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.

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.

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.

Ultra fast quantum key distribution over a 97 km installed telecom fiber with wavelength division multiplexing clock synchronization.

PubMed

Tanaka, Akihiro; Fujiwara, Mikio; Nam, Sae W; Nambu, Yoshihiro; Takahashi, Seigo; Maeda, Wakako; Yoshino, Ken-ichiro; Miki, Shigehito; Baek, Burm; Wang, Zhen; Tajima, Akio; Sasaki, Masahide; Tomita, Akihisa

2008-07-21

We demonstrated ultra fast BB84 quantum key distribution (QKD) transmission at 625 MHz clock rate through a 97 km field-installed fiber using practical clock synchronization based on wavelength-division multiplexing (WDM). We succeeded in over-one-hour stable key generation at a high sifted key rate of 2.4 kbps and a low quantum bit error rate (QBER) of 2.9%. The asymptotic secure key rate was estimated to be 0.78- 0.82 kbps from the transmission data with the decoy method of average photon numbers 0, 0.15, and 0.4 photons/pulse.

A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock.

PubMed

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

2016-09-15

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

Motivational Modulation of Rhythms of the Expression of the Clock Protein PER2 in the Limbic Forebrain.

PubMed

Amir, Shimon; Stewart, Jane

2009-05-15

Key molecular components of the mammalian circadian clock are expressed rhythmically in many brain areas and peripheral tissues in mammals. Here we review findings from our work on rhythms of expression of the clock protein Period2 (PER2) in four regions of the limbic forebrain known to be important in the regulation of motivational and emotional states. These regions include the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), and the dentate gyrus (DG). Daily rhythms in the expression of PER2 in these regions are controlled by the master circadian pacemaker, the suprachiasmatic nucleus (SCN), but, importantly, they are also sensitive to homeostatic perturbations and to hormonal states that directly influence motivated behavior. Thus, circadian information from the SCN and homeostatic signals are integrated in these regions of the limbic forebrain to affect the temporal organization of motivational and emotional processes.

Compact atomic clocks and stabilised laser for space applications

NASA Astrophysics Data System (ADS)

Mileti, Gaetano; Affolderbach, Christoph; Matthey-de-l'Endroit, Renaud

2016-07-01

We present our developments towards next generation compact vapour-cell based atomic frequency standards using a tunable laser diode instead of a traditional discharge lamp. The realisation of two types of Rubidium clocks addressing specific applications is in progress: high performance frequency standards for demanding applications such as satellite navigation, and chip-scale atomic clocks, allowing further miniaturisation of the system. The stabilised laser source constitutes the main technological novelty of these new standards, allowing a more efficient preparation and interrogation of the atoms and hence an improvement of the clock performances. However, before this key component may be employed in a commercial and ultimately in a space-qualified instrument, further studies are necessary to demonstrate their suitability, in particular concerning their reliability and long-term operation. The talk will present our preliminary investigations on this subject. The stabilised laser diode technology developed for our atomic clocks has several other applications on ground and in space. We will conclude our talk by illustrating this for the example of a recently completed ESA project on a 1.6 microns wavelength reference for a future space-borne Lidar. This source is based on a Rubidium vapour cell providing the necessary stability and accuracy, while a second harmonic generator and a compact optical comb generated from an electro-optic modulator allow to transfer these properties from the Rubidium wavelength (780nm) to the desired spectral range.

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 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

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

Epigenetic and Posttranslational Modifications in Light Signal Transduction and the Circadian Clock in Neurospora crassa

PubMed Central

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

2015-01-01

Blue light, a key abiotic signal, regulates a wide variety of physiological processes in many organisms. One of these phenomena is the circadian rhythm presents in organisms sensitive to the phase-setting effects of blue light and under control of the daily alternation of light and dark. Circadian clocks consist of autoregulatory alternating negative and positive feedback loops intimately connected with the cellular metabolism and biochemical processes. Neurospora crassa provides an excellent model for studying the molecular mechanisms involved in these phenomena. The White Collar Complex (WCC), a blue-light receptor and transcription factor of the circadian oscillator, and Frequency (FRQ), the circadian clock pacemaker, are at the core of the Neurospora circadian system. The eukaryotic circadian clock relies on transcriptional/translational feedback loops: some proteins rhythmically repress their own synthesis by inhibiting the activity of their transcriptional factors, generating self-sustained oscillations over a period of about 24 h. One of the basic mechanisms that perpetuate self-sustained oscillations is post translation modification (PTM). The acronym PTM generically indicates the addition of acetyl, methyl, sumoyl, or phosphoric groups to various types of proteins. The protein can be regulatory or enzymatic or a component of the chromatin. PTMs influence protein stability, interaction, localization, activity, and chromatin packaging. Chromatin modification and PTMs have been implicated in regulating circadian clock function in Neurospora. Research into the epigenetic control of transcription factors such as WCC has yielded new insights into the temporal modulation of light-dependent gene transcription. Here we report on epigenetic and protein PTMs in the regulation of the Neurospora crassa circadian clock. We also present a model that illustrates the molecular mechanisms at the basis of the blue light control of the circadian clock. PMID:26198228

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.

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.

Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

PubMed Central

Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

2014-01-01

Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

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.

Regulatory principles and experimental approaches to the circadian control of starch turnover

PubMed Central

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

2014-01-01

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

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.

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.

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.

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.

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.

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.

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.

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.

The clock and wavefront model revisited.

PubMed

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

2011-08-21

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

Multiple circadian transcriptional elements cooperatively regulate cell-autonomous transcriptional oscillation of Period3, a mammalian clock gene.

PubMed

Matsumura, Ritsuko; Akashi, Makoto

2017-09-29

Cell-autonomous oscillation in clock gene expression drives circadian rhythms. The development of comprehensive analytical techniques, such as bioinformatics and ChIP-sequencing, has enabled the genome-wide identification of potential circadian transcriptional elements that regulate the transcriptional oscillation of clock genes. However, detailed analyses using traditional biochemical and molecular-biological approaches, such as binding and reporter assays, are still necessary to determine whether these potential circadian transcriptional elements are actually functional and how significantly they contribute to driving transcriptional oscillation. Here, we focused on the molecular mechanism of transcriptional oscillations in the mammalian clock gene Period3 ( Per3 ). The PER3 protein is essential for robust peripheral clocks and is a key component in circadian output processes. We found three E box-like elements located upstream of human Per3 transcription start sites that additively contributed to cell-autonomous transcriptional oscillation. However, we also found that Per3 is still expressed in a circadian manner when all three E box-like elements are functionally impaired. We noted that Per3 transcription was activated by the synergistic actions of two D box-like elements and the three E box-like elements, leading to a drastic increase in circadian amplitude. Interestingly, circadian expression of Per3 was completely disrupted only when all five transcriptional elements were functionally impaired. These results indicate that three E box-like and two D box-like elements cooperatively and redundantly regulate cell-autonomous transcriptional oscillation of Per3 . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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...

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...

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.

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.

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.

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.

Quantum key distribution with 1.25 Gbps clock synchronization.

PubMed

Bienfang, J; Gross, A; Mink, A; Hershman, B; Nakassis, A; Tang, X; Lu, R; Su, D; Clark, Charles; Williams, Carl; Hagley, E; Wen, Jesse

2004-05-03

We have demonstrated the exchange of sifted quantum cryptographic key over a 730 meter free-space link at rates of up to 1.0 Mbps, two orders of magnitude faster than previously reported results. A classical channel at 1550 nm operates in parallel with a quantum channel at 845 nm. Clock recovery techniques on the classical channel at 1.25 Gbps enable quantum transmission at up to the clock rate. System performance is currently limited by the timing resolution of our silicon avalanche photodiode detectors. With improved detector resolution, our technique will yield another order of magnitude increase in performance, with existing technology.

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.

PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP.

PubMed

Yeom, Miji; Lee, HansongI; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

2018-03-23

Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

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.

Characterisation of circadian rhythms of various duckweeds.

PubMed

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

2015-01-01

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

Mapping the magnetic field vector in a fountain clock

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

Gertsvolf, Marina; Marmet, Louis

2011-12-15

We show how the mapping of the magnetic field vector components can be achieved in a fountain clock by measuring the Larmor transition frequency in atoms that are used as a spatial probe. We control two vector components of the magnetic field and apply audio frequency magnetic pulses to localize and measure the field vector through Zeeman spectroscopy.

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.

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

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.

Ultralow-Power Digital Correlator for Microwave Polarimetry

NASA Technical Reports Server (NTRS)

Piepmeier, Jeffrey R.; Hass, K. Joseph

2004-01-01

A recently developed high-speed digital correlator is especially well suited for processing readings of a passive microwave polarimeter. This circuit computes the autocorrelations of, and the cross-correlations among, data in four digital input streams representing samples of in-phase (I) and quadrature (Q) components of two intermediate-frequency (IF) signals, denoted A and B, that are generated in heterodyne reception of two microwave signals. The IF signals arriving at the correlator input terminals have been digitized to three levels (-1,0,1) at a sampling rate up to 500 MHz. Two bits (representing sign and magnitude) are needed to represent the instantaneous datum in each input channel; hence, eight bits are needed to represent the four input signals during any given cycle of the sampling clock. The accumulation (integration) time for the correlation is programmable in increments of 2(exp 8) cycles of the sampling clock, up to a maximum of 2(exp 24) cycles. The basic functionality of the correlator is embodied in 16 correlation slices, each of which contains identical logic circuits and counters (see figure). The first stage of each correlation slice is a logic gate that computes one of the desired correlations (for example, the autocorrelation of the I component of A or the negative of the cross-correlation of the I component of A and the Q component of B). The sampling of the output of the logic gate output is controlled by the sampling-clock signal, and an 8-bit counter increments in every clock cycle when the logic gate generates output. The most significant bit of the 8-bit counter is sampled by a 16-bit counter with a clock signal at 2(exp 8) the frequency of the sampling clock. The 16-bit counter is incremented every time the 8-bit counter rolls over.

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer.

PubMed

Maiese, Kenneth

2017-01-01

The mammalian circadian clock and its associated clock genes are increasingly been recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis. In experimental models, lifespan is significantly reduced with the introduction of arrhythmic mutants and leads to an increase in oxidative stress exposure. Interestingly, patients with Alzheimer's disease and Parkinson's disease may suffer disease onset or progression as a result of alterations in the DNA methylation of clock genes as well as prolonged pharmacological treatment for these disorders that may lead to impairment of circadian rhythm function. Tumorigenesis also can occur with the loss of a maintained circadian rhythm and lead to an increased risk for nasopharyngeal carcinoma, breast cancer, and metastatic colorectal cancer. Interestingly, the circadian clock system relies upon the regulation of the critical pathways of autophagy, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) as well as proliferative mechanisms that involve the wingless pathway of Wnt/β-catenin pathway to foster cell survival during injury and block tumor cell growth. Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm may hold the key for the development of novel and effective therapies against aging- related disorders, neurodegenerative disease, and tumorigenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Accuracy Performance Evaluation of Beidou Navigation Satellite System

NASA Astrophysics Data System (ADS)

Wang, W.; Hu, Y. N.

2017-03-01

Accuracy is one of the key elements of the regional Beidou Navigation Satellite System (BDS) performance standard. In this paper, we review the definition specification and evaluation standard of the BDS accuracy. Current accuracy of the regional BDS is analyzed through the ground measurements and compared with GPS in terms of dilution of precision (DOP), signal-in-space user range error (SIS URE), and positioning accuracy. The Positioning DOP (PDOP) map of BDS around Chinese mainland is compared with that of GPS. The GPS PDOP is between 1.0-2.0 and does not vary with the user latitude and longitude, while the BDS PDOP varies between 1.5-5.0, and increases as the user latitude increases, and as the user longitude apart from 118°. The accuracies of the broadcast orbits of BDS are assessed by taking the precise orbits from International GNSS Service (IGS) as the reference, and by making satellite laser ranging (SLR) residuals. The radial errors of the BDS inclined geosynchronous orbit (IGSO) and medium orbit (MEO) satellites broadcast orbits are at the 0.5m level, which are larger than those of GPS satellites at the 0.2m level. The SLR residuals of geosynchronous orbit (GEO) satellites are 65.0cm, which are larger than those of IGSO, and MEO satellites, at the 50.0cm level. The accuracy of broadcast clock offset parameters of BDS is computed by taking the clock measurements of Two-way Satellite Radio Time Frequency Transfer as the reference. Affected by the age of broadcast clock parameters, the error of the broadcast clock offset parameters of the MEO satellites is the largest, at the 0.80m level. Finally, measurements of the multi-GNSS (MGEX) receivers are used for positioning accuracy assessment of BDS and GPS. It is concluded that the positioning accuracy of regional BDS is better than 10m at the horizontal component and the vertical component. The combined positioning accuracy of both systems is better than one specific system.

A Circadian Clock in Antarctic Krill: An Endogenous Timing System Governs Metabolic Output Rhythms in the Euphausid Species Euphausia superba

PubMed Central

Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

2011-01-01

Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9–12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9–12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle. PMID:22022521

A circadian clock in Antarctic krill: an endogenous timing system governs metabolic output rhythms in the euphausid species Euphausia superba.

PubMed

Teschke, Mathias; Wendt, Sabrina; Kawaguchi, So; Kramer, Achim; Meyer, Bettina

2011-01-01

Antarctic krill, Euphausia superba, shapes the structure of the Southern Ocean ecosystem. Its central position in the food web, the ongoing environmental changes due to climatic warming, and increasing commercial interest on this species emphasize the urgency of understanding the adaptability of krill to its environment. Krill has evolved rhythmic physiological and behavioral functions which are synchronized with the daily and seasonal cycles of the complex Southern Ocean ecosystem. The mechanisms, however, leading to these rhythms are essentially unknown. Here, we show that krill possesses an endogenous circadian clock that governs metabolic and physiological output rhythms. We found that expression of the canonical clock gene cry2 was highly rhythmic both in a light-dark cycle and in constant darkness. We detected a remarkable short circadian period, which we interpret as a special feature of the krill's circadian clock that helps to entrain the circadian system to the extreme range of photoperiods krill is exposed to throughout the year. Furthermore, we found that important key metabolic enzymes of krill showed bimodal circadian oscillations (∼9-12 h period) in transcript abundance and enzymatic activity. Oxygen consumption of krill showed ∼9-12 h oscillations that correlated with the temporal activity profile of key enzymes of aerobic energy metabolism. Our results demonstrate the first report of an endogenous circadian timing system in Antarctic krill and its likely link to metabolic key processes. Krill's circadian clock may not only be critical for synchronization to the solar day but also for the control of seasonal events. This study provides a powerful basis for the investigation into the mechanisms of temporal synchronization in this marine key species and will also lead to the first comprehensive analyses of the circadian clock of a polar marine organism through the entire photoperiodic cycle.

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.

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.

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

Optoelectrical clock recovery with dispersion monitoring for high speed transmission

NASA Astrophysics Data System (ADS)

Wen, He; Liao, Jinxin; Zheng, Xiaoping; Zhang, Hanyi; Guo, Yili

2010-12-01

The proposed clock recovery scheme introduces electrooptical modulation to down convert the clock frequency facilitating succeeding narrow band filtering by a phase locked loop (PLL) with ordinary radio frequency (RF) devices, further, employs a quadrature phase detector in the PLL to provide an indication signal for monitoring residual dispersion. It was demonstrated in a polarization multiplexed 160-Gbit/s optical non-return to zero quadrature phase shift keying (NRZ-QPSK) transmission system.

Circadian rhythms synchronize mitosis in Neurospora crassa.

PubMed

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

2014-01-28

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

Targeting the Circadian Clock to Treat Cancer

Cancer.gov

Two compounds that target components of the circadian clock killed several types of cancer cells in the lab and slowed the growth of brain cancer in mice without harming healthy cells, as this Cancer Currents post reports.

Simultaneous Faraday filtering of the Mollow triplet sidebands with the Cs-D1 clock transition.

PubMed

Portalupi, Simone Luca; Widmann, Matthias; Nawrath, Cornelius; Jetter, Michael; Michler, Peter; Wrachtrup, Jörg; Gerhardt, Ilja

2016-11-25

Hybrid quantum systems integrating semiconductor quantum dots (QDs) and atomic vapours become important building blocks for scalable quantum networks due to the complementary strengths of individual parts. QDs provide on-demand single-photon emission with near-unity indistinguishability comprising unprecedented brightness-while atomic vapour systems provide ultra-precise frequency standards and promise long coherence times for the storage of qubits. Spectral filtering is one of the key components for the successful link between QD photons and atoms. Here we present a tailored Faraday anomalous dispersion optical filter based on the caesium-D 1 transition for interfacing it with a resonantly pumped QD. The presented Faraday filter enables a narrow-bandwidth (Δω=2π × 1 GHz) simultaneous filtering of both Mollow triplet sidebands. This result opens the way to use QDs as sources of single as well as cascaded photons in photonic quantum networks aligned to the primary frequency standard of the caesium clock transition.

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

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.

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.

A clock network for geodesy and fundamental science

PubMed Central

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

2016-01-01

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

A clock network for geodesy and fundamental science.

PubMed

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

2016-08-09

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

Diurnal Cycling Transcription Factors of Pineapple Revealed by Genome-Wide Annotation and Global Transcriptomic Analysis

PubMed Central

Sharma, Anupma; Wai, Ching Man; Ming, Ray

2017-01-01

Abstract Circadian clock provides fitness advantage by coordinating internal metabolic and physiological processes to external cyclic environments. Core clock components exhibit daily rhythmic changes in gene expression, and the majority of them are transcription factors (TFs) and transcription coregulators (TCs). We annotated 1,398 TFs from 67 TF families and 80 TCs from 20 TC families in pineapple, and analyzed their tissue-specific and diurnal expression patterns. Approximately 42% of TFs and 45% of TCs displayed diel rhythmic expression, including 177 TF/TCs cycling only in the nonphotosynthetic leaf tissue, 247 cycling only in the photosynthetic leaf tissue, and 201 cycling in both. We identified 68 TF/TCs whose cycling expression was tightly coupled between the photosynthetic and nonphotosynthetic leaf tissues. These TF/TCs likely coordinate key biological processes in pineapple as we demonstrated that this group is enriched in homologous genes that form the core circadian clock in Arabidopsis and includes a STOP1 homolog. Two lines of evidence support the important role of the STOP1 homolog in regulating CAM photosynthesis in pineapple. First, STOP1 responds to acidic pH and regulates a malate channel in multiple plant species. Second, the cycling expression pattern of the pineapple STOP1 and the diurnal pattern of malate accumulation in pineapple leaf are correlated. We further examined duplicate-gene retention and loss in major known circadian genes and refined their evolutionary relationships between pineapple and other plants. Significant variations in duplicate-gene retention and loss were observed for most clock genes in both monocots and dicots. PMID:28922793

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

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

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

RACE and Calculations of Three-dimensional Distributed Cavity Phase Shifts

NASA Technical Reports Server (NTRS)

Li, Ruoxin; Gibble, Kurt

2003-01-01

The design for RACE, a Rb-clock flight experiment for the ISS, is described. The cold collision shift and multiple launching (juggling) have important implications for the design and the resulting clock accuracy and stability. We present and discuss the double clock design for RACE. This design reduces the noise contributions of the local oscillator and simplifies and enhances an accuracy evaluation of the clock. As we try to push beyond the current accuracies of clocks, new systematic errors become important. The best fountain clocks are using cylindrical TE(sub 011) microwave cavities. We recently pointed out that many atoms pass through a node of the standing wave microwave field in these cavities. Previous studies have shown potentially large frequency shifts for atoms passing through nodes in a TE(sub 013) cavity. The shift occurs because there is a small traveling wave component due to the absorption of the copper cavity walls. The small traveling wave component leads to position dependent phase shifts. To study these effects, we perform Finite Element calculations. Three-dimensional Finite Element calculations require significant computer resources. Here we show that the cylindrical boundary condition can be Fourier decomposed to a short series of two-dimensional problems. This dramatically reduces the time and memory required and we obtain (3D) phase distributions for a variety of cavities. With these results, we will be able to analyze this frequency shift in fountain and future space clocks.

Real-Time Distributed Embedded Oscillator Operating Frequency Monitoring

NASA Technical Reports Server (NTRS)

Pollock, Julie; Oliver, Brett; Brickner, Christopher

2012-01-01

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

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.

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.

Temporal Ordering of Dynamic Expression Data from Detailed Spatial Expression Maps.

PubMed

Bailey, Charlotte S L; Bone, Robert A; Murray, Philip J; Dale, J Kim

2017-02-09

During somitogenesis, pairs of epithelial somites form in a progressive manner, budding off from the anterior end of the pre-somitic mesoderm (PSM) with a strict species-specific periodicity. The periodicity of the process is regulated by a molecular oscillator, known as the "segmentation clock," acting in the PSM cells. This clock drives the oscillatory patterns of gene expression across the PSM in a posterior-anterior direction. These so-called clock genes are key components of three signaling pathways: Wnt, Notch, and fibroblast growth factor (FGF). In addition, Notch signaling is essential for synchronizing intracellular oscillations in neighboring cells. We recently gained insight into how this may be mechanistically regulated. Upon ligand activation, the Notch receptor is cleaved, releasing the intracellular domain (NICD), which moves to the nucleus and regulates gene expression. NICD is highly labile, and its phosphorylation-dependent turnover acts to restrict Notch signaling. The profile of NICD production (and degradation) in the PSM is known to be oscillatory and to resemble that of a clock gene. We recently reported that both the Notch receptor and the Delta ligand, which mediate intercellular coupling, themselves exhibit dynamic expression at both the mRNA and protein levels. In this article, we describe the sensitive detection methods and detailed image analysis tools that we used, in combination with the computational modeling that we designed, to extract and overlay expression data from distinct points in the expression cycle. This allowed us to construct a spatio-temporal picture of the dynamic expression profile for the receptor, the ligand, and the Notch target clock genes throughout an oscillation cycle. Here, we describe the protocols used to generate and culture the PSM explants, as well as the procedure to stain for the mRNA or protein. We also explain how the confocal images were subsequently analyzed and temporally ordered computationally to generate ordered sequences of clock expression snapshots, hereafter defined as "kymographs," for the visualization of the spatiotemporal expression of Delta-like1 (Dll1) and Notch1 throughout the PSM.

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.

The design and development of low- and high-voltage ASICs for space-borne CCD cameras

NASA Astrophysics Data System (ADS)

Waltham, N.; Morrissey, Q.; Clapp, M.; Bell, S.; Jones, L.; Torbet, M.

2017-12-01

The CCD remains the pre-eminent visible and UV wavelength image sensor in space science, Earth and planetary remote sensing. However, the design of space-qualified CCD readout electronics is a significant challenge with requirements for low-volume, low-mass, low-power, high-reliability and tolerance to space radiation. Space-qualified components are frequently unavailable and up-screened commercial components seldom meet project or international space agency requirements. In this paper, we describe an alternative approach of designing and space-qualifying a series of low- and high-voltage mixed-signal application-specific integrated circuits (ASICs), the ongoing development of two low-voltage ASICs with successful flight heritage, and two new high-voltage designs. A challenging sub-system of any CCD camera is the video processing and digitisation electronics. We describe recent developments to improve performance and tolerance to radiation-induced single event latchup of a CCD video processing ASIC originally developed for NASA's Solar Terrestrial Relations Observatory and Solar Dynamics Observatory. We also describe a programme to develop two high-voltage ASICs to address the challenges presented with generating a CCD's bias voltages and drive clocks. A 0.35 μm, 50 V tolerant, CMOS process has been used to combine standard low-voltage 3.3 V transistors with high-voltage 50 V diffused MOSFET transistors that enable output buffers to drive CCD bias drains, gates and clock electrodes directly. We describe a CCD bias voltage generator ASIC that provides 24 independent and programmable 0-32 V outputs. Each channel incorporates a 10-bit digital-to-analogue converter, provides current drive of up to 20 mA into loads of 10 μF, and includes current-limiting and short-circuit protection. An on-chip telemetry system with a 12-bit analogue-to-digital converter enables the outputs and multiple off-chip camera voltages to be monitored. The ASIC can drive one or more CCDs and replaces the many discrete components required in current cameras. We also describe a CCD clock driver ASIC that provides six independent and programmable drivers with high-current capacity. The device enables various CCD clock parameters to be programmed independently, for example the clock-low and clock-high voltage levels, and the clock-rise and clock-fall times, allowing configuration for serial clock frequencies in the range 0.1-2 MHz and image clock frequencies in the range 10-100 kHz. Finally, we demonstrate the impact and importance of this technology for the development of compact, high-performance and low-power integrated focal plane electronics.

A 2-to-48-MHz Phase-Locked Loop

NASA Technical Reports Server (NTRS)

Koudelka, Robert D.

2004-01-01

A 2-to-48-MHz phase-locked loop (PLL), developed for the U.S. space program, meets or exceeds all space shuttle clock electrical interface requirements by taking as its reference a 2-to-48-MHz clock signal and outputting a phaselocked clock signal set at the same frequency as the reference clock with transistor- transistor logic (TTL) voltage levels. Because it is more adaptable than other PLLs, the new PLL can be used in industries that employ signaling devices and as a tool in future space missions. A conventional PLL consists of a phase/frequency detector, loop filter, and voltage-controlled oscillator in which each component exists individually and is integrated into a single device. PLL components phase-lock to a single frequency or to a narrow bandwidth of frequencies. It is this design, however, that prohibits them from maintaining phase lock to a dynamically changing reference clock when a large bandwidth is required a deficiency the new PLL overcomes. Since most PLL components require their voltage-controlled oscillators to operate at greater than 2-MHz frequencies, conventional PLLs often cannot achieve the low-frequency phase lock allowed by the new PLL. The 2-to-48-MHz PLL is built on a wire-wrap board with pins wired to three position jumpers; this makes changing configurations easy. It responds to variations in voltage-controlled oscillator (VCO) ranges, duty cycle, signal-to-noise ratio (SNR), amplitude, and jitter, exceeding design specifications. A consensus state machine, implemented in a VCO range detector which assures the PLL continues to operate in the correct range, is the primary control state machine for the 2-to-48-MHz PLL circuit. By using seven overlapping frequency ranges with hysteresis, the PLL output sets the resulting phase-locked clock signal at a frequency that agrees with the reference clock with TTL voltage levels. As a space-shuttle tool, the new PLL circuit takes the noisy, degraded reference clock signals as input and outputs phase-locked clock signals of the same frequency but with a corrected wave shape. Since its configuration circuit can be easily changed, the new PLL can do the following: readily respond to variations in VCO ranges, duty cycle, SNR, amplitude, and jitter; continuously operate in the correct VCO range because of its consensus state machine; and use its range detector implements to overlap seven frequency ranges with hysteresis, thus giving the current design a flexibility that exceeds anything available at the time of this development. These features will benefit any industry in which safe and timely clock signals are vital to operation.

Transcription factors involved in retinogenesis are co-opted by the circadian clock following photoreceptor differentiation

PubMed Central

Laranjeiro, Ricardo; Whitmore, David

2014-01-01

The circadian clock is known to regulate a wide range of physiological and cellular processes, yet remarkably little is known about its role during embryo development. Zebrafish offer a unique opportunity to explore this issue, not only because a great deal is known about key developmental events in this species, but also because the clock starts on the very first day of development. In this study, we identified numerous rhythmic genes in zebrafish larvae, including the key transcriptional regulators neurod and cdx1b, which are involved in neuronal and intestinal differentiation, respectively. Rhythmic expression of neurod and several additional transcription factors was only observed in the developing retina. Surprisingly, these rhythms in expression commenced at a stage of development after these transcription factors are known to have played their essential role in photoreceptor differentiation. Furthermore, this circadian regulation was maintained in adult retina. Thus, once mature photoreceptors are formed, multiple retinal transcription factors fall under circadian clock control, at which point they appear to play a new and important role in regulating rhythmic elements in the phototransduction pathway. PMID:24924194

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.

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

Anabolic Heterogeneity Following Resistance Training: A Role for Circadian Rhythm?

PubMed

Camera, Donny M

2018-01-01

It is now well established that resistance exercise stimulates muscle protein synthesis and promotes gains in muscle mass and strength. However, considerable variability exists following standardized resistance training programs in the magnitude of muscle cross-sectional area and strength responses from one individual to another. Several studies have recently posited that alterations in satellite cell population, myogenic gene expression and microRNAs may contribute to individual variability in anabolic adaptation. One emerging factor that may also explain the variability in responses to resistance exercise is circadian rhythms and underlying molecular clock signals. The molecular clock is found in most cells within the body, including skeletal muscle, and principally functions to optimize the timing of specific cellular events around a 24 h cycle. Accumulating evidence investigating the skeletal muscle molecular clock indicates that exercise-induced contraction and its timing may regulate gene expression and protein synthesis responses which, over time, can influence and modulate key physiological responses such as muscle hypertrophy and increased strength. Therefore, the circadian clock may play a key role in the heterogeneous anabolic responses with resistance exercise. The central aim of this Hypothesis and Theory is to discuss and propose the potential interplay between the circadian molecular clock and established molecular mechanisms mediating muscle anabolic responses with resistance training. This article begins with a current review of the mechanisms associated with the heterogeneity in muscle anabolism with resistance training before introducing the molecular pathways regulating circadian function in skeletal muscle. Recent work showing members of the core molecular clock system can regulate myogenic and translational signaling pathways is also discussed, forming the basis for a possible role of the circadian clock in the variable anabolic responses with resistance exercise.

Further evidence for Clock△19 mice as a model for bipolar disorder mania using cross-species tests of exploration and sensorimotor gating

PubMed Central

van Enkhuizen, Jordy; Minassian, Arpi; Young, Jared W.

2013-01-01

Bipolar disorder (BD) is a pervasive neuropsychiatric disorder characterized by episodes of mania and depression. The switch between mania and depression may reflect seasonal changes and certainly can be affected by alterations in sleep and circadian control. The circadian locomotor output cycles kaput (CLOCK) protein is a key component of the cellular circadian clock. Mutation of the Clock gene encoding this protein in Clock△19 mutant mice leads to behavioral abnormalities reminiscent of BD mania. To date, however, these mice have not been assessed in behavioral paradigms that have cross-species translational validity. In the present studies of Clock△19 and wildtype (WT) littermate mice, we quantified exploratory behavior and sensorimotor gating, which are abnormal in BD manic patients. We also examined the saccharin preference of these mice and their circadian control in different photoperiods. Clock△19 mice exhibited behavioral alterations that are consistent with BD manic patients tested in comparable tasks, including hyperactivity, increased specific exploration, and reduced sensorimotor gating. Moreover, compared to WT mice, Clock△19 mice exhibited a greater preference for sweetened solutions and greater sensitivity to altered photoperiod. In contrast with BD manic patients however, Clock△19 mice exhibited more circumscribed movements during exploration. Future studies will extend the characterization of these mice in measures with cross-species translational relevance to human testing. PMID:23623885

Clock genes and salt-sensitive hypertension: a new type of aldosterone-synthesizing enzyme controlled by the circadian clock and angiotensin II.

PubMed

Okamura, Hitoshi; Doi, Masao; Goto, Kaoru; Kojima, Rika

2016-10-01

With the current societal norm of shiftwork and long working hours, maintaining a stable daily life is becoming very difficult. An irregular lifestyle disrupts circadian rhythms, resulting in the malfunction of body physiology and ultimately leading to lifestyle-related diseases, including hypertension. By analyzing completely arrhythmic Cry1/Cry2 double-knockout (Cry-null) mice, we found salt-sensitive hypertension accompanied by hyperaldosteronism. On the basis of a DNA microarray analysis of the adrenal gland and subsequent biochemical analyses, we discovered that Hsd3b6/HSD3B1, a subtype of 3β-HSD, is markedly overexpressed in aldosterone-producing cells in the Cry-null adrenal cortex. In addition, we found that Hsd3b6/HSD3B1, which converts pregnenolone to progesterone, is a clock-controlled gene and might also be a key enzyme for the regulation of aldosterone biosynthesis, in addition to the previously established CYP11B2, which synthesizes aldosterone from deoxycorticosterone. Importantly, angiotensin II induces HSD3B1 via the transcription factor NGFIB in human adrenocortical H295R cells, similarly to CYP11B2. As HSD3B1 levels are abnormally high in the adrenal aldosterone-producing cells of idiopathic hyperaldosteronism (IHA), the temporal component of this system in the pathophysiology of IHA is a promising area for future research.

Entrainment of the Mammalian Cell Cycle by the Circadian Clock: Modeling Two Coupled Cellular Rhythms

PubMed Central

Gérard, Claude; Goldbeter, Albert

2012-01-01

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

The orphan receptor Rev-erbα gene is a target of the circadian clock pacemaker

PubMed Central

Triqueneaux, Gérard; Thenot, Sandrine; Kakizawa, Tomoko; Antoch, Marina P; Safi, Rachid; Takahashi, Joseph S; Delaunay, Franck; Laudet, Vincent

2013-01-01

Rev-erbα is a ubiquitously expressed orphan nuclear receptor which functions as a constitutive transcriptional repressor and is expressed in vertebrates according to a robust circadian rhythm. We report here that two Rev-erbα mRNA isoforms, namely Rev-erbα1 and Rev-erbα2, are generated through alternative promoter usage and that both show a circadian expression pattern in an in vitro system using serum-shocked fibroblasts. Both promoter regions P1 (Rev-erbα1) and P2 (Rev-erbα2) contain several E-box DNA sequences, which function as response elements for the core circadian-clock components: CLOCK and BMAL1. The CLOCK–BMAL1 heterodimer stimulates the activity of both P1 and P2 promoters in transient transfection assay by 3–6-fold. This activation was inhibited by the overexpression of CRY1, a component of the negative limb of the circadian transcriptional loop. Critical E-box elements were mapped within both promoters. This regulation is conserved in vertebrates since we found that the CLOCK–BMAL1 heterodimer also regulates the zebrafish Rev-erbα gene. In line with these data Rev-erbα circadian expression was strongly impaired in the livers of Clock mutant mice and in the pineal glands of zebrafish embryos treated with Clock and Bmal1 antisense oligonucleotides. Together these data demonstrate that CLOCK is a critical regulator of Rev-erbα circadian gene expression in evolutionarily distant vertebrates and suggest a role for Rev-erbα in the circadian clock output. PMID:15591021

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.

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

Diurnal Cycling Transcription Factors of Pineapple Revealed by Genome-Wide Annotation and Global Transcriptomic Analysis.

PubMed

Sharma, Anupma; Wai, Ching Man; Ming, Ray; Yu, Qingyi

2017-09-01

Circadian clock provides fitness advantage by coordinating internal metabolic and physiological processes to external cyclic environments. Core clock components exhibit daily rhythmic changes in gene expression, and the majority of them are transcription factors (TFs) and transcription coregulators (TCs). We annotated 1,398 TFs from 67 TF families and 80 TCs from 20 TC families in pineapple, and analyzed their tissue-specific and diurnal expression patterns. Approximately 42% of TFs and 45% of TCs displayed diel rhythmic expression, including 177 TF/TCs cycling only in the nonphotosynthetic leaf tissue, 247 cycling only in the photosynthetic leaf tissue, and 201 cycling in both. We identified 68 TF/TCs whose cycling expression was tightly coupled between the photosynthetic and nonphotosynthetic leaf tissues. These TF/TCs likely coordinate key biological processes in pineapple as we demonstrated that this group is enriched in homologous genes that form the core circadian clock in Arabidopsis and includes a STOP1 homolog. Two lines of evidence support the important role of the STOP1 homolog in regulating CAM photosynthesis in pineapple. First, STOP1 responds to acidic pH and regulates a malate channel in multiple plant species. Second, the cycling expression pattern of the pineapple STOP1 and the diurnal pattern of malate accumulation in pineapple leaf are correlated. We further examined duplicate-gene retention and loss in major known circadian genes and refined their evolutionary relationships between pineapple and other plants. Significant variations in duplicate-gene retention and loss were observed for most clock genes in both monocots and dicots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Ambient temperature response establishes ELF3 as a required component of the Arabidopsis core circadian clock

USDA-ARS?s Scientific Manuscript database

Circadian clocks synchronize internal processes with environmental cycles to ensure optimal timing of biological events on daily and seasonal timescales. External light and temperature cues set the core molecular oscillator to local conditions. In Arabidopsis, EARLY FLOWERING 3 (ELF3) is thought to ...

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

Impaired light detection of the circadian clock in a zebrafish melanoma model

PubMed Central

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

2015-01-01

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

Impaired light detection of the circadian clock in a zebrafish melanoma model.

PubMed

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

2015-01-01

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

A quantum network of clocks

NASA Astrophysics Data System (ADS)

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

2014-05-01

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

[Chrono-nutrition and chrono-exercise].

PubMed

Shibata, Shigenobu; Sasaki, Hiroyuki; Ikeda, Yuko

2013-12-01

The circadian rhythm controls many physiological functions, such as feeding, motor activity, endocrine secretion and autonomic nerve. Regular feeding pattern can entrain the peripheral circadian clock, whereas peripheral clock systems can control the absorption distribution, metabolism and excretion of nutrients, suggesting mutual interactions between circadian clocks and nutrition/food. The interactions were so-called by "chrono-nutrition", and bigger meals for breakfast were good for entrainment of peripheral clock and protection of obesity. Similar to chrono-nutrition the timing of exercise ("chrono-exercise") is important for both entrainment signals and energy expenditure. Evening exercise and/or feeding then exercise was good timing exercise for protection of obesity. Taken all, it is suggested that timing of feeding and exercise is now one of key factors for metabolic syndrome.

[Identification of proteins interacting with the circadian clock protein PER1 in tumors using bacterial two-hybrid system technique].

PubMed

Zhang, Yu; Yao, Youlin; Jiang, Siyuan; Lu, Yilu; Liu, Yunqiang; Tao, Dachang; Zhang, Sizhong; Ma, Yongxin

2015-04-01

To identify protein-protein interaction partners of PER1 (period circadian protein homolog 1), key component of the molecular oscillation system of the circadian rhythm in tumors using bacterial two-hybrid system technique. Human cervical carcinoma cell Hela library was adopted. Recombinant bait plasmid pBT-PER1 and pTRG cDNA plasmid library were cotransformed into the two-hybrid system reporter strain cultured in a special selective medium. Target clones were screened. After isolating the positive clones, the target clones were sequenced and analyzed. Fourteen protein coding genes were identified, 4 of which were found to contain whole coding regions of genes, which included optic atrophy 3 protein (OPA3) associated with mitochondrial dynamics and homo sapiens cutA divalent cation tolerance homolog of E. coli (CUTA) associated with copper metabolism. There were also cellular events related proteins and proteins which are involved in biochemical reaction and signal transduction-related proteins. Identification of potential interacting proteins with PER1 in tumors may provide us new insights into the functions of the circadian clock protein PER1 during tumorigenesis.

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.

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

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.

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.

SEU/SET Tolerant Phase-Locked Loops

NASA Technical Reports Server (NTRS)

Shuler, Robert L., Jr.

2010-01-01

The phase-locked loop (PLL) is an old and widely used circuit for frequency and phase demodulation, carrier and clock recovery, and frequency synthesis [1]. Its implementations range from discrete components to fully integrated circuits and even to firmware or software. Often the PLL is a highly critical component of a system, as for example when it is used to derive the on-chip clock, but as of this writing no definitive single-event upset (SET)/single-event transient (SET) tolerant PLL circuit has been described. This chapter hopes to rectify that situation, at least in regard to PLLs that are used to generate clocks. Older literature on fault-tolerant PLLs deals with detection of a hard failure, which is recovered by replacement, repair, or manual restart of discrete component systems. Several patents exist along these lines (6349391, 6272647, and 7089442). A newer approach is to harden the parts of a PLL system, to one degree or another, such as by using a voltage-based charge pump or a triple modular redundant (TMR) voted voltage-controlled oscillator (VCO). A more comprehensive approach is to harden by triplication and voting (TMR) all the digital pieces (primarily the divider) of a frequency synthesis PLL, but this still leaves room for errors in the VCO and the loop filter. Instead of hardening or voting pieces of a system, such as a frequency synthesis system (i.e., clock multiplier), we will show how the entire system can be voted. There are two main ways of doing this, each with advantages and drawbacks. We will show how each has advantages in certain areas, depending on the lock acquisition and tracking characteristics of the PLL. Because of this dependency on PLL characteristics, we will briefly revisit the theory of PLLs. But first we will describe the characteristics of voters and their correct application, as some literature does not follow the voting procedure that guarantees elimination of errors. Additionally, we will find that voting clocks is a bit trickier than voting data where an infallible clock is assumed. It is our job here to produce (or recover) that assumed infallible clock!

Obesity in mice with adipocyte-specific deletion of clock component Arntl

PubMed Central

Paschos, Georgios K; Ibrahim, Salam; Song, Wen-Liang; Kunieda, Takeshige; Grant, Gregory; Reyes, Teresa M; Bradfield, Christopher A; Vaughan, Cheryl H; Eiden, Michael; Masoodi, Mojgan; Griffin, Julian L; Wang, Fenfen; Lawson, John A; FitzGerald, Garret A

2013-01-01

Adipocytes store excess energy in the form of triglycerides and signal the levels of stored energy to the brain. Here we show that adipocyte-specific deletion of Arntl (also known as Bmal1), a gene encoding a core molecular clock component, results in obesity in mice with a shift in the diurnal rhythm of food intake, a result that is not seen when the gene is disrupted in hepatocytes or pancreatic islets. Changes in the expression of hypothalamic neuropeptides that regulate appetite are consistent with feedback from the adipocyte to the central nervous system to time feeding behavior. Ablation of the adipocyte clock is associated with a reduced number of polyunsaturated fatty acids in adipocyte triglycerides. This difference between mutant and wild-type mice is reflected in the circulating concentrations of polyunsaturated fatty acids and nonesterified polyunsaturated fatty acids in hypothalamic neurons that regulate food intake. Thus, this study reveals a role for the adipocyte clock in the temporal organization of energy regulation, highlights timing as a modulator of the adipocyte-hypothalamic axis and shows the impact of timing of food intake on body weight. PMID:23142819

2 GHz clock quantum key distribution over 260 km of standard telecom fiber.

PubMed

Wang, Shuang; Chen, Wei; Guo, Jun-Fu; Yin, Zhen-Qiang; Li, Hong-Wei; Zhou, Zheng; Guo, Guang-Can; Han, Zheng-Fu

2012-03-15

We report a demonstration of quantum key distribution (QKD) over a standard telecom fiber exceeding 50 dB in loss and 250 km in length. The differential phase shift QKD protocol was chosen and implemented with a 2 GHz system clock rate. By careful optimization of the 1 bit delayed Faraday-Michelson interferometer and the use of the superconducting single photon detector (SSPD), we achieved a quantum bit error rate below 2% when the fiber length was no more than 205 km, and of 3.45% for a 260 km fiber with 52.9 dB loss. We also improved the quantum efficiency of SSPD to obtain a high key rate for 50 km length.

Transcription factors involved in retinogenesis are co-opted by the circadian clock following photoreceptor differentiation.

PubMed

Laranjeiro, Ricardo; Whitmore, David

2014-07-01

The circadian clock is known to regulate a wide range of physiological and cellular processes, yet remarkably little is known about its role during embryo development. Zebrafish offer a unique opportunity to explore this issue, not only because a great deal is known about key developmental events in this species, but also because the clock starts on the very first day of development. In this study, we identified numerous rhythmic genes in zebrafish larvae, including the key transcriptional regulators neurod and cdx1b, which are involved in neuronal and intestinal differentiation, respectively. Rhythmic expression of neurod and several additional transcription factors was only observed in the developing retina. Surprisingly, these rhythms in expression commenced at a stage of development after these transcription factors are known to have played their essential role in photoreceptor differentiation. Furthermore, this circadian regulation was maintained in adult retina. Thus, once mature photoreceptors are formed, multiple retinal transcription factors fall under circadian clock control, at which point they appear to play a new and important role in regulating rhythmic elements in the phototransduction pathway. © 2014. Published by The Company of Biologists Ltd.

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.

A gallium-arsenide digital phase shifter for clock and control signal distribution in high-speed digital systems

NASA Technical Reports Server (NTRS)

Fouts, Douglas J.

1992-01-01

The design, implementation, testing, and applications of a gallium-arsenide digital phase shifter and fan-out buffer are described. The integrated circuit provides a method for adjusting the phase of high-speed clock and control signals in digital systems, without the need for pruning cables, multiplexing between cables of different lengths, delay lines, or similar techniques. The phase of signals distributed with the described chip can be dynamically adjusted in eight different steps of approximately 60 ps per step. The IC also serves as a fan-out buffer and provides 12 in-phase outputs. The chip is useful for distributing high-speed clock and control signals in synchronous digital systems, especially if components are distributed over a large physical area or if there is a large number of components.

Interrelationship between 3,5,3´-triiodothyronine and the circadian clock in the rodent heart.

PubMed

Peliciari-Garcia, Rodrigo Antonio; Prévide, Rafael Maso; Nunes, Maria Tereza; Young, Martin Elliot

2016-01-01

Triiodothyronine (T3) is an important modulator of cardiac metabolism and function, often through modulation of gene expression. The cardiomyocyte circadian clock is a transcriptionally based molecular mechanism capable of regulating cardiac processes, in part by modulating responsiveness of the heart to extra-cardiac stimuli/stresses in a time-of-day (TOD)-dependent manner. Although TOD-dependent oscillations in circulating levels of T3 (and its intermediates) have been established, oscillations in T3 sensitivity in the heart is unknown. To investigate the latter possibility, euthyroid male Wistar rats were treated with vehicle or T3 at distinct times of the day, after which induction of known T3 target genes were assessed in the heart (4-h later). The expression of mRNA was assessed by real-time quantitative polymerase chain reaction (qPCR). Here, we report greater T3 induction of transcript levels at the end of the dark phase. Surprisingly, use of cardiomyocyte-specific clock mutant (CCM) mice revealed that TOD-dependent oscillations in T3 sensitivity were independent of this cell autonomous mechanism. Investigation of genes encoding for proteins that affect T3 sensitivity revealed that Dio1, Dio2 and Thrb1 exhibited TOD-dependent variations in the heart, while Thra1 and Thra2 did not. Of these, Dio1 and Thrb1 were increased in the heart at the end of the dark phase. Interestingly, we observed that T3 acutely altered the expression of core clock components (e.g. Bmal1) in the rat heart. To investigate this further, rats were injected with a single dose of T3, after which expression of clock genes was interrogated at 3-h intervals over the subsequent 24-h period. These studies revealed robust effects of T3 on oscillations of both core clock components and clock-controlled genes. In summary, the current study exposed TOD-dependent sensitivity to T3 in the heart and its effects in the circadian clock genes expression.

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.

Illuminating the circadian clock in monarch butterfly migration.

PubMed

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

2003-05-23

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

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.

A Methodology for the Design and Verification of Globally Asynchronous/Locally Synchronous Architectures

NASA Technical Reports Server (NTRS)

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

2005-01-01

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

Oscillator Noise Analysis

NASA Astrophysics Data System (ADS)

Demir, Alper

2005-08-01

Oscillators are key components of many kinds of systems, particularly electronic and opto-electronic systems. Undesired perturbations, i.e. noise, that exist in practical systems adversely affect the spectral and timing properties of the signals generated by oscillators resulting in phase noise and timing jitter. These are key performance limiting factors, being major contributors to bit-error-rate (BER) of RF and optical communication systems, and creating synchronization problems in clocked and sampled-data electronic systems. In noise analysis for oscillators, the key is figuring out how the various disturbances and noise sources in the oscillator end up as phase fluctuations. In doing so, one first computes transfer functions from the noise sources to the oscillator phase, or the sensitivity of the oscillator phase to these noise sources. In this paper, we first provide a discussion explaining the origins and the proper definition of this transfer or sensitivity function, followed by a critical review of the various numerical techniques for its computation that have been proposed by various authors over the past fifteen years.

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.

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

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

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.

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.

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

Prediction of the protein components of a putative Calanus finmarchicus (Crustacea, Copepoda) circadian signaling system using a de novo assembled transcriptome

PubMed Central

Christie, Andrew E.; Fontanilla, Tiana M.; Nesbit, Katherine T.; Lenz, Petra H.

2013-01-01

Diel vertical migration and seasonal diapause are critical life history events for the copepod Calanus finmarchicus. While much is known about these behaviors phenomenologically, little is known about their molecular underpinnings. Recent studies in insects suggest that some circadian genes/proteins also contribute to the establishment of seasonal diapause. Thus, it is possible that in Calanus these distinct timing regimes share some genetic components. To begin to address this possibility, we used the well-established Drosophila melanogaster circadian system as a reference for mining clock transcripts from a 200,000+ sequence Calanus transcriptome; the proteins encoded by the identified transcripts were also deduced and characterized. Sequences encoding homologs of the Drosophila core clock proteins CLOCK, CYCLE, PERIOD and TIMELESS were identified, as was one encoding CRYPTOCHROME 2, a core clock protein in ancestral insect systems, but absent in Drosophila. Calanus transcripts encoding proteins known to modulate the Drosophila core clock were also identified and characterized, e.g. CLOCKWORK ORANGE, DOUBLETIME, SHAGGY and VRILLE. Alignment and structural analyses of the deduced Calanus proteins with their Drosophila counterparts revealed extensive sequence conservation, particularly in functional domains. Interestingly, reverse BLAST analyses of these sequences against all arthropod proteins typically revealed non-Drosophila isoforms to be most similar to the Calanus queries. This, in combination with the presence of both CRYPTOCHROME 1 (a clock input pathway protein) and CRYPTOCHROME 2 in Calanus, suggests that the organization of the copepod circadian system is an ancestral one, more similar to that of insects like Danaus plexippus than to that of Drosophila. PMID:23727418

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.

Timescales Of The Influence Of IMF Clock Angle In Controlling The Characteristics Of Magnetospheric Dynamics

NASA Astrophysics Data System (ADS)

Grocott, A.; Milan, S. E.

2013-12-01

We exploit a database of high-latitude ionospheric electric potential patterns, derived from radar observations of plasma convection in the northern hemisphere from the years 2000 - 2006, to investigate the timescales of interplanetary magnetic field (IMF) penetration into the magnetosphere. We parameterise the convection observations by IMF clock angle, θ (the angle between geocentric solar magnetic (GSM) north and the projection of the IMF vector onto the GSM Y-Z plane), and by an IMF timescale, τB (the length of time that a similar clock angle has been maintained prior to the convection observations being made). We find that the nature of the ionospheric convection changes with IMF clock angle, as expected from previous time-averaged studies, and that for τB ~ 30 mins the convection patterns closely resemble their time-averaged counterparts. However, we also find that for certain IMF clock angles, in particular those with a northward BZ component and significant BY (dusk-dawn) component, the patterns evolve with increasing τB to less resemble their time-averaged counterparts, showing a marked enhancement in dusk-dawn asymmetry as τB approaches 10 hours. We discuss these findings in terms of the effects of the persistent penetration of a quasi-steady IMF into the magnetosphere, and its implications for understanding different modes of magnetospheric dynamics.

PHARAO space atomic clock: new developments on the laser source

NASA Astrophysics Data System (ADS)

Saccoccio, Muriel; Loesel, Jacques; Coatantiec, Claude; Simon, Eric; Laurent, Philippe; Lemonde, Pierre; Maksimovic, I.; Abgrall, M.

2017-11-01

The PHARAO project purpose is to open the way for a new atomic clock generation in space, where laser cooling techniques and microgravity allow high frequency stability and accuracy. The French space agency, CNES is funding and managing the clock construction. The French SYRTE and LKB laboratories are scientific and technical advisers for the clock requirements and the follow-up of subsystem development in industrial companies. EADS SODERN is developing two main subsystems of the PHARAO clock: the Laser Source and the Cesium Tube where atoms are cooled, launched, selected and detected by laser beams. The Laser Source includes an optical bench and electronic devices to generate the laser beams required. This paper describes PHARAO and the role laser beams play in its principle of operation. Then we present the Laser Source design, the technologies involved, and the status of development. Lastly, we focus of a key equipment to reach the performances expected, which is the Extended Cavity Laser Diode.

25 MHz clock continuous-variable quantum key distribution system over 50 km fiber channel

PubMed Central

Wang, Chao; Huang, Duan; Huang, Peng; Lin, Dakai; Peng, Jinye; Zeng, Guihua

2015-01-01

In this paper, a practical continuous-variable quantum key distribution system is developed and it runs in the real-world conditions with 25 MHz clock rate. To reach high-rate, we have employed a homodyne detector with maximal bandwidth to 300 MHz and an optimal high-efficiency error reconciliation algorithm with processing speed up to 25 Mbps. To optimize the stability of the system, several key techniques are developed, which include a novel phase compensation algorithm, a polarization feedback algorithm, and related stability method on the modulators. Practically, our system is tested for more than 12 hours with a final secret key rate of 52 kbps over 50 km transmission distance, which is the highest rate so far in such distance. Our system may pave the road for practical broadband secure quantum communication with continuous variables in the commercial conditions. PMID:26419413

25 MHz clock continuous-variable quantum key distribution system over 50 km fiber channel.

PubMed

Wang, Chao; Huang, Duan; Huang, Peng; Lin, Dakai; Peng, Jinye; Zeng, Guihua

2015-09-30

In this paper, a practical continuous-variable quantum key distribution system is developed and it runs in the real-world conditions with 25 MHz clock rate. To reach high-rate, we have employed a homodyne detector with maximal bandwidth to 300 MHz and an optimal high-efficiency error reconciliation algorithm with processing speed up to 25 Mbps. To optimize the stability of the system, several key techniques are developed, which include a novel phase compensation algorithm, a polarization feedback algorithm, and related stability method on the modulators. Practically, our system is tested for more than 12 hours with a final secret key rate of 52 kbps over 50 km transmission distance, which is the highest rate so far in such distance. Our system may pave the road for practical broadband secure quantum communication with continuous variables in the commercial conditions.

Time-of-Day Effects on Metabolic and Clock-Related Adjustments to Cold.

PubMed

Machado, Frederico Sander Mansur; Zhang, Zhi; Su, Yan; de Goede, Paul; Jansen, Remi; Foppen, Ewout; Coimbra, Cândido Celso; Kalsbeek, Andries

2018-01-01

Daily cyclic changes in environmental conditions are key signals for anticipatory and adaptive adjustments of most living species, including mammals. Lower ambient temperature stimulates the thermogenic activity of brown adipose tissue (BAT) and skeletal muscle. Given that the molecular components of the endogenous biological clock interact with thermal and metabolic mechanisms directly involved in the defense of body temperature, the present study evaluated the differential homeostatic responses to a cold stimulus at distinct time-windows of the light/dark-cycle. Male Wistar rats were subjected to a single episode of 3 h cold ambient temperature (4°C) at one of 6 time-points starting at Zeitgeber Times 3, 7, 11, 15, 19, and 23. Metabolic rate, core body temperature, locomotor activity (LA), feeding, and drinking behaviors were recorded during control and cold conditions at each time-point. Immediately after the stimulus, rats were euthanized and both the soleus and BAT were collected for real-time PCR. During the light phase (i.e., inactive phase), cold exposure resulted in a slight hyperthermia ( p  < 0.001). Light phase cold exposure also increased metabolic rate and LA ( p  < 0.001). In addition, the prevalence of fat oxidative metabolism was attenuated during the inactive phase ( p  < 0.001). These metabolic changes were accompanied by time-of-day and tissue-specific changes in core clock gene expression, such as DBP ( p  < 0.0001) and REV-ERBα ( p  < 0.01) in the BAT and CLOCK ( p  < 0.05), PER2 ( p  < 0.05), CRY1 ( p  < 0.05), CRY2 ( p  < 0.01), and REV-ERBα ( p  < 0.05) in the soleus skeletal muscle. Moreover, genes involved in substrate oxidation and thermogenesis were affected in a time-of-day and tissue-specific manner by cold exposure. The time-of-day modulation of substrate mobilization and oxidation during cold exposure provides a clear example of the circadian modulation of physiological and metabolic responses. Interestingly, after cold exposure, time-of-day mostly affected circadian clock gene expression in the soleus muscle, despite comparable changes in LA over the light-dark-cycle. The current findings add further evidence for tissue-specific actions of the internal clock in different peripheral organs such as skeletal muscle and BAT.

A functional genomics approach reveals CHE as a component of the Arabidopsis circadian clock.

PubMed

Pruneda-Paz, Jose L; Breton, Ghislain; Para, Alessia; Kay, Steve A

2009-03-13

Transcriptional feedback loops constitute the molecular circuitry of the plant circadian clock. In Arabidopsis, a core loop is established between CCA1 and TOC1. Although CCA1 directly represses TOC1, the TOC1 protein has no DNA binding domains, which suggests that it cannot directly regulate CCA1. We established a functional genomic strategy that led to the identification of CHE, a TCP transcription factor that binds specifically to the CCA1 promoter. CHE is a clock component partially redundant with LHY in the repression of CCA1. The expression of CHE is regulated by CCA1, thus adding a CCA1/CHE feedback loop to the Arabidopsis circadian network. Because CHE and TOC1 interact, and CHE binds to the CCA1 promoter, a molecular linkage between TOC1 and CCA1 gene regulation is established.

Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior.

PubMed

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

2016-11-01

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

Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior

PubMed Central

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

2016-01-01

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

Chip-based quantum key distribution

NASA Astrophysics Data System (ADS)

Sibson, P.; Erven, C.; Godfrey, M.; Miki, S.; Yamashita, T.; Fujiwara, M.; Sasaki, M.; Terai, H.; Tanner, M. G.; Natarajan, C. M.; Hadfield, R. H.; O'Brien, J. L.; Thompson, M. G.

2017-02-01

Improvement in secure transmission of information is an urgent need for governments, corporations and individuals. Quantum key distribution (QKD) promises security based on the laws of physics and has rapidly grown from proof-of-concept to robust demonstrations and deployment of commercial systems. Despite these advances, QKD has not been widely adopted, and large-scale deployment will likely require chip-based devices for improved performance, miniaturization and enhanced functionality. Here we report low error rate, GHz clocked QKD operation of an indium phosphide transmitter chip and a silicon oxynitride receiver chip--monolithically integrated devices using components and manufacturing processes from the telecommunications industry. We use the reconfigurability of these devices to demonstrate three prominent QKD protocols--BB84, Coherent One Way and Differential Phase Shift--with performance comparable to state-of-the-art. These devices, when combined with integrated single photon detectors, pave the way for successfully integrating QKD into future telecommunications networks.

Chip-based quantum key distribution

PubMed Central

Sibson, P.; Erven, C.; Godfrey, M.; Miki, S.; Yamashita, T.; Fujiwara, M.; Sasaki, M.; Terai, H.; Tanner, M. G.; Natarajan, C. M.; Hadfield, R. H.; O'Brien, J. L.; Thompson, M. G.

2017-01-01

Improvement in secure transmission of information is an urgent need for governments, corporations and individuals. Quantum key distribution (QKD) promises security based on the laws of physics and has rapidly grown from proof-of-concept to robust demonstrations and deployment of commercial systems. Despite these advances, QKD has not been widely adopted, and large-scale deployment will likely require chip-based devices for improved performance, miniaturization and enhanced functionality. Here we report low error rate, GHz clocked QKD operation of an indium phosphide transmitter chip and a silicon oxynitride receiver chip—monolithically integrated devices using components and manufacturing processes from the telecommunications industry. We use the reconfigurability of these devices to demonstrate three prominent QKD protocols—BB84, Coherent One Way and Differential Phase Shift—with performance comparable to state-of-the-art. These devices, when combined with integrated single photon detectors, pave the way for successfully integrating QKD into future telecommunications networks. PMID:28181489

A High-Speed Design of Montgomery Multiplier

NASA Astrophysics Data System (ADS)

Fan, Yibo; Ikenaga, Takeshi; Goto, Satoshi

With the increase of key length used in public cryptographic algorithms such as RSA and ECC, the speed of Montgomery multiplication becomes a bottleneck. This paper proposes a high speed design of Montgomery multiplier. Firstly, a modified scalable high-radix Montgomery algorithm is proposed to reduce critical path. Secondly, a high-radix clock-saving dataflow is proposed to support high-radix operation and one clock cycle delay in dataflow. Finally, a hardware-reused architecture is proposed to reduce the hardware cost and a parallel radix-16 design of data path is proposed to accelerate the speed. By using HHNEC 0.25μm standard cell library, the implementation results show that the total cost of Montgomery multiplier is 130 KGates, the clock frequency is 180MHz and the throughput of 1024-bit RSA encryption is 352kbps. This design is suitable to be used in high speed RSA or ECC encryption/decryption. As a scalable design, it supports any key-length encryption/decryption up to the size of on-chip memory.

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.

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

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

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

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

Around-the-clock nursing care for the elderly in Japan.

PubMed

Murashima, S; Zerwekh, J V; Yamada, M; Tagami, Y

1998-01-01

To describe the first phase of creating a Japanese model of community-based long-term care, called around-the-clock care (ACC), by operationally defining the components of ACC, identifying those eligible for the program, clarifying methods of planning and organization, and exploring outcomes. Exploratory evaluation for the population of frail elderly Japanese citizens living at home. A convenience sample of 44 patients receiving care from four visiting-nurse-service stations during 3 months in 1994 was used. Needs assessments; record reviews of patient encounters; evaluations by patients, families, and visiting nurses; and reviews of administrative data. Nurses perceived that ACC stabilized medical status, reduced the emotional and physical burden of treatment, and improved hygiene. It also reduced family caregiving burdens and the stress of family caregivers' employment responsibilities. The highest rating of ACC by patient and families was for those with the most complex physical needs. Skilled nursing at home permitted early identification and treatment of problems before they became crises or required hospitalization. Early findings suggest 24-hour nurse-home helper teamwork may be an effective system of community-based long-term care and should be considered a key element of future Japanese health policy.

Interrelationship between 3,5,3′-triiodothyronine and the circadian clock in the rodent heart

PubMed Central

Peliciari-Garcia, Rodrigo Antonio; Prévide, Rafael Maso; Nunes, Maria Tereza; Young, Martin Elliot

2017-01-01

Triiodothyronine (T3) is an important modulator of cardiac metabolism and function, often through modulation of gene expression. The cardiomyocyte circadian clock is a transcriptionally-based molecular mechanism capable of regulating cardiac processes, in part by modulating responsiveness of the heart to extra-cardiac stimuli/stresses in a time-of-day- (TOD) dependent manner. Although TOD-dependent oscillations in circulating levels of T3 (and its intermediates) have been established, whether oscillations in T3 sensitivity in the heart occur is unknown. To investigate the latter possibility, euthyroid male Wistar rats were treated with vehicle or T3 at distinct times of the day, after which induction of known T3 target genes were assessed in the heart (4-h later). The expression of mRNA was assessed by Real-Time qPCR. Here, we report greater T3 induction of transcript levels at the end of the dark phase. Surprisingly, use of cardiomyocyte-specific clock mutant (CCM) mice revealed that TOD-dependent oscillations in T3 sensitivity were independent of this cell autonomous mechanism. Investigation of genes encoding for proteins that affect T3 sensitivity revealed that Dio1, Dio2, and Thrb1 exhibited TOD-dependent variations in the heart, while Thra1 and Thra2 did not. Of these, Dio1 and Thrb1 were increased in the heart at the end of the dark phase. Interestingly, we observed that T3 acutely altered the expression of core clock components (e.g., Bmal1) in the rat heart. To investigate this further, rats were injected with a single dose of T3, after which expression of clock genes were interrogated at 3-h intervals over the subsequent 24h-period. These studies revealed robust effects of T3 on oscillations of both core clock components and clock-controlled genes. In summary, the current study exposed time-of-day-dependent rhythms in cardiac T3 sensitivity, and that T3 alters the circadian clock in the heart. PMID:27661292

Proposed Role for KaiC-Like ATPases as Major Signal Transduction Hubs in Archaea

PubMed Central

2017-01-01

ABSTRACT All organisms must adapt to ever-changing environmental conditions and accordingly have evolved diverse signal transduction systems. In bacteria, the most abundant networks are built around the two-component signal transduction systems that include histidine kinases and receiver domains. In contrast, eukaryotic signal transduction is dominated by serine/threonine/tyrosine protein kinases. Both of these systems are also found in archaea, but they are not as common and diversified as their bacterial and eukaryotic counterparts, suggesting the possibility that archaea have evolved other, still uncharacterized signal transduction networks. Here we propose a role for KaiC family ATPases, known to be key components of the circadian clock in cyanobacteria, in archaeal signal transduction. The KaiC family is notably expanded in most archaeal genomes, and although most of these ATPases remain poorly characterized, members of the KaiC family have been shown to control archaellum assembly and have been found to be a stable component of the gas vesicle system in Halobacteria. Computational analyses described here suggest that KaiC-like ATPases and their homologues with inactivated ATPase domains are involved in many other archaeal signal transduction pathways and comprise major hubs of complex regulatory networks. We predict numerous input and output domains that are linked to KaiC-like proteins, including putative homologues of eukaryotic DEATH domains that could function as adapters in archaeal signaling networks. We further address the relationships of the archaeal family of KaiC homologues to the bona fide KaiC of cyanobacteria and implications for the existence of a KaiC-based circadian clock apparatus in archaea. PMID:29208747

The circadian clock of Neurospora crassa.

PubMed

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

2012-01-01

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

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

PubMed Central

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

2006-01-01

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

Discrete Functions of Nuclear Receptor Rev-erbα Couple Metabolism to the Clock

PubMed Central

Zhang, Yuxiang; Fang, Bin; Emmett, Matthew J.; Damle, Manashree; Sun, Zheng; Feng, Dan; Armour, Sean M.; Remsberg, Jarrett R.; Jager, Jennifer; Soccio, Raymond E.; Steger, David J.; Lazar, Mitchell A.

2015-01-01

SUMMARY Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes. Here we show that Rev-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbα and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erbα utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. PMID:26044300

GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.

PubMed

Zhang, Yuxiang; Fang, Bin; Emmett, Matthew J; Damle, Manashree; Sun, Zheng; Feng, Dan; Armour, Sean M; Remsberg, Jarrett R; Jager, Jennifer; Soccio, Raymond E; Steger, David J; Lazar, Mitchell A

2015-06-26

Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both as a core repressive component of the cell-autonomous clock and as a regulator of metabolic genes. Here, we show that Rev-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα regulates metabolic genes primarily by recruiting the HDAC3 co-repressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbα and ROR TFs provides a universal mechanism for self-sustained control of the molecular clock across all tissues, whereas Rev-erbα uses lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. Copyright © 2015, American Association for the Advancement of Science.

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.

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

Photoperiodic Modulation of Circadian Clock and Reproductive Axis Gene Expression in the Pre-Pubertal European Sea Bass Brain

PubMed Central

Martins, Rute S. T.; Gomez, Ana; Zanuy, Silvia; Carrillo, Manuel; Canário, Adelino V. M.

2015-01-01

The acquisition of reproductive competence requires the activation of the brain-pituitary-gonad (BPG) axis, which in most vertebrates, including fishes, is initiated by changes in photoperiod. In the European sea bass long-term exposure to continuous light (LL) alters the rhythm of reproductive hormones, delays spermatogenesis and reduces the incidence of precocious males. In contrast, an early shift from long to short photoperiod (AP) accelerates spermatogenesis. However, how photoperiod affects key genes in the brain to trigger the onset of puberty is still largely unknown. Here, we investigated if the integration of the light stimulus by clock proteins is sufficient to activate key genes that trigger the BPG axis in the European sea bass. We found that the clock genes clock, npas2, bmal1 and the BPG genes gnrh, kiss and kissr share conserved transcription factor frameworks in their promoters, suggesting co-regulation. Other gene promoters of the BGP axis were also predicted to be co-regulated by the same frameworks. Co-regulation was confirmed through gene expression analysis of brains from males exposed to LL or AP photoperiod compared to natural conditions: LL fish had suppressed gnrh1, kiss2, galr1b and esr1, while AP fish had stimulated npas2, gnrh1, gnrh2, kiss2, kiss1rb and galr1b compared to NP. It is concluded that fish exposed to different photoperiods present significant expression differences in some clock and reproductive axis related genes well before the first detectable endocrine and morphological responses of the BPG axis. PMID:26641263

Natural changes in light interact with circadian regulation at promoters to control gene expression in cyanobacteria

PubMed Central

2017-01-01

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

New forms of spin-orbit coupling in a strontium optical lattice clock

NASA Astrophysics Data System (ADS)

Perlin, Michael; Safavi-Naini, Arghavan; Ozeri, Roee; Rey, Ana Maria

2017-04-01

Ultracold atomic systems allow for the simulation of a variety of condensed matter phenomena, including spin-orbit coupling (SOC), a key ingredient behind recently discovered topological insulators and a path for the realization of topological superfluids. While many experimental efforts have used alkali atoms to engineer SOC via Raman transitions, undesirable heating mechanisms have limited the observation of many-body phenomena manifest at long timescales. Alkaline earth atoms (AEA) have been recently shown to be a potentially better platform for the implementation of SOC due to their reduced sensitivity to spontaneous emission. While previous work has used electronic clock states as a pseudo-spin degree of freedom, we consider the effects of clock side-band transitions. We discuss the richer SOC dynamics which emerges as a result of this extension, and present methods to probe these dynamics in current AEA optical lattice clocks. AFOSR, NSF-PFC and DARPA.

Strategies for synchronisation in an evolving telecommunications network

NASA Astrophysics Data System (ADS)

Avery, Rob

1992-06-01

The achievement of precise synchronization in the telecommunications environment is addressed. Transmitting the timing from node to node has been the inherent problem for all digital networks. Traditional network equipment used to transfer synchronization, such as digital switching ststems, adds impairments to the once traceable signal. As the synchronization signals are passed from node to node, they lose stability by passing through intervening clocks. Timing would be an integrated part of all new network and service deployments. New transmission methods, such as the Synchronous Digital Hierarchy (SDH), survivable network topologies and the issues that arise from them, necessitate a review of current network synchronization strategies. Challenges that face the network are itemized. A demonstration of why localized Primary Reference Clocks (PRC) in key nodes and the Synchronization Supply Unit (SSU) clock architecture of transit and local node clocks is a technically and economically viable solution to the issues facing network planners today is given.

Reproducibility in a multiprocessor system

DOEpatents

Bellofatto, Ralph A; Chen, Dong; Coteus, Paul W; Eisley, Noel A; Gara, Alan; Gooding, Thomas M; Haring, Rudolf A; Heidelberger, Philip; Kopcsay, Gerard V; Liebsch, Thomas A; Ohmacht, Martin; Reed, Don D; Senger, Robert M; Steinmacher-Burow, Burkhard; Sugawara, Yutaka

2013-11-26

Fixing a problem is usually greatly aided if the problem is reproducible. To ensure reproducibility of a multiprocessor system, the following aspects are proposed; a deterministic system start state, a single system clock, phase alignment of clocks in the system, system-wide synchronization events, reproducible execution of system components, deterministic chip interfaces, zero-impact communication with the system, precise stop of the system and a scan of the system state.

Frequency standards based on ultracold atoms in tests of general relativity, navigation and gravimetry

NASA Astrophysics Data System (ADS)

Khabarova, K. Yu.; Kudeyarov, K. S.; Kolachevsky, N. N.

2017-06-01

Research and development in the field of optical clocks based on ultracold atoms and ions have enabled the relative uncertainty in frequency to be reduced down to a few parts in 1018. The use of novel, precise frequency comparison methods opens up new possibilities for basic research (sensitive tests of general relativity, a search for a drift of fundamental constants and a search for ‘dark matter’) as well as for state-of-the-art navigation and gravimetry. We discuss the key methods that are used in creating precision clocks (including transportable clocks) based on ultracold atoms and ions and the feasibility of using them in resolving current relativistic gravimetry issues.

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.

Light quality modulates metabolic synchronization over the diel phases of crassulacean acid metabolism

PubMed Central

Ceusters, Johan; Borland, Anne M.; Taybi, Tahar; Frans, Mario; Godts, Christof; De Proft, Maurice P.

2014-01-01

Temporal compartmentation of carboxylation processes is a defining feature of crassulacean acid metabolism and involves circadian control of key metabolic and transport steps that regulate the supply and demand for carbon over a 24h cycle. Recent insights on the molecular workings of the circadian clock and its connection with environmental inputs raise new questions on the importance of light quality and, by analogy, certain photoreceptors for synchronizing the metabolic components of CAM. The present work tested the hypothesis that optimal coupling of stomatal conductance, net CO2 uptake, and the reciprocal turnover of carbohydrates and organic acids over the diel CAM cycle requires both blue and red light input signals. Contrasting monochromatic wavelengths of blue, green, and red light (i.e. 475, 530, 630nm) with low fluence rates (10 μmol m–2 s–1) were administered for 16 hours each diel cycle for a total treatment time of 48 hours to the obligate CAM bromeliad, Aechmea ‘Maya’. Of the light treatments imposed, low-fluence blue light was a key determinant in regulating stomatal responses, organic acid mobilization from the vacuole, and daytime decarboxylation. However, the reciprocal relationship between starch and organic acid turnover that is typical for CAM was uncoupled under low-fluence blue light. Under low-fluence red or green light, the diel turnover of storage carbohydrates was orchestrated in line with the requirements of CAM, but a consistent delay in acid consumption at dawn compared with plants under white or low-fluence blue light was noted. Consistent with the acknowledged influences of both red and blue light as input signals for the circadian clock, the data stress the importance of both red and blue-light signalling pathways for synchronizing the metabolic and physiological components of CAM over the day/night cycle. PMID:24803500

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.

The Importance of Stochastic Effects for Explaining Entrainment in the Zebrafish Circadian Clock.

PubMed

Heussen, Raphaela; Whitmore, David

2015-01-01

The circadian clock plays a pivotal role in modulating physiological processes and has been implicated, either directly or indirectly, in a range of pathological states including cancer. Here we investigate how the circadian clock is entrained by external cues such as light. Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal. Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

5-Gb/s 0.18-μm CMOS 2:1 multiplexer with integrated clock extraction

NASA Astrophysics Data System (ADS)

Changchun, Zhang; Zhigong, Wang; Si, Shi; Peng, Miao; Ling, Tian

2009-09-01

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 μm CMOS technology. The chip area is 670 × 780 μm2. At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

Quantum Clock Synchronization with a Single Qudit

NASA Astrophysics Data System (ADS)

Tavakoli, Armin; Cabello, Adán; Żukowski, Marek; Bourennane, Mohamed

2015-01-01

Clock synchronization for nonfaulty processes in multiprocess networks is indispensable for a variety of technologies. A reliable system must be able to resynchronize the nonfaulty processes upon some components failing causing the distribution of incorrect or conflicting information in the network. The task of synchronizing such networks is related to Byzantine agreement (BA), which can classically be solved using recursive algorithms if and only if less than one-third of the processes are faulty. Here we introduce a nonrecursive quantum algorithm, based on a quantum solution of the detectable BA, which achieves clock synchronization in the presence of arbitrary many faulty processes by using only a single quantum system.

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

Detecting an atomic clock frequency anomaly using an adaptive Kalman filter algorithm

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

Shift Work in Nurses: Contribution of Phenotypes and Genotypes to Adaptation

PubMed Central

Gamble, Karen L.; Motsinger-Reif, Alison A.; Hida, Akiko; Borsetti, Hugo M.; Servick, Stein V.; Ciarleglio, Christopher M.; Robbins, Sam; Hicks, Jennifer; Carver, Krista; Hamilton, Nalo; Wells, Nancy; Summar, Marshall L.; McMahon, Douglas G.; Johnson, Carl Hirschie

2011-01-01

Background Daily cycles of sleep/wake, hormones, and physiological processes are often misaligned with behavioral patterns during shift work, leading to an increased risk of developing cardiovascular/metabolic/gastrointestinal disorders, some types of cancer, and mental disorders including depression and anxiety. It is unclear how sleep timing, chronotype, and circadian clock gene variation contribute to adaptation to shift work. Methods Newly defined sleep strategies, chronotype, and genotype for polymorphisms in circadian clock genes were assessed in 388 hospital day- and night-shift nurses. Results Night-shift nurses who used sleep deprivation as a means to switch to and from diurnal sleep on work days (∼25%) were the most poorly adapted to their work schedule. Chronotype also influenced efficacy of adaptation. In addition, polymorphisms in CLOCK, NPAS2, PER2, and PER3 were significantly associated with outcomes such as alcohol/caffeine consumption and sleepiness, as well as sleep phase, inertia and duration in both single- and multi-locus models. Many of these results were specific to shift type suggesting an interaction between genotype and environment (in this case, shift work). Conclusions Sleep strategy, chronotype, and genotype contribute to the adaptation of the circadian system to an environment that switches frequently and/or irregularly between different schedules of the light-dark cycle and social/workplace time. This study of shift work nurses illustrates how an environmental “stress” to the temporal organization of physiology and metabolism can have behavioral and health-related consequences. Because nurses are a key component of health care, these findings could have important implications for health-care policy. PMID:21533241

Body weight, metabolism and clock genes

PubMed Central

2010-01-01

Biological rhythms are present in the lives of almost all organisms ranging from plants to more evolved creatures. These oscillations allow the anticipation of many physiological and behavioral mechanisms thus enabling coordination of rhythms in a timely manner, adaption to environmental changes and more efficient organization of the cellular processes responsible for survival of both the individual and the species. Many components of energy homeostasis exhibit circadian rhythms, which are regulated by central (suprachiasmatic nucleus) and peripheral (located in other tissues) circadian clocks. Adipocyte plays an important role in the regulation of energy homeostasis, the signaling of satiety and cellular differentiation and proliferation. Also, the adipocyte circadian clock is probably involved in the control of many of these functions. Thus, circadian clocks are implicated in the control of energy balance, feeding behavior and consequently in the regulation of body weight. In this regard, alterations in clock genes and rhythms can interfere with the complex mechanism of metabolic and hormonal anticipation, contributing to multifactorial diseases such as obesity and diabetes. The aim of this review was to define circadian clocks by describing their functioning and role in the whole body and in adipocyte metabolism, as well as their influence on body weight control and the development of obesity. PMID:20712885

Metabolism as an Integral Cog in the Mammalian Circadian Clockwork

PubMed Central

Gamble, Karen L.; Young, Martin E.

2013-01-01

Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g., DNA synthesis) to the whole organism (e.g., behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell autonomous circadian clocks and metabolism, and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases. PMID:23594144

Progress Toward a Compact, Highly Stable Ion Clock

NASA Technical Reports Server (NTRS)

Prestage, John; Chung, Sang

2009-01-01

There was an update on the subject of two previous NASA Tech Briefs articles: Compact, Highly Stable Ion Clock (NPO-43075), Vol. 32, No. 5 (May 2008), page 63; and Neon as a Buffer Gas for a Mercury-Ion Clock (NPO-42919), Vol. 32, No. 7 (July 2008), page 62. To recapitulate: A developmental miniature mercury-ion clock has stability comparable to that of a hydrogen-maser clock. The ion-handling components are housed in a sealed vacuum tube, wherein a getter pump maintains the partial vacuum, and the evacuated tube is backfilled with mercury vapor in a neon buffer gas. There was progress in the development of the clock, with emphasis on the design, fabrication, pump-down, and bake-out of the vacuum tube (based on established practice in the travelingwave- tube-amplifier industry) and the ability of the tube to retain a vacuum after a year of operation. Other developments include some aspects of the operation of mercury-vapor source (a small appendage oven containing HgO) so as to maintain the optimum low concentration of mercury vapor, and further efforts to miniaturize the vacuum and optical subsystems to fit within a volume of 2 L.

Data and clock transmission interface for the WCDA in LHAASO

NASA Astrophysics Data System (ADS)

Chu, S. P.; Zhao, L.; Jiang, Z. Y.; Ma, C.; Gao, X. S.; Yang, Y. F.; Liu, S. B.; An, Q.

2016-12-01

The Water Cherenkov Detector Array (WCDA) is one of the major components of the Large High Altitude Air Shower Observatory (LHAASO). In the WCDA, 3600 Photomultiplier Tubes (PMTs) and the Front End Electronics (FEEs) are scattered over a 90000 m2 area, while high precision time measurements (0.5 ns RMS) are required in the readout electronics. To meet this requirement, the clock has to be distributed to the FEEs with high precision. Due to the ``triggerless'' architecture, high speed data transfer is required based on the TCP/IP protocol. To simplify the readout electronics architecture and be consistent with the whole LHAASO readout electronics, the White Rabbit (WR) switches are used to transfer clock, data, and commands via a single fiber of about 400 meters. In this paper, a prototype of data and clock transmission interface for LHAASO WCDA is developed. The performance tests are conducted and the results indicate that the clock synchronization precision of the data and clock transmission is better than 50 ps. The data transmission throughput can reach 400 Mbps for one FEE board and 180 Mbps for 4 FEE boards sharing one up link port in WR switch, which is better than the requirement of the LHAASO WCDA.

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.

Quantum key distribution with an efficient countermeasure against correlated intensity fluctuations in optical pulses

NASA Astrophysics Data System (ADS)

Yoshino, Ken-ichiro; Fujiwara, Mikio; Nakata, Kensuke; Sumiya, Tatsuya; Sasaki, Toshihiko; Takeoka, Masahiro; Sasaki, Masahide; Tajima, Akio; Koashi, Masato; Tomita, Akihisa

2018-03-01

Quantum key distribution (QKD) allows two distant parties to share secret keys with the proven security even in the presence of an eavesdropper with unbounded computational power. Recently, GHz-clock decoy QKD systems have been realized by employing ultrafast optical communication devices. However, security loopholes of high-speed systems have not been fully explored yet. Here we point out a security loophole at the transmitter of the GHz-clock QKD, which is a common problem in high-speed QKD systems using practical band-width limited devices. We experimentally observe the inter-pulse intensity correlation and modulation pattern-dependent intensity deviation in a practical high-speed QKD system. Such correlation violates the assumption of most security theories. We also provide its countermeasure which does not require significant changes of hardware and can generate keys secure over 100 km fiber transmission. Our countermeasure is simple, effective and applicable to wide range of high-speed QKD systems, and thus paves the way to realize ultrafast and security-certified commercial QKD systems.

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

Role of melatonin combined with exercise as a switch-like regulator for circadian behavior in advanced osteoarthritic knee.

PubMed

Hong, Yunkyung; Kim, Hyunsoo; Lee, Seunghoon; Jin, Yunho; Choi, Jeonghyun; Lee, Sang-Rae; Chang, Kyu-Tae; Hong, Yonggeun

2017-11-14

Here, we show the role of melatonin combined with or without exercise as a determinant of multicellular behavior in osteoarthritis. We address the relationship between the molecular components governing local circadian clock and changes in the osteoarthritic musculoskeletal axis. Melatonin was injected subcutaneously in animals with advanced knee osteoarthritis (OA) for 4 weeks. Concurrently, moderate treadmill exercise was applied for 30 min/day. Morphometric, histological, and gene/protein-level analyses were performed in the cartilage, synovium, bone, and gastrocnemius muscle. Primary cultured chondrocytes repeatedly exposed to TNF-α were used in an in vitro study. The symptoms of OA include gait disturbance, osteophyte formation, and abnormal metabolism of the extracellular matrix (ECM) of the cartilage. Low-level expression of clock genes was accompanied by aberrant changes in cartilage specimens. Nanomolar doses of melatonin restored the expression of clock-controlled genes and corrected the abnormal chondrocyte phenotype. Melatonin combined with or without exercise prevented periarticular muscle damage as well as cartilage degeneration. But prolonged melatonin administration promoted the proteolytic cleavage of RANKL protein in the synovium, leading to severe subchondral bone erosion. These musculoskeletal changes apparently occurred via the regulation of molecular clock components, suggesting a role of melatonin as a switch-like regulator for the OA phenotype.

Clock distribution system for digital computers

DOEpatents

Wyman, Robert H.; Loomis, Jr., Herschel H.

1981-01-01

Apparatus for eliminating, in each clock distribution amplifier of a clock distribution system, sequential pulse catch-up error due to one pulse "overtaking" a prior clock pulse. The apparatus includes timing means to produce a periodic electromagnetic signal with a fundamental frequency having a fundamental frequency component V'.sub.01 (t); an array of N signal characteristic detector means, with detector means No. 1 receiving the timing means signal and producing a change-of-state signal V.sub.1 (t) in response to receipt of a signal above a predetermined threshold; N substantially identical filter means, one filter means being operatively associated with each detector means, for receiving the change-of-state signal V.sub.n (t) and producing a modified change-of-state signal V'.sub.n (t) (n=1, . . . , N) having a fundamental frequency component that is substantially proportional to V'.sub.01 (t-.theta..sub.n (t) with a cumulative phase shift .theta..sub.n (t) having a time derivative that may be made uniformly and arbitrarily small; and with the detector means n+1 (1.ltoreq.n

A role for clock genes in sleep homeostasis.

PubMed

Franken, Paul

2013-10-01

The timing and quality of both sleep and wakefulness are thought to be regulated by the interaction of two processes. One of these two processes keeps track of the prior sleep-wake history and controls the homeostatic need for sleep while the other sets the time-of-day that sleep preferably occurs. The molecular pathways underlying the latter, circadian process have been studied in detail and their key role in physiological time-keeping has been well established. Analyses of sleep in mice and flies lacking core circadian clock gene proteins have demonstrated, however, that besides disrupting circadian rhythms, also sleep homeostatic processes were affected. Subsequent studies revealed that sleep loss alters both the mRNA levels and the specific DNA-binding of the key circadian transcriptional regulators to their target sequences in the mouse brain. The fact that sleep loss impinges on the very core of the molecular circadian circuitry might explain why both inadequate sleep and disrupted circadian rhythms can similarly lead to metabolic pathology. The evidence for a role for clock genes in sleep homeostasis will be reviewed here. Copyright © 2013 Elsevier Ltd. All rights reserved.

A comparison of high-throughput techniques for assaying circadian rhythms in plants.

PubMed

Tindall, Andrew J; Waller, Jade; Greenwood, Mark; Gould, Peter D; Hartwell, James; Hall, Anthony

2015-01-01

Over the last two decades, the development of high-throughput techniques has enabled us to probe the plant circadian clock, a key coordinator of vital biological processes, in ways previously impossible. With the circadian clock increasingly implicated in key fitness and signalling pathways, this has opened up new avenues for understanding plant development and signalling. Our tool-kit has been constantly improving through continual development and novel techniques that increase throughput, reduce costs and allow higher resolution on the cellular and subcellular levels. With circadian assays becoming more accessible and relevant than ever to researchers, in this paper we offer a review of the techniques currently available before considering the horizons in circadian investigation at ever higher throughputs and resolutions.

Atomic clock ensemble in space (ACES) data analysis

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Research on key technologies of LADAR echo signal simulator

NASA Astrophysics Data System (ADS)

Xu, Rui; Shi, Rui; Ye, Jiansen; Wang, Xin; Li, Zhuo

2015-10-01

LADAR echo signal simulator is one of the most significant components of hardware-in-the-loop (HWIL) simulation systems for LADAR, which is designed to simulate the LADAR return signal in laboratory conditions. The device can provide the laser echo signal of target and background for imaging LADAR systems to test whether it is of good performance. Some key technologies are investigated in this paper. Firstly, the 3D model of typical target is built, and transformed to the data of the target echo signal based on ranging equation and targets reflection characteristics. Then, system model and time series model of LADAR echo signal simulator are established. Some influential factors which could induce fixed delay error and random delay error on the simulated return signals are analyzed. In the simulation system, the signal propagating delay of circuits and the response time of pulsed lasers are belong to fixed delay error. The counting error of digital delay generator, the jitter of system clock and the desynchronized between trigger signal and clock signal are a part of random delay error. Furthermore, these system insertion delays are analyzed quantitatively, and the noisy data are obtained. The target echo signals are got by superimposing of the noisy data and the pure target echo signal. In order to overcome these disadvantageous factors, a method of adjusting the timing diagram of the simulation system is proposed. Finally, the simulated echo signals are processed by using a detection algorithm to complete the 3D model reconstruction of object. The simulation results reveal that the range resolution can be better than 8 cm.

The JPL near-real-time VLBI system and its application to clock synchronization and earth orientation measurements

NASA Technical Reports Server (NTRS)

Callahan, P. S.; Eubanks, T. M.; Roth, M. G.; Steppe, J. A.; Esposito, P. B.

1983-01-01

The JPL near-real-time VLBI system called Block I is discussed. The hardware and software of the system are described, and the Time and Earth Motion Precision Observations (TEMPO) which utilize Block I are discussed. These observations are designed to provide interstation clock synchronization to 10 nsec and to determine earth orientation (UT1 and polar motion - UTPM) to 30 cm or better in each component. TEMPO results for clock synchronization and UTPM are presented with data from the July 1980-August 1981 analyzed using the most recent JPL solution software and source catalog. Future plans for TEMPO and Block I are discussed.

Neon as a Buffer Gas for a Mercury-Ion Clock

NASA Technical Reports Server (NTRS)

Prestage, John; Chung, Sang

2008-01-01

A developmental miniature mercury-ion clock has stability comparable to that of a hydrogen-maser clock. The ion-handling components are housed in a sealed vacuum tube, wherein a getter pump is used to maintain the partial vacuum, and the evacuated tube is backfilled with mercury vapor in a buffer gas. Neon was determined to be the best choice for the buffer gas: The pressure-induced frequency pulling by neon was found to be only about two-fifths of that of helium. Furthermore, because neon diffuses through solids much more slowly than does helium, the operational lifetime of a tube backfilled with neon could be considerably longer than that of a tube backfilled with helium.

Constructive polarization modulation for coherent population trapping clock

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

Yun, Peter, E-mail: enxue.yun@obspm.fr; Danet, Jean-Marie; Holleville, David

2014-12-08

We propose a constructive polarization modulation scheme for atomic clocks based on coherent population trapping (CPT). In this scheme, the polarization of a bichromatic laser beam is modulated between two opposite circular polarizations to avoid trapping the atomic populations in the extreme Zeeman sublevels. We show that if an appropriate phase modulation between the two optical components of the bichromatic laser is applied synchronously, the two CPT dark states which are produced successively by the alternate polarizations add constructively. Measured CPT resonance contrasts up to 20% in one-pulse CPT and 12% in two-pulse Ramsey-CPT experiments are reported, demonstrating the potentialmore » of this scheme for applications to high performance atomic clocks.« less

A Timer for Synchronous Digital Systems

NASA Technical Reports Server (NTRS)

McKenney, Elizabeth; Irwin, Philip

2003-01-01

The Real-Time Interferometer Control Systems Testbed (RICST) timing board is a VersaModule Eurocard (VME)-based board that can generate up to 16 simultaneous, phase-locked timing signals at a rate defined by the user. It can also generate all seven VME interrupt requests (IRQs). The RICST timing board is suitable mainly for robotic, aerospace, and real-time applications. Several circuit boards on the market are capable of generating periodic IRQs. Most are associated with Global Positioning System (GPS) receivers and Inter Range Instrumentation Group (IRIG) time-code generators, whereas this board uses either an internal VME clock or an externally generated clock signal to synchronize multiple components of the system. The primary advantage of this board is that there is no discernible jitter in the output clock waveforms because the signals are divided down from a high-frequency clock signal instead of being phase-locked from a lower frequency. The primary disadvantage to this board, relative to other periodic-IRQ-generating boards, is that it is more difficult to synchronize the system to wall clock time.

The circadian molecular clock regulates adult hippocampal neurogenesis by controlling the timing of cell-cycle entry and exit.

PubMed

Bouchard-Cannon, Pascale; Mendoza-Viveros, Lucia; Yuen, Andrew; Kærn, Mads; Cheng, Hai-Ying M

2013-11-27

The subgranular zone (SGZ) of the adult hippocampus contains a pool of quiescent neural progenitor cells (QNPs) that are capable of entering the cell cycle and producing newborn neurons. The mechanisms that control the timing and extent of adult neurogenesis are not well understood. Here, we show that QNPs of the adult SGZ express molecular-clock components and proliferate in a rhythmic fashion. The clock proteins PERIOD2 and BMAL1 are critical for proper control of neurogenesis. The absence of PERIOD2 abolishes the gating of cell-cycle entrance of QNPs, whereas genetic ablation of bmal1 results in constitutively high levels of proliferation and delayed cell-cycle exit. We use mathematical model simulations to show that these observations may arise from clock-driven expression of a cell-cycle inhibitor that targets the cyclin D/Cdk4-6 complex. Our findings may have broad implications for the circadian clock in timing cell-cycle events of other stem cell populations throughout the body. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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.

Time-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage.

PubMed

Wang, Hong; van Spyk, Elyse; Liu, Qiang; Geyfman, Mikhail; Salmans, Michael L; Kumar, Vivek; Ihler, Alexander; Li, Ning; Takahashi, Joseph S; Andersen, Bogi

2017-08-01

The epidermis is a highly regenerative barrier protecting organisms from environmental insults, including UV radiation, the main cause of skin cancer and skin aging. Here, we show that time-restricted feeding (RF) shifts the phase and alters the amplitude of the skin circadian clock and affects the expression of approximately 10% of the skin transcriptome. Furthermore, a large number of skin-expressed genes are acutely regulated by food intake. Although the circadian clock is required for daily rhythms in DNA synthesis in epidermal progenitor cells, RF-induced shifts in clock phase do not alter the phase of DNA synthesis. However, RF alters both diurnal sensitivity to UVB-induced DNA damage and expression of the key DNA repair gene, Xpa. Together, our findings indicate regulation of skin function by time of feeding and emphasize a link between circadian rhythm, food intake, and skin health. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals

PubMed Central

Montagner, Alexandra; Korecka, Agata; Polizzi, Arnaud; Lippi, Yannick; Blum, Yuna; Canlet, Cécile; Tremblay-Franco, Marie; Gautier-Stein, Amandine; Burcelin, Rémy; Yen, Yi-Chun; Je, Hyunsoo Shawn; Maha, Al-Asmakh; Mithieux, Gilles; Arulampalam, Velmurugesan; Lagarrigue, Sandrine; Guillou, Hervé; Pettersson, Sven; Wahli, Walter

2016-01-01

The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function. PMID:26879573

Epigenetic control and the circadian clock: linking metabolism to neuronal responses.

PubMed

Orozco-Solis, R; Sassone-Corsi, P

2014-04-04

Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape. Published by Elsevier Ltd.

Design and implementation of fast bipolar clock drivers for CCD imaging systems in space applications

NASA Astrophysics Data System (ADS)

Jayarajan, Jayesh; Kumar, Nishant; Verma, Amarnath; Thaker, Ramkrishna

2016-05-01

Drive electronics for generating fast, bipolar clocks, which can drive capacitive loads of the order of 5-10nF are indispensable for present day Charge Coupled Devices (CCDs). Design of these high speed bipolar clocks is challenging because of the capacitive loads that have to be driven and a strict constraint on the rise and fall times. Designing drive electronics circuits for space applications becomes even more challenging due to limited number of available discrete devices, which can survive in the harsh radiation prone space environment. This paper presents the design, simulations and test results of a set of such high speed, bipolar clock drivers. The design has been tested under a thermal cycle of -15 deg C to +55 deg C under vacuum conditions and has been designed using radiation hardened components. The test results show that the design meets the stringent rise/fall time requirements of 50+/-10ns for Multiple Vertical CCD (VCCD) clocks and 20+/-5ns for Horizontal CCD (HCCD) clocks with sufficient design margins across full temperature range, with a pixel readout rate of 6.6MHz. The full design has been realized in flexi-rigid PCB with package volume of 140x160x50 mm3.

Development of diabetes does not alter behavioral and molecular circadian rhythms in a transgenic rat model of type 2 diabetes mellitus.

PubMed

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

2017-08-01

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

Involvement of adenosine monophosphate-activated protein kinase in the influence of timed high-fat evening diet on the hepatic clock and lipogenic gene expression in mice.

PubMed

Huang, Yan; Zhu, Zengyan; Xie, Meilin; Xue, Jie

2015-09-01

A high-fat diet may result in changes in hepatic clock gene expression, but potential mechanisms are not yet elucidated. Adenosine monophosphate-activated protein kinase (AMPK) is a serine/threonine protein kinase that is recognized as a key regulator of energy metabolism and certain clock genes. Therefore, we hypothesized that AMPK may be involved in the alteration of hepatic clock gene expression under a high-fat environment. This study aimed to examine the effects of timed high-fat evening diet on the activity of hepatic AMPK, clock genes, and lipogenic genes. Mice with hyperlipidemic fatty livers were induced by orally administering high-fat milk via gavage every evening (19:00-20:00) for 6 weeks. Results showed that timed high-fat diet in the evening not only decreased the hepatic AMPK protein expression and activity but also disturbed its circadian rhythm. Accordingly, the hepatic clock genes, including clock, brain-muscle-Arnt-like 1, cryptochrome 2, and period 2, exhibited prominent changes in their expression rhythms and/or amplitudes. The diurnal rhythms of the messenger RNA expression of peroxisome proliferator-activated receptorα, acetyl-CoA carboxylase 1α, and carnitine palmitoyltransferase 1 were also disrupted; the amplitude of peroxisome proliferator-activated receptorγcoactivator 1α was significantly decreased at 3 time points, and fatty liver was observed. These findings demonstrate that timed high-fat diet at night can change hepatic AMPK protein levels, activity, and circadian rhythm, which may subsequently alter the circadian expression of several hepatic clock genes and finally result in the disorder of hepatic lipogenic gene expression and the formation of fatty liver. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.

PubMed

Cedernaes, Jonathan; Osler, Megan E; Voisin, Sarah; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Zierath, Juleen R; Schiöth, Helgi B; Benedict, Christian

2015-09-01

Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

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

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

VRILLE Controls PDF Neuropeptide Accumulation and Arborization Rhythms in Small Ventrolateral Neurons to Drive Rhythmic Behavior in Drosophila.

PubMed

Gunawardhana, Kushan L; Hardin, Paul E

2017-11-20

In Drosophila, the circadian clock is comprised of transcriptional feedback loops that control rhythmic gene expression responsible for daily rhythms in physiology, metabolism, and behavior. The core feedback loop, which employs CLOCK-CYCLE (CLK-CYC) activators and PERIOD-TIMELESS (PER-TIM) repressors to drive rhythmic transcription peaking at dusk, is required for circadian timekeeping and overt behavioral rhythms. CLK-CYC also activates an interlocked feedback loop, which uses the PAR DOMAIN PROTEIN 1ε (PDP1ε) activator and the VRILLE (VRI) repressor to drive rhythmic transcription peaking at dawn. Although Pdp1ε mutants disrupt activity rhythms without eliminating clock function, whether vri is required for clock function and/or output is not known. Using a conditionally inactivatable transgene to rescue vri developmental lethality, we show that clock function persists after vri inactivation but that activity rhythms are abolished. The inactivation of vri disrupts multiple output pathways thought to be important for activity rhythms, including PDF accumulation and arborization rhythms in the small ventrolateral neuron (sLN v ) dorsal projection. These results demonstrate that vri acts as a key regulator of clock output and suggest that the primary function of the interlocked feedback loop in Drosophila is to drive rhythmic transcription required for overt rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.

A single chip 2 Gbit/s clock recovery subsystem for digital communications

NASA Astrophysics Data System (ADS)

Hickling, Ronald M.

A self-contained clock recovery/data resynchronizer phase locked loop (PLL) for use in microwave and fiber optic digital communications has been fabricated using GaAs integrated circuit technology. The IC contains the analog and digital components for the PLL: an edge-triggered phase detector based on a 1.2 GHz phase/frequency comparator, an op amp for creating the loop filter, and a VCO based on a differential source-coupled pair amplifier.

Study of additive manufactured microwave cavities for pulsed optically pumped atomic clock applications

NASA Astrophysics Data System (ADS)

Affolderbach, C.; Moreno, W.; Ivanov, A. E.; Debogovic, T.; Pellaton, M.; Skrivervik, A. K.; de Rijk, E.; Mileti, G.

2018-03-01

Additive manufacturing (AM) of passive microwave components is of high interest for the cost-effective and rapid prototyping or manufacture of devices with complex geometries. Here, we present an experimental study on the properties of recently demonstrated microwave resonator cavities manufactured by AM, in view of their applications to high-performance compact atomic clocks. The microwave cavities employ a loop-gap geometry using six electrodes. The critical electrode structures were manufactured monolithically using two different approaches: Stereolithography (SLA) of a polymer followed by metal coating and Selective Laser Melting (SLM) of aluminum. The tested microwave cavities show the desired TE011-like resonant mode at the Rb clock frequency of ≈6.835 GHz, with a microwave magnetic field highly parallel to the quantization axis across the vapor cell. When operated in an atomic clock setup, the measured atomic Rabi oscillations are comparable to those observed for conventionally manufactured cavities and indicate a good uniformity of the field amplitude across the vapor cell. Employing a time-domain Ramsey scheme on one of the SLA cavities, high-contrast (34%) Ramsey fringes are observed for the Rb clock transition, along with a narrow (166 Hz linewidth) central fringe. The measured clock stability of 2.2 × 10-13 τ-1/2 up to the integration time of 30 s is comparable to the current state-of-the-art stabilities of compact vapor-cell clocks based on conventional microwave cavities and thus demonstrates the feasibility of the approach.

Frequency Measurements of Superradiance from the Strontium Clock Transition

NASA Astrophysics Data System (ADS)

Norcia, Matthew A.; Cline, Julia R. K.; Muniz, Juan A.; Robinson, John M.; Hutson, Ross B.; Goban, Akihisa; Marti, G. Edward; Ye, Jun; Thompson, James K.

2018-04-01

We present the first characterization of the spectral properties of superradiant light emitted from the ultranarrow, 1-mHz-linewidth optical clock transition in an ensemble of cold Sr 87 atoms. Such a light source has been proposed as a next-generation active atomic frequency reference, with the potential to enable high-precision optical frequency references to be used outside laboratory environments. By comparing the frequency of our superradiant source to that of a state-of-the-art cavity-stabilized laser and optical lattice clock, we observe a fractional Allan deviation of 6.7 (1 )×10-16 at 1 s of averaging, establish absolute accuracy at the 2-Hz (4 ×10-15 fractional frequency) level, and demonstrate insensitivity to key environmental perturbations.

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.

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.

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.

Timing Embryo Segmentation: Dynamics and Regulatory Mechanisms of the Vertebrate Segmentation Clock

PubMed Central

Resende, Tatiana P.; Andrade, Raquel P.; Palmeirim, Isabel

2014-01-01

All vertebrate species present a segmented body, easily observed in the vertebrate column and its associated components, which provides a high degree of motility to the adult body and efficient protection of the internal organs. The sequential formation of the segmented precursors of the vertebral column during embryonic development, the somites, is governed by an oscillating genetic network, the somitogenesis molecular clock. Herein, we provide an overview of the molecular clock operating during somite formation and its underlying molecular regulatory mechanisms. Human congenital vertebral malformations have been associated with perturbations in these oscillatory mechanisms. Thus, a better comprehension of the molecular mechanisms regulating somite formation is required in order to fully understand the origin of human skeletal malformations. PMID:24895605

New Leeway on Horizon under NCLB

ERIC Educational Resources Information Center

McNeil, Michele

2011-01-01

As the clock ticks toward President Barack Obama's back-to-school deadline for rewriting the No Child Left Behind Act, U.S. Secretary of Education Arne Duncan is preparing to grant states relief from key provisions of the federal school accountability law in exchange for what he calls "commitments to key reforms." The move comes as…

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.).

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

PubMed

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

2003-12-03

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

Effects of Different PER Translational Kinetics on the Dynamics of a Core Circadian Clock Model

PubMed Central

Nieto, Paula S.; Revelli, Jorge A.; Garbarino-Pico, Eduardo; Condat, Carlos A.; Guido, Mario E.; Tamarit, Francisco A.

2015-01-01

Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis. PMID:25607544

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

PubMed

Nieto, Paula S; Revelli, Jorge A; Garbarino-Pico, Eduardo; Condat, Carlos A; Guido, Mario E; Tamarit, Francisco A

2015-01-01

Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.

Molecular analyses of the principal components of response strength.

PubMed Central

Killeen, Peter R; Hall, Scott S; Reilly, Mark P; Kettle, Lauren C

2002-01-01

Killeen and Hall (2001) showed that a common factor called strength underlies the key dependent variables of response probability, latency, and rate, and that overall response rate is a good predictor of strength. In a search for the mechanisms that underlie those correlations, this article shows that (a) the probability of responding on a trial is a two-state Markov process; (b) latency and rate of responding can be described in terms of the probability and period of stochastic machines called clocked Bernoulli modules, and (c) one such machine, the refractory Poisson process, provides a functional relation between the probability of observing a response during any epoch and the rate of responding. This relation is one of proportionality at low rates and curvilinearity at higher rates. PMID:12216975

Daily Eating Patterns and Their Impact on Health and Disease.

PubMed

Zarrinpar, Amir; Chaix, Amandine; Panda, Satchidananda

2016-02-01

Cyclical expression of cell-autonomous circadian clock components and key metabolic regulators coordinate often discordant and distant cellular processes for efficient metabolism. Perturbation of these cycles, either by genetic manipulation, disruption of light/dark cycles, or, most relevant to the human population, via eating patterns, contributes to obesity and dysmetabolism. Time-restricted feeding (TRF), during which time of access to food is restricted to a few hours, without caloric restriction, supports robust metabolic cycles and protects against nutritional challenges that predispose to obesity and dysmetabolism. The mechanism by which TRF imparts its benefits is not fully understood but likely involves entrainment of metabolically active organs through gut signaling. Understanding the relationship of feeding pattern and metabolism could yield novel therapies for the obesity pandemic. Copyright © 2015. Published by Elsevier Ltd.

Wireless neural recording with single low-power integrated circuit.

PubMed

Harrison, Reid R; Kier, Ryan J; Chestek, Cynthia A; Gilja, Vikash; Nuyujukian, Paul; Ryu, Stephen; Greger, Bradley; Solzbacher, Florian; Shenoy, Krishna V

2009-08-01

We present benchtop and in vivo experimental results from an integrated circuit designed for wireless implantable neural recording applications. The chip, which was fabricated in a commercially available 0.6- mum 2P3M BiCMOS process, contains 100 amplifiers, a 10-bit analog-to-digital converter (ADC), 100 threshold-based spike detectors, and a 902-928 MHz frequency-shift-keying (FSK) transmitter. Neural signals from a selected amplifier are sampled by the ADC at 15.7 kSps and telemetered over the FSK wireless data link. Power, clock, and command signals are sent to the chip wirelessly over a 2.765-MHz inductive (coil-to-coil) link. The chip is capable of operating with only two off-chip components: a power/command receiving coil and a 100-nF capacitor.

Daily Eating Patterns and Their Impact on Health and Disease

PubMed Central

Zarrinpar, Amir; Chaix, Amandine; Panda, Satchidananda

2016-01-01

Cyclical expression of cell-autonomous circadian clock components and key metabolic regulators coordinate often discordant and distant cellular processes for efficient metabolism. Perturbation of these cycles, either by genetic manipulation, disruption of light/dark cycles, or, most relevant to the human population, via eating patterns, contributes to obesity and dysmetabolism. Time-restricted feeding (TRF), during which time of access to food is restricted to a few hours, without caloric restriction, supports robust metabolic cycles and protects against nutritional challenges that predispose to obesity and dysmetabolism. The mechanism by which TRF imparts its benefits is not fully understood but likely involves entrainment of metabolically active organs through gut signaling. Understanding the relationship of feeding pattern and metabolism could yield novel therapies for the obesity pandemic. PMID:26706567

Critical role for CCA1 and LHY in maintaining circadian rhythmicity in Arabidopsis.

PubMed

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

2002-04-30

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

Circadian Rhythms in Cyanobacteria

PubMed Central

Golden, Susan S.

2015-01-01

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

Atomic Clocks with Suppressed Blackbody Radiation Shift

NASA Astrophysics Data System (ADS)

Yudin, V. I.; Taichenachev, A. V.; Okhapkin, M. V.; Bagayev, S. N.; Tamm, Chr.; Peik, E.; Huntemann, N.; Mehlstäubler, T. E.; Riehle, F.

2011-07-01

We develop a concept of atomic clocks where the blackbody radiation shift and its fluctuations can be suppressed by 1-3 orders of magnitude independent of the environmental temperature. The suppression is based on the fact that in a system with two accessible clock transitions (with frequencies ν1 and ν2) which are exposed to the same thermal environment, there exists a “synthetic” frequency νsyn ∝ (ν1-ɛ12ν2) largely immune to the blackbody radiation shift. For example, in the case of Yb+171 it is possible to create a synthetic-frequency-based clock in which the fractional blackbody radiation shift can be suppressed to the level of 10-18 in a broad interval near room temperature (300±15K). We also propose a realization of our method with the use of an optical frequency comb generator stabilized to both frequencies ν1 and ν2, where the frequency νsyn is generated as one of the components of the comb spectrum.

An open-source, extensible system for laboratory timing and control

NASA Astrophysics Data System (ADS)

Gaskell, Peter E.; Thorn, Jeremy J.; Alba, Sequoia; Steck, Daniel A.

2009-11-01

We describe a simple system for timing and control, which provides control of analog, digital, and radio-frequency signals. Our system differs from most common laboratory setups in that it is open source, built from off-the-shelf components, synchronized to a common and accurate clock, and connected over an Ethernet network. A simple bus architecture facilitates creating new and specialized devices with only moderate experience in circuit design. Each device operates independently, requiring only an Ethernet network connection to the controlling computer, a clock signal, and a trigger signal. This makes the system highly robust and scalable. The devices can all be connected to a single external clock, allowing synchronous operation of a large number of devices for situations requiring precise timing of many parallel control and acquisition channels. Provided an accurate enough clock, these devices are capable of triggering events separated by one day with near-microsecond precision. We have achieved precisions of ˜0.1 ppb (parts per 109) over 16 s.

Clock and carrier recovery in high-speed coherent optical communication systems

NASA Astrophysics Data System (ADS)

Amado, Sofia B.; Ferreira, Ricardo; Costa, Pedro S.; Guiomar, Fernando P.; Ziaie, Somayeh; Teixeira, António L.; Muga, Nelson J.; Pinto, Armando N.

2014-08-01

In this paper, the implementations of clock and carrier recovery in digital domain are analyzed. Hardware implementation details, resources estimation and real-time results are presented. Analog-to-Digital Converters (ADC), operating at 1.25Gsa/s, and a Virtex-6 Field-Programmable Gate Array (FPGA), have been used, allowing the implementation of a real-time Quadrature Phase Shift Keying (QPSK) system operating at 1.25Gb/s. The real-time mode operation is successfully demonstrated over 80 km of Standard Single Mode Fiber (SSMF).

Light and the circadian clock mediate time-specific changes in sensitivity to UV-B stress under light/dark cycles

PubMed Central

Takeuchi, Tomomi; Newton, Linsey; Burkhardt, Alyssa; Mason, Saundra; Farré, Eva M.

2014-01-01

In Arabidopsis, the circadian clock regulates UV-B-mediated changes in gene expression. Here it is shown that circadian clock components are able to inhibit UV-B-induced gene expression in a gene-by-gene-specific manner and act downstream of the initial UV-B sensing by COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1) and UVR8 (UV RESISTANCE LOCUS 8). For example, the UV-B induction of ELIP1 (EARLY LIGHT INDUCIBLE PROTEIN 1) and PRR9 (PSEUDO-RESPONSE REGULATOR 9) is directly regulated by LUX (LUX ARRYTHMO), ELF4 (EARLY FLOWERING 4), and ELF3. Moreover, time-dependent changes in plant sensitivity to UV-B damage were observed. Wild-type Arabidopsis plants, but not circadian clock mutants, were more sensitive to UV-B treatment during the night periods than during the light periods under diel cycles. Experiments performed under short cycles of 6h light and 6h darkness showed that the increased stress sensitivity of plants to UV-B in the dark only occurred during the subjective night and not during the subjective day in wild-type seedlings. In contrast, the stress sensitivity of Arabidopsis mutants with a compromised circadian clock was still influenced by the light condition during the subjective day. Taken together, the results show that the clock and light modulate plant sensitivity to UV-B stress at different times of the day. PMID:25147271

10Gbit/s all-optical NRZ to RZ conversion based on TOAD

NASA Astrophysics Data System (ADS)

Yan, Yumei; Yin, Lina; Zhou, Yunfeng; Liu, Guoming; Wu, Jian; Lin, Jintong

2006-01-01

Future network will include wavelength division multiplexing (WDM) and optical time division multiplexing (OTDM) technologies. All-optical format conversion between their respective preferable data formats, non-return-to-zero (NRZ) and return-to-zero (RZ), may become an important technology. In this paper, 10Gbit/s all-optical NRZ-to-RZ conversion is demonstrated based on terahertz optical asymmetric demultiplexer (TOAD) using clock all-optically recovered from the NRZ signal for the first time. The clock component is enhanced in an SOA and the pseudo-return-to-zero (PRZ) signal is filtered. The PRZ signal is input into an injection mode-locked fiber ring laser for clock recovery. The recovered clock and the NRZ signal are input into TOAD as pump signal and probe signal, respectively, and format conversion is performed. The quality of the converted RZ signal is determined by that of the recovered clock and the NRZ signal, whereas hardly influenced by gain recovery time of the SOA. In the experimental demonstration, the obtained RZ signal has an extinction ratio of 8.7dB and low pattern dependency. After conversion, the spectrum broadens obviously and shows multimode structure with spectrum interval of 0.08nm, which matches with the bit rate 10Gbit/s. Furthermore, this format conversion method has some tolerance on the pattern dependency of the clock signal.

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

PubMed

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

2018-02-01

A molecular circadian oscillator resides in neurons of the cerebral cortex, but its role is unknown. Using the Cre-LoxP method, we have here abolished the core clock gene Arntl in those neurons. This mouse represents the first model carrying a deletion of a circadian clock component specifically in an extrahypothalamic cell type of the brain. Molecular analyses of clock gene expression in the cerebral cortex of the Arntl conditional knockout mouse revealed disrupted circadian expression profiles, whereas clock gene expression in the suprachiasmatic nucleus was still rhythmic, thus showing that Arntl is required for normal function of the cortical circadian oscillator. Daily rhythms in running activity and temperature were not influenced, whereas the resynchronization response to experimental jet-lag exhibited minor though significant differences between genotypes. The tail-suspension test revealed significantly prolonged immobility periods in the knockout mouse indicative of a depressive-like behavioral state. This phenotype was accompanied by reduced norepinephrine levels in the cerebral cortex. Our data show that Arntl is required for normal cortical clock function and further give reason to suspect that the circadian oscillator of the cerebral cortex is involved in regulating both circadian biology and mood-related behavior and biochemistry. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

An improved grey model for the prediction of real-time GPS satellite clock bias

NASA Astrophysics Data System (ADS)

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

2008-07-01

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

Population specific biomarkers of human aging: a big data study using South Korean, Canadian and Eastern European patient populations.

PubMed

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

2018-01-11

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

Circadian Rhythms Regulate Amelogenesis

PubMed Central

Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A.; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

2013-01-01

Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24h) intervals both at RNA and protein levels. This study also reveals that two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stage of amelogenesis might be under circadian control. Changes in clock genes expression patterns might result in significant alterations of enamel apposition and mineralization. PMID:23486183

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.

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.

Quantum Cryptography in Existing Telecommunications Infrastructure

NASA Astrophysics Data System (ADS)

Rogers, Daniel; Bienfang, Joshua; Mink, Alan; Hershman, Barry; Nakassis, Anastase; Tang, Xiao; Ma, Lijun; Su, David; Williams, Carl; Clark, Charles

2006-03-01

Quantum cryptography has shown the potential for ultra-secure communications. However, all systems demonstrated to date operate at speeds that make them impractical for performing continuous one-time-pad encryption of today's broadband communications. By adapting clock and data recovery techniques from modern telecommunications engineering practice, and by designing and implementing expeditious error correction and privacy amplification algorithms, we have demonstrated error-corrected and privacy-amplified key rates up to 1.0 Mbps over a free-space link with a 1.25 Gbps clock. Using new detectors with improved timing resolution, careful wavelength selection and an increased clock speed, we expect to quadruple the transmission rate over a 1.5 km free-space link. We have identified scalable solutions for delivering sustained one-time-pad encryption at 10 Mbps, thus making it possible to integrate quantum cryptography with first-generation Ethernet protocols.

Mapping the co-localization of the circadian proteins PER2 and BMAL1 with enkephalin and substance P throughout the rodent forebrain.

PubMed

Frederick, Ariana; Goldsmith, Jory; de Zavalia, Nuria; Amir, Shimon

2017-01-01

Despite rhythmic expression of clock genes being found throughout the central nervous system, very little is known about their function outside of the suprachiasmatic nucleus. Determining the pattern of clock gene expression across neuronal subpopulations is a key step in understanding their regulation and how they may influence the functions of various brain structures. Using immunofluorescence and confocal microscopy, we quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and Enkephalin (Enk), expressed in distinct neuronal populations throughout the forebrain. Regions examined included the limbic forebrain (dorsal striatum, nucleus accumbens, amygdala, stria terminalis), thalamus medial habenula of the thalamus, paraventricular nucleus and arcuate nucleus of the hypothalamus and the olfactory bulb. In most regions examined, BMAL1 was homogeneously expressed in nearly all neurons (~90%), and PER2 was expressed in a slightly lower proportion of cells. There was no specific correlation to SubP- or Enk- expressing subpopulations. The olfactory bulb was unique in that PER2 and BMAL1 were expressed in a much smaller percentage of cells, and Enk was rarely found in the same cells that expressed the clock proteins (SubP was undetectable). These results indicate that clock genes are not unique to specific cell types, and further studies will be required to determine the factors that contribute to the regulation of clock gene expression throughout the brain.

Exposure to light enhances pre-adult fitness in two dark-dwelling sympatric species of ants

PubMed Central

Lone, Shahnaz Rahman; Sharma, Vijay Kumar

2008-01-01

Background In insects, circadian clocks play a key role in enhancing fitness by regulating life history traits such as developmental time and adult lifespan. These clocks use environmental light/dark (LD) cycles to fine-tune a wide range of behavioral and physiological processes. To study the effect of environmental LD conditions on pre-adult fitness components, we used two dark-dwelling sympatric species of ants (the night active Camponotus compressus and the day active Camponotus paria), which normally develop underground and have fairly long pre-adult developmental time. Results Our results suggest that ants develop fastest as pre-adults when maintained under constant light (LL), followed closely by 12:12 hr light/dark (LD), and then constant darkness (DD). While light exposure alters developmental rates of almost all stages of development, the overall pre-adult development in LL is speeded-up (relative to DD) by ~37% (34 days) in C. compressus and by ~35% (31 days) in C. paria. In LD too, development is faster (relative to DD) by ~29% (26 days) in C. compressus and by ~28% (25 days) in C. paria. Pre-adult viability of both species is also higher under LL and LD compared to DD. While pre-adult development time and viability is enhanced in LL and LD, clutch-size undergoes reduction, at least in C. compressus. Conclusion Exposure to light enhances pre-adult fitness in two dark-dwelling species of Camponotus by speeding-up development and by enhancing viability. This suggests that social ants use environmental light/dark cycles to modulate key life history traits such as pre-adult development time and viability. PMID:19046462

A Plant Cryptochrome Controls Key Features of the Chlamydomonas Circadian Clock and Its Life Cycle.

PubMed

Müller, Nico; Wenzel, Sandra; Zou, Yong; Künzel, Sandra; Sasso, Severin; Weiß, Daniel; Prager, Katja; Grossman, Arthur; Kottke, Tilman; Mittag, Maria

2017-05-01

Cryptochromes are flavin-binding proteins that act as blue light receptors in bacteria, fungi, plants, and insects and are components of the circadian oscillator in mammals. Animal and plant cryptochromes are evolutionarily divergent, although the unicellular alga Chlamydomonas reinhardtii ( Chlamydomonas throughout) has both an animal-like cryptochrome and a plant cryptochrome (pCRY; formerly designated CPH1). Here, we show that the pCRY protein accumulates at night as part of a complex. Functional characterization of pCRY was performed based on an insertional mutant that expresses only 11% of the wild-type pCRY level. The pcry mutant is defective for central properties of the circadian clock. In the mutant, the period is lengthened significantly, ultimately resulting in arrhythmicity, while blue light-based phase shifts show large deviations from what is observed in wild-type cells. We also show that pCRY is involved in gametogenesis in Chlamydomonas pCRY is down-regulated in pregametes and gametes, and in the pcry mutant, there is altered transcript accumulation under blue light of the strictly light-dependent, gamete-specific gene GAS28 pCRY acts as a negative regulator for the induction of mating ability in the light and for the loss of mating ability in the dark. Moreover, pCRY is necessary for light-dependent germination, during which the zygote undergoes meiosis that gives rise to four vegetative cells. In sum, our data demonstrate that pCRY is a key blue light receptor in Chlamydomonas that is involved in both circadian timing and life cycle progression. © 2017 American Society of Plant Biologists. All Rights Reserved.

Isoform switching facilitates period control in the Neurospora crassa circadian clock.

PubMed

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

2008-01-01

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

The CRTC1-SIK1 Pathway Regulates Entrainment of the Circadian Clock

PubMed Central

Jagannath, Aarti; Butler, Rachel; Godinho, Sofia I.H.; Couch, Yvonne; Brown, Laurence A.; Vasudevan, Sridhar R.; Flanagan, Kevin C.; Anthony, Daniel; Churchill, Grant C.; Wood, Matthew J.A.; Steiner, Guido; Ebeling, Martin; Hossbach, Markus; Wettstein, Joseph G.; Duffield, Giles E.; Gatti, Silvia; Hankins, Mark W.; Foster, Russell G.; Peirson, Stuart N.

2013-01-01

Summary Retinal photoreceptors entrain the circadian system to the solar day. This photic resetting involves cAMP response element binding protein (CREB)-mediated upregulation of Per genes within individual cells of the suprachiasmatic nuclei (SCN). Our detailed understanding of this pathway is poor, and it remains unclear why entrainment to a new time zone takes several days. By analyzing the light-regulated transcriptome of the SCN, we have identified a key role for salt inducible kinase 1 (SIK1) and CREB-regulated transcription coactivator 1 (CRTC1) in clock re-setting. An entrainment stimulus causes CRTC1 to coactivate CREB, inducing the expression of Per1 and Sik1. SIK1 then inhibits further shifts of the clock by phosphorylation and deactivation of CRTC1. Knockdown of Sik1 within the SCN results in increased behavioral phase shifts and rapid re-entrainment following experimental jet lag. Thus SIK1 provides negative feedback, acting to suppress the effects of light on the clock. This pathway provides a potential target for the regulation of circadian rhythms. PMID:23993098

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.

Organization of the Drosophila circadian control circuit.

PubMed

Nitabach, Michael N; Taghert, Paul H

2008-01-22

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

Free-Space Quantum Key Distribution using Polarization Entangled Photons

NASA Astrophysics Data System (ADS)

Kurtsiefer, Christian

2007-06-01

We report on a complete experimental implementation of a quantum key distribution protocol through a free space link using polarization-entangled photon pairs from a compact parametric down-conversion source [1]. Based on a BB84-equivalent protocol, we generated without interruption over 10 hours a secret key free-space optical link distance of 1.5 km with a rate up to 950 bits per second after error correction and privacy amplification. Our system is based on two time stamp units and relies on no specific hardware channel for coincidence identification besides an IP link. For that, initial clock synchronization with an accuracy of better than 2 ns is achieved, based on a conventional NTP protocol and a tiered cross correlation of time tags on both sides. Time tags are used to servo a local clock, allowing a streamed measurement on correctly identified photon pairs. Contrary to the majority of quantum key distribution systems, this approach does not require a trusted large-bandwidth random number generator, but integrates that into the physical key generation process. We discuss our current progress of implementing a key distribution via an atmospherical link during daylight conditions, and possible attack scenarios on a physical timing information side channel to a entanglement-based key distribution system. [1] I. Marcikic, A. Lamas-Linares, C. Kurtsiefer, Appl. Phys. Lett. 89, 101122 (2006).

Existence of a photoinducible phase for ovarian development and photoperiod-related alteration of clock gene expression in a damselfish.

PubMed

Takeuchi, Yuki; Hada, Noriko; Imamura, Satoshi; Hur, Sung-Pyo; Bouchekioua, Selma; Takemura, Akihiro

2015-10-01

The sapphire devil, Chrysiptera cyanea, is a reef-associated damselfish and their ovarian development can be induced by a long photoperiod. In this study, we demonstrated the existence of a photoinducible phase for the photoperiodic ovarian development in the sapphire devil. Induction of ovarian development under night-interruption light schedules and Nanda-Hamner cycles revealed that the photoinducible phase appeared in a circadian manner between ZT12 and ZT13. To characterize the effect of photoperiod on clock gene expression in the brain of this species, we determined the expression levels of the sdPer1, sdPer2, sdCry1, and sdCry2 clock genes under constant light and dark conditions (LL and DD) and photoperiodic (short and long photoperiods). The expression of sdPer1 exhibited clear circadian oscillation under both LL and DD conditions, while sdPer2 and sdCry1 expression levels were lower under DD than under LL conditions and sdCry2 expression was lower under LL than under DD conditions. These results suggest a key role for sdPer1 in circadian clock cycling and that sdPer2, sdCry1, and sdCry2 are light-responsive clock genes in the sapphire devil. After 1 week under a long photoperiod, we observed photoperiod-related changes in sdPer1, sdPer2, and sdCry2 expression, but not in sdCry1 expression. These results suggest that the expression patterns of some clock genes exhibit seasonal variation according to seasonal changes in day length and that such seasonal alteration of clock gene expression may contribute to seasonal recognition by the sapphire devil. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

High resolution time interval meter

DOEpatents

Martin, A.D.

1986-05-09

Method and apparatus are provided for measuring the time interval between two events to a higher resolution than reliability available from conventional circuits and component. An internal clock pulse is provided at a frequency compatible with conventional component operating frequencies for reliable operation. Lumped constant delay circuits are provided for generating outputs at delay intervals corresponding to the desired high resolution. An initiation START pulse is input to generate first high resolution data. A termination STOP pulse is input to generate second high resolution data. Internal counters count at the low frequency internal clock pulse rate between the START and STOP pulses. The first and second high resolution data are logically combined to directly provide high resolution data to one counter and correct the count in the low resolution counter to obtain a high resolution time interval measurement.

Homomorphic Filtering for Improving Time Synchronization in Wireless Networks

PubMed Central

Castillo-Secilla, José María; Palomares, José Manuel; León, Fernando; Olivares, Joaquín

2017-01-01

Wireless sensor networks are used to sample the environment in a distributed way. Therefore, it is mandatory for all of the measurements to be tightly synchronized in order to guarantee that every sensor is sampling the environment at the exact same instant of time. The synchronization drift gets bigger in environments suffering from temperature variations. Thus, this work is focused on improving time synchronization under deployments with temperature variations. The working hypothesis demonstrated in this work is that the clock skew of two nodes (the ratio of the real frequencies of the oscillators) is composed of a multiplicative combination of two main components: the clock skew due to the variations between the cut of the crystal of each oscillator and the clock skew due to the different temperatures affecting the nodes. By applying a nonlinear filtering, the homomorphic filtering, both components are separated in an effective way. A correction factor based on temperature, which can be applied to any synchronization protocol, is proposed. For testing it, an improvement of the FTSP synchronization protocol has been developed and physically tested under temperature variation scenarios using TelosB motes flashed with the IEEE 802.15.4 implementation supplied by TinyOS. PMID:28425955

Homomorphic Filtering for Improving Time Synchronization in Wireless Networks.

PubMed

Castillo-Secilla, José María; Palomares, José Manuel; León, Fernando; Olivares, Joaquín

2017-04-20

Wireless sensor networks are used to sample the environment in a distributed way. Therefore, it is mandatory for all of the measurements to be tightly synchronized in order to guarantee that every sensor is sampling the environment at the exact same instant of time. The synchronization drift gets bigger in environments suffering from temperature variations. Thus, this work is focused on improving time synchronization under deployments with temperature variations. The working hypothesis demonstrated in this work is that the clock skew of two nodes (the ratio of the real frequencies of the oscillators) is composed of a multiplicative combination of two main components: the clock skew due to the variations between the cut of the crystal of each oscillator and the clock skew due to the different temperatures affecting the nodes. By applying a nonlinear filtering, the homomorphic filtering, both components are separated in an effective way. A correction factor based on temperature, which can be applied to any synchronization protocol, is proposed. For testing it, an improvement of the FTSP synchronization protocol has been developed and physically tested under temperature variation scenarios using TelosB motes flashed with the IEEE 802.15.4 implementation supplied by TinyOS.

The Arabidopsis SRR1 gene mediates phyB signaling and is required for normal circadian clock function

PubMed Central

Staiger, Dorothee; Allenbach, Laure; Salathia, Neeraj; Fiechter, Vincent; Davis, Seth J.; Millar, Andrew J.; Chory, Joanne; Fankhauser, Christian

2003-01-01

Plants possess several photoreceptors to sense the light environment. In Arabidopsis cryptochromes and phytochromes play roles in photomorphogenesis and in the light input pathways that synchronize the circadian clock with the external world. We have identified SRR1 (sensitivity to red light reduced), a gene that plays an important role in phytochrome B (phyB)-mediated light signaling. The recessive srr1 null allele and phyB mutants display a number of similar phenotypes indicating that SRR1 is required for normal phyB signaling. Genetic analysis suggests that SRR1 works both in the phyB pathway but also independently of phyB. srr1 mutants are affected in multiple outputs of the circadian clock in continuous light conditions, including leaf movement and expression of the clock components, CCA1 and TOC1. Clock-regulated gene expression is also impaired during day–night cycles and in constant darkness. The circadian phenotypes of srr1 mutants in all three conditions suggest that SRR1 activity is required for normal oscillator function. The SRR1 gene was identified and shown to code for a protein conserved in numerous eukaryotes including mammals and flies, implicating a conserved role for this protein in both the animal and plant kingdoms. PMID:12533513

Joint CPT and N resonance in compact atomic time standards

NASA Astrophysics Data System (ADS)

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

2008-05-01

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

Design and Evaluation of a Clock Multiplexing Circuit for the SSRL Booster Accelerator Timing System - Oral Presentation

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

Araya, Million

2015-08-25

SPEAR3 is a 234 m circular storage ring at SLAC’s synchrotron radiation facility (SSRL) in which a 3 GeV electron beam is stored for user access. Typically the electron beam decays with a time constant of approximately 10hr due to electron lose. In order to replenish the lost electrons, a booster synchrotron is used to accelerate fresh electrons up to 3GeV for injection into SPEAR3. In order to maintain a constant electron beam current of 500mA, the injection process occurs at 5 minute intervals. At these times the booster synchrotron accelerates electrons for injection at a 10Hz rate. A 10Hzmore » 'injection ready' clock pulse train is generated when the booster synchrotron is operating. Between injection intervalswhere the booster is not running and hence the 10 Hz ‘injection ready’ signal is not present-a 10Hz clock is derived from the power line supplied by Pacific Gas and Electric (PG&E) to keep track of the injection timing. For this project I constructed a multiplexing circuit to 'switch' between the booster synchrotron 'injection ready' clock signal and PG&E based clock signal. The circuit uses digital IC components and is capable of making glitch-free transitions between the two clocks. This report details construction of a prototype multiplexing circuit including test results and suggests improvement opportunities for the final design.« less

Design and Evaluation of a Clock Multiplexing Circuit for the SSRL Booster Accelerator Timing System - Final Paper

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

Araya, Million

2015-08-21

SPEAR3 is a 234 m circular storage ring at SLAC’s synchrotron radiation facility (SSRL) in which a 3 GeV electron beam is stored for user access. Typically the electron beam decays with a time constant of approximately 10hr due to electron lose. In order to replenish the lost electrons, a booster synchrotron is used to accelerate fresh electrons up to 3GeV for injection into SPEAR3. In order to maintain a constant electron beam current of 500mA, the injection process occurs at 5 minute intervals. At these times the booster synchrotron accelerates electrons for injection at a 10Hz rate. A 10Hzmore » 'injection ready' clock pulse train is generated when the booster synchrotron is operating. Between injection intervals-where the booster is not running and hence the 10 Hz ‘injection ready’ signal is not present-a 10Hz clock is derived from the power line supplied by Pacific Gas and Electric (PG&E) to keep track of the injection timing. For this project I constructed a multiplexing circuit to 'switch' between the booster synchrotron 'injection ready' clock signal and PG&E based clock signal. The circuit uses digital IC components and is capable of making glitch-free transitions between the two clocks. This report details construction of a prototype multiplexing circuit including test results and suggests improvement opportunities for the final design.« less

Wireless Neural Recording With Single Low-Power Integrated Circuit

PubMed Central

Harrison, Reid R.; Kier, Ryan J.; Chestek, Cynthia A.; Gilja, Vikash; Nuyujukian, Paul; Ryu, Stephen; Greger, Bradley; Solzbacher, Florian; Shenoy, Krishna V.

2010-01-01

We present benchtop and in vivo experimental results from an integrated circuit designed for wireless implantable neural recording applications. The chip, which was fabricated in a commercially available 0.6-μm 2P3M BiCMOS process, contains 100 amplifiers, a 10-bit analog-to-digital converter (ADC), 100 threshold-based spike detectors, and a 902–928 MHz frequency-shift-keying (FSK) transmitter. Neural signals from a selected amplifier are sampled by the ADC at 15.7 kSps and telemetered over the FSK wireless data link. Power, clock, and command signals are sent to the chip wirelessly over a 2.765-MHz inductive (coil-to-coil) link. The chip is capable of operating with only two off-chip components: a power/command receiving coil and a 100-nF capacitor. PMID:19497825

Melatonin promotes circadian rhythm-induced proliferation through Clock/histone deacetylase 3/c-Myc interaction in mouse adipose tissue.

PubMed

Liu, Zhenjiang; Gan, Lu; Luo, Dan; Sun, Chao

2017-05-01

Melatonin is synthesized in the pineal gland and controls circadian rhythm of peripheral adipose tissue, resulting in changes in body weight. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms of circadian rhythm-mediated proliferation in adipose tissue is still limited. Here, we showed that melatonin (20 mg/kg/d) promoted circadian and proliferation processes in white adipose tissue. The circadian amplitudes of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1, P<.05) and circadian locomotor output cycles kaput (Clock, P<.05), period 2 (Per2, P<.05), cyclin E (P<.05), and c-Myc (P<.05) were directly increased by melatonin in adipose tissue. Melatonin also promoted cell cycle and increased cell numbers (P<.05), which was correlated with the Clock expression (P<.05). Further analysis demonstrated that Clock bound to the E-box elements in the promoter region of c-Myc and then directly stimulated c-Myc transcription. Moreover, Clock physically interacted with histone deacetylase 3 (HDAC3) and formed a complex with c-Myc to promote adipocyte proliferation. Melatonin also attenuated circadian disruption and promoted adipocyte proliferation in chronic jet-lagged mice and obese mice. Thus, our study found that melatonin promoted adipocyte proliferation by forming a Clock/HDAC3/c-Myc complex and subsequently driving the circadian amplitudes of proliferation genes. Our data reveal a novel mechanism that links circadian rhythm to cell proliferation in adipose tissue. These findings also identify a new potential means for melatonin to prevent and treat sleep deprivation-caused obesity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex

PubMed Central

Chun, Lauren E.; Hinds, Laura R.; Spencer, Robert L.

2016-01-01

Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation. PMID:26901093

Cryptochrome 2 expression level is critical for adrenocorticotropin stimulation of cortisol production in the capuchin monkey adrenal.

PubMed

Torres-Farfan, C; Abarzua-Catalan, L; Valenzuela, F J; Mendez, N; Richter, H G; Valenzuela, G J; Serón-Ferré, M

2009-06-01

Timely production of glucocorticoid hormones in response to ACTH is essential for survival by coordinating energy intake and expenditure and acting as homeostatic regulators against stress. Adrenal cortisol response to ACTH is clock time dependent, suggesting that an intrinsic circadian oscillator in the adrenal cortex contributes to modulate the response to ACTH. Circadian clock gene expression has been reported in the adrenal cortex of several species. However, there are no reports accounting for potential involvement of adrenal clock proteins on cortisol response to ACTH. Here we explored whether the clock protein cryptochrome 2 (CRY2) knockdown modifies the adrenal response to ACTH in a primate. Adrenal gland explants from adult capuchin monkey (n = 5) were preincubated for 6 h with transfection vehicle (control) or with two different Cry2 antisense and sense probes followed by 48 h incubation in medium alone (no ACTH) or with 100 nm ACTH. Under control and sense conditions, ACTH increased cortisol production, whereas CRY2 suppression inhibited ACTH-stimulated cortisol production. Expression of the steroidogenic enzymes steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase at 48 h of incubation was increased by ACTH in control explants and suppressed by Cry2 knockdown. Additionally, we found that Cry2 knockdown decreased the expression of the clock gene brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (Bmal1) at the mRNA and protein levels. Altogether these results strongly support that the clock protein CRY2 is involved in the mechanism by which ACTH increases the expression of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase. Thus, adequate expression levels of components of the adrenal circadian clock are required for an appropriate cortisol response to ACTH.

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

PubMed

Lelito, Katherine R; Shafer, Orie T

2012-04-01

The relatively simple clock neuron network of Drosophila is a valuable model system for the neuronal basis of circadian timekeeping. Unfortunately, many key neuronal classes of this network are inaccessible to electrophysiological analysis. We have therefore adopted the use of genetically encoded sensors to address the physiology of the fly's circadian clock network. Using genetically encoded Ca(2+) and cAMP sensors, we have investigated the physiological responses of two specific classes of clock neuron, the large and small ventrolateral neurons (l- and s-LN(v)s), to two neurotransmitters implicated in their modulation: acetylcholine (ACh) and γ-aminobutyric acid (GABA). Live imaging of l-LN(v) cAMP and Ca(2+) dynamics in response to cholinergic agonist and GABA application were well aligned with published electrophysiological data, indicating that our sensors were capable of faithfully reporting acute physiological responses to these transmitters within single adult clock neuron soma. We extended these live imaging methods to s-LN(v)s, critical neuronal pacemakers whose physiological properties in the adult brain are largely unknown. Our s-LN(v) experiments revealed the predicted excitatory responses to bath-applied cholinergic agonists and the predicted inhibitory effects of GABA and established that the antagonism of ACh and GABA extends to their effects on cAMP signaling. These data support recently published but physiologically untested models of s-LN(v) modulation and lead to the prediction that cholinergic and GABAergic inputs to s-LN(v)s will have opposing effects on the phase and/or period of the molecular clock within these critical pacemaker neurons.

The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light

PubMed Central

Ben-Moshe, Zohar; Alon, Shahar; Mracek, Philipp; Faigenbloom, Lior; Tovin, Adi; Vatine, Gad D.; Eisenberg, Eli; Foulkes, Nicholas S.; Gothilf, Yoav

2014-01-01

Light constitutes a primary signal whereby endogenous circadian clocks are synchronized (‘entrained’) with the day/night cycle. The molecular mechanisms underlying this vital process are known to require gene activation, yet are incompletely understood. Here, the light-induced transcriptome in the zebrafish central clock organ, the pineal gland, was characterized by messenger RNA (mRNA) sequencing (mRNA-seq) and microarray analyses, resulting in the identification of multiple light-induced mRNAs. Interestingly, a considerable portion of the molecular clock (14 genes) is light-induced in the pineal gland. Four of these genes, encoding the transcription factors dec1, reverbb1, e4bp4-5 and e4bp4-6, differentially affected clock- and light-regulated promoter activation, suggesting that light-input is conveyed to the core clock machinery via diverse mechanisms. Moreover, we show that dec1, as well as the core clock gene per2, is essential for light-entrainment of rhythmic locomotor activity in zebrafish larvae. Additionally, we used microRNA (miRNA) sequencing (miR-seq) and identified pineal-enhanced and light-induced miRNAs. One such miRNA, miR-183, is shown to downregulate e4bp4-6 mRNA through a 3′UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis. Together, this genome-wide approach and functional characterization of light-induced factors indicate a multi-level regulation of the circadian clockwork by light. PMID:24423866

Biochemical Frequency Control by Synchronisation of Coupled Repressilators: An In Silico Study of Modules for Circadian Clock Systems

PubMed Central

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

2011-01-01

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

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

PubMed

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

2015-07-10

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

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

PubMed Central

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

2015-01-01

Many cosmological observations point towards the existence of dark-matter(DM) particles and consider them as the main component of the matter content of the universe. The goal of revealing the nature of dark-matter has triggered the development of new, extremely sensitive detectors. It has been demonstrated that the frequencies and phases of optical clock have a transient shift during the DMs’ arrival due to the DM-SM(Standard Model) coupling. A simple, reliable and feasible experimental scheme is firstly proposed in this paper, based on “frequency-delay system” to search dark-matter by “self-frequency comparison” of an optical clock. During the arrival of a dark-matter, frequency discrepancy is expected between two signals with a short time difference(~ms) of the same optical clock to exhibit the interaction between atoms and dark-matter. Furthermore, this process can determine the exact position of dark-matter when it is crossing the optical clocks, therefore a network of detecting stations located in different places is recommended to reduce the misjudgment risk to an acceptable level. PMID:26159113

Multiple layers of posttranslational regulation refine circadian clock activity in Arabidopsis.

PubMed

Seo, Pil Joon; Mas, Paloma

2014-01-01

The circadian clock is a cellular time-keeper mechanism that regulates biological rhythms with a period of ~24 h. The circadian rhythms in metabolism, physiology, and development are synchronized by environmental cues such as light and temperature. In plants, proper matching of the internal circadian time with the external environment confers fitness advantages on plant survival and propagation. Accordingly, plants have evolved elaborated regulatory mechanisms that precisely control the circadian oscillations. Transcriptional feedback regulation of several clock components has been well characterized over the past years. However, the importance of additional regulatory mechanisms such as chromatin remodeling, protein complexes, protein phosphorylation, and stability is only starting to emerge. The multiple layers of circadian regulation enable plants to properly synchronize with the environmental cycles and to fine-tune the circadian oscillations. This review focuses on the diverse posttranslational events that regulate circadian clock function. We discuss the mechanistic insights explaining how plants articulate a high degree of complexity in their regulatory networks to maintain circadian homeostasis and to generate highly precise waveforms of circadian expression and activity.

Atomic Clock Based on Opto-Electronic Oscillator

NASA Technical Reports Server (NTRS)

Maleki, Lute; Yu, Nan

2005-01-01

A proposed highly accurate clock or oscillator would be based on the concept of an opto-electronic oscillator (OEO) stabilized to an atomic transition. Opto-electronic oscillators, which have been described in a number of prior NASA Tech Briefs articles, generate signals at frequencies in the gigahertz range characterized by high spectral purity but not by longterm stability or accuracy. On the other hand, the signals generated by previously developed atomic clocks are characterized by long-term stability and accuracy but not by spectral purity. The proposed atomic clock would provide high spectral purity plus long-term stability and accuracy a combination of characteristics needed to realize advanced developments in communications and navigation. In addition, it should be possible to miniaturize the proposed atomic clock. When a laser beam is modulated by a microwave signal and applied to a photodetector, the electrical output of the photodetector includes a component at the microwave frequency. In atomic clocks of a type known as Raman clocks or coherent-population-trapping (CPT) clocks, microwave outputs are obtained from laser beams modulated, in each case, to create two sidebands that differ in frequency by the amount of a hyperfine transition in the ground state of atoms of an element in vapor form in a cell. The combination of these sidebands produces a transparency in the population of a higher electronic level that can be reached from either of the two ground-state hyperfine levels by absorption of a photon. The beam is transmitted through the vapor to a photodetector. The components of light scattered or transmitted by the atoms in the two hyperfine levels mix in the photodetector and thereby give rise to a signal at the hyperfine- transition frequency. The proposed atomic clock would include an OEO and a rubidium- or cesium- vapor cell operating in the CPT/Raman regime (see figure). In the OEO portion of this atomic clock, as in a typical prior OEO, a laser beam would pass through an electro-optical modulator, the modulated beam would be fed into a fiber-optic delay line, and the delayed beam would be fed to a photodetector. The electrical output of the photodetector would be detected, amplified, filtered, and fed back to the microwave input port of the modulator. The laser would be chosen to have the same wavelength as that of the pertinent ground-state/higher-state transition of the atoms in the vapor. The modulator/ filter combination would be designed to operate at the microwave frequency of the hyperfine transition. Part of the laser beam would be tapped from the fiberoptic loop of the OEO and introduced into the vapor cell. After passing through the cell, this portion of the beam would be detected differentially with a tapped portion of the fiber-optically-delayed beam. The electrical output of the photodetector would be amplified and filtered in a loop that would control a DC bias applied to the modulator. In this manner, the long-term stability and accuracy of the atomic transition would be transferred to the OEO.

Circadian rhythms regulate amelogenesis.

PubMed

Zheng, Li; Seon, Yoon Ji; Mourão, Marcio A; Schnell, Santiago; Kim, Doohak; Harada, Hidemitsu; Papagerakis, Silvana; Papagerakis, Petros

2013-07-01

Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization. Copyright © 2013 Elsevier Inc. All rights reserved.

Blue Light- and Low Temperature-Regulated COR27 and COR28 Play Roles in the Arabidopsis Circadian Clock.

PubMed

Li, Xu; Ma, Dingbang; Lu, Sheen X; Hu, Xinyi; Huang, Rongfeng; Liang, Tong; Xu, Tongda; Tobin, Elaine M; Liu, Hongtao

2016-11-01

Light and temperature are two key environmental signals that profoundly affect plant growth and development, but underlying molecular mechanisms of how light and temperature signals affect the circadian clock are largely unknown. Here, we report that COR27 and COR28 are regulated not only by low temperatures but also by light signals. COR27 and COR28 are negative regulators of freezing tolerance but positive regulators of flowering, possibly representing a trade-off between freezing tolerance and flowering. Furthermore, loss-of-function mutations in COR27 and COR28 result in period lengthening of various circadian output rhythms and affect central clock gene expression. Also, the cor27 cor28 double mutation affects the pace of the circadian clock. Additionally, COR27 and COR28 are direct targets of CCA1, which represses their transcription via chromatin binding. Finally, we report that COR27 and COR28 bind to the chromatin of TOC1 and PRR5 to repress their transcription, suggesting that their effects on rhythms are in part due to their regulation of TOC1 and PRR5 These data demonstrate that blue light and low temperature-regulated COR27 and COR28 regulate the circadian clock as well as freezing tolerance and flowering time. © 2016 American Society of Plant Biologists. All rights reserved.

Involvement of circadian clock in crowing of red jungle fowls (Gallus gallus).

PubMed

Ito, Shuichi; Hori, Shuho; Hirose, Makiko; Iwahara, Mari; Yatsushiro, Azusa; Matsumoto, Atsushi; Tanaka, Masayuki; Okamoto, Chinobu; Yayou, Ken-Ichi; Shimmura, Tsuyoshi

2017-04-01

The rhythmic locomotor behavior of flies and mice provides a phenotype for the identification of clock genes, and the underlying molecular mechanism is well studied. However, interestingly, when examining locomotor rhythm in the wild, several key laboratory-based assumptions on circadian behavior are not supported in natural conditions. The rooster crowing 'cock-a-doodle-doo' is a symbol of the break of dawn in many countries. Previously, we used domestic inbred roosters and showed that the timing of roosters' crowing is regulated by the circadian clock under laboratory conditions. However, it is still unknown whether the regulation of crowing by circadian clock is observed under natural conditions. Therefore, here we used red jungle fowls and first confirmed that similar crowing rhythms with domesticated chickens are observed in red jungle fowls under the laboratory conditions. Red jungle fowls show predawn crowing before light onset under 12:12 light : dim light conditions and the free-running rhythm of crowing under total dim light conditions. We next examined the crowing rhythms under semi-wild conditions. Although the crowing of red jungle fowls changed seasonally under semi-wild conditions, predawn crowing was observed before sunrise in all seasons. This evidence suggests that seasonally changed crowing of red jungle fowls is under the control of a circadian clock. © 2016 Japanese Society of Animal Science.

Performance Analysis of Beidou-2/Beidou-3e Combined Solution with Emphasis on Precise Orbit Determination and Precise Point Positioning

PubMed Central

Xu, Xiaolong; Li, Min; Li, Wenwen; Liu, Jingnan

2018-01-01

In 2015, the plan for global coverage by the Chinese BeiDou Navigation Satellite System was launched. Five global BeiDou experimental satellites (BeiDou-3e) are in orbit for testing. To analyze the performances of precise orbit determination (POD) and precise point positioning (PPP) of onboard BeiDou satellites, about two months of data from 24 tracking stations were used. According to quality analysis of BeiDou-2/BeiDou-3e data, there is no satellite-induced code bias in BeiDou-3e satellites, which has been found in BeiDou-2 satellites. This phenomenon indicates that the quality issues of pseudorange data in BeiDou satellites have been solved well. POD results indicate that the BeiDou-3e orbit precision is comparable to that of BeiDou-2 satellites. The ambiguity fixed solution improved the orbit consistency of inclined geosynchronous orbit satellites in along-track and cross-track directions, but had little effect in the radial direction. Satellite laser ranging of BeiDou-3e medium Earth orbit satellites (MEOs) achieved a standard deviation of about 4 cm. Differences in clock offset series after the removal of reference clock in overlapping arcs were used to assess clock quality, and standard deviation of clock offset could reach 0.18 ns on average, which was in agreement with the orbit precision. For static PPP, when BeiDou-3e satellites were included, the positioning performance for horizontal components was improved slightly. For kinematic PPP, when global positioning satellites (GPS) were combined with BeiDou-2 and BeiDou-3e satellites, the convergence time was 13.5 min with a precision of 2–3 cm for horizontal components, and 3–4 cm for the vertical component. PMID:29304000

Involvement of the Clock Gene Rev-erb alpha in the Regulation of Glucagon Secretion in Pancreatic Alpha-Cells

PubMed Central

Vieira, Elaine; Marroquí, Laura; Figueroa, Ana Lucia C.; Merino, Beatriz; Fernandez-Ruiz, Rebeca; Nadal, Angel; Burris, Thomas P.; Gomis, Ramon; Quesada, Ivan

2013-01-01

Disruption of pancreatic clock genes impairs pancreatic beta-cell function, leading to the onset of diabetes. Despite the importance of pancreatic alpha-cells in the regulation of glucose homeostasis and in diabetes pathophysiology, nothing is known about the role of clock genes in these cells. Here, we identify the clock gene Rev-erb alpha as a new intracellular regulator of glucagon secretion. Rev-erb alpha down-regulation by siRNA (60–70% inhibition) in alphaTC1-9 cells inhibited low-glucose induced glucagon secretion (p<0.05) and led to a decrease in key genes of the exocytotic machinery. The Rev-erb alpha agonist GSK4112 increased glucagon secretion (1.6 fold) and intracellular calcium signals in alphaTC1-9 cells and mouse primary alpha-cells, whereas the Rev-erb alpha antagonist SR8278 produced the opposite effect. At 0.5 mM glucose, alphaTC1-9 cells exhibited intrinsic circadian Rev-erb alpha expression oscillations that were inhibited by 11 mM glucose. In mouse primary alpha-cells, glucose induced similar effects (p<0.001). High glucose inhibited key genes controlled by AMPK such as Nampt, Sirt1 and PGC-1 alpha in alphaTC1-9 cells (p<0.05). AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha. Nampt inhibition decreased Sirt1, PGC-1 alpha and Rev-erb alpha mRNA expression (p<0.01) and glucagon release (p<0.05). These findings identify Rev-erb alpha as a new intracellular regulator of glucagon secretion via AMPK/Nampt/Sirt1 pathway. PMID:23936124

Design concept for the microwave interrogation structure in PARCS

NASA Technical Reports Server (NTRS)

Dick, G. J.; Klipstein, W. M.; Heavner, T. P.; Jefferts, S. R.

2002-01-01

In this paper we will describe key aspects of the conceptual design of the microwave interrogation structure in the laser-cooled cesium frequency standard that is part of the Primary Atomic Reference Clock in Space (PARCS) experiment.

Entropy-as-a-Service: Unlocking the Full Potential of Cryptography.

PubMed

Vassilev, Apostol; Staples, Robert

2016-09-01

Securing the Internet requires strong cryptography, which depends on the availability of good entropy for generating unpredictable keys and accurate clocks. Attacks abusing weak keys or old inputs portend challenges for the Internet. EaaS is a novel architecture providing entropy and timestamps from a decentralized root of trust, scaling gracefully across diverse geopolitical locales and remaining trustworthy unless much of the collective is compromised.

Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock.

PubMed

Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

2017-01-30

Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit.

Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock

PubMed Central

Sabado, Virginie; Vienne, Ludovic; Nunes, José Manuel; Rosbash, Michael; Nagoshi, Emi

2017-01-01

Circadian locomotor behaviour is controlled by a pacemaker circuit composed of clock-containing neurons. To interrogate the mechanistic relationship between the molecular clockwork and network communication critical to the operation of the Drosophila circadian pacemaker circuit, we established new fluorescent circadian reporters that permit single-cell recording of transcriptional and post-transcriptional rhythms in brain explants and cultured neurons. Live-imaging experiments combined with pharmacological and genetic manipulations demonstrate that the neuropeptide pigment-dispersing factor (PDF) amplifies the molecular rhythms via time-of-day- and activity-dependent upregulation of transcription from E-box-containing clock gene promoters within key pacemaker neurons. The effect of PDF on clock gene transcription and the known role of PDF in enhancing PER/TIM stability occur via independent pathways downstream of the PDF receptor, the former through a cAMP-independent mechanism and the latter through a cAMP-PKA dependent mechanism. These results confirm and extend the mechanistic understanding of the role of PDF in controlling the synchrony of the pacemaker neurons. More broadly, our results establish the utility of the new live-imaging tools for the study of molecular-neural interactions important for the operation of the circadian pacemaker circuit. PMID:28134281

Enhancing Kondo coupling in alkaline-earth-metal atomic gases with confinement-induced resonances in mixed dimensions

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Circadian redox signaling in plant immunity and abiotic stress.

PubMed

Spoel, Steven H; van Ooijen, Gerben

2014-06-20

Plant crops are critically important to provide quality food and bio-energy to sustain a growing human population. Circadian clocks have been shown to deliver an adaptive advantage to plants, vastly increasing biomass production by efficient anticipation to the solar cycle. Plant stress, on the other hand, whether biotic or abiotic, prevents crops from reaching maximum productivity. Stress is associated with fluctuations in cellular redox and increased phytohormone signaling. Recently, direct links between circadian timekeeping, redox fluctuations, and hormone signaling have been identified. A direct implication is that circadian control of cellular redox homeostasis influences how plants negate stress to ensure growth and reproduction. Complex cellular biochemistry leads from perception of stress via hormone signals and formation of reactive oxygen intermediates to a physiological response. Circadian clocks and metabolic pathways intertwine to form a confusing biochemical labyrinth. Here, we aim to find order in this complex matter by reviewing current advances in our understanding of the interface between these networks. Although the link is now clearly defined, at present a key question remains as to what extent the circadian clock modulates redox, and vice versa. Furthermore, the mechanistic basis by which the circadian clock gates redox- and hormone-mediated stress responses remains largely elusive.

Mutations in EID1 and LNK2 caused light-conditional clock deceleration during tomato domestication.

PubMed

Müller, Niels A; Zhang, Lei; Koornneef, Maarten; Jiménez-Gómez, José M

2018-05-22

Circadian period and phase of cultivated tomato ( Solanum lycopersicum ) were changed during domestication, likely adapting the species to its new agricultural environments. Whereas the delayed circadian phase is mainly caused by allelic variation of EID1 , the genetic basis of the long circadian period has remained elusive. Here we show that a partial deletion of the clock gene LNK2 is responsible for the period lengthening in cultivated tomatoes. We use resequencing data to phylogenetically classify hundreds of tomato accessions and investigate the evolution of the eid1 and lnk2 mutations along successive domestication steps. We reveal signatures of selection across the genomic region of LNK2 and different patterns of fixation of the mutant alleles. Strikingly, LNK2 and EID1 are both involved in light input to the circadian clock, indicating that domestication specifically targeted this input pathway. In line with this, we show that the clock deceleration in the cultivated tomato is light-dependent and requires the phytochrome B1 photoreceptor. Such conditional variation in circadian rhythms may be key for latitudinal adaptation in a variety of species, including crop plants and livestock.

Field test of quantum key distribution in the Tokyo QKD Network.

PubMed

Sasaki, M; Fujiwara, M; Ishizuka, H; Klaus, W; Wakui, K; Takeoka, M; Miki, S; Yamashita, T; Wang, Z; Tanaka, A; Yoshino, K; Nambu, Y; Takahashi, S; Tajima, A; Tomita, A; Domeki, T; Hasegawa, T; Sakai, Y; Kobayashi, H; Asai, T; Shimizu, K; Tokura, T; Tsurumaru, T; Matsui, M; Honjo, T; Tamaki, K; Takesue, H; Tokura, Y; Dynes, J F; Dixon, A R; Sharpe, A W; Yuan, Z L; Shields, A J; Uchikoga, S; Legré, M; Robyr, S; Trinkler, P; Monat, L; Page, J-B; Ribordy, G; Poppe, A; Allacher, A; Maurhart, O; Länger, T; Peev, M; Zeilinger, A

2011-05-23

A secure communication network with quantum key distribution in a metropolitan area is reported. Six different QKD systems are integrated into a mesh-type network. GHz-clocked QKD links enable us to demonstrate the world-first secure TV conferencing over a distance of 45km. The network includes a commercial QKD product for long-term stable operation, and application interface to secure mobile phones. Detection of an eavesdropper, rerouting into a secure path, and key relay via trusted nodes are demonstrated in this network.

Blocking synaptic transmission with tetanus toxin light chain reveals modes of neurotransmission in the PDF-positive circadian clock neurons of Drosophila melanogaster.

PubMed

Umezaki, Yujiro; Yasuyama, Kouji; Nakagoshi, Hideki; Tomioka, Kenji

2011-09-01

Circadian locomotor rhythms of Drosophila melanogaster are controlled by a neuronal circuit composed of approximately 150 clock neurons that are roughly classified into seven groups. In the circuit, a group of neurons expressing pigment-dispersing factor (PDF) play an important role in organizing the pacemaking system. Recent studies imply that unknown chemical neurotransmitter(s) (UNT) other than PDF is also expressed in the PDF-positive neurons. To explore its role in the circadian pacemaker, we examined the circadian locomotor rhythms of pdf-Gal4/UAS-TNT transgenic flies in which chemical synaptic transmission in PDF-positive neurons was blocked by expressed tetanus toxin light chain (TNT). In constant darkness (DD), the flies showed a free-running rhythm, which was similar to that of wild-type flies but significantly different from pdf null mutants. Under constant light conditions (LL), however, they often showed complex rhythms with a short period and a long period component. The UNT is thus likely involved in the synaptic transmission in the clock network and its release caused by LL leads to arrhythmicity. Immunocytochemistry revealed that LL induced phase separation in TIMELESS (TIM) cycling among some of the PDF-positive and PDF-negative clock neurons in the transgenic flies. These results suggest that both PDF and UNT play important roles in the Drosophila circadian clock, and activation of PDF pathway alone by LL leads to the complex locomotor rhythm through desynchronized oscillation among some of the clock neurons. Copyright © 2011 Elsevier Ltd. All rights reserved.

Drosophila TIM binds importin α1, and acts as an adapter to transport PER to the nucleus.

PubMed

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

2015-02-01

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

CULLIN-3 Controls TIMELESS Oscillations in the Drosophila Circadian Clock

PubMed Central

Lamouroux, Annie; Chélot, Elisabeth; Rouyer, François

2012-01-01

Eukaryotic circadian clocks rely on transcriptional feedback loops. In Drosophila, the PERIOD (PER) and TIMELESS (TIM) proteins accumulate during the night, inhibit the activity of the CLOCK (CLK)/CYCLE (CYC) transcriptional complex, and are degraded in the early morning. The control of PER and TIM oscillations largely depends on post-translational mechanisms. They involve both light-dependent and light-independent pathways that rely on the phosphorylation, ubiquitination, and proteasomal degradation of the clock proteins. SLMB, which is part of a CULLIN-1-based E3 ubiquitin ligase complex, is required for the circadian degradation of phosphorylated PER. We show here that CULLIN-3 (CUL-3) is required for the circadian control of PER and TIM oscillations. Expression of either Cul-3 RNAi or dominant negative forms of CUL-3 in the clock neurons alters locomotor behavior and dampens PER and TIM oscillations in light-dark cycles. In constant conditions, CUL-3 deregulation induces behavioral arrhythmicity and rapidly abolishes TIM cycling, with slower effects on PER. CUL-3 affects TIM accumulation more strongly in the absence of PER and forms protein complexes with hypo-phosphorylated TIM. In contrast, SLMB affects TIM more strongly in the presence of PER and preferentially associates with phosphorylated TIM. CUL-3 and SLMB show additive effects on TIM and PER, suggesting different roles for the two ubiquitination complexes on PER and TIM cycling. This work thus shows that CUL-3 is a new component of the Drosophila clock, which plays an important role in the control of TIM oscillations. PMID:22879814

Compact Optical Atomic Clock Based on a Two-Photon Transition in Rubidium

NASA Astrophysics Data System (ADS)

Martin, Kyle W.; Phelps, Gretchen; Lemke, Nathan D.; Bigelow, Matthew S.; Stuhl, Benjamin; Wojcik, Michael; Holt, Michael; Coddington, Ian; Bishop, Michael W.; Burke, John H.

2018-01-01

Extralaboratory atomic clocks are necessary for a wide array of applications (e.g., satellite-based navigation and communication). Building upon existing vapor-cell and laser technologies, we describe an optical atomic clock, designed around a simple and manufacturable architecture, that utilizes the 778-nm two-photon transition in rubidium and yields fractional-frequency instabilities of 4 ×10-13/√{τ (s ) } for τ from 1 to 10 000 s. We present a complete stability budget for this system and explore the required conditions under which a fractional-frequency instability of 1 ×10-15 can be maintained on long time scales. We provide a precise characterization of the leading sensitivities to external processes, including magnetic fields and fluctuations of the vapor-cell temperature and 778-nm laser power. The system is constructed primarily from commercially available components, an attractive feature from the standpoint of the commercialization and deployment of optical frequency standards.

BMAL1-dependent regulation of the mTOR signaling pathway delays aging

PubMed Central

Khapre, Rohini V.; Kondratova, Anna A.; Patel, Sonal; Dubrovsky, Yuliya; Wrobel, Michelle; Antoch, Marina P.; Kondratov, Roman V.

2014-01-01

The circadian clock, an internal time-keeping system, has been linked with control of aging, but molecular mechanisms of regulation are not known. BMAL1 is a transcriptional factor and core component of the circadian clock; BMAL1 deficiency is associated with premature aging and reduced lifespan. Here we report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is increased upon BMAL1 deficiency both in vivo and in cell culture. Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1−/− mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1 signaling. We propose that the circadian clock controls the activity of the mTOR pathway through BMAL1-dependent mechanisms and this regulation is important for control of aging and metabolism. PMID:24481314

BMAL1-dependent regulation of the mTOR signaling pathway delays aging.

PubMed

Khapre, Rohini V; Kondratova, Anna A; Patel, Sonal; Dubrovsky, Yuliya; Wrobel, Michelle; Antoch, Marina P; Kondratov, Roman V

2014-01-01

The circadian clock, an internal time-keeping system, has been linked with control of aging, but molecular mechanisms of regulation are not known. BMAL1 is a transcriptional factor and core component of the circadian clock; BMAL1 deficiency is associated with premature aging and reduced lifespan. Here we report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is increased upon BMAL1 deficiency both in vivo and in cell culture. Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1-/- mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1 signaling. We propose that the circadian clock controls the activity of the mTOR pathway through BMAL1-dependent mechanisms and this regulation is important for control of aging and metabolism.

Mapping the core of the Arabidopsis circadian clock defines the network structure of the oscillator.

PubMed

Huang, W; Pérez-García, P; Pokhilko, A; Millar, A J; Antoshechkin, I; Riechmann, J L; Mas, P

2012-04-06

In many organisms, the circadian clock is composed of functionally coupled morning and evening oscillators. In Arabidopsis, oscillator coupling relies on a core loop in which the evening oscillator component TIMING OF CAB EXPRESSION 1 (TOC1) was proposed to activate a subset of morning-expressed oscillator genes. Here, we show that TOC1 does not function as an activator but rather as a general repressor of oscillator gene expression. Repression occurs through TOC1 rhythmic association to the promoters of the oscillator genes. Hormone-dependent induction of TOC1 and analysis of RNA interference plants show that TOC1 prevents the activation of morning-expressed genes at night. Our study overturns the prevailing model of the Arabidopsis circadian clock, showing that the morning and evening oscillator loops are connected through the repressing activity of TOC1.

Laser Cooled Atomic Clocks in Space

NASA Technical Reports Server (NTRS)

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

2000-01-01

The goals of the Glovebox Laser-cooled Atomic Clock Experiment (GLACE) are: (1) first utilization of tunable, frequency-stabilized lasers in space, (2) demonstrate laser cooling and trapping in microgravity, (3) demonstrate longest 'perturbation-free' interaction time for a precision measurement on neutral atoms, (4) Resolve Ramsey fringes 2-10 times narrower than achievable on Earth. The approach taken is: the use of COTS components, and the utilization of prototype hardware from LCAP flight definition experiments. The launch date is scheduled for Oct. 2002. The Microgravity Science Glovebox (MSG) specifications are reviewed, and a picture of the MSG is shown.

Optical interconnections and networks; Proceedings of the Meeting, The Hague, Netherlands, Mar. 14, 15, 1990

NASA Technical Reports Server (NTRS)

Bartelt, Hartmut (Editor)

1990-01-01

The conference presents papers on interconnections, clock distribution, neural networks, and components and materials. Particular attention is given to a comparison of optical and electrical data interconnections at the board and backplane levels, a wafer-level optical interconnection network layout, an analysis and simulation of photonic switch networks, and the integration of picosecond GaAs photoconductive devices with silicon circuits for optical clocking and interconnects. Consideration is also given to the optical implementation of neural networks, invariance in an optoelectronic implementation of neural networks, and the recording of reversible patterns in polymer lightguides.

Proceedings of the Annual Precise Time and Time Interval (PTTI) Applications and Planning Meeting (15th) Held at Washington, DC on 6-8 December 1983,

DTIC Science & Technology

1984-04-02

clock is an absolute technique with a 14 0 • ,4 precision of about 0.1 )us The results of the portable clock experiment indicate that LF sync...also gains direct access to the U. S. primary frequency standard, NBS-6. Access to1 BS-6 makes it possible to set an absolute limit of one part in 10...of the components in these equations are uncorrelated we may take vari- ances of each of these equations and the cross terms will average to zero 117

Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype.

PubMed

Samsa, William E; Vasanji, Amit; Midura, Ronald J; Kondratov, Roman V

2016-03-01

The circadian clock is an endogenous time keeping system that controls the physiology and behavior of many organisms. The transcription factor Brain and Muscle ARNT-like Protein 1 (BMAL1) is a component of the circadian clock and necessary for clock function. Bmal1(-/-) mice display accelerated aging and many accompanying age associated pathologies. Here, we report that mice deficient for BMAL1 have a low bone mass phenotype that is absent at birth and progressively worsens over their lifespan. Accelerated aging of these mice is associated with the formation of bony bridges occurring across the metaphysis to the epiphysis, resulting in shorter long bones. Using micro-computed tomography we show that Bmal1(-/-) mice have reductions in cortical and trabecular bone volume and other micro-structural parameters and a lower bone mineral density. Histology shows a deficiency of BMAL1 results in a reduced number of active osteoblasts and osteocytes in vivo. Isolation of bone marrow derived mesenchymal stem cells from Bmal1(-/-) mice demonstrate a reduced ability to differentiate into osteoblasts in vitro, which likely explains the observed reductions in osteoblasts and osteocytes, and may contribute to the observed osteopenia. Our data support the role of the circadian clock in the regulation of bone homeostasis and shows that BMAL1 deficiency results in a low bone mass phenotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Deficiency of Circadian Clock Protein BMAL1 in Mice Results in a Low Bone Mass Phenotype

PubMed Central

Samsa, William E.; Vasanji, Amit; Midura, Ronald J.; Kondratov, Roman V.

2016-01-01

The circadian clock is an endogenous time keeping system that controls the physiology and behavior of many organisms. The transcription factor Brain and Muscle ARNT-like Protein 1 (BMAL1) is a component of the circadian clock and necessary for clock function. Bmal1−/− mice display accelerated aging and many accompanying age associated pathologies. Here, we report that mice deficient for BMAL1 have a low bone mass phenotype that is absent at birth and progressively worsens over their lifespan. Accelerated aging of these mice is associated with the formation of bony bridges occurring across the metaphysis to the epiphysis, resulting in shorter long bones. Using micro-computed tomography we show that Bmal1−/− mice have reductions in cortical and trabecular bone volume and other micro-structural parameters and a lower bone mineral density. Histology shows a deficiency of BMAL1 results in a reduced number of active osteoblasts and osteocytes in vivo. Isolation of bone marrow derived mesenchymal stem cells from Bmal1−/− mice demonstrate a reduced ability to differentiate into osteoblasts in vitro, which likely explains the observed reductions in osteoblasts and osteocytes, and may contribute to the observed osteopenia. Our data support the role of the circadian clock in the regulation of bone homeostasis and shows that BMAL1 deficiency results in a low bone mass phenotype. PMID:26789548

Effects of caffeine on circadian phase, amplitude and period evaluated in cells in vitro and peripheral organs in vivo in PER2::LUCIFERASE mice

PubMed Central

Narishige, Seira; Kuwahara, Mari; Shinozaki, Ayako; Okada, Satoshi; Ikeda, Yuko; Kamagata, Mayo; Tahara, Yu; Shibata, Shigenobu

2014-01-01

Background and Purpose Caffeine is one of the most commonly used psychoactive substances. Circadian rhythms consist of the main suprachiasmatic nucleus (SCN) clocks and peripheral clocks. Although caffeine lengthens circadian rhythms and modifies phase changes in SCN-operated rhythms, the effects on caffeine on the phase, period and amplitude of peripheral organ clocks are not known. In addition, the role of cAMP/Ca2+ signalling in effects of caffeine on rhythm has not been fully elucidated. Experimental Approach We examined whether chronic or transient application of caffeine affects circadian period/amplitude and phase by evaluating bioluminescence rhythm in PER2::LUCIFERASE knock-in mice. Circadian rhythms were monitored in vitro using fibroblasts and ex vivo and in vivo for monitoring of peripheral clocks. Key Results Chronic application of caffeine (0.1–10 mM) increased period and amplitude in vitro. Transient application of caffeine (10 mM) near the bottom of the decreasing phase of bioluminescence rhythm caused phase advance in vitro. Caffeine (0.1%) intake caused a phase delay under light–dark or constant dark conditions, suggesting a period-lengthening effect in vivo. Caffeine (20 mg·kg−1) at daytime or at late night-time caused phase advance or delay in bioluminescence rhythm in the liver and kidney respectively. The complicated roles of cAMP/Ca2+ signalling may be involved in the caffeine-induced increase of period and amplitude in vitro. Conclusions and Implications Caffeine affects circadian rhythm in mice by lengthening the period and causing a phase shift of peripheral clocks. These results suggest that caffeine intake with food/drink may help with food-induced resetting of peripheral circadian clocks. PMID:25160990

Transcriptional regulation of arylalkylamine-N-acetyltransferase-2 gene in the pineal gland of the gilthead seabream.

PubMed

Zilberman-Peled, B; Appelbaum, L; Vallone, D; Foulkes, N S; Anava, S; Anzulovich, A; Coon, S L; Klein, D C; Falcón, J; Ron, B; Gothilf, Y

2007-01-01

Pineal serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase; AANAT) is considered the key enzyme in the generation of circulating melatonin rhythms; the rate of melatonin production is determined by AANAT activity. In all the examined species, AANAT activity is regulated at the post-translational level and, to a variable degree, also at the transcriptional level. Here, the transcriptional regulation of pineal aanat (aanat2) of the gilthead seabream (Sparus aurata) was investigated. Real-time polymerase chain reaction quantification of aanat2 mRNA levels in the pineal gland collected throughout the 24-h cycle revealed a rhythmic expression pattern. In cultured pineal glands, the amplitude was reduced, but the daily rhythmic expression pattern was maintained under constant illumination, indicating a circadian clock-controlled regulation of seabream aanat2. DNA constructs were prepared in which green fluorescent protein was driven by the aanat2 promoters of seabream and Northern pike. In vivo transient expression analyses in zebrafish embryos indicated that these promoters contain the necessary elements to drive enhanced expression in the pineal gland. In the light-entrainable clock-containing PAC-2 zebrafish cell line, a stably transfected seabream aanat2 promoter-luciferase DNA construct exhibited a clock-controlled circadian rhythm of luciferase activity, characteristic for an E-box-driven expression. In NIH-3T3 cells, the seabream aanat2 promoter was activated by a synergistic action of BMAL/CLOCK and orthodenticle homeobox 5 (OTX5). Promoter sequence analyses revealed the presence of the photoreceptor conserved element and an extended E-box (i.e. the binding sites for BMAL/CLOCK and OTX5 that have been previously associated with pineal-specific and rhythmic gene expression). These results suggest that seabream aanat2 is a clock-controlled gene that is regulated by conserved mechanisms.

Redox regulation and pro-oxidant reactions in the physiology of circadian systems.

PubMed

Méndez, Isabel; Vázquez-Martínez, Olivia; Hernández-Muñoz, Rolando; Valente-Godínez, Héctor; Díaz-Muñoz, Mauricio

2016-05-01

Rhythms of approximately 24 h are pervasive in most organisms and are known as circadian. There is a molecular circadian clock in each cell sustained by a feedback system of interconnected "clock" genes and transcription factors. In mammals, the timing system is formed by a central pacemaker, the suprachiasmatic nucleus, in coordination with a collection of peripheral oscillators. Recently, an extensive interconnection has been recognized between the molecular circadian clock and the set of biochemical pathways that underlie the bioenergetics of the cell. A principle regulator of metabolic networks is the flow of electrons between electron donors and acceptors. The concomitant reduction and oxidation (redox) reactions directly influence the balance between anabolic and catabolic processes. This review summarizes and discusses recent findings concerning the mutual and dynamic interactions between the molecular circadian clock, redox reactions, and redox signaling. The scope includes the regulatory role played by redox coenzymes (NAD(P)+/NAD(P)H, GSH/GSSG), reactive oxygen species (superoxide anion, hydrogen peroxide), antioxidants (melatonin), and physiological events that modulate the redox state (feeding condition, circadian rhythms) in determining the timing capacity of the molecular circadian clock. In addition, we discuss a purely metabolic circadian clock, which is based on the redox enzymes known as peroxiredoxins and is present in mammalian red blood cells and in other biological systems. Both the timing system and the metabolic network are key to a better understanding of widespread pathological conditions such as the metabolic syndrome, obesity, and diabetes. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

PubMed

Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

Altered Dynamics in the Circadian Oscillation of Clock Genes in Dermal Fibroblasts of Patients Suffering from Idiopathic Hypersomnia

PubMed Central

Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues – mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep – wake rhythms in IH. PMID:24454829

Circadian control of p75 neurotrophin receptor leads to alternate activation of Nrf2 and c-Rel to reset energy metabolism in astrocytes via brain-derived neurotrophic factor.

PubMed

Ishii, Tetsuro; Warabi, Eiji; Mann, Giovanni E

2018-05-01

Circadian clock genes regulate energy metabolism partly through neurotrophins in the body. The low affinity neurotrophin receptor p75 NTR is a clock component directly regulated by the transcriptional factor Clock:Bmal1 complex. Brain-derived neurotrophic factor (BDNF) is expressed in the brain and plays a key role in coordinating metabolic interactions between neurons and astrocytes. BDNF transduces signals through TrkB and p75 NTR receptors. This review highlights a novel molecular mechanism by which BDNF via circadian control of p75 NTR leads to daily resetting of glucose and glycogen metabolism in brain astrocytes to accommodate their functional interaction with neurons. Astrocytes store glycogen as an energy reservoir to provide active neurons with the glycolytic metabolite lactate. Astrocytes predominantly express the truncated receptor TrkB.T1 which lacks an intracellular receptor tyrosine kinase domain. TrkB.T1 retains the capacity to regulate cell morphology through regulation of Rho GTPases. In contrast, p75 NTR mediates generation of the bioactive lipid ceramide upon stimulation with BDNF and inhibits PKA activation. As ceramide directly activates PKCζ, we discuss the importance of the TrkB.T1-p75 NTR -ceramide-PKCζ signaling axis in the stimulation of glycogen and lipid synthesis and activation of RhoA. Ceramide-PKCζ-casein kinase 2 signaling activates Nrf2 to support oxidative phosphorylation via upregulation of antioxidant enzymes. In the absence of p75 NTR , TrkB.T1 functionally interacts with adenosine A 2A R and dopamine D1R receptors to enhance cAMP-PKA signaling and activate Rac1 and NF-κB c-Rel, favoring glycogen hydrolysis, gluconeogenesis and aerobic glycolysis. Thus, diurnal changes in p75 NTR levels in astrocytes resets energy metabolism via BDNF to accommodate their metabolic interaction with neurons. Copyright © 2018 Elsevier Inc. All rights reserved.

Circadian rhythms, Wnt/beta-catenin pathway and PPAR alpha/gamma profiles in diseases with primary or secondary cardiac dysfunction

PubMed Central

Lecarpentier, Yves; Claes, Victor; Duthoit, Guillaume; Hébert, Jean-Louis

2014-01-01

Circadian clock mechanisms are far-from-equilibrium dissipative structures. Peroxisome proliferator-activated receptors (PPAR alpha, beta/delta, and gamma) play a key role in metabolic regulatory processes, particularly in heart muscle. Links between circadian rhythms (CRs) and PPARs have been established. Mammalian CRs involve at least two critical transcription factors, CLOCK and BMAL1 (Gekakis et al., 1998; Hogenesch et al., 1998). PPAR gamma plays a major role in both glucose and lipid metabolisms and presents circadian properties which coordinate the interplay between metabolism and CRs. PPAR gamma is a major component of the vascular clock. Vascular PPAR gamma is a peripheral regulator of cardiovascular rhythms controlling circadian variations in blood pressure and heart rate through BMAL1. We focused our review on diseases with abnormalities of CRs and with primary or secondary cardiac dysfunction. Moreover, these diseases presented changes in the Wnt/beta-catenin pathway and PPARs, according to two opposed profiles. Profile 1 was defined as follows: inactivation of the Wnt/beta-catenin pathway with increased expression of PPAR gamma. Profile 2 was defined as follows: activation of the Wnt/beta-catenin pathway with decreased expression of PPAR gamma. A typical profile 1 disease is arrhythmogenic right ventricular cardiomyopathy, a genetic cardiac disease which presents mutations of the desmosomal proteins and is mainly characterized by fatty acid accumulation in adult cardiomyocytes mainly in the right ventricle. The link between PPAR gamma dysfunction and desmosomal genetic mutations occurs via inactivation of the Wnt/beta-catenin pathway presenting oscillatory properties. A typical profile 2 disease is type 2 diabetes, with activation of the Wnt/beta-catenin pathway and decreased expression of PPAR gamma. CRs abnormalities are present in numerous pathologies such as cardiovascular diseases, sympathetic/parasympathetic dysfunction, hypertension, diabetes, neurodegenerative diseases, cancer which are often closely inter-related. PMID:25414671

Real-Time PPP Based on the Coupling Estimation of Clock Bias and Orbit Error with Broadcast Ephemeris.

PubMed

Pan, Shuguo; Chen, Weirong; Jin, Xiaodong; Shi, Xiaofei; He, Fan

2015-07-22

Satellite orbit error and clock bias are the keys to precise point positioning (PPP). The traditional PPP algorithm requires precise satellite products based on worldwide permanent reference stations. Such an algorithm requires considerable work and hardly achieves real-time performance. However, real-time positioning service will be the dominant mode in the future. IGS is providing such an operational service (RTS) and there are also commercial systems like Trimble RTX in operation. On the basis of the regional Continuous Operational Reference System (CORS), a real-time PPP algorithm is proposed to apply the coupling estimation of clock bias and orbit error. The projection of orbit error onto the satellite-receiver range has the same effects on positioning accuracy with clock bias. Therefore, in satellite clock estimation, part of the orbit error can be absorbed by the clock bias and the effects of residual orbit error on positioning accuracy can be weakened by the evenly distributed satellite geometry. In consideration of the simple structure of pseudorange equations and the high precision of carrier-phase equations, the clock bias estimation method coupled with orbit error is also improved. Rovers obtain PPP results by receiving broadcast ephemeris and real-time satellite clock bias coupled with orbit error. By applying the proposed algorithm, the precise orbit products provided by GNSS analysis centers are rendered no longer necessary. On the basis of previous theoretical analysis, a real-time PPP system was developed. Some experiments were then designed to verify this algorithm. Experimental results show that the newly proposed approach performs better than the traditional PPP based on International GNSS Service (IGS) real-time products. The positioning accuracies of the rovers inside and outside the network are improved by 38.8% and 36.1%, respectively. The PPP convergence speeds are improved by up to 61.4% and 65.9%. The new approach can change the traditional PPP mode because of its advantages of independence, high positioning precision, and real-time performance. It could be an alternative solution for regional positioning service before global PPP service comes into operation.

Real-Time PPP Based on the Coupling Estimation of Clock Bias and Orbit Error with Broadcast Ephemeris

PubMed Central

Pan, Shuguo; Chen, Weirong; Jin, Xiaodong; Shi, Xiaofei; He, Fan

2015-01-01

Satellite orbit error and clock bias are the keys to precise point positioning (PPP). The traditional PPP algorithm requires precise satellite products based on worldwide permanent reference stations. Such an algorithm requires considerable work and hardly achieves real-time performance. However, real-time positioning service will be the dominant mode in the future. IGS is providing such an operational service (RTS) and there are also commercial systems like Trimble RTX in operation. On the basis of the regional Continuous Operational Reference System (CORS), a real-time PPP algorithm is proposed to apply the coupling estimation of clock bias and orbit error. The projection of orbit error onto the satellite-receiver range has the same effects on positioning accuracy with clock bias. Therefore, in satellite clock estimation, part of the orbit error can be absorbed by the clock bias and the effects of residual orbit error on positioning accuracy can be weakened by the evenly distributed satellite geometry. In consideration of the simple structure of pseudorange equations and the high precision of carrier-phase equations, the clock bias estimation method coupled with orbit error is also improved. Rovers obtain PPP results by receiving broadcast ephemeris and real-time satellite clock bias coupled with orbit error. By applying the proposed algorithm, the precise orbit products provided by GNSS analysis centers are rendered no longer necessary. On the basis of previous theoretical analysis, a real-time PPP system was developed. Some experiments were then designed to verify this algorithm. Experimental results show that the newly proposed approach performs better than the traditional PPP based on International GNSS Service (IGS) real-time products. The positioning accuracies of the rovers inside and outside the network are improved by 38.8% and 36.1%, respectively. The PPP convergence speeds are improved by up to 61.4% and 65.9%. The new approach can change the traditional PPP mode because of its advantages of independence, high positioning precision, and real-time performance. It could be an alternative solution for regional positioning service before global PPP service comes into operation. PMID:26205276

Entropy-as-a-Service: Unlocking the Full Potential of Cryptography

PubMed Central

Vassilev, Apostol; Staples, Robert

2016-01-01

Securing the Internet requires strong cryptography, which depends on the availability of good entropy for generating unpredictable keys and accurate clocks. Attacks abusing weak keys or old inputs portend challenges for the Internet. EaaS is a novel architecture providing entropy and timestamps from a decentralized root of trust, scaling gracefully across diverse geopolitical locales and remaining trustworthy unless much of the collective is compromised. PMID:28003687

Coding for Single-Line Transmission

NASA Technical Reports Server (NTRS)

Madison, L. G.

1983-01-01

Digital transmission code combines data and clock signals into single waveform. MADCODE needs four standard integrated circuits in generator and converter plus five small discrete components. MADCODE allows simple coding and decoding for transmission of digital signals over single line.

QPPM receiver for free-space laser communications

NASA Technical Reports Server (NTRS)

Budinger, J. M.; Mohamed, J. H.; Nagy, L. A.; Lizanich, P. J.; Mortensen, D. J.

1994-01-01

A prototype receiver developed at NASA Lewis Research Center for direct detection and demodulation of quaternary pulse position modulated (QPPM) optical carriers is described. The receiver enables dual-channel communications at 325-Megabits per second (Mbps) per channel. The optical components of the prototype receiver are briefly described. The electronic components, comprising the analog signal conditioning, slot clock recovery, matched filter and maximum likelihood data recovery circuits are described in more detail. A novel digital symbol clock recovery technique is presented as an alternative to conventional analog methods. Simulated link degradations including noise and pointing-error induced amplitude variations are applied. The bit-error-rate performance of the electronic portion of the prototype receiver under varying optical signal-to-noise power ratios is found to be within 1.5-dB of theory. Implementation of the receiver as a hybrid of analog and digital application specific integrated circuits is planned.

Optical Communication with Semiconductor Laser Diode. Interim Progress Report. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Davidson, Frederic; Sun, Xiaoli

1989-01-01

Theoretical and experimental performance limits of a free-space direct detection optical communication system were studied using a semiconductor laser diode as the optical transmitter and a silicon avalanche photodiode (APD) as the receiver photodetector. Optical systems using these components are under consideration as replacements for microwave satellite communication links. Optical pulse position modulation (PPM) was chosen as the signal format. An experimental system was constructed that used an aluminum gallium arsenide semiconductor laser diode as the transmitter and a silicon avalanche photodiode photodetector. The system used Q=4 PPM signaling at a source data rate of 25 megabits per second. The PPM signal format requires regeneration of PPM slot clock and word clock waveforms in the receiver. A nearly exact computational procedure was developed to compute receiver bit error rate without using the Gaussion approximation. A transition detector slot clock recovery system using a phase lock loop was developed and implemented. A novel word clock recovery system was also developed. It was found that the results of the nearly exact computational procedure agreed well with actual measurements of receiver performance. The receiver sensitivity achieved was the closest to the quantum limit yet reported for an optical communication system of this type.

How to fix a broken clock

PubMed Central

Schroeder, Analyne M.; Colwell, Christopher S.

2013-01-01

Fortunate are those who rise out of bed to greet the morning light well rested with the energy and enthusiasm to drive a productive day. Others however, depend on hypnotics for sleep and require stimulants to awaken lethargic bodies. Sleep/wake disruption is a common occurrence in healthy individuals throughout their lifespan and is also a comorbid condition to many diseases (neurodegenerative) and psychiatric disorders (depression and bipolar). There is growing concern that chronic disruption of the sleep/wake cycle contributes to more serious conditions including diabetes (type 2), cardiovascular disease and cancer. A poorly functioning circadian system resulting in misalignments in the timing of clocks throughout the body may be at the root of the problem for many people. In this article, we discuss environmental (light therapy) and lifestyle changes (scheduled meals, exercise and sleep) as interventions to help fix a broken clock. We also discuss the challenges and potential for future development of pharmacological treatments to manipulate this key biological system. PMID:24120229

CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial.

PubMed

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

2016-01-07

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

A Neural Network Underlying Circadian Entrainment and Photoperiodic Adjustment of Sleep and Activity in Drosophila.

PubMed

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

2016-08-31

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

46 CFR 78.47-23 - Supervised patrol stations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 3 2012-10-01 2012-10-01 false Supervised patrol stations. 78.47-23 Section 78.47-23... Fire and Emergency Equipment, Etc. § 78.47-23 Supervised patrol stations. (a) Each supervised patrol clock or key station shall be numbered. (b) [Reserved] ...

46 CFR 78.47-23 - Supervised patrol stations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 3 2011-10-01 2011-10-01 false Supervised patrol stations. 78.47-23 Section 78.47-23... Fire and Emergency Equipment, Etc. § 78.47-23 Supervised patrol stations. (a) Each supervised patrol clock or key station shall be numbered. (b) [Reserved] ...

46 CFR 78.47-23 - Supervised patrol stations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 3 2010-10-01 2010-10-01 false Supervised patrol stations. 78.47-23 Section 78.47-23... Fire and Emergency Equipment, Etc. § 78.47-23 Supervised patrol stations. (a) Each supervised patrol clock or key station shall be numbered. (b) [Reserved] ...

Drosophila TIM Binds Importin α1, and Acts as an Adapter to Transport PER to the Nucleus

PubMed Central

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

2015-01-01

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

Tales around the clock: Poly(A) tails in circadian gene expression.

PubMed

Beta, Rafailia A A; Balatsos, Nikolaos A A

2018-06-17

Circadian rhythms are ubiquitous time-keeping processes in eukaryotes with a period of ~24 hr. Light is perhaps the main environmental cue (zeitgeber) that affects several aspects of physiology and behaviour, such as sleep/wake cycles, orientation of birds and bees, and leaf movements in plants. Temperature can serve as the main zeitgeber in the absence of light cycles, even though it does not lead to rhythmicity through the same mechanism as light. Additional cues include feeding patterns, humidity, and social rhythms. At the molecular level, a master oscillator orchestrates circadian rhythms and organizes molecular clocks located in most cells. The generation of the 24 hr molecular clock is based on transcriptional regulation, as it drives intrinsic rhythmic changes based on interlocked transcription/translation feedback loops that synchronize expression of genes. Thus, processes and factors that determine rhythmic gene expression are important to understand circadian rhythms. Among these, the poly(A) tails of RNAs play key roles in their stability, translational efficiency and degradation. In this article, we summarize current knowledge and discuss perspectives on the role and significance of poly(A) tails and associating factors in the context of the circadian clock. This article is categorized under: RNA Turnover and Surveillance > Regulation of RNA Stability RNA Processing > 3' End Processing. © 2018 Wiley Periodicals, Inc.

Robust Entrainment of Circadian Oscillators Requires Specific Phase Response Curves

PubMed Central

Pfeuty, Benjamin; Thommen, Quentin; Lefranc, Marc

2011-01-01

The circadian clocks keeping time in many living organisms rely on self-sustained biochemical oscillations entrained by external cues, such as light, to the 24-h cycle induced by Earth's rotation. However, environmental cues are unreliable due to the variability of habitats, weather conditions, or cue-sensing mechanisms among individuals. A tempting hypothesis is that circadian clocks have evolved so as to be robust to fluctuations in the signal that entrains them. To support this hypothesis, we analyze the synchronization behavior of weakly and periodically forced oscillators in terms of their phase response curve (PRC), which measures phase changes induced by a perturbation applied at different times of the cycle. We establish a general relationship between the robustness of key entrainment properties, such as stability and oscillator phase, on the one hand, and the shape of the PRC as characterized by a specific curvature or the existence of a dead zone, on the other hand. The criteria obtained are applied to computational models of circadian clocks and account for the disparate robustness properties of various forcing schemes. Finally, the analysis of PRCs measured experimentally in several organisms strongly suggests a case of convergent evolution toward an optimal strategy for maintaining a clock that is accurate and robust to environmental fluctuations. PMID:21641300

Spatial and temporal transcriptome changes occurring during flower opening and senescence of the ephemeral hibiscus flower, Hibiscus rosa-sinensis

PubMed Central

Trivellini, Alice; Cocetta, Giacomo; Hunter, Donald A.; Vernieri, Paolo; Ferrante, Antonio

2016-01-01

Flowers are complex systems whose vegetative and sexual structures initiate and die in a synchronous manner. The rapidity of this process varies widely in flowers, with some lasting for months while others such as Hibiscus rosa-sinensis survive for only a day. The genetic regulation underlying these differences is unclear. To identify key genes and pathways that coordinate floral organ senescence of ephemeral flowers, we identified transcripts in H. rosa-sinensis floral organs by 454 sequencing. During development, 2053 transcripts increased and 2135 decreased significantly in abundance. The senescence of the flower was associated with increased abundance of many hydrolytic genes, including aspartic and cysteine proteases, vacuolar processing enzymes, and nucleases. Pathway analysis suggested that transcripts altering significantly in abundance were enriched in functions related to cell wall-, aquaporin-, light/circadian clock-, autophagy-, and calcium-related genes. Finding enrichment in light/circadian clock-related genes fits well with the observation that hibiscus floral development is highly synchronized with light and the hypothesis that ageing/senescence of the flower is orchestrated by a molecular clock. Further study of these genes will provide novel insight into how the molecular clock is able to regulate the timing of programmed cell death in tissues. PMID:27591432

Multifrequency zero-jitter delay-locked loop

NASA Astrophysics Data System (ADS)

Efendovich, Avner; Afek, Yachin; Sella, Coby; Bikowsky, Zeev

1994-01-01

The approach of an all-digital phase locked loop is used in this delay-locked loop circuit. This design is designated to a system with two processing units, a master CPU and a slave system chip, that share the same bus. It allows maximum utilization of the bus, as the minimal skew between the clocks of the two components significantly reduces idle periods, and also set-up and hold times. Changes in the operating frequency are possible, without falling out of synchronization. Due to the special lead-lag phase detector, the jitter of the clock is zero, when the loop is locked, under any working conditions.

Ultra-stable clock laser system development towards space applications.

PubMed

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

2016-09-26

The increasing performance of optical lattice clocks has made them attractive for scientific applications in space and thus has pushed the development of their components including the interrogation lasers of the clock transitions towards being suitable for space, which amongst others requires making them more power efficient, radiation hardened, smaller, lighter as well as more mechanically stable. Here we present the development towards a space-compatible interrogation laser system for a strontium lattice clock constructed within the Space Optical Clock (SOC2) project where we have concentrated on mechanical rigidity and size. The laser reaches a fractional frequency instability of 7.9 × 10 -16 at 300 ms averaging time. The laser system uses a single extended cavity diode laser that gives enough power for interrogating the atoms, frequency comparison by a frequency comb and diagnostics. It includes fibre link stabilisation to the atomic package and to the comb. The optics module containing the laser has dimensions 60 × 45 × 8 cm 3 ; and the ultra-stable reference cavity used for frequency stabilisation with its vacuum system takes 30 × 30 × 30 cm 3 . The acceleration sensitivities in three orthogonal directions of the cavity are 3.6 × 10 -10 /g, 5.8 × 10 -10 /g and 3.1 × 10 -10 /g, where g ≈ 9.8 m/s 2 is the standard gravitational acceleration.

TEMPORAL PATTERNS OF LIPOPEROXIDATION AND ANTIOXIDANT ENZYMES ARE MODIFIED IN THE HIPPOCAMPUS OF VITAMIN A-DEFICIENT RATS

PubMed Central

Navigatore Fonzo, Lorena S.; Golini, Rebeca S.; Delgado, Silvia M.; Ponce, Ivana T.; Bonomi, Myrta R.; Rezza, Irma G.; Gimenez, María S.; Anzulovich, Ana C.

2011-01-01

Animals can adapt their behavior to predictable temporal fluctuations in the environment through both, memory-and-learning processes and an endogenous time-keeping mechanism. Hippocampus plays a key role in memory and learning and is especially susceptible to oxidative stress. In compensation, antioxidant enzymes activity, such as Catalase (CAT) and Glutathione peroxidase (GPx), has been detected in this brain region. Daily rhythms of antioxidant enzymes activitiy, as well as of glutathione and lipid peroxides levels, have been described in brain. Here, we investigate day/night variations in lipoperoxidation, CAT and GPx expression and activity, as well as the temporal fluctuations of two key components of the endogenous clock, BMAL1 and PER1, in the rat hippocampus and evaluate to which extent vitamin A deficiency may affect their amplitude or phase. Holtzman male rats from control, vitamin A-deficient and vitamin A-refed groups were sacrificed throughout a 24-h period. Daily levels of clock proteins, lipoperoxidation, CAT and GPx mRNA, protein, and activity, were determined in the rat hippocampus obtained every 4 or 5 h. Gene expression of RARα and RXRβ was also quantified in the hippocampus of the three groups of rats. Our results show significant daily variations of BMAL1 and PER1 protein expression. Rhythmic lipoperoxidation, CAT, and GPx, expression and activity, were also observed in the rat hippocampus. Vitamin A deficiency reduced RXRβ mRNA level, as well as the amplitude of BMAL1 and PER1 daily oscillation, phase-shifted the daily peak of lipoperoxidation, and had a differential effect on the oscillating CAT and GPx mRNA, protein, and activity. Learning how vitamin A deficiency affects the circadian gene expression in the hippocampus may have an impact on the neurobiology, nutritional and chronobiology fields, emphasizing for the first time the importance of nutritional factors, such as dietary micronutrients, in the regulation of circadian parameters in this brain memory-and-learning-related region. PMID:19308957

The circadian modulation of leptin-controlled bone formation

USDA-ARS?s Scientific Manuscript database

Mice with circadian gene Period and Cryptochrome mutations develop high bone mass early in life. Such a phenotype is accompanied by an increase in osteoblast numbers in mutant bone and cannot be corrected by leptin intracerebroventricular infusion. Thus, the molecular clock plays a key role in lepti...

Benefit of Complete State Monitoring For GPS Realtime Applications With Geo++ Gnsmart

NASA Astrophysics Data System (ADS)

Wübbena, G.; Schmitz, M.; Bagge, A.

Today, the demand for precise positioning at the cm-level in realtime is worldwide growing. An indication for this is the number of operational RTK network installa- tions, which use permanent reference station networks to derive corrections for dis- tance dependent GPS errors and to supply corrections to RTK users in realtime. Gen- erally, the inter-station distances in RTK networks are selected at several tens of km in range and operational installations cover areas of up to 50000 km x km. However, the separation of the permanent reference stations can be increased to sev- eral hundred km, while a correct modeling of all error components is applied. Such networks can be termed as sparse RTK networks, which cover larger areas with a reduced number of stations. The undifferenced GPS observable is best suited for this task estimating the complete state of a permanent GPS network in a dynamic recursive Kalman filter. A rigorous adjustment of all simultaneous reference station data is re- quired. The sparse network design essentially supports the state estimation through its large spatial extension. The benefit of the approach and its state modeling of all GPS error components is a successful ambiguity resolution in realtime over long distances. The above concepts are implemented in the operational GNSMART (GNSS State Monitoring and Representation Technique) software of Geo++. It performs a state monitoring of all error components at the mm-level, because for RTK networks this accuracy is required to sufficiently represent the distance dependent errors for kine- matic applications. One key issue of the modeling is the estimation of clocks and hard- ware delays in the undifferenced approach. This pre-requisite subsequently allows for the precise separation and modeling of all other error components. Generally most of the estimated parameters are considered as nuisance parameters with respect to pure positioning tasks. As the complete state vector of GPS errors is available in a GPS realtime network, additional information besides position can be derived e.g. regional precise satellite clocks, orbits, total ionospheric electron content, tropospheric water vapor distribution, and also dynamic reference station movements. The models of GNSMART are designed to work with regional, continental or even global data. Results from GNSMART realtime networks with inter-station distances of several hundred km are presented to demonstrate the benefits of the operational implemented concepts.

NASA Adds Leap Second to Master Clock

NASA Image and Video Library

2017-12-08

On Dec. 31, 2016, official clocks around the world will add a leap second just before midnight Coordinated Universal Time — which corresponds to 6:59:59 p.m. EST. NASA missions will also have to make the switch, including the Solar Dynamics Observatory, or SDO, which watches the sun 24/7. Clocks do this to keep in sync with Earth's rotation, which gradually slows down over time. When the dinosaurs roamed Earth, for example, our globe took only 23 hours to make a complete rotation. In space, millisecond accuracy is crucial to understanding how satellites orbit. "SDO moves about 1.9 miles every second," said Dean Pesnell, the project scientist for SDO at NASA's Goddard Space Flight Center in Greenbelt, Maryland. "So does every other object in orbit near SDO. We all have to use the same time to make sure our collision avoidance programs are accurate. So we all add a leap second to the end of 2016, delaying 2017 by one second." The leap second is also key to making sure that SDO is in sync with the Coordinated Universal Time, or UTC, used to label each of its images. SDO has a clock that counts the number of seconds since the beginning of the mission. To convert that count to UTC requires knowing just how many leap seconds have been added to Earth-bound clocks since the mission started. When the spacecraft wants to provide a time in UTC, it calls a software module that takes into consideration both the mission's second count and the number of leap seconds — and then returns a time in UTC.

Phase noise in oscillators as differential-algebraic systems with colored noise sources

NASA Astrophysics Data System (ADS)

Demir, Alper

2004-05-01

Oscillators are key components of many kinds of systems, particularly electronic and opto-electronic systems. Undesired perturbations, i.e. noise, in practical systems adversely affect the spectral and timing properties of the signals generated by oscillators resulting in phase noise and timing jitter, which are key performance limiting factors, being major contributors to bit-error-rate (BER) of RF and possibly optical communication systems, and creating synchronization problems in clocked and sampled-data electronic systems. In this paper, we review our work on the theory and numerical methods for nonlinear perturbation and noise analysis of oscillators described by a system of differential-algebraic equations (DAEs) with white and colored noise sources. The bulk of the work reviewed in this paper first appeared in [1], then in [2] and [3]. Prior to the work mentioned above, we developed a theory and numerical methods for nonlinear perturbation and noise analysis of oscillators described by a system of ordinary differential equations (ODEs) with white noise sources only [4, 5]. In this paper, we also discuss some open problems and issues in the modeling and analysis of phase noise both in free running oscillators and in phase/injection-locked ones.

Quantum key distribution in a multi-user network at gigahertz clock rates

NASA Astrophysics Data System (ADS)

Fernandez, Veronica; Gordon, Karen J.; Collins, Robert J.; Townsend, Paul D.; Cova, Sergio D.; Rech, Ivan; Buller, Gerald S.

2005-07-01

In recent years quantum information research has lead to the discovery of a number of remarkable new paradigms for information processing and communication. These developments include quantum cryptography schemes that offer unconditionally secure information transport guaranteed by quantum-mechanical laws. Such potentially disruptive security technologies could be of high strategic and economic value in the future. Two major issues confronting researchers in this field are the transmission range (typically <100km) and the key exchange rate, which can be as low as a few bits per second at long optical fiber distances. This paper describes further research of an approach to significantly enhance the key exchange rate in an optical fiber system at distances in the range of 1-20km. We will present results on a number of application scenarios, including point-to-point links and multi-user networks. Quantum key distribution systems have been developed, which use standard telecommunications optical fiber, and which are capable of operating at clock rates of up to 2GHz. They implement a polarization-encoded version of the B92 protocol and employ vertical-cavity surface-emitting lasers with emission wavelengths of 850 nm as weak coherent light sources, as well as silicon single-photon avalanche diodes as the single photon detectors. The point-to-point quantum key distribution system exhibited a quantum bit error rate of 1.4%, and an estimated net bit rate greater than 100,000 bits-1 for a 4.2 km transmission range.

KPNB1 mediates PER/CRY nuclear translocation and circadian clock function.

PubMed

Lee, Yool; Jang, A Reum; Francey, Lauren J; Sehgal, Amita; Hogenesch, John B

2015-08-29

Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals. However, the precise molecular mechanism is not fully understood. Here, we report that KPNB1, an importin β component of the ncRNA repressor of nuclear factor of activated T cells (NRON) ribonucleoprotein complex, mediates nuclear translocation and repressor function of the PER/CRY complex. RNAi depletion of KPNB1 traps the PER/CRY complex in the cytoplasm by blocking nuclear entry of PER proteins in human cells. KPNB1 interacts mainly with PER proteins and directs PER/CRY nuclear transport in a circadian fashion. Interestingly, KPNB1 regulates the PER/CRY nuclear entry and repressor function, independently of importin α, its classical partner. Moreover, inducible inhibition of the conserved Drosophila importin β in lateral neurons abolishes behavioral rhythms in flies. Collectively, these data show that KPNB1 is required for timely nuclear import of PER/CRY in the negative feedback regulation of the circadian clock.

Automated analysis of long-term grooming behavior in Drosophila using a k-nearest neighbors classifier

PubMed Central

Allen, Victoria W; Shirasu-Hiza, Mimi

2018-01-01

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

Development of high precision digital driver of acoustic-optical frequency shifter for ROG

NASA Astrophysics Data System (ADS)

Zhang, Rong; Kong, Mei; Xu, Yameng

2016-10-01

We develop a high precision digital driver of the acoustic-optical frequency shifter (AOFS) based on the parallel direct digital synthesizer (DDS) technology. We use an atomic clock as the phase-locked loop (PLL) reference clock, and the PLL is realized by a dual digital phase-locked loop. A DDS sampling clock up to 320 MHz with a frequency stability as low as 10-12 Hz is obtained. By constructing the RF signal measurement system, it is measured that the frequency output range of the AOFS-driver is 52-58 MHz, the center frequency of the band-pass filter is 55 MHz, the ripple in the band is less than 1 dB@3MHz, the single channel output power is up to 0.3 W, the frequency stability is 1 ppb (1 hour duration), and the frequency-shift precision is 0.1 Hz. The obtained frequency stability has two orders of improvement compared to that of the analog AOFS-drivers. For the designed binary frequency shift keying (2-FSK) and binary phase shift keying (2-PSK) modulation system, the demodulating frequency of the input TTL synchronous level signal is up to 10 kHz. The designed digital-bus coding/decoding system is compatible with many conventional digital bus protocols. It can interface with the ROG signal detecting software through the integrated drive electronics (IDE) and exchange data with the two DDS frequency-shift channels through the signal detecting software.

Time-related dynamics of variation in core clock gene expression levels in tissues relevant to the immune system.

PubMed

Mazzoccoli, G; Sothern, R B; Greco, A; Pazienza, V; Vinciguerra, M; Liu, S; Cai, Y

2011-01-01

Immune parameters show rhythmic changes with a 24-h periodicity driven by an internal circadian timing system that relies on clock genes (CGs). CGs form interlocked transcription-translation feedback loops to generate and maintain 24-h mRNA and protein oscillations. In this study we evaluate and compare the profiles and the dynamics of variation of CG expression in peripheral blood, and two lymphoid tissues of mice. Expression levels of seven recognized key CGs (mBmal1, mClock, mPer1, mPer2, mCry1, mCry2, and Rev-erbalpha) were evaluated by quantitative RT- PCR in spleen, thymus and peripheral blood of C57BL/6 male mice housed on a 12-h light (L)-dark (D) cycle and sacrificed every 4 h for 24 h (3-4 mice/time point). We found a statistically significant time-effect in spleen (S), thymus (T) and blood (B) for the original values of expression level of mBmal1 (S), mClock (T, B), mPer1 (S, B), mPer2 (S), mCry1 (S), mCry2 (B) and mRev-Erbalpha (S, T, B) and for the fractional variation calculated between single time-point expression value of mBmal1 (B), mPer2 (T), mCry2 (B) and mRev-Erbalpha (S). A significant 24-h rhythm was validated for five CGs in blood (mClock, mPer1, mPer2, mCry2, mRev-Erbalpha), for four CGs in the spleen (mBmal1, mPer1, mPer2, mRev-Erbalpha), and for three CGs in the thymus (mClock, mPer2, mRev-Erbalpha). The original values of acrophases for mBmal1, mClock, mPer1, mPer2, mCry1 and mCry2 were very similar for spleen and thymus and advanced by several hours for peripheral blood compared to the lymphoid tissues, whereas the phases of mRev-Erbalpha were coincident for all three tissues. In conclusion, central and peripheral lymphoid tissues in the mouse show different sequences of activation of clock gene expression compared to peripheral blood. These differences may underlie the compartmental pattern of web functioning in the immune system.

Compact, Highly Stable Ion Atomic Clock

NASA Technical Reports Server (NTRS)

Prestage, John

2008-01-01

A mercury-ion clock now at the breadboard stage of development (see figure) has a stability comparable to that of a hydrogen-maser clock: In tests, the clock exhibited an Allan deviation of between 2 x 10(exp -13) and 3 x 10(exp -13) at a measurement time of 1 second, averaging to about 10(exp -15) at 1 day. However, the clock occupies a volume of only about 2 liters . about a hundredth of the volume of a hydrogen-maser clock. The ion-handling parts of the apparatus are housed in a sealed vacuum tube, wherein only a getter pump is used to maintain the vacuum. Hence, this apparatus is a prototype of a generation of small, potentially portable high-precision clocks for diverse ground- and space-based navigation and radio science applications. Furthermore, this new ion-clock technology is about 100 times more stable and precise than the rubidium atomic clocks currently in use in the NAV STAR GPS Earth-orbiting satellites. In this clock, mercury ions are shuttled between a quadrupole and a 16-pole linear radio-frequency trap. In the quadrupole trap, the ions are tightly confined and optical state selection from a Hg-202 radio-frequency-discharge ultraviolet lamp is carried out. In the 16-pole trap, the ions are more loosely confined and atomic transitions resonant at frequency of about 40.507 GHz are interrogated by use of a microwave beam at that frequency. The trapping of ions effectively eliminates the frequency pulling caused by wall collisions inherent to gas-cell clocks. The shuttling of the ions between the two traps enables separation of the state-selection process from the clock microwave- resonance process, so that each of these processes can be optimized independently of the other. The basic ion-shuttling, two-trap scheme as described thus far is not new: it has been the basis of designs of prior larger clocks. The novelty of the present development lies in major redesigns of its physics package (the ion traps and the vacuum and optical subsystems) to effect the desired reduction of size to a volume of no more than a couple of liters. The redesign effort has included selection of materials for the vacuum tube, ion trap, and ultraviolet windows that withstand bakeout at a temperature of approx.450 C in preparation for sealing the tube to contain the vacuum. This part of the redesign effort follows the approach taken in the development of such other vacuum-tube electronic components as flight traveling- wave-tube amplifiers having operational and shelf lives as long as 15 years. The redesign effort has also included a thorough study of residual-gas-induced shifts of the ion-clock frequency and a study of alternative gases as candidates for use as a buffer gas within the sealed tube. It has been found that neon is more suitable than is helium, which has been traditionally used for this purpose, in that the pressure-induced frequency pulling by neon is between a third and a half of that of helium. In addition, because neon diffuses through solids much more slowly than does helium, the loss of neon by diffusion over the operational lifetime is expected to be negligible.

Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging

PubMed Central

Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y.; Yang, Jian-Bo; Zheng, Lei

2015-01-01

The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R2, 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants. PMID:26059057

Nondestructive and intuitive determination of circadian chlorophyll rhythms in soybean leaves using multispectral imaging

NASA Astrophysics Data System (ADS)

Pan, Wen-Juan; Wang, Xia; Deng, Yong-Ren; Li, Jia-Hang; Chen, Wei; Chiang, John Y.; Yang, Jian-Bo; Zheng, Lei

2015-06-01

The circadian clock, synchronized by daily cyclic environmental cues, regulates diverse aspects of plant growth and development and increases plant fitness. Even though much is known regarding the molecular mechanism of circadian clock, it remains challenging to quantify the temporal variation of major photosynthesis products as well as their metabolic output in higher plants in a real-time, nondestructive and intuitive manner. In order to reveal the spatial-temporal scenarios of photosynthesis and yield formation regulated by circadian clock, multispectral imaging technique has been employed for nondestructive determination of circadian chlorophyll rhythms in soybean leaves. By utilizing partial least square regression analysis, the determination coefficients R2, 0.9483 for chlorophyll a and 0.8906 for chlorophyll b, were reached, respectively. The predicted chlorophyll contents extracted from multispectral data showed an approximately 24-h rhythm which could be entrained by external light conditions, consistent with the chlorophyll contents measured by chemical analyses. Visualization of chlorophyll map in each pixel offers an effective way to analyse spatial-temporal distribution of chlorophyll. Our results revealed the potentiality of multispectral imaging as a feasible nondestructive universal assay for examining clock function and robustness, as well as monitoring chlorophyll a and b and other biochemical components in plants.

Temperature-dependent resetting of the molecular circadian oscillator in Drosophila

PubMed Central

Goda, Tadahiro; Sharp, Brandi; Wijnen, Herman

2014-01-01

Circadian clocks responsible for daily time keeping in a wide range of organisms synchronize to daily temperature cycles via pathways that remain poorly understood. To address this problem from the perspective of the molecular oscillator, we monitored temperature-dependent resetting of four of its core components in the fruitfly Drosophila melanogaster: the transcripts and proteins for the clock genes period (per) and timeless (tim). The molecular circadian cycle in adult heads exhibited parallel responses to temperature-mediated resetting at the levels of per transcript, tim transcript and TIM protein. Early phase adjustment specific to per transcript rhythms was explained by clock-independent temperature-driven transcription of per. The cold-induced expression of Drosophila per contrasts with the previously reported heat-induced regulation of mammalian Period 2. An altered and more readily re-entrainable temperature-synchronized circadian oscillator that featured temperature-driven per transcript rhythms and phase-shifted TIM and PER protein rhythms was found for flies of the ‘Tim 4’ genotype, which lacked daily tim transcript oscillations but maintained post-transcriptional temperature entrainment of tim expression. The accelerated molecular and behavioural temperature entrainment observed for Tim 4 flies indicates that clock-controlled tim expression constrains the rate of temperature cycle-mediated circadian resetting. PMID:25165772

A multi-channel tunable source for atomic sensors

NASA Astrophysics Data System (ADS)

Bigelow, Matthew S.; Roberts, Tony D.; McNeil, Shirley A.; Hawthorne, Todd; Battle, Phil

2015-09-01

We have designed and completed initial testing on a laser source suitable for atomic interferometry from compact, robust, integrated components. Our design is enabled by capitalizing on robust, well-commercialized, low-noise telecom components with high reliability and declining costs which will help to drive the widespread deployment of this system. The key innovation is the combination of current telecom-based fiber laser and modulator technology with periodicallypoled waveguide technology to produce tunable laser light at rubidium D1 and D2 wavelengths (and expandable to other alkalis) using second harmonic generation (SHG). Unlike direct-diode sources, this source is immune to feedback at the Rb line eliminating the need for bulky high-power isolators in the system. In addition, the source has GHz-level frequency agility and in our experiments was found to only be limited by the agility of our RF generator. As a proof-of principle, the source was scanned through the Doppler-broadened Rb D2 absorption line. With this technology, multiple channels can be independently tuned to produce the fields needed for addressing atomic states in atom interferometers and clocks. Thus, this technology could be useful in the development cold-atom inertial sensors and gyroscopes.

Real-time machine vision system using FPGA and soft-core processor

NASA Astrophysics Data System (ADS)

Malik, Abdul Waheed; Thörnberg, Benny; Meng, Xiaozhou; Imran, Muhammad

2012-06-01

This paper presents a machine vision system for real-time computation of distance and angle of a camera from reference points in the environment. Image pre-processing, component labeling and feature extraction modules were modeled at Register Transfer (RT) level and synthesized for implementation on field programmable gate arrays (FPGA). The extracted image component features were sent from the hardware modules to a soft-core processor, MicroBlaze, for computation of distance and angle. A CMOS imaging sensor operating at a clock frequency of 27MHz was used in our experiments to produce a video stream at the rate of 75 frames per second. Image component labeling and feature extraction modules were running in parallel having a total latency of 13ms. The MicroBlaze was interfaced with the component labeling and feature extraction modules through Fast Simplex Link (FSL). The latency for computing distance and angle of camera from the reference points was measured to be 2ms on the MicroBlaze, running at 100 MHz clock frequency. In this paper, we present the performance analysis, device utilization and power consumption for the designed system. The FPGA based machine vision system that we propose has high frame speed, low latency and a power consumption that is much lower compared to commercially available smart camera solutions.

The trigger card system for the MAJORANA DEMONSTRATOR

NASA Astrophysics Data System (ADS)

Thompson, William; Anderson, John; Howe, Mark; Meijer, Sam; Wilkerson, John; Majorana Collaboration

2014-09-01

The aim of the MAJORANA DEMONSTRATOR is to demonstrate the feasibility of providing low enough background levels to search for neutrinoless double-beta decay (0 νββ) in an array of germanium detectors enriched to 87% in 76Ge. Currently, it is unknown if this decay process occurs; however, observation of such a decay process would show that lepton number is violated, confirm that neutrinos are Majorana particles, and yield information on the absolute mass scale of the neutrino. With current experimental results indicating a half-life greater than 2 x 1025 years for this decay, the minimization of background events is of critical importance. Utilizing time correlation, coincidence testing is able to reject multi-detector events that may otherwise be mistaken for 0 νββ when viewed independently. Here, we present both the hardware and software of the trigger card system, which provides a common clock to all digitizers and the muon veto system, thereby enabling the rejection of background events through coincidence testing. Current experimental results demonstrate the accuracy of the distributed clock to be within two clock pulses (20 ns) across all system components. A test system is used to validate the data acquisition system. The aim of the MAJORANA DEMONSTRATOR is to demonstrate the feasibility of providing low enough background levels to search for neutrinoless double-beta decay (0 νββ) in an array of germanium detectors enriched to 87% in 76Ge. Currently, it is unknown if this decay process occurs; however, observation of such a decay process would show that lepton number is violated, confirm that neutrinos are Majorana particles, and yield information on the absolute mass scale of the neutrino. With current experimental results indicating a half-life greater than 2 x 1025 years for this decay, the minimization of background events is of critical importance. Utilizing time correlation, coincidence testing is able to reject multi-detector events that may otherwise be mistaken for 0 νββ when viewed independently. Here, we present both the hardware and software of the trigger card system, which provides a common clock to all digitizers and the muon veto system, thereby enabling the rejection of background events through coincidence testing. Current experimental results demonstrate the accuracy of the distributed clock to be within two clock pulses (20 ns) across all system components. A test system is used to validate the data acquisition system. We acknowledge support from the Office of Nuclear Physics in the DOE Office of Science, the Particle Astrophysics and REU Programs of the NSF, and the Sanford Underground Research Laboratory.

The circatidal rhythm persists without the optic lobe in the mangrove cricket Apteronemobius asahinai.

PubMed

Takekata, Hiroki; Numata, Hideharu; Shiga, Sakiko

2014-02-01

Whether the circatidal rhythm is generated by a machinery common to the circadian clock is one of the important and interesting questions in chronobiology. The mangrove cricket Apteronemobius asahinai shows a circatidal rhythm generating active and inactive phases and a circadian rhythm modifying the circatidal rhythm by inhibiting activity during the subjective day simultaneously. In the previous study, RNA interference of the circadian clock gene period disrupted the circadian rhythm but not the circatidal rhythm, suggesting a difference in molecular mechanisms between the circatidal and circadian rhythms. In the present study, to compare the neural mechanisms of these 2 rhythms, we observed locomotor activity in the mangrove cricket after surgical removal of the optic lobe, which has been shown to be the locus of the circadian clock in other crickets. We also noted the pigment-dispersing factor immunoreactive neurons (PDF-IRNs) in the optic lobe, because PDF is a key output molecule in the circadian clock system in some insects. The results showed that the circadian modulation was disrupted after the removal of the optic lobes but that the circatidal rhythm was maintained with no remarkable changes in its free-running period. Even in crickets in which some PDF-immunoreactive somata remained after removal of the optic lobe, the circadian rhythm was completely disrupted. The remnants of PDF-IRNs were not correlated to the occurrence and free-running period of the circatidal rhythm. These results indicate that the principal circatidal clock is located in a region(s) different from the optic lobe, whereas the circadian clock is located in the optic lobe, as in other crickets, and PDF-IRNs are not important for circatidal rhythm. Therefore, it is suggested that the circatidal rhythm of A. asahinai is driven by a neural basis different from that driving the circadian rhythm.

Circadian Rhythm Disruption Promotes Lung Tumorigenesis.

PubMed

Papagiannakopoulos, Thales; Bauer, Matthew R; Davidson, Shawn M; Heimann, Megan; Subbaraj, Lakshmipriya; Bhutkar, Arjun; Bartlebaugh, Jordan; Vander Heiden, Matthew G; Jacks, Tyler

2016-08-09

Circadian rhythms are 24-hr oscillations that control a variety of biological processes in living systems, including two hallmarks of cancer, cell division and metabolism. Circadian rhythm disruption by shift work is associated with greater risk for cancer development and poor prognosis, suggesting a putative tumor-suppressive role for circadian rhythm homeostasis. Using a genetically engineered mouse model of lung adenocarcinoma, we have characterized the effects of circadian rhythm disruption on lung tumorigenesis. We demonstrate that both physiologic perturbation (jet lag) and genetic mutation of the central circadian clock components decreased survival and promoted lung tumor growth and progression. The core circadian genes Per2 and Bmal1 were shown to have cell-autonomous tumor-suppressive roles in transformation and lung tumor progression. Loss of the central clock components led to increased c-Myc expression, enhanced proliferation, and metabolic dysregulation. Our findings demonstrate that both systemic and somatic disruption of circadian rhythms contribute to cancer progression. Copyright © 2016 Elsevier Inc. All rights reserved.

Synchrony and entrainment properties of robust circadian oscillators

PubMed Central

Bagheri, Neda; Taylor, Stephanie R.; Meeker, Kirsten; Petzold, Linda R.; Doyle, Francis J.

2008-01-01

Systems theoretic tools (i.e. mathematical modelling, control, and feedback design) advance the understanding of robust performance in complex biological networks. We highlight phase entrainment as a key performance measure used to investigate dynamics of a single deterministic circadian oscillator for the purpose of generating insight into the behaviour of a population of (synchronized) oscillators. More specifically, the analysis of phase characteristics may facilitate the identification of appropriate coupling mechanisms for the ensemble of noisy (stochastic) circadian clocks. Phase also serves as a critical control objective to correct mismatch between the biological clock and its environment. Thus, we introduce methods of investigating synchrony and entrainment in both stochastic and deterministic frameworks, and as a property of a single oscillator or population of coupled oscillators. PMID:18426774

Metabolic rate does not calibrate the molecular clock

PubMed Central

Lanfear, Robert; Thomas, Jessica A.; Welch, John J.; Brey, Thomas; Bromham, Lindell

2007-01-01

Rates of molecular evolution vary widely among lineages, but the causes of this variation remain poorly understood. It has been suggested that mass-specific metabolic rate may be one of the key factors determining the rate of molecular evolution, and that it can be used to derive “corrected” molecular clocks. However, previous studies have been hampered by a paucity of mass-specific metabolic rate data and have been largely limited to vertebrate taxa. Using mass-specific metabolic rate measurements and DNA sequence data for >300 metazoan species for 12 different genes, we find no evidence that mass-specific metabolic rate drives substitution rates. The mechanistic basis of the metabolic rate hypothesis is discussed in light of these findings. PMID:17881572

Time is honey: circadian clocks of bees and flowers and how their interactions may influence ecological communities.

PubMed

Bloch, Guy; Bar-Shai, Noam; Cytter, Yotam; Green, Rachel

2017-11-19

The interactions between flowering plants and insect pollinators shape ecological communities and provide one of the best examples of coevolution. Although these interactions have received much attention in both ecology and evolution, their temporal aspects are little explored. Here we review studies on the circadian organization of pollination-related traits in bees and flowers. Research, mostly with the honeybee, Apis mellifera , has implicated the circadian clock in key aspects of their foraging for flower rewards. These include anticipation, timing of visits to flowers at specified locations and time-compensated sun-compass orientation. Floral rhythms in traits such as petal opening, scent release and reward availability also show robust daily rhythms. However, in only few studies was it possible to adequately determine whether these oscillations are driven by external time givers such as light and temperature cycles, or endogenous circadian clocks. The interplay between the timing of flower and pollinator rhythms may be ecologically significant. Circadian regulation of pollination-related traits in only few species may influence the entire pollination network and thus affect community structure and local biodiversity. We speculate that these intricate chronobiological interactions may be vulnerable to anthropogenic effects such as the introduction of alien invasive species, pesticides or environmental pollutants.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'. © 2017 The Author(s).

Genetic Correlates of Individual Differences in Sleep Behavior of Free-Living Great Tits (Parus major)

PubMed Central

Stuber, Erica F.; Baumgartner, Christine; Dingemanse, Niels J.; Kempenaers, Bart; Mueller, Jakob C.

2016-01-01

Within populations, free-living birds display considerable variation in observable sleep behaviors, reflecting dynamic interactions between individuals and their environment. Genes are expected to contribute to repeatable between-individual differences in sleep behaviors, which may be associated with individual fitness. We identified and genotyped polymorphisms in nine candidate genes for sleep, and measured five repeatable sleep behaviors in free-living great tits (Parus major), partly replicating a previous study in blue tits (Cyanistes caeruleus). Microsatellites in the CLOCK and NPAS2 clock genes exhibited an association with sleep duration relative to night length, and morning latency to exit the nest box, respectively. Furthermore, microsatellites in the NPSR1 and PCSK2 genes associated with relative sleep duration and proportion of time spent awake at night, respectively. Given the detection rate of associations in the same models run with random markers instead of candidate genes, we expected two associations to arise by chance. The detection of four associations between candidate genes and sleep, however, suggests that clock genes, a clock-related gene, or a gene involved in the melanocortin system, could play key roles in maintaining phenotypic variation in sleep behavior in avian populations. Knowledge of the genetic architecture underlying sleep behavior in the wild is important because it will enable ecologists to assess the evolution of sleep in response to selection. PMID:26739645

The Circadian Clock Modulates Global Daily Cycles of mRNA Ribosome Loading[OPEN

PubMed Central

Missra, Anamika; Ernest, Ben; Jia, Qidong; Ke, Kenneth

2015-01-01

Circadian control of gene expression is well characterized at the transcriptional level, but little is known about diel or circadian control of translation. Genome-wide translation state profiling of mRNAs in Arabidopsis thaliana seedlings grown in long day was performed to estimate ribosome loading per mRNA. The experiments revealed extensive translational regulation of key biological processes. Notably, translation of mRNAs for ribosomal proteins and mitochondrial respiration peaked at night. Central clock mRNAs are among those subject to fluctuations in ribosome loading. There was no consistent phase relationship between peak translation states and peak transcript levels. The overlay of distinct transcriptional and translational cycles can be expected to alter the waveform of the protein synthesis rate. Plants that constitutively overexpress the clock gene CCA1 showed phase shifts in peak translation, with a 6-h delay from midnight to dawn or from noon to evening being particularly common. Moreover, cycles of ribosome loading that were detected under continuous light in the wild type collapsed in the CCA1 overexpressor. Finally, at the transcript level, the CCA1-ox strain adopted a global pattern of transcript abundance that was broadly correlated with the light-dark environment. Altogether, these data demonstrate that gene-specific diel cycles of ribosome loading are controlled in part by the circadian clock. PMID:26392078

Spatial and temporal transcriptome changes occurring during flower opening and senescence of the ephemeral hibiscus flower, Hibiscus rosa-sinensis.

PubMed

Trivellini, Alice; Cocetta, Giacomo; Hunter, Donald A; Vernieri, Paolo; Ferrante, Antonio

2016-10-01

Flowers are complex systems whose vegetative and sexual structures initiate and die in a synchronous manner. The rapidity of this process varies widely in flowers, with some lasting for months while others such as Hibiscus rosa-sinensis survive for only a day. The genetic regulation underlying these differences is unclear. To identify key genes and pathways that coordinate floral organ senescence of ephemeral flowers, we identified transcripts in H. rosa-sinensis floral organs by 454 sequencing. During development, 2053 transcripts increased and 2135 decreased significantly in abundance. The senescence of the flower was associated with increased abundance of many hydrolytic genes, including aspartic and cysteine proteases, vacuolar processing enzymes, and nucleases. Pathway analysis suggested that transcripts altering significantly in abundance were enriched in functions related to cell wall-, aquaporin-, light/circadian clock-, autophagy-, and calcium-related genes. Finding enrichment in light/circadian clock-related genes fits well with the observation that hibiscus floral development is highly synchronized with light and the hypothesis that ageing/senescence of the flower is orchestrated by a molecular clock. Further study of these genes will provide novel insight into how the molecular clock is able to regulate the timing of programmed cell death in tissues. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Analysis of an all-digital maximum likelihood carrier phase and clock timing synchronizer for eight phase-shift keying modulation

NASA Astrophysics Data System (ADS)

Degaudenzi, Riccardo; Vanghi, Vieri

1994-02-01

In all-digital Trellis-Coded 8PSK (TC-8PSK) demodulator well suited for VLSI implementation, including maximum likelihood estimation decision-directed (MLE-DD) carrier phase and clock timing recovery, is introduced and analyzed. By simply removing the trellis decoder the demodulator can efficiently cope with uncoded 8PSK signals. The proposed MLE-DD synchronization algorithm requires one sample for the phase and two samples per symbol for the timing loop. The joint phase and timing discriminator characteristics are analytically derived and numerical results checked by means of computer simulations. An approximated expression for steady-state carrier phase and clock timing mean square error has been derived and successfully checked with simulation findings. Synchronizer deviation from the Cramer Rao bound is also discussed. Mean acquisition time for the digital synchronizer has also been computed and checked, using the Monte Carlo simulation technique. Finally, TC-8PSK digital demodulator performance in terms of bit error rate and mean time to lose lock, including digital interpolators and synchronization loops, is presented.

The Satellite Clock Bias Prediction Method Based on Takagi-Sugeno Fuzzy Neural Network

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

PubMed

Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

2016-04-01

Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms. © FASEB.

Giant gain from spontaneously generated coherence in Y-type double quantum dot structure

NASA Astrophysics Data System (ADS)

Al-Nashy, B.; Razzaghi, Sonia; Al-Musawi, Muwaffaq Abdullah; Rasooli Saghai, H.; Al-Khursan, Amin H.

A theoretical model was presented for linear susceptibility using density matrix theory for Y-configuration of double quantum dots (QDs) system including spontaneously generated coherence (SGC). Two SGC components are included for this system: V, and Λ subsystems. It is shown that at high V-component, the system have a giga gain. At low Λ-system component; it is possible to controls the light speed between superluminal and subluminal using one parameter by increasing SGC component of the V-system. This have applications in quantum information storage and spatially-varying temporal clock.

The OPTIS satellite-improved tests of Special and General Relativity

NASA Astrophysics Data System (ADS)

Scheithauer, Silvia; Laemmerzahl, Claus; Dittus, Hansjoerg; Schiller, Stephan; Peters, Achim

2005-06-01

The OPTIS satellite mission is an international collaboration initiated by three German University institutes aiming at improving tests regarding the foundations of Special and General Relativity. The mission idea - which has already passed the state of the initial feasibility study - is to contribute to the most challenging project of physics in this century - the search for a Theory of Quantum Gravity. This theory should resolve the incompatibilities between the quantum theory and Einstein's General Relativity. All approaches for a Quantum Gravity Theory predict small deviations from Special and General Relativity. If such deviations could be found (e.g. an anisotropy of the speed of light, violations of the universality of gravitational red shift or of the universality of free fall) the way to a new understanding of the time and space structure of the universe would be open. Therefore the goal of the OPTIS satellite mission is an accuracy improvement of tests regarding the foundations of Special and General Relativity by up to three orders of magnitude. For that purpose several experiments will be carried out on board the OPTIS satellite testing (i) the isotropy of the speed of light, (ii) the independence of the speed of light from the velocity of the laboratory system, (iii) the universality of the gravitational redshift, (iv) the absolute gravitational redshift and (v) the special relativistic time-dilation. Furthermore, orbit analyses will be done in order to measure (vi) the Lense-Thirring effect and (vii) perigee advance as well as to test (viii) the Newtonian View the MathML source gravitational potential. The benefit from bringing these experiments into space is the nearly disturbance free environment allowing precise measurements and large measurement times. The OPTIS mission will use already available key technologies like optical cavities, highly stabilised lasers, atomic clocks, frequency combs, capacitive gravitational reference sensors, drag-free control, laser tracking and laser linking systems. For most of the proposed tests the measurements are done by comparing the rates of different clocks. For the test of the isotropy of the velocity of light (Michelson-Morley experiment) the frequencies of resonators ("light clocks") pointing in different directions are compared. Concerning the constancy of the speed of light (Kennedy-Thorndike experiment) a resonator and atomic clocks under varying velocities are compared. For tests of the time dilation the rates of clocks in different states of motion and for testing the universality of the gravitational redshift clocks at different positions in the gravitational field are compared. This paper will give an overview about the OPTIS satellite mission, including the science goals, science requirements, key technologies, measurement principles and devices.

Continuous-variable quantum key distribution with 1 Mbps secure key rate.

PubMed

Huang, Duan; Lin, Dakai; Wang, Chao; Liu, Weiqi; Fang, Shuanghong; Peng, Jinye; Huang, Peng; Zeng, Guihua

2015-06-29

We report the first continuous-variable quantum key distribution (CVQKD) experiment to enable the creation of 1 Mbps secure key rate over 25 km standard telecom fiber in a coarse wavelength division multiplexers (CWDM) environment. The result is achieved with two major technological advances: the use of a 1 GHz shot-noise-limited homodyne detector and the implementation of a 50 MHz clock system. The excess noise due to noise photons from local oscillator and classical data channels in CWDM is controlled effectively. We note that the experimental verification of high-bit-rate CVQKD in the multiplexing environment is a significant step closer toward large-scale deployment in fiber networks.

Circadian oscillatory transcriptional programs in grapevine ripening fruits

PubMed Central

2014-01-01

Background Temperature and solar radiation influence Vitis vinifera L. berry ripening. Both environmental conditions fluctuate cyclically on a daily period basis and the strength of this fluctuation affects grape ripening too. Additionally, a molecular circadian clock regulates daily cyclic expression in a large proportion of the plant transcriptome modulating multiple developmental processes in diverse plant organs and developmental phases. Circadian cycling of fruit transcriptomes has not been characterized in detail despite their putative relevance in the final composition of the fruit. Thus, in this study, gene expression throughout 24 h periods in pre-ripe berries of Tempranillo and Verdejo grapevine cultivars was followed to determine whether different ripening transcriptional programs are activated during certain times of day in different grape tissues and genotypes. Results Microarray analyses identified oscillatory transcriptional profiles following circadian variations in the photocycle and the thermocycle. A higher number of expression oscillating transcripts were detected in samples carrying exocarp tissue including biotic stress-responsive transcripts activated around dawn. Thermotolerance-like responses and regulation of circadian clock-related genes were observed in all studied samples. Indeed, homologs of core clock genes were identified in the grapevine genome and, among them, VvREVEILLE1 (VvRVE1), showed a consistent circadian expression rhythm in every grape berry tissue analysed. Light signalling components and terpenoid biosynthetic transcripts were specifically induced during the daytime in Verdejo, a cultivar bearing white-skinned and aromatic berries, whereas transcripts involved in phenylpropanoid biosynthesis were more prominently regulated in Tempranillo, a cultivar bearing black-skinned berries. Conclusions The transcriptome of ripening fruits varies in response to daily environmental changes, which might partially be under the control of circadian clock components. Certain cultivar and berry tissue features could rely on specific circadian oscillatory expression profiles. These findings may help to a better understanding of the progress of berry ripening in short term time scales. PMID:24666982

Melatonin: a universal time messenger.

PubMed

Erren, Thomas C; Reiter, Russel J

2015-01-01

Temporal organization plays a key role in humans, and presumably all species on Earth. A core building block of the chronobiological architecture is the master clock, located in the suprachi asmatic nuclei [SCN], which organizes "when" things happen in sub-cellular biochemistry, cells, organs and organisms, including humans. Conceptually, time messenging should follow a 5 step-cascade. While abundant evidence suggests how steps 1 through 4 work, step 5 of "how is central time information transmitted througout the body?" awaits elucidation. Step 1: Light provides information on environmental (external) time; Step 2: Ocular interfaces between light and biological (internal) time are intrinsically photosensitive retinal ganglion cells [ipRGS] and rods and cones; Step 3: Via the retinohypothalamic tract external time information reaches the light-dependent master clock in the brain, viz the SCN; Step 4: The SCN translate environmental time information into biological time and distribute this information to numerous brain structures via a melanopsin-based network. Step 5: Melatonin, we propose, transmits, or is a messenger of, internal time information to all parts of the body to allow temporal organization which is orchestrated by the SCN. Key reasons why we expect melatonin to have such role include: First, melatonin, as the chemical expression of darkness, is centrally involved in time- and timing-related processes such as encoding clock and calendar information in the brain; Second, melatonin travels throughout the body without limits and is thus a ubiquitous molecule. The chemial conservation of melatonin in all tested species could make this molecule a candidate for a universal time messenger, possibly constituting a legacy of an all-embracing evolutionary history.

Contractor point of view for system development and test program

NASA Technical Reports Server (NTRS)

Koide, F. K.; Ringer, D. E.; Earl, C. E.

1981-01-01

Industry's practice of testing space qualified hardware is examined. An overview of the Global Positioning System (GPS) Test Program is discussed from the component level to the sub-system compatibility tests with the space vehicle and finally to the launch site tests, all related to the Rubidium clock.

With Great Measurements Come Great Results

NASA Astrophysics Data System (ADS)

Williams, Carl

Measurements are the foundation for science and modern life. Technologies we take for granted every day depend on them-cell phones, CAT scans, pharmaceuticals, even sports equipment. Metrology, or measurement science, determines what industry can make reliably and what they cannot. At the National Institute of Standards and Technology (NIST) we specialize in making world class measurements that an incredibly wide range of industries use to continually improve their products - computer chips with nanoscale components, atomic clocks that you can hold in your hand, lasers for both super-strong welds and delicate eye surgeries. Think of all the key technologies developed over the last 100 years and better measurements, standards, or analysis techniques played a role in making them possible. NIST works collaboratively with industry researchers on the advanced metrology for tomorrow's technologies. A new kilogram based on electromagnetic force, cars that weigh half as much but are just as strong, quantum computers, personalized medicine, single atom devices - it's all happening in our labs now. This talk will focus on how metrology creates the future.

A CMOS 0.18 μm 600 MHz clock multiplier PLL and a pseudo-LVDS driver for the high speed data transmission for the ALICE Inner Tracking System front-end chip

NASA Astrophysics Data System (ADS)

Lattuca, A.; Mazza, G.; Aglieri Rinella, G.; Cavicchioli, C.; Chanlek, N.; Collu, A.; Degerli, Y.; Dorokhov, A.; Flouzat, C.; Gajanana, D.; Gao, C.; Guilloux, F.; Hillemanns, H.; Hristozkov, S.; Junique, A.; Keil, M.; Kim, D.; Kofarago, M.; Kugathasan, T.; Kwon, Y.; Mager, M.; Sielewicz, K. Marek; Marin Tobon, C. Augusto; Marras, D.; Martinengo, P.; Mugnier, H.; Musa, L.; Pham, T. Hung; Puggioni, C.; Reidt, F.; Riedler, P.; Rousset, J.; Siddhanta, S.; Snoeys, W.; Song, M.; Usai, G.; Van Hoorne, J. Willem; Yang, P.

2016-01-01

This work presents the 600 MHz clock multiplier PLL and the pseudo-LVDS driver which are two essential components of the Data Transmission Unit (DTU), a fast serial link for the 1.2 Gb/s data transmission of the ALICE inner detector front-end chip (ALPIDE). The PLL multiplies the 40 MHz input clock in order to obtain the 600 MHz and the 200 MHz clock for a fast serializer which works in Double Data Rate mode. The outputs of the serializer feed the pseudo-LVDS driver inputs which transmits the data from the pixel chip to the patch panel with a limited number of signal lines. The driver drives a 5.3 m-6.5 m long differential transmission line by steering a maximum of 5 mA of current at the target speed. To overcome bandwidth limitations coming from the long cables the pre-emphasis can be applied to the output. Currents for the main and pre-emphasis driver can individually be adjusted using on-chip digital-to-analog converters. The circuits will be integrated in the pixel chip and are designed in the same 0.18 μm CMOS technology and will operate from the same 1.8 V supply. Design and test results of both circuits are presented.

The young age of Earth

NASA Astrophysics Data System (ADS)

Zhang, Youxue

1998-09-01

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

Codon usage affects the structure and function of the Drosophila circadian clock protein PERIOD.

PubMed

Fu, Jingjing; Murphy, Katherine A; Zhou, Mian; Li, Ying H; Lam, Vu H; Tabuloc, Christine A; Chiu, Joanna C; Liu, Yi

2016-08-01

Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period (dper), a core clock gene that encodes a critical component of the circadian oscillator, we showed that dper codon usage is important for circadian clock function. Codon optimization of dper resulted in conformational changes of the dPER protein, altered dPER phosphorylation profile and stability, and impaired dPER function in the circadian negative feedback loop, which manifests into changes in molecular rhythmicity and abnormal circadian behavioral output. This study provides an in vivo example that demonstrates the role of codon usage in determining protein structure and function in an animal system. These results suggest a universal mechanism in eukaryotes that uses a codon usage "code" within genetic codons to regulate cotranslational protein folding. © 2016 Fu et al.; Published by Cold Spring Harbor Laboratory Press.

New Approaches for DC Balanced SpaceWire

NASA Technical Reports Server (NTRS)

Kisin, Alex; Rakow, Glenn

2016-01-01

Direct Current (DC) line balanced SpaceWire is attractive for a number of reasons. Firstly, a DC line balanced interface provides the ability to isolate the physical layer with either a transformer or capacitor to achieve higher common mode voltage rejection and/or the complete galvanic isolation in the case of a transformer. Secondly, it provides the possibility to reduce the number of conductors and transceivers in the classical SpaceWire interface by half by eliminating the Strobe line. Depending on the modulator scheme - the clock data recovery frequency requirements may be only twice that of the transmit clock, or even match the transmit clock: depending on the Field Programmable Gate Array (FPGA) decoder design. In this paper, several different implementation scenarios will be discussed. Two of these scenarios are backward compatible with the existing SpaceWire hardware standards except for changes at the character level. Three other scenarios, while decreasing by half the standard SpaceWire hardware components, will require changes at both the character and signal levels and work with fixed rates. Other scenarios with variable data rates will require an additional SpaceWire interface handshake initialization sequence.

A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

PubMed

El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

2018-06-20

Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Q-factor improvement of degenerate four-wave-mixing regenerators for ASE degraded signals

NASA Astrophysics Data System (ADS)

Lu, Hang; Wu, Bao-jian; Geng, Yong; Zhou, Xing-yu; Sun, Fan

2017-11-01

All-optical regenerators can be used to suppress amplified spontaneous emission (ASE) noise introduced by cascaded erbium doped fiber amplifiers (EDFAs) in optical fiber communication systems and lead to the improvement of optical receiver sensitivity. By introducing the Q-factor transfer function (QTF), we evaluate the Q-factor performance of degenerate four-wave mixing (DFWM) regenerators with clock pump and reveal the differences between the optimal input powers determined from the static and dynamic power tranfer function (PTF) and the QTF curves. Our simulation shows that the clock-pump regnerator is capable of improving the Q-facor and receiver sensitivity for 40 Gbit/s ASE-degraded return-to-zero on-off keying (RZ-OOK) signal by 2.58 dB and 4.2 dB, respectively.

The circadian coordination of cell biology.

PubMed

Chaix, Amandine; Zarrinpar, Amir; Panda, Satchidananda

2016-10-10

Circadian clocks are cell-autonomous timing mechanisms that organize cell functions in a 24-h periodicity. In mammals, the main circadian oscillator consists of transcription-translation feedback loops composed of transcriptional regulators, enzymes, and scaffolds that generate and sustain daily oscillations of their own transcript and protein levels. The clock components and their targets impart rhythmic functions to many gene products through transcriptional, posttranscriptional, translational, and posttranslational mechanisms. This, in turn, temporally coordinates many signaling pathways, metabolic activity, organelles' structure and functions, as well as the cell cycle and the tissue-specific functions of differentiated cells. When the functions of these circadian oscillators are disrupted by age, environment, or genetic mutation, the temporal coordination of cellular functions is lost, reducing organismal health and fitness. © 2016 Chaix et al.

Nine-channel mid-power bipolar pulse generator based on a field programmable gate array

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

Haylock, Ben, E-mail: benjamin.haylock2@griffithuni.edu.au; Lenzini, Francesco; Kasture, Sachin

Many channel arbitrary pulse sequence generation is required for the electro-optic reconfiguration of optical waveguide networks in Lithium Niobate. Here we describe a scalable solution to the requirement for mid-power bipolar parallel outputs, based on pulse patterns generated by an externally clocked field programmable gate array. Positive and negative pulses can be generated at repetition rates up to 80 MHz with pulse width adjustable in increments of 1.6 ns across nine independent outputs. Each channel can provide 1.5 W of RF power and can be synchronised with the operation of other components in an optical network such as light sourcesmore » and detectors through an external clock with adjustable delay.« less

Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

PubMed

Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

2016-09-26

As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

Candidate genes have sex-specific effects on timing of spring migration and moult speed in a long-distance migratory bird.

PubMed

Bazzi, Gaia; Podofillini, Stefano; Gatti, Emanuele; Gianfranceschi, Luca; Cecere, Jacopo G; Spina, Fernando; Saino, Nicola; Rubolini, Diego

2017-10-01

The timing of major life-history events, such as migration and moult, is set by endogenous circadian and circannual clocks, that have been well characterized at the molecular level. Conversely, the genetic sources of variation in phenology and in other behavioral traits have been sparsely addressed. It has been proposed that inter-individual variability in the timing of seasonal events may arise from allelic polymorphism at phenological candidate genes involved in the signaling cascade of the endogenous clocks. In this study of a long-distance migratory passerine bird, the willow warbler Phylloscopus trochilus , we investigated whether allelic variation at 5 polymorphic loci of 4 candidate genes ( Adcyap1 , Clock , Creb1 , and Npas2 ), predicted 2 major components of the annual schedule, namely timing of spring migration across the central Mediterranean sea and moult speed, the latter gauged from ptilochronological analyses of tail feathers moulted in the African winter quarters. We identified a novel Clock gene locus ( Clock region 3) showing polyQ polymorphism, which was however not significantly associated with any phenotypic trait. Npas2 allele size predicted male (but not female) spring migration date, with males bearing longer alleles migrating significantly earlier than those bearing shorter alleles. Creb1 allele size significantly predicted male (but not female) moult speed, longer alleles being associated with faster moult. All other genotype-phenotype associations were statistically non-significant. These findings provide new evidence for a role of candidate genes in modulating the phenology of different circannual activities in long-distance migratory birds, and for the occurrence of sex-specific candidate gene effects.

THE mPER2 CLOCK GENE MODULATES COCAINE ACTIONS IN THE MOUSE CIRCADIAN SYSTEM

PubMed Central

Brager, Allison J.; Stowie, Adam C.; Prosser, Rebecca A.; Glass, J. David

2014-01-01

Cocaine is a potent disruptor of photic and non-photic pathways for circadian entrainment of the master circadian clock of the suprachiasmatic nucleus (SCN). These actions of cocaine likely involve its modulation of molecular (clock gene) components for SCN clock timekeeping. At present, however, the physiological basis of such an interaction is unclear. To address this question, we compared photic and non-photic phase-resetting responses between wild-type (WT) and Per2 mutant mice expressing nonfunctional PER2 protein to systemic and intra-SCN cocaine administrations. In the systemic trials, cocaine was administered i.p. (20 mg/kg) either at midday or prior to a light pulse in the early night to assess its non-photic and photic behavioral phase-resetting actions, respectively. In the intra-SCN trial, cocaine was administered by reverse microdialysis at midday to determine if the SCN is a direct target for its non-photic phase-resetting action. Non-photic phase-advancing responses to i.p. cocaine at midday were significantly (~3.5-fold) greater in Per2 mutants than WTs. However, the phase-advancing action of intra-SCN cocaine perfusion at midday did not differ between genotypes. In the light pulse trial, Per2 mutants exhibited larger photic phase-delays than did WTs, and the attenuating action of cocaine on this response was proportionately larger than in WTs. These data indicate that the Per2 clock gene is a potent modulator of cocaine’s actions in the circadian system. With regard to non-photic phase-resetting, the SCN is confirmed as a direct target of cocaine action; however, Per2 modulation of this effect likely occurs outside of the SCN. PMID:23333842

Applying Laser Cutting Techniques through Horology for Teaching Effective STEM in Design and Technology

ERIC Educational Resources Information Center

Jones, Lewis C. R.; Tyrer, John R.; Zanker, Nigel P.

2013-01-01

This paper explores the pedagogy underpinning the use of laser manufacturing methods for the teaching of science, technology, engineering and mathematics (STEM) at key stage 3 design and technology. Clock making (horology) has been a popular project in design and technology (D&T) found in many schools, typically it focuses on aesthetical…

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.

PubMed

Derous, Davina; Mitchell, Sharon E; Green, Cara L; Chen, Luonan; Han, Jing-Dong J; Wang, Yingchun; Promislow, Daniel E L; Lusseau, David; Speakman, John R; Douglas, Alex

2016-04-01

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti-ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin-like growth factor 1 (IGF-1), insulin, and tumor necrosis factor alpha (TNF-α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF-α, leptin and IGF-1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

PubMed Central

Green, Cara L.; Chen, Luonan; Han, Jing‐Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Lusseau, David; Speakman, John R.; Douglas, Alex

2016-01-01

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes. PMID:26945906

Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue Scan Simulations

NASA Astrophysics Data System (ADS)

Zhou, Hongyu; Zoltowski, Brian D.; Tao, Peng

2017-04-01

VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations. Key residues were identified with distinctive impacts on Dark and Light states, respectively. All the simulations display wide range of distribution on a two-dimensional(2D) plot upon structural root-mean-square deviations(RMSD) from either Dark or Light state. Clustering analysis of the 2D RMSD distribution leads to 15 representative structures with drastically different conformation of N-terminus, which is also a key difference between Dark and Light states of VVD. Further principle component analyses(PCA) of RRS simulations agree with the observation of distinctive impact from individual residues on Dark and Light states.

Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue Scan Simulations

PubMed Central

Zhou, Hongyu; Zoltowski, Brian D.; Tao, Peng

2017-01-01

VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations. Key residues were identified with distinctive impacts on Dark and Light states, respectively. All the simulations display wide range of distribution on a two-dimensional(2D) plot upon structural root-mean-square deviations(RMSD) from either Dark or Light state. Clustering analysis of the 2D RMSD distribution leads to 15 representative structures with drastically different conformation of N-terminus, which is also a key difference between Dark and Light states of VVD. Further principle component analyses(PCA) of RRS simulations agree with the observation of distinctive impact from individual residues on Dark and Light states. PMID:28425502

Measurement-Device-Independent Quantum Key Distribution over 200 km

NASA Astrophysics Data System (ADS)

Tang, Yan-Lin; Yin, Hua-Lei; Chen, Si-Jing; Liu, Yang; Zhang, Wei-Jun; Jiang, Xiao; Zhang, Lu; Wang, Jian; You, Li-Xing; Guan, Jian-Yu; Yang, Dong-Xu; Wang, Zhen; Liang, Hao; Zhang, Zhen; Zhou, Nan; Ma, Xiongfeng; Chen, Teng-Yun; Zhang, Qiang; Pan, Jian-Wei

2014-11-01

Measurement-device-independent quantum key distribution (MDIQKD) protocol is immune to all attacks on detection and guarantees the information-theoretical security even with imperfect single-photon detectors. Recently, several proof-of-principle demonstrations of MDIQKD have been achieved. Those experiments, although novel, are implemented through limited distance with a key rate less than 0.1 bit /s . Here, by developing a 75 MHz clock rate fully automatic and highly stable system and superconducting nanowire single-photon detectors with detection efficiencies of more than 40%, we extend the secure transmission distance of MDIQKD to 200 km and achieve a secure key rate 3 orders of magnitude higher. These results pave the way towards a quantum network with measurement-device-independent security.

Global Profiling of Rice and Poplar Transcriptomes Highlights Key Conserved Circadian-Controlled Pathways and cis-Regulatory Modules

PubMed Central

Filichkin, Sergei A.; Breton, Ghislain; Priest, Henry D.; Dharmawardhana, Palitha; Jaiswal, Pankaj; Fox, Samuel E.; Michael, Todd P.; Chory, Joanne; Kay, Steve A.; Mockler, Todd C.

2011-01-01

Background Circadian clocks provide an adaptive advantage through anticipation of daily and seasonal environmental changes. In plants, the central clock oscillator is regulated by several interlocking feedback loops. It was shown that a substantial proportion of the Arabidopsis genome cycles with phases of peak expression covering the entire day. Synchronized transcriptome cycling is driven through an extensive network of diurnal and clock-regulated transcription factors and their target cis-regulatory elements. Study of the cycling transcriptome in other plant species could thus help elucidate the similarities and differences and identify hubs of regulation common to monocot and dicot plants. Methodology/Principal Findings Using a combination of oligonucleotide microarrays and data mining pipelines, we examined daily rhythms in gene expression in one monocotyledonous and one dicotyledonous plant, rice and poplar, respectively. Cycling transcriptomes were interrogated under different diurnal (driven) and circadian (free running) light and temperature conditions. Collectively, photocycles and thermocycles regulated about 60% of the expressed nuclear genes in rice and poplar. Depending on the condition tested, up to one third of oscillating Arabidopsis-poplar-rice orthologs were phased within three hours of each other suggesting a high degree of conservation in terms of rhythmic gene expression. We identified clusters of rhythmically co-expressed genes and searched their promoter sequences to identify phase-specific cis-elements, including elements that were conserved in the promoters of Arabidopsis, poplar, and rice. Conclusions/Significance Our results show that the cycling patterns of many circadian clock genes are highly conserved across poplar, rice, and Arabidopsis. The expression of many orthologous genes in key metabolic and regulatory pathways is diurnal and/or circadian regulated and phased to similar times of day. Our results confirm previous findings in Arabidopsis of three major classes of cis-regulatory modules within the plant circadian network: the morning (ME, GBOX), evening (EE, GATA), and midnight (PBX/TBX/SBX) modules. Identification of identical overrepresented motifs in the promoters of cycling genes from different species suggests that the core diurnal/circadian cis-regulatory network is deeply conserved between mono- and dicotyledonous species. PMID:21694767

Oscillator metrology with software defined radio.

PubMed

Sherman, Jeff A; Jördens, Robert

2016-05-01

Analog electrical elements such as mixers, filters, transfer oscillators, isolating buffers, dividers, and even transmission lines contribute technical noise and unwanted environmental coupling in time and frequency measurements. Software defined radio (SDR) techniques replace many of these analog components with digital signal processing (DSP) on rapidly sampled signals. We demonstrate that, generically, commercially available multi-channel SDRs are capable of time and frequency metrology, outperforming purpose-built devices by as much as an order-of-magnitude. For example, for signals at 10 MHz and 6 GHz, we observe SDR time deviation noise floors of about 20 fs and 1 fs, respectively, in under 10 ms of averaging. Examining the other complex signal component, we find a relative amplitude measurement instability of 3 × 10(-7) at 5 MHz. We discuss the scalability of a SDR-based system for simultaneous measurement of many clocks. SDR's frequency agility allows for comparison of oscillators at widely different frequencies. We demonstrate a novel and extreme example with optical clock frequencies differing by many terahertz: using a femtosecond-laser frequency comb and SDR, we show femtosecond-level time comparisons of ultra-stable lasers with zero measurement dead-time.

Genome-wide binding site analysis of FAR-RED ELONGATED HYPOCOTYL3 reveals its novel function in Arabidopsis development.

PubMed

Ouyang, Xinhao; Li, Jigang; Li, Gang; Li, Bosheng; Chen, Beibei; Shen, Huaishun; Huang, Xi; Mo, Xiaorong; Wan, Xiangyuan; Lin, Rongcheng; Li, Shigui; Wang, Haiyang; Deng, Xing Wang

2011-07-01

FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its homolog FAR-RED IMPAIRED RESPONSE1 (FAR1), two transposase-derived transcription factors, are key components in phytochrome A signaling and the circadian clock. Here, we use chromatin immunoprecipitation-based sequencing (ChIP-seq) to identify 1559 and 1009 FHY3 direct target genes in darkness (D) and far-red (FR) light conditions, respectively, in the Arabidopsis thaliana genome. FHY3 preferentially binds to promoters through the FHY3/FAR1 binding motif (CACGCGC). Interestingly, FHY3 also binds to two motifs in the 178-bp Arabidopsis centromeric repeats. Comparison between the ChIP-seq and microarray data indicates that FHY3 quickly regulates the expression of 197 and 86 genes in D and FR, respectively. FHY3 also coregulates a number of common target genes with PHYTOCHROME INTERACTING FACTOR 3-LIKE5 and ELONGATED HYPOCOTYL5. Moreover, we uncover a role for FHY3 in controlling chloroplast development by directly activating the expression of ACCUMULATION AND REPLICATION OF CHLOROPLASTS5, whose product is a structural component of the latter stages of chloroplast division in Arabidopsis. Taken together, our data suggest that FHY3 regulates multiple facets of plant development, thus providing insights into its functions beyond light and circadian pathways.

Common features in diverse insect clocks.

PubMed

Numata, Hideharu; Miyazaki, Yosuke; Ikeno, Tomoko

2015-01-01

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

Global synchronization of parallel processors using clock pulse width modulation

DOEpatents

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

2013-04-02

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

Transgenic Perturbation of the Decarboxylation Phase of Crassulacean Acid Metabolism Alters Physiology and Metabolism But Has Only a Small Effect on Growth

DOE PAGES

Dever, Louisa V.; Boxall, Susanna F.; Knerova, Jana; ...

2014-11-05

Here, mitochondrial NAD-malic enzyme (ME) and/or cytosolic/plastidic NADP-ME combined with the cytosolic/plastidic pyruvate orthophosphate dikinase (PPDK) catalyze two key steps during light-period malate decarboxylation that underpin secondary CO 2 fixation in some Crassulacean acid metabolism (CAM) species. We report the generation and phenotypic characterization of transgenic RNA interference lines of the obligate CAM species Kalanchoë fedtschenkoi with reduced activities of NAD-ME or PPDK. Transgenic line rNAD-ME1 had 8%, and rPPDK1 had 5% of the wild-type level of activity, and showed dramatic changes in the light/dark cycle of CAM CO 2 fixation. In well-watered conditions, these lines fixed all of theirmore » CO 2 in the light; they thus performed C 3 photosynthesis. The alternative malate decarboxylase, NADP-ME, did not appear to compensate for the reduction in NAD-ME, suggesting that NAD-ME was the key decarboxylase for CAM. The activity of other CAM enzymes was reduced as a consequence of knocking out either NAD-ME or PPDK activity, particularly phosphoenolpyruvate carboxylase (PPC) and PPDK in rNAD-ME1. Furthermore, the circadian clock-controlled phosphorylation of PPC in the dark was reduced in both lines, especially in rNAD-ME1. This had the consequence that circadian rhythms of PPC phosphorylation, PPC kinase transcript levels and activity, and the classic circadian rhythm of CAM CO 2 fixation were lost, or dampened toward arrhythmia, under constant light and temperature conditions. Surprisingly, oscillations in the transcript abundance of core circadian clock genes also became arrhythmic in the rNAD-ME1 line, suggesting that perturbing CAM in K. fedtschenkoi feeds back to perturb the central circadian clock.« less

Transgenic Perturbation of the Decarboxylation Phase of Crassulacean Acid Metabolism Alters Physiology and Metabolism But Has Only a Small Effect on Growth

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

Dever, Louisa V.; Boxall, Susanna F.; Knerova, Jana

Here, mitochondrial NAD-malic enzyme (ME) and/or cytosolic/plastidic NADP-ME combined with the cytosolic/plastidic pyruvate orthophosphate dikinase (PPDK) catalyze two key steps during light-period malate decarboxylation that underpin secondary CO 2 fixation in some Crassulacean acid metabolism (CAM) species. We report the generation and phenotypic characterization of transgenic RNA interference lines of the obligate CAM species Kalanchoë fedtschenkoi with reduced activities of NAD-ME or PPDK. Transgenic line rNAD-ME1 had 8%, and rPPDK1 had 5% of the wild-type level of activity, and showed dramatic changes in the light/dark cycle of CAM CO 2 fixation. In well-watered conditions, these lines fixed all of theirmore » CO 2 in the light; they thus performed C 3 photosynthesis. The alternative malate decarboxylase, NADP-ME, did not appear to compensate for the reduction in NAD-ME, suggesting that NAD-ME was the key decarboxylase for CAM. The activity of other CAM enzymes was reduced as a consequence of knocking out either NAD-ME or PPDK activity, particularly phosphoenolpyruvate carboxylase (PPC) and PPDK in rNAD-ME1. Furthermore, the circadian clock-controlled phosphorylation of PPC in the dark was reduced in both lines, especially in rNAD-ME1. This had the consequence that circadian rhythms of PPC phosphorylation, PPC kinase transcript levels and activity, and the classic circadian rhythm of CAM CO 2 fixation were lost, or dampened toward arrhythmia, under constant light and temperature conditions. Surprisingly, oscillations in the transcript abundance of core circadian clock genes also became arrhythmic in the rNAD-ME1 line, suggesting that perturbing CAM in K. fedtschenkoi feeds back to perturb the central circadian clock.« less

Integer ambiguity resolution in precise point positioning: method comparison

NASA Astrophysics Data System (ADS)

Geng, Jianghui; Meng, Xiaolin; Dodson, Alan H.; Teferle, Felix N.

2010-09-01

Integer ambiguity resolution at a single receiver can be implemented by applying improved satellite products where the fractional-cycle biases (FCBs) have been separated from the integer ambiguities in a network solution. One method to achieve these products is to estimate the FCBs by averaging the fractional parts of the float ambiguity estimates, and the other is to estimate the integer-recovery clocks by fixing the undifferenced ambiguities to integers in advance. In this paper, we theoretically prove the equivalence of the ambiguity-fixed position estimates derived from these two methods by assuming that the FCBs are hardware-dependent and only they are assimilated into the clocks and ambiguities. To verify this equivalence, we implement both methods in the Position and Navigation Data Analyst software to process 1 year of GPS data from a global network of about 350 stations. The mean biases between all daily position estimates derived from these two methods are only 0.2, 0.1 and 0.0 mm, whereas the standard deviations of all position differences are only 1.3, 0.8 and 2.0 mm for the East, North and Up components, respectively. Moreover, the differences of the position repeatabilities are below 0.2 mm on average for all three components. The RMS of the position estimates minus those from the International GNSS Service weekly solutions for the former method differs by below 0.1 mm on average for each component from that for the latter method. Therefore, considering the recognized millimeter-level precision of current GPS-derived daily positions, these statistics empirically demonstrate the theoretical equivalence of the ambiguity-fixed position estimates derived from these two methods. In practice, we note that the former method is compatible with current official clock-generation methods, whereas the latter method is not, but can potentially lead to slightly better positioning quality.

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

PubMed Central

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

2017-01-01

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

The Drosophila Clock Neuron Network Features Diverse Coupling Modes and Requires Network-wide Coherence for Robust Circadian Rhythms.

PubMed

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

2016-12-13

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

A Distributed Synchronization and Timing System on the EAST Tokamak

NASA Astrophysics Data System (ADS)

Luo, Jiarong; Wu, Yichun; Shu, Yantai

2008-08-01

A key requirement for the EAST distributed control system (EASTDCS) is time synchronization to an accuracy of <1 mus. In 2006 a Distributed Synchronization and Timing System (DSTS) was set up, which is based on the ATmega128 AVR microcontroller and the Nut/OS embedded Real Time Operating System (RTOS). The DSTS provides the control and the data acquisition systems with reference clocks (0.01 Hz 10 MHz) and delayed trigger times ( 1 mus 4294 s). These are produced by a Core Module Unit (CMU) connected by optical fibres to many Local Synchronized Node Units (LSNU). The fibres provide immunity from electrical noise and are of equal length to match clock and trigger delays between systems. This paper describes the architecture of the DSTS on the EAST tokamak and provides an overview of the characteristics of the main and local units.

USNO Master Clock - Naval Oceanography Portal

Science.gov Websites

section Advanced Search... Sections Home Time Earth Orientation Astronomy Meteorology Oceanography Ice You are here: Home › USNO › Precise Time › Master Clock USNO Logo USNO Navigation Master Clock GPS Display Clocks TWSTT Telephone Time NTP Info USNO Master Clock clock vault The USNO Master Clock is the

A laboratory simulation of Arabidopsis seed dormancy cycling provides new insight into its regulation by clock genes and the dormancy-related genes DOG1, MFT, CIPK23 and PHYA.

PubMed

Footitt, Steven; Ölçer-Footitt, Hülya; Hambidge, Angela J; Finch-Savage, William E

2017-08-01

Environmental signals drive seed dormancy cycling in the soil to synchronize germination with the optimal time of year, a process essential for species' fitness and survival. Previous correlation of transcription profiles in exhumed seeds with annual environmental signals revealed the coordination of dormancy-regulating mechanisms with the soil environment. Here, we developed a rapid and robust laboratory dormancy cycling simulation. The utility of this simulation was tested in two ways: firstly, using mutants in known dormancy-related genes [DELAY OF GERMINATION 1 (DOG1), MOTHER OF FLOWERING TIME (MFT), CBL-INTERACTING PROTEIN KINASE 23 (CIPK23) and PHYTOCHROME A (PHYA)] and secondly, using further mutants, we test the hypothesis that components of the circadian clock are involved in coordination of the annual seed dormancy cycle. The rate of dormancy induction and relief differed in all lines tested. In the mutants, dog1-2 and mft2, dormancy induction was reduced but not absent. DOG1 is not absolutely required for dormancy. In cipk23 and phyA dormancy, induction was accelerated. Involvement of the clock in dormancy cycling was clear when mutants in the morning and evening loops of the clock were compared. Dormancy induction was faster when the morning loop was compromised and delayed when the evening loop was compromised. © 2017 The Authors Plant, Cell & Environment Published by John Wiley & Sons Ltd.

Circadian Timing in the Lung; A Specific Role for Bronchiolar Epithelial Cells

PubMed Central

Gibbs, J. E.; Beesley, S.; Plumb, J.; Singh, D.; Farrow, S.; Ray, D. W.; Loudon, A. S. I.

2015-01-01

In addition to the core circadian oscillator, located within the suprachiasmatic nucleus, numerous peripheral tissues possess self-sustaining circadian timers. In vivo these are entrained and temporally synchronized by signals conveyed from the core oscillator. In the present study, we examine circadian timing in the lung, determine the cellular localization of core clock proteins in both mouse and human lung tissue, and establish the effects of glucocorticoids (widely used in the treatment of asthma) on the pulmonary clock. Using organotypic lung slices prepared from transgenic mPER2::Luc mice, luciferase levels, which report PER2 expression, were measured over a number of days. We demonstrate a robust circadian rhythm in the mouse lung that is responsive to glucocorticoids. Immunohistochemical techniques were used to localize specific expression of core clock proteins, and the glucocorticoid receptor, to the epithelial cells lining the bronchioles in both mouse and human lung. In the mouse, these were established to be Clara cells. Murine Clara cells retained circadian rhythmicity when grown as a pure population in culture. Furthermore, selective ablation of Clara cells resulted in the loss of circadian rhythm in lung slices, demonstrating the importance of this cell type in maintaining overall pulmonary circadian rhythmicity. In summary, we demonstrate that Clara cells are critical for maintaining coherent circadian oscillations in lung tissue. Their coexpression of the glucocorticoid receptor and core clock components establishes them as a likely interface between humoral suprachiasmatic nucleus output and circadian lung physiology. PMID:18787022

Circadian Enhancers Coordinate Multiple Phases of Rhythmic Gene Transcription In Vivo

PubMed Central

Fang, Bin; Everett, Logan J.; Jager, Jennifer; Briggs, Erika; Armour, Sean M.; Feng, Dan; Roy, Ankur; Gerhart-Hines, Zachary; Sun, Zheng; Lazar, Mitchell A.

2014-01-01

SUMMARY Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of eRNAs that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed novel mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed new light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ. PMID:25416951

Irradiation setup at the U-120M cyclotron facility

NASA Astrophysics Data System (ADS)

Křížek, F.; Ferencei, J.; Matlocha, T.; Pospíšil, J.; Príbeli, P.; Raskina, V.; Isakov, A.; Štursa, J.; Vaňát, T.; Vysoká, K.

2018-06-01

This paper describes parameters of the proton beams provided by the U-120M cyclotron and the related irradiation setup at the open access irradiation facility at the Nuclear Physics Institute of the Czech Academy of Sciences. The facility is suitable for testing radiation hardness of various electronic components. The use of the setup is illustrated by a measurement of an error rate for errors caused by Single Event Transients in an SRAM-based Xilinx XC3S200 FPGA. This measurement provides an estimate of a possible occurrence of Single Event Transients. Data suggest that the variation of error rate of the Single Event Effects for different clock phase shifts is not significant enough to use clock phase alignment with the beam as a fault mitigation technique.

Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo.

PubMed

Fang, Bin; Everett, Logan J; Jager, Jennifer; Briggs, Erika; Armour, Sean M; Feng, Dan; Roy, Ankur; Gerhart-Hines, Zachary; Sun, Zheng; Lazar, Mitchell A

2014-11-20

Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of enhancer RNAs (eRNAs) that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ.

Quantum key distribution over a 72 dB channel loss using ultralow dark count superconducting single-photon detectors.

PubMed

Shibata, Hiroyuki; Honjo, Toshimori; Shimizu, Kaoru

2014-09-01

We report the first quantum key distribution (QKD) experiment over a 72 dB channel loss using superconducting nanowire single-photon detectors (SSPD, SNSPD) with the dark count rate (DCR) of 0.01 cps. The DCR of the SSPD, which is dominated by the blackbody radiation at room temperature, is blocked by introducing cold optical bandpass filter. We employ the differential phase shift QKD (DPS-QKD) scheme with a 1 GHz system clock rate. The quantum bit error rate (QBER) below 3% is achieved when the length of the dispersion shifted fiber (DSF) is 336 km (72 dB loss), which is low enough to generate secure keys.

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

NASA Astrophysics Data System (ADS)

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

2009-07-01

We present the results from an optical and near-infrared (NIR) spectroscopic study of the ultraviolet-luminous z = 2.73 galaxy, the 8 o'clock arc. Due to gravitational lensing, this galaxy is magnified by a factor of μ > 10, allowing in-depth measurements which are usually unfeasible at such redshifts. In the optical spectra, we measured the systemic redshift of the galaxy, z = 2.7322± 0.0012, using stellar photospheric lines. This differs from the redshift of absorption lines in the interstellar medium, z = 2.7302 ± 0.0006, implying gas outflows on the order of 160 km s-1. With H- and K-band NIR spectra, we have measured nebular emission lines of Hα, Hβ, Hγ, [N II], and [O III], which have a redshift z = 2.7333 ± 0.0001, consistent with the derived systemic redshift. From the Balmer decrement, we measured the dust extinction in this galaxy to be A 5500 = 1.17 ± 36 mag. Correcting the Hα line flux for dust extinction as well as the assumed lensing factor, we measure a star formation rate (SFR) of ~270 M sun yr-1, which is higher than ~85% of star-forming galaxies at z ~ 2-3. Using combinations of all detected emission lines, we find that the 8 o'clock arc has a gas-phase metallicity of ~0.8 Z sun, showing that enrichment at high redshift is not rare, even in blue, star-forming galaxies. Studying spectra from two of the arc components separately, we find that one component dominates both the dust extinction and SFR, although the metallicities between the two components are similar. We derive the mass via stellar population modeling, and find that the arc has a total stellar mass of ~4.2 × 1011 M sun, which falls on the mass-metallicity relation at z ~ 2. Finally, we estimate the total gas mass, and find it to be only ~12% of the stellar mass, implying that the 8 o'clock arc is likely nearing the end of a starburst. Based partly on observations obtained at the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (USA), the Science and Technology Facilities Council (UK), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministerio da Ciencia e Tecnologia (Brazil), and SECYT (Argentina). Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

Field trial of differential-phase-shift quantum key distribution using polarization independent frequency up-conversion detectors.

PubMed

Honjo, T; Yamamoto, S; Yamamoto, T; Kamada, H; Nishida, Y; Tadanaga, O; Asobe, M; Inoue, K

2007-11-26

We report a field trial of differential phase shift quantum key distribution (QKD) using polarization independent frequency up-conversion detectors. A frequency up-conversion detector is a promising device for achieving a high key generation rate when combined with a high clock rate QKD system. However, its polarization dependence prevents it from being applied to practical QKD systems. In this paper, we employ a modified polarization diversity configuration to eliminate the polarization dependence. Applying this method, we performed a long-term stability test using a 17.6-km installed fiber. We successfully demonstrated stable operation for 6 hours and achieved a sifted key generation rate of 120 kbps and an average quantum bit error rate of 3.14 %. The sifted key generation rate was not the estimated value but the effective value, which means that the sifted key was continuously generated at a rate of 120 kbps for 6 hours.

[Elevated expression of CLOCK is associated with poor prognosis in hepatocellular carcinoma].

PubMed

Li, Bo; Yang, Xiliang; Li, Jiaqi; Yang, Yi; Yan, Zhaoyong; Zhang, Hongxin; Mu, Jiao

2018-02-01

Objective To evaluate the expression of circadian locomotor output cycles kaput (CLOCK) and its effects on cell growth in hepatocellular carcinoma (HCC). Methods The expression of CLOCK in 158 pairs of human HCC tissues and matched noncancerous samples was detected by immunohistochemical (IHC) staining. The expression of CLOCK in HCC patients was also verified using the data from GEO and TCGA (a total of 356 cases). The relationship between CLOCK expression and clinicopathological features of HCC patients was analyzed by single factor statistical analysis. Kaplan-Meier survival curves of HCC patients were drawn to study the relationship between the expression level of CLOCK and the survival state. The effect of CLOCK on the growth of HepG2 cells was detected by MTS assay. Results The expression of CLOCK in HCC tissues was significantly higher than that in the adjacent tissues, and the up-regulation of CLOCK expression in HCC tissue was also confirmed in the public data of HCC (356 cases). HCC patients were divided into low CLOCK expression group and high CLOCK expression group. Univariate analysis showed that the expression of CLOCK was related to tumor size, TNM stage, and portal vein invasion in HCC patients. HCC patients with low CLOCK expression had longer overall survival time and relapse-free survival time than those with high CLOCK expression. The proliferation of cells significantly decreased after the expression of CLOCK was knocked down in HepG2 cells. Conclusion The expression of CLOCK in HCC tissues was much higher than that in normal liver tissues, and the high expression of CLOCK indicated the poor prognosis. The knockdown of CLOCK in HCC cells could inhibit the proliferation of HepG2 cells.

Cocaine Modulates Mammalian Circadian Clock Timing by Decreasing Serotonin Transport in the SCN

PubMed Central

Prosser, Rebecca A.; Stowie, Adam; Amicarelli, Mario; Nackenoff, Alex G.; Blakely, Randy D.; Glass, J. David

2014-01-01

Cocaine abuse disrupts reward and homeostatic processes through diverse processes, including those involved in circadian clock regulation. Recently we showed that cocaine administration to mice disrupts nocturnal photic phase resetting of the suprachiasmatic (SCN) circadian clock, whereas administration during the day induces non-photic phase shifts. Importantly, the same effects are seen when cocaine is applied to the SCN in vitro, where it blocks photic-like (glutamate-induced) phase shifts at night and induces phase advances during the day. Furthermore, our previous data suggest that cocaine acts in the SCN by enhancing serotonin (5-HT) signaling. For example, the in vitro actions of cocaine mimic those of 5-HT and are blocked by the 5-HT antagonist, metergoline, but not the dopamine receptor antagonist, fluphenazine. Although our data are consistent with cocaine acting through enhance 5-HT signaling, the nonselective actions of cocaine as an antagonist of monoamine transporters raises the question of whether inhibition of the 5-HT transporter (SERT) is key to its circadian effects. Here we investigate this issue using transgenic mice expressing a SERT that exhibits normal 5-HT recognition and transport but significantly reduced cocaine potency (SERT Met172). Circadian patterns of SCN behavioral and neuronal activity did not differ between WT and SERT Met172 mice, nor did they differ in the ability of the 5-HT1A,2,7 receptor agonist, 8-OH-DPAT to reset SCN clock phase, consistent with the normal SERT expression and activity in the transgenic mice. However, 1) cocaine administration does not induce phase advances when administered in vivo or in vitro in SERT Met172 mice; 2) cocaine does not block photic or glutamate-induced (phase shifts in SERT Met172 mice; and 3) cocaine does not induce long-term changes in free-running period in SERT Met172 mice. We conclude that SERT antagonism is required for the phase shifting of the SCN circadian clock induced by cocaine. PMID:24950119

Temporal Requirements of the Fragile X Mental Retardation Protein in Modulating Circadian Clock Circuit Synaptic Architecture

PubMed Central

Gatto, Cheryl L.; Broadie, Kendal

2009-01-01

Loss of fragile X mental retardation 1 (FMR1) gene function is the most common cause of inherited mental retardation and autism spectrum disorders, characterized by attention disorder, hyperactivity and disruption of circadian activity cycles. Pursuit of effective intervention strategies requires determining when the FMR1 product (FMRP) is required in the regulation of neuronal circuitry controlling these behaviors. In the well-characterized Drosophila disease model, loss of the highly conserved dFMRP causes circadian arrhythmicity and conspicuous abnormalities in the circadian clock circuitry. Here, a novel Sholl Analysis was used to quantify over-elaborated synaptic architecture in dfmr1-null small ventrolateral neurons (sLNvs), a key subset of clock neurons. The transgenic Gene-Switch system was employed to drive conditional neuronal dFMRP expression in the dfmr1-null mutant background in order to dissect temporal requirements within the clock circuit. Introduction of dFMRP during early brain development, including the stages of neurogenesis, neuronal fate specification and early pathfinding, provided no rescue of dfmr1 mutant phenotypes. Similarly, restoring normal dFMRP expression in the adult failed to restore circadian circuit architecture. In sharp contrast, supplying dFMRP during a transient window of very late brain development, wherein synaptogenesis and substantial subsequent synaptic reorganization (e.g. use-dependent pruning) occur, provided strong morphological rescue to reestablish normal sLNvs synaptic arbors. We conclude that dFMRP plays a developmentally restricted role in sculpting synaptic architecture in these neurons that cannot be compensated for by later reintroduction of the protein at maturity. PMID:19738924

Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock

PubMed Central

Fustin, Jean-Michel; Kojima, Rika; Itoh, Kakeru; Chang, Hsin-Yi; Shiqi, Ye; Zhuang, Bowen; Oji, Asami; Gibo, Shingo; Narasimamurthy, Rajesh; Kurosawa, Gen; Doi, Masao; Manabe, Ichiro; Ishihama, Yasushi; Okamura, Hitoshi

2018-01-01

The N6-methylation of internal adenosines (m6A) in mRNA has been quantified and localized throughout the transcriptome. However, the physiological significance of m6A in most highly methylated mRNAs is unknown. It was demonstrated previously that the circadian clock, based on transcription-translation negative feedback loops, is sensitive to the general inhibition of m6A. Here, we show that the Casein Kinase 1 Delta mRNA (Ck1δ), coding for a critical kinase in the control of circadian rhythms, cellular growth, and survival, is negatively regulated by m6A. Inhibition of Ck1δ mRNA methylation leads to increased translation of two alternatively spliced CK1δ isoforms, CK1δ1 and CK1δ2, uncharacterized until now. The expression ratio between these isoforms is tissue-specific, CK1δ1 and CK1δ2 have different kinase activities, and they cooperate in the phosphorylation of the circadian clock protein PER2. While CK1δ1 accelerates the circadian clock by promoting the decay of PER2 proteins, CK1δ2 slows it down by stabilizing PER2 via increased phosphorylation at a key residue on PER2 protein. These observations challenge the previously established model of PER2 phosphorylation and, given the multiple functions and targets of CK1δ, the existence of two isoforms calls for a re-evaluation of past research when CK1δ1 and CK1δ2 were simply CK1δ. PMID:29784786

Analysis of smear in high-resolution remote sensing satellites

NASA Astrophysics Data System (ADS)

Wahballah, Walid A.; Bazan, Taher M.; El-Tohamy, Fawzy; Fathy, Mahmoud

2016-10-01

High-resolution remote sensing satellites (HRRSS) that use time delay and integration (TDI) CCDs have the potential to introduce large amounts of image smear. Clocking and velocity mismatch smear are two of the key factors in inducing image smear. Clocking smear is caused by the discrete manner in which the charge is clocked in the TDI-CCDs. The relative motion between the HRRSS and the observed object obliges that the image motion velocity must be strictly synchronized with the velocity of the charge packet transfer (line rate) throughout the integration time. During imaging an object off-nadir, the image motion velocity changes resulting in asynchronization between the image velocity and the CCD's line rate. A Model for estimating the image motion velocity in HRRSS is derived. The influence of this velocity mismatch combined with clocking smear on the modulation transfer function (MTF) is investigated by using Matlab simulation. The analysis is performed for cross-track and along-track imaging with different satellite attitude angles and TDI steps. The results reveal that the velocity mismatch ratio and the number of TDI steps have a serious impact on the smear MTF; a velocity mismatch ratio of 2% degrades the MTFsmear by 32% at Nyquist frequency when the TDI steps change from 32 to 96. In addition, the results show that to achieve the requirement of MTFsmear >= 0.95 , for TDI steps of 16 and 64, the allowable roll angles are 13.7° and 6.85° and the permissible pitch angles are no more than 9.6° and 4.8°, respectively.

Disruption of adolescents' circadian clock: The vicious circle of media use, exposure to light at night, sleep loss and risk behaviors.

PubMed

Touitou, Yvan; Touitou, David; Reinberg, Alain

2016-11-01

Although sleep is a key element in adolescent development, teens are spending increasing amounts of time online with health risks related to excessive use of electronic media (computers, smartphones, tablets, consoles…) negatively associated with daytime functioning and sleep outcomes. Adolescent sleep becomes irregular, shortened and delayed in relation with later sleep onset and early waking time due to early school starting times on weekdays which results in rhythm desynchronization and sleep loss. In addition, exposure of adolescents to the numerous electronic devices prior to bedtime has become a great concern because LEDs emit much more blue light than white incandescent bulbs and compact fluorescent bulbs and have therefore a greater impact on the biological clock. A large number of adolescents move to evening chronotype and experience a misalignment between biological and social rhythms which, added to sleep loss, results in e.g. fatigue, daytime sleepiness, behavioral problems and poor academic achievement. This paper on adolescent circadian disruption will review the sensitivity of adolescents to light including LEDs with the effects on the circadian system, the crosstalk between the clock and the pineal gland, the role of melatonin, and the behavior of some adolescents(media use, alcohol consumption, binge drinking, smoking habits, stimulant use…). Lastly, some practical recommendations and perspectives are put forward. The permanent social jet lag resulting in clock misalignment experienced by a number of adolescents should be considered as a matter of public health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Precise orbit determination and rapid orbit recovery supported by time synchronization

NASA Astrophysics Data System (ADS)

Guo, Rui; Zhou, JianHua; Hu, XiaoGong; Liu, Li; Tang, Bo; Li, XiaoJie; Wu, Shan

2015-06-01

In order to maintain optimal signal coverage, GNSS satellites have to experience orbital maneuvers. For China's COMPASS system, precise orbit determination (POD) as well as rapid orbit recovery after maneuvers contribute to the overall Positioning, Navigation and Timing (PNT) service performance in terms of accuracy and availability. However, strong statistical correlations between clock offsets and the radial component of a satellite's positions require long data arcs for POD to converge. We propose here a new strategy which relies on time synchronization between ground tracking stations and in-orbit satellites. By fixing satellite clock offsets measured by the satellite station two-way synchronization (SSTS) systems and receiver clock offsets, POD and orbital recovery performance can be improved significantly. Using the Satellite Laser Ranging (SLR) as orbital accuracy evaluation, we find the 4-hr recovered orbit achieves about 0.71 m residual root mean square (RMS) error of fit SLR data, the recovery time is improved from 24-hr to 4-hr compared with the conventional POD without time synchronization support. In addition, SLR evaluation shows that for 1-hr prediction, about 1.47 m accuracy is achieved with the new proposed POD strategy.

New Approaches for Direct Current (DC) Balanced SpaceWire

NASA Technical Reports Server (NTRS)

Kisin, Alex; Rakow, Glenn

2016-01-01

Direct Current (DC) line balanced SpaceWire is attractive for a number of reasons. Firstly, a DC line balanced interface provides the ability to isolate the physical layer with either a transformer or capacitor to achieve higher common mode voltage rejection and or the complete galvanic isolation in the case of a transformer. And secondly, it provides the possibility to reduce the number of conductors and transceivers in the classical SpaceWire interface by half by eliminating the Strobe line. Depending on the modulator scheme the clock data recovery frequency requirements may be only twice that of the transmit clock, or even match the transmit clock: depending on the Field Programmable Gate Array (FPGA) decoder design. In this paper, several different implementation scenarios will be discussed. Two of these scenarios are backward compatible with the existing SpaceWire hardware standards except for changes at the character level. Three other scenarios, while decreasing by half the standard SpaceWire hardware components, will require changes at both the character and signal levels and work with fixed rates. Other scenarios with variable data rates will require an additional SpaceWire interface handshake initialization sequence.

A Technology Demonstration Experiment for Laser Cooled Atomic Clocks in Space

NASA Technical Reports Server (NTRS)

Klipstein, W. M.; Kohel, J.; Seidel, D. J.; Thompson, R. J.; Maleki, L.; Gibble, K.

2000-01-01

We have been developing a laser-cooling apparatus for flight on the International Space Station (ISS), with the intention of demonstrating linewidths on the cesium clock transition narrower than can be realized on the ground. GLACE (the Glovebox Laser- cooled Atomic Clock Experiment) is scheduled for launch on Utilization Flight 3 (UF3) in 2002, and will be mounted in one of the ISS Glovebox platforms for an anticipated 2-3 week run. Separate flight definition projects funded at NIST and Yale by the Micro- gravity Research Division of NASA as a part of its Laser Cooling and Atomic Physics (LCAP) program will follow GLACE. Core technologies for these and other LCAP missions are being developed at JPL, with the current emphasis on developing components such as the laser and optics subsystem, and non-magnetic vacuum-compatible mechanical shutters. Significant technical challenges in developing a space qualifiable laser cooling apparatus include reducing the volume, mass, and power requirements, while increasing the ruggedness and reliability in order to both withstand typical launch conditions and achieve several months of unattended operation. This work was performed at the Jet Propulsion Laboratory under a contract with the National Aeronautics and Space Administration.

Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation.

PubMed

Pariollaud, Marie; Gibbs, Julie E; Hopwood, Thomas W; Brown, Sheila; Begley, Nicola; Vonslow, Ryan; Poolman, Toryn; Guo, Baoqiang; Saer, Ben; Jones, D Heulyn; Tellam, James P; Bresciani, Stefano; Tomkinson, Nicholas Co; Wojno-Picon, Justyna; Cooper, Anthony Wj; Daniels, Dion A; Trump, Ryan P; Grant, Daniel; Zuercher, William; Willson, Timothy M; MacDonald, Andrew S; Bolognese, Brian; Podolin, Patricia L; Sanchez, Yolanda; Loudon, Andrew Si; Ray, David W

2018-06-01

Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models, we now identify the rhythmic circadian repressor REV-ERBα as essential to the mechanism coupling the pulmonary clock to innate immunity, involving both myeloid and bronchial epithelial cells in temporal gating and determining amplitude of response to inhaled endotoxin. Dual mutation of REV-ERBα and its paralog REV-ERBβ in bronchial epithelia further augmented inflammatory responses and chemokine activation, but also initiated a basal inflammatory state, revealing a critical homeostatic role for REV-ERB proteins in the suppression of the endogenous proinflammatory mechanism in unchallenged cells. However, REV-ERBα plays the dominant role, as deletion of REV-ERBβ alone had no impact on inflammatory responses. In turn, inflammatory challenges cause striking changes in stability and degradation of REV-ERBα protein, driven by SUMOylation and ubiquitination. We developed a novel selective oxazole-based inverse agonist of REV-ERB, which protects REV-ERBα protein from degradation, and used this to reveal how proinflammatory cytokines trigger rapid degradation of REV-ERBα in the elaboration of an inflammatory response. Thus, dynamic changes in stability of REV-ERBα protein couple the core clock to innate immunity.

Drifts and Environmental Disturbances in Atomic Clock Subsystems: Quantifying Local Oscillator, Control Loop, and Ion Resonance Interactions.

PubMed

Enzer, Daphna G; Diener, William A; Murphy, David W; Rao, Shanti R; Tjoelker, Robert L

2017-03-01

Linear ion trap frequency standards are among the most stable continuously operating frequency references and clocks. Depending on the application, they have been operated with a variety of local oscillators (LOs), including quartz ultrastable oscillators, hydrogen-masers, and cryogenic sapphire oscillators. The short-, intermediate-, and long-term stability of the frequency output is a complicated function of the fundamental performances, the time dependence of environmental disturbances, the atomic interrogation algorithm, the implemented control loop, and the environmental sensitivity of the LO and the atomic system components. For applications that require moving these references out of controlled lab spaces and into less stable environments, such as fieldwork or spaceflight, a deeper understanding is needed of how disturbances at different timescales impact the various subsystems of the clock and ultimately the output stability. In this paper, we analyze which perturbations have an impact and to what degree. We also report on a computational model of a control loop, which keeps the microwave source locked to the ion resonance. This model is shown to agree with laboratory measurements of how well the feedback removes various disturbances and also with a useful analytic approach we developed for predicting these impacts.

CRY1 circadian gene variant interacts with carbohydrate intake for insulin resistance in two independent populations: Mediterranean and North American

USDA-ARS?s Scientific Manuscript database

Dysregulation in the circadian system induced by variants of clock genes has been associated with type 2 diabetes. Evidence for the role of cryptochromes, core components of the system, in regulating glucose homeostasis is not supported by CRY1 candidate gene association studies for diabetes and ins...

CLOCK regulates mammary epithelial cell growth and differentiation

PubMed Central

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

2016-01-01

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

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

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

The Drosophila Receptor Protein Tyrosine Phosphatase LAR Is Required for Development of Circadian Pacemaker Neuron Processes That Support Rhythmic Activity in Constant Darkness But Not during Light/Dark Cycles

PubMed Central

Agrawal, Parul

2016-01-01

In Drosophila, a transcriptional feedback loop that is activated by CLOCK-CYCLE (CLK-CYC) complexes and repressed by PERIOD-TIMELESS (PER-TIM) complexes keeps circadian time. The timing of CLK-CYC activation and PER-TIM repression is regulated post-translationally, in part through rhythmic phosphorylation of CLK, PER, and TIM. Although kinases that control PER, TIM, and CLK levels, activity, and/or subcellular localization have been identified, less is known about phosphatases that control clock protein dephosphorylation. To identify clock-relevant phosphatases, clock-cell-specific RNAi knockdowns of Drosophila phosphatases were screened for altered activity rhythms. One phosphatase that was identified, the receptor protein tyrosine phosphatase leukocyte-antigen-related (LAR), abolished activity rhythms in constant darkness (DD) without disrupting the timekeeping mechanism in brain pacemaker neurons. However, expression of the neuropeptide pigment-dispersing factor (PDF), which mediates pacemaker neuron synchrony and output, is eliminated in the dorsal projections from small ventral lateral (sLNv) pacemaker neurons when Lar expression is knocked down during development, but not in adults. Loss of Lar function eliminates sLNv dorsal projections, but PDF expression persists in sLNv and large ventral lateral neuron cell bodies and their remaining projections. In contrast to the defects in lights-on and lights-off anticipatory activity seen in flies that lack PDF, Lar RNAi knockdown flies anticipate the lights-on and lights-off transition normally. Our results demonstrate that Lar is required for sLNv dorsal projection development and suggest that PDF expression in LNv cell bodies and their remaining projections mediate anticipation of the lights-on and lights-off transitions during a light/dark cycle. SIGNIFICANCE STATEMENT In animals, circadian clocks drive daily rhythms in physiology, metabolism, and behavior via transcriptional feedback loops. Because key circadian transcriptional activators and repressors are regulated by phosphorylation, we screened for phosphatases that alter activity rhythms when their expression was reduced. One such phosphatase, leukocyte-antigen-related (LAR), abolishes activity rhythms, but does not disrupt feedback loop function. Rather, Lar disrupts clock output by eliminating axonal processes from clock neurons that release pigment-dispersing factor (PDF) neuropeptide into the dorsal brain, but PDF expression persists in their cell bodies and remaining projections. In contrast to flies that lack PDF, flies that lack Lar anticipate lights-on and lights-off transitions normally, which suggests that the remaining PDF expression mediates activity during light/dark cycles. PMID:27030770

A clock-aided positioning algorithm based on Kalman model of GNSS receiver clock bias

NASA Astrophysics Data System (ADS)

Zhu, Lingyao; Li, Zishen; Yuan, Hong

2017-10-01

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

Variable frequency microprocessor clock generator

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

Branson, C.N.

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

A Primer on Architectural Level Fault Tolerance

NASA Technical Reports Server (NTRS)

Butler, Ricky W.

2008-01-01

This paper introduces the fundamental concepts of fault tolerant computing. Key topics covered are voting, fault detection, clock synchronization, Byzantine Agreement, diagnosis, and reliability analysis. Low level mechanisms such as Hamming codes or low level communications protocols are not covered. The paper is tutorial in nature and does not cover any topic in detail. The focus is on rationale and approach rather than detailed exposition.

Entanglement of quantum clocks through gravity

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Entanglement of quantum clocks through gravity.

PubMed

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

2017-03-21

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

Geopotential measurements with synchronously linked optical lattice clocks

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Oscillator networks with tissue-specific circadian clocks in plants.

PubMed

Inoue, Keisuke; Araki, Takashi; Endo, Motomu

2017-09-08

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

Entanglement of quantum clocks through gravity

PubMed Central

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

2017-01-01

In general relativity, the picture of space–time assigns an ideal clock to each world line. Being ideal, gravitational effects due to these clocks are ignored and the flow of time according to one clock is not affected by the presence of clocks along nearby world lines. However, if time is defined operationally, as a pointer position of a physical clock that obeys the principles of general relativity and quantum mechanics, such a picture is, at most, a convenient fiction. Specifically, we show that the general relativistic mass–energy equivalence implies gravitational interaction between the clocks, whereas the quantum mechanical superposition of energy eigenstates leads to a nonfixed metric background. Based only on the assumption that both principles hold in this situation, we show that the clocks necessarily get entangled through time dilation effect, which eventually leads to a loss of coherence of a single clock. Hence, the time as measured by a single clock is not well defined. However, the general relativistic notion of time is recovered in the classical limit of clocks. PMID:28270623

Circadian Rhythms and Sleep in Drosophila melanogaster

PubMed Central

Dubowy, Christine; Sehgal, Amita

2017-01-01

The advantages of the model organism Drosophila melanogaster, including low genetic redundancy, functional simplicity, and the ability to conduct large-scale genetic screens, have been essential for understanding the molecular nature of circadian (∼24 hr) rhythms, and continue to be valuable in discovering novel regulators of circadian rhythms and sleep. In this review, we discuss the current understanding of these interrelated biological processes in Drosophila and the wider implications of this research. Clock genes period and timeless were first discovered in large-scale Drosophila genetic screens developed in the 1970s. Feedback of period and timeless on their own transcription forms the core of the molecular clock, and accurately timed expression, localization, post-transcriptional modification, and function of these genes is thought to be critical for maintaining the circadian cycle. Regulators, including several phosphatases and kinases, act on different steps of this feedback loop to ensure strong and accurately timed rhythms. Approximately 150 neurons in the fly brain that contain the core components of the molecular clock act together to translate this intracellular cycling into rhythmic behavior. We discuss how different groups of clock neurons serve different functions in allowing clocks to entrain to environmental cues, driving behavioral outputs at different times of day, and allowing flexible behavioral responses in different environmental conditions. The neuropeptide PDF provides an important signal thought to synchronize clock neurons, although the details of how PDF accomplishes this function are still being explored. Secreted signals from clock neurons also influence rhythms in other tissues. SLEEP is, in part, regulated by the circadian clock, which ensures appropriate timing of sleep, but the amount and quality of sleep are also determined by other mechanisms that ensure a homeostatic balance between sleep and wake. Flies have been useful for identifying a large set of genes, molecules, and neuroanatomic loci important for regulating sleep amount. Conserved aspects of sleep regulation in flies and mammals include wake-promoting roles for catecholamine neurotransmitters and involvement of hypothalamus-like regions, although other neuroanatomic regions implicated in sleep in flies have less clear parallels. Sleep is also subject to regulation by factors such as food availability, stress, and social environment. We are beginning to understand how the identified molecules and neurons interact with each other, and with the environment, to regulate sleep. Drosophila researchers can also take advantage of increasing mechanistic understanding of other behaviors, such as learning and memory, courtship, and aggression, to understand how sleep loss impacts these behaviors. Flies thus remain a valuable tool for both discovery of novel molecules and deep mechanistic understanding of sleep and circadian rhythms. PMID:28360128

Electromagnetic synchronisation of clocks with finite separation in a rotating system

NASA Astrophysics Data System (ADS)

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

1984-11-01

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

Biological timing and the clock metaphor: oscillatory and hourglass mechanisms.

PubMed

Rensing, L; Meyer-Grahle, U; Ruoff, P

2001-05-01

Living organisms have developed a multitude of timing mechanisms--"biological clocks." Their mechanisms are based on either oscillations (oscillatory clocks) or unidirectional processes (hourglass clocks). Oscillatory clocks comprise circatidal, circalunidian, circadian, circalunar, and circannual oscillations--which keep time with environmental periodicities--as well as ultradian oscillations, ovarian cycles, and oscillations in development and in the brain, which keep time with biological timescales. These clocks mainly determine time points at specific phases of their oscillations. Hourglass clocks are predominantly found in development and aging and also in the brain. They determine time intervals (duration). More complex timing systems combine oscillatory and hourglass mechanisms, such as the case for cell cycle, sleep initiation, or brain clocks, whereas others combine external and internal periodicities (photoperiodism, seasonal reproduction). A definition of a biological clock may be derived from its control of functions external to its own processes and its use in determining temporal order (sequences of events) or durations. Biological and chemical oscillators are characterized by positive and negative feedback (or feedforward) mechanisms. During evolution, living organisms made use of the many existing oscillations for signal transmission, movement, and pump mechanisms, as well as for clocks. Some clocks, such as the circadian clock, that time with environmental periodicities are usually compensated (stabilized) against temperature, whereas other clocks, such as the cell cycle, that keep time with an organismic timescale are not compensated. This difference may be related to the predominance of negative feedback in the first class of clocks and a predominance of positive feedback (autocatalytic amplification) in the second class. The present knowledge of a compensated clock (the circadian oscillator) and an uncompensated clock (the cell cycle), as well as relevant models, are briefly re viewed. Hourglass clocks are based on linear or exponential unidirectional processes that trigger events mainly in the course of development and aging. An important hourglass mechanism within the aging process is the limitation of cell division capacity by the length of telomeres. The mechanism of this clock is briefly reviewed. In all clock mechanisms, thresholds at which "dependent variables" are triggered play an important role.

The Clock mutant mouse is a novel experimental model for nocturia and nocturnal polyuria.

PubMed

Ihara, Tatsuya; Mitsui, Takahiko; Nakamura, Yuki; Kira, Satoru; Miyamoto, Tatsuya; Nakagomi, Hiroshi; Sawada, Norifumi; Hirayama, Yuri; Shibata, Keisuke; Shigetomi, Eiji; Shinozaki, Yoichi; Yoshiyama, Mitsuharu; Andersson, Karl-Erik; Nakao, Atsuhito; Takeda, Masayuki; Koizumi, Schuichi

2017-04-01

The pathophysiologies of nocturia (NOC) and nocturnal polyuria (NP) are multifactorial and their etiologies remain unclear in a large number of patients. Clock genes exist in most cells and organs, and the products of Clock regulate circadian rhythms as representative clock genes. Clock genes regulate lower urinary tract function, and a newly suggested concept is that abnormalities in clock genes cause lower urinary tract symptoms. In the present study, we investigated the voiding behavior of Clock mutant (Clock Δ19/Δ19 ) mice in order to determine the effects of clock genes on NOC/NP. Male C57BL/6 mice aged 8-12 weeks (WT) and male C57BL/6 Clock Δ19/Δ19 mice aged 8 weeks were used. They were bred under 12 hr light/dark conditions for 2 weeks and voiding behavior was investigated by measuring water intake volume, urine volume, urine volume/void, and voiding frequency in metabolic cages in the dark and light periods. No significant differences were observed in behavior patterns between Clock Δ19/Δ19 and WT mice. Clock Δ19/Δ19 mice showed greater voiding frequencies and urine volumes during the sleep phase than WT mice. The diurnal change in urine volume/void between the dark and light periods in WT mice was absent in Clock Δ19/Δ19 mice. Additionally, functional bladder capacity was significantly lower in Clock Δ19/Δ19 mice than in WT mice. We demonstrated that Clock Δ19/Δ19 mice showed the phenotype of NOC/NP. The Clock Δ19/Δ19 mouse may be used as an animal model of NOC and NP. Neurourol. Urodynam. 36:1034-1038, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Design of high-speed burst mode clock and data recovery IC for passive optical network

NASA Astrophysics Data System (ADS)

Yan, Minhui; Hong, Xiaobin; Huang, Wei-Ping; Hong, Jin

2005-09-01

Design of a high bit rate burst mode clock and data recovery (BMCDR) circuit for gigabit passive optical networks (GPON) is described. A top-down design flow is established and some of the key issues related to the behavioural level modeling are addressed in consideration for the complexity of the BMCDR integrated circuit (IC). Precise implementation of Simulink behavioural model accounting for the saturation of frequency control voltage is therefore developed for the BMCDR, and the parameters of the circuit blocks can be readily adjusted and optimized based on the behavioural model. The newly designed BMCDR utilizes the 0.18um standard CMOS technology and is shown to be capable of operating at bit rate of 2.5Gbps, as well as the recovery time of one bit period in our simulation. The developed behaviour model is verified by comparing with the detailed circuit simulation.

Role of Circadian Rhythms in Potassium Homeostasis

PubMed Central

Gumz, Michelle L.; Rabinowitz, Lawrence

2013-01-01

It has been known for decades that urinary potassium excretion varies with a circadian pattern. In this review, we consider the historical evidence for this phenomenon and present an overview of recent developments in the field. Extensive evidence from the latter part of the last century clearly demonstrates that circadian potassium excretion does not depend on endogenous aldosterone. Of note is the recent discovery that the expression of several renal potassium transporters varies with a circadian pattern that appears to be consistent with substantial clinical data regarding daily fluctuations in urinary potassium levels. We propose the circadian clock mechanism as a key regulator of renal potassium transporters, and consequently renal potassium excretion. Further investigation into the mechanism of regulation of renal potassium transport by the circadian clock is warranted in order to increase our understanding of the clinical relevance of circadian rhythms to potassium homeostasis. PMID:23953800

Ag/BiOBr Film in a Rotating-Disk Reactor Containing Long-Afterglow Phosphor for Round-the-Clock Photocatalysis.

PubMed

Yin, Haibo; Chen, Xiaofang; Hou, Rujing; Zhu, Huijuan; Li, Shiqing; Huo, Yuning; Li, Hexing

2015-09-16

Ag/BiOBr film coated on the glass substrate was synthesized by a solvothermal method and a subsequent photoreduction process. Such a Ag/BiOBr film was then adhered to a hollow rotating disk filled with long-afterglow phosphor inside the chamber. The Ag/BiOBr film exhibited high photocatalytic activity for organic pollutant degradation owing to the improved visible-light harvesting and the separation of photoinduced charges. The long-afterglow phosphor could absorb the excessive daylight and emit light around 488 nm, activating the Ag/BiOBr film to realize round-the-clock photocatalysis. Because the Ag nanoparticles could extend the light absorbance of the Ag/BiOBr film to wavelengths of around 500 nm via a surface plasma resonance effect, they played a key role in realizing photocatalysis induced by long-afterglow phosphor.

An Energy-Aware Runtime Management of Multi-Core Sensory Swarms.

PubMed

Kim, Sungchan; Yang, Hoeseok

2017-08-24

In sensory swarms, minimizing energy consumption under performance constraint is one of the key objectives. One possible approach to this problem is to monitor application workload that is subject to change at runtime, and to adjust system configuration adaptively to satisfy the performance goal. As today's sensory swarms are usually implemented using multi-core processors with adjustable clock frequency, we propose to monitor the CPU workload periodically and adjust the task-to-core allocation or clock frequency in an energy-efficient way in response to the workload variations. In doing so, we present an online heuristic that determines the most energy-efficient adjustment that satisfies the performance requirement. The proposed method is based on a simple yet effective energy model that is built upon performance prediction using IPC (instructions per cycle) measured online and power equation derived empirically. The use of IPC accounts for memory intensities of a given workload, enabling the accurate prediction of execution time. Hence, the model allows us to rapidly and accurately estimate the effect of the two control knobs, clock frequency adjustment and core allocation. The experiments show that the proposed technique delivers considerable energy saving of up to 45%compared to the state-of-the-art multi-core energy management technique.

An Energy-Aware Runtime Management of Multi-Core Sensory Swarms

PubMed Central

Kim, Sungchan

2017-01-01

In sensory swarms, minimizing energy consumption under performance constraint is one of the key objectives. One possible approach to this problem is to monitor application workload that is subject to change at runtime, and to adjust system configuration adaptively to satisfy the performance goal. As today’s sensory swarms are usually implemented using multi-core processors with adjustable clock frequency, we propose to monitor the CPU workload periodically and adjust the task-to-core allocation or clock frequency in an energy-efficient way in response to the workload variations. In doing so, we present an online heuristic that determines the most energy-efficient adjustment that satisfies the performance requirement. The proposed method is based on a simple yet effective energy model that is built upon performance prediction using IPC (instructions per cycle) measured online and power equation derived empirically. The use of IPC accounts for memory intensities of a given workload, enabling the accurate prediction of execution time. Hence, the model allows us to rapidly and accurately estimate the effect of the two control knobs, clock frequency adjustment and core allocation. The experiments show that the proposed technique delivers considerable energy saving of up to 45%compared to the state-of-the-art multi-core energy management technique. PMID:28837094

The circadian rhythm of core temperature: effects of physical activity and aging.

PubMed

Weinert, Dietmar; Waterhouse, Jim

2007-02-28

The circadian rhythm of core temperature depends upon several interacting rhythms, of both endogenous and exogenous origin, but an understanding of the process requires these two components to be separated. Constant routines remove the exogenous (masking) component at source, but they are severely limited in their application. By contrast, several purification methods have successfully reduced the masking component of overt circadian rhythms measured in field circumstances. One important, but incidental, outcome from these methods is that they enable a quantitative estimate of masking effects to be obtained. It has been shown that these effects of activity upon the temperature rhythm show circadian rhythmicity, and more detailed investigations of this have aided our understanding of thermoregulation and the genesis of the circadian rhythm of core temperature itself. The observed circadian rhythm of body temperature varies with age; in comparison with adults, it is poorly developed in the neonate and deteriorates in the aged subject. Comparing masked and purified data enables the reasons for these differences--whether due to the body clock, the effector pathways or organs, or irregularities due to the individual's lifestyle--to begin to be understood. Such investigations stress the immaturity of the circadian rhythm in the human neonate and its deterioration in elderly compared with younger subjects, but they also indicate the robustness of the body clock itself into advanced age, at least in mice.

Radiation hard programmable delay line for LHCb calorimeter upgrade

NASA Astrophysics Data System (ADS)

Mauricio, J.; Gascón, D.; Vilasís, X.; Picatoste, E.; Machefert, F.; Lefrancois, J.; Duarte, O.; Beigbeder, C.

2014-01-01

This paper describes the implementation of a SPI-programmable clock delay chip based on a Delay Locked Loop (DLL) in order to shift the phase of the LHC clock (25 ns) in steps of 1ns, with less than 5 ps jitter and 23 ps of DNL. The delay lines will be integrated into ICECAL, the LHCb calorimeter front-end analog signal processing ASIC in the near future. The stringent noise requirements on the ASIC imply minimizing the noise contribution of digital components. This is accomplished by implementing the DLL in differential mode. To achieve the required radiation tolerance several techniques are applied: double guard rings between PMOS and NMOS transistors as well as glitch suppressors and TMR Registers. This 5.7 mm2 chip has been implemented in CMOS 0.35 μm technology.

A Circadian Clock Gene, Cry, Affects Heart Morphogenesis and Function in Drosophila as Revealed by Optical Coherence Microscopy

PubMed Central

Zeng, Xianxu; Tate, Rebecca E.; McKee, Mary L.; Capen, Diane E.; Zhang, Zhan; Tanzi, Rudolph E.; Zhou, Chao

2015-01-01

Circadian rhythms are endogenous, entrainable oscillations of physical, mental and behavioural processes in response to local environmental cues such as daylight, which are present in the living beings, including humans. Circadian rhythms have been related to cardiovascular function and pathology. However, the role that circadian clock genes play in heart development and function in a whole animal in vivo are poorly understood. The Drosophila cryptochrome (dCry) is a circadian clock gene that encodes a major component of the circadian clock negative feedback loop. Compared to the embryonic stage, the relative expression levels of dCry showed a significant increase (>100-fold) in Drosophila during the pupa and adult stages. In this study, we utilized an ultrahigh resolution optical coherence microscopy (OCM) system to perform non-invasive and longitudinal analysis of functional and morphological changes in the Drosophila heart throughout its post-embryonic lifecycle for the first time. The Drosophila heart exhibited major morphological and functional alterations during its development. Notably, heart rate (HR) and cardiac activity period (CAP) of Drosophila showed significant variations during the pupa stage, when heart remodeling took place. From the M-mode (2D + time) OCM images, cardiac structural and functional parameters of Drosophila at different developmental stages were quantitatively determined. In order to study the functional role of dCry on Drosophila heart development, we silenced dCry by RNAi in the Drosophila heart and mesoderm, and quantitatively measured heart morphology and function in those flies throughout its development. Silencing of dCry resulted in slower HR, reduced CAP, smaller heart chamber size, pupal lethality and disrupted posterior segmentation that was related to increased expression of a posterior compartment protein, wingless. Collectively, our studies provided novel evidence that the circadian clock gene, dCry, plays an essential role in heart morphogenesis and function. PMID:26348211

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

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

The Drosophila Circadian Clock Gates Sleep through Time-of-Day Dependent Modulation of Sleep-Promoting Neurons.

PubMed

Cavanaugh, Daniel J; Vigderman, Abigail S; Dean, Terry; Garbe, David S; Sehgal, Amita

2016-02-01

Sleep is under the control of homeostatic and circadian processes, which interact to determine sleep timing and duration, but the mechanisms through which the circadian system modulates sleep are largely unknown. We therefore used adult-specific, temporally controlled neuronal activation and inhibition to identify an interaction between the circadian clock and a novel population of sleep-promoting neurons in Drosophila. Transgenic flies expressed either dTRPA1, a neuronal activator, or Shibire(ts1), an inhibitor of synaptic release, in small subsets of neurons. Sleep, as determined by activity monitoring and video tracking, was assessed before and after temperature-induced activation or inhibition using these effector molecules. We compared the effect of these manipulations in control flies and in mutant flies that lacked components of the molecular circadian clock. Adult-specific activation or inhibition of a population of neurons that projects to the sleep-promoting dorsal Fan-Shaped Body resulted in bidirectional control over sleep. Interestingly, the magnitude of the sleep changes were time-of-day dependent. Activation of sleep-promoting neurons was maximally effective during the middle of the day and night, and was relatively ineffective during the day-to-night and night-to-day transitions. These time-ofday specific effects were absent in flies that lacked functional circadian clocks. We conclude that the circadian system functions to gate sleep through active inhibition at specific times of day. These data identify a mechanism through which the circadian system prevents premature sleep onset in the late evening, when homeostatic sleep drive is high. © 2016 Associated Professional Sleep Societies, LLC.

Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness.

PubMed

Prakash, Pavitra; Nambiar, Aishwarya; Sheeba, Vasu

2017-01-01

In Drosophila, neuropeptide Pigment Dispersing Factor (PDF) is expressed in small and large ventral Lateral Neurons (sLNv and lLNv), among which sLNv are critical for activity rhythms in constant darkness. Studies show that this is mediated by rhythmic accumulation and likely secretion of PDF from sLNv dorsal projections, which in turn synchronises molecular oscillations in downstream circadian neurons. Using targeted expression of a neurodegenerative protein Huntingtin in LNv, we evoke a selective loss of neuropeptide PDF and clock protein PERIOD from sLNv soma. However, PDF is not lost from sLNv dorsal projections and lLNv. These flies are behaviourally arrhythmic in constant darkness despite persistence of PDF oscillations in sLNv dorsal projections and synchronous PERIOD oscillations in downstream circadian neurons. We find that PDF oscillations in sLNv dorsal projections are not sufficient for sustenance of activity rhythms in constant darkness and this is suggestive of an additional component that is possibly dependent on sLNv molecular clock and PDF in sLNv soma. Additionally, despite loss of PERIOD in sLNv, their activity rhythms entrain to light/dark cycles indicating that sLNv molecular clocks are not necessary for entrainment. Under constant light, these flies lack PDF from both soma and dorsal projections of sLNv, and when subjected to light/dark cycles, show morning and evening anticipation and accurately phased morning and evening peaks. Thus, under light/dark cycles, PDF in sLNv is not necessary for morning anticipation.

Oscillating PDF in termini of circadian pacemaker neurons and synchronous molecular clocks in downstream neurons are not sufficient for sustenance of activity rhythms in constant darkness

PubMed Central

Prakash, Pavitra; Nambiar, Aishwarya; Sheeba, Vasu

2017-01-01

In Drosophila, neuropeptide Pigment Dispersing Factor (PDF) is expressed in small and large ventral Lateral Neurons (sLNv and lLNv), among which sLNv are critical for activity rhythms in constant darkness. Studies show that this is mediated by rhythmic accumulation and likely secretion of PDF from sLNv dorsal projections, which in turn synchronises molecular oscillations in downstream circadian neurons. Using targeted expression of a neurodegenerative protein Huntingtin in LNv, we evoke a selective loss of neuropeptide PDF and clock protein PERIOD from sLNv soma. However, PDF is not lost from sLNv dorsal projections and lLNv. These flies are behaviourally arrhythmic in constant darkness despite persistence of PDF oscillations in sLNv dorsal projections and synchronous PERIOD oscillations in downstream circadian neurons. We find that PDF oscillations in sLNv dorsal projections are not sufficient for sustenance of activity rhythms in constant darkness and this is suggestive of an additional component that is possibly dependent on sLNv molecular clock and PDF in sLNv soma. Additionally, despite loss of PERIOD in sLNv, their activity rhythms entrain to light/dark cycles indicating that sLNv molecular clocks are not necessary for entrainment. Under constant light, these flies lack PDF from both soma and dorsal projections of sLNv, and when subjected to light/dark cycles, show morning and evening anticipation and accurately phased morning and evening peaks. Thus, under light/dark cycles, PDF in sLNv is not necessary for morning anticipation. PMID:28558035

Circadian, Carbon, and Light Control of Expansion Growth and Leaf Movement1[OPEN

PubMed Central

Flis, Anna

2017-01-01

We used Phytotyping4D to investigate the contribution of clock and light signaling to the diurnal regulation of rosette expansion growth and leaf movement in Arabidopsis (Arabidopsis thaliana). Wild-type plants and clock mutants with a short (lhycca1) and long (prr7prr9) period were analyzed in a T24 cycle and in T-cycles that were closer to the mutants’ period. Wild types also were analyzed in various photoperiods and after transfer to free-running light or darkness. Rosette expansion and leaf movement exhibited a circadian oscillation, with superimposed transients after dawn and dusk. Diurnal responses were modified in clock mutants. lhycca1 exhibited an inhibition of growth at the end of night and growth rose earlier after dawn, whereas prr7prr9 showed decreased growth for the first part of the light period. Some features were partly rescued by a matching T-cycle, like the inhibition in lhycca1 at the end of the night, indicating that it is due to premature exhaustion of starch. Other features were not rescued, revealing that the clock also regulates expansion growth more directly. Expansion growth was faster at night than in the daytime, whereas published work has shown that the synthesis of cellular components is faster in the day than at nighttime. This temporal uncoupling became larger in short photoperiods and may reflect the differing dependence of expansion and biosynthesis on energy, carbon, and water. While it has been proposed that leaf expansion and movement are causally linked, we did not observe a consistent temporal relationship between expansion and leaf movement. PMID:28559360

Is It Time to Start Reconsidering the Teaching of Time?

ERIC Educational Resources Information Center

Hurrell, Derek

2017-01-01

When teaching the measurement attribute of time, most teachers are aware that just getting students to read a clock is a task with its own challenges, but is developing this skill and understanding enough? What else do teachers need to make sure they cover, in order to give students a chance of developing this important component of being a…

Components of the Motor Program: The Cerebellum as an Internal Clock. Cognitive Science Program, Technical Report No 86-7.

ERIC Educational Resources Information Center

Ivry, Richard B.; Keele, Steven W.

This report summarizes the initial phase of research with neurological patients on timing functions. Parkinsonian, cerebellar, cortical and peripheral neuropathy patients as well as college aged and elderly control subjects were tested on two separate measures of timing functions. The first task involved the production of timed intervals and used…

Free-running InGaAs single photon detector with 1 dark count per second at 10% efficiency

NASA Astrophysics Data System (ADS)

Korzh, B.; Walenta, N.; Lunghi, T.; Gisin, N.; Zbinden, H.

2014-02-01

We present a free-running single photon detector for telecom wavelengths based on a negative feedback avalanche photodiode (NFAD). A dark count rate as low as 1 cps was obtained at a detection efficiency of 10%, with an afterpulse probability of 2.2% for 20 μs of deadtime. This was achieved by using an active hold-off circuit and cooling the NFAD with a free-piston stirling cooler down to temperatures of -110 °C. We integrated two detectors into a practical, 625 MHz clocked quantum key distribution system. Stable, real-time key distribution in the presence of 30 dB channel loss was possible, yielding a secret key rate of 350 bps.

Food-anticipatory activity and liver per1-luc activity in diabetic transgenic rats

NASA Technical Reports Server (NTRS)

Davidson, Alec J.; Stokkan, Karl-Arne; Yamazaki, Shin; Menaker, Michael

2002-01-01

The mammalian Per1 gene is an important component of the core cellular clock mechanism responsible for circadian rhythms. The rodent liver and other tissues rhythmically express Per1 in vitro but typically damp out within a few cycles. In the liver, the peak of this rhythm occurs in the late subjective night in an ad lib-fed rat, but will show a large phase advance in response to restricted availability of food during the day. The relationship between this shift in the liver clock and food-anticipatory activity (FAA), the circadian behavior entrained by daily feeding, is currently unknown. Insulin is released during feeding in mammals and could serve as an entraining signal to the liver. To test the role of insulin in the shift in liver Per1 expression and the generation of FAA, per-luciferase transgenic rats were made diabetic with a single injection of streptozotocine. Following 1 week of restricted feeding and locomotor activity monitoring, liver was collected for per-luc recording. In two separate experiments, FAA emerged and liver Per1 phase-shifted in response to daytime 8-h food restriction. The results rule out insulin as a necessary component of this system.

A component of retinal light adaptation mediated by the thyroid hormone cascade.

PubMed

Bedolla, Diana E; Torre, Vincent

2011-01-01

Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2-3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4-8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation.

A Component of Retinal Light Adaptation Mediated by the Thyroid Hormone Cascade

PubMed Central

Bedolla, Diana E.; Torre, Vincent

2011-01-01

Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2–3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4–8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand-inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation. PMID:22039463

Extensive circadian and light regulation of the transcriptome in the malaria mosquito Anopheles gambiae

PubMed Central

2013-01-01

Background Mosquitoes exhibit 24 hr rhythms in flight activity, feeding, reproduction and development. To better understand the molecular basis for these rhythms in the nocturnal malaria vector Anopheles gambiae, we have utilized microarray analysis on time-of-day specific collections of mosquitoes over 48 hr to explore the coregulation of gene expression rhythms by the circadian clock and light, and compare these with the 24 hr rhythmic gene expression in the diurnal Aedes aegypti dengue vector mosquito. Results In time courses from An. gambiae head and body collected under light:dark cycle (LD) and constant dark (DD) conditions, we applied three algorithms that detect sinusoidal patterns and an algorithm that detects spikes in expression. This revealed across four experimental conditions 393 probes newly scored as rhythmic. These genes correspond to functions such as metabolic detoxification, immunity and nutrient sensing. This includes glutathione S-transferase GSTE5, whose expression pattern and chromosomal location are shared with other genes, suggesting shared chromosomal regulation; and pulsatile expression of the gene encoding CYP6M2, a cytochrome P450 that metabolizes pyrethroid insecticides. We explored the interaction of light and the circadian clock and highlight the regulation of odorant binding proteins (OBPs), important components of the olfactory system. We reveal that OBPs have unique expression patterns as mosquitoes make the transition from LD to DD conditions. We compared rhythmic expression between An. gambiae and Ae. aegypti heads collected under LD conditions using a single cosine fitting algorithm, and report distinct similarities and differences in the temporal regulation of genes involved in tRNA priming, the vesicular-type ATPase, olfaction and vision between the two species. Conclusions These data build on our previous analyses of time-of-day specific regulation of the An. gambiae transcriptome to reveal additional rhythmic genes, an improved understanding of the co-regulation of rhythms in gene expression by the circadian clock and by light, and an understanding of the time-of-day specific regulation of some of these rhythmic processes in comparison with a different species of mosquito. Improved understanding of biological timing at the molecular level that underlies key physiological aspects of mosquito vectors may prove to be important to successful implementation of established and novel insect control methods. PMID:23552056

Functional and evolutionary relationships between bacteriorhodopsin and halorhodopsin in the archaebacterium, halobacterium halobium

NASA Technical Reports Server (NTRS)

Lanyi, J. K.

1986-01-01

The archaebacteria occupy a unique place in phylogenetic trees constructed from analyses of sequences from key informational macromolecules, and their study continues to yield interesting ideas on the early evolution and divergence of biological forms. It is now known that the halobacteria among these species contain various retinal-proteins, resembling eukaryotic rhodopsins, but with different functions. Two of these pigments, located in the cytoplasmic membranes of the bacteria, are bacteriorhodopsin (a light-driven proton pump) and halorhodopsin (a light-driven chloride pump). Comparison of these systems is expected to reveal structure/function relationships in these simple (primitive?) energy transducing membrane components and evolutionary relationships which had produced the structural features which allow the divergent functions. Findings indicate that very different primary structures are needed for these proteins to accomplish their different functions. Indeed, analysis of partial amino acid sequences from halo-opsin shows already that few if any long segments exist which are homologous to bacterio-opsin. Either these proteins diverged a very long time ago to allow for the observed differences, or the evolutionary clock in the halobacteria runs faster than usual.

All-optical clock recovery, photonic balancing, and saturated asymmetric filtering for fiber optic communication systems

NASA Astrophysics Data System (ADS)

Parsons, Earl Ryan

In this dissertation I investigated a multi-channel and multi-bit rate all-optical clock recovery device. This device, a birefringent Fabry-Perot resonator, had previously been demonstrated to simultaneously recover the clock signal from 10 wavelength channels operating at 10 Gb/s and one channel at 40 Gb/s. Similar to clock signals recovered from a conventional Fabry-Perot resonator, the clock signal from the birefringent resonator suffers from a bit pattern effect. I investigated this bit pattern effect for birefringent resonators numerically and experimentally and found that the bit pattern effect is less prominent than for clock signals from a conventional Fabry-Perot resonator. I also demonstrated photonic balancing which is an all-optical alternative to electrical balanced detection for phase shift keyed signals. An RZ-DPSK data signal was demodulated using a delay interferometer. The two logically opposite outputs from the delay interferometer then counter-propagated in a saturated SOA. This process created a differential signal which used all the signal power present in two consecutive symbols. I showed that this scheme could provide an optical alternative to electrical balanced detection by reducing the required OSNR by 3 dB. I also show how this method can provide amplitude regeneration to a signal after modulation format conversion. In this case an RZ-DPSK signal was converted to an amplitude modulation signal by the delay interferometer. The resulting amplitude modulated signal is degraded by both the amplitude noise and the phase noise of the original signal. The two logically opposite outputs from the delay interferometer again counter-propagated in a saturated SOA. Through limiting amplification and noise modulation this scheme provided amplitude regeneration and improved the Q-factor of the demodulated signal by 3.5 dB. Finally I investigated how SPM provided by the SOA can provide a method to reduce the in-band noise of a communication signal. The marks, which represented data, experienced a spectral shift due to SPM while the spaces, which consisted of noise, did not. A bandpass filter placed after the SOA then selected the signal and filtered out what was originally in-band noise. The receiver sensitivity was improved by 3 dB.

Evaluation and analysis of real-time precise orbits and clocks products from different IGS analysis centers

NASA Astrophysics Data System (ADS)

Zhang, Liang; Yang, Hongzhou; Gao, Yang; Yao, Yibin; Xu, Chaoqian

2018-06-01

To meet the increasing demands from the real-time Precise Point Positioning (PPP) users, the real-time satellite orbit and clock products are generated by different International GNSS Service (IGS) real-time analysis centers and can be publicly received through the Internet. Based on different data sources and processing strategies, the real-time products from different analysis centers therefore differ in availability and accuracy. The main objective of this paper is to evaluate availability and accuracy of different real-time products and their effects on real-time PPP. A total of nine commonly used Real-Time Service (RTS) products, namely IGS01, IGS03, CLK01, CLK15, CLK22, CLK52, CLK70, CLK81 and CLK90, will be evaluated in this paper. Because not all RTS products support multi-GNSS, only GPS products are analyzed in this paper. Firstly, the availability of all RTS products is analyzed in two levels. The first level is the epoch availability, indicating whether there is outage for that epoch. The second level is the satellite availability, which defines the available satellite number for each epoch. Then the accuracy of different RTS products is investigated on nominal accuracy and the accuracy degradation over time. Results show that Root-Mean-Square Error (RMSE) of satellite orbit ranges from 3.8 cm to 7.5 cm for different RTS products. While the mean Standard Deviations of Errors (STDE) of satellite clocks range from 1.9 cm to 5.6 cm. The modified Signal In Space Range Error (SISRE) for all products are from 1.3 cm to 5.5 cm for different RTS products. The accuracy degradation of the orbit has the linear trend for all RTS products and the satellite clock degradation depends on the satellite clock types. The Rb clocks on board of GPS IIF satellites have the smallest degradation rate of less than 3 cm over 10 min while the Cs clocks on board of GPS IIF have the largest degradation rate of more than 10 cm over 10 min. Finally, the real-time kinematic PPP is carried out to investigate the effects of different real-time products. The CLK90 has the best performance and mean RMSE of 26 globally distributed IGS stations in three components are 3.2 cm, 6.6 cm and 8.5 cm. And the second-best positioning results are using IGS03 products.

The light cycle controls the hatching rhythm in Bombyx mori via negative feedback loop of the circadian oscillator.

PubMed

Tao, Hui; Li, Xue; Qiu, Jian-Feng; Liu, Heng-Jiang; Zhang, Da-Yan; Chu, Feng; Sima, Yanghu; Xu, Shi-Qing

2017-10-01

Hatching behavior is a key target in silkworm (Bombyx mori) rearing, especially for the control of Lepidoptera pests. According to previous research, hatching rhythms appear to be controlled by a clock mechanism that restricts or "gates" hatching to a particular time. However, the underlying mechanism remains elusive. Under 12-h light:12-h dark photoperiod (LD) conditions, the transcriptional levels of the chitinase5 (Cht5) and hatching enzyme-like (Hel) genes, as well as the enzymatic activities of their gene products, oscillated in time with ambient light cycles, as did the transcriptional levels of the cryptochrome 1, cryptochrome 2, period (per), and timeless genes, which are key components of the negative feedback loop of the circadian rhythm. These changes were related to the expression profile of the ecdysteroid receptor gene and the hatching behavior of B. mori eggs. However, under continuous light or dark conditions, the hatching behavior, the expression levels of Cht5 and Hel, as well as the enzymatic activities of their gene products, were not synchronized unlike under LD conditions. In addition, immunohistochemistry experiments showed that light promoted the translocation of PER from the cytoplasm to the nucleus. In conclusion, LD cycles regulate the hatching rhythm of B. mori via negative feedback loop of the circadian oscillator. © 2017 Wiley Periodicals, Inc.

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

miR-132 Couples the Circadian Clock to Daily Rhythms of Neuronal Plasticity and Cognition

ERIC Educational Resources Information Center

Aten, Sydney; Hansen, Katelin F.; Snider, Kaitlin; Wheaton, Kelin; Kalidindi, Anisha; Garcia, Ashley; Alzate-Correa, Diego; Hoyt, Kari R.; Obrietan, Karl

2018-01-01

The microRNA miR-132 serves as a key regulator of a wide range of plasticity-associated processes in the central nervous system. Interestingly, miR-132 expression has also been shown to be under the control of the circadian timing system. This finding, coupled with work showing that miR-132 is expressed in the hippocampus, where it influences…

Resolving Phase Ambiguities In OQPSK

NASA Technical Reports Server (NTRS)

Nguyen, Tien M.

1991-01-01

Improved design for modulator and demodulator in offset-quaternary-phase-key-shifting (OQPSK) communication system enables receiver to resolve ambiguity in estimated phase of received signal. Features include unique-code-word modulation and detection and digital implementation of Costas loop in carrier-recovery subsystem. Enchances performance of carrier-recovery subsystem, reduces complexity of receiver by removing redundant circuits from previous design, and eliminates dependence of timing in receiver upon parallel-to-serial-conversion clock.

The design and demonstration of an advanced data collection/position locating system, addendum. [coherent demodulator

NASA Technical Reports Server (NTRS)

1978-01-01

The theoretical background for a coherent demodulator for minimum shift keying signals generated by the advanced data collection/position locating system breadboard is presented along with a discussion of the design concept. Various tests and test results, obtained with the breadboard system described, include evaluation of bit-error rate performance, acquisition time, clock recovery, recycle time, frequency measurement accuracy, and mutual interference.

Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a Gating Mechanism Rather Than a Period-phase Locking Process.

PubMed

Laranjeiro, Ricardo; Tamai, T Katherine; Letton, William; Hamilton, Noémie; Whitmore, David

2018-04-01

Studies from a number of model systems have shown that the circadian clock controls expression of key cell cycle checkpoints, thus providing permissive or inhibitory windows in which specific cell cycle events can occur. However, a major question remains: Is the clock actually regulating the cell cycle through such a gating mechanism or, alternatively, is there a coupling process that controls the speed of cell cycle progression? Using our light-responsive zebrafish cell lines, we address this issue directly by synchronizing the cell cycle in culture simply by changing the entraining light-dark (LD) cycle in the incubator without the need for pharmacological intervention. Our results show that the cell cycle rapidly reentrains to a shifted LD cycle within 36 h, with changes in p21 expression and subsequent S phase timing occurring within the first few hours of resetting. Reentrainment of mitosis appears to lag S phase resetting by 1 circadian cycle. The range of entrainment of the zebrafish clock to differing LD cycles is large, from 16 to 32 hour periods. We exploited this feature to explore cell cycle entrainment at both the population and single cell levels. At the population level, cell cycle length is shortened or lengthened under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable of either speeding up or slowing down the cell cycle. However, analysis at the single cell level reveals that this, in fact, is not true and that a gating mechanism is the fundamental method of timed cell cycle regulation in zebrafish. Cell cycle length at the single cell level is virtually unaltered with varying T-cycles.

Circadian Clock Synchronization of the Cell Cycle in Zebrafish Occurs through a Gating Mechanism Rather Than a Period-phase Locking Process

PubMed Central

Tamai, T. Katherine; Letton, William; Hamilton, Noémie; Whitmore, David

2018-01-01

Studies from a number of model systems have shown that the circadian clock controls expression of key cell cycle checkpoints, thus providing permissive or inhibitory windows in which specific cell cycle events can occur. However, a major question remains: Is the clock actually regulating the cell cycle through such a gating mechanism or, alternatively, is there a coupling process that controls the speed of cell cycle progression? Using our light-responsive zebrafish cell lines, we address this issue directly by synchronizing the cell cycle in culture simply by changing the entraining light-dark (LD) cycle in the incubator without the need for pharmacological intervention. Our results show that the cell cycle rapidly reentrains to a shifted LD cycle within 36 h, with changes in p21 expression and subsequent S phase timing occurring within the first few hours of resetting. Reentrainment of mitosis appears to lag S phase resetting by 1 circadian cycle. The range of entrainment of the zebrafish clock to differing LD cycles is large, from 16 to 32 hour periods. We exploited this feature to explore cell cycle entrainment at both the population and single cell levels. At the population level, cell cycle length is shortened or lengthened under corresponding T-cycles, suggesting that a 1:1 coupling mechanism is capable of either speeding up or slowing down the cell cycle. However, analysis at the single cell level reveals that this, in fact, is not true and that a gating mechanism is the fundamental method of timed cell cycle regulation in zebrafish. Cell cycle length at the single cell level is virtually unaltered with varying T-cycles. PMID:29444612

The frequency of Th17 cells in the small intestine exhibits a day-night variation dependent on circadian clock activity.

PubMed

Thu Le, Ha Pham; Nakamura, Yuki; Oh-Oka, Kyoko; Ishimaru, Kayoko; Nakajima, Shotaro; Nakao, Atsuhito

2017-08-19

Interleukin-17-producing CD4 + T helper (Th17) cells are a key immune lineage that protects against bacterial and fungal infections at mucosal surfaces. At steady state, Th17 cells are abundant in the small intestinal mucosa of mice. There are several mechanisms for regulating the population of Th17 cells in the small intestine, reflecting the importance of maintaining their numbers in the correct balance. Here we demonstrate the existence of a time-of-day-dependent variation in the frequency of Th17 cells in the lamina propria of the small intestine in wild-type mice, which was not observed in mice with a loss-of-function mutation of the core circadian gene Clock or in mice housed under aberrant light/dark conditions. Consistent with this, expression of CCL20, a chemokine that regulates homeostatic trafficking of Th17 cells to the small intestine, exhibited circadian rhythms in the small intestine of wild-type, but not Clock-mutated, mice. In support of these observations, the magnitude of ovalbumin (OVA)-specific antibody and T-cell responses in mice sensitized with OVA plus cholera toxin, a mucosal Th17 cell-dependent adjuvant, was correlated with daily variations in the proportion of Th17 cells in the small intestine. These results suggest that the proportion of Th17 cells in the small intestine exhibits a day-night variation in association with CCL20 expression, which depends on circadian clock activity. The findings provide novel insight into the regulation of the Th17 cell population in the small intestine at steady state, which may have translational potential for mucosal vaccination strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Fossil butterflies, calibration points and the molecular clock (Lepidoptera: Papilionoidea).

PubMed

Jong, Rienk DE

2017-05-25

Fossil butterflies are extremely rare. Yet, they are the only direct evidence of the first appearance of particular characters and as such, they are crucial for calibrating a molecular clock, from which divergence ages are estimated. In turn, these estimates, in combination with paleogeographic information, are most important in paleobiogeographic considerations. The key issue here is the correct allocation of fossils on the phylogenetic tree from which the molecular clock is calibrated.The allocation of a fossil on a tree should be based on an apomorphic character found in a tree based on extant species, similar to the allocation of a new extant species. In practice, the latter is not done, at least not explicitly, on the basis of apomorphy, but rather on overall similarity or on a phylogenetic analysis, which is not possible for most butterfly fossils since they usually are very fragmentary. Characters most often preserved are in the venation of the wings. Therefore, special attention is given to possible apomorphies in venational characters in extant butterflies. For estimation of divergence times, not only the correct allocation of the fossil on the tree is important, but also the tree itself influences the outcome as well as the correct determination of the age of the fossil. These three aspects are discussed.        All known butterfly fossils, consisting of 49 taxa, are critically reviewed and their relationship to extant taxa is discussed as an aid for correctly calibrating a molecular clock for papilionoid Lepidoptera. In this context some aspects of age estimation and biogeographic conclusions are briefly mentioned in review. Specific information has been summarized in four appendices.

Predicted Role of NAD Utilization in the Control of Circadian Rhythms during DNA Damage Response

PubMed Central

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

2015-01-01

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

Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation

PubMed Central

Amador, Ariadna; Huitron-Resendiz, Salvador; Roberts, Amanda J.; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

2016-01-01

The circadian clock maintains appropriate timing for a wide range of behaviors and physiological processes. Circadian behaviors such as sleep and wakefulness are intrinsically dependent on the precise oscillation of the endogenous molecular machinery that regulates the circadian clock. The identical core clock machinery regulates myriad endocrine and metabolic functions providing a link between sleep and metabolic health. The REV-ERBs (REV-ERBα and REV-ERBβ) are nuclear receptors that are key regulators of the molecular clock and have been successfully targeted using small molecule ligands. Recent studies in mice suggest that REV-ERB-specific synthetic agonists modulate metabolic activity as well as alter sleep architecture, inducing wakefulness during the light period. Therefore, these small molecules represent unique tools to extensively study REV-ERB regulation of sleep and wakefulness. In these studies, our aim was to further investigate the therapeutic potential of targeting the REV-ERBs for regulation of sleep by characterizing efficacy, and optimal dosing time of the REV-ERB agonist SR9009 using electroencephalographic (EEG) recordings. Applying different experimental paradigms in mice, our studies establish that SR9009 does not lose efficacy when administered more than once a day, nor does tolerance develop when administered once a day over a three-day dosing regimen. Moreover, through use of a time response paradigm, we determined that although there is an optimal time for administration of SR9009 in terms of maximal efficacy, there is a 12-hour window in which SR9009 elicited a response. Our studies indicate that the REV-ERBs are potential therapeutic targets for treating sleep problems as those encountered as a consequence of shift work or jet lag. PMID:27603791

Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver.

PubMed

Kudo, T; Akiyama, M; Kuriyama, K; Sudo, M; Moriya, T; Shibata, S

2004-08-01

An increase in PAI-1 activity is thought to be a key factor underlying myocardial infarction. Mouse Pai-1 (mPai-1) activity shows a daily rhythm in vivo, and its transcription seems to be controlled not only by clock genes but also by humoral factors such as insulin and triglycerides. Thus, we investigated daily clock genes and mPai-1 mRNA expression in the liver of db/db mice exhibiting high levels of glucose, insulin and triglycerides. Locomotor activity was measured using an infrared detection system. RT-PCR or in situ hybridisation methods were applied to measure gene expression. Humoral factors were measured using measurement kits. The db/ db mice showed attenuated locomotor activity rhythms. The rhythmic expression of mPer2 mRNA was severely diminished and the phase of mBmal1 oscillation was advanced in the db/db mouse liver, whereas mPai-1 mRNA was highly and constitutively expressed. Night-time restricted feeding led to a recovery not only from the diminished locomotor activity, but also from the diminished Per2 and advanced mBmal1 mRNA rhythms. Expression of mPai-1 mRNA in db/db mice was reduced to levels far below normal. Pioglitazone treatment slightly normalised glucose and insulin levels, with a slight reduction in mPai-1 gene expression. We demonstrated that Type 2 diabetes impairs the oscillation of the peripheral oscillator. Night-time restricted feeding rather than pioglitazone injection led to a recovery from the diminished locomotor activity, and altered oscillation of the peripheral clock and mPai-1 mRNA rhythm. Thus, we conclude that scheduled restricted food intake may be a useful form of treatment for diabetes.

Clocks to Computers: A Machine-Based “Big Picture” of the History of Modern Science.

PubMed

van Lunteren, Frans

2016-12-01

Over the last few decades there have been several calls for a “big picture” of the history of science. There is a general need for a concise overview of the rise of modern science, with a clear structure allowing for a rough division into periods. This essay proposes such a scheme, one that is both elementary and comprehensive. It focuses on four machines, which can be seen to have mediated between science and society during successive periods of time: the clock, the balance, the steam engine, and the computer. Following an extended developmental phase, each of these machines came to play a highly visible role in Western societies, both socially and economically. Each of these machines, moreover, was used as a powerful resource for the understanding of both inorganic and organic nature. More specifically, their metaphorical use helped to construe and refine some key concepts that would play a prominent role in such understanding. In each case the key concept would at some point be considered to represent the ultimate building block of reality. Finally, in a refined form, each of these machines would eventually make its entry in scientific research, thereby strengthening the ties between these machines and nature.

Decadal Cycles in the Human Cardiovascular System

PubMed Central

Halberg, Franz; Cornelissen, Germaine; Sothern, Robert B.; Hillman, Dewayne; Watanabe, Yoshihiko; Haus, Erhard; Schwartzkopff, Othild; Best, William R.

2013-01-01

Seven of the eight authors of this report each performed physiologic self-surveillance, some around the clock for decades. We here document the presence of long cycles (decadals, including circaundecennians) in the time structure of systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR). Because of the non-stationary nature in time and space of these and other physiologic and environmental periodic components that, like the wind, can appear and disappear in a given or other geographic location at one or another time, they have been called “Aeolian”. The nonlinear estimation of the uncertainties of the periods (τs) of two or more variables being compared has been used to determine whether these components are congruent or not, depending on whether their CIs (95% confidence intervals) overlap or not. Among others, congruence has been found for components with τs clustering around 10 years in us and around us. There is a selective assortment among individuals, variables and cycle characteristics (mean and circadian amplitude and acrophase). Apart from basic interest, like other nonphotic solar signatures such as transyears with periods slightly longer than one year or about 33-year Brückner-Egeson-Lockyer (BEL) cycles, about 10-year and longer cycles present in 7 of 7 self-monitoring individuals are of interest in the diagnosis of Vascular Variability Anomalies (VVAs), including MESOR-hypertension, and others. Some of the other VVAs, such as a circadian overswing, i.e., CHAT (Circadian Hyper-Aplitude-Tension), or an excessive pulse pressure, based on repeated 7-day around-the-clock records, can represent a risk of severe cardiovascular events, greater than that of a high BP. The differential diagnosis of physiologic cycles, infradians (components with a τ longer than 28 hours) as well as circadians awaits the collection of reference values for the infradian parameters of the cycles described herein. Just as in stroke-prone spontaneously hypertensive rats during the weeks after weaning CHAT precedes an elevation of the BP MESOR, a decadal overswing seems to precede the occurrence of high BP in two of the subjects here examined. Only around-the-clock monitoring in health for the collection of reference values will allow on their basis the differential diagnosis of the onsets of a circadian versus a circadecadal overswing in BP and the specification whether, and if so, when to initiate hypotensive non-drug or drug treatment. PMID:24860279

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.

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.

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

Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis.

PubMed

Thaiss, Christoph A; Zeevi, David; Levy, Maayan; Zilberman-Schapira, Gili; Suez, Jotham; Tengeler, Anouk C; Abramson, Lior; Katz, Meirav N; Korem, Tal; Zmora, Niv; Kuperman, Yael; Biton, Inbal; Gilad, Shlomit; Harmelin, Alon; Shapiro, Hagit; Halpern, Zamir; Segal, Eran; Elinav, Eran

2014-10-23

All domains of life feature diverse molecular clock machineries that synchronize physiological processes to diurnal environmental fluctuations. However, no mechanisms are known to cross-regulate prokaryotic and eukaryotic circadian rhythms in multikingdom ecosystems. Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation. Together, these findings provide evidence of coordinated metaorganism diurnal rhythmicity and offer a microbiome-dependent mechanism for common metabolic disturbances in humans with aberrant circadian rhythms, such as those documented in shift workers and frequent flyers.

A seafloor electromagnetic receiver for marine magnetotellurics and marine controlled-source electromagnetic sounding

NASA Astrophysics Data System (ADS)

Chen, Kai; Wei, Wen-Bo; Deng, Ming; Wu, Zhong-Liang; Yu, Gang

2015-09-01

In planning and executing marine controlled-source electromagnetic methods, seafloor electromagnetic receivers must overcome the problems of noise, clock drift, and power consumption. To design a receiver that performs well and overcomes the abovementioned problems, we performed forward modeling of the E-field abnormal response and established the receiver's characteristics. We describe the design optimization and the properties of each component, that is, low-noise induction coil sensor, low-noise Ag/AgCl electrode, low-noise chopper amplifier, digital temperature-compensated crystal oscillator module, acoustic telemetry modem, and burn wire system. Finally, we discuss the results of onshore and offshore field tests to show the effectiveness of the developed seafloor electromagnetic receiver and its performance: typical E-field noise of 0.12 nV/m/rt(Hz) at 0.5 Hz, dynamic range higher than 120 dB, clock drift lower than 1 ms/day, and continuous operation of at least 21 days.

An immune clock of human pregnancy

PubMed Central

Aghaeepour, Nima; Ganio, Edward A.; Mcilwain, David; Tsai, Amy S.; Tingle, Martha; Van Gassen, Sofie; Gaudilliere, Dyani K.; Baca, Quentin; McNeil, Leslie; Okada, Robin; Ghaemi, Mohammad S.; Furman, David; Wong, Ronald J.; Winn, Virginia D.; Druzin, Maurice L.; El-Sayed, Yaser Y.; Quaintance, Cecele; Gibbs, Ronald; Darmstadt, Gary L.; Shaw, Gary M.; Stevenson, David K.; Tibshirani, Robert; Nolan, Garry P.; Lewis, David B.; Angst, Martin S.; Gaudilliere, Brice

2017-01-01

The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling–based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2–dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies. PMID:28864494

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.

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

Combination of precise GNSS orbit and clock solutions in a multi-constellation, multi-frequency environment

NASA Astrophysics Data System (ADS)

Ortiz Geist, Estefania

2015-04-01

Precise GNSS orbit and clock solutions are essential for the generation of the Terrestrial Reference Frame (TRF) and required for a broad variety of applications. Over the last decades the combination products of the International GNSS Service (IGS) have become the standard for all kinds of GNSS applications requiring highest accuracy. The emerging new GNSS constellations Galileo, BeiDou and the QZSS as well as the modernization of the already established GPS and GLONASS constellations will stimulate a new development in the GNSS data processing in order to gain be best benefit from the new signals and systems for geodetic and geodynamic applications. This introduces the question regarding the influence of this development on the orbit and clock products. What are the consequences for the consistency of the contributions from the Analysis Centres (ACs) of the IGS and how does the combination procedure need to react on his development? Another set of questions is related to the expected scenario in which not all IGS ACs will likely include all GNSS. The algorithm for the orbit and clock combination needs to be adapted for a multi-system combination to keep on one hand the internal consistency between the GNSS during the combination procedure but also consider the differences in the expected orbit qualities between the satellite systems (e.g., due to the number of satellites or network coverage). To investigate these questions ESOC and AIUB have agreed on a joint research fellowship for three years. The objective of this research is to analyse the capabilities and challenges when combining hybrid multi-GNSS solutions and to develop a concept, which compares and combines orbit and clock contributions to come up with a consistent, reliable, truly combined multi-GNSS combination product. Well-defined test scenarios shall be constructed and analysed based on the GNSS data processing software packages in the two institutions, namely "NAPEOS" and "Bernese GNSS Software". The presentation will show selected results from the on-going research, to address the impact of several key elements, on the potential combination, which will ultimately give the criteria for the weighting scheme undertaken in the combination.

Genome-Wide Analysis of SREBP1 Activity around the Clock Reveals Its Combined Dependency on Nutrient and Circadian Signals

PubMed Central

Naldi, Aurélien; Baruchet, Michaël; Canella, Donatella; Le Martelot, Gwendal; Guex, Nicolas; Desvergne, Béatrice; Delorenzi, Mauro; Deplancke, Bart; Desvergne, Béatrice; Guex, Nicolas; Herr, Winship; Naef, Felix; Rougemont, Jacques; Schibler, Ueli; Deplancke, Bart; Guex, Nicolas; Herr, Winship; Guex, Nicolas; Andersin, Teemu; Cousin, Pascal; Gilardi, Federica; Gos, Pascal; Martelot, Gwendal Le; Lammers, Fabienne; Canella, Donatella; Gilardi, Federica; Raghav, Sunil; Fabbretti, Roberto; Fortier, Arnaud; Long, Li; Vlegel, Volker; Xenarios, Ioannis; Migliavacca, Eugenia; Praz, Viviane; Guex, Nicolas; Naef, Felix; Rougemont, Jacques; David, Fabrice; Jarosz, Yohan; Kuznetsov, Dmitry; Liechti, Robin; Martin, Olivier; Delafontaine, Julien; Sinclair, Lucas; Cajan, Julia; Krier, Irina; Leleu, Marion; Migliavacca, Eugenia; Molina, Nacho; Naldi, Aurélien; Rey, Guillaume; Symul, Laura; Guex, Nicolas; Naef, Felix; Rougemont, Jacques; Bernasconi, David; Delorenzi, Mauro; Andersin, Teemu; Canella, Donatella; Gilardi, Federica; Martelot, Gwendal Le; Lammers, Fabienne; Baruchet, Michaël; Raghav, Sunil

2014-01-01

In mammals, the circadian clock allows them to anticipate and adapt physiology around the 24 hours. Conversely, metabolism and food consumption regulate the internal clock, pointing the existence of an intricate relationship between nutrient state and circadian homeostasis that is far from being understood. The Sterol Regulatory Element Binding Protein 1 (SREBP1) is a key regulator of lipid homeostasis. Hepatic SREBP1 function is influenced by the nutrient-response cycle, but also by the circadian machinery. To systematically understand how the interplay of circadian clock and nutrient-driven rhythm regulates SREBP1 activity, we evaluated the genome-wide binding of SREBP1 to its targets throughout the day in C57BL/6 mice. The recruitment of SREBP1 to the DNA showed a highly circadian behaviour, with a maximum during the fed status. However, the temporal expression of SREBP1 targets was not always synchronized with its binding pattern. In particular, different expression phases were observed for SREBP1 target genes depending on their function, suggesting the involvement of other transcription factors in their regulation. Binding sites for Hepatocyte Nuclear Factor 4 (HNF4) were specifically enriched in the close proximity of SREBP1 peaks of genes, whose expression was shifted by about 8 hours with respect to SREBP1 binding. Thus, the cross-talk between hepatic HNF4 and SREBP1 may underlie the expression timing of this subgroup of SREBP1 targets. Interestingly, the proper temporal expression profile of these genes was dramatically changed in Bmal1 −/− mice upon time-restricted feeding, for which a rhythmic, but slightly delayed, binding of SREBP1 was maintained. Collectively, our results show that besides the nutrient-driven regulation of SREBP1 nuclear translocation, a second layer of modulation of SREBP1 transcriptional activity, strongly dependent from the circadian clock, exists. This system allows us to fine tune the expression timing of SREBP1 target genes, thus helping to temporally separate the different physiological processes in which these genes are involved. PMID:24603613

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

Free-running InGaAs single photon detector with 1 dark count per second at 10% efficiency

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

Korzh, B., E-mail: Boris.Korzh@unige.ch; Walenta, N.; Lunghi, T.

We present a free-running single photon detector for telecom wavelengths based on a negative feedback avalanche photodiode (NFAD). A dark count rate as low as 1 cps was obtained at a detection efficiency of 10%, with an afterpulse probability of 2.2% for 20 μs of deadtime. This was achieved by using an active hold-off circuit and cooling the NFAD with a free-piston stirling cooler down to temperatures of −110 °C. We integrated two detectors into a practical, 625 MHz clocked quantum key distribution system. Stable, real-time key distribution in the presence of 30 dB channel loss was possible, yielding a secret key rate of 350 bps.

Decoy-state quantum key distribution with polarized photons over 200 km.

PubMed

Liu, Yang; Chen, Teng-Yun; Wang, Jian; Cai, Wen-Qi; Wan, Xu; Chen, Luo-Kan; Wang, Jin-Hong; Liu, Shu-Bin; Liang, Hao; Yang, Lin; Peng, Cheng-Zhi; Chen, Kai; Chen, Zeng-Bing; Pan, Jian-Wei

2010-04-12

We report an implementation of decoy-state quantum key distribution (QKD) over 200 km optical fiber cable through photon polarization encoding. This is achieved by constructing the whole QKD system operating at 320 MHz repetition rate, and developing high-speed transmitter and receiver modules. A novel and economic way of synchronization method is designed and incorporated into the system, which allows to work at a low frequency of 40kHz and removes the use of highly precise clock. A final key rate of 15 Hz is distributed within the experimental time of 3089 seconds, by using super-conducting single photon detectors. This is longest decoy-state QKD yet demonstrated up to date. It helps to make a significant step towards practical secure communication in long-distance scope.

New Discrete Fibonacci Charge Pump Design, Evaluation and Measurement

NASA Astrophysics Data System (ADS)

Matoušek, David; Hospodka, Jiří; Šubrt, Ondřej

2017-06-01

This paper focuses on the practical aspects of the realisation of Dickson and Fibonacci charge pumps. Standard Dickson charge pump circuit solution and new Fibonacci charge pump implementation are compared. Both charge pumps were designed and then evaluated by LTspice XVII simulations and realised in a discrete form on printed circuit board (PCB). Finally, the key parameters as the output voltage, efficiency, rise time, variable power supply and clock frequency effects were measured.

High-power Al-free active region (λ= 852nm) DFB laser diodes for atomic clocks and interferometry applications

NASA Astrophysics Data System (ADS)

Ligeret, V.; Vermersch, F.-J.; Bansropun, S.; Lecomte, M.; Calligaro, M.; Parillaud, O.; Krakowski, M.

2017-11-01

Atomic clocks will be used in the future European positioning system Galileo. Among them, the optically pumped clocks provide a better alternative with comparable accuracy for a more compact system. For these systems, diode lasers emitting at 852nm are strategic components. The laser in a conventional bench for atomic clocks presents disadvantages for spatial applications. A better approach would be to realise a system based on a distributed-feedback laser (DFB). We have developed the technological foundations of such lasers operating at 852nm. These include an Al free active region, a single spatial mode ridge waveguide and a DFB structure. The device is a separate confinement heterostructure with a GaInP large optical cavity and a single compressive strained GaInAsP quantum well. The broad area laser diodes are characterised by low internal losses (<3cm -1 ), a high internal efficiency (94%) and a low transparency current density (100A/cm2). For an AR-HR coated ridge Fabry Perot laser, we obtain a power of 230mW with M2=1.3. An optical power of 150mW was obtained at 854nm wavelength, 20°C for AR-HR coated devices. We obtain a single spatial mode emission with M2=1.21 and a SMSR over 30dB, both at 150mW. DFB Lasers at 852.12nm, corresponding to the D2 caesium transition, were then realised with a power of 40mW, 37°C for uncoated devices. The SMSR is over 30dB and the M2=1.33 at 40mW. Furthermore, the preliminary results of the linewidth obtained with a Fabry Perot interferometer give a value of less than 2MHz.

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.

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.

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.

Global Transcriptome Sequencing Reveals Molecular Profiles of Summer Diapause Induction Stage of Onion Maggot, Delia antiqua (Diptera: Anthomyiidae)

PubMed Central

Ren, Shuang; Hao, You-Jin; Chen, Bin; Yin, You-Ping

2017-01-01

The onion maggot, Delia antiqua, is a worldwide subterranean pest and can enter diapause during the summer and winter seasons. The molecular regulation of the ontogenesis transition remains largely unknown. Here we used high-throughput RNA sequencing to identify candidate genes and processes linked to summer diapause (SD) induction by comparing the transcriptome differences between the most sensitive larval developmental stage of SD and nondiapause (ND). Nine pairwise comparisons were performed, and significantly differentially regulated transcripts were identified. Several functional terms related to lipid, carbohydrate, and energy metabolism, environmental adaption, immune response, and aging were enriched during the most sensitive SD induction period. A subset of genes, including circadian clock genes, were expressed differentially under diapause induction conditions, and there was much more variation in the most sensitive period of ND- than SD-destined larvae. These expression variations probably resulted in a deep restructuring of metabolic pathways. Potential regulatory elements of SD induction including genes related to lipid, carbohydrate, energy metabolism, and environmental adaption. Collectively, our results suggest the circadian clock is one of the key drivers for integrating environmental signals into the SD induction. Our transcriptome analysis provides insight into the fundamental role of the circadian clock in SD induction in this important model insect species, and contributes to the in-depth elucidation of the molecular regulation mechanism of insect diapause induction. PMID:29158334

The ability to entrain to long photoperiods differs between 3 Drosophila melanogaster wild-type strains and is modified by twilight simulation.

PubMed

Rieger, Dirk; Peschel, Nicolai; Dusik, Verena; Glotz, Silvia; Helfrich-Förster, Charlotte

2012-02-01

The ability to adapt to different environmental conditions including seasonal changes is a key feature of the circadian clock. Here, we compared the ability of 3 Drosophila melanogaster wild-type strains to adapt rhythmic activity to long photoperiods simulated in the laboratory. Fruit flies are predominantly crepuscular with activity bouts in the morning (M) and evening (E). The M peak follows dawn and the E peak follows dusk when the photoperiod is extended. We show that this ability is restricted to a certain extension of the phase angle between M and E peaks, such that the E peak does not delay beyond a certain phase under long days. We demonstrate that this ability is significantly improved by simulated twilight and that it depends additionally on the genetic background and the ambient temperature. At 20 °C, the laboratory strain CantonS had the most flexible phase angle between M and E peaks, a Northern wild-type strain had an intermediate one, and a Southern wild-type strain had the lowest flexibility. Furthermore, we found that the 3 strains differed in clock light sensitivity, with the CantonS and the Northern strains more light sensitive than the Southern strain. These results are generally in accord with the recently discovered polymorphisms in the timeless gene (tim) that affect clock light sensitivity.

Retinoic Acid-Related Orphan Receptor γ (RORγ): A Novel Participant in the Diurnal Regulation of Hepatic Gluconeogenesis and Insulin Sensitivity

PubMed Central

Takeda, Yukimasa; Kang, Hong Soon; Freudenberg, Johannes; DeGraff, Laura M.; Jothi, Raja; Jetten, Anton M.

2014-01-01

The hepatic circadian clock plays a key role in the daily regulation of glucose metabolism, but the precise molecular mechanisms that coordinate these two biological processes are not fully understood. In this study, we identify a novel connection between the regulation of RORγ by the clock machinery and the diurnal regulation of glucose metabolic networks. We demonstrate that particularly at daytime, mice deficient in RORγ exhibit improved insulin sensitivity and glucose tolerance due to reduced hepatic gluconeogenesis. This is associated with a reduced peak expression of several glucose metabolic genes critical in the control of gluconeogenesis and glycolysis. Genome-wide cistromic profiling, promoter and mutation analysis support the concept that RORγ regulates the transcription of several glucose metabolic genes directly by binding ROREs in their promoter regulatory region. Similar observations were made in liver-specific RORγ-deficient mice suggesting that the changes in glucose homeostasis were directly related to the loss of hepatic RORγ expression. Altogether, our study shows that RORγ regulates several glucose metabolic genes downstream of the hepatic clock and identifies a novel metabolic function for RORγ in the diurnal regulation of hepatic gluconeogenesis and insulin sensitivity. The inhibition of the activation of several metabolic gene promoters by an RORγ antagonist suggests that antagonists may provide a novel strategy in the management of metabolic diseases, including type 2 diabetes. PMID:24831725

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