Dragon09/odtu_chatbot huggingface dataset:
deep mutational scanning of target protein resistance to molecular glues

interactions between proteins and small molecules are rich in nature across organisms tissues and cellular contexts they underly crucial biological functions in health and disease one class of small biochemicals molecular glues mgs can selectively induce de novo proteinprotein dimerization particularly in the context of targeted protein inhibition and degradation mgs are praised as clinical alternatives to treating diseases driven by proteins that are otherwise pharmacologically intractable prominent examples like rapamycin a mg used in the therapy of kidney tumours illustrate a key research challenge however up until now most mgs have been discovered by chance our limited understanding of their biophysical characteristics prevents us from rationally designing mgs and from tracing drug resistance mechanisms by target proteins mutational escape during cancer evolutionhere i propose a scalable experimental strategy to determine the binding profiles of mgs to thousands of target protein mutants in parallel to perform comparisons of the biophysical impact of mutations on distinct mg mechanisms i have three major aims 1 to develop a deep mutational scanning assay to quantify mgproteinprotein complexation 2 to produce the first global atlas of resistance mutations for a classic mg system rapamycin in complex with mtor and fkbp12 and 3 to characterise aba a plant hormone which induces heterodimer formation by extensive structural remodelling of only one of its target proteinsdeepglue will take place under the experienced supervision of prof ben lehner crg barcelona whose group has pioneered the use of deep mutagenesis to understand protein structures dynamics and interactions within this environment my action will be uniquely positioned to transcend the dynamic fields of chemical biology protein biophysics and cancer evolution aspiring to deliver fundamental insights that ultimately shape new and better therapies
remaking sex observing representing and explaining sex difference in early modern european vernaculars

since thomas laqueurs controversial arguments in making sex body and gender from the greeks to freud 1990 scholars of gender history have debated the shift from socalled onesex model in which the bodily differences between male and female human beings were thought to exist on a continuum from a fully formed human male body to an inferior less male female body to the modern twosex model at the beginning of the nineteenth century building on critiques of laqueurs arguments this project analyzes vernacular texts treating sex differences hermaphroditism and human reproduction circa 16001800 in german french english and spanish in medical and nonmedical sources although the onesex model did not dominate premodern and early modern medical discussions of sex difference as laqueur argues in the learned latin traditions taught in medical faculties in universities european vernacular literatures in the seventeenth and eighteenth centuries paid special attention to specific visual and spatial analogies between male and female anatomies and debated the possibilities and implications of sex ambiguity and sex change the project analyzes how vernacular texts described the determination of sex difference the extent to which male and female bodies were different and in what sense what the stakes were of failing to determine the maleness or femaleness of a body and the specific social political and religious anxieties about gender roles and norms the family literacy sexuality and religious piety were expressed and developed in the discussions of sex difference and determination
beyondclassical machine learning and ai for quantum physics

a primary challenge in quantum computing qc is finding its ideal application ie an essential problem with the largest advantage of quantum over classical computing to resolve it i propose to focus on the notoriously complex area of quantum manybody systems this project will characterise which quantum manybody problems in various physics domains allow for significant quantum advantages even over any future machine learning datadriven methods by exploiting my pioneering research in this area i will also develop new quantum machine learning qml methods to solve them better than classically possible using a twostage approachin the first stage we will develop the projects theoretical foundations my recent works on quantumoverclassical learning advantages provide the starting points for the development of new mathematical machinery which facilitates the proving of quantum advantages in selected manybody settings in parallelbuilding on circuitdecomposition methods i recently developed we will elucidate the role of quantum phenomena in qml in order to design new qml methods which can be better tuned to quantum manybody settings in the second stage we will identify suitable concrete quantum manybody problems with substantial realworld interest apply the newly designed highperforming quantum learners and formally prove learning advantages using the developed theoretical machinery the positive results of the project will resolve some of the main open problems in qml and will have a major impact on both qc theory and aspects of foundations and applications of qml in our search for the best application we will consider manybody problems from diverse areas of physics condensed matter highenergy and quantum control the project will therefore also establish new bridges between quantum manybody physics machine learning and quantum computing
shaping consumerinclusive data pathways towards the energy transition through a reference energy data space implementation

synergies introduces a reference energy data space implementation that will attempt to unleash the datadriven innovation and sharing potential across the energy data value chain by leveraging on data and intelligence coming from diverse energy actors prioritizing on consumers and introducing them as data owners providers and coupled sectors buildings mobility and effectively making them reachable and widely accessible in turn it will facilitate the transition from siloed data management approaches to collaborative ones which promote the creation of a data and intelligence ecosystem around energy and other types of data and enable the realization of data intelligencedriven innovative energy services that i value the flexibility capacity of consumers in optimizing energy networks operation maximizing res integration and selfconsumption at different levels of the system community building ii evidently support network operators in optimally monitoring operating maintaining and planning their assets and coordinating between each other tsodso collaboration for enhancing system resilience iii create an inclusive pathway towards the energy transition through consumer empowerment awareness and informed involvement in flexibility market transactions iv step on real data streams and intelligence to deliver personalized and automated features to increase prosumer acceptance and remove intrusiveness v facilitate the establishment of sustainable lecs by enhancing their role with aggregator and bsp functions and vi establish solid grounds for the creation of a new economy around energy data produced and shared across a complex value chain in a secure trustful fair and acceptable manner synergies will be extensively validated in 3 largescale demonstration sites in greece spain and denmark involving complete value chains diverse data sources heterogeneous energy systemsassets and spanning different socioeconomic characteristics
supplychain mechanisms for safeguarding south american chacos last intact forests

agricultural expansion continues to drive the loss of tropical forests resulting in huge socialecological tradeoffs including biodiversity loss carbon emissions and the erosion of the resource base of forestdependent communities halting deforestation has thus become a global policy goal but is currently hindered by four main knowledge gaps all of which this action will address first not all tropical forests are equal and many are degraded but where remaining highnaturevalue hnv forests are is often unknown second many forest conservation tools are available but their effectiveness in protecting hnv forests is unclear third supplychain interventions are potentially powerful but missing supplychain data limits their application finally the relative importance of domestic vs foreign consumption is often unknown focussing on the south american chaco an understudied global deforestation hotspot this action will use stateoftheart remote sensing impact evaluation and supplychain analyses to provide the first assessments of the distribution of hnv forests in the chaco which policy options effectively protect them and what the environmental footprints of domestically used vs traded forestrisk commodities produced are through the action the er will broaden his research scope acquire new technical and transferable skills and train leadership ability together this will make him a very competitive candidate for independent positions in sustainability science the outcomes of the action include highimpact publications as well as policyrelevant information delivered to key stakeholders in south america and europe through various dissemination pathways overall this action will impact our understanding of the status and governance of hnv forests in the neglected dry tropics which is critical for the eus due diligence initiatives seeking clean supply chains and for maintaining socialecological integrity in the global south
ice modelling the global multicentury evolution of glacier ice in 3d

glaciers are key contributors to sealevel rise and are critical water resources that supply fresh water to hundreds of millions of people around the world it is therefore of paramount importance to accurately simulate the future evolution of these precious ice bodiesdespite recent progress in modelling the global evolution of glaciers existing simulations suffer from vast uncertainties related to i model input ii a simplified representation of glacier processes and iii an important mismatch between the timescales over which models are calibrated multiannual to decadal and those over which the future glacier projections occur century timescale ice will revolutionise the regional to globalscale modelling of glaciers by i strongly reducing uncertainties in model input through innovative inversion of climatic information ii developing new approaches to model glacier processes in 3d and iii for the first time simulating past glacier evolution globally over centennial time scales with an icedynamic modelthese improvements will culminate in new global glacier evolution projections under a range of future emission scenarios which will in turn inform the next generation of sealevel rise and water availability projections while redefining the landscape of largescale glacier modelling ice will also ensure that the novelties it produces are incorporated in climate change impact models to guide policymakers and practitioners in adapting to a changing environment
climate impacts on diatom genomes over micro and macroevolutionary timescales

diatoms are a group of highly diverse globally dominant microalgae which contribute significantly to global carbon fixation and biogeochemical cycling understanding how diatoms adapt to changes in their environment is therefore a major research interest however whereas the phenotypic outcomes of adaptation have received considerable attention we understand little about the genomic underpinnings of evolution and adaptation in diatoms within diadapt i will investigate the genomic processes that underlie adaptation to climate shifts in diatoms to this end i will focus on two evolutionary radiations of nonmodel diatoms that are characterized by the repeated colonization of different climate zones throughout their evolutionary history yet that played out in different ecological conditions the aquatic and terrestrial realm comparative analyses of genomes and transcriptomes obtained from taxa that inhabit polar temperate or tropical regions will be complemented with experimental evolution as such i will investigate the roles of both genome and gene expression evolution in climatedriven adaptation over macro and microevolutionary timescales thus capturing different stages of the adaptation process by implementing diadapt within a robust phylogenetic framework and contrasting the two evolutionary radiations i will i formulate general insights into the genomic basis of climatedriven adaptation in diatoms ii reveal the degree of divergence and repeated evolution in adaptive solutions and iii discern if and how adaptation is constrained by evolutionary history including differences in ecology population size and historical patterns of climate zone transitions altogether the integration of macro and microevolutionary approaches on the scale of genome and gene expression divergence will generate a deep understanding of climatedriven adaptation in a keystone microbial lineage on an unprecedented geographic and taxonomic scale
analysis of dynamics and amorphization of metal oxides mox

the adamox project analysis of dynamics and amorphization of metal oxides mox addresses a critical need in catalysis particularly for the shift from traditional fossil fuels to clean and renewable energy sources aligning with the european green deals sustainability goals mox catalysts play a central role in these chemical transformations but their structural complexity poses challenges in designing efficient catalysts therefore adamox leverages advanced computational methods to explore the structural dynamics of mox catalysts during operando conditions this project aims to uncover vital structureactivity relationships offering theoretical guidance to advance highperformance catalysts key objectives include understanding the formation of disorderedamorphous ensembles on mox surfaces exploring structureactivity relationships in catalytic reactions and developing a universal operando simulation workflow for thermoselectrochemical catalytic systemsthe interdisciplinary approach integrates computational chemistry machine learning and experimental techniques enhancing the fundamental understanding of heterogenous catalysis furthermore this project adheres to open science practices ensuring transparency and collaboration within the scientific community for the researcher dr li under the guidance of prof nria lpez at iciq this project offers her a unique scientific career development opportunity to excel in a traditionally maledominated area it provides a platform to contribute to groundbreaking research while championing openness and diversity in sciencein summary adamox advances catalysis for clean energy and sustainable processes offering exciting career prospects for the researcher while promoting open science and gender diversity in research
hernando colns universal library european culture and intellectual production at the dawn of the global world

while newly printed books were circulating widely around europe when more than half a century had passed since gutenbergs invention hernando coln 14881539 second son of christopher columbus undertook the extraordinary challenge of keeping physical track of the proliferation of knowledge he not only purchased everything incessantly and everywhere marking on the books place and date of purchase the local price and the conversion to spanish currency for accessing managing and reusing his colossal library he and his invisible technicians also developed a sophisticated crossindexing and symbols system which is foundational in the history of bibliography and knowledge management the colombina library of seville still preserves over one third of the almost 16000 titles which coln left at his death as well a dozen manuscript indexes and catalogues that recording all sorts of information make it possible to reconstruct the lost portions of the collection including the volumes famously shipwrecked on their way from venice to seville in 1521 financing gathering cataloguing and managing a library of such scale required widespread connections the support of an international network and a vision deeply intertwined with the politics of knowledge acquisition of the newborn spanish empire colibri aims at opening the doors and explore the legacy of the most important library of the early modern period completing the reconstruction of its content in order to investigate it understanding how it worked as the first largescale information processing system of modern times and as a place for the production not only for the storage and preservation of knowledge exploring the still new relationship between written and print culture and the early european and intercontinental book market finally showing how the movement and the stories of colons books reflect the developments of western culture of the last five centuries
regions and edihs alliance for aiattheedge adoption by european industry 50 manufacturing smes

the i4ms program in h2020 has been and is a great success for the digital transformation of european manufacturing smes phase iv of the program was focussing on dihs and on highly innovative technologies like digital twins and ai in particular the ai regio innovation action developed a virtuous alliance between regions dihs ai solution providers and manufacturing smes which is materialised by a new methodology for dihs service portfolio and customer journey analysis an ai4eu oriented toolkit of data and ai resources a network of didactic factories and their technology and regulatory sandboxes teresa and an ecosystem of smedriven experiments and their digital transformation pathways it is time now to align such important outcomes to the evolution of manufacturing towards industry 50 the evolution of cloud ai technologies to aiattheedge the evolution of h2020 to horizon and digital europe programmes eg to edih data spaces and ai tefs testing and experimentation facilities for manufacturing some of the ai regio i4ms phase iv motivations are now evolved it is time for ai redgio 50 for keeping momentum of ai technologies adoption in manufacturing smes ai redgio 50 aims at renovating and extending the h2020 i4ms ai regio alliance between vanguard eu regions and dihs for a competitive aiattheedge digital transformation of industry 50 manufacturing smes ai regio outcomes methods and tools for dihs governance and crossdih collaboration data space and ai for manufacturing toolkit didactic factories network and teresa facilities smedriven experimentations in 14 vanguard regions will be i extended to the i50 principles ii enabled by the newest trusted technologies along the edgetocloud continuum iii supported by european open source hwsw reference implementations preserving eu values and ethical principles iv interconnected with the edih network in dep as well as with the ai tef nodes and the data spaces deployment program
beyond renormalization in parabolic dynamics

the ergodic theory of parabolic dynamical systems is an area in smooth ergodic theory that is relevant for its connections to mathematical physics and to analytic number theory a dynamical system is parabolic whenever its orbits diverge at an intermediate often polynomial rate between boundedlogarithmic called elliptic and exponential called hyperbolic ratethe proposal tackles several outstanding questions in the ergodic theory of parabolic flows with emphasis on quantitative aspects the main goal is to go beyond renormalization techniques that have proved extremely powerful in several classes of examples interval exchange transformations and flows on surfaces horocycle flows nilflows on quotients of steptwo nilpotent groups and gauss sums renormalization methods are not available in other equally fundamental examples of similar nature billiards in nonrational polygons higher step nilflows and nonhorospherical unipotent flows in homogeneous dynamics a unified approach to effective ergodicity is proposed that encompasses all of the above mentioned examples outstanding questions include ergodicity and existence of periodic orbits of nonrational billiards in polygons effective ergodicity of higher step nilflows with optimal deviation exponents and applications to bounds on weyl sums for higher degree polynomials and effective ergodicity of nonhorospherical unipotent flows on semisimple finitevolume quotients the analytical foundations of the method lie in the study of invariant distributions for parabolic flows in the examples considered the analysis can be carried out by methods of nonabelian fourier analysis theory of unitary representations in general for nonhomogeneous parabolic flows all questions concerning invariant distributions and their relevance for smooth ergodic theory are wide open several problems to probe the question of existence of invariant distributions are proposed
photonic chip based highthroughput multimodal and scalable optical nanoscopy platform

the invention of superresolution optical microscopy nanoscopy has given us a glimpse of its impact in all fields of science and medical care imagine the new scientific discoveries that can be realized if every research and clinical laboratory is equipped with an optical nanoscope that can deliver superresolution imaging enabling researchers a window to nanoscale biology however several pain points of the available solutions currently hinder wide scale penetration of optical nanoscopy such as cost complexity small throughput and limited flexibility in terms of choice of resolution and fieldofview fov nanovision will fill this pressing gap in the market with an affordable compact multimodal and highthroughput photonicchip based optical nanoscopy present day nanoscope uses a simple glass slide to hold the sample and a complex and bulky microscope setup to illuminate and image we change the current paradigm to a massproducible photonicchip to hold and illuminate the sample and a simple and compact optical microscope to image it our radical idea is thus to take out laser light steering and delivery from the microscope and transfer it to a photonicchip photonicchip based nanoscopy improves the throughput by a factor of 100x reduces the cost by a factor of 2x and provide flexibility in terms of resolution and fov these key differentiator of nanovision will not only extend the present market of nanoscopy but could also open new market opportunities founded on two patent families it has been brought up to trl 4 a spinoff chip nanoimaging cni has been incorporated nanovision will propel the technology to trl 6 by developing a userfriendly prototype and validating its impact during yearlong user tests the business and market development activities will enable us to attract investments of euro2m by 2024 with an estimated revenue of euro60m by 2029