Search Results (7,722)

We formulate the Peaceman–Rachford (PR) and Douglas–Rachford (DR) operator splitting schemes for multidimensional parabolic evolution equations in the tensor-train (TT) format. The resulting TT-PR and TT-DR algorithms maintain the evolving state and the split operators in TT form, solve the implicit subproblems approximately with the Alternating Minimal Energy (AMEn) method, and control TT ranks through preventive rounding and a rank cap enforced within the inner solves. We analyze per-step computational complexity, practical rank behavior, and total error decomposition, and we validate the algorithms on benchmark problems in two to eight spatial dimensions, with additional higher-dimensional scaling illustrations. Full article

Dengue virus (DENV) serotypes 1–4 cause dengue, a major re-emerging disease in tropical and subtropical regions. This study evaluated the antigenicity of a recombinant DENV-2 premembrane protein (rprM-DENV-2) and its ability to detect anti-DENV human IgA antibodies. The rprM-DENV-2 protein was expressed in Escherichia coli, purified, and assessed for immunogenicity and antigenicity. The recombinant protein induced IgG antibodies in rats, which detected DENV infection in Vero cells. Importantly, in paired saliva and serum samples from patients diagnosed with dengue, IgA antibodies were detected by ELISA using the rprM-DENV-2 antigen, but not in samples from the negative control group (subjects residing in a non-endemic area), with a significant difference (p < 0.0001). These findings demonstrate that rprM-DENV-2 retains antigenic properties similar to the native viral protein; this may be useful for in vitro studies of DENV infection and IgA detection in non-invasive clinical samples. Full article

Background/Objectives: Wide-field swept-source optical coherence tomography angiography (WF-SS-OCTA) enables non-invasive, layer-specific retinal microvascular assessment. We explored treatment-associated microvascular change in acute leukemia and its concurrent association with post-induction response. Methods: In this prospective single-center cohort (ChiCTR2300077558), 111 newly diagnosed adults (58 AML, 53 ALL) and 40 healthy controls underwent pre-induction 16 × 16 mm WF-SS-OCTA; 77 were re-imaged at first response assessment. Response (complete remission (CR)/CRi vs. partial/no response (PR/NR)) was adjudicated independently of OCTA. The focal exploratory outcome was deep capillary plexus vessel density change (ΔDCP-VD). This outcome was designated after completion of data collection, and all analyses are exploratory and hypothesis-generating. Results: DCP-VD showed an AML < ALL < control baseline gradient (42.49 ± 3.15%, 43.45 ± 2.89%, 44.27 ± 2.78%; ANOVA p = 0.014), and 10 of 20 baseline metrics survived false-discovery-rate correction. ΔDCP-VD was higher in CR/CRi than PR/NR (1.50 (1.00, 2.00) vs. 0.50 ± 0.83 percentage points; difference 0.97, 95% CI 0.57–1.37; p < 0.01) and correlated with hemoglobin change (r_s = +0.546, p < 0.01); in-sample discrimination gave an AUC of 0.799 (95% CI 0.674–0.907). Conclusions: ΔDCP-VD differed by concurrent response and tracked hemoglobin change; findings establish no causality, prediction, or clinical threshold and require independent prospective validation. Full article

Background and Objectives: Codon usage bias (CUB), the non-uniform usage of synonymous codons, is prevalent in plant chloroplast genomes and plays important roles in gene expression and genome evolution. However, systematic comparisons of CUB patterns across genera in the Cucurbitaceae family remain limited. This study aimed to characterize CUB patterns and identify their driving forces in the chloroplast genomes of six Cucurbitaceae species. Methods: We analyzed the complete chloroplast genomes of six Cucurbitaceae species, watermelon (Citrullus lanatus), melon (Cucumis melo), cucumber (Cucumis sativus), pumpkin (Cucurbita moschata), wax gourd (Benincasa hispida), and bitter gourd (Momordica charantia). CUB patterns were assessed using ENC-plot, neutrality plot, and PR2-plot analyses, all implemented through a custom, reproducible Python-based workflow. Results: The overall codon usage bias was weak across all six species, with a clear preference for A/U-ending codons. Candidate preferred codons (hereafter referred to as optimal codons for brevity) identified independently within each species were largely shared across the six species, although species-specific codons were also detected. Combined ENC-plot, neutrality plot, and PR2-plot analyses suggest that natural selection, rather than mutation pressure, is the dominant force shaping CUB in these genomes, although these approaches provide indirect evidence. Conclusions: These findings provide a reference for codon optimization of exogenous genes in chloroplast genetic engineering of Cucurbitaceae crops. The Python-based workflow developed in this study also offers a transparent, reproducible alternative to conventional CUB analysis approaches. Full article

Uterine health indicators are essential tools for managing reproduction in dairy herds. This study evaluated the associations between vaginal discharge scores (VDS) assessed during the first 21 days postpartum and subsequent days open and pregnancy rate (PR) across 14 commercial dairy herds comprising 2860 calvings (2023–2025). VDS were evaluated on a 10-point scale and classified as normal (0–2; clear/bloody), moderate (3–4; presence of pus), or high (5–9; purulent and foul-smelling). Concurrently, parity, metabolic (body condition score and acetonuria), and digestive (fecal consistency) indicators were recorded. Two independent multivariate models, Cox proportional-hazards regression and binary logit generalized linear mixed model (GLMM), were used. VDS was the most significant and consistent factor associated with prolonged days open and reduced PR. A higher hazard ratio (HR) for pregnancy failure was observed in cows with moderate (HR = 1.45; 95% CI: 1.20–1.65) and high (HR = 1.59; 95% CI: 1.25–2.01) VDS compared with those with normal VDS (p < 0.0001), thereby extending the days open at the first artificial insemination. The odds ratio (OR) for becoming pregnant at the first artificial insemination was lower (p < 0.01) in cows with moderate (OR = 0.5; adjusted 95% CI: 0.4–0.8) and high (OR = 0.4; adjusted 95% CI: 0.3–0.8) VDS than in those with normal VDS. This likelihood was also lower for multiparous cows compared with primiparous cows (p < 0.001). No other factors were significantly associated with PR (p > 0.05) in the GLMM. In conclusion, scoring vaginal discharge in the early postpartum period was a relevant health indicator associated with days open and PR. Implementing specific reproductive management protocols for cows presenting moderate VDS is suggested to improve overall herd reproductive performance. Full article

Malicious packages in open source-software supply chains are a growing security concern, yet machine learning detectors built on registry metadata are difficult to interpret and are typically evaluated under protocols susceptible to data leakage. We construct a dataset of 3330 package versions from NPM and PyPI in which every attribute is reconstructed at its exact publication timestamp, and we partition the data so that all versions of a package, all packages of a maintainer, and all members of a name-similarity family reside within a single fold. The primary analysis is restricted to NPM, where 18 of 456 point-in-time attributes attain an AU-PR of 0.9972 against a positive-class baseline of 0.8755 and an AUC-ROC of 0.9828 on 763 held-out versions. A secondary pooled analysis over both ecosystems is reported: the class priors differ by nearly a factor of nine, a classifier using only the ecosystem of origin attains an AUC-ROC of 0.8036, and the pooled figures should be read with that composition in mind. Confidence intervals are obtained by cluster-bootstrap resampling at the composite-group level and are 3.7-times wider than version-level intervals in AU-PR (0.0201 against 0.0055); at that scale, none of the differences between feature subsets, selection-stage orderings, or metadata families reported here is distinguishable from sampling variation. At an operational prevalence of 0.1%, the positive predictive value is 4.3% and recall at the selected threshold is 0.537, indicating that metadata-based detection functions as a triage filter rather than a definitive verdict. Full article

There is a growing need for high-efficiency power electronic converters that can effectively convert energy, regulate voltages, and enhance power quality in standalone power generators, as the use of renewable energy sources and battery energy storage devices increases. The quasi-impedance-source inverter (qZSI) has attracted significant interest due to its single-stage buck-boost operation, continuous input current, reduced reliance on passive elements, and increased reliability. In this paper, the control strategy and implementation of the qZSI with battery assistance for standalone photovoltaic energy generation are discussed. To analyze the operational characteristics and design the control strategy of the qZSI, the system equations are linearized around the nominal operating point to develop a small-signal model, from which the direct current (DC) side and alternative current (AC) side transfer functions are derived and used as the basis for controller design. Using the proposed model, hybrid controllers are designed to control the shoot-through duty cycle, maintain DC link voltage stability, and battery charging to achieve stable power generation. Furthermore, the SPWM technique is applied to produce AC power with minimal harmonic content and higher efficiency. Application results show stable dynamic behavior, effective battery energy management, improved voltage regulation, and reduced harmonic distortion in the output waveform. The main contribution is a low-complexity coordinated PI and PR control framework for standalone battery-assisted qZSI operation, experimentally validated under DC- and AC-side disturbances without requiring an additional battery-side power-conversion stage. Full article

The Hatay province, which was most affected by the 6 February 2023 Kahramanmaraş earthquakes, causing significant losses in both Türkiye and Syria, is the main study area of this research. Furthermore, following this pair of earthquakes, Hatay became the province with the most structural and geotechnical damage. The low seismic performance of reinforced concrete (RC) structures, which constitute the dominant urban building stock of the province with its rich historical architecture, has clearly revealed critical structural weaknesses and defects. This study first provides information about the seismicity of the province and its surroundings, and then obtains intensity values for four major earthquakes using two different approaches. Considering the last two earthquake hazard maps, a comparison of seismic design parameters was made for all districts within the province. Considering the high incidence of damage in RC structures built before 2000, numerical analyses were performed on structural models created using the seismic design codes of that period. The results of the numerical analysis were consistent with the damage observed in the field. In columns where shear force capacities were exceeded, reinforcement with fiber-reinforced polymer (FRP) was applied, and the results were compared. Nonlinear static pushover analyses of a 5-story RC reference building showed that the 1968-code model had shear-capacity exceedances in a significant number of columns, whereas only two ground-story columns exceeded their shear capacity in the 1975-code model. The corresponding performance ratios (PRs) reached approximately 1.46–1.48 and 1.10 for the 1968 and 1975 models, respectively. Targeted FRP strengthening reduced the PR values of deficient members to 0.14–0.17 and eliminated the identified shear-capacity exceedances. This study aims to assess geotechnical and structural damage after earthquakes, compare seismic parameters, perform structural analysis, and determine the applicability of strengthening methods. The results of this study will be an important resource, especially for the evaluation and strengthening of RC structures built before the year 2000. Full article

Churn prediction research is largely accuracy-oriented, and the link between prediction and financial decision-making remains underdeveloped. This study builds and tests the chain from prediction to profit as follows: calibrated prediction, SHAP-based explanation, a profit-maximizing threshold, and EMP-based evaluation, across five datasets in three sectors. Resampling and class weighting do not improve ranking quality (PR-AUC) and degrade calibration up to 19-fold (ECE); shifting the threshold recovers the same recall without retraining. SHAP-based analysis shows no driver is consistently strong across sectors: usage volume has the broadest reach, but the strongest drivers are dataset-specific, and models do not transfer after semantic alignment. The profit-maximizing threshold matches or beats the fixed 0.5 threshold in all 100 cost-success scenarios examined, and a paired test across datasets and seeds confirms the difference (Wilcoxon p < 0.001); a threshold that looks reasonable by accuracy can still cause a loss. Predictability and profitability rank inversely across datasets (Spearman ρ = −0.90): the most predictable dataset yields the lowest EMP, driven by churners’ value distribution. Compared with ProfLogit, which embeds the profit objective in training, a threshold on a well-calibrated model proves sufficient. Value comes from turning calibrated probabilities into decisions with a financial criterion, not from balancing data. Full article

Enterprise Resource Planning (ERP) systems generate transactional data, but their value for process improvement depends on converting these records into reliable event logs and useful predictions. This study evaluated a framework combining event-log readiness assessment, process mining, predictive process monitoring, transparent machine learning, and domain validation in an Ecuadorian steel manufacturer. The analysis used 3740 production orders and 31,791 ERP-recorded events, split chronologically into training, validation, and out-of-time test samples. Process discovery identified execution heterogeneity; rework, accumulated waiting, route deviations, and resource congestion were positively associated with deadline violation. At production start, the process-aware ridge logistic model achieved a PR-AUC of 0.839, compared with 0.419 for the static representation and 0.683 for the remaining-slack benchmark, with an ROC-AUC of 0.893, a Brier score of 0.123, and a sensitivity of 0.804. The first material transaction was the earliest operationally useful checkpoint, preserving a median intervention window of 98.7 h before the committed completion date among predicted-positive cases. Additive model decomposition highlighted material-related waiting, queue waiting, partial material issues, and accumulated deviations as contributors to fitted risk. A nine-expert panel translated the evidence into six operational and tactical improvement opportunities. Findings support ERP-based early-warning process intelligence when readiness, temporal validation, calibration, transparency, and actionability are addressed jointly. Full article

Potato production is severely threatened by the oomycete Phytophthora infestans, the fungus Alternaria solani, and the bacterium Ralstonia solanacearum; however, strategies capable of simultaneously managing these three pathogen classes remain relatively scarce. In this study, we designed a series of signal peptide (SP)-fused recombinant constructs containing four functional modules with distinct antimicrobial and immune-inducing properties: GAFP1-2×FYVE, an oomycete-inhibiting antimicrobial protein; BbAFP1-ErBD, a fungal-suppressive protein fragment; the pathogen-associated molecular pattern (PAMP) csp22 derived from R. solanacearum, which elicits effective anti-bacterial immunity; and the microbe-associated molecular pattern (MAMP) PpEli2 identified from Pythium periplocum, which triggers broad-spectrum plant defense responses. Through systematic evaluation of six module order rearrangements, we identified SP-cBG as the optimal multi-domain combination. Further optimization via the introduction of a rigid alpha-helical linker (HL4) yielded SP-cBG-HL4, which tended to show superior resistance against all three pathogens, as reflected in smaller lesion diameters and decreased bacterial titers. qRT-PCR analyses revealed that SP-cBG-HL4 significantly upregulated PTI (CYP71D20, PTI5), SA (PR1, PR2), and JA/ET (PR3, PR4) defense marker genes. Collectively, these findings show that modular domain assembly combined with linker-mediated modular combinatorial optimization represents a powerful engineering strategy for achieving broad-spectrum disease resistance, offering a promising approach to simultaneously control oomycete, fungal, and bacterial pathogens of plants. Full article

Background/Objective: Activated coagulation factor XII (FXIIa) is a component of the contact activation pathway and a pharmacologically relevant target in contact-system-associated processes. In this study, scaffold-aware and interpretable machine-learning QSAR models were developed for human FXIIa activity. Methods: Bioactivity records for the human single protein target CHEMBL2821 were retrieved from ChEMBL release 37. Modeling was restricted to exact IC50 measurements from assays explicitly referring to FXIIa, Factor XIIa, or activated Factor XII. Median-consolidated pIC50 values and two-dimensional Mordred descriptors were evaluated using leakage-safe preprocessing, scaffold-disjoint validation, Y-randomization, applicability domain analysis, structural similarity auditing, and SHAP interpretation. Results: The regression dataset comprised 424 compounds and 166 Bemis–Murcko scaffolds in this study. The Gradient Boosting regressor achieved R² = 0.7560, RMSE = 0.6924, and MAE = 0.4965 on the locked scaffold-disjoint test set (n = 85); across 50 repeated scaffold partitions, the mean R² was 0.6892 ± 0.1515. The classification model achieved ROC-AUC = 0.9453, PR-AUC = 0.9807, balanced accuracy = 0.7561, and MCC = 0.5972 (n = 73). Y-randomization supported nonrandom predictive signals (empirical p = 0.0099). Conclusions: The models support computational prioritization within the represented FXIIa chemical domain, while prospective evaluation of independently generated compounds remains necessary. Full article

Alcohol consumption is associated with increased breast cancer risk, partly due to the accumulation of toxic aldehydes like acetaldehyde, a carcinogenic byproduct of ethanol metabolism. Acetaldehyde Dehydrogenase 2 (ALDH2), a key mitochondrial enzyme, detoxifies acetaldehyde and other reactive aldehydes that drive oxidative stress, DNA damage, and hormonal dysregulation—processes central to carcinogenesis. Although alcohol consumption has been implicated in breast cancer, the role of ALDH2 deficiency itself, in the absence of exogenous alcohol exposure, in mammary gland biology and cancer susceptibility remains unclear. Genetic variants that impair ALDH2 activity are highly prevalent in East Asian populations, where carriers of inactive ALDH2 alleles exhibit impaired aldehyde detoxification. While such individuals are more susceptible to alcohol-related cancers, the effects of ALDH2 deficiency on mammary gland development and homeostasis without alcohol exposure remain unexplored. To investigate the effects of ALDH2 deficiency on mammary proliferation and development, we utilized a C57BL/6-based ALDH2 knockout (Aldh2−/−) mouse model. Our findings revealed that Aldh2−/− mice displayed hyperproliferative mammary glands with increased epithelial cell density, ductal expansion, and increased numbers of Ki67+ cells. Flow cytometry analysis revealed expansion of luminal and basal epithelial subpopulations, accompanied by enhanced mammary epithelial stemness, as indicated by increased mammosphere formation and colony-forming efficiency. At the molecular level, ALDH2 deficiency activated oxidative stress pathways, reflected by elevated 8-OHdG, p38 MAPK, NF-κB, and Nrf2 signaling, along with DNA damage responses involving p53 and H2A.X. We also identified a novel upregulation of RANK and RANKL in Aldh2−/− mammary glands, identifying the RANK/RANKL upregulation associated with NF-κB/p38 MAPK activation and enhanced mammary stemness. Furthermore, hormonal dysregulation was observed, with a significant increase in ERα and PR expression and phosphorylation. Dysregulated ER signaling correlated with enhanced erbB3 activation and downstream signaling, including the cyclin D1–pRb-E2F1 axis. These findings suggest that ALDH2 deficiency, possibly through accumulated endogenous aldehydes, profoundly alters mammary morphogenesis, epithelial repopulation, and stemness. These effects are associated with activation of oxidative stress and DNA damage pathways, together with upregulation of RANKL, estrogen receptor and receptor tyrosine kinase signaling. This study is the first to identify ALDH2 deficiency as a novel factor associated with mammary epithelial alterations that may create a tissue state that could predispose to oncogenic transformation. Full article

Coke breeze, a solid waste generated during coke production, transportation and utilization, possesses physicochemical properties akin to metallurgical coke except for its finer particle size. Recycling this material offers an effective route to conserve and reuse coal resources, yielding notable environmental and economic benefits. In this study, a composite binder composed of phenolic resin (PR) and coal tar pitch (CTP) was developed for producing high-strength metallurgical coke substitutes from coke breeze. This strategy complementarily combines the excellent binding and curing properties of PR with the superior high-temperature carbonization performance of CTP. Thermal and structural analyses elucidated distinct pyrolysis characteristics and functional group distributions between the two binders, providing a theoretical foundation for their complementary interaction. Systematic investigations into briquette strength, performance, and microstructure established that the optimal composite binder dosage is 15 wt.% of coke breeze, with a CTP-to-PR mass ratio of 7:3. This complementary system substantially enhanced the compressive strength of the formed coke, reaching 37.73 MPa after carbonization at 1000 °C, and improved its thermal stability, as reflected by a Coke Strength after Reaction (CSR) of 41.21%. Compared to the individual binders, the composite binder exhibited superior consolidation efficiency and structural integrity, presenting a promising approach for solid waste valorization and sustainable coke production. Full article

Lumbricin, a classic proline-rich antimicrobial peptide (PrAMP), has been primarily characterized in terrestrial clitellates, with limited reports in other annelid lineages, leaving a critical knowledge gap regarding its presence and immune roles in marine invertebrates. The echiuran worm Urechis unicinctus lives in microbe-laden intertidal mudflats and depends on innate immunity against pathogens, yet its lumbricin homologs have remained unreported. In this study, we aimed to clone full-length lumbricin cDNA and systematically characterize its molecular traits, tissue distribution, LPS (lipopolysaccharide)-triggered transcription and in vitro antibacterial function. Sequence analysis showed the deduced 67-amino-acid U. unicinctus lumbricin contained 10.4% proline and lacked a signal peptide, retaining the conserved N-terminal cationic patch and C-terminal motifs of earthworm lumbricins. Phylogenetic analysis confirmed its close evolutionary linkage to Eisenia andrei lumbricin-related peptide. Quantitative PCR (qPCR) detected ubiquitous constitutive expression, peaking in the body wall, followed by the hindgut and midgut. LPS induced rapid 3 h upregulation in the body wall for acute local defense, with massive late-stage elevation at 48 h in the hindgut, anal sacs and coelomic fluid. Recombinant lumbricin exerted broad-spectrum growth-inhibitory effects against Gram-positive and Gram-negative bacteria. This study is the first to identify a functional lumbricin homolog in marine non-clitellate annelids (echiurans), which expands the taxonomic range of the lumbricin family and provides new insights into innate immune defense of marine benthic organisms. Full article