Project acronym AROMA-CFD
Project Advanced Reduced Order Methods with Applications in Computational Fluid Dynamics
Researcher (PI) Gianluigi Rozza
Host Institution (HI) SCUOLA INTERNAZIONALE SUPERIORE DI STUDI AVANZATI DI TRIESTE
Country Italy
Call Details Consolidator Grant (CoG), PE1, ERC-2015-CoG
Summary The aim of AROMA-CFD is to create a team of scientists at SISSA for the development of Advanced Reduced Order Modelling techniques with a focus in Computational Fluid Dynamics (CFD), in order to face and overcome many current limitations of the state of the art and improve the capabilities of reduced order methodologies for more demanding applications in industrial, medical and applied sciences contexts. AROMA-CFD deals with strong methodological developments in numerical analysis, with a special emphasis on mathematical modelling and extensive exploitation of computational science and engineering. Several tasks have been identified to tackle important problems and open questions in reduced order modelling: study of bifurcations and instabilities in flows, increasing Reynolds number and guaranteeing stability, moving towards turbulent flows, considering complex geometrical parametrizations of shapes as computational domains into extended networks. A reduced computational and geometrical framework will be developed for nonlinear inverse problems, focusing on optimal flow control, shape optimization and uncertainty quantification. Further, all the advanced developments in reduced order modelling for CFD will be delivered for applications in multiphysics, such as fluid-structure interaction problems and general coupled phenomena involving inviscid, viscous and thermal flows, solids and porous media. The advanced developed framework within AROMA-CFD will provide attractive capabilities for several industrial and medical applications (e.g. aeronautical, mechanical, naval, off-shore, wind, sport, biomedical engineering, and cardiovascular surgery as well), combining high performance computing (in dedicated supercomputing centers) and advanced reduced order modelling (in common devices) to guarantee real time computing and visualization. A new open source software library for AROMA-CFD will be created: ITHACA, In real Time Highly Advanced Computational Applications.
Summary
The aim of AROMA-CFD is to create a team of scientists at SISSA for the development of Advanced Reduced Order Modelling techniques with a focus in Computational Fluid Dynamics (CFD), in order to face and overcome many current limitations of the state of the art and improve the capabilities of reduced order methodologies for more demanding applications in industrial, medical and applied sciences contexts. AROMA-CFD deals with strong methodological developments in numerical analysis, with a special emphasis on mathematical modelling and extensive exploitation of computational science and engineering. Several tasks have been identified to tackle important problems and open questions in reduced order modelling: study of bifurcations and instabilities in flows, increasing Reynolds number and guaranteeing stability, moving towards turbulent flows, considering complex geometrical parametrizations of shapes as computational domains into extended networks. A reduced computational and geometrical framework will be developed for nonlinear inverse problems, focusing on optimal flow control, shape optimization and uncertainty quantification. Further, all the advanced developments in reduced order modelling for CFD will be delivered for applications in multiphysics, such as fluid-structure interaction problems and general coupled phenomena involving inviscid, viscous and thermal flows, solids and porous media. The advanced developed framework within AROMA-CFD will provide attractive capabilities for several industrial and medical applications (e.g. aeronautical, mechanical, naval, off-shore, wind, sport, biomedical engineering, and cardiovascular surgery as well), combining high performance computing (in dedicated supercomputing centers) and advanced reduced order modelling (in common devices) to guarantee real time computing and visualization. A new open source software library for AROMA-CFD will be created: ITHACA, In real Time Highly Advanced Computational Applications.
Max ERC Funding
1 656 579 €
Duration
Start date: 2016-05-01, End date: 2021-10-31
Project acronym BOOST
Project Biomimetic trick to re-balance Osteblast-Osteoclast loop in osteoporoSis treatment: a Topological and materials driven approach
Researcher (PI) Chiara Silvia Vitale Brovarone
Host Institution (HI) POLITECNICO DI TORINO
Country Italy
Call Details Consolidator Grant (CoG), PE8, ERC-2015-CoG
Summary One out of 5 people in their fifties will experience a bone fracture due to osteoporosis (OP)-induced fragility in their lifetime. The OP socio-economic burden is dramatic and involves tens of millions of people in the EU, with a steadily increasing number due to population ageing. Current treatments entail drug-therapy coupled with a healthy lifestyle but OP fractures need mechanical fixation to rapidly achieve union: the contribution of biomaterial scientists in this field is still far from taking its expected leading role in cutting-edge research. Bone remodelling is a well-coordinated process of bone resorption by osteoclasts followed by the production of new bone by osteoblasts. This process occurs continuously throughout life in a coupling with a positive balance during growth and negative with ageing, which can result in OP. We believe that an architecture driven stimulation of the osteoclast/osteoblast coupling, with an avant-garde focus on osteoclasts activity, is the key to success in treating unbalanced bone remodelling. We aim to manufacture a scaffold that mimics healthy bone features which will establish a new microenvironment favoring a properly stimulated and active population of osteoclasts and osteoblasts, i.e. a well-balanced bone cooperation. After 5 years we will be able to prove the efficacy of this approach. A benchmark will be set up for OP fracture treatment and for the realization of smart bone substitutes that will be able to locally “trick” aged bone cells stimulating them to act as healthy ones. BOOST results will have an unprecedented impact on the scientific research community, opening a new approach to set up smart, biomimetic strategies to treat aged, unbalanced bone tissues and to reduce OP-associated disabilities and financial burdens.
Summary
One out of 5 people in their fifties will experience a bone fracture due to osteoporosis (OP)-induced fragility in their lifetime. The OP socio-economic burden is dramatic and involves tens of millions of people in the EU, with a steadily increasing number due to population ageing. Current treatments entail drug-therapy coupled with a healthy lifestyle but OP fractures need mechanical fixation to rapidly achieve union: the contribution of biomaterial scientists in this field is still far from taking its expected leading role in cutting-edge research. Bone remodelling is a well-coordinated process of bone resorption by osteoclasts followed by the production of new bone by osteoblasts. This process occurs continuously throughout life in a coupling with a positive balance during growth and negative with ageing, which can result in OP. We believe that an architecture driven stimulation of the osteoclast/osteoblast coupling, with an avant-garde focus on osteoclasts activity, is the key to success in treating unbalanced bone remodelling. We aim to manufacture a scaffold that mimics healthy bone features which will establish a new microenvironment favoring a properly stimulated and active population of osteoclasts and osteoblasts, i.e. a well-balanced bone cooperation. After 5 years we will be able to prove the efficacy of this approach. A benchmark will be set up for OP fracture treatment and for the realization of smart bone substitutes that will be able to locally “trick” aged bone cells stimulating them to act as healthy ones. BOOST results will have an unprecedented impact on the scientific research community, opening a new approach to set up smart, biomimetic strategies to treat aged, unbalanced bone tissues and to reduce OP-associated disabilities and financial burdens.
Max ERC Funding
1 977 500 €
Duration
Start date: 2016-05-01, End date: 2022-06-30
Project acronym BOPNIE
Project Boundary value problems for nonlinear integrable equations
Researcher (PI) Jonatan Carl Anders Lenells
Host Institution (HI) KUNGLIGA TEKNISKA HOEGSKOLAN
Country Sweden
Call Details Consolidator Grant (CoG), PE1, ERC-2015-CoG
Summary The purpose of this project is to develop new methods for solving boundary value problems (BVPs) for nonlinear integrable partial differential equations (PDEs). Integrable PDEs can be analyzed by means of the Inverse Scattering Transform, whose introduction was one of the most important developments in the theory of nonlinear PDEs in the 20th century. Until the 1990s the inverse scattering methodology was pursued almost entirely for pure initial-value problems. However, in many laboratory and field situations, the solution is generated by what corresponds to the imposition of boundary conditions rather than initial conditions. Thus, an understanding of BVPs is crucial.
In an exciting sequence of events taking place in the last two decades, new tools have become available to deal with BVPs for integrable PDEs. Although some important issues have already been resolved, several major problems remain open.
The aim of this project is to solve a number of these open problems and to find solutions of BVPs which were heretofore not solvable. More precisely, the proposal has eight objectives:
1. Develop methods for solving problems with time-periodic boundary conditions.
2. Answer some long-standing open questions raised by series of wave-tank experiments 35 years ago.
3. Develop a new approach for the study of space-periodic solutions.
4. Develop new approaches for the analysis of BVPs for equations with 3 x 3-matrix Lax pairs.
5. Derive new asymptotic formulas by using a nonlinear version of the steepest descent method.
6. Construct disk and disk/black-hole solutions of the stationary axisymmetric Einstein equations.
7. Solve a BVP in Einstein's theory of relativity describing two colliding gravitational waves.
8. Extend the above methods to BVPs in higher dimensions.
Summary
The purpose of this project is to develop new methods for solving boundary value problems (BVPs) for nonlinear integrable partial differential equations (PDEs). Integrable PDEs can be analyzed by means of the Inverse Scattering Transform, whose introduction was one of the most important developments in the theory of nonlinear PDEs in the 20th century. Until the 1990s the inverse scattering methodology was pursued almost entirely for pure initial-value problems. However, in many laboratory and field situations, the solution is generated by what corresponds to the imposition of boundary conditions rather than initial conditions. Thus, an understanding of BVPs is crucial.
In an exciting sequence of events taking place in the last two decades, new tools have become available to deal with BVPs for integrable PDEs. Although some important issues have already been resolved, several major problems remain open.
The aim of this project is to solve a number of these open problems and to find solutions of BVPs which were heretofore not solvable. More precisely, the proposal has eight objectives:
1. Develop methods for solving problems with time-periodic boundary conditions.
2. Answer some long-standing open questions raised by series of wave-tank experiments 35 years ago.
3. Develop a new approach for the study of space-periodic solutions.
4. Develop new approaches for the analysis of BVPs for equations with 3 x 3-matrix Lax pairs.
5. Derive new asymptotic formulas by using a nonlinear version of the steepest descent method.
6. Construct disk and disk/black-hole solutions of the stationary axisymmetric Einstein equations.
7. Solve a BVP in Einstein's theory of relativity describing two colliding gravitational waves.
8. Extend the above methods to BVPs in higher dimensions.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-05-01, End date: 2022-02-28
Project acronym CAVE
Project Challenges and Advancements in Virtual Elements
Researcher (PI) Lourenco Beirao da veiga
Host Institution (HI) UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Country Italy
Call Details Consolidator Grant (CoG), PE1, ERC-2015-CoG
Summary The Virtual Element Method (VEM) is a novel technology for the discretization of partial differential equations (PDEs), that shares the same variational background as the Finite Element Method. First but not only, the VEM responds to the strongly increasing interest in using general polyhedral and polygonal meshes in the approximation of PDEs without the limit of using tetrahedral or hexahedral grids. By avoiding the explicit integration of the shape functions that span the discrete space and introducing an innovative construction of the stiffness matrixes, the VEM acquires very interesting properties and advantages with respect to more standard Galerkin methods, yet still keeping the same coding complexity. For instance, the VEM easily allows for polygonal/polyhedral meshes (even non-conforming) with non-convex elements and possibly with curved faces; it allows for discrete spaces of arbitrary C^k regularity on unstructured meshes.
The main scope of the project is to address the recent theoretical challenges posed by VEM and to assess whether this promising technology can achieve a breakthrough in applications. First, the theoretical and computational foundations of VEM will be made stronger. A deeper theoretical insight, supported by a wider numerical experience on benchmark problems, will be developed to gain a better understanding of the method's potentials and set the foundations for more applicative purposes. Second, we will focus our attention on two tough and up-to-date problems of practical interest: large deformation elasticity (where VEM can yield a dramatically more efficient handling of material inclusions, meshing of the domain and grid adaptivity, plus a much stronger robustness with respect to large grid distortions) and the cardiac bidomain model (where VEM can lead to a more accurate domain approximation through MRI data, a flexible refinement/de-refinement procedure along the propagation front, to an exact satisfaction of conservation laws).
Summary
The Virtual Element Method (VEM) is a novel technology for the discretization of partial differential equations (PDEs), that shares the same variational background as the Finite Element Method. First but not only, the VEM responds to the strongly increasing interest in using general polyhedral and polygonal meshes in the approximation of PDEs without the limit of using tetrahedral or hexahedral grids. By avoiding the explicit integration of the shape functions that span the discrete space and introducing an innovative construction of the stiffness matrixes, the VEM acquires very interesting properties and advantages with respect to more standard Galerkin methods, yet still keeping the same coding complexity. For instance, the VEM easily allows for polygonal/polyhedral meshes (even non-conforming) with non-convex elements and possibly with curved faces; it allows for discrete spaces of arbitrary C^k regularity on unstructured meshes.
The main scope of the project is to address the recent theoretical challenges posed by VEM and to assess whether this promising technology can achieve a breakthrough in applications. First, the theoretical and computational foundations of VEM will be made stronger. A deeper theoretical insight, supported by a wider numerical experience on benchmark problems, will be developed to gain a better understanding of the method's potentials and set the foundations for more applicative purposes. Second, we will focus our attention on two tough and up-to-date problems of practical interest: large deformation elasticity (where VEM can yield a dramatically more efficient handling of material inclusions, meshing of the domain and grid adaptivity, plus a much stronger robustness with respect to large grid distortions) and the cardiac bidomain model (where VEM can lead to a more accurate domain approximation through MRI data, a flexible refinement/de-refinement procedure along the propagation front, to an exact satisfaction of conservation laws).
Max ERC Funding
980 634 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
Project acronym DELMIT
Project Maintaining the Human Mitochondrial Genome
Researcher (PI) Maria Falkenberg Gustafsson
Host Institution (HI) GOETEBORGS UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), LS1, ERC-2015-CoG
Summary Mitochondria are required to convert food into usable energy forms and every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes (mtDNA) that encode for 13 of the about 90 proteins present in the respiratory chain. All proteins necessary for mtDNA replication, as well as transcription and translation of mtDNA-encoded genes, are encoded in the nucleus. Mutations in nuclear-encoded proteins required for mtDNA maintenance is an important cause of neurodegeneration and muscle diseases. The common result of these defects is either mtDNA depletion or accumulation of multiple deletions of mtDNA in postmitotic tissues.
The long-term goal (or vision) of research in my laboratory is to understand in molecular detail how mtDNA is replicated and how this process is regulated in mammalian cells. To this end we use a protein biochemistry approach, which we combine with in vivo verification in cell lines. My group was in 2004 the first to reconstitute mtDNA replication in vitro and we have continued to develop even more elaborate system ever since. In the current application, the major focus is studies of the mitochondrial D-loop region, a triple-stranded structure in the mitochondrial genome. The D-loop functions as a regulatory hub and we will determine how initiation and termination of mtDNA replication is controlled from this region. We will also determine the physical organization of the mtDNA replication machinery at the replication fork and establish how mtDNA deletions, a classical hallmark of human ageing, are formed.
Summary
Mitochondria are required to convert food into usable energy forms and every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes (mtDNA) that encode for 13 of the about 90 proteins present in the respiratory chain. All proteins necessary for mtDNA replication, as well as transcription and translation of mtDNA-encoded genes, are encoded in the nucleus. Mutations in nuclear-encoded proteins required for mtDNA maintenance is an important cause of neurodegeneration and muscle diseases. The common result of these defects is either mtDNA depletion or accumulation of multiple deletions of mtDNA in postmitotic tissues.
The long-term goal (or vision) of research in my laboratory is to understand in molecular detail how mtDNA is replicated and how this process is regulated in mammalian cells. To this end we use a protein biochemistry approach, which we combine with in vivo verification in cell lines. My group was in 2004 the first to reconstitute mtDNA replication in vitro and we have continued to develop even more elaborate system ever since. In the current application, the major focus is studies of the mitochondrial D-loop region, a triple-stranded structure in the mitochondrial genome. The D-loop functions as a regulatory hub and we will determine how initiation and termination of mtDNA replication is controlled from this region. We will also determine the physical organization of the mtDNA replication machinery at the replication fork and establish how mtDNA deletions, a classical hallmark of human ageing, are formed.
Max ERC Funding
1 999 985 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym ECOHERB
Project Drivers and impacts of invertebrate herbivores across forest ecosystems globally.
Researcher (PI) Daniel Metcalfe
Host Institution (HI) UMEA UNIVERSITET
Country Sweden
Call Details Consolidator Grant (CoG), PE10, ERC-2015-CoG
Summary Forests slow global climate change by absorbing atmospheric carbon dioxide but this ecosystem service is limited by soil nutrients. Herbivores potentially alter soil nutrients in a range of ways, but these have mostly only been recorded for large mammals. By comparison, the impacts of the abundant invertebrates in forests have largely been ignored and are not included in current models used to generate the climate predictions so vital for designing governmental policies
The proposed project will use a pioneering new interdisciplinary approach to provide the most complete picture yet available of the rates, underlying drivers and ultimate impacts of key nutrient inputs from invertebrate herbivores across forest ecosystems worldwide. Specifically, we will:
(1) Establish a network of herbivory monitoring stations across all major forest types, and across key environmental gradients (temperature, rainfall, ecosystem development).
(2) Perform laboratory experiments to examine the effects of herbivore excreta on soil processes under different temperature and moisture conditions.
(3) Integrate this information into a cutting-edge ecosystem model, to generate more accurate predictions of forest carbon sequestration under future climate change.
The network established will form the foundation for a unique long-term global monitoring effort which we intend to continue long after the current funding time scale. This work represents a powerful blend of several disciplines harnessing an array of cutting edge tools to provide fundamentally novel insights into an area of direct and urgent importance for the society.
Summary
Forests slow global climate change by absorbing atmospheric carbon dioxide but this ecosystem service is limited by soil nutrients. Herbivores potentially alter soil nutrients in a range of ways, but these have mostly only been recorded for large mammals. By comparison, the impacts of the abundant invertebrates in forests have largely been ignored and are not included in current models used to generate the climate predictions so vital for designing governmental policies
The proposed project will use a pioneering new interdisciplinary approach to provide the most complete picture yet available of the rates, underlying drivers and ultimate impacts of key nutrient inputs from invertebrate herbivores across forest ecosystems worldwide. Specifically, we will:
(1) Establish a network of herbivory monitoring stations across all major forest types, and across key environmental gradients (temperature, rainfall, ecosystem development).
(2) Perform laboratory experiments to examine the effects of herbivore excreta on soil processes under different temperature and moisture conditions.
(3) Integrate this information into a cutting-edge ecosystem model, to generate more accurate predictions of forest carbon sequestration under future climate change.
The network established will form the foundation for a unique long-term global monitoring effort which we intend to continue long after the current funding time scale. This work represents a powerful blend of several disciplines harnessing an array of cutting edge tools to provide fundamentally novel insights into an area of direct and urgent importance for the society.
Max ERC Funding
1 750 000 €
Duration
Start date: 2016-03-01, End date: 2022-02-28
Project acronym ENUBET
Project Enhanced NeUtrino BEams from kaon Tagging
Researcher (PI) Andrea Longhin
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Country Italy
Call Details Consolidator Grant (CoG), PE2, ERC-2015-CoG
Summary ENUBET has been designed to open a new window of opportunities in accelerator neutrino physics.
The proposed project enables for the first time the measurement of the positrons produced in the decay tunnel of conventional neutrino beams: these particles signal uniquely the generation of an electron neutrino at source.
Neutrino facilities enhanced by the ENUBET technique will have an unprecedented control of the neutrino flux. This will allow to reduce by one order of magnitude the uncertainties on neutrino cross sections: a leap that has been sought after since decades and that is needed to address the challenges of discovering matter-antimatter asymmetries in the leptonic sector.
The apparatus is a highly specialized electromagnetic calorimeter with fast response, sustaining particle rates as high as 0.5 MHz/cm^2, having excellent electron/pion separation capabilities with a reduced number of read-out channels. ENUBET will boost technologies that have been envisaged for high energy colliders to address this new challenge. On the other hand it will operate in a substantially different configuration. The experiment will be performed at the CERN Neutrino Platform, a recently approved facility where innovative neutrino detectors will be developed exploiting dedicated hadron beam-lines from the SPS accelerator. In the first phase of the project, ENUBET will address the challenges of particle identification from extended sources, developing innovative optical readout systems and cost-effective solutions for radiation imaging. This approach is based on cutting-edge technologies for single photon sensitive devices. During the second phase, the detector will be assembled and characterized at CERN with particle beams. Finally, it will be operated in time coincidence with Liquid Argon neutrino detectors, achieving a major step towards the realization of the concept of tagging individual neutrinos both at production and interaction level, on an event-by-event basis.
Summary
ENUBET has been designed to open a new window of opportunities in accelerator neutrino physics.
The proposed project enables for the first time the measurement of the positrons produced in the decay tunnel of conventional neutrino beams: these particles signal uniquely the generation of an electron neutrino at source.
Neutrino facilities enhanced by the ENUBET technique will have an unprecedented control of the neutrino flux. This will allow to reduce by one order of magnitude the uncertainties on neutrino cross sections: a leap that has been sought after since decades and that is needed to address the challenges of discovering matter-antimatter asymmetries in the leptonic sector.
The apparatus is a highly specialized electromagnetic calorimeter with fast response, sustaining particle rates as high as 0.5 MHz/cm^2, having excellent electron/pion separation capabilities with a reduced number of read-out channels. ENUBET will boost technologies that have been envisaged for high energy colliders to address this new challenge. On the other hand it will operate in a substantially different configuration. The experiment will be performed at the CERN Neutrino Platform, a recently approved facility where innovative neutrino detectors will be developed exploiting dedicated hadron beam-lines from the SPS accelerator. In the first phase of the project, ENUBET will address the challenges of particle identification from extended sources, developing innovative optical readout systems and cost-effective solutions for radiation imaging. This approach is based on cutting-edge technologies for single photon sensitive devices. During the second phase, the detector will be assembled and characterized at CERN with particle beams. Finally, it will be operated in time coincidence with Liquid Argon neutrino detectors, achieving a major step towards the realization of the concept of tagging individual neutrinos both at production and interaction level, on an event-by-event basis.
Max ERC Funding
2 000 000 €
Duration
Start date: 2016-06-01, End date: 2022-05-31
Project acronym EPIScOPE
Project Reversing the epigenetic state of oligodendrocyte precursors cells in multiple sclerosis
Researcher (PI) Goncalo DE Sa E SOUSA DE CASTELO BRANCO
Host Institution (HI) KAROLINSKA INSTITUTET
Country Sweden
Call Details Consolidator Grant (CoG), LS7, ERC-2015-CoG
Summary Oligodendrocytes (OL) are glial cells that mediate myelination of neurons, a process that is defective in multiple sclerosis (MS). Although OL precursor cells (OPCs) can initially promote remyelination in MS, this regenerative mechanism eventually fails in progressive MS. OPCs go through several epigenetic states that ultimately define their potential to differentiate and myelinate. OPCs in progressive MS stall in a distinct epigenetic state, incompatible with differentiation and remyelination. We hypothesize that these OPCs regress to an epigenetic state reminiscent of the state of embryonic OPCs, which remain undifferentiated.
In this proposal, we aim to uncover the causes behind the remyelination failure upon disease progression in MS. We will determine the epigenetic/transcriptional states of OPCs during development and in MS, using single cell and bulk RNA sequencing and quantitative proteomics. We will further investigate how the interplay between transcription factors (TFs), chromatin modifiers (ChMs) and non-coding RNAs (ncRNAs) contributes to the transition between epigenetic states of OPCs. The results will allow the identification of ChMs and ncRNAs that can modulate these states and thereby control OPC differentiation and myelination. We will use this knowledge to investigate whether we can reverse the epigenetic state of OPCs in MS, in order to promote their differentiation and remyelination. The unique combination of leading-edge techniques such as SILAC coupled with immunoprecipitation and mass-spectrometry, single-cell RNA sequencing, ChIP-Sequencing, among others, will allow us to provide insights into novel epigenetic mechanisms that might be underlying the effects of environmental and lifestyle risk factors for MS. Moreover, this project has the potential to lead to the discovery of new targets for epigenetic-based therapies for MS, which could provide major opportunities for improved clinical outcome of MS patients in the near future.
Summary
Oligodendrocytes (OL) are glial cells that mediate myelination of neurons, a process that is defective in multiple sclerosis (MS). Although OL precursor cells (OPCs) can initially promote remyelination in MS, this regenerative mechanism eventually fails in progressive MS. OPCs go through several epigenetic states that ultimately define their potential to differentiate and myelinate. OPCs in progressive MS stall in a distinct epigenetic state, incompatible with differentiation and remyelination. We hypothesize that these OPCs regress to an epigenetic state reminiscent of the state of embryonic OPCs, which remain undifferentiated.
In this proposal, we aim to uncover the causes behind the remyelination failure upon disease progression in MS. We will determine the epigenetic/transcriptional states of OPCs during development and in MS, using single cell and bulk RNA sequencing and quantitative proteomics. We will further investigate how the interplay between transcription factors (TFs), chromatin modifiers (ChMs) and non-coding RNAs (ncRNAs) contributes to the transition between epigenetic states of OPCs. The results will allow the identification of ChMs and ncRNAs that can modulate these states and thereby control OPC differentiation and myelination. We will use this knowledge to investigate whether we can reverse the epigenetic state of OPCs in MS, in order to promote their differentiation and remyelination. The unique combination of leading-edge techniques such as SILAC coupled with immunoprecipitation and mass-spectrometry, single-cell RNA sequencing, ChIP-Sequencing, among others, will allow us to provide insights into novel epigenetic mechanisms that might be underlying the effects of environmental and lifestyle risk factors for MS. Moreover, this project has the potential to lead to the discovery of new targets for epigenetic-based therapies for MS, which could provide major opportunities for improved clinical outcome of MS patients in the near future.
Max ERC Funding
1 895 155 €
Duration
Start date: 2016-09-01, End date: 2021-08-31
Project acronym Feel your Reach
Project Non-invasive decoding of cortical patterns induced by goal directed movement intentions and artificial sensory feedback in humans
Researcher (PI) Gernot Rudolf Mueller-Putz
Host Institution (HI) TECHNISCHE UNIVERSITAET GRAZ
Country Austria
Call Details Consolidator Grant (CoG), PE7, ERC-2015-CoG
Summary In Europe estimated 300.000 people are suffering from a spinal cord injury (SCI) with 11.000 new injuries per year. The consequences of spinal cord injury are tremendous for these individuals. The loss of motor functions especially of the arm and grasping function – 40% are tetraplegics – leads to a life-long dependency on care givers and therefore to a dramatic decrease in quality of life in these often young individuals. With the help of neuroprostheses, grasp and elbow function can be substantially improved. However, remaining body movements often do not provide enough degrees of freedom to control the neuroprosthesis.
The ideal solution for voluntary control of an upper extremity neuroprosthesis would be to directly record motor commands from the corresponding cortical areas and convert them into control signals. This would realize a technical bypass around the interrupted nerve fiber tracts in the spinal cord.
A Brain-Computer Interface (BCI) transform mentally induced changes of brain signals into control signals and serve as an alternative human-machine interface. We showed first results in EEG-based control of a neuroprosthesis in several persons with SCI in the last decade, however, the control is still unnatural and cumbersome.
The objective of FEEL YOUR REACH is to develop a novel control framework that incorporates goal directed movement intention, movement decoding, error processing, processing of sensory feedback to allow a more natural control of a neuroprosthesis. To achieve this aim a goal directed movement decoder will be realized, and continuous error potential decoding will be included. Both will be finally joined together with an artificial kinesthetic sensory feedback display attached to the user. We hypothesize that with these mechanisms a user will be able to naturally control an neuroprosthesis with his/ her mind only.
Summary
In Europe estimated 300.000 people are suffering from a spinal cord injury (SCI) with 11.000 new injuries per year. The consequences of spinal cord injury are tremendous for these individuals. The loss of motor functions especially of the arm and grasping function – 40% are tetraplegics – leads to a life-long dependency on care givers and therefore to a dramatic decrease in quality of life in these often young individuals. With the help of neuroprostheses, grasp and elbow function can be substantially improved. However, remaining body movements often do not provide enough degrees of freedom to control the neuroprosthesis.
The ideal solution for voluntary control of an upper extremity neuroprosthesis would be to directly record motor commands from the corresponding cortical areas and convert them into control signals. This would realize a technical bypass around the interrupted nerve fiber tracts in the spinal cord.
A Brain-Computer Interface (BCI) transform mentally induced changes of brain signals into control signals and serve as an alternative human-machine interface. We showed first results in EEG-based control of a neuroprosthesis in several persons with SCI in the last decade, however, the control is still unnatural and cumbersome.
The objective of FEEL YOUR REACH is to develop a novel control framework that incorporates goal directed movement intention, movement decoding, error processing, processing of sensory feedback to allow a more natural control of a neuroprosthesis. To achieve this aim a goal directed movement decoder will be realized, and continuous error potential decoding will be included. Both will be finally joined together with an artificial kinesthetic sensory feedback display attached to the user. We hypothesize that with these mechanisms a user will be able to naturally control an neuroprosthesis with his/ her mind only.
Max ERC Funding
1 994 161 €
Duration
Start date: 2016-05-01, End date: 2021-07-31
Project acronym FricLess
Project A seamless multi-scale model for contact, friction, and solid lubrication
Researcher (PI) Lucia Nicola
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Country Italy
Call Details Consolidator Grant (CoG), PE8, ERC-2015-CoG
Summary Friction and wear are liable for enormous losses in terms of energy and resources in modern society. Costs related to unwanted friction in industrialised countries are estimated to be about 3% of the gross domestic product. Urgency is even greater nowadays as friction between micro-components has become the bottleneck of several applications for which miniaturisation is critical.
Lubrication is a commonly adopted solution to reduce friction. Graphite is a broadly used solid lubricant for large scale applications, while the lubricating properties of a few-layers graphene hold great promise especially for smaller scale applications. At present, our knowledge of the friction and lubrication of rough surfaces is essentially phenomenological. This is because friction is only deceivingly a simple mechanisms, which instead requires understanding of physical phenomena simultaneously acting at different length scales. The change in contact size, which controls the friction stress, depends on nano-scale phenomena such as atomic de-adhesion, sliding, dislocation nucleation in metals, but also on micro- and macro-scale phenomena as (size-dependent) plastic deformation.
The objective of this proposal is to reach an unprecedented understanding of metal friction and lubrication by accounting, for the first time, for all relevant phenomena occurring from the atomic to the macro-scale, and their interplay.
To this end, a seamless concurrent multi-scale model will be developed. The power of this new model lies in its capability of describing three-dimensional bodies with realistic roughness in sliding lubricated contact, with the accuracy of an atomistic simulation.
This research builds towards a complete picture of metal friction and lubrication. The materials chosen for the proposed research are copper and multi-layer graphene. However, the model that will be developed is general and can be used to study different materials, lubricants and environmental conditions.
Summary
Friction and wear are liable for enormous losses in terms of energy and resources in modern society. Costs related to unwanted friction in industrialised countries are estimated to be about 3% of the gross domestic product. Urgency is even greater nowadays as friction between micro-components has become the bottleneck of several applications for which miniaturisation is critical.
Lubrication is a commonly adopted solution to reduce friction. Graphite is a broadly used solid lubricant for large scale applications, while the lubricating properties of a few-layers graphene hold great promise especially for smaller scale applications. At present, our knowledge of the friction and lubrication of rough surfaces is essentially phenomenological. This is because friction is only deceivingly a simple mechanisms, which instead requires understanding of physical phenomena simultaneously acting at different length scales. The change in contact size, which controls the friction stress, depends on nano-scale phenomena such as atomic de-adhesion, sliding, dislocation nucleation in metals, but also on micro- and macro-scale phenomena as (size-dependent) plastic deformation.
The objective of this proposal is to reach an unprecedented understanding of metal friction and lubrication by accounting, for the first time, for all relevant phenomena occurring from the atomic to the macro-scale, and their interplay.
To this end, a seamless concurrent multi-scale model will be developed. The power of this new model lies in its capability of describing three-dimensional bodies with realistic roughness in sliding lubricated contact, with the accuracy of an atomistic simulation.
This research builds towards a complete picture of metal friction and lubrication. The materials chosen for the proposed research are copper and multi-layer graphene. However, the model that will be developed is general and can be used to study different materials, lubricants and environmental conditions.
Max ERC Funding
1 999 985 €
Duration
Start date: 2016-06-01, End date: 2022-11-30
