Wikidata: Q154804
FundRef: 501100008678
ISNI: 0000000476699786
RRID: RRID:nlx_149130 , RRID:SCR_004960
Wikidata: Q154804
FundRef: 501100008678
ISNI: 0000000476699786
RRID: RRID:nlx_149130 , RRID:SCR_004960
Since decades the bulk of cancer research focusses on the genetic and molecular level. To complement this knowledge, I will focus on the collective behaviour of cancer cells in cell clusters and in the extracellular matrix (ECM). Conventional cancer research tackles issues like genetic changes, signalling pathways or intracellular mechanisms, I want to answer the question: When is a cancer cell jammed or when can it overcome the yield stress to actively “flow” in a dense microenvironment (ME)? I have brought forward the basic idea within the concept of Physics of Cancer that changes in a cancer cell’s material properties determine its metastatic potential. As follows I propose the next breakthrough by determining a predictive phase diagram for unjamming transitions of cancer cells. Cancer cell jamming is quantified by cell speed as a measure of the motile forces and by cellular shape to account for the interplay between cell contractility and adhesion. Our self-propelled Voronoi model (SPV) will explain whether a cell is jammed by its neighbours or the ECM, overcoming the limitations of existing theories which only apply to specific environments. Building on my leadership in cell biomechanics and the exclusive access to two types of carcinomas (mamma, cervix), I will introduce highly innovative bionic modulators of intracellular mechanics and develop live cancer cell tracking in biopsies as a ground-breaking alternative to vital imaging. While these approaches are perfect to prove that unjamming transitions are key to tumour progression, I will investigate to what extent fluid, i.e. unjammed, tissue behaviour can be detected by magnetic resonance imaging elastography (MRE) as an individual predictive marker for metastasis. Moreover the results may guide surgeons when concerning the local spreading of cancer and thus greatly empower surgery in tumour therapies.
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This research project is an investigation of identity- and nation-building in eighteenth-century Bhutan with a particular focus on the agency of Buddhist masters as important diplomats and Bhutan's entangled history with Tibet. This will enable a novel understanding of Bhutan's religious and political history, particularly its Buddhism-induced development model of Gross National Happiness (GNH) that has not yet received systematic historical analysis in religious studies in Europe despite its global popularity as an example of alternative sustainable economic models. Furthermore, for the first time, Bhutan's historical role in linking South Asia, the British Raj, and East Asia will be systematically addressed. The research output will significantly advance both fields - that of Tibetology and religious studies. The innovative research design combines historical-philological methods by analyzing a thus far untranslated corpus of Bhutanese/Tibetan primary sources with a theoretical framework from religious studies focusing on identity and social differentiation. Therefore, the project is in its methodology, output, and impact inter-disciplinary. The researcher will produce a draft for a single monograph publication for habilitation in Germany. The proposed project involves as the researcher a German Tibetologist trained in Germany, Canada, India, and Bhutan reintegrating to Germany to work with a religious/Buddhist studies scholar at Leipzig University. This will enable substantial training for the researcher in religious studies and impactful two-way knowledge exchange between the researcher and the host institution due to the international experience of the researcher. An intersectional secondment at The British Library Endangered Archives Programme (London) will provide further Tibetological training in (digital) archival work, palaeography, and codicology, and produce globally accessible research data about this digitized Bhutanese/Tibetan primary source corpus.
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This project is devoted to integrable probability. The key feature of the field is the prominent role of methods and ideas from other parts of mathematics (such as representation theory, combinatorics, integrable systems, and others) which are applied to stochastic models. This philosophy often leads to very precise limit theorems which seem to be inaccessible by more standard probabilistic techniques. The proposed research is a study of a variety of probabilistic models. Specific examples include the single- and multi-species asymmetric simple exclusion process, a six vertex model, random walks on Hecke, Temperley-Lieb, and Brauer algebras, random tilings models, and random representations. The suggested methodology consists of a range of probabilistic, algebraic, analytic, and combinatorial techniques. The project involves two circles of questions. The first one focuses on random walks on algebras and their applications to interacting particle systems. The specific objectives include studying the Kardar-Parisi-Zhang type fluctuations for the multi-species asymmetric simple exclusion process, computing limit shapes and fluctuations around them for a general six vertex model, introducing and studying integrable three-dimensional analogues of a six vertex model, and developing a general theory of random walks on algebras. The second one focuses on asymptotic representation theory. This area deals with the probabilistic description of representations of “big” groups. Such questions turn out to be related to a plethora of other probabilistic models, in particular, to models of statistical mechanics. The goals of this part include bringing this interplay to a new level, developing asymptotic representation theory of quantum groups, and studying random tilings in random environment. The unifying idea behind these questions is a systematic use of precise relations for the study of asymptotic behavior of stochastic models which are out of reach of any other techniques.
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Atrial fibrillation (AF) may be categorized as an epidemic disease associated with an increased risk for heart failure, thromboembolism, dementia and mortality. The underlying mechanisms behind AF describe multiple pathological states leading to various remodeling processes. One of the easiest available diagnostical tools is an electrocardiogram (ECG). Numerous P wave indices have been identified, demonstrating associations with increased risk for adverse cardiovascular outcomes and mortality. Prolonged signal-averaged P wave duration (SAPWD) measured from the non-invasive signal averaged electrocardiogram (SAECG) using a vector composite of filtered orthogonal leads accurately measures cardiac activation times. In comparison with analysis of a standard 12-lead ECG, the SAECG is superior in detection of P wave prolongation as a risk marker for AF. However, there are only limited data analyzing this issue. Current project is aimed to perform P wave SAECGs in Framingham Heart Study (Boston, US) and LIFE Health Care Study (Leipzig, Germany) and to investigate their role in AF incidence. Furthermore, estimation of corresponding lifetime risk will be performed using multistate modeling phenomapping of AF, e.g. classification of AF patients based on a broad range of data (clinical, laboratory, ECG, echocardiography, biomarkers) predicting adverse clinical outcomes. The current project represents an innovative and authentic multidisciplinary research in AF and includes different future perspectives. It paves the way for fruitful international cooperation with Framingham cohort - the one the most renowned epidemiological studies, intensive exchange of experience and researcher mobility as well as academical and practical implementation of cardiovascular epidemiology and prevention at European institution.
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