Data-Gouv-ML/pcri-erc-participations-et-projets-laureats huggingface dataset:
Projet ERC : VirBAcous (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : KU Leuven — Pays : Belgique — Rôle : PI
Acronyme de l'entité : KUL
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1386875.0 €

Achieving a sufficient sound insulation of buildings is a complex problem since multiple transmission paths are important, uncertainties can have a large effect, and acoustic performance requirements often conflict with structural and thermal requirements. Furthermore, accurate vibro-acoustic modelling across the entire building acoustics frequency range presently requires a huge computational effort. As a result, the acoustic development of building systems is usually based on general design rules, insufficiently accurate prediction models and many experimental prototype tests. Such development is costly and time consuming, and leads to suboptimal designs. This project therefore aims to develop an efficient yet sufficiently accurate prediction framework for the acoustic design of building systems which takes all uncertainties into account and which opens the way for design optimization. Four fundamental breakthroughs are required. First, a new approach to high-frequency subsystem modelling will overcome the limitations of the current statistical energy analysis paradigm and handle a high degree of geometric and material complexity. Second, a modelling framework for built-up systems will be developed, which incorporates different component model types and which switches between them as the frequency increases. The third development consists of quantifying the combined effect of all uncertain parameters on the overall sound insulation performance in a logically consistent and computationally efficient way. Finally, a robust optimization approach that spans the entire building acoustics frequency range and that accounts for all relevant non-acoustic performance criteria as well will be developed. Each development will be complemented by showcase applications in building acoustics, yet the fundamental nature of the developments make that they will have a profound impact in all disciplines where the study and/or control of mechanical wave propagation are important.

Mots-clés : building acoustics,sound transmission,numerical simulations,diffuse fields,uncertainty quantification,design optimization,topology optimization
Projet ERC : TENDON_MECHBIO (Horizon 2020, appel 2020, Consolidator grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Lund University — Pays : Suède — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 2002622.0 €

Achilles tendon ruptures are common and costly, and more than 50% heal unsuccessfully. Tendons respond to mechanical load over time and loading is fundamental for good mechanical performance. However, the regulatory mechanisms are still largely unknown. The main objective of this proposal is to clarify how intact and ruptured healing Achilles tendons are responding to mechanical load. The hypothesis is that the underlying mechanisms can be elucidated through an advanced multimodal approach that combines novel experimental and numerical models across several length scales to clarify the distinct adaptive response of elastic and viscoelastic mechanical behaviour. The proposal combines well-controlled in vivo animal experiments that are uniquely characterized (in situ) to develop and validate novel adaptive computational (in silico) models that can comprehensively predict the spatial and temporal tissue distributions and biomechanical behavior of healthy intact and ruptured healing tendons. On each length scale, experimental mechanical tests are carried out concurrently with 3D/2D high resolution imaging/scattering (in situ), to clarify how the inhomogeneous meso-, micro- and nanostructures behave under loading, in a setup planned to deliver optimal data for development and validation of computational models. The interdisciplinary project will deliver high-impact science where the multimodal approach on several length scales could establish new paradigms in tendon biomechanics and mechanobiology. Further, it will lift bioengineering to new levels by unravelling the link between load-controlled molecular mechanisms and viscoelastic mechanical response. It will deliver a novel validated computational framework that the research community may use to propose enhanced solutions for managing tendon injuries. As such, it approaches a well-defined clinical problem from an engineering view, where the PI’s well-received published and ongoing work is the foundation for the idea.

Mots-clés : biomaterials,biomechanics,mechano regulation,mechanical properties,synchrotron,phase contrast x ray tomography,small angle x ray scattering,computational modeling,finite element modeling
Projet ERC : HOLOMAN (Horizon 2020, appel 2017, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : University of Stuttgart — Pays : Allemagne — Rôle : Partner
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 362500.0 €

Acoustic waves exert forces when they interact with matter. Sound, and in particular ultrasound, which has a wavelength of a few hundred microns in water, is a benign and versatile tool, that has been successfully used to manipulate, trap and levitate microparticles and cells. The acoustic contrast between the material and the medium, and the spatial variation of the ultrasound field determine the interaction. Resonators and arrays of a few hundred transducers have thus far been used to generate the sound fields, but the former only yields highly symmetrical pressure patterns, and the latter cannot be scaled to achieve complex fields. Our radically new approach uses a finely contoured 3D printed acoustic hologram to generate pressure fields with orders of magnitude higher complexity than what has been possible to date. The acoustic hologram technology is a route towards truly sophisticated and 3D sound fields. This project will research the necessary computational and experimental tools to generate designed 3D ultrasound fields. We will investigate ways to use acoustic holograms for rapid manufacturing, the controlled manipulation of microrobots, and the assembly of cells. The 3D pressure fields promise the assembly and fabrication of an entire 3D object in “one shot”, something that has not been realized to date. We will also study the formation of 3D cellular assemblies, and more realistic 3D tumour models. This project will develop the technology, materials, processes, and understanding needed for the generation and use of sophisticated 3D ultrasound fields, which opens up entirely new possibilities in physical acoustics and the manipulation of matter with sound.

Mots-clés : holography,directed assembly,rapid 3d fabrication,cells
Projet ERC : FREEMIND (Horizon 2020, appel 2016, Starting grants)
Domaine scientifique : Social Sciences and Humanities
Panel : The Human Mind and Its Complexity
Entité participante : Cardiff University — Pays : Royaume-Uni — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1487908.0 €

Acting based on intention is a fundamental ability to our lives. Apple or orange, cash or card: we constantly make intentional decisions to fulfil our desires, even when the options have no explicit difference in their rewards. Recently, I and others have offered the first evidence to support that intentional decision and externally guided decision share similar computational principles. However, how the brain implements these principles for intentional decision remains unknown. This project aims to establish a multilevel understanding of intentional decision, spanning from neurons to brain networks to behaviour, through a powerful combination of novel paradigms, cutting-edge brain imaging, and innovative methods. Central to my approach is formal computational modelling, allowing me to establish a quantitative link between data and theory at multiple levels of abstraction. Subproject 1 will ask which brain regions encode intentional information, when intentional processes occur, and how neurochemical concentration influences intentional decision. Subproject 2 will focus on theoretically predicted changes in intentional decision under behavioural and neural interventions. I will use brain imaging and brain stimulation to test the flexibility of intentional decision within individuals. Subproject 3 will launch the largest study to date on intentional decision. I will characterize individual differences in intentional decision from 2,000 representative samples. I will then investigate, with high statistical power, the contributions of neurochemistry and brain microstructure to individual differences in intentional decision. This project premises to establish the first neurobiological theory of intentional behaviour, and provide mechanistic understanding of its changes within and between individuals. The new theory and innovative methodology will open further research possibilities to explore intentional deficits in diseases, and the neural basis of human volition.

Mots-clés : intention,decision making,modelling,brain imaging
Projet ERC : OrFuNCo (Horizon 2020, appel 2017, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : Centre national de la recherche scientifique — Pays : France — Rôle : PI
Acronyme de l'entité : CNRS
Type d'entité : Recherche
Financement ERC de l'entité : 1411402.5 €

Activation and transformation of dinitrogen (N2) into other nitrogen-containing compounds is a challenge for chemists due to the inertness of this molecule. The well-established Haber-Bosch process allows transformation of dinitrogen into ammonia (NH3) at the industrial scale through heterogeneous catalysis, but it is an energy-demanding process (1-2% of the World's annual energy consumption). The ammonia thus produced is almost totally converted into more value-added chemicals. Similarly, in Nature, the nitrogenase enzymes are able to convert N2 into NH3 catalytically, spending a high amount of energy to produce a molecule which is subsequently transformed into amino-acids or nucleotides. At a time where energy savings have become a major issue, alternatives to the Haber-Bosch process are desirable. Improving ammonia synthesis still prevails in current dinitrogen chemistry, despite the relative lack of utility of this molecule. Conversely, a catalytic process affording a nitrogen-containing product directly from N2 does not exist yet, and remains a highly attractive, though challenging, goal. Given this context, the PI proposes to investigate novel molecular chemical tools capable of direct conversion of N2 into nitrogen-containing organic compounds under mild conditions, while approaching the catalysis problem from a new direction. Two unprecedented strategies relying on the symbiotic reactivity of two partners towards dinitrogen will be detailed herein. In the first one, metal-boron frustrated Lewis pairs (FLPs) will help activate and functionalise N2, thus unlocking the thus far missing FLP chemistry of this small molecule. In the second one, it is proposed to explore the virgin territory of N2's cycloaddition reactivity, thanks to bimetallic cooperativity. By the careful examination of stoichiometric reactions considered as key steps of putative catalytic cycles, tackling the "Holy Grail" of catalysis will be facilitated.

Mots-clés : dinitrogen,frustrated lewis pairs,organometallic chemistry,cycloadditions
Projet ERC : E-MOTION (Horizon 2020, appel 2020, Advanced grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : Université de Toulouse — Pays : France — Rôle : Partner
Acronyme de l'entité : UT
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 54375.0 €

Actuator devices converting energy into motion are a fundamental part of everyday life. However, there is currently an unmet need in actuation technologies to provide soft, smooth, noiseless movement that can mimic human motion and dexterity. The development of such “artificial muscles” is burgeoning in both interest and importance as it would enable significant advances in areas as important as robotics, medicine and aeronautics. To enable a step-change in this field, E·MOTION proposes to develop unprecedented macroscopic-scale soft materials based on switchable spin crossover molecules with remarkable actuating performances. Using an innovative combination of material engineering methods these materials will be endowed with electrical actuation, self-sensing and energy harvesting properties, which will be a major breakthrough. More fundamentally, E·MOTION aims at understanding in-depth structure vs. mechanical property relationships in these switchable materials, which is essential for processing and optimizing their function. A multiscale experimental and theoretical approach will be used to assess how the molecular deformation and change in molecular connectivity under external stimuli affect macroscopic mechanical properties as well as the cycle life. Finally, E·MOTION will take a major shift on the side of actuator design by the development of original fibre-braided actuators as well as 3D-printed, microfluidic actuator devices made of these materials. These advanced actuator designs will then be thoroughly analysed for their ability to mimic complex muscular schemes. This ambitious, multidisciplinary project that brings together various aspects of molecular and polymer chemistry, condensed matter physics, mechanical engineering and advanced manufacturing, will enable a new departure in my career and a significant leap forward in the state-of-the-art that shall expedite the societal exploitation of these novel, molecule-based actuator technologies.

Mots-clés : molecular materials,spin crossover,polymer composites,mechanical properties,actuators
Projet ERC : LapIt (Horizon 2020, appel 2018, Proof of concept grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Synthetic Chemistry and Materials
Entité participante : University of Cambridge — Pays : Royaume-Uni — Rôle : PI
Acronyme de l'entité : U. Cambridge
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 150000.0 €

Acute Myeloid Leukemia (AML), a cancer of the myeloid line of blood cells, is the most common type of leukemia in adults (~350.000 new cases yearly worldwide), yet continues to have the lowest overall survival rate of all leukemias (26.9%). The disease is characterized by clonal expansion of undifferentiated myeloid precursors, leading to anomalous hematopoiesis and bone marrow failure. Current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) with treatment costs up to €300k per patient. Although some AML patients respond to chemotherapy and HSCT, most patients that go into remission show disease relapse (up to and 70%). In addition, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. This presses the need for new AML treatments that are (1) more effective and (2) tolerated by all patients. In LapIt, we will further develop a novel treatment strategy for AML, based on targeting a macromolecular target that is marker of poor prognosis for AML patients with the drug Lap. Importantly, to guarantee specific uptake of Lap by AML cells and minimize side effects to healthy cells, the drug will be further developed as an antibody-drug conjugate targeting a validated receptor which is overexpressed in AML and other leukemias. As such, our drug will not only be more effective than currently used AML therapies, but will also be tolerated by patients unable to tolerate intensive treatments. With our proposed drug candidate we are able to make, for the first time, AML treatment a clinical reality for any AML patient.

Mots-clés : leukemia,therapy,antibody drug conjugate,natural products
Projet ERC : ContraNPM1AML (Horizon 2020, appel 2016, Consolidator grants)
Domaine scientifique : Life Science
Panel : Prevention, Diagnosis and Treatment of Human Diseases
Entité participante : University of Perugia — Pays : Italie — Rôle : PI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1883749.68 €

Acute myeloid leukemia (AML) is a group of hematologic malignancies which, due to their molecular and clinical heterogeneity, have been traditionally difficult to classify and treat. Recently, next-generation, whole-genome sequencing has uncovered several recurrent somatic mutations that better define the landscape of AML genomics. Despite these advances in deciphering AML molecular subsets, there have been no concurrent improvements in AML therapy which still relies on the ‘antracycline+cytarabine’ scheme. Hereto, only about 40-50% of adult young patients are cured whilst most of the elderly succumb to their disease. Therefore, new therapeutic approaches which would take advantage of the new discoveries are clearly needed. In the past years, we discovered and characterized nucleophosmin (NPM1) mutations as the most frequent genetic alteration (about 30%) in AML, and today NPM1-mutated AML is a new entity in the WHO classification of myeloid neoplasms. However, mechanisms of leukemogenesis and a specific therapy for this leukemia are missing. Here, I aim to unravel the complex network of molecular interactions that take place in this distinct genetic subtype, and find their vulnerabilities to identify new targets for therapy. To address this issue, I will avail of relevant pre-clinical models developed in our laboratories and propose two complementary strategies: 1) a screening-based approach, focused either on the target, by analyzing synthetic lethal interactions through CRISPR-based genome-wide interference, or on the drug, by high-throughput chemical libraries screenings; 2) a hypothesis-driven approach, based on our recent gained novel insights on the role of specific intracellular pathways/genes in NPM1-mutated AML and on pharmacological studies with ‘old’ drugs, which we have revisited in the specific AML genetic context. I expect our discoveries will lead to find novel therapeutic approaches and make clinical trials available to patients as soon as possible.

Mots-clés : acute myeloid leukemia,npm1,gene mutations,target therapy,synthetic lethality,preclinical models
Projet ERC : MemoChrom (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Life Science
Panel : Physiology in Health, Disease and Ageing
Entité participante : Hebrew University of Jerusalem — Pays : Israël — Rôle : PI
Acronyme de l'entité : HUJI
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1500000.0 €

Adaptation to recurring environmental challenges (food availability, seasonal rhythms etc.) is a mainstay of physiology. As such, mammals are exquisitely fitted to tolerate frequent bouts of fasting owing to hepatic production of fuels (glucose, ketones). Indeed, studies show significant health benefits of intermittent fasting. Due to the reliance of the fasting response on chromatin and transcriptional regulation, I hypothesize that mammals adapt to recurring fasting by sensitizing transcriptional programs and maximizing future responses, thereby increasing survival. I plan to uncover transcriptional mechanisms of ‘fasting memory’ that mediate the health benefits of recurrent fasting. I will profile the hepatic transcriptome and genome-wide chromatin landscape of intermittently-fasted mice to discover the mediators of such memory. I will evaluate three plausible mechanisms: (1) Enhancer priming whereby the DNA regulatory elements dictating gene expression are kept in a primed state between fasting episodes. (2) Promoter priming in which RNA polymerase is paused at gene bodies during feeding and rapidly released upon re-fasting. (3) Transcriptional cascades whereby genes induced in the previous fasting bout are active in the next one, directing a second wave of gene expression. The molecular mechanisms mediating memory will be examined in a series of gain/loss of function experiments targeting various components of transcriptional regulation (transcription factors, RNA polymerase, histone and DNA modifications etc.). Both the notion of fasting memory and the cellular mechanisms driving it are supported by preliminary results. The concept raised here has the potential to unravel a fundamental homeostatic response and significantly advance fasting research. More broadly, such a discovery would reshape our view of transcriptional regulation as a cellular adaptation mechanism to recurring challenges and of physiological habituation to the environment.

Mots-clés : fasting,chromatin,transcription,enhancers,transcription factors,liver,hepatology,metabolism
Projet ERC : GAMMA (Horizon 2020, appel 2020, Starting grants)
Domaine scientifique : Physical Sciences and Engineering
Panel : Products and processes engineering
Entité participante : École polytechnique — Pays : France — Rôle : PI
Acronyme de l'entité : X
Type d'entité : Enseignement supérieur ou secondaire
Financement ERC de l'entité : 1499877.0 €

Additive manufacturing (AM) holds the potential to revolutionize the alloy manufacturing sector through its ability to provide unprecedented control over the design of alloy microstructures during manufacturing. However, the main roadblock preventing its widespread adoption is the inability to design microstructures with desired mechanical responses. An AM process results in the formation of hierarchical microstructures that are extremely sensitive to the process parameters. Minor changes to these parameters can result in very different microstructures that exhibit significant differences in their mechanical response at multiple length scales. Controlling the mechanical response of hierarchical microstructures requires first understanding their formation during the AM process. Current experimental and modeling research efforts are heavily focused on studying the role of melt-pool dynamics and rapid solidification during the AM process. This project aims at tackling the crucial missing link, which is the microstructure evolution occurring during the long period after solidification and till the end of an AM process, i.e. during Solid-State Thermal Cycling (SSTC), at varying temperature rates and amplitudes. Using novel experimental procedures involving electron microscopy and x-ray synchrotron studies, I will quantify microstructural changes and identify micro-mechanisms caused by SSTC. This will be complemented with development of novel models at intragranular and polycrystalline levels to gain a comprehensive understanding of the role of transient thermal gradients on microstructure evolution. The experiment-modeling synergy will then be harnessed to tailor AM process parameters and suggest in-process/post-process routes to engineer AM microstructures. The approaches developed and the knowledge gained from this project will have far reaching benefits including, but not limited to, guiding emerging solid-state AM technologies such as additive friction stir.