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Keywords = stability of clocks

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28 pages, 2841 KiB  
Article
A Multi-Constraint Co-Optimization LQG Frequency Steering Method for LEO Satellite Oscillators
by Dongdong Wang, Wenhe Liao, Bin Liu and Qianghua Yu
Sensors 2025, 25(15), 4733; https://doi.org/10.3390/s25154733 (registering DOI) - 31 Jul 2025
Abstract
High-precision time–frequency systems are essential for low Earth orbit (LEO) navigation satellites to achieve real-time (RT) centimeter-level positioning services. However, subject to stringent size, power, and cost constraints, LEO satellites are typically equipped with oven-controlled crystal oscillators (OCXOs) as the system clock. The [...] Read more.
High-precision time–frequency systems are essential for low Earth orbit (LEO) navigation satellites to achieve real-time (RT) centimeter-level positioning services. However, subject to stringent size, power, and cost constraints, LEO satellites are typically equipped with oven-controlled crystal oscillators (OCXOs) as the system clock. The inherent long-term stability of OCXOs leads to rapid clock error accumulation, severely degrading positioning accuracy. To simultaneously balance multi-dimensional requirements such as clock bias accuracy, and frequency stability and phase continuity, this study proposes a linear quadratic Gaussian (LQG) frequency precision steering method that integrates a four-dimensional constraint integrated (FDCI) model and hierarchical weight optimization. An improved system error model is refined to quantify the covariance components (Σ11, Σ22) of the LQG closed-loop control system. Then, based on the FDCI model that explicitly incorporates quantization noise, frequency adjustment, frequency stability, and clock bias variance, a priority-driven collaborative optimization mechanism systematically determines the weight matrices, ensuring a robust tradeoff among multiple performance criteria. Experiments on OCXO payload products, with micro-step actuation, demonstrate that the proposed method reduces the clock error RMS to 0.14 ns and achieves multi-timescale stability enhancement. The short-to-long-term frequency stability reaches 9.38 × 10−13 at 100 s, and long-term frequency stability is 4.22 × 10−14 at 10,000 s, representing three orders of magnitude enhancement over a free-running OCXO. Compared to conventional PID control (clock bias RMS 0.38 ns) and pure Kalman filtering (stability 6.1 × 10−13 at 10,000 s), the proposed method reduces clock bias by 37% and improves stability by 93%. The impact of quantization noise on short-term stability (1–40 s) is contained within 13%. The principal novelty arises from the systematic integration of theoretical constraints and performance optimization within a unified framework. This approach comprehensively enhances the time–frequency performance of OCXOs, providing a low-cost, high-precision timing–frequency reference solution for LEO satellites. Full article
(This article belongs to the Section Remote Sensors)
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14 pages, 4407 KiB  
Article
Timekeeping Method with Dual Iterative Algorithm for GNSS Disciplined OCXO
by Linghe Zhang, Longwei Xu, Xiaobin Wang, Zhongwang Wu, Jiangfeng Lai and Wenqian Yu
Electronics 2025, 14(14), 2870; https://doi.org/10.3390/electronics14142870 - 18 Jul 2025
Viewed by 201
Abstract
After the interruption of the timing service, the increase in clock offset is a critical issue for the global navigation satellite system (GNSS)-disciplined oven-controlled crystal oscillator (OCXO). Current timekeeping methods for GNSS-disciplined OCXO have some drawbacks, such as high computational complexity, inadequate consideration [...] Read more.
After the interruption of the timing service, the increase in clock offset is a critical issue for the global navigation satellite system (GNSS)-disciplined oven-controlled crystal oscillator (OCXO). Current timekeeping methods for GNSS-disciplined OCXO have some drawbacks, such as high computational complexity, inadequate consideration of temperature effects, and insufficient separation of the impacts of temperature and aging. To address this issue, this study proposes a timekeeping method using a dual iterative algorithm. First, the external iteration separates the clock offset caused by temperature and aging. Then, the internal Gauss–Seidel iterative algorithm estimates the temperature and aging coefficients. During the timing service interruption phase, the model estimates and compensates for the frequency offset in real time using the coefficients. The proposed method demonstrates improved performance compared with OCXO in the free state and compensated by a second-order polynomial model, with better accuracy, drift rate, and long-term stability. The time offset is better than 4 μs over 24 h, representing an improvement of over 95% compared with the OCXO in the free state. Full article
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21 pages, 4409 KiB  
Article
Differences in Time Comparison and Positioning of BDS-3 PPP-B2b Signal Broadcast Through GEO
by Hongjiao Ma, Jinming Yang, Xiaolong Guan, Jianfeng Wu and Huabing Wu
Remote Sens. 2025, 17(14), 2351; https://doi.org/10.3390/rs17142351 - 9 Jul 2025
Viewed by 256
Abstract
The BeiDou-3 Navigation Satellite System (BDS-3) precise point positioning (PPP) service through the B2b signal (PPP-B2b) leverages precise correction data disseminated by satellites to eliminate or mitigate key error sources, including satellite orbit errors, clock biases, and ionospheric delays, thereby enabling high-precision timing [...] Read more.
The BeiDou-3 Navigation Satellite System (BDS-3) precise point positioning (PPP) service through the B2b signal (PPP-B2b) leverages precise correction data disseminated by satellites to eliminate or mitigate key error sources, including satellite orbit errors, clock biases, and ionospheric delays, thereby enabling high-precision timing and positioning. This paper investigates the disparities in time comparison and positioning capabilities associated with the PPP-B2b signals transmitted by the BDS-3 Geostationary Earth Orbit (GEO) satellites (C59 and C61). Three stations in the Asia–Pacific region were selected to establish two time comparison links. The study evaluated the time transfer accuracy of PPP-B2b signals by analyzing orbit and clock corrections from BDS-3 GEO satellites C59 and C61. Using multi-GNSS final products (GBM post-ephemeris) as a reference, the performance of PPP-B2b-based time comparison was assessed. The results indicate that while both satellites achieve comparable time transfer accuracy, C59 demonstrates superior stability and availability compared to C61. Additionally, five stations from the International GNSS Service (IGS) and the International GNSS Monitoring and Assessment System (iGMAS) were selected to assess the positioning accuracy of PPP-B2b corrections transmitted by BDS-3 GEO satellites C59 and C61. Using IGS/iGMAS weekly solution positioning results as a reference, the analysis demonstrates that PPP-B2b enables centimeter-level static positioning and decimeter-level simulated kinematic positioning. Furthermore, C59 achieves higher positioning accuracy than C61. Full article
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14 pages, 2907 KiB  
Article
Switching Noise Harmonic Reduction for EMI Improvement Through Rising and Falling Time Control Using Gate Resistance
by Jeonghyeon Cheon and Dongwook Kim
Electronics 2025, 14(13), 2729; https://doi.org/10.3390/electronics14132729 - 7 Jul 2025
Viewed by 298
Abstract
Electromagnetic interference (EMI) has become a significant issue as electronic devices become more integrated and achieve high performance. In order to operate at high performance in an integrated system, a high-frequency clock signal is essential to enhance processing speed. However, the harmonic component [...] Read more.
Electromagnetic interference (EMI) has become a significant issue as electronic devices become more integrated and achieve high performance. In order to operate at high performance in an integrated system, a high-frequency clock signal is essential to enhance processing speed. However, the harmonic component of the clock signal or gate signal is one of the major EMI sources that can cause peripheral devices to malfunction and affect their stability and reliability. In this paper, harmonic component analysis of the MOSFET gate signal which depends on gate resistance is conducted. Based on theoretical analysis using Fourier series expansion, gate resistance contributes to harmonic components that are determined by the rising and falling times of a gate signal. Simulation and measurement are conducted using a buck converter as a practical application. The theoretical analysis is validated by simulation and experimental results demonstrate that the magnitude of the harmonics is reduced because increasing the gate resistance extends the rising and falling times. Full article
(This article belongs to the Section Electrical and Autonomous Vehicles)
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21 pages, 951 KiB  
Article
Bit Synchronization-Assisted Frequency Correction in Low-SNR Wireless Systems
by Junfeng Gao, Peiji Yang, Shaoxiang Chen, Zhenghua Luo, Yilin Zhang and Tao Liu
Electronics 2025, 14(12), 2319; https://doi.org/10.3390/electronics14122319 - 6 Jun 2025
Viewed by 348
Abstract
In wireless communication systems, traditional frequency synchronization methods struggle to effectively track carrier frequency in low signal-to-noise ratio (SNR) environments, leading to degraded demodulation performance and severely impacting the stability and reliability of communication systems. To address this challenge, an innovative frequency synchronization [...] Read more.
In wireless communication systems, traditional frequency synchronization methods struggle to effectively track carrier frequency in low signal-to-noise ratio (SNR) environments, leading to degraded demodulation performance and severely impacting the stability and reliability of communication systems. To address this challenge, an innovative frequency synchronization framework is introduced, enhancing frequency synchronization accuracy and robustness in low-SNR environments through bit synchronization techniques. Specifically, the approach constructs a “bit synchronization-frequency synchronization” joint correction mechanism, where clock offset information extracted during the bit synchronization process is utilized to estimate frequency offset. This method enables an indirect measurement and compensation of carrier frequency offset, forming a hierarchical error compensation system. Furthermore, to overcome the limited convergence speed of the classical Gardner algorithm under significant phase offset conditions, an improved error feedback structure is proposed, accelerating bit synchronization convergence and reducing timing synchronization errors, thereby enhancing overall system performance. The effectiveness of the proposed method is validated through theoretical analysis and simulation experiments. Simulation results demonstrate that, compared to conventional frequency synchronization schemes, the proposed method achieves higher frequency correction accuracy in low-SNR scenarios, thereby improving the robustness and anti-interference capability of wireless communication systems in complex environments. Full article
(This article belongs to the Section Microwave and Wireless Communications)
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15 pages, 545 KiB  
Review
DNA Methylation, Aging, and Cancer
by Himani Vaidya, Jaroslav Jelinek and Jean-Pierre J. Issa
Epigenomes 2025, 9(2), 18; https://doi.org/10.3390/epigenomes9020018 - 3 Jun 2025
Viewed by 1337
Abstract
Aging and cancer, though distinct biological processes, share overlapping molecular pathways, particularly in epigenetic regulation. Among these, DNA methylation is central to mediating gene expression, maintaining cellular identity, and regulating genome stability. This review explores how age-associated changes in DNA methylation, characterized by [...] Read more.
Aging and cancer, though distinct biological processes, share overlapping molecular pathways, particularly in epigenetic regulation. Among these, DNA methylation is central to mediating gene expression, maintaining cellular identity, and regulating genome stability. This review explores how age-associated changes in DNA methylation, characterized by both global hypomethylation and focal hypermethylation, contribute to the emergence of cancer. We discuss mechanisms of DNA methylation drift, the development of epigenetic clocks, and the role of entropy and epigenetic mosaicism, in aging and tumorigenesis. Emphasis is placed on how stochastic methylation errors accumulate in aging cells and lead to epiallelic shifts and gene silencing, predisposing tissues to malignant transformation, even despite recently increased cancer incidences at younger ages. We also highlight the translational potential of DNA methylation-based biomarkers, and therapeutic targets, in age-related diseases. By framing cancer as a disease of accelerated epigenetic aging, this review offers a unifying perspective and calls for age-aware approaches to both basic research and clinical oncology. Full article
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19 pages, 1676 KiB  
Article
Performance Assessment of Undifferenced GPS/Galileo Precise Time Transfer with a Refined Clock Model
by Wei Xu, Pengfei Zhang, Lei Wang, Chao Yan and Jian Chen
Remote Sens. 2025, 17(11), 1910; https://doi.org/10.3390/rs17111910 - 30 May 2025
Viewed by 429
Abstract
Conventional Global Navigation Satellite System (GNSS) time transfer algorithms typically model receiver clock offsets as white noise for estimation, neglecting the physical characteristics of atomic clocks, which consequently limits the performance of GNSS time transfer. To overcome this limitation, this study proposes an [...] Read more.
Conventional Global Navigation Satellite System (GNSS) time transfer algorithms typically model receiver clock offsets as white noise for estimation, neglecting the physical characteristics of atomic clocks, which consequently limits the performance of GNSS time transfer. To overcome this limitation, this study proposes an undifferenced GPS/Galileo combined Precise Point Positioning (PPP) time transfer model, incorporating both one-state (only clock offset parameter) and two-state (both clock offset and frequency offset parameters) refined clock models with clock instantaneous re-initialization (CIR) strategy at the day boundary epoch. Using observations from International GNSS Service (IGS) Multi-GNSS Experiment (MGEX) stations equipped with external hydrogen masers, precise time transfer performance under refined clock models was evaluated based on undifferenced GPS/Galileo combined PPP float solutions and PPP ambiguity resolutions. Experimental results demonstrate that, compared to traditional models, the refined clock models improve time transfer accuracy and frequency stability by an average of 6.7% and 25.8%, respectively. The improvement is most significant for short term frequency stability, with a maximum enhancement exceeding 85%. As the averaging time increases, the improvement in long term frequency stability gradually diminishes. Notably, the two-state refined clock model slightly outperforms the one-state model in time transfer performance, with the two-state refined clock model improving short-, medium-, and long term frequency stability by 11.5%, 8.0%, and 0.2%, respectively, compared to the one-state refined clock model. These findings strongly advocate adopting the two-state refined clock model to optimize both time transfer precision and short term stability in high-accuracy applications. Full article
(This article belongs to the Special Issue Advances in Multi-GNSS Technology and Applications)
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44 pages, 2528 KiB  
Review
A Comprehensive Review of Rubidium Two-Photon Vapor Cell Optical Clock: Long-Term Performance Limitations and Potential Improvements
by Asagwegbe C. Obaze-Adeleke, Bryan Semon and Thejesh N. Bandi
Photonics 2025, 12(5), 513; https://doi.org/10.3390/photonics12050513 - 20 May 2025
Viewed by 1656
Abstract
Two-photon vapor cell-based optical clocks are strong candidates for next-generation portable atomic standards, offering simplicity, compactness, and high performance. Their narrow clock transitions with counter-propagating beams enable first-order Doppler-free operation. However, systematic perturbations such as the AC Stark shift, temperature-induced shift, and drifts [...] Read more.
Two-photon vapor cell-based optical clocks are strong candidates for next-generation portable atomic standards, offering simplicity, compactness, and high performance. Their narrow clock transitions with counter-propagating beams enable first-order Doppler-free operation. However, systematic perturbations such as the AC Stark shift, temperature-induced shift, and drifts resulting from the laser system pose challenges cause instabilities to medium- to long-term performance. This paper provides a comprehensive overview of Rb two-photon vapor cell optical standards, focusing on the long-term performance-limiting effects and potential mitigation strategies, aiming for clock stabilities better than 1 × 10−15 over the averaging time of a day and beyond. Full article
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18 pages, 1111 KiB  
Review
BMAL1 in Ischemic Heart Disease: A Narrative Review from Molecular Clock to Myocardial Pathology
by Jingyi Yang, Junxin Zhao, Zhuoyang Chen, Lincheng Duan, Hong Yang and Dingjun Cai
Int. J. Mol. Sci. 2025, 26(10), 4626; https://doi.org/10.3390/ijms26104626 - 12 May 2025
Viewed by 670
Abstract
The biological clock is crucial for controlling the circadian rhythm of the human body and maintaining the stable cyclic changes of various human life activities. Cardiovascular disease has become one of the primary problems affecting human life and health in today’s society. Cardiovascular [...] Read more.
The biological clock is crucial for controlling the circadian rhythm of the human body and maintaining the stable cyclic changes of various human life activities. Cardiovascular disease has become one of the primary problems affecting human life and health in today’s society. Cardiovascular disease exhibits distinct circadian rhythms, with the core clock gene protein Brain and muscle ARNT-like protein 1 (BMAL1) playing critical roles in both physiological cardiac function and pathological processes. BMAL1 regulates myocardial gene expression, maintains normal structures, and stabilizes circadian rhythms to preserve cardiac homeostasis. In the pathological state of myocardial ischemia, BMAL1 ameliorates myocardial ischemic injury by regulating intrinsic mechanisms such as oxidative stress response, energy metabolism, immune-inflammatory response, and apoptosis and autophagy in cardiomyocytes. This review systematically examines BMAL1’s involvement in myocardial ischemic injury through the circadian regulation of cardiac function. We analyze its multidimensional impacts on oxidative stress, energy metabolism, immune-inflammatory responses, apoptosis, and autophagy, highlighting the biological significance of this clock gene in ischemic pathophysiology. Full article
(This article belongs to the Section Molecular Biology)
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10 pages, 906 KiB  
Proceeding Paper
Evaluation and Simulation of Ultra-Wide Band (UWB) Transceiver Timebases
by Václav Navrátil and Josef Krška
Eng. Proc. 2025, 88(1), 40; https://doi.org/10.3390/engproc2025088040 - 29 Apr 2025
Viewed by 327
Abstract
Ultra-Wide Band (UWB) real-time localization systems usually require either precise and robust synchronization of the anchor transceivers or sufficiently stable clocks for methods referred to as “synchronization-free”. Typically, reasonably priced crystals or TCXOs are utilized as frequency references for the UWB transceivers. Clock [...] Read more.
Ultra-Wide Band (UWB) real-time localization systems usually require either precise and robust synchronization of the anchor transceivers or sufficiently stable clocks for methods referred to as “synchronization-free”. Typically, reasonably priced crystals or TCXOs are utilized as frequency references for the UWB transceivers. Clock characterization and simulation are necessary to evaluate and tune the synchronization or positioning algorithms without the need of hardware-pulling of the UWB reference oscillators. In this paper, the method of transceiver clock stability measurement is presented, and several modules with various clock sources are evaluated. As a reference, a UWB module with a clock derived from a Caesium standard is utilized. A method for simulating typical timestamp-series errors attributed to UWB transceiver clocks is provided as well. Full article
(This article belongs to the Proceedings of European Navigation Conference 2024)
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29 pages, 1843 KiB  
Review
Molecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review
by Kemal Hüsnü Can Baser, Ismail Celil Haskologlu and Emine Erdag
Molecules 2025, 30(9), 1888; https://doi.org/10.3390/molecules30091888 - 23 Apr 2025
Cited by 3 | Viewed by 3364
Abstract
Circadian rhythms are molecular oscillations governed by transcriptional–translational feedback loops (TTFLs) operating in nearly all cell types and are fundamental to physiological homeostasis. Key circadian regulators, such as circadian locomotor output cycles kaput (CLOCK), brain and muscle ARNT-like 1 (BMAL1), period [...] Read more.
Circadian rhythms are molecular oscillations governed by transcriptional–translational feedback loops (TTFLs) operating in nearly all cell types and are fundamental to physiological homeostasis. Key circadian regulators, such as circadian locomotor output cycles kaput (CLOCK), brain and muscle ARNT-like 1 (BMAL1), period (PER), and cryptochrome (CRY) gene families, regulate intracellular metabolism, oxidative balance, mitochondrial function, and synaptic plasticity. Circadian disruption is known as a central contributor to the molecular pathophysiology of neurodegenerative disorders. Disease-specific disruptions in clock gene expression and melatoninergic signaling are known as potential early-stage molecular biomarkers. Melatonin, a neurohormone secreted by the pineal gland, modulates clock gene expression, mitochondrial stability, and inflammatory responses. It also regulates epigenetic and metabolic processes through nuclear receptors and metabolic regulators involved in circadian and cellular stress pathways, thereby exerting neuroprotective effects and maintaining neuronal integrity. This review provides recent findings from the past five years, highlighting how circadian dysregulation mediates key molecular and cellular disturbances and the translational potential of circadian-based therapies in neurodegenerative diseases. Full article
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20 pages, 7507 KiB  
Article
Undifferenced Ambiguity Resolution for Precise Multi-GNSS Products to Support Global PPP-AR
by Junqiang Li, Jing Guo, Shengyi Xu and Qile Zhao
Remote Sens. 2025, 17(8), 1451; https://doi.org/10.3390/rs17081451 - 18 Apr 2025
Cited by 1 | Viewed by 608
Abstract
Precise point positioning ambiguity resolution (PPP-AR) is a key technique for high-precision global navigation satellite system (GNSS) observations, with phase bias products playing a critical role in its implementation. The multi-GNSS experiment analysis center at Wuhan University (WUM) has adopted the undifferenced ambiguity [...] Read more.
Precise point positioning ambiguity resolution (PPP-AR) is a key technique for high-precision global navigation satellite system (GNSS) observations, with phase bias products playing a critical role in its implementation. The multi-GNSS experiment analysis center at Wuhan University (WUM) has adopted the undifferenced ambiguity resolution (UDAR) approach to generate high-precision orbit, clock, and observable-specific bias (OSB) products to support PPP-AR since day 162 of 2023. This study presents the analysis strategy employed and assesses the impact of the transition to ambiguity resolution on the orbit precision, using metrics such as orbit boundary discontinuities (OBD) and satellite laser ranging (SLR) validation. Additionally, the stability of the OSB products and the overall performance of PPP-AR solutions are evaluated. The OBD demonstrates specific improvements of 7.1% and 9.5% for GPS and Galileo, respectively, when UDAR is applied. Notably, BDS-3 medium Earth orbit satellites show a remarkable 15.2% improvement compared to the double-differenced results. However, for the remaining constellations, the improvements are either minimal or result in degradation. Using GPS and GLONASS solutions from the International GNSS Service (IGS) and other solutions from the European Space Agency (ESA) as references, the orbit differences of WUM solutions based on UDAR exhibit a significant reduction. However, the improvements in SLR validation are limited, as the radial orbit precision is primarily influenced by the dynamic model. The narrow-lane ambiguity fixing rate for static PPP-AR, based on data from approximately 430 globally distributed stations, reaches 99.2%, 99.2%, 88.8%, and 98.6% for GPS, Galileo, BDS-2, and BDS-3, respectively. The daily repeatability of station coordinates is approximately 1.4 mm, 1.9 mm, and 3.9 mm in the east, north, and up directions, respectively. Overall, these results demonstrate the effectiveness and potential of WUM’s undifferenced ambiguity resolution approach in enhancing GNSS data processing and facilitating PPP-AR applications. Full article
(This article belongs to the Section Earth Observation Data)
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17 pages, 6539 KiB  
Article
Charge Pump Phase-Locked Loop-Based Frequency Conditioning of a MEMS Resonator
by Xinyuan Hu and Yanfeng Jiang
J. Low Power Electron. Appl. 2025, 15(2), 23; https://doi.org/10.3390/jlpea15020023 - 12 Apr 2025
Cited by 1 | Viewed by 2901
Abstract
MEMS resonators have attracted attention for their wide applications in highly accurate clock references, sensors, wireless communications, frequency control, etc. Most of the output frequencies of MEMS resonators require post-processing or calibration to be accurate enough. In this paper, a charge pump phase-locked [...] Read more.
MEMS resonators have attracted attention for their wide applications in highly accurate clock references, sensors, wireless communications, frequency control, etc. Most of the output frequencies of MEMS resonators require post-processing or calibration to be accurate enough. In this paper, a charge pump phase-locked loop-based frequency conditioning method for MEMS resonators is explored. An optimization scheme is proposed to enhance the frequency stability and signal quality of MEMS resonators. The experimental results show that the method significantly improves the resonator performance and achieves effective control of the resonant frequency. This research provides a new technical path for the design of high-performance MEMS oscillators, which has important theoretical significance and practical application value. Full article
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25 pages, 7652 KiB  
Article
A High-Precision Frequency Synchronization Method Based on a Novel Geostationary Communication Satellite Phase-Locked Transponder
by Xueyi Tang, Chenhao Yan, Haiyuan Sun, Lijiaoyue Meng, Yibin He, Rui Liu, Shiguang Wang and Lijun Wang
Remote Sens. 2025, 17(7), 1280; https://doi.org/10.3390/rs17071280 - 3 Apr 2025
Viewed by 577
Abstract
Equipping satellites with a series of high-precision frequency references is essential; however, even advanced active hydrogen masers can often be too heavy and expensive for the current satellite payload constraints. Moreover, in geostationary Earth-orbit communication satellites lacking atomic clocks, onboard oscillators can degrade [...] Read more.
Equipping satellites with a series of high-precision frequency references is essential; however, even advanced active hydrogen masers can often be too heavy and expensive for the current satellite payload constraints. Moreover, in geostationary Earth-orbit communication satellites lacking atomic clocks, onboard oscillators can degrade the performance of time–frequency transmission methods. To address these challenges, this study proposes a novel phase-locked transponder that leverages Einstein’s synchronization theory and real-time carrier-phase compensation to improve the transmission performance of satellite frequency transfer systems while mitigating the noise from onboard satellite oscillators. Notably, this requires only simple modifications to the existing transponder structure. By replicating the high-precision atomic frequency standards from ground stations to satellites, the proposed system achieves enhanced frequency synchronization without additional onboard clocks. The feasibility of the satellite-to-ground link was validated through both a theoretical analysis and an experimental verification. Specifically, ground experiments demonstrated a reproducibility of 6.33 ps (1σ) over a 24 h period, with a long-term frequency stability of 3.36 × 10−16 at an average time of 10,000 s under dynamic conditions, showcasing the potential of this approach for advanced frequency synchronization. This paper presents a cost-effective and scalable solution for enhancing frequency synchronization in geostationary satellites, improving communication reliability, supporting advanced scientific and navigational applications, and enabling the development of high-precision, space-air-ground integrated time–frequency synchronization networks. Full article
(This article belongs to the Section Engineering Remote Sensing)
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23 pages, 5019 KiB  
Article
Core Molecular Clock Factors Regulate Osteosarcoma Stem Cell Survival and Behavior via CSC/EMT Pathways and Lipid Droplet Biogenesis
by Sukanya Bhoumik and Yool Lee
Cells 2025, 14(7), 517; https://doi.org/10.3390/cells14070517 - 31 Mar 2025
Cited by 1 | Viewed by 1050
Abstract
The circadian clock, an intrinsic 24 h cellular timekeeping system, regulates fundamental biological processes, including tumor physiology and metabolism. Cancer stem cells (CSCs), a subpopulation of cancer cells with self-renewal and tumorigenic capacities, are implicated in tumor initiation, recurrence, and metastasis. Despite growing [...] Read more.
The circadian clock, an intrinsic 24 h cellular timekeeping system, regulates fundamental biological processes, including tumor physiology and metabolism. Cancer stem cells (CSCs), a subpopulation of cancer cells with self-renewal and tumorigenic capacities, are implicated in tumor initiation, recurrence, and metastasis. Despite growing evidence for the circadian clock’s involvement in regulating CSC functions, its precise regulatory mechanisms remain largely unknown. Here, using a human osteosarcoma (OS) model (143B), we have shown that core molecular clock factors are critical for OS stem cell survival and behavior via direct modulation of CSC and lipid metabolic pathways. In single-cell-derived spheroid formation assays, 143B OS cells exhibited robust spheroid-forming capacity under 3D culture conditions. Furthermore, siRNA-mediated depletion of core clock components (i.e., BMAL1, CLOCK, CRY1/2, PER1/2)—essential positive and negative elements of the circadian clock feedback loop—significantly reduced spheroid formation in 143B CSCs isolated from in vivo OS xenografts. In contrast, knockdown of the secondary clock-stabilizing factor genes NR1D1 and NR1D2 had little effect. We also found that knockdown of BMAL1, CLOCK, or CRY1/2 markedly impaired the migration and invasion capacities of 143B CSCs. At the molecular level, silencing of BMAL1, CLOCK, or CRY1/2 distinctly altered the expression of genes associated with stem cell properties and the epithelial–mesenchymal transition (EMT) in 143B CSCs. In addition, disruption of BMAL1, CLOCK, or CRY1/2 expression significantly reduced lipid droplet formation by downregulating the expression of genes involved in lipogenesis (e.g., DGAT1, FASN, ACSL4, PKM2, CHKA, SREBP1), which are closely linked to CSC/EMT processes. Furthermore, transcriptomic analysis of human OS patient samples revealed that compared with other core clock genes, CRY1 was highly expressed in OS tumors relative to controls, and its expression exhibited strong positive correlations with patient prognosis, survival, and LD biogenesis gene expression. These findings highlight the critical role of the molecular circadian clock in regulating CSC properties and metabolism, underscoring the therapeutic potential of targeting the core clock machinery to enhance OS treatment outcomes. Full article
(This article belongs to the Special Issue The Role of Stem Cells and Circadian Clock in Cancer Immunotherapy)
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