Feedback Loop Research Articles

Evaluating for learning and sustainability (ELS) framework: a realist synthesis

BackgroundLearning Health Systems (LHS), in which continuous and equitable improvements support optimization of healthcare practices, outcomes, experience, and costs, offer enormous potential for health system transformation. Within the LHS model, evaluation of health innovations assists in question identification, data collection, and targeted action, which facilitates continuous improvement. Evaluation that catalyzes learning may contribute to health innovation implementation, refinement, and sustainability, however, there is little consensus as to why certain evaluations support learning, while others impede it.MethodsEmbedded in the implementation science literature, we conducted a realist synthesis to understand evaluative contextual factors and underlying mechanisms that best support health system learning and sustainable implementation of innovations. We sought to understand whether evaluations can ‘work’ to support learning and sustainability, in which contexts, for whom, and why. Working with an Expert Committee comprised of leaders in evaluation, innovation, sustainability, and realist methodology, we followed a five-stage process of: 1. Scoping the Review, 2. Building Theories, 3. Identifying the Evidence, 4. Evidence Selection and Appraisal, and 5. Data Extraction and Synthesis. Our Review Team and Expert Committee participated in iterative cycles of results interpretation and feedback.ResultsOur synthesis includes 60 articles capturing the mechanisms and contextual factors driving learning and sustainability through evaluation. We found that evaluations that support learning and sustainability incorporate favourable organizational preconditions and focus on implementing rapid cyclical feedback loops that contribute to a culture of innovation and evaluation sustainability. Our findings have been organized into 6 Context-Mechanism-Outcome Configurations (CMOCs): 1. Embracing Risk & Failure; 2. Increasing Capacity for Evaluation; 3. Co-Producing Evaluation; 4. Implementing Learning Feedback Loops; 5. Creating Sustainability Culture; and 6. Becoming a Learning Organization. We have also translated findings into a series of Action Strategies for evaluation implementation to support health systems learning and sustainability.ConclusionsWe identified key contextual factors and underlying mechanisms that make evaluations ‘work’ (or ‘not work’) to support learning and sustainability. Findings support the operationalization of LHS by translating CMOCs into Action Strategies for those tasked with completing evaluations with a view toward health system learning and innovation sustainability.

Electro-acoustic control of radiation impedance for brass instrument timbre shaping: design of a vocalizing mute.

The application of active control to musical instruments brings many benefits to composers and performers, by expanding their sound possibilities. This paper addresses the active control of a brass instrument to design a vocalizing mute. To this end, a sensor (pressure transducer) and an actuator (loudspeaker) with a feedback loop are placed at the bell extremity. A single-input single-output controller is designed to simulate the insertion of a flow-to-flow vocal filter, upstream of the natural radiation impedance load. The vocal transfer function with its target resonances is basically derived using the transfer matrix method for a vocal tract composed of concatenated acoustic cylinders. The loudspeaker model is based on the Thiele and Small description. Numerical experiments are presented on the controller, for a simplified trombone model that admits a Kelly-Lochbaum structure (mouthpiece, bore, bell and radiation are cascaded using the transfer matrix method). Finally, the sensitivity of the control to air temperature, bell opening angle and loudspeakers parameters is studied.

Hyaluronidase-1 mediates postprandial suppression of hepatic gluconeogenesis

Abstract Hepatic gluconeogenesis is a critical process that generates glucose from non-carbohydrate precursors during fasting to support vital organs like the brain and red blood cells. Postprandially, this process is rapidly suppressed to allow for glucose storage as glycogen and lipids in the liver. Failure to suppress gluconeogenesis after meals leads to elevated postprandial glucose levels, a key feature of type 2 diabetes. This dynamic switch is regulated by insulin and glucagon, but insulin resistance impairs this regulation. In this study, we identified a novel mechanism involving postprandial circulating hyaluronan (HA) and lysosomal hyaluronidase-1 (HYAL1) that suppresses hepatic gluconeogenesis by rewiring hepatic metabolism and mitochondrial function. Hyal1 knockout (Hyal1 KO) mice exhibited increased gluconeogenesis, while liver-specific Hyal1 overexpression (Liv-Hyal1) mice showed reduced gluconeogenic activity. Transcriptomic analysis revealed minimal changes in liver gene expression due to Hyal1 deletion, but metabolomic profiling demonstrated that Hyal1 overexpression mitigated high-fat diet (HFD)-induced elevations in gluconeogenic pathway metabolites. Mechanistically, HYAL1-mediated HA digestion activates a feedback loop in HA synthesis, repartitioning the cellular uridine diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc) pool. This reduces O-linked N-acetylglucosamine modification (O-GlcNAcylation) of mitochondrial ATP synthase subunits, decreasing ATP production and suppressing gluconeogenesis. Importantly, this pathway remains intact in the livers of HFD-fed, insulin-resistant mice. In summary, our findings reveal a new postprandial mechanism for regulating hepatic gluconeogenesis, highlighting the potential of enhancing postprandial HA levels or hepatic HYAL1 activity as a therapeutic strategy for managing excessive gluconeogenesis in insulin-resistant conditions, such as type 2 diabetes.

Basic features of cellular inositol metabolism as revealed by a newly developed LC-MS method.

Inositol plays key roles in many cellular processes. Several studies focussed on the quantitative analysis of phosphorylated forms of inositol, enabled by analytical tools developed to detect these highly charged molecules. Direct measurement of free inositol however has been challenging, because the molecule is uncharged and polar. As a result, the mechanisms maintaining the homeostasis of the inositol remains poorly understood. In this study, we overcome these challenges by developing a quantitative liquid chromatography - mass spectrometry (LC-MS) protocol that can resolve and quantify the three main sugar molecules present inside cells: glucose, fructose, and inositol, as well as distinguish the clinically relevant isomers of inositol: myo-, scyllo-, and chiro-inositol. The quantitative power of the new method was validated by accurately monitoring the changes of inositol levels under well-established conditions in Saccharomyces cerevisiae, where the endogenous synthesis of inositol is increased in the transcription repressor OPI1 knockout opi1D and decreased when wild type yeast is fed with exogenous inositol. The method also revealed a new layer of regulation that takes place when exogenous inositol is added to further boost endogenous inositol synthesis in opi1D in a positive feedback loop. Analyses of mammalian cell lines provided many new insights into inositol metabolism. First, different cell lines displayed distinct sugar profiles and inositol concentrations and responded differently to inositol starvation. Second, mammalian cells can synthesize and import scyllo- but not chiro-inositol. Importantly, our method lent direct evidence to the previous hypothesis that lithium treatment could significantly reduce inositol levels in primary cortical neurons, thus diminishing the pool of free inositol available to the phosphoinositide cycle.

Understanding the underlying systems dynamics contributing to the continued predominance of the unhealthy motorway food environment in the Netherlands: identifying leverage points and actions for change

BackgroundMotorway food environments are dominated by roadside restaurants and petrol station stores offering predominantly unhealthy quick-service meals and foods for on-the-go consumption. Improving these environments to promote healthier diets is necessary, but how to achieve this is not fully understood. Therefore, this study aims to identify the complex underlying systems dynamics contributing to the continued predominance of the unhealthy motorway food environment as well as to identify potential leverage points and corresponding actions for change to improve the healthiness of the motorway food environment.MethodsTwo Group Model Building workshops were held in October 2023 with motorway food environment stakeholders (e.g. food providers, producers, national policymakers, truck drivers). In the first workshop, a Causal Loop Diagram (CLD) was created to identify the system that contributes to the continued predominance of the unhealthy motorway food environment. The research team then identified leverage points for change based on the CLD. During the second workshop, stakeholders formulated actions to improve the motorway food environment for each identified leverage point. Leverage points and actions were classified based on the Action Scales Model (ASM).ResultsThe resulting CLD comprised six interconnected subsystems (food providers, supply chain collaboration, government, social culture, road users, global trends) with six reinforcing feedback loops, underlying the continued predominance of the unhealthy motorway food environment. Additionally, 14 potential leverage points and 31 corresponding actions for change were identified at different levels of the system based on the ASM (i.e. events, structures, goals and beliefs).ConclusionsThe findings show many interrelated factors and mechanisms underlying the continued predominance of the unhealthy motorway food environment. Actions for change were proposed together with stakeholders aimed at leverage points at different system levels. The results show that the motorway food environment is shaped by broader societal goals and beliefs (e.g. the profitability of unhealthy products) and social-cultural beliefs particularly evident to the on-the-go setting, including the motorway food environment. Together they present the strongest potential for leveraging systems change. There is a need for a coherent multidimensional action plan targeting these leverage points, which is broadly supported by various stakeholders, to induce systemic change.

CPT1A/HIF-1α positive feedback loop induced fatty acid oxidation metabolic pathway contributes to the L-ascorbic acid-driven angiogenesis in breast cancer

BackgroundIn tumors rich in adipose tissue, angiogenesis is a critical factor in promoting cancer cell metastasis. However, the connection between angiogenesis and the mechanisms driving adipose metabolic remodeling in breast cancer (BC) remains insufficiently understood. This research seeks to explore whether and how CPT1A, a crucial rate-limiting enzyme in fatty acid oxidation (FAO), supports angiogenesis through metabolic pathways in BC.MethodsFirst, cell functional assays and animal models were employed to elucidate the pro-carcinogenic effects of CPT1A on BC and its role in metabolic alterations. Following this, the reciprocal regulatory relationship between CPT1A and HIF-1α was elucidated using transcriptomic studies, ubiquitination analysis, and dual-luciferase assays. Matrigel tube formation assays, vasculogenic mimicry assays, and chick chorioallantoic membrane (CAM) assays were utilized to evaluate the effect of CPT1A on the pro-angiogenic properties of BC. Subsequently, untargeted metabolomics was employed to identify specific metabolic changes in supernatants with and without CPT1A expression and verified by functional recovery experiments. Finally, the prognostic significance of CPT1A and the vascular marker VEGF in BC tissues was evaluated using tissue microarrays and public databases.ResultsCPT1A overexpression significantly enhanced cell proliferation, motility, and angiogenesis via activating the FAO metabolic pathway, as demonstrated by both in vivo and in vitro experiments. Mechanistically, CPT1A regulates the ubiquitination level of hypoxia-inducible factor-1α (HIF-1α), which directly binds to the CPT1A promoter. Mutations at the 63–74 and 434–445 regions significantly reduced CPT1A promoter activity, indicating that these sites are critical for its transcriptional regulation. Ultimately, this interaction creates a reinforcing feedback loop between CPT1A and HIF-1α. Subsequently, this feedback loop alters changes in extracellular L-ascorbic acid (LAA) levels. Interestingly, LAA affects ROS homeostasis through the Nrf2/NQO1 pathway, specifically influencing angiogenesis in BC and HUVECs, while having no significant effect on their proliferation or EMT process. Moreover, increased expression levels of CPT1A and vascular endothelial growth factor (VEGF) were significantly associated with lymph node metastasis and adverse outcomes in BC patients.ConclusionThe CPT1A/HIF-1α positive feedback loop critically regulates angiogenesis through activation of the Nrf2/NQO1 pathway, modulated by LAA. These findings highlight CPT1A and VEGF as promising therapeutic targets and prognostic biomarkers for angiogenesis in BC.Graphical abstract

Integrated mathematical and experimental modeling uncovers enhanced EMT plasticity upon loss of the DLC1 tumor suppressor.

Epithelial-mesenchymal transition (EMT) plays an essential role in embryonic development, wound healing, and tumor progression. Partial EMT states have been linked to metastatic dissemination and drug resistance. Several interconnected feedback loops at the RNA and protein levels control the transition between different cellular states. Using a combination of mathematical modeling and experimental analyses in the TGFβ-responsive breast epithelial MCF10A cell model, we identify a central role for the tumor suppressor protein Deleted in Liver Cancer 1 (DLC1) during EMT. By extending a previous model of EMT comprising key transcription factors and microRNAs, our work shows that DLC1 acts as a positive regulator of TGFβ-driven EMT, mainly by promoting SNAIL1 expression. Our model predictions indicate that DLC1 loss impairs EMT progression. Experimental analyses confirm this prediction and reveal the acquisition of a partial EMT phenotype in DLC1-depleted cells. Furthermore, our model results indicate a possible EMT reversion to partial or epithelial states upon DLC1 loss in MCF10A cells induced toward mesenchymal phenotypes. The increased EMT plasticity of cells lacking DLC1 may explain its importance as a tumor suppressor.

Spectral unmixing of a multi-decadal Landsat time sequence to reconstruct herbaceous fractional cover dynamics in wildfire-prone Mediterranean-type ecosystems

ABSTRACT Portions of Southern California’s native shrubland communities are being invaded and sometimes replaced by herbaceous vegetation that increases the risk of wildfire ignition and spread in a positive feedback loop called the grass-fire cycle. The objective of this study was to assess the extent to which herbaceous cover has expanded and replaced woody vegetation over the last three decades in San Diego County shrublands. To do this, we reconstructed the spatial-temporal distribution of herbaceous growth form cover using spectral mixture analysis (SMA) applied to Landsat multispectral data from 1988 to 2020. The average error in herbaceous cover maps generated from images captured during four single years within the 33-year study period exhibited a mean absolute error (MAE) = 13.30%, root mean square error (RMSE) = 17.62%, and coefficient of determination (R2) = 0.76 relative to reference data derived from orthoimagery. Error estimates for absolute change in herbaceous cover from the earliest (1988) and recent (2020) dates were MAE = 12.17% and RMSE = 15.57% (assessed using 94 reference sampling grids). Between 1988 and 2020, 26.61% of the full study area exhibited an increase in herbaceous cover >20% and 4.98% experienced a decrease in herbaceous cover <−20%, with the greatest concentration of change occurring in wildland-urban interface (WUI) areas. The factors most strongly associated with a substantial increase in herbaceous cover included fire return interval, drought, proximity to development, and elevation. In addition to the overall expansion of herbaceous cover, we also identified locations with evidence of vegetation-type conversion from woody- to herbaceous-dominated fractional cover. These results suggest that a grass-fire cycle has been established in Southern California. The methods from this work can be applied to Mediterranean-type ecosystems around the world to quantify and monitor herbaceous vegetation change over time.

Melatonin enhances everolimus efficacy in breast cancer by suppressing mTOR pathway activation and promoting apoptosis and mitochondrial function

BackgroundEverolimus is used in the treatment of breast cancer by targeting the PI3K/AKT/mTOR pathway, particularly during anti-hormonal therapy. The efficacy of everolimus is limited due to a feedback loop that supresses mTOR while simultaneously enhancing Akt activation in endocrine-resistant breast cancer. Melatonin (N-acetyl-5-methoxytryptamine) regulates mitochondrial activity, cell death, and autophagy due to its strong free radical scavenging, antioxidant, and anti-inflammatory characteristics. Melatonin, a naturally occurring oncostatic agent, slows tumor growth in a range of malignancies, including breast cancer. Due to its ability to protect healthy cells from oxidative stress and inflammation, along with its anti-cancer properties, melatonin has the potential to serve asan effective adjuvant in breast cancer therapy. It also inhibits the phosphorylation of mTOR and Akt, two essential pathways implicated in breast cancer growth, which may aid in overcoming resistance to targeted treatments like everolimus. The combination effects of melatonin and everolimus on hormone receptor-positive breast cancer remains unexplored. This study examined the effectiveness of melatonin when combined with everolimus for the treatment of hormone receptor-positive breast cancer.MethodsTo investigate the effects of melatonin and everolimus combination, we divided MCF-7 cells into four experimental groups: the control, Melatonin (3 mM), Everolimus (30 nM), and a combination of Melatonin and Everolimus (3 mM + 30 nM). Cell viability, apoptosis, autophagy activation, and mitochondrial function were evaluated using established techniques.ResultsBased on the cell viability test, the combination of 30 nM everolimus and 3 mM melatonin inhibited phosphorylation of 4E-BP1 and p70S6K, which are downstream effectors of the mTOR pathway, and reduced cell growth. In addition, co-administration of melatonin and everolimus increased apoptosis and led to Sub-G1 phase accumulation. LC3 protein expression and LC3 puncta analysis demonstrated autophagic activity. In terms of mitochondrial function, co-administration of melatonin with everolimus did not cause proton leakage or mitochondrial uncoupling, but did restore everolimus-induced respiratory inhibition.ConclusionsIn conclusion, melatonin is thought to improve the effectiveness of everolimus by inhibiting mTOR downstream effectors, enhancing apoptosis, activating autophagy, improving mitochondrial respiration, and reducing MCF-7 growth.Graphical

Coherent Feedback Control of Indirectly Coupled Mode Multipartite Entanglement in a Cavity Opto‐Magnomechanical System

AbstractThis study is based on a theoretical proposal for the generation and enhancement of multipartite entanglements of indirectly coupled modes using the coherent feedback loop scheme. The coherent feedback‐control mechanism that is presented here significantly improves the bipartite and tripartite entanglements among the indirectly coupled modes. The numerical study shows that the entanglements can be sufficiently tuned by the effective couplings and the reflective parameter of the beam splitter. In addition, the robustness and survival of the generated entanglement in the proposed system have shown to be significantly dependent on the reflectivity parameter. The existence of a genuine tripartite entanglement state in the dynamical state of the system is proven. Finally, the effect of the reflective parameter on three different tripartite entanglements is observed. The findings pave the way for tuning and enhancing multipartite entanglements of indirectly coupled modes in current cavity Opto‐magnomechanical systems and may have various vital applications in quantum information.

Unpacking determinants of knowledge quality in an online knowledge community: group heterogeneity, interactive processes, and feedback effect

PurposeAn online knowledge community (OKC) is an important platform for people to produce and share knowledge. Many factors affecting the knowledge quality of OKC have been explored, but the feedback effect of knowledge quality has been ignored while feedback is a potentially powerful tool to enhance organizational effectiveness. This paper explores the cyclical causal feedback relationship among group heterogeneity, interactive processes, and knowledge quality.Design/methodology/approachWe drew on the Input-Mediator-Output-Input model (IMOI) to explore the cyclical causal feedback among group heterogeneity, interactive processes, and knowledge quality, then used panel data with the editing history of 117 articles extracted from Wikipedia to test the causality among these variables via the two-step system GMM estimation method.FindingsThere is a positive feedback loop among knowledge heterogeneity, interactive processes, and knowledge quality. Experience heterogeneity had no significant impact on interactive processes and knowledge quality, while knowledge quality in the previous stage had a significant negative feedback effect on experience heterogeneity in the next stage.Research limitations/implicationsThis research was conducted in the context of Wikipedia. We expect that the results will generalize to other OKC platforms.Practical implicationsThe findings could assist OKC managers in understanding the dynamic evolution of knowledge quality. Enriching members’ knowledge heterogeneity and promoting interaction are the keys to continuously improving knowledge quality.Originality/valueThis study extends the IMOI framework to an OKC context and finds the cyclical causal feedback relationship among group heterogeneity, interactive processes, and knowledge quality.

Landsat spectral unmixing analysis for mapping herbaceous fractional cover in wildfire-prone Mediterranean-type ecosystems

ABSTRACT Portions of Southern California’s native shrubland communities are being replaced by invasive herbaceous vegetation. These non-native species can increase the risk of wildfire ignition and spread. Expansion of these competitive invasive species in recently burned areas following a wildfire can lead to complete conversion and replacement of native shrubs and trees, which in turn increases the likelihood of future wildfire that spreads rapidly and widely through a positive feedback loop: the grass-fire cycle. Despite the association between herbaceous abundance and wildfire risk, image processing approaches for identification and quantification of fractional herbaceous cover in Southern California shrublands are not well established. The objective of this study is to comparatively assess the accuracy of herbaceous cover estimation and mapping based on three different unmixing models applied to Landsat multispectral data for San Diego County, U.S.A. during 2020. The models included: spectral mixture analysis (SMA) using a single set of spectral endmembers; multiple endmember SMA (MESMA); and temporal mixture model (TMM) analysis of year-long stacks of spectral indices computed from multiple Landsat acquisitions. Feature inputs included single date, multi-date, and spectral reflectance and spectral vegetation index (normalized difference infrared index (NDII) and normalized difference vegetation index (NDVI)) combinations. When compared to reference data generated from aerial imagery, results demonstrated that SMA applied to a date during the summer season (August) estimated unburned and intact herbaceous cover most accurately (mean absolute error (MAE), root mean square error (RMSE), and coefficient of determination (R2) values of 8.85%, 12.02%, and 0.85, respectively). Therefore, Landsat unmixing model results suggest that mapping, reconstructing, and monitoring of herbaceous cover at the 10% accuracy level is appropriate. These methods will enable improved detection of sensitive habitats in Mediterranean-type ecosystems around the world by satellite for wildfire-prone communities and identify target areas for monitoring and mitigating the grass-fire cycle.

Functionally differentiated GL2-interacting-repressor 1 homoeologs regulate epidermal hair development in Gossypium hirsutum.

Cotton (Gossypium. spp) stem trichomes and seed fibers are unicellular epidermal hairs regulated by relevant molecular networks. Genetic analysis of the glabrous stem landrace (Palmeri37) of Gossypium hirsutum L. has pinpointed GL2-interacting-repressor 1 (GhGIR1D), featuring a RING-like zinc finger domain, as the candidate gene underlying the stem glabrous trait. Overexpressing and silencing experiments confirm GhGIR1D as a negative regulator specifically for stem trichome initiation, without influencing leaf trichome or seed fiber. High endogenous expression of GhGIR1D is associated with a SNP-573 T/G variation within the promoter region, and GhGIR1D Hap I confers the absence of stem trichomes. The homoeologous protein, GhGIR1A, inhibits trichome and fuzz fiber initiation by disrupting the GhHD1D-GhHOX3A module (a complex of two Homeodomain-Leucine Zipper IV transcription factors, HD-ZIP IV), and repressing downstream transcription of GhRDL1. Trichome density was enhanced in GhHD1A overexpression transgenic lines but reduced in ghhd1a mutants, demonstrating the positive regulatory role of GhHD1A on stem trichome initiation. GhHD1 displays distinct effects on stem trichome and fuzz fiber initiation due to its tissue-specific dosage. In the ghhd1a mutants, repression of GhGIR1D restores the wild-type pubescent phenotype, suggesting the presence of a potential negative feedback loop between GhGIR1D and GhHD1A, or that GhGIR1D and GhHD1A may function within the same regulatory pathway with opposite functions in regulation of trichome development. These findings enhance our comprehension of the GhGIR1-GhHD1-GhHOX3 interaction module in epidermal hair initiation and development.

Intrapleural dual blockade of IL-6 and PD-L1 reprograms CAF dynamics and the tumor microenvironment in lung cancer-associated malignant pleural effusion

BackgroundMalignant pleural effusion (MPE) is a severe complication in lung cancer, characterized by an immunosuppressive tumor microenvironment (TME) and limited therapeutic options. This study investigates the role of IL-6 in regulating immune suppression and tumor progression in MPE and evaluates the efficacy of dual IL-6 and PD-L1 blockade.MethodsIL-6 levels were measured in MPE and paired serum samples from lung cancer patients, and correlations with PD-L1 expression and clinical outcomes were analyzed using publicly available datasets. RNA sequencing and immune deconvolution were used to assess immune cell infiltration. CAFs and immune cell infiltration were further evaluated using flow cytometry, immunohistochemistry, and multiplex immunofluorescence. In vitro co-culture systems were employed to simulate the MPE microenvironment and explore IL-6 interactions with CAFs, as well as its regulatory effect on tumor cell PD-L1 expression.ResultsIL-6 levels were significantly elevated in MPE compared to paired serum and correlated with higher PD-L1 expression and poor survival outcomes in lung cancer patients. In the MPE mouse model, combination therapy with IL-6 and PD-L1 blockade reduced MPE volume, tumor burden, and PD-L1 expression, while enhancing T cell infiltration and alleviating TME immunosuppression. IL-6 was found to drive a positive feedback loop with iCAFs, promoting an immunosuppressive environment. In vitro, IL-6 from the MPE upregulated tumor cell PD-L1 expression the IL-6/STAT3 pathway.ConclusionThis study identifies IL-6 as a critical contributor of immune suppression and tumor progression in MPE. The combination of IL-6 and PD-L1 blockade effectively alleviated immunosuppression and reduced tumor burden, offering a potential therapeutic approach for MPE management.

Frizbie: An AI-Powered Web-Based Trip Planner

Abstract - Travel planning poses unique challenges for students who must balance limited budgets and tight schedules. Frizbie is a web-based, AI-powered trip planner designed to streamline this process by generating personalized itineraries, providing smart recommendations, and offering real-time updates. Built with React.js, Firebase, and Google Gemini AI, Frizbie delivers a responsive and engaging user experience while prioritizing data security and cost-effectiveness. Unlike existing solutions, Frizbie specifically addresses student needs through budget-conscious recommendations, schedule flexibility, and campus-integrated planning. This paper presents the design, architecture, implementation, and potential impact of Frizbie as an intelligent, affordable, and efficient travel solution for students. In addition to the core functionalities, this article further explores the integration of user feedback loops and continuous enhancement cycles. Detailed case studies, extended performance metrics, and iterative improvements are discussed to reinforce the system's adaptability in a dynamic travel market.

Evaluating Ireland’s Deposit Return Scheme: Policy, Behaviour, and Response

This study analyses the early implementation of Ireland’s Deposit Return Scheme (DRS) through the lens of Edgar Morin’s complex thinking. Adopting a mixed-methods approach, it explores the economic, behavioural, and environmental impacts of the DRS in its first ten months, drawing on survey data, official statistics, stakeholder feedback, and media discourse. The find-ings reveal a nuanced landscape: while return rates have increased, significant tensions persist around cost perception, infra-structural access, and public frustration. Particularly among rural consumers and small retailers, the scheme is viewed as bur-densome and intrusive. Using a complexity-informed analytical framework, the study demonstrates that the DRS functions not as a linear intervention but as a dynamic governance system characterised by feedback loops and emergent effects. The research contributes to political science by highlighting how environmental policy interacts with legitimacy, freedom, and behavioural adaptation in real-world settings. It also provides a critique of top-down regulatory models and calls for more adaptive, citi-zen-centred approaches. This case illustrates the political dimensions of sustainability policy and underscores the value of com-plexity theory in analysing contested governance processes. Future research is recommended to assess long-term impacts, de-mographic variations, and comparative lessons from other European contexts. Subject Areas Environmental Policy and Governance, Political Science / Public Policy, Complexity Theory in Social Sciences, Behavioural Economics, Sustainability Studies

Analyzing X mentions to uncover micro-clusters interfering in political campaigns: a case study during the Spanish elections

IntroductionCoordinated influence campaigns on social networks pose a growing threat to democratic discourse, especially during electoral periods. This study investigates such efforts within political conversations during the Spanish regional elections of May 2023.MethodsWe analyzed a dataset of 345,000 messages posted on X (formerly Twitter) by 17,074 unique users. Using advanced quantitative techniques, we focused on the analysis of mentions to detect coordination patterns. We identified micro-clusters—groups of users engaging in synchronized messaging strategies—by tracking distribution lists and repeated amplification behaviors.ResultsOur findings reveal patterns of coordinated activity targeting political figures, journalists, and other influential actors. The Gephi-generated network maps visualize these micro-clusters and expose homophilic behavior and feedback loops that enhance the virality of messages.DiscussionThese results demonstrate the sophistication of digital tactics employed to manipulate political discourse. The study highlights the urgent need for effective detection mechanisms and regulatory frameworks to protect the integrity of public debate during electoral campaigns.

Human-artificial interaction in the age of agentic AI: a system-theoretical approach

This paper presents a novel perspective on human-computer interaction (HCI), framing it as a dynamic interplay between human and computational agents within a networked system. Going beyond traditional interface-based approaches, we emphasize the importance of coordination and communication among heterogeneous agents with different capabilities, roles, and goals. The paper distinguishes between Multi-Agent Systems (MAS)—where agents maintain autonomy through structured cooperation—and Centaurian systems, which integrate human and AI capabilities for unified decision making. To formalize these interactions, we introduce a framework for communication spaces, structured into surface, observation, and computation layers, ensuring seamless integration between MAS and Centaurian architectures, where colored Petri nets effectively represent structured Centaurian systems and high-level reconfigurable networks address the dynamic nature of MAS. We recognize that elements such as task recommendation, feedback loops, and natural language interfaces are common in contemporary adaptive HCI. What distinguishes our framework is not the introduction of these elements per se, but the synthesis of architectural principles that systematically accommodate both autonomy-preserving and integration-seeking configurations within a shared formal foundation. Our research has practical applications in autonomous robotics, human-in-the-loop decision making, and AI-driven cognitive architectures, and provides a foundation for next-generation hybrid intelligence systems that balance structured coordination with emergent behavior.

Transient Stiffness Patterning in Hydrogels Driven by Dissipative Mechanochemical Coupling

AbstractLiving systems adapt to mechanical forces through a series of biochemical feedback loops and dissipative signal transduction mechanisms across multiple length scales. By contrast, synthetic materials are static, closed systems with minimal interaction with their surroundings and lack the ability to adapt to mechanical deformations. Here, a strategy that enables a hydrogel to adapt to mechanical forces through the temporal modulation of its stiffness properties is reported. It is demonstrated that force‐induced bond rupture at the disulfide linkages of the hydrogel, coupled with their chemical reoxidation leads to dissipative, transient stiffness functions. The electrochemical generation of the oxidant as the output of a feedback loop triggered by an externally applied force provides high spatiotemporal control over the dissipative process, enabling the engineering of hydrogels with out‐of‐equilibrium stiffness patterns. Additionally, dose‐controlled, spatiotemporal transient release of model protein payloads from the hydrogel is demonstrated. The proposed concept has the potential to enhance the autonomous and interactive functionalities of hydrogels, advancing their applications in the biomedical field and soft robotics.

Integration of photoperiod and time-restricted feeding on the circadian gene rhythms in juvenile salmon

The circadian clock has evolved to synchronize animal behaviour and physiology with the external environment. Present in almost all cells, the clock is made up of a transcription-translation feedback loop that is responsive to cues such as light/dark cycles (photoperiod) and the time of feeding. Chinook salmon (Oncorhynchus tshawytscha) is a fish species whose clock is thought to be adapted in natural populations according to their latitude, where photoperiod variation can be extreme in northern spring/summer conditions. Here, we probed for the expression of circadian clock genes in four tissues of juvenile Chinook salmon under different environmental conditions. We find that the circadian clock is optimal when photoperiod is coupled with regular feeding during daylight hours. We further tested the effects of constant light and time-restricted feeding, environmental factors that are known to affect daily gene expression rhythms, on the expression of clock genes, appetite-regulating hormones, and metabolic regulators in the intestine of juvenile Chinook. We find that overall constant light is chrono-disruptive irrespective of the timing of food. The resulting disruption in gene expression produces aberrant rhythms, and affects glucose homeostasis, despite an increase in growth. Our data suggests photoperiod and time-restricted feeding could be optimized in Chinook aquaculture and raise the question of whether and how photoperiod changes are compensated in northern-adapted populations.