Dragon09/odtu_chatbot huggingface dataset:
publicprivate insurance partnerships for adapting to multihazard climate change risks

natural disasters cause substantial economic losses which are expected to increase due to climate change the insurance sector plays a central role in managing these risks it is thus imperative that insurers accurately assess and address climate risks risk assessment methods currently fall short in accurately understanding climate risks because they focus on single hazards eg floods instead of correlated multihazard risks eg windstorms and floods affected by climate change they also insufficiently account for human climate adaptation processes leading to risk reduction which are characterized by bounded rationality and social interaction furthermore additional insights are needed into how to design insurance arrangements that address climate change and stimulate policyholders to adapt to multihazard climate risks by limiting natural disaster damagethis project aims to design insurance arrangements to enhance policyholders adaptation to multihazard climate risks by combining financial coverage with comprehensive strategies for stimulating risk reduction its interdisciplinary approach goes beyond the stateoftheart by creating novel multihazard climate risk assessments for insurance and by developing agentbased models abms that account for boundedly rational human adaptation decisions and social interaction the abms evaluate natural disaster insurance arrangements for eu countries with diverse risk contexts and assess strategies for stimulating adaptation by policyholders based on input from behavioural economic studies repeated and realtime surveys and economic experiments will identify comprehensive strategies for triggering behavioural change to stimulate adaptation to the multitude of climate change risks individuals face these strategies linked to publicprivate insurance combine communication on risk and risk reduction measures insurance incentives eg deductibles premium discounts and nudges
twinning for new graphenebased composites in electromagnetic interference shielding

intensive growth of both the telecommunication and electronic industry in recent years is occurring with the spreading of electronic device usage in everyday life the pollution caused by electromagnetic waves ews is ubiquitous ews are predominantly emitted from cell phones wifi microwave ovens etc electromagnetic interference emi demonstrates a strong negative impact on electrical devices and affects human health causing leukemia and brain tumors and the danger of emi is underlined for those with implanted active medical devices thus textile fabric that can absorb ews is in high demand in resolving such a lifethreatening matter another arising problem with ews is their effect on the working performance of electronic devices leading to untrusted signals and noise to prevent degradation by unwanted currents and voltages instrument obstruction false results and to reduce measuring time materials able to neutralize emi effects are highly needed the grinshield project will bring innovation in the field of shielding materials by exploring new nanomaterials as a protective barrierthe goal of this project is twofold to increase significantly the scientific excellence of the consortium by addressing a scientific issue with potential economicindustrial impact producing efficient shielding material based on nanotechnology materials for emi protectionto improve the administrative skills of the coordinator institution from the widening country staff through collaboration with members of the consortium from fra ger and slo offices by working with topclass partners researchers from the widening country will improve scientific skills work with cuttingedge instruments and gain frontier education enhance project writing skills and improve publication records while the administration will become a competitive dynamic and efficient instrument for preparation of international projects as well as their implementation
molecular design and application of spliceswitching antibodyoligonucleotide conjugate for hypertrophic cardiomyopathyrelated mybpc3 splice modulation

familial hypertrophic cardiomyopathy hcm is the most common inherited heart disease and is predominately caused by mutations in genes that encode proteins associated with cardiac sarcomeres the functional unit critical for basic contractile heart function nearly twothirds of individuals with hcm experience mild to no symptoms whereas the remaining onethird experience dyspnea chest pain or arrythmias that can progress into heart failure causing sudden cardiac death particularly in young competitive athletes current strategies to treat hcm include invasive procedures such as septal or left ventricular reduction therapies or cardiac implantation such methods are not curative but rather aimed to treat symptoms and not the pathophysiological cause of the disease thus highlighting the importance of new molecular therapies that can prevent hcm one potential method to correct hcm mutations is through the use of antisense oligonucleotides asos short polymeric nucleic acid biomolecules that can correct aberrant rna splicing a fundamental biological process for gene expression by binding to premrna splice sites and block recognition by the spliceosome however delivery of asos to cardiac cell models including cardiomyocytes differentiated from human induced pluripotent stem cells ipsccms remains to be one of the biggest challenges in aso efficacy herein this project proposes to design and test the effects of chemicallymodified spliceswitching antisense oligonucleotides conjugated to an antibody an antibodyoligonucleotide conjugate aoc using a unique traceless linker strategy that has the potential to not only treat splicing defects in hcm but also provide proofofconcept of improved cell delivery of asos aocs will be tested in ipsccms bearing cryptic splice mutations in mybpc3 myosin binding protein c a gene whose mutations are commonly associated with hcm
assessing philosophical authors and texts from herculaneum and elsewhere on early stoicism insights into ancient logic physics and ethics towards a new von arnim

alongside epicurus school stoicism is the most important current of thought in hellenistic philosophy the first phase of this school extends from zeno of citium 334333262261 bce to chrysippus followers viz up to the end of the 2nd century bce apart from some fragments transmitted by the medieval manuscript tradition and by the herculaneum papyri only indirect witnesses on the early stoics remain today the huge corpus of this material was collected mostly in hans von arnims stoicorum veterum fragmenta 190305 despite some partial attempts to correct and integrate this collection von arnims pioneering work is still the reference point in studies on early stoicism the present project aims to remake this work entirely through an innovative interdisciplinary methodology incorporating classical philology the history of ancient philosophy doxography papyrology and epigraphy new technologies for deciphering ancient manuscripts and will be divided into the following steps 1 a new critical edition of most of the fragments and testimonia at issue 2 a wider selection of the sources and a revision of some manuscripts 3 a new methodology for reading and reconstructing the papyrological sources 4 an innovative historicophilosophical methodology for commenting on and interpreting the extant sources 5 the creation of a website along with a digital database publication of partial and comprehensive outcomes for the project the editions will be divided into four parts focused on zeno of citium the disciples of zeno including the heterodox stoics chrysippus and the disciples of chrysippus respectively each volume will be accompanied by commentaries also devoted to stoic figures sometimes neglected in scholarship eg diogenes of babylon this project aims to revolutionize our knowledge of this fundamental phase of hellenistic philosophy by throwing new light on the history of ancient physics logic and ethics
towards early cancer detection and tumor classification using epigenomic biomarkers in blood

early cancer detection could increase curative treatment and longterm survival dying cells release small dna fragments wrapped around a core of histone proteins into the bloodstream socalled circulating cellfree nucleosomes cfnucleosomes they carry dna sequence information and histone modifications stable in blood reflecting promising epigenomic disease biomarkers but the low proportion of cfnucleosomes originating from cancerous cells versus the large background of nucleosomes arising from dying blood cells poses significant challenges for early cancer detection using circulating cfnucleosomes in epicblood i will tackle these challenges and propose two complementary strategies to increase the number of cancersignature cfnucleosomes for cancer detection and tumor classification in the first strategy i will employ my previously developed synthetic histone modification readers to profile abundant histone modifications on cfnucleosomes allowing me to seize up to 35 percent of the human genome noninvasively i will prove this technologys concept by detecting earlier stages of pancreatic cancer and simultaneously classifying molecular tumor subtypes furthermore i hypothesize that tumorigenesis gives rise to cancerspecific genomic sites decorated with combinatorial histone marks socalled bivalent regions found explicitly in cancer and not in healthy adult cell types in the second strategy i will employ a computational pipeline to map cancerspecific bivalent sites across multiple cancer genomes i will use my wellestablished combinatorial histone mark readers to test their diagnostic potential as cancerspecific biomarkers in blood plasma from healthy donors and cancer patients my genomics expertise and proven technology provide an excellent basis for accomplishing the planned goals epicblood will be a major step towards developing precise and rich liquid biopsy assays for multiple clinical applications in cancer management
econometric machine learning for better heterogeneity representation

modeling behavioral patterns of commuters and their decisionmaking process is crucial to develop sustainable and effective transport policies predict and forecast the travel mode choices of a certain population with respect to changes in some attributes or components of the transportation system and determine the different sources of heterogeneity in tastes and preferences econml is about developing hybrid frameworks that combine several machine learning techniques with econometric discrete choice models to better account for different aspects of unobserved heterogeneity within a population such as systematic and random taste variations in addition to market segmentation the proposed models would abide by mcfaddens vision of an appropriate econometric choice model in order to maintain the behavioral interpretability while improving the prediction and forecasting capabilities moreover this project will focus on estimating the proposed models using bayesian variational inference vi techniques and on providing solutions to overcome the corresponding limitations of such methods in addition a comparison of traditional estimation techniques such as maximum simulated likelihood estimation msle and expectationmaximization em with bayesian variational inference techniques will be conducted with the aim of providing recommendations on when each estimation method should be used the ultimate goal is to apply the proposed framework to realworld case studies eg shared mobility biking behavior in copenhagen adoption of electric vehicles etc and provide the authorities and operators with forecasts and recommendations for new policies that might mitigate the negative impacts of the transportation system
compositional higherorder reasoning about distributed systems

software systems are critical for the infrastructure of modern society and software errors and security breaches pose enormous costs and risks the traditional method of testing software systems is famously inadequate for guaranteeing the absence of errors and security breaches since not all execution paths are covered by testing this is espcially true for concurrent and distributed systems where there are simply too many execution paths to test and it has motivated research in formal methods for program verification that can offer mathematical proofs that all system behaviors meet some desirable property to formally analyze and reason about software systems it is important to consider models at many different levels of abstraction since many real software errors and security breaches stem from subtle problems in implementations of software systems we focus on detailed socalled semantic models of program execution while there has been much research on abstract models for reasoning about distributed systems there has been very little work on compositional verification of implementations of distributed systems compositional verification enables specification and verification of individual software modules and their composition and is key to achieving scalable methods that apply to large programs but the devel opment of logics and methods for compositional reasoning is hard for concurrent nondistributed programs there has been tremendous progress in the last decade on program logics for compositional verification in particular through the development of socalled higher order concurrent separation logics leveraging this progress chords will research and develop new theories program logics and methods for mathematically rigorous compositional reasoning about implementations of distributed systems and thus lay the foundation for tools that will help programmers make more correct and secure distributed systems
longread sequencing to resolve the missing heritability in patients suspected of pten hamartoma tumour syndrome

individuals with a genetic tumour risk syndrome are at high risk to develop cancer one of these syndromes is pten hamartoma tumour syndrome phts phts is associated with pathogenic variants pvs in the pten gene unfortunately in the majority of patients suspected of phts no pv in pten is identified these patients are considered phtslike the low diagnosis rate in this group of patients suggests the possibility of pvs in regions of pten that are not covered in routine diagnostics or suggests that pvs in other genes in the pi3kaktmtor pathway result in phtslike disease in order to identify the missing heritability in phts i aim to develop a longread sequencing lrs approach for phtslike patients which will go beyond the currently stateoftheart shortread sequencing approaches i will o1 develop a ptentargeted lrs assay and o2 perform this assay on a highly selective cohort of phtslike families n94 i then will o3 perform whole genome lrs on 25 families that were not solved by targeted lrs to identify novel genedisease associations at last i will o4 validate these new associations in a wider cohortvia this work i will improve the diagnostic yield for phts by identifying novel genetic mechanisms and genes underlying disease in phtslike patients the unique interdisciplinary structure of the department of human genetics at radboudumc will allow to rapidly implement genetic testing for the newly identified genetic causes for phts identification of the precise underlying cause of phts will enable cascade genetic testing of atrisk family members to determine their status for the causal variant and thus risk of disease to them and any future offspring furthermore this approach will allow the implementation of preventive care strategies for the family members at risk overall my proposal will facilitate a personalized care approach for phtslike patients and their families for improved clinical outcomes and reduced disease morbidity
mental illness substance use and cardiovascular disease unravelling causal relationships

serious mental illness depression bipolar and psychotic disorder is among the leading causes of disability worldwide disproportionately affecting people of noneuropean ancestry on top of the burden posed by its symptoms mental illness is also associated with comorbid health problems the two most important comorbidities of mental illness given their driving role in decreasing quality and duration of life are substance misuse and cardiovascular disease whether these comorbidities arise due to causal relationships is surprisingly unclear the causal direction is also uncertain does mental illness lead to comorbidities and or do comorbidities increase the risk of more severe mental illness through several prestigious fellowships i have established myself as an expert in epidemiological and genetic causal inference methods in this ambitious project i will bring together innovative approaches to unravel the relationships of mental illness with substance misuse and cardiovascular disease my aims are to 1 assess bidirectional relationships between mental illness and its comorbidities by conducting longitudinal analyses in multiancestry prospective cohort studies 2 distinguish bidirectional relationships from shared genetic liability by jointly modelling the complete genetic architecture of mental illness and its comorbidities genomic structural equation modelling 3 establish causality by using only highly significant genetic variants as instruments for one variable and testing causal effects on another mendelian randomization 4 fully unravel the nature of relationships between mental illness and its comorbidities by triangulating evidence from aims 1 to 3 and 5 assess how informing medical doctors about the outcomes of aim 4 influences their clinical decisions in a randomized online experiment this interdisciplinary project sets the stage for more effective prevention and treatment of mental illness across ancestry groups
circular fuel supply for air transport via negative emission htl conversion

achieving climate neutrality in europe requires large volumes of truly sustainable fuels to provide longterm solutions for transport sectors where direct electrification is not viable circulair addresses this challenge with an integrated biofuel pathway that produces costeffective aviation fuels and generates negative emissions key innovations of circulair involve a close thermal coupling of hydrothermal liquefaction htl conversion based on abundant and available agricultural residues and lignocellulosic crops with exothermic wet oxidation of htl process water in this way autothermal operation can be achieved carbon is fully utilized and the process water disposal problem of htl is solved in addition circulair develops innovative approaches to upgrade htl biocrudes to jet fuel and accelerates the approval of htl fuels for civil aviation the biomass resource utilization is maximized by developing valorisation schemes for all relevant side streams along the process chain in particular acetic acid will be extracted from residual process waters and methanol will be synthesized from effluent gas streams and renewable hydrogen importantly circulair will close a knowledge gap regarding the utilization of fixed carbon in the htl solids for carbon sequestration and soil amendment ie for a negative contribution to the carbon balance the targeted overall netnegative emission will be quantified based on life cycle analysis finally techno and socioeconomic analyses will identify important benefits and tradeoffs associated with the advanced biofuel process in summary circulair will investigate and develop an innovative process for resourceefficient production of sustainable aviation biofuels alongside further marketable renewable chemicals and fuel products the utilization of biomass feedstock that is abundant in agricultural environments ensures costefficiency relevant scale and the potential to create netnegative carbon emissions
skeletal muscles antagonize t cell exhaustion in chronic viral infections

although skeletal muscles are not traditionally considered to be constituents of the immune system the loss of skeletal muscle mass in chronic infection is frequently associated with impaired t cell function or t cell exhaustion whether and how muscles regulate t cell exhaustion is unknown we found that skeletal muscles antagonized t cell exhaustion in mice chronically infected with lymphocytic choriomeningitis virus lcmv clone 13 spleenderived exhausted cd8 skeletal muscleinfiltrating lymphocytes smiles formed clusters in muscles where their antiviral function and proliferative potential were restored these revived cd8 smiles egressed from muscles and migrated back to lymphoid organs to sustain longterm antiviral immunity we aim to understand how skeletal muscles regulate antiviral cd8 t cell function metabolism and migration1 using metabolomics and rnasequencing approaches we identified 46 metabolites that were enriched in muscle interstitial fluid and two myokineencoding genes that were upregulated in muscle tissue respectively we plan to test whether and how these metabolites and myokines restore the antiviral functions of exhausted cd8 t cells2 we found that the cd8 t cell migration between the spleen and skeletal muscles was guided by a protein gradient of regulator of g protein signaling 16 rgs16 we plan to identify the rgs16interacting partners and the molecular mechanisms underlying rgs16 protein gradientdriven cd8 t cell migration 3 we observed that increasing muscle mass using a genetic approach resulted in both increased numbers of cd8 smiles and decreased viral titers in lcmv clone 13 infected mice we plan to explore the therapeutic potential of increasing muscle mass for enhancing protective t cell responses in chronic infectionscollectively we will study the role of muscles in recharging exhausted t cells and will evaluate the therapeutic potential of increasing muscle mass in chronic infections
central and peripheral nervous system action of gipr in obesity and diabetes

obesity is a major health threat but efficient pharmacotherapies are yet not available first demonstrated by us to decrease body weight and hyperglycemia in obese mice unimolecular coagonists at the receptors for glucagonlike peptide1 glp1 and the glucosedependent insulinotropic polypeptide gip efficiently corrected obesity and type2 diabetes in recent phase 3 clinical trials while glp1rgipr coagonists are safe and effective gip regulation of metabolism remains enigmatic with gipr agonists and antagonists both decreasing body weight and blood glucosemy lab recently identified the cns gip receptor as a key regulator of energy metabolism by showing that cns loss of gipr renders mice resistant to gipinduced body weight loss emphasizing the relevance of this discovery we showed that glp1rgipr coagonism loses its superior body weight lowering potency over glp1r agonism in cnsgipr ko mice my studies now finally enable assessment of how gipr antagonists and glp1rgipr coagonists regulate energy and glucose metabolism whether gipr antagonists improve metabolism through central and peripheral mechanisms which central regionsneuronscells are targeted by gipr antagonists and by glp1rgipr coagonists and the molecular mechanisms through which they control energy and glucose metabolism remain unknown in this project i will solve the conundrum of how gipr antagonists and glp1rgipr coagonists improve energy and glucose metabolism i will map regional gipr distribution aim 1 identify the central target regions of gipr antagonists and of glp1rgipr coagonists aim 2 delineate their cellular and molecular signal mechanisms aim 3 and assess functional relevance of gipr signal modification in key neuronalcellular populations and the periphery aim 4 my studies will significantly advance the knowledge on how gipr signaling regulates metabolism and will illuminate the paths for the development of future obesity drugs