Dragon09/odtu_chatbot huggingface dataset:
structural variants impacting peripheral neurodegeneration

many mendelian diseases have benefited from nextgeneration sequencing ngs technologies for gene discovery and the establishment of molecular diagnosis however the technical limitations of ngs pose a challenge for identifying mutational mechanisms in genomic regions impenetrable by these technologies i hypothesize that complex genomic rearrangements called structural variants in these loci can explain a significant proportion of missing heritability in many monogenic diseases to this end i propose to investigate the involvement of structural variants in the pathogenesis of charcotmarietooth disease cmt the most common genetic affliction of the peripheral nervous system i will utilize longread nanopore sequencing in a unique patient cohort to look for potentially diseasecausing structural variants i will then adopt genetic and functional in vitro and in vivo approaches to characterize the identified genomic variants and ascertain the associated functional genes that most likely underlie molecular pathology the findings of my pioneering study will highlight the contribution of structural variants in peripheral neurodegeneration discover nonconventional mutational mechanisms long overlooked by stateoftheart technologies and deliver in vivo models that might provide clues for therapeutic approaches for peripheral nerve disorders with common etiology
unraveling parkinsons disease diagnostic

parkinsons disease pd is a progressive chronic and debilitating neurodegenerative disease for which there is no cure and no diagnostic test available about 10 million people live with pd worldwide 12 million in europe and this number is expected to double by 2030 due to the aging population pd has a high social and economic burden and there is the need to improve pd timely detection and diagnosis especially in young peopleunmask aims to validate the technological and business feasibility of the olfactioninspired technology developed in the erc starting grant scent by establishing the proofofconcept for the noninvasive and fast pd diagnostics to accomplish this we will approach the project from both technical and business perspectives with a perfect synergy between the research and business teams and a close contact with clinical collaborators and stakeholders
interfacesensitive spectroscopy of atomicallydefined solidliquid interfaces under operating conditions

chargetransfer reactions are key not only to the way that nature fuels life in photosynthesis but also in synthesizing sustainable fuels like hydrogen charge transfer occurs at interfaces with an applied potential yet almost all our understanding of electrocatalytic activity trends comes from the bulk material properties in the asprepared state we still lack interfacesensitive spectroscopy tools that can probe the composition and electronic structure under reaction conditions only with such interfacesensitive operando information can we fully understand the underlying reaction mechanisms and devise strategies for efficient energy conversion and storagein interfaces at work i will overcome these limitations by developing novel interfacesensitive operando xray spectroscopies combined with model electrochemical surfaces with atomiclayer compositional control merging the fields of surface science and liquid electrochemistry my aim is to fully visualize the physicochemical properties of the solidliquid interface under operating conditions specifically i will develop a new laboratorybased multicolour operando meniscus xps xray photoelectron spectroscopy and transform the recently invented membrane xps by making it accessible to the relevant electrochemical materials using these materials themselves as new membranes i will apply these novel techniques to electrocatalyst and pseudocapacitor model systems based on epitaxial oxide thin films and 2d carbidesultimately the proposed approach will allow me to track the surface and subsurface properties under applied potential to shed light on the electrochemical mechanisms the operando insights will result in design rules for efficient energy conversion and storage on the chemical and electronic properties of a true electrochemically active surface under operating conditions rather than the asprepared bulk this will help our transition towards sustainability
unlocking the complexities of wind farmatmosphere interaction a multiscale approach

turbulence drives transport processes in the atmosphere and determines earths weather and climate wind farm performance depends on atmospheric turbulence as it entrains energy into wind turbine arrays as wind turbines and farms expand in size they increasingly interact with an unexplored atmospheric region and largescale weather phenomena in ways that are not fully understood typical wind farm simulations assume idealized cases and do not capture the influence of i dynamic changes in atmospheric conditions ii the interaction between the atmosphere and ocean and iii the influence of clouds in reality these effects are dynamic and influence atmospheric turbulent flow across a wind farm understanding these interactions is crucial to optimize wind farm design control and power production forecasts far beyond the local scale wind farm physics impact largescale atmospheric processes outstanding questions include how wind farms influence largescale weather phenomena atmospheric stability moisture dispersion and clouds the influence of wind farms on heat and momentum exchange between the atmosphere and ocean is also not fully understoodto bridge these knowledge gaps i envision using 3d simulations to locally model the wind farm flow physics microscale in a weather model mesoscale this is a conceptually different approach from typical weather models that use a limited refinement of microscale processes throughout the domain using highresolution simulations i will go beyond idealized cases and explore dynamic interaction between atmosphere ocean clouds and wind farms the goal is to study wind farm interaction with realistic weather conditions and provide more accurate wind production forecasts i will develop novel computational techniques to increase the domain size of highresolution simulations addressing these fundamental modeling challenges is crucial to unlock the complex interaction between wind farms and the atmosphere
fishers of corpses an anthropological archive of border communities and their responses to migrants death in the central mediterranean through art and ethnography

what is left of migrants death at sea and how do migrant corpses bodies and body remains enter the lives of those who encounter them are such remains lost forever or do they live through the narratives of the borderland communities who accidentally receive them as ethnography reveals most powerfully border deaths primarily affect the families of the dead andor missing at sea the aftermath of this violence is however manifold and its impact on the neighbouring communities remains an important yet neglected topic in both scholarship and practice fishers of corpses begins to fill this gap by addressing how the remains of the migrants who die in the central mediterranean routes to europe affect borderland communities leaving traces in their stories practices and memories by doing so the main objective of the project is to reframe border deaths from a local perspective focusing on its borderless reverberations and exploring it as a pervasive phenomenon that concerns not only the dead and their families but also the mediterranean societies at large this inclusive shift of attention from border death to its manifold effects requires an epistemic change in conventional perspectives and debate that incorporates the lived experiences of borderland inhabitants in this tragically normalised dimension to do so the project sensitively bridges a more traditional participant observation approach on board a fishing vessel ethnographic dimension with art methods artistic dimension to explore novel methodological and conceptual approaches to better comprehend and communicate the pervasive effects of border death and its aftermaths this methodological advance is a key element of the project as it will allow to produce an anthropological archive of border death in the mediterranean based on pictures videos oral histories and artwork produced during the research and digitally stored to be made available in open access archival dimension
global amyloid mapping solving amyloid nucleation by deep mutagenesis

amyloid fibrils form and precipitate in more than 50 incurable human diseases including alzheimers and parkinsons disease all proteins may be able to form amyloids at least under certain circumstances however aggregation is actually rare as the process of amyloid formation is controlled by a high kinetic barrier protein sequences have to cross a free energy barrier to nucleate transition states which then seed irreversible fibril formation shortlived transition states are extremely challenging to study using biophysical methods we have recently developed a massively parallel genomics approach to quantify the rate of aggregation of thousands of protein sequences we also have evidence that by quantifying the interactions between mutations we can capture the key interactions between residues in the transition state here we will unleash the potential of this approach by targeting the following aims1 map the impact on amyloid nucleation of all possible mutations in 60 human and functional amyloids generating reference atlases for clinical variant interpretation2 build an energetic and structural model of the transition state of diseaseassociated amyloids3 uncover sequences across the genome that nucleate amyloids in response to environmental stressthis project will uncover the rules required to understand predict and engineer amyloid formation by identifying the mutations that do and do not lead to amyloid formation we will reveal which variants accelerate aggregation and cause disease we will also address one of the most important questions in the field ie identifying the interactions established in the transition states of amyloid nucleation guiding the development of therapeutic approaches in amyloid diseases including the worst kinds of dementia finally our results will feed a new generation of models and predictors of protein aggregation to employ for disease variant interpretation and the synthetic design of novel proteins
european viral outbreak response alliance

covid19 has highlighted the need for eu preparedness towards the growing number of virus outbreaks research infrastructures are strategic tools for providing resources and access to technologies for research promoting innovation and supporting public health actions but their impact is limited when they operate individually the european viral outbreak research alliance evora project brings together three ris eva erinhaesfri and elixiresfri with unique and complementary expertise in biobanking high containment facilities and data management solutions respectively under a single concerted interoperable framework with a common and longterm perspective evora aims to strengthen eu capacity for concerted preparedness and response to viral diseases unify ri operations to achieve optimal ri responsiveness sustainability and worldwide competitiveness and address specific regulatory ethical and security challenges related to emerging pathogens evora will create synergies between the ris through common governance and concerted decisionmaking mechanisms the interoperability of evora services will be integrated through unified operational procedures and quality standards in order to support user needs and eu healthtech in either intercrisis or viral emergence response conditions finally the project will address the complex regulatory aspects of preclinical research involving highrisk pathogens to ensure the operability of the structure by paving the way for a sustainable alliance of stateoftheart ris for preparedness and response to viral emergence evora will strengthen the cohesiveness of the ri landscape in the field contribute to the competitiveness of the european research area era and ultimately improve the eus resilience to emerging communicable diseases
wildfires and climate change physicsbased modelling of fire spread in a changing world

fire has long been a ubiquitous and essential part of the global environment as many ecosystems and societal life fundamentally depend on fire despite this we still lack a fundamental theory of fire spread which becomes crucial in a changing world if we want to understand and predict the occurrence of uncontrolled fires uncontrolled fires are a global phenomena that are becoming commonplace as changes in moisture and local temperature driven by climate change affect local fuel properties and ecosystems as we construct more housing and industry in areas that were previously wildlands the wildlandurban interface becomes more critical as wildfires now affect infrastructure and urban systemsthe societal scientific and engineering problem of uncontrolled fires is a complex one it requires the harmonisation of both engineering and environmental science methods including combustion engineering real time modelling data assimilation and management and the development of techniques that can adequately support the needs of fire management the aim of this proposal is ambitious but essential to understand and predict the occurrence of uncontrolled fires we need a fundamental physical model to understand the process of fire spread it needs to be validated and it needs to work for all conditions and fuel types we will develop this physical model focusing on three different methods in paralleli study fire across temporal and spatial scales to understand changing fire regimes including vegetation dynamics ii understanding of fire on multiple scales will help with scaling up from smallscale fine mesh models to much larger grid sizes iii integrate the effect of smouldering combustion into modelling of fire spread the scientific outcomes of our work will ensure that there is a fundamental stepchange in the approach of modelling wildfire ignition and spread with the proposed methodology and tools then widely available for scientists to adapt
acting out disease how patient organizations shaped modern medicine

this project will provide crucial insights into the development of modern medicine and the role of lay involvement in science through analysis of so far largely neglected but central actors in 20th century medical history patient organizations these groups first emerged in the late 19th century and worked towards increased attention to particular illnesses shared information on disease management promoted treatments and developed healthcare resources this project is the first historical analysis of these early patient organizations role in shaping ideas about illness and medical practices and the first systematic account of how disease became an object of civic organization it will argue that modern medicine was to a significant degree shaped by organized patients who helped establish disease concepts and associated practices and that this deep involvement of patients in medicine facilitated an extended reach of medical power which resonates in contemporary society it will also investigate how patients in acting out medical knowledge assumed notions of selfhood that overlapped and interacted with those of medical scientistsi will lead a team of researchers to analyse the publications and archives of patient organizations from four european nations sweden germany united kingdom and france a vast source material previously not considered by historians studying these rich sources will answer some of the core questions related to medicine in the 20th century and in particular the role of patients how was the idea of diseases as distinct entities established how has it changed the medical landscape and the way we regard ourselves in relation to health and illness what was the role of patients themselves in this transformative process how has their involvement in knowledge generation and decisionmaking developed over the past century and to what extent has it lived up to the hopes of being a democratizing force in medicine
the chemical exposome of pregnant women with gestational diabetes mellitus

there is a lack of knowledge on the multitude of chemicals that we are exposed to and even less is known about the exposure during pregnancy the most critical window for adverse health effects on both mother and offspring in turn the prevalence of gestational diabetes mellitus gdm has incredibly increased during the last decades and it is now diagnosed in up to 18 of the pregnancies in this context i propose the project the chemical exposome of pregnant women with gestational diabetes mellitus mango to be cosupervised by dr navasacien and prof gary miller at columbia mailman school of public health usa third country for the outgoing phase and by prof domingo at universitat rovira i virgili urv spain beneficiary institution and host for the incoming phase the main scientific goals of mango are 1 to determine the occurrence of nontarget chemicals in biological samples of 400 pregnant women 2 to evaluate the association between the exposure to chemicals and clinical data exploring the effect modification by sociodemographic dietary and lifestyle factors 3 to implement a pilot prevention programme to minimize the exposure to hazardous chemicals during pregnancy these objectives will be tackled by integrating last advances in highresolution mass spectrometry wp1 mathematical models wp2 and risk assessment and prevention strategies wp3 mango will leverage biological samples of diabetes and pregnancy cohort from institut dinvestigaci sanitria pere virgilihospital universitari joan xxiii iispvhjxxiii associated partner and will return the knowledge to europe by implementing the first pilot programme to increase the awareness of the exposure to hazardous chemicals through this mscapfgf my training in environmental epidemiology in usa would capitalize upon my skills on nontarget chemical analysis msca cofund in insulin tecniospring facilitating the start of a new research line and a tracktenure at urv
addressing unknowns and unmet needs of vexas syndrome by multiomics clonal tracking and targeted gene editing

hematopoietic stem cells hscs accumulate somatic mutations during aging which may drive clonal expansion of their progeny this clonal imbalance promotes cancer and often establish systemic inflammation contributing to frequent diseases of aging disentangling and tackling clonal imbalance of hematopoiesis is thus an urgent challenge with substantial medical implications for a progressively aging population vexas syndrome is a novel adultonset devastating disease with growing number of patients it is caused by the expansion of proinflammatory hematopoietic clones acquiring somatic mutations of the uba1 gene its pathophysiology is elusive and treatments are unsatisfactory leading to dismal prognosis in this project i will address knowledge gaps and unmet medical needs of vexas syndrome here proposed as paradigmatic example of a hematologic disease of aging caused by clonal expansion to unveil the uncharted pathogenesis underlying vexas clonal expansion and inflammation i will develop and apply to patients samples innovative multiomics technologies simultaneously informing on phenotype and genetic mutations of clones while reconstructing hierarchical relationships and retrospectively tracing expansion dynamics to validate these findings in stringent settings i will leverage cuttingedge gene editing systems for the generation of vexas models by installing in human wildtype hscs the pathogenic mutations found in patients and study differentiation clonal expansion and inflammatory properties of their outgrowth in transplanted immunodeficient mice finally i will investigate an autologous hsc gene editing approach in vexas models based on the hypothesis that targeted disruption or correction of mutant uba1 alleles can erase fitness advantage of pathogenic clones this project will transform current understanding and management of clonal imbalance of hematopoiesis by developing new models and technologies and proposing ambitious strategies to tackle it
dementia in ankara and the nature of surroundings the effects of everyday home and family environments on the health wellbeing and identity of aging women

the covid19 pandemic continues to have a globally disproportionate impact on the wellbeing of people living with dementia particularly those who are communitydwelling who have seen reduced access to healthcare and increased risk of loneliness isolation and depression consequently the home has become a vital space of care that remains lesserresearched in dementia studies this can be richly explored in the country of trkiye which borders the west east and global south and has a distinctly blended modern and collectivistic outlook regarding familial ties and gender roles focusing on trkiyes capital city ankara this project will explore the physical natural built material biophilic and social spousal familial communal features of home environments examining the relations between dementia placebased experiences daily living and wellbeing inspired by integrated theories on relational and inthemoment wellbeing this project adopts a mixed methods case study design and asks the overarching research question how do everyday interactions with both physical and social features of home environments promote or hinder the health wellbeing and identity of older women living with dementia this timely holistic project seeks to develop new scientific knowledge about the complex relations between and intersectionality of dementia gender landscapes socioeconomic status familial dynamics and daily living in the context of trkiye the research has strong interdisciplinary links across architecture human geography anthropology and gerontology with exchange of knowledge between the candidate and host bilkent universitys interior architecture and environmental design department the findings coincide with un and eu research plans will fulfil an existing knowledge gap on people living with dementia in turkish urban landscapes and will lead to outputs on future dementiafriendly designs of urbanbased apartments and housing