Dragon09/odtu_chatbot huggingface dataset:
implementation of affordable gene correction therapies

rare genetic diseases affect over 30 million people in europe although individually rare and very diverse they are all caused by genetic mutations recent progress in genetic technologies now holds the promise to correct the root cause of these diseases however it remains difficult to develop these innovative technologies into affordable therapies for these diseases that only affect few patients limiting commercial interestimpact aims to overcome the translational gap between scientific gene editing and in human gene correction therapies that will be affordable and readily available for patients with rare genetic diseasesto overcome this gap we will use a multifaceted approach to set up the infrastructure for a gene correction therapy for methylmalonic acidemia mma by elucidating and addressing the essential 1 regulatory 2 manufacturing and 3 financial requirements this approach involves preclinical testing of the therapy in a perfused ex vivo human liver clarifying the intellectual property strategy and involving experts stakeholders and end users to define the regulatory manufacturing and financial strategies required for academic development and clinical implementation as such impact aims to valorise the innovative gene correction strategy developed with the erc starting grant to deliver prime editing tools as mrna encapsulated in lipid nanoparticles to correct the diseasecausing mutation in the liver of patients with mmawith impact we do not only aim to develop gene correction therapies in our academic hospital for mma through our efforts in generating the infrastructure for a therapeutic platform approach with only slight adaptations to target different mutations we ultimately aim to develop therapies for the many patients with different genetic diseases
advanced numerics for uncertainty and bayesian inference in science

scientific knowledge enters computers through data on the one side and laws of nature implicit equations like differential equations and symmetries on the other they both provide information empirical and mechanistic respectively crucial to the deduction of new insights but the algorithms that operate on these sources of information stem from different communities and different eras machine learning big data on the one hand and simulation methods high performance computing on the other one of the problems that arise from this disconnect is that inferring latent forces that drive dynamical systems from data requires shoehorning different algorithms together in inefficient optimization loops
deciphering the origins of cell differentiation and developmental gene regulation in animals

during animal development the process of cell differentiation gives rise to terminally differentiated cell types with celltypespecific gene expression programs in the most closely related group to animals the choanoflagellates cell differentiation occurs but cells do not commit irreversibly to specific fates instead they transition through cell identities as they progress through their life cycle known as temporal cell differentiation animal cell differentiation is thought to have evolved from temporal differentiation but the mechanisms are largely unknown due to a lack of information on the molecular processes underpinning temporal differentiationthis proposal will test the hypothesis that chromatinbased transcriptional regulation underlies temporal cell differentiation in choanoflagellates utilizing s rosetta as a model i will compare transcription and chromatin across cell types using genomewide omics techniques this will allow me to assess the role of different histone modifications in cellfate transitions and discover whether various aspects of animal developmental gene regulation eg the use of repressive histone modifications in celltypespecific gene regulation are also utilised in choanoflagellates i will also examine the cisregulatory landscape in s rosetta and use both molecular and functional assays to examine the types of cisregulatory elements present and particularly if enhancer elements are used to regulate gene expression finally i will test the role of selected chromatin regulators in temporal cell differentiation and celltypespecific gene expression this groundbreaking work will be the first to study these processes in choanoflagellates thus pioneering the comparison between definitive cell differentiation seen in animals and choanoflagellate temporal differentiation in a broader context this will deliver fundamental new insights into the evolution of animal generegulation during development
cooperative business models for biobased chains in rural areas

aiming at increasing farmers income and to be fully aligned with the common agricultural policy cap while addressing also green deal and bioeconomy strategy objectives brilian will support the adoption of sustainable cooperative business models in rural areas these business models will enhance rural development biodiversity preservation and climateneutrality for that brilian will implement a multiactor approach for the validation of a group of actions for the bio innovation abi both at macro and micro levelthe actions for the bioinnovation are abi 1 forging robust rural biocommunities abi 2 achieving circularity and sustainability abi 3 integration of short supply chains and abi 4 production of valueadded bioproducts therefore brilian innovations will allow primary producers to diversify their incomes while reducing risks these abi will be particularized for 3 pilots in italy spain and denmark within these pilots a set of business models will be enhanced and tested for the validation of 10 value chains 6 in italy 2 in spain and 2 in denmark brilian pilots will make use of existing rural infrastructures but implementing adaptations to the current main processes and contractual agreements between actors to strength that business model design aproaches will be supported by modules dealing with logistic organizational and sustainability factors weighted in the brilian optimization toolkit a toolkit based on complex models which will provide support for the design and optimization of biobased value chains putting primary producers in the centre as a result brilian will set longterm strategies for the adoption of cooperative business models in eu facilitated by the generation of 11 key exploitable results during the project including technical socioeconomic policy regulation and academic ones the implementation of such an ambitious project requires of a consortium of 13 partners with 11 bic members
real time 2d polymerization studied using atomic force microscopy

twodimensional polymers are a crucial category of lowdimensional materials that have garnered significant attention from both academia and industry despite the synthesis of various types of 2dcofs reported in the literature there remains a significant gap in our fundamental understanding of their nucleation and growth mechanism on the surfaces highspeed atomic force microscopy hsafm offers the potential to observe molecular processes in realtime providing valuable insights into singlemolecule dynamics this project aims to develop scientific and technical methodologies for investigating 2d polymerization processes using hsafm on solid surfaces i target the acquisition of qualitative as well as quantitative data in relation to the nucleation growth and ripening phenomena transpiring during 2d polymerization this research will shed light on numerous unknown aspects of dynamic covalent chemical reactions occurring on solid surfaces which often differ substantially from those in solution or bulk complementary techniques such as xps and afmir will be employed to chemically characterize the material this comprehensive approach will enhance our understanding of surfacebased 2d cof design the quantitative insight obtained into the 2d polymerization processes will be used to fabricate large domains of defectfree polymer films on various surfaces such as slgsisio2 hbn and mica the high quality polymer films formed on dielectric substrates would pave way for the direct characterization of their electrical properties such as charge carrier mobility
enhancing the implementation security of quantum key distribution

the advent of quantum computers poses a severe threat to the security of our existing communication infrastructure quantum key distribution qkd which bases its security on the laws of physics rather than unproven computational assumptions has been proposed as the ultimate solution to protect the longterm security of our communications however due to inevitable imperfections in the devices used to implement qkd protocolsparticularly the sourcespractical qkd systems suffer from security vulnerabilities that could be exploited by attackers to gain unauthorized information thus invalidating qkds seemingly ironclad security guaranteesrecently the scientific community has started to address this critical issue with initiatives aimed at both developing security proofs resistant against device imperfections and at experimentally quantifying their magnitude however these security proofs have tended to consider imperfections in isolation and are thus unsuitable for realworld implementations suffering from multiple imperfections simultaneously moreover the existing experimental works have not focused on quantifying the specific parameters required to apply these security proofs limiting their practical utilityin this project we aim to significantly enhance the implementation security of qkd through two primary objectives the first is the development of a rigorous and robust security proof that by integrating previous approaches incorporates all possible device imperfections and could thus secure practical implementations against all attacks aiming to exploit them the second objective is the development of source characterization tests that can measure the specific parameters needed to apply this security proof demonstrating its ability to secure reallife implementations achieving these objectives would significantly strengthen qkds potential as a solution to ensure the longterm security of our communication infrastructure
bioabsorbable metallic endovascular medical devices biomend doctoral network

biomend is an industrial doctorate network dn programme that will provide worldclass interdisciplinary training to 15 highachieving doctoral candidates dcs in the area of bioabsorbable metallic endovascular medical devices biomend the consortium spans seven european countries and comprises of leading academic clinical and industry experts to promote international interdisciplinary and intersectoral aspects of dc skill development the research objective of biomend is to develop nextgeneration bioabsorbable metals for endovascular medical devices for both cardiovascular and peripheral applications biomend will achieve this through the development of ultrafine grain magnesium and zinc alloys that exhibit high strength excellent creep performance and high ductility with enhanced corrosion properties delivered by multilayer coating technologies these novel magnesium and zinc metal alloys will be leveraged to develop design and fabricate a range of innovate bioabsorbable metallic endovascular medical devices across both cardiovascular and peripheral applications preclinical evaluation will be conducted to demonstrate enhanced functional performance of bioabsorbable metal endovascular medical devices in both acute and longterm animal models these medical devices have the potential to be technology disruptors in endovascular medicine and all dcs will be involved in establishing a clear roadmap for their commercialisation through exploitation activities apart from these technological breakthroughs biomend programme will make significant scientific impact by developing novel ultrafine grain mg zn alloys and establishing new structurepropertyprocessing relationships describing their performance the comprehensive skillset delivered by the programme will enhance career development and employability of dcs within the medical technology sector and promote their development into leading innovators in the european medical technology sector
dynamic modeling of nonpharmacological interventions for type 2 diabetes

the prevalence of type 2 diabetes t2d is projected to increase by 100 million within years however while lifestyle changes are recommended by the who to counter mitigate diabetes comprehensive intervention experiments that consider the interplay of different lifestyle factors are lacking as are clinical tools to evaluate such interplay the present project will address these outstanding issues through two major undertakings1 a first longterm dynamic intervention experiment encompassing multiple lifestyle factors diet sleep exercise will be conducted in 200 subjects with without t2d the participants daily multimodal health data biochemical markers sleep questionnaires etc will be recorded to form a highresolution dynamic intervention database with unprecedented integrative temporal resolution which will be stored securely and made available for fellow scholars and the public to take advantage of2 the project will for the first time use the concept order parameters from statistical physics to represent different health states treated as distinct ordered statuses thus a novel multimodal model will be built to characterize the temporal evolution of health variables that the modelling pinpoints as being the most predictive longitudinal parameters the project will thus enable personalized predictions for holistic health trajectory by analyzing the general physical laws followed by the temporal evolution of model parameters also in relevant t2d healthy subgroupsthe two undertakings provide excellent quality control risk assessment via six tailored work packages consisting of 32 milestones and 4 deliverables this will provide an effective assessment tool for public health monitoring at both the individual policy level more importantly it will enable a paradigm shift from traditional grouplevel descriptive statistics to precise quantitative assessment for longitudinal evaluation of key clinical health parameters
binding the self how cortical oscillations bind sensory stimuli into a multisensory representation of the physical self

binding the self tests the idea that cortical oscillations temporally bind different sensory stimuli into a multisensory representation of the physical self to generate the sense of body ownership ie the experience of ones body as ones own the project combines psychophysical tasks with electroencephalography and brain stimulation providing unique insights on the mechanism that binds bodily sensory information multisensory temporal integration of visuotactile signals is thought to occur within individual alpha frequencies iaf while integration of tactile stimuli occurs within individual beta frequencies ibf stimuli are integrated when they fall within the same cortical cycle and segregated for different cycles the speed of cortical oscillations is modulated by task demand cortical frequencies decrease when the task requires temporal sensory integration compared with segregation here my first objective is to show that individual temporal resolution of perception in simultaneity judgments correlates with temporal resolution of multisensory integration involved in body ownership both when body ownership is induced by visuotactile signals and when it is induced by proprioceptivetactile signals without vision next i will demonstrate if i the integration of visuotactile stimuli that underpins body ownership occurs within iaf and if ii iaf is modulated by simultaneity judgments which require temporal segregation or ownership judgments which require integration finally i will clarify if i ibf integrates tactile information to produce body ownership without vision and if ii ibf is differentially modulated by tactile simultaneity or ownership judgments binding the self reveals the similarities and differences between multisensory integration occurring for external events and for ownbody perception results have implications for clinical conditions with an impaired body representation and for the field of the brainmachine interfaces
scalable control approximations for resource constrained environments

this project aims at making a breakthrough contribution in optimal control and decision making for nonlinear processes that take place on network structures and are dynamic in time andor space the setting has a wide range of potential domains of applicability comprising thermal electric or fluid dynamics in energy networks logistics disease spreading dynamics or cell signalling in biomedicine the project will pursue the following objectives to contribute new theory to develop numerical approximation methods to implement algorithmic methods in software and to conduct proofofconcept studies research in the young field of mixedinteger optimal control mioc has recently seen increased momentum together with numerical approximation algorithms and control theory despite initial successes key questions remain unsolved because of a lack of analytical understanding a lack of tractable formulations the unavailability of efficient solvers or the insufficiency of existing implementations this project focuses on pivotal but poorly understood topics decomposition relaxation and approximation domains admitting homogenization and limiting processes using weak topologies tractable approximations of direct costs of decisions efficient distributed and parallel nonlinear solvers and robustness of approximate nonlinear decision policies under uncertainty these key issues appear systematically in a wide range of control tasks of high societal relevance by addressing them the project helps to bridge a persistent and pronounced gap in simulation optimization practice due to nontrivial interactions emerging in theory and the unavailability of comprehensive algorithms these topics cannot be suitably handled by merely combining the respective states of the art a focused effort to decisively extend mioc to optimal decisions for dynamics on networks is therefore a timely endeavour that will help to address the challenging demands of practitioners
smart sensors and selfhealing functionalities embedded for battery longevity with manufacturability and economical recyclability

the core concept of the salamander project is to develop and integrate embedded sensors and selfhealing functionality in liion batteries lib to enhance their quality reliability and lifetime this is achieved by demonstrating smart aspects in the battery which analyze indicators of its own degradation and independently respond with external stimuli to trigger ondemand selfhealing to achieve this goal the project proposes 3 types of sensors with 2 types of selfhealing mechanisms to counteract the most threatening and damaging reactions that occur in a typical lib on the anode a resistance sensor array will be printed onto its surface to sense the degree of electrode fracture in the siliconcarbon composite anode the anode will be embedded with a selfhealing polymer network which upon thermal activation helps rebind the silicon nanoparticles for the cathode an electrochemical sensor array is printed onto the separator to sense the dissolution of mn from the linimncoo2 nmc cathode to prevent mn ions from critically degrading the cell the cathode will be embedded with heatactivated scavenging species which remove these ions lastly an internal temperature sensor helps control the degree of thermal activation in each degradation scenario the sensors communicate with the battery management system bms which uses a physicsbased model to trigger controlled heating to activate selfhealing additionally a life cycle assessment will be conducted to validate the recyclability of the salamander battery and quantify how the environmental impact of manufacturing is offset by longerlasting batteries thus although the projects technology is anticipated to be disruptive at the cell and bms levels its design would remain compatible with existing manufacturing and recycling processes these outcomes thereby help meet the goal of battery 2030 for a competitive sustainable european battery value chain and a more circular economy
polyphonic singing and communities of music writing in medieval britain and ireland c 1150 to c 1350

brokensong examines polyphonic singing in medieval britain and ireland during a transformative period of western music history c 11501350 when written books devoted to polyphony begin to proliferate using methodologies from musicology music analysis medieval and manuscript studies practicebased research and digital humanities brokensong aims to answer the principal research question what does it mean for a culture to write its music down brokensong investigates what this act of writingdown meant to and for musical communities the insular sources extant from this periodjust over a hundred mostly fragmentary sourceshint at stories of music practice and creation different from those suggested by the highly curated continental anthologies of polyphony that survive from continental europe and around which the history of western music was constructed these are mostly broken books transmitting broken songs yet brokensong proposes that indepth study of them will provide a breakthrough on fundamental questions regarding processes of and contexts for artistic creation in the later middle ages tackling the issue of style headon brokensong uses it to address the problem of anonymity in medieval cultural products and develops an innovative methodology for understanding the relationships between cultural products that lack extramusical evidence for associating them to specific individuals communities or regions three intersecting work packages reconstruct the fragmentary material artifacts develop historical understandings of music and community and analyse communities of musical style through a combination of practicebased and computational approaches brokensong reveals the layered interactions between individual creativity communal ritual activities institutional agendas and the written medium of music notationwith its particular techniques limitations and possibilitiesand the realization of those artefacts into sound then and now
aidriven ip intelligence engine for drug discovery

today new drug development on average costs 26 billion and takes 1014 years but for example the global health emergencyover the spread of the deadly new coronavirus is proving to be a crucial reallife test case for industry to aim dramatically reduce thetime it takes to create new vaccines and drugs to combat emerging pandemics while ai technologies help to identify thousands ofnew molecules that could be turned into potential medicines its crucial to quickly establish the novelty of the most promisingcandidates therefore more than 135 million patents 70 million journal articles and 4 billion web pages are published creating a vastcorpus big data of information that potentially needs to be searched to establish for example the novelty of a product the state ofthe art in the field of interest or the variety of components within complex compositions besides 88 of the big data is unstructuredin form of texts and its volume increases by a staggering 62 annually according to idc it leads to the main challenge there issimply way too much data for any human to read analyze and understandsemantic intelligence develops an aidriven ip intelligence engine enabling users to search analyze and extract complex knowledgeon chemicalbiological interactions in patents our proprietary stateoftheart technology combines natural language processing machine learning full linguistic data analysis chemical structure processing and image recognition delivering novel ways byintegrating two languages chemical structure and words into a single semantic meaning the target audience for this solution issmall and mediumsized life science companies which currently have limitations in accessing expensive biochemistry databases weare aiming to disrupt the life science industry by delivering a lowcost solution to enable small medium market players to create value by protecting their ip