The Experts below are selected from a list of 75246 Experts worldwide ranked by ideXlab platform
Domitilla Del Vecchio - One of the best experts on this subject based on the ideXlab platform.
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Signaling architectures that transmit unidirectional information despite retroactivity
2017Co-Authors: Rushina Shah, Domitilla Del VecchioAbstract:A signaling pathway transmits information from an Upstream System to downstream Systems, ideally in a unidirectional fashion. A key obstacle to unidirectional transmission is retroactivity, the additional reaction flux that affects a System once its species interact with those of downstream Systems. This raises the fundamental question of whether signaling pathways have developed specialized architectures that overcome retroactivity and transmit unidirectional signals. Here, we propose a general procedure based on mathematical analysis that provides an answer to this question. Using this procedure, we analyze the ability of a variety of signaling architectures to transmit one-way (from Upstream to downstream) signals, as key biological parameters are tuned. We find that single stage phosphorylation and phosphotransfer Systems that transmit signals from a kinase show a stringent design trade-off that hampers their ability to overcome retroactivity. Interestingly, cascades of these architectures, which are highly represented in nature, can overcome this trade-off and thus enable unidirectional transmission. By contrast, phosphotransfer Systems, and single and double phosphorylation cycles that transmit signals from a substrate are unable to mitigate retroactivity effects, even when cascaded, and hence are not well suited for unidirectional information transmission. Our results identify signaling architectures that, allowing unidirectional transmission of signals, embody modular processes that conserve their input/output behavior across multiple contexts. These findings can be used to decompose natural signal transduction networks into modules, and, at the same time, they establish a library of devices that can be used in synthetic biology to facilitate modular circuit design.
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Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity.
Biophysical Journal, 2017Co-Authors: Rushina Shah, Domitilla Del VecchioAbstract:A signaling pathway transmits information from an Upstream System to downstream Systems, ideally in a unidirectional fashion. A key obstacle to unidirectional transmission is retroactivity, the additional reaction flux that affects a System once its species interact with those of downstream Systems. This raises the fundamental question of whether signaling pathways have developed specialized architectures that overcome retroactivity and transmit unidirectional signals. Here, we propose a general procedure based on mathematical analysis that provides an answer to this question. Using this procedure, we analyze the ability of a variety of signaling architectures to transmit one-way (from Upstream to downstream) signals, as key biological parameters are tuned. We find that single stage phosphorylation and phosphotransfer Systems that transmit signals from a kinase show a stringent design tradeoff that hampers their ability to overcome retroactivity. Interestingly, cascades of these architectures, which are highly represented in nature, can overcome this tradeoff and thus enable unidirectional transmission. By contrast, phosphotransfer Systems, and single and double phosphorylation cycles that transmit signals from a substrate, are unable to mitigate retroactivity effects, even when cascaded, and hence are not well suited for unidirectional information transmission. These results are largely independent of the specific reaction-rate constant values, and depend on the topology of the architectures. Our results therefore identify signaling architectures that, allowing unidirectional transmission of signals, embody modular processes that conserve their input/output behavior across multiple contexts. These findings can be used to decompose natural signal transduction networks into modules, and at the same time, they establish a library of devices that can be used in synthetic biology to facilitate modular circuit design.
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ECC - An N-stage cascade of phosphorylation cycles as an insulation device for synthetic biological circuits
2016 European Control Conference (ECC), 2016Co-Authors: Rushina Shah, Domitilla Del VecchioAbstract:Single phosphorylation cycles have been found to have insulation device abilities, that is, they attenuate the effect of retroactivity applied by downstream Systems and hence facilitate modular design in synthetic biology. It was recently discovered that this retroactivity attenuation property comes at the expense of an increased retroactivity to the input of the insulation device, wherein the device slows down the signal it receives from its Upstream System. In this paper, we demonstrate that insulation devices built of cascaded phosphorylation cycles can break this tradeoff, allowing to attenuate the retroactivity applied by downstream Systems while keeping a small retroactivity to the input. In particular, we show that there is an optimal number of cycles that maximally extends the linear operating region of the insulation device while keeping the desired retroactivity properties, when a common phosphatase is used. These findings provide optimal design strategies of insulation devices for synthetic biology applications.
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ACC - Stochastic analysis of retroactivity in transcriptional networks through singular perturbation
2012 American Control Conference (ACC), 2012Co-Authors: Reza Ghaemi, Domitilla Del VecchioAbstract:The input/output dynamic behavior of a biomolec-ular System is affected by interconnection to other downstream Systems through impedance-like effects called retroactivity. In this paper, we study the effects of retroactivity at the interconnection between two transcriptional modules, focusing on stochastic behavior. In particular, we describe the System through the Master equation and develop a singular perturbation theory to obtain a reduced Master equation. We prove that the solution of the original Master equation converges fast to an e neighbor of the solution of the reduced Master equation, in which e is the singular perturbation parameter. Our analysis shows that the Upstream System and the downstream one are statistically independent at the steady state. However, the interconnection slows down the dynamics of both the expectation and the variance of the output of the Upstream transcriptional module.
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CDC - On the compromise between retroactivity attenuation and noise amplification in gene regulatory networks
Proceedings of the 48h IEEE Conference on Decision and Control (CDC) held jointly with 2009 28th Chinese Control Conference, 2009Co-Authors: Shridhar Jayanthi, Domitilla Del VecchioAbstract:A bio-molecular System can be rendered insensitive to impedance-like effects, called retroactivity, at its downstream interconnections by implementing a large input amplification gain in a negative feedback loop. This type of design, however, relying on large amplifications, may have undesired effects on the internal noise of the System. We investigate this problem on a simple transcriptional component connected to downstream load by performing a stochastic analysis based on the Ω-expansion. While high gains increase the signal-to-noise ratio of the species in the Upstream System and attenuate retroactivity, they also contribute to a shift toward high frequency of the internal noise of the System. We mathematically study this compromise by employing the Langevin equation and by analyzing the noise-to-state transfer function of the linearized System.
Dileep Silva - One of the best experts on this subject based on the ideXlab platform.
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Analysing public sector institutional capacity for health workforce governance in the South-East Asia region of WHO
Human Resources for Health, 2019Co-Authors: Giorgio Cometto, Esther Nartey, Tomas Zapata, Mikiko Kanda, Yunus Md, Kavita Narayan, Kirana Pritasari, Aishath Irufa, Ramkrishna Lamichhane, Dileep SilvaAbstract:Background In order to analyse the institutional capacity for health workforce policy development and implementation in countries in the South-East Asia region, the WHO facilitated a cross-sectional analysis of functions performed, structure, personnel, management and information Systems of human resources for health (HRH) units in Ministries of Health. Case presentation A self-assessment survey on the characteristics and roles of HRH units was administered to relevant Government officials; the responses were validated through face-to-face workshops and by the WHO staff. Findings were tabulated to produce frequency distributions of the variables examined, and qualitative elements categorized according to a framework for capacity building in the health sector. Ten countries out of the 11 in the region responded to the survey. Seven out of 10 reported having an HRH unit, though their scope, roles, capacity and size displayed considerable variability. Some functions (such as planning and health workforce data management) were reportedly carried out in all countries, while others (inter-sectoral coordination, research, labour relations) were only performed in few. Discussion and conclusions The strengthening of the HRH governance capacity in countries should follow a logical hierarchy, identifying first and foremost the essential functions that the public sector is expected to perform to optimize HRH governance. The definition of expected roles and functions will in turn allow identifying the Upstream System-wide factors and the downstream capacity requirements for the strengthening of the HRH units. The focus should ultimately be on ensuring that all the key strategic functions are performed to quality standards, irrespective of institutional arrangements.
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Analysing public sector institutional capacity for health workforce governance in the South-East Asia region of WHO.
Human Resources for Health, 2019Co-Authors: Giorgio Cometto, Esther Nartey, Tomas Zapata, Mikiko Kanda, Kavita Narayan, Kirana Pritasari, Aishath Irufa, Ramkrishna Lamichhane, Yunus, Dileep SilvaAbstract:In order to analyse the institutional capacity for health workforce policy development and implementation in countries in the South-East Asia region, the WHO facilitated a cross-sectional analysis of functions performed, structure, personnel, management and information Systems of human resources for health (HRH) units in Ministries of Health. A self-assessment survey on the characteristics and roles of HRH units was administered to relevant Government officials; the responses were validated through face-to-face workshops and by the WHO staff. Findings were tabulated to produce frequency distributions of the variables examined, and qualitative elements categorized according to a framework for capacity building in the health sector. Ten countries out of the 11 in the region responded to the survey. Seven out of 10 reported having an HRH unit, though their scope, roles, capacity and size displayed considerable variability. Some functions (such as planning and health workforce data management) were reportedly carried out in all countries, while others (inter-sectoral coordination, research, labour relations) were only performed in few. The strengthening of the HRH governance capacity in countries should follow a logical hierarchy, identifying first and foremost the essential functions that the public sector is expected to perform to optimize HRH governance. The definition of expected roles and functions will in turn allow identifying the Upstream System-wide factors and the downstream capacity requirements for the strengthening of the HRH units. The focus should ultimately be on ensuring that all the key strategic functions are performed to quality standards, irrespective of institutional arrangements.
Mario Grosso - One of the best experts on this subject based on the ideXlab platform.
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Discussion on methods to include prevention activities in waste management LCA
The International Journal of Life Cycle Assessment, 2013Co-Authors: Simone Nessi, Lucia Rigamonti, Mario GrossoAbstract:PurposeWaste prevention has been assigned increasing attention worldwide during recent years, and it is expected to become one of the core elements of waste management planning in the near future. In this framework, this paper presents and discusses two possible LCA approaches for the evaluation of the environmental and energetic performance of municipal solid waste (MSW) management Systems which include the effects of waste prevention activities.MethodsThe two approaches are conceived for the comparison of waste management scenarios including waste prevention activities with baseline scenarios without waste prevention. For both of them, the functional unit is defined and the System boundaries are described with reference to different typologies of waste prevention activities identified in an extensive review. The procedure for the calculation of the LCA impacts of scenarios is also reported and an example illustrating the processes to be included in System boundaries for a specific waste prevention activity is provided.Results and discussionThe presented approaches lead to the same result in terms of difference between the LCA impacts of a waste prevention scenario and of a baseline one. However, because of the partially different Upstream System boundaries, different values of the impacts of single scenarios are obtained and the application of the two approaches is more suitable in different situations and in analyses with different purposes. The methodological aspects that can complicate the applicability of the two approaches are discussed lastly.ConclusionsThe environmental and energetic performance of MSW management scenarios including waste prevention activities can be evaluated with the two LCA approaches presented in this paper. They can be used for many purposes such as, among the most general, evaluating the Upstream and downstream environmental consequences of implementing particular waste prevention activities in a given waste management System, complementing waste reduction indicators with LCA-based indicators and supporting with quantitative evidence the strategic and policy relevance of waste prevention.
Giorgio Cometto - One of the best experts on this subject based on the ideXlab platform.
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Analysing public sector institutional capacity for health workforce governance in the South-East Asia region of WHO
Human Resources for Health, 2019Co-Authors: Giorgio Cometto, Esther Nartey, Tomas Zapata, Mikiko Kanda, Yunus Md, Kavita Narayan, Kirana Pritasari, Aishath Irufa, Ramkrishna Lamichhane, Dileep SilvaAbstract:Background In order to analyse the institutional capacity for health workforce policy development and implementation in countries in the South-East Asia region, the WHO facilitated a cross-sectional analysis of functions performed, structure, personnel, management and information Systems of human resources for health (HRH) units in Ministries of Health. Case presentation A self-assessment survey on the characteristics and roles of HRH units was administered to relevant Government officials; the responses were validated through face-to-face workshops and by the WHO staff. Findings were tabulated to produce frequency distributions of the variables examined, and qualitative elements categorized according to a framework for capacity building in the health sector. Ten countries out of the 11 in the region responded to the survey. Seven out of 10 reported having an HRH unit, though their scope, roles, capacity and size displayed considerable variability. Some functions (such as planning and health workforce data management) were reportedly carried out in all countries, while others (inter-sectoral coordination, research, labour relations) were only performed in few. Discussion and conclusions The strengthening of the HRH governance capacity in countries should follow a logical hierarchy, identifying first and foremost the essential functions that the public sector is expected to perform to optimize HRH governance. The definition of expected roles and functions will in turn allow identifying the Upstream System-wide factors and the downstream capacity requirements for the strengthening of the HRH units. The focus should ultimately be on ensuring that all the key strategic functions are performed to quality standards, irrespective of institutional arrangements.
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Analysing public sector institutional capacity for health workforce governance in the South-East Asia region of WHO.
Human Resources for Health, 2019Co-Authors: Giorgio Cometto, Esther Nartey, Tomas Zapata, Mikiko Kanda, Kavita Narayan, Kirana Pritasari, Aishath Irufa, Ramkrishna Lamichhane, Yunus, Dileep SilvaAbstract:In order to analyse the institutional capacity for health workforce policy development and implementation in countries in the South-East Asia region, the WHO facilitated a cross-sectional analysis of functions performed, structure, personnel, management and information Systems of human resources for health (HRH) units in Ministries of Health. A self-assessment survey on the characteristics and roles of HRH units was administered to relevant Government officials; the responses were validated through face-to-face workshops and by the WHO staff. Findings were tabulated to produce frequency distributions of the variables examined, and qualitative elements categorized according to a framework for capacity building in the health sector. Ten countries out of the 11 in the region responded to the survey. Seven out of 10 reported having an HRH unit, though their scope, roles, capacity and size displayed considerable variability. Some functions (such as planning and health workforce data management) were reportedly carried out in all countries, while others (inter-sectoral coordination, research, labour relations) were only performed in few. The strengthening of the HRH governance capacity in countries should follow a logical hierarchy, identifying first and foremost the essential functions that the public sector is expected to perform to optimize HRH governance. The definition of expected roles and functions will in turn allow identifying the Upstream System-wide factors and the downstream capacity requirements for the strengthening of the HRH units. The focus should ultimately be on ensuring that all the key strategic functions are performed to quality standards, irrespective of institutional arrangements.
Simone Nessi - One of the best experts on this subject based on the ideXlab platform.
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Discussion on methods to include prevention activities in waste management LCA
The International Journal of Life Cycle Assessment, 2013Co-Authors: Simone Nessi, Lucia Rigamonti, Mario GrossoAbstract:PurposeWaste prevention has been assigned increasing attention worldwide during recent years, and it is expected to become one of the core elements of waste management planning in the near future. In this framework, this paper presents and discusses two possible LCA approaches for the evaluation of the environmental and energetic performance of municipal solid waste (MSW) management Systems which include the effects of waste prevention activities.MethodsThe two approaches are conceived for the comparison of waste management scenarios including waste prevention activities with baseline scenarios without waste prevention. For both of them, the functional unit is defined and the System boundaries are described with reference to different typologies of waste prevention activities identified in an extensive review. The procedure for the calculation of the LCA impacts of scenarios is also reported and an example illustrating the processes to be included in System boundaries for a specific waste prevention activity is provided.Results and discussionThe presented approaches lead to the same result in terms of difference between the LCA impacts of a waste prevention scenario and of a baseline one. However, because of the partially different Upstream System boundaries, different values of the impacts of single scenarios are obtained and the application of the two approaches is more suitable in different situations and in analyses with different purposes. The methodological aspects that can complicate the applicability of the two approaches are discussed lastly.ConclusionsThe environmental and energetic performance of MSW management scenarios including waste prevention activities can be evaluated with the two LCA approaches presented in this paper. They can be used for many purposes such as, among the most general, evaluating the Upstream and downstream environmental consequences of implementing particular waste prevention activities in a given waste management System, complementing waste reduction indicators with LCA-based indicators and supporting with quantitative evidence the strategic and policy relevance of waste prevention.
