System Clock Research Articles

Design of Clock Synchronization of Base Station by Using 8A34002

The stability of the entire base station depends on the synchronization of the base station’s clock. The clock synchronization management chip 8A34002 supports SyncE Ethernet and IEEE 1588. In this architecture, the GPS receiver, SSI, and master/slave switching device all emit PPS/TOD signals. PPS/TOD signals are input into the FPGA, which outputs one PPS/TOD signal. The PPS/TOD signal enters 8A34002 in this design scheme, and the DPLL of 8A34002 provides filtering and clock-following output. The 8A34002‘s signal output is used as the system’s clock after processing. The switching chip, X86 main control chip, and BBU base station board are all driven by the system clock, which serves as a reference clock. The 8A34002 uses four DPLLs, one each for the SyncE, PTP, GNSS, and test functions.

ID: 221007 Bioelectronic Zeitgebers: Towards Neuromodulation Devices Synchronized to Biological Rhythms

Biological rhythms pervade physiology and pathophysiology across multiple timescales. Implantable bioelectronic systems that stimulate the nervous system have been shown as an effective adjunct therapy for medically refractory neurological disorders. However, due to limited sensing and algorithm capabilities of previous device generations, exploring the influence of biological rhythms on therapy efficacy has not been feasible. Devices to date have been limited to running fixed stimulation parameters without consideration of the impact of rhythms on therapy efficacy and therapy’s influence on rhythm-related symptoms and physiology. To maximize therapeutic benefits, bioelectronic devices should integrate chronobiology by considering time-related variations in disease symptoms and how to optimally alter therapy output. The aim is to both account for time-based symptom variance, and potentially promote, healthy biological rhythms, using the embedded clocks in bioelectronic systems to provide an additional exogenous “zeitgeber” (time giver).

A 10-Gb/s 275-fsec Jitter Cryo-CMOS Charge-Sampling CDR for Quantum Computing Application

This letter presents the first clock and data recovery (CDR) system operating at 4.2 K designed for quantum computing (QC) applications. By considering the benefits and challenges of cryogenic operation, a dedicated analog CDR structure is employed so as to maintain high performance at 300 and 4.2 K. The CDR incorporates a new complementary charge-sampling phase detector (PD) that achieves low power and low jitter. Fabricated in 40-nm CMOS, the proposed CDR operates at 10 Gb/s, achieving a recovered clock jitter of 260 fs and a jitter tolerance of 2 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${\rm UI}_{{\rm PP}}$</tex-math> </inline-formula> at a 5-MHz jitter frequency while consuming 4.7 mW at room temperature (RT). At 4.2 K, the power consumption reduces to 3.1 mW with a recovered clock jitter of 275 fs and a jitter tolerance of 0.85 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${\rm UI}_{{\rm PP}}$</tex-math> </inline-formula> at a 5-MHz jitter frequency, demonstrating its functionality for a high-speed cryogenic wireline link.

Design and Simulation of HiGBt, a 5 Gb/s SerDes for Heavy-Ion Physics Experiments

The Heavy Ion Research Facility on Lanzhou (HIRFL) and the High-Intensity heavy-ion Accelerator Facility (HIAF) are the leading heavy-ion physics centers. The increased scale of physics experiments at HIRFL and HIAF has put forward urgent requirements on high-speed serial data transmission links. Also, the intense radiation environment is a significant challenge to commercial ASIC. This paper presents the HiGBt, a general-purpose 5 Gbps SerDes ASIC designed in a 0.13 μm CMOS process for data transmission at HIRFL and HIAF. The HiGBt mainly consists of a Serializer, a Deserializer, and a high-speed clock system. The Serializer includes three stages to realize high-speed serialization. The Deserializer adopts a high linearity phase-interpolator-based structure to avoid coupling multi-VCOs. Finally, the high-speed clock system has a Single Event Upsets (SEUs)-protected divider. The simulation results indicate that the power consumption of the SerDes is 146.3 mW, while the layout area is 310 μm × 310 μm.

Evaluation of 3 northwest European seaweed species on enteric methane production and lactational performance of Holstein-Friesian dairy cows

Seaweeds have been studied for their ability to reduce enteric methane emissions of ruminants when fed as a feed supplement. In vivo research with dairy cattle is mainly limited to the seaweed species Ascophyllum nodosum and Asparagopsis taxiformis, whereas in vitro gas production research covers a broader range of brown, red, and green seaweed species from different regions. The objective of the present study was to determine the effect of Chondrus crispus (Rhodophyta), Saccharina latissima (Phaeophyta), and Fucus serratus (Phaeophyta), 3 common northwest European seaweeds, on enteric methane production and lactational performance of dairy cattle. Sixty-four Holstein-Friesian dairy cattle (16 primiparous, 48 multiparous) averaging (mean ± standard deviation) 91 ± 22.6 d in milk and 35.4 ± 8.13 kg/d fat- and protein-corrected milk yield (FPCM) were randomly assigned to 1 of 4 treatments in a randomized complete block design. Cows were fed a partial mixed ration [54.2% grass silage, 20.8% corn silage, and 25.0% concentrate; dry matter (DM) basis] with additional concentrate bait in the milking parlor and the GreenFeed system (C-Lock Inc.). The 4 treatments consisted of a control diet without seaweed supplement (CON), or CON supplemented with 150 g/d (fresh weight of dried seaweed) of either C. crispus (CC), S. latissima (SL), or a 50/50 mix (DM basis) of F. serratus and S. latissima. Milk yield (28.7 vs. 27.5 kg/d, respectively), fat- and protein-corrected milk (FPCM) yield (31.4 vs. 30.2 kg/d, respectively), milk lactose content (4.57 vs. 4.52%, respectively), and lactose yield (1,308 vs. 1,246 g/d, respectively) increased for SL compared with CON. Milk protein content was lower for SL compared with the other treatments. Milk fat and protein contents; yields of fat, protein, lactose, and FPCM; feed efficiency; milk nitrogen efficiency; and somatic cell count did not differ between CON and the other treatments. Depending on week of experiment, milk urea content was higher for SL compared with CON and CC. No effects were observed of the treatments compared with CON for DM intake, number of visits to the GreenFeed, or gas emission (production, yield, or intensity) of CO2, CH4, and H2. In conclusion, the seaweeds evaluated did not decrease enteric CH4 emissions and did not negatively affect feed intake and lactational performance of dairy cattle. Milk yield, FPCM yield, milk lactose content, and lactose yield increased, and milk protein content decreased, with S. latissima.

Circadian Activity and Clock Genes in Pachycrepoideus vindemmiae: Implications for Field Applications and Circadian Clock Mechanisms of Parasitoid Wasps.

Despite the importance of circadian rhythms in insect behavior, our understanding of circadian activity and the molecular oscillatory mechanism in parasitoid wasp circadian clocks is limited. In this study, behavioral activities expected to be under the control of the endogenous circadian system were characterized in an ectoparasitoid wasp, Pachycrepoideus vindemmiae. Most adults exhibited emergence between late night and early morning, while mating only occurred during the daytime, with a peak at midday. Oviposition had three peaks in the early morning, late day, or early night and late night. Additionally, we identified eight putative clock genes from P. vindemmiae. The quantitative PCR (qPCR) results indicate that most clock genes showed significant rhythmic expressions. Our comparative analysis of clock genes in P. vindemmiae and 43 other parasitoid wasps revealed that none of the wasps possessed the timeless and cry1 genes commonly found in some other insect species, suggesting that the circadian clock system in parasitoid wasps is distinct from that in other non-Hymenoptera insects such as Drosophila. Thus, this study attempted to build the first hypothetical circadian clock model for a parasitoid wasp, thus generating hypotheses and providing a platform for the future functional characterization of P. vindemmiae clock genes as well as those of other parasitoid wasps. Finally, these findings on P. vindemmiae circadian activity will aid the development of effective field release programs for biological control, which can be tested under field conditions.

Exhaled volatile fatty acids, ruminal methane emission, and their diurnal patterns in lactating dairy cows

To date, the commonly used methods to assess rumen fermentation are invasive. Exhaled breath contains hundreds of volatile organic compounds (VOC) that can reflect animal physiological processes. In the present study, for the first time, we aimed to use a noninvasive metabolomics approach based on high-resolution mass spectrometry to identify rumen fermentation parameters in dairy cows. Enteric methane (CH4) production from 7 lactating cows was measured 8 times over 3 consecutive days using the GreenFeed system (C-Lock Technology Inc.). Simultaneously, exhalome samples were collected in Tedlar gas sampling bags and analyzed offline using a secondary electrospray ionization high-resolution mass spectrometry system. In total, 1,298 features were detected, among them targeted exhaled volatile fatty acids (eVFA; i.e., acetate, propionate, butyrate), which were putatively annotated using their exact mass-to-charge ratio. The intensity of eVFA, in particular acetate, increased immediately after feeding and followed a similar pattern to that observed for ruminal CH4 production. The average total eVFA concentration was 35.5 count per second (CPS), and among the individual eVFA, acetate had the greatest concentration, averaging 21.3 CPS, followed by propionate at 11.5 CPS, and butyrate at 2.67 CPS. Further, exhaled acetate was on average the most abundant of the individual eVFA at around 59.3%, followed by 32.5 and 7.9% of the total eVFA for propionate and butyrate, respectively. This corresponds well with the previously reported proportions of these VFA in the rumen. The diurnal patterns of ruminal CH4 emission and individual eVFA were characterized using a linear mixed model with cosine function fit. The model characterized similar diurnal patterns for eVFA and ruminal CH4 and H2 production. Regarding the diurnal patterns of eVFA, the phase (time of peak) of butyrate occurred first, followed by that of acetate and propionate. Importantly, the phase of total eVFA occurred around 1 h before that of ruminal CH4. This corresponds well with existing data on the relationship between rumen VFA production and CH4 formation. Results from the present study revealed a great potential to assess the rumen fermentation of dairy cows using exhaled metabolites as a noninvasive proxy for rumen VFA. Further validation, with comparisons to rumen fluid, and establishment of the proposed method are required.

Restricted Feeding Resets the Peripheral Clocks of the Digestive System.

All organisms maintain an internal clock that matches the Earth's rotation over a period of 24 h, known as the circadian rhythm. Previously, we established Period1 luciferase (Per1::luc) transgenic (Tg) mice in order to monitor the expression rhythms of the Per1 clock gene in each tissue in real time using a bioluminescent reporter. The Per1 gene is a known key molecular regulator of the mammalian clock system in the autonomous central clock in the suprachiasmatic nucleus (SCN), and the peripheral tissues. Per1::luc Tg mice were used as a biosensing system of circadian rhythms. They were maintained by being fed ad lib (FF) and subsequently subjected to 4 hour (4 h) restricted feeding (RF) during the rest period under light conditions in order to examine whether the peripheral clocks of different parts in the digestive tract could be entrained. The peak points of the bioluminescent rhythms in the Per1::luc Tg mouse tissue samples were analyzed via cosine fitting. The bioluminescent rhythms of the cultured peripheral tissues of the esophagus and the jejunum exhibited phase shift from 5 to 11 h during RF, whereas those of the SCN tissue remained unchanged for 7 days during RF. We examined whether RF for 4 h during the rest period in light conditions could reset the activity rhythms, the central clock in the SCN, and the peripheral clock in the different points in the gastrointestinal tract. The fasting signals during RF did not entrain the SCN, but they did entrain each peripheral clock of the digestive system, the esophagus, and the jejunum. During RF for 7 days, the peak time of the esophagus tended to return to that of the FF control, unlike that of the jejunum; hence, the esophagus was regulated more strongly under the control of the cultured SCN compared to the jejunum. Thus, the peripheral clocks of the digestive system can entrain their molecular clock rhythms via RF-induced fasting signals in each degree, independently from the SCN.

Research on high‐precision synchronous output technology of multi‐reference source weighted synthesis in power system

AbstractThe massive perception data based on efficient analysis and intelligent decision have put forward higher requirements for high‐precision time synchronisation with the construction and development of smart power grid. However, multi‐reference source time‐frequency synchronisation of power system only selects the best method after comparison, which cannot make the most efficient use of the existing resources. It also cannot meet the need for high‐precision time synchronisation of future power system. The existing multi‐reference source synthesis algorithms cannot take into account both long‐term stability and high‐precision synchronous output. This article presents a multi‐reference source weighted improved noise model and the high‐precision output method. The multi‐reference source error after classification is eliminated by leading into classification vector and classification coefficient. The synthesised frequency offset or the time precision of output can be optimised as the objective function by weighted classification algorithm and genetic algorithm. A simulation example based on the synthesis of two satellite system clock sources and three local caesium reference sources shows that the peak value of long‐term output accuracy is controlled within 10 ns after classification weighted synthesis and optimisation, which is better than that of any single reference source.

The scaffold protein PDZK1 governs diurnal localization of CNT2 on the plasma membrane in mouse intestinal epithelial cells.

Diurnal oscillations in the expression of several types of cell surface transporters have been demonstrated in the intestinal epithelial cells, which are mainly generated at transcriptional or degradation processes. Concentrative nucleoside transporter-2 (CNT2) is expressed at the apical site of intestinal epithelial cells and contributes to the uptake of nucleosides and their analogs from the intestinal lumen into the epithelial cells. In this study, we demonstrated that the localization of CNT2 protein in the plasma membrane of mouse intestinal epithelial cells exhibited a diurnal oscillation without changing its protein level in the whole cell. The scaffold protein PDZK1 interacted with CNT2 and stabilized its plasmalemmal localization. The expression of PDZK1 was under the control of molecular components of the circadian clock. Temporal accumulation of PDZK1 protein in intestinal epithelial cells enhanced the plasmalemmal localization of CNT2 at certain times of the day. The temporal increase in CNT2 protein levels at the plasma membrane also facilitated the uptake of adenosine into the intestinal epithelial cells. These results suggest a novel molecular mechanism for the diurnal localization of cell surface transporters and extend our understanding of the biological clock system that generates apparent physiological rhythms.

Execution of stored programs by a rapid single-flux-quantum random-access-memory-embedded bit-serial microprocessor using 50-GHz clock frequency

We have demonstrated the execution of several programs stored in an instruction memory by a rapid single-flux-quantum bit-serial 8-bit microprocessor named CORE e2h. We employed a minimal instruction set architecture composed of 13 instructions based on the reduced instruction set computer. We integrated a 128-bit instruction memory and a 128-bit data memory with an arithmetic logic unit, two registers, a program counter, an instruction register, and a controller unit on a single chip. The bit-serial operation was performed by an on-chip clock generator, while the system clocks are provided from room-temperature electronics. The CORE e2h was made up of 11 000 Nb/AlOx/Nb Josephson junctions and fabricated with the Advanced Industrial Science and Technology 10-kA/cm2, 9-Nb-layer process. We obtained the correct results for all the executed programs, including the integer division, the two kinds of summation algorithms, the Euclidean algorithm, and finding the greatest divisor. These test programs contained a single or nested double loop, and the maximum number of executed instructions was 205. We confirmed the stable operation with the DC bias margins of around 10% at 50-GHz for different test programs. The measured electric power consumption was 2.5 mW at 4.2 K, and the estimated computing power was 500 × 106 instructions/s.

Role of the Circadian Clock System in Trans-sulfuration Pathway and Tissue Remodeling

Previous studies from our laboratory revealed that the gaseous molecule; hydrogen sulfide (H2S), a metabolic product of epigenetics which involves trans-sulfuration pathway for ensuring the metabolism and clearance of homocysteine (Hcy) from the body, helped mitigate the skeletal muscle’s pathological remodeling. Although the master circadian clock regulator that is known as the b rain and m uscle a ryl hydrocarbon receptor nuclear translocator l ike protein 1 (i.e., BMAL1) is intimately associated with S-adenosylhomocysteine hydrolase (SAHH) and Hcy metabolism but how trans-sulfuration pathway is influenced by the circadian clock system remains unexplored. We hypothesize that potential alterations in the functioning of circadian clock during sleep and wake cycle affect the skeletal muscle’s biology. To test this hypothesis, we measured serum matrix metalloproteinases (MMPs) activities using gelatin gels for analyzing the MMP-2 and MMP-9 activities. Further, employing the casein gels we also studied MMP-13 that is known to be influenced by the growth arrest and DNA damage-45 (GADD45) protein during sleep and wake cycle. The wild type (WT) and cystathionine β synthase deficient (CBS-/+) mice strains were treated with H2S and subjected for measurement of trans-sulfuration factors from their skeletal muscle tissues. The results suggested highly robust activation of MMPs activities in the wake mice versus sleep mice that appears somewhat akin to that of the “ 1-carbon metabolic dysregulation” which takes place during remodeling of extracellular matrix (ECM) in muscular dystrophy affected tissues. Interestingly, the levels of trans-sulphuration factors such as CBS, cystathionine γ lyase (CSE), methyl tetrahydrofolate reductase (MTHFR), phosphatidylethanolamine N-methyltransferase (PEMT), and Hcy-protein bound paraoxonase 1 (PON1) were attenuated in the CBS-/+ mice. However, treatment with H2S mitigated the attenuation occurring in the trans-sulfuration pathway. In addition, levels of mitochondrial peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC 1-α) and mitofusin-2 (MFN-2) were significantly improved by H2S intervention. Our findings suggest participation of the circadian clock system in trans-sulfuration pathway that affect the skeletal muscle remodeling and mitochondrial regeneration. HL-139047, DK116591 and AR-71789 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

An unconstrained relaxation digital‐to‐analog converter using optimal bit sequence

AbstractBased on the relaxation digital‐to‐analog converter (ReDAC) architecture and the capacitor charge/discharge function under discrete time conditions, this paper proposes a new mathematical model for the output voltage of the ReDAC to implement the unconstrained relaxation DAC (Uc‐ReDAC). The system clock calibration is not required. An adaptive probabilistic binary particle swarm optimization (AP‐BPSO) algorithm is proposed for solving the binary coding configuration problem under the Uc‐ReDAC model. Simulation results show that the 8‐bit (10‐bit) Uc‐ReDAC has an average sampling rate of 7.9 MS/s (6.76 MS/s).

Structured dynamics of the cell-cycle at multiple scales

The eukaryotic cell cycle comprises 4 phases (G1, S, G2, and M) and is an essential component of cellular health, allowing the cell to repair damaged DNA prior to division. Facilitating this processes, p53 is activated by DNA-damage and arrests the cell cycle to allow for the repair of this damage, while mutations in the p53 gene frequently occur in cancer. As such, this process occurs on the cell-scale but affects the organism on the cell population-scale. Here, we present two models of cell cycle progression: The first of these is concerned with the cell-scale process of cell cycle progression and the temporal biochemical processes, driven by cyclins and underlying progression from one phase to the next. The second of these models concerns the cell population-scale process of cell-cycle progression and its arrest under the influence of DNA-damage and p53-activation. Both systems take advantage of structural modeling conventions to develop novels methods for describing and exploring cell-cycle dynamics on these two divergent scales. The cell-scale model represents the accumulations of cyclins across an internal cell space and demonstrates that such a formalism gives rise to a biological clock system, with definite periodicity. The cell population-scale model allows for the exploration of interactions between various regulating proteins and the DNA-damage state of the system and quantitatively demonstrates the structural dynamics which allow p53 to regulate the G2- to M-phase transition and to prevent the mitosis of genetically damaged cells. A divergent periodicity and clear distribution of transition times is observed, as compared with the single-cell system. Comparison to a system with a reduced genetic repair rate shows a greater delay in cell cycle progression and an increased accumulation of cell in the G2-phase, as a result of the p53 biochemical feedback mechanism.

Source Switched Charge-Pump PLLs for High-Dose Radiation Environments

This paper presents a radiation tolerant charge-pump Phase-Locked Loop (PLL) with low static phase error variability suitable for high-performance clock systems in high-dose radiation environments. We investigate the use of source switching charge-pump architectures to minimize any voltage-or dose-dependent charge injection and address the limitations of Enclosed Layout Transistors (ELTs) in the conventional drain switched charge-pump. The circuit has been processed in a 65nm Complementary Metal Oxide Semiconductor (CMOS) technology and has been experimentally verified with X-rays up to a total ionizing dose of 180 Mrad.

CD36 regulates diurnal glucose metabolism and hepatic clock to maintain glucose homeostasis in mice

The mammalian circadian clock and glucose metabolism are highly interconnected, and disruption of this coupling is associated with multiple negative health outcomes. Liver is the major source of endogenous glucose production and liver clock is one of the most vital peripheral clock systems. We demonstrate that fatty acid translocase (CD36) is expressed rhythmically in mouse liver and autonomously modulates the diurnal oscillations of liver clock and glucose homeostasis. CD36 knockout in hepatocytes inhibits the relay of insulin signaling and provokes FoxO1 nuclear shuttling, consequently increasing Per1 nuclear expression. Moreover, FoxO1 can activate the central clock gene Per1 at the transcriptional level. These changes lead to a disrupted clock oscillation and behavioral rhythm. Our study first reveal that CD36 is a key regulator of the circadian oscillator and its deficiency may cause liver clock disruption, which aggravates the imbalance of glucose homeostasis and contribute to augmentation and progression of metabolic disease.

Multi-omics analyses reveal the crosstalk between the circadian clock and the response to herbicide application in Oryza sativa.

Plants have evolved circadian clock systems that enable biological processes to occur in tandem with periodic changes in the environment. However, it is largely unknown whether crosstalk occurs between the circadian clock and the response to herbicide in rice. We identified 19 conserved rhythmic metabolites which were response to pesticide application and their metabolic abundance peaked mainly at ZT2 or ZT14-ZT18. We found a series of glyphosate, s-Metolachlor, fenclorim, metcamifen and GA3 response genes were expressed following stable circadian rhythms. In order to determine the patterns of their temporal expression, co-expression network analysis was done on 10,467 genes that were periodically expressed throughout a 24-hour period. Next, we identified 4,031 potential direct target genes of OsCCA1 in using DAP-seq data for OsCCA1. Of these, 339, 22, 53, 53 and 63 genes showed a response to glyphosate, s-Metolachlor, fenclorim, metcamifen and GA3 application, respectively. And they were mainly phased from dusk to midnight. Interestingly, we identified significant OsCCA1 binding peaks in the promoter regions of four herbicide resistance genes, including OsCYP81A12, OsCYP81E22, OsCYP76C2, and OsCYP76C4. Finally, we found that herbicide application could affects the expression of some of the central oscillator genes of the rice circadian clock. Here, we used multi-omics data to reveal the crosstalk between the circadian clock and herbicide response processes at the epigenomics, transcriptome, and metabolome levels in rice. This work will serve as a theoretical guide for identifying rhythmic herbicide targets, leading to the creation of new herbicides or the breeding of crops resistant to herbicides.

An evaluation method of GPS satellite clock in-orbit with periodic terms deducted

The performance of the atomic clock in orbit is of terrific significance for the Global Navigation Satellite System (GNSS). With the rapid development of satellite navigation and atomic clock technology, the periodic error of satellite clocks caused by the environment is more prominent. This paper focuses on the analysis and quantification of the systematic periodic error in the clock offset and proposes a more accurate evaluation method for GPS satellite clocks. The fact that the J2 relativistic effect and orbit radial error are the main sources of the systematic periodic term has been revealed. Then, the Fast Fourier Transform (FFT) is employed using the sliding window to investigate the periodic influence caused by satellite orbit and the J2 relativistic effect on clock offset through six GPS satellites with different orbital planes, these satellites also cover all four types of GPS satellite blocks. The results show that there is an obvious relationship between the sun elevation and orbit radial error, clock offset fitting precision, frequency stability and amplitude. The different geometric configurations of the satellite and the varying environment make this relationship different. Based on the clock offset provided by European Space Agency (ESA), the period of clock offset is extracted and quantized, with the period of 24 h, 12 h, 8 h, 6 h, 4 h, and 3 h. According to the daily extraction results of the time-varying periodic terms, the two most noticeable terms correction on satellite clock offset has been proven to be effective in eliminating periodic errors. Compared to those without periodic correction, the fitting precision and frequency stability can improve by 48.5% and 42.6%, respectively. In addition, all GPS satellite clocks in orbit are evaluated by this periodic correction method, and the results are more approach to the actual performance of the satellite clock. Furthermore, this method can also be adapted to evaluate satellite clocks of other GNSS systems. Therefore, when we evaluate the high-precision atomic clock flying on board GNSS satellites and compare them with the manufacturers’ specifications, the periodic error cannot be neglected.

BMAL1 regulates osteoblast differentiation through mTOR/GSK3β/β-catenin pathway.

Bone mass declines with age and its maintenance is tightly linked to osteoblasts (crucial bone-building cells). Although disruption of the peripheral circadian clock is involved in various pathologies including aging-related diseases, evidence regarding how the peripheral clock regulates bone mass remains elusive. In the present study, we aimed to elucidate the effects of Bmal1 (the key activator of the peripheral circadian clock system) knockdown by lentivirus-mediated shRNA on osteoblast differentiation and its related mechanisms. We found that the expression of osteogenic markers, alkaline phosphatase activity, and mineralization were decreased, whereas apoptosis and inflammatory response were increased in Bmal1 knockdown osteoblasts. In addition, Bmal1 knockdown promoted ERK and JNK phosphorylation, as well as mTOR activity, whereas mTOR inhibition by rapamycin abrogated Bmal1 knockdown-mediated effects on osteoblast differentiation and mineralization capacity. Remarkably, Bmal1 knockdown in osteoblasts inhibited GSK3β/β-catenin signaling with decreased β-catenin expression and GSK-3β phosphorylation at serine 9, while GSK3β inhibition with TDZD-8, but not WNT3a or SKL2001, rescued Bmal1 knockdown-induced defects in osteoblast differentiation. Moreover, rapamycin partly nullified the suppression of Bmal1 knockdown on β-catenin expression and GSK-3β phosphorylation. Collectively, overall data indicated that circadian gene Bmal1 regulated osteoblast differentiation and inflammatory response in an mTOR/GSK3β/β-catenin-dependent manner, and thereby may contribute to the mineralization process and bone modeling/remodeling.

Transparent and Tamper-Proof Event Ordering in the Internet of Things Platforms

Today, the audit and diagnosis of the causal relationships between the events in a trigger-action-based event chain (e.g., why is a light turned on in a smart home?) in the Internet of Things (IoT) platforms are untrustworthy and unreliable. The current IoT platforms lack techniques for transparent and tamper-proof ordering of events due to their device-centric logging mechanism. In this article, we develop a framework that facilitates tamper-proof transparency and event order in an IoT platform by proposing a Blockchain protocol and adopting the vector clock system, both tailored for the resource-constrained heterogeneous IoT devices, respectively. To cope with the unsuited storage (e.g., ledger) and computing power (e.g., proof-of-work puzzle) requirements of the Blockchain in the commercial off-the-shelf IoT devices, we propose a partial consistent cut protocol and engineer a modular arithmetic-based lightweight proof of work puzzle, respectively. To the best of our knowledge, this is the first Blockchain designed for resource-constrained heterogeneous IoT platforms. Our event ordering protocol based on the vector clock system is also novel for the IoT platforms. We implement our framework using an IoT gateway and 30 IoT devices. We experiment with ten concurrent trigger-action-based event chains while each chain involves 20 devices, and each device participates in five different chains. The results show that our framework may order these events in 2.5 s while consuming approximately 140 mJ of energy per device. The results, hence, demonstrate the proposed platform as a practical choice for many IoT applications, such as smart home, traffic monitoring, and crime investigation.