Internal Clock Research Articles

Chrono-nutrition and post-bariatric weight loss: insights from the Portuguese ChronoWise cohort

Abstract Background Post-bariatric weight loss varies substantially, and a large proportion of patients respond poorly. The literature highlights the importance of chrono-nutrition for weight regulation. This study aims to explore the chrono-related factors associated with poorer weight loss. Methods This study was conducted within the ChronoWise project, an ongoing prospective cohort study following patients undergoing bariatric surgery at the Santo António Local Health Unit, Porto. The sample included patients evaluated at both pre-surgery and 3 months post-surgery. Baseline information on meal timing was gathered through the Chrononutrition Profile-Questionnaire. The eating midpoint (midpoint between first and last meal) was calculated for work and free days. Chronotype was determined using the Munich Chronotype Questionnaire. Weight loss was expressed as the percent of total weight loss (%TWL = [(initial weight − current weight)/(initial weight)]×100). Chrono-related variables were compared according to %TWL (dichotomized by the median) using the Mann-Whitney test. Results Sixty patients were included (72% female; mean age 45±11.8). The mean baseline BMI was 44±5.6 kg/m2, which decreased to 35±5.3 kg/m2 at 3 months post-surgery, resulting in an average 20±3.9 %TWL. On free days, participants with lower %TWL tend to do the first meal later in the day (9h45 vs. 9h10, р=0.367), and later lunch on workdays (12h45 vs 12h30, р=0.531) compared with individuals with higher %TWL. Lower %TWL is typically observed in individuals having later eating midpoints (15h00 vs. 14h15 for workdays, р=0.011; 15h07 vs. 14h44 for free days, р=0.205). A later chronotype (3h37 vs 3h30, р=0.347) was also linked with poorer weight loss. Conclusions Eating later during the day and later chronotype may contribute to poorer post-bariatric weight loss. Funding: This work was supported by FCT - Fundação para a Ciência e Tecnologia [2021.01096.CEECIND, UIDB/04750/2020,LA/P/0064/2020&SGITR2023/EPIUnit]. Key messages • Recognizing meal timing as a modifiable lifestyle factor may optimize current approaches by aligning food intake with circadian clock. • A later chronotype, i.e. a behavioural expression of an individual’s internal circadian clock system as a preference for eveningness or later sleep timing, may negatively influence weight loss.

Differences in time perception in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a condition that occurs due to complete (apnea) and partial (hypopnea) obstruction in the upper airways during sleep. Hypoxia is one of the key factors contributing to the development of symptoms of obstructive sleep apnea and OSA-related diseases. The present study aimed to evaluate time perception differences between patients with OSA and healthy individuals, as well as among different OSA severity groups. Twenty severe OSA, twenty moderate OSA, twenty mild OSA patients, and twenty healthy volunteers without OSA were included in the study. Scales were administered to the participants. Time perception tests were administered to evaluate perceptual timing. In the paced motor timing test, a difference was observed between the OSA ( +) group and the OSA (-) group. In the Time Estimation Test, a difference was observed between the OSA ( +) group and the OSA (-) group and their subgroups. The internal clock works slower in the OSA ( +) group. When subgroups were compared based on the degree of OSA, the internal clock worked slower as we transitioned from the OSA (-) group to the severe OSA group. It is considered that as you move from the OSA (-) group to the severe OSA group, the switch between pacemaker and accumulator is disrupted due to the decrease in attention. Recurrent hypoxia observed in OSA may alter the perception of time by affecting attention.

Light-driven synchronization of optogenetic clocks

Synthetic genetic oscillators can serve as internal clocks within engineered cells to program periodic expression. However, cell-to-cell variability introduces a dispersion in the characteristics of these clocks that drives the population to complete desynchronization. Here, we introduce the optorepressilator, an optically controllable genetic clock that combines the repressilator, a three-node synthetic network in E. coli, with an optogenetic module enabling to reset, delay, or advance its phase using optical inputs. We demonstrate that a population of optorepressilators can be synchronized by transient green light exposure or entrained to oscillate indefinitely by a train of short pulses, through a mechanism reminiscent of natural circadian clocks. Furthermore, we investigate the system’s response to detuned external stimuli observing multiple regimes of global synchronization. Integrating experiments and mathematical modeling, we show that the entrainment mechanism is robust and can be understood quantitatively from single cell to population level.

Light-driven synchronization of optogenetic clocks.

Synthetic genetic oscillators can serve as internal clocks within engineered cells to program periodic expression. However, cell-to-cell variability introduces a dispersion in the characteristics of these clocks that drives the population to complete desynchronization. Here, we introduce the optorepressilator, an optically controllable genetic clock that combines the repressilator, a three-node synthetic network in E. coli, with an optogenetic module enabling to reset, delay, or advance its phase using optical inputs. We demonstrate that a population of optorepressilators can be synchronized by transient green light exposure or entrained to oscillate indefinitely by a train of short pulses, through a mechanism reminiscent of natural circadian clocks. Furthermore, we investigate the system's response to detuned external stimuli observing multiple regimes of global synchronization. Integrating experiments and mathematical modeling, we show that the entrainment mechanism is robust and can be understood quantitatively from single cell to population level.

A new methodology for evaluating the neighbor discovery time in schedule-based asynchronous duty-cycling wireless sensor networks

Duty cycling is a fundamental mechanism for battery-operated wireless networks, such as wireless sensor networks. Due to its importance, it is an integral part of several Medium Access Protocols and related wireless technologies. In Schedule-based Asynchronous Duty Cycle, nodes activate and deactivate their radio interfaces according to a pre-designed schedule of slots, which guarantees overlapping uptime between two neighbors, independent of the offset between their internal clocks, making communication between them possible. This paper presents a new methodology for evaluating the Neighbor Discovery Time (NDT) of Schedule-based Asynchronous Duty Cycle. Differently from previous methodologies, it accounts for the possibility of the slots in the schedules of the two neighbors not being perfectly border-aligned — an unrealistic assumption in practice. By means of simulation, we show that not taking this under consideration can lead to an overestimate of the NDT by a factor of 2 depending on the particular scenario, thus justifying the importance of our work.•We propose a new subslot-based methodology for computing the NDT of a wakeup schedule used for asynchronous duty cycling.•It replaces the traditional slot-based methodology, by dividing slots into subslots, allowing for the analysis of non-integer clock offsets between nodes, and further allowing mathematical models to consider the more realistic continuous-time case.•Our validation data shows that the slot-based methodology may overestimate NDT by a factor of up to 2, making the proposed subslot-based methodology much more precise.

A novel strategy to map a locus associated with flowering time in canola (Brassica napus L.).

Flowering time is an important agronomic trait for canola breeders, as it provides growers with options for minimizing exposure to heat stress during flowering and to more effectively utilize soil moisture. Plants have evolved various systems to control seasonal rhythms in reproductive phenology including an internal circadian clock that responds to environmental signals. In this study, we used canola cultivar 'Westar' as a recurrent parent and canola cultivar 'Surpass 400' as the donor parent to generate a chromosome segment substitution line (CSSL) and to map a flowering time locus on chromosome A10 using molecular marker-assisted selection. This CSSL contains an introgressed 4.6 mega-bases (Mb) segment (between 13 and 17.6Mb) of Surpass 400, which substantially delayed flowering compared with Westar. To map flowering time gene(s) within this locus, eight introgression lines (ILs) were developed carrying a series of different lengths of introgressed chromosome A10 segments using five co-dominant polymorphic markers located at 13.5, 14.0, 14.5, 15.0, 15.5, and 16.0Mb. Eight ILs were crossed with Westar reciprocally and flowering time of resultant 16 F1 hybrids and parents were evaluated in a greenhouse (2021 and 2022). Four ILs (IL005, IL017, IL035, and IL013) showed delayed flowering compared to Westar (P < 0.0001), and their reciprocal crosses displayed a phenotype intermediate in flowering time of both homozygote parents. These results indicated that flowering time is partial or incomplete dominance, and the flowering time locus mapped within a 1Mb region between two co-dominant polymorphic markers at 14.5-15.5Mb on chromosome A10. The flowering time locus was delineated to be between 14.60 and 15.5Mb based on genotypic data at the crossover site, and candidate genes within this region are associated with flowering time in canola and/or Arabidopsis. The co-dominant markers identified on chromosome A10 should be useful for marker assisted selection in breeding programs but will need to be validated to other breeding populations or germplasm accessions of canola.

7861 Estrogen Receptor Alpha Regulates the Sex Difference in Jet Lag in Mice

Abstract Disclosure: M.A. Venegas: None. N. Westray: None. J.S. Pendergast: None. The circadian system aligns 24-hour cycles of internal biological processes with the environmental light-dark cycle. Abrupt shifts in the timing of the light-dark cycle that occur during travel across time zones misalign internal circadian clocks with the environment and cause jet lag. The symptoms of jet lag subside when circadian clocks resynchronize to the new light-dark cycle. Female mice in proestrus resynchronize to shifted light-dark cycles faster than males. The objective of this study was to investigate the estrogen signaling mechanisms underlying this sex difference in jet lag in mice. We measured wheel-running activity rhythms in C57BL/6J male and female wild-type (WT) and ERα knockout (ERαKO) mice. Female WT mice had 2-fold greater daily activity than male mice. Disabling the function of ERα ablated the sex difference in daily activity; both male and female ERαKO mice had markedly reduced activity compared to WT mice. Next, we advanced the timing of the light-dark cycle by 6 hours to simulate eastward travel. Female WT mice resynchronized to the new light-dark cycle faster than WT males. This sex difference was abolished in ERαKO mice. The rate of resynchronization was slower in female ERaKO mice compared to WT females and was indistinguishable from males. We next investigated 2 putative mechanisms underlying the accelerated rate of resynchronization in WT females. First, mice with faster endogenous clocks resynchronize to new light-dark cycles faster. However, we found that the velocity of the endogenous clock (circadian period) did not differ between WT and ERαKO male and female mice. Second, mice with greater phase advances to light exposure in the late night also resynchronize faster. To determine the magnitude of phase advances, we housed mice in constant darkness and then exposed them to a 15-minute light pulse during the late subjective night. We found no differences in the magnitudes of phase shifts between WT and ERαKO male and female mice. Together these studies show that ERα regulates the rate of resynchronization to shifted light-dark cycles in female mice but does not do so by altering conventional circadian rhythm parameters. Uncovering the mechanisms underlying the sex difference in resynchronization to shifted light-dark cycles can be used to develop strategies to alleviate jet lag and shift work symptoms. Presentation: 6/3/2024

Research on automated verification method for temperature-related tests of electrical energy meters

Abstract Program of pattern evaluation of fixed electrical energy meters-alternating current and GB/T 17215 series of national standards for the examination of energy meter performance by the impact of temperature change, set up a variety of temperature-related test items. Systematic research is possible to conclude that temperature-related tests can be divided into two categories according to the test procedure: Hold at test temperature for a certain period of time, return to the reference temperature and then measure the relevant parameters; measurement of the relevant parameters immediately after a certain period of time at the test temperature. Relevant parameters include errors at different load points and daily timing error of the internal clock of the energy meter. Data processing is undertaken after the test mainly consists of deriving error shift and mean temperature coefficient. This automated calibration method allows you to freely set the test temperature, test duration, reference temperature, stabilization duration, detection parameters, test points and data processing according to the test requirements. The paper explains in detail the application of the automated calibration method to realize typical temperature dependence, test of time-keeping accuracy of the energy meter with temperature and climatic tests (high temperature test, low temperature test and durability test of accuracy) The method breaks the shackles of the traditional calibration method of fixed test temperature, fixed test points and fixed test duration. It can adapt to the development needs of different levels of pattern evaluation of energy meter and national standards, for the laboratory to realize automated testing to provide the basis for industry standards and product testing commissioned inspection.

Estimation of seismometer clock time offsets using Kalman Filter towards accurate seismic velocity change

SUMMARY Monitoring seismic velocity changes obtained from ambient noise correlations is widely used to understand changes in rock properties in response to earthquakes, volcanic activities and environmental changes. Since continuous seismic data have been accumulated, this method can estimate long-term changes in seismic velocity, such as crustal recovery after a major earthquake and temporal variations in seismic velocity related to long-term environmental change. Changes in seismic velocity can be estimated with a high temporal resolution by measuring the phase differences of ambient noise correlations based on a seismic interferometry method. Still, these phase differences are influenced not only by seismic wave velocity changes but also by errors in clock timing in seismometers. The clock drift occurs due to out-of-synchronization with the GPS clock and the drift of the internal clock. Therefore, to accurately monitor temporal changes in crustal structure by measuring the phase differences of noise correlations, it is crucial to evaluate the contribution of errors in clock timing to the phase differences. Recently, a method using an extended Kalman filter based on a state-space model was developed for reliable detection of temporal changes in the waveforms of ambient noise correlations, with the state-space model offering the advantage of flexible modelling of time-series data. In this study, we incorporated the time-shifts caused by clock time errors of the seismometer into the state-space model of the temporal changes in ambient noise correlations. We estimated seismic velocity changes, amplitude changes of noise correlations and clock time errors from 2010 April to 2021 September at seismic stations around the Shinmoe-dake volcano in Japan, which experienced eruptions in 2011 and 2018, respectively. Several stations exhibited clear clock time offsets, and the occurrence of clock time-shifts coincided with the dates when the data logger was turned off for seismic station maintenance or replacement of the seismometer. The proposed method provides stable estimations with respect to the signal-to-noise ratio of the waveform, and this stable estimation facilitates accurate timing of seismic recordings, enabling precise analysis of seismic phase arrival times.

Internal clock errors in synchrophasor ambient data: Effects, detection, and a posteriori estimation-based correction

Synchrophasor data from real world power systems are exposed to numerous adverse cyber-and-physical operating conditions that can negatively impact their fitness for use in PMU applications. Although the most significant impairments such as GPS loss, instrument transformer failure, data drop-off, etc., have been studied in the literature, there exist other more complex nuisances that impact PMU data quality. This is the case of differences in how clock synchronization, time disciplining, and phasor estimation is performed by different PMU vendors, which have important implications on the PMUs’ data fitness for use in PMU applications. In particular, ambient data applications, which have increasingly become a focus for tracking grid performance indicators, are extremely sensitive to periodic clock errors. Using synchrophasor and waveform data from Dominion Energy’s power system, this article provides an in-depth analysis of the effect of seemingly minor device clock errors on the measurement signals’ content. Finally, a method to distinguish clock errors from normal system dynamics and to correct them is proposed.

On Some Forgotten Formulas of L. de Broglie and the Nature of Thermal Time.

From 1948 until around 1965, Louis de Broglie, awarded the Nobel Prize for Physics in 1929 for his fundamental contributions to quantum theory, pursued a systematic study of the formal analogies between wave mechanics and the thermomechanics of Boltzmann and Helmholtz. As part of this line of research, he produced several interesting observations, which were, however, published only in French, and, therefore, had a very limited diffusion. Here, we reconsider, in particular, a result of his relating to the analogy between the internal clock (de Broglie phase) of a free particle and a cyclic isothermal process in a thermomechanical system. We show that the fundamental equivalence obtained by him can be derived under more convenient hypotheses than the original ones, essentially tied to the quantization of the action exchanged by the particle with a suitable thermostat. In this emended formulation, the relations proposed by de Broglie describe the emergence of the particle proper time from a thermal background. They also suggest a specific physical meaning of the Wick rotation, often used in quantum mechanical calculations, and the thermal time that appears in it.

Exploring the associations between chronotype, meal frequency, and physical activity: A population-based study in adults

ABSTRACT Chronotype is an established concept designed to capture the internal clock’s phase in real-life conditions. It is vital in many aspects of daily life and can interfere considerably with numerous factors in a given population. Recognizing nonmodifiable and modifiable factors is crucial for identifying covariates of interest when studying the link between chronotype and health status. To date, chronotype and its related factors have not been extensively investigated. The present study aimed to explore the association of chronotypes with meal frequency, physical activity, and demographic factors among the Saudi population. This cross-sectional web-based questionnaire involved 1369 adults (aged 18 years and above) from the general public in Saudi Arabia and was conducted between March and May 2019. Chronotype was assessed using the reduced version of the original Horne and Ostberg morningness-eveningness questionnaire (MEQ). Meal frequencies and demographics data (age, gender, marital status, place of residence, educational level, employment status, income) were obtained. Physical activity level was also obtained using the international physical activity questionnaire. The MEQ scores group individuals into three categories: morning-type, neither-type, and evening-type. The neither-type individuals represented 41.6% (95% confidence interval [CI], 37.5% − 45.6%) of the study population, followed by the morning-type (34.1%; 95% [CI], 29.8% − 38.4%), then the evening-type (24.3%, 95% [CI], 19.6% − 28.9%). Chronotype was significantly associated with age, marital status, employment status and monthly income (All p < 0.05). Significant associations between chronotype with meal frequencies (number of meals per day, breakfast frequency, lunch frequency, and dinner frequency) and physical activity were also observed (All p < 0.05). This study highlights that meal frequencies and physical activity levels are associated with chronotype distribution. Furthermore, demographics, including age, marital status, employment status, and income, were associated with chronotype distribution.

Toward an endophenotype for ADHD: Exploring the duration mismatch negativity in drug-free children with ADHD

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent disorders in children that is considered to affect early stages of information processes. Inefficient processing of temporal information, which is a vital auditory processing skill suggests itself as a potential candidate for investigating ADHD deficits. The Research Domain Criteria (RDoC), a neuroscience-based research framework, has been introduced to study mental illness without relying on pre-established diagnostic categories. In this regard, Mismatch Negativity (MMN) has been considered an ideal electrophysiological marker for investigating ADHD deficits. This study investigates alterations in the amplitude and latency of the MMN component in response to changes in the duration and Inter-Stimulus Interval (ISI) of basic sound stimuli within an oddball task. The MMN paradigm was employed to examine duration deviations in ADHD (n = 25, 84% male, mean age: 7.3 years, SD = 2.01) compared to Control group of typically developing (TD) children (n = 25, 72% male, mean age: 7.2 years, SD = 1.92). Participants with ADHD were introduced from an accredited psychiatrist. TD children were recruited from social media and online forms. Both groups were matched in terms of gender, age and IQ. The psychological tests conducted in this study included Conners’ Parent Rating Scale (CPRS), Gilliam Autism Rating Scale|Third Edition (Gars3), Sensory profile questionnaire and Edinburgh Handedness inventory. Our findings revealed reduced MMN amplitudes in response to two blocks of duration and ISI-based deviations in ADHD children. To elaborate in greater detail, at Fz, in Duration and ISI block, respectively, the ADHD group showed an amplitude of −1.2097 ± 0.2938 and −0.8553 ± 0.4423, while the normal group showed an amplitude of −1.8325 ± 0.3689 and −2.0855 ± 0.3802. Additionally, at Cz, the ADHD group exhibited a shorter amplitude (-1.2515 ± 0.3261 and −0.9367 ± 0.3432) compared to the normal group (−2.1319 ± 0.4445 and −2.7561 ± 0.4883), in the duration and ISI blocks, respectively. Furthermore, children with ADHD display longer MMN latencies in both experimental blocks, suggesting atypical responses. To provide more detail, at Fz, the ADHD group displayed MMN latencies of 239.68 ± 5.059 and 226.88 ± 4.885 in the Duration and ISI blocks, respectively, whereas the normal group showed MMN latencies of 228.56 ± 6.584 and 213.56 ± 4.153. Similarly, at Cz, the ADHD group exhibited longer MMN latencies (234.40 ± 5.741 and 231.44 ± 5.464) compared to the normal group (227.52 ± 6.710 and 218.00 ± 5.261) in the Duration and ISI blocks, respectively. Our findings were interpreted in the context of the internal clock model, which involves the pace of an internal pacemaker regulated by dopamine (DA) levels. The convergence of MMN and auditory timing abnormalities within the RDoC framework suggests their potential as endophenotypes for ADHD, highlighting the significance of sensory processing in understanding the disorder.

The time course of Temporal Binding in social and nonsocial interactions.

Temporal Binding (TB) is the subjective compression of action-effect intervals. While the effects of nonsocial actions are highly predictable, it is not the case when interacting with conspecifics, who often act under their own volition, at a time of their choosing. Given the relative differences in action-effect predictability in non-social and social interactions, it is plausible that TB and its properties differ across these situations. To examine this, in two experiments, we compared the time course of TB in social and nonsocial interactions, systematically varying action-effect intervals (200-2,100 ms). Participants were told they were (a) interacting with another person via a live webcam, who was in fact a confederate (social condition), (b) interacting with pre-recorded videos (nonsocial condition), or (c) observing two pre-recorded videos (control condition; Experiment 2). Results across experiments showed greater TB for social compared to nonsocial conditions, and the difference was proportional to the action-effect intervals. Further, in Experiment 1, TB was consistently observed throughout the experiment for social interactions, whereas nonsocial TB decreased from the first to the second half of the experiment. In Experiment 2, the nonsocial condition did not differ from control, whereas the social condition did, exhibiting enhanced binding. We argue these results suggest that the sociality of an interaction modulates the 'internal clock' of time perception.

Melatonin as a Circadian Marker for Plasmodium Rhythms.

Plasmodium, a digenetic parasite, requires a host and a vector for its life cycle completion. Most Plasmodium species display circadian rhythmicity during their intraerythrocytic cycle within the host, aiding in immune evasion. This rhythmicity, however, diminishes in in vitro cultures, highlighting the importance of host-derived signals for synchronizing the parasite's asexual cycle. Studies indicate a species-specific internal clock in Plasmodium, dependent on these host signals. Melatonin, a hormone the pineal gland produces under circadian regulation, impacts various physiological functions and is extensively reviewed as the primary circadian marker affecting parasite rhythms. Research suggests that melatonin facilitates synchronization through the PLC-IP3 signaling pathway, activating phospholipase C, which triggers intracellular calcium release and gene expression modulation. This evidence strongly supports the role of melatonin as a key circadian marker for parasite synchronization, presenting new possibilities for targeting the melatonin pathway when developing novel therapeutic approaches.

Late chronotype and associated health problems

Introduction: Chronotype reflects an individual's preference for activity and rest within a 24-hour period, governed by the internal circadian clock system located in the suprachiasmatic nuclei of the hypothalamus. There are three chronotypes: Morning, Evening, and Intermediate. The evening type is also called “night owls” or late chronotype. Night owls prefer to be active in the evening and sleep and wake up late. The misalignment between the sleep patterns in late chronotype and the social schedules puts the night owls in danger of physical and mental health issues. Purpose of work: The primary aim of this review is to provide a comprehensive overview of current knowledge on the impact of late chronotype on health. Methods and materials: A review of the literature available in the PubMed database, the following keywords and their combinations were searched: "chronotype", “mental health", "cancer", “late chronotype”, “circadian rhythm”, “type 2 diabetes”, “depression”. State of knowledge: Studies have confirmed that late chronotype is associated with a higher risk of type 2 diabetes, obesity, cancer, alcohol and cigarette addiction, and unhealthy eating habits. Furthermore, the evening chronotype is an independent risk factor for depression. It is also linked with anxiety, bipolar disorder, and schizophrenia. Summary: In this review, we have summarized the latest research on late chronotype, circadian misalignment, and their potential consequences on human health. Most studies on evening chronotype and related health issues are cross-sectional. Further longitudinal or experimental research is needed to examine the potential cause-and-effect relationships on this cause.

Was the clock correct? Exploring timestamp interpretation through time anchors for digital forensic event reconstruction

Timestamps and their correct interpretation play a crucial role in digital forensic investigations, particularly when the objective is to establish a timeline of events a.k.a. event reconstruction. However, the way these timestamps are generated heavily depends on an internal clock, or ‘system time’, from which many are derived. Consequently, when this system time is skewed due to tampering, natural clock drift, or system malfunctions, recorded timestamps will not reflect the actual times the (real-world) events occurred. This raises the question of how to validate the correctness of the system clock when recording timestamps and, if found incorrect, how to determine system clock skew. To address this problem, this paper defines several important concepts such as time anchors, anchoring events, non-anchoring events and time anomalies which can be used to determine if the system time was correct. Using two examples - a Google search and a file creation - and comparing correct and skewed versions of the same set of performed actions, we illustrate the use and potential benefits of time anchors to demonstrate the correctness of the system clock for event reconstruction.

Ideal Time to Practice Yoga: Insights from Traditional Yoga Texts and Observations from Scientific Studies: A Narrative Review

Background: Those interested in practicing yoga often lack clarity on what would be the best time to practice yoga. This paper intends to review the ancient, scientific and contemporary literature to understand this. Ancient texts on yoga mention that the best time to practice yoga is early morning hours. Lack of information and standardization regarding timing of the yoga practice is a key indicator for us to explore current study on the influence of time on yoga practice which can set a direction for the future studies and possible outcomes that can be derived by choosing the best time to practice yoga. Methods: In this review article we searched the scientific and traditional literature to find an answer to this question. We searched Google Scholar and PubMed using the following criteria: 1) Research studies examining the influence of timing on practice of Yoga, exercise, meditation or mindfulness on various variables 2) Studies published in English language until March 1, 2024. Results: We found sixteen studies; most of them were surveys that tried to assess the influence of time of physical activity/mindfulness on various health parameters. We observed that there are studies that suggest that the best time to practice yoga could depend on the specific outcome that is attempted to be achieved. Awareness of the appropriate time to practice yoga is important for several reasons, including enhancing the effectiveness of the practice, to regulating the body's internal clock, reducing the chances of distractions and developing a consistent regimen for practice. Conclusion: Engaging in morning vigorous exercise or yoga is better than evening vigorous yoga or exercise for enhancing the state of mind/mood of the practitioner and improving sleep quality in the night. Evening yoga should be less intense, relaxing and more meditative. Intense exercise / yoga in the evening may reduce the sleep quality in night. Studies also suggest that the difference in chronotype of the individual could possibly play a role in determining the best time to practice yoga.

Human primary cells can tell body time: Dedicated to Steven A. Brown.

The field of chronobiology has advanced significantly since ancient observations of natural rhythms. The intricate molecular architecture of circadian clocks, their hierarchical organization within the mammalian body, and their pivotal roles in organ physiology highlight the complexity and significance of these internal timekeeping mechanisms. In humans, circadian phenotypes exhibit considerable variability among individuals and throughout the individual's lifespan. A fundamental challenge in mechanistic studies of human chronobiology arises from the difficulty of conducting serial sampling from most organs. The concept of studying circadian clocks in vitro relies on the groundbreaking discovery by Ueli Schibler and colleagues that nearly every cell in the body harbours autonomous molecular oscillators. The advent of circadian bioluminescent reporters has provided a new perspective for this approach, enabling high-resolution continuous measurements of cell-autonomous clocks in cultured cells, following in vitro synchronization pulse. The work by Steven A. Brown has provided compelling evidence that clock characteristics assessed in primary mouse and human skin fibroblasts cultured in vitro represent a reliable estimation of internal clock properties in vivo. The in vitro approach for studying molecular human clocks in cultured explants and primary cells, pioneered by Steve Brown, represents an invaluable tool for assessing inter-individual differences in circadian characteristics alongside comprehensive genetic, biochemical and functional analyses. In a broader context, this reliable and minimally invasive approach offers a unique perspective for unravelling the functional inputs and outputs of oscillators operative in nearly any human tissue in physiological contexts and across various pathologies.

Prototype development of a three-stage, high-precision, low-jitter, wide-range digital delay generator fully utilizing on-chip resources.

This paper introduces the design and implementation of a prototype Digital Delay Generator (DDG) characterized by high precision, low jitter, and a wide delay range, fully realized within a Field Programmable Gate Array (FPGA). The DDG's architecture is based on an innovative combination of an embedded time-to-digital converter (TDC) and Multi-stage Time Interpolation (MTI) delay logic. The paper explores the factors influencing delay jitter during external trigger mode and carefully selects the optimal design approach for each element. The embedded TDC, which undergoes automatic calibration, accurately measures the time difference between the arrival of an external trigger and the FPGA's internal clock signal. When paired with the MTI delay logic, this allows for highly precise control over delay durations. A key aspect of this design is its sole dependence on the FPGA's built-in resources, ensuring simplicity in implementation and adaptability to various applications. Evaluation of the prototype has shown promising results, demonstrating a delay resolution as fine as 20ps and maintaining a low jitter of 105ps peak-to-peak (20ps rms) when operated in the externally triggered mode.