Dragon09/odtu_chatbot huggingface dataset:
uncovering the cortical cellular basis of specificity and chronicity of pain

chronic pain remains a fundamental unsolved puzzle in biology and an unmet global challenge in clinical practice progress is limited by major gaps in knowledge on neural substrates owing to overwhelming redundancy of implicated regions and pathways with several painunrelated sensory cognitive and emotional functions as well as lack of understanding on the origins of plasticity and cellular substrates for diverse psychosocial and environmental influences on pain here we propose that neocortical neuronal ensembles ie discrete cohorts of coactive neurons intermingled within seemingly redundant pathways represent a mechanistic correlate for imparting specificity to pain perception while also providing adaptive flexibility to context and introspective bodily states and serve as convergent substrates for divergent influences such as past experience of pain fear memory and expectation using cuttingedge in vivo methods such as multiphoton imaging of activity and structure electrophysiological parallel recordings of hundreds of neurons finegrained behavioral analyses activitybased cell tagging approaches optochemogenetic manipulations and single cell transcriptomics in mouse models of acute and chronic pain we aim to i identify neocortical pain ensembles that delineate pain from other sensory percepts valence states and cognitive functions and determine their composition connectivity coordinated activity in local and across distant networks and functional relevance to pain ii study their dynamic plasticity over the transition from acute to chronic pain and delineate bottomup peripheralspinal and topdown brain intrinsic influences with a focus on studying the role of the salience network in channeling context expectation and fear memory and its dysfunction in chronic pain and iii study the potential of reversing plasticity of neuronal ensembles by noninvasive neurostimulation and behavioral approaches for achieving pain relief
applying acoustic streaming to enhance mass transfer in liquid chromatography of large molecules

liquid chromatography lc is a prominent analytical technique serving lifesciences chemical and pharmaceutical sciences which plays a key role in virtually all research and development concerned with liquid phase biochemistry the performance of pressuredriven lc has continuously increased during the past century with improvements realized by ordering the packing and reducing the particle size now that the point is reached where submicron ordered packings can be reliably produced the performance limitation of lc lies in the principle itself more precisely in the slow mass transport of analytes between the field lines with varying crosssectional poiseuille velocity vectors distribution of analytes in the sample bands over different local velocities results in tayloraris dispersion an effect that becomes increasingly important at high velocities or at low diffusion coefficients acolc addresses this lateral diffusion limitation by inducing acoustically generated lateral flows obtained in resonance mode the resulting vortices in this socalled acoustic streaming regime carry the analytes much faster than purely diffusive processes therewith reducing the dispersion dependency on size and mobile phase velocity while the efficacy of this acoustic vortex lc methodology has been recently shown in microfluidic channels in the host group the channel dimensions need to be scaled to the micronscale range with the resonance condition maintained in acolc innovative geometrical approaches will be pursued to overcome frequency limitations of commercial piezoceramic actuators improved separations of glycosylated hemoglobin variants are aimed for in glass substrates which are compatible with integrated uvvis absorption this improved separation application is of interest to millions of diabetes patients for routine separations and tackles an additional separation challenge encountered in multiethnic groups
latestage photocatalytic functionalization of alkenes and 13dienes

the latestage functionalization lsf of bioactive compounds is currently a hot topic in the chemistry community as it allows for the rapid and divergent construction of molecule complexity and avoids the need for timeconsuming de novo synthesis this is especially relevant in the fields of drug discovery and medicinal chemistry where the fast identification of structureactivity relationships is crucial especially intriguing in this context are alkenes and 13dienes as they are frequently occurring motifs in natural products and drug molecules including important antibiotics and antivirals however methods for the introduction of a broad variety of functional groups via the lsf of these moieties remain underdeveloped latefun aims to create new chemical space by developing a firstinclass methodology for the incorporation of a highly versatile functional handle via the lsf of alkenes and 13dienes whose wellestablished subsequent transformations will allow for the rapid assembly of diverse structures applying this innovative protocol to the lsf of complex natural products and drug molecules will be of great importance and impact going beyond the current state of art the reallife applications of this cuttingedge research proposal will be explored during a secondment phase in novartis basel providing for valuable industry insights and interdisciplinary aspects the hosts expertise in latestage functionalization of bioactive molecules using catalytically generated carbyne equivalents perfectly complements the applicants strong background in photocatalysis and therefore guarantees twowaytransfer of knowledge between the host group and the er experienced researcher the successful implementation of this action in the highly international and interdisciplinary environment of iciq and novartis will enable the fellow to develop a unique research profile and will be crucial in building an independent academic career
improving lastkilometer navigation transportation of emergency personnel equipment and relief items in hazardous and challenging environments

considering response operations and relevant tasks in an urban fire or wildfire performance of first and second responders is dramatically affected due to the low or even zero visibility conditionsforesight will design develop integrate deploy test evaluate and demonstrate a set of bespoke response tools and services at the service of civil protection agencies fire brigades civil protection organisations and emergency medical which ensures a catalytic upgrade when managing urban fire or wildfire these tools and services a effectively allow frs to see unobtrusively through fire smoke fog and dust b boost situational awareness tactical reconnaissance and lastkilometre logistics related not only to heavy equipment and emergency relief items delivery but also comprehending the entire route from start point of resources to entering and navigating to the hot zone c enhance decision and sense making of individual responders and teams from the onsite to the closure of an incident notably the tools and services delivered by foresight shall be evaluated against a rich technology inventory created within the project that extensively analyses existing technologies supporting first and second responders in their immediate response to natural disasters highlighting their strengths and weaknesses moreover the foresight technologies follow by design privacy ethical security and legal constraints to expedite their inclusion in response tasks and their abidance to standard operational procedures finally a rich integration testing and validation activities programme is followed of round tables rts technical integration workshop tiws component field tests cfts and system field tests sfts towards empowering collaborative response and handling of complex incidents to its fullest whilst facilitating implementation of most promising usercentred technologies in realworld conditions
impact of spectrin mutations on the cytoskeleton and organelle organization in neurodegeneration

spectrins are an integral part of the submembranous cytoskeleton providing both mechanical scaffolding and organization hub for other proteins in metazoan cells the importance of spectrins to neuronal health is demonstrated by their association with a wide range of human neurological disorders spectrinopathies currently more than forty mutations in the gene encoding nonerythroid spectrin sptan1 are associated with developmental and epileptic encephalopathies hereditary motor neuropathy hmn spastic paraplegia hsp and ataxia the underlying pathomechanisms remain largely unknown in drosophila the highly conserved spec homolog similarly plays an important role in the nervous system development as well as in synapse formation its function and maintenance interestingly synaptic defects associated with loss of spec can be suppressed via neuronal mitochondria repositioning conversely increased levels of spec rescue a range of neuronal phenotypes linked to actindependent mitochondrial dysfunction in an synuclein neurodegeneration drosophila model these findings suggest that modulating the levels of spec in neurons might have an important and understudied impact on tuning mitochondrial dynamics and preserving neuronal health thus the goal of my msca proposal is to deepen our knowledge on how neuronal actin and spectrin cytoskeleton regulate mitochondria and assess mitochondrial dysfunction at the basis of spectrinopathies with a combined use of drosophila as a model organism and human ipscderived neurons as a platform to translate the findings to human neuronal health and disease my project will provide insights on whether spectrinassociated mitochondrial dysfunction is a shared or specific feature for hmn hsp and ataxiaassociated spectrin mutants i will deploy these findings to tailor a pharmacological treatment in the spectrinopathy neuronal cellular models and develop a therapeutic strategy
naturebased solutions education network

the overall objective of nbs eduworld is to nurture an nbs literate society supporting a just transition to a sustainable future for this nbs eduworld will create an nbs community that facilitates synergies between nbs professionals and education providers and ensures free and easy access to nbs knowledge and resources for all to achieve this goal nbs eduworld will summarise the state of play of nbs education in europe and evaluate the initiatives already in place determine how to expand and replicate them and establish a basis and framework for the project itself and future initiatives resulting in guidance and policy recommendations in parallel the project will analyse nbs demonstrators with an educational dimension tier1 across europe nbs edusystems to support the testing and improvement of approaches and resources with nbs demonstrators with no or a limited educational dimension tier2 and create the means and opportunities for all nbs practitioners to engage with educators inter alia via tier3 nbs edusystems this will be done whilst supporting the overarching goal of promoting nbs as a viable career prospect for european citizens of all ages to adequately engage educators who are at different points on their nbs journey the project will provide specific activities for those who are not yet familiar with the concept and benefits of nbs and those already aware but in need of support to progress to the next stage these activities will be scaled upout by extensive dissemination and communication activities to maximise the projects outreach and ensure its longterm success only by joining with nbs experts education experts civil society supportive policies can we create an nbs eduworld a community that makes a difference
repair mechanisms of topoisomerase ii dna lesions

topoisomerase ii top2 chemotherapeutics such as etoposide have been widely used in the clinic to treat leukemias lymphomas lung testicular and ovarian cancers etoposide was first approved for clinical usage in 1983 by intercalating into dna etoposide stalls the top2 catalytic cycle generating toxic dna lesions known as top2dnaprotein crosslinks top2dpcs after 40 years of intense research the mechanisms employed by cells that counteract these lesions are starting to emerge these include enzymes that reverse the crosslink degrade the protein adduct or remove the lesion by dna incisions moreover the protein zatt was recently described as an essential regulatory enzyme that sumoylates top2 and thereby stimulates top2dpc resolution important and longstanding questions in the field relate to our understanding of how the different modes of repair are activated coordinated between one another and preferentially used by cells based on genetic data zatt appears to be the primary responder to top2dpcs but how zatt coordinates the different modes of repair via top2sumoylation is currently unclear to address these questions and study top2dpc repair we propose to use a novel approach based on xenopus egg extracts which can recapitulate dna repair mechanisms in a soluble environment as part of our preliminary data we show that these extracts can recapitulate top2dpc repair via zatt sumoylation providing a unique opportunity to delineate the molecular mechanisms underlying this reaction by combining this system with complementary and innovative approaches we seek to obtain a clear molecular understanding of the different mechanisms counteracting top2 lesions and unravel the molecular triggers that activate the different routes of repair by doing this we will provide new opportunities and targets to improve cancer treatment
advancing phage therapy through synergistic strategies phagemediated killing and competitive exclusion using engineered prophages

amid the antibiotic resistance crisis the centuryold practice of phage therapy the use of bacterial viruses to treat bacterial infections has gained renewed attention despite extensive research and clearcut advantages over antibiotics phage therapy has yet to gain momentum this is primarily due to remaining limitations eg the timeconsuming process of identifying suitable phages and limited in vivo efficacy with phagepro i propose a new technology to overcome the shortcomings of traditional phage therapy unlike the conventional use of lytic phages i will capitalize on prophages viruses that integrate into bacterial genomes capable of excision and replication by integrating prophages into safe carrier strains originating from probiotics i will unlock two pivotal benefits 1 rapid identification of suitable phages using advanced machine learning 2 sustained invivo efficacy yet the core advantage of phagepro lies in its unparalleled synergy of phage killing and pathogen competitive exclusion imposed by the probioticto realize this concept the development of predictive tools is essential to quickly identify the most promising prophages and probiotic combinations for each pathogen wp1 prophage engineering wp2 followed by rigorous in vitro testing will ensure a high safety and efficacy highthroughput in vivo experiments using wax moth larvae will reveal the most promising candidate which i will subsequently validate through a proof of principle experiment using a poultry model wp3although i initially tailored phagepro to treat salmonella infections in poultry its impact extends far beyond this new technology holds the potential for transformative changes in phage therapy not only advancing infection management in livestock farming through the enhancement of animal health and the assurance of food product safety but also by opening the door for targeted preventive and therapeutic interventions in human medicine
transformative rotations for adaptation and sustainable future outcome and resilience mapping

the vision of the horizonmiss2023clima0101 call is that europes regions will be responsible for their sustainable and resilient adaptation to climate change cc by developing roadmaps for adaptation of agriculture to cc these roadmaps will need to empower regional stakeholders to innovate new naturebased solutions that meet societys needs for cc adaptation through better planning that is compatible with national and international policy transform proposes that innovating new crop rotations the sequences of crops that farmers use to achieve their farming goals will deliver naturebased solutions for sustainable and resilient cc adaptation in arable and mixed farming working in the atlantic biogeographic region bioregion of europe we adopt an explicitly multiactor approach in which stakeholders are in charge of the innovation transform will cocreate with stakeholders tools and methods for regionallevel roadmaps that describe the needs for adaptation of local people in agriculture for farmers to innovate crop rotations for their region using the future rotations explorer tool and a toolbox of spatiotemporal methods and tools for stakeholders to explore and evaluate the societal economic and environmental indicators of impact of rotations when embedded within our social science methods these methods and tools will leverage an iterative pipeline to innovation for cc adaptation in agriculture that produces lists of acceptable crop rotations and maps for planning across the atlantic bioregion and ultimately the whole of europe this will allow the european commission eu member states and associated countries and their regions and stakeholders to make progress in attaining the goals of the eu mission adaptation to climate change
universal data compression with circular context trees

within the itul project funded by an erc consolidator grant we have developed a data compression algorithm based on circular context trees the proposed algorithm is universal in that it can compress any type of data the proposed compression algorithm offers unprecedented compression performance and shows an average of at least 82 improvement over commercial algorithms like lempelziv zip burrowswheeler transform compression bzip and more complex stateoftheart algorithms like prediction by partial matching ppm and context tree weighting ctw the proposed algorithm has linear decoding complexity the proposed poc is intended to extend the current binary implementation to arbitrary alphabets provide fast encoderdecoder implementation develop specific applications to compress satellite observation data and genomic data develop an indexed version of the compression algorithm in order to access some of the data without full decompression and investigate specific software licensing options and opportunities
deep utube heat exchanger breakthrough combining laser and cryogenic gas for geothermal energy exploitation

the future disruptive technology envisioned in deep utube heat exchanger breakthrough combining laser and cryogenics gas for geothermal energy exploitation deepu project is expected to revolutionize the deep geothermal energy sector the ultimate goal is to create a deep 4 km closedloop connection in the shape of a utube exchanger combining laser and cryogenic gas in a single technological drilling solution specific temperature control analysis and innovative laser lenses able to convey the heat and to sustain multilateral drilling will be developed alongside the utube creation guaranteeing liquefaction and vitrification of the rocks from ground surface to greater depths then a utube system ready to exchange heat with the underground becomes the main tool to exploit or store geothermal energy meeting energy needs in power and thermal energy production hence deepu project targets a novel and ambitious scienceto technology breakthrough in the field of geothermal exploitation the overall aim is the creation in laboratory of a vitrified waterproof noncracked utube exchanger for different kind of rocks this will be achieved by a laser drill head combined with special drill strings sustaining the coupled action of laser and cryogenic gas responsible for melting evaporating and cooling even the hardest rocks then i the physicalthermal phenomena affecting the rocks ii an evaluation of the legislative aspects and environmental standard related to the innovation proposed iii the modelling of the deepu geothermal exploitation potential considering some virtual case studies will be assessed the highrisk innovation proposed has the potential to make geothermal energy systems accessible anywhere in a targeted and demandoriented manner offering a complimentary approach and an alternative solution to traditional energy storage and production decentralizing the power supply also in areas where this is currently deemed uneconomic
paleogenomic analysis of tuberculosis epidemiological histories over geocultural and ecological networks in south america

tuberculosis tb the infectious disease produced by the mycobacterium tuberculosis complex mtbc remains one of the highestglobal disease burdens however the current body of knowledge on the mtbc is biased towards certain lineages particularly lineage 4 that spread from europe to the americas during colonial expansion recent advances in ancient dna research have the potential to broaden this picture with the recovery and analysis of whole genomes from strains that infected human populations in the past indeed these approaches have been recently used to identify ancient mtbc animal associated strains infecting humans in south american before the arrival of europeans analysis of these strains estimated that the mtbc most likely emerged during the neolithic approximately 6000 years ago much later than previously thought the pathogen project will seek to use these approaches to shed new light on the emergence diversity and spread of mtbc strains in the southern cone of the americas a neglected region concerning the epidemiological history of tb by employing ancient dna methods to examine and screen putatively positive tb infections of humans from archaeological and historic contexts of the current territory of argentina i will potentially provide genomic representation of tb histories over a broad time transect from precolonial populations to postcolonial cemeteries with these data i will perform phylogenomic and molecular clock analyses to investigate i changes in strain diversity over time in the region ii the historical and socioeconomical contexts that favoured the emergence and spread of the detected strains iii the emergence of genetic changes with potential clinical relevance identified in mtbc strains over the past centuries by offering a view of the past the pathogen project will increase our understanding of the diversity of mtbc across time and contribute a new perspective of the evolutionary and epidemiological histories of tb