Dragon09/odtu_chatbot huggingface dataset:
exploiting ex vivo expansion and deep multiomics profiling to bring novel efficient and safer hematopoietic stem cell gene therapies to clinical application

hematopoietic stem cells hsc are an elusive cell type whose presence can only be inferred retrospectively from the outcome of timeconsuming transplantation experiments since current stateoftheart does not allow prospective hsc identification todays cell and gene therapy technology has been mostly optimized on surrogate progenitor cells which differ biologically from hsc the technological breakthrough of this proposal is to capture hsc in the ex vivo culture achieved by a combination of innovative expansion conditions iterative cell sorting and multiomics single cell profiling rapid quantitative and qualitative in vitro hsc assessment predictive of in vivo function may become a sustainable alternative to mouse xenotransplantation experiments applied to a stateoftheart toolbox of genetic engineering technologies including clinicallyproven lentiviral vectors as well as established and emerging targeted genome editing approaches our in vitro hsc readout sets new standards in terms of throughput and turnaround time allowing to efficiently test a multitude of hsc engineering conditions and tailor the most suitable technological approach to a specific disease or therapeutic application this new precisionbased approach to ex vivo hsc gene therapy will be applied to inherited bone marrow failure syndromes and cancer as paradigmatic examples where gene therapy may be used to correct a cellintrinsic genetic defect or turn hematopoietic progeny into therapeutic vehicles provided with novel functions bringing together experts in cuttingedge gene editing technologies ex vivo hsc manipulation assessment of hsc responses to genetic engineering and bioinformatics analysis integration of multidimensional single cell data will maximize the chances of delivering safer and more effective nextgeneration hscbased gene therapy products extending the reach of gene therapy to new disease contexts and making the outcome after gene therapy more predictable
boosting the exposome space coverage in the aquatic environment by multidimensional integrated analytical platforms

the increase of anthropogenic chemicals released by human activities poses a growing threat to natural and manmade environments characterizing the mixture of chemicals that an individual encounters throughout lifetime namely exposome is a complex analytical task that is only partially fulfilled by current stateoftheart methods nontargeted analysis approaches based on liquid reversedphase chromatography hyphenated with highresolution mass spectrometry restrict the detectable exposome chemical space to mediumtolow polarity chemicals the bespace project seeks to untangle sample complexity and expand the detectable exposome through advanced separation approaches combined in a twodimensional fashion and hyphenated with highresolution mass spectrometers on this basis it shall boost the profiling of chemicals of environmental concern in relevant exposome matrices like environmental and treated water samples thanks to the collaboration with kwr water research institute even though twodimensional liquid chromatography approaches provide increased separation selectivity and capacity boosting the detectable chemical space coverage of the aqueous samples their application in exposomics is limited the complex twodimensional data structure and the lack of standardized procedures hamper the exposome chemical identification requiring the implementation of composite cheminformatics tools therefore bespace will develop advanced wet and dry lab analytical platforms to expand the detectable chemical space of the aqueous compartment largescale qualiquantitative exposomics datasets will be project final outputs providing cuttingedge data to be publicly shared to enrich present databases and to develop novel risk assessment approaches the implicit multidisciplinarity of the project grants multipleway knowledge transfer among the host institution the researcher and the associate partner
nonlinear existential arithmetic theories

arithmetic theories are logical theories about systems of numbers that found important applications in several areas of computer science for instance those theories have a fundamental role in satisfiability modulo theory smt abstract interpretation and symbolic execution the three most prominent algorithmic techniques to type check or bug test programs against rich specification languages in optimisation integer linear programming offers a general framework to model many scheduling planning and network problems using linear integer arithmetic in theoretical computer science several computational problems stemming from formal logic and automata theory require arithmetic theories procedures to be solved arithmetic theories are simple to describe but their algorithms are based on profound mathematical theories the goal of this proposal is to achieve a major advance in algorithms for decision and optimisation problems of existential arithmetic theories featuring the nonlinear operators of exponentiation and divisibility we choose to focus on these two operators for both theoretical and practical reasons on the theory side whereas multiplication often causes decidability issues see eg the undecidability of hilberts 10th problem exponentiation and divisibility are much more algorithmically robust on the practical side these two nonlinear operators have recently found several applications in the aforementioned areas of computer science to achieve our goal our methodology combines several areas of mathematics and theoretical computer science automata theory combinatorics nonconvex geometry model theory and number theory while the content of the proposal is foundational in nature the longterm goal is for algorithms developed during the project to serve as a basis to expand the capabilities of smt solvers static analysers and optimization tools making them able to handle very expressive languages of arithmetic
sensing as a service

water utilities face growing challenges due to urbanization water scarcity rising energy prices and aging water supply networksto improve resource efficiency utilities are integrating smarter technology in their networks however there are some constraints that make implementation difficult such as reasonable and easy access to sufficient power for technological solutions furthermore these solutions need to be pieced together using different components from various manufacturers sensors battery data logger connectivity and software in addition experts are needed to making the entire system work with our selfpowered and smart plugandplay sensorswe provide more data to water system managers and help them better understand and manage their pipe networks
mental files new foundations

this project is about the representation of particular objects in language and thought a topic which has been at the forefront of philosophical attention for more than a centuryabout fifty years ago descriptivism was demoted from its dominant position in philosophy in favour of the theory of direct reference a similar shift away from descriptivism has been a noticeable feature of work on the representation of objects in cognitive science where the notion of an object file has made it possible to unify research on perception and on infant cognition the object file construct is in many respects similar to the philosophical idea of direct nondescriptive grounding for thoughts about particulars and this has given rise to a new research program the generalization of the file idea from perception to thought thus the last decade has seen the development of the mental file framework according to which nondescriptive thoughts about particulars socalled singular thoughts whether or not they are based on perception involve mental files whose reference does not depend on category information to be found in the file but on certain relations to the object the obtaining of which triggers the opening of the file the mental file framework has attracted considerable attention not only in philosophy but also in psychology perner and linguistics kamp it has also inspired work in aesthetics and the philosophy of fictionsuccessful though it is the mental file framework currently faces what may be described as a foundational crisis according to a recurrent piece of criticism it fails to provide appropriate identity and persistence conditions for mental files this threatens the credibility of the framework reduced to a convenient metaphor and puts it at risk despite its high promises and considerable appeal the aim of this philosophical project is to end the crisis by entirely rethinking the foundations of the framework
investigation of endocrinedisrupting chemicals as contributors to progression of metabolic dysfunctionassociated steatotic liver disease

masld is the condition of excessive accumulation of liver fat unrelated to alcohol intake ranging from simple steatosis to metabolic dysfunctionassociated steatohepatitis mash with a 25 prevalence in the general population masld is currently the most common liver disease and a major healthcare and economic burden while hyperlipidaemia obesity and insulin resistance are the major risk factors for masld and contribute to its rising prevalence growing evidence suggests that exposure to endocrinedisrupting chemicals edcs can initiate andor cause progression of masld edcmasld will focus on investigating the impact of environmental exposure to edcs on the internal exposome metabolome gut microbiome epigenome proteome immunome and degree of liver damage in masld in prospective study settings with a focus on the period of transition to progressive stages of masld edcmasld is particularly focused on interactions between edc exposure sex genotype diet socioeconomic and lifestyle factors via the data and biosamples available in the unique european nafld registry comprising over 9000 patients with histologically characterised masld edc exposure studies will be performed in murine models of masld zebrafish models and human 2d3d in vitro models with an aim to understand respective mechanismsofaction and to develop novel edc screening tools the edcmasld consortium has diverse and complementary expertise in the domains of hepatology endocrinology toxicology exposome research metabolomics systems biology environmental economics and communications technology research with respective pis being global leaders in their fields taken together edcmasld will significantly contribute to the actions centred on identification and mechanistic assessment of impact of edcs strategies to monitor and reduce exposure and regulatory actions that could better protect human and environmental health
restorative genderspecific experiences in urban natural environments

regenerate explores gender differences in how urban natural environments une comprising parks seaside and other green and blue spaces in cities can support psychological restoration ie recovery of depleted cognitive and psychophysiological resources including recovery from psychological stress it addresses challenges of urban sustainability gender inequality and poor mental health all key for europe and horizon the naturehealth research field suggests that nature contact is restorative and promotes longterm health benefits however to date naturehealth theories and evidence tend to lack a gender focus this is despite women are up to seven times more likely than men to report depression regenerate explores how restorative benefits of une can be affected by gender eg sociocultural norms attitudes and behaviours due to gender roles and relations eg childcare responsibilities gender stereotypes ie what is socioculturally appropriate for women and sexrelated biological attributes ie needs to use restroom more often than men thus addressing a key theoretical and empirical blind spot specific objectives include i reviewing evidence and identify factors affecting womens naturehealth restorative pathways in une ii exploring genderspecific experiences in une and related longterm restorative benefits and iii integrate findings into policy the methodology includes a review of the evidence and analyses of secondary data on naturehealth from four european countries representing diverse european regions results then inform realworld policy regenerate contributes to policies for healthy gender inclusive and sustainable cities sdg3 good health wellbeing sdg5 gender equality sdg11 sustainable cities and communities it contributes to making cities good for all guided by the feminist urbanism principle that if public spaces are good for women they will be good enough for everyone
scaling up secure processing anonymization and generation of health data for eu cross border collaborative research and innovation

the overall goal of the secured project is to scale up multiparty computation data anonymization and synthetic data generation by increasing efficiency and improving security with a focus on private and unbiased artificial intelligence and data analytics healthrelated data and data hubs and crossborder cooperation the project will address the limitations that are currently preventing the widespread use of secure multiparty computation and effective anonymization namely the limited practical capabilities of current cryptographic schemes for secure multiparty computation protocols and their performance the lack of well understood and standardized data anonymization methods for health data the absence of dynamic and on demand services for generating synthetic data the complex and adhoc nature of current federation protocols for machine learning and aibased data analytics the lack of support for health technology providers to implement privacy enhancing technologies in particular smessecured will tackle these challenges by focusing on scaling up privacy technologies via algorithmic improvements and implementation efficiency hw and sw as well as the generalization of primitives and definitions with the aim of speeding up and facilitating privacy preserving datadriven tools and services for wellbeing prevention diagnosis treatment and followup care secured will also analyse the current ethical and legal challenges to data sharing and is targeted at overcoming current limited adoption of advanced multiparty computation and data anonymization technologies by providing direct support to health technology smes through a funding call to ensure relevance to realworld settings secured will showcase the technologies developed in four healthrelated use cases provided by partner hospitals and health stakeholders namely realtime tumor classification telemonitoring for children synthetic data generation for education access to genomic data
novel effect biomarkers for metabolic disruptors evidence on health impacts to answer science and policy needs

endocrinedisrupting chemicals edcs disturb lipid and glucose metabolism in several metabolically active organs such as liver and pancreas besides being able to interfere with many aspects of hormonal action there is accumulating evidence linking edcs or their mixtures with an increased incidence of obesity atherosclerosis and type 2 diabetes developmental exposure to edcs can exert lifelong even transgenerational effects and affects the susceptibility to many diseases however the metabolic effects of edcs are still poorly understood and the lack of mechanistic data and predictive models of adverse metabolic outcomes of edcs hinders their risk assessment the novel effect biomarkers for metabolic disruptors evidence on health impacts to science and policy needs nemesis consortium brings together experts in toxicology medicine risk assessment and social sciences and humanities to respond to the unmet regulatory needs of edcs within silico in vitro in vivo epidemiological and systems biology data on edcmediated metabolic effects in multifactorial models we will assess mechanistic data on metabolic disruption in liver and pancreas and how edcs or their mixtures affect the microbiota enhanced with data on doseresponse relationships and the causality of these actions in addition nemesis will provide human exposure data of edcs and explore effect biomarkers for metabolic disruption nemesis results will improve assessment of metabolic endpoints in testing guidelines and adopt alternative models to animal testing adverse outcome pathways aops and integrated approaches to testing and assessment iata approaches will be developed to assess adverse metabolic effects of edcs and improve the risk assessment towards a more holistic approach citizens are engaged from the beginning of the project to develop effective risk communication practices on edcs and to maximize the sciencetopolicy impact of nemesis together with relevant stakeholders
reversing the advantage of cancers with hypoxia and homologous recombination defect hrd by using a pancancer composite lesionsspecific biomarker

hypoxiaactivated prodrugs haps are a great concept in particular in association therapies more efficient on welloxygenated cells such as immunotherapies cp506 is a third generation hap with optimal pk for which we confirmed in more than 20 tumor models that presence of tumor hypoxia is a requisite for prodrug activation we already had an airadiomicsbased proprietary ip on a solution to identify hypoxia from standard imaging another important determinant for efficacy was the presence of a defective homologous recombination hrd a pathway needed to repair the dna damage of the alkylating warhead of cp506 a genomewide mutational scarbased pancancer classifier of homologous recombination deficiency chord available open source is able to detect hrd better as compared to assessing mutation of key genes it is therefore essential to have a validated software solution integrating both biomarkers this solution further developed in this project will be able to capture intrapatient heterogeneity and make a outcome prediction per patient and per lesion
beyond the tipping point cascading transitions in the behavioral and social sciences

tipping points or phase transitions separate stable states in psychosocial systems examples are quitting smoking radicalization and droppingout of school two knowledge gaps prevent our ability to predict and control these tipping points first we miss explanatory mathematical models of such nonlinear processes second we ignore the multilevel character of psychosocial transitions i contend that important changes in many psychosocial systems are cascading transitions where individual transitions trigger or are triggered by social transitions the cascade of radicalization of individuals in the context of political polarization in societies is an example of such a multilevel process being able to predict and control cascading transitions in psychosocial systems would be a major scientific breakthroughas an expert of complex systems research in the behavioural and social sciences with an extensive track record in studying single level psychological transition processes eg in perception sleep disorders cognition and attitudes my key objective is to develop a novel and broadly applicable methodology to study multilevel cascading transitions in psychosocial systems this methodology comprises theory construction in the form of mathematical modelling and innovative empirical analyses i will do so by studying three important examples a opinion change from individuals to populations and back b learning where progression and dropout are embedded in collective processes c addiction where transitions to addiction or abstinence within individuals are part of cascading epidemiological changes of substance use in populationsbeyond its immediate utility in these three cases i envisage this novel highly interdisciplinary project to stimulate future scientific research on cascading transitions in other disciplines such as climate research and to have significant impact on practices in conflict management healthcare and education
sustainability performances evidence and scenarios

the aim of the spes project is to generate new knowledge and evidence about the nexus between economic growth human flourishing and sustainability contributing to the creation and uptake of a novel integrated framework fostering the transition towards the sustainable human development in european countries and regions the spes project focusing its attention both theoretically and empirically on the four pillars of the sustainable human development a productivity conceived as pursuing an efficient use of economic human and natural resources through innovation processes b equality for all conceived as fostering equal political economic social and cultural opportunities c sustainability conceived as promoting climate change mitigation and adaptation and ensuring the protection restoration and improvement of the environment d participation and empowerment conceived as enabling citizens social groups and communities to be active agents of their future focusing on these four pillars allows both an indepth analysis of their synergies and tradeoffs and their contribution to transition performances across europe and the global south spes will combine diverse methods including 1 econometric analysis including microsimulation and panel data analysis 2 codesign workshops with key stakeholders 3 scenario analysis 4 casestudy analysis the strong involvement of a carefully structured international stakeholder committee and of a scientific advisory board as well as the adoption of tailored communication dissemination and impact strategies will decisively contribute to foster spes impact the newly produced policy and measurement framework will give further strengths to the transition towards sustainable human development by informing both the public debate and the implementation of existing policy frameworks with a particular focus on the 2030 agenda the european green deal and the just transition mechanisms and the nextgeneration eu
preclinical development of a lentiviral gene therapy to treat hearing and balance loss in usher 1b patients

the most prevalent genetic sensory defect sensorineural hearing loss snhl affects 430 million people and results in substantial financial and social consequences current treatment options are limited achieving only temporary or partial relief and are restricted to a subgroup of patients therefore novel treatment options are of high clinical need genetic mutations play a role in the majority of snhl cases which makes snhl an ideal setting for innovative clinical gene therapy approaches usher syndrome is an especially severe form of snhl with loss of vision and balance accompanying the profound deafness the size of the underlying genes mutations of which are causative for usher syndrome exceeds the cargo capacity of gene therapy vectors currently employed to treat inner ear disorders in my ercfunded consolidator project ihear we have provided the first groundbreaking evidence of efficient gene transfer into inner ear cell types using beyond stateoftheart lentiviral vectors lv as these lv have the capacity to deliver large genetic payloads we acquired initial data demonstrating functional improvement in a knockout mouse hearing loss model following lv application the myosenses poc proposal aims to advance these valuable research results towards clinical application by completing preclinical development securing ip rights and commercializing a formulated medicinal product to launch a firstinhuman clinical lv gene therapy trial to treat usher syndrome patients this groundbreaking concept can be extended to treat lateonset hearing loss in patients with heterozygous mutations and can be transferred to similar diseases with a genetic or acquired cause the myosenses product will be the first and only treatment that addresses the debilitating vertigo in combination with treating hearing loss in usher syndrome patients having the potential to drastically improve patients lives and benefit society