Dragon09/odtu_chatbot huggingface dataset:
cease or persist a multivariate mechanistic account of effortful persistence

is this worth my effort should i persist and push through or give up and move on we are constantly confronted with this fundamental question persisting through effortful endeavors at all costs is often the key to success in modern society reduced or excessive persistence is a hallmark dysfunction in many neuropsychiatric disorders anxiety depression ocd apathy etc with massive individual and societal cost despite the urgency to better understand this process how exactly we decide to cease or persist and which cognitive neural and neurochemical systems support persistence remains unclear with cope i propose a novel neurocomputational theory of effortful persistence able to predict decisions to cease or persist cope and how they emerge from the dynamic multivariate optimization of costs and benefits across momentary and longterm time scales i propose that persistence depends on how much reward or punishment we expect how effective our efforts are and how surprising and unstable the environment is i will 1 establish and test a neurocomputational model able to simulate effortful persistence and the neural and neurochemical systems involved in supporting it 2 i will causally test the neural circuit involved in effortful persistence combining transcranial focused ultrasound stimulation with advanced neuroimaging protocols designed to capture activity in small brainstem and midbrain nuclei 3 i will probe the contribution of 3 key neurochemicals dopamine noradrenaline and serotonin and use the cope model as a prediction tool of the impact of pharmacological manipulation on brain systems and behaviour cope integrates the algorithmic neural and neurochemical levels of explanation in a unifying model of effortful persistence laying the grounds for phenotyping of abnormal decisionmaking in psychiatric disorders and personalization of treatment selection
understanding the ion distribution in lecs

sustainable recyclable and lowcost lightemitting technologies are projected to revolutionize the lighting market by introducing new applications in disease treatment packaging architecture and fashion the lightemitting electrochemical cell lec may become such a disruptive lighting technology it can be fabricated from biodegradable materials using costefficient printing or coating and offers soft areal emission from flexible and thin luminaires in contrast to established organic leds an lec comprises only one active layer in which an organic semiconductor is blended with an electrolyte under operating voltage the mobile ions redistribute and form selforganized chargeinjection and transport regions while being a promising concept for versatile nextgeneration lighting lecs currently suffer from inadequate operating lifetime and efficiency recent data suggest that the same ion redistribution that enables singlelayer functionality also induces severe excitonpolaron quenching this causes a reduction in light emission by about a factor of two and fast material degradation building on this new insight i want to combine the expertise of opeg a leading group in lec research with my knowledge in optoelectronic characterization and modeling to develop a better understanding and control of the ion redistribution process in lecs the associated suppression of ioninduced excitonpolaron quenching has the potential to enhance the lec efficiency and lifetime towards industrial relevance rendering it a promising nextgeneration light source
organic reactivities in biorenewable solvents

reactivity studies for organic reactions have so far mainly been done in classical organic solvents dichloromethane acetonitrile dmso which need oil or gas as feedstock are hazardous and cause problems with the waste treatment given that almost all organic synthesis protocols need to be revised in a postoilgas era nontoxic sustainablebydesign solvents which are based on renewable plantbased raw materials will rapidly gain importance without reactivity data however an informed redesign of organic synthesis is impossible resolvebybio will deliver the data for defining the scope of electrophilenucleophile reactions in biobased solvents which will be used in the future eulocated chemical suppliers have recently started to commercialize some of these biobased solvents though they have been considered expensive the steep increase of prices for oilgasbased chemicals makes them more and more attractive once established scaling effects will make biobased solvents strong price competitors of conventional solvents however these biobased solvents are still awaiting broader acceptance in academia and commercial chemical applications integrating them in the currently most comprehensive reactivity scales mayrs database of reactivity parameters will foster their applications and significantly contribute to reducing the negative impacts of chemistry research and businesses on the environment thus the data generated by the proposed project will deliver important building blocks for the conversion of the eu chemistry towards reaching the goals of the eu green deal by empowering chemists with the some of the most fundamental data that are required to change chemical processes
discovering how plants sense water stress

water stress is an increasing problewater stress is an increasing problem for global agriculture given the impact of climate change despite the fundamental importance of water exactly how plants sense its availability remains unknown this new knowledge is vital for designing more climate resilient crops yet currently remains a critical gap in scientific understanding our unique synergy is ideal to take on this ambitious project and discover how plants sense water after identifying membrane proteins from a proofofprinciple multitargeted genetic screen designed to reveal components of the watersensing hydrosensing machinery we hypothesise changes in plant hydraulic fluxes driven by transient water stress are sensed by a specialised cell type termed phloem companion cells that controls the synthesis and release of the abiotic stress signal aba release of aba by water stress is triggered by perturbations in plasma membranecell wall contact sensed by kinases like theseus1 the1 and additional missing components which we will identify using our custom multitargeted cirspr libraries our discoveries will unlock the mechanism enabling sensing of the most important molecule on the planet water in the most abundant lifeform biomasswise plantssolving how plants sense water demands a highly interdisciplinary strategy that goes beyond the cutting edge by pioneering the development of innovative genome editing functional imaging and structural biology approaches the breadth and depth of capabilities and expertise to undertake this strategy necessitates a synergistic partnership between worldleading groups to go beyond the current state of the art by pursuing this highriskhighgain strategy our project promises to reveal common design principles that underpin the core mechanisms for water stress signalling in plants this new knowledge is crucial for international efforts to design climateresilient crops and underpin global food security
open geometry pet with 150ps tof resolution for real time molecular imaging

openimaging will develop an innovative open imaging system highly flexible and adaptable to the organ to be examined the system of the proof of concept will consist of two large paddle detectors built with the novel pet positron emission tomography technology developed in 4dpet ercadg outstanding 150ps coincidence time resolution and placing the detectors closer to the field of view fov will dramatically increase the sensitivity allowing high resolution and high contrast images at lower dose factor 10 than current commercial scanners it will open up new venues for real time imageguided interventions surgery radiation therapy and invivo tracking of small number of cells it will also enable performing repeated scans for active surveillance of suspect patients diminishing the number of false positives and a safer posttreatment for instance chemotherapy followup
using ex vivo functional genomics as biomarker to predict the effectivity of venetoclax in patients with acute leukemias

for decades oncologists treating cancer patients desire biomarkers that predict drug sensitivity on a patient individual level unfortunately the challenge remains unsolved until today as treating clinicians are unable to identify the patients who benefit most and despite advanced multiomics diagnostics the majority of cancer patients are treated according to risk groups as a result patients receive inactive drugs without benefit but adverse effects and european healthcare systems lose significant resources without gain during my erc cog work we developed a completely new test principle which has the potential to bridge the gap the group of targeted anticancer drugs causes tumor cells to die by inhibiting a single specific signalling molecule we used the crisprcas9 mediated gene knockout to mimic the activity of such targeted drugs in proofofprinciple work we used patientderived xenograft pdx leukemia models to show that the knockout of a target gene in vitro was able to predict which patients pdx model responded to treatment with the respective drug in vivo here we plan to optimize our test system by studying knockout of bcl2 to predict sensitivity to the bcl2 targeting drug venetoclax the planned work harbours the potential of a major breakthrough to solve a longstanding challenge in anticancer treatment namely to predict which individual patients tumor responds to which targeted
pharmacoepigenetics for precision medicine in type 2 diabetes

the prevalence of diabetes will rise to 592 million in 2035 type 2 diabetes t2d is a leading cause of death through its vascular complications high glucose increases the risk for complications and thereby suffering for patients and costs for society it is important that patients with t2d receive an optimal therapy that lowers blood glucose metformin is firstline t2d therapy however 30 of patients do not respond to metformin currently there are no biomarkers that predict the response to metformin we discovered bloodbased epigenetic markers that could discriminate between respondersnonresponders to metformin in drugnave patients with t2d this epigenetic tool may be further developed to help patients with t2d receive an optimal therapy the aim of proceed is therefore to develop and commercialize our pharmacoepigenetic tool we expect this biomarker tool to aid clinical decisionmaking in t2d therapy
brainstem circuits supporting adaptive instinctive behaviours

instinctive behaviours that achieve defence feeding aggression and parental care have evolved across animal phyla to ensure survival without the need for learning contrary to common belief instinctive behaviours are not hardwired reflexes but can be flexible in both action selection and execution they are modulated by internal states such as stress hunger or oestrous cycle and may undergo short and longlasting adaptations in order to accommodate environmental changes and individual needs the aim of this proposal is to gain a mechanistic understanding of adaptive instinctive behaviour output within a quantitative neuroethological framework and by combining molecular cellular and circuitlevel approaches i will focus on the vertebrate periaqueductal gray pag an evolutionarily conserved brainstem region that plays a crucial role in the initiation and execution of virtually all instinctive behaviours despite this a comprehensive analysis of the cellular and network properties of the pag and their behavioural correlates is lacking in addition to generating the first dataset of pag network topology using high resolution in vitro anatomical and electrophysiological approaches we will study its neural computations across multiple instinctive behaviours and during motivational conflict using neural activity recordings in freely behaving mice building on these results we will test the role of neuromodulation in imparting flexibility to this circuit and the selection of appropriate behaviours focussing on naturallyoccurring neuromodulatory changes during the oestrous cycle by establishing how the pag a critical circuit that closely precedes motor neuron recruitment controls and imparts flexibility to instinctive behaviours this proposal will expand our knowledge on the neural and molecular basis of adaptive behavioural output that is fundamental for the survival of all animals with an emphasis on the female brain
deconstructing and rewiring rnarbp regulatory networks

rnabinding proteins rbps are critical regulators of gene expression programs they regulate all aspects of rna life including transcription splicing modification localization stability translation and decay and consequently perturbations in these rbprna networks underlie the origin of many diseases recent proteomicsbased studies have vastly expanded the repertoire of rbps to the thousands uncovering unconventional rbps such as metabolic enzymes moonlighting in rnabinding activity or rnas riboregulating protein function this represents a much broader layer of biological control that was previously envisaged which adds an entirely new dimension to rbpdependent regulation of cellular homeostasis rbpregunet has been conceived to leverage these new discoveries to identify druggable targets for a range of untreatable diseases including cancer neurological disorders liver diseases and infectious disease our ambition in rbpregunet is to create a highlevel training program based on basic research but with a strong impact on clinical translation rbpregunet will provide advanced multidisciplinary scientific training that spans from computational structural molecular and cellular biology to medicinal chemistry and pharmacological screening to the next generation of european researchers in an intersectoral environment to pursue ambitious and high gain research on the development of new therapies based on rbp biology they will be trained in a range of core and stateoftheart disciplinespecific research skills complementary transferable skills and entrepreneurial skills by secondments to nonacademic partners with a common focus to discover actionable targets this network of excellence will push the boundaries of knowledge in the proteinrna interactions universe and at the same time provide the next generation of students with the skills to become future leaders in the field
strengthening farm health and safety knowledge and innovation systems

safehabitus will make farming a safer occupation farming is amongst the most dangerous jobs in europe european statistics show that the fatality rate in farming is 233 higher than other industries and the accident rate is 18 higher these figures underestimate the scale of the problem as a significant proportion of farm workplace fatalities injuries and ill health go unreported uninvestigated and prevention approaches are not learned improving farmers and farm workers health and safety requires action by a range of stakeholders to empower and support them to change unsafe practices and adopt new safer and healthier ways of working safehabitus is a multiactor project that has come together to strengthen farm health and safety knowledge innovation systems fhs kis and support the eu transition to social sustainability in farming our premise is that driving health and safety on farms is not about dissemination but changing habitual practices to achieve this safehabitus applies a range of novel methods digital story telling methods with people who experienced accidents application of the multiactor approach to codesign farm work risk management tools foresight analysis analyses of consumer willingness to pay for food production that protects health and safety benchmarking policies and elite interviews with policy makers our consortia include endusers stakeholders and researchers in case study member states these work together in ten national cops covering a representative variety of countries and sectors safehabitus also engages with european bodies and stakeholders who provide critical bridges between eu and national regional actors and who can influence eu policy such as the geopa copacogeca ceja effat oxfam svlfg and aeidl this multilevel and transnational approach will allow safehabitus advance safer practices on farms across the eu
integrated protection and restoration approaches for natural lake ecosystems

eurolakes project proposes an innovative holistic and sciencebased approach to safeguarding and restoring european natural lakes and their ecosystems this project builds upon the 4 returns framework for landscape restoration a practical methodology designed to seek sustainable longterm solutions at the landscape level with the aim of achieving four types of returns inspiration social benefits natural restoration and financial gains this holistic approach is realized through five key elements establishing a landscape partnership fostering shared understanding collaboratively envisioning the landscape taking coordinated action and continuously monitoring and learning the eurolakes project will establish local communities of practice and in collaboration with them develop and showcase innovative integrated protection and restoration solutions with a particular focus on naturebased solutions nbs these solutions will be demonstrated in three specific areas lake vico in italy lake bistre in romania and lake dümmer in germany furthermore the project will highlight the longterm potential for replication by enhancing local capacity in denmark ireland and moldova these approaches will be complemented by modeling activities and the dissemination of knowledge regarding nature finance contributing to a comprehensive adaptive management strategy aimed at restoring the ecological and chemical health of natural lakes to a good statusin this way the eurolakes project will directly contribute to the objectives of various eu instruments and policies including the water framework directive the green deal and its mission objective to restore protect and preserve the health of our oceans seas and waters by 2030
ethme the ethics of mortality measurement

there are around 55 million deaths in the world each year how should we evaluate these deathsdiseases and injuries give rise to both morbidity and mortality until the 1950s epidemiologists were concerned with counting the number of deaths since then evaluative measures concerned with the disvalue of death have grown in parallel there has been a debate in analytic philosophy since the 1970s that concerns whether death can harm those who die the philosophers in this latter debate have not focused on deaths at a population levelin all societies the demand for health care exceeds the available resources however to prioritizescarce resources in a consistent and meaningful manner we need reliable health measurements to begin with in society we use considerable resources to prevent deaths and the majority of the global disease burden springs from mortality rather than morbidity thus it is remarkable that so few resources are used to provide theoretically robust death measurements peoples attitudes toward death are naturally ambivalent on the one hand death is the worst thing that can happen to us on the other hand death is nothing to us sophisticated methods have been developed to measure morbidity such work remains for mortalitythere have been almost no crossfertilizations between epidemiology and philosophy regarding mortality measurement accordingly ethme announces the ethics of mortality measurement as a novel and developing field within the philosophy of epidemiology the core objectives of ethme are to a develop and refine the understanding of the nature of the harm of death b reconcile the evaluation of deaths in summary measures of population health with the most promising accounts of the harm of death and c develop a theoretical grounding for evaluating procreation in future individuals one work package will be devoted to each objective wp1wp3
from behavior to values an unexplored process of personal value development

given their role as powerful motivators of behavior values are a key focus of educational programs but are difficult to remold once set our and others recent longitudinal studies of youth indicate that changes in behavior may lead to changes in valuesand may be a more efficient way to alter values than seeking to directly modify them this behaviorvalue link opens a new theoretical avenue for studying value changesin bevalue i propose to conduct the firstever systematic assessment of the bahaviorvalue link i will build a novel comprehensive theoretical model for understanding and testing how behavioral changes affect values the theoretical model will answer three fundamental questions what is the impact of behaviors on values what are the mechanisms that explain this process what conditions or factors allow or prevent this processbevalue will focus primarily on adolescents address multiple levels individuals peers parents cultural characteristics and combine the following diverse methodologies natural field experiments to assess how presocialenvironmental behavioral change leads to value change wp1 appbased and virtual reality experiments to examine the cognitive and emotional mechanisms of the behaviorvalue link wp2longitudinal survey to trace construct development wp3 schoolbased intervention designed to enhance proenvironmental behavior as a means to examine how behavioral change predicts value change and the role of selfconsciousness in this process wp4 diary study to assess micro behaviorvalue longitudinal relations and the contribution of parental attribution wp5 largescale stateoftheart natural language process analysis of how behavior in social media platforms relates to future values in a broad population across various cultureswp6 the behavioral change model will potentially serve as a practical tool for educators parents and policy makers to advance prosocial proenvironmental and other values
towards advanced multidisciplinary fault observatory systems

near fault observatories nfo are natural laboratories undergoing active and complex geophysical processes at or in proximity to densely populated urban areas nfos bound relatively small areas and are ideal sites for indepth monitoring and advanced research six nfos in europe have been identified by the european plate observing system as longterm research infrastructures three additional nfos are in observer status nfos target the enhanced understanding of the mechanics of earthquakes to unravel the anatomy of complex seismogenic faults this can only be achieved by the acquisition of continuous longterm highresolution highquality and highdensity multidisciplinary data and the application of consistent high quality and stateoftheart data processing transform has the ambitious goal of improving and transforming the existing nfos by integrating cuttingedge methodological and technological solutions paving the road for the next generation nfos across europe this will be achieved through the development of four concepts i innovative sensors new generation of sensors in basic and applied research related to earthquake processes ii elevated detectability novel automatic workflow for enhanced detectability and characterization of earthquakes iii early warning new platforms for supporting decisionmakers during earthquake alerts iv testbed next generation of accessibility for testing and development of new cuttingedge sensors and algorithms a focus will be on bringing transformative concepts such as machine learning and fiber optic cable sensing to the nfo community breakthrough ideas will be explored and addressed with focus on analytical and feasibility control detecting weaknesses and missing elements that will be resolved within the project awareness and engagement of stakeholders as well as societal needs will be a priority issues concerning nfo funding and sustainability will be addressed