Feedback Loop Model Research Articles

Symmetry breaking and fate divergence during lateral inhibition in Drosophila.

Lateral inhibition mediates alternative cell fate decision and produces regular cell fate patterns with fate symmetry breaking (SB) relying on the amplification of small stochastic differences in Notch activity via an intercellular negative feedback loop. Here, we used quantitative live imaging of endogenous Scute (Sc), a proneural factor, and of a Notch activity reporter to study the emergence of Sensory Organ Precursor cells (SOPs) in the pupal abdomen of Drosophila. SB was observed at low Sc levels and was not preceded by a phase of intermediate Sc expression and Notch activity. Thus, mutual inhibition may only be transient in this context. In support of the intercellular feedback loop model, cell-to-cell variations in Sc levels promoted fate divergence. The size of the apical area of competing cells did not detectably bias this fate choice. Surprisingly, cells that were in direct contact at the time of SB could adopt the SOP fate, albeit at low frequency (10%). These lateral inhibition defects were corrected by cellular rearrangements, not cell fate change, highlighting the role of cell-cell intercalation in pattern refinement.

FLM-based AFL improves physics engagement and conceptual understanding

Assessment for learning (AFL) is a pedagogical approach that enhances student learning outcomes through high-quality feedback. This study investigates the effectiveness of integrating the feedback loop model (FLM) with AFL to improve students' engagement and understanding of physics, specifically in kinematics and motion dynamics. The study employs a mixed-methods research design, combining quantitative and qualitative data to assess the impact of the FLM-based AFL approach. A one-group pretest-posttest design was used, supported by research instruments that measured student engagement and their conceptual grasp of physics. The findings indicate that integrating FLM into AFL led to significant improvements, evidenced by Cohen’s effect size of 1.91, highlighting a substantial impact on student learning. These results affirm that FLM-based AFL positively affects student engagement and understanding of physics. The study contributes to the existing research on effective assessment methods, providing valuable insights for educators and policymakers in developing enhanced assessment and teaching strategies. This study emphasizes the potential benefits of incorporating FLM-based AFL in diverse educational settings to elevate student learning experiences and outcomes.

Neurobiological Correlates of Psychedelic Experiences and Psychedelic-Associated Adverse Effects.

This chapter offers a comprehensive overview of our current understanding of the neural mechanisms underlying the effects of psychedelic drugs, with a primary focus on human neuroimaging studies. Whenever possible, we explore the neurobiological mechanisms that may underly acute and subacute adverse effects and describe hypotheses on how these results may inform on the pathophysiology of psychiatric illnesses. We delve into the general effects of psychedelics on EEG, fMRI, and PET measurements, drawing insights from experiments that have assessed their acute biological mechanisms. Additionally, we review the relatively limited literature exploring pre- to postdrug changes. Throughout this chapter, we explore the prevailing models of psychedelic drug actions, including the Cortico-Striato-Thalamo-Cortical (CSTC) feedback loop model, the entropic brain hypothesis, the REBUS principle (an extension of predictive brain theories), and the claustrum hypothesis. Finally, we delve into the neural correlates of distinct features of the psychedelic experience, encompassing visual effects, social and emotional impacts, and the phenomenon of ego dissolution. We offer speculations on how our current understanding of acute drug effects might relate to the rarely occurring long-term adverse effects. It is important to note that due to the scarcity of data, these speculations remain tentative.

A critical signal for phenotype transition driven by negative feedback loops

The biological rhythms governed by negative feedback loops have undergone extensive investigation. However, developing reliable and versatile warning signals to predict periodic fluctuations in physiological processes and behaviors associated with these rhythms remains a challenge. Here, we monitored the heart rate and tracked ovulation dates of 91 fertile women. The finding strongly links the velocity (derivative) of heart rate with ovulation in menstrual cycles, providing a predictive warning signal. Similarly, an analysis of calcium signaling in the suprachiasmatic nucleus (SCN) of mice reveals that the maximum velocity of rising calcium signal aligns with locomotor activity offsets. To demonstrate the generality of derivative-transitions link, numerical simulations using a negative feedback loop model were conducted. Statistical analysis indicated that over 90% of the oscillations exhibited a correlation between maximum velocity and transition points. Consequently, the maximum velocity derived from oscillatory curves holds significant potential as an early warning signal for critical transitions.

The Case for the Target of Rapamycin Pathway as a Candidate Circadian Oscillator.

The molecular mechanisms that drive circadian (24 h) rhythmicity have been investigated for many decades, but we still do not have a complete picture of eukaryotic circadian systems. Although the transcription/translation feedback loop (TTFL) model has been the primary focus of research, there are many examples of circadian rhythms that persist when TTFLs are not functioning, and we lack any good candidates for the non-TTFL oscillators driving these rhythms. In this hypothesis-driven review, the author brings together several lines of evidence pointing towards the Target of Rapamycin (TOR) signalling pathway as a good candidate for a non-TTFL oscillator. TOR is a ubiquitous regulator of metabolism in eukaryotes and recent focus in circadian research on connections between metabolism and rhythms makes TOR an attractive candidate oscillator. In this paper, the evidence for a role for TOR in regulating rhythmicity is reviewed, and the advantages of TOR as a potential oscillator are discussed. Evidence for extensive feedback regulation of TOR provides potential mechanisms for a TOR-driven oscillator. Comparison with ultradian yeast metabolic cycles provides an example of a potential TOR-driven self-sustained oscillation. Unanswered questions and problems to be addressed by future research are discussed.

Impactof formative assessment based on feedback loop model on high school students conceptual understanding and engagement with physics

Impactof formative assessment based on feedback loop model on high school students conceptual understanding and engagement with physics

Delayed closed-loop neurostimulation for the treatment of pathological brain rhythms in mental disorders: a computational study.

Mental disorders are among the top most demanding challenges in world-wide health. A large number of mental disorders exhibit pathological rhythms, which serve as the disorders characteristic biomarkers. These rhythms are the targets for neurostimulation techniques. Open-loop neurostimulation employs stimulation protocols, which are rather independent of the patients health and brain state in the moment of treatment. Most alternative closed-loop stimulation protocols consider real-time brain activity observations but appear as adaptive open-loop protocols, where e.g., pre-defined stimulation sets in if observations fulfil pre-defined criteria. The present theoretical work proposes a fully-adaptive closed-loop neurostimulation setup, that tunes the brain activities power spectral density (PSD) according to a user-defined PSD. The utilized brain model is non-parametric and estimated from the observations via magnitude fitting in a pre-stimulus setup phase. Moreover, the algorithm takes into account possible conduction delays in the feedback connection between observation and stimulation electrode. All involved features are illustrated on pathological α- and γ-rhythms known from psychosis. To this end, we simulate numerically a linear neural population brain model and a non-linear cortico-thalamic feedback loop model recently derived to explain brain activity in psychosis.

Hemodynamic alterations response to Chinese acupuncture therapy monitored by a custom near-infrared spectroscopy probe with an open hole.

Traditional acupuncture, a popular traditional Chinese medicine (TCM) technique, has demonstrated potential in relieving various ailments' symptoms. However, its black-box feedback loop model has limited proper evaluation and use by unskilled practitioners. This study aimed to analyze hemodynamic signals around acupoints during acupuncture to identify significant parameter changes. We designed hollow near-infrared spectroscopy (NIRS) probes for real-time measurements during acupuncture at acupoints, monitoring oxy-hemoglobin (HbO), deoxy-hemoglobin (Hb), and blood volume (HbT) changes. Acupuncture was performed on the "Xuehai" acupoint in 17 healthy subjects, with NIRS measuring hemodynamic alterations. Results showed significant and consistent increases in Hb and HbT around the acupoint, returning to baseline values after needle removal. One case of fainting revealed a significant Hb increase and HbO decrease. Acupuncture may induce tissue vasodilation and enhance oxygen consumption. This research provides a potential explanation for acupuncture's mechanism and emphasizes NIRS's potential in TCM.

The human-centric Industry 5.0 collaboration architecture

While the primary focus of Industry 4.0 revolves around extensive digitalization, Industry 5.0, on the other hand, seeks to integrate innovative technologies with human actors, signifying an approach that is more value-driven than technology-centric. The key objectives of the Industry 5.0 paradigm, which were not central to Industry 4.0, underscore that production should not only be digitalized but also resilient, sustainable, and human-centric. This paper is focusing on the human-centric pillar of Industry 5.0. The proposed methodology addresses the need for a human-AI collaborative process design and innovation approach to support the development and deployment of advanced AI-driven co-creation and collaboration tools. The method aims to solve the problem of integrating various innovative agents (human, AI, IoT, robot) in a plant-level collaboration process through a generic semantic definition, utilizing a time event-driven process. It also encourages the development of AI techniques for human-in-the-loop optimization, incorporating cross-checking with alternative feedback loop models. Benefits of this methodology include the Industry 5.0 collaboration architecture (I5arc), which provides new adaptable, generic frameworks, concepts, and methodologies for modern knowledge creation and sharing to enhance plant collaboration processes.•The I5arc aims to investigate and establish a truly integrated human-AI collaboration model, equipped with methods and tools for human-AI driven co-creation.•Provide a framework for the co-execution of processes and activities, with humans remaining empowered and in control.•The framework primarily targets human-AI collaboration processes and activities in industrial plants, with potential applicability to other societal contexts.

A Brief History of Ends/Goals: How Can Goals (Motivation) Emerge from a Goalless World?

This paper will be devoted to the discussion of the concept of goal in human understanding. The scientific discussion of it can be traced back to ancient Greece, where it was called teleology. This triggered a lot of questions: as theories prostrating the universe as uniformed emerged, these types of teleological ideas were attracted by natural philosophers studying determinism: things do not exist to serve a purpose, they exist only because, under the influence of other things in the world, they have to be there. The sun is not there to provide brightness to the world, it was there long before the exitance of the world. Nevertheless, the unsettling problem is that human beings do, a lot of times, think in a goal-directed way, so how to reconcile the fact that no teleological language can explain natural phenomena with the fact that teleological thinking exists in human understanding becomes the million dollar question. Still, there could be a solution, not as straightforward as the problem, but sufficient to demonstrate how goals can emerge from a goalless nature. With the conatus theory as the basis, this paper is going to review how it can be the building block of the nowadays negative feedback loop model and such a model is also a variation of Hume theory of association and passion.

Transcriptional regulation of Sis1 promotes fitness but not feedback in the heat shock response.

The heat shock response (HSR) controls expression of molecular chaperones to maintain protein homeostasis. Previously, we proposed a feedback loop model of the HSR in which heat-denatured proteins sequester the chaperone Hsp70 to activate the HSR, and subsequent induction of Hsp70 deactivates the HSR (Krakowiak et al., 2018; Zheng et al., 2016). However, recent work has implicated newly synthesized proteins (NSPs) - rather than unfolded mature proteins - and the Hsp70 co-chaperone Sis1 in HSR regulation, yet their contributions to HSR dynamics have not been determined. Here, we generate a new mathematical model that incorporates NSPs and Sis1 into the HSR activation mechanism, and we perform genetic decoupling and pulse-labeling experiments to demonstrate that Sis1 induction is dispensable for HSR deactivation. Rather than providing negative feedback to the HSR, transcriptional regulation of Sis1 by Hsf1 promotes fitness by coordinating stress granules and carbon metabolism. These results support an overall model in which NSPs signal the HSR by sequestering Sis1 and Hsp70, while induction of Hsp70 - but not Sis1 - attenuates the response.

Effects of Feedback Loop Model on Teachers’ Attitudes, Self-Efficacy and Classroom Practices towards Formative Assessment

This research endeavor that aimed to determine the changes in the Senior High School (SHS) teachers’ attitudes, self-efficacy, and classroom practices toward formative assessment (FA) as they implemented Feedback Loop Model (FLM) in their Physics classes was examined to assess any improvement in their attitudes, self-efficacy and teachers’ FA practices. Using a concurrent triangulation design to address the objectives of this study, a convenient sampling method was employed. Out of the 23 teacher-participants who attended the webinar series on FLM, only 3 Physics teachers agreed and participated in the follow-up process, which requires implementing FLM in their classrooms. These teachers approved recording their online classes, which were used for observation by external observers or cross-examiners. Likewise, they agreed to keep journals or reflections as they implemented the FLM in their Physics classes. Results have shown that teachers’ attitudes, self-efficacy, and classroom practices on FA were affected significantly, leading to positive attitudes toward utilizing the assessment and improved self-confidence in applying FA in their classes. Teachers were also able to manifest and build a classroom environment that supports formative assessment, signifying the positive effect of the FLM. Therefore, it is suggested that FLM be recommended to strengthen the use of FA by conducting more professional development programs. This way, teachers would have opportunities to refine their strategies and enhance collaboration and professional growth.

Effect of Mach number on the aeroacoustic feedback loop generating airfoil tonal noise

Airfoil tonal noise emission at low-to-moderate Reynolds number and flow conditions featuring a laminar separation bubble close to the trailing edge is often related to an aeroacoustic feedback mechanism and, therefore, the Mach number is a primary parameter for the flow field and noise generation. This study experimentally explores the effect of the Mach number on airfoil tonal noise generation in the nominally incompressible flow regime. Using airfoil profiles of different chord lengths, the Mach number is varied for a constant Reynolds number. Acoustic and flow field measurements for a range of combinations of Reynolds and Mach numbers were conducted. At zero incidence, the tonal noise regime in the Reynolds number domain is found to be sensitive to the Mach number. At non-zero angle of attack (2°), the noise generation is found to be dominated by vortex shedding over a separation bubble on the pressure side. The details of the separation bubble and shedding process depend on the Mach number. The frequencies of the dominant tones and the frequency intervals between tones increase with the Mach number. Moreover, the measured frequency interval can be collapsed using a relation based on the aeroacoustic feedback loop model. The relation is rewritten to separate the effects of the Reynolds and Mach numbers. As a result, the dependence on the Mach number is identified and tested. In contrast, the tonal noise level shows a more complex dependence on details of the laminar separation bubble and the vortex shedding process.

Promoter methylation in a mixed feedback loop circadian clock model.

We investigate how epigenetic modifications to clock gene promoters affect transcriptomic activity in the circadian clock. Motivated by experimental observations that link DNA methylation with the behavior of the clock, we introduce and analyze an extension of the mixed feedback loop (MFL) model of François and Hakim. We extend the original model to include an additional methylated promoter state and allow for reversible protein sequestration, an important feature for circadian applications. First, working with the general form of the MFL model, we find that the qualitative behavior of the model is dictated by the promoter state with the highest transcription rate. We then build on the work of Kim and Forger, who analyzed the stability of the mammalian circadian clock by using a reduced form of the MFL model. We present a rigorous procedure for translating between the MFL model and the reduction of Kim and Forger. We then propose a model reduction more appropriate for the study of oscillatory promoter states, making use of a fully coupled quasi-steady-state approximation rather than the standard partially uncoupled quasi-steady-state approach. Working with the novel reduced form of the model, we find substantial differences in the transcription function and show that, although methylation contributes to period control, excessive methylation can abolish rhythmicity. Altogether our results show that even in a minimal clock model, DNA methylation has a nontrivial influence on the system's ability to oscillate.

Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice

A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal that glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We also demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a feedback loop model within the lysine/tryptophan oxidation pathway in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues and can be relieved by SIRT5 deacylation activity.

The psychological role of music and attentional control for religious experiences in worship.

This study investigated the psychological dynamics during worship experiences under the influence of different music conditions. In total, 60 believers were recruited to participate in experiments where they were asked to engage in worship and to connect with God while continuously ranking how strongly they sensed the presence of the divine. After each condition, they were asked to rate how well they were able to focus on God during the worship procedure. Based on a previously published Feedback Loop Model that portrays global psychological mechanisms in worship, we deduced two hypotheses: (1) the ability to focus on God is positively associated with how strong the subjective religious experience becomes, and (2) the different musical conditions yield varying degrees in the intensity of the felt presence of God. Our statistical analyses on the current sample demonstrate that both alternative hypotheses can be accepted. For the latter thesis, two further assumptions were at play: (1) we speculated that religious worship songs were associated with stronger divine experiences than with secular ones, and (2) it was assumed that if they could worship to their own selection of songs, the experience would be more powerful than with the ones that were provided by the research team. Whereas upon our investigation the former assumption can be deemed correct, the latter shows a positive but insignificant association.

Cellular Tango: how extracellular matrix adhesion choreographs Rac-Rho signaling and cell movement

The small GTPases Rac and Rho are known to regulate eukaryotic cell shape, promoting front protrusion (Rac) or rear retraction (Rho) of the cell edge. Such cell deformation changes the contact and adhesion of cell to the extracellular matrix (ECM), while ECM signaling through integrin receptors also affects GTPase activity. We develop and investigate a model for this three-way feedback loop in 1D and 2D spatial domains, as well as in a fully deforming 2D cell shapes with detailed adhesion-bond biophysics. The model consists of reaction–diffusion equations solved numerically with open-source software, Morpheus, and with custom-built cellular Potts model simulations. We find a variety of patterns and cell behaviors, including persistent polarity, flipped front-back cell polarity oscillations, spiral waves, and random protrusion-retraction. We show that the observed spatial patterns depend on the cell shape, and vice versa.

The feedback loops of discrete tones in under-expanded impinging jets

The upstream-propagating waves of feedback loops in under-expanded impinging jets are investigated through several typical flow conditions. Schlieren image capturing and far-field acoustic measurement are applied to the jet. The flow structures related to the discrete tones are extracted through dynamic mode decomposition (DMD), and the standing waves formed by the resonance are identified from the normalized amplitude fields of the chosen DMD modes. Spatial Fourier transforms are applied along the axial direction on the chosen DMD modes to obtain the spatial wavenumber spectra, from which the two wave disturbances caused by the interaction between Kelvin–Helmholtz (K–H) waves and shock cells can be identified. The upstream and downstream-propagating components of the feedback loop are rebuilt, respectively, via bandpass filtering. The wavenumbers of the upstream-propagating components in the feedback loop and the wavenumbers of disturbance waves are compared along the jet shear layer; the results suggest more than one closure mechanism of the feedback loop. For the impinging tones which have the same frequencies as the A1 and B modes in free jet, the closure mechanism of the feedback loop is the Mach radiation generated by the interaction between K–H waves and shock cells. For the other tones, their frequencies are consistent well with the allowable frequency ranges of the neutral wave mode. The combination of the neutral wave mode with the classical feedback loop model also gives strong evidence that the upstream-propagating waves for these tones may be the jets' inherent neutral wave.

How To Stay in the Loop. A Think-Aloud Study on Dictionary Use by Excellent Secondary-School Students of Ancient Greek

AbstractDictionary use in secondary-school classics education in the Netherlands is problematic and an important cause of poor translations and text comprehension. Research on the topic is scarce and dictionary training plays a marginal role in the classics teaching practice. This explorative, qualitative think-aloud study examines which dictionary activities lead to success. We observed excellent secondary-school students while they were translating an Ancient Greek text. A feedback loop model, characterised as a slow process of constant verification, is used to analyse their dictionary behaviour. The findings show that successful dictionary activities depend on moving back and forth between text and dictionary, while the students reduce the cognitive load by activating schemata. Performing informed searches and using their fingers or the ribbon bookmark facilitate this process. In addition, closely monitoring the process with a critical mind, and linguistic reflection using appropriate metalanguage seem crucial.

Mathematical Model with Feedback Loop in Company Control

This article is devoted to the further development of feedback loop models. They are used in the management of a single-industry firm. The development of the studying consists in the mathematical modeling of transients and assessing their impact on economic indicators. To solve this problem, the following was done in the article. A structural model of the functioning of a single-industry firm (SIF) is presented. It is built in accordance with the theory of automatic control (TAC) and includes elements: a management unit, a production unit, a sales unit, information nodes, as well as a feedback loop (FL). Equations and relationships describing the logic of the functioning of the company as a production system are presented. They allowed us to derive dynamic relationships and differential equations that reflect feedback loops on revenue and production costs. The system of expressions in operator form is presented, which describes the contour of the FL SIF. It has the form of a system of differential equations. It forms the basis of the mathematical model of SIF in the control system. This model made it possible to obtain a graphical interpretation of transients with closed and open FL based on the use of the Mathcad editor. Transients are fluctuations in sales volumes and production costs in the presence of disturbing influences. This is the scientific result and determines the novelty of the article.