Search Results (332)

Non-contact ultrasonic thickness measurement is important for industrial metrology, particularly for metallic components where surface temperature, motion, geometry, or contamination can limit conventional contact probes. In this study, we present a fully non-contact thickness measurement system for aluminum plates integrating laser-ultrasound excitation, 3×3 interferometric detection, and deep learning-based phase demodulation. Broadband ultrasonic waves were generated using a pulsed 532 nm laser in the ablation regime, while rear-surface displacement was detected using a 1550 nm fiber-optic interferometric probe. Two phase-shifted outputs from a 3×3 coupler were processed by a neural interferometric demodulator (NID), which directly reconstructed continuous optical phase without separate quadrature reconstruction, arctangent phase extraction, or phase unwrapping during inference. PZT-modulated measurements at 10, 15, 20, and 25 kPa provided additional validation against conventional 3×3 standard ellipse fitting (3×3-SEF), including phase excursions exceeding $2\mathsf{\pi }$. The NID reduced the phase RMSE from 0.048 to 0.071 rad to 0.029–0.041 rad and the processing time from 481 ± 22 μs to 295 ± 30 μs per sequence. For thickness measurement, the reconstructed phase was converted into out-of-plane displacement, and acoustic time-of-flight (TOF) features were extracted. For 2, 6, and 10 mm aluminum plates, the estimated thicknesses were 1.911 ± 0.024 mm, 6.102 ± 0.070 mm, and 10.516 mm with a partial standard uncertainty of 0.127 mm, respectively. These results demonstrate accurate and efficient deep learning-assisted phase demodulation for fully non-contact laser-ultrasonic thickness gauging. Full article

Background/Objectives: Standard hereditary breast cancer gene panels fail to identify causative variants in some patients meeting hereditary breast and ovarian cancer (HBOC) criteria. This exploratory, hypothesis-generating study characterised germline variants in MCPH1, functionally related DNA damage response genes, and selected low-evidence candidate genes in breast cancer patients with uninformative standard panel results. Methods: A total of 185 patients meeting NCCN/ACMG criteria, with normal 42-gene panel and BRCA1/2/PALB2 MLPA results, underwent second-tier targeted sequencing. Group 1 comprised MCPH1 and related genes (TP53BP1, MDC1, TOPBP1, UBE2N, RAD52); Group 2 consisted of Genomics England PanelApp candidates (ATRIP, ESR1, PPM1D, RAD54L, RRAS2, XRCC2). No ethnically matched control cohort was available. Variants were classified per ACMG 2015 guidelines and confirmed by Sanger sequencing. Results: Rare variants meeting reporting criteria were identified in 20/185 patients (10.8%): one likely pathogenic (LP) MCPH1 frameshift deletion (c.1869_1870del) in a luminal B invasive ductal carcinoma patient, nineteen variants of uncertain significance (VUS), and one unconfirmed copy number variant. ATRIP was the most frequently implicated Group 2 gene (4 patients), including a homozygous variant; RAD54L variants were identified in three patients, including the only male breast cancer case. Conclusions: These descriptive findings identify MCPH1, ATRIP, MDC1, TOPBP1, and RAD54L as candidates warranting evaluation in case–control studies with ancestry-matched cohorts, functional validation, and family segregation analysis before any consideration for panel inclusion. Full article

The transformation of a diffuse molecular cloud into a star necessarily increases the entropy of the universe, chiefly through the radiation emitted as gravitational binding energy is released. We present a compact, fully closed-form thermodynamic model of this process: the Sackur–Tetrode equation gives the entropy of the initial cloud and, generously, of the stellar material itself, while the released gravitational potential energy is converted into a radiation-entropy term $S_{\mathrm{rad}}=\Delta E_{\mathrm{pot}}/\left(2T_{\mathrm{eff}}\right)$, the factor of one-half following from the virial theorem for a self-gravitating star in hydrostatic equilibrium. For a solar-type star we obtain $\Delta S\simeq 1.9\times {10}^{37}\mathrm{J}{\mathrm{K}}^{-1}$, consistent with independent literature estimates of stellar and interstellar entropy. Extending the calculation across the main sequence (O through M) gives $\Delta S\propto M^{0.71}$, rising from $1.2\times {10}^{37}\mathrm{J}{\mathrm{K}}^{-1}$ for a $0.3M_{\odot }$ M dwarf to $2.0\times {10}^{38}\mathrm{J}{\mathrm{K}}^{-1}$ for a $20M_{\odot }$ O star. We then map the full $(M,R,T_{\mathrm{eff}})$ parameter space to locate the locus of $\Delta S=0$—the formal boundary of thermodynamic feasibility for a single monolithic collapse—and show that every real main-sequence star lies deep in the entropy-producing region, with the boundary itself displaced to radii and masses far outside the stellar regime. Applying the same closed-form model to representative red giants, supergiants, white dwarfs and neutron stars (not as a model of their true formation, but as a diagnostic of how compactness controls radiative entropy production) shows that $\Delta S$ is set primarily by the compactness $G{M}^2/\left(R{T}_{\mathrm{eff}}\right)$ of the final configuration, so that degenerate remnants—if they were assembled by a single collapse from a diffuse cloud—would be substantially larger entropy sources than main-sequence stars, while extended giants are comparatively modest ones. The same closed-form machinery gives direct access to a full thermodynamic feasibility map, something that would otherwise require a large grid of numerical simulations to reconstruct, and we compare our results throughout with the current literature on stellar and cosmic entropy rather than with ad hoc benchmarks. Full article

Trajectory tracking remains one of the main challenges in mobile robotics, particularly when robots operate under real-world disturbances and modeling uncertainties. Model Predictive Control (MPC) has become one of the most effective solutions for this problem because of its ability to optimize future control actions while explicitly handling system constraints. However, despite the variety of predictive models reported in the literature, there is still limited experimental evidence regarding how predictive-model selection influences the closed-loop behavior of mobile robots. This work presents an experimental comparison between two MPC implementations: a Kinematic MPC and a multiple-input multiple-output MPC (MIMO-MPC) based on an experimentally identified state-space model. Both controllers were implemented on the same four-wheel differential-drive mobile robot running Robot Operating System 2 (ROS 2) and were configured with identical prediction horizons, weighting matrices, constraints, reference trajectories, and disturbance sequences, enabling a direct experimental comparison of the influence of predictive-model selection on closed-loop performance. Performance was assessed through trajectory-tracking accuracy, disturbance recovery, and control smoothness metrics under both nominal and externally perturbed operating conditions. The experimental evaluation was performed on real hardware at 50 Hz using a closed-loop trajectory of approximately 20 m. Under nominal conditions, the kinematic MPC achieved a lower lateral root mean square error (RMSE) (0.1031 m versus 0.1187 m) and maintained 93.23% of the trajectory within the $\pm 0.20$ m tolerance band. Under external perturbations, however, the MIMO-MPC reduced the heading RMSE from 0.7617 rad to 0.6503 rad, shortened the recovery time after the two largest disturbances by up to 35.6%, and decreased the angular-velocity rate root mean square (RateRMS) and jerk root mean square (JerkRMS) by approximately 24.7% and 24.8%, respectively. These results demonstrate that predictive-model selection has a significant influence on the transient behavior of MPC. While a conventional kinematic model provides excellent nominal tracking performance, an experimentally identified MIMO predictive model offers faster recovery and smoother control under disturbed conditions. The proposed experimental methodology provides practical evidence that can assist the selection of predictive models for MPC-based mobile robots according to the expected operating conditions. Full article

Timeless and its fission yeast ortholog Swi1 are evolutionarily conserved components of the replication fork protection complex that ensures faithful DNA replication and genome stability. While their nuclear roles are well-characterized, their roles in mitochondrial genome maintenance remain unknown. Here, we demonstrate a previously unrecognized connection between Timeless/Swi1 and mitochondrial homeostasis. In fission yeast, swi1 deletion increased association of the DNA repair protein Rad52 with mitochondrial DNA sequences across the mitochondrial genome, suggesting altered mitochondrial genome maintenance. Unexpectedly, swi1∆ cells showed an increased mtDNA copy number and improved growth under respiratory conditions, suggesting activation of compensatory mechanisms that promote mitochondrial genome maintenance. The loss of Swi1 also partially rescued the growth defect under respiratory conditions and mtDNA loss associated with depletion of mitochondrial DNA polymerase γ, linking Swi1 to pathways regulating mitochondrial replication under stress. Consistent with these phenotypes, transcriptomic and pathway enrichment analyses revealed transcriptional changes indicative of reduced glycolysis and enhanced oxidative phosphorylation, suggesting a shift toward respiratory metabolism. In human cells, Timeless depletion elicited distinct mitochondrial responses depending on the cell type. While Timeless-depleted TE-11 and Saos-2 cells elicited mitochondrial phenotypes comparable to those observed in fission yeast, Timeless depletion in U-2 OS cells led to reduced mtDNA copy number, elevated mitochondrial reactive oxygen species, and decreased mitochondrial membrane potential and mass, consistent with mitochondrial dysfunction. Despite these phenotypic differences, both fission yeast and human cells exhibited elevated levels of orthologs of the mitochondrial transcription factor A (TFAM) and the oxidative stress regulator NRF2, suggesting the conserved activation of compensatory mitochondrial and antioxidant pathways. Together, these findings identify an evolutionarily conserved connection between Timeless/Swi1 and mitochondrial homeostasis and reveal distinct adaptive responses to mitochondrial stress. Full article

In the European Alps, plant species have persisted through major geological and climatic changes, leaving distinct genetic signatures of divergence. While these patterns are often attributed to Pleistocene glacial refugia, they may also reflect older, pre-Quaternary events. In mountain systems, lineage-specific ecological divergence, recurrent hybridization, and polyploidization can further complicate interpretations of genetic structure. Here, we combined RAD sequencing phylogenomic, demographic modelling, and ecological analyses to determine whether genetic variation in ten alpine willows (Salix spp.) reflects pre-glacial divergence or glacial dynamics, and to assess the role of extant environmental differentiation. Across all species, genetic data revealed consistent East–West structure. Demographic analyses indicate that lineage divergences predate Quaternary glaciations by several million years and are best explained by ancient founder events followed by periods of secondary contact. Ecological niche analyses identified differences in climatic and edaphic preferences, suggesting ecological divergence as an additional driver of lineage differentiation. Together, these findings demonstrate that the persistence of spatially differentiated yet incompletely diverged Salix lineages in the Alps was likely shaped by the combined effects of pre-Quaternary divergence, ecological selection, and recurrent gene flow, highlighting the importance of integrating ecological processes to understand evolutionary responses to climatic oscillations. Full article

Surgical robot navigation in a restricted pelvic workspace requires accurate target localization, directional consistency and robot-feasible execution. This study proposes a physically constrained dual-branch front-end network (PCD-Net) for DDH-oriented navigation using public CT-derived pelvis geometries. PCD-Net maps a 21-dimensional input comprising the target geometry, current joint state, workspace bounds and constraint parameters to a base-frame target position, principal insertion direction and seven-joint correction vector for MoveIt2 and OMPL planning. Training combines supervised pretraining with direction consistency, joint limit, correction magnitude and workspace gap penalties. Evaluation comprised 15 complete simulation trials per method and target sequence-level fivefold cross-validation of 999 samples from five complete sequences. PCD-Net achieved a position error of $0.736\pm 0.202$ mm, a direction error of $0.428\pm 0.130°$, a planning time of $0.0162\pm 0.0040$ s and successful execution in all 15 trials. In cross-validation, the complete constraint setting produced the lowest joint correction MAE ($0.755\pm 0.034$ rad) and temporal correction variation ($3.270\pm 0.589$ rad) while maintaining sub-millimeter position and sub-degree direction errors. Removing the joint limit penalty increased the violation rate by 42.35%. These results support PCD-Net as a lightweight, planner-compatible front end that balances geometric accuracy and joint-level feasibility. All evidence is simulation-based; phantom experiments, physical robot validation and evaluation using clinically characterized DDH cases remain necessary before surgical translation. Full article

Stem blight, caused by Phomopsis asparagi, is the most serious disease affecting the cultivation of asparagus (Asparagus officinalis L.) in the warm regions of East and Southeast Asia, including Japan. Although Asparagus kiusianus, a wild species endemic to Japan, shows strong resistance to this disease and is cross-compatible with cultivated asparagus, the genetic basis of this resistance remains unclear. In this study, we used BC₁ populations from interspecific crosses between A. officinalis and A. kiusianus to dissect stem blight resistance inheritance and identify markers suitable for marker-assisted selection. Disease severity was evaluated using P. asparagi inoculation, and RAD sequencing was used to construct a linkage map and perform QTL analysis. Segregation patterns suggested that resistance was controlled by major genes and polygenic factors which depended on the cross combination. A major QTL was detected on chromosome 1 and SNP_PRK showed a significant association (LOD > 3). A dCAPS marker derived from SNP_PRK was associated with resistance, with approximately 80% of individuals carrying the associated genotype showing resistance. CAPS marker PR1 distinguished the same genotype classes and produced results consistent with those obtained using PRK in the evaluated materials. PR1 may therefore facilitate resistant individual selection in breeding programs. Full article

Background: Inter-species hybridization has been extensively used in breeding cervids to improve productive traits by hybrid vigor, but the genomic processes behind the process are not well studied. Methods: In this study, we investigated restriction-site-associated DNA sequencing (RAD-seq) to conduct a whole-genome analysis of Hua-Ma hybrid individuals (a cross of sika deer and Tianshan red deer). Results: A total of 571,835 SNPs were obtained and 427,121 high-quality SNPs were obtained from five individuals upon strict filtering. An analysis of genetic diversity has shown that the observed heterozygosity (Ho = 0.2130) was lower than expected heterozygosity (He = 0.3560). Although these estimates provide preliminary insights into the genetic diversity of the sampled Hua-Ma hybrids, they should be interpreted cautiously because of the limited sample size. After the pruning of linkage disequilibrium, 189,975 independent SNPs underwent principal component analysis (PCA). The first two principal components (PC1 = 32.6%, PC2 = 26.2%) indicate relative genomic clustering rather than definitive ancestry assignments. These patterns reflect relative genomic clustering rather than definitive ancestry assignments. Conclusions: The high polymorphic loci were functionally annotated and revealed the existence of synonymous and nonsynonymous variants, including a conserved locus adjacent to the BEND5 gene that exhibited a nonsynonymous mutation generating a valine-to-isoleucine amino acid substitution which may have potential functional relevance, although no phenotypic effects were evaluated in this study. On the whole, these results suggest heterozygosity and mixed ancestry in Hua-Ma hybrids. This exploratory study provides an initial SNP resource that may support future genomic selection, parentage analysis, and breeding optimization efforts. Full article

Tousled-like kinases 1 and 2 (TLK1 and TLK2) are paralogous serine/threonine kinases that share high sequence similarity yet exhibit functional divergence in cellular processes such as DNA replication, damage response, and chromatin organization. This study elucidates the paralog-specific co-phosphoregulatory networks underlying this divergence through a comprehensive analysis of 3825 human phosphoproteomic articles. Predominant phosphosites were identified as S134 and T38 for TLK1 and S73, S99, and S111 for TLK2, revealing context-dependent regulation across cancers and perturbations. Co-phosphoregulation analyses uncovered distinct networks: TLK1 associates with DNA damage signaling via proteins like ABRAXAS1, PML, and RAD9A, while TLK2 integrates with chromatin remodeling and replication through CHD4, DOT1L, NASP, and RNF20. Upstream kinases for TLK2, predominantly CDKs, link it to cell-cycle progression, whereas downstream substrates and binary interactors converge on genome stability pathways with paralog-specific nuances. These findings highlight the potential role of TLK1 on checkpoint activation and TLK2 on replication-coupled chromatin maintenance, providing insights into their roles in cancer amplification and therapeutic resistance, as well as neurodevelopmental disorders, where emerging evidence also support the involvement of TLK1 alongside TLK2. Full article

Background/Objectives: Breast cancer (BC) is the most frequently diagnosed malignancy among women worldwide, yet tumor genomic data from Latin American and admixed populations remain limited. This gap affects the interpretation of cancer-associated variants and may limit the representation of these populations in genomic research. This study aimed to characterize the genomic landscape of breast tumors from Ecuadorian women and contextualize variant interpretation through genetic ancestry analysis. Methods: Breast tissue samples from 23 Ecuadorian mestizo women with suspected malignancy were analyzed. After histopathological confirmation, 21 breast tumors were included in the final cohort. Targeted next-generation sequencing was performed using a 94-gene cancer panel. Variants were annotated and classified according to clinical significance. Because matched normal DNA was unavailable, variant allele frequency was used as an exploratory approach to infer putative somatic, putative germline, indeterminate, or putative homozygous germline profiles. Putative germline and indeterminate variants were interpreted using ACMG/AMP criteria, whereas putative somatic variants were evaluated using the AMP/ASCO/CAP framework. Genetic ancestry was inferred using ancestry-informative insertion/deletion markers. Results: Seventy-two unique variants across 40 genes were identified, including 14 pathogenic, 10 likely pathogenic, and 48 variants of uncertain significance. Pathogenic and likely pathogenic alterations were detected in clinically relevant genes, including TP53, BRCA2, PTEN, CDH1, RAD51C, MSH6, NF1, CYLD, and SDHB. Variants of uncertain significance represented 66.7% of all detected variants and affected several cancer-associated and DNA repair genes. The cohort showed a trihybrid ancestry profile, with predominant Native American ancestry, followed by European and African contributions. Conclusions: This study expands BC genomic data from an underrepresented Ecuadorian cohort and highlights the coexistence of clinically relevant alterations with a high burden of variants of uncertain significance. The findings underscore the limitations of tumor-only sequencing and current variant interpretation frameworks in admixed populations. Larger studies integrating matched normal DNA, ancestry-informed analyses, functional validation, and broader sequencing strategies could help improve variant interpretation in Latin American populations. Full article

Pathogenicity islands (PAIs) are regions of bacterial genomes that harbor genes encoding virulence factors. Identifying molecules that enhance pathogenicity is crucial for understanding the mechanisms pathogens employ to cause disease and their evolution. Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a pathogenic microorganism that causes caseous lymphadenitis (CLA) in sheep and goats. Despite its prevalence in Mexico, its genetic material has not been analyzed for virulence factors acquired through horizontal gene transfer. Therefore, the aim of this study was to characterize the complete genomes of Mexican C. pseudotuberculosis strains and identify virulence-related genes harbored with PAIs. Seventeen strains of C.pseudotuberculosis biovar ovis isolated from Mexico were whole-genome sequenced using illumina technology, assembled de novo with SPAdes, and annotated using Prokka. PAIs were predicted with GIPSy based on genomic signatures associated with horizontal gene transfer, including G + C deviation, codon usage, virulence factors, transposases, and tRNA-flanking regions. Positive selection was assessed using POTION v1.2 by identifying orthologous groups enriched in non-synonymous substitutions. This represents the first comprehensive PAI analysis of Mexican C. pseudotuberculosis strains, identifying 14 putative pathogenicity islands harboring 51 virulence-associated genes. Additionally, positive selection analysis identified five coding sequences, including radA and rpiB, that are undergoing adaptive evolutionary changes. These findings elucidate the pathogenic mechanisms and genomic plasticity of Mexican C. pseudotuberculosis strains. They also highlight novel genetic targets for vaccine and therapeutic development against CLA. Full article

Background/Objectives: Merkel cell polyomavirus (MCPyV) is a ubiquitous virus strictly associated with Merkel cell carcinoma (MCC), a rare and aggressive skin cancer. MCPyV oncogenic properties are associated mainly with early protein expression, integration, and LT truncation. MCPyV can also interact with DNA Damage Response (DDR) mechanisms, contributing to oncogenesis and tumor progression. In this work, we investigated the correlation between MCPyV and MCC and evaluated the mRNA expression profiles of DDR genes in virus-positive and -negative tumors. Methods: A total of 19 formalin-fixed paraffin-embedded biopsies were acquired from patients diagnosed with MCC. After DNA and RNA extraction, the DNA was used for MCPyV detection via qPCR and for sequencing analysis of the early, late, and non-coding control viral regions and the extracted RNA was used for MCPyV transcripts, miRNA detection and for the evaluation of several DDR genes expression such as ATM, ATR, CHK1, CHK2, H2AX, Rad51, p53, and p21, in MCPyV-positive and -negative samples via reverse transcription, PCR, and qPCR. Results: MCPyV presence was detected in 11/19 samples, all characterized by viral integration, LT truncation, and early region expression only. Furthermore, higher mRNA levels of DDR genes were observed in MCPyV-positive tumors compared with the negative ones. Conclusions: Our findings support the role of MCPyV in MCC formation and suggest its involvement in the transcriptional regulation of DDR genes, which may influence tumor progression. Understanding the molecular interplay between MCPyV and the DDR may guide future research into plausible novel diagnostic and therapeutic strategies for virus-induced tumors. Full article

Wilms tumor (WT), the most common kidney neoplasm in children, is closely associated with hereditary factors. This study included 134 WT patients (62 males, median age of 7 years, age at diagnosis of 24.9 months) with unilateral (n = 90, 67%) or bilateral WT (n = 44, 33%). Genetic testing was performed using targeted sequencing of 415 genes and multiplex ligation–dependent probe amplification (MLPA). Twenty-five mutations in eight genes were found in 17% (n = 23) of patients: WT1 (n = 10), TRIM28 (n = 4), REST (n = 3), CHEK2 (n = 3), BRCA2 (n = 2), NF1 (n = 1), RAD50 (n = 1), and CDC73 (n = 1). Large deletions of the 11p13 region were revealed in 6% (n = 5) of patients. The 11p15 locus methylation was studied in blood, tumor, and healthy kidney tissue of nine patients suspected of Beckwith–Wiedemann syndrome (BWS) using methylation-sensitive MLPA (MS–MLPA). BWS was diagnosed in 3% (n = 4) of cases (one patient had mosaic disease). Thus, genetic and epigenetic aberrations were identified in 32 WT patients (24%). These patients had a higher frequency of bilateral WT and a higher rate of abnormalities compared to patients without aberrations (56% vs. 25%, p = 0.002; and 86% vs. 25%, p < 0.0001, respectively). The detection of WT hereditary predisposing factors is crucial for treatment strategies and long-term patient surveillance. Full article

Background: Acute erythroid leukemia (AEL) or AML-M6 predominantly affects older adults and is rare in childhood. Compared with other AML subtypes, AEL remains relatively understudied because of its rarity. We established LS-CHM, a novel AEL cell line derived from the ascitic fluid of a patient with congenital leukemia. Interestingly, leukemic cells persisted in the ascitic fluid even after successful eradication from the bone marrow and extramedullary sites. Method: Leukemia cells from the ascites fluid exhibited robust proliferation in culture independent of cytokine requirement and were further characterized by flow cytometric immunophenotyping, cytogenetics, cell cycle and doubling time analysis, colony formation, genome and RNA sequencing, myeloid gene next generation sequencing, and cytotoxicity analysis. Results: LS-CHM displayed CD36, partial CD235a, CD31, CD43, and CD71 expression and demonstrated in vitro robust growth and high sensitivity to chemotherapeutic agents. A PDX mouse model showed development of leukemia. Genomic analysis revealed a frameshift BCOR mutation in the absence of additional mutations and downregulated TP53 expression with an exonic non-deleterious mutation. RNA sequencing of LS-CHM cells revealed upregulation of two cohesin complex genes, RAD21 and SMC3, whose high levels are associated with hematopoietic stem cell differentiation into erythroid lineage. Conclusions: LS-CHM represents the first congenital AEL-derived cell line, in contrast to the predominantly adult-origin and often secondary erythroid leukemia cell lines available currently. Thus, LS-CHM provides a unique pediatric and extramedullary AEL model, expanding the existing spectrum of AEL cell lines and offering valuable opportunities for biologic and therapeutic investigations. Full article