Clock Phase Research Articles

Red Light Resets the Expression Pattern, Phase, and Period of the Circadian Clock in Plants: A Computational Approach.

Simple SummaryProgress in computational biology has provided a comprehensive understanding of the dynamics of the plant circadian clock. Previously proposed models of the plant circadian clock have intended to model its entrainment using white-light/dark cycles. However, these models have failed to take into account the effect of light quality on circadian rhythms, which has been experimentally observed. In this work, we developed a computational approach to characterizing the effects of light quality on plant circadian rhythms. The results demonstrated that red light can reset the expression patterns, phases, and periods of clock component genes. The circadian period, amplitude, and phase can be co-optimized for high-quality and efficient breeding.Recent research in the fields of biochemistry and molecular biology has shown that different light qualities have extremely different effects on plant development, and optimizing light quality conditions can speed up plant growth. Clock-regulated red-light signaling, can enhance hypocotyl elongation, and increase seedling height and flower and fruit productivity. In order to investigate the effect of red light on circadian clocks in plants, a novel computational model was established. The expression profiles of the circadian element CCA1 from previous related studies were used to fit the model. The simulation results were validated by the expression patterns of CCA1 in Arabidopsis, including wild types and mutants, and by the phase shifts of CCA1 after red-light pulse. The model was used to further explore the complex responses to various photoperiods, such as the natural white-light/dark cycles, red/white/dark cycles, and extreme 24 h photoperiods. These results demonstrated that red light can reset the expression pattern, period, and phase of the circadian clock. Finally, we identified the dependence of phase shifts on the length of red-light pulse and the minimum red-light pulse length required for producing an observable phase shift. This work provides a promising computational approach to investigating the response of the circadian clock to other light qualities.

Inter-layer and inter-subject variability of diurnal gene expression in human skin.

The skin is the largest human organ with a circadian clock that regulates its function. Although circadian rhythms in specific functions are known, rhythms in the proximal clock output, gene expression, in human skin have not been thoroughly explored. This work reports 24 h gene expression rhythms in two skin layers, epidermis and dermis, in a cohort of young, healthy adults, who maintained natural, regular sleep-wake schedules. 10% of the expressed genes showed such diurnal rhythms at the population level, of which only a third differed between the two layers. Amplitude and phases of diurnal gene expression varied more across subjects than layers, with amplitude being more variable than phases. Expression amplitudes in the epidermis were larger and more subject-variable, while they were smaller and more consistent in the dermis. Core clock gene expression was similar across layers at the population-level, but were heterogeneous in their variability across subjects. We also identified small sets of biomarkers for internal clock phase in each layer, which consisted of layer-specific non-core clock genes. This work provides a valuable resource to advance our understanding of human skin and presents a novel methodology to quantify sources of variability in human circadian rhythms.

A low power high speed single phase clock level restoring 16T master-slave flip-flop

PurposeA low power flip-flop circuit is designed for energy-efficient devices. Digital sequential circuits are in huge demand because every processor has most of the parts of digital circuit. The sequential circuits consist of a basic data storing element, a latch is used to store single bit data. The flip-flop takes a sufficient portion of the total chip area and overall power consumption as well. This study aims to the low power energy-efficient applications like laptops, mobile phones and palmtops.Design/methodology/approachThis paper proposes a new type of flip-flop that consists of the only 16 transistors with a single-phase clock. The flip-flop has two blocks, master and slave latch. In this design, the authors have focused on only master latch, which includes a level restoring circuit. It is used to help the master latch in data retention process. The latch circuit has two inverters in back-to-back arrangement. The proposed flip-flop is implemented on 65 nm complementary metal oxide semiconductor technology using Cadence Virtuoso environment and compared with other reported flip-flops.FindingsThe proposed flip-flop architecture outperformed the peak percentage, i.e. 79.25% as compared to transmission gate flip-flop and a minimum of 20.02% compared to 18 T true single phase clocking (TSPC) improvement in terms of power. It also improved C to Q delay and power delay product. In addition, by reducing the number of transistors the total area of the proposed flip-flop is reduced by a minimum of 13.76% with respect to 18TSPC and existing flip-flop. For reliability checking the Monte Carlo simulation is performed for thousand samples and it is compared with the recently reported 18TSPC flip-flop.Originality/valueThis work is tested by using a test circuit with a load capacitor of 0.2 fF. The proposed work uses a new topology to work as master-slave. Power consumption of this technique is very less and it is best suitable for low power applications. This circuit is working properly up to 2 GHz frequency.

A 0.9‐V human body communication receiver using a dummy electrode and clock phase inversion scheme

This paper presents a low-power and lightweight human body communication (HBC) receiver with an embedded dummy electrode for improved signal acquisition. The clock data recovery (CDR) circuit in the receiver operates with a low supply voltage and utilizes a clock phase inversion scheme. The receiver is equipped with a main electrode and dummy electrode that strengthen the capacitive-coupled signal at the receiver frontend. The receiver CDR circuit exploits a clock inversion scheme to allow 0.9-V operation while achieving a shorter lock time than at 3.3-V operation. In experiments, a receiver chip fabricated using 130-nm complementary metal–oxide–semiconductor technology was demonstrated to successfully receive the transmitted signal when the transmitter and receiver are placed separately on each hand of the user while consuming only 4.98 mW at a 0.9-V supply voltage.

True Single Phase Clock based UP-DOWN Counter using GDI Cell for Low Power Applications

True Single Phase Clock based UP-DOWN Counter using GDI Cell for Low Power Applications

Single‐bit digital comparator circuit design using quantum‐dot cellular automata nanotechnology

AbstractThe large amount of secondary effects in complementary metal–oxide–semiconductor technology limits its application in the ultra‐nanoscale region. Circuit designers explore a new technology for the ultra‐nanoscale region, which is the quantum‐dot cellular automata (QCA). Low‐energy dissipation, high speed, and area efficiency are the key features of the QCA technology. This research proposes a novel, low‐complexity, QCA‐based one‐bit digital comparator circuit for the ultra‐nanoscale region. The performance of the proposed comparator circuit is presented in detail in this paper and compared with that of existing designs. The proposed QCA structure for the comparator circuit only consists of 19 QCA cells with two clock phases. QCA Designer‐E and QCA Pro tools are applied to estimate the total energy dissipation. The proposed comparator saves 24.00% QCA cells, 25.00% cell area, 37.50% layout cost, and 78.11% energy dissipation compared with the best reported similar design.

Time for Exercise? Exercise and Its Influence on the Skeletal Muscle Clock.

Circadian rhythms drive our daily behaviors to coincide with the earth's rotation on an approximate 24-h cycle. The circadian clock mechanism present in nearly every cell is responsible for our circadian rhythms and is comprised of a transcriptional-translational feedback loop in mammals. The central clock resides in the hypothalamus responding to external light cues, whereas peripheral clocks receive signals from the central clock and are also sensitive to cues from feeding and activity. Of the peripheral clocks, the skeletal muscle clock is particularly sensitive to exercise which has shown to be an important time-cue with the ability to influence and adjust the muscle clock phase in response to exercise timing. Since the skeletal muscle clock is also involved in the expression of tissue-specific gene expression-including glucoregulatory genes-this might suggest a role for exercise timing as a therapeutic strategy in metabolic diseases, like type 2 diabetes. Notably, those with type 2 diabetes have accompanied disruptions in their skeletal muscle clock mechanism which may also be related to the increased risk of type 2 diabetes seen among shift workers. Therefore, the direct influence of exercise on the skeletal muscle clock might support the use of exercise timing to provide disease-mitigating effects. Here, we highlight the potential use of time-of-day exercise as a chronotherapeutic tool within circadian medicine to improve the metabolic profile of type 2 diabetes and support long-term glycemic control, potentially working through the skeletal muscle clock and circadian physiology.

A Multichannel, High-Bandwidth Wirelane Receiver for D2D Interconnects

This paper proposes a multichannel and high-bandwidth (BW) receiver for standard packaging die-to-die (D2D) interconnects. The receiver adopts forward clock (FCK) architecture of the high-density transmission standard, which consists of 16 high-speed data paths and a pair of low-speed differential clocks for 512 Gbps BW. To reduce the chip area and power consumption, a common minimal phase-locked loop (MINI-PLL) and data adjustment (CDA) circuit to replaces the clock data recovery circuit (CDR) in the traditional receiver. A delay-matching circuit is adopted to combat PVT variation and lane skew. In addition, a high linearity phase interpolator (PI) circuit design is used in the minimum phase-locked loop (MINI-PLL) to adjust the clock phase and improve the clock jitter performance. Using 28 nm CMOS technology, the overall link power consumption is 1.56 pJ/b. Bit error rate (BER) is less than 10−15 under the real S-parameters with a channel loss of 10db@16GHz.

An Effective Frequency Drift and Phase Offset Estimation Based on Two-Way Message Exchange for WSNs Time Synchronization

Time synchronization is one of the key technologies of wireless sensor networks. At present, most studies assume that the transmission delay is a fixed value, and there is no effective processing of historical clock data. Therefore, this paper proposes a clock frequency drift and phase offset estimation scheme which is considering variable transmission delay and historical clock data. This paper has clarified the effectiveness of the Gaussian delay model in the calculation of time synchronization error. On this basis, this paper calculated the maximum likelihood estimations of frequency drift and phase offset and the corresponding Cramer-Rao lower bound. Meanwhile, the transmission delay is optimized by comparing the chi-square distance between measured and standard data. Also, this paper conducts autonomous training on historical data to provide services for improving the accuracy of fitting estimation. Simulation results validate the performance of the proposed scheme.

A novel efficient coplanar QCA full adder and full subtractor design

ABSTRACT Quantum-dot Cellular Automata (QCA) nanotechnology is an alternative technology with high speed, high density and low power for designing nanoscale circuits. A novel design of Full Adder-Subtractor based on full subtractor using single layer is proposed. The proposed architecture has a major advantage in terms of complexity, area, latency, and power consumption as compared to previous designs. The proposed QCA full subtractor showed higher performance concerning area with a reduction of 66%, and complexity with a reduction of 51% over best existing circuit designs. However, the proposed design of full Adder-Subtractor achieved a reduction of 74% in area, with 70% improvement in complexity, 33% reduction in latency by using two clock phases, and 95% improvement in cost needed over the best reported circuits using single-layer design. Total cell area and cost for the Full Adder-Subtractor were 0.01 μm2 and 0.07, respectively. Results showed that power consumption for the novel design was minimal. Therefore, the suggested Full Adder-Subtractor provides 86% less total energy consumption for 0.5Ek tunnelling energy level. These designs were tested and simulated using the freely known QCA Designer tool version 2.0.3. The energy dissipation result was realised by using the QCAPro energy estimation tool.

A constant charging-current relaxation oscillator with a duty-cycled main comparator and an adaptive auxiliary comparator

A low-power constant charging-current relaxation oscillator that outputs a frequency-tunable sawtooth signal and a pulse signal is proposed and implemented in 0.5-μm CMOS process. At the architecture level, two comparators with 10 times difference in power consumption are proposed to break up the tight tradeoff between power consumption and oscillation performance. Most of the time, only the low-power auxiliary comparator works to save power. The high-power main comparator is controlled by the auxiliary comparator output and only works when a ramping voltage is close to a reference voltage. At the circuit level, an adaptive current control technique that makes current adversely proportional to input voltage differences is used to further reduce the power consumed in the low-power comparator. The measured clock phase noise at the offset frequency of 100 kHz is −115.07 dBc/Hz at the output frequency of 1 MHz. The measured output frequency variations are 124 ppm/°C over temperatures from −55 °C to 125 °C, and −0.13%–0.18% over power supplies from 3 V to 5.5 V. The frequency range from 200 kHz to 1350 kHz is achieved. The power consumption at the 1 MHz output frequency is 9.5 μW, which is comparable with state-of-the-art designs in the literature.

Performance Analysis of BDS-3 SAIM and Enhancement Research on Autonomous Satellite Ephemeris Monitoring

Integrity is one of the key indicators used to characterize the performance of the global navigation satellite systems (GNSSs) and is closely related to user safety. In order to realize real-time global integrity monitoring, the BeiDou Global Navigation Satellite System (BDS-3) has realized the “satellite autonomous integrity monitoring” (SAIM) function in its satellites for the first time. BDS-3 SAIM has the monitoring functions of signal power, pseudo-range, satellite clock frequency and phase, but not the monitoring function of broadcast ephemeris. In this study, the long-term stability and distribution characteristics of BDS-3 SAIM monitoring data were analyzed by using the actual telemetry data for the first time. The results show that the SAIM monitoring data have good long-term stability and basically follow a normal distribution, which meets the design expectations. Meanwhile, in view of the fact that BDS-3 SAIM does not have the ability to independently monitor broadcast ephemerides, which may lead to the over-tolerance of BDS-3 to the probability risk of risks of integrity in the active space environment, a SAIM enhancement design for ephemeris monitoring is proposed, which integrates three relatively independent methods, with the ephemeris extrapolated from the previous cycle, and the ephemeris generated by autonomous orbit determination, inter-satellite link distance measurement data as reference data, respectively. The three methods are analyzed and verified. The results show that each of the three methods has advantages and disadvantages in terms of monitoring accuracy and resource dependence. The integration of the three methods can combine their complementary advantages and can also provide valuable as an important reference for engineering applications.

Circadian-period variation underlies the local adaptation of photoperiodism in the short-day plant Lemna aequinoctialis

SummaryPhenotypic variation is the basis for trait adaptation via evolutionary selection. However, the driving forces behind quantitative trait variations remain unclear owing to their complexity at the molecular level. This study focused on the natural variation of the free-running period (FRP) of the circadian clock because FRP is a determining factor of the phase phenotype of clock-dependent physiology. Lemna aequinoctialis in Japan is a paddy field duckweed that exhibits a latitudinal cline of critical day length (CDL) for short-day flowering. We collected 72 strains of L. aequinoctialis and found a significant correlation between FRPs and locally adaptive CDLs, confirming that variation in the FRP-dependent phase phenotype underlies photoperiodic adaptation. Diel transcriptome analysis revealed that the induction timing of an FT gene is key to connecting the clock phase to photoperiodism at the molecular level. This study highlights the importance of FRP as a variation resource for evolutionary adaptation.

Bright Light Increases Alertness and Not Cortisol in Healthy Men: A Forced Desynchrony Study Under Dim and Bright Light (I).

Light-induced improvements in alertness are more prominent during nighttime than during the day, suggesting that alerting effects of light may depend on internal clock time or wake duration. Relative contributions of both factors can be quantified using a forced desynchrony (FD) designs. FD designs have only been conducted under dim light conditions (<10 lux) since light above this amount can induce non-uniform phase progression of the circadian pacemaker (also called relative coordination). This complicates the mathematical separation of circadian clock phase from homeostatic sleep pressure effects. Here we investigate alerting effects of light in a novel 4 × 18 h FD protocol (5 h sleep, 13 h wake) under dim (6 lux) and bright light (1300 lux) conditions. Hourly saliva samples (melatonin and cortisol assessment) and 2-hourly test sessions were used to assess effects of bright light on subjective and objective alertness (electroencephalography and performance). Results reveal (1) stable free-running cortisol rhythms with uniform phase progression under both light conditions, suggesting that FD designs can be conducted under bright light conditions (1300 lux), (2) subjective alerting effects of light depend on elapsed time awake but not circadian clock phase, while (3) light consistently improves objective alertness independent of time awake or circadian clock phase. Reconstructing the daily time course by combining circadian clock phase and wake duration effects indicates that performance is improved during daytime, while subjective alertness remains unchanged. This suggests that high-intensity indoor lighting during the regular day might be beneficial for mental performance, even though this may not be perceived as such.

A passive second‐order noise‐shaping SAR ADC architecture with increased freedom in NTF synthesis and relaxed clock‐jitter issue

Noise-shaping (NS) successive approximation register (SAR) analogue-to-digital converters (ADCs) are an attractive architecture for power and area efficiency in moderate resolution and bandwidth applications. NS SAR ADCs employing a passive integrator are good candidates for their omission of power-hungry and scaling-unfriendly amplifiers. However, existing passive NS SAR ADCs have a very limited degree of freedom in realising their noise transfer function (NTF), resulting in poor in-band noise suppression. In this letter, a passive switched-capacitor 2nd-order NS SAR ADC that is the first of its kind to offer controllable complex poles to optimise the NTF is proposed. This is achieved by eliminating a capacitor charge clearing operation in a conventional 1st-order NS SAR. The proposed NS SAR ADC also offers simple circuits insensitive to process–voltage–temperature (PVT) variations, and small area with only two extra clock phases. Transistor-level circuit simulation of a 7-bit, 8-MHz bandwidth, 128 MS/s prototype in a 65-nm CMOS shows a 70 dB signal to noise and distortion ratio (SNDR), an improvement of 19 dB compared to that of a regular 7-bit SAR ADC.

TSPC-HNTL: True Single Phase Clock technique for High speed, Noise Tolerance, and Low power

TSPC-HNTL: True Single Phase Clock technique for High speed, Noise Tolerance, and Low power

Time Restricted Feeding to the Light Cycle Dissociates Canonical Circadian Clocks and Physiological Rhythms in Heart Rate.

Circadian rhythms are approximate 24-h biological cycles that optimize molecular and physiological functions to predictable daily environmental changes in order to maintain internal and organismal homeostasis. Environmental stimuli (light, feeding, activity) capable of altering the phase of molecular rhythms are important tools employed by circadian biologists to increase understanding of the synchronization of circadian rhythms to the environment and to each other within multicellular systems. The central circadian clock, located in the suprachiasmatic nucleus (SCN) of the hypothalamus is largely responsive to light and is thought to entrain the phase of peripheral clocks via neurohumoral signals. Mice are nocturnal and consume most of their food during the dark cycle. Early studies demonstrated that altered metabolic cues in the form of time restricted feeding, specifically, feeding mice during the light cycle, resulted in an uncoupling of molecular clocks in peripheral tissues with those from the SCN. These studies showed as much as a 12-h shift in gene expression in some peripheral tissues but not others. The shifts occurred without corresponding changes in the central clock in the brain. More recent studies have demonstrated that changes in cardiac physiology (heart rate, MAP) in response to time of food intake occur independent of the cardiac molecular clock. Understanding differences in the physiology/function and gene expression in other organs both independently and in relation to the heart in response to altered feeding will be important in dissecting the roles of the various clocks throughout the body, as well as, understanding their links to cardiovascular pathology.

Effect of Prenatal Glucocorticoid Exposure on Circadian Rhythm Gene Expression in the Brains of Adult Rat Offspring.

Circadian clocks control many vital aspects of physiology from the sleep-wake cycle to metabolism. The circadian clock operates through transcriptional-translational feedback loops. The normal circadian signaling relies on a ‘master clock’, located in the suprachiasmatic nucleus (SCN), which synchronizes peripheral oscillators. Glucocorticoid receptor (GR) signaling has the ability to reset the phase of peripheral clocks. It has been shown that maternal exposure to glucocorticoids (GCs) can lead to modification of hypothalamic-pituitary-adrenal (HPA) function, impact stress-related behaviors, and result in a hypertensive state via GR activation. We previously demonstrated altered circadian rhythm signaling in the adrenal glands of offspring exposed to the synthetic GC, dexamethasone (Dex). Results from the current study show that prenatal exposure to Dex affects circadian rhythm gene expression in a brain region-specific and a sex-specific manner within molecular oscillators of the amygdala, hippocampus, paraventricular nucleus, and prefrontal cortex, as well as the main oscillator in the SCN. Results also show that spontaneously hypertensive rats (SHR) exhibited dysregulated circadian rhythm gene expression in these same brain regions compared with normotensive Wistar-Kyoto rats (WKY), although the pattern of dysregulation was markedly different from that seen in adult offspring prenatally exposed to GCs.

A light-induced small G-protein gem limits the circadian clock phase-shift magnitude by inhibiting voltage-dependent calcium channels.

Calcium signaling is pivotal to the circadian clockwork in the suprachiasmatic nucleus (SCN), particularly in rhythm entrainment to environmental light-dark cycles. Here, we show that a small G-protein Gem, an endogenous inhibitor of high-voltage-activated voltage-dependent calcium channels (VDCCs), is rapidly induced by light in SCN neurons via the calcium (Ca2+)-mediated CREB/CRE transcriptional pathway. Gem attenuates light-induced calcium signaling through its interaction with VDCCs. The phase-shift magnitude of locomotor activity rhythms by light, at night, increases in Gem-deficient (Gem-/-) mice. Similarly, in SCN slices from Gem-/- mice, depolarizing stimuli induce larger phase shifts of clock gene transcription rhythms that are normalized by the application of an L-type VDCC blocker, nifedipine. Voltage-clamp recordings from SCN neurons reveal that Ca2+ currents through L-type channels increase in Gem-/- mice. Our findings suggest that transcriptionally activated Gem feeds back to suppress excessive light-evoked L-type VDCC activation, adjusting the light-induced phase-shift magnitude to an appropriate level in mammals.

The macroscopic limit to synchronization of cellular clocks in single cells of Neurospora crassa

We determined the macroscopic limit for phase synchronization of cellular clocks in an artificial tissue created by a “big chamber” microfluidic device to be about 150,000 cells or less. The dimensions of the microfluidic chamber allowed us to calculate an upper limit on the radius of a hypothesized quorum sensing signal molecule of 13.05 nm using a diffusion approximation for signal travel within the device. The use of a second microwell microfluidic device allowed the refinement of the macroscopic limit to a cell density of 2166 cells per fixed area of the device for phase synchronization. The measurement of averages over single cell trajectories in the microwell device supported a deterministic quorum sensing model identified by ensemble methods for clock phase synchronization. A strong inference framework was used to test the communication mechanism in phase synchronization of quorum sensing versus cell-to-cell contact, suggesting support for quorum sensing. Further evidence came from showing phase synchronization was density-dependent.