Dragon09/odtu_chatbot huggingface dataset:
improving cart cell therapies through aavmediated genetic engineering

t cells expressing chimeric antigen receptors car have transformed cell therapies against some hematological cancers as a postdoc i evolved a synthetic adenoassociated virus aav with tropism against murine t cells providing a unique tool to study gene targeted t cells in immunocompetent cancer models in this proposal capitalizing on my breakthrough i will develop novel strategies to generate gene targeted cart cells in vivo optimizing aav delivery in immunocompetent mouse models and combining these methods with technologies for cas9 delivery for t cellspecific gene editing the ultimate goal of my proposal is to develop methods that can be translated to clinical trials in humans therefore i will establish a humanized mouse model that allows for targeting of human t cells in vivo in which key findings from this research project will be translated for proofofconcept experiments as the first ever study of gene targeted t cells in vivo this groundbreaking research will provide indepth profiling of in vivo engineered cart cells and their therapeutic potential this study is a necessary first step forwards toward accessible and affordable in vivo generated cart cell therapies in humans furthermore to extend the use of cart cells against solid tumor i have developed an aavbased platform to perform pooled knockin t cell screens in immunocompetent solid tumor mouse models for this research proposal i have designed a library of synthetic costimulatory receptors to be expressed with a car at the trac locus to improve t cell fitness and persistence by combining advanced t cell engineering with analysis on singlecell level these pioneering experiments will answer crucial questions for t cell therapies and tumor biology to succeed with my ambitious and unconventional proposal i plan to join the department of medicine huddinge at the karolinska institute building a collaborative team in an excellent translational research environment
sustainable antimicrobial and antiviral nanocoating

infectious diseases pose a significant threat to both human health and the global economy they account for more than 20 of global mortality and viruses are responsible for about onethird of these deaths to date we know of about 200 infectious diseases and about 80 of infectious diseases are transmitted by unclean hands touching contaminated surfacessusaan project is focussed on development of new sustainable antiviral and antimicrobial coatings for textiles and high traffic objects made of plastics and metal involving textile bathrooms and switches manufacture industries in this context it can be stated that most of the common handtouch sites andor objects are covered by the project so final impact would be extensive after the successful project execution being the results of the project validated in three main market sectors through end users consortium partners and core business are one of the strongest points of susaan technological and scientific partners lurederra ncsrd ivw ceit and itene are experts on main areas of nanoparticles coatings pretreatment biobased nanocapsules and toxicity assessment companies involved cover the whole value change based on their core business including coatings production tecnan biobased products celabor bathrooms manufacturing eczacibasi home appliances panasonic and textiles almaxtex last but not least inter it will cover the activities on bpr assessment being virhealth the expert on virology on charge of standardized testing to determine virucidal and antimicrobial activity of the coatings and arditec on charge of sustainability assessmentthe final outcome of susaan project is the validation of the new sustainable antimicrobialantiviral nanocoating in different final products high traffic objects plastic and metallic and textiles technical advantages and comparative results to current solutions will be used to present susaan solutions to potential clients
the roots of civility french renaissance literature as a laboratory of modern civility

renaissance men and women had a passion for virtue and a genius for cruelty they had wonderful manners and barbaric inclinations lovely clothes and terrible diseases can they really teach us something about civility i think they can they were made of contradictions and so are we and both we and they dream of a society where politeness and respect reduce tensions and allow a peaceful and pleasant cohabitation for all the goal of this research project executed at the university of lille under the supervision of marieclaire thomine is to prove that the roots of civility go back to the 16th century and that there was a mature form of civility in the renaissance france a century before what is usually considered to be the beginning of the politesse française i will identify its main models and situate them in relation to the previous medieval ones and those from the century of louis xiv i will argue that renaissance authors used the literature as the principal means of wide diffusion of this new civility and this is precisely what makes this century a turning point in the history of manners in france and a part of the cultural reform initiated by the kings and queens of france to build a more cohesive and peaceful society furthermore i want also to prove that this evolution can be observed using the modern tools of historical pragmatics a branch of pragmatics that had developed strongly over the last twenty years but was not yet used to study the phenomenon of impoliteness in france during the renaissance i will accomplish those goals through a program of close reading of prose texts essentially literary dialogues and collections of short stories of the 15th and 16th centuries informed by the literature of civility and through corpusbased research to detect and define evolution in verbal and nonverbal behaviors in the time of the last kings of the valois dynasty
crispr pointofcare diagnostics

monitoring of human health and the preventiontreatment of infectious diseases strongly depend on accurate and efficient detection identification and tracking of pathogens or biomarkers key features of such a diagnostic tool that enable this are speed accuracy and availability at the pointofcare current molecular diagnostic solutions do not meet these requirements due to the fact that they often need to be performed in a centralized fashion however the incredible advances in crisprcas technology in recent years provide an opportunity to change this by taking advantage of the innate specificity of crisprcas we have previously developed a highly sensitive and accurate proofofconcept diagnostic tool with promising results the potential for implementation is unfortunately impaired by the fact that the workflow comprises of multiple steps that increases handson time room for human error and the undesirable implications this has to mitigate this we propose a solution that entails developing a novel approach based on a thermostable rna polymerase that allows for the condensation of the current workflow into a shorter 1step protocol once such a protocol has been developed an assay will be developed for one of the causative pathogens of chronic obstructive pulmonary disease copd technical feasibility of the assay will be demonstrated in collaboration with an academic hospital by characterizing the developed assay on relevant clinical samples this will provide insight into the reallife performance when compared to the current gold standard pcr as well as easeofuse in a relevant context furthermore the feasibility of the value proposition and potential for commercialization will be thoroughly assessed not only will this ercpoc project shed light on the potential for our improved crisprcas based diagnostic tool in the context of copd a sense of broad applicability in other human pointofcare diagnostics applications will be gained
decoding and targeting the pge2mef2a axis in tumorassociated macrophages

inflammation is a complex spectrum of processes whose outcomes range from cell killing to tissue regeneration in this context a major goal in immune oncology is the development of treatments that stimulate cytotoxic immunity while limiting repair in the tumor microenvironment tme as these approaches have the potential to synergize with available immunotherapies and provide benefit to otherwise resistant patients pancreatic cancer is a largely incurable disease in which aberrant inflammation and profound immune suppression conspire to sustain disease initiation progression and immune escape accumulating evidence supports the view that tumorassociated macrophages tams are key orchestrators of the balance between cytotoxicity and regeneration and thus represent promising therapeutic targets in pancreatic cancer in mefhisto we aim at elucidating the molecular control the functional implications and the therapeutic potential of the pge2mef2a axis a newly described pathway enabling selective control of inflammatory gene expression in macrophages by combining advanced genomic analyses in human samples functional experiments in preclinical models and mechanistic studies in key cell types this proposal will expand our knowledge of the organizing principles of innate immune responses in tumors the ensuing results may lead to novel combinatorial treatments for diseases such as pancreatic cancer that are refractory to immunotherapy
avoiding the negative impacts produced by plastic materials in humanitarian contexts

biobased and biodegradable plastics products bbpps are emerging as a key piece to solve the negative impact of fossilbased plastics in the environment a relevant case where bbpps can play a key role in avoiding pollution is in single use applications used in humanitarian contexts such as natural disasters or armed conflicts where appropriate waste management systems are usually not feasible plastic waste mainly health care packaging waste is largely contributing to uncontrolled waste in humanitarian contexts and addressing their environmental impacts is required one of the most promising biodegradable biopolymers is the polyhydroxyalkanoates phas family which offer functionalities are biocompatible but also fully biodegradable in relevant environments without causing microplastic pollutionaniph will create a new pha value chain to produce modern wound dressings and recyclable water barrier packaging while being biodegradable in all relevant environments soil freshwater marine the biodegradation will be programmed during the pha production formulation compounding and conversion stages an ai predictive tool and a digital traceability tool will support these aims by predicting the biodegradation properties ecotoxicity and ensuring the traceability of the materials and products moreover sustainable choices proper use and safe disposal of bbpps will be fostered through aniph contribution to information labelling systems and by delivering capacity building resourcesour project gathers eight partners from six european countries leaders in different fields of knowledge from bioplastic production to end of life assessmentadoption of aniph value chain will produce relevant outcomes yearly saving 2243 kt of crude oil thanks to a reduction of 43 and 68 of co2 emissions compared to packaging and wound dressing respective fossil counterparts recirculating 1475 kt of biomass avoiding the use of 1293kt of hazardous substances
the organization of the archaeal cell

archaea are microbes that form one of the three domains of life while sharing similarities with both bacteria and eukarya archaea possess unique features such as atypical lipid membranes the archaellum motility apparatus and exclusive metabolic pathways like methanogenesis studies over the last decade have substantially expanded the archaeal tree of life revealing the tremendous diversity widespread distribution and vital ecological roles mediated by these organisms as well as their crucial evolutionary placement as close relatives of eukaryotes despite these major advances regarding archaea diversity ecology and evolution our knowledge of archaeal cell biology remains limited particularly due to the scarcity of model systems and suitable genetic and imaging tools in archcellorg we propose to explore recent methodological advances including the ability to perform live cell imaging on the model archaeum haloferax volcanii combined with genetics physiology biochemistry and structural approaches to unravel the mechanisms governing three fundamental aspects of archaea cellular organization cell division polarity and shape regulation in aim 1 we will elucidate the molecular composition of the archaeal division machinery and the mechanisms involved in its organization and placement at the division plane in aim 2 we will identify the main regulators of cell polarity and characterize their modes of action in aim 3 we will investigate regulators of shape transition and define the mechanisms by which they coordinate shape changes and motility elucidating these processes will not only contribute to further our understanding of archaeal cell organization but will likely also provide valuable insights into the evolution of cellular life on earth including the processes that led to the emergence of eukaryotes
strategies of 3d growth in brown algae

alter egrow aims to identify the mechanisms underlying the development of tridimensional 3d tissues in multicellular organisms many physical factors influence the shape of an organism growing from a single cell or a small group of cells the direction of growth along the x y and z axis when and how rapidly growth occurs and whether the region of growth is diffuse or localised an almost infinite number of combinations of these factors are possible most animals and land plants grow in 3d from the onset of embryogenesis other multicellular organisms however grow in 3d later in their development for example by emergence of a 3d bud from a single row of cells as in mosses or by aggregation of hyphae as in fungi the large phylogenetic distances between current model organisms complicate the investigation of the mechanisms underlying this diversity of 3d growth strategies brown algae by contrast display all of these 3d growth modes in a single clade making them a unique subject for investigation of the mechanisms moreover their independent and recent evolution when compared to the other clades suggests that they have developed divergent 3d growth mechanisms in this project my team will observe and quantify parameters of 3d growth in four species of brown algae each representative of one of the main types of 3d growth mechanisms also found in animals plants and fungi then we will build dynamic mathematical models that describe these mechanisms by integrating quantitative data on cell shape cell wall thickness and stiffness cytoskeleton organisation turgor and cellcell tension in dynamic 3d growth simulations and test them by comparing the 3d growth pattern of wild type algae and genetic mutants thus this project will pioneer what is currently a black box of knowledge about the development of brown algae examining how these organisms raise multicellular structures in 3d space
unequal education the role of educational constraints in shaping inequalities

project unequaled aims to study educational constraints faced by individuals at a stage when they are planning their future investments in human capital despite its importance understanding the determinants of educational choices has been a longstanding challenge for two important reasons first it requires broad representative data secondly because the environment in which individuals educational plans are formed and adjust is typically endogenous to their characteristics i will tackle these issues using large interventions on nationally representative samples of individualsdifferent parts of project unequaled target specific questions that will help construct an overall picture the project will seek to understand and quantify the role of the different barriers in leading to unequal learning and opportunities and the effects of easing the constraints specifically asking can the easing of technological constraints reduce learning inequality what role does ict access and training play for distance learning does differential social exposure within the classroom impact student outcomes can role models help an individual reach their goal how important are psychological or socioemotional barriers for achievementi will address each part using detailed micro longitudinal data but at a macro level large scale nationally representative samples i plan to combine economic concepts with field interventions experiments and rich econometric and computer sciences tools to analyse big datasets and to causally estimate the impact of the components that drive the adjustment in educational plans and ultimately how these factors into later educational outcomes all projects will aim to capture the short and longrun impacts to carry off this ambitious research project i will work with a large and interdisciplinary network of researchers specializing in economics statistics computer science management science and public policy
multirotor estimation of wind

in the last decade both remotelypiloted and autonomous multirotor aerial systems have been employed for a wide range of challenging tasks including visual inspection and physical maintenance that were previously either dangerous or impractical widespread adoption is however hindered by the sensitivity of existing systems to unpredictable disturbances caused by wind forces that they are not able to estimate and hence mitigate with funding provided by marie skodowskacurie actions programme the mew project seeks to use recently developed acoustic wind sensors in a sophisticated and mathematically sound estimation framework researchers will design entirely new algorithms for the estimation of wind forces so that they may be compensated for by the multirotor flight control system realworld tests and experiments will demonstrate the soundness of the research and lead to software implementations that are ready to be adopted by industry the results of the mew project will lead to a new wave of application domains for multirotor technology and will create new approaches to estimating wind dynamics that may extend to other engineering and scientific questions around fluid dynamics
cognitive computational neuroscience approach to the development of mathematical competence

learning the association between numerals symbolic numbers and quantity nonsymbolic numbers is the initial step toward comprehending symbolic mathematics according to the symbolic estrangement hypothesis extensive experience of exposure to numerals and their manipulation may significantly weaken any preexisting relation between symbolic and nonsymbolic numbers previous studies have independently reported representational shifts of brain activity patterns in young children and simulation of number processing systems using artificial neural networks anns nonetheless it has remained largely unclear how such brain representations and ann features are related to each other in terms of development the current project aims to address these issues by constructing computational models that integrate multimodal neuroimaging data of young children and ann models for symbolic and nonsymbolic numbers functional magnetic resonance imaging fmri and electroencephalogram eeg data will be collected while children engage in number perception tasks at the outset 5yearolds and after two years 7yearolds of formal education in parallel with the neuroimaging experiments i will implement anns that learn the association between symbolic and nonsymbolic numbers to determine whether anns exhibit a similar developmental trajectory as the human brain i will construct voxelwise encoding models based on the latent ann features encoding models based on the fmri and eeg data will be further integrated into finescale spatiotemporal data showing functional dynamics across multiple brain regions finally i will investigate how these dynamics change with formal education by comparing data from 5 and 7yearolds this project integrates interdisciplinary knowledge from cognitive neuroscience developmental psychology and artificial intelligence to establish a novel computational approach to understanding the development of mathematical abilities
decentralized microfluidic in vitro diagnostic patch for pandemic control

in vitro diagnostic ivd technologies have revolutionized healthcare yet remain confined to the laboratories this traditional approach massively failed to manage viral outbreak during the covid19 pandemic because it lacked quick and costeffective diagnosis moreover an urgent need was evident for bringing quantitative labquality diagnosis to the hands of end users ie pointofcare poc despite high expectations from labonchip technologies they failed so far to disrupt the ivd market due to their complexity high cost offchip sample preparation poor scalability to mention a few the decipher consortium aims to revolutionize the poc ivd field by developing innovative microfluidicbased decipher patch capable of both biofluids selfsampling via hollow microneedles hmns and immediate analysis of this sample on the very same patch in a completely selfpowered manner producing quantitative result to be read out with a repurposed glucose meter ebola and lassa viruses are selected as relevant model systems because they are highly contagious with humantohuman transmission high mortality rate and no vaccinetreatment available thus having meaningful potential for new pandemic threats to offer such a genuine sampletoresult quantitative poc solution the decipher value chain from lab to market will cover 1 investigation of highthroughput manufacturing processes with 2 novel polymers innovations in the fields of 3 microfluidics 4 hmns and 5 quantitative molecular bioassays 6 decipher patch analytical and clinical validation both retrospective and prospective as well as 7 aibased models 8 socioeconomicsystems analysis and 9 life cycle assessment of decipher patch this true interdisciplinarity will be represented by highly experienced decipher consortium with partners from 3 universities 5 research institutes 1 sme 1 large company and 1 nongovernmental organization from 6 countries