Dragon09/odtu_chatbot huggingface dataset:
generalisation into sentence and predicate positions

generalisations are fundamental to every scientific discipline every cell has a plasma membrane every electron has a negative charge every natural number has a unique successor by means of generalisation we turn a statement about a particular individual into a statement about a class of entities generalisations are essential to valid deductive reasoning they are the building blocks of virtually every scientific theory and therefore essential to understanding explaining and making predictions the most basic and best understood form of generalisation is generalisation over objects eg cells electrons numbers in formal logic this form of generalisation is achieved via firstorder quantifiers ie operators that bind variables in argument position but many theoretical contexts require generalisation into sentence and predicate positions a highlevel form of generalisation where we make a general statement about a class of statements eg mathematical induction laws of logic there are two competing methods for achieving this form of generality ie higherorder logic and selfapplicable theories of truth properties and sets respectively as both methods come with their own ideological and ontological commitments it makes a substantial difference which one is chosen as the framework for formulating our mathematical scientific and philosophical theories some research has been done in this direction but it is still very much in its early stages this research project will significantly advance this foundational project it will provide the first sustained systematic investigation of the two methods from a unified perspective and develop novel formal tools to articulate deductively strong theories due to its foundational character it will have an impact on many disciplines especially the foundations of mathematics logic formal semantics metaphysics philosophy of language and theoretical computer science
sifting through the 3d genome computational models of homology search in dna repair

homologydirected repair is an essential evolutionary conserved dna repair pathway that accurately restores genetic information lost due to doublestranded breaks its key step is the homology search where the broken dna end locates its matching sequence typically located on a sister chromatid to use as a repair template despite its significance the biophysical mechanism of this search within the complex environment of vertebrate genomes remains debated emerging hypotheses propose that this search is driven by nucleoprotein filaments comprised of repair proteins bound to the broken dna ends that actively traverse the nuclear space to find and recognize homologous sequences we will explore this mechanism by developing quantitative biophysical models that integrate the latest experimental insights on the 3d architecture of sister chromatids and dynamics of nucleoprotein filaments our specific aims are 1 model the homology search in 3d to understand how broken dna sites navigate the complex nuclear environment and identify homologous sequences on intricately folded vertebrate sister chromatids 2 explore the microscopic mechanisms that drive the largescale motions and efficient homology search by nucleoprotein filaments 3 understand the role of filamentdriven homology search in the pairing of homologous chromosomes during meiosis by integrating these complementary aims we will build a detailed biophysical mechanistic picture of homology search we will calibrate our models against genomic and microscopic datasets and test their predictions in collaborations with several experimental biology groups this modeling will provide mechanistic insights into homology search rigorously test longstanding hypotheses and generate predictions to guide future experiments the proposed research will significantly advance our understanding of this key dna repair process and its potential roles in maintaining genome stability and meiotic recombination
map and manipulate sleep oscillations to reveal their role in healthy cognitive development

sleep is essential to all animal life but why are sleep needs greater in young mammals evidence points to a key role in cognitive development sleep correlates with brain immaturity and sleep dysfunctions are frequent comorbidities of neurodevelopment disorders as screens invade their bedrooms children are sleeping less and less and learning disorders are on the rise this is a growing public health concernthere is increasing evidence that poor sleep at critical development stages may facilitate the emergence of neural disorders yet this is only correlative but not causal evidence how does sleep architecture differ in immature brains are specific sleep oscillations needed for neural maturation what type of neural computations do they support can sleep dysfunctions directly contribute to social cognitive or learning impairments these crucial questions are still largely unanswered due to technical limitationsi propose to harness new concepts and tools from diverse fields of research to launch an ambitious program bridging neurodevelopment biology systems neuroscience and sleep research because of our interdisciplinary approach my team is in the unique position to pioneer breakthrough in vivo recordings and optogenetics in rat pups i plan to record and decode neural activity from multiple brain areas while automatically scoring sleep in freely behaving pups this in order to elucidate the computational mechanisms at play during developmental sleepi will combine high density recordings with recent advances in viral molecular and cripsr tools to 1 map and 2 impair sleep or associated oscillatory mechanisms with the aim to reveal their 3 impact on healthy development my ambition is to set the stage for a new line of research in developmental systems neuroscience i propose to study the emergence of neural computations infer their roles across the lifespan and reveal sleep as a prime target for therapeutics in development disorders
assessdht development and harmonisation of methodologies for assessing digital health technologies in europe

assessdht will increase the adoption of trustworthy and effective digital health technologies dht across europe enabling a more coherent digital single market for health systems and patients to access dht from all over europe and giving industry a european market we will develop a new assessment framework beyond the existing models capable of uniform hta adoption across europe addressing new assessment challenges in digital therapeutics ai and telehealth our consortium comprises 4 hta bodies the european observatory on health systems and policies 5 academic and not for profit organisations with expertise in eu regulation dht development and assessment methodologies data protection data quality interoperability and cybersecurity patients and health professionals are included through the international diabetes federation and european society of cardiology we include the dht industry through companies with products for us to assess through a formal methodology mimicking actual hta assessments 3 as partners some through an open call and industrywide consultation via digital europe we will engage healthcare payers and ministries through our advisory board we will cocreate our overarching assessment framework with specialised pathways for different categories of dht specified through a novel evidencebased typology we will cater for phased adoption going beyond fast track models like diga complex lifecycles iteratively developed ai consolidated in a comprehensive hta assessment manual plus specific guides in topics like cybersecurity we will develop a sustainable repository containing the assessdht framework pathways and unambiguous criteria a semantically searchable evidence library checklists and tools to support companies with evidence generation evidence of health system value from dht and online communities of practice
first line randomized study platform to optimize treatment in patients with metastatic renal cell carcinoma

in 2020 there were an estimated 431 288 new cases of kidney cancer renal cell carcinoma rcc globally with 138 611 cases in europe leading to 179 368 deaths worldwide including 54 054 deaths in europe source iarcglobocan to define high priority topics in academic research and launch dedicated trials european rcc academic physicians have gathered into a european initiative the care group systemic therapy for rcc relies on two classes of agents antiangiogenic targeted therapy vascular endothelial growth factor tyrosine kinase inhibitor vegfr tki and immune checkpoint inhibitor ici targeting either pd1pdl1 axis or ctla4 combination therapy is standard of care soc for clear cell rcc in all guidelines with either iciici or icivegfr tki however no headtohead comparison have been performed between the two approaches and patients are treated based on physician decision without clinical or biomarker factors to guide treatment selection pdl1 staining is to date the biomarker that has demonstrated its ability to enrich for overall survival benefit favoring iciici strategy in pdl1 and icivegfr tki in pdl1 patientscare1 pct is a prospective randomize phase iii study in first line setting for patients with metastatic clear cell rcc comparing iciici vs icivegfr tki approaches stratified on pdl1 by local determination primary endpoint is overall survival os the trial will enroll 1250 patients over 3 years across eight european countries that are part of the care consortium study sponsor is gustave roussy institute within the getug network for france cosponsor is developed through main academic networks eg sogug in spain and main institutions across europe eg cancer core europe cce study design has been develop to demonstrate that iciici is superior to icivegfr tki in prolonging os for pdl1 patients and that icivegfr tki is superior to iciici in prolonging os for pdl1 patients care1 pct has been designed and will be conducted with patient advocacy group representatives artur and ikcc input care1 is an academic phase iii study designed to define the optimal combination using a pragmatic routinely implementable biomarker therefore care1 will inform practice and has the potential to change treatment guidelines taken all together care1 is a unique opportunity to build a largescale platform to define new biomarker based therapy guidelines as well as to investigate quality of life patient reported outcome and healtheconomic in front line setting as well as pathological and blood biobank collection for further translational work this action is part of the cancer mission cluster of projects ondiagnosis and treatment
targeting the polycomb machinery in bap1related pathologies

bap1related mutations are common genetic lesions of several cancers and neurodevelopmental disorders ndds bap1 is a deubiquitinase that removes the repressive monoubiquitination at histone h2ak119 h2aub1 deposited by the polycomb repressive complex 1 prc1 by associating with several regulatory subunits to form the polycomb repressive deubiquitinase prdub complexbap1 inactivating mutations represent a hallmark in malignant mesothelioma mm for which genetic models proved its oncogenic role mutations further extend to several other cancers also involving other essential prdub regulatory subunits this makes prdub inactivation a major oncogenic event with 40k new diagnosis each year between eu and us for which no precision therapeutic approaches exist the work of my dissectpcg erc project found that the major role of bap1 is to counteract h2aub1 diffusion across the entire chromatin this preserves chromatin plasticity enhancing polycombmediated control of transcriptional identity which is decommissioned when bap1 is inactivated and oncogenic h2aub1 accumulates we also found that diffused h2aub1 is controlled by a specific form of prc1 namely prc135 immediately suggesting a strategy to correct the effects of bap1related mutations indeed we found that specific prc135 loss restored normal h2aub1 levels while compromising mm cells viability demonstrating the therapeutic potential of targeting this nonessential arm of prc1 repressive machineryby building a multidisciplinary team the tbap project aims to develop compounds that can target prc135 in living cells we propose to use prc135 structural data to identify specific binders that can function as warheads for the development of protac degraders this will generate a new class of molecules for the development of therapeutic strategies that can aid oncological patients with bap1related mutations with a further potential application in specific ndd syndromes
protecting threatened river fish against predation

freshwater ecosystems are heavily impacted by human activities and climate change overall at least 37 of europes freshwater fishes are threatened at a continental scale and 39 are threatened at the eu level this is one of the highest threat levels of any major taxonomic group dg environment 2011 many species of river fish are in a very poor conservation status and even those that are protected by eg the habitats directive are not regularly monitored and documentation of the population trend and status is often lacking a recent great increase in predation pressure has further increased pressure on river fish even in healthy restored or leastimpacted areas in the eu predation may be the main reason for widespread loss of populations of habitats directive listed grayling thymallus thymallus there is a genuine and widespread concern among managers and stakeholders regarding protection of wild populations of river fish as grayling from unsustainable predation pressure the conflicts involving fish protection and predation have been intense in most member states for decades and despite protective measures including culling birds directive article 9derogations the conflicts have remained intense protectfish aim to investigate the monitoring and protective measures of habitat directivelisted river fish species answering area a of the call we will develop and test protective actions using cormorants phalocorax carbo sinensis and grayling as a case small and large scale field experiments will be conducted to measure the effect of relieving cormorant predation pressure on fish populations we will examine the background for the conflicts by estimating the current population status of cormorants and grayling in eu as well as quantify the culling of cormorants the results of protectfish will directly aid to achievement of eu biodiversity strategy natura 2000 and the wfd as well as improved adaptive nature management on local levels
polycatechollignin hybrid electrodes for sustainable batteries

designing safe and sustainable batteries is of great importance for sustainable development of our modern society hereof rechargeable aqueous metalpolymer batteries rampbs that combine inherently sustainable redoxactive polymer rap organic cathodes safe and abundant metal anodes in waterbased electrolytes are identified as promising candidates however to date most of the tested raps are synthetic ones and their commercial exploitation hasnt been accomplished due to high costperformance factor subpol proposal aims to develop sustainable rampbs by hybridizing costoriented biopolymer lignin lig and performanceoriented synthetic raps polycatechols pc into organic cathodes and combining with appropriate metal anodes zn pb etc targeting their performance beyond stateoftheart 150600whkg 150kwh subpol will follow an integrated approach of macromolecular engineeringtailor made pcs biopolymer platformease of lig modification novel electrode fabrication methodslbl of complimentary charged pc and lig polyelectrolytes or polyelectrolyte complexes and device optimization this fellowship will provide er strong technical professional and transferable skills especially with acquisition of biopolymer batteries and scaleup which will complete his practical expertise in synthetic raps their applicability in different batteries the success of subpol depends on material design device fabrication scaleup and all members of this consortium dr patiler supervisors prof crispinlinköping university at host dr marcillaimdea energia secondment dr nilssonligna energy placement in nonacademia have already demonstrated required skills in this regard optimistically subpol will cover some of the priorities of hewp for energetic future of eu and also its multidisciplinary aspect provide a true opportunity to reach his career goal of becoming an independent researcher in either a leading university or rd batteries company
proton electron and neutron sources for nondestructive testing and investigations and treatment of materials

the main goal of the pantani project is to complete the design of an innovative laserdriven radiation source suitable for applications in materials science inspection and treatment as well as the development of some of its key components accelerators are exploited to produce particles and radiation needed for applications of high industrial and social relevance like analysis of objects of historical artistic and environmental interest sterilisation of medical instrumentation inspection of cargos and goods largescale diffusion of these applications is prevented by the intrinsic limits of the available particle sources in terms of costs dimensions and flexibility in this frame laserdriven particle sources represent an appealing solution to overcome these limitations they are potentially cheaper and more compact compared to conventional accelerators moreover they can provide several kinds of particles to perform multiple applications with the same source these novel sources are subject to active research but no industrial applications are currently available starting from the results obtained with the erc cog ensure and erc poc inter projects pantani aims to address key aspects never considered before to develop a laserdriven particle source dedicated for the applications 1 the development of an applicationoriented design of the entire acceleration system 2 the identification of commercial laser solutions compatible with the source requirements 3 the production and test of a prototype radiation detector 4 radiation protection assessment of the designed system also from the legislative point of view all these results achieved by exploiting the expertise from both academy politecnico di milano host institution and industry the raylab and sourcelab partners will allow bridging the gap between fundamental research and the development of a realistic multipurpose laserdriven particle source suitable for applications
multiscale ocean models and information for climate risk assessment and impact mitigation

moirai named after the three greek goddesses of fate stands as a pioneering project at the intersection of past present and future moirai endeavors to weave a comprehensive understanding of the oceans dynamics and biogeochemical cycles through advanced models integrating historical data current observations and future projections integrated into the frameworks of destination earth de and the european digital twin of the ocean dto key components of the broader digital and green transitions moirai aims to significantly advance our comprehension and mitigation of climaterelated challenges moirai is set to advance the next generation of regional to coastal ocean and biogeochemical climate models in european seas bridging the gaps between operational and regional ocean climate models benchmarked with improved climate modelling and prediction capacities in the estuarialcoastalopen sea continuum the developed models will contribute to the european green deal addressing resilience to climate change both mitigation and adaptation in coastal areas the quality of its coastal models forms the backbone of moirais commitment to delivering reliable outcomes for endusers at its core moirai in conjunction with the establishment of reasshore resilience and adaptation strategies selection hub for ocean risks assessment and endusers feedback aims to create replicable scientific frameworks and pave the way for basinscale services fostering collaborative initiatives across european regional seas designed to be modular and interoperable reasshore will seamlessly integrate with existing and future digital infrastructures for ocean climate and risk services
development of a complete triple action injectable treatment for osteoarthritis

osteoarthritis oa is an incurable complex disease affecting an estimated 240 million people globally including 40 million europeans oa is the fastest growing cause of disability due to an aging population and the obesity epidemic and affects more people each year than cancer and heart disease in knee oa progressive degradation of bone and cartilage in the joint results in severe pain and reduced mobility current treatments for knee oa target only one aspect of the disease yet most recent scientific data highlight the need for multimodal therapeutics to treat this complex disease furthermore the limitations of treatments force 80 of patients to rely on strong addictive pain medication through the hydrolieve erc proof of concept grant it was proven that hydrobloc statistically significantly reduced pain sensations in an in vivo pain model these exciting results led dr alison liddy to spinout relevium ltdhydrobloc unique synergistic triple action addresses all aspects of this debilitating disease hydrobloc is the only therapeutic that regenerates the damaged cartilage whilst providing immediate superior pain relief and improving the physical function of the joint through a cushioning lubricant effect preclinical studies have proven that hydrobloc returns the oa joint to 90 of normal nonoa physical functionwith this eic grant relevium is partnering with nui galway to validate the preclinical results in larger animals and preclinically test for other oa indications relevium will compile the clinical trial dossier and develop a business model towards the maturation and transition to commercialisation
easy to use contactless dualmode ultrasound technology for high accuracy treatment of atrial fibrillation improving outcomes

our mission is to radically change the landscape of cardiac ablation our products based on proprietary ultrasound technology allow contactless tissue ablation with realtime lesion monitoring bringing healium to the forefront of the cardiac ablation market our team backed by scientific and business advisors includes dr eckhouse chairman leading medical entrepreneur who has founded 20 companies and cumulated 1b in exits ventor for 325m synron and lumenis both ipo 1b ran sela ceo and cofounder 15 years of medical device development and project management dr megel cto and cofounder 25 years in ultrasoundbased medical devices now we are at the toprisk phase of our development journey the transition from preclinical to clinical studies leveraging an ec investment of 1275m we can demonstrate the efficacy and safety of our product establish a manufacturing line and regulatory framework and access the market as a selfsustained company