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Artificial intelligence (AI) advances and the rapid adoption of generative AI tools, like ChatGPT, present new opportunities and challenges for higher education. While substantial literature discusses AI in higher education, there is a lack of a systems approach that captures a holistic view of the structure and dynamics of the AI transformation of higher education institutions (HEIs). To fill this gap, this article develops a causal loop diagram (CLD) to map the causal feedback mechanisms of AI transformation in a typical HEI. We identify important variables and their relationships and map multiple reinforcing and balancing feedback loops accounting for the forces that drive the AI transformation and its impact on value creation in a typical HEI. The model shows how, motivated by AI technology advances, the HEI can invest in AI to improve student learning, research, and administration while dealing with academic integrity problems and adapting to job market changes by emphasizing AI-complementary student skills. We explore model insights, scenarios, and policy interventions and recommend that HEI leaders become systems thinkers to manage the complexity of the AI transformation and benefit from the AI feedback loops while avoiding policy traps that may lead to decline. We also discuss the notion of HEIs influencing the direction of AI and directions for future research on AI transformation and the sustainability of HEIs. [ABSTRACT FROM AUTHOR]

Abstract Radiotherapy is one of the mainstream approaches for cancer treatment, although the clinical outcomes are limited due to the radioresistance of tumor cells. Hypoxia and metabolic reprogramming are the hallmarks of tumor initiation and progression and are closely linked to radioresistance. Inside a tumor, the rate of angiogenesis lags behind cell proliferation, and the underdevelopment and abnormal functions of blood vessels in some loci result in oxygen deficiency in cancer cells, i.e., hypoxia. This prevents radiation from effectively eliminating the hypoxic cancer cells. Cancer cells switch to glycolysis as the main source of energy, a phenomenon known as the Warburg effect, to sustain their rapid proliferation rates. Therefore, pathways involved in metabolic reprogramming and hypoxia-induced radioresistance are promising intervention targets for cancer treatment. In this review, we discussed the mechanisms and pathways underlying radioresistance due to hypoxia and metabolic reprogramming in detail, including DNA repair, role of cancer stem cells, oxidative stress relief, autophagy regulation, angiogenesis and immune escape. In addition, we proposed the existence of a feedback loop between energy metabolic reprogramming and hypoxia, which is associated with the development and exacerbation of radioresistance in tumors. Simultaneous blockade of this feedback loop and other tumor-specific targets can be an effective approach to overcome radioresistance of cancer cells. This comprehensive overview provides new insights into the mechanisms underlying tumor radiosensitivity and progression.

Real-time fault detection via sensor signal analyses is widely performed in electromechanical systems to prevent sudden stops and the resulting losses, which requires a sufficient amount of fault data. Because it is difficult to obtain sufficient fault data with actual physical systems, fault detection is usually conducted using unsupervised detection models with datasets collected under health operations. Supervised models with few fault datasets of limited types have been developed, often with sophisticatedly augmented fault datasets. However, actual faults occur cumulatively with machine use, and the information contained in the actual data is very valuable. Therefore, this study proposes a feedback loop-based fault detection method that can be adjusted depending on the fault datasets during operation. Unsupervised fault detection is conducted using a long short-term memory autoencoder-based deep learning model and statistical process control chart with a derived anomaly score before observing any fault state. After obtaining even a small amount of fault datasets, fully connected layers are added for supervised classification, such as transfer learning techniques, to determine whether the current state is healthy or faulty. The performance of the proposed continuous learning method for fault detection is verified using datasets from a fused filament fabrication three-dimensional printer under several scenarios: no fault, one type of fault, and two types of faults. The detection performance improves as informative feedback is provided by the newly added layers. It was observed that even small fault datasets have the potential to improve the performance of trained unsupervised fault detection model. Since it is possible to detect fault occurrence from the initial state of the product life cycle, and the performance would be automatically updated as the printer is used, it is expected that it can be installed in a commercial three-dimensional printer and used directly for maintenance, without analyzing other machine's datasets. [ABSTRACT FROM AUTHOR]

The effects of the front wall and aft wall sub-cavities in the flow field of a confined supersonic deep cavity are numerically investigated. The turbulent simulations are carried out by deploying a finite volume-based explicit density-based solver in the OpenFOAM framework in conjunction with the k - ω SST (Shear Stress Transport) turbulence model. A cavity with a length-to-depth ratio of three placed in a confined passage is considered in the study. The freestream Mach number at the entrance of the passage is approximately 1.71. The addition of the sub-cavity of lengths ranging between 0.2 and 0.3 times the length of the main cavity in the front wall and the aft wall, significantly affects the frequencies of cavity oscillations as obtained from the spectral signature. The front wall subcavity of length ratio 0.2 reduces the dominant frequency by almost 60 percent as compared to the baseline cavity. The analysis and comparison of the flow field using the numerical schlieren in both configurations reveal a significant alteration in the flow field. The flow visualization provides a distinct understanding of the attenuation and enhancement of pressure oscillations obtained through spectral analysis in the presence of sub-cavities. [ABSTRACT FROM AUTHOR]

Radiotherapy is one of the mainstream approaches for cancer treatment, although the clinical outcomes are limited due to the radioresistance of tumor cells. Hypoxia and metabolic reprogramming are the hallmarks of tumor initiation and progression and are closely linked to radioresistance. Inside a tumor, the rate of angiogenesis lags behind cell proliferation, and the underdevelopment and abnormal functions of blood vessels in some loci result in oxygen deficiency in cancer cells, i.e., hypoxia. This prevents radiation from effectively eliminating the hypoxic cancer cells. Cancer cells switch to glycolysis as the main source of energy, a phenomenon known as the Warburg effect, to sustain their rapid proliferation rates. Therefore, pathways involved in metabolic reprogramming and hypoxia-induced radioresistance are promising intervention targets for cancer treatment. In this review, we discussed the mechanisms and pathways underlying radioresistance due to hypoxia and metabolic reprogramming in detail, including DNA repair, role of cancer stem cells, oxidative stress relief, autophagy regulation, angiogenesis and immune escape. In addition, we proposed the existence of a feedback loop between energy metabolic reprogramming and hypoxia, which is associated with the development and exacerbation of radioresistance in tumors. Simultaneous blockade of this feedback loop and other tumor-specific targets can be an effective approach to overcome radioresistance of cancer cells. This comprehensive overview provides new insights into the mechanisms underlying tumor radiosensitivity and progression. [ABSTRACT FROM AUTHOR]

The mammalian circadian clock plays a crucial role in regulating the 24-h physiological and behavioral processes. This work presents an improved model for the mammalian circadian clock by integrating physiologically plausible modifications into the Kim–Forger model, and investigates the oscillatory dynamics of the mammalian circadian clock induced by the core delayed negative feedback loop using bifurcation theory. The modifications involve introducing time delays in PER protein transcription, translation, and translocation, replacing the first-order law for PER degradation rate with the Michaelis-Menten law, and revising the transcription rate of Per genes. The modified model accurately captures circadian oscillations and overcomes the unrealistic constraints of the Kim–Forger model. In addition, by utilizing the time delay as a control parameter, the theoretical results reveal that the delay induces a supercritical Hopf bifurcation, leading to the emergence of circadian oscillations with enhanced robustness, longer periods, increased amplitudes, and phase delays. Finally, numerical simulations are presented to assess the efficacy of the modified model and to validate the theoretical analysis. [ABSTRACT FROM AUTHOR]

Aiming at the problems of long computation time, error-prone results, and difficulty in verification associated with the traditional determinant feedback loop calculation method in system dynamics, a rapid calculation method for system dynamics feedback loops was proposed.This method utilizes the Loops function of Vensim software, the feedback loop set of the system was generated by taking each level bit variable as the starting point, followed by the removal of duplicate feedback loops to obtain a set of all non-repetitive feedback loops in the system. Taking the "Base+Farmers" supply chain complex system of Mingxin Farm in Pingxiang as an example, 11 strongly simplified flow rate basic in-tree models that have been constructed, and both the determinant calculation method and this new method were used to compute all feedback loops in the system.The research showed that both methods yielded the same results, but the fast calculation method of the feedback loop significantly reduced the calculation time and improved the calculation accuracy.Based on this, the system structure can be deeply analyzed to put forward corresponding management countermeasures. [ABSTRACT FROM AUTHOR]

Building community resilience has been widely recognized as a learning process at multiple societal levels, yet few prior studies have examined the feedback loop between community‐ and policy‐level learning. Following a qualitative research approach, we document experiential and transformative forms of learning from coastal cyclones in Bangladesh that help local community and their institutions mitigating the impact of cyclonic shocks and recovering from disaster‐related losses, both in the shorter and longer term. This study discovers that such community‐level learning (when scaled‐up) as well as learning from policy failure significantly enhanced programmatic interventions, which in turn enhanced community resilience to cyclones and future disasters. However, this feedback loop can be attenuated by multiple factors, such as lack of attention to community‐level learning by policy/decision makers in non‐disaster settings and the presence of a strong vested interest group, may impede learning‐based policy instrumentation. Boundary spanners or organizations can significantly improve the feedback loop, thus enhancing community resilience and improving policy. [ABSTRACT FROM AUTHOR]

Background: Medical students' social media addiction disrupts and lowers sleep quality, hurting their everyday life and academic performance, stressing the need for effective ways to promote their well-being and achievement. The study aims to estimate the prevalence of social media addiction and to find out the association with sleep quality among medical students in private medical college. Methodology: A cross-sectional study involving 792 MBBS students from a private medical college in Chengalpattu district, Tamil Nadu, utilized the Bergen Social Media Addiction Scale (BSMAS) to assess social media addiction and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Data were collected through a pre-tested semi-structured questionnaire and analysed using SPSS version 25. Results: The study revealed a 17.7% prevalence of social media addiction among medical students, significantly associated with poor sleep quality, female gender, and morning social media use. Other factors included dependence on social media for updates, more than three hours of daily use, eye discomfort, Snapchat use, compulsion to post at least six photos and subjective sleep quality, sleep latency, duration, disturbances, use of sleeping medication, and Daytime dysfunction. Conclusions: Research demonstrates a significant correlation between social media addiction and poor sleep quality among medical students, highlighting the need for focused interventions and awareness activities to counteract its harmful influence.

Engineering or mimicking living materials found in nature has the potential to transform the use of materials. Unlike classic synthetic materials which are typically optimized for static properties, economics, and recently also for sustainability, materials of life are dynamic, feedback‐controlled, evolving, and adaptive. Although synthetic materials do not typically exhibit such complicated functionalities, researchers are increasingly challenging this viewpoint and expanding material concepts toward dynamic systems inspired by selected life‐like functions. Herein, it is suggested that such materials can be approached from two perspectives: through engineering of biological organisms and their functions to provide the basis for new materials, or by producing synthetic materials with selected rudimentary life‐inspired functions. Current advances are discussed from the perspectives of (i) new material features based on built‐in memory and associative learning, (ii) emergent structures and self‐regulated designs using non‐equilibrium systems, and (iii) interfacing living and non‐living systems in the form of cellular community control and growth to open new routes for material fabrication. Strategies combining (i)–(iii) provide materials with increasingly life‐inspired responses and potential for applications in interactive autonomous devices, helping to realize next‐generation sensors, autonomous and interactive soft robots, and external control over the bioproduction of self‐organizing structural materials. [ABSTRACT FROM AUTHOR]

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This audio-visual essay is a methodological approach to a document of my current doctoral practice as research investigating the embodied dance improvisatory approaches within motion capture environments. The research explores the emergence of sculptural qualities as a shaping process between the movement practitioner's body–mind, movement, technology, and the environment. This video essay demonstrates these emerging relationships through the document(ation) and expands the understanding of live performance and its possibilities within digital environments. This audio-visual essay combines movement practitioners' living experiences and improvisatory responses with reflective insights into the dynamic and unfolding relationships within the digital environment. Film techniques capture(ing) the improvisatory explorations at that moment, and the transformative potential of performance reveals the fluid, abstract, and temporal unfolding of sculptural qualities that arise from the interplay between improvising bodies, actual and virtual, and motion-capture environments. The audio-visual essay also observes a few initial thoughts on how movement practitioners can access (Range of Coupling ROC and visualisation of digital trace-forms) and activate (T-pose with Stillness) sculptural qualities within digital environments. The accompanying written text expands on the ideas in the video essay and offers contextualising interactions through the post-phenomenological lens and how sculptural qualities are a potential framework within live performances in digital environments. [ABSTRACT FROM AUTHOR]

One of the artistic motivations and main contributions of the late war photographer Tim Hetherington was to visually explain how young men fighting in war are influenced by representations of war--a process he referred to as a 'feedback loop'. This article accompanies Hetherington's 'visual explanations' with a theoretical one. Drawing on Gadamer's hermeneutics and Merleau-Ponty's phenomenology, I develop a framework for understanding how representations influence realities of war. In particular, I theorize how aesthetic forms are understood, embodied, and enacted, and how they thereby become historically continuous. To illustrate this framework, I conduct a brief genealogy of three aesthetic themes of war captured by Hetherington--of militarized masculinity, of the ideal of the professional soldier, and of the paradoxical absurdity of war. This article will be of interest to scholars seeking to better understand the culture of modern war and the intimate relationship between war and broader society. [ABSTRACT FROM AUTHOR]

In the face of the elevated incidence and mortality rate of septic shock in the ICU, this retrospective study seeks to investigate the indicative and predictive value of high-mobility group box 1 (HMGB1) and miR-146b in patients with septic shock. Quantitative RTPCR was employed in this study to quantify the HMGB1 and miR-146b levels in plasma samples obtained from the patient group and healthy controls. The investigation involved the comparison between the two groups and tracking changes in the patient group over time. The finding revealed that upon admission, the patient group exhibited markedly elevated relative expression levels of HMGB1, which subsequently decreased over time. Conversely, the patient group displayed significantly reduced relative expression levels of miR-146b upon admission, which subsequently increased over time compared to the control group. Receiver operating characteristic (ROC) curves showed good predictive value for HMGB1 and miR-146b. The experimental results suggest that HMGB1 and miR-146b serve as valuable and convenient biomarkers for evaluating the severity of septic shock and predicting mortality. Additionally, it is proposed that serum miR-146b may be inducible and potentially exerts a negative regulatory effect on the expression of HMGB1. [ABSTRACT FROM AUTHOR]

This study investigates the role of Stanniocalcin-1 (STC1) in melanoma progression, with a focus on its impact on metastasis, angiogenesis, and immune evasion. Systematic bioinformatics analysis revealed the potential influence of STC1 dysregulation on prognosis, immune cell infiltration, response to immune therapy, and cellular functions. In vitro assays were conducted to assess the proliferation, invasion, migration, and angiogenesis capabilities of A375 cells. In vivo experiments utilizing C57BL/6 J mice established a lung metastasis model using B16-F10 cells to evaluate macrophage infiltration and M2 polarization. A Transwell co-culture system was employed to explore the crosstalk between melanoma and macrophages. Molecular interactions among STC1, YAP, βPIX, and CCL2 are investigated using mass spectrometry, Co-Immunoprecipitation, Dual-Luciferase Reporter Assay, and Chromatin Immunoprecipitation experiments. STC1 was found to enhance lung metastasis by promoting the recruitment and polarization of M2 macrophages, thereby fostering an immunosuppressive microenvironment. Mechanistically, STC1 competes with YAP for binding to βPIX within the KER domain in melanoma cells, leading to YAP activation and subsequent CCL2 upregulation. CCL2-induced M2 macrophages secrete VEGFA, which enhances tumor vascularization and increases STC1 expression via the AKT signaling pathway in melanoma cells, establishing a pro-metastatic feedback loop. Notably, STC1-induced YAP activation increases PD-L1 expression, promoting immune evasion. Silencing STC1 enhances the efficacy of PD-1 immune checkpoint therapy in mice. This research elucidates STC1's role in melanoma metastasis and its complex interactions with tumor-associated macrophages, proposing STC1 as a potential therapeutic target for countering melanoma metastasis and augmenting the efficacy of PD-1 immunotherapy.

The effects of the front wall and aft wall sub-cavities in the flow field of a confined supersonic deep cavity are numerically investigated. The turbulent simulations are carried out by deploying a finite volume-based explicit density-based solver in the OpenFOAM framework in conjunction with the k − ω SST (Shear Stress Transport) turbulence model. A cavity with a length-to-depth ratio of three placed in a confined passage is considered in the study. The freestream Mach number at the entrance of the passage is approximately 1.71. The addition of the sub-cavity of lengths ranging between 0.2 and 0.3 times the length of the main cavity in the front wall and the aft wall, significantly affects the frequencies of cavity oscillations as obtained from the spectral signature. The front wall sub-cavity of length ratio 0.2 reduces the dominant frequency by almost 60 percent as compared to the baseline cavity. The analysis and comparison of the flow field using the numerical schlieren in both configurations reveal a significant alteration in the flow field. The flow visualization provides a distinct understanding of the attenuation and enhancement of pressure oscillations obtained through spectral analysis in the presence of sub-cavities.

Contemporary communication is often characterized using metaphors as “echo chambers” or “filter bubbles.” Despite the popularity of these terms, however, growing concerns about vague definitions are complemented by empirical evidence that contests their widespread existence. Nonetheless, today’s media environment offers ample opportunities for human and/or algorithmic selection processes with undesirable outcomes. To reconcile these two observations, I propose taking a feedback-loop perspective. Such a perspective explains how processes can reinforce themselves without producing catastrophic consequences. This can solve the paradox that while extrapolating from typical filter bubble and/or echo chamber models results in full radicalization within a short period, this outcome has not, despite the long-standing presence of the relevant technologies, become omnipresent. After mapping different types of feedback loops in communication research, I review various empirical approaches, discuss how they can improve research on feedback-loop phenomena, and consider how this can enable us to build better theories of communication in the digital society.

Plants can sense temperature changes and adjust their growth accordingly. In Arabidopsis, high ambient temperatures stimulate stem elongation by activating a key thermoresponsive regulator, PHYTOCHROME INTERACTING FACTOR 4 (PIF4). Here, we show that warmth promotes the nighttime transcription of GI, which is necessary for the high temperature-induced transcription of TOC1. Genetic analyses suggest that GI prevents excessive thermoresponsive growth by inhibiting PIF4, with this regulatory mechanism being partially reliant on TOC1. GI transcription is repressed by ELF3 and HY5, which concurrently inhibit PIF4 expression and activity. Temperature elevation causes the deactivation or degradation of ELF3 and HY5, leading to PIF4 activation and relief of GI transcriptional repression at high temperatures. This allows PIF4 to further activate GI transcription in response to elevated temperatures. GI, in turn, inhibits PIF4, establishing a negative feedback loop that fine-tunes PIF4 activity. In addition, we demonstrate that ELF3, HY5, and PIF4 regulate GI transcription by modulating the enrichment of histone variant H2A.Z at the GI locus. Together, our findings suggest that thermal release of a negative feedback loop finely adjusts plant thermomorphogenesis.

Adenosine-to-inosine (A-to-I) RNA editing, mediated by metazoan ADAR enzymes, is a prevalent post-transcriptional modification that diversifies the proteome and promotes adaptive evolution of organisms. The Drosophila Adar gene has an auto-recoding site (termed S>G site) that forms a negative-feedback loop and stabilizes the global editing activity. However, the evolutionary trajectory of Adar S>G site in many other insects remains largely unknown, preventing us from a deeper understanding on the significance of this auto-editing mechanism. In this study, we retrieved the well-annotated genomes of 375 arthropod species including the five major insect orders (Lepidoptera, Diptera, Coleoptera, Hymenoptera and Hemiptera) and several outgroup species. We performed comparative genomic analysis on the Adar auto-recoding S>G site. We found that the ancestral state of insect S>G site was an uneditable serine codon (unSer) and that this state was largely maintained in Hymenoptera. The editable serine codon (edSer) appeared in the common ancestor of Lepidoptera, Diptera and Coleoptera and was almost fixed in the three orders. Interestingly, Hemiptera species possessed comparable numbers of unSer and edSer codons, and a few ‘intermediate codons’, demonstrating a multi-step evolutionary trace from unSer-to-edSer with non-synchronized mutations at three codon positions. We argue that the evolution of Adar S>G site is the best genomic evidence supporting the ‘proteomic diversifying hypothesis’ of RNA editing. Our work deepens our understanding on the evolutionary significance of Adar auto-recoding site which stabilizes the global editing activity and controls transcriptomic diversity.

We present a method for regulating the laser energy output with a software-controlled waveplate–polariser configuration. By implementing this technology, we have effectively eliminated energy output fluctuations over time, allowing for the laser to reach its nominal energy up to 2 h earlier. Our testing demonstrates a stability of 2.8% (RMS), verifying the system’s reliability. We provide an overview of the software and its basic operation, along with practical evidence of the system’s efficacy in maintaining a stable laser energy output.

Genetically encoded biological clocks are found broadly throughout life on Earth, where they generate circadian (about a day) rhythms that synchronize physiology and behavior with the daily light/dark cycle. Although the genetic networks that give rise to circadian timing are now fairly well established, our understanding of how the proteins that constitute the molecular 'cogs' of this biological clock regulate the intrinsic timing, or period, of circadian rhythms has lagged behind. New studies probing the biochemical and structural basis of clock protein function are beginning to reveal how assemblies of dedicated clock proteins form and evolve through post-translational regulation to generate circadian rhythms. This review will highlight some recent advances providing important insight into the molecular mechanisms of period control in mammalian clocks with an emphasis on structural analyses related to CK1-dependent control of PER stability.

We present a method for regulating the laser energy output with a software-controlled waveplate–polariser configuration. By implementing this technology, we have effectively eliminated energy output fluctuations over time, allowing for the laser to reach its nominal energy up to 2 h earlier. Our testing demonstrates a stability of 2.8% (RMS), verifying the system's reliability. We provide an overview of the software and its basic operation, along with practical evidence of the system's efficacy in maintaining a stable laser energy output. [ABSTRACT FROM AUTHOR]

We have derived conditions when unintended feedback loops occur in supervised machine learning systems. In this paper, we study an important problem of discovering and measuring hidden feedback loops. Such feedback loops occur in web search, recommender systems, healthcare, predictive public policing and other systems. As a possible cause of echo chambers and filter bubbles, these feedback loops tend to produce concept drifts in user behavior. We study systems in their context of use, because both learning algorithms and user interactions are important. Then we decompose the automation bias from the use of the system into users adherence to predictions and their usage rate to derive conditions for a feedback loop to occur. We also provide estimates for the size of a concept drift caused by the loop. A series of controlled simulation experiments with real-world and synthetic data support our findings. This paper builds on our prior results and elaborates the analytical model of feedback loops, extends the experiments, and provides practical application guidelines. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown that traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases (NDs). However, molecular mechanisms that underlie this risk are largely unidentified. TBI triggers widespread epigenetic modifications. Similarly, NDs such as Alzheimer’s or Parkinson’s are associated with numerous epigenetic changes. Although epigenetic changes can persist after TBI, it is unresolved if these modifications increase the risk of later ND development and/or dementia. We briefly review TBI-related epigenetic changes, and point out putative feedback loops that might contribute to longterm persistence of some modifications. We then focus on evidence suggesting persistent TBI-associated epigenetic changes may contribute to pathological processes (e.g., neuroinflammation) which may facilitate the development of specific NDs – Alzheimer’s disease, Parkinson’s disease, or chronic traumatic encephalopathy. Finally, we discuss possible directions for TBI therapies that may help prevent or delay development of NDs. [ABSTRACT FROM AUTHOR]

How environmental cues influence peroxisome proliferation, particularly through organelles, remains largely unknown. Yeast peroxisomes metabolize fatty acids (FA), and methylotrophic yeasts also metabolize methanol. NADH and acetyl-CoA, produced by these pathways enter mitochondria for ATP production and for anabolic reactions. During the metabolism of FA and/or methanol, the mitochondrial oxidative phosphorylation (OXPHOS) pathway accepts NADH for ATP production and maintains cellular redox balance. Remarkably, peroxisome proliferation in Pichia pastoris was abolished in NADH-shuttling- and OXPHOS mutants affecting complex I or III, or by the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), indicating ATP depletion causes the phenotype. We show that mitochondrial OXPHOS deficiency inhibits expression of several peroxisomal proteins implicated in FA and methanol metabolism, as well as in peroxisome division and proliferation. These genes are regulated by the Snf1 complex (SNF1), a pathway generally activated by a high AMP/ATP ratio. In OXPHOS mutants, Snf1 is activated by phosphorylation, but Gal83, its interacting subunit, fails to translocate to the nucleus. Phenotypic defects in peroxisome proliferation observed in the OXPHOS mutants, and phenocopied by the Δgal83 mutant, were rescued by deletion of three transcriptional repressor genes (MIG1, MIG2, and NRG1) controlled by SNF1 signaling. Our results are interpreted in terms of a mechanism by which peroxisomal and mitochondrial proteins and/or metabolites influence redox and energy metabolism, while also influencing peroxisome biogenesis and proliferation, thereby exemplifying interorganellar communication and interplay involving peroxisomes, mitochondria, cytosol, and the nucleus. We discuss the physiological relevance of this work in the context of human OXPHOS deficiencies.

Abstract Background Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. Methods Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. Results CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. Conclusion Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer.

Brassinosteroids (BRs) are a class of polyhydroxylated steroidal phytohormones that are essential for plant growth and development. Rice BRASSINOSTEROID-INSENSITIVE1 (BRI1)-ASSOCIATED RECEPTOR KINASES (OsBAKs) are plasma membrane-localized receptor kinases belonging to the subfamily of leucine-rich repeat receptor kinases. It has been found that in Arabidopsis, BRs induce the formation of a BRI1–BAK1 heterodimer complex and transmit the cascade signal to BRASSINAZOLE RESISTANT1/ bri1 -EMS-SUPPRESSOR1 (BZR1/BES1) to regulate BR signaling. Here, in rice (Oryza sativa ssp. japonica), we found that OsBZR1 binds directly to the promoter of OsBAK2 , but not OsBAK1 , and represses the expression of OsBAK2 to form a BR feedback inhibition loop. Additionally, the phosphorylation of OsBZR1 by OsGSK3 reduced its binding to the OsBAK2 promoter. The osbak2 mutant displays a typical BR-deficiency phenotype and negative modulates the accumulation of OsBZR1. Interestingly, the grain length of the osbak2 mutant was increased whereas in the cr-osbak2 / cr-osbzr1 double mutant, the reduced grain length of the cr-osbzr1 mutant was restored, implying that the increased grain length of osbak2 may be due to the rice somatic embryogenesis receptor kinase-dependent pathway. Our study reveals a novel mechanism by which OsBAK2 and OsBZR1 engage in a negative feedback loop to maintain rice BR homeostasis, facilitating a deeper understanding of the BR signaling network and grain length regulation in rice. [ABSTRACT FROM AUTHOR]

This article applied the theory of "Voice and Exit" developed by Hirschman to the European Court of Human Rights' (ECtHR or Court) interaction with its member States. According to this theory, if the organisation cannot be changed through Voice, the Exit of its members is more likely. This article argues that there are avenues for the Contracting Parties to the European Convention on Human Rights (ECHR) to Voice their concerns to the ECtHR, however it is important that the Court reacts to these concerns through feedback loops. The feedback loops do not come without a cost and the Court needs to be cognisant of their dangers. The article applies this framework to existing practices of the ECtHR and considers whether the Court used the feedback loops that have already been developed with maximum efficiency. This article establishes a typology of feedback loops and explains how they are operationalised by the ECtHR in practice. [ABSTRACT FROM AUTHOR]

Autophagy is a cell’s evolutionary conserved process for degrading and recycling cellular proteins and removing damaged organelles. There has been an increasing interest in identifying the basic cellular mechanism of autophagy and its implications in health and illness during the last decade. Many proteinopathies such as Alzheimer’s and Huntington’s disease are reported to be associated with impaired autophagy. The functional significance of autophagy in exfoliation syndrome/exfoliation glaucoma (XFS/XFG), remains unknown though it is presumed to be impaired autophagy to be responsible for the aggregopathy characteristic of this disease. In the current study we have shown that autophagy or ATG5 is enhanced in response to TGF-β1 in human trabecular meshwork (HTM) cells and TGF-β1 induced autophagy is necessary for increased expression of profibrotic proteins and epithelial to mesenchymal (EMT) through Smad3 that lead to aggregopathy. Inhibition of ATG5 by siRNA mediated knockdown reduced profibrotic and EMT markers and increased protein aggregates in the presence of TGF-β1 stimulation. The miR-122-5p, which was increased upon TGF exposure, was also reduced upon ATG5 inhibition. We thus conclude that TGF-β1 induces autophagy in primary HTM cells and a positive feedback loop exists between TGF-β1 and ATG5 that regulated TGF downstream effects mainly mediated by Smad3 signaling with miR-122-5p also playing a role.

Abstract Background Metastasis is the leading cause of mortality in patients with breast cancer (BC). Studies demonstrate that circular RNAs (circRNAs) were involved in BC progression, while the molecular mechanisms remain largely unclear. Methods The microArray circRNA profiles were used to explore the differential expression circRNAs in BC and paracancerous normal tissues, and the quantitative reverse transcription-polymerase chain reaction was used to validate their expression level in clinical samples and cell lines. Nuclear/cytosolic fractionation and fluorescence in situ hybridization (FISH) assays were performed to examine circRRM2 (hsa_circ_0052582) subcellular location. The scratch wound healing and transwell assays were conducted to evaluate the impact of circRRM2 on BC cell migration and invasion. We predicted miRNAs that might bind with cricRRM2 and the downstream target genes using bioinformatics analysis and explored their expression levels and prognostic value in BC. FISH, RNA immunoprecipitation, Co-immunoprecipitation, Western blot, and rescue experiments were implemented to figure out circRRM2 function and underlying mechanisms in BC. Results The present study revealed several aberrant circRNAs in BC tissues and observed that circRRM2 was upregulated in tumor tissues of 40 patients with BC. High circRRM2 was significantly associated with advanced N stage in patients with BC. Gain- and loss- of function experiments revealed that circRRM2 promoted the migration and invasion of cells and functioned as an oncogene in BC. Mechanism studies showed that circRRM2 competed with miR-31-5p/miR-27b-3p to upregulate the IGF2BP1 expression. Furthermore, IGF2BP1 upregulated the circRRM2 level via interacting with MYC, which functioned as the transcriptional factor of circRRM2. Thus, the positive feedback loop that was composed of circRRM2/IGF2BP1/MYC was identified. Conclusion This study confirms that upregulated circRRM2 functions an oncogenic role in BC metastasis. The positive feedback loop of circRRM2/IGF2BP1/MYC enforces the circRRM2 expression, which might offer a potential target for BC treatment.

The proximity of obstacles in a ventilation network can result in a significant increase of the noise production. In this paper, a tandem diaphragm inserted in a rigid duct with rectangular cross section is investigated and compared to a single diaphragm obstruction. The disturbed flow which reaches the second obstacle causes an amplification of the radiated noise which goes beyond a simple doubling of the power. Experimental results, carried with various spacing between the two diaphragms and bulk velocity, allows identifying other aeroacoustic source mechanisms which does not appear with a single diaphragm. Depending on the configuration, the broadband level can increase by more than 10 dB and feedback phenomena can appear at low frequency. Explanations and illustrations of those phenomena are given thanks to compressible-fluid simulations.

Epidemiological studies have shown that traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases (NDs). However, molecular mechanisms that underlie this risk are largely unidentified. TBI triggers widespread epigenetic modifications. Similarly, NDs such as Alzheimer’s or Parkinson’s are associated with numerous epigenetic changes. Although epigenetic changes can persist after TBI, it is unresolved if these modifications increase the risk of later ND development and/or dementia. We briefly review TBI-related epigenetic changes, and point out putative feedback loops that might contribute to long-term persistence of some modifications. We then focus on evidence suggesting persistent TBI-associated epigenetic changes may contribute to pathological processes (e.g., neuroinflammation) which may facilitate the development of specific NDs – Alzheimer’s disease, Parkinson’s disease, or chronic traumatic encephalopathy. Finally, we discuss possible directions for TBI therapies that may help prevent or delay development of NDs.

Aim: Artificial intelligence (AI) and machine learning (ML) are important areas of computer science that have recently attracted attention for their application to medicine. However, as techniques continue to advance and become more complex, it is increasingly challenging for clinicians to stay abreast of the latest research. This overview aims to translate research concepts and potential concerns to healthcare professionals interested in applying AI and ML to resuscitation research but who are not experts in the field. Main text: We present various research including prediction models using structured and unstructured data, exploring treatment heterogeneity, reinforcement learning, language processing, and large-scale language models. These studies potentially offer valuable insights for optimizing treatment strategies and clinical workflows. However, implementing AI and ML in clinical settings presents its own set of challenges. The availability of high-quality and reliable data is crucial for developing accurate ML models. A rigorous validation process and the integration of ML into clinical practice is essential for practical implementation. We furthermore highlight the potential risks associated with self-fulfilling prophecies and feedback loops, emphasizing the importance of transparency, interpretability, and trustworthiness in AI and ML models. These issues need to be addressed in order to establish reliable and trustworthy AI and ML models. Conclusion: In this article, we overview concepts and examples of AI and ML research in the resuscitation field. Moving forward, appropriate understanding of ML and collaboration with relevant experts will be essential for researchers and clinicians to overcome the challenges and harness the full potential of AI and ML in resuscitation.

Background: Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear. Methods: Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings. Results: CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo. Conclusion: Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer. [ABSTRACT FROM AUTHOR]

The main aim of this paper is to present the machine learning (ML) extension to the authors' original conceptual framework for implementing temporal big data analytics (TBDA) in organizations. The framework has been also supplemented with a ML-supported feedback loop aimed at ongoing verification of the organization's maturity for TBDA in light of changing needs, requirements, and the company's environment. Such extension is needed to make the TBDA more flexible and adaptable to market environment, thus augmenting organizational agility. The research has been carried following the Design Science Research in Information Systems (DSRIS) methodological approach with the addition of creative thinking. As a result, the extended framework is elaborated, and further improvements and research directions are identified. [ABSTRACT FROM AUTHOR]

Background: Endometriosis (EM) is a benign, multifactorial, immune-mediated inflammatory disease that is characterized by persistent activation of the NF-κB signaling pathway and some features of malignancies, such as proliferation and lymphangiogenesis. To date, the pathogenesis of EM is still unclear. In this study, we investigated whether BST2 plays a role in the development of EM. Methods: Bioinformatic analysis was performed with data from public databases to identify potential candidate targets for drug treatment. Experiments were conducted at the cell, tissue, and mouse EM model levels to characterize the aberrant expression patterns, molecular mechanisms, biological behaviors of endometriosis as well as treatment outcomes. Results: BST2 was significantly upregulated in ectopic endometrial tissues and cells compared with control samples. Functional studies indicated that BST2 promoted proliferation, migration, and lymphangiogenesis and inhibited apoptosis in vitro and in vivo. The transcription factor (TF) IRF6 induced high BST2 expression by directly binding the BST2 promoter. The underlying mechanism by which BST2 functions in EM was closely related to the canonical NF-kB signaling pathway. New lymphatic vessels may serve as a channel for the infiltration of immune cells into the endometriotic microenvironment; these immune cells further produce the proinflammatory cytokine IL-1β, which in turn further activates the NF-κB pathway to promote lymphangiogenesis in endometriosis. Conclusion: Taken together, our findings provide novel insight into the mechanism by which BST2 participates in a feedback loop with the NF-κB signaling pathway and reveal a novel biomarker and potential therapeutic target for endometriosis. [ABSTRACT FROM AUTHOR]

In this study, nanoscale protuberances were fabricated on poly(methyl methacrylate) (PMMA) thin-film surface by mechanical scanning probe lithography, namely dynamic plowing lithography (DPL). However, the formation mechanism of protuberances by DPL remains unclear. Therefore, this paper investigated the formation mechanism and fine control of the protuberances. Considering the influence of the dynamic response of the probe cantilever, proportional gain and integral gain were investigated when the tip scratched PMMA film in scan mode. Using feedback loop control, the increased depth of the groove at the beginning was attributed to the peak of the oscillation amplitude caused by the interplay between lithography and feedback. The cantilever vibrated dramatically when integral gain was increased. When the integral gain was increased to 5, the machined depth was approximately 82 nm, which exposed the substrate. Furthermore, the machined depth depended on the proportional gain when the integral gain was 0. The increased steady-state error that occurred at decreased proportional gain caused the tip to penetrate the sample deeper. In addition, the volume of the pile-up was larger than the removed material. And the material pile-up contributed to the fabrication of the protuberance. Finally, uniform and reliable protuberances were fabricated without proportional gain and integral gain. [Display omitted] • Explored the machinability of dynamic plowing lithography in relation to feedback loop control. • Identified the effects of proportional gain and integral gain on the formation of protuberances. • Revealed the formation of reliable and uniform protuberances consisting of material pile-up. [ABSTRACT FROM AUTHOR]

Our physiology and behavior follow precise daily programs that adapt us to the alternating opportunities and challenges of day and night. Under experimental isolation, these rhythms persist with a period of approximately one day (circadian), demonstrating their control by an internal autonomous clock. Circadian time is created at the cellular level by a transcriptional/translational feedback loop (TTFL) in which the protein products of the Period and Cryptochrome genes inhibit their own transcription. Because the accumulation of protein is slow and delayed, the system oscillates spontaneously with a period of ∼24 hours. This cell-autonomous TTFL controls cycles of gene expression in all major tissues and these cycles underpin our daily metabolic programs. In turn, our innumerable cellular clocks are coordinated by a central pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. When isolated in slice culture, the SCN TTFL and its dependent cycles of neural activity persist indefinitely, operating as "a clock in a dish". In vivo, SCN time is synchronized to solar time by direct innervation from specialized retinal photoreceptors. In turn, the precise circadian cycle of action potential firing signals SCN-generated time to hypothalamic and brain stem targets, which co-ordinate downstream autonomic, endocrine, and behavioral (feeding) cues to synchronize and sustain the distributed cellular clock network. Circadian time therefore pervades every level of biological organization, from molecules to society. Understanding its mechanisms offers important opportunities to mitigate the consequences of circadian disruption, so prevalent in modern societies, that arise from shiftwork, aging, and neurodegenerative diseases, not least Huntington's disease. [ABSTRACT FROM AUTHOR]