Dragon09/odtu_chatbot huggingface dataset:
cd22cd19 dual redirection dual targeting of cd22 and cd19 with bitesecreting and carexpressing bispecific tcells for adoptive cellular immunotherapy in advanced bcell acute lymphoblastic leukemia

anticd19 immunotherapies based on bispecific tcell engagers bite or chimeric antigen receptor carexpressing tcells have revolutionized the treatment of refractoryrelapse rr bcell acute lymphoblastic leukemia ball however despite initial impressive complete response cr rates many patients relapse few months after anticd19 immunotherapy in many cases with cd19 antigen loss such relapses are devastating and patients are left with virtually no further treatment options dual targeting of the panb antigens cd19 and cd22 has been proposed as a therapeutic strategy to distribute the antigenic pressure over two molecules and to reduce immune escape by covering practically all ball blast subclones cd19cd22directed dual cars have in fact been proposed to overcome ball immunoediting during car tcell therapy but unfortunately cd19cd22 dual cartreated rr ball patients showed cr rates not sustained over time and relapse with limited car tcell expansion in contrast to car tcells bitessecreting tcells represent a unique strategy capable of redirecting bystander tcells to tumor cells because tcellproduced bites will be continuously secreted and will decorate through the cd3scfv the cell surface of practically all circulating and ex vivo manufactured bystander tcells our overarching goal is to provide a novel and innovative tcell redirecting immunotherapy for the treatment of rr ball by dual targeting both cd22 and cd19 with tcells modified to simultaneously secrete cd22xcd3 bites and express cd19 car referred to bitecar this strategy harnesses the biological advantages of both cars and bites while minimizing their limitations and will circumvent the potential low transduction efficiencies of the bitecar construct because the cd22bite secreted by transduced tcells will decorate the bystander untransduced tcells boosting the durability and strength of tcell responses
the mystery of differentiation exploring the link between enhancer priming and cell cycle in ventral foregut stem cells

pluripotent stem cell differentiation to disease targeted cell types has historically produced poor or inconsistent outcomes the brickman lab recently suggested that pausing differentiation allowing cells to grow and catch up at the level of the enhancer network leads to improved differentiation in particular the brickman lab has demonstrated that expansion of endoderm at the ventral foregut stage vfg increases the efficiency and efficacy of pancreatic endocrine differentiation the mechanism by which this occurs is unknown but it involves the reequilibration of enhancer networks and rearrangements in the cell cycle i hypothesise that these two processes are tightly connected and to address cause and effects and understand the nature of this link i will focus on how foxa1 a factor required for expansionspecific pancreatic enhancer reorganization acts to couple growth to genome rearrangement how it interacts with the restcorestkbtbd4 complex to facilitate enhancer commissioningdecommissioning and finally whether proliferationinduced alterations to specific cell cycles phases drive this enhancer reconfiguration the results of this project will significantly impact on regenerative medicine research as they will help formulating a differentiation protocol that produces in a more efficient way pancreatic endoderm and pancreatic endocrine cells although this fellowship exploits pancreatic differentiation as a model its implications are broad as a role of proliferation in preparing appropriate transcriptional responses for differentiating cells would represent a new paradigm for the link between growth and lineage specification
which building blocks for coordinating resource distribution are so basic that they manifest even in infancy

coordinate will do political psychology with infants to reveal meaningful mechanisms for coordinating resource distribution so basic that they manifest even in the preverbal mind the distribution of resources help territory and priority decision rights are central dilemmas for groupliving species and the core of politics navigating these dilemmas young children must discover the structure of their social world who is friend or foe superior or subordinate and what does this mean for how people interact to solve this learnability problem i argue that early and reliablydeveloping core representations and motives have evolved for navigating basic kinds of social relationships with critical adaptive value consistent with this theoretical proposal i discovered that preverbal human infants mentally represent social dominance and like other animals use relative size to predict the outcome of zerosum conflict spawning a new field of research thomsen et al 2011 science however human society is also defined by reciprocity and by distributing resources according to need effort and prior possession yet it remains unknown if these coordination mechanism are inscribed already in the preverbal mind here we test the highrisk proposals that 1 preverbal infants expect direct reciprocity to govern resource donations 2 infants and preschoolers use gratitude to predict the future reciprocal altruism of others 3 infants also use asymmetries of prior possession hunger need and relative effort to predict who will prevail in resource conflict 4 that beyond the dyadic and triadic relationships typically studied in the field preschoolers and preverbal infants use the abstract structural forms of pyramidal hierarchy clique and lines to represent the group relationships of social hierarchy communality and equality respectively these mechanisms likely operate intuitively across life and so we will test if they undergird political ideology and psychology
europe covid politics and the unexpected surge of nationalistic narratives

in the face of the outbreak of the novel coronavirus the unity of the european union at least at the beginning of the crisis started to crumble by closing their borders and introducing a travel ban for the schengen area european countries have retreated into national fortresses these initial policies and the recent vaccinerelated management of the pandemic shows the role nationalism plays in the context of public health responses to emergencies including evacuations and quarantines travel and sociocultural constraints while many scholars have started to document the impact of these measures on citizens human rights migrants and so on almost no attention has been paid 1 to examine and to compare configurations of different european national identities that were generated in the course of the management of the pandemic and 2 to a sociohistorical perspective to investigate the possible links between those nationalistic and warrelated discourse and the exclusionary and inefficient policies and practices that surge in europe and beyond eurosick will innovatively conjoin the sociology of migration and nationalism with research on historical disasters to fill this gap it will do so benefitting from my expertise in the analysis of discoursepractice nexus and through an examination of media coverage of the covid19 pandemic and the related policy documents in three european countries belgium italy and switzerland and in three points in time before the outbreak in europe at the time of the outbreak and at the beginning of 2021 following the implementation of the covid19 vaccination programmes the analysis will be carried out using critical discourse analysis an interdisciplinary approach used to study oral and textual discourses which views language as a social practice these learned lessons will impact the capacity of europe to tackle the future crises in a more collective and efficient way
counteracting the pandemic potential of flaviviruses addressing virushost interactions and defense strategies to design new therapeutics against wnv and denv

to strengthen eus ability to fight denv and wnv epidemic and pandemic threats and elaborate effective emergency plans the project is based on three pillars 1 clinical investigation of host factors related to severe disease 2 therapeutic development ie hostviral protein binding inhibitors and 3 onehealthbased surveillance of the infections open science practices will guarantee quality efficiency of the research and maximise the impact of the project the declaration of interest in the inflame project of a company world leader in the field supports the thrustable of the network and the impact of the projects expected outcomes the projects tasks will proactively be addressed in 7 sounding work packages and will go beyond the stateoftheart the partners have outstanding experience in all the aspects of the project collaborated previously and working together on emerging flaviviral infections the team includes fondazione irccs policlinico san matteo as coordinator it fausto baldanti the national institute of molecular genetics it renata grifantini antonio lanzavecchia and raffaele de francesco pasteur institute fr jouvenet nolween cic biogune institute es jesus jimenosbarberez and nicola abrescia university of florence it cristina nativi centro nazionale per le ricerche it giovanni maga and paolo mazzetti istituto zooprofilattico sperimentale della lombardia e dellemilia romagna it ana maria moreno martin imagine institute fr jean laurent casanova and shenying zhang university of vienna at judith aberle and karin stiasny and university of masaryk daniel ruzek this truly complementary and collaborating network has a robust knowhow in diagnosis of flaviviruses in humans and animals on hostpathogen interaction and drug discovery
unobtrusive technologies for secure and seamless border crossing for travel facilitation

the world economic forum suggests that transnational travel will increase by 50 over the next ten years bringing the number of arrivals to 18bn by 2030 before the covid19 pandemic given the everincreasing travel both on land and sea delays and queues are often observed at cases where people are crossing border these delays create huge frustration for the citizens and at the same time put extra burden to the border authorities staff in europe airports have managed to improve to a certain extend the border crossing through the facial recognition booths for european citizens that own an rfid enabled passport however there are still huge queues observed for noneuropean citizens the situation is even worse the border control for land and sea are placing all the effort to the border authorities staff requiring from them to check the passports of the travellers as well as to control the luggage and baggage reasonably even without huge number of travellers large delays and queues are observedodysseus will enable citizens to seamlessly cross the border without stopping while reducing the workload and improving productivity for border guard authorities by providing highly detailed risk analysis odysseus will leverage the power of digital technology offering to citizens the appropriate tools to cross land and sea borders in a secure and seamless manner without stopping while equipping the border authorities with novel tools for secure identity verification and unobtrusive vehicleluggagecargo checks eliminating long delays at border areas the proposed technologies will allow citizens to cross borders without any intervention by just leveraging their smartphones combined with strong and continuous identity verification remote vehicleluggage scanning through xrays and uavs will allow authorities to remotely perform the appropriate controls
timevarying nanophotonics for new regimes of qed lightmatter interactions

controlling light and its interaction with matter at the nanoscale is one of the major aims of current science with applications ranging from energyefficient photonicbased communications quantum information processing or high precision sensors owing to the hybrid lightmatter modes supported by nanophotonic structures from thz and ir polaritons in 2d materials to optical plasmonic resonances nanophotonics offers an ideal platform for an exquisite control of lightmatter interactions even at room temperature light concentrated at the nanoscale is a natural playground for quantum electrodynamical qed processes whereby lightmatter interactions reveal their quantum nature however conventional approaches to nanophotonicsbased qed are limited by two fundamental principles energy conservation and reciprocity overcoming these limitations would enable nonphoton conserving devices and oneway channels opening the door to a compact route to quantum photonic circuits timelight proposes the use of timemodulated media whose optical parameters eg permittivity are dynamically modulated by an external actuation to realise fundamentally new nonhermitian and nonreciprocal qed effects this theoretical project roots in recent experimental advances that have shown unprecedentedly large and fast modulations of nanophotonic structures timelight will deliver advances in the following areas 1 tuning of spontaneous emission and collective interactions of quantum emitters 2 new forms of free electron radiation 3 novel mechanisms for enhancing spontaneous photon generation and 4 syntheticmotion based fluctuationinduced forces timelight will open the door to timevarying nanophotonics as a new paradigm to tailoring lightmatter interactions at room temperature with nonhermitian and nonreciprocal effects this will shed light in the understanding of fundamental qed processes and ultimately be of interest to quantum photonic technologies
chronic pain eradication by targeting schwann cells

about 25 of the adult population experiences chronic pain which disrupts daily activities and severely affects the patients quality of life in europe the socioeconomic burden of chronic pain runs into billions of euros annually and represents 310 of the gdp the current mainstays of pain treatment are nonsteroidal antiinflammatory drugs nsaids and opioids but their prolonged use is frequently associated with lifethreatening adverse events and physical dependence there is therefore an urgent need for new pharmacological strategies with superior efficacy and safety than those of nsaids and opioidspaincare proposes to address chronic pain signaling using inhibitors targeting the schwann cell proalgesic pathway previous research has shown the crucial role of schwann cells in sustaining chronic pain this project aims at developing schwann cell selective drugs for chronic pain treatment creating more clinically ready compounds based on bifunctional chimeric antagonists with an inhibitory activity 100 higher than that of the combination of the two individual antagonists in mouse chronic pain models the new schwann cell selective analgesic drugs scads will provide a dramatic change in the pain treatment paradigm reducing treatmentrelated side effects and improving persistenceduring this poc we aim to identify lead bifunctional chimeric molecules that preferentially antagonise two schwann cell proteins we will carry out tests in vitro and in vivo to demonstrate the novel compounds feasibility and superior inhibition efficiency when compared to the currently used compounds furthermore our aim is to translate the results to a precommercialisation phase through the definition of the innovation commercial feasibility and potential which will then be validated in discussions with relevant market players a strong ipr strategy will be designed to ensure an advantageous position in the value chain of analgesics for pain treatment
scalable systems modelling to simulate bodylevel interplays among noncommunicable diseases

noncommunicable diseases ncd that involve loadbearing organs emerge silently according to complex mechanisms that are likely to involve interdisease systemic communications clinical explorations cannot apprehend such intricate emergence but i postulate that multiscale in silico models can the digital twin for health has progressed a lot in the last decades but multidisease transversal modelling has not happened it requires unique developments to couple small to largescale model components with appropriate balance of phenomenological and mechanistic approaches to cope with overwhelming biological complexity preserve interpretability and incorporate realworld data this is the niche of ohealth that proposes a scalable ecosystem of multiscale ncd models interrelated through a systemic model of lowgrade inflammation the project tackles such vertical and transversal physiologybased computational modelling through four major ncd lung emphysema atherosclerosis intervertebral disc degeneration and knee osteoarthritis that affect loadbearing organs at different anatomical locations the cellular molecular scale components of each ncd model will vertically share predicted variables with an interface model of endothelial cell dysfunction that communicates with a transversal model of bodywide systemic communications the ohealth ecosystem will be modular and interoperable mechanistic modelling will be covered by finite element models at the organ tissue scales and by agentbased ab models at the cell molecular scales ab models will incorporate highlevel interaction graphs for interpretable phenomenological modelling where necessary graphs will merge knowledge projection and correlation models extracted from longitudinal population cohort data also used to evaluate ohealth interoperability will be ensured through standard languages such as field and systems biology markup languages enabling the scalability of the ohealth ecosystem
advanced characterisation methodologies to assess and predict the health and environmental risks of advanced materials

macrams central objective is todetect characterise and quantify advanced materials during their processing and productlifecycle incl recyclingendoflife to assess eg ecotoxtoxtest the resulting impact on human health and the environment ifwhen they pose intended or unintended exposures to humans andor the environment and to advance ie prepare for standardisation harmonisationregulatory validation the widespread applicability and application of the developed test and characterisation methods by demonstrating their effectiveness and efficiency in the context of existing marketrelevant industrial materials processes and productsin alignment with the eu strategies to secure the safety and sustainability of enabling and emerging technologies incl those based on chemicals and materials as addressed in the eus chemical strategy for sustainability 2020 and in the european green deal 2021 the macram project focusses on the development of methodologies that are applicable to advanced materials admas a categories that includes but surpasses that of nanomaterials eu definition of a nanomaterial and that is aligned with the futureoriented innovation safety and sustainability considerations at the oecd oecd 2020 the eu eu 2022 and several of its member states eg germany 2021 this will be achieved by focussing the development and demonstration of novel methods and methodologies as well as the advancement of their harmonisation and standardisation on planned inhalable carbonbased admas in a variety of morphologies and dimensions moving beyond spherical particles a graphenerelated material grm b carbon fibres cnts and c poly lacticcoglycolic acid plga the focus on carbonbased adma is due to unsolved detection and characterisation issues especially in complex media
unravelling the first babbles of the earth inner core history

the existence of earths inner core was a major discovery almost a century ago and since then the timing of its nucleation remains highly debated this major event in the earths history enhanced the energy necessary to maintain the magnetic field to the presentday making our planet habitable earth has thus escaped the fate of planets like mars that lost its protective shield while the community agreed to place the inner core formation at 600 million years ago in the ediacaran period new evidence of a change in the earths magnetic field regime during the midpaleozoic 416332 ma challenge this hypothesis can we better constrain the earth inner core history ubeich will tackle this issue with a new kind of experimental data describing the longterm evolution of the earths dynamo strength in paleomagnetism the conventional approaches fail to retrieve ancient magnetic signal from old rocks due to their weathering along their complex geological history to this end i will develop a promising but challenging multispecimensingle crystal paleointensity this pioneering approach can significantly increase the number of observations by extracting the magnetic signal from the protected nanometric magnetic inclusion in silicate crystals with the multispecimen technique developed for other purposes by providing challengingtoobtain but theoretically reliable data ubeich has the ambition to bring a new light on the deep earth history between 11 and 03 billion years by unravelling the inner core nucleation farreaching implications beyond the earths evolution and the origin of the magnetic field are expected with new clues about the planetary core evolution of all rocky planets to understand the relationships between thermal evolution dynamo and planet habitability this is of paramount importance at a time where amateur astronomers and scientists are discovering many new exoplanets and especially superearth located in the habitable zone of their star
towards modulator therapy for ada2 deficiency

human ada2 deficiency is a rare inborn error of immunity caused by pathogenic variants in ada2 the disease has a wide array of presentations ranging from vasculitis of the skin to the central nervous system with strokes fevers and immunodeficiency to cytopenia and bone marrow failure mortality is 10 and occurs mostly in childhood tnf inhibitor treatment is efficient for treating the vasculitis but the bone marrow failure is refractory to treatment and requires hematopoietic stem cell transplantation hsct in the context of dada2 hsct is complicated by graft failure in a high percentage of patients therefore the treatment of cytopenia in dada2 represents an urgent medical need this project is built on the discovery made during the course of the erc st grant more2dada2 that it is possible to restore ada2 expression in missense mutant cells by drug intervention in vitro providing a first layer of evidence for the possibility to use modulator therapy in ada2 deficiency therefore in this project we wish to identify additional modulators for ada2 our goal is to identify drugs that are able to restore in part or completely the ada2 expression and function as well as the transcriptomic and metabolomic signature of ada2 mutant cells the ultimate goal is to take these modulators to the dada2 patients
the first miniaturized nonresonant antenna tailored to internet of things applications

our solution is a novel antenna technology called virtual antenna that our company has invented and patented 40 patents granted due to its nonresonant nature our antenna yields numerous benefits when designing internet of things iot devices the virtual antenna can work at any frequency ranging from 400 mhz to 106 ghz and with any protocol wifi gps 4g 5g bluetooth and more thus providing design versatility and scalability the virtual antenna fits on tiny devices because it is about 10 times smaller than stateoftheart resonant antennas while the design process of standard antennas requires numerous physical prototypes the electromagnetic behavior of the virtual antenna can be accurately simulated via software thus leading to shorter and cheaper design processes while resonant antennas can be designed only by electromagnetic experts any electrical engineer or technologysavvy has the knowledge to use the virtual antenna in an iot product