Search Results (19,746)

Biaxial contouring systems are widely used in planar precision motion applications, where the assigned feedrate profile strongly affects motion smoothness, contour-following accuracy, and robustness during servo execution. However, many existing studies mainly focus on either controller-side contour-error regulation or planning-layer time optimality, while the influence of jerk-sensitive feedrate transitions on downstream contouring behavior is still insufficiently examined. To address this issue, this paper proposes a jerk-constrained and execution-aware feedrate scheduling framework for biaxial contouring systems. Starting from the admissible feedrate boundary determined by contour geometry and motion constraints, an acceleration-feasible baseline schedule is first generated through bidirectional reachability propagation. Then, jerk-oriented smoothness refinement and critical-region-preserving correction are introduced to suppress abrupt local transitions while maintaining dynamic admissibility and practical traversal efficiency. The refined path-domain schedule is further reconstructed into time-domain axis-level references for closed-loop contouring evaluation. A planning-to-execution simulation study is conducted on three representative contours, including a rounded triangular contour, an elliptical contour, and a butterfly-cross contour. The proposed method is compared with several baseline scheduling strategies under nominal, low-bandwidth, flexible-resonance, and parameter-mismatch conditions. The simulation results indicate that the proposed scheduler can reduce concentrated jerk responses and resonance-sensitive high-frequency excitation while achieving a more balanced tradeoff among traversal time, contouring accuracy, and robustness. The results also show that the benefit of the proposed method becomes more evident for geometrically complex contours and deteriorated servo conditions. The present study provides simulation-based evidence that execution-aware feedrate scheduling is an effective way to improve biaxial contouring performance without redesigning the low-level servo controller. Full article

The interaction of corneal keratocytes with biochemical (e.g., composition, growth factors) and biophysical (e.g., topography) cues present in the cornea regulates their morphology during normal homeostasis and wound healing. In this study, we developed a novel method of fabricating substrates with micropatterns of Type I aligned collagen fibrils in a 6-well format that allowed for time-lapse imaging of dynamic changes in keratocyte morphology. Culturing keratocytes on aligned collagen fibrils in the presence of platelet-derived growth factor BB (PDGF-BB) allowed us to characterize the dynamics of cell alignment and migration. To investigate the roles of topography and protein composition on the dynamic features of cell spreading, cell protrusions, and cell motility, we cultured keratocytes on either hydrophobic-coated glass, aligned collagen fibrils, or monomeric collagen with or without a fibronectin coating. The presence of a fibronectin coating delayed the formation of cell protrusions during spreading on all of the substrates tested (e.g., Aquasil-coated glass, monomeric collagen, aligned collagen fibrils), while the presence of aligned collagen fibrils resulted in a ~2-fold reduction in the cell spreading area. The experimental platform developed here allows for parallel experiments and real-time imaging and thus providing a valuable new tool to study the dynamic activity and cell–substrate interactions of corneal keratocytes. This approach will allow for systematic screening of the response of keratocytes and other cell types (e.g., tenocytes, cardiomyocytes, cancer cells) that normally are exposed to aligned collagen topographies. Full article

Bone regeneration is governed by a tightly coordinated interplay between skeletal cells, immune cells, vascular components, and signaling networks within a dynamic microenvironment. Increasing evidence from osteoimmunology demonstrates that immune regulation is not merely supportive but mechanistically determinative of regenerative outcomes. Dysregulated or persistent inflammation can impair osteogenesis, whereas timely immune resolution promotes angiogenesis and matrix deposition. In this context, nanotechnology has enabled the development of nanoparticles (NPs) that function not only as delivery vehicles but also as active modulators of the bone immune microenvironment. Immunomodulatory NPs can be engineered to deliver bioactive agents, regulate cytokine networks, and influence immune cell phenotypes, particularly macrophage polarization, at defined stages of healing. Through tailored surface chemistry, targeting ligands, and stimuli-responsive release mechanisms, NPs can achieve spatially localized and temporally controlled modulation of inflammatory and reparative phases, thereby enhancing osteogenesis and vascular integration. This review provides a comprehensive overview of organic, inorganic, and hybrid NP platforms applied to bone regeneration, with emphasis on their mechanisms of immune modulation, strategies for cell-specific targeting, and approaches for sequential regulation of inflammatory resolution and tissue repair. By integrating advances in materials science and immunology, NP-enabled platforms have the potential to transform bone regeneration from passive structural repair into precision immune-guided healing. Full article

Large language models (LLMs) are undergoing a paradigm shift from fast generation to deliberate System-2 reasoning, where scaling test-time compute is critical for unlocking complex reasoning capabilities. Yet, more computation does not guarantee better reasoning: under unconstrained test-time scaling, models frequently fall into “overthinking” traps, repeatedly elaborating on incorrect trajectories while wasting token budgets. We propose Dynamic Closed-Loop Steering, a training-free framework that treats reasoning as a monitored control process rather than a static decoding run. The framework follows a sense–decide–act design: lightweight latent signals sense trajectory divergence, a feedback regulator determines adaptive intervention timing and intensity, and a geometry-preserving actuation step redirects hidden states while maintaining their norm structure. This design emphasizes adaptive control and macro-level trajectory observability over static hidden-state addition. Across mathematical and reasoning benchmarks, Dynamic Closed-Loop Steering improves final-answer accuracy while curbing excess token consumption, yielding Pareto-favorable trade-offs across the large majority of evaluated configurations, with graceful degradation near the model’s capability floor. Trajectory analysis confirms the method effectively suppresses repetitive self-justification and accelerates recovery from erroneous episodes. These results establish closed-loop, geometry-preserving intervention as a practical foundation for robust System-2 reasoning. Full article

Background/Objectives: People aging with HIV (PAWHs) face distinct health challenges, including early onset of aging and heightened risk for chronic comorbidities despite effective antiretroviral therapy (ART). However, significant gaps persist in understanding the lived experience and how PAWHs perceive the interplay between their controlled HIV and the aging process. This study examined PAWHs’ illness perceptions of aging, health, and relationship of HIV to other health conditions. Methods: Semi-structured interviews were conducted with a convenience sample of 25 PAWHs (mean age 63.5; mean time living with HIV 22.3 years; 24 virally suppressed) recruited through an academic HIV specialty clinic. Demographic and clinical data were collected from Electronic Health Records (EHRs), and interviews were analyzed using inductive thematic analysis. Results: A central finding was the disconnect between participants’ illness perceptions of controlled HIV and other aging-related health concerns. Absence of acute somatic symptoms and sustained viral suppression fostered a view of HIV as chronologically remote, leading to an apparent unawareness of HIV’s systemic links to accelerated aging and comorbidities. Two primary themes around aging emerged: acceptance/disengagement and fear of future debility (prevalent among older, socially isolated individuals concerned about dementia and finances). Conclusions: This pervasive disconnect, understandable through the lens of the Common Sense Model of Self-Regulation, highlights a critical need to adjust health counseling strategies for PAWHs. Clinicians can leverage existing trusted provider relationships to explicitly address and refine PAWHs’ illness models, clarifying that viral suppression is not a cure and educating on HIV’s systemic links to chronic conditions (e.g., ‘inflammaging’). Tailored educational interventions are crucial for fostering shared decision-making, encouraging early screening, and improving health outcomes for this vulnerable and growing population. Generalizability may be limited by sample characteristics. Full article

In large-scale fluid transport systems, distributed pump and valve stations must coordinate their operations to prevent overpressure while minimizing energy use and control effort. This paper presents a communication-aware, game-theoretic coordination framework in which stations act as rational agents that iteratively adjust operating setpoints based on locally computed utilities. Existing station-level pressure controllers regulate local pressures and flows, while a slower supervisory negotiation layer governs inter-station coordination using steady-state hydraulic surrogates derived from pump affinity laws and pipeline loss relationships. The proposed framework does not rely on centralized optimization or exhaustive enumeration of strategies. Instead, stations update setpoints sequentially, evaluating incremental changes in utility to determine beneficial adjustments and detect equilibrium conditions. Cooperative behavior emerges naturally when communication is available, enabling stations to internalize the hydraulic impact of their actions on neighboring stations. When communication is lost, the system transitions seamlessly to a non-cooperative mode in which each station optimizes its local objective while maintaining safe operation. Simulation studies conducted on a multi-station pipeline with mixed actuator types demonstrate measurable performance improvements over fixed-setpoint operation. Cooperative coordination reduces total system energy usage from 39.6 MW to 38.8 MW while increasing average control valve openness from 60.4% to 63.7%. Non-cooperative operation converges more rapidly but results in higher energy consumption (39.2 MW) and greater valve throttling. Under partial communication loss, the system preserves near-cooperative energy performance (38.8 MW) with a modest increase in convergence time, demonstrating robustness to degraded communication. Across all simulated scenarios, the iterative game converged to stationary operating points consistent with Nash-equilibrium behavior in non-cooperative settings and Pareto-stationary solutions in cooperative communication settings. Full article

Human fertility has declined sharply since 1950, and a growing body of evidence suggests that while conventional socioeconomic factors are well-established drivers of the broader demographic transition, they do not fully account for the timing and breadth of this trend. This review examines the Circadian-Light-Hygiene hypothesis, which proposes that daily light exposure is a fundamental regulator of reproductive health. We synthesize findings from photobiology, endocrinology, reproductive medicine, and epidemiology to evaluate how artificial light at night, insufficient daytime light, and irregular light–dark patterns may disrupt the hormonal timing systems that support reproduction. The available evidence indicates that such disruption can alter melatonin signaling, circadian gene regulation, and neuroendocrine rhythms, with downstream effects on ovulation, sperm quality, endometriosis, polycystic ovary syndrome, pregnancy outcomes, and developmental programming. Urbanization, screen use, and shift work appear to amplify these effects, while genetic variation may modify individual susceptibility. Although direct causal evidence in humans remains limited for several endpoints, the convergence of observational, experimental, and translational data supports circadian-light misalignment as a plausible, additional modulator of fertility decline, and a potentially modifiable contributor. Optimizing daily light exposure may therefore represent a low-cost and scalable strategy for improving reproductive health. Full article

Central tolerance is provided by the autoimmune regulator (AIRE) expressing medullary thymic epithelial cells through high-avidity recognition of self-antigens. Peripheral mechanisms regulate adaptive immunity by deleting autoreactive T-cells that escape thymic selection, or by inducing their functional unresponsiveness through interaction with antigen-presenting cells, exposing cognate antigens. Multiple types of extrathymic AIRE-expressing cells residing in secondary lymphoid organs have been consistently described. We investigated whether AIRE binds to promoters of known autoantigens in human peripheral blood mononuclear cells by chromatin immunoprecipitation from four healthy donors using an anti-AIRE monoclonal antibody. Quantitative real-time PCR was used to detect AIRE occupancy at promoters of selected autoantigens. Accordingly, we revealed promoter amplicons of all tested autoantigen genes, and their corresponding transcripts. Expression of AIRE was further confirmed at both transcriptional and protein levels. Overall, although the role of AIRE in regulating autoantigen expression in thymic epithelial cells has been well reported, our study provides preliminary descriptive evidence of AIRE occupancy at promoters of known autoantigens in human bulk peripheral blood mononuclear cells, suggesting the presence of AIRE-mediated regulatory events in peripheral blood. Our data provide a rationale for future investigations aimed at elucidating the underlying molecular and immunological mechanisms. Full article

This study analyzes the combined effects of non-Newtonian rheology and electrostatics on the transient electroosmotic flow of Maxwell fluids in soft channels. The walls of the rigid channels are hydrophobic, ionically charged, and coated with a polyelectrolyte layer (PEL). This design is intended to regulate both the surface electric potential and the flow velocity. The mathematical model is based on modified Poisson–Boltzmann and momentum equations, which are solved numerically using a one-dimensional (1D) approach. The results indicate that high potentials, exceeding the Debye–Hückel limit, are achieved under conditions of thick polyelectrolyte layers, high surface charge density, and a higher concentration of fixed charges compared to the electrolyte ionic concentration. In this regime, steric effects increase the electric potential; however, this potential increase is limited by the formation of a Donnan potential. The hydrodynamic analysis demonstrates that the velocity magnitude is influenced not only by the wall potential but also by the spatial distribution of free charge density and electroosmotic force, which, in turn, are affected by steric effects. Additionally, changing the polarity and concentration of fixed charge in the PEL produces asymmetric flows, and while hydrodynamic slip enhances velocity, the drag parameter reduces it. Finally, the dimensionless parameters that control the time required to dampen the oscillatory flow induced by viscoelastic effects and reach steady-state are mainly the relaxation time, the drag parameter, the PEL thickness, and the electrokinetic parameter of the PEL, while the surface charge density and the external pressure gradient exert a comparatively minor influence. Full article

Glycogen synthase kinase 3 (GSK3/Shaggy-like) belongs to evolutionarily conserved serine/threonine protein kinases that regulate plant morphological development, multi-hormone crosstalk and adaptation to abiotic stresses. However, systematic genome-wide characterization of CmGSK3 is still absent in melon (Cucumis melo L.). This study identified six CmGSK3 members on a whole-genome level, unevenly distributed among four chromosomes. Combined phylogenetic and synteny profiling separated these six genes into four conserved subclades; orthologous links were discovered between melon, Arabidopsis, and rice, revealing evolutionary conservation between monocot and dicot crops. Prediction of promoter cis-regulatory motifs combined with transcriptome datasets suggested that CmGSK3 genes participate in hormone transduction and environmental stress adaptation. Quantitative real-time PCR further verified that exogenous brassinosteroid (BR) application dramatically induced transcriptional accumulation of CmSK21 and CmSK22. Heterologous overexpression of these two genes in wild-type Arabidopsis significantly lowered plant sensitivity to BR, confirming they may function as negative modulators of the BR signaling cascade. Collectively, CmGSK3 members coordinate multiple metabolic routes, dominated by BR-related signal transduction, to manipulate melon growth and stress adaptability. This study establishes the first systematic research on the melon GSK3 family and supplies elite candidate genes for molecular breeding targeting fruit quality and stress resistance improvement in melon. Full article

In this paper we implement robust switching model predictive control to solve the dual control problem of simultaneous regulation and system identification, for linear time varying systems subject to bounded external disturbances and confined instances of variation. We leverage the piece-wise linear control law resulting from a fictitious switching architecture to generate closed-loop data that ensures strong system identifiability, while guaranteeing stability and constraint satisfaction under unknown—but bounded—disturbances and parameter variation. We pair the switching controller with a standard recursive estimation algorithm with forgetting factor, which yields unbiased estimates with variance associated to the external disturbance, showcasing the success of the switching at producing information in the closed-loop trajectories. Full article

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, leading to multi-organ dysfunction. Toll-like receptor signaling via MYD88- and TRIF-dependent pathways plays a central role in this process; however, its temporal and tissue-specific dynamics remain incompletely understood. The aim of this study was to investigate time-dependent transcriptional changes in MYD88- and TRIF-dependent signaling pathways across multiple organs in a murine model of sepsis. mRNA expression of MYD88, IRAK1, IRAK4, NF-kB, CCL4, CCL20, CCR2, IFN-β, IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-18, Klotho, KLF4, HOXA5, NANOG and HIF1α was quantified using qRT-PCR in intestinal, kidney, liver and lung tissues at 24, 48, and 72 h following cecal ligation and puncture-induced sepsis in male C57BL/6J mice. Significant upregulation of innate immune signaling molecules, cytokines, chemokines, and interferon-related genes was observed in all tissues compared with controls. Genes associated with hypoxia and cellular regulation were also increased. These responses were tissue-specific and progressively intensified over time. Sepsis represents a dynamic, time-dependent, and tissue-specific process characterized by sustained activation of immune and hypoxic pathways, providing potential targets for time-stratified therapeutic strategies. Full article

Bolting time is a pivotal agronomic trait that determines the yield and commercial quality of Brassica rapa ssp. chinensis var. utilis. To investigate the molecular basis of early bolting, an early-bolting line ‘m662’ and a late-bolting line ‘t151’ were used in this study. Phenotypic evaluation combined with shoot apical meristem (SAM) observation showed that 10 days of low-temperature vernalization markedly accelerated bolting in ‘t151’. Subsequently, SAM samples from ‘m662’, non-vernalized ‘t151’, and 10-day vernalized ‘V10-t151’ were collected at five developmental stages (7, 10, 13, 16, and 19 d after transplanting) for transcriptome sequencing. Weighted gene co-expression network analysis revealed that key module genes related to gibberellin signaling were specifically enriched in ‘m662’ before bolting, whereas those in the middle and late bolting stages were enriched in hormone response, cell cycle regulation, and floral organ development. In ‘t151’, hub genes detected at 7–13 d included three paralogs of the floral integrator gene SOC1 and BraA06.FPF1. BrSOC1 (BraA03g024230.4C) was significantly upregulated in response to vernalization. DEGs identified during the late developmental stage (16–19 d) included genes involved in transmembrane transport processes, flower development, reproductive shoot system development. Expression analysis across the three materials showed that vernalization accelerated bolting in ‘t151’ by repressing BrFLC expression and promoting BrSOC1 expression. This study elucidates the dynamic transcriptomic network underlying early bolting in non-heading Chinese cabbage, providing key functional genes and mechanistic insights for bolting regulation and molecular breeding. Full article

Glioblastoma multiforme (GBM) remains one of the most aggressive primary brain tumors with poor prognosis despite multimodal therapy. Photodynamic therapy (PDT) using indocyanine green (ICG) is an emerging adjuvant approach aimed at eliminating residual tumor cells after resection. While ICG-PDT exerts cytotoxic effects, its impact on molecular pathways regulating programmed cell death in glioma cells is not fully understood. In this study, T98G and U-118MG glioblastoma cells were divided into four groups: untreated control, light-only (10 min broadband irradiation), ICG-only (15 min incubation), and ICG-PDT (15 min ICG + 10 min broadband irradiation). Relative mRNA expression of apoptosis-related genes (BAX, BCL2, CASP3, FAS) and ferroptosis-related genes (GPX4, ACSL4, SLC7A11, GCH1) was quantified 24 h post-treatment by RT-qPCR using the 2^−ΔΔCt method. ICG-PDT significantly reduced cell viability to 67.79% ± 3.39% (vs. 86.66% ± 4.33% in control), confirming effective phototoxicity. No statistically significant differences in mRNA levels were observed for any of the investigated genes across the groups (one-way ANOVA and Kruskal–Wallis, all p > 0.05). The largest non-significant deviation was a mild decrease in GPX4 (fold change 0.87) in the ICG-PDT group. Fluctuations in GCH1 were accompanied by high variance, likely reflecting technical noise rather than a true biological trend. The mRNA BAX/BCL2 ratio remained stable (~30) across all conditions. In contrast, the U-118MG line showed greater transcriptional sensitivity, with statistically significant decreases in CASP3 (p = 0.012) and ACSL4 (p = 0.031) expression, along with downward trends in BCL2 and GPX4 following ICG-PDT. ICG-PDT does not induce significant transcriptional changes in the analyzed genes T98G at the 24 h time point under the applied experimental conditions. In U-118MG cells, moderate transcriptional engagement of both apoptotic and ferroptotic routes was observed. Further studies at the protein and functional levels, across multiple time points and models, are warranted to fully elucidate the mechanisms of ICG-PDT in glioblastoma. Full article

Craniosynostosis is a congenital bone developmental condition characterized by the premature ossification of calvarial sutures, leading to restricted skull expansion and potential neurological complications. Although little is known about the signaling that governs this accelerated fusion, our research group has previously identified a stiffness-dependent upregulation of osteogenic genes in cells derived from fused sutures, highlighting the role of mechanotransduction in disease progression. Building on these findings, the present study describes the development of a unique patient-derived three-dimensional (3D) tissue-engineering (TE) model of non-syndromic craniosynostosis (NS-CS) to investigate how extracellular matrix (ECM) composition and biochemical cues regulate ossification timing and patterns. Cells isolated from clinically relevant tissues, surgically obtained from patent and prematurely fused calvarial sutures of pediatric NS-CS patients, were characterized and cultured under both two-dimensional (2D) and 3D suture-mimicking conditions. Comparative analysis revealed differences in cellular responsiveness between cells isolated from fused and patent sutures across the different experimental conditions, with cells from fused sutures consistently exhibiting higher expression of osteogenic markers. Notably, the elevated expression of osteogenic and chondrogenic markers suggested the possible involvement of endochondral-like ossification mechanisms during the pathological process of suture fusion. This patient-derived model was designed to recapitulate biophysical and biochemical features of the extracellular matrix of healthy and pathological sutures, serving as a tool for future research, helping us to understand the underlying mechanisms behind the pathophysiology of craniosynostosis. Full article