ERC FUNDED PROJECTS

Elucidating how neural circuits coordinate behaviour, and how molecules underpin the properties of individual neurons are major goals of neuroscience. Optogenetics and neural imaging combined with the powerful genetics and well-described nervous system of C. elegans offer special opportunities to address these questions. Previously, we identified a series of sensory neurons that modulate aggregation of C. elegans. These include neurons that respond to O2, CO2, noxious cues, satiety state, and pheromones. We propose to take our analysis to the next level by dissecting how, in mechanistic molecular terms, these distributed inputs modify the activity of populations of interneurons and motoneurons to coordinate group formation. Our strategy is to develop new, highly parallel approaches to replace the traditional piecemeal analysis. We propose to: 1) Harness next generation sequencing (NGS) to forward genetics, rapidly to identify a molecular ¿parts list¿ for aggregation. Much of the genetics has been done: we have identified almost 200 mutations that inhibit or enhance aggregation but otherwise show no overt phenotype. A pilot study of 50 of these mutations suggests they identify dozens of genes not previously implicated in aggregation. NGS will allow us to molecularly identify these genes in a few months, providing multiple entry points to study molecular and circuitry mechanisms for behaviour. 2) Develop new methods to image the activity of populations of neurons in immobilized and freely moving animals, using genetically encoded indicators such as the calcium sensor cameleon and the voltage indicator mermaid. This will be the first time a complex behaviour has been dissected in this way. We expect to identify novel conserved molecular and circuitry mechanisms.

2 439 996 €

Start date: 2011-04-01, End date: 2017-03-31

Our affective and motivational state is important for our decisions, actions and quality of life. Many pathological conditions affect this state. For example, addictive drugs are hyperactivating the reward system and trigger a strong motivation for continued drug intake, whereas many somatic and psychiatric diseases lead to an aversive state, characterized by loss of motivation. I will study specific neural circuits and mechanisms underlying reward and aversion, and how pathological signaling in these systems can trigger relapse in drug addiction. Given the important role of the dopaminergic neurons in the midbrain for many aspects of reward signaling, I will study how synaptic plasticity in these cells, and in their target neurons in the striatum, contribute to relapse in drug seeking. I will also study the circuits underlying aversion. Little is known about these circuits, but my hypothesis is that an important component of aversion is signaled by a specific neuronal population in the brainstem parabrachial nucleus, projecting to the central amygdala. We will test this hypothesis and also determine how this aversion circuit contributes to the persistence of addiction and to relapse. To dissect this complicated system, I am developing new genetic methods for manipulating and visualizing specific functional circuits in the mouse brain. My unique combination of state-of-the-art competence in transgenics and cutting edge knowledge in the anatomy and functional organization of the circuits behind reward and aversion should allow me to decode these systems, linking discrete circuits to behavior. Collectively, the results will indicate how signals encoding aversion and reward are integrated to control addictive behavior and they may identify novel avenues for treatment of drug addiction as well as aversion-related symptoms affecting patients with chronic inflammatory conditions and cancer.

1 500 000 €

Start date: 2010-10-01, End date: 2015-09-30

"AIME is an inquiry to make more precise what is lumped together into the confusing word ""modernization"". The work done in the field of science studies (STS) on the progress and practice of science and technology has had the consequence of deeply modifying the definition of ""modernity"", resulting into the provocative idea that ""we (meaning the Europeans) have never been modern"". This is, however only a negative definition. To obtain a positive rendering of the European current situation, it is necessary to start an inquiry in the complex and conflicting set of values that have been invented. This inquiry is possible only if there is a clear and shareable way to judge the differences in the set of truth-conditions that make up those conflicting sets of values. AIME offers a grammar of those differences based on the key notion of modes of existence. Then it builds a procedure and an instrument to test this grammar into a selected set of situations where the definitions of the differing modes of existence is redefined and renegotiated. The result is a set of shareable definitions of what modernization has been in practice. This is important just at the moment when Europe has lost its privileged status and needs to be able to present itself in a new ways to the other cultures and civilizations which are making up the world of globalization with very different views on what it is to modernize themselves."

1 334 720 €

Start date: 2011-09-01, End date: 2015-06-30

Methane, a key greenhouse gas, is cycled by microorganisms via two pathways, aerobically and anaerobically. Research on the marine methane cycle has mainly concentrated on anaerobic processes. Recent biomarker work has provided compelling evidence that aerobic methane oxidation (AMO) can play a more significant role in cycling methane emitted from sediments than previously considered. AMO, however, is not well studied requiring novel proxies that can be applied to the sedimentary record. A group of complex lipids biosynthesised by aerobic methanotrophs known as aminobacteriohopanepolyols represent an ideal target for developing such poxies. Recently BHPs have been identified in a wide range of modern and recent environments including a continuous record from the Congo deep sea fan spanning the last 1.2 million years. In this integrated study, the regulation and expression of BHP will be investigated and calibrated against environmental variables including temperature, pH, salinity and, most importantly, methane concentrations. The work program has three complementary strands. (1) Pure culture and sedimentary microcosm experiments providing an approximation to natural conditions. (2) Calibration of BHP signatures in natural marine settings (e.g. cold seeps, mud volcanoes, pockmarks) against measured methane gradients. (3) Application of this novel approach to the marine sedimentary record to approximate methane fluxes in the past, explore the age and bathymetric limits of this novel molecular proxy, and identify and potentially 14C date palaeo-pockmarks structures. Crucial to the success is also the refinement of the analytical protocols to improve both accuracy and sensitivity, using a more sensitive analytical instrument (triple-quadrupole mass spectrometer).

1 496 392 €

Start date: 2010-11-01, End date: 2016-04-30

The project is the first comprehensive study to assess contemporary parenting norms and practices and their diffusion. The project develops a comparative framework to study prevalent motherhood and fatherhood norms, images, identities and behaviour in current societies. The project will focus on how parenting roles are constructed by professionals, welfare states, and popular media, and will assess how cultural and institutional norms and images are perceived and realized by expecting and new parents. In 4 subprojects this study investigates 1) How standards of 'good' mothering and fathering are perceived, shaped and disseminated by professionals (gynaecologists, midwives, family councils); 2) How welfare states, labour markets and family policies target at mothers and fathers roles as earners and care givers, and how this has changed in recent decades; 3) How images of mothers and fathers roles have been portrayed in print media from 1980 until 2010; 4) How (expecting) mothers and fathers perceive, embody and represent parenting norms and images in their own work and family roles; 5) How new parents divide paid and unpaid work and how these divisions shape career patterns over the life course; 6) How these patterns differ cross-nationally. The international collaboration includes Sweden, the Netherlands, Germany, Italy, the Czech Republic, and Poland. The aim of this project is to develop a contemporary sociology of adult sex roles and parenting norms: A theory of the social creation of parenting norms and a comprehensive framework to study empirically the change of men's and women's roles, identities and practices as earners and care givers in the early phase of family formation. By combining expert interviews, policy analysis and content analysis of print media with analyses of qualitative and quantitative data on (nascent) parents, the project will address the diverse layers associated with changing gender roles and parenting norms over the adult life course.

1 393 751 €

Start date: 2011-01-01, End date: 2016-12-31

Despite its importance for human health and climate change organic aerosol (OA) remains one of the least understood aspects of atmospheric chemistry. We propose to develop an innovative new framework for the description of OA in chemical transport and climate models that will be able to overcome the challenges posed by the chemical complexity of OA while capturing its essential features. The objectives of ATMOPACS are: (i) The development of a new unified framework for the description of OA based on its two most important parameters: volatility and oxygen content. (ii) The development of measurement techniques for the volatility distribution and oxygen content distribution of OA. This will allow the experimental characterization of OA in this new “coordinate system”. (iii) The study of the major OA processes (partitioning, chemical aging, hygroscopicity, CCN formation, nucleation) in this new framework combining lab and field measurements. (iv) The development and evaluation of the next generation of regional and global CTMs using the above framework. (v) The quantification of the importance of the various sources and formation pathways of OA in Europe and the world, of the sensitivity of OA to emission control strategies, and its role in the direct and indirect effects of aerosols on climate. The proposed work involves a combination of laboratory measurements, field measurements including novel “atmospheric perturbation experiments”, OA model development, and modelling in urban, regional, and global scales. Therefore, it will span the system scales starting from the nanoscale to the global. The modelling tools that will be developed will be made available to all other research groups.

2 496 000 €

Start date: 2011-01-01, End date: 2015-12-31

A fundamental challenge of pancreas biology is to understand and manipulate the determinants of beta cell mass. The homeostatic maintenance of adult beta cell mass relies largely on replication of differentiated beta cells, but the triggers and signaling pathways involved remain poorly understood. Here I propose to investigate the physiological and molecular mechanisms that control beta cell replication. First, novel transgenic mouse tools will be used to isolate live replicating beta cells and to examine the genetic program of beta cell replication in vivo. Information gained will provide insights into the molecular biology of cell division in vivo. Additionally, these experiments will address critical unresolved questions in beta cell biology, for example whether duplication involves transient dedifferentiation. Second, genetic and pharmacologic tools will be used to dissect the signaling pathways controlling the entry of beta cells to the cell division cycle, with emphasis on the roles of glucose and insulin, the key physiological input and output of beta cells. The expected outcome of these studies is a detailed molecular understanding of the homeostatic maintenance of beta cell mass, describing how beta cell function is linked to beta cell number in vivo. This may suggest new targets and concepts for pharmacologic intervention, towards the development of regenerative therapy strategies in diabetes. More generally, the experiments will shed light on one of the greatest mysteries of developmental biology, namely how organs achieve and maintain their correct size. A fundamental challenge of pancreas biology is to understand and manipulate the determinants of beta cell mass. The homeostatic maintenance of adult beta cell mass relies largely on replication of differentiated beta cells, but the triggers and signaling pathways involved remain poorly understood. Here I propose to investigate the physiological and molecular mechanisms that control beta cell replication. First, novel transgenic mouse tools will be used to isolate live replicating beta cells and to examine the genetic program of beta cell replication in vivo. Information gained will provide insights into the molecular biology of cell division in vivo. Additionally, these experiments will address critical unresolved questions in beta cell biology, for example whether duplication involves transient dedifferentiation. Second, genetic and pharmacologic tools will be used to dissect the signaling pathways controlling the entry of beta cells to the cell division cycle, with emphasis on the roles of glucose and insulin, the key physiological input and output of beta cells. The expected outcome of these studies is a detailed molecular understanding of the homeostatic maintenance of beta cell mass, describing how beta cell function is linked to beta cell number in vivo. This may suggest new targets and concepts for pharmacologic intervention, towards the development of regenerative therapy strategies in diabetes. More generally, the experiments will shed light on one of the greatest mysteries of developmental biology, namely how organs achieve and maintain their correct size.

1 445 000 €

Start date: 2010-09-01, End date: 2015-08-31

This research project investigates the dynamics of private and public property in contemporary biomedical research. It will develop an analytical framework combining insights from science and technology studies, economic sociology, and legal and political philosophy, and pursues a social scientific investigation of the evolution of intellectual property rights in three fields of bioscientific research: 1) the use of transgenic research mice; 2) the legal status of totipotent and pluripotent stem cell lines; and 3) modes of collaboration for research and development on neglected diseases. These three domains, and their attendant modes of appropriation, will be compared across three general research themes: a) the production of public scientific goods; b) categories of appropriation; and c) the moral economy of research. The project rests on close observation of research practices in these three domains. The BioProperty research programme will track the trajectories of property rights and property objects in each of the three fields of biomedical research.

887 602 €

Start date: 2011-03-01, End date: 2014-12-31

Challenging the notion of Fortress Europe , the research investigates relations between the European Union and its southern periphery through the concept of borderlands . The concept emphasises the disaggregation of the triple function of borders demarcating state territory, authority, and national identity inherent in the Westphalian model of statehood. This process is most visible in (although not limited to) Europe, where integration has led to supranational areas of sovereignty, an internal market, a common currency, and a zone of free movement of people, each with a different territorial span. The project explores the complex and differentiated process by which the EU extends its unbundled functional and legal borders to the so-called southern Mediterranean (North Africa and parts of the Middle East), thereby transforming it into borderlands . They connect the European core with the periphery through various legal and functional border regimes, governance patterns, and the selective outsourcing of some EU border control duties. The overarching questions informing this research is whether, first, the borderland policies of the EU, described by some as a neo-medieval empire, is a functional consequence of the specific integration model pursued inside the EU, a matter of foreign policy choice or a local manifestation of a broader global phenomenon. Second, the project addresses the question of power dynamics that underwrite borderland governance, presuming a growing leverage of third country governments resulting from their co-optation as gatekeepers. Thus, while adopting an innovative approach, the project will enhance our understanding of EU-Mediterranean relations while also addressing crucial theoretical questions in international relations.

1 353 920 €

Start date: 2011-10-01, End date: 2017-03-31

Damage to parietal cortex after stroke causes patients to become unaware of large parts of their surroundings and body parts. This so-called spatial neglect is hypothesised to be brought about by a stroke-induced imbalance between the left and right hemisphere. Some patients experience a partial recovery of lost abilities, but the factors that drive this rebalancing are unknown. The research proposed here will overcome this bottleneck in our understanding of the brain recovery phenomenon, and develop therapeutic approaches that for the first time will control, steer and speed up brain rebalancing after stroke. To that goal, we introduce a revolutionary approach in which TMS, fMRI, and EEG are applied simultaneously in healthy human volunteers to artificially unbalance the brain, and then study and control processes of rebalancing. Because we are one of the few groups worldwide that has accomplished this methodology, and that has the expertise to fully analyse the data it will yield, we are in a unique position to deliver both fundamental insights into brain plasticity, and derived new therapies. In brief, we will use TMS to (i) mimic spatial neglect in healthy volunteers while simultaneously monitoring the underlying neural network effects using fMRI/EEG, and to (ii) determine which exact brain reorganisation leads to an optimal behavioral recovery after injury. Importantly, we will use cutting-edge fMRI pattern recognition and machine learning algorithms to predict which concrete TMS treatment will specifically support this optimal functional reorganisation in the unbalanced brain. Finally, we will directly translate these fundamental findings into clinical practise and apply novel TMS protocols to rebalance the brain in patients suffering from parietal stroke.

1 344 853 €

Start date: 2011-04-01, End date: 2016-03-31

Humans and other primates possess an exquisite capacity to grasp and manipulate objects. The seemingly effortless interaction with objects in everyday life is subserved by a number of cortical areas of the visual and the motor system. Recent research has highlighted that dorsal stream areas in the posterior parietal cortex are involved in object processing. Because parietal lesions do not impair object recognition, the encoding of object shape in posterior parietal cortex is considered to be important for the planning of actions towards objects. In order to succesfully grasp an object, the complex pattern of visual information impinging on the retina has to be transformed into a motor plan that can control the muscle contractions. The neural basis of visuomotor transformations necessary for directing actions towards objects, however, has remained largely unknown. This proposal aims to unravel the pathways and mechanisms involved in programming actions towards objects - an essential capacity for our very survival. We envision an integrated approach to study the transformation of visual information into motor commands in the macaque brain, combining functional imaging, single-cell recording, microstimulation and reversible inactivation. Our research efforts will be focussed on parietal area AIP and premotor area F5, two key brain areas for visually-guided grasping. Above all, this proposal will move beyond purely descriptive measurements of neural activity by implementing manipulations of brain activity to reveal behavioral effects and interdependencies of cortical areas. Finally the data obtained in this project will pave the way to use the neural activity recorded in visuomotor areas to act upon the environment by grasping objects by means of a robot hand.

1 499 200 €

Start date: 2010-11-01, End date: 2015-10-31

The study of several genetic disorders is hampered by the lack of suitable in vitro human models. We hypothesize that the generation of patient-specific induced pluripotent stem cells (iPSCs) will allow the development of disease-specific in vitro models; yielding new pathophysiologic insights into several genetic disorders and offering a unique platform to test novel therapeutic strategies. In the current proposal we plan utilize this novel approach to establish human iPSC (hiPSC) lines for the study of a variety of inherited cardiac disorders. The specific disease states that will be studied were chosen to reflect abnormalities in a wide-array of different cardiomyocyte cellular processes. These include mutations leading to: (1) abnormal ion channel function (“channelopathies”), such as the long QT and Brugada syndromes; (2) abnormal intracellular storage of unnecessary material, such as in the glycogen storage disease type IIb (Pompe’s disease); and (3) abnormalities in cell-to-cell contacts, such as in the case of arrhythmogenic right ventricular cardiomyopathy-dysplasia (ARVC-D). The different hiPSC lines generated will be coaxed to differentiate into the cardiac lineage. Detailed molecular, structural, functional, and pharmacological studies will then be performed to characterize the phenotypic properties of the generated hiPSC-derived cardiomyocytes, with specific emphasis on their molecular, ultrastructural, electrophysiological, and Ca2+ handling properties. These studies should provide new insights into the pathophysiological mechanisms underlying the different familial arrhythmogenic and cardiomyopathy disorders studied, may allow optimization of patient-specific therapies (personalized medicine), and may facilitate the development of novel therapeutic strategies. Moreover, the concepts and methodological knowhow developed in the current project could be extended, in the future, to derive human disease-specific cell culture models for a plurality of genetic disorders; enabling translational research ranging from investigation of the most fundamental cellular mechanisms involved in human tissue formation and physiology through disease investigation and the development and testing of novel therapies that could potentially find their way to the bedside

1 500 000 €

Start date: 2011-03-01, End date: 2016-02-29

The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (“multitasking cell types”), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform “a single computation” or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.

1 499 000 €

Start date: 2010-11-01, End date: 2015-10-31

The household and family structure in every major industrialized country changed in a fundamental way during the last couple of decades. First, marriage is less important today, as divorce, cohabitation, and single-motherhood are much more common. Second, female labor force participation has increased dramatically. As a result of these changes, today s households are very far from traditional breadwinner husband and housekeeper wife paradigm. These dramatic changes generated significant public interest and a large body of literature that tries to understand causes and consequences of these changes. This project has two main goals. First, it studies changes in household and family structure. The particular questions that it tries to answer are: 1) What are economic factors behind the rise in premarital sex and its destigmatization? What determines parents incentives to socialize their children and affect their attitudes? 2) What are the causes and consequences of the recent rise in assortative mating and diverging marriage patterns by different educational groups? 3) Why are marriage patterns among blacks so different than whites in the U.S.? The second aim of this project is to improve our understanding of income risk, the role of social insurance policies and labor market dynamics by building models that explicitly considers two-earner households. In particular, we ask the following set of questions: 1) What is the role of social insurance policies (income maintenance programs or progressive taxation) in an economy populated by two-earner households facing uninsurable idiosyncratic risk? 2) How does marriage and labor market dynamics interact and how important this interaction for our understanding of labor supply and marriage decisions?

1 037 000 €

Start date: 2010-11-01, End date: 2015-10-31

Over the past several decades, childbearing within cohabitation has risen sharply throughout most of Europe, Australia, and the U.S. This project aims to study the diffusion of childbearing within cohabitation using a number of analytic levels and methodological perspectives. We will explore the following questions: 1) Trends: How does fertility differ by union status, and how do these differences change over time? Are there differences by parity, age pattern, or timing? How does the decline in marital fertility contribute to the increase in share of nonmarital births? 2) Explanations: What are the underlying reasons for increasing childbearing within cohabitation? What has produced variation across countries? How do policies impact and/or respond to childbearing within cohabitation? How do societal-level perceptions of cohabitation, marriage, and childbearing differ across countries? 3) Lifecourse trajectories: How do the lifecourse trajectories for women who bear children differ by union status? Are women who give birth within cohabitation more likely to experience changes in family structure? Is childbearing within cohabitation associated with future negative social, emotional, or economic outcomes? To answer these questions, we will use an innovative mixed-methods strategy that 1) analyzes a unique database of harmonized reproductive and union histories, 2) conducts qualitative research into the role of policies and general perspectives on nonmarital childbearing, and 3) examines longitudinal surveys in comparative perspective. Ultimately, we aim to develop a new theoretical framework for understanding the diffusion of family change. This research will provide insights into whether lifecourse trajectories are diverging, potentially exacerbating social inequality.

1 131 600 €

Start date: 2011-03-01, End date: 2016-05-31

Human impact on the deep ocean is rapidly increasing, with largely unknown consequences. Effective management and conservation, based on an ecosystem approach, is hampered by our poor understanding of the deep-sea environment. Measuring biodiversity, the main indicator of ecosystem status and functioning, is a major challenge in deep water: traditional sampling schemes are expensive and time-consuming, and their limited coverage makes it difficult to relate the results to regional patterns. Complex deep-sea environments are especially problematic. Ecosystem hotspots such as canyons or coral reefs contain true 3D morphology that cannot be surveyed with conventional techniques. CODEMAP will quantify habitat heterogeneity in complex deep-sea terrains, and will evaluate its potential as a proxy for benthic biodiversity at a variety of scales. Habitat heterogeneity has been suggested as a major driver for deep-sea biodiversity, but is rarely quantified in a spatial context in the marine realm. To achieve its goal, CODEMAP will combine the fields of marine geology, ecology, remote sensing and underwater vehicle technology to establish an integrated, statistically robust and fully 3D methodology to map complex deep-sea habitats. Statistical techniques will be developed to extrapolate quantitative habitat information from fine-scale surveys to broad-scale maps. The optimal parameters to measure habitat heterogeneity will be defined, and their potential as biodiversity indicators tested through correlation with traditional approaches. The project focuses on submarine canyons, but the techniques will also be transferred to other environments. CODEMAP is expected to have a strong impact on the fundamental understanding of the deep sea and on ecosystem-based deep-sea management.

1 401 012 €

Start date: 2011-04-01, End date: 2017-01-31

Nowadays, ageing is one of the main problems in Western society. The increase in the percentage of elderly people serves to strain the Social Security to the point of bankruptcy. The only way to alleviate the suffering caused by age-related degenerative disease is to fully understand the underlying forces which drive ageing and design strategies to delay it. Mitochondria are considered as central modulators of longevity in different species. It has been proposed that free radicals cause the accumulation of oxidative damage and as a result ageing. In accordance with this, production of Reactive Oxygen Species (ROS) by complex I negatively correlates with longevity. However, the overexpression of antioxidants or the reduction of ROS levels does not increase lifespan. These contradictory data can only be reconciled if complex I is modulating longevity through a ROS independent mechanism. We have expressed the alternative internal NADH dehydrogenase 1 (NDI1) from Saccharomyces cerevisiae in Drosophila melanogaster. The expression of NDI1 does not change the level of ROS but increases both the ratio of NAD+/NADH and Drosophila longevity. The main objective of this proposal is to study the mechanisms by which complex I regulates longevity. My general hypothesis is that complex I regulates longevity through a ROS independent mechanism. I propose that complex I controls the cellular levels of NAD+/NADH, keeping their levels at an equilibrium that favours the optimal functioning of the cell. When the ratio is moved towards NADH ageing is promoted, whereas when it is moved towards NAD+ pro-survival pathways are activated. I proposed two specific mechanisms downstream of complex I that promote cellular longevity or senescence: 1) activation of sirtuins, which would increase genome stability and 2) reduction of methylglyoxal generation, which would decrease the accumulation of cellular garbarge .

1 491 600 €

Start date: 2011-02-01, End date: 2016-09-30

Control of migration is becoming an increasingly important task of contemporary policing and criminal justice agencies. The purpose of this project is to map the progressive intertwining and merging of crime control and migration control practices in Europe and to examine their implications. The project is guided by three sets of research questions: 1) How do contemporary police and criminal justice institutions deal with unwanted mobility and the influx of „aliens‟ (i.e. non-citizens) to their territories? 2) What is the relevance of citizenship for European penal systems? and 3) How do contemporary crime control practices support and perform the task of (cultural and territorial) border control? The project aims to analyse the impact of the growing emphasis on migration control on criminal justice agencies such as the police, prisons and detention facilities. The basic hypothesis of the project is that migration control objectives are contributing to the development of novel forms of punishment and new rationalities of social control termed „crimmigration‟. The project aims to describe these novel hybrid forms of control since they constitute important conceptual challenges for criminal justice scholarship and require new theoretical perspectives. A question will be asked: what kind of break from traditional criminal justice practices and principles do they represent? Is the focus on punishment and reintegration of offenders gradually being replaced by a focus on diversion, immobilisation and deportation? Moreover what kind of legal, organisational and normative responses do they require?

1 309 800 €

Start date: 2011-04-01, End date: 2016-03-31

In the Arabian peninsula, before the advent of Islam some distinctive civilizations flourished with a remarkable cultural level and left behind an important epigraphic and artistic wealth in terms of quality and interest. The history of these cultures is known almost exclusively by epigraphic material. In fact, the majority of texts that the inhabitants of Arabia have left us are the inscriptions that are found in their tens of thousands all over the lands. However, the inscriptions of pre-Islamic Arabia are only relatively known and often difficult to interpret, and scholars are obliged to draw on resources which are outdated or overly narrow in scope. On the basis of these considerations, DASI would like to apply the modern computer technology to the study of pre-Islamic inscriptions. The main objective of DASI is to improve and enrich the existing CSAI project (Corpus of South Arabian Inscriptions: http://csai.humnet.unipi.it) in terms of methodology and contents creating a digital archive of the whole corpus of pre-Islamic Arabian inscriptions. This archive is intended to become the virtual place where all the existing inscriptions from Arabia are gathered and can be managed, consulted and studied: the virtual ambient will collect the inscriptions that are physically located in different, faraway places such as archaeological sites in Arabia, as well as museums or private collections all over the world, but it will also document inscriptions by now physically lost and known only thorough previous publications. By actually cataloguing and studying these texts, the aim of DASI is to achieve a better overall perception and knowledge of the epigraphic heritage of pre-Islamic Arabia - yet a very young field - and consequently of its languages and cultures.

2 129 200 €

Start date: 2011-05-01, End date: 2016-04-30

This project aims at revolutionizing the way the emission of mineral dust from natural soils is treated in numerical models of the Earth system. Dust significantly affects weather and climate through its influences on radiation, cloud microphysics, atmospheric chemistry and the carbon cycle via the fertilization of ecosystems. To date, quantitative estimates of dust emission and deposition are highly uncertain. This is largely due to the strongly nonlinear dependence of emissions on peak winds, which are often underestimated in models and analysis data. The core objective of this project is therefore to explore ways of better representing crucial meteorological processes such as daytime downward mixing of momentum from nocturnal low-level jets, convective cold pools and small-scale dust devils and plumes in models. To achieve this, we shall undertake (A) a detailed analysis of observations including station data, measurements from recent field campaigns, analysis data and novel satellite products, (B) a comprehensive comparison between output from a wide range of global and regional dust models, and (C) extensive sensitivity studies with regional and large-eddy simulation models in realistic and idealized set-ups to explore effects of resolution and model physics. In contrast to previous studies, all evaluations will be made on a process level concentrating on specific meteorological phenomena. Main deliverables are guidelines for optimal model configurations and novel parameterizations that link gridscale quantities with probabilities of winds exceeding a given threshold within the gridbox. The results will substantially advance our quantitative understanding of the global dust cycle and reduce uncertainties in predicting climate, weather and impacts on human health.

1 355 025 €

Start date: 2010-10-01, End date: 2015-09-30

This project involves developing and applying new methods in palaeography, bringing digital resources to bear in innovative ways. It comprises three components: a web resource, a database, and a monograph. The web resource will allow the study of medieval script in the context of the manuscripts and charters that preserve it. It will focus on discovery and citation, allowing users to retrieve digital images, verbal descriptions, and detailed characterisations of the writing, as well as the larger context including the content and structure of the manuscript or charter. It will incorporate different ways of exploring the material such as images, maps and timelines as well as text-based browse and search. It will provide a flexible, extensible framework to integrate external data-sources and so applies to any period or area of palaeography. It will therefore enable new developments in palaeographical method which have been discussed in theory but not yet achieved in practice. To demonstrate these methods, content will be provided for handwriting from England in the vernacular, particularly that of AD 990-1100. This period saw rapid change in vernacular script despite relative stability in that of Latin, something that has never been fully explained. This problem will be addressed by integrating existing datasets but also by producing and incorporating an entirely new database of scripts. The result will provide access to the complete corpus of surviving examples of the script for the first time, bringing an unprecedented rigour to palaeographical analysis. A monograph will then draw on this research, demonstrating the new methods in practice and providing the first comprehensive account of English vernacular script from the period. The work will address issues in Digital Humanities (integration, interface design, visualisation and standards), in palaeographical method (quantitative methods, terminology and evidential rigour), and in the history of vernacular script

995 531 €

Start date: 2010-10-01, End date: 2014-09-30

I propose to develop and apply a novel method for the integrated reconstruction of past changes in carbon cycling and climate change. This method will be based on combining a well-established sensitive paleoclimate proxy with a recent discovery: the stable carbon isotopic composition (δ13C) of marine dinoflagellates (algae) and their organic fossils (dinocysts) reflects seawater carbonate chemistry, particularly pCO2. Biological (culture) experiments will lead to new insights in dinoflagellate carbon acquisition, and enable quantification of the effect of carbon speciation on dinoflagellate δ13C. The rises in CO2 concentrations during the last century, and at the termination of the last glacial period will be used to test and calibrate the new method. The δ13C of fossil dinoflagellate cysts will subsequently be used to reconstruct surface ocean pCO2 and ocean acidification during a past analogue of rapidly rising carbon dioxide concentrations, 55 million years ago. My research will shed new light on processes such as ocean acidification and the marine carbon cycle as a whole. Past analogues of rapid carbon injection can aid in the quantification of climate change and identification of vulnerable biological groups, critical to identify ‘tipping points’ in system Earth. The study of dinoflagellate carbon isotopes comprises the initiation of a new research field and will provide constraints on ocean acidification in the past and its consequences in the future.

1 498 800 €

Start date: 2010-09-01, End date: 2016-08-31

Breast, prostate, lung and colorectal cancer as solid tumours derived from epithelial tissues are responsible for 90% of all new cancers in Europe. Present tumour staging is mainly based on local tumour extension, metastatic lymph node involvement and evidence of overt distant metastasis obtained by imaging technologies. However, these staging procedures are not sensitive enough to detect early tumour cell dissemination as a key event in tumour progression. Our team has therefore focused on the development of ultrasensitive assays that allow the specific detection and molecular characterization of single tumour cells in bone marrow (DTC) and blood (CTC) of cancer patients. These methods allow the direct assessment of disseminating tumour cells including the detection of therapeutic targets and mechanisms of resistance in patients undergoing therapy. Based on our established network of clinical collaborations, the DISSECT project will detect and characterize DTC/CTC in patients with the four most frequent tumour entities in the EU by high resolution methods. We will investigate representative clinical studies for current interventions that may have an impact on tumour cell dissemination, including diagnostic biopsies, surgical resection of the primary tumour, radiotherapy, chemotherapy and in particular targeted therapies. The technologies for DTC/CTC analyses previously developed by our team will be complemented by cutting-edge technologies and adapted to the analysis to decisive molecular processes underlying the particular intervention. The results obtained in the DISSECT project will provide unique insights into the biology of tumour cell spread in humans and these insights might lead to improved concepts in the clinical management of cancer patients.

2 499 000 €

Start date: 2011-08-01, End date: 2016-07-31

"Distinguishing between conscious and unconscious processes is a fundamental issue for our understanding of the human mind. Most research on this topic has been limited to a static perspective, by studying static stimuli, by considering processing as a function of present information, and by focusing on a single, adult stage of development. Yet, both conscious and unconscious mental processes are intrinsically driven by dynamic properties. We will study these properties by relying on behavioral and brain imaging methods along three tracks: 1) Unconscious perception: Our visual system is, in real life, constantly receiving unconscious sequences of information that will generate dynamic and constantly updated processing streams. We will study these dynamic unconscious streams, thanks to Gaze-Contingent Substitution, a novel approach allowing for the presentation of subliminal videos and sequences of stimuli. 2) Conscious perception: Construction of a conscious percept does not only depend on present stimulation but also on interactions with prior knowledge. Relying on the Bayesian framework, we will study the mechanisms by which prior knowledge leads to the reconstruction of perceptual contents, by ""filling-in"" missing information during situations of partial awareness. 3) The maturation of consciousness: Using both psychophysical measures of visibility thresholds and high-density EEG, we will study the neural distinction between conscious and unconscious processes in pre-verbal infants, and whether consciousness develops through the maturation of posterior brain regions encoding sensory information, or rather anterior prefrontal regions related to attention and executive control. The expected impact of the project will be 1) to evidence sequential and complex forms of subliminal influences 2) to specify the cognitive mechanisms leading to perceptual illusions 3) to provide new insights on the mystery of how consciousness develops in humans."

1 437 520 €

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