Dragon09/odtu_chatbot huggingface dataset:
improving cellular cancer immunotherapy using chemotactic metabolite receptors

chimeric antigen receptor t cell car t cellular immunotherapy has revolutionized treatment for patients with hematological cancers but largely failed to provide benefits for patients with solid tumors ineffective car t migration into solid tumors caused by the lack of recruitment signals including chemokines is a key gap for current cellular immunotherapies the very common accumulation of metabolites in tumors provides a yet unrecognized opportunity to guide immune cells into tumors therefore my overall research objective for this project is to generate and use novel chemotactic metabolite receptors metabotract to enhance the efficacy of car t and natural killer nk in solid tumors this innovative approach is expected to impact the therapeutic options for cancer patients with poorly infiltrated tumors and enhance the eus competitiveness in the rapidly expanding market of cellular immunotherapies applying the gained knowledge on car nk cells could additionally reduce treatment costs and accelerate deployment of cellular therapies to patients during the msca fellowship i will learn vital new skills including cell migration assays in vivo models for immunotherapies project management exploitation and leadership in the renowned laboratory of prof sebastian kobold at the ludwigmaximiliansuniversity lmu in munich the expertise of prof kobolds lab with chemokine receptor car t cells and in vivo models together with my complementary skills in cellular immunology nk cells imaging and bioinformatics gives the project a high likelihood of success the publication of the results the gained knowledge and skills and the demonstrated mobility will strengthen my scientific independence and help me achieve my career goal of becoming a research group leader in cellular cancer immunotherapy
epigenome establishment and maintenance of the inactive x chromosome in response to dna doublestrand breaks in mammalian cells

the dna damage response takes place on a chromatin substrate and triggers profound chromatin alterations chromatin states vary substantially between genomic regions driving distinct gene expression profiles and also different dna damage repair responses one striking example is the heterochromatinization of an entire chromosome the inactive x chromosome in female mammals that is silenced during embryonic development by facultative heterochromatin formation how the facultative heterochromatin state of the inactive x responds to dna damage and impacts dna repair is poorly understood my research project aims at identifying chromatin changes that accompany the repair of the most cytotoxic form of dna damage dna doublestrand breaks dsbs in facultative heterochromatin and the mechanisms that ensure the establishment and maintenance of the inactive x chromosome in response to dna damage in mammalian cells to generate dsbs i use the crisprcas9 technology that allows sequencespecific targeting of the cas9 nuclease thanks to available bioinformatic tools i can discriminate between active and inactive x chromosomes analyze the genomic instability profiles induced around the break sites and decipher the repair pathway involved in parallel i will profile the chromatin marks associated with the inactive x chromosome in the vicinity of dsbs to assess the impact of dna damage and repair on heterochromatin maintenance moreover i will test the hypothesis that the high level of replicative stressinduced breaks in embryonic stem cells could drive heterochromatin establishment and thus skew the choice of the inactive x chromosome for this i will study the impact of generating dsbs on one x chromosome of mouse stem cells on their differentiation potential and their propension to inactivate the damaged x chromosome together this work should shed light on the interplay between the dsb response and facultative heterochromatin states
analysis of skills training research and innovation opportunities in space

the goal of the astraios project is to provide an exhaustive view and understanding of the current and future offer of space curricula and courses in the eu27 characterise the demand from european space industry in the next 1015 years and identify actionable ways towards the alignment of the european space sectors curricula and qualification capabilities with skills required by the sector to foster innovation and increase eu competitivenessthese goals will be achieved by mapping the educational offer across the eu27 at bachelor master postgraduate and continuing education levels and measuring the average time and cost required for a degree leading to a career in the space sector a socioeconomic analysis of the population of students enrolled in spacerelated studies will be performed which together with the education data will create a europewide space competencies and skills taxonomy to support the identification and analysis of the excellences and shortcomings within the european academic offer for the space sectorthe project will analyse future trends and challenges of the eu space sector through desk research direct industry consultation and automated methods the analysis will cover current and future needs in both technicalhard skills and soft skills such as collaborative working multidisciplinary approaches and creative thinking that future european students need to develop final outputs will include recommendations of actions towards a better alignment between the european space sectors curricula and the skills required by the future eu space sector new materials to promote space related jobs and careers and educational material developed for the copernicus and galileo sectors the consorium in place to achieve this has extensive coverage of the eu27 space education and industry sector
biomechanical modelling and computational imaging to identify different causes of back pain in large epidemiological studies

chronic back pain is a major burden and source of disability worldwide it is primarily attributed to different biomechanical factors but can also have inflammatory neurological or psychological causes clinical findings and conventional imaging cannot reliably distinguish different causes of back pain in contrast individual biomechanical models can quantify diverse pathologic loading patterns and thus could be used to distinguish different aetiologies of back pain to better understand individual pathophysiology and guide preventive strategiesduring my recent ercstg iback i developed quantitative imaging methods and deeplearning based image processing to automatically generate a fully individualized biomechanical model of the thoracolumbar spine simultaneously two largescale epidemiologic studies collected clinical and highresolution imaging data of the spine of more than 15000 participants so far aiming at more than 35000 participants by mid 2022 the highlevel objective of ibackepic is to use such novel image analysis techniques to identify different biomechanical and inflammatory causes of back pain in study participants i will adopt and extend my recently developed deeplearning based spine labelling and segmentation algorithms to fully automatically calculate individual biomechanical functional and morphometric parameters of the spine in this largescale population data i will identify different biomechanical loading patterns use quantitative imagebased parameters to discriminate normal ageing from pathologic degeneration and identify pathological conditions that are linked to back pain or subsequent development of chronic back pain such a differentiation for the first time based on quantitative image data will allow for a better understanding of the underlying pathophysiology of back pain an improved risk stratification a tailored investigation of genetic causes and thus will help to better guide preventive strategies
ground operations of liquid hydrogen aircraft

developing aircraft using hydrogen is seen as a major lever to reach netzero co2 emissions by 2050 and to secure the longterm sustainability of air travel in order to enable a widespread development of hydrogen aviation it is essential for airport operators that a future regulatory framework is implemented for the handling of large quantities of hydrogen at airports and that there is a clear understanding of how hydrogenpowered aircraft will be integrated into airport operations and the required changes to current aircraft ground handling operations are known in parallel to this and for industrial partners it is also necessary to develop new groundhandling equipment for hydrogen aircraft and more specifically liquid hydrogen refuelling equipment that will enable safe and efficient turnaround operations goliat will demonstrate liquid hydrogen aircraft ground operations at three different types of european airports using a small hydrogen operated aircraft allowing the necessary procedures to be developed it will also through two demonstrators showcase several critical technologies needed for future certified highperformance liquid hydrogen refuelling in parallel goliat will answer key questions that will lay the foundations for the standardisation and certification framework of future safe hydrogen operations indeed a key output of the project will be the gap analysis of certification rules and requirements for ground operations and equipment finally goliat will also assess the sizing and economics of hydrogen value chains for airports critical for the competitive development of hydrogen powered aviation to achieve its goals goliat reunites technology providers aircraft manufacturers liquid hydrogen suppliers logistics experts cryogenic component manufacturers and standardisation experts and academia as well as several european airport operators all of whom will be supported by easa
biomarker based diagnostic toolkit to personalize pharmacological approaches in congestive heart failure

heart failure hf is a chronic clinical condition involving up to 65 million people in europe the most frequent cause of hospitalization in adults with a 5year mortality rate up to 70 several drugs positively modify the course of disease in the patients with hf with reduced ejection fraction hfref with a high level of evidence besides the use of diuretics the basic cornerstone of symptoms relief in hfref by targeting congestion is supported by poor and outdated evidence congestion drives symptoms worsening leading to hospital admission clinical evaluation of congestion is often inaccurate and insensitive to detect interstitial or intravascular fluid overload and thus insufficient to guide use of diuretics indeed their use is inefficient with studies showing that up to 70 of patients with chronic hfref show congestion despite diuretic therapy the use of diuretics does prevent clinical events in patients discharged after an acute heart failure episode and diuretics may represent a barrier to adherence to disease modifier therapies an appropriate management of diuretic therapy is therefore crucial to overcome the risk of rehospitalisation manage patients symptoms and achieve target guidelinedirected medical therapy to fill these gaps biotoolchf will 1 validate a set of qualified biomarkers estimating congestion 2 define a multiparametric artificial intelligencebased score predicting congestion and prognosis 3 develop a decisionmaking tool to manage congestion by diuretics 4 develop a point of care companion diagnostic cd to assess biomarkers concentrations 5 set up a strategy plan for industrial development and market access of the cd this approach will support the definition of a framework to regulatory agencies and scientific societies to disseminate recommendations for a more efficient use of existing pharmaceuticals and allow a personalised strategy for the management of hfref by using new tools and digital solutions
exchangecoupled nanowirenanoplatelet composites for highperformance sustainable magnets

in the magwire project we will explore the fundamental mechanisms optimize the performance and upscale the synthetic protocol for the next generation of sustainable highperformance nanocomposite permanent magnets the project will combine and exploit the key individual expertises of dr matilde saura muzquiz experienced researcher in the synthesis and structuralmagnetic characterization of nanostructured ferrite magnets and of prof lucas perez project supervisor in the field of nanomagnetism and nanowires synthesischaracterization the research will build on considerable recent improvements in the performance of strontium hexaferrite magnets achieved through crystal engineering ca and aldoping and bottomup nanostructuring size and morphology control as well as on promising preliminary results for hexaferritenanowire magnetic composites in magwire we will develop a novel highperformance exchangespring nanocomposite magnetic material based on a synergistic nanoscale combination of highcoercivity plateletshaped sr1xcaxfe12yalyo19 nanoparticles and highmagnetization fexco1x nanowires the anisotropic shape plates and wires of the constituent nanoscale components will drive an inherent selfinduced alignment which will further improve performance in addition we will establish scalable synthesis routes based on a fundamental understanding of the mechanisms in play that will be elucidated by in situ synchrotron xray scattering investigations of the nanoplatelet and nanowire formation
just transition to a green and digital future for all

the policies driving the green and digital transitions or twin transitions are intended to level the field to achieve the european growth model and attain the eu green deal and the uns sdgs however these policies have had unintended and unforeseen effects creating new inequalities andor aggravating existing ones those primarily affected are social groups already at risk and eus most vulnerable regions public authorities and policymakers at local national and european levels therefore need evidencebased understanding of these inequalities and concrete ways to prevent andor mitigate these the readjust project aims to suggest policy options for overcoming these potential tradeoffs between efficiency and equality in twin transitions in the key sectors of mobility and agrifood the green and digital policies are intended to level the field for attaining sdgs however they may return uneven distribution of access to the transitions and their benefits readjust aims to suggest options for overcoming the perceived tradeoff between efficiency and equality in policy and to make inclusive growth a reality policymakers portray a future that is green and digital for the eu and they aim to continuously contain the unintended consequences of the green and digital transitions in terms of inequalities generating zero negative effects on the climate can be efficiently achievable by twining green and digital transitions nonetheless individually and jointly the transitions might widen the existing inequality gaps this project aims to contribute to policies for fair and just twin transitions to mitigate existing inequalities driven by the twin transitions and minimize the transitions unintended consequences for equality in this project we strive to address the inequalities created or exacerbated by the twin transitions policies in certain domains policies of green and digital transitions which are aimed at the growth of the entire or its subsections
dissecting the molecular mechanisms of cellular heterogeneity controlling infectionassociated development in plant pathogenic fungi

clonal microorganisms display cellular heterogeneity at the transcriptional level to survive under unfavourable conditions or differentiate into specialised structures this is the basis of antibiotic and fungicide resistance but very little is known about how cellular heterogeneity originates and operates in the infection biology of agricultural fungi magnaporthe oryzae is one of the most devastating fungal pathogens in the world that destroys enough rice to feed 60m people every year it produces 50000 new spores a day from a single lesion in the fields but it remains unknown whether they are transcriptionally different spores contain three cells that display cellular heterogeneity between them during appressorium development a specialised cell necessary for infection two of the cells undergo autophagy rapidly and the third undergoes a mitotic division leading to the formation of the appressorium the mechanism by which cellular heterogeneity operates in spores has never been elucidated this proposal will identify for the first time the molecular mechanisms driving cellular heterogeneity and genes subjected to it an unparalleled resolution of the infectionassociated developmental program of individual spore cells will be obtained by scrnaseq which will identify a cohort of virulence factors critical for infection i propose that the underlying mechanism of cellular heterogeneity is the cell cycle through the activity of cyclin dependent kinases cdks and a novel group called nonpstare cdks reported to be regulators of transcription in other organisms by a stateoftheart chemical genetic approach combined with phosphoproteomics their role and signalling pathways will be determined overall with this proposal novel components associated to the infection process of one of the most threatening fungal pathogens in the world will be determined opening avenues that up to date have not been explored and whose potential is inestimable
climate change impacts on trees reproduction and forecasts of forest recruitment change

the capacity of future forests to support biodiversity and deliver ecosystem services will depend on reproductive capacities that keep pace with 21st century climate change the european continent is warming and drying out fast and similar changes are happening word wide the decadescale trends in biodiversity will be governed by tree fecunditythe capacity of trees to produce seed and to disperse it to the habitats where populations can survive in the future from the boreal to the tropical forests including in majority of european tree species reproduction happens through synchronized quasiperiodic nonstationary variation in fruit production termed masting or mast seeding despite the crucial role of mast seeding in plant regeneration and wider ecological processes our understanding of this process is rudimentary poor understanding of the mechanisms that govern it are challenges for anticipating alternations in forest reproduction and function reliable predictive models are consequently not available and the unpredictable recruitment of trees has become a key obstacle to understanding forest change recruitment including reproduction and dispersal is the most undeveloped demographic process in earth system models this work will transform our understanding of mechanisms governing trees reproduction and deliver tools for predicting forest reproduction trajectories under climate change the main outcomes will be the first experimental description of how masting emerge at proximal level and how this is conserved among species this will be also the first explicit test of how variation in masting patterns matters for forest regeneration trajectories together with analysis of global reproductive patterns our work will deliver a stepchange in identifying species and regions of special conservation care
modelling the chemiosmotic mode of atp synthesis in protocells

all modern organisms feature chemiosmosis ionmotiveforce driven processes including membrane transport and atp production and therefore the last common universal ancestor luca is believed to be chemiosmotic although contradictorily as for chemiosmosis to happen cells utilise membranes relatively impermeable to the coupling ion h or na it has previously been shown that theoretically luca could drive chemiosmosis using a geochemical hgradient but only if it had a leaky membrane however a leaky membrane rapidly achieves electrochemical equilibrium offsetting theh influx for the h influx and therefore chemiosmosis to continue the membrane needs a system to pump hparadoxically pumping h across a leaky membrane is futile a potential solution has previously been hypothesised in the form of membranes leaky to h that harboured an atpsynthase coupled to both h and na and an antiporter that pumps out na for incoming h such a nah antiporter could convert the geochemical h gradient into a nagradient it would be advantageous to do so as a nagradient could be better sustained by the luca membrane and could drive atp production via the promiscuous atpsynthase my project aims at obtaining empiricalmvalidation for this hypothesis to do so a promiscuous atpsynthase will be coreconstituted alongside a nah antiporter into fattyacidcontaining hybrid liposomes made from fatty acids and other amphiphilic phospholipids iongradients will be imposed on the liposomes by phjump ordecarboxylasecatalysed alkalisation methods to test whether the system could a convert the hgradient into a nagradient via the nah antiporter and b use the na gradient to drive atp production via the promiscuous atpsynthase this study is critical to understand the evolution of chemiosmotic systems and will have implications in evolutionary and synthetic biology as well as astrobiology
designing and thin film engineering of organic plastic ionic ferroelectrics towards multisensor electronic skin

organic plastic ferroelectrics with inherent pyroelectric and piezoelectric properties have the potential to outperform traditional ceramic ferroelectrics particularly in terms of sustainability and large area fabrication as flexible coatings the latter is highly sought as means to continue the current evolution of humanoid robots by offering touch sensitive electronic skins ferroplast focuses on development of plastic ionic crystals pics as the active sensitive component of such skins pics are comprised of globular ions tethered by weak intermolecular forces and demonstrate plastic crystal phase at higher temperatures the pic ferroelectrics possess intriguing features as high pyro and piezoelectric coefficients malleability and multiaxial polarization suitable to realize multisensor property in flexible thin films ferroplast proposes 1 rational designing of pics based on chirality ionic size and intermolecular interaction strength to have high pyropiezoelectric coefficients 2 fabrication of crystalline and phase pure pic thin films embedded in elastomer by molecular layer deposition mld for application as flexible electronic skin 3 study of crystal phase landscape in thin films under variable temperature and pressure using grazing incidence xrd to estimate multisensor ability of pics 4 selection of ions by insight in entropy of phase transitions as calculated by first principle dft studies at the core of ferroplast is knowledge building and exchange between the experienced researchers background in supramolecular chemistry to design and synthesize pic ferroelectrics and the hosts core focus on mld thin film engineering and characterization of physical properties in thin film structures and the secondment on first principle dft calculation of lattice phonon density of state ferroplast will expand the competence and focus of all parties by mutual aid and competence building to push our respective fields further beyond state of art