Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Inequalities on Function Spaces and Properties of Integral Operators with Applications (IFIOP)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2009-IEF, 2009)
Start date: 2010-08-16
End date: 2012-08-15
Duration (months): 24.0
Total project cost (EUR): 233089.6
EU funding (EUR): 233089.6
Participants: 1
Project status: CLOSED

Our investigation is in the area of functional analysis and concerns boundedness and compactness properties of mappings between function spaces, estimates and asymptotic behaviour of characteristic numbers of integral operators and also embeddings between function spaces. The expected results may be useful for solutions of a number of actual problems in neighbouring mathematical areas such as the theory of differential and integral equations, interpolation theory, harmonic analysis, probability theory, etc.

Keywords: functional analysis,integral and differential operators,function spaces,boundedness,compactness,characteristic numbers,inequalities on subclasses of functions
Exploring decaprenyl-phosphoryl ribose epimerase (DprE1) as a validated target for TB drug discovery: Assay development, high-throughput screening and search for novel DprE1 inhibitor scaffolds (DPRETB)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Incoming Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Switzerland
Call:  (FP7-PEOPLE-2009-IIF, 2009)
Start date: 2010-05-01
End date: 2012-04-30
Duration (months): 24.0
Total project cost (EUR): 174065.2
EU funding (EUR): 174065.2
Participants: 1
Project status: CLOSED

Tuberculosis (TB) still claims 1.8 million deaths worldwide each year, and is the leading cause of infectious disease mortality by a bacterial pathogen. Current therapy for TB includes a combination of at least four different drugs and has a duration of at least 6 months. There is an urgent need for novel drugs against TB, in order to fight this disease more efficiently and with shorter course treatments, therefore increasing the likelihood for their success. Here we propose to pursue a novel target for anti-TB drugs which was recently and fully validated, namely decaprenyl-phosphoryl ribose epimerase (DprE1), an enzyme that in conjunction with DprE2 catalyses the transformation of decaprenyl-phosphoryl ribose into decaprenyl-phosphoryl arabinose, in the arabinan biosynthetic pathway in Mycobacterium tuberculosis. Arabinan biosynthesis is essential for the assembly of the mycobacterial cell wall. A novel fluorescence polarization assay for DprE1 will be designed and optimized, involving the synthesis of fluorescent substrates, in order to overcome the complexity and low-throughput of the currently used TLC assay. The novel assay will be used for high-throughput screening of libraries of commercially available compounds in order to find novel DprE1 inhibitor scaffolds. Novel inhibitors that are amenable to structure-activity relationship studies will be subject to medicinal chemistry work in order to improve their potency against DprE1, and their anti-mycobacterial activity. This work will be performed at EPFL, in a close collaboration between the Global Health Institute and the Institute of Chemical Sciences and Engineering, in Prof. Stewart Cole and Prof. Paul Dyson’s laboratories, respectively.

Keywords: tuberculosis,drug discovery,decaprenyl-phosphoryl arabinose,cell wall,high-throughput screening
Evolution Meets MAcroecology - integrating rapid adaptation into predictions of future plant species' ranges (EMMA)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2009-IEF, 2009)
Start date: 2010-06-01
End date: 2012-05-31
Duration (months): 24.0
Total project cost (EUR): 165645.6
EU funding (EUR): 165645.6
Participants: 1
Project status: CLOSED

The current rate of anthropogenic climate change is predicted to be unmatched in earth&apos;s history. The associated potential loss of biodiversity and ecosystem function is one of the most critical issues our society is facing. Thus, a major aim of global change research is the development of reliable predictions on future geographic distributions of species, communities and functional diversity. These predictions allow to assess the impacts of climatic changes on ecosystem goods and services, to develop adaptive management and conservation strategies and to demonstrate the magnitude of the problem to decision makers. However, the reliability of recent model-based assessments for future species&apos; range dynamics suffers from the fact that most macroecological modeling approaches lack in ecological mechanisms and evolutionary dynamics. The present project seeks to improve the quality and reliability of species distribution models by bridging the gap between macroecological approaches and the accumulating evidence of the importance of evolutionary dynamics for species&apos; response to climate change. In particular, we will (i) evaluate the potential of rapid adaptive evolution for a set of 50 alpine plant species using a novel Bayesian approach to population-based phylogenetics (ii) develop a software module &apos;xEvol&apos; that incorporates evolutionary dynamics into the existent species distribution model BIOMOVE, and (iii) simulate and evaluate the species&apos; range dynamics for an ensemble of IPCC AR4 climate change scenarios. The scientific output the project will assist the EU in progressing towards meeting the targets set by the Convention on Biological Diversity and the UN Framework Convention on Climate Change. Finally, the expertise developed through the proposed research initiative can be used to address issues raised by the &quot;Climate change, pollution, and risks&quot; thematic priority within the 7th Framework programme of the Marie-Curie Action.

Keywords: plant ecology,climate change impact (climate change),global change mitigation strategies (climate change),evolutionary biology,phylogeny
Analysis of the pathological implications of the abnormal accumulation of glycogen in specific cell types. (MGS AND DISEASE)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2009-IEF, 2009)
Start date: 2010-07-01
End date: 2012-07-13
Duration (months): 24.0
Total project cost (EUR): 212554.0
EU funding (EUR): 212554.0
Participants: 1
Project status: CLOSED

Glucose is stored in specialized tissues (mainly liver and muscle) in the form of a branched polymer called glycogen. Glycogen Synthase is the only enzyme able to catalyze this polymerization and its two isoforms (LGS and MGS) are mainly expressed in liver and in muscle, respectively. However, MGS is also expressed in all other tissues, regardless of their limited capacity to produce Glycogen. MGS activity is tightly controlled by several mechanisms. Recent results from the receiving group show that demise of these mechanisms in neurons causes apoptosis and may be the cause of Lafora disease. Our working hypothesis is that deregulation of MGS protein levels and/or activity is causative of several pathologies. Therefore, we aim to dissect the consequences of the loss of regulation of MGS in several cell types and tissues, using a state-of-the-art genetic approach. Our results will bring new evidence for the understanding of many unresolved human health conditions, and help to identify potential therapeutical strategies. The specific research objectives are: 1. To elucidate the mechanism by which the accumulation of glycogen triggers apoptosis. 2. To study whether aberrant accumulation of glycogen is responsible for some degenerative conditions. 3. To establish whether GS has a moonlighting function. These questions will be addressed both in vitro, using cell culture and diverse cell biology techniques, and in vivo, using newly available conditional mouse models. The applicant will join a group of reference in the study of the metabolism of glycogen, and will offer his extensive experience in the generation and use of mouse models for human disease. It is the applicant’s aim to become a skilled, independent research manager, either as a group leader or as scientific manager for research institutions. This project will provide the applicant with excellent scientific and managerial training opportunities.

Keywords: glycogen,glycogen synthase,accumulation,lafora disease,lafora bodies,conditional mouse models,cell type specific,apoptosis
Root longevity and the impact on soil N fertility (LEGUME ROOT IMPACT)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Sweden
Call:  (FP7-PEOPLE-2009-IEF, 2009)
Start date: 2011-07-01
End date: 2013-06-30
Duration (months): 24.0
Total project cost (EUR): 179669.4
EU funding (EUR): 179669.4
Participants: 1
Project status: CLOSED

Efficient utilization of nutrients in agricultural systems is essential in order to meet a sustainable production of food. Grain and forage legumes add nitrogen (N) to the soil via biological N2-fixation which reduces the need for energy demanding mineral fertilizers. Management of the increased soil fertility found after legumes requires knowledge of the processes underlying soil fertility build-up. One of the most important processes in soil fertility build-up under legumes is the growth, death, and turnover of legume root systems, which is at present poorly understood. In particular there is a lack of knowledge of the longevity and turnover of legume roots in forage mixtures, due to methodological difficulties in investigating the roots of one specific specie in a species mixture. The aim of the proposed project is to develop and test a new approach to estimate single species root longevity in forage mixtures, and use this new approach to estimate the longevity of legume roots in forage mixtures as well as quantify the deposition of C and N from legume roots. The proposed project will add a new state-of-the-art approach to study root longevity in species mixtures, and furthermore increase our knowledge regarding the processes involved in soil fertility build-up. Thus, this project will aid a development towards greater self-supply in European agriculture by reducing the energy consumption needed in the agricultural production, which is important for solving the present climate change challenge.

Keywords: natural sciences,soil fertility,carbon dioxide capture,storage,disposal (climate change),environmental protection
Political Philosophy and Vernaculars in late Middle Ages (13th-14th c.) (PPVMA2)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: France
Call:  (FP7-PEOPLE-2009-IEF, 2009)
Start date: 2010-05-01
End date: 2012-04-30
Duration (months): 24.0
Total project cost (EUR): 158445.6
EU funding (EUR): 158445.6
Participants: 1
Project status: CLOSED

The aim of the project is to investigate the changes in the political conceptual paradigm of the 13th and 14th century European Western culture. The research will focus, in particular, on the influence of national languages (vernaculars) in political theory, the meaning of the learned bilingualism of Latin and the use of vernaculars, translations, as well as new political genres, which radically change the reflection on politics and its ends. As a matter of fact, on the one hand, vernacular becomes increasingly refined in the translations of Latin texts, as in the case of Brunetto’s translations in French and Italian. On the other hand, vernacular becomes increasingly employed in autonomous political works and of new philosophical political genres. Particular aims: 1) The main aim of the project is the reconstruction of the context of the changes in the intellectual debate of 13th and 14th century France and Italy with a focus on linguistic and national identity through authors and texts such as for instance Brunetto, Dante, Rolandino, &quot;Novellino&quot;, Giles of Rome&apos;s De Regimine, Raoul de Presles, Oresme, and through specific topics and case studies. 2) Specific and important aim of the project is to detect a “political lexicon” in Vernacular in Brunetto’s (1220-1295) works in French (langue d’oil) and Italian (Tuscan). Author of a dense Tresor in French, including free translations from the Latin versions of Aristotle’s Politcs, Ethics and Rhetorics, from Cicero, Isidore, and from John of Viterbo’s Liber de regimine civitatum, he also writes Rettorica, free translation of Cicero’s De inventione in Italian. 3) Lexical analysis of the anonymous Florentine translation of Giles of Rome’s De regimine principum (1280), which follows the French version by Henri de Gauchi constitutes a further aim. This will shed further light on the transition from Latin to Vernaculars, as well as on the effective change that the translation brings about from French to Italian

Keywords: humanities,political philosophy,middle ages,medieval philosophy
Cultural and genetic variation in emotion regulation (EMOTION REGULATION)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: International Outgoing Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2009-IOF, 2009)
Start date: 2011-03-01
End date: 2014-02-28
Duration (months): 36.0
Total project cost (EUR): 207616.0
EU funding (EUR): 207616.0
Participants: 1
Project status: CLOSED

Cross cultural research has revealed differences in the expression and experience of emotions related to individualistic/collectivist (IC) cultural values. The in- versus out-group context and the level of self-relevance of a situation affect these IC differences. Williams syndrome (WS) is a genetic disorder associated with abnormalities in emotional responding. Individuals with WS show heighted emotional responses and amygdala activity to happy faces and fearful/threatening non-social scenes but a reduced amygdala response to fearful faces. Thus, cultural and genetic factors can affect emotional responding in specific situations. Emotion regulation involves the processes by which individuals influence the emotions that they experience and express, and may be related to individual differences in emotional responding. There are notable differences in the neural substrates and effects on emotional responding of different emotion regulation processes used in different contexts. fMRI, EEG, behavioural observation, physiological measurement and self-reported emotional experience will be used to investigate the variation in emotion regulation associated with IC factors. IC variation will be measured at a group level (cultural group comparison), at an individual level (affiliation towards specific IC cultural values) and within individuals (manipulation of the temporary salience of a particular IC value), within the context of spontaneous emotion regulation and instructed antecedent and response focussed up- or down-regulation of positive or negative emotional responses. Variation in emotion regulation associated with the WS genotype will be investigated by comparing individuals with WS to individuals without WS matched on age, socialisation and executive functioning. Regulation of emotions resulting from social versus non-social stimuli will be compared to the regulation of empathic emotional responses to facial expressions.

Keywords: neuropsychology,cognitive science,clinical psychology,social psychology,rare diseases,clinical genetics,neuroimaging,social neuroscience
Characterization of signalling and physiologic roles of the class II PI 3-kinases (PI3KC2)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: United Kingdom
Call:  (FP7-PEOPLE-2009-IEF, 2009)
Start date: 2010-08-01
End date: 2012-07-31
Duration (months): 24.0
Total project cost (EUR): 171740.8
EU funding (EUR): 171740.8
Participants: 1
Project status: CLOSED

Phosphoinositide 3-kinases (PI3Ks) are a conserved family of lipid kinases that generate lipid second messengers inside cells. Mammals have 8 isoforms of PI3K, divided in three classes (I, II and III). The focus of research has thus far almost exclusively been on class I PI3Ks, which have been implicated in cancer, inflammation and diabetes and which are the target of ongoing drug development efforts in Pharma. Very little is known about the other PI3Ks, in particular the class II PI3Ks, which comprises the PI3K-C2alpha, PI3K-C2beta and PI3K-C2gamma isoforms. This research proposal aims to delineate the physiological roles of PI3K-C2alpha and PI3K-C2beta, their integration in signalling by tyrosine kinases and G protein-coupled receptors, the lipid products they produce in cells and their downstream intracellular signalling pathways. The focus of these studies will be on metabolic signalling and cancer. For this proposal, I have access to two new unpublished mouse lines with inactivating mutations in the PI3K-C2alpha and PI3K-C2beta genes, which will be subjected to whole-organism studies and phenotypic screening, in parallel to cell-based studies using various techniques, including new proteomic techniques which have been developed in the Host Laboratory. The Host Laboratory uses an innovative mouse gene targeting strategy whereby PI3K isoforms are inactivated in a "drug-like" fashion. This is achieved by the replacement of the wild-type gene by a germline knock-in allele that encodes a kinase-dead protein, mutated in the ATP-binding site. The proposed work is expected to uncover the biological roles of an evolutionary conserved signalling module. This work also has potential implications for the ongoing drug development in the PI3K area where inhibitors often also hit class II PI3Ks. It is critical for further drug development to be able to assess what the possible biological impact is of such drug target profile.

Keywords: kinases,signaling,cancer,metabolism,phospholipides,health sciences
Rational design of a lipopolysaccharide adjuvant for tuberculosis vaccines (ADJUTUB)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Netherlands,Netherlands
Call:  (FP7-PEOPLE-2009-IEF, 2009)
Start date: 2010-12-01
End date: 2012-11-30
Duration (months): 24.0
Total project cost (EUR): 222885.6
EU funding (EUR): 222885.6
Participants: 2
Project status: CLOSED

Tuberculosis, a disease caused by the bacterium Mycobacterium tuberculosis, kills 2-3 million people per year. Although an attenuated strain of M.bovis called BCG is widely used as vaccine against TB, its effectiveness is generally considered as insufficient. Our new approach for BCG improvement is to add a novel type of adjuvant, based on genetically engineered versions of the lipopolysaccharide (LPS) from Neisseria meningitidis (Nm). The modifications aim at (i) specific targeting to dendritic cells where an immune response is initiated, and (ii) reduction of toxicity by making the lipid A part less active for the LPS receptor TLR4/MD2. The inactivation of the lgtB gene results in Nm LPS with a truncated oligosaccharide lacking the terminal galactose which specifically binds to the receptor DC-SIGN on human dendritic cells and this binding skews the resulting T-cell response in a Th1-direction. Heterologous expression in N.meningitidis of the pagL gene from Bordetella bronchiseptica, which encodes a lipid A deacylase, results in penta-acylated Nm LPS of strongly reduced TLR4-activating ability. By controlling the degree of PagL-mediated deacylation, different ratios between penta- and hexa-acylated forms can be obtained which display a continuous range of TLR4-activating capacity. Moreover, mass spectrometric analyses of the Nm LPS have shown that, in addition to penta- and hexa-acylated LPS forms, at least eight other structural variations in the molecular species may occur. At present, the relevance of these structural variants for adjuvant activity and reactogenicity is only partially known. Therefore we will develop a methodology to isolate and structurally identify the different LPS molecular species and test them for the desired level of adjuvant activity without concomitant high reactogenicity. This novel LPS-based targeted adjuvant will be investigated in the context of BCG improvement, but if successful will find application for many other vaccines.

Keywords: biological engineering,lipopolysaccharide,adjuvant,tuberculosis,vaccine,separation
Intestinal stem cells and their role in colorectal cancer progression (CSC PROGRAM)

Framework: FP7 — People
Programme: Marie-Curie Actions
Theme: Marie Skłodowska-Curie
Destination: Intra-European Fellowships
Action type: Support for training and career development of researchers (Marie Curie)
Countries involved: Spain
Call:  (FP7-PEOPLE-2009-IEF, 2009)
Start date: 2010-06-01
End date: 2012-05-31
Duration (months): 24.0
Total project cost (EUR): 154417.0
EU funding (EUR): 154417.0
Participants: 1
Project status: CLOSED

Constitutive activation of the Wnt pathway is the key step for initiation of colorectal cancer (CRC). Wnt signaling also plays an essential role in the maintenance of intestinal stem cells (ISCs). In addition, acquisition of a constitutive crypt stem/progenitor phenotype represents the first step towards malignancy. The identification of the Wnt target gene Lgr5 as a marker for ISCs and the finding that Lgr5+ ISCs represent the origin of intestinal cancer suggest that specific features of ISC are required to initiate CRC. Given the critical role of ISCs in CRC onset, we intend to study their contribution to CRC progression, tumor recurrence, and metastasis. Characterization of Lgr5+ CRC cells at different disease stages will clarify, which part of the “stemness” genetical program remains conserved during progression of malignancy. We will also address to which extent an Lgr5+ CRC cell residing in a primary tumor or in metastasis resembles a crypt Lgr5+ ISC. To achieve this, progression of intestinal cancer derived from ISCs or differentiated cells will be studied using a novel transgenic mouse model system: Starting from defined, targeted cells which have acquired Wnt activation combined with mutation in KRAS, tumor progression can be tracked by fluorescent proteins concomitantly induced with compound mutations. “State-of the art” flow-cytometry-based sorting techniques will be used to isolate different tumor sub-populations in order to characterize them in detail. Interestingly, only a rare sub-population of tumor cells in CRC patients, so-called “cancer stem cells” (CSCs), is able to re-establish tumor growth in immune-deficient animals. We seek to understand how these tumor-promoting cells are genetically and functionally related to Lgr5+ ISC and Lgr5+ cells in CRC. Our results will achieve significant advancement in understanding the relationship between CSCs and ISCs and hold potential for the future development of both therapeutic and diagnostic tools.

Keywords: wnt signaling,k-ras,compound mutation,colorectal cancer,metastasis,intestinal stem cell,cancer stem cell,tumor profiling,tumor recurrence,transgenic mouse model