Dragon09/odtu_chatbot huggingface dataset:
glycans as master switches of b cell activity in autoimmunity

autoimmune diseases including rheumatoid arthritis ra are often lifethreatening disorders with increasing disability having a negative impact on patients quality of life mechanisms leading to the breach of tolerance in development of autoimmunity are still largely unknown protein glycosylation is an essential regulatory mechanism in the immune system we recently demonstrated that nglycosylation of the variable region fab of autoantibodies is a hallmark of ra development and progression we also demonstrated that autoantibodies acquire these fab glycosylation signatures already many years before disease onset we herein hypothesize that fab glycosylation at the level of the b cell receptor is a key molecular switch promoting the selection activation and proliferation of autoreactive b cells leading to the concomitant breach of immunotolerance within glycanswitch we will map the fab glycome of various types of ra autoantibodies and autoreactive b cells we will study the factors and underlying cellular mechanisms that regulate fab glycosylation of b cell receptors and autoantibodies we will investigate the immunological effects of fab glycosylation and the impact in b cells signalling and activation in the context of molecular and cellular interacting partners in the immune microenvironment finally we will test in relevant mouse models how fab glycosylation of autoantibodies and autoreactive b cells contributes to the breach of tolerance we expect that the obtained insights into the role of glycans as key checkpoint for the selection of autoreactive b cells and the rise of autoimmunity will provide leads for targeted therapeutic interventions as well as rationales for the early detection of ra and autoimmune diseases in general we foresee that the knowledge generated will allow us to embark on a targeted prevention clinical study in patients at risk for ra to turn off the glycanswitch leading to chronic ra
enhancing palliative care in icu

about 10 of all decedents in the population die after admission to an intensive care unit icu these patients often have distressing symptoms and may receive more intense lifeprolonging treatment than they would have chosen their family members often experience lasting distress from the experience and many icu physicians and nurses are burdened by their perception of potentially nonbeneficial carethe epic project aims to sustainably improve palliative care for critically ill patients and their families in the icu an interdisciplinary consortium collaborates to provide a novel harmonized palliative care practice model using telemedicine the project is the first european interventional study on palliative care in the icu using a systemsbased approach with proactive patient identification checklist and blended learning targeted to specific requirements of icu clinicians effectiveness of the new model is assessed through a stepped wedge randomized trial with 7 clinical centers from 5 european countries 23 multidisciplinary icus and enrolment of 2001 patients primary outcome is a reduction in icu stay to relieve suffering cost implications and cost effectiveness will be assessed from different perspectives an evidencebased patient decision aid for critically ill patients is developed additional outcomes serve deepen our understanding of barriers and facilitators and provide ethical recommendations for the use of telepalliative care in civic society the vision of epic is to contribute to a mind shift from a narrow focus on prolonging life towards more holistic care a european patient and family advisory group is implemented to engage patients and family members from the start and cocreate openaccess information to increase acceptance of palliative care telemedicine offers a lowcost solution to spread the model to all regions in europe and open new avenues for patientcentered care
advanced battery system and integration for generation4 solid state cells

the global ev market is largely reliant on battery electric vehicles bevs that employ lithiumion liion batteries mostly based on liquid electrolytes due to extensive research and development of liion we are gradually reaching the maximum chemical potential of todays electrode materials regarding nickelrich cathodes yet liion based battery systems based on liquid electrolytes still face significant limitations due to their chemistries such as high flammability potential safety risks burning and explosions electrochemical instabilities and low ion selectivity in this regard promising solutions are emerging in the form of solidstate battery ev ssbev technology however the inherent differences between ssbs and traditional liion batteries such as fundamentally distinct operating temperatures charging rates form factor and cell safety characteristics introduce complexities in integrating them into existing bev systems necessitating a redesign of the several systems to meet this need arise will develop an advanced solidstate fourth generation gen4 liion battery system that offers advanced highperformance features based on a celltochassis concept with expandable modules that is applicable to any next generation s sbev arise will cover 3 different development paths 1 a new city car chassis design utilizing ssbs that is expandable when needed 2 a novel battery and pack level thermal management system compatible with ssbs 3 smart battery management system that controls battery expansion fast charging and safety
quantum estimation and control for advanced noisy metrology

in recent years the idea of building quantum technologies has quickly moved from being an intellectual curiosity to a practical reality and quantum metrology and quantum sensors are prominent ones already in use in scientific and commercial applications the underlying idea is to exploit genuinely quantum effects to perform extremely accurate measurements with a precision not achievable by classical meanswhile many important theoretical and experimental milestones have already been reached there are still many open theoretical questions left on the path to understanding the ultimate capabilities of quantum metrology especially in realistic operating conditionswe have identified three main pillars that are currently subject to very active research i understanding the ultimate limits of the quantum estimation of multiple parameters simultaneously either because all of them are of practical interest or because a full prior characterization of additional systems parameters is not possible ii assessing the impact of environmental noise on the quantum probe in particular beyond the standard assumption of uncorrelated noise iii understanding the limits of metrological schemes based on timecontinuous measurements nowadays feasible in many physical systems eg superconducting qubits optomechanics which open the possibility to perform measurementbased feedback control on the systemthe overarching goal of this action is to advance the state of the art in these three areas and to connect these three pillars by devising new theoretical tools to assess the ultimate precision limits in novel and physically relevant scenarios these tools will be rooted in quantum estimation theory and quantum control theory and they will provide fundamental benchmarks for the next generation of quantum sensors
descending control of pain

pain is a large societal and health problem although often thought of as an invariant representation of active nociceptors pain varies a lot under the influence of different affective states sometimes with near complete analgesia such modulation of pain is thought to occur through a descending pathway originating in the brain and to be executed by rostral ventromedial medulla rvm neurons that project to the spinal cord deciphering the complexity of the cell types involved and how they contribute to the descending control of pain has been challenging but recent advances in singlecell omics computational biology and advanced genetic technologies now open for unbiased systemwide insightsdescendpain will uncover the power of the brain to control pain we will classify rvm neuron types by singlecell rnasequencing and use scrnaseqbased stimulustocelltype mapping to identify neuronal ensembles conferring analgesia and hyperalgesia during morphine naloxone stress sleepdeprivation and exercise using activitybased mouse genetics we will reveal the full complexity of the combinations of neurons engaged and unravel their role in pain modulation thus identifying for the first time the cellular basis for how affective states modulate pain we will also use novel intersectional strategies for dual capturing of active neurons to determine how the descending rvm controls the transmission of pain in the ascending pathway of the spinal cord finally we will identify the memory substrate underlying chronic pain providing evidence for the existence of rvm neuron ensembles of chronic pain and revealing underlying cellular and molecular mechanisms this project takes a new systemwide strategy in the pain field that should fundamentally change the view of pain by providing a cellular basis for how it is continuously scaled by mental states and uncovering mechanisms of chronic pain which may provide strategies for designing effective pain therapies
drugloaded nanobots for transmucosal delivery to mucinous tumours

mucus is a defensive barrier that protects the underlying cells from pathogens and toxic compounds although it also hinders the delivery of drugs whenever they are administered locally there are different types of mucussecreting tumours such as pseudomyxoma peritonei pmp that could benefit from more efficient transmucosal delivery of anticancer drugs pmp is a rare disease and the most mucinous tumour type thus it will be used as a proof of concept for this project in fact it is characterised by the production of abundant mucus in the peritoneal cavity and is treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy usually mitomycin c this approach has extended patient survival but there is a significant proportion of recurrence most probably due to the shielding effect of mucus therefore there is an urgent need to offer new therapeutic strategies to pmp patients recently dr palmers lab has established a collection of pmp patientderived organoids and xenografts and has shown that some pmp patients present oncogenic brafv600e mutations introducing a new druggable targeted mutation in this proposal dr snchezs lab ibec in collaboration with dr palmers research group vhio aims to use nanobots able to overcome the mucus barrier that will be loaded with mitomycin c or encorafenib braf inhibitor to treat pmp a comparative study will be performed to assess the treatments efficacy compared to the standard of care and medical advice will be received from dr lez vhuh to ensure the translation of the results to the clinic we believe that using this allinone system will certainly enhance the delivery and efficacy of the active therapeutic compound thus potentially improving current treatments
the development of a predictive biomarker for immunotherapy outcome based on flow cytometry test

immunotherapy has revolutionised clinical oncology with the use of immune checkpoint inhibitors icis these agents are in clinical use for almost a decade treating over 20 types of cancers they have shown a remarkable therapeutic benefit even in patients with advanced disease yet only a small proportion of patients benefit from this therapy leaving the rest resistant for reasons that are still not clear while there are certain clinical biomarkers to predict ici therapy outcome their prevalence and prediction power is rather limited therefore there is a clinical unmet need to develop more powerful biomarkers to predict response to immunotherapy in our ongoing erc consolidator grant we discovered a unique subpopulation of neutrophils present in peripheral blood that predicts response to immunotherapy in a very high probability we designated these cells as immunotherapyresponsiveness cells ircs using various mouse models we demonstrate that the levels of circulating ircs measured at baseline are significantly higher in responding tumours to ici therapy these results were confirmed in a limited number of nonsmall cell lung cancer nsclc and melanoma patients hence our aim is to further test irc levels in clinical samples to evaluate their predictive power for ici therapy and to develop a clinical liquid biopsybased predictive biomarker using flow cytometry test the development of clinical irc detection based on flow cytometry bioflow can serve two markets 1 clinicians enabling oncologists to easily predict response to ici therapy thus improving personalised immunotherapy treatment and 2 pharmaceutical companies developing immunotherapies that can use irc detection in development stages and through clinical studies enabling tight regulative assessment of rd success rates the bioflow goal is to technically validate and develop a predictive biomarker platform for both markets that will lead to its commercialisation
realtime monitoring of earthquake nucleation for faults near urban areas

a longstanding lingering question in geoscience is whether earthquakes show a precursory nucleation process precursory signals from wellrecorded large earthquakes displayed widely different amplitude or duration and some large earthquakes displayed no detectable precursors the main objectives of quakehunter are 1 to determine the most effective approaches to detect faultrelated transients preceding moderate to large earthquakes and 2 to monitor seismic and aseismic processes and infer from them the fault conditions under which earthquake nucleation processes emerge and the optimal instrumentation required to capture them to achieve these we will develop different methodologies based on a combination of supervised and unsupervised artificial intelligence to identify retrospectively earthquake nucleation processes for active faults near earthquakethreatened urban areas the ultimate goal will be to test the performance of this novel earthquake forecasting methodology in nearreal time we will analyze data from northwestern turkey where the north anatolian fault is overdue for a magnitude m7 earthquake directly adjacent to the istanbul megalopolis with its 15m inhabitants the groundbreaking part of quakehunter is that if earthquake nucleation processes could be discerned prior to large earthquakes in the marmara region then automated nearrealtime detection could provide extended warning and preparation time if successful this could become in the future an essential ingredient for activating civil protection protocols to mitigate seismic risk quakehunter aims at having a strong scientific impact on earthquake physics we will be able to refine our knowledge on the physics of earthquakes shortly before their start as well as the fault conditions favoring the identification of earthquake precursors the firsttime testing of such methodology in realtime will have a strong societal impact potentially advancing earthquakes forecasting
new endtoend digital framework for optimized manufacturing and maintenance of next generation aircraft composite structures

genex project aims at developing a novel endtoend digital twindriven framework based on enhanced computational models which embed the interdisciplinary knowledge of the aircraft components and the manufacturingrepairing processes to support the optimized manufacturing of composites parts enable the continuous operation of aircrafts and improve the composites repairing processes for ensuring aircrafts safety and airworthiness first automated atl process coupled with thzbased inprocess monitoring together with hybridtwin simulation methods will be developed for ecoefficient and advance manufacturing of innovative reprocessablerepairablerecyclable 3rresinand stateoftheart thermoplastic composites second innovative data and physicsbased machine learning algorithms for damage detection and location combined with advanced highperformance computing hpcbased multiphysics and artificial intelligentpowered digital twin tools for fatigue life prediction will be implemented to transform information from optimized onboard piezoresistive sensors data networks interfaced with lowpower wireless communication platform to health and usage assessment and prognosis third augmented reality tools together with novel laserassisted methods for surface cleaning and monitoring smart monitoring and insitu tailored heating of composite repair blankets will be further developed to provide additional assistance in manual scarf repair operations increasing reliability of repair process while supporting the modification and virtual certification of mro practices thus a novel digital twindriven framework will be implemented into a common iiot platform to integrate the developed models and data acquired providing bidirectional dataflow and enabling the implementation of a holistic and comprehensive data management methodology ensuring to adequately create capture share and reuse knowledge along the entire aircraft lifecycle
recycled metals for aboveground hydrogen storage

the main objective of remedhys is to advance the maturity of aboveground solidstate hydrogen storage solutions based on metal hydrides with hydrogen chemically bounded to the metals and operation at ambient conditions this is a compact and safe hydrogen storage method and with significant advantages compared to both compressed and liquid hydrogen storage solutions the hydrogen storage system in remedys with capacity of 100 kg h2 will operate at a pressure below 50 bar the metal hydrides will be produced from lowcost recycles metals sourced in europe and then minimizing the needs to import critical raw materials to europe the modular hydrogen storage system will be validated in an enduser scenario with a 2 mw pem electrolyzer and supplies of hydrogen to a hydrogenpowered offshore service supply vessel remedhys will contribute to implementation of regulations codes and standards for largescale aboveground storage systems for solidstate hydrogen storage systems the project will also address sustainability and circularity aspects by employing a life cycle assessment and make recycling of critical raw materials as an integrated part of the materials development the remedhys consortium consists of the leading research institutions in europe on solidstate hydrogen carriers four research centers and two universities and four partners from the industry remedhys will build on the experiences from the eu funded project hycare 20192023 which had six of the remedhys partners
realizing healthcare 40 exploiting the 6g network evolution

elixirion will create the first fullyintegrated inter and multidisciplinary highlyinnovative training and research network that will set the foundations of the emerging healthcare 40 paradigm by leveraging 6g technologies targeting to i provide all citizenspatients with a wide range of services of different requirements such as ultralow latency for latencycritical applications high speed for data hungry services and ubiquitous secure access to healthcare resources anytime anywhere respecting all privacy aspects and ii ensure a secure efficient and profitable healthcare ecosystem to all involved stakeholders while creating a sustainable open market easing access to new players to achieve the aforementioned objective elixirion will 1 leverage a gamut of 6g technologies towards a powerful interconnected network for ultrahigh performance access to the healthcare ecosystem targeting up to 9999999 reliability 100 coverage down to subms e2e latency up to 1 tbps capacity high energy and costefficiency while supporting a massive number of connections 2 design edgeaware algorithms leveraging diverse computing capabilities offering ultrafast task execution through parallelization serverless and distributed computing by intra and inter edge node orchestration techniques for realtime mission critical healthcare applications 3 provide an e2e slicing and zerotouch orchestration framework for optimized 6g network performance across the healthcare ecosystem targeting at full network automation and secure information handling especially when a massive number of medical devices is considered by leveraging aiml while considering all different network parts and data analytics to derive useful information helping in the decisionmaking process and 4 create a sustainable healthcare ecosystem and new business models leveraging blockchainbased incentive engineering for secure incentivized collaboration among the involved stakeholders
flux race investigation for dissection of metabolicbottlenecks leveraging the tremendous potential of algal metabolic diversity

a 70 increase in food production is required to feed the world population by 2050 putting increased productivity on a collision course with environmental and sustainability goals aiming to meet this growing demand photosynthesisrelated pathways are regarded as a promising target for crop improvement to increase agricultural yield however they remain mostly unexploited furthermore while empirical studies have shown that photosynthetic efficiency is higher in microalgae than in both c3 or c4 crops the underlying reasons remain unclear identifying metabolic bottlenecks in photosynthetic cells remains a holy grail of plant research however with recent progress made in crosskingdom plant flux analyses the time is ripe to tackle photosynthetic metabolism with stateoftheart experimental and computational approaches as a target for plant yield improvement in this project i propose to address the following key questions 1 what role is played by photosynthetic metabolism in setting the upper limits for growth of photosynthetic cells and in this respect 2 what makes some photosynthetic cells grow faster than others we will combine cuttingedge tools for comparative flux analyses with genetic approaches applied on algae and higherplants to identify and validate metabolic bottlenecks for plant growth as targets for crop yield improvement these research aims fall well within my unique set of expertise ive characterized the metabolism of the fastest growing photosynthetic cells and mapped the metabolic networks of algae compared with c3 and c4 plant models using a novel microfluidics setup which i developed facilitating nonstationary stable isotope analysis at steady state conditions in liquid algal cultures successful outcome of this project will shed light on the magnitude of photosynthetic metabolism effects on plant growth and help reshape the field of targeting photosyntheticrelated pathways for cropplant yield improvements