental constant variation, and improved tests of relativity. Recent progress in optical lattice clock to the accuracy of 2E-18 has benefited from the understanding of atomic interactions. Also the precision of clock spectroscopy has been applied to explore many-body interactions including SU(N) symmetry. In our previous 1D optical lattice, atomic interactions cause suppression and broadening of the atomic resonance, limiting the clock stability. To overcome this limitation, we demonstrate a scalable solution that takes advantage of the high density of a degenerate Fermi gas in a three-dimensional optical lattice to protect against on-site interaction shifts. Using an ultrastable laser, we achieve an unprecedented level of atom-light coherence, reaching a spectroscopic quality factor 5.2E15. We investigate clock systematics unique to this design; on-site interactions are resolved so that their contribution to clock shifts is orders of magnitude suppressed compared to the 1D optical lattice experiments. Also, we measure the combined scalar and tensor magic wavelengths for state-independent trapping along all three lattice axes. We acknowledge support from NIST, DARPA and the NSF JILA Physics Frontier Center.

Casein Kinase 1 Promotes Synchrony of the Circadian Clock Network

PubMed Central

Zheng, Xiangzhong; Sowcik, Mallory; Chen, Dechun

2014-01-01

Casein kinase 1, known as DOUBLETIME (DBT) in Drosophila melanogaster, is a critical component of the circadian clock that phosphorylates and promotes degradation of the PERIOD (PER) protein. However, other functions of DBT in circadian regulation are not clear, in part because severe reduction of dbt causes preadult lethality. Here we report the molecular and behavioral phenotype of a viable dbtEY02910 loss-of-function mutant. We found that DBT protein levels are dramatically reduced in adult dbtEY02910 flies, and the majority of mutant flies display arrhythmic behavior, with a few showing weak, long-period (∼32 h) rhythms. Peak phosphorylation of PER is delayed, and both hyper- and hypophosphorylated forms of the PER and CLOCK proteins are present throughout the day. In addition, molecular oscillations of the circadian clock are dampened. In the central brain, PER and TIM expression is heterogeneous and decoupled in the canonical clock neurons of the dbtEY02910 mutants. We also report an interaction between dbt and the signaling pathway involving pigment dispersing factor (PDF), a synchronizing peptide in the clock network. These data thus demonstrate that overall reduction of DBT causes long and arrhythmic behavior, and they reveal an unexpected role of DBT in promoting synchrony of the circadian clock network. PMID:24820422

Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants[OPEN

PubMed Central

Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Havaux, Michel; Schmülling, Thomas

2016-01-01

The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. PMID:27354555

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures.

PubMed

Petrenko, Volodymyr; Saini, Camille; Perrin, Laurent; Dibner, Charna

2016-11-11

Circadian clocks are functional in all light-sensitive organisms, allowing for an adaptation to the external world by anticipating daily environmental changes. Considerable progress in our understanding of the tight connection between the circadian clock and most aspects of physiology has been made in the field over the last decade. However, unraveling the molecular basis that underlies the function of the circadian oscillator in humans stays of highest technical challenge. Here, we provide a detailed description of an experimental approach for long-term (2-5 days) bioluminescence recording and outflow medium collection in cultured human primary cells. For this purpose, we have transduced primary cells with a lentiviral luciferase reporter that is under control of a core clock gene promoter, which allows for the parallel assessment of hormone secretion and circadian bioluminescence. Furthermore, we describe the conditions for disrupting the circadian clock in primary human cells by transfecting siRNA targeting CLOCK. Our results on the circadian regulation of insulin secretion by human pancreatic islets, and myokine secretion by human skeletal muscle cells, are presented here to illustrate the application of this methodology. These settings can be used to study the molecular makeup of human peripheral clocks and to analyze their functional impact on primary cells under physiological or pathophysiological conditions.

Circadian clocks in the cnidaria: environmental entrainment, molecular regulation, and organismal outputs.

PubMed

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

2013-07-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-07-08

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

Shining a light on the Arabidopsis circadian clock.

PubMed

Oakenfull, Rachael J; Davis, Seth J

2017-11-01

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

Vane clocking effects in an embedded compressor stage

NASA Astrophysics Data System (ADS)

Key, Nicole Leanne

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

Coherent Population Trapping and Optical Ramsey Interference for Compact Rubidium Clock Development

NASA Astrophysics Data System (ADS)

Warren, Zachary Aron

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

Common View Time Transfer Using Worldwide GPS and DMA Monitor Stations

NASA Technical Reports Server (NTRS)

Reid, Wilson G.; McCaskill, Thomas B.; Oaks, Orville J.; Buisson, James A.; Warren, Hugh E.

1996-01-01

Analysis of the on-orbit Navstar clocks and the Global Positioning System (GPS) monitor station reference clocks is performed by the Naval Research Laboratory using both broadcast and postprocessed precise ephemerides. The precise ephemerides are produced by the Defense Mapping Agency (DMA) for each of the GPS space vehicles from pseudo-range measurements collected at five GPS and at five DMA monitor stations spaced around the world. Recently, DMA established an additional site co-located with the US Naval Observatory precise time site. The time reference for the new DMA site is the DoD Master Clock. Now, for the first time, it is possible to transfer time every 15 minutes via common view from the DoD Master Clock to the 11 GPS and DMA monitor stations. The estimated precision of a single common-view time transfer measurement taken over a 15-minute interval was between 1.4 and 2.7 nanoseconds. Using the measurements from all Navstar space vehicles in common view during the 15-minute interval, typically 3-7 space vehicles, improved the estimate of the precision to between 0.65 and 1.13 nanoseconds. The mean phase error obtained from closure of the time transfer around the world using the 11 monitor stations and the 25 space vehicle clocks over a period of 4 months had a magnitude of 31 picoseconds. Analysis of the low noise time transfer from the DoD Master Clock to each of the monitor stations yields not only the bias in the time of the reference clock, but also focuses attention on structure in the behaviour of the reference clock not previously seen. Furthermore, the time transfer provides a a uniformly sampled database of 15-minute measurements that make possible, for the first time, the direct and exhaustive computation of the frequency stability of the monitor station reference clocks. To lend perspective to the analysis, a summary is given of the discontinuities in phase and frequency that occurred in the reference clock at the Master Control Station during the period covered by the analysis.

Protein malnutrition after weaning disrupts peripheral clock and daily insulin secretion in mice.

PubMed

Borck, Patricia Cristine; Batista, Thiago Martins; Vettorazzi, Jean Franciesco; Camargo, Rafael Ludemann; Boschero, Antonio Carlos; Vieira, Elaine; Carneiro, Everardo Magalhães

2017-12-01

Changes in nutritional state may alter circadian rhythms through alterations in expression of clock genes. Protein deficiency has a profound effect on body metabolism, but the effect of this nutrient restriction after weaning on biological clock has not been explored. Thus, this study aims to investigate whether the protein restriction affects the daily oscillation in the behavior and metabolic rhythms, as well as expression of clock genes in peripheral tissues. Male C57BL/6 J mice, after weaning, were fed a normal-protein (NP) diet or a low-protein (LP) diet for 8 weeks. Mice fed an LP diet did not show difference in locomotor activity and energy expenditure, but the food intake was increased, with parallel increased expression of the orexigenic neuropeptide Npy and disruption of the anorexigenic Pomc oscillatory pattern in the hypothalamus. LP mice showed disruption in the daily rhythmic patterns of plasma glucose, triglycerides and insulin. Also, the rhythmic expression of clock genes in peripheral tissues and pancreatic islets was altered in LP mice. In pancreatic islets, the disruption of clock genes was followed by impairment of daily glucose-stimulated insulin secretion and the expression of genes involved in exocytosis. Pharmacological activation of REV-ERBα could not restore the insulin secretion in LP mice. The present study demonstrates that protein restriction, leading to development of malnutrition, alters the peripheral clock and metabolic outputs, suggesting that this nutrient provides important entraining cues to regulate the daily fluctuation of biological clock. Copyright © 2017 Elsevier Inc. All rights reserved.

Pregnancy Suppresses the Daily Rhythmicity of Core Body Temperature and Adipose Metabolic Gene Expression in the Mouse.

PubMed

Wharfe, Michaela D; Wyrwoll, Caitlin S; Waddell, Brendan J; Mark, Peter J

2016-09-01

Maternal adaptations in lipid metabolism are crucial for pregnancy success due to the role of white adipose tissue as an energy store and the dynamic nature of energy needs across gestation. Because lipid metabolism is regulated by the rhythmic expression of clock genes, it was hypothesized that maternal metabolic adaptations involve changes in both adipose clock gene expression and the rhythmic expression of downstream metabolic genes. Maternal core body temperature (Tc) was investigated as a possible mechanism driving pregnancy-induced changes in clock gene expression. Gonadal adipose tissue and plasma were collected from C57BL/6J mice before and on days 6, 10, 14, and 18 of pregnancy (term 19 d) at 4-hour intervals across a 24-hour period. Adipose expression of clock genes and downstream metabolic genes were determined by quantitative RT-PCR, and Tc was measured by intraperitoneal temperature loggers. Adipose clock gene expression showed robust rhythmicity throughout pregnancy, but absolute levels varied substantially across gestation. Rhythmic expression of the metabolic genes Lipe, Pnpla2, and Lpl was clearly evident before pregnancy; however, this rhythmicity was lost with the onset of pregnancy. Tc rhythm was significantly altered by pregnancy, with a 65% decrease in amplitude by term and a 0.61°C decrease in mesor between days 6 and 18. These changes in Tc, however, did not appear to be linked to adipose clock gene expression across pregnancy. Overall, our data show marked adaptations in the adipose clock in pregnancy, with an apparent decoupling of adipose clock and lipolytic/lipogenic gene rhythms from early in gestation.

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

PubMed

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

2017-04-01

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

Intracellular high cholesterol content disorders the clock genes, apoptosis-related genes and fibrinolytic-related genes rhythmic expressions in human plaque-derived vascular smooth muscle cells.

PubMed

Lin, Changpo; Tang, Xiao; Xu, Lirong; Qian, Ruizhe; Shi, Zhenyu; Wang, Lixin; Cai, Tingting; Yan, Dong; Fu, Weiguo; Guo, Daqiao

2017-07-10

The clock genes are involved in regulating cardiovascular functions, and their expression disorders would lead to circadian rhythm disruptions of clock-controlled genes (CCGs), resulting in atherosclerotic plaque formation and rupture. Our previous study revealed the rhythmic expression of clock genes were attenuated in human plaque-derived vascular smooth muscle cells (PVSMCs), but failed to detect the downstream CCGs expressions and the underlying molecular mechanism. In this study, we examined the difference of CCGs rhythmic expression between human normal carotid VSMCs (NVSMCs) and PVSMCs. Furthermore, we compared the cholesterol and triglycerides levels between two groups and the link to clock genes and CCGs expressions. Seven health donors' normal carotids and 19 carotid plaques yielded viable cultured NVSMCs and PVSMCs. The expression levels of target genes were measured by quantitative real-time PCR and Western-blot. The intracellular cholesterol and triglycerides levels were measured by kits. The circadian expressions of apoptosis-related genes and fibrinolytic-related genes were disordered. Besides, the cholesterol levels were significant higher in PVSMCs. After treated with cholesterol or oxidized low density lipoprotein (ox-LDL), the expressions of clock genes were inhibited; and the rhythmic expressions of clock genes, apoptosis-related genes and fibrinolytic-related genes were disturbed in NVSMCs, which were similar to PVSMCs. The results suggested that intracellular high cholesterol content of PVSMCs would lead to the disorders of clock genes and CCGs rhythmic expressions. And further studies should be conducted to demonstrate the specific molecular mechanisms involved.

Clock and trigger distribution for CBM-TOF quality evaluation of RPC super module detector assemblies

NASA Astrophysics Data System (ADS)

Li, C.; Huang, X.; Cao, P.; Wang, J.; An, Q.

2018-03-01

RPC Super module (SM) detector assemblies are used for charged hadron identification in the Time-of-Flight (TOF) spectrometer at the Compressed Baryonic Matter (CBM) experiment. Each SM contains several multi-gap Resistive Plate Chambers (MRPCs) and provides up to 320 electronic channels in total for high-precision time measurements. Time resolution of the Time-to-Digital Converter (TDC) is required to be better than 20 ps. During mass production, the quality of each SM needs to be evaluated. In order to meet the requirements, the system clock signal as well as the trigger signal should be distributed precisely and synchronously to all electronics modules within the evaluation readout system. In this paper, a hierarchical clock and trigger distribution method is proposed for the quality evaluation of CBM-TOF SM detectors. In a first stage, the master clock and trigger module (CTM) allocated in a 6U PXI chassis distributes the clock and trigger signals to the slave CTM in the same chassis. In a second stage, the slave CTM transmits the clock and trigger signals to the TDC readout module (TRM) through one optical link. In a third stage, the TRM distributes the clock and trigger signals synchronously to 10 individual TDC boards. Laboratory test results show that the clock jitter at the third stage is less than 4 ps (RMS) and the trigger transmission latency from the master CTM to the TDC is about 272 ns with 11 ps (RMS) jitter. The overall performance complies well with the required specifications.

A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes

PubMed Central

Nakahata, Yasukazu; Yoshida, Mayumi; Takano, Atsuko; Soma, Haruhiko; Yamamoto, Takuro; Yasuda, Akio; Nakatsu, Toru; Takumi, Toru

2008-01-01

Background The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG). The non-canonical E-boxes or E-box-like sequences have also been reported to be necessary for circadian oscillation. Results We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-box or a non-canonical E-box and an E-box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-box or E-box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-box-like elements in their promoter region. Conclusion We propose a novel possible mechanism regulated by double E-box-like elements, not to a single E-box, for circadian transcriptional oscillation. The direct repeat of the E-box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes. PMID:18177499

Modulation of learning and memory by the targeted deletion of the circadian clock gene Bmal1 in forebrain circuits

PubMed Central

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

2017-01-01

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

Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null mice.

PubMed

Sheward, W John; Maywood, Elizabeth S; French, Karen L; Horn, Jacqueline M; Hastings, Michael H; Seckl, Jonathan R; Holmes, Megan C; Harmar, Anthony J

2007-04-18

The master clock driving mammalian circadian rhythms is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained by daily light/dark cycles. SCN lesions abolish circadian rhythms of behavior and result in a loss of synchronized circadian rhythms of clock gene expression in peripheral organs (e.g., the liver) and of hormone secretion (e.g., corticosterone). We examined rhythms of behavior, hepatic clock gene expression, and corticosterone secretion in VPAC2 receptor-null (Vipr2-/-) mice, which lack a functional SCN clock. Unexpectedly, although Vipr2-/- mice lacked robust circadian rhythms of wheel-running activity and corticosterone secretion, hepatic clock gene expression was strongly rhythmic, but advanced in phase compared with that in wild-type mice. The timing of food availability is thought to be an important entrainment signal for circadian clocks outside the SCN. Vipr2-/- mice consumed food significantly earlier in the 24 h cycle than wild-type mice, consistent with the observed timing of peripheral rhythms of circadian gene expression. When restricted to feeding only during the daytime (RF), mice develop rhythms of activity and of corticosterone secretion in anticipation of feeding time, thought to be driven by a food-entrainable circadian oscillator, located outside the SCN. Under RF, mice of both genotypes developed food-anticipatory rhythms of activity and corticosterone secretion, and hepatic gene expression rhythms also became synchronized to the RF stimulus. Thus, food intake is an effective zeitgeber capable of coordinating circadian rhythms of behavior, peripheral clock gene expression, and hormone secretion, even in the absence of a functional SCN clock.

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

USDA-ARS?s Scientific Manuscript database

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

Clocking and Synchronization Circuits in Multiprocessor Systems

DTIC Science & Technology

1989-04-01

18 3.4 Inter -chip Clocking Strategies...may occur when two or more of the switches make transitions at different times during the inter - val during which those inputs are being processed...increased without any fruitful computation. The sources of the inter -chip clock skew are the electromagnetic propagation delay, the buffer delay within

Egyptian "Star Clocks"

NASA Astrophysics Data System (ADS)

Symons, Sarah

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

Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures

USDA-ARS?s Scientific Manuscript database

To examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock ...

Time and Time Again

ERIC Educational Resources Information Center

Pass, Lynn DiCamillo

2004-01-01

This article describes one classroom's experience engaging in a lesson that challenged introductory art students to design a functional ceramic clock in an art-historical style of their choice. The clocks were sculpted in low-relief so that the hands of the clockworks could move freely around the face of the clock. Students were given an…

Clocked combustor can array

DOEpatents

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

2017-01-17

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

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

PubMed

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

2011-05-20

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

Optical Lattice Clocks with Weakly Bound Molecules.

PubMed

Borkowski, Mateusz

2018-02-23

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

Logical synchronization: how evidence and hypotheses steer atomic clocks

NASA Astrophysics Data System (ADS)

Myers, John M.; Madjid, F. Hadi

2014-05-01

A clock steps a computer through a cycle of phases. For the propagation of logical symbols from one computer to another, each computer must mesh its phases with arrivals of symbols from other computers. Even the best atomic clocks drift unforeseeably in frequency and phase; feedback steers them toward aiming points that depend on a chosen wave function and on hypotheses about signal propagation. A wave function, always under-determined by evidence, requires a guess. Guessed wave functions are coded into computers that steer atomic clocks in frequency and position—clocks that step computers through their phases of computations, as well as clocks, some on space vehicles, that supply evidence of the propagation of signals. Recognizing the dependence of the phasing of symbol arrivals on guesses about signal propagation elevates `logical synchronization.' from its practice in computer engineering to a dicipline essential to physics. Within this discipline we begin to explore questions invisible under any concept of time that fails to acknowledge the unforeseeable. In particular, variation of spacetime curvature is shown to limit the bit rate of logical communication.

A Self-Stabilizing Byzantine-Fault-Tolerant Clock Synchronization Protocol

NASA Technical Reports Server (NTRS)

Malekpour, Mahyar R.

2009-01-01

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

Transportable Optical Lattice Clock with 7×10^{-17} Uncertainty.

PubMed

Koller, S B; Grotti, J; Vogt, St; Al-Masoudi, A; Dörscher, S; Häfner, S; Sterr, U; Lisdat, Ch

2017-02-17

We present a transportable optical clock (TOC) with ^{87}Sr. Its complete characterization against a stationary lattice clock resulted in a systematic uncertainty of 7.4×10^{-17}, which is currently limited by the statistics of the determination of the residual lattice light shift, and an instability of 1.3×10^{-15}/sqrt[τ] with an averaging time τ in seconds. Measurements confirm that the systematic uncertainty can be reduced to below the design goal of 1×10^{-17}. To our knowledge, these are the best uncertainties and instabilities reported for any transportable clock to date. For autonomous operation, the TOC has been installed in an air-conditioned car trailer. It is suitable for chronometric leveling with submeter resolution as well as for intercontinental cross-linking of optical clocks, which is essential for a redefinition of the International System of Units (SI) second. In addition, the TOC will be used for high precision experiments for fundamental science that are commonly tied to precise frequency measurements and its development is an important step to space-borne optical clocks.

Transportable Optical Lattice Clock with 7 ×10-17 Uncertainty

NASA Astrophysics Data System (ADS)

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

2017-02-01

We present a transportable optical clock (TOC) with Sr 87 . Its complete characterization against a stationary lattice clock resulted in a systematic uncertainty of 7.4 ×10-17, which is currently limited by the statistics of the determination of the residual lattice light shift, and an instability of 1.3 ×10-15/√{τ } with an averaging time τ in seconds. Measurements confirm that the systematic uncertainty can be reduced to below the design goal of 1 ×10-17. To our knowledge, these are the best uncertainties and instabilities reported for any transportable clock to date. For autonomous operation, the TOC has been installed in an air-conditioned car trailer. It is suitable for chronometric leveling with submeter resolution as well as for intercontinental cross-linking of optical clocks, which is essential for a redefinition of the International System of Units (SI) second. In addition, the TOC will be used for high precision experiments for fundamental science that are commonly tied to precise frequency measurements and its development is an important step to space-borne optical clocks.

Transforming growth factor-beta inhibits the expression of clock genes.

PubMed

Gast, Heidemarie; Gordic, Sonja; Petrzilka, Saskia; Lopez, Martin; Müller, Andreas; Gietl, Anton; Hock, Christoph; Birchler, Thomas; Fontana, Adriano

2012-07-01

Disturbances of sleep-wake rhythms are an important problem in Alzheimer's disease (AD). Circadian rhythms are regulated by clock genes. Transforming growth factor-beta (TGF-β) is overexpressed in neurons in AD and is the only cytokine that is increased in cerebrospinal fluid (CSF). Our data show that TGF-β2 inhibits the expression of the clock genes Period (Per)1, Per2, and Rev-erbα, and of the clock-controlled genes D-site albumin promoter binding protein (Dbp) and thyrotroph embryonic factor (Tef). However, our results showed that TGF-β2 did not alter the expression of brain and muscle Arnt-like protein-1 (Bmal1). The concentrations of TGF-β2 in the CSF of 2 of 16 AD patients and of 1 of 7 patients with mild cognitive impairment were in the dose range required to suppress the expression of clock genes. TGF-β2-induced dysregulation of clock genes may alter neuronal pathways, which may be causally related to abnormal sleep-wake rhythms in AD patients. © 2012 New York Academy of Sciences.

Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor

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

Hou, Zhiqiang; Su, Lijing; Pei, Jimin

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

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

NASA Astrophysics Data System (ADS)

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

2017-07-01

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

The Plant Circadian Clock: From a Simple Timekeeper to a Complex Developmental Manager.

PubMed

Sanchez, Sabrina E; Kay, Steve A

2016-12-01

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

Optical Lattice Clocks with Weakly Bound Molecules

NASA Astrophysics Data System (ADS)

Borkowski, Mateusz

2018-02-01

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

Gut microbiota directs PPARγ-driven reprogramming of the liver circadian clock by nutritional challenge.

PubMed

Murakami, Mari; Tognini, Paola; Liu, Yu; Eckel-Mahan, Kristin L; Baldi, Pierre; Sassone-Corsi, Paolo

2016-09-01

The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high-fat diet, the gut microbiota drives PPARγ-mediated activation of newly oscillatory transcriptional programs in the liver. Moreover, antibiotics treatment prevents PPARγ-driven transcription in the liver, underscoring the essential role of gut microbes in clock reprogramming and hepatic circadian homeostasis. Thus, a specific molecular signature characterizes the influence of the gut microbiome in the liver, leading to the transcriptional rewiring of hepatic metabolism. © 2016 The Authors.

Clock jitter generator with picoseconds resolution

NASA Astrophysics Data System (ADS)

Jovanović, Goran; Stojčev, Mile; Nikolić, Tatjana

2013-06-01

The clock is one of the most critical signals in any synchronous system. As CMOS technology has scaled, supply voltages have dropped chip power consumption has increased and the effects of jitter due to clock frequency increase have become critical and jitter budget has become tighter. This article describes design and development of low-cost mixed-signal programmable jitter generator with high resolution. The digital technique is used for coarse-grain and an analogue technique for fine-grain clock phase shifting. Its structure allows injection of various random and deterministic jitter components in a controllable and programmable fashion. Each jitter component can be switched on or off. The jitter generator can be used in jitter tolerance test and jitter transfer function measurement of high-speed synchronous digital circuits. At operating system clock frequency of 220 MHz, a jitter with 4 ps resolution can be injected.

Extended Salecker-Wigner formula for optimal accuracy in reading a clock via a massive signal particle

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

Kudaka, Shoju; Matsumoto, Shuichi

2007-07-15

In order to acquire an extended Salecker-Wigner formula from which to derive the optimal accuracy in reading a clock with a massive particle as the signal, von Neumann's classical measurement is employed, by which simultaneously both position and momentum of the signal particle can be measured approximately. By an appropriate selection of wave function for the initial state of the composite system (a clock and a signal particle), the formula is derived accurately. Valid ranges of the running time of a clock with a given optimal accuracy are also given. The extended formula means that contrary to the Salecker-Wigner formulamore » there exists the possibility of a higher accuracy of time measurement, even if the mass of the clock is very small.« less

A quantum network of clocks

NASA Astrophysics Data System (ADS)

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

2014-08-01

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

Circadian aspects of adipokine regulation in rodents.

PubMed

Challet, Etienne

2017-12-01

Most hormones display daily fluctuations of secretion during the 24-h cycle. This is also the case for adipokines, in particular the anorexigenic hormone, leptin. The temporal organization of the endocrine system is principally controlled by a network of circadian clocks. The circadian network comprises a master circadian clock, located in the suprachiasmatic nucleus of the hypothalamus, synchronized to the ambient light, and secondary circadian clocks found in various peripheral organs, such as the adipose tissues. Besides circadian clocks, other factors such as meals and metabolic status impact daily profiles of hormonal levels. In turn, the precise daily pattern of hormonal release provides temporal signaling information. This review will describe the reciprocal links between the circadian clocks and rhythmic secretion of leptin, and discuss the metabolic impact of circadian desynchronization and altered rhythmic leptin. Copyright © 2017 Elsevier Ltd. All rights reserved.

KSC-2014-4585

NASA Image and Video Library

2014-11-25

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, the first of 24 light emitting diode LED panels have arrived for installation in the new countdown clock at the spaceport's Press Site. A new modern, multimedia display soon will be installed, similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Jim Grossmann

KSC-2014-4586

NASA Image and Video Library

2014-11-25

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, assembly has begun on the first of 24 light emitting diode LED panels for installation in the new countdown clock at the spaceport's Press Site. The new modern, multimedia display will be similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Jim Grossmann

KSC-2014-4587

NASA Image and Video Library

2014-11-25

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, assembly has begun on the first of 24 light emitting diode LED panels for installation in the new countdown clock at the spaceport's Press Site. The new modern, multimedia display will be similar to the screens seen at sporting venues. The new screen will be nearly 26 feet wide by 7 feet high, a foot taller than the original clock. The historic countdown clock was designed by Kennedy engineers and built by space center technicians before Apollo 12 in 1969. NASA has requested to acquire the countdown clock from the agency’s Artifact Working Group at the agency's Headquarters for likely display at the Kennedy Space Center Visitor Complex. For more information on the countdown clock, go to http://go.nasa.gov/10Zku10. Photo credit: NASA/Jim Grossmann

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

Shi, Xin, E-mail: xinshih86029@gmail.com; Zhao, Xiangmo, E-mail: xinshih86029@gmail.com; Hui, Fei, E-mail: xinshih86029@gmail.com

Clock synchronization in wireless sensor networks (WSNs) has been studied extensively in recent years and many protocols are put forward based on the point of statistical signal processing, which is an effective way to optimize accuracy. However, the accuracy derived from the statistical data can be improved mainly by sufficient packets exchange, which will consume the limited power resources greatly. In this paper, a reliable clock estimation using linear weighted fusion based on pairwise broadcast synchronization is proposed to optimize sync accuracy without expending additional sync packets. As a contribution, a linear weighted fusion scheme for multiple clock deviations ismore » constructed with the collaborative sensing of clock timestamp. And the fusion weight is defined by the covariance of sync errors for different clock deviations. Extensive simulation results show that the proposed approach can achieve better performance in terms of sync overhead and sync accuracy.« less

Government and industry interactions in the development of clock technology

NASA Technical Reports Server (NTRS)

Hellwig, H.

1981-01-01

It appears likely that everyone in the time and frequency community can agree on goals to be realized through the expenditure of resources. These goals are the same as found in most fields of technology: lower cost, better performance, increased reliability, small size and lower power. Related aspects are examined in the process of clock and frequency standard development. Government and industry are reviewed in a highly interactive role. These interactions include judgements on clock performance, what kind of clock, expenditure of resources, transfer of ideas or hardware concepts from government to industry, and control of production. Successful clock development and production requires a government/industry relationship which is characterized by long-term continuity, multidisciplinary team work, focused funding and a separation of reliability and production oriented tasks from performance improvement/research type efforts.

Comparison of clock drawing with Mini Mental State Examination as a screening test in elderly acute hospital admissions.

PubMed Central

Death, J.; Douglas, A.; Kenny, R. A.

1993-01-01

Clock drawing is a quick, easy to remember test that is well received by patients. It is a good screening test for Alzheimer's disease in the outpatient setting. We evaluated its usefulness compared with the standard Mini Mental State Examination (MMSE) in elderly acute medical and surgical hospital admissions. Within 48 hours of admission, 117 patients over 70 years old were administered the MMSE and asked to draw a clock. Using the MMSE as the standard, clock drawing had a sensitivity of 77% and a specificity of 87%. Patients with discrepant scores were then further evaluated. The findings suggest that normal clock drawing ability reasonably excludes cognitive impairment or other causes of an abnormal MMSE in elderly acute medical and surgical hospital admissions, where cognitive impairment is common and frequently missed. PMID:8255833

Electrical Hyperexcitation of Lateral Ventral Pacemaker Neurons Desynchronizes Downstream Circadian Oscillators in the Fly Circadian Circuit and Induces Multiple Behavioral Periods

PubMed Central

Nitabach, Michael N.; Wu, Ying; Sheeba, Vasu; Lemon, William C.; Strumbos, John; Zelensky, Paul K.; White, Benjamin H.; Holmes, Todd C.

2008-01-01

Coupling of autonomous cellular oscillators is an essential aspect of circadian clock function but little is known about its circuit requirements. Functional ablation of the pigment-dispersing factor-expressing lateral ventral subset (LNV ) of Drosophila clock neurons abolishes circadian rhythms of locomotor activity. The hypothesis that LNVs synchronize oscillations in downstream clock neurons was tested by rendering the LNVs hyperexcitable via transgenic expression of a low activation threshold voltage-gated sodium channel. When the LNVs are made hyperexcitable, free-running behavioral rhythms decompose into multiple independent superimposed oscillations and the clock protein oscillations in the dorsal neuron 1 and 2 subgroups of clock neurons are phase-shifted. Thus, regulated electrical activity of the LNVs synchronize multiple oscillators in the fly circadian pacemaker circuit. PMID:16407545

Lattice-Induced Frequency Shifts in Sr Optical Lattice Clocks at the 10{sup -17} Level

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

Westergaard, P. G.; Lodewyck, J.; Lecallier, A.

2011-05-27

We present a comprehensive study of the frequency shifts associated with the lattice potential in a Sr lattice clock by comparing two such clocks with a frequency stability reaching 5x10{sup -17} after a 1 h integration time. We put the first experimental upper bound on the multipolar M1 and E2 interactions, significantly smaller than the recently predicted theoretical upper limit, and give a 30-fold improved upper limit on the effect of hyperpolarizability. Finally, we report on the first observation of the vector and tensor shifts in a Sr lattice clock. Combining these measurements, we show that all known lattice relatedmore » perturbations will not affect the clock accuracy down to the 10{sup -17} level, even for lattices as deep as 150 recoil energies.« less

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

Sadowski, Greg

In one form, a logic circuit includes an asynchronous logic circuit, a synchronous logic circuit, and an interface circuit coupled between the asynchronous logic circuit and the synchronous logic circuit. The asynchronous logic circuit has a plurality of asynchronous outputs for providing a corresponding plurality of asynchronous signals. The synchronous logic circuit has a plurality of synchronous inputs corresponding to the plurality of asynchronous outputs, a stretch input for receiving a stretch signal, and a clock output for providing a clock signal. The synchronous logic circuit provides the clock signal as a periodic signal but prolongs a predetermined state ofmore » the clock signal while the stretch signal is active. The asynchronous interface detects whether metastability could occur when latching any of the plurality of the asynchronous outputs of the asynchronous logic circuit using said clock signal, and activates the stretch signal while the metastability could occur.« less

Upper Limit of Weights in TAI Computation

NASA Technical Reports Server (NTRS)

Thomas, Claudine; Azoubib, Jacques

1996-01-01

The international reference time scale International Atomic Time (TAI) computed by the Bureau International des Poids et Mesures (BIPM) relies on a weighted average of data from a large number of atomic clocks. In it, the weight attributed to a given clock depends on its long-term stability. In this paper the TAI algorithm is used as the basis for a discussion of how to implement an upper limit of weight for clocks contributing to the ensemble time. This problem is approached through the comparison of two different techniques. In one case, a maximum relative weight is fixed: no individual clock can contribute more than a given fraction to the resulting time scale. The weight of each clock is then adjusted according to the qualities of the whole set of contributing elements. In the other case, a parameter characteristic of frequency stability is chosen: no individual clock can appear more stable than the stated limit. This is equivalent to choosing an absolute limit of weight and attributing this to to the most stable clocks independently of the other elements of the ensemble. The first technique is more robust than the second and automatically optimizes the stability of the resulting time scale, but leads to a more complicated computatio. The second technique has been used in the TAI algorithm since the very beginning. Careful analysis of tests on real clock data shows that improvement of the stability of the time scale requires revision from time to time of the fixed value chosen for the upper limit of absolute weight. In particular, we present results which confirm the decision of the CCDS Working Group on TAI to increase the absolute upper limit by a factor of 2.5. We also show that the use of an upper relative contribution further helps to improve the stability and may be a useful step towards better use of the massive ensemble of HP 507IA clocks now contributing to TAI.

Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms

PubMed Central

Gérard, Claude; Goldbeter, Albert

2012-01-01

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

Regulation of the clock gene expression in human adipose tissue by weight loss.

PubMed

Pivovarova, O; Gögebakan, Ö; Sucher, S; Groth, J; Murahovschi, V; Kessler, K; Osterhoff, M; Rudovich, N; Kramer, A; Pfeiffer, A F H

2016-06-01

The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters. Subcutaneous adipose tissue (SAT) samples were collected before and after 8 weeks of weight loss on an 800 kcal per day hypocaloric diet (plus 200 g per day vegetables) at the same time of the day. Fifty overweight subjects who lost at least 8% weight after 8 weeks were selected for the study. The expression of 10 clock genes and key metabolic and inflammatory genes in adipose tissue was determined by quantitative real-time PCR. The expression of core clock genes PER2 and NR1D1 was increased after the weight loss. Correlations of PERIOD expression with body mass index (BMI) and serum total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol levels and of NR1D1 expression with total and LDL cholesterol were found that became non-significant after correction for multiple testing. Clock gene expression levels and their weight loss-induced changes tightly correlated with each other and with genes involved in fat metabolism (FASN, CPT1A, LPL, PPARG, PGC1A, ADIPOQ), energy metabolism (SIRT1), autophagy (LC3A, LC3B) and inflammatory response (NFKB1, NFKBIA, NLRP3, EMR1). Clock gene expression in human SAT is regulated by body weight changes and associated with BMI, serum cholesterol levels and the expression of metabolic and inflammatory genes. Our data confirm the tight crosstalk between molecular clock and metabolic and inflammatory pathways involved in adapting adipose tissue metabolism to changes of the energy intake in humans.

Clock Drawing Test and the diagnosis of amnestic mild cognitive impairment: can more detailed scoring systems do the work?

PubMed

Rubínová, Eva; Nikolai, Tomáš; Marková, Hana; Siffelová, Kamila; Laczó, Jan; Hort, Jakub; Vyhnálek, Martin

2014-01-01

The Clock Drawing Test is a frequently used cognitive screening test with several scoring systems in elderly populations. We compare simple and complex scoring systems and evaluate the usefulness of the combination of the Clock Drawing Test with the Mini-Mental State Examination to detect patients with mild cognitive impairment. Patients with amnestic mild cognitive impairment (n = 48) and age- and education-matched controls (n = 48) underwent neuropsychological examinations, including the Clock Drawing Test and the Mini-Mental State Examination. Clock drawings were scored by three blinded raters using one simple (6-point scale) and two complex (17- and 18-point scales) systems. The sensitivity and specificity of these scoring systems used alone and in combination with the Mini-Mental State Examination were determined. Complex scoring systems, but not the simple scoring system, were significant predictors of the amnestic mild cognitive impairment diagnosis in logistic regression analysis. At equal levels of sensitivity (87.5%), the Mini-Mental State Examination showed higher specificity (31.3%, compared with 12.5% for the 17-point Clock Drawing Test scoring scale). The combination of Clock Drawing Test and Mini-Mental State Examination scores increased the area under the curve (0.72; p < .001) and increased specificity (43.8%), but did not increase sensitivity, which remained high (85.4%). A simple 6-point scoring system for the Clock Drawing Test did not differentiate between healthy elderly and patients with amnestic mild cognitive impairment in our sample. Complex scoring systems were slightly more efficient, yet still were characterized by high rates of false-positive results. We found psychometric improvement using combined scores from the Mini-Mental State Examination and the Clock Drawing Test when complex scoring systems were used. The results of this study support the benefit of using combined scores from simple methods.

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

PubMed

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

2009-10-01

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

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

PubMed

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

2016-09-01

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

CSAC Characterization and Its Impact on GNSS Clock Augmentation Performance

PubMed Central

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

2017-01-01

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

CSAC Characterization and Its Impact on GNSS Clock Augmentation Performance.

PubMed

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

2017-02-14

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

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

PubMed Central

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

2016-01-01

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 (Clkout) genetic background (p{dClk-Δ};Clkout), 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};Clkout 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};Clkout 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};Clkout 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

Circadian Rhythms in Diet-Induced Obesity.

PubMed

Engin, Atilla

2017-01-01

The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronizes these with daily cycles, feeding patterns also regulates circadian clocks. The clock genes and adipocytokines show circadian rhythmicity. Dysfunction of these genes are involved in the alteration of these adipokines during the development of obesity. Food availability promotes the stimuli associated with food intake which is a circadian oscillator outside of the suprachiasmatic nucleus (SCN). Its circadian rhythm is arranged with the predictable daily mealtimes. Food anticipatory activity is mediated by a self-sustained circadian timing and its principal component is food entrained oscillator. However, the hypothalamus has a crucial role in the regulation of energy balance rather than food intake. Fatty acids or their metabolites can modulate neuronal activity by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. The timing of three-meal schedules indicates close association with the plasma levels of insulin and preceding food availability. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition can lead to uncoupling of peripheral clocks from the central pacemaker and to the development of metabolic disorders. Metabolic dysfunction is associated with circadian disturbances at both central and peripheral levels and, eventual disruption of circadian clock functioning can lead to obesity. While CLOCK expression levels are increased with high fat diet-induced obesity, peroxisome proliferator-activated receptor (PPAR) alpha increases the transcriptional level of brain and muscle ARNT-like 1 (BMAL1) in obese subjects. Consequently, disruption of clock genes results in dyslipidemia, insulin resistance and obesity. Modifying the time of feeding alone can greatly affect body weight. Changes in the circadian clock are associated with temporal alterations in feeding behavior and increased weight gain. Thus, shift work is associated with increased risk for obesity, diabetes and cardio-vascular diseases as a result of unusual eating time and disruption of circadian rhythm.

Prevalence of Cam Deformity with Associated Femoroacetabular Impingement Syndrome in Hip Joint Computed Tomography of Asymptomatic Adults

PubMed Central

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

2018-01-01

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

Design and performance of clock-recovery GaAs ICs for high-speed optical communication systems

NASA Astrophysics Data System (ADS)

Imai, Yuhki; Sano, Eiichi; Nakamura, Makoto; Ishihara, Noboru; Kikuchi, Hiroyuki; Ono, Takashi

1993-05-01

Design and performance of clock-recovery GaAs ICs are presented. Four kinds of ICs were developed: a limiting amplifier, a tuning amplifier, a rectifier, and a differentiator. The cascaded limiting amplifier together with a tuning amplifier achieved a 58-dB gain and a 10-degree phase deviation with 20-dB input dynamic range at 10 GHz. A clock-recovery circuit successfully extracts a low-jitter 10-GHz clock signal of 1-dBm constant power from 10-Gb/s NRZ pseudorandom bit streams using a pulse pattern generator.

A High Performance 50% Clock Duty Cycle Regulator

NASA Astrophysics Data System (ADS)

Huang, Peng; Deng, Hong-Hui; Yin, Yong-Sheng

A low-jitter clock duty cycle corrector circuit applied in high performance ADC is presented in the paper, such circuits can change low accuracy input signals with different frequencies into 50% pulse width clock. The result have show that the circuit could lock duty cycle rapidly with an accuracy of 50% ± 1% in 200ns. This circuit have 10%-90% of duty cycle input, and clock jitter could be suppressed to less than 5ps. The method used in the circuit, which provides little relationship with the noise and process mismatch, is widely used Implemented in 0.18μm CMOS process.

A hydrogen maser clock for space - Clocks in future possible and improbable applications

NASA Astrophysics Data System (ADS)

Vessot, Robert F. C.

The development of atomic-H maser clocks for space applications since 1967 is reviewed, with a focus on the 39-kg instrument built for a rocket-flight test of gravitational redshift in 1976. The stability of the oscillator and the instability of earth-space propagation in that test are described, and techniques for overcoming the latter effects are considered. More recent maser clocks employ an H sorption manifold rather than heavy ion pumps; their application to precise satellite position determination for space-based VLBI astronomy is discussed in detail. Extensive diagrams, drawings, and photographs are provided.

An atomic clock with 10(-18) instability.

PubMed

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

2013-09-13

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

Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage.

PubMed

Dodd, Antony N; Salathia, Neeraj; Hall, Anthony; Kévei, Eva; Tóth, Réka; Nagy, Ferenc; Hibberd, Julian M; Millar, Andrew J; Webb, Alex A R

2005-07-22

Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long- and short-circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.

A quantum analogy to the classical gravitomagnetic clock effect

NASA Astrophysics Data System (ADS)

Faruque, S. B.

2018-06-01

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

Preliminary Observations from the 2014 Sand Dunes Experiment

DTIC Science & Technology

2014-10-01

sync (start) 06/01/2014 09:00 0.00 ms ( latched ) Clock sync (end) 06/18/2014 11:55:00 10.846 ms slow Drift rate 633.471 μs/day (slowing) 22...10m (faired Kevlar) 210.0 m Sample rate 9765.625 Hz Clock sync (start) 06/01/2014 (YD 152) 01:33 0.00s ( latched ) Clock sync (end) 06/19/2014 (YD...02/2014 07:43 0.00s ( latched ) Clock sync (end) 06/16/2014 01:10 38.527 ms fast Drift rate 2.8066 ms/day (fast) 32 Figure 30. SBE39

System and method for adaptively deskewing parallel data signals relative to a clock

DOEpatents

Jenkins, Philip Nord; Cornett, Frank N.

2006-04-18

A system and method of reducing skew between a plurality of signals transmitted with a transmit clock is described. Skew is detected between the received transmit clock and each of received data signals. Delay is added to the clock or to one or more of the plurality of data signals to compensate for the detected skew. Each of the plurality of delayed signals is compared to a reference signal to detect changes in the skew. The delay added to each of the plurality of delayed signals is updated to adapt to changes in the detected skew.

Alternative Splicing of Barley Clock Genes in Response to Low Temperature

PubMed Central

Calixto, Cristiane P. G.; Simpson, Craig G.; Waugh, Robbie; Brown, John W. S.

2016-01-01

Alternative splicing (AS) is a regulated mechanism that generates multiple transcripts from individual genes. It is widespread in eukaryotic genomes and provides an effective way to control gene expression. At low temperatures, AS regulates Arabidopsis clock genes through dynamic changes in the levels of productive mRNAs. We examined AS in barley clock genes to assess whether temperature-dependent AS responses also occur in a monocotyledonous crop species. We identify changes in AS of various barley core clock genes including the barley orthologues of Arabidopsis AtLHY and AtPRR7 which showed the most pronounced AS changes in response to low temperature. The AS events modulate the levels of functional and translatable mRNAs, and potentially protein levels, upon transition to cold. There is some conservation of AS events and/or splicing behaviour of clock genes between Arabidopsis and barley. In addition, novel temperature-dependent AS of the core clock gene HvPPD-H1 (a major determinant of photoperiod response and AtPRR7 orthologue) is conserved in monocots. HvPPD-H1 showed a rapid, temperature-sensitive isoform switch which resulted in changes in abundance of AS variants encoding different protein isoforms. This novel layer of low temperature control of clock gene expression, observed in two very different species, will help our understanding of plant adaptation to different environments and ultimately offer a new range of targets for plant improvement. PMID:27959947

ACES microwave link requirements.

PubMed

Uhrich, P M; Guillernot, P; Aubry, P; Gonzalez, F; Salomon, C

2000-01-01

Atomic Clock Ensemble in Space (ACES) is a project of the European Space Agency on-board the future International Space Station (ISS). The payload consists mainly of two atomic frequency standards, one space hydrogen maser (SHM) prepared by the Observatoire de Neuchatel (Switzerland), and one cold atom caesium clock called PHARAO prepared by the CNES (France), with the participation of the BNM-LPTF, the ENS-LKB, and the CNRS-LHA. Because of the anticipated performances of these clocks on-board the ISS, the requirements of the links between the payload and the clocks on the Earth are at the limits of the known potential of the optical or microwave techniques. The microwave link (MWL) requirements are described in this paper. Taking into account the characteristics of the ISS orbit, and fixing an arbitrary limit to the additional noise brought to the clock readings by the MWL, the computation of the required stability leads to two kinds of requirements: the first one at the subpicosecond level over each single continuous pass of the ISS above any Earth station, and the second one at the level of one part in 10(16) and below over a one day or more averaging period. Moreover, the ISS orbit parameters should lead to a knowledge of the ACES clock position at the m level, and of the ACES clock speed at the mm/s level.

Circadian expression of clock genes in human oral mucosa and skin: association with specific cell-cycle phases.

PubMed

Bjarnason, G A; Jordan, R C; Wood, P A; Li, Q; Lincoln, D W; Sothern, R B; Hrushesky, W J; Ben-David, Y

2001-05-01

We studied the relative RNA expression of clock genes throughout one 24-hour period in biopsies obtained from the oral mucosa and skin from eight healthy diurnally active male study participants. We found that the human clock genes hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin, with a circadian profile consistent with that found in the suprachiasmatic nuclei and the peripheral tissues of rodents. hPer1, hCry1, and hBmal1 have a rhythmic expression, peaking early in the morning, in late afternoon, and at night, respectively, whereas hClock and hTim are not rhythmic. This is the first human study to show a circadian profile of expression for all five clock genes as documented in rodents, suggesting their functional importance in man. In concurrent oral mucosa biopsies, thymidylate synthase enzyme activity, a marker for DNA synthesis, had a circadian variation with peak activity in early afternoon, coinciding with the timing of S phase in our previous study on cell-cycle timing in human oral mucosa. The major peak in hPer1 expression occurs at the same time of day as the peak in G(1) phase in oral mucosa, suggesting a possible link between the circadian clock and the mammalian cell cycle.

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

PubMed Central

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

2015-01-01

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

Influence of temperature on the liver circadian clock in the ruin lizard Podarcis sicula.

PubMed

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

2007-07-01

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

Circadian Stress Regimes Affect the Circadian Clock and Cause Jasmonic Acid-Dependent Cell Death in Cytokinin-Deficient Arabidopsis Plants.

PubMed

Nitschke, Silvia; Cortleven, Anne; Iven, Tim; Feussner, Ivo; Havaux, Michel; Riefler, Michael; Schmülling, Thomas

2016-07-01

The circadian clock helps plants measure daylength and adapt to changes in the day-night rhythm. We found that changes in the light-dark regime triggered stress responses, eventually leading to cell death, in leaves of Arabidopsis thaliana plants with reduced cytokinin levels or defective cytokinin signaling. Prolonged light treatment followed by a dark period induced stress and cell death marker genes while reducing photosynthetic efficiency. This response, called circadian stress, is also characterized by altered expression of clock and clock output genes. In particular, this treatment strongly reduced the expression of CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). Intriguingly, similar changes in gene expression and cell death were observed in clock mutants lacking proper CCA1 and LHY function. Circadian stress caused strong changes in reactive oxygen species- and jasmonic acid (JA)-related gene expression. The activation of the JA pathway, involving the accumulation of JA metabolites, was crucial for the induction of cell death, since the cell death phenotype was strongly reduced in the jasmonate resistant1 mutant background. We propose that adaptation to circadian stress regimes requires a normal cytokinin status which, acting primarily through the AHK3 receptor, supports circadian clock function to guard against the detrimental effects of circadian stress. © 2016 American Society of Plant Biologists. All rights reserved.

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

PubMed Central

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

2013-01-01

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

CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial

USDA-ARS?s Scientific Manuscript database

Background Circadian rhythms regulate key biological processes influencing metabolic pathways. Dysregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK...

A Simple Electromagnetic Model for the Light Clock of Special Relativity

ERIC Educational Resources Information Center

Smith, Glenn S.

2011-01-01

Thought experiments involving a light clock are common in introductory treatments of special relativity, because they provide a simple way of demonstrating the non-intuitive phenomenon of time dilation. The properties of the ray or pulse of light that is continuously reflected between the parallel mirrors of the clock are often stated vaguely and…