Search Results (314)

Chronological age can be estimated from molecular profiles; however, predictive accuracy alone does not establish a biologically validated ageing clock. We therefore evaluated whether plasma protein intensities measured by data-independent acquisition mass spectrometry (DIA-MS) support chronological-age estimation in a cross-sectional cohort from Moscow, Russia, while explicitly examining acquisition-order and MS-batch confounding. Plasma samples from 350 adult participants aged 19.8 to 99.1 years were analyzed as single-shot, single-injection DIA-MS acquisitions on a Q Exactive HFX platform. The final matrix comprised 222 protein groups and was generated with DIA-NN version 1.8.1 using a two-pass predicted-library-assisted workflow, cross-run precursor-level normalization, normalized MaxLFQ-like protein–group quantification, and 1% precursor and protein–group false-discovery-rate thresholds. Descriptive associations were assessed using Spearman rank correlation with Bonferroni correction. Feature selection and missing-value imputation were confined to each training subset. Generalization was assessed primarily by holding out complete MS batches, with repeated, nested, and random five-fold analyses retained as internal comparators. Of the 222 proteins, 148 were associated with chronological age at the nominal threshold p < 0.05, and 98 remained significant after Bonferroni correction. The strongest descriptive associations involved fibrinogen beta chain (FGB; rs = 0.590), SERPINA3 (rs = 0.560), ITIH4 (rs = 0.542), complement C5 (rs = 0.538), and ceruloplasmin (rs = 0.518). In internal random-split analyses, a 50-feature Gradient Boosting strategy yielded MAE = 8.90 ± 1.06 years in repeated five-fold cross-validation and MAE = 9.10 ± 1.10 years in nested cross-validation. However, when complete MS batches were held out, aggregate MAE increased to 10.56 years (R² = 0.554) using a batch-stratified assignment and 11.87 years (R² = 0.461) using GroupKFold. These batch-held-out results constitute the primary estimate of generalization from the present dataset. To assess the trade-off between error and assay complexity, strategies using 5, 8, 10, 12, 15, 20, 30, and 50 proteins selected within each training fold were compared. The 8-feature strategy yielded MAE = 11.83 years in repeated random cross-validation, whereas the 50-feature strategy yielded MAE = 8.90 years. These estimates concern feature-number strategies, not fixed panels. The post hoc eight-protein list is reported only as an exploratory candidate set for future independent validation. Acquisition order was associated with chronological age (rs = 0.336, p = 1.03 × 10⁻¹⁰), and age and sex distributions differed strongly across 27 MS batches. Order alone predicted age with MAE = 3.98 years in a negative-control model, demonstrating that age information was encoded in the acquisition design. Accordingly, the present findings support only a proof-of-concept for plasma-proteomic prediction of chronological age within this dataset; they do not establish a batch-independent model, a clinical tool, or a biologically validated ageing clock. Full article

Light resets the mammalian circadian clock, but whether this response is determined solely by integrated light intensity (irradiance) or is also influenced by the spatial distribution of light remains unclear. We tested whether high-contrast or low-spatial-frequency patterns modulate circadian responses in mice independently of scene irradiance. Circadian phase shifts were measured following exposure to spatially patterned illumination, including high-contrast checkerboards and spot stimuli positioned at the horizon or zenith. Across all experiments, redistributing light within the visual field did not measurably alter phase-shift amplitude when irradiance was matched between paired conditions. Circadian responses were well predicted by total scene irradiance whereas a metric based on the region of highest radiance provided a poorer account of the data. These findings are consistent with effective spatial integration of light by the mouse circadian system. Within the range of spatial and irradiance conditions tested, our results support irradiance as a simple and effective metric for predicting circadian responses across light environments with divergent spatial distributions. Full article

This study compares active-computation energy and latency for twelve compression, security/integrity and signal-processing workloads on ESP32, RP2040 and STM32F446. Common scalar C kernels process fixed 2048-byte inputs on one application core under two operating profiles: maximum nominal CPU clocks of 240, 200 and 180 MHz, respectively, and a common nominal 160 MHz. A Nordic PPK2 supplies each target domain at 3.3 V and records the current and one execution marker at nominal 100 kS/s. External regulators are removed on ESP32/RP2040; Nucleo retains its LDO with JP6 open. Sixty separate power-on captures provide ten observations per board and profile for arithmetic means and sample standard deviations. Energy integrates the full RUN current without baseline subtraction. At maximum clocks, ESP32 has the lowest observed mean latency for ten workloads, RP2040 for LZ77 and STM32F446 for DCT. At 160 MHz, the counts become six, one and five; minimum mean energy is distributed across six, two and four workloads. Relative to the maximum-clock profiles, ESP32’s mean energy falls by 1.29–3.54%, whereas RP2040’s rises by 3.35–4.00%. STM32’s mean energy is lower in eleven workloads but 15.38% higher for FIR. Equal nominal CPU frequency does not equalize internal supply settings, memory clocks or software execution. These results support the workload-specific comparison of documented operating configurations. The small cross-profile energy changes remain descriptive because capture SD characterizes repeatability, while absolute accuracy and cross-session systematic errors are not fully quantified. Full article

Global Navigation Satellite Systems (GNSSs) are widely used in daily life, and the popularity of GNSS-based applications has triggered concerns about the potential vulnerabilities of GNSS. One of the major threats is the spoofing signal, and localizing the spoofer enables the threat to be mitigated at its source. Most spoofer localization methods rely on a spatially distributed sensor network with accurate time synchronization requirements. Recent research has used a least-squares (LS) estimator to localize a static spoofer using clock bias or clock drift from a single antenna. In this paper, we propose and test an extension to a method recently published in the IEEE Sensors Journal that used an LS estimator to localize a spoofer using clock bias as an observation. Specifically, we propose to extend this work with an extended Kalman filter-based algorithm to locate a dynamic spoofer using clock-bias measurements obtained from a single antenna as observations. Therefore, dynamic spoofer tracking can be realized without deploying multiple spatially distributed receivers. We demonstrate the efficiency of the proposed method by comparing it with the static spoofer localization method using a properly designed simulation. The results show that the proposed method achieves better spoofer localization accuracy than the original LS method for static spoofer localization and can be applied to track a dynamic spoofer. Full article

This paper examines the multifractal organization of hourly wind-speed dynamics at nine automatic stations of the Brazilian National Institute of Meteorology in Paraíba, Northeast Brazil, over the common interval from 3 November 2017 to 17 November 2019. Missing records and values outside the inclusive 1.0–18.0 m/s analytical range are removed before station-level standardization, and multifractal detrended fluctuation analysis is applied to compacted retained-observation sequences. The stability-potential index (SPI) is defined as |α₀ − 0.5|, where α₀ is the singularity-spectrum peak and 0.5 is the uncorrelated benchmark. SPI therefore measures departure from random-like scaling and is interpreted as a temporal-organization indicator, not as a stand-alone measure of wind-power resource. Rolling windows of 720 retained observations, advanced by 168 observations, are assigned to seasons, El Niño, La Niña, neutral conditions, and tropical Atlantic-gradient regimes. The empirical design combines full-sample rankings, rolling spectra, two-way clustered ordinary least squares, Frisch–Newton bootstrap quantile regression, non-overlapping and coverage-threshold sensitivities, clock-span diagnostics, analytical-range and moment-order checks, 200 shuffled surrogates per station, and station-anchored inverse-distance-weighted maps. All full-sample α₀ estimates exceed 0.5, with SPI ranging from 0.1108 in Cabaceiras to 0.3937 in Areia. El Niño is associated with lower rolling SPI in both baseline and controlled mean regressions and in the lower and median quantiles; this sign persists after excluding low-coverage Camaratuba. La Niña is not significant at the mean but is negative at the 0.90 quantile. No north-warm Atlantic-gradient windows occur in the common sample, while the south-warm gradient is positive only near the median quantile. Four of nine stations have original raw spectrum widths above the shuffled 97.5% bound. Across stations, exact two-sided Spearman tests show no supported monotonic association between coverage, wind-distribution descriptors, or altitude and α₀, SPI, or W (n = 9; all p ≥ 0.194). The results document sample-specific spatial heterogeneity and climate-regime associations while showing that compacted-window duration, calm-wind screening, and the modest nine-station network require explicit sensitivity analysis and cautious generalization. Full article

Complex distribution-network topologies limit the accuracy of traveling-wave fault location, because the zero-mode velocity decays nonlinearly while conventional double-ended methods still require synchronized clocks. A clock-offset-invariant multi-terminal scheme combining mathematical morphology (MM), support vector regression (SVR), and particle swarm optimization (PSO) is proposed to remove dependence on double-ended synchronization and constant zero-mode velocity. SVR first fits the nonlinear mapping between fault distance and zero-mode velocity to establish a velocity-decay predictor. Backward fault-current traveling waves measured at multiple nodes are then processed through cycle subtraction and dynamic-window denoising, constrained by the underlying zero-mode physics. A morphological-gradient operator identifies the line- and zero-mode arrival times, from which a cross-dispersion sum-of-products equation that eliminates zero-mode velocity is constructed. Preliminary auxiliary-node solutions are obtained, and PSO performs a global search by minimizing the residual between the measured modal time difference and the theoretical value obtained from the SVR-predicted velocity. Weighted fusion yields the final fault distance. Simulations of a 35 kV distribution network in the power systems computer-aided design/electromagnetic transients including DC (PSCAD/EMTDC) environment show that the method maintains high accuracy at different fault locations and under high transition resistance within the tested parameter range, demonstrating adaptability and reliability under these conditions. Full article

GABAergic neurotransmission plays a central role in regulating the mammalian circadian clock. However, the precise contribution of GABA type A receptor (GABA_AR) subunits to timekeeping within the suprachiasmatic nucleus (SCN) remains incompletely defined. Here, we investigated the spatiotemporal expression patterns of four GABA_AR subunits (α1, α5, β3, and γ2) in the SCN of male and female C57BL/6 mice. Our aim was to determine whether these subunits exhibit circadian, regional, and sex-specific variation under entrained (LD12:12) and free-running (DD) conditions. Fluorescence immunohistochemistry revealed the expression of all four subunits in the SCN, with several displaying rhythmic profiles. The α1 subunit peaked during the day in both sexes and was preferentially expressed in the shell region. The α5 subunit also varied across time but lacked strong regional specificity. Temporal variation in β3 and γ2 expression was observed in males but not females, indicating potential sex-dependent regulation. Notably, the γ2 subunit showed a dynamic shift in regional distribution over the circadian cycle, with higher shell expression during the day and core enrichment at night. Under DD conditions, rhythmic expression of the α1 and γ2 subunits persisted, suggesting endogenous control independent of external light cues. However, overall amplitude and regional specificity were reduced in the absence of light. These findings demonstrate that GABA_AR subunit expression within the SCN is regulated by circadian phase, SCN subregion, and biological sex. This study provides new insight into the molecular architecture of the SCN and supports the hypothesis that subunit-specific GABAergic signalling contributes to the temporal organisation of the circadian clock. Further investigation into the functional significance of these subunit patterns will help clarify their roles in SCN synchrony, photic entrainment, and sex-specific circadian regulation. Full article

The circadian clock is an endogenous timekeeping system that coordinates plant growth, development, metabolism, and responses to environmental stimuli. Although circadian regulation has been implicated in multiple abiotic stress responses, its potential involvement in aluminum (Al) stress adaptation in peanut (Arachis hypogaea L.) remains poorly understood. A genome-wide analysis was performed to identify and characterize circadian clock genes in peanut and investigate their transcriptional responses to Al stress. A total of 74 circadian clock genes from Arabidopsis thaliana were used as reference sequences to identify homologous genes in the peanut genome. A total of 71 encoding circadian clock proteins were identified and comprehensively characterized through analyses of chromosomal distribution, conserved domains, motif composition, transmembrane regions, subcellular localization, phylogenetic relationships, functional annotation, and protein interaction networks. Transcriptome data (RNA-seq accession PRJNA525247) from Al-sensitive ZH2 (Zhonghua 2) and Al-tolerant 99-1507 peanut cultivars were further analyzed to evaluate gene expression patterns under Al stress. The identified genes were unevenly distributed across all 20 peanut chromosomes and exhibited diverse structural features and predicted biological functions. Phylogenetic analysis demonstrated a high degree of evolutionary conservation between peanut and Arabidopsis circadian clock genes. Functional annotation indicated that many identified genes are associated with transcriptional regulation, light perception, signal transduction, phytohormone signaling, and stress-responsive pathways. Comparative transcriptome analysis revealed distinct expression profiles between the Al-sensitive and Al-tolerant cultivars, with several genes, including homologs of XAP5, PIF3, GIGANTEA (GI), FLOWERING LOCUS T (FT), and AGL15, displaying cultivar-dependent responses to Al treatment, where these were upregulated in ZH2 but downregulated in 99-1507. These findings provide the first comprehensive overview of the circadian clock genes in peanut and suggest that circadian regulatory pathways may contribute to transcriptional responses associated with Al stress adaptation. This study establishes a valuable genomic resource for future functional characterization of circadian clock genes and supports molecular breeding efforts for rhythmic traits for Al tolerance in cultivated peanuts. Full article

Background/Objectives: Sleep and circadian disturbances are common in neurodevelopmental conditions, yet the developmental cortical programs linking clock-related transcriptional regulators to disease vulnerability remain unclear. Methods: Here, we integrated human developmental brain transcriptomes, weighted gene co-expression network analysis (WGCNA), human and mouse cortical single-cell atlases, prenatal immune activation transcriptomes, and ASD postmortem brain datasets to characterize the developmental architecture of BrainSpan-derived cortical programs and examine their behavior in perturbational and disease contexts. Results: In the BrainSpan frontal cortex, canonical clock-related genes followed structured but heterogeneous developmental trajectories rather than behaving as a coordinated oscillator-like unit. WGCNA identified a postnatal-rising BrainSpan-derived primary developmental module that was strongly associated with developmental age and enriched for synaptic signaling, neurotransmitter transport, ion transport, membrane excitability, cellular respiration, metabolic regulation, and proteostatic processes. Network analysis placed multiple canonical clock-related and clock-regulatory genes, including NPAS2, BHLHE40, BHLHE41, PER family members, RORA, NR1D1/2, and CLOCK, within a broader neuronal and homeostatic co-expression architecture, although their module-membership strengths varied substantially. Projection onto a human cortical developmental single-cell atlas revealed a non-uniform distribution of the corrected BrainSpan-derived developmental signature, with relatively higher scores in excitatory and inhibitory neuronal populations and lower scores in neuroblast and radial glial populations. A mouse cortical developmental single-cell atlas provided a comparative view of the stage- and cell-type-dependent expression of clock-related genes and the transferred developmental signature during corticogenesis. In a Poly(I:C)-based maternal immune activation dataset, litter-aware reanalysis identified stage-resolved genome-wide transcriptional responses following E12.5 exposure. However, neither the aggregate core clock-gene expression score nor the independently transferred BrainSpan-derived developmental signature showed a significant overall treatment effect or collection-stage-by-treatment interaction, indicating that this bulk dataset provides a perturbational context rather than evidence for selective disruption of the developmental program. An exploratory region-stratified analysis of GSE28521 yielded near-null effects for the BrainSpan-derived developmental signature, with confidence intervals crossing zero across all examined regions. These ASD postmortem findings were therefore treated as a boundary assessment rather than evidence of ASD-specific convergence. Conclusions: Collectively, these findings position clock-related genes as components of a developmentally regulated cortical maturation program enriched for neuronal signaling, synaptic maturation, metabolic regulation, and stress-response processes. Full article

Clock steering, the core time-frequency technology for high-precision single-satellite time reference generation in global navigation satellite systems, can effectively combine the excellent short-term stability of Oven-Controlled Crystal Oscillators (OCXOs)—whose top performance indicators have already surpassed many space-borne atomic clocks in recent years—with the superior long-term stability of atomic clocks, to obtain time signals with optimal full-range stability. This paper proposes a novel clock steering scheme that integrates an adaptive variational Bayesian Kalman filter and a Proportional-Integral-Derivative (PID) automatic controller: the filter constructs a separable variational approximation for the joint posterior distribution of clock states and measurement noise parameters, to achieve real-time adaptive estimation of noise at each timestamp, while the PID controller performs closed-loop fine adjustment on the output frequency. Comparative simulations with the classic Linear Quadratic Gaussian (LQG) control scheme verify that the proposed method can generate steered time signals with better stability performance in both short-term and long-term dimensions. This work further investigates the influence of measurement noise at different intensity levels on clock steering performance and conducts corresponding mechanism analysis supported by quantitative data. The proposed scheme and conclusions can provide a reliable reference for selecting appropriate clock steering strategies under different noise conditions. Full article

Although cryptocurrency markets trade continuously, the intraday distribution of Bitcoin’s volatility has migrated toward United States trading hours as the asset has institutionalized. Using ten years of hourly Kraken XBT/USD data (2016–2025; 87,672 observations), I document this migration and tie its timing to the U.S. trading calendar with two natural experiments. When U.S. clocks change, the intraday volatility peak shifts by one hour in UTC, tracking the displaced equity open; the shift appears only in the institutionalized period. On weekday NYSE holidays, when the U.S. cash market is closed while most other markets trade, the U.S.-hours share of realized variance falls by 13.9 percentage points relative to matched weekdays, close to the uniform benchmark of 0.375 (the share expected if variance were distributed evenly across the 24 h day), and this effect is also absent before 2019. Neither result is consistent with an explanation fixed in UTC. A window-free circular index of intraday concentration rises by more than 40% over the decade, with a structural break in November 2021, and no local break at the 2017 futures launch or the 2024 spot-ETF approval. A placebo simulation shows that naive whole-sample event contrasts on this trending series are significant for 100% of random pseudo-event dates. The microstructure of a nominally 24/7 market increasingly bears the imprint of the U.S. equity calendar. Full article

Privacy amplification (PA) is a critical process in quantum key distribution (QKD) systems, essential for eliminating information leakage to eavesdroppers and extracting unconditionally secure keys. In practical high-speed QKD systems, a large input size enables the PA scheme to approach the asymptotic limit of the secure-key rate. Concurrently, the throughput of the PA scheme must keep pace with the GHz-level clock rates of modern QKD systems to prevent it from becoming a systemic bottleneck. To globally optimize these objectives, this paper proposes a scalable and highly efficient PA scheme combining a novel $\delta$-almost-universal hash family (FM3H) with modular arithmetic hashing (MH), and proves the security of this hybrid scheme, within the information-theoretic and quantum-side framework. The proposed scheme achieves a throughput of 283 Mbps on a common mobile CPU with an input size of ${10}^{10}$ bits. NIST statistical tests and avalanche-effect measurements are reported as characterizations of the statistical properties of the output sequences. To our knowledge, this work presents the first FPGA-based implementation of a modular hashing-based PA scheme, thereby breaking the dependence of modular hashing schemes on general software platforms. In DV-QKD systems, the FPGA-based scheme achieves a throughput of $1.706$ Gbps while maintaining low resource overhead. Full article

The rapid growth of artificial-intelligence (AI) and high-performance computing workloads has reshaped the power-delivery requirements of high-bandwidth memory (HBM), neural processing units (NPUs), and advanced systems-on-chip (SoCs). These platforms draw large currents that vary rapidly at aggressively scaled supply voltages, so their on-chip regulators must combine high current density, nanosecond-scale settling with minimal droop, wideband power-supply rejection (PSR), and stable capacitor-less operation, while also mitigating issues such as power supply-induced jitter (PSIJ) in high-speed clock and data paths. On-chip low-dropout (LDO) regulators have become the key building block at the point of load, and a wide range of architectures have emerged to meet these demands. This paper reviews on-chip LDOs for HBM and SoC power integrity. We translate application-level power-integrity requirements, including PSIJ, into circuit specifications; organize the design space into fast-transient, wideband high-PSR, high-current and distributed, and capacitor-less and digital/hybrid architectures; benchmark representative state-of-the-art designs using both conventional and application-relevant metrics such as data rate, jitter, and eye margin; and distill the resulting technology trends. Full article

Light is a key environmental factor regulating plant photosynthesis, yet the coordinated effects of photoperiod and light intensity on photosynthetic dynamics in non-heading Chinese cabbage remain unclear. Using experimental data, we developed a circadian clock-controlled photosynthesis model integrating photoperiod and light-intensity inputs. The model was calibrated and evaluated against experimental observations and was then used to analyze circadian gene expression, diurnal net photosynthetic rate ($Pn$), light-period net CO₂ assimilation, and the marginal carbon benefit of increasing daily light integral (DLI). Under a constant DLI of 9.216 mol·m⁻²·d⁻¹, extending the photoperiod from 8 to 20 h while reducing light intensity from 320 to 128 µmol·m⁻²·s⁻¹ lowered and delayed the instantaneous $Pn$ peak but progressively increased light-period net CO₂ assimilation. Among the treatments examined, 20L:4D produced the highest net CO₂ assimilation. Moreover, across the simulated DLI range of 5–19 mol·m⁻²·d⁻¹, the 20-h photoperiod consistently produced the highest net assimilation, whereas the marginal carbon benefit of additional light declined by approximately 62%. The results suggest that distributing a fixed daily light input over a longer photoperiod at lower instantaneous light intensity can enhance daily carbon gain within the tested range, whereas increasing DLI produces progressively diminishing photosynthetic returns. This study provides a modeling framework for evaluating photoperiod–light intensity coordination and provides a quantitative basis for optimizing light–environment management in controlled-environment agriculture. Full article

Objective: To evaluate whether structural entropy of liver histological sections reflects tissue disorganization in a rat model of constant light exposure (dark deprivation) and to explore its associations with morphofunctional parameters of hepatic remodeling. Methods: Male Wistar rats (n = 120) were divided into a control group (12:12 h light/dark) and a constant light group (24 h/day, 3 months). Biochemical, histological, immunohistochemical (p16, p21, p53, BMAL1, CLOCK, PER2, Ki-67) and ultrastructural parameters were assessed. Shannon entropy was calculated on hematoxylin and eosin-stained sections using a graph-based approach based on nuclear spatial distribution and size heterogeneity. Results: Constant light exposure caused a >2-fold decrease in serum melatonin, suppression of BMAL1 and CLOCK expression (3.7- and 3.5-fold, respectively), a rise in PER2 (+29.8%), and marked increases in p16 (23.8-fold), p21 (6.7-fold), p53 (+80.9%), steatosis, hyperglycemia, and mitochondrial dysfunction (decreased cristae count, reduced circularity index). Entropy increased by 21.4% and showed strong correlations with steatosis score (r = 0.93), p53-positive cells (r = 0.88), PER2-positive cells (r = 0.86), and an inverse correlation with melatonin (r = −0.81). Partial correlations adjusted for treatment revealed that entropy remained associated with local morphological and ultrastructural parameters but not with systemic biochemical markers, suggesting that entropy primarily reflects tissue-level remodeling. An exploratory regression model, albeit with substantial multicollinearity, explained 87.5% of entropy variance, with steatosis and circadian markers as major contributors. Conclusion: Constant light exposure induces hepatic alterations that share multiple features with aging-associated phenotypes, including steatosis, cellular senescence, mitochondrial dysfunction, and circadian disruption. Structural entropy is an exploratory quantitative index of tissue disorganization that correlates with key morphofunctional parameters of hepatic remodeling. However, because the study lacked aged comparator groups, melatonin replacement, recovery models, and independent validation, entropy should not be considered a validated biomarker of biological liver age. Its potential applicability in digital pathology and geroprotective research requires confirmation in future studies with appropriate experimental designs. Full article