Dragon09/odtu_chatbot huggingface dataset:
varifn understanding variation in the type i interferon response and its impact on infection susceptibility in humans

both antiviral immunity and susceptibility to viral infections are remarkably variable factors such as older age increased body mass index and male sex can increase the risk of developing severe viral disease yet the impact of these features on antiviral immunity particularly the type i interferon system ifni is not understood here we propose to use a systems immunology approach to identify features that influence ifni responses and understand their impact on infection susceptibility we will use datasets and samples from the milieu interieur mi cohort of 1000 donors consisting 500 males and 500 females aged 2069 years old using simoa digital elisas we have quantified ifni ifna and ifnb in the supernatants of whole blood from the 1000 donors that was stimulated ex vivo with 7 agonists that activate the ifni system preliminary analysis of these results shows interesting age and sex differences in the ifni response we will integrate the ifni cytokine data with existing demographic microbiome immune cell phenotyping and plasma protein data from the cohort and determine their associations with ifni levels to investigate sex differences in ifni we will quantify sex hormones in the plasma of the 1000 donors we will perform rnasequencing on ifnastimulated whole blood on a subset n200 of the donors to investigate the factors that shape the response to ifna itself we will perform genome wide association studies of the ifni response in the cohort to identify variants that influence ifni production using snp genotyping data from mi to determine the impact of these features on ifni and influenza infectivity in vitro we will develop an organ on chip model encompassing features that we find to be associated with ifni levels in mi results from this project will identify novel regulators of ifni and shed light on new strategies to boost the antiviral response to better protect against viral infection
a right to repair for a postgrowth society controversies opportunities and challenges

the need to continuously stimulate consumer demand within saturated capitalist markets has driven manufacturers of electronic equipment to adopt dubious marketing practices associated with planned obsolescence eg they might artificially shorten the lifespan of their products downplay issues of durability and maintenance during the design stage and on the social and ecological costs of these trends are enormous and the world is currently on track to produce 74 million tonnes of ewaste by 2030 in this context there is mounting pressure on manufacturers and policymakers to facilitate consumers the right to repair r2r their electronic devices rather than relying on the manufacturer to makeauthorise repairs with proprietary components this demand has sparked a controversy concerning the limits of the r2r with large multinational corporations such as apple microsoft amazon or john deere disputing this concept on economic technical legal or safety grounds in this regard the present project aims at elucidating how ongoing debates and policies about the right to repair can be conceptualised and implemented to support a transition towards a postgrowth society the methodology adopted will be based on controversy mapping which is widely used in the field of science and technology studies first a controversy map will be elaborated showing the different stakeholders and their evolving positions both for and against regarding the r2r next fieldwork will be conducted with grassroots organisations and technology activists involved in the r2r campaign finally i will analyse the r2r in light of contemporary postgrowth frameworks to establish key challengesopportunities for transforming societytechnology relations in more sustainable ways by doing so this project pushes forward the boundaries of current knowledge and advances our understanding of the role of technology and innovation in postgrowth transitions
evolution of novel contacts in orthologous regulatory elements

thousands of conserved noncoding elements cnes are shared by jawed vertebrates some of which were shown to be important developmental enhancers however how these intriguing elements evolve at the functional level and why they are so conserved in sequence remain some of the biggest mysteries in the field of regulatory genomics in this project i build a novel view of cne function and evolution based on my preliminary data and recent breakthroughs on enhancer pleiotropy this working hypothesis posits that cnes are ancient transcription factor binding hubs that act as dynamic multigenic regulators to which new gene targets can be addedremoved during evolution taking advantage of the exceptional conservation of cnes i propose the experimental framework to test this hypothesis on orthologous elements across major vertebrate clades using cuttingedge methodology combining capturehic rnaseq and atacseq in shark chicken and mouse this approach will provide comparative cnetarget contact maps that will reveal conserved as well as gained and lost interactions in each species whose functional impact will be tested using crispr knockout and interference in mouse neuronal differentiation in summary this project will address longstanding questions on the evolution of the regulatory genome and offer insights into the flexibility of enhancers to acquire and lose targets in evolution expanding our understanding on the pervasiveness and evolution of regulatory pleiotropy
development of a next generation ammonia fc system

amon project aims at developing a novel system for the utilization and conversion of ammonia into electric power at high efficiency using a solid oxide fuel cell high temperature electrolysers have demonstrated in several activities the capacity to outreach high performances in lab scale prototypes and validation tests the project will deal with the design of the basic components of the system including the fuel cell the ammonia cracker the ammonia burner and an anode gas recirculation the engineering of the whole balance of plants and the validation of the compliance with ammonia use for all the specific parts and components for the development of the solid oxide fuel cell a g8x cell from solidpower will be utilized first validated in a laboratory at the level of single cells for electrochemical properties degradation and post mortem analysis at the level of single repeating units for the validation of interconnects and sealing components and at the level of stacks and stack modules an overall ammonia fuel cell system will be engineered and manufactured to be tested in a relevant environment in a port area the final system will be in the size of 8 kw stack module with an ammonia cracker and a heat management system it will aim at a overall electrical efficiency in the range of 70 amon will be supported alongside the engineering by horizontal strategic support on critical and open issues involving use of ammonia with fuel cells such as safety assessment on technoeconmic analysis on modelling at a multiscale and multiphysic levels to consolidate confirm and direct the engineering of the technology despite the small pilot demostration scale amon will propose a scaled engineering for a system suitable to be applied in end uses such as ports interports maritime environment besides autonomous power systemsamon will promote the use of ammonia as a hydrogen carrier to enhance the flexibility of the energy system
decrypting neurocancer crosstalk in pediatric cancers of the peripheral nervous system

cancer neuroscience has emerged as a major axis of cancer biology at the crossroad of two biological areas multilayered dialogs between cancer and nervous contingents have started to be unravelled with pivotal roles of the nervous system in tumor initiation growth and invasion in turn amplified by cancerinduced hijacking of nervous functions specifically brain tumors were shown to be integrated in bona fide neurontocancer synaptic networks but also to capture neuralactivity dependent released factors that boost their tumor properties in the last years this completely rewired the view of highgrade gliomas especially those arising in the pediatric population suggesting specific vulnerabilities when neural networks are being shaped the knowledge regarding neurocancer crosstalk in the peripheral nervous system pns is far more fragmented and is even obscure in malignancies arising within peripheral nervous tissues neuroblastoma nb is an emblematic deadly pediatric cancer of the pns with primary tumors that develop in sympathetic ganglia or in the adrenal gland despite its occurrence in sites of active centraltopns synaptic contacts whether neural activity impacts on nb tumor features and metastatic progression is fully unknown we have conceived a model of nb that reproduces the embryonic and nervous microenvironment in which it arises but also the sequence of its metastatic progression guided by preliminary data the objective of the proposal is to decrypt the panel of neurocancer functional interplays in nb at the anatomical electrophysiological and molecular level we will deploy multidisciplinary and cuttingedge approaches to provide a comprehensive and dynamic picture of neuronb dialogs in relevant models for this pediatric cancer our underlying aims are to identify novel entry points for therapeutic strategies and to define subtypes of nb that would benefit from neurorelated therapies
a versatile biosensor of strigolactone responses in plants

strigolactones sls are a class of plant hormones that participate in many plant environmental interactions including responses to drought much still has to be understood about how they mediate plant responses to abiotic stresses but their mapping and quantification in plant tissues is extremely difficult some sl biosensors have been developed in recent years but they all suffer from some technical limitations namely they are negative sensors whose signal is degraded in the presence of sls and they require laborious and invasive techniques for signal detection the aim of this fellowship is thus to combine knowledge in the fields of plant synthetic biology and plant molecular physiology to construct a novel sl biosensor called strigosense which is positively activated in the presence of sls strigosense will be constructed using the principles of modularity and reusability this will allow to pair it with many customisable reporter systems creating a tool which can accomodate a variety of users and research applications in this project strigosense is coupled to fluorescent and bioluminescent reporters for the noninvasive monitoring of plant sl responses at the cell and system level the biosensor will be developed in arabidopsis and tomato plants seeking to transfer the research conducted on model organisms to a crop of enormous relevance narrowing the gap between basic research and the development of slbased agricultural solutions after finetuning the biosensor will be used to monitor plant responses to different abiotic stresses and to an array of sllike compounds and biostimulants with the potential of acting as priming agents that help plants cope with recurring water deficits this will be the first example of the testing of a sl biosensor under physiological stress conditions the technical advantages of strigosense will make sl biosensors faster cheaper and more highthroughput with benefits for basic and applied research
recyclingoriented alloy design for nextgeneration of sustainable metallic materials

european industry increasingly focusses on recycling pushing towards circular economy as part of eu green deal this offers enormous energy savings and co2 reductions however there are several problems hindering the metals recyclingeffective solution to counter these problems is the development of new alloys recyclingfriendly by designone of the rising problems during recycling is the progressive accumulation of impurities in alloys produced from scrapmetal elements such as tin cannot be effectively removed during manufacturing alloys from scrap therefore the nextgeneration of alloys will have be able to tolerate more impurities therefore inclusions than current alloys such materialsalso have to be more resistant to fracture due to the potential damage nucleation at inclusions however impurities causesignificant changes of properties and induce considerable complexity even in simple alloy systems therefore thedevelopment of the recyclingoriented alloys based on understanding of changes caused by various compositionaldeviations require a significant volume of researchconcentrated solid solution alloys including some of the established compositions of austenitic steels have the attributesessential for recyclingoriented alloys they show enhanced tolerance to compositional deviations due to the extendedcompositional space with desired microstructures and intrinsically high ductility levelsin this project we first aim to analyze the consequences of the compositional changes and impurities to the changes ofmechanical properties and damagetolerance of said materials ultimately scrapcompatible alloys for sustainablemetallurgy will be prepared special attention will be placed on the effects of the elemental partitioning and their interactionswith defects the project outcomes will contribute to the development of recyclingoriented alloys on the global level for future green metallurgy with reduced environmental impact
integrated shortterm palliative rehabilitation to improve quality of life and equitable care access in incurable cancer

disability related to incurable cancer affects over a million europeans each year our objective is to test the clinical and cost effectiveness of an integrated shortterm palliative rehabilitation intervention to improve function and quality of life in people affected by incurable cancerat the core of inspire is a multinational randomised controlled trial across six european countries we will recruit 340 participants to assess the clinical and costeffectiveness of palliative rehabilitation on quality of life disability symptom burden and goal attainment in people with incurable cancer if positive the trial could result in a scalable and equitable intervention that improves function and quality of life in people with incurable cancer and reduces the burden of care for their families the intervention can be adapted and integrated into different health systems using existing staff and services with little or no additional costto support our ambition to make palliative rehabilitation part of routine care for people with incurable cancer we also conduct comparative analysis of health services to understand current integration of rehabilitation across oncology and palliative care services mixedmethod evaluations of equity and inclusivity processes and implementation for the intervention at patient health service and health system levels evidence synthesis and a delphi consensus on indicators core interventions outcomes and integration methods to develop a framework for palliative rehabilitation practice and policythe inspire consortium brings together leaders in palliative care oncology and rehabilitation from nordic southern northern and central european countries with complementary expertise in health services research trials of complex interventions mixed method evaluations statistics and economics we are partnering with european civil society organisations to ensure citizen engagement and dissemination at the highest level
breaking into the brain basement membranes and the perivascular niche

in neuroinflammation leukocytes reside for several days in the perivascular niche of cerebral blood vessels defined by the basal surface of the endothelium the endothelial basement membrane bm and an outer parenchymal bm with associated astrocyte endfeet fig 1 a poorly studied site but of utmost fundamental and clinical relevance this site is also emerging as harbouring genetically distinct resident cell populations the function of which are unclear bms define the perivascular niche and the sealed nature of this compartment in an unknown manner b3m will explore the perivascular niche of cerebral vessels using our new dextranhydrogel with tuneable adhesive stiffness and degradability properties and cerebral endothelial cells derived from induced pluripotent stem cells ipsc we will recreate the subendothelial site we will sequentially increase its complexity to reflect the in vivo spatial arrangement of cells and bms within the most correctly mimicked environmental properties in a system that permits perfusion with immune cells and live imaging parallel ex vivo and synthetic approaches will further break down the complexity of this site into discrete steps and using multiscale imaging of new splitcre transgenic mice we will track target and profile perivascular cells lacking bm receptors studies to date on leukocyte entry into the brain focus on endothelial properties or immune cell behaviour with little consideration of the 3d relationship between cellular and bm barriers and their functional interdependence my unique knowledge on extracellular matrix structurefunction of cerebral vessels and leukocyte migration into the brain allows me to identify key elements of the perivascular niche and how they can be mimicked in vitro and targeted in vivo b3ms crossdisciplinary approach will decipher cellular and molecular events occurring after leukocyte penetration of the endothelium in the perivascular niche shedding light on a black box
transnationalizing parliaments investigating the voting power of europes arab diasporas

as some arab states are moving towards more open political processes diasporas have become an increasingly important electoral factor they contribute to political discourse and possess the capacity to inject ideas norms and expectations informed by their host societies into the political sphere of their country of origin in the european context these phenomena have been elaborately discussed with respect to the turkish diaspora among others however due to its relative novelty and much greater complexity europes arab diasporas and their ability to influence parliamentary outcomes in their states of origin has comparatively been understudied vopad will fill gaps in current research by examining the influence of diasporic voting on arab parliaments with a specific focus on the diaspora hailing from algeria egypt lebanon morocco syria and tunisia this will provide new insight into europes arab diasporas role in the postarab spring parliamentary development and importantly shed new light on the potential and limitations for transnational forces from europe in theform of external voting to influence parliaments and parliamentary activity in arab statesas a case and countrybased comparative investigation vopad is organised around three interrelated objectives 1 mapping the design procedures and institutional integration of diasporic voting and how these influence parliamentary composition and subsequent outcomes 2 identifying the voting preferences of the europebased diasporas and whether residence or citizenship in europe influences voting decisions and 3 investigating the competition over diasporas and their political engagement ie how homecountries try to solicit support from diaspora communities abroad and the response this solicits in the public sphere of their countries of residence
piezoceutical biomaterial scaffolds for immunomodulatorybased myocardial repair

cardiac injury in the form of a myocardial infarction leads to cardiac muscle death and replacement scar tissue that cannot compensate lost heart tissue this disease does not improve with traditional drugs and places significant burden on healthcare budgets worldwide with a reduced quality of life for patients often leading to heart failure current engineered cardiac patches do not reduce inflammation and do not integrate in a sufficient manner to compensate the pumping power lost with the heart tissuethe piezomac patch differs fundamentally from patches reported up to now it will contain an optimised piezoelectric capability that will yield electric fields generated by the stretching of the heart this electric field stimulation will be optimised to drive immunomodulate and regeneration of the cardiac muscle the shape of the patch is predesigned using finite element modelling to conform the directional dependent stretching of the heart wall with information of patient anatomy and extent of heart attack damage derived from xray ct and mri scans these smart patches will be 3d printed using melt electrowriting into accurate microfibrous ordered patches whose density microorientation and fibre laydown will be informed using in silico modelling of piezoelectric generation and mechanical anisotropy we will shortlist candidate mesh designs to match the anisotropy of the heart using finite element analysis and refine the design process using a bayesian optimisation approach to strike a balance between mechanical anisotropy and piezoelectric output and ultimately halt cardiac deterioration this pragmatic and rational approach gathers and advances cuttingedge technologies in this interdisciplinary project to address a significant unmet need in healthcare today
a joint music making game augmenting social skills in autistic individuals

autism spectrum disorder asd is a condition marked by communication difficulties but some individuals with asd excel in understanding and responding to music joint musical activities have shown promise in improving social behavior among people with asd however existing musicbased interventions have limitations they lack precise control flexibility and accessibility often requiring training or therapist presence to address these issues the autismus project aims to create technology that allows asd individuals to easily access engaging and interactive musical activities even from home this project leverages a pillar of my erc stg the emusic box emb a device developed to enable nonmusicians to make music together mutually adapting to each others performance we will assess if individuals with asd can use the emb effectively and whether it enhances their social functioning if successful we plan to bring this technology to market considering insights from endusers the embs impact spans various stakeholders including individuals with asd caregivers educational institutions healthcare professionals therapy centers research organizations and autism support groups its versatility suits asd individuals of different ages and abilities compared to existing technologies the emb offers superior accessibility flexibility and interactivity our exploitation route involves patenting the technology and licensing it to a market leader for broad distribution to both b2b and b2c customers fostering innovation and enhancing global products and services