ERC FUNDED PROJECTS

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.

1 656 579 €

Start date: 2016-05-01, End date: 2021-04-30

Asymmetric cell division is a key mechanism for the generation of cell diversity in eukaryotes. During this process, a polarized mother cell divides into non-equivalent daughters. These may differentially inherit fate determinants, irreparable damages or age determinants. Our aim is to decipher the mechanisms governing the individualization of daughters from each other. In the past ten years, our studies identified several lateral diffusion barriers located in the plasma membrane and the endoplasmic reticulum of budding yeast. These barriers all restrict molecular exchanges between the mother cell and its bud, and thereby compartmentalize the cell already long before its division. They play key roles in the asymmetric segregation of various factors. On one side, they help maintain polarized factors into the bud. Thereby, they reinforce cell polarity and sequester daughter-specific fate determinants into the bud. On the other side they prevent aging factors of the mother from entering the bud. Hence, they play key roles in the rejuvenation of the bud, in the aging of the mother, and in the differentiation of mother and daughter from each other. Recently, we accumulated evidence that some of these barriers are subject to regulation, such as to help modulate the longevity of the mother cell in response to environmental signals. Our data also suggest that barriers help the mother cell keep traces of its life history, thereby contributing to its individuation and adaption to the environment. In this project, we will address the following questions: 1 How are these barriers assembled, functioning, and regulated? 2 What type of differentiation processes are they involved in? 3 Are they conserved in other eukaryotes, and what are their functions outside of budding yeast? These studies will shed light into the principles underlying and linking aging, rejuvenation and differentiation.

2 200 000 €

Start date: 2010-05-01, End date: 2015-04-30

Shape Memory Alloys (SMAs) are nowadays widely exploited for the realization of innovative devices and have a great impact on the development of a variety of biomedical applications ranging from orthodontic archwires to vascular stents. The design, realization, and optimization of such devices are quite demanding tasks. Mathematics is involved in this process as a major tool in order to let the modeling more accurate, the numerical simulations more reliable, and the design more effective. Many material properties of SMAs such as martensitic reorientation, training, and ferromagnetic behavior, are still to be properly and efficiently addressed. Therefore, new modeling ideas, along with original analytical and numerical techniques, are required. This project is aimed at addressing novel mathematical issues in order to move from experimental materials results toward the solution of real-scale biomechanical Engineering problems. The research focus will be multidisciplinary and include modeling, analytic, numerical, and computational issues. A progress in the macroscopic description of SMAs, the computational simulation of real-scale SMA devices, and the optimization of the production processes will contribute to advance in the direction of innovative applications.

700 000 €

Start date: 2008-09-01, End date: 2013-08-31

My goal is to study several important open mathematical problems in non-equilibrium (NEQ) systems and to build a bridge between these problems and NEQ aspects of soft sciences, in particular biological questions. Traffic on this bridge is going to be two-way, the mathematics carrying a long history as a language of science towards the soft sciences, and the soft sciences fruitfully asking new questions and building new paradigms for mathematical research. Out-of-equilibrium systems pose several fascinating problems: The Fourier law which says that resistance of a wire is proportional to its length is still presenting hard problems for research, and even the existence and the convergence to a NEQ steady state are continuously posing new puzzles, as do questions of smoothness and correlations of such states. These will be addressed with stochastic differential equations, and with particlescatterer systems, both canonical and grand-canonical. The latter are extensions of the well-known Lorentz gas and the study of hyperbolic billiards. Another field where NEQ plays an important role is the study of glassy systems. They were studied with molecular dynamics (MD) but I have used a topological variant, which mimics astonishingly well what happens in MD simulations. The aim is to extend this to 3 dimensions, where new problems appear. Finally, I will apply the NEQ studies to biological systems: How a system copes with the varying environment,adapting in this way to a novel type of NEQ. I will study networks of communication among neurons,which are like random graphs with the additional property of being embedded, and the arrangement of genes on chromosomes in such a way as to optimize the adaptation to the different cell types which must be produced using the same genetic information. I will answer such questions with students and collaborators, who will specialize in the subprojects but will interact with my help across the common bridge.

2 135 385 €

Start date: 2012-04-01, End date: 2017-07-31

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).

980 634 €

Start date: 2016-07-01, End date: 2021-06-30

Cell fusion is critical for fertilization and development, for instance underlying muscle or bone formation. Cell fusion may also play important roles in regeneration and cancer. A conceptual understanding is emerging that cell fusion requires cell-cell communication, polarization of the cells towards each other, and assembly of a fusion machinery, in which an actin-based structure promotes membrane juxtaposition and fusogenic factors drive membrane fusion. However, in no single system have the molecular nature of all these parts been described, and thus the molecular basis of cell fusion remains poorly understood. This proposal aims to depict the complete fusion process in a single organism, using the simple yeast model Schizosaccharomyces pombe, which has a long track record of discoveries in fundamental cellular processes. These haploid cells, which fuse to generate a diploid zygote, use highly conserved mechanisms of cell-cell communication (through pheromones and GPCR signaling), cell polarization (centred around the small GTPase Cdc42) and fusion. Indeed, we recently showed that these cells assemble an actin-based fusion structure, dubbed the actin fusion focus. Our five aims probe the molecular nature of, and the links between, signaling, polarization and the fusion machinery from initiation to termination of the process. These are: 1: To define the roles and feedback regulation of Cdc42 during cell fusion 2: To understand the molecular mechanisms of actin fusion focus formation 3: To identify the fusogen(s) promoting membrane fusion 4: To probe the GPCR signal for fusion initiation 5: To define the mechanism of fusion termination By combining genetic, optogenetic, biochemical, live-imaging, synthetic and modeling approaches, this project will bring a molecular and conceptual understanding of cell fusion. This work will have far-ranging relevance for cell polarization, cytoskeletal organization, cell signalling and communication, and cell fate regulation.

1 999 956 €

Start date: 2016-10-01, End date: 2021-09-30

"Centrioles are critical for the formation of cilia, flagella and centrosomes, as well as for human health. The mechanisms governing centriole formation constitute a long-standing question in cell biology. We will pursue an innovative multidisciplinary research program to gain further insight into these mechanisms, using human cells, C. elegans and Trichonympha as model systems. This program is expected to also have a major impact by contributing a novel cell free assay to the field, thus paving the way towards making synthetic centrioles. Six specific aims will be pursued: 1) Deciphering HsSAS-6/STIL distribution and dynamics. We will use super-resolution microscopy, molecular counting, photoconversion and FCS to further characterize these two key components required for centriole formation in human cells. 2) The SAS-6 ring model as a tool to redirect centriole organization. Utilizing predictions from the SAS-6 ring model, we will assay the consequences for centrioles and cilia of altering the diameter and symmetry of the structure. 3) Determining the architecture of C. elegans centrioles. We will conduct molecular counting and cryo-ET of purified C. elegans centrioles to determine if they contain a spiral or a cartwheel, as well as identify SAS-6-interacting components. 4) Comprehensive 3D map and proteomics of Trichonympha centriole. We will obtain a ~35 Å 3D map of the complete T. agilis centriole, perform proteomic analysis to identify its constituents and test their function using RNAi. 5) Regulation of cartwheel height and centriole length. We will explore whether cartwheel height is set by SAS-6 proteins and perform screens in human cells to identify novel components regulating cartwheel height and centriole length. 6) Novel cell free assay for cartwheel assembly and centriole formation. Using SAS-6 proteins on a lipid monolayer as starting point, we will develop and utilize a cell-free assay to reconstitute cartwheel assembly and centriole format"

2 499 270 €

Start date: 2014-04-01, End date: 2019-03-31

Centrioles assemble centrosomes and cilia/flagella, critical structures for cell division, polarity, motility and signalling, which are often deregulated in human disease. Centriole inheritance, in particular the preservation of their copy number and position in the cell is critical in many eukaryotes. I propose to investigate, in an integrative and quantitative way, how centrioles are formed in the right numbers at the right time and place, and how they are maintained to ensure their function and inheritance. We first ask how centrioles guide their own assembly position and centriole copy number. Our recent work highlighted several properties of the system, including positive and negative feedbacks and spatial cues. We explore critical hypotheses through a combination of biochemistry, quantitative live cell microscopy and computational modelling. We then ask how the centrosome and the cell cycle are both coordinated. We recently identified the triggering event in centriole biogenesis and how its regulation is akin to cell cycle control of DNA replication and centromere assembly. We will explore new hypotheses to understand how assembly time is coupled to the cell cycle. Lastly, we ask how centriole maintenance is regulated. By studying centriole disappearance in the female germline we uncovered that centrioles need to be actively maintained by their surrounding matrix. We propose to investigate how that matrix provides stability to the centrioles, whether this is differently regulated in different cell types and the possible consequences of its misregulation for the organism (infertility and ciliopathy-like symptoms). We will take advantage of several experimental systems (in silico, ex-vivo, flies and human cells), tailoring the assay to the question and allowing for comparisons across experimental systems to provide a deeper understanding of the process and its regulation.

2 000 000 €

Start date: 2017-01-01, End date: 2021-12-31

The simulation of Partial Differential Equations (PDEs) is an indispensable tool for innovation in science and technology. Computer-based simulation of PDEs approximates unknowns defined on a geometrical entity such as the computational domain with all of its properties. Mainly due to historical reasons, geometric design and numerical methods for PDEs have been developed independently, resulting in tools that rely on different representations of the same objects. CHANGE aims at developing innovative mathematical tools for numerically solving PDEs and for geometric modeling and processing, the final goal being the definition of a common framework where geometrical entities and simulation are coherently integrated and where adaptive methods can be used to guarantee optimal use of computer resources, from the geometric description to the simulation. We will concentrate on two classes of methods for the discretisation of PDEs that are having growing impact: isogeometric methods and variational methods on polyhedral partitions. They are both extensions of standard finite elements enjoying exciting features, but both lack of an ad-hoc geometric modelling counterpart. We will extend numerical methods to ensure robustness on the most general geometric models, and we will develop geometric tools to construct, manipulate and refine such models. Based on our tools, we will design an innovative adaptive framework, that jointly exploits multilevel representation of geometric entities and PDE unknowns. Moreover, efficient algorithms call for efficient implementation: the issue of the optimisation of our algorithms on modern computer architecture will be addressed. Our research (and the team involved in the project) will combine competencies in computer science, numerical analysis, high performance computing, and computational mechanics. Leveraging our innovative tools, we will also tackle challenging numerical problems deriving from bio-mechanical applications.

2 199 219 €

Start date: 2016-10-01, End date: 2021-09-30

This project is devoted to the mathematical analysis of important physical properties of many-body quantum systems. We will be interested in properties of the ground state and low-energy excitations but also of non-equilibrium dynamics. We are going to consider systems with different statistics and in different regimes. The questions we are going to address have a common aspect: correlations among particles play a crucial role. Our main goal consists in developing new tools that allow us to correctly describe many-body correlations and to understand their effects. The starting point of our proposal are ideas and techniques that have been introduced in a series of papers establishing the validity of Bogoliubov theory for Bose gases in the Gross-Pitaevskii regime, and in a recent preprint showing how (bosonic) Bogoliubov theory can also be used to study the correlation energy of Fermi gases. In this project, we plan to develop these techniques further and to apply them to new contexts. We believe they have the potential to approach some fundamental open problem in mathematical physics. Among our most ambitious objectives, we include the proof of the Lee-Huang-Yang formula for the energy of dilute Bose gases and of the corresponding Huang-Yang formula for dilute Fermi gases, as well as the derivation of the Gell-Mann--Brueckner expression for the correlation energy of a high density Fermi system. Furthermore, we propose to work on long-term projects (going beyond the duration of the grant) aiming at a rigorous justification of the quantum Boltzmann equation for fermions in the weak coupling limit and at a proof of Bose-Einstein condensation in the thermodynamic limit, two very challenging and important questions in the field.

1 876 050 €

Start date: 2019-09-01, End date: 2024-08-31

This project is about the racialization of migrant labourers across political boundaries, with a main focus on impoverished Europeans who served in huge numbers as indentured labourers in nineteenth-century Guianese, Caribbean and Hawaiian sugar plantations and in the workforce of late nineteenth and early twentieth century New England cotton mills. With this project I aim to provide major, innovative contributions on three fronts: (i) theory-making, by working the concepts of race, racism, racialization, embodiment and memory in association with migrant work across political boundaries and imperial classifications; (ii) social relevance of basic research, by linking an issue of pressing urgency in contemporary Europe to substantive, broad-scope, and multi-sited anthropological/historical research on the wider structures of domination, rather than to targeted problem-solving research of immediate applicability; (iii) disciplinary scope, by proposing to unsettle historical anthropology and ethnographic history from within the boundaries of a single empire, and to overcome the limitations of existing comparative studies, by inquiring into the flows and interactions between competing empires. I will also: (iv) strengthen the methodology for multi-sited, multi-period research in anthropology; (v) contribute to an anthropology of global connections and trans-local approaches; (vi) promote the multidisciplinary and combined-methods approach to complex subjects; (vii) narrate a poorly known set of historical situations of labour racializations involving Europeans and document the ways they reverberate through generations; and (viii) make the analysis available to both academic audiences and the different communities involved in the research.

2 161 397 €

Start date: 2016-09-01, End date: 2021-08-31

The collective behavior of quantum and classical many body systems such as ultracold atomic gases, nanowires, cuprates and micromagnets are currently subject of an intense experimental and theoretical research worldwide. Understanding the fascinating phenomena of Bose-Einstein condensation, Luttinger liquid vs non-Luttinger liquid behavior, high temperature superconductivity, and spontaneous formation of periodic patterns in magnetic systems, is an exciting challenge for theoreticians. Most of these phenomena are still far from being fully understood, even from a heuristic point of view. Unveiling the exotic properties of such systems by rigorous mathematical analysis is an important and difficult challenge for mathematical physics. In the last two decades, substantial progress has been made on various aspects of many-body theory, including Fermi liquids, Luttinger liquids, perturbed Ising models at criticality, bosonization, trapped Bose gases and spontaneous formation of periodic patterns. The techniques successfully employed in this field are diverse, and range from constructive renormalization group to functional variational estimates. In this research project we propose to investigate a number of statistical mechanics models by a combination of different mathematical methods. The objective is, on the one hand, to understand crossover phenomena, phase transitions and low-temperature states with broken symmetry, which are of interest in the theory of condensed matter and that we believe to be accessible to the currently available methods; on the other, to develop new techiques combining different and complementary methods, such as multiscale analysis and localization bounds, or reflection positivity and cluster expansion, which may be useful to further progress on important open problems, such as Bose-Einstein condensation, conformal invariance in non-integrable models, existence of magnetic or superconducting long range order.

650 000 €

Start date: 2010-01-01, End date: 2014-12-31

This project focuses on nontrivial solutions of systems of differential equations characterized by strongly nonlinear interactions. We are interested in the effect of the nonlinearities on the emergence of non trivial self-organized structures. Such patterns correspond to selected solutions of the differential system possessing special symmetries or shadowing particular shapes. We want to understand, from the mathematical point of view, what are the main mechanisms involved in the aggregation process in terms of the global variational structure of the problem. Following this common thread, we deal with both with the classical N-body problem of Celestial Mechanics, where interactions feature attractive singularities, and competition-diffusion systems, where pattern formation is driven by strongly repulsive forces. More precisely, we are interested in periodic and bounded solutions, parabolic trajectories with the final intent to build complex motions and possibly obtain the symbolic dynamics for the general N–body problem. On the other hand, we deal with elliptic, parabolic and hyperbolic systems of differential equations with strongly competing interaction terms, modeling both the dynamics of competing populations (Lotka- Volterra systems) and other interesting physical phenomena, among which the phase segregation of solitary waves of Gross-Pitaevskii systems arising in the study of multicomponent Bose-Einstein condensates. In particular, we will study existence, multiplicity and asymptotic expansions of solutions when the competition parameter tends to infinity. We shall be concerned with optimal partition problems related to linear and nonlinear eigenvalues

1 346 145 €

Start date: 2014-02-01, End date: 2019-01-31

The goal of this project is to study conformally invariant fractal structures from the perspectives of analysis, dynamics, probability, geometry and physics, emphasizing interrelations of these fields. In the last two decades such structures emerged in several areas: continuum scaling limits of 2D critical models in statistical physics (percolation, Ising model); extremal configurations for various problems in complex analysis (multifractal harmonic measures, coefficient growth of univalent maps, Brennan's conjecture); chaotic sets for complex dynamical systems (Julia sets, Kleinian groups). Capitalizing on recent successes, I plan to continue my work in these areas, exploiting their interactions and connections to physics. I intend to achieve at least some of the following goals: * To establish that several critical lattice models have conformally invariant scaling limits, by building upon results on percolation and Ising models and finding discrete holomorphic observables. * To study geometric properties of arising fractal curves and random fields by connecting them to Schramm's SLE curves and Gaussian Free Fields. * To investigate massive scaling limits by describing them geometrically with generalizations of SLEs. * To lay mathematical framework behind relevant physical notions, such as Coulomb Gas (by relating height functions to GFFs) and Quantum Gravity (by identifying limits of random planar graphs with Liouville QGs). * To improve known bounds in several old questions in complex analysis by studying multifractal spectra of harmonic measures. * To estimate extremal behavior of such spectra by using holomorphic motions of (quasi) conformal maps and thermodynamic formalism. * To understand nature of extremal multifractals for harmonic measure by studying random and dynamical fractals. The topics involved range from century old to very young ones. Recently connections between them started to emerge, opening exciting possibilities for new developments in some long standing open problems.

1 278 000 €

Start date: 2009-01-01, End date: 2013-12-31

The developments of Statistical Mechanics and Quantum Field Theory are among the major achievements of the 20th century's science. During the second half of the century, these two subjects started to converge. In two dimensions, this resulted in a most remarkable chapter of mathematical physics: Conformal Field Theory (CFT) reveals deep structures allowing for extremely precise investigations, making such theories powerful building blocks of many subjects of mathematics and physics. Unfortunately, this convergence has remained non-rigorous, leaving most of the spectacular field-theoretic applications to Statistical Mechanics conjectural. About 15 years ago, several mathematical breakthroughs shed new light on this picture. The development of SLE curves and discrete complex analysis has enabled one to connect various statistical mechanics models with conformally symmetric processes. Recently, major progress was made on a key statistical mechanics model, the Ising model: the connection with SLE was established, and many formulae predicted by CFT were proven. Important advances towards connecting Statistical Mechanics and CFT now appear possible. This is the goal of this proposal, which is organized in three objectives: (I) Build a deep correspondence between the Ising model and CFT: reveal clear links between the objects and structures arising in the Ising and CFT frameworks. (II) Gather the insights of (I) to study new connections to CFT, particularly for minimal models, current algebras and parafermions. (III) Combine (I) and (II) to go beyond conformal symmetry: link the Ising model with massive integrable field theories. The aim is to build one of the first rigorous bridges between Statistical Mechanics and CFT. It will help to close the gap between physical derivations and mathematical theorems. By linking the deep structures of CFT to concrete models that are applicable in many subjects, it will be potentially useful to theoretical and applied scientists.

998 005 €

Start date: 2017-03-01, End date: 2022-02-28

Organismal development requires proper timing of events such as cell fate choices, but the mechanisms that control temporal patterning remain poorly understood. In particular, we know little of the cyclical timers, or ‘clocks’, that control recurring events such as vertebrate segmentation or nematode molting. Furthermore, it is unknown how cyclical timers are coordinated with the global, or linear, timing of development, e.g. to ensure an appropriate number of cyclical repeats. We propose to elucidate the components, wiring, and properties of a prototypic developmental clock by studying developmental timing in the roundworm C. elegans. We build on our recent discovery that nearly 20% of the worm’s transcriptome oscillates during larval development – an apparent manifestation of a clock that times the various recurring events that encompass each larval stage. Our aims are i) to identify components of this clock using genetic screens, ii) to gain insight into the system’s architecture and properties by employing specific perturbations such as food deprivation, and iii) to understand the coupling of this cyclic clock to the linear heterochronic timer through genetic manipulations. To achieve our ambitious goals, we will develop tools for mRNA sequencing of individual worms and for their developmental tracking and microchamber-based imaging. These important advances will increase temporal resolution, enhance signal-to-noise ratio, and achieve live tracking of oscillations in vivo. Our combination of genetic, genomic, imaging, and computational approaches will provide a detailed understanding of this clock, and biological timing mechanisms in general. As heterochronic genes and rhythmic gene expression are also important for controlling stem cell fates, we foresee that the results gained will additionally reveal regulatory mechanisms of stem cells, thus advancing our fundamental understanding of animal development and future applications in regenerative medicine.

2 358 625 €

Start date: 2017-10-01, End date: 2022-09-30

Dendritic cell (DC) activation and homing from the periphery to lymph nodes is a critical first event in the immune response. It involves upregulation of the chemokine receptor CCR7 and chemoinvasion towards lymphatic vessels. Despite its critical importance in adaptive immunity, the mechanisms of DC migration towards and entry into lymphatics are still poorly understood; this severely limits new therapeutic strategies for immunomodulation and even strategies for treating lymphedema, which is exacerbated by poor immune functioning. We propose a battery of physiological, cell-biological, molecular, and computational studies to determine both the mechanisms of DC homing to lymphatic vessels and how DCs modulate lymphatic function. We approach this from the perspectives of both the DC and the lymphatic vessel. Regarding the DC, we will examine computationally and experimentally how draining flows toward the lymphatic alter their migration tactics and test our hypothesis that DCs possess a biomolecular flow-detector network (which we refer to as autologous chemotaxis) and are thus able to sense the direction of the subtle flow of fluid toward the lymphatics. Regarding the lymphatic vessel, we will elucidate how biochemical and biophysical inflammatory signals regulate their drainage function, alter cell-cell adhesions and overall permeability, and alter adhesion receptors to facilitate DC homing and entry. Finally, we will examine DC migration in mice with dysfunctional lymphatics and explore strategies to improve immune response. These will be carried out in 4 main projects, and will complement our recent work in lymphatic functional biology as well as our more therapeutic investigations in DC targeting and activation (Reddy et al., Nature Biotechnol., 2007). This deeper knowledge of mechanisms of DC-lymphatic cross-talk in a relevant biophysical context will enable our long-term goal of rational design for therapeutic immunomodulation and lymphedema.

1 730 966 €

Start date: 2008-05-01, End date: 2013-04-30

Diophantine problems have always been a central topic in Number Theory, and have shown deep links with other basic mathematical topics, like Algebraic and Complex Geometry. Our research plan focuses on some issues in this realm, which are strictly interrelated. In the last years the PI and collaborators obtained several results on integral and algebraic points on varieties, which have inspired much subsequent research by others, and which we plan to develop further. In particular: We plan a further study of integral points on varieties, and applications to Algebraic Dynamics, a possibility which has emerged recently. We plan to study further the so-called `Unlikely intersections'. This theme contains celebrated issues like the Manin-Mumford conjecture. After work of the PI with Bombieri and Masser in the last 10 years, it has been the object of much recent work and also of new conjectures by R. Pink and B. Zilber. Here a new method has recently emerged in work of the PI with Masser and Pila, which also leads (as shown by Pila) to signi_cant new cases of the Andr_e-Oort conjecture. We intend to pursue in this kind of investigation, exploring further the range of the methods. Finally, we plan further study of topics of Diophantine Approximation and Hilbert Irreducibility, connected with the above ones in the contents and in the methodology.

928 500 €

Start date: 2011-02-01, End date: 2016-01-31

The connections between the circulation of news of extreme events, the making of influential narratives of collective traumas and the development of emergency response policies lie at the heart of this research proposal, which focuses on four Southern European areas: Catalonia, Naples, Sicily and Valencia, from the 16th to the 18th century. How did accounts and individual memories of extreme events amount to authoritative interpretations? In which ways, and to what extent, did the latter orient collective behaviours and the recovery process, in both the short and the long term? Starting from the assumption that human relations are enhanced by the increased levels of socialisation that commonly occur in the aftermath of shocking events, which trigger the sharing of information, opinions and memories; and that the emotional impact of such events is likely to create a public opinion that draws attention to government’s action; the research proposal aims to contribute new insights into these issues by adopting an original methodology, developed across a variety of disciplines, including Cultural and Social History, Textual Criticism, Philology and Anthropology. Moreover, it will adopt a transnational perspective: since the selected regions belonged to the Spanish Monarchy, the development of practices and polices aimed to respond to disruption depended not only on the specific social and cultural features of local societies, but also on the circulation of political and technical staff, as well as on the sharing of knowledge, experiences and policy models, among the various areas of the Empire and its colonies. Studying the information exchange in the aftermath of disasters and the formation of an imagery of extraordinary events, will allow a comprehensive perspective on the policies and practices adopted by early modern societies to manage uncertainty, and on the potential impact that such narratives could have on the renegotiation of political and social relations.

1 481 813 €

Start date: 2018-02-01, End date: 2023-01-31

The Torah’s notion of divine law fundamentally transforms the nature of law found in its ancient Near Eastern context. Typically kings—not gods—took on the role of the promulgation of laws. The Torah’s conception of God as lawgiver emerged gradually through historical processes, rather than constituting the bedrock of the Bible’s literary and legal history. And, while scholars have long recognized the uniqueness of the Torah’s conception, its early historical development has received little attention. Only tangential analysis exists on the forces surrounding the genesis of the Torah’s notion of divine laws within ancient Near Eastern legal history or its impact on religion and politics in the early historical contexts of ancient Israel and Judah. This project therefore aims: 1) to explicate the anchoring of law in the religious ether of the Ancient Near East; 2) to elucidate for the first time the intellectual processes in ancient Israel and Judah that led to the notion of divine laws and God as lawgiver, drawing comparisons with other legal understandings and practices from the ancient Near East; 3) to assess the socio-political and religious impact of this notion with ancient Judaism through the Hellenistic Period; and 4) to contextualize this development in the ancient world in comparison to parallel developments in Greek polities. The project’s innovative potential lies in: 1) the evaluation of the divine laws as a historical phenomenon; 2) the neglected effort to understand their intellectual genesis and early development in a reciprocal relation to their socio-political context; 3) the cross-cultural analysis of ancient Israel and Judah and its neighbouring cultures in this regard; and 4) the application of a longue durée and realgeschichtliche perspective to largely literary and philological disciplines. These investigations offer a new paradigm for elucidating the webs connecting divinity, law, and socio-political developments in the first millennium BCE.

2 500 000 €

Start date: 2020-01-01, End date: 2024-12-31

Dunes are now protected environments, being top priority for coastal managers, because of their important role as coastal defences. But, it was not like that in the past. For centuries dunes were considered unproductive and dangerous. The sand blown by the wind was taken inland, invading fields, silting rivers and destroying villages. In the eighteenth century, a strategy was developed to fight against the dunes: trapping them with trees, with the double purpose of preventing the destruction of arable land and increasing their economic value converting them into forest areas. Different governments, in different countries supported the immobilization of the shifting sands. The strategy, developed in Europe, was taken to other places in the world. These works caused profound changes in vast coastal areas transforming arid landscapes of sandy dunes into green tree forests. This project aims to explore human-environment relations in coastal areas worldwide, since the eighteenth century until today, through the study of dunes as hybrid landscapes. Based on selected case-studies and comparative approaches, the project will focus on the origins, reasons and means of dunes afforestation; the impacts of the creation of new landscapes to local communities and ecosystems; and the present situation of dunes as coastal defences and rehabilitated environments. The final purpose is to produce an innovative global history of coastal dunes, combining knowledges from both Humanities and Social Sciences and Physical and Life Sciences, which has never been done. Supported by an interdisciplinary team, this research will result in new developments in the field of the Environmental History studies; provide relevant knowledge considering the need of efficient management solutions to adapt to the expected mean sea level rise; and stimulate environmental citizenship by disseminating the idea that the future of the world coasts depends on today’s actions.

1 062 330 €

Start date: 2018-11-01, End date: 2023-10-31

The focus of this project is the competing confessional discourses on cosmology of the seventeenth century, an epoch in which religious conflicts originated opposing ‘epistemic cultures’, which were embodied in scholarly institutions and networks such as the Protestant web of northern European universities or the global web of Jesuit colleges. In the Early Modern Period cosmological controversies (over issues such as heliocentrism, plurality of worlds, space, infinity, cometary theory, celestial matter and fluidity) were heated and amplified by increasing political and confessional fragmentation. The Roman prohibition of the Copernican system (1616) and the extraordinary condemnation of Galileo (1633) accelerated the formation of competing cosmological cultures along confessional and political lines of alliance and opposition. This research project addresses the interrelations between [1.] cosmological debates in the northern European Protestant institutional networks of scholars and institutions and [2.] cosmological debates in Jesuit institutional networks aiming at [3.] a comparative assessment of early formations and transformations of epistemic webs. It considers parallelisms and contrasts, negotiations and intersections of seventeenth-century cosmological discourses between scholars, institutions and scientific communities belonging to different epistemic cultures. This endeavor brings into focus the political-confessional dimension of early-modern cosmology and shows how science is embedded in struggles for cultural hegemony, struggles which were at once institutional and ideological. While there is a great deal of in-depth study on the history of science in various early-modern confessional contexts, a comparative study bringing together the history of knowledge institutions and their metaphysical legitimation is still a desideratum.

1 999 976 €

Start date: 2017-11-01, End date: 2022-10-31

"The aim of EINITE is to clarify the dynamics of economic inequality in Europe from the late Middle Ages up until the beginning of the Industrial Revolution. Very little data about economic inequality during such an early period is available today. Apart from some studies focussed on single years and small areas (usually only one city or a village), the only European region which has been the object of a large research project is Holland. The project will collect an extensive database about economic inequality, mainly of wealth (for which better documentation exists), focussing on Italy from a wider European perspective. Archival research will be concentrated on Italy where particularly good sources exist, but the Italian case will be placed in the varying European context. Published data and existing databases from all over the continent will be collected as terms of comparison. The final version of the project database will be made public. The activity of ENITE will be organized around four main research questions: 1) What is the long-term relationship between economic growth and inequality? This is the main question to which the others are all connected. 2) What were the effects of plagues and other severe mortality crises on property structures? 3) What is the underlying relationship between immigration and urban inequality? 4) How was economic inequality perceived in the past, and how did its perception change over time? The project will also help to explain the origin of the property structures and inequality levels to be found on the eve of the Industrial Revolution. Then, it will provide information relevant to the ‘Kuznets curve’ debate. Overall the project will lead to a better knowledge of economic inequality in the past, which is also expected to help understanding recent developments in inequality levels in Europe and elsewhere."

995 400 €

Start date: 2012-01-01, End date: 2016-12-31

This project will explore the idea – and gather the evidence to prove it – that the so-called printing revolution does not consist in a change in book-making technology but in the process, prolonged over the entire course of the early modern age, of the formation of the printed book market and the creation of readers as purchasers and consumers of books. In order to demonstrate this, the project will reconstruct the economic and legal framework of the European book market by applying an interdisciplinary approach to the economic study of book history. By using unique and hitherto unexplored documentary evidence, this project addresses four fundamental questions relating to the growth of a fully developed book trade and the rise of a society of book consumers within the social and religious context of early modern Europe: the economic issue of book prices; the juridical and political issue of the book privilege system (which in turn influenced the process of book pricing); the management of the bookselling business (focusing on businesses in two major cities in the European book trade, Venice (Bernardino Giunti) and Antwerp (Christopher Plantin)); the technique of building and managing a transnational network for book distribution and sale (analyzing groundbreaking new evidence, an entire year (1522) of correspondence from a Venetian wholesale bookseller, Giovanni Bartolomeo Gabiano). These four research areas will feed into an overarching project which will examine the impact of books and the access of readers to them, together with the development in patterns of cultural consumption which meant that printed books lost the luxury status which they had had throughout the incunabula period to become transformed into ‘popoluxe’ goods.

1 434 375 €

Start date: 2016-09-01, End date: 2021-08-31