Search Results (3,183)

Background/Objectives: Lipid metabolism is fundamental to energy homeostasis and cellular structural integrity, and its dysregulation is a hallmark of biological aging. While DNA methylation clocks are well-established, it remains unclear whether epigenetic sites associated with specific lipid markers—High-Density Lipoprotein (HDL), Total Cholesterol (TCH), and Triglycerides (TGY)—are evolutionarily conserved across mammals and how they manifest across different metabolic tissues. Methods: We identified lipid-associated CpG sites in humans using the Korean Genome and Epidemiology Study (KoGES) cohort and projected these sites onto the Mammalian Methylation Consortium (GSE223748) dataset. Using the Hybrid Pi (HyPi) score, we selected robust markers to analyze their evolutionary conservation, tissue specificity, and age-related dynamics across over 300 mammalian species. Specifically, we examined the phylogenetic concordance between blood and three major metabolic organs (Liver, Adipose, Muscle) in five representative species. Results: Lipid-related CpGs were highly conserved across diverse mammals. t-SNE analysis revealed that these epigenetic signatures clustered samples by tissue identity and species. Methylation levels of these CpGs showed significant correlations with maximum lifespan and distinct aging rates across tissues. Notably, phylogenetic tanglegram analysis revealed a high degree of concordance between blood and key metabolic organs, suggesting that blood methylation profiles mirror the evolutionary trajectory of internal metabolic tissues. Furthermore, these patterns were consistent between sexes, indicating a fundamental, non-dimorphic regulation of lipid epigenetics. Conclusions: Our findings suggest that epigenetic mechanisms governing lipid metabolism are deeply conserved to maintain tissue identity and regulate biological aging, with blood serving as a reliable evolutionary proxy for internal metabolic states. Full article

UAVs are widely used for all-weather, round-the-clock security inspections in urban and industrial areas. However, pure visible-light systems fail at night or in adverse weather conditions, while pure infrared methods are limited by thermal noise, low spatial resolutions, and high false alarm rates. Multispectral images render the task of object detection highly reliable and robust by providing complementary target feature information. This study suggests a frequency-based cross-attention transformer (FCAT) for multispectral object detection as a solution to this issue. This approach collects cross-modal complementary characteristics, effectively learns and integrates global contextual information via the cross-attention mechanism, and greatly increases multispectral object detection accuracy. At the same time, spatial-domain features are mapped to the frequency domain via the Fourier transform, and the scaled dot product attention is estimated via element-wise product operations, which break through the limitation of traditional spatial-domain matrix multiplication and effectively reduce the computational cost of the model. Additionally, this study independently builds a multi-scene multi-time climate visible–infrared dataset (OPVM-VIRD), which contains 20,025 target instances, to address the issue of the lack of all-weather cross-spectral data in object detection tasks from the perspective of UAVs. Experimental findings from the OPVM-VIRD, M3FD, and FLIR datasets demonstrate that our proposed approach outperforms prevailing state-of-the-art multispectral object detection algorithms on public benchmarks, while the FCAT model achieves an mAP50 score of 94.7% on our custom-built dataset—10.8% higher than ICAF. At the same time, the number of FCAT parameters is 85.26 M, which is significantly lower than that of mainstream models, such as ICAF. Therefore, the FCAT is a change detection strategy with strong model generalization abilities, and it has important application value in the all-day and all-weather security patrol of cities and industrial parks carried out by UAVs. Full article

The topic of sustainability reporting by SMEs is gaining significant importance in European contexts such as Italy. However, recent regulations, constantly evolving in terms of legal requirements and practical standards, do not yet provide solid foundations to guide small and medium-sized enterprises. This study aims to examine how Italian listed SMEs address sustainability issues in terms of Sustainable Development Goals (SDGs) in their sustainability reports, in light of the recent requirements set out in European directives (i.e., Directive 2022/2464/EU—Corporate Sustainability Reporting Directive (CSRD) and Directive 2025/794/EU—Stop the Clock). The analysis is based on a content review of 17 sustainability reports published in 2023 by Italian SMEs listed on Euronext Growth Milan of Borsa Italiana. The research protocol was structured around the key SDG themes found in the reports, using Python 3.14.2 libraries including Pandas, NumPy, NLTK, and Matplotlib. The findings highlight heterogeneous approaches to sustainability. Most firms adopt symbolic approaches based on formal narrative disclosures without addressing sustainability reporting’s substantive dimensions. They overlook both the principle of double materiality, actually recommended by the CSR Directive, and the provision of assurance statements on reports. Although mandatory sustainability reporting is not imminent, particularly in light of the “Stop the Clock” measure, this research offers significant insights into both theoretical and practical implications. From a theoretical standpoint, it contributes to the growing body of literature on sustainability practices among SMEs. From a managerial standpoint, it underscores the importance of designing tailored reporting practices for SMEs that avoid administrative costs and overload issues, at the same time fostering a substantive approach to disclosure able to convey meaningful information to stakeholders. Full article

We present a covariant geometric extension of General Relativity formulated within a controlled effective field theory framework. The gravitational action is supplemented by curvature-dependent operators parametrized by three coefficients $\alpha$, $\beta$, and $\gamma$, chosen such that the resulting field equations remain second order in time derivatives and free of Ostrogradsky instabilities. In a homogeneous and isotropic cosmological background, the modified dynamics generically replaces the classical Big Bang singularity with a smooth, nonsingular bounce driven by a repulsive curvature core proportional to $a^{-6}$. A distinctive feature of the framework is the presence of a geometric slip term proportional to $\dot{H}$, which encodes curvature-memory effects at the level of the background evolution without introducing additional propagating degrees of freedom. This term dynamically correlates the expansion rate with its temporal variation, leading to effective ultraviolet damping and enhanced dynamical stability across the high-curvature regime. As a consequence, the cosmological solutions admit the definition of an intrinsic relational time variable that is strictly monotonic throughout the evolution, including across the bounce. The emergent temporal ordering arises purely from geometric dynamics and does not rely on matter clocks, nonlocality, or fundamental violations of time-reversal or CPT symmetry. We discuss the consistency of the framework within its effective field theory domain of validity and comment on its implications for the conceptual problems of singularity resolution and the emergence of time in cosmology. Full article

Sine and cosine wave synthesis is utilized for generating sinusoidal-like values in the digital domain. While this task is commonly handled through software, dedicated hardware like Direct Digital Synthesis (DDS) is also available. However, both methods rely on memory resources, such as look-up tables and Read-Only Memories (ROMs), which face latency limitations related to additional memory access times on top of additional $Si$ area. With the advent of real-time arithmetic for sine wave approximation, this paper presents a digital module that employs iterative multiply-accumulate (MAC) operations for sine and cosine synthesis. To support the integration of this module into Systems-on-Chip (SoCs), Field-Programmable Gate Arrays (FPGAs), and standalone Application-Specific Integrated Circuits (ASICs), a comprehensive figure of merit (FoM) comparison against various ROM-less methods is provided. When implemented on a Xilinx (AMD) XC7A100T-3CSG324 FPGA, the proposed architecture compared to other ROM-less solutions like the Taylor approximation, achieves 80.80% lower resource utilization, 80.89% reduced propagation delay, and 36.66% higher accuracy in sine and cosine wave approximation, both operating as 32-bit systems with one sample per clock cycle. Furthermore, the proposed sine accelerator, accompanying control and communication IPs, and custom firmware were deployed on an FPGA-based function generator platform and experimentally validated. Full article

In this paper, a programmable clock divider with a 50% duty cycle and low jitter for analog-to-digital converters (ADCs) is presented. The proposed divider, using a 180 nm CMOS process, can handle an input clock range from 40 MHz to 1 GHz. It supports integer division ratios from 1 to 8, with programmable phase shifting corresponding to each division ratio. To address the issue of the non-50% duty cycle with odd division ratios, this design combines edge-triggered and level-triggered flip-flops to simultaneously perform logical operations during the falling edge and high-level periods of the input clock, ensuring that the output clock maintains an accurate 50% duty cycle under all integer division ratios. Moreover, a clock-edge synthesis technique is adopted: three dividing timing signals are first generated to extract the pure edges of the input clock, which suppresses the excess jitter introduced by conventional multi-stage flip-flop chains. Simulation results show that, with a 1 GHz input clock, the RMS value of the jitter is less than 85.12 fs under the worst process corner, and the power consumption is less than 3.037 mW. Full article

Background: In Pakistan, the number of Human immunodeficiency virus (HIV) cases is increasing significantly, attributed to risk factors such as injection drug use, sexual transmission, etc. However, transmission through hemodialysis units is not well documented. In 2024, an outbreak of HIV cases in Multan, Pakistan, drew alarm from local health authorities due to reports linking it to a large public hospital in South Punjab. Here, we report the molecular epidemiological investigation of the outbreak. Methods: Twenty-five hemodialysis patients identified during the outbreak were enrolled. Blood samples were subjected to DNA extraction and polymerase chain reaction (PCR) amplification. Phylogenetic analysis was conducted using the maximum-likelihood approach in IQ-TREE. For dating phylogenetics, a maximum clade credibility tree (MCC) was constructed using the BEAST tool. The MCC tree was constructed using the Bayesian Skyline model with an uncorrelated lognormal relaxed clock. The VESPA program was used to identify amino acid signatures unique to outbreak sequences compared with Pakistani reference sequences. Results: A total of 25 patients (identified as part of the HIV outbreak) were enrolled. 96% (24 out of 25) also tested positive for Hepatitis C, while none tested positive for Hepatitis B. The age range of patients in the study was 23 to 72 years (median age: 44.88 years). In terms of gender distribution, 13 out of 25 were male. All the sequences were identified as HIV subtype CRF02_AG. Phylogenetic analysis revealed that Multan sequences formed a well-supported monophyletic cluster, indicating shared recent origin. Signature pattern analysis identified a unique molecular fingerprint at 26 nucleotide positions, whereas molecular dating placed the emergence of the cluster between 2023 and 2024, consistent with the outbreak timing. Conclusions: Findings provide biologically plausible evidence of a point-source HIV outbreak linked to lapses in infection prevention and control practices at the hemodialysis unit. Full article

Background: Reverse shoulder arthroplasty (RSA) relies on secure baseplate fixation to the glenoid. This carries a risk of suprascapular nerve (SSN) injury during peripheral screw insertion. Although fixed safe zones have been described, it remains unclear whether these scale with scapular morphometry or whether common screw positions confer differential SSN risk. Methods: Twenty cadaveric shoulders (ten pairs) were dissected. The superior safe zone (distance from the supraglenoid tubercle to SSN at the suprascapular notch) and posterior safe zone (distance from the glenoid rim to SSN at the spinoglenoid notch) were measured. Scapular dimensions (height, spine length, width) were measured. In ten shoulders, simulated RSA baseplate fixation was performed with superior screws placed at 11, 12, or 1 o’clock and posterior screws at 8, 9, or 10 o’clock. Screw lengths were based on glenoid depth. Cortical breach and SSN proximity were recorded. Linear regression assessed relationships between scapular dimensions and safe zones. Results: The superior safe zone (mean 2.9 ± 0.5 cm) significantly correlated with scapular dimensions (r = 0.78–0.86; p < 0.0001). All superior screws remained intraosseous across configurations. The posterior safe zone (1.9 ± 0.6 cm) showed no correlation. Posterior cortical breach occurred in 50% of specimens across all tested positions and was associated with smaller scapular spine length (p = 0.027). No significant difference in SSN proximity was observed between posterior screw positions. Conclusions: Scapular dimensions predict the superior, but not posterior, safe zone. Scapulae with shorter spine lengths demonstrated increased risk of posterior cortical breach, independent of screw position. These findings establish anatomical scalability of the superior safe zone and suggest that scapular morphometry may inform preoperative RSA planning; however, prospective validation is needed before routine clinical implementation. Full article

Preeclampsia (PE) has traditionally been regarded as a pregnancy-limited hypertensive disorder; however, accumulating evidence increasingly positions it as a pivotal early-life vascular stress test that manifests underlying vulnerabilities and accelerates biological aging. Women with a history of PE exhibit a heightened susceptibility to premature-onset multi-systemic diseases, specifically cardiovascular, ovarian, renal, and metabolic decline. This suggests that PE acts as a catalyst for accelerated aging, driven by shared pathophysiological pathways that represent common mechanisms of systemic senescence. This review provides a comprehensive analysis of the epidemiological links and pathogenic drivers underpinning accelerated systemic aging following PE, with a specific focus on the cardiovascular-ovarian axis. Epidemiological data consistently demonstrate that women with prior PE exhibit significantly reduced anti-Müllerian hormone (AMH) levels, translating to an estimated 1.5-year acceleration in reproductive aging. In parallel, PE is associated with a twofold increase in lifetime cardiovascular disease (CVD) risk and the onset of chronic hypertension occurring an average of 7.7 years earlier. However, reconciling the phenotypic heterogeneity of PE and transcending the constraints of non-experimental designs are essential for firmly establishing this accelerated aging paradigm. At the molecular level, PE and ovarian aging converge on shared pathways—including mitochondrial dysfunction, oxidative stress, inflammation, and epigenetic dysregulation—collectively defining a distinct pathogenic ovarian–vascular aging axis. Proposed geroscience-based strategies advocate for refined risk stratification by incorporating molecular aging biomarkers—such as epigenetic clocks and inflammatory profiles—alongside conventional clinical indicators. This integrative framework facilitates the early identification of high-risk aging phenotypes, enabling targeted monitoring and timely interventions to preemptively modulate accelerated aging pathways. Pharmacological approaches within this framework emphasize the judicious repurposing of established agents, such as metformin, statins, and SGLT2 inhibitors, while emerging gerotherapeutics, including senolytics and senomorphics, provide a conceptual foundation for targeting the fundamental biological drivers of senescence. Although these geroprotective strategies, including the repurposing of established agents and the use of senolytics, offer innovative conceptual frameworks for targeting the fundamental drivers of senescence, they remain largely exploratory and require further clinical validation. Such strategies offer novel opportunities to shift the clinical focus from treating isolated comorbidities to modulating the shared molecular substrates of aging, ultimately promoting healthy aging and functional longevity in the elderly female population. Full article

Pharmaceutical industries require a continuous heat supply to sustain around-the-clock operations such as sterilization. While fossil-fuel systems ensure reliability, they increase emissions and fuel dependence. Integrating a small-scale parabolic trough collector (PTC) with concrete thermal energy storage (C-TES) enables continuous and stable solar heat delivery, offering a flexible solution for pharmaceutical manufacturing. This study investigates the integration of PTC and C-TES to provide continuous heat supply using 12 representative days of the year based on weather data for Makkah City obtained from the Renewable Resource Atlas (RRA) developed by the King Abdullah City for Atomic and Renewable Energy (K.A.CARE). Model validation was performed using experimental PTC–C-TES charging data and a simplified C-TES module model. The results show that the C-TES system successfully maintained operating temperatures between 120 °C and 310 °C. Demand coverage was identified as a key design parameter. Full demand coverage requires approximately 73 PTC units and 1600 C-TES modules, representing increases of about 4.5 and 5 times compared with the 25% coverage case. Techno-economic analysis indicates that the levelized cost of heat (LCOH) reaches an optimum of approximately 89.7 USD/MWh at 25% coverage, while overall efficiency peaks at about 41%. The results indicate that a moderate solar contribution of around 25% provides the optimal balance between cost and operational flexibility. Full article

Population ageing and the growing burden of immune-mediated disease have prompted efforts to quantify immunosenescence with clinically usable biomarkers. Immune ageing clocks have been built from immunophenotyping, transcriptomics, proteomics, epigenomics and adaptive receptor repertoires, but heterogeneous task definitions, assay protocols and evaluation criteria limit comparability and translation. We review major immune data modalities and outline an end-to-end workflow from cohort design and assay standardisation to preprocessing, feature engineering, model development, validation and recalibration. We propose a task–modality–model taxonomy separating (i) chronological age clocks, (ii) outcome-anchored risk clocks and (iii) cell lineage/state clocks, while treating bulk blood transcriptomics (whole blood or PBMC) as a molecular-layer modality that can support either age-scale or outcome-anchored tasks depending on supervision. Across studies, common limitations include batch effects, compositional confounding, endpoint mismatch, scarce external validation and limited mechanistic anchoring. We conclude with priorities for the field, including multimodal integration, longitudinal designs with digital phenotypes, tissue- and cell-type-specific models, and pathway-grounded clocks that can be linked to interventions. Full article

This paper presents a high-temperature silicon resonant pressure microsensor capable of stable operation up to 175 °C and 175 MPa, addressing the critical need for reliable pressure monitoring in deep well drilling and petroleum exploration. To overcome the inherent trade-off between pressure range and sensitivity in diaphragm-based sensors, the sensor incorporates V-shaped micro-beam supports that convert radial compressive stress into supplementary axial tensile stress on the resonant beams. This innovative force-transmission structure enhances both pressure resistance and positive stress sensitivity, enabling range extension while maintaining adequate sensitivity. A key feature of this work is the implementation of a frequency-ratio measurement scheme utilizing a dedicated pressure-insensitive reference resonator. This approach effectively eliminates the dependence on the stability of the external crystal oscillator frequency, a significant source of error in high-temperature environments where stable clock sources are costly or unavailable. Experimental results demonstrate that the fabricated sensor achieves a pressure sensitivity of 723.56 ppm/MPa for Resonator I and −436.60 ppm/MPa for Resonator II. The frequency-ratio output scheme maintains a measurement accuracy better than 0.02% FS (within the 0–36 MPa verification range) even when using a low-stability oscillator at 125 °C, significantly outperforming conventional direct-frequency measurement methods. The sensor’s combination of an extended pressure range, high-temperature capability, and robust frequency-ratio output offers a promising solution for high-precision pressure sensing in extreme downhole conditions. Full article

In environments where Global Navigation Satellite Systems are denied, a common solution to estimate one’s position on the Earth is to use stars as inertial references, as was done centuries ago by navigators using a sextant. Nowadays, sextants have been replaced by star-sighting devices, composed of inertial sensors, precise clocks, and one or more star sensors, combining the short-term precision of inertial navigation techniques and the long-term precision of celestial ones. In this context, this paper aims at developing a star classifier for geopositioning purposes, i.e., a way to discriminate stars in the sky so that an observer can choose the stars that would provide the most precise estimate of their position regarding the sighting performances of the device used (sensor definition, precision of the inertial sensor, etc.). The star classifier proposed in this paper is based on differential calculations and spherical trigonometry, and leads to closed-form expressions that are easily embeddable to evaluate the potential of a star. These closed-form expressions are then validated on an experimental setup. Full article

This paper proposes a method to generate a low-noise 10.23 MHz time-frequency reference signal based on high-order harmonic locking of the repetition rate (f_r) of an optical frequency comb (OFC). An all-polarization-maintaining (PM) Erbium-doped fiber laser with a 122.76 MHz f_r is constructed using the nonlinear amplifying loop mirror (NALM) principle. By applying a feedback control to the intracavity piezoelectric actuator (PZT) and electro-optic modulator (EOM), the 10th harmonic of f_r is phase-locked to a high-performance rubidium atomic clock (Rb clock), achieving low-noise conversion from the Rb clock to the target signal. Experimental results show that the generated 10.23 MHz signal exhibits residual phase noise of −123.4 dBc/Hz at 1 Hz offset and −158 dBc/Hz at 1 MHz offset, and achieves a residual frequency stability of 3.52 × 10⁻¹³ @ 1 s and 3.65 × 10⁻¹⁵ @ 10,000 s. This harmonic locking scheme validates the advantages of photonic microwave generation in achieving ultra-low phase noise while preserving the long-term stability of atomic clocks, providing a strategic solution for next-generation BeiDou Navigation Satellite System (BDS) time-frequency payloads. Full article