Abstract: Joint-embedding predictive architectures (JEPAs) learn representations by predicting embeddings rather than reconstructing observations, but isotropic Gaussian constraints leave their coordinates undetermined up to orthogonal rotation. We introduce the factorized autoregressive joint-embedding predictive architecture (FAR-JEPA), a decoder-free method that selects temporal factor axes by fitting a context-conditioned autoregressive law to each embedding coordinate. An invertible shared encoder preserves the latent state, while an auxiliary network predicts coordinate-wise means, innovation variances, and autoregressive coefficients without source labels or true process parameters. Within the orthogonal JEPA solution class, we show that the population factorized conditional score identifies source coordinates up to signed permutation provided that, for every factor pair, at least one retained-lag Jacobian or innovation-variance profile differs on a context set of positive probability. Equal process signatures retain rotations within their shared subspaces, and an under-specified autoregressive order fails when it hides all axis-selecting statistics. In the primary generic-flow comparison on controlled nonlinear mixtures, FAR-JEPA attains matched component correlations of $0.9965$ and $0.986$ under exact unit marginals and rich conditional modulation, respectively, versus $0.743$ and $0.692$ for a JEPA-flow control using the same flow backbone. In separate matched-inverse mechanism experiments, context shuffling, signature collapse, and omission of the sole informative lag remove the gain. These controlled results support factorized autoregressive process laws as a mechanism for converting a state-equivalent JEPA representation into temporally factor-aligned coordinates.

Abstract: Non-specific lipid transfer proteins (nsLTPs) are plant-specific proteins involved in lipid transport, cuticle formation, and responses to abiotic and biotic stresses. Here, we functionally characterized AtLTP12, a member of the nsLTP1 subfamily in Arabidopsis thaliana, using a T-DNA insertion knockout mutant. The atltp12 mutant exhibited reduced seed germination rates, increased leaf water loss, and enhanced sensitivity to salt, drought, osmotic, and oxidative stress. Additionally, the mutant plants also showed compromised basal resistance, while their response to inducing systemic acquired resistance remained unaffected. In vitro assays confirmed lipid-binding activity of recombinant AtLTP12, with a preference for phospholipids. Subcellular localization analysis indicated its targeting to the extracellular space. These results demonstrate that AtLTP12 positively regulates multi-stress tolerance through lipid homeostasis and ROS regulation and contributes to basal immune responses. AtLTP12, therefore, represents a potential target for improving stress-resilience in plants.

Abstract: Background: Left ventricular noncompaction (LVNC) is a myocardial abnormality char-acterized by prominent trabeculations, a thin compacted layer, and deep intertrabecular recesses. LVNC is a heterogeneous myocardial disorder of uncertain etiology, which may occur as a congenital or acquired condition or develop in association with other cardio-myopathies. Genetic factors have also been implicated in its pathogenesis. Objectives: The aim of this study was to investigate the genetic background of patients with LVNC through next-generation sequencing (NGS) analysis and to identify potentially dis-ease-associated variants. Methods: Twenty-five patients with LVNC underwent genetic testing by NGS using the Ion Torrent™ platform. Variants identified by NGS were con-firmed by Sanger sequencing. The interpretation was performed according to ACMG guidelines using multiple bioinformatic and clinical databases. Results: Genetic variants were identified in 13 patients, with 14 variants detected in 9 genes (TTN, MYH7, CTNNA3, DSG2, FLNC, JPH2, NKX2-6, TNNC1, and JUP). Eight variants (57%) were nov-el, four (29%) had been previously reported in clinical cases without scientific discussion, and two (14%) were already described in the literature. According to ACMG criteria, vari-ants were classified as pathogenic (n=1), likely pathogenic (n=7), or variants of uncertain significance (n=5). Conclusions: These findings highlight the marked genetic heterogenei-ty of LVNC and support the role of genetic testing in improving diagnosis, risk stratifica-tion and clinical management.

Abstract: This work is related to the extension of the well-known problem of Roman domination in graph theory to fuzzy graphs. A variety of approaches have been used to explore the concept of domination in fuzzy graphs. This study uses the concept of strong domination, considering the weights of the strong edges. We introduce the strong-neighbors Roman domination number of a fuzzy graph and establish some correlations with the Roman domination in graphs. The strong-neighbors Roman domination number is determined for specific fuzzy graphs, including complete and complete bipartite fuzzy graphs. Besides, several general bounds are given. In addition, we characterize the fuzzy graphs that reach the extreme values with particular attention to fuzzy strong cycles and paths.

Abstract: Evaluating multiple-object trackers is challenging due to the variable number of quantities involved and the mixed discrete--continuum nature of the problem. Existing methodologies primarily address detection and tracking challenges. These challenges aim at whole computer-vision pipelines as opposed to isolated tracker algorithms. However, modern tracker algorithms have become sufficiently sophisticated to merit a stand-alone analysis. The most critical component of a tracker is the association procedure, as its outcome strongly affects the overall tracking quality. We propose a straightforward quality assessment framework to evaluate the association quality of trackers. The framework relies on a minimal, query-oriented instrumentation of the tracker. This instrumentation exposes the tracker's internal association decisions, allowing for a binary classification of detection-target matches. The proposed methodology is simple to implement, introduces minimal computational overhead, and agrees with the well-known ClearMOT metrics. The comparison is implemented through our accompanying open-source software packages.

Abstract: Powder mixing is a critical step in pharmaceutical manufacturing, as the uniform distribution of an active pharmaceutical ingredient (API) affects the quality of the final dosage form. This study investigated the relationship between powder mixing performance and tablet quality attributes using sodium naproxen as a model API with limited flowability. Powder mixtures were prepared in a V-type blender, and the mixing index evolution was evaluated at different rotational speeds. Tablets were subsequently produced either by direct compression or by pan granulation followed by compression, and their critical quality attributes, including tablet mass, thickness, crushing strength, abrasiveness, and API content variability, were evaluated. The mixing index rapidly increased during blending and reached high values for all investigated conditions; however, similar mixing efficiency did not result in equivalent tablet properties. Directly compressed tablets exhibited higher crushing strength, lower abrasiveness, and lower API content variability compared with tablets obtained after pan granulation. The results demonstrated that the powder processing route had a stronger influence on final tablet performance than differences in mixing speed within the investigated range. The combination of mixing index evaluation with tablet quality assessment provides a comprehensive approach for understanding the influence of powder processing conditions on pharmaceutical tablet performance.

Abstract: This article presents a summary of recent theoretical investigations on the residence time distribution (RTD) of particles in laminar flow tubes, based on stochastic simulation of particles trajectories, and also a formerly unpublished comparison of the numerical simulation results with experimental data. The RTD depends on the flow velocity profile of the fluid. For the two extreme flow types, plug or uniform flow (UF) and fully developed or parabolic flow (PF), the RTD is a function of two dimensionless numbers: the particle diffusivity, D, and the tube aspect ratio, a. A third additional dimensionless variable, the Reynolds number, Re, should also be considered when the stationary fluid velocity profile gradually develops along the tube (steady transition flow, TF). The role of D can be split up into two contributions: one due to diffusion along the main fluid flow direction, the other to cross-stream diffusion; the first moment of the RTD depends on the product aD in the first case, but only on D in the second one. In the ideal case in which the fluid velocity is constant throughout the tube (plug flow) and particle axial diffusion is absent, the particle RTD coincides with that of the fluid. In any other circumstances the RTD of the particles shifts to smaller residence times in comparison with the RTD of the fluid: the mean particle residence time in the tube is smaller than that of the fluid. This surprising outcome is explained in terms of the particle survival probability, the mean particle radial coordinate and the mean axial displacement of the particles per unit time along the tube. In the last section of the paper, theoretical particle survival probability and residence time distribution are both favorably compared with the presently available experimental results.

Abstract: Microglia are key regulators of central nervous system homeostasis and neuroinflammation, with cannabinoid type 2 receptors (CB2Rs) proposed as important modulators of microglial phenotype and function. This study investigated the pharmacological properties of several CB2R ligands in resting BV2 microglial cells using [35S]GTPγS binding and forskolin-stimulated cAMP assays. Classical CB2R agonists (CP 55,940, WIN 55,212-2, JWH 133, and JWH 015), protean agonists ((R)-AM 1241 and GW 405833), and inverse agonists (SR144528, AM630, and JTE907) were evaluated. In the [35S]GTPγS assay, WIN 55,212-2 displayed the highest intrinsic activity, while protean agonists behaved as partial agonists and inverse agonists reduced basal CB2R signalling, indicating constitutive receptor activity. In contrast, cAMP measurements revealed greater signal amplification, with (R)-AM 1241 and GW 405833 acting as full agonists and SR144528 producing marked inverse agonism. These significant differences in ligand rank, order and efficacy between assays highlighted the influence of downstream signalling and ligand-dependent signalling bias. Notably, GW 405833 exhibited a strongly biased profile, whereas SR144528 showed the most pronounced inverse agonist properties. These findings demonstrate that CB2R ligands display distinct pharmacological behaviours in native resting microglia and suggest that constitutive receptor activity and signalling bias are important determinants of CB2R function. The results support further investigation of CB2R inverse agonists, particularly SR144528, as tools to explore microglial regulation across different neuroinflammatory and neurodegenerative disease states.

Abstract:

Background: Autistic children may follow a qualitatively different trajectory of motor development, with differences in timing, speed and movement accuracy often leading to compensatory strategies later in childhood. Delays in identifying motor difficulties can affect intervention and long-term quality of life. Advances in sensor technology now offer opportunities for seamless collection of movement data during play. Method: “TangiBall”, developed iteratively with autistic children, families and patient groups, and engineered by a university medical device department, is an interactive toy designed to assess motor function. The device consists of a multi-coloured hub with sensor-equipped faceplates and animal-headed insertion jacks that light up and provide auditory rewards when correctly inserted. The system records movement accuracy and speed. This pilot study aimed to: (1) identify motor signatures in pre-school autistic children during play; (2) assess toy acceptability through parent and clinician interviews; and (3) obtain parent and clinician ratings. Results: Five autistic children (mean age 3 years 5 months) and five control children (mean age 4 years) participated. Mean age difference could explain some of the variance. More than 100,000 data points of real-time movement were collected across 5–10-minute sessions. Autistic children showed less controlled insertion and removal movements, greater variability in motor performance, and reduced engagement with the toy. Parents and clinicians rated TangiBall positively. Conclusion: Findings suggest differences in motor control between autistic and non-autistic children. This pilot study presents descriptive findings from a small sample (n = 5 per group). As such, results should be interpreted as exploratory and hypothesis-generating.

Abstract: Exceptional points (EPs) offer new paradigms in non-Hermitian physics, but their realization has long relied on active gain-and-loss mechanisms. In our previous work, we established that clusters of innumerable EP loci can be achieved within purely real-parameter passive systems under single-fixed and semi-definite boundaries. However, extending this framework to double-ended boundaries introduces highly coupled transcendental boundary conditions, thereby increasing the complexity of the conventional exact tracking. This study addresses this challenge by considering a both-fixed two-degree-of-freedom (2DOF) passive system. Through rigorous algebraic proofs, we achieve an analytical mapping of the global coalescing trajectories, specifically encompassing the complex degenerate roots (loci of EPs) and real double roots (loci of critical damping points) within a purely real state-space via discrete boundary points. We demonstrate that the dual-boundary constraints fundamentally morph the topologies of the EP clusters, giving rise to novel localized phase transitions and critical damping loci. These exact analytical boundaries reveal that dual confinement acts not as a restriction but as an unprecedented design flexibility to precisely manipulate non-Hermitian singularities, even under purely real-parameter passive conditions. Our exact formulation provides a foundational theoretical framework that is potentially applicable to the environmentally robust passive tuning of next-generation device architectures, ranging from micro-scale electromechanical resonators to high-frequency communication components, offering a passive alternative to mitigate the instabilities inherent in conventional active non-Hermitian systems.

Abstract: Introduction: It is generally accepted that emotions are represented more in the right than in the left hemisphere and that temporal and frontal brain structures play a prominent role in functions of representation and of control of emotions. It is, however unclear if the right hemisphere prevalence concerns both the generation and the control of emotions. Aims of the study: In this study, I tried to clarify this problem by reviewing the emotional and behavioral disorders shown by patients with a right/left and a temporal/frontal variant of frontotemporal degeneration. Results: A strong prevalence of right-sided atrophy was found in patients with emotion comprehesion disorders, but different emotional comprehension defects were observed in patients with temporal and with frontal lesions. In the first case the defect mainly affected the ‘basic emotions’, whereas in patients with frontal atrophy the defect concerned more social and cognitive ‘complex emotions’. A weaker prevalence of right-sided atrophy was found in patients with emotional generation disorders (apathy and empathy) and in those with defects of emotional control (disinhibition). Discussion: This quantitative difference between results obtained on tasks of ‘emotional comprehension’ and of generation and control of emotions can de due to the fact that some of the latter behavioral disorders (such as ‘apathy’, ‘empathy’ and ‘disinhibition’) cannot be precisely defined and identified, because they can be considered as ‘umbrella terms’, covering behavioral domains larger than those allowed by a strict definition of emotions.

Abstract: The P versus NP problem is a cornerstone of theoretical computer science: it asks whether every problem whose solution can be checked quickly can also be solved quickly. Here, “quickly” means in polynomial time, where the running time grows as a fixed power of the input size. The question traces back to John Nash’s 1955 letter to the National Security Agency, and was later formalized by Stephen Cook and Leonid Levin. Despite decades of research, it remains open. At the heart of the problem lies the notion of NP-completeness: if any single NP-complete problem, such as SAT, admitted a polynomial-time algorithm, then every problem in NP would, proving P = NP. This paper presents such an algorithm for SAT, thereby establishing that P equals NP.

Abstract: Antibiotic-, biocide-, and metal-resistance genes co-occur in the genomes of multidrug-resistant bacteria. This relationship is more complex than mere physical co-localization. Instead, it arises from co-selection pressures that favor co-regulation and co-resistance. The genomic basis of this co-occurrence remains unclear. Our studies on the co-occurrence of Cu(I)-ATPases with other metal-extrusion systems in the Methylobacterium extorquens AM1 genome revealed 3 Multimetal Homeostasis Gene Clusters (MHGCs) presumed to confer resistance to Cu/Ni/Co/Zn/Cd/Pb. In this study, we identified a more complex co-occurrence of Cu(I)-ATPases in the pathogen Brucella anthropi ATCC 49188. It comprises five collinear gene clusters (CGCs) spanning 48.5 kb and involved in multimetal and redox homeostasis, conjugation, and the transport of miscellaneous molecules. Highly homologous clusters were found in 43 strains across 3 alpha-proteobacterial orders, isolated from diverse habitats in different countries. Despite these geographical differences and phylogenetic distances, most orthologous genes remain syntenic. This arrangement of genes was named a Collinear Synteny Block (CSB). In some species, these CSBs reside within a ~110-kb genomic island, which explains their widespread occurrence. The CSB co-occurs with potential antibiotic-resistant genes scattered across the same replicon. This study will advance our understanding of the organization, evolution, and dispersal of resistance genes in bacteria.

Abstract: This article examines a women-led Jewish–Arab dialogue initiative in the Western Galilee and advances the concept of relational capacity as a mechanism of grassroots peacebuilding in protracted asymmetrical conflict. Drawing on qualitative interviews with twenty-one participants and supplementary descriptive survey data from an additional cohort, the study integrates intergroup contact theory, feminist peace scholarship, and everyday peace frameworks to analyse how sustained dialogue generates relational endurance rather than ideological convergence. The findings suggest that participants develop the capacity to maintain cross-community engagement during periods of political tension, translating interpersonal trust into forms of civic agency. Transnational exposure through a delegation visit further amplifies symbolic legitimacy and internal cohesion. Rather than conceptualising reconciliation as attitudinal harmony, the article proposes that grassroots peacebuilding operates as a layered relational process across micro, meso, and transnational levels. The study contributes a transferable analytical framework for examining women-led dialogue initiatives in other protracted conflicts.

Abstract: The integration of artificial intelligence (AI) into health systems requires instruments capable of diagnosing student performance beyond global scores, explaining why a failure occurs and how to remediate it, without delegating decisions to opaque algorithms. This study, guided by Design Science Research, presents the design and specification of the LIPS platform (Integrated Laboratory of Simulated Practices), a closed-loop, seven-layer sociotechnical architecture for the granular assessment of competencies in health professions education. The architecture decomposes clinical activities into observable micro-skills, paired with assessment items through a Q-matrix, and isolates the deterministic computation of scores from interpretation by generative AI, restricted to the formulation of explanatory hypotheses linked to evidence and submitted to instructor validation (human-in-the-loop). The demonstration applied the method to an illustrative airway suctioning scenario: the decomposition generated ten micro-skills and twenty items fully linked through the Q-matrix, and the diagnostic pathway showed how a global performance of 90% would mask a critical safety failure localized in a specific micro-skill. The formative evaluation is presented as a structured protocol, prior to application with human participants. The central contribution lies in the method for granularity of competencies and for containment of generative AI, transferable to other health professions education systems.

Abstract: Ecuador experienced one of the fastest escalations of lethal violence in Latin America, with the intentional homicide rate rising from 7.8 per 100,000 inhabitants in 2020 to 47.25 in 2023. This study develops a replicable, algorithm-selection framework for forecasting the temporal evolution of four key patterns of intentional homicide (monthly case volume, firearm share, mean victim age, and geographic concentration in the province of Guayas) using official open data comprising 24,000+ incident records (January 2020–December 2024). Individual incidents were aggregated into monthly time series, and three forecasting algorithms with distinct inductive biases (SARIMA, Prophet, and Holt–Winters exponential smoothing) were compared under an out-of-sample protocol that reserves the 12 months of 2024 as a test set, using MAE, RMSE, and MAPE. No single algorithm dominated: SARIMA was the most accurate for the volume and geographic series, Holt–Winters for the firearm-share series (MAPE 2.85%), and Prophet for the volatile mean-age series (MAPE 5.73%). Re-trained on the full sample, the selected models project a five-year horizon (2025–2029) in which homicides stabilize at historically high levels, roughly four times the 2020 baseline, with firearm involvement consolidating above 85% and violence remaining concentrated in Guayas. The results support pattern-specific algorithm selection for criminological forecasting and provide a quantitative baseline for security policy evaluation in Ecuador.

Abstract: This study presents a data-driven Digital Twin framework designed to optimize closed-loop Adaptive Cruise Control (ACC) operational parameters for eco-driving without modifying electronic control unit (ECU) firmware. High-frequency telematics data (OBD-II and GPS) were recorded from a production vehicle over an 11.57 km test corridor to engineer and calibrate a virtual Digital Twin in PTV Vissim using Wiedemann 99 car-following logic. The validated model demonstrated high empirical fidelity, achieving a mean velocity error of 2.84 km/h, a GEH statistic of 2.67, and an absolute fuel consumption variance of just 0.01 L/100 km. An iterative parametric optimization (~100 simulation runs) was executed to tune acceleration limits, convergence time constants, and target velocity bounds while maintaining strict safety constraints. The optimized Eco configuration achieved a 12% reduction in fuel consumption (4.91 to 4.33 L/100 km) alongside a 14% increase in trip duration (893 to 1019 s). Bivariate state-space analysis confirmed the complete elimination of high-intensity accelerations and a 0.48 percentage point reduction in hard braking. The framework serves as an algorithmic decision support tool for energy-aware fleet management and adaptive vehicle control.

Abstract: Three-flavor oscillation theory parametrizes neutrino mixing and mass-squared splittings but does not explain the observed PMNS orientation or the absolute mass spectrum. This paper develops a structural reconstruction of both within a proposed neutral-parent carrier-closure framework. The construction distinguishes a premetric selection layer from the effective field theory that governs dynamics after spacetime read-out. At the premetric layer, automorphism-inequivalent admissible branches receive equal primitive weight; their multiplicities select a tribimaximal leading frame, while previously derived charged-lepton root ratios determine two controlled deformations. For the mass sector, a linear exposure map sends three neutral continuation modes to a two-dimensional transverse closure quotient. Under explicit assumptions of strict factorization, protection covariance, and transverse saturation, the associated positive mass-squared operator has rank two and one exactly massless eigenstate. A minimal two-seam complex then fixes the two nonzero eigenvalues. The resulting normal-ordering spectrum is m₁ = 0, m₂ = 8.686 meV, and m₃ = 50.092 meV, with a mass sum of 58.778 meV and mass-squared splittings close to current global-fit values. No measured neutrino angle, phase, splitting, or absolute mass is inserted into the structural formulas; the measured electron mass only converts dimensionless ratios to electronvolts. The construction supplies spectral boundary data that a post-read-out Lagrangian theory must reproduce rather than replacing standard quantum field theory. Present numerical agreement is retrospective; the frozen rank, spectrum, and mixing correlations provide prospective tests.

Abstract: Kounis syndrome (KS) is an increasingly recognized cause of acute coronary syndromes triggered by allergic or hypersensitivity reactions. The syndrome results from a complex interplay between mast-cell degranulation and platelet activation during allergic reactions, leading to the release of vasoactive, pro-inflammatory and prothrombotic mediators. These mechanisms may induce coronary vasospasm (type I KS) or thrombosis of plaque (type II KS), stent (type III KS) or coronary artery bypass graft (type IV KS). KS remains largely underdiagnosed in routine clinical practice, with significant gaps in epidemiology, diagnosis and management. This narrative review critically appraises current evidence, integrating historical perspectives with contemporary insights into classification, pathophysiology, triggers, diagnostic strategies and thera-peutic approaches, focusing on the most frequent manifestation represented by vasospastic variant. Despite increasing recognition over the past three decades, its true pathophysiological mechanisms, diagnostic boundaries, and therapeutic implications remain incompletely understood. Available data indicate that angiographically documented epicardial coronary spasm is observed in only a minority of patients, while normal or non-obstructive coronary arteries are frequently encountered. Emerging evidence from provocative testing, coronary physiology assessment, cardiac magnetic resonance and nuclear imaging suggests that coronary microvascular dysfunction may contribute substantially to the clinical phenotype, expanding the traditional concept of allergic epicardial vasospasm. A comprehensive diagnostic approach, including signs, symptoms, biochemical findings, electrocardiography, echocardiography, coronary angiography, and multimodality imaging including invasive assessment in selected cased, can be recommended, although its implementation in routine practice remains limited. Current evidence supports the recognition of type I KS as a distinct allergic vasomotor acute coronary syndrome within the myocardial infarction non-obstructive cor-onary artery (MINOCA) spectrum, deserving greater recognition in future diagnostic classifications and clinical practice guidelines.

Abstract: Quantum field theory in curved spacetime allows time-dependent gravitational backgrounds to generate field excitations, while semiclassical gravity feeds the renormalized stress-energy expectation value back into the geometry. This suggests a logically possible feedback loop: a geometric perturbation modifies quantum matter, the resulting stress response perturbs the geometry, and the combined response may either decay or amplify. The purpose of this paper is not to assume that such a loop is unstable, nor to identify it a priori with the Big Bang, but to formulate a minimal mathematical closure in which the stability question can be answered exactly. Starting from the semiclassical Einstein equation and the linear-response form of the stress tensor, we introduce two signed perturbation variables: a coarse-grained curvature amplitude and a matter-stress response. A local Markovian closure leads to a coupled reaction–diffusion system with four linear response coefficients. Its dimensionless feedback gain is \[ G=\frac{bc}{ad}. \] For a bounded connected spatial domain with homogeneous Neumann boundary conditions, we prove from the spectral and energy formulations that the linear system is exponentially stable when \(G< 1\), has a neutral homogeneous mode at \(G=1\), and possesses a genuinely growing homogeneous mode when \(G>1\). No instability is therefore postulated: it occurs if and only if the positive cross-response exceeds the product of the two intrinsic damping rates. We then examine a nonlinear homogeneous reduction with cubic geometric saturation. We prove global existence, boundedness, global exponential attraction of the vacuum branch for \(G< 1\), and the appearance of two locally asymptotically stable nonzero branches for \(G>1\), constituting a supercritical pitchfork in the signed perturbation variables. The resulting framework distinguishes three notions that are often conflated: gravitational particle production, semiclassical backreaction, and self-amplifying curvature–matter feedback. The analysis also shows why a Big-Bang singularity does not follow from feedback alone: the minimal unstable closure produces exponential growth, while nonlinear saturation can instead generate a bounded high-curvature phase. The model is therefore proposed as a mathematically controlled metaframework for testing curvature--matter feedback mechanisms, not as a completed theory of quantum gravity.