Dragon09/odtu_chatbot huggingface dataset:
nanovast a novel non viral lnp for precision payload delivery of genome editors and other cargo

cellspecific cargo delivery is a key remaining problem in the field of rnabased therapeutics thus far delivery has relied on lipid nanoparticles lnps which encapsulate rna with high efficiency but broadly lack in specificity viral vectors are currently the only fda approved tissuespecific cargo delivery option with specificity being the result of manipulation of outer capsid proteins however viral systems are also associated with drawbacks such as oncogenicity antigenicity and preexisting immunity to the viral carrier itself the ideal carrier system would involve lnpefficient cargo encapsulation together with specific targeting in the absence of oncogenicity or immunogenicity dkfz and panosome gmbh have together developed this exact particle the nanovast a patented vesicular phospholipid bilayer densely decorated with a single protein that can be fused to a targeting molecule of interest through specific efficient and separately patented chemistry importantly the attachment of the targeting component relies on a coupling of the vesicle to the targeting moiety rather than a genetic manipulation of the carrier itself as is the case with viral vectors giving this system an unparalleled level of versatility additionally our vesicular system is inherently fusogenic with target membranes thus permitting cargo delivery directly to the cytoplasm and avoiding the reliance on the incredibly inefficient endosomal escape mechanism that plagues lnps it is estimated that conventional lnps only deliver approximately 1 or less of their payload into the cytoplasm this erc poc proposes to use the nanovast particle to a deliver specific rna cargo to cd19 b cells b transport within the cells this cargo to the endogenous rna editing machinery and c functionally alter the surface of the targeted cells through the poc we aim to accelerate nanovast our precision payload delivery system towards direct clinical applications
user behaviour informed learning and intelligent control for charging of vehicle battery packs

the realisation of the eu industrial and political ambition of promoting transportation electrification to reduce carbon emissions depends heavily on the continued advancement of battery technologies however rapid battery pack degradation caused by improper charging behaviours is one of the most crucial factors restricting the wide usage of electric vehicles this project aims to make step changes in research and innovation of battery management by developing 1 a user charging preference learning and demand prediction model methodology 2 a user demandinformed optimisation methodology of charging trajectory and 3 a distributed trajectory trackingbased battery pack charging control and realise an advanced career development for the experienced researcher as an mscapf fellow the experienced researcher dr quan ouyang will receive crucial career development at the chalmers university of technology and engage in detailed battery charging control works which span the areas of automatic control and artificial intelligence using a clearly defined trainingthroughresearch approach the project results will include a generic smart charging system to prolong battery life and improve the vehicles resource efficiency and convenience the incorporated battery pack charging strategies will benefit from revolutionarily considering the user preferences and demand where the designed charging currents can be intelligently adjusted according to different user demands that can effectively restrict battery degradation the hosting group at the chalmers university of technology has a tradition of projects in close cooperation with the vehicle industry eg volvo cars scania and cevt making it highly likely that the results of this project will be taken up by the industry ultimately this project will contribute to the eus carbon neutrality goal and the un sustainable development goals in affordable and clean energy and sustainable cities
capacity opportunity and desire in heritage language variation codev

capacity opportunity and desire in heritage language variation codev offers a novel approach never used in this capacity in this context before to examine a significantly understudied natural laboratory population of heritage language bilingualism hlb moving above and beyond the current stateoftheart in hlb studies codev works with highperforming heritage language speakers hhss and aims to understand the relationship between their heritage language hl competence and nature of their hl experience through the lens of their community center engagement patterns through its novel adaptation of socioculturaleducational framework codev examines this severely understudied hlb context decoding in a systematic way i formal and informal capacity c development activities socialcultural opportunity o creation efforts and individualparental desires d ii what underlying linguistic competence hhss possess and iii how such linguistic competence develops and changes over time and across generations in relation to the relative weighting of linguistic and environmental factors ie community center engagement that predict their hhs status codev maintains that studying one extreme end of the hl outcome continuum will be a unique position to offer novel evidence addressing the variation in hl outcomes that has posed challenges to our understanding of native language acquisition and the role of input codevs findings both formaltheoretical methodological and societalsociolinguistic will make significant contributions to a more complete picture of bilingualism heritage language bilingualism more specifically and its societal dynamics for theory building as well as addressing hss societal and educational needs
transmission and distribution hybrid networks with enhanced resilience and robustness

the eus ambition to achieve climate neutrality by 2050 and increase networks interconnection makes the proliferation of hybrid acdc grids a promising solution towards a more interoperable and resilient paneuropean system in this context theus project aims to showcase advanced methodologies and tools supporting hybrid grids implementation across high voltage hv medium voltage mv and low voltage lv levels to successfully achieve its objectives the project will develop a set of six planning and six operation solutions that will be validated in five use cases addressing the most representative challenges faced by european grids these use cases will rely on accurate models and will be fed with data from five real grids representing different project stages and voltage levels a planned transnational hvachvdc transmission interconnector connecting cretecyprusisrael an existing distribution hybrid grid in italy a planned mvdc distribution grid in turkey an existing hvachvdc link between atticacrete an existing mvacmvdclvdc microgrid in spain the validation will be conducted on six test benches that will allow to reach trl 5 by the end of the project theus assembles a competitive consortium of 15 partners from 8 eu countries including research organizations technology manufacturers electric system operators a wind farm operator a sme to guarantee the exploitation of the project solutions and a european association to ensure the successful dissemination of the project outcomestheus will directly impact in the electricity system orchestration of future paneuropean acdc hybrid architecture by performing a validation campaign in which 2 underplanning networks will be designed and 3 existing networks will be improved in terms of management and operation overall theus is expected to achieve 1030 reductions in energy losses and 1520 in om costs while ensuring the safe operation of hybrid grids with a higher penetration of res
marine climate change refugia for insular mesophotic ecosystems in the south pacific ocean

the mesophotic coral ecosystems are described as warm water lightdependent corals and associated communities inhabiting depths from 30 m to over 150 m in tropical and subtropical regions these ecosystems present high ecological relevance as they can act as potential reseeding areas for shallow ecosystems harbor endemic and rare species and provide suitable habitats to support the populations of many species of fishes and crustaceans moana will address the knowledge gaps in how these ecosystems respond to climaterelated stressors in the remote southpacific oceanic islands and seamounts by providing maps of future refugia and vulnerable areas for a selection of ecologically and socioeconomically relevant species the innovative approach envisaged in moana using global highresolution earth system model outputs combined with species distribution models will provide essential information to assist in the implementation of adaptation and mitigation policies in south pacific areas through the potential creation of marine protection tools as mobile marine protected areas andor blue corridors moreover moana methodology and tools could be easily applied to assist other ecosystem preservation in similar areas such as the small island developing states eg caribbean islands north pacific islands largescale systems from the north pacific marquise islands american samoa hawaii japan middle scale systems from the atlantic basin azores madeira canarias and even smaller scale systems from the mediterranean baleares corse sicily cerdenya maltatwo leading research centers will be involved in the project the host institution the barcelona supercomputing center bsc spain and the ecology and sustainable management of oceanic islands esmoi chile a research center focused on biodiversity and local management of the southeast pacific islands
the mathematical analysis of extremal black holes and gravitational radiation

the einstein equations constitute a system of geometric nonlinear partial differential equations that describe gravitational dynamics in the framework of einsteins theory of general relativity the last decade has seen tremendous progress towards understanding dynamical aspects of the einstein equations at the mathematical level great insight has been gained due to recent advances in the study of partial differential equations differential geometry and microlocal analysis the present proposal builds upon these advances in the context of the following two mathematical problemsstability and instability of extremal black holes extremal kerr black holes describe rapidly rotating solutions to the einstein equations they sit at the transition between black holes and naked singularities and exhibit critical geometric featuresthis proposal addresses the stability and instability properties of extremal kerr black holes and is motivated by recent advances by the pi which cover linear and nonlinear aspects a successful resolution would give fundamental new insights into the fate of perturbed extremal black holes and the transition between black holes and naked singularitiesthe latetime analysis of gravitational radiation gravitational radiation provides an observational window into deep mathematical aspects of general relativity in this proposal we investigate a key feature that is amenable to mathematical analysis the existence of latetime tails in gravitational radiationrecent work by the pi and collaborators has lead to the first proof of the existence of latetime tails in a toy model setting also known as prices law this proposal considers the full setting of the nonlinear einstein equations via the analysis of latetime tails in the dynamics of perturbations of both flat spacetime and black hole spacetimes a successful resolution would have important implications for the strong cosmic censorship conjecture
molecular strategies against viral entry and glycan shielding

the shield consortium targets two closely related steps in the viral replication cycle that are as yet difficult to study and to exploit for therapeutic interventions 1 virion glycosylation in the context of uptake maturation and viral immunity 2 virion dynamics of entry into cells where the plasticity of the involved proteins and their glycosylation status have key roles the viruses studied in shield are from the genera of flavivirus denv wnv yfv zika mammarenaviruses lasv and henipaviruses hendra nipah we bring a broad spectrum of methodical expertise to understand and exploit the interrelated processes of viral glycosylation and viral dynamics molecular simulations will enable the identification of cryptic pockets in viral proteins that form during the entry process and the design of inhibitory ligands that bind to such pockets theoretical methods will be used to identify ligands for glycosylated viral proteins this is intertwined with cryoem and nanoresolution optical microscopy which enable a detailed analysis of these events their sensitivity to biological and chemical interference and will allow a rational optimization of specificity and affinity novel chemical and biological entities nces nbes as tool compounds and potential starting points for drug development are obtained by targeted chemical synthesis xray fragment screening and nanobody library screens additionally we study biological processes and the influence of interactions in systems of increasing complexity which range from biochemical invitro to cellular assays and in vivo animal models as the glycan shield in lassahendranipah plays a major role in immune evasion we explore the immunological effects of an interference with protein glycosylation leading to novel starting point towards the development of effective and robust vaccines in conclusion shield delivers a deeper understanding and molecular tools to prepare the eu for future pandemic events
structural studies of the human mitochondrial rna life cycle

mitochondria maintain an organellar genome that encodes for subunits of the respiratory chain its coordinated expression is essential for eukaryotic life and defects in this process lead to severe disease in humans mitochondrial gene expression is carried out by unique dedicated molecular machineries but the underlying molecular mechanisms remain poorly characterized during my previous work as a phd student and project leader i provided the structural basis of human mitochondrial transcription at the same time structural insights on mitochondrial translation were reported however our understanding of mitochondrial gene expression remains limited due to two fundamental knowledge gaps first we lack a molecular understanding of the complex mitochondrial rna life cycle that takes place in between transcription and translation second we do not know how the different steps of mitochondrial gene expression are functionally coupled as they are not separated by membranes with mitorna we propose to take the next big leap towards a mechanistic understanding of mitochondrial gene expression by addressing these blind spots using an innovative integrated structural biology approach we will define the molecular basis of the human mitochondrial rna life cycle and how it is embedded in the concert of mitochondrial gene expression in particular we will investigate the structural basis of various key steps of mitochondrial rna metabolism in vitro and in situ and dissect how they are coupled to each other this groundbreaking work will open up the next frontier in mitochondrial biology by drawing a molecular picture of human mitochondrial rna metabolism and providing insights into the functional organization of mitochondrial gene expression in addition it will also advance methods to study mitochondrial biology from the atomic to the organellar scale
mechanistic understanding towards how progerin contributes to premature ageing

the nuclear lamina is a meshwork of lamin proteins that underlie the inner nuclear membrane and confer mechanical stability to the nuclear envelope mutations in lamins are associated with many disorders including progeria a fatal premature ageing disease in progeroid cells expression of a truncated form of lamin a named progerin drastically deforms the nuclear envelope causing premature cellular senescence however the underlying molecular mechanisms remain unclearthe nuclear pore complexes npcs enable selective transport across the nuclear envelope the diameter of the npc central channel and the resulting nucleocytoplasmic exchange is governed by membrane tension which is predicted to alter in the progeroid nuclei therefore i postulate that the structural integrity of the npcs is disrupted in progeroid cells as a result of the deformed nuclear envelope andor direct interaction with progerin this may lead to further deregulation of nuclear transport that potentially drives cellular senescencei aim to investigate whether the npcs indeed undergo compositional and conformational change in progeria patientderived primary cells and to what extent nuclear transport is impacted to do so i will apply in cellulo cryoelectron tomography to unveil the molecular organisation of the progeroid npcs i will further employ fluorescence microscopybased cellular assays to identify proteins with nucleocytoplasmic mislocalisation the proposed work will have three major significances 1 to date in cellulo structures of the npcs in disease states have rarely been examined visualisation of the npcs directly in patientderived cells will provide pivotal insights into npc biology 2 investigation of nuclear transport in progeroid cells will reveal the mechanisms contributing to premature ageing 3 since progerin is also produced during normal ageing its mechanistic investigation may add to understanding of the natural ageing processes
safe and sustainable by design framework for the next generation of chemicals and materials

ssbd4chem brings together stakeholders from industry government academia and civil society to develop and promote best practices for safe and sustainable product and process design through demonstration in 3 case studies ssbd4chem aims to meet the eus strategic objectives for digital enabling and emerging technologies sectors and value chains by developing a comprehensive safe and sustainable by design ssbd framework that uses new sciencebased approaches to identify and address potential hazards and risks and innovative technologies to support the design of safer and more sustainable products and processes ssbd4chem objectives include 1 ssbd framework to facilitate development of the next generation of chemicals and materials applicable to renewable composites in automotive value chain pfasfree coatings for textile and cellulose nanofibers as additive in cosmetics to replace plastic microbeads 2 development of efficient hazard screening tools for alternative assessment of next generation chemicalsmaterialsproducts combining in silico tools and multicriteria analysis 3 advanced explorative exante lca method supported by molecular and datadriven modelling to fill data gaps for novel materials and chemicals 4 integration of chemicalnanomaterial characterization methods to assess products environmental safety quantify emissions to support occupational and consumer safety limits 5 development of alternative in vitro models as part of new approach methodologies for adequate exposure scenarios 6 harmonization and validation of analytical and toxicological methods for proposition to regulatory and standardization bodies to contribute to the development of new standards and facilitate market acceptance of ssbd4chem project results and 7 enhance overall ssbd4chem impact through stakeholder engagement training dissemination and exploitation and drive industrial innovation
targeting the vascularimmune interface to induce antitumor immunity

in this erc synergy grant we will characterize the vascularimmune interface in melanoma and glioblastoma and explore the perivascular niche as a site for local antitumor immune activationcancer immunotherapy has made tremendous progress in the last two decades but a vast majority of cancer patients do not benefit from this progress yet refinement of established immunotherapies will undoubtedly increase response rates however conceptually brave new therapies must be developed to make additional breakthroughs the tumor vasculature plays a key role in orchestrating antitumor immunity by regulating recruitment and activation of tcell and other immune cells we propose to make a detailed characterization of vascular immune landscapes in melanoma and glioblastoma and to utilize this to optimize vascularimmune crosstalk and immune response as a new breakthrough immunotherapythis proposal builds upon new knowledge on how immune hubs can form around tumor vasculature which to a large part is based upon novel findings and development by the applicants 1 2 on the importance of perivascular antigenpresenting niches in activating sustaining and executing cd8 and cd4 tcellmediated immune attacks on cancer we will develop tumor vessel targeting aav vectors that can enable therapeutic induction of immune hubs in cancer this new form of immunotherapy will be evaluated alone and in combination with established cancer immunotherapiescombined our research teams are in a unique position to achieve this goal synergistic advancements will be obtained by joining dimbergs expertise in the vascular and immune microenvironment in tumors especially glioblastoma tütings expertise in tumor immunology and cell plasticity especially melanoma and essands expertise in translational gene therapy and cancer immunotherapy the project is timely and if successful can bring immunotherapy to the next level rendering new hope to millions of cancer patients
photoelectrochemical oxidation of methane using single atom catalysts

natural gas primarily methane ch4 is still a major energy source that is often simply flared into the atmosphere without being harnessed as a cumulative result unprecedented ch4 spikes have been reported lately in earths atmosphere combined with the already existing global warming concerns posed by other greenhouse gases such as co2 co nox etc ch4 abundance will lead to a worldwide catastrophe various attempts to convert and utilize ch4 into useful chemicals in mild reaction conditions have only seen limited success in this proposal we aim to target the ch4 molecule by fixing the co2 molecule to produce acetic acid ch3cooh a highvalue industrial chemical the global acetic acid market attained a value of over 87 billion eur in 2020 and is expected to grow at a compound annual growth rate cagr of 55 from 2022 to 2027 via photoelectrochemistry pec using light and electricity employing a new generation of heterogeneous catalysts called single atom catalysts sacs containing abundantly available single transition metal atom embedded on transition metal oxide semiconductors that can rival catalytic efficacy of a welldefined homogeneous catalyst to achieve this goal we will mainly study 1 different bandenergies of sacs using optical and electrochemical methods 2 select and examine appropriate sacs with band energies that can enable ch4 oxidation and co2 reduction 3 examine their selectivity efficiency and recyclability through catalyst and reaction optimizations 4 characterize the best performing sacs and 5 decipher the reaction mechanism with the aid of computational methods we will disseminate the results through papers conference presentations public outreach events social media etc while gaining several scientific and transferable skills required for career progress a new pathway towards methane valorization is foreseen through this project which can be highly attractive in an academic and industrial setting