ERC FUNDED PROJECTS

Dysregulation of capillary permeability is a severe problem in critically ill patients, but the mechanisms involved are poorly understood. Further, there are no targeted therapies to stabilize leaky vessels in various common, potentially fatal diseases, such as systemic inflammation and sepsis, which affect millions of people annually. Although a multitude of signals that stimulate opening of endothelial cell-cell junctions leading to permeability have been characterized using cellular and in vivo models, approaches to reverse the harmful process of capillary leakage in disease conditions are yet to be identified. I propose to explore a novel autocrine endothelial permeability regulatory system as a potentially universal mechanism that antagonizes vascular stabilizing ques and sustains vascular leakage in inflammation. My group has identified inflammation-induced mechanisms that switch vascular stabilizing factors into molecules that destabilize vascular barriers, and identified tools to prevent the barrier disruption. Building on these discoveries, my group will use mouse genetics, structural biology and innovative, systematic antibody development coupled with gene editing and gene silencing technology, in order to elucidate mechanisms of vascular barrier breakdown and repair in systemic inflammation. The expected outcomes include insights into endothelial cell signaling and permeability regulation, and preclinical proof-of-concept antibodies to control endothelial activation and vascular leakage in systemic inflammation and sepsis models. Ultimately, the new knowledge and preclinical tools developed in this project may facilitate future development of targeted approaches against vascular leakage.

1 999 770 €

Start date: 2018-05-01, End date: 2023-04-30

"Large bodies usually follow the classical equations of motion. Deviations from this can be called macroscopic quantum behavior. These phenomena have been experimentally verified with cavity Quantum Electro Dynamics (QED), trapped ions, and superconducting Josephson junction systems. Recently, evidence was obtained that also moving objects can display such behavior. These objects are micromechanical resonators (MR), which can measure tens of microns in size and are hence quite macroscopic. The degree of freedom is their vibrations: phonons. I propose experimental research in order to push quantum mechanics closer to the classical world than ever before. I will try find quantum behavior in the most classical objects, that is, slowly moving bodies. I will use MR's, accessed via electrical resonators. Part of it will be in analogy to the previously studied macroscopic systems, but with photons replaced by phonons. The experiments are done in a cryogenic temperature mostly in dilution refrigerator. The work will open up new perspectives on how nature works, and can have technological implications. The first basic setup is the coupling of MR to microwave cavity resonators. This is a direct analogy to optomechanics, and can be called circuit optomechanics. The goals will be phonon state transfer via a cavity bus, construction of squeezed states and of phonon-cavity entanglement. The second setup is to boost the optomechanical coupling with a Josephson junction system, and reach the single-phonon strong-coupling for the first time. The third setup is the coupling of MR to a Josephson junction artificial atom. Here we will access the MR same way as the motion of a trapped ions is coupled to their internal transitions. In this setup, I am proposing to construct exotic quantum states of motion, and finally entangle and transfer phonons over mm-distance via cavity-coupled qubits. I believe within the project it is possible to perform rudimentary Bell measurement with phonons."

2 004 283 €

Start date: 2015-01-01, End date: 2019-12-31

Not very long ago, it was still common to hold that little of interest took place in Islamic philosophy, theology and science after the death of the Peripatetic commentator Averroes in 1198. Recent research has produced increasing evidence against this view, and experts now commonly agree that texts from the so-called post-classical period merit serious analysis. That evidence, however, is still fragmentary, and we lack a clear understanding of the large scale and long run development in the various fields of Islamic intellectual culture after the twelfth century. This project will investigate debates concerning the nature and methods of knowledge in four of the most ambitious strands of Islamic theoretical thought, that is, philosophy, theology, natural science, and philosophically inclined Sufism. Its temporal scope extends from the end of the twelfth century to the beginning of the colonial era, and it focuses on foundational epistemological questions (how knowledge is defined, what criteria are used to distinguish it from less secure epistemic attitudes, what methods are identified as valid in the acquisition of knowledge) as well as questions concerning knowledge as the goal of our existence (in particular, whether perceptual experience is inherently valuable). Our study of the four strands is based on the hypothesis that the post-classical period is witness to a sophisticated discussion of knowledge, in which epistemic realism, intuitionism, phenomenalism, and subjectivism are pitted against each other in a nuanced manner. Hence, the project will result in a well-founded reassessment of the common view according to which post-classical Islamic intellectual culture is authoritarian and stuck to an epistemic paradigm that stifles insight and creativity. Thereby it will provide new ingredients for projects of endogenous reform and reorientation in Islam, and corroborate the view that our future histories of philosophy should incorporate the Islamic tradition.

1 526 429 €

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

This proposal is concerned with the mathematical theory of inverse problems. This is a vibrant research field at the intersection of pure and applied mathematics, drawing techniques from PDE, geometry, and harmonic analysis as well as generating new research questions inspired by applications. Prominent questions include the Calderón problem related to electrical imaging, the Gel'fand problem related to seismic imaging, and geometric inverse problems such as inversion of the geodesic X-ray transform. Recently, exciting new connections between these different topics have begun to emerge in the work of the PI and others, such as: - The explicit appearance of the geodesic X-ray transform in the Calderón problem. - An unexpected connection between the Calderón and Gel’fand problems involving control theory. - Pseudo-linearization as a potential unifying principle for reducing nonlinear problems to linear ones. - The introduction of microlocal normal forms in inverse problems for PDE. These examples strongly suggest that there is a larger picture behind various different inverse problems, which remains to be fully revealed. This project will explore the possibility of a unified theory for several inverse boundary problems. Particular objectives include: 1. The use of normal forms and pseudo-linearization as a unified point of view, including reductions to questions in integral geometry and control theory. 2. The solution of integral geometry problems, including the analysis of convex foliations, invertibility of ray transforms, and a systematic Carleman estimate approach to uniqueness results. 3. A theory of inverse problems for nonlocal models based on control theory arguments. Such a unified theory could have remarkable consequences even in other fields of mathematics, including controllability methods in transport theory, a solution of the boundary rigidity problem in geometry, or a general pseudo-linearization approach for solving nonlinear operator equations.

920 880 €

Start date: 2018-05-01, End date: 2023-04-30