Project acronym DMEA
Project The Dynamics of Migration and Economic Adjustment
Researcher (PI) Christian Dustmann
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Advanced Grant (AdG), SH1, ERC-2012-ADG_20120411
Summary The research proposed here is concerned with the dynamics of immigrant impacts and the process of economic adaptation in receiving societies. The immigration process is inherently dynamic: many new immigrants return home within a short time; and those that remain undergo a long term series of investments and behavioural changes that gradually alter the way that they interact with the economy of the receiving country. Moreover, in the longer run the presence of immigrants affects the choices of firms over new technology investments, and the choices of native workers over schooling and occupations. Thus simple static frameworks provide an incomplete and even potentially misleading perspective for understanding modern immigration patterns. The point of departure for this proposed research is the recognition that we need to reformulate the analysis of immigrant impacts in a fully dynamic framework, acknowledging the inter-temporal choices of immigrants, firms, and native workers and the ways that these three groups of agents interact over a longer horizon. Our approach involves treating immigration as a dynamic shock, where the dynamics relates to the different agents involved: immigrants, who change their position in the native skill distribution over time as a result of their life-cycle decisions; firms, who react by adjusting their technologies, product mix, and their involvement with institutions and regulatory environment; and native workers, who adjust by changing their career plans. Our work will combine highly innovative theoretical perspectives with state-of-the-art empirical analyses exploiting unique policy experiments and exceptional data sources, merging longitudinal administrative population data with data from firm and individual surveys. This agenda will enable us to construct a comprehensive picture of the adjustment process in response to immigration and open new horizons for future research on the impact of immigration in a dynamic framework.
Summary
The research proposed here is concerned with the dynamics of immigrant impacts and the process of economic adaptation in receiving societies. The immigration process is inherently dynamic: many new immigrants return home within a short time; and those that remain undergo a long term series of investments and behavioural changes that gradually alter the way that they interact with the economy of the receiving country. Moreover, in the longer run the presence of immigrants affects the choices of firms over new technology investments, and the choices of native workers over schooling and occupations. Thus simple static frameworks provide an incomplete and even potentially misleading perspective for understanding modern immigration patterns. The point of departure for this proposed research is the recognition that we need to reformulate the analysis of immigrant impacts in a fully dynamic framework, acknowledging the inter-temporal choices of immigrants, firms, and native workers and the ways that these three groups of agents interact over a longer horizon. Our approach involves treating immigration as a dynamic shock, where the dynamics relates to the different agents involved: immigrants, who change their position in the native skill distribution over time as a result of their life-cycle decisions; firms, who react by adjusting their technologies, product mix, and their involvement with institutions and regulatory environment; and native workers, who adjust by changing their career plans. Our work will combine highly innovative theoretical perspectives with state-of-the-art empirical analyses exploiting unique policy experiments and exceptional data sources, merging longitudinal administrative population data with data from firm and individual surveys. This agenda will enable us to construct a comprehensive picture of the adjustment process in response to immigration and open new horizons for future research on the impact of immigration in a dynamic framework.
Max ERC Funding
1 129 428 €
Duration
Start date: 2013-06-01, End date: 2018-05-31
Project acronym DYNACORP
Project Dynamic Structural Corporate Finance: Linking Theory and Empirical Testing
Researcher (PI) Christopher Anthony Hennessy
Host Institution (HI) LONDON BUSINESS SCHOOL
Call Details Starting Grant (StG), SH1, ERC-2011-StG_20101124
Summary There are three components to this project: Theory; Empirical Testing; and Dissemination. All components are linked to the current policy question of how taxes influence debt and systemic risk, and all use novel dynamic structural models. I am unique in explicitly linking such models to empirical testing.
Theory: “Learning, Capital Structure and Systemic Risk.” Standard dynamic structural models of financing assume firms know the stochastic process governing cash flow. I will first consider a partial equilibrium model. Here firms are exposed to rare event risk, with the true probability being unknown. Firms learn and update beliefs regarding risk. Relative to standard models, firms are debt conservative and there is leverage persistence. In many cases, firms increase leverage only if they have avoided a negative shock long enough. In order to analyze asset pricing implications, I plan to embed such firms in a general equilibrium setting with a common catastrophic risk having unknown probability. Firms rationally respond to “Great Moderations” by increasing leverage. Recessions are more severe after long tranquil periods due to high debt overhang. A third paper, Re-Examining the Link Between Leverage and Systematic Risk, considers cross sectional asset pricing implications of credit shocks. The standard levered beta formula is erroneous, and the pre-tax cost of capital increases with debt. Together, the models show privately optimal debt is lower than recognized, and that tax breaks for debt reduce welfare.
Empirical Testing: “Natural Experiment Policy Evaluation—A Structural Critique.” A common approach to testing whether taxes influence corporate financing and investment decisions is to compare leverage and investment before/after tax changes. I use a structural model as a laboratory to show that lack of a statistically significant change is not sufficient to reject the null that “taxes matter.” I will first consider an economy where the tax rate is a Markov process. Flotation costs on debt and real irreversibility limit the response of financing and investment to changes in shadow prices. More importantly, responses to tax changes are attenuated whenever they are partially anticipated and not permanent. Standard tests violate rational expectations by implicitly assuming tax changes come as surprises, with each new change being viewed as permanent, until the next surprise. My argument implies that standard tax experiments cannot falsify the null that taxes affect behaviour. Further, one cannot generalize elasticities if the policy transition matrix differs. I will propose an alternative Bayesian approach to hypothesis testing. My argument casts doubt on standard interpretations of historical evidence of tax change effects, suggesting true elasticities may be much higher. I will consider extending this argument to settings with endogenous policy choices.
“Dissemination. The objective of this phase is to lower entry barriers by making the methodology accessible via a non-technical primer, and by making the models readily available using a user-friendly online platform.
Summary
There are three components to this project: Theory; Empirical Testing; and Dissemination. All components are linked to the current policy question of how taxes influence debt and systemic risk, and all use novel dynamic structural models. I am unique in explicitly linking such models to empirical testing.
Theory: “Learning, Capital Structure and Systemic Risk.” Standard dynamic structural models of financing assume firms know the stochastic process governing cash flow. I will first consider a partial equilibrium model. Here firms are exposed to rare event risk, with the true probability being unknown. Firms learn and update beliefs regarding risk. Relative to standard models, firms are debt conservative and there is leverage persistence. In many cases, firms increase leverage only if they have avoided a negative shock long enough. In order to analyze asset pricing implications, I plan to embed such firms in a general equilibrium setting with a common catastrophic risk having unknown probability. Firms rationally respond to “Great Moderations” by increasing leverage. Recessions are more severe after long tranquil periods due to high debt overhang. A third paper, Re-Examining the Link Between Leverage and Systematic Risk, considers cross sectional asset pricing implications of credit shocks. The standard levered beta formula is erroneous, and the pre-tax cost of capital increases with debt. Together, the models show privately optimal debt is lower than recognized, and that tax breaks for debt reduce welfare.
Empirical Testing: “Natural Experiment Policy Evaluation—A Structural Critique.” A common approach to testing whether taxes influence corporate financing and investment decisions is to compare leverage and investment before/after tax changes. I use a structural model as a laboratory to show that lack of a statistically significant change is not sufficient to reject the null that “taxes matter.” I will first consider an economy where the tax rate is a Markov process. Flotation costs on debt and real irreversibility limit the response of financing and investment to changes in shadow prices. More importantly, responses to tax changes are attenuated whenever they are partially anticipated and not permanent. Standard tests violate rational expectations by implicitly assuming tax changes come as surprises, with each new change being viewed as permanent, until the next surprise. My argument implies that standard tax experiments cannot falsify the null that taxes affect behaviour. Further, one cannot generalize elasticities if the policy transition matrix differs. I will propose an alternative Bayesian approach to hypothesis testing. My argument casts doubt on standard interpretations of historical evidence of tax change effects, suggesting true elasticities may be much higher. I will consider extending this argument to settings with endogenous policy choices.
“Dissemination. The objective of this phase is to lower entry barriers by making the methodology accessible via a non-technical primer, and by making the models readily available using a user-friendly online platform.
Max ERC Funding
1 103 996 €
Duration
Start date: 2011-10-01, End date: 2015-09-30
Project acronym EMATTER
Project New materials for energy production and sustainable energy use
Researcher (PI) Stoyan Smoukov
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), PE8, ERC-2011-StG_20101014
Summary The proposed research is in the field of nanofiber materials, focusing on the development of functional nanofibers for the complementary purposes of energy production and sustainable energy use. Significant opportunities exist in these areas, stemming from the development of several methods in the last decade for higher capacity nanofiber production, as well as the strategic need to find alternatives to current production of energy and its uses. Nanofibers are expected to bring revolutionary advances to these and many other fields of science and technology, including catalysis, filtration, protein separations, tissue engineering, and flexible electronics. We will work on creating such materials with potential applications in multi-exciton photovoltaics and catalysis for energy production. For sustainable energy use, we will develop bioinspired responsive materials and architectures, which would store energy, release it on demand, and act as life-like, efficient, and autonomous entities. Fundamental questions we will address in the research include: How do we tailor semiconductor band structures, as well as achieve nanoscale morphologies for efficient dissociation of photogenerated excitons? Can we develop general predictive rules for the conditions needed to fabricate nanofibers from any polymer solution by liquid shear processing? Can the molecular crystallinity and porosity be controlled in the fibers? What are the simplest life-like, autonomous devices that could be made with synthetic materials?
This work will include extensive solution-based synthesis, processing, structural and chemical characterization (by optical and electron microscopy, small angle X-rays), physical property measurements (mechanical, optical, electronic), device fabrication and assembly, and computer simulations. Most of the facilities needed for the research are available in Cambridge, and some will be arranged for through external collaborations.
Summary
The proposed research is in the field of nanofiber materials, focusing on the development of functional nanofibers for the complementary purposes of energy production and sustainable energy use. Significant opportunities exist in these areas, stemming from the development of several methods in the last decade for higher capacity nanofiber production, as well as the strategic need to find alternatives to current production of energy and its uses. Nanofibers are expected to bring revolutionary advances to these and many other fields of science and technology, including catalysis, filtration, protein separations, tissue engineering, and flexible electronics. We will work on creating such materials with potential applications in multi-exciton photovoltaics and catalysis for energy production. For sustainable energy use, we will develop bioinspired responsive materials and architectures, which would store energy, release it on demand, and act as life-like, efficient, and autonomous entities. Fundamental questions we will address in the research include: How do we tailor semiconductor band structures, as well as achieve nanoscale morphologies for efficient dissociation of photogenerated excitons? Can we develop general predictive rules for the conditions needed to fabricate nanofibers from any polymer solution by liquid shear processing? Can the molecular crystallinity and porosity be controlled in the fibers? What are the simplest life-like, autonomous devices that could be made with synthetic materials?
This work will include extensive solution-based synthesis, processing, structural and chemical characterization (by optical and electron microscopy, small angle X-rays), physical property measurements (mechanical, optical, electronic), device fabrication and assembly, and computer simulations. Most of the facilities needed for the research are available in Cambridge, and some will be arranged for through external collaborations.
Max ERC Funding
1 963 835 €
Duration
Start date: 2012-02-01, End date: 2018-01-31
Project acronym GEPIDIAB
Project Genetics and epigenetics of Type 2 Diabetes physiology
Researcher (PI) Philippe Froguel
Host Institution (HI) IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
Call Details Advanced Grant (AdG), LS4, ERC-2011-ADG_20110310
Summary "Failure to elucidate Type 2 Diabetes (T2D) physiology frustrates efforts to improve therapeutics. Although GWAS has identified 40 T2D genes, mostly expressed in pancreatic beta-cells, this explains no more than 10% of T2D inheritance. Up to 5% of T2D patients have dominantly inherited maturity-onset diabetes of the young (MODY), characterized by beta-cell dysfunction. Elucidating the genetics of familial early-onset T2D, using Whole-Exome Sequencing (WES) can bring breakthroughs in understanding insulin secretion physiology. DNA methylation, particularly in insulin sensitive tissues may also contribute to T2D. Newly-developed genome-wide methylation arrays can be used to identify associations with these epigenetic elements and T2D. In the proposed project, GEPIDIAB, I will take advantage of our MODY family DNA collection and multi-tissue biobank to 1: identify novel genetic causes of familial T2D (WP1) and 2: identify DNA methylation variation associated with T2D (WP2). In WP1, unresolved MODY-X families will be studied using WES to identify novel sequence changes. Then we will elucidate the cellular and metabolic mechanisms leading to beta-cell dysfunction caused by these novel mutations. In WP2, variation in DNA methylation at 450K sites across the genome will be studied in normoglycemic or diabetic bariatric surgery patients. Five separate tissue samples will be studied to identify tissue-specific variation, individual-specific variation and that which varies between cases and controls. We will explore whether there are T2D-specific patterns of methylation that are distinct from those in lean or obese normoglycemic subjects using bisulfite-whole genome sequencing. Overall, we will identify genome-wide methylation patterns that are cell and tissue-specific and disease-specific for five main tissues important in T2D. Together, genetics and epigenetics will complement each other to give a deeper understanding of both insulin deficiency and resistance."
Summary
"Failure to elucidate Type 2 Diabetes (T2D) physiology frustrates efforts to improve therapeutics. Although GWAS has identified 40 T2D genes, mostly expressed in pancreatic beta-cells, this explains no more than 10% of T2D inheritance. Up to 5% of T2D patients have dominantly inherited maturity-onset diabetes of the young (MODY), characterized by beta-cell dysfunction. Elucidating the genetics of familial early-onset T2D, using Whole-Exome Sequencing (WES) can bring breakthroughs in understanding insulin secretion physiology. DNA methylation, particularly in insulin sensitive tissues may also contribute to T2D. Newly-developed genome-wide methylation arrays can be used to identify associations with these epigenetic elements and T2D. In the proposed project, GEPIDIAB, I will take advantage of our MODY family DNA collection and multi-tissue biobank to 1: identify novel genetic causes of familial T2D (WP1) and 2: identify DNA methylation variation associated with T2D (WP2). In WP1, unresolved MODY-X families will be studied using WES to identify novel sequence changes. Then we will elucidate the cellular and metabolic mechanisms leading to beta-cell dysfunction caused by these novel mutations. In WP2, variation in DNA methylation at 450K sites across the genome will be studied in normoglycemic or diabetic bariatric surgery patients. Five separate tissue samples will be studied to identify tissue-specific variation, individual-specific variation and that which varies between cases and controls. We will explore whether there are T2D-specific patterns of methylation that are distinct from those in lean or obese normoglycemic subjects using bisulfite-whole genome sequencing. Overall, we will identify genome-wide methylation patterns that are cell and tissue-specific and disease-specific for five main tissues important in T2D. Together, genetics and epigenetics will complement each other to give a deeper understanding of both insulin deficiency and resistance."
Max ERC Funding
2 476 325 €
Duration
Start date: 2012-11-01, End date: 2017-10-31
Project acronym GOVERN
Project Local Governance and Dynamic Conflict in Developing Countries
Researcher (PI) Gerard Padro Miquel
Host Institution (HI) LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE
Call Details Starting Grant (StG), SH1, ERC-2011-StG_20101124
Summary "This proposal is divided into two main strands.
The first strand seeks to understand the effects of local marginal institutional change in autocracies. In particular, we will examine the introduction of local democracy in rural China. Our first contribution is to collect a representative panel of villages in rural China. With this unique data we will examine three main questions: First, we will establish the effect of the introduction of local elections on policies that are determined at the village level: land allocation, tax collection, public good provision and the enforcement of the one child policy. Second, the data will provide a unique opportunity to explore the interaction between formal and informal institutions of accountability by leveraging our information on social infrastructure in these villages. Third, we will determine whether leaders' characteristics change with the introduction of elections. These unique data will also set the stage for examining many other recent policy reforms in rural China.
The second strand of the proposal seeks to focus the formal conflict literature to the study of insurgencies, a currently prevalent form of organized violence in developing countries. To capture the basic characteristics of these conflicts, we need models that allow for (i) meaningful conflict dynamics, (ii) a central role for the non-combatant population, (iii) fundamental asymmetry between government and insurgents and (iv) economic transfers and service provision as a strategic ability of the contenders. To reach this goal we will build a series of models whose main contribution to the formal literature of conflict is the introduction of tools from the dynamic principal agent framework. Several building blocks will be analyzed before integrating them in a coherent theory of insurgency from which optimal policy and empirical implications can be derived."
Summary
"This proposal is divided into two main strands.
The first strand seeks to understand the effects of local marginal institutional change in autocracies. In particular, we will examine the introduction of local democracy in rural China. Our first contribution is to collect a representative panel of villages in rural China. With this unique data we will examine three main questions: First, we will establish the effect of the introduction of local elections on policies that are determined at the village level: land allocation, tax collection, public good provision and the enforcement of the one child policy. Second, the data will provide a unique opportunity to explore the interaction between formal and informal institutions of accountability by leveraging our information on social infrastructure in these villages. Third, we will determine whether leaders' characteristics change with the introduction of elections. These unique data will also set the stage for examining many other recent policy reforms in rural China.
The second strand of the proposal seeks to focus the formal conflict literature to the study of insurgencies, a currently prevalent form of organized violence in developing countries. To capture the basic characteristics of these conflicts, we need models that allow for (i) meaningful conflict dynamics, (ii) a central role for the non-combatant population, (iii) fundamental asymmetry between government and insurgents and (iv) economic transfers and service provision as a strategic ability of the contenders. To reach this goal we will build a series of models whose main contribution to the formal literature of conflict is the introduction of tools from the dynamic principal agent framework. Several building blocks will be analyzed before integrating them in a coherent theory of insurgency from which optimal policy and empirical implications can be derived."
Max ERC Funding
805 089 €
Duration
Start date: 2012-07-01, End date: 2017-06-30
Project acronym Identification
Project Identification, Estimation and Implementation of Structural Economic Models
Researcher (PI) Dennis Kristensen
Host Institution (HI) UNIVERSITY COLLEGE LONDON
Call Details Starting Grant (StG), SH1, ERC-2012-StG_20111124
Summary Structural economic models are getting increasingly complex. This complicates their implementation. In particular, for many models, (i) identification of the relevant components from data is still unresolved; (ii) estimation and testing procedures tend to be somewhat ad hoc and with no theoretical underpinning; (iii) the implementation of model and estimators often require numerical approximations since model solutions are not available on closed form.
The proposed research aims at addressing these three issues, (i)-(iii), by developing new methods and results for identification, estimation, testing and implementation of structural models. Particular emphasis is put on the use of nonparametric techniques. Many of the projects involve empirical applications where the proposed methods will be taken to data.
The individual projects making up the proposal are: Identification and inference in discrete choice models; identification and inference in continuous choice models; Implementation and estimation of parametric structural models; Filtering and likelihood inference in dynamic latent variable models; Bandwidth selection in estimation and testing of non- and semiparametric models.
Summary
Structural economic models are getting increasingly complex. This complicates their implementation. In particular, for many models, (i) identification of the relevant components from data is still unresolved; (ii) estimation and testing procedures tend to be somewhat ad hoc and with no theoretical underpinning; (iii) the implementation of model and estimators often require numerical approximations since model solutions are not available on closed form.
The proposed research aims at addressing these three issues, (i)-(iii), by developing new methods and results for identification, estimation, testing and implementation of structural models. Particular emphasis is put on the use of nonparametric techniques. Many of the projects involve empirical applications where the proposed methods will be taken to data.
The individual projects making up the proposal are: Identification and inference in discrete choice models; identification and inference in continuous choice models; Implementation and estimation of parametric structural models; Filtering and likelihood inference in dynamic latent variable models; Bandwidth selection in estimation and testing of non- and semiparametric models.
Max ERC Funding
1 067 000 €
Duration
Start date: 2012-10-01, End date: 2017-09-30
Project acronym IM Targeting CVD
Project Accelerated Atherosclerosis in Patients with Immune Mediated Disorders as a Model to Investigate the Link between Inflammation and Cardiovascular Disease: From Basic Mechanisms to Clinical Application
Researcher (PI) Ziad Mallat
Host Institution (HI) THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Call Details Starting Grant (StG), LS4, ERC-2011-StG_20101109
Summary Atherosclerosis is a chronic inflammatory disease of the arterial wall with (auto)immune component, initiated in response to modified (phospho)lipids. Despite important advances in our understanding of the inflammatory response in atherosclerosis, the critical pathways responsible for the breakdown of immune tolerance to lipoproteins and other self-antigens remain largely unknown. An important feature of ruptured/thrombosed atherosclerotic lesions is the accumulation of apoptotic, and secondary necrotic, lipid-laden macrophages and smooth muscle cells due to defective efferocytosis (clearance of apoptotic cells). This leads to the formation of a large ‘necrotic’ lipid core, associated with enhanced vascular inflammation. Interestingly, defective efferocytosis has been associated with the development of autoimmunity, and patients with systemic lupus erythematosus who show increased accumulation of apoptotic material are at very high risk of accelerated atherosclerosis and myocardial infarction. We hypothesize that accumulation of apoptotic/secondary necrotic cells due to defective efferocytosis, together with modified lipids, activate critical immuno-inflammatory pathways in macrophages and B cells, and break immune tolerance in atherosclerosis and post-myocardial infarction. This is consistent with the critical role played by defective efferocytosis and macrophage activation in atherosclerotic lesion progression, and with our recent unsuspected data showing a critical role for B cell activation in driving lesion development in several models of atherosclerosis. We also propose that interactions between macrophages and B cells are essential for the perpetuation of the pathogenic immuno-inflammatory response in cardiovascular disease. Finally, we will harness this knowledge for a better identification of patients at risk of cardiovascular complications, and will target these pathways to limit the progression and complications of cardiovascular disease.
Summary
Atherosclerosis is a chronic inflammatory disease of the arterial wall with (auto)immune component, initiated in response to modified (phospho)lipids. Despite important advances in our understanding of the inflammatory response in atherosclerosis, the critical pathways responsible for the breakdown of immune tolerance to lipoproteins and other self-antigens remain largely unknown. An important feature of ruptured/thrombosed atherosclerotic lesions is the accumulation of apoptotic, and secondary necrotic, lipid-laden macrophages and smooth muscle cells due to defective efferocytosis (clearance of apoptotic cells). This leads to the formation of a large ‘necrotic’ lipid core, associated with enhanced vascular inflammation. Interestingly, defective efferocytosis has been associated with the development of autoimmunity, and patients with systemic lupus erythematosus who show increased accumulation of apoptotic material are at very high risk of accelerated atherosclerosis and myocardial infarction. We hypothesize that accumulation of apoptotic/secondary necrotic cells due to defective efferocytosis, together with modified lipids, activate critical immuno-inflammatory pathways in macrophages and B cells, and break immune tolerance in atherosclerosis and post-myocardial infarction. This is consistent with the critical role played by defective efferocytosis and macrophage activation in atherosclerotic lesion progression, and with our recent unsuspected data showing a critical role for B cell activation in driving lesion development in several models of atherosclerosis. We also propose that interactions between macrophages and B cells are essential for the perpetuation of the pathogenic immuno-inflammatory response in cardiovascular disease. Finally, we will harness this knowledge for a better identification of patients at risk of cardiovascular complications, and will target these pathways to limit the progression and complications of cardiovascular disease.
Max ERC Funding
1 499 731 €
Duration
Start date: 2012-04-01, End date: 2017-03-31
Project acronym IMPUNEP
Project Innovative Materials Processing Using Non-Equilibrium Plasmas
Researcher (PI) Allan Matthews
Host Institution (HI) THE UNIVERSITY OF MANCHESTER
Call Details Advanced Grant (AdG), PE8, ERC-2012-ADG_20120216
Summary Current bulk materials processing methods are nearing their limit in terms of ability to produce innovative materials with compositional and structural consistency.
The aim of this ambitious project is to remove barriers to materials development, by researching novel methods for the processing of engineering materials, using advanced non-equilibrium plasma systems, to achieve a paradigm shift in the field of materials synthesis. These new processes have the potential to overcome the constraints of existing methods and also be environmentally friendly and produce novel materials with enhanced properties (mechanical, chemical and physical).
The research will utilise plasmas in ways not used before (in bulk materials synthesis rather than thin film formation) and it will investigate different types of plasmas (vacuum, atmospheric and electrolytic), to ensure optimisation of the processing routes across the whole range of material types (including metals, ceramics and composites).
The materials synthesised will have benefits for products across key applications sectors, including energy, healthcare and aerospace. The processes will avoid harmful chemicals and will make optimum use of scarce material resources.
This interdisciplinary project (involving engineers, physicists, chemists and modellers) has fundamental “blue skies” and transformative aspects. It is also high-risk due to the aim to produce “bulk” materials at adequate rates and with consistent uniform structures, compositions and phases (and therefore properties) throughout the material. There are many challenges to overcome, relating to the study of the plasma systems and materials produced; these aspects will be pursued using empirical and modelling approaches. The research will pursue new lines of enquiry using an unconventional synthesis approach whilst operating at the interface with more established discipline areas of plasma physics, materials chemistry, process diagnostics, modelling and control.
Summary
Current bulk materials processing methods are nearing their limit in terms of ability to produce innovative materials with compositional and structural consistency.
The aim of this ambitious project is to remove barriers to materials development, by researching novel methods for the processing of engineering materials, using advanced non-equilibrium plasma systems, to achieve a paradigm shift in the field of materials synthesis. These new processes have the potential to overcome the constraints of existing methods and also be environmentally friendly and produce novel materials with enhanced properties (mechanical, chemical and physical).
The research will utilise plasmas in ways not used before (in bulk materials synthesis rather than thin film formation) and it will investigate different types of plasmas (vacuum, atmospheric and electrolytic), to ensure optimisation of the processing routes across the whole range of material types (including metals, ceramics and composites).
The materials synthesised will have benefits for products across key applications sectors, including energy, healthcare and aerospace. The processes will avoid harmful chemicals and will make optimum use of scarce material resources.
This interdisciplinary project (involving engineers, physicists, chemists and modellers) has fundamental “blue skies” and transformative aspects. It is also high-risk due to the aim to produce “bulk” materials at adequate rates and with consistent uniform structures, compositions and phases (and therefore properties) throughout the material. There are many challenges to overcome, relating to the study of the plasma systems and materials produced; these aspects will be pursued using empirical and modelling approaches. The research will pursue new lines of enquiry using an unconventional synthesis approach whilst operating at the interface with more established discipline areas of plasma physics, materials chemistry, process diagnostics, modelling and control.
Max ERC Funding
2 499 283 €
Duration
Start date: 2013-02-01, End date: 2018-09-30
Project acronym INTEG-CV-SIM
Project An Integrated Computer Modelling Framework for Subject-Specific Cardiovascular Simulation: Applications to Disease Research, Treatment Planning, and Medical Device Design
Researcher (PI) Carlos Alberto Figueroa Alvarez
Host Institution (HI) KING'S COLLEGE LONDON
Call Details Starting Grant (StG), PE8, ERC-2012-StG_20111012
Summary Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Research efforts have been focused mainly on three areas: pathogenesis of vascular disease, development of medical devices, and virtual surgical planning. However, despite great initial promise, the actual use of patient-specific computer modelling in the clinic has been very limited. Clinical diagnosis still relies entirely on traditional methods based on imaging and invasive measurements and sampling. The same invasive trial-and-error paradigm is often seen in vascular disease research, where animal models are used profusely to quantify simple metrics that could perhaps be evaluated via non-invasive computer modelling techniques. Lastly, medical device manufacturers rely mostly on in-vitro models to investigate the anatomic variations, arterial deformations, and biomechanical forces needed for the design of stents and stent-grafts. In this project, I aim to develop an integrated image-based computer modelling framework for subject-specific cardiovascular simulation with dynamically adapting boundary conditions capable of representing alterations in the physiologic state of the patient. This computer framework will be directly applied in clinical settings to complement and enhance current diagnostic practices, working towards the goal of personalized cardiovascular medicine.
Summary
Advances in numerical methods and three-dimensional imaging techniques have enabled the quantification of cardiovascular mechanics in subject-specific anatomic and physiologic models. Research efforts have been focused mainly on three areas: pathogenesis of vascular disease, development of medical devices, and virtual surgical planning. However, despite great initial promise, the actual use of patient-specific computer modelling in the clinic has been very limited. Clinical diagnosis still relies entirely on traditional methods based on imaging and invasive measurements and sampling. The same invasive trial-and-error paradigm is often seen in vascular disease research, where animal models are used profusely to quantify simple metrics that could perhaps be evaluated via non-invasive computer modelling techniques. Lastly, medical device manufacturers rely mostly on in-vitro models to investigate the anatomic variations, arterial deformations, and biomechanical forces needed for the design of stents and stent-grafts. In this project, I aim to develop an integrated image-based computer modelling framework for subject-specific cardiovascular simulation with dynamically adapting boundary conditions capable of representing alterations in the physiologic state of the patient. This computer framework will be directly applied in clinical settings to complement and enhance current diagnostic practices, working towards the goal of personalized cardiovascular medicine.
Max ERC Funding
1 491 593 €
Duration
Start date: 2012-12-01, End date: 2018-11-30
Project acronym KATP-DIABETES
Project ATP-sensitive potassium channels: from atomic structure to human disease
Researcher (PI) Frances Mary Ashcroft
Host Institution (HI) THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Call Details Advanced Grant (AdG), LS4, ERC-2012-ADG_20120314
Summary We are currently experiencing a fast-growing diabetes pandemic. Both type 2 diabetes and rare monogenic forms of diabetes, such as neonatal diabetes, are characterised by impaired insulin secretion. This project seeks to resolve the fundamental mechanisms underlying insulin secretion and its failure in diabetes. We have shown that activating mutations in the ATP-sensitive potassium (KATP) channel cause neonatal diabetes, which has enabled children with this disease to switch from insulin injections to oral sulphonylurea drugs (which block their open KATP channels and stimulate insulin release). The most severe mutations also cause neurological symptoms that, for unknown reasons, are less well treated by sulphonylureas. We aim to: obtain a detailed mechanistic understanding of how nucleotides and drugs regulate KATP channel activity by combining state-of-the-art structural and functional approaches; define how drug therapy affects glucose homeostasis in neonatal diabetes; and explore how activating KATP channel mutations affect glucagon release from pancreatic alpha-cells. We will also investigate how severe KATP channel mutations cause neurological symptoms (such as developmental delay, reduced sensitivity to general anaesthetics and impaired eye movements) and determine how these might be alleviated by drug therapy. While underpinned by my previous work, this project takes my research in new directions, including structural analysis of eukaryotic membrane proteins, stimulus-secretion coupling in other types of islet cell, and neurological studies in humans as well as animal models. It involves a broad multidisciplinary approach, addresses questions of fundamental scientific importance, and has a strong translational element. We expect our studies will be of direct benefit to patients with neonatal or type 2 diabetes.
Summary
We are currently experiencing a fast-growing diabetes pandemic. Both type 2 diabetes and rare monogenic forms of diabetes, such as neonatal diabetes, are characterised by impaired insulin secretion. This project seeks to resolve the fundamental mechanisms underlying insulin secretion and its failure in diabetes. We have shown that activating mutations in the ATP-sensitive potassium (KATP) channel cause neonatal diabetes, which has enabled children with this disease to switch from insulin injections to oral sulphonylurea drugs (which block their open KATP channels and stimulate insulin release). The most severe mutations also cause neurological symptoms that, for unknown reasons, are less well treated by sulphonylureas. We aim to: obtain a detailed mechanistic understanding of how nucleotides and drugs regulate KATP channel activity by combining state-of-the-art structural and functional approaches; define how drug therapy affects glucose homeostasis in neonatal diabetes; and explore how activating KATP channel mutations affect glucagon release from pancreatic alpha-cells. We will also investigate how severe KATP channel mutations cause neurological symptoms (such as developmental delay, reduced sensitivity to general anaesthetics and impaired eye movements) and determine how these might be alleviated by drug therapy. While underpinned by my previous work, this project takes my research in new directions, including structural analysis of eukaryotic membrane proteins, stimulus-secretion coupling in other types of islet cell, and neurological studies in humans as well as animal models. It involves a broad multidisciplinary approach, addresses questions of fundamental scientific importance, and has a strong translational element. We expect our studies will be of direct benefit to patients with neonatal or type 2 diabetes.
Max ERC Funding
2 478 420 €
Duration
Start date: 2013-09-01, End date: 2018-08-31
