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Structural equation models (SEMs) involving feedback loops may offer advantages over standard instrumental variables estimators in terms of modelling causal effects in the presence of bidirectional relationships. In the following note, we show that in the case of a single "exposure" and "outcome" variable, modelling relationships using a SEM with a simple bidirectional linear feedback loop offers no advantage over traditional instrumental variables estimators in terms of consistency (i.e. both approaches yield consistent estimates of the causal effect, provided that causal estimates are obtained in both directions). In the case of finite samples, traditional IV estimators and SEM exhibited similar power across many of the conditions we examined, although which method performed best depended on the residual correlation between variables and the strength of the instruments. In particular, the power of SEM was insensitive to the residual correlation between variables, whereas the power of the Wald estimator/2SLS improved (deteriorated) relative to SEM as the magnitude of the residual correlation increased (decreased) assuming a positive causal effect of the exposure on the outcome. The power of SEM improved relative to the Wald estimator/2SLS as the instruments explained more residual variance in the "outcome" variable. [ABSTRACT FROM AUTHOR]

Green transition is in the core of the European policy agenda to achieve the ambitious goal of climate neutrality following the launch of the European Green Deal. The cornerstone of the new growth strategy of Europe is resource efficiency which focuses on shifting to a more sustainable production paradigm by conserving scarce resources and by prioritizing enhanced environmental performance. Scattered efforts to investigate the drivers of resource efficiency measures have shed light on the key drivers, however, those consider resource efficiency measures in isolation neglecting for feedback loops influencing green transition. Therefore, we develop a conceptual framework to study green transition as a system of resource efficiency measures affected by feedback loops, path dependence, green technologies, and green policy tools. We mobilize the analysis by devising a unique balanced panel covering the EU-28 from 2010 through 2019, including policy efforts paving the way for green transition. Econometric results based on a system of fractional probit models, indicate that resource efficiency measures are intertwined via feedback loops, especially in the case of environmental efficiency. Green technologies affect green transition, however, rebound effects emerge in the case of energy efficiency. Past performance affects current levels pushing towards divergence. Evidence suggests that green taxation fosters energy efficiency whereas hinders environmental efficiency. The asymmetric operation of feedback loops and green taxation on energy and environmental efficiency highlights that horizontal policies hinder rather than foster green transition. This study contributes to SDGs 7, 12, 13 and 16. [ABSTRACT FROM AUTHOR]

A software project measurement model plays a crucial role in assessing, monitoring, and improving software development processes and product quality. However, existing models often focus on localized optimization, limiting their effectiveness. This study introduces the 5P model to software project measurement, aiming to achieve global optimization and control. The article presents a conceptual overview of the 5P model and a detailed illustration of its steps using a real development process. By adopting a system thinking approach, the proposed model enables global optimization by aligning project objectives, product outcomes, and stakeholders' needs. Three feedback loops are utilized to ensure the alignment of project purposes, performance measurement, and stakeholder requirements. The 5P model provides transparent metrics, enabling stakeholders to track progress and make informed decisions. Results confirm the model's significant value in software project measurement, facilitating improved project outcomes and stakeholder satisfaction. [ABSTRACT FROM AUTHOR]

A central and fundamental issue in ecology is to understand the relationship between complexity and stability. Increased empirical evidences demonstrated no clear relationships between complexity metrics and stability, and recent food web loop analyses suggested that maximum loop weight as well as the summation ratio between 3- and 2-link feedback loop weights could be better estimators of system stability. However, the importance of longer loops than 3-link on the stability remains unclear. Here, we use 127 marine food webs and the matrix product and trace method to investigate the relationship between loops with maximum of 7 links and food web stability. We found that feedback metrics | a 2 n + 1 / a 2 n | , i.e., the ratio of the sums of (2n + 1)-link and 2n-link loop weights, are strongly related with stability. These sum weight ratios can be regarded as the coupling strength between omnivory loops and their one-species-delete subloops, including the smallest three species and high-level omnivory ones. Further theoretical simulations of bioenergetic consumer-resource models with allometric constraints strengthen this finding. These results suggest that both longer loops and omnivory are important drivers of the food web stability. [ABSTRACT FROM AUTHOR]

In many fields of science, various types of models are available to describe phenomena, observations and the results of experiments. In the last decades, given the enormous advances of information gathering technologies, also machine learning techniques have been systematically deployed to extract models from the large available databases. However, regardless of their origins, no universal criterion has been found so far to select the most appropriate model given the data. A unique solution is probably a chimera, particularly in applications involving complex systems. Consequently, in this work a utility-based approach is advocated. However, the solutions proposed are not purely subjective but all based on "objective" criteria, rooted in the properties of the data, to preserve generality and to allow comparative assessments of the results. Several methods have been developed and tested, to improve the discrimination capability of basic Bayesian and information theoretic criteria, with particular attention to the BIC (Bayesian Information Criterion) and AIC (Akaike Information Criterion) indicators. Both the quality of the fits and the evaluation of model complexity are aspects addressed by the advances proposed. The competitive advantages of the individual alternatives, for both cross sectional data and time series, are clearly identified, together with their most appropriate fields of application. The proposed improvements of the criteria allow selecting the right models more reliably, more efficiently in terms of data requirements and can be adjusted to very different circumstances and applications. Particular attention has been paid to ensure that the developed versions of the indicators are easy to implement in practice, in both confirmatory and exploratory settings. Extensive numerical tests have been performed to support the conceptual and theoretical considerations. [ABSTRACT FROM AUTHOR]

In this paper, we develop a network-based methodology to investigate the problems related to matrix stability and bifurcations in nonlinear dynamical systems. By matching a matrix with a network, i.e., interaction graph, we propose a new network-based matrix analysis method by proving a theorem about matrix determinant under which matrix stability can be considered in terms of feedback loops. Especially, the approach can tell us how a node, a path, or a feedback loop in the interaction graph affects matrix stability. In addition, the roles played by a node, a path, or a feedback loop in determining bifurcations in nonlinear dynamical systems can also be revealed. Therefore, the approach can help us to screen optimal node or node combinations. By perturbing them, unstable matrices can be stabilized more efficiently or bifurcations can be induced more easily to realize desired state transitions. To illustrate feasibility and efficiency of the approach, some simple matrices are used to show how single or combinatorial perturbations affect matrix stability and induce bifurcations. In addition, the main idea is also illustrated through a biological problem related to T cell development with three nodes: TCF-1, GATA3, and PU.1, which can be considered to be a three-variable nonlinear dynamical system. The approach is especially helpful in understanding crucial roles of single or molecule combinations in biomolecular networks. The approach presented here can be expected to analyze other biological networks related to cell fate transitions and systematic perturbation strategy selection. [ABSTRACT FROM AUTHOR]

Asian developing countries are frequently devastated by tropical cyclones. While the literature is replete with their impacts on economic growth, the impacts on critical sustainable development indicators, namely income inequality, health, and human capital accumulation, have seldom been explored. In this study, we measure the direct, indirect, and spillover impacts of tropical cyclones on the sustainable development of eight developing countries in Asia. This study uses the dynamic generalized method of moments model to estimate the impact of occurrences and casualties in these countries over 28 years. Our results indicate that recurrent tropical cyclones increase income inequality, reaching the threshold at 0.4 cyclone. The mortality rate tends to rise, which decreases after 2.5 cyclonic occurrences. Similarly, cyclones seem to initially reduce the expected years of schooling, which starts increasing after one cyclonic occurrence. These weakening impacts provide evidence of negative feedback loops. We also find evidence of domino effects and gender effects. The resilience factors are controlled for, as it helps the developing countries recover from the vicious cycles. The feedback loops can be broken by taking timely interventions, mitigation and adaptation. [ABSTRACT FROM AUTHOR]

Abstract Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole‐cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth‐mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth‐mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.

In current philosophy of mind, there is lively debate over whether emotions, moods, and other affects can extend to comprise elements beyond one’s organismic boundaries. At the same time, there has been growing interest in the nature and significance of so-called existential feelings, which, as the term suggests, are feelings of one’s overall being in the world. In this article, I bring these two strands of investigation together to ask: can the material underpinnings of existential feelings extend beyond one’s skull and skin? To begin, I introduce and adopt a componential-systemic view of extended affectivity. In doing so, I specify the vehicle externalist criteria for extension employed in my analysis. I then define what existential feelings are and pinpoint several key issues in their potential extension. More specifically, I identify sensorimotor ‘know-how’ as a possibly extending component of existential feeling and posit it as the fulcrum of my argument. Finally, I move on to consider the extension of existential feeling via sensory substitution, especially through so-called tactile visual sensory substitution (TVSS) devices. Informed by both philosophical and empirical studies, I argue that, under certain conditions, (a) the agent’s implicit sensorimotor processing and a TVSS device can become coupled into a new systemic whole, which in turn (b) reconfigures the material underpinnings of the agent’s preintentional world-experience. This, I conclude, counts as a cogent case for extended existential feeling. [ABSTRACT FROM AUTHOR]

The complex relationship that exists between water resources and agricultural production has been increasing constantly globally. Several factors are interacting to influence the management of water resources making the system complex and dynamic. To increase the understanding of these complex and dynamic systems, relevant tools are needed to identify the causal relationships that exist between the drivers and their influences on the system. Participatory modelling based on the system dynamics approach provides a simplistic and visualisation tool that can improve the understanding of the functioning of a complex and dynamic system. A multi-stage participatory approach was used in this study involving relevant stakeholders in the development of an integrated conceptual system dynamic model using causal loop diagrams. This approach was used because it captures the thought process and mental model of relevant stakeholders in the development of the model, making it a valuable tool for policy and decision making at government and individual levels. The integrated model built in this study used causal loop diagrams to address problems of water management and agricultural sustainability in the Breede River Catchment. The model shows major causal-relationships and feedback loops that determine the functioning of the overall system. The model demonstrates the usefulness of the participatory approach in solving problems related to water management and agricultural development in the catchment. [ABSTRACT FROM AUTHOR]

Abstract Quorum sensing is a chemical signaling mechanism used by bacteria to communicate and orchestrate group behaviors. Multiple feedback loops exist in the quorum‐sensing circuit of the model bacterium Vibrio harveyi. Using fluorescence microscopy of individual cells, we assayed the activity of the quorum‐sensing circuit, with a focus on defining the functions of the feedback loops. We quantitatively investigated the signaling input–output relation both in cells with all feedback loops present as well as in mutants with specific feedback loops disrupted. We found that one of the feedback loops regulates receptor ratios to control the integration of multiple signals. Together, the feedback loops affect the input–output dynamic range of signal transmission and the noise in the output. We conclude that V. harveyi employs multiple feedback loops to simultaneously control quorum‐sensing signal integration and to ensure signal transmission fidelity.

The paper demonstrates the use of systems archetypes as a practical method to understand the impact of urban policies and programs on urban dynamics. Systems archetypes are generic templates to represent the structural and behavioral insights in dynamic systems. They highlight counterintuitive behavior of social systems and the recursive nature of complex systems. This paper maps systems archetypes pertaining to the failures in urban programs, as described by Prof. J.W. Forrester in his classic book Urban Dynamics. 'Fixes that backfire' is a systems archetype that construes a situation where a fix effective in a short term creates long term behavioral side effects which might need even more fixes. This archetype is mapped onto the failures in urban programs. The insights to the reasons of failures of urban programs through the systems archetypes lens will enable us bring a change in the society and assist policy makers by being cautious of the unintended consequences while devising urban policies. Therefore, an approach has been proposed to deal with urban change by applying archetypal structures to urban problems. The approach illustrated in this paper will enable urban governors and planners, distinguish programs and policies that may or may not lead to desired dynamics. [ABSTRACT FROM AUTHOR]

Aims: This review was developed to introduce the essential components and variants of structural equation modeling (SEM), synthesize the common issues in SEM applications, and share our views on SEM's future in ecological research. Methods: We searched the Web of Science on SEM applications in ecological studies from 1999 through 2016 and summarized the potential of SEMs, with a special focus on unexplored uses in ecology. We also analyzed and discussed the common issues with SEM applications in previous publications and presented our view for its future applications. Results: We searched and found 146 relevant publications on SEM applications in ecological studies. We found that five SEM variants had not commenly been applied in ecology, including the latent growth curve model, Bayesian SEM, partial least square SEM, hierarchical SEM, and variable/model selection. We identified ten common issues in SEM applications including strength of causal assumption, specification of feedback loops, selection of models and variables, identification of models, methods of estimation, explanation of latent variables, selection of fit indices, report of results, estimation of sample size, and the fit of model. Conclusions: In previous ecological studies, measurements of latent variables, explanations of model parameters, and reports of key statistics were commonly overlooked, while several advanced uses of SEM had been ignored overall. With the increasing availability of data, the use of SEM holds immense potential for ecologists in the future. [ABSTRACT FROM AUTHOR]

Changes in the seascape often result in altered hydrodynamics that lead to coinciding changes in sediment dynamics. Little is known on how altered sediment dynamics affect long-term seagrass persistence. We studied the thresholds of sediment dynamics in relation to seagrass presence by comparing sediment characteristics and seagrass presence data of seven separate seagrass meadows. All meadows had a long-term (>20 years) presence. Within these meadows, we distinguish so-called 'hotspots' (areas within a meadow where seagrass was found during all mapping campaigns) and 'coldspots' (with infrequent seagrass presence). We monitored static sediment characteristics (median grain size, bulk density, silt content) and sediment dynamics (that is, bed level change and maximum sediment disturbance depth), bioturbation (that is, lugworm densities and induced fecal pit and mound relief), and seagrass cover. We statistically analyzed which sediment characteristic best explains seagrass cover. Densely vegetated hotspots were shown to have lower sediment dynamics than sparsely vegetated hotspots and coldspots, whereas static sediment characteristics were similar (grain size, bulk density). The vegetation cover was either low (2-15%) or high (>30%) and sediment dynamics showed a threshold for vegetation cover. From this correlative finding, we postulate a self-sustaining feedback of relatively dense seagrass via sediment stabilization and accordingly a runaway feedback once the seagrass cover becomes too sparse. The sensitivity for sediment dynamics shown in our study implies that future existence of seagrass meadows may be at risk as ongoing climate change might directly (increased environmental extremes) or indirectly (changing seascapes) negatively affect seagrass beds. [ABSTRACT FROM AUTHOR]

Stability of a dynamic equilibrium in a predator-prey system depends both on the type of functional response and on the point of equilibrium on the response curve. Saturation effects from Holling type II responses are known to destabilise prey populations, while a type III (sigmoid) response curve has been shown to provide stability at lower levels of saturation. These effects have also been shown in multi-trophic model systems. However, stability analyses of observed equilibria in real complex ecosystems have as yet not assumed non-linear functional responses. Here, we evaluate the implications of saturation in observed balanced material-flow structures, for system stability and sustainability. We first make the effects of the non-linear functional responses on the interaction strengths in a food web transparent by expressing the elements of Jacobian 'community' matrices for type II and III systems as simple functions of their linear (type I) counterparts. We then determine the stability of the systems and distinguish two critical saturation levels: (1) a level where the system is just as stable as a type I system and (2) a level above which the system cannot be stable unless it is subsidised, separating a stable materially sustainable regime from an unsustainable one. We explain the stabilising and destabilising effects in terms of the feedbacks in the systems. The results shed light on the robustness of observed patterns of interaction strengths in complex food webs and suggest the implausibility of saturation playing a significant role in the equilibrium dynamics of sustainable ecosystems. [ABSTRACT FROM AUTHOR]

A revised concept for urban water metabolism (UWM) is presented in this study to address the inadequacies in current research on UWM and the problems associated with the traditional urban water metabolic process. Feedback loops can be analyzed to increase the water environmental carrying capacity (WECC) of the new urban water metabolism system (UWMS) over that of a traditional UWMS. An analysis of the feedback loops of an UWMS was used to construct a system dynamics (SD) model for the system under a WECC restriction. Water metabolic processes were simulated for different scenarios using the Tongzhou District in Beijing as an example. The results for the newly developed UWM case showed that a water environment of Tongzhou District could support a population of 1.1926 × 10, an irrigation area of 375.521 km, a livestock of 0.7732 × 10, and an industrial value added of ¥193.14 × 10 (i.e. about US$28.285× 10) in 2020. A sensitivity analysis showed that the WECC could be improved to some extent by constructing new sewage treatment facilities or by expanding the current sewage treatment facilities, using reclaimed water and improving the water circulation system. [ABSTRACT FROM AUTHOR]

Creek bank salt marsh die-off is a conservation problem in New England, driven by predator depletion, which releases herbivores from consumer control. Many marshes, however, have begun to recover from die-off. We examined the hypothesis that the loss of the foundation species Spartina alterniflora has decreased facilitator populations, weakening reciprocal positive plant/animal feedbacks, resilience, and slowing recovery. Field surveys and experiments revealed that loss of Spartina leads to decreased biodiversity, and increased mortality and decreased growth of the ribbed mussel Geukensia demissa, a key facilitator of Spartina. Experimental addition of Geukensia facilitators to creek banks accelerated Spartina recovery, showing that their loss limits recovery and the reciprocal feedbacks that drive community resilience. Reciprocal positive feedbacks involving foundation species, often lost to human impacts, may be a common, but generally overlooked mechanism of ecosystem resilience, making their reestablishment a valuable restoration tool. [ABSTRACT FROM AUTHOR]

Molecular systems are uncertain: The variability of reaction parameters and the presence of unknown interactions can weaken the predictive capacity of solid mathematical models. However, strong conclusions on the admissible dynamic behaviors of a model can often be achieved without detailed knowledge of its specific parameters. In systems with a sign-definite Jacobian, for instance, cycle-based criteria related to the famous Thomas' conjectures have been largely used to characterize oscillatory and multistationary dynamic outcomes. We build on the rich literature focused on the identification of potential oscillatory and multistationary behaviors using parameter-free criteria. We propose a classification for sign-definite non-autocatalytic biochemical networks, which summarizes several existing results in the literature. We call weak (strong) candidate oscillators systems which can possibly (exclusively) transition to instability due to the presence of a complex pair of eigenvalues, while we call weak (strong) candidate multistationary systems those which can possibly (exclusively) transition to instability due to the presence of a real eigenvalue. For each category, we provide a characterization based on the exclusive or simultaneous presence of positive and negative cycles in the associated sign graph. Most realistic examples of biochemical networks fall in the gray area of systems in which both positive and negative cycles are present: Therefore, both oscillatory and bistable behaviors are in principle possible. However, many canonical example circuits exhibiting oscillations or bistability fall in the categories of strong candidate oscillators/multistationary systems, in agreement with our results. [ABSTRACT FROM AUTHOR]

Three points discussed in Glenn () are reviewed in the context of current events: the discipline of behavior analysis as a cultural system, the importance of that discipline in the training and regulation of behavior analytic practitioners, and Association for Behavior Analysis International (ABAI) as a cultural subsystem that links to all the other parts and therefore links the other parts to one another. Noting similarities between behavior analysis and biology, I consider the growth of biological sciences as a model for behavior analysis. Of particular importance for biology has been the role of basic biological sciences in the practice of medicine and the resulting feedback loops that have developed among its basic sciences, applied sciences, and medical practice. I suggest that behavior analysis explicitly follow this model and that ABAI has a critical role to play in leading the field to developing the feedback loops that have integrated the biological sciences and medicine. [ABSTRACT FROM AUTHOR]

A technique for bandwidth extension and noise optimization of wideband low-noise amplifier with dual feedback loops is presented. A LC-ladder matching network has been added in front of conventional amplifier with dual feedback loops. Detailed circuit analysis and general design procedures for the modified amplifier have been provided. The technique is applied to an amplifier covering the frequency range from DC to 6 GHz in a 0.5 μm InGaAs E-mode pHEMT process. Post-layout simulation shows S below −10 dB, S below −10 dB, flat S of 16 ± 0.2 dB, and flat NF of 1.85 ± 0.35 dB across the entire band, which confirms the improvement in bandwidth and noise performance. [ABSTRACT FROM AUTHOR]

Plant-soil feedbacks have been observed in many forest communities, but the role of the mycorrhizal community in perpetuating feedback loops is still poorly understood. Mycorrhizal community composition is closely linked to soil properties and host plant composition, which highlights their potential importance in plant-soil-fungus loops. Eastern hemlock (hemlock; Tsuga canadensis) seedlings were grown in soil bioassays in growth chambers and transplanted under closed forest canopy to examine the effect of hardwood and hemlock forest soil on seedling growth, survival, and ectomycorrhizal fungi (EMF) colonization. Seedlings propagated in hemlock forest soil had greater height growth compared with sterile control soil and achieved greater mycorrhizal colonization than seedlings grown in hardwood forest soils after 9 months in a growth chamber. Outplanted seedlings grown in hemlock communities achieved significantly greater increment growth than those seedlings grown in hardwood communities (mean height difference (95% CI) = 0.39 cm (0.14-0.63 cm)), although final survival and EMF colonization was similar between forest types. EMF diversity (Shannon-Wiener index (SE) = 1.88 (0.28) and 1.23 (0.44) for hardwood and hemlock, respectively) and community assemblage (Jaccard index (SE) = 19.0% (4%)) differed between the two forest communities. EMF community assemblage was associated with both the forest type (i.e. plant community/microsite effects) and initial soil type (i.e. soil characteristics/resistant inoculum). The results support previously observed positive feedbacks between conspecifics under hemlock forest communities and provides evidence for the role of the EMF community within this feedback loop. Alternatively, the reduced growth of hemlocks under hardwoods may be attributed to the different EMF community associated with that forest. [ABSTRACT FROM AUTHOR]

The GAL regulatory system is highly conserved in yeast species of Saccharomyces cerevisiae and Kluyveromyces lactis. While the GAL system is a well studied system in S. cerevisiae, the dynamic behavior of the KlGAL system in K. lactis has not been characterized. Here, we have characterized the GAL system in yeast K. lactis by developing a dynamic model and comparing its performance to its not-so-distant cousin S. cerevisiae. The present analysis demonstrates the significance of the autoregulatory feedbacks due to KlGal4p, KlGal80p, KlGal1p and Lac12p on the dynamic performance of the KlGAL switch. The model predicts the experimentally observed absence of bistability in the wild type strain of K. lactis, unlike the short term memory of preculturing conditions observed in S. cerevisiae. The performance of the GAL switch is distinct for the two yeast species although they share similarities in the molecular components. The analysis suggests that the whole genome duplication of S. cerevisiae, which resulted in a dedicated inducer protein, Gal3p, may be responsible for the high sensitivity of the system to galactose concentrations. On the other hand, K. lactis uses a bifunctional protein as an inducer in addition to its galactokinase activity, which restricts its regulatory role and hence higher galactose levels in the medium are needed to trigger the GAL system. [ABSTRACT FROM AUTHOR]

Background, aims, and scope: Life cycle assessment (LCA) according to ISO 14040 standard (ISO-LCA) is applied to assess the environmental impact per functional unit of new or modified products. However, new or modified products can also induce demand changes-so-called rebound effects. If overall environmental impact is of interest, there is a need to assess the potential magnitude of such rebound effects and to allow recommendations on how to mitigate these effects. To do so, this study proposes to complement the constant demand assumption (implicitly assumed by the ISO-LCA), commonly known as the ceteris paribus assumption, with a consumption-as-usual assumption allowing a systematic stepwise inclusion of rebound effects. Materials and methods: We base our results on a formal description of household consumption. To indicate the relevance of the proposed integration of rebound effects, different comparative LCAs are reviewed and the concept is applied to mobility as illustrative examples. Results: Based on a description of household demand and consumption feedback loops, we propose the consumption-as-usual concept, which in contrast to the constant demand assumption assumes that (1) the use of household resources for consumption does not change and (2) preferences remain the same. Household resources for example are purchasing power (we assume that households do not work less), time, and living space. We outline how this concept allows integrating potential rebound effects into ISO-LCA by considering three different cases of reallocating freed household resources. To illustrate the use of the consumption-as-usual concept, we draw implications for different comparative LCAs from the literature and illustrate cases with income and time rebound for different personal travel modes. Discussion: The consumption-as-usual concept is applicable to a broad range of product modifications and allows an important complementation of the LCA regarding rebound effects. For products with various changes in the need for household resources, the assessment becomes however a challenging task. The limits of the consumption-as-usual concept are mainly given by its two underlying assumptions. Therefore, new or modified products with the potential to change consumer preferences or even the amount of household resources used for consumption go beyond this concept. Conclusions: The integration of rebound effects is feasible for many comparative LCAs. It helps in increasing the reliability of the assessment of overall environmental impact reduction through new or modified products. In addition, a basis is provided with which to mitigate rebound effects and give appropriate recommendations to product users. Recommendations and perspectives: Potential rebound effects should be included in LCA in order to guide consumers and policy towards sustainable consumption. We recommend the consumption-as-usual concept for this purpose. To predict rebound effects under consumption as usual instead of outlining potential amplitudes, further research on household preferences is needed and an optimisation model should be applied for household consumption. However, even if data are available for such a prediction, the assessment of potential rebound effects is still recommended in order to recognise dangers and opportunities in consumption changes. [ABSTRACT FROM AUTHOR]

Kinase cascades in ERK5 (Extracellular signal-regulated kinases) and JNK (c-Jun N-terminal kinases) signaling pathways mediate the sensing and processing of stimuli. Cross-talks between signaling cascades is a likely phenomenon that can cause apparently different biological responses from a single pathway, on its activation. Feedback loops have the potential to greatly alter the properties of a pathway and its response to stimuli. Based on enzyme kinetic reactions, mathematical models have been developed to predict and analyze the impacts of cross-talks and feedback loops in ERK5 and JNK cascades. It has been observed that, there is no significant impact on neither ERK5 activation nor JNKs’ activation due to cross-talks between them. But it is due to cross-talks and feedback loops in ERK5 and JNK cascade, ERK5 gets activated in a transient manner in the absence of input signals. Planning to obtain the parameter values from the experimentalist and the result should be validated by experimental verification. [ABSTRACT FROM AUTHOR]

Feedback circuits are crucial dynamic motifs which occur in many biomolecular regulatory networks. They play a pivotal role in the regulation and control of many important cellular processes such as gene transcription, signal transduction, and metabolism. In this study, we develop a novel computationally efficient method to identify feedback loops embedded in intracellular networks, which uses only time-series experimental data and requires no knowledge of the network structure. In the proposed approach, a non-parametric system identification technique, as well as a spectral factor analysis, is applied to derive a graphical criterion based on non-causal components of the system’s impulse response. The appearance of non-causal components in the impulse response sequences arising from stochastic output perturbations is shown to imply the presence of underlying feedback connections within a linear network. In order to extend the approach to nonlinear networks, we linearize the intracellular networks about an equilibrium point, and then choose the magnitude of the output perturbations sufficiently small so that the resulting time-series responses remain close to the chosen equilibrium point. In this way, the impulse response sequences of the linearized system can be used to determine the presence or absence of feedback loops in the corresponding nonlinear network. The proposed method utilizes the time profile data from intracellular perturbation experiments and only requires the perturbability of output nodes. Most importantly, the method does not require any a priori knowledge of the system structure. For these reasons, the proposed approach is very well suited to identifying feedback loops in large-scale biomolecular networks. The effectiveness of the proposed method is illustrated via two examples: a synthetic network model with a negative feedback loop and a nonlinear caspase function model of apoptosis with a positive feedback loop. [ABSTRACT FROM AUTHOR]

Despite our increasing knowledge on the transcriptional networks connecting abscisic acid (ABA) signalling with the circadian clock, the molecular nodes in which both pathways converge to translate the environmental information into a physiological response are not known. Here, we provide evidence of a feedback mechanism linking the circadian clock with plant responses to drought. A key clock component (TOC1, timing of CAB expression 1) binds to the promoter of the ABA-related gene (ABAR/CHLH/GUN5) and controls its circadian expression. TOC1 is in turn acutely induced by ABA and this induction advances the phase of TOC1 binding and modulates ABAR circadian expression. Moreover, the gated induction of TOC1 by ABA is abolished in ABAR RNAi plants suggesting that the reciprocal regulation between ABAR and TOC1 expression is important for sensitized ABA activity. Genetic studies with TOC1 and ABAR over-expressing and RNAi plants showed defective responses to drought, which support the notion that clock-dependent gating of ABA function is important for cellular homeostasis under dry environments. [ABSTRACT FROM AUTHOR]

Molecular and genetic studies in the fruit fly Drosophila melanogaster have revealed that the circadian timekeeping mechanism is based on feedback loops in gene expression. These feedback loops, which are highly conserved in mammals, can be divided into temporally distinct transcriptional activation, repression, and reactivation phases. Determining how different phases of the transcriptional feedback cycle are controlled and integrated is necessary to understand the molecular basis of circadian timekeeping. In Drosophila, feedback loop function is initiated when hypophosphorylated CLOCK (CLK) forms a heterodimer with CYCLE (CYC) and binds E-boxes to activate transcription of clock genes including period ( per), timeless ( tim), vrille ( vri), PAR domain protein 1ε ( Pdp1ε), and clockwork orange ( cwo). Such activation is reduced in cwo mutants, suggesting that CWO supports CLK-CYC dependent transcription. After PER accumulates to high levels during the night, complexes containing PER, DOUBLETIME (DBT) kinase, and possibly TIM, bind to and remove CLK-CYC from E-boxes to repress transcription. PER-CLK binding isn't sufficient to remove CLK-CYC from E-boxes, but PER-DBT-mediated hyperphosphorylation of CLK by one or more unidentified kinase(s) coincides with CLK-CYC release from E-boxes, which implies that CLK phosphorylation promotes CLK-CYC release from E-boxes. After lights-on, PER is degraded due to DBT-dependent phosphorylation, thereby releasing CLK-CYC. Over the course of 4–6 h, phosphorylated CLK is then replaced by transcriptionally competent hypophosphorylated CLK to initiate the next cycle of transcription. [ABSTRACT FROM AUTHOR]

p73, a transcription factor rarely mutated in cancer, regulates a subset of p53 target genes that cause cells to respond to genotoxic stress by growth arrest and apoptosis. p73 is produced in two main forms; only TAp73 reiterates the roles of p53, while ΔNp73 can be oncogenic in character. We show that the TAp73 form produced by TP73 P1 promoter has five distinct Egr1-binding sites, each contributing to the transcriptional upregulation of TAp73 by Egr1 in several cell types. In contrast, TP73 P2 promoter transcribes ΔNp73, is not induced by Egr1, but is induced by TAp73 and p53. Induction of TAp73 by genotoxic stress requires Egr1 in mouse in vivo. Newly discovered non-consensus p53-binding sites in p73, p53 and Egr1 promoters reveal inter-regulating networks and sustained expression by feedback loops in response to stress, resulting in prolonged expression of the p53 family of genes and efficient apoptosis.Cell Death and Differentiation (2007) 14, 436–446. doi:10.1038/sj.cdd.4402029; published online 22 September 2006 [ABSTRACT FROM AUTHOR]

The p53 pathway is composed of hundreds of genes and their products that respond to a wide variety of stress signals. These responses to stress include apoptosis, cellular senescence or cell cycle arrest. In addition the p53-regulated genes produce proteins that communicate these stress signals to adjacent cells, prevent and repair damaged DNA and create feedback loops that enhance or attenuate p53 activity and communicate with other signal transduction pathways. Many questions remain to be explored in our understanding of how this network of genes plays a role in protection from cancers, therapy and integrating the homeostatic mechanisms of stress management and fidelity in a cell and organism. The goal of this chapter is to elucidate some of those questions and suggest new directions for this area of research.Cell Death and Differentiation (2006) 13, 1027–1036. doi:10.1038/sj.cdd.4401910; published online 24 March 2006 [ABSTRACT FROM AUTHOR]

The p53 pathway responds to stresses that can disrupt the fidelity of DNA replication and cell division. A stress signal is transmitted to the p53 protein by post-translational modifications. This results in the activation of the p53 protein as a transcription factor that initiates a program of cell cycle arrest, cellular senescence or apoptosis. The transcriptional network of p53-responsive genes produces proteins that interact with a large number of other signal transduction pathways in the cell and a number of positive and negative autoregulatory feedback loops act upon the p53 response. There are at least seven negative and three positive feedback loops described here, and of these, six act through the MDM-2 protein to regulate p53 activity. The p53 circuit communicates with the Wnt-beta-catenin, IGF-1-AKT, Rb-E2F, p38 MAP kinase, cyclin-cdk, p14/19 ARF pathways and the cyclin G-PP2A, and p73 gene products. There are at least three different ubiquitin ligases that can regulate p53 in an autoregulatory manner: MDM-2, Cop-1 and Pirh-2. The meaning of this redundancy and the relative activity of each of these feedback loops in different cell types or stages of development remains to be elucidated. The interconnections between signal transduction pathways will play a central role in our understanding of cancer.Oncogene (2005) 24, 2899-2908. doi:10.1038/sj.onc.1208615 [ABSTRACT FROM AUTHOR]

Mechanisms underlying circadian clock function in Drosophila melanogaster have been revealed by genetic and molecular approaches. Two interlocked transcriptional feedback loops involving at least the period, timeless, Clock, and cycle genes generate molecular oscillations that are believed to control behavioral rhythmicity and other clock outputs. These oscillations are further enhanced and fine-tuned to match the duration of the solar day by post-transcriptional and post-translational mechanisms depending on the PERIOD and TIMELESS proteins and on the protein kinases DOUBLE-TIME and SHAGGY. Light is the principal zeitgeber for synchronizing molecular and behavioral rhythmicity via the blue-light photoreceptor CRYPTOCHROME and the TIMELESS protein. In addition, light seems required for maintaining robust molecular oscillations at least in peripheral clock-gene-expressing tissues like the eyes, antennae, or Malpighian tubules. Relaying temporal information to cells and tissues expressing overt biological rhythms involves regulation of "output genes" at multiple levels. Although their regulation depends on the major clock genes, the majority of the clock-controlled genes are not direct targets of clock factors. [ABSTRACT FROM AUTHOR]

Vibra tome sections of male hamster brains were treated immunohistochemically with LHRH antiserum, and the anatomical distribution of LHRH immunoreactive cells and nerve fibers was assessed. LHRH-cell bodies are found in the ventral hypothalamus that includes its preoptic, anterior and central parts, in the septum, the olfactory tubercle, the main and accessory olfactory bulb, and the prepiriform cortex. In addition, extracerebral LHRH-neurons and ganglia exist in LHRH-positive nerves at the ventromedial surface of the olfactory tubercle and bulb as well as in olfactory nerves. Dense networks of LHRH-immunoreactive fibers are found in all regions where LHRH-cell bodies exist. Intraseptal connections reach the organum vasculosum of the lamina terminalis, the subfornical organ, and the lateral ventricle. Dorsolateral projections from the septum can be traced via the fimbria hippocampi and alveus to the ventral hippocampus, via the stria terminalis to the amygdala and piriform cortex. Ventrolateral projections extend from the level of the olfactory tubercle and preoptic-anterior hypothalamic area via the ventral amygdalofugal pathway to the prepiriform and piriform cortex as well as the amygdala. Dorsal supracallosal projections via the stria longitudinalis are seen in the induseum griseum and the cingulate cortex. Caudal efferents reach the habenula, interpeduncular nucleus, midbrain raphe, and central gray of the rostral fourth ventricle via the stria medullaris and fasciculus retroflexus and by a ventral projection via the periventricular and subventricular hypothalamus. A major portion of this ventrocaudal projection gives rise to a dense network in the median eminence. Anatomical relationships of LHRH-fibers to certain regions of the inner ventricular and outer brain surface are noted. [ABSTRACT FROM AUTHOR]