Search Results (100)

Colorectal cancer (CRC) is a life-threatening malignancy, but our understanding of its pathogenic mechanisms remains incomplete—posing a major constraint on the development of effective therapeutic strategies. The transcription-translation feedback loop of clock genes (e.g., BMAL1, CLOCK, PER1/2/3, and CRY1/2) provides a promising novel avenue for deciphering the initiation and progression of CRC. Mounting evidence indicates that core circadian clock genes play pivotal roles in CRC oncogenesis by orchestrating the regulation of the cell cycle, epithelial–mesenchymal transition (EMT), metabolic reprogramming, and the tumor microenvironment. This review systematically summarizes the expression patterns and mechanistic roles of core clock genes in CRC, while elucidating their molecular underpinnings in tumor progression via key signaling cascades (e.g., Wnt/β-catenin and c-Myc/p21 pathways). We emphasize the associations between circadian disruption and CRC—including diagnostic markers, prognostic assessment, and chemosensitivity—and provide an in-depth discussion of chronotherapeutic strategies and their translational potential. Finally, we identify unaddressed scientific questions and propose future research directions to facilitate the development of novel targeted therapies for CRC. Full article

Background/Objectives: The circadian regulator, circadian locomotor output cycles kaput (CLOCK), is well-established in maintaining sleep–wake rhythms, yet its cell-type-specific functions in sleep regulation remain largely unexplored. While ventromedial hypothalamic (VMH) prodynorphin (PDYN)-expressing (VMH^PDYN+) neurons are known to modulate homeostatic and motivational processes, their potential role in circadian sleep regulation has not been investigated. Methods: To address this, we developed mice with PDYN neuron-specific functional suppression of CLOCK activity (mClkΔ19) by interfering with their internal clock through Adeno-Associated Virus (AAV)-mediated overexpression of dominant-negative CLOCKΔ19 in PDYN-Cre mice. Results: We found that mClkΔ19 mice exhibited reduced locomotor activity during the dark phase, earlier activity peaks, and impaired rhythmicity of rapid eye movement (REM) and non-REM (NREM) sleep. Sleep analysis in mClkΔ19 mice showed selective reductions and fragmentation of light-phase REM sleep, more frequent sleep–wake transitions, and shorter REM cycles during the dark phase, indicating disrupted REM sleep timing. EEG spectral analysis in mClkΔ19 mice revealed decreased gamma activity during REM sleep in the light phase and an increase in delta activity coupled with decreased gamma during wakefulness in the dark phase. Conclusions: These findings suggest that the CLOCK activity in VMH^PDYN+ neurons is vital for circadian accuracy, REM sleep stability, and brain oscillations during sleep–wake cycles. Full article

Foot-and-mouth disease virus (FMDV) serotype SAT3 is a rarely studied serotype primarily circulating in southern Africa, with African buffalo (Syncerus caffer) serving as its key reservoir. In this study, we performed a comprehensive phylogenetic and phylodynamic analysis of SAT3 based on 81 full-length VP1 gene sequences collected between 1934 and 2018. Maximum likelihood and Bayesian analyses revealed five distinct topotypes, each with clear geographic and host associations. Notably, topotypes I, II and III were observed in both African buffalo and cattle (Bos taurus), while topotype IV appeared restricted to African buffalo. Likelihood mapping indicated moderate to strong phylogenetic signal, and the mean substitution rate was estimated at 3.709 × 10⁻³ substitutions/site/year under a relaxed molecular clock. The time to the most recent common ancestor (TMRCA) was traced back to 1875. Discrete phylogeographic reconstruction identified Zimbabwe as a major center, with multiple supported cross-border transmission routes. Host transition analysis further confirmed strong directional flow from buffalo to cattle (BF = 1631.09, pp = 1.0), highlighting the wildlife–livestock interface as a key driver of SAT3 persistence. Together, these results underscore the evolutionary complexity of SAT3 and the importance of integrating molecular epidemiology, spatial modeling, and host ecology to inform FMD control strategies in endemic regions. Full article

The pursuit of youth and longevity has accompanied human societies for millennia, evolving from mythological and esoteric traditions toward a scientific understanding of aging. Early concepts such as Greek ambrosia, Taoist elixirs, and medieval “aqua vitae” reflected symbolic or spiritual interpretations. A major conceptual transition occurred between the late nineteenth and early twentieth centuries, when aging began to be framed as a biological process. Pioneering ideas by Metchnikoff, together with early and sometimes controversial attempts such as Voronoff’s grafting experiments, marked the first efforts to rationalize aging scientifically. In the mid-twentieth century, discoveries including the Hayflick limit, telomere biology, oxidative stress, and mitochondrial dysfunction established gerontology as an experimental discipline. Contemporary geroscience integrates these insights into a coherent framework linking cellular pathways to chronic disease risk. Central roles are played by nutrient-sensing networks such as mTOR, AMPK, and sirtuins, together with mitochondrial regulation, proteostasis, and cellular senescence. Interventions, including caloric restriction, fasting-mimicking diets, rapalogues, sirtuin activators, metformin, NAD⁺ boosters, senolytics, and antioxidant combinations such as GlyNAC, show consistent benefits across multiple model organisms, with early human trials reporting improvements in immune function, mitochondrial activity, and biomarkers of aging. Recent advances extend to epigenetic clocks, multi-omic profiling, gender-specific responses, and emerging regenerative and gene-based approaches. Overall, the evolution from historical elixirs to molecular geroscience highlights a shift toward targeting aging itself as a modifiable biological process and outlines a growing translational landscape aimed at extending healthspan and reducing age-related morbidity. Full article

In vapor-cell atomic clocks, a buffer gas is employed to slow the collision rate of atoms with the vapor-cell’s walls, which dephases the atomic coherence and thereby contributes to the 0-0 hyperfine transition’s linewidth. However, the buffer gas also gives rise to a temperature-dependent pressure shift in the hyperfine transition, Δν_hfs. As a consequence, the clock’s frequency develops a temperature dependence, manifesting as a clock environmental sensitivity, which can degrade the clock’s long-term frequency stability. To mitigate this problem, it is routine to employ a buffer-gas mixture in a vapor cell. With an appropriate choice of buffer gases, d[Δν_hfs]/dT = 0 at a vapor temperature T_c, “zeroing out” the clock’s buffer-gas temperature sensitivity. Unfortunately, T_c depends on the exact mix of buffer-gas partial pressures, and if not properly achieved, T_c will be far from the vapor temperature that yields useful atomic clock signals, T_o. Therefore, understanding buffer-gas partial pressures in sealed vapor cells is crucial for optimizing a vapor cell clock’s performance, yet, to date, there have been no easy means for measuring buffer-gas partial pressures non-destructively in sealed glass vapor cells. Here, we demonstrate an optical technique that can accurately assess partial pressures in binary buffer-gas mixtures. Moreover, this technique is relatively simple and can be easily implemented. Full article

Femtosecond lasers have evolved continuously over the past three decades, enabling the transition of research from fundamental studies in atomic and molecular physics to the realm of practical applications. In femtosecond laser amplifiers, to ensure strict synchronization between the seed laser pulse and the pump laser, enabling their precise overlap during the amplification process and avoiding a decline in pulse amplification efficiency and the generation of undesired phase noise, this study designed a synchronous timing signal generation system based on the combination of FPGA and analog delay. This system was investigated from three aspects: delay pulse width adjustment within a certain range, precise delay resolution, and external trigger jitter compensation. By using a FPGA digital counter to achieve coarse-delay control over a wide range and combining it with the method of passive precise fine delay, the system can generate synchronous delay signals with a large delay range, high precision, and multiple channels. Regarding the problem of asynchronous phase between the external trigger and the internal clock, a jitter compensation circuit was proposed, consisting of an active gated integrator and an output comparator, which compensates for the uncertainty of trigger timing through analog delay. The verification of this study shows that the system operates stably under an external trigger with a repetition frequency of 80 MHz. The output delay range is from 10 ns to 100 $\mu$s, the coarse-delay resolution is 10 ns, the fine-delay adjustment step is 1.25 ns, and the pulse jitter is reduced from a maximum of 10 ns to the hundred-picosecond level. This meets the requirements of femtosecond laser amplifiers for synchronous trigger signals and offers essential technical support and fundamental assurance for the high-power and high-efficiency amplification of Ti:sapphire ultrashort laser pulses. Full article

The advancement of Internet of Things (IoT) technology has enabled battery-powered devices to be deployed across a wide range of applications; however, it also introduces challenges such as high energy consumption and security vulnerabilities. To address these issues, adiabatic logic circuits offer a promising solution for achieving energy efficiency and enhancing the security of IoT devices. Adiabatic logic circuits are well suited for energy harvesting systems, especially in applications such as sensor nodes, RFID tags, and other IoT implementations. In these systems, the harvested bipolar sinusoidal RF power is directly used as the power supply for the adiabatic logic circuit. However, adiabatic circuits require a peak detector to provide bulk biasing for pMOS transistors. To meet this requirement, a diode-connected MOS transistor-based voltage doubler circuit is used to convert the sinusoidal input into a usable DC signal. In this paper, we propose a novel adiabatic logic design that maintains low power consumption while optimizing energy and current fluctuations across various input transitions. By ensuring uniform and complementary current flow in each transition within the logic circuit’s functional blocks, the design reduces energy variation and enhances resistance against power analysis attacks. Evaluation under different clock frequencies and load capacitances demonstrates that the proposed adiabatic logic circuit exhibits lower fluctuation and improved security, particularly at load capacitances of 50 fF and 100 fF. The results show that the proposed circuit achieves lower power dissipation compared to conventional designs. As an application example, we implemented an ultrasonic transmitter circuit within a LoRaWAN network at the end-node sensor level, which serves as both a communication protocol and system architecture for long-range communication systems. Full article

We introduce a synchronization procedure for clocks based on the Einstein–Landauer framework. Clocks are modeled as discrete, macroscopic devices operating at a thermal equilibrium temperature T. Synchronization is achieved by transmitting photons from one clock to another; the absorption of a photon by a clock reduces the uncertainty in its timekeeping. The minimum energy required for this reduction in uncertainty is determined by the Landauer bound. We distinguish between the time-bearing and non-time-bearing degrees of freedom of the clocks. A reduction in uncertainty under synchronization in the time-bearing degrees of freedom necessarily leads to heat dissipation in the non-time-bearing ones. The minimum energy dissipation in these non-time-bearing degrees of freedom is likewise given by the Landauer limit. The same is true for mechanical synchronization of clocks. We also consider lattices of clocks and analyze synchronization using a Ramsey graph approach. Notably, clocks operating at the same temperature may be synchronized using photons of different frequencies. Each clock is categorized as either synchronized or non-synchronized, resulting in a bi-colored complete graph of clocks. By Ramsey’s theorem, such a graph inevitably contains a triad (or loop) of clocks that are either all synchronized or all non-synchronized. The extension of the Ramsey approach to infinite lattices of clocks is reported. Full article

We present high-precision multi-configuration Dirac–Hartree–Fock (MCDHF) calculations for the metastable states of ${\mathrm{Pr}}^{9+}$ and ${\mathrm{Nd}}^{10+}$ ions, systematically investigating their energy levels, transition properties, Landé $g_J$ factors, and hyperfine interaction constants. Our results show excellent agreement with available experimental data and theoretical benchmarks, while resolving critical configuration assignment discrepancies through detailed angular momentum coupling analysis. The calculations highlight the significant role of Breit interaction and provide the first theoretical predictions of electric quadrupole hyperfine constants ($B_{\mathrm{hfs}}$). These findings deliver essential atomic data for the development of next-generation optical clocks and establish lanthanide highly charged ions as exceptional candidates for precision tests of fundamental physics. Full article

Daylight Saving Time (DST), involving clock shifts forward in spring and backward in autumn, was introduced to promote energy savings. However, its effectiveness remains controversial, especially in buildings with temporary occupancy like academic institutions, which have high daytime use but low summer occupancy. This study investigates the impact of DST transitions on energy consumption across seven campuses of two higher education institutions (HEIs) in northern Portugal and Spain, located in different time zones, using measured data from 2023. The analysis accounted for the structural and operational characteristics of each campus to contextualize consumption patterns. Weekly electricity consumption before and after DST changes were compared using independent samples t-tests to assess statistical significance. Results show that the spring transition to DST led to an average energy saving of 1.7%, while the autumn return to standard time caused an average increase of 1.2%. Significant differences (p < 0.05) were found in five of the seven campuses. Descriptive statistics and confidence intervals indicated that only sites with intervals excluding zero exhibited consistent changes. Seasonal energy demand appeared more influenced by academic schedules and thermal comfort needs—particularly heating—than by DST alone. Higher consumption coincided with periods of intense academic activity and extreme temperatures, while lower demand aligned with holidays and longer daylight months. Although DST yielded modest energy savings, its overall impact on academic campus energy use is limited and highly dependent on local conditions. The findings highlight the need to consider regional climate, institutional policies, user behavior, and smart technology integration in future energy efficiency analyses in academic settings. Full article

Within the turbomachinery industry, components are currently assessed deploying standard second-order steady solvers. These are unable to capture complicated unsteady phenomena that have a critical impact on component performance. In this work, the high-order spectral h/p solver Nektar++ will be applied to a compressor blade to study the turbulent transition mechanisms and assess the effect of incoming disturbances with quasi-DNS resolution. The case will be modelled at an angle of incidence of $53.5°$ to match the original experimental loading at $52.8°$. At clean inflow conditions, Kelvin–Helmholtz instabilities appear on both sides of the blade due to a double separation, with the pressure side one not being reported in the experiments. The separation is gradually removed by the incoming turbulent structures but at different rates on the two sides of the blade. It will be shown that there is an optimal amount of turbulence intensity that minimises momentum thickness, which is strongly related to losses. Moreover, a discussion on the spanwise extrusion will be included, this being a major player in the modelling costs. Finally, the wall-clock time and the exact expenditure to run this case will be outlined, providing quantitative evidence of the feasibility of considering a quasi-DNS resolution in an industrial setting. Full article

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

We have employed a time-domain behavioral simulator to analyze how different design options for bang-bang Clock and Data Recovery (CDR) impact the Jitter Tolerance (JTOL) performance of High-Speed Serial Interfaces (HSSIs) with PAM-4 signaling. The simulator includes the effect of Inter-Symbol Interference (ISI) due to the transmission channel, various equalization schemes and a detailed description of the CDR architecture. Many design options have been investigated, with particular focus on transition filtering and on the algorithm to identify the Early/Late (E/L) information from data and edge samples after deserialization. It has been found that if majority voting is employed to derive a single set of E/L information from an array of phase detectors working on deserialized data and edges, the different filtering strategies provide the same JTOL, meaning that one can avoid transition filtering and furthermore use a single edge sampler with a zero threshold, significantly simplifying the CDR architecture. Instead, if summation of the E/L information from deserialized data and edges is performed, the decision to use one or three thresholds for the edge sampling and the choice of whether to implement transition filtering both impact JTOL; however, better performance is achieved under these conditions than when employing majority voting on the deserialized E/L signals. Full article

In this study, we introduce a decentralized architecture aimed at enhancing the efficiency of precise point positioning real-time kinematics (PPP-RTK) in large-scale networks with a common pivot station. Initially, we partition the extensive network into multiple smaller subnetworks (SNs), each with a common pivot station. The augmentation parameters for each SN are then computed using the precise orbit corrections and ionosphere-weighted constraints. However, directly applying the estimated augmentation parameters to users across subnetworks poses challenges due to inter-subnetwork discontinuities. These discontinuities arise from variations in the network configurations and the time correlation of the Kalman filters, despite the use of the same pivot station. To address this, common augmentation parameters, such as the satellite clocks and phase biases from each SN, are integrated into a unified set of parameters and broadcast to users. The aligned common augmentation parameters are then fed back into each SN, and the Kalman filter is re-updated to mitigate the inter-subnetwork discontinuities. The proposed architecture offers a reduced computational burden compared to the centralized PPP-RTK architecture, which handles a full-scale network simultaneously. Unlike previous research on decentralized PPP-RTK, the use of a common pivot station ensures a consistent basis for the common augmentation parameters. This approach enables seamless user positioning during transitions between SNs, eliminating the need to reset the user navigation filter during handover operations and simplifying the integration process. To evaluate the effectiveness of our proposed architecture, we gather dual-frequency global positioning system (GPS) observation data from over 40 continuously observed reference stations (CORSs) in Korea. These data are then partitioned into four SNs, each sharing a common pivot station. Subsequently, we compare the static positioning error and processing time of our proposed architecture with those of the centralized architecture. Additionally, the mitigation performance of the inter-network discontinuities is shown. Full article

Ramsey analysis is applied to the problem of the relativistic and quantum synchronization of clocks. Various protocols of synchronization are addressed. Einstein and Eddington special relativity synchronization procedures are considered, and quantum synchronization is discussed. Clocks are seen as the vertices of the graph. Clocks may be synchronized or unsynchronized. Thus, introducing complete, bi-colored, Ramsey graphs emerging from the lattices of clocks becomes possible. The transitivity of synchronization plays a key role in the coloring of the Ramsey graph. Einstein synchronization is transitive, while general relativity and quantum synchronization procedures are not. This fact influences the value of the Ramsey number established for the synchronization graph arising from the lattice of clocks. Any lattice built of six clocks, synchronized with quantum entanglement, will inevitably contain the mono-chromatic triangle. The transitive synchronization of logical clocks is discussed. Interrelation between the symmetry of the clock lattice and the structure of the synchronization graph is addressed. Ramsey analysis of synchronization is important for the synchronization of computers in networks, LIGO, and Virgo instruments intended for the registration of gravitational waves and GPS tame-based synchronization. Full article