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Limb wounds in horses are common, however healing is exceedingly slow and fraught with complications. Contrary to body wounds, limb wounds demonstrate only a small amount of wound contraction. The specialist procedure of applying split-thickness skin grafts to limb wounds stimulates wound contraction by unknown mechanisms. The objective of this project is to identify those mechanisms to develop a treatment strategy for equine limb wounds for use in general  practice. Limb wounds are severely impacting animal welfare due to an extended healing/treatment duration, and the risk of euthanasia due to a poor functional outcome. By stimulating wound contraction, healing time will be reduced, and the functional outcome improved, directly benefitting the welfare of wounded horse and reducing treatment cost for the owner. Aim: To identify dermal components stimulating wound contraction, and to develop this knowledge into future state-of-the-art treatment of equine limb wounds for use in general practice. Hypotheses: i) Application of dermal fractions to collagen gels seeded with equine fibroblasts will increase gel contraction in vitro; ii) Application of dermal fractions to experimental limb wounds in vivo, will increase wound contraction resulting in a faster healing time versus wounds treated by conventional methods. Methods: i) The contractile effect of different dermal components will be assessed in a collagen gel/ fibroblast model; ii) Identified dermal components will be tested in a standardized experimental limb wound model in vivo (n=5). Ultimately, results from this project are expected to improve wound treatment in horses, directly impacting animal welfare by reducing healing time and improving the functional outcome of wounded horses. This will also directly benefit horse owners and caretakers and making veterinarians able to offer better treatment solutions.

HESTEFORSK - Raskere og bedre sårheling hos hest med autologe hudkomponenter

The goal of the Bilingual Experiences, Cognitive Ageing and underlying Mechanisms (BECAME) project is to examine the functional neuroplastic mechanisms underlying mitigatory effects of bilingual experience on age-related cognitive decline. While evidence is available for structural brain changes supporting bilingualism-induced effects on cognitive aging (CA), functional mechanisms underlying such effects are not yet well understood. BECAME aims to fill this gap by investigating the trajectory of bilingualism-induced functional neuroplasticity across the adult lifespan (ages 18-85), crucially adopting an individual differences approach related to measurable degree of bilingual engagement. Importantly, although such benefits are thought to be rooted early in the lifespan, evidence for the timeframe and conditions of their early emergence is scarce. The choice of including the whole adult lifespan allows us to investigate these mechanisms and their emergence more directly from a lifespan perspective. I combine behavioral testing with brain recordings via electroencephalography (EEG). EEG is widely used in cognitive neuroscience to assess brain activity and the degree of communication between brain regions (functional connectivity) in response to stimuli and at rest. Combining behavioral and EEG modalities will allow me to test bilingualism’s effect on functional connectivity, as well as its consequences for functional efficiency, the minimum required neural activation to successfully perform a task. This will enable a detailed, evidence-based account of the protective effects observed in older-aged bilinguals, and how they are built from earlier life stages. By illuminating the relationship between multilingualism and resulting neurocognitive adaptations, BECAME will enable to capitalize on it as a health initiative, with manifold societal implications and the potential to be translated into actionable policies exploiting multilingualism to ameliorate effects of CA.

Bilingual Experiences, Cognitive Ageing and underlying Mechanisms

Hovedmålet med kreftbehandling er å eliminere kreftceller og dette er tradisjonelt oppnådd ved kirurgi, bruk av giftige medikamenter (cellegift) og stråling. En ny og betydningsfull tilnærming til kreftbehandling kalt immunterapi, har derimot fått mye oppmerksomhet det siste tiåret; Her forsøker leger og forskere å utnytte immunsystemet vårt for å målrettet  ødelegge kreftceller. En nøkkelaktør i denne banebrytende tilnærmingen er en gruppe «drapsmenn» i immunsystemet kjent som cytotoxiske T-lymfocytter (CTL-er). Disse cellene har en bemerkelsesverdig evne til å oppdage kreftceller ved å gjenkjenne unormale molekyler på overflaten av kreftcellene - molekyler som friske celler ikke har. Når CTL-er gjenkjenner kreftcellene ødelegger de dem ved å frigjøre giftige molekyler som initierer kreftcellenes selvdestruksjon. 
 
Selv om betydelige innsats har blitt dedikert til å forstå hvordan CTL-er aktiveres og hvordan de gjenkjenner kreftceller, vet vi mindre om de påfølgende hendelsene inne i kreftcellene som fører til deres død. Fra før vet vi at CTL-er kan initiere to forskjellige typer celledød i kreft: den første, kalt apoptose, er en stille og ordnet prosess der kreftcellene krymper og brytes opp uten å varsle immunsystemet; den andre, kalt pyroptose, er en mer dramatisk prosess som involverer dannelse av åpninger i cellemembranen, noe som fører til at cellene svulmer opp og sprekker. Under denne cellebristen blir innholdet inne i cellene frigitt i omgivelsene, og dette kan fungere som 'faretegn' som kan stimulere en sterkere immunrespons mot kreftcellene. Betydningen av denne cellebristen for å forsterke anti-tumorresponsene vil bli undersøkt i dette prosjektet. 
 
Videre er vi fascinert av muligheten for å avdekke ytterligere, ennå ukjente, former for celledød indusert av CTL-er. Utforsking av disse dødsrelaterte prosessene i kreftcellene kan potensielt øke effektiviteten av immunterapi og bidra betydelig i den pågående kampen mot kreft.

The primary goal of most cancer therapies is to induce cancer cell death. Immunotherapy relies on the cytotoxic activity of lymphocytes such as natural killer cells (NKs) and cytotoxic T lymphocytes (CTLs) to achieve this. While a significant amount of research in immunotherapy focuses on the events within cytotoxic lymphocytes or at the interface between cytotoxic lymphocytes and cancer cells, less is known about the molecular mechanisms that orchestrate cancer cell death, particularly in the case of CTL-mediated death.
CTLs are known to induce two types of cell death in cancer: non-inflammatory apoptosis and proinflammatory pyroptosis. Pyroptotic cancer cells release proinflammatory signals that attract immune cells to the tumor site, thereby enhancing the anti-tumor response. Cell lysis is a common outcome of pyroptotic cell death. It is unclear whether lysis can be decoupled from pyroptosis in cancer cells and whether the proinflammatory properties of pyroptotic cancer cell death depend on lysis. Moreover, it remains unknown whether CTLs can induce other forms of cell death in cancer, apart from apoptosis and pyroptosis.
Studying the mechanisms of CTL-mediated cancer cell death is challenging because CTLs selectively target cells expressing specific antigens. However, given the critical role of CTLs in immunotherapy, it is essential to deepen our understanding of CTL-induced cancer cell death.
This project aims to develop novel methodologies to investigate the death mechanisms that are initiated by CTLs. In addition, we will identify new pathways and mediators involved in CTL-induced cancer cell death. Furthermore, we will assess the contribution of proinflammatory cell death and lysis in promoting anti-tumor responses in vivo. Overall, this research will improve our knowledge of the molecular mechanisms of CTL-mediated cancer cell death and potentially reveal novel targets to enhance the efficacy of cancer immunotherapy.

T-cell-mediated proinflammatory cell death and lysis in cancer

En av de vanligste, men minst studerte, utfordringene med å bli eldre er problemer med å kommunisere. Mange eldre sliter spesielt med pragmatiske ferdigheter, som å forstå undertekst, eller tilpasse det de sier til personen de snakker med. 

La oss si at en lege må gi en alvorlig beskjed til en pasient. For å gjøre det litt lettere å takle, bruker legen vagere språk, som "kanskje" i stedet for "sannsynligvis". Mens yngre voksne ofte tar hensyn til høflighetsstrategier i måten de tolker det som blir sagt på, har eldre ofte vanskelig for å forstå når noen snakker indirekte. Mange eldre voksne har vanskelig for å forstå ikke-bokstavelig språk og kan misforstå alvorlighetsgraden av diagnosen. Dette kan påvirke beslutningen deres om behandling, noe som kan føre til utilsiktede konsekvenser. 

Siden god kommunikasjon er viktig både i viktige medisinske samtaler og i hverdagen, er det viktig at vi finner ut hva som gjør at eldre kan ha vansker med å forstå og bli forstått. RESILIENCE skal hjelpe til med denne utfordringen ved å samle data om praktiske, kognitive og språklige ferdigheter hos voksne i alderen 18-90 år over tid. Dette vil gi oss en stor mengde data om pragmatiske, kognitive og språk ferdigheter og gjøre det tilgjengelig for forskning. Med denne dataen som grunnlag har vi følgende mål: 

• Forstå hvordan praktiske evner endrer seg generelt gjennom voksenlivet. 
• Finne ut hvilke mekanismer som påvirker pragmatiske evner på forskjellige tidspunkter i livet.
 • Utvikle en teoretisk modell som forklarer hvordan pragmatiske ferdigheter endrer seg med alderen.
 • Lage algoritmer som kan forutsi hvordan pragmatiske evner vil utvikle seg for enkeltpersoner i årene som kommer. 
• Utvikle og teste et verktøy som kan måle pragmatisk helse (både pragmatiske ferdigheter og deres underliggende mekanismer), noe som kan åpne  for å iverksette tiltak. 

Dette vil gi oss muligheten til å forstå bedre hvordan folk kan utvikle pragmatisk resiliens gjennom livsløpet.

A cornerstone of human communication is our reliance on pragmatic skills to guide linguistic interactions (e.g., reasoning about others' mental states to bridge the gap between what is said and intended in conversation). However these skills are highly sensitive to age-related decline, leading to miscommunication and uninformed decision making in the older adult population. This raises an important question, one which has puzzled linguistics and psychologists for decades: if pragmatic competence is fundamental to communication, why do individuals vary so much in this capacity? 

Traditionally, psychologists have approached pragmatic competence from a cognitive angle, reasoning that individual differences in executive functions (i.e., the cognitive skills associated with goal-directed actions) are what underlie effective pragmatic behavior. In a similar vein, language scientists have taken a linguistic approach, reasoning that one’s language background (e.g., the frequency with which individuals shift between languages) shapes pragmatic skills by enhancing sensitivity to the communicative context. This focus on either cognitive or linguistic influences has resulted in two expansive yet disparate areas of research.

RESILIENCE will unite these disciplines to pursue a longstanding debate on what underlies pragmatic resilience and decline using a large-scale, interdisciplinary and longitudinal approach. By gathering data on adults' (ages 18-90) pragmatic, cognitive and language skills over multiple time points, we will develop a comprehensive theoretical model that explains how cognitive and linguistic systems interact to shape pragmatic competence as we age, and create algorithms that predict the trajectory of an individual’s pragmatic abilities in upcoming years. Based on these results we will design a multidimensional tool that detects the earliest signs of pragmatic deficits, leading to future interventions, allowing us to uncover the paths to pragmatic resilience.

Uncovering the paths to pragmatic resilience

Sink er et essensielt mikronæringsstoff som kreves for funksjonen til hundrevis av proteiner involvert i et bredt spekter av biologiske prosesser. Etter inntak av sink fra kosten reguleres nivåene i kroppen nøye gjennom absorpsjon, sekresjon og ekskresjon via spesialiserte proteiner, såkalte sinktransportører, i tarmen. Enhver ubalanse er skadelig for menneskers helse, spesielt er tarmen følsom for sinkfluktuasjoner, hvilket påvirker tarmbarrieren og kan føre til inflammatoriske sykdommer og kreft i tarmen. 
På molekylært nivå er de presise mekanismene som styrer funksjonen til de ulike sinktransportørene fortsatt uklare. Hos mennesker finnes det over tjue slike proteiner, og de fleste inneholder områder rike på aminosyren histidin. Disse histidinene mistenkes å spille en avgjørende rolle i å binde sink. Nylig oppdaget vi et enzym som modifiserer disse områdene ved å sette metylgrupper på histidin, og viste at metylerte histidiner har en lavere affinitet for sink. Dette prosjektet har som mål å identifisere nye mekanismer som regulerer sinknivåer gjennom histidinmetylering av sinktransportører, å utvikle forskningsverktøy for effektiv studie av histidinmetylering, og å legge grunnlaget for nye behandlinger av tarmsykdommer.

The delicate balance of zinc levels in the body is essential for human health. Zinc is absorbed and excreted via intestinal zinc transporter proteins, and perturbations of this process are associated with pathologies, including inflammatory diseases and cancers of the bowel. The precise molecular mechanisms regulating zinc transport, however, remain a major knowledge gap. Based on the recent discovery of an enzyme methylating histidine residues in zinc transporters, and drawing on preliminary findings which demonstrate reduced affinity of methylated histidines to zinc, this project aims to identify novel mechanisms regulating zinc homeostasis through histidine methylation. We will examine the regulation and effect of histidine methylation on zinc transport in intestinal cell culture and organoids, and examine how knockout of the methylhistidine-generating enzyme affects the integrity and pathology of the intestinal tract in mouse models. In addition, we will identify reader proteins specifically recognizing methylhistidines and develop anti-methylhistidine antibodies and inhibitors to use as tools for detection, enrichment, and inhibition of histidine methylation. Such tools are urgently needed by the international research community, as none are currently available commercially. Overall, this project will lead to great advances in the field of protein regulation, and may uncover novel mechanisms in intestinal zinc transport and pathology.

Zinc transport regulation through histidine methylation

Noen av oss tåler stressende livshendelser godt. Andre derimot utvikler vedvarende fysiske og psykiske plager som følger av stress. Hvor godt vi håndterer stress avhenger av et komplekst samspill mellom miljøfaktorer, sosiale forhold, biologisk sårbarhet og indre motstandskraft. Forskning på stressreaksjonene til dyr og pasientgrupper som til vanlig lever under mye stress viser at en gruppe signalstoffer i kroppen som aktiverer det samme hjernesystemet som cannabis – endocannabinoidene – kan begrense styrken på stressreaksjoner og bidra til at man raskere kommer seg til hektene. I dette prosjektet skal vi undersøke hvordan mestring av stress på kort og lang sikt henger sammen med nivåer av endocannabinoider i kroppen for å forstå hvorfor noen personer er mer motstandsdyktige mot stress enn andre. I den ene studien følger vi pasienter som skal gjennomgå en stressende, men veldig vanlig, situasjon: kirurgi. Her måler vi pasientenes opplevelse av stress, samt mentale og fysiske helse, fra tiden før til to år etter operasjonen og undersøker hvordan dette henger sammen med nivåene deres av endocannabinoider og andre stresshormoner. I den andre studien bruker vi data fra et eksperiment hvor deltakerne har blitt utsatt for psykososialt stress til å undersøke om endocannabinoidnivået deres påvirker hvordan de reagerer på stress, og om stresset i seg selv kan påvirke kroppens produksjon av endocannabinoider. Til syvende og sist er målet med studien å vurdere hvorvidt målinger av endocannabinoidnivåer kan brukes til å forebygge helseplager og til å evaluere behovet for økt oppfølging etter alvorlig stressende påkjenninger i livet.

In the face of major life stressors, some individuals cope well whereas others develop ill health and long-term adverse outcomes. Predicting who needs additional support in response to major life stressors is essential for targeted prevention and more efficient allocation of resources. The endocannabinoid system is emerging as a promising target for understanding vulnerability and resilience to stress. This system appears to buffer stress in two ways: by limiting the magnitude of the stress response, and by facilitating recovery after a stressful event. While the early findings are intriguing, they mainly stem from studies in rodents and small clinical groups with high stress burden. What role endocannabinoids have more globally for human resilience, health and well-being remains elusive. 

In this project we address this gap by leveraging comprehensive experimental and clinical data on two potent stress models: psychosocial stress and surgery. Drawing on these unique datasets, which combine experimental control with ecological validity, we will decipher how endocannabinoid levels influence people’s stress response and recovery across minutes, days, weeks and years. The project represents a novel directional shift for endocannabinoid research and will (i) determine the value of endocannabinoid levels as a biomarker to predict outcomes after surgery, (ii) quantify sex differences, (iii) assess endocannabinoid interplay with opioid analgesics, sex hormones and other stress markers (iv) spearhead open and reproducible science practices in endocannabinoid research, and (v) make this fine-grained and novel data available through an interactive web application. 

This project represents an ambitious effort to understand endocannabinoids’ role in stress resilience and will determine the value of endocannabinoids as a predictive biomarker and potential target for individualized treatment.

Deciphering endocannabinoid stress buffering in humans: 
Mechanistic and clinical investigations

WHeelchair Activity Monitoring project (WHAM)

Wheelchair users (WCU) are three to five times more inactive than the general population, leading to a high risk of developing preventable secondary conditions. Although physical activity (PA) guidelines have been specifically developed for WCU, we lack systematic approaches to implement them in practice, as well as valid algorithms to monitor PA change in WCU through sensor-based solutions. Accordingly, the overall scientific aim of the WHeelchair Activity Monitoring project (WHAM) is to advance PA research and practice in WCU by developing valid digital markers for monitoring of and providing feedback on PA, paving the way for implementation and intervention. I will accomplish this through combining the complementary research fields of 1) behavioural intervention studies focusing on increasing PA in WCU (core competence University of British Columbia, UBC; outgoing phase) and 2) sensor-based PA monitoring (core competence Norwegian University of Science and Technology, NTNU; returning phase – consolidated by non-academic placement at Maastricht Instruments, which develop research prototypes including PA monitors). WHAM’s scientific aim is achieved through three objectives: 1) Measure the effect of a pragmatic exercise intervention trial on self-reported physical activity levels and cardio-respiratory fitness, 2) Develop valid algorithms for tracking PA markers in WCU, and 3) Co-create a framework that outlines how PA can be conjointly monitored and provided feedback on in WCU. This fellowship will enable me to become established as an internationally recognized researcher in the field of “physical activity and disability”, while bringing together ongoing national disjointed research activities in this field. Altogether, my overall ambition is to contribute to reducing inequalities in daily-life participation among WCU compared to the rest of the population.

BOLD MINDS aspires to enhance the understanding of vulnerability factors underlying the emergence of borderline personality disorder (BPD), with an ultimate aim of increasing the potential for young individuals to receive early, evidence-based help when their mental health is at risk. BOLD MINDS will achieve this by investigating whether disruptions in two aspects of autobiographical memory (AM), narrative identity (NI) and involuntary AM (IAM), are associated with BPD features and problem behaviours in adolescents concurrently and over time. In doing so, BOLD MINDS will strengthen the understanding of mechanisms underlying the emergence of BPD in adolescence and lay a groundwork for developing evidence-based early interventions for BPD. While currently limited, the study of AM in this field is essential for two reasons. Firstly, because the aspects of AM under investigation, NI and IAM, are known to be involved in identity formation and emotion regulation which represent two key psychological processes that are disrupted in adults with BPD and are linked to problem behaviours such as self-harm and suicidality. Secondly, because promising research is emerging on the use of AM targets in the treatment of emotional disorder in adults, and provides a strong model for future treatment development with vulnerable adolescents. In addition, this timely research program aligns with calls from international organizations to prioritize early interventions to promote adolescent mental health. BOLD MINDS will adopt and adapt state-of-the-art ecological momentary assessment and analytical techniques and work at the crossroads of clinical and cognitive psychological perspectives, allowing for a multidimensional approach to understanding BPD vulnerability. Training-through-research and formalized training of the experienced researcher will prepare her for a permanent academic position and the founding of her own research lab specializing in AM and early interventions for BPD.

Borderline Personality Disorder: Memory and Identity in Adolescence

Per- og polyfluorerte stoffer (PFAS) er en stor gruppe menneskeskapte kjemikalier med høyt fluorinnhold som antas å ha negative helseeffekter. Kilder til PFAS kan være produksjon av vann-, varme- og flekkbestandige produkter og disse kjemikaliene er en del av hverdagen vår. PFAS påvirkning av biologiske systemer er ikke fullstendig forstått. Noen PFAS er antatt å øke risikoen for å utvikling av ikke-alkoholisk fettleversykdom (NAFLD) og øke risikoen for diabetes. 

For å forstå hvordan PFAS påvirker organene våre ønsker vi å bruke små laboratoriedyrkede organmodeller, kalt organoider. Disse miniatyrorganene kan dyrkes fra menneskelige stamceller og tilbyr et kontrollert miljø for å studere hvordan PFAS påvirker f.eks lever og bukspyttkjertelen vår, uten bruk av dyreforsøk.

For å studere helseeffekter må vi kunne måle nivået av biomolekyler som fettstoffer i leveren og hormoner i bukspyttkjertelen. Til dette trenger vi å utvikle analytiske verktøy for å måle effektene. Først vil vi bekrefte at når leverorganoidene eksponeres for enkelte PFAS-forbindelser utvikles det NAFLD-lignende sykdom ved å sammenligne den biokjemiske profilen (proteiner og metabolitter) til organoider av lever med PFAS-eksponerte organoider. Deretter vil vi utvide den analytiske verktøykassen for å undersøke hvilke metabolske veier som påvirkes, og om effekten er den samme i NAFLD-induserte og PFAS-eksponerte organoider. Vi vil også eksponere insulinproduserende bukspyttkjertelorganoider for PFAS for å undersøke effekten av PFAS på hormonproduksjon. Når effektene av PFAS-eksponering på lever- og bukspyttkjertel-organoider er etablert, vil organoidene bli samkultivert i en chip, og effektene av PFAS-eksponering vil bli undersøkt og sammenlignet med individuelle organoider.

Persistent organic pollutants (POPs) are believed to contribute to metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD) and type 1 diabetes. HE-POP aims to investigate the effects of per- and polyfluoroalkyl compounds (PFAS), a type of POPs), on organ function in a controlled environment.

Organoids are multicellular laboratory-grown miniature organs, that are grown from stem cells. HE-POP will use organoids to examine how PFAS affects our organs and develop cutting-edge bioanalytical tools and methodology to measure these effects using liquid chromatography-mass spectrometry. HE-POP hypothesizes that PFAS negatively affects organ function, as evidenced by changes in hormone and lipid levels characteristic of NAFLD and type 1 diabetes. 

Organoids offer a controlled environment to study the effects of PFAS on the liver and pancreas, without the use of animal models. HE-POP aims to gain evidence of the negative effects of PFAS on organ function through controlled experiments on organoids and aid in understanding the biological mechanisms underlying NAFLD and type 1 diabetes.

HE-POP has fundaments in UN sustainable development goals, specifically #3, #12, and #14/15, seeking an understanding of diseases with worldwide prevalence, and understanding how POPs affect our life and surroundings and help enable the right regulatory actions and replacement chemicals.

HE-POP: Studying the Health Effects of Persistent Organic Pollutants, Using Mass Spectrometry, Organoids, and Organ-On-A-Chip

Dette prosjektet, kalt Hukommelse for musikk, fokuserer på det økende antallet mennesker over hele verden som lever med demens, spesielt Alzheimer's sykdom (AD). AD starter typisk med hukommelsesproblemer og påvirker etter hvert daglige aktiviteter. Aktive musikkintervensjoner, spesielt sang, har vist positive effekter på humør, atferd og livskvalitet for personer med demens, men deres innvirkning på kognisjon er ikke godt forstått. Prosjektet har som mål å fylle dette kunnskapsgapet ved å studere effektene av å lære nye sanger på kognitiv, atferdsmessig og hjernemessig funksjon.

Studien vil omfatte hjemmeboende voksne over 65 år med AD fra Argentina, Østerrike og Norge. Deltakerne vil gjennomgå 5 måneder med intensiv musikalsk opplæring (to ganger i uken) og 5 måneder med minimal opplæring (en gang i måneden) i tilfeldig rekkefølge, med en to måneders pause imellom. Intervensjonene inkluderer å lære nye sanger med en personlig musikklærer. Generell kognisjon vil bli målt ved bruk av Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog), og hukommelse for musikk vil bli vurdert gjennom ulike metoder, inkludert atferdsoppgaver og hjerneaktivitet (EEG). Humør vil også bli evaluert i hver økt.

Målet er å inkludere 113 deltakere for å sikre pålitelig påvisning av meningsfulle effekter. Studien vil utforske hvordan humør og hukommelse for musikk bidrar til endringer i kognitive evner, og om disse effektene varierer basert på faktorer som kjønn, alder, AD-stadium, eller tidligere musikalsk opplæring og generell utdanning. Prosjektet vektlegger samarbeid mellom forskere, tjenesteytere og brukere for å sikre studiens relevans og anvendelighet.

The number of people living with dementia is increasing and is high in low, middle, and high-income countries. Alzheimer’s disease (AD), the most common type of dementia, manifests itself initially with cognitive impairment in memory domains, and later affects all activities of daily living. Active music interventions, particularly singing, can help to improve mood, behaviour problems, and quality of life. Too little is known about their effects on cognition, although some promising studies exist. The M4M project aims to fill this gap by measuring effects of learning new songs on clinical, behavioural and brain functioning. Specifically, M4M aims to examine changes in general cognitive functioning and memory for music in non-musician adults with AD undergoing intensive individual musical training based on singing novel songs, compared to minimal training.
        Home-dwelling adults with AD, 65 years or older, in 3 countries (Argentina, Austria, Norway), will receive 5 months of intensive intervention (2x/week) and 5 months of minimal intervention (1x/month), in random order, with a 2-month break in between. Interventions will entail learning new songs with an individual music teacher. At the end of each intervention period, general cognition will be measured with the Alzheimer's Disease Assessment Scale – Cognitive (ADAS-cog) by a person who is unaware of the intervention received. Memory for music will be tested with observations, behavioural tasks, and brain responses (EEG). Mood will be assessed in each session. We aim to include 113 participants; this will help us to reliably detect clinically meaningful effects. We will also examine how mood and memory for music lead to changes in cognitive abilities, and whether effects depend on sex, age, AD stage, or previous musical training or general education. M4M will be conducted in close collaboration between academic researchers, service providers, and service users to ensure relevance and applicability.

Memory for Music: Effects of individual intensive musical training based on singing in non-musicians with Alzheimer’s disease

Midlene fra FRIMUF-Miljø- og utviklingsforskning fordelt på år

Midlene fra FRIMUF-Miljø- og utviklingsforskning fordelt på fylker

Midlene fra FRIMUF-Miljø- og utviklingsforskning fordelt på fagområde

Director

Predicting the Population Dynamics of Large Mammals

The project “New integrated approach for fungal natural product discovery based on co-occurrence networks of interacting microbes” is a collaborative effort between UiT – The Arctic University of Norway and the University of Bremen, Germany, involving research exchange activities of three early career scientists (ECSs) and two principal investigators (PIs). The main objective of the scientific project that forms the basis for the collaborative effort is to test and introduce a new integrated approach for natural product discovery to the natural product community. Secondary objectives include preparing a joint European Horizon application based on results from this project, increase cultivability of marine fungi using co-culturing and increase the production of marine fungal bioactive secondary metabolites. The collaborative project is based on data mining of high-throughput sequencing datasets from Dyrøy (Troms, Norway) and Helgoland Roads (North Sea, Germany) using co-occurrence networks to find interacting microbes (amongst thousands of co-existing microbes) that live in close association with each other. Putatively interacting pairs/groups of microbes will be isolated from both study localities and brought into laboratory, where they are cultured in multi-partner co-cultures and studied for new bioactive secondary metabolites, with the focus in detecting antimicrobial molecules that possess medicinal potential. The project contributes to more targeted culturing campaigns for different scientific or applied purposes in academia and industry and better integration of molecular ecologists in natural product discovery. It also provides ECSs and PIs with scientific and transferrable skills and contributes to boosting their international scientific careers. Major impacts of the project may be realized in the form of new antibiotics that increase society’s ability to meet the threat of antimicrobial resistance (AMR).

New integrated approach for fungal natural product discovery based on co-occurrence networks of interacting microbes

Non-minimum phase systems are relevant class of dynamic systems with unstable internal dynamics. For such systems, even though the complementary external dynamics are stabilized by state-feedback control, internal states may still converge slowly or even diverge. Focusing on linear systems, transfer functions of non-minimum phase systems show zeros in the positive complex half-plane. It is known that if there is an odd number of real-valued positive zeros in the transfer function, then the associated step response shows at least one undershoot which is more pronounced the more such zero is closer to the imaginary axis. This performance impairment cannot be easily counteracted by classical compensators as unstable pole/zero cancellation would internally destabilize the entire control loop. Thus, customary controller designs accept a lower performance. In past common research, the involved PIs found a feasible pole/zero cancellation technique that compensates some fractional-order minimum phase components of the numerator polynomial. Such action will still render the control loop internally stable. Since this approach is entirely novel, there is a number of open questions that shall be addressed and answered in the solicited project. The main scope of the collaborative research encompasses the analysis of system dynamics, the compensator design for the non-minimum phase systems, and its application in case studies. In order to reach the individual project targets, the project will implement several practical measures and further strengthen the academic relationship between the research groups at UiA in Norway and TU-Ilmenau in Germany. Synergies expected from the complementary cooperative research will increase visibility of both groups on national level and within the international communities of control and systems engineering. It will also contribute to an enhanced education quality of the master and doctoral students, and postdoc experience at both institutions.

New Compensators for Non-Minimum Phase Systems

Artificial intelligence (AI) developers predict altering of business models and customer behaviour, cost reduction, improvement of forecasting, and customization of the services. AI has the ability to acquire, process, interpret and learn from different types of data, and make autonomous decisions. In doing so, it can automate some of the tasks performed by humans and thereby threatens existing human jobs. The potential to obscure the borders between biological, digital and physical aspects of the contemporary world explicitly increases the level of fear and anxiety of frontline workers. 
However, focussing only on AI, while ignoring human intelligence leaves great potential aside. While AI outperforms humans on objective and structured  tasks, they can only learn from the past. Humans excel in creative and affective aspect, e.g.,  managing relationships, providing customized solutions or developing and experimenting with innovative ideas.
While AI implications are heavily discussed in business and management literature, the implications and requirements for human-AI collaboration are still at its infancy stage. Previous research primarily focuses on technological and economic aspects of AI. However, research on the organizational transformation that is shaped by human-AI collaboration requires further theorizing and empirical evidence.
In this project, we plan to work on several goals while conducting a series of case studies. First, we contemplate to extend our understanding of how human-AI collaboration transforms job characteristics and organizational routines. Particularly, we will investigate the complementary benefits of human-AI collaboraiton for service work. Further, we intend (ii) to explain how managerial practices change in response to the change in job characteristics caused by the AI implementation. Finally, we intend (iv) to investigate how humans perceive AI-empowered digital actors that collaborate with them in organizational routines.

Implementation of Artificial Intelligence Applications in Service Sector

We propose to construct and study Lie groups of paths of bounded variation with values in a Lie group. The driving motivation for this construction comes from the theory of rough paths. Rough path theory was invented by T. Lyons in the 90s and provides a fresh look at integration and differential equations driven by rough signals. A rough path can be completely characterised by its signature, which is a series of tensors satisfying certain algebraic constraints. Associating rough paths of a fixed p-variation to their signatures, one ends up with a subgroup of the group of all signatures. To understand the geometry of these groups, we propose to construct (infinite-dimensional) Lie groups of p-variation paths with values in a Lie group (in this setting, the pointwise product of the paths yields the group structure). First studies indicate that these groups provide a proper framework to exploit geometric properties of the signature. Further, the groups envisaged here are also of interest in infinite-dimensional Lie theory and are related to the open problem of J. Milnor whether each infinite-dimensional Lie group is regular.

Our second (related aim) is the development of exponential laws for mappings of mixed differentiability. In recent years  functions on a product U x V of manifolds which are up to m times differentiable in the second variable and up to n times differentiable in the first variable. For suitable topological spaces X, Y, and Z, an exponential law C(X x Y,Z) ~ C(X, C(Y,Z)) is well known for continuous functions, with analogous results for smooth mappings (under suitable hypotheses). Our goal is to establish a natural smooth manifold structure on manifolds of mappings of mixed differentiability together with a version of the exponential law. When the target is a Lie group, we strive to obtain a Lie group structure. The new constructions will enhance the toolbox of infinite-dimensional calculus for non-smooth objects, and the scope of its applications.

Lie groups and manifolds of non-smooth mappings

Ruptured brain aneurysms account for 3-5% of all new strokes worldwide and are fatal in about 50% of cases. Analysis of cardiovascular diseases through the simulation of the blood flow has the potential to identify aneurysms (in particular intracranial aneurysms) of high rupture risk and to optimise treatments. 

A critical input of patient-specific blood flow simulations is the geometry of the patient’s aneurysm and surrounding blood vessels. Today this segmentation is typically performed semi-automatically from imaging data, using the experience of the researcher at task. However, a recent study asked 26 research groups to perform segmentations and hemodynamic simulations to identify the ruptured aneurysm in a patient. The results showed clear differences exist with respect to the analysis of aneurysm shape and blood flow results from the different research groups, highlighting the limitations of a semi-automatic geometry reconstruction.

In this project, we advocate an automatic segmentation approach for blood vessel segmentation that incorporates physical constraints already during the segmentation process. From a mathematical point of view this results in a shape optimization problem with the time-dependent Navier-Stokes equation on polygonal-type domains with mixed-boundary conditions in two space dimensions. The project addresses two challenges: 1) theory and 2) algorithm development of shape optimization problems with fluid structure interaction. To achieve this, fundamental research with respect to (possibly automatic) derivation of tube derivatives via a domain mapping approach will be conducted. We will also address appropriate shape priors in this setting of a dynamic domain. The theoretical and numerical results will deepen the knowledge shape optimization of fluid structure interaction and make contribution to cardiovascular flow modelling.

Optimal shape design for cardiovascular flows

Type 2 diabetes is associated with insulin resistance in skeletal muscle, in which the transmission of signals within the cells is impaired. This results in an aberrant glucose and lipid metabolism that negatively impacts whole body glycemic control. Importantly, alterations in insulin signaling can be detected very early on in the development of the disease, even in the absence of clinical phenotypes, implicating a causative role of muscle insulin resistance in the onset of diabetes.
The signal transmission of insulin is based on a cascade-like, rapid and reversible phosphorylation of proteins in which, in the end, specific effectors, enzymes and transcription factors are activated or inhibited. Both contraction and insulin stimulation result in increased glucose uptake and are thought to share common signaling pathways in skeletal muscle. It is currently unknown at which point the pathways converge, and where impairments in signal transduction occur in the insulin-resistant state.
Insulin-dependent signaling pathways in cultured skeletal muscle cells of metabolically healthy individuals and individuals with T2D are studied using quantitative metabolic measurements and high-resolution mass spectroscopy. In addition, the cultured skeletal muscle cells will be exposed to a model of in vitro exercise (electrical pulse stimulation, EPS), and potential antidiabetic drugs targeting skeletal muscle. Signal transduction is investigated with the help of mass spectroscopy through time and dose-dependent measurements of the global phosphoproteome. The aim is to investigate how and at what level the signaling cascade is altered or interrupted in diabetes, and if and how this can be counteracted by exercise and/or pharmacological agents. Also metabolic characteristics of the cells will be measured.

Insulin signaling pathways in skeletal muscle

Geodesy is the science of determining the shape of the Earth and its gravity field and provides the basis for many applications in mapping, engineering, navigation and monitoring of the Earth system. Integral to these activities, geodetic reference frames basically consist of a list of coordinates of selected reference stations to which all subsequent measurements can be referred to, ensuring consistency over long distances and time periods. It allows, e.g., continuous monitoring of sea-level rise or quantifying mass transport in the Earth’s hydrological cycle, including melting of polar ice sheets and glaciers.
Of specific interest for studying sea- level rise and mass distributions are the reference frames for height and gravity. For more than 10 years, NMBU and BAdW cooperate on theory of regional geoid modelling. In the initial phase (2010-2011), the cooperation was supported by DAAD-PPP. The current proposal aims at strengthening the existing cooperation taking advantage of newly funded PhD and postdoctoral positions at NMBU. Additional networking activities will strengthen existing connections to the Norwegian Water Resources and Energy Directorate (NVE) on questions of hydrological modelling and glacier monitoring.
When realizing reference frames, temporal variations caused by mass transport in the earth system, e.g., caused by continental hydrology or glacial isostatic adjustment must be accounted for. 
NMBU’s current PhD student (Mr. Bramanto) is working on time-variable effects in time series of terrestrial absolute gravimetry, with focus on contributions from continental hydrology. The cooperation with BAdW will allow an extension from terrestrial to areal observations by means of satellite gravimetry.  The new postdoctoral and PhD projects are related to realization of a seamless height reference frame for land and ocean areas, thus exploiting NMBU’s expertise in satellite altimetry and BAdW’s expertise in combined regional geoid modelling.

On the modernization of geodetic reference frames

The project deals with the role of integrin alpha11 in rheumatoid arthritis (RA)  using a genetic mosue model, the hTNFtg mice. Starting point for project was based on the finding that that beta1 integrins are involved in the attachment of synovial fibroblasts (effector cells in RA) to components of the extracellular matrix and, upon attachment, regulate migratory and invasive processes. 
 The group of Adelheid Korb-Pap could already show that integrin alpha11- integrin is expressed at increased levels both in human RA synovial fibroblasts and in the hTNFtg mice vs. controls. 
Isolated hTNFtg synovial fibroblasts showed  - in line with the human data – an increase of alpha11- integrin expression levels.
 - Analyses in various  functional assays showed a reduced proliferation rate and invasiveness of Itga11-/- fibroblasts (isolated from Itga11-/- mice provided by Donald Gullberg)
- In vivo evaluations of offspring from Itga11-/- and hTNFtg mice revealed a milder arthritis score and less cartilage and bone destructions in Itga11-/-hTNFtg compared to hTNFtg mice.

 Remaining questions to be addressed in the project period :
- Determine how the activation of alpha11- integrin is involved in the transformation of synovial fibroblasts and subsequently in cell adhesion and invasion resulting in cartilage destruction.
- Determine if alpha11 integrin contributes to fibroblast heterogeneity in the synovial tissue.
- Determine if the specific inhibition of alpha11- integrin activation may serve as a therapeutic target

Role of integrin alpha11beta1 in joint destruction in inflammatory arthritis.

Adequate education for Europe is ensured through language teaching for all. However, the demands and implementation of inclusive teaching diverge greatly, since legislation and the implementation of joint schooling are regulated differently in different countries or, as a result of federalism (e.g. Germany), within countries . The DINGLE project is conceived as a preliminary study for the conception of a theoretical framework for digitally enhanced inclusive foreign language teaching in Europe, which is to ensure the quality of teaching and research in the long term and in line with the requirements of the Council of Europe. Further international research activities in this application domain are to follow. DINGLE will take the conceptual and didactic starting points of English as an example for foreign languages and will take into account the variable tasks of practitioners and future teachers in various European educational contexts. The collaborative and research-based transfer of knowledge and the empirical analysis of the universities ' own conditions for success in Norway and two different parts of Germany, Schleswig-Holstein and Baden-Württemberg,  make it possible to examine which aspects a theoretical framework for digitally enhanced inclusive foreign language teaching should include in order to enable self-determined, personalised, adaptive learning and to remove obstacles in dealing with digital learning formats. This strengthening of the academic relations between Germany and Norway addresses the technical  questions in connection with inclusion, heterogeneity and diversity and develops them further in order to create the empirical basis for an applicable, multidimensional, modular, university-based framework that adheres to principles of media didactics. The bilateral project can thus make a contribution to future theoretical frameworks for digitally enhanced inclusive foreign language teaching in Europe.

Digital and inclusive challenges for Norwegian and German Learning and Education

The impending transition from a petrol-based to a sustainable bio-based economy requires the valorisation of a variety of renewable biological resources. Due to its compositional variety, lignocellulosic biomass is a promising renewable feedstock for the production of different chemicals. The production of fungal lipids from lignocellulose sugars has attracted a lot of attention during the last five years. Fungal lipids are produced by oleaginous fungi, which under nutrient-limited conditions, are able to accumulate up to 80% of lipids per dry biomass. Fungal lipids consist mainly of triacylglycerols (TAGs). Fatty acid profiles of fungal TAGs are very similar to essential fatty acids in plant oils or they can be similar to highly valuable fish oil. Fungal lipids are a promising feedstock of high-value lipids for food, feed and chemical industry as well as low-value lipids for biodiesel industry. The process of microbial lipid production is still not competitive with the agricultural production of vegetable oils, which has a significantly lower market price. Our hypothesis is that the production of microbial lipids from lignocellulose sugars can become economically feasible if a process allowing the co-production of chitin and chitosan can be established. Utilizing oleaginous Zygomycetes fungi for the lipid production from lignocellulose sugars gives an opportunity for the co-production of important biopolymers such as chitosan in addition to lipids.  The research hypothesis jointly developed by the NMBU and WWU team is that oleaginous Zygomycetes fungi grown on sugar-rich lignocellulose hydrolysates are, under certain nutrient conditions, able to co-produce high-value lipids and chitosans. Thus, by establishing cooperation between NMBU and WWU, it would be possible to develop a co-production concept for the concomitant production of lipids and chitosans in oleaginous Zygomycetes fungi grown on waste feedstocks sourced from forestry.

Developing co-production of lipids and chitosan in oleaginous filamentous fungi

Automata theory (and more generally speaking, formal languages) is one of the most traditional areas in (theoretical) computer science. Hence, this field has found applications in quite diverse areas of science, as linguistics, biology, and clearly many more applied areas of computer science, such as compiler construction, software engineering, or hardware design, to mention only a few.

On the other hand, the field of multivariate algorithms deals with the development of techniques to handle computationally hard problems by finding clever ways to deal with certain properties of the inputs which are quantified by numerical parameters. In particular, the running time of algorithms developed in this framework have a polynomial dependence on the size of the input and potentially, an exponential dependence on the magnitude of the parameters. It turns out that in many situations of practical relevance, these parameters are very small. Therefore, multivariate algorithms very often perform well on instances inspired by practical applications. 

Currently, techniques from the theory of multivariate algorithms have been hardly applied to the study of problems in automata theory. Similarly, there are only a few examples of situations in which techniques from automata theory have been used in the development of faster multivariate algorithms. The goal of this project is to establish deep connections between these fields, by using techniques from automata theory to attack hard problems in the field of multivariate algorithms and vice versa.

Algorithmic Automata Theory: A multivariate approach

Real algebraic geometry is concerned with the real solutions of equations and inequalities defined over the real numbers and has both a distinguished history (for example, Hilbert’s 17th problem) and many applications in the natural sciences and engineering. An important modern branch connects real algebraic geometry with techniques from optimization. Prominent roots of these developments go back to N.Z. Shor (in the 1980’s) and were substantially advanced by Parrilo and Lasserre (around the year 2000) through their insights of how to use semidefinite programming within polynomial optimization. An important link between real algebraic geometry and optimization has been provided through sums of squares. While some fundamental theorems connecting nonnegative polynomials with sums of squares already date back to Hilbert, the modern developments have recognized that sums of squares of polynomials can be computationally handled much better than nonnegative polynomials and that this general idea can also be effectively applied to rather general constrained polynomial optimization problems. With the strategic goal to strengthen the academic relations between Germany and Norway, the main scientific purpose of the project is to advance various lines of research concerning real algebraic geometry and optimization.
The focus of the project will be on some lines of research which have raised new challenges in the last years. These subtopics both allow complementary cooperative research work on a leading international level as well as the training of young researchers in an international framework.

Real Algebraic Geometry and Optimization

The Project aims to unite forces of the Norwegian and German research groups and to focus on several important research problems of common interest described below. 

1. Computation of number and form of differential invariants characterizing Riemannian and pseudo-Riemannian spaces admitting Killing vectors and Killing tensors. Both groups have an active interest in this problem and some partial results. 

2. Recognition and classification of metrics with a simply or multiply transitive local group of isometries, in submaximally symmetric cases and in low dimensions. For Kundt metrics, indistinguishable by scalar curvature invariants, address their integrability via first and second order integrals. Both group have sufficient expertise required for these tasks.

3. Generalization, in particular, to parabolic geometries, like conformal and projective. Investigation which differential invariants are responsible for existence of normal solutions to BGG-type invariant differential operators, estimation of the number and order of such invariants. Both sides have own approaches, which are complementary, and so a joint study should be very prolific.

4. Investigation of projective invariance and integrability for Finsler metrics. The Jena partners have a considerable knowledge in this area, to be shared with the Norwegian group. In response the Lie representation-theoretic methods, known to Tromsø group, will be applied to the problems in Finsler geometry. In particular, we are going to work on Finsler metrics with sub maximal symmetry dimension.

5. Extensions of the results to low regularity problems. Applications to recognition of symmetric metrics via stable joint invariant techniques.

The two groups have had preliminary contacts and meetings, which give a definite hope to construct a fruitful dialog and lay a foundation for future collaborations.

Differential-Geometric Structures: Invariants and Integrals

The modern internet infrastructure relies on key exchange and key establishment protocols for initiation of secure communications. In such protocols, two (or more) parties agree on some key material to use later on, in a way that an eavesdropper (that sees the entire transcript) cannot extract this key material - either due to the beautiful properties of public-key encryption techniques or as a result of some a priori shared information between the parties.
 
A property widely expected of key exchange protocols is forward secrecy: if a long-term secret key of one party is corrupted then prior sessions should still remain secure. This is usually achieved using so-called "ephemeral" values instead of wholly relying on the secret key. This approach has been widely deployed for many years in diverse applications such as Transport Layer Security (TLS), instant messaging (the Signal protocol and WhatsApp, plus many others) and IPSec. Understanding and defining forward secrecy has been an ongoing research effort for many years now, and in fact numerous primitives that are related to key exchange have modelled their own flavors of forward secrecy. The proliferation of these models, some generic and some specific, have created a confusing landscape for practitioners and researchers seeking to gauge the security levels that can be achieved in their specific application. This project will focus on defining and unifying models for forward secrecy, and applying such models in Internet applications.

Key Exchange for Today's Internet

Interventions that combine physical activity with cognitive tasks and decision-making promote the development of both motor and cognitive function. Therefore, the use of exergames in the health care sector may be beneficial to increase both physical activity and cerebral activity, thus providing improved cognitive function. An important field of practical application of simultaneous motor-cognitive training is fall prevention in elderly. Exergaming, being able to improve both physical and cognitive abilities and to train both parts simultaneously, has therefore large potential as a fall preventive exercise. This application aims to further contribute to the existing evidence of exergaming in older adults and the potential implementation in fall prevention. Furthermore, a specific focus  will be set on the cognitive demands of exergaming and its effect on the level of brain activity. The current project will be conducted in two phases. In a cross-sectional approach (PHASE 1), brain activity will be compared while playing different balance exergames (static vs. dynamic) in older adults using EEG. The findings will be transferred to a longitudinal approach (PHASE 2). This will exclude the novelty effect of playing an exergame and can describe how the cognitive demands change over a longer period of exergaming. The latter has not been studied before, even though this information is crucial for the development of future intervention programs to prevent falls in elderly.

Exergaming for Physical and Cognitive Activity (EPCA)

A functional hallmark of the brain is its rhythmic activity. Brain rhythms consist of neuronal network oscillations in various frequency bands, and these oscillations are generated by synchronized firing of many neurons in the network. Neuronal oscillations are an evolutionary conserved feature and can be observed in nearly all brain regions. These rhythmic activities play a key role in neuronal coding and higher cognitive processes. Although brain rhythms have been studied extensively for nearly a century, the mechanisms of neuronal oscillations are not fully understood. An important question is how neurons are entrained by the rhythmic activity. To be able to answer this, it is important to determine how neurons integrate synchronized synaptic inputs during network oscillations.
Dendrites represent the main input structure of neurons. They determine neuronal activity by integrating incoming synaptic signals in space and time. Research in the past few decades has demonstrated that dendrites are capable of performing a wide range of complex computations. However, most of these studies analyzed dendritic functions under conditions in which the surrounding neuronal network is sparsely active, while neurons in the intact brain constantly receive barrages of synaptic inputs. How dendrites process synaptic inputs in a highly active network, such as during natural rhythmic activity, remains an interesting and yet entirely open question. Addressing this question is critical for understanding neuronal computations in vivo.

The long-term goal of the project is to combine complementary expertise of the Norwegian and German groups to analyze dendritic computation during rhythmic activities of the brain. To reach this goal, we planned a strong interaction based on the following joint activities: (1) Developing the proposed scientific project; (2) Performing pilot experiments; (3) Transferring skills and techniques; (4) Preparing a common grant application (ERC synergy grant).

Dendritic computation during hippocampal network oscillations

A strong persisting trend in computer and software systems is the 
omni-presence of distributed and concurrent systems, as witnessed by
multi-core architectures, networks and multiprocessor systems on chip,
cloud computing, IoT, smartdust, blockchain, etc. The speed at which these
innovations take place bears the risk that we lose control of the
reliability and predictability of the software fabric on which our world
increasingly depends.  The increasing degree of concurrency introduces new
dimensions of complexity when it comes to guarantee the safety, security
and functional correctness, creating non-determinism and tangled
synchronisation problems that are extremely difficult to deal
with. Qualitative synchronisation problems involve deadlock, livelock,
priority inversion, data inconsistency or security attacks. Quantitative
synchronisation problems concern violation of realtime deadlines,
bottlenecks of throughput and utility or set up latencies. Traditional
testing and exploratory debugging methods cannot cope with synchronisation
problems.  Therefore, in our view, it is of paramount importance to give
more emphasis to the formal verification, analysis, and synthesis of
concurrency aspects in the practical software development process.  This
project combines recent work on weak memory models and static type-checking for memory-safe multi-threaded programming with recent advances in the SP technology. This will produce a first uniform methodology for ensuring memory safety and determinacy for general abstract data types. This advances the state of the art on both sides: It will support more powerful data abstraction, where main-stream concurrent programming typically only permits primitive memory registers. It will support genuinely concurrent
execution models and the consideration of weak-memory models, where SP compilers typically only generate sequential C code and ignore data races in the instruction set architecture.

Synthesis and analysis for concurrent programs (Syncopia)

The research project AUREAS aims to develop and evaluate a prototypical AR decision-making support system for crisis management. We focus on the potential of AR for enhancing the integration of social media data into decision-making processes. The project brings together the domain-specific knowledge and contacts to EMA professionals of the Centre for Integrated Emergency Management (CIEM) at the University of Agder (UiA) as well as the methodological expertise in social media analytics of the University of Duisburg-Essen (UDE). Moreover, methods of social media analytics mastered by UDE can be tried out in the control room (CIEMLab) run by UiA in a life-like AR setting. We propose that VR/AR can be employed to improve crisis response of emergency management agencies (EMAs).
Making the right decisions in crisis situations is particularly important as lives depend on these. However, decision-making is highly complex because these situations are characterized by a high degree of uncertainty and ambiguity. Thus, having access to a sufficient amount of valid information is critical. Nowadays, an increasing amount of crisis-related information can be found on social media and EMAs are slowly starting to make use of these. However, EMAs are confronted with challenges such as information overload and the perceived lack of methods to filter information. The intuitive approach of displaying additional information gained through social media analytics on control room screens would likely intensify the problem of information overload. In this situation, AR would be useful for showing additional information from social media based on the screen the decision-maker is looking on.
In our research project, we will investigate the possibilities of AR in a control-room setting together with crisis management practitioners. We will start by scrutinizing the literature, work with experts, and aim at providing an experimental tool.

Augmented Reality Support for Decision-Making in Crisis Management

In software engineering, demand of customers for configuration options that address various different business concerns creates the need to manage variability by developing not just a single software system but, in fact, an entire family of software systems with similar functionality. A Software Product Line (SPL) is a software engineering method to efficiently develop a family of software systems by capitalizing on their similarities while explicitly handling their differences in terms of configurable features. Due to the size and complexity of these systems, SPLs constitute a major investment with long-term strategic value. Over the course of time, SPLs have to be adapted as part of software evolution to address new or changed requirements, which is particularly complicated because an entire software family has to be adapted at once where features have multiple interdependencies.
While concepts exist for the construction and modification of SPLs, evolution is performed mostly as an informal procedure relying on the intuition and experience of individual engineers with, at most,medium-term goals in mind. The lack of long-term planning for SPL evolution creates a risk of potentially significantly increased development costs, deviation from intended development direction (if any) in collaborative efforts and, ultimately, missing long-term goals, which potentially causes a loss of clients and market shares for SPL vendors due to not addressing market needs properly. To counter these issues, the goal of the proposed project is to devise a methodology for long-term evolution planning in highly variable software systems to capture planned changes, to give assurances for reaching intended evolution goals and to allow collaboration which requires theoretical and practical knowledge in software engineering, variability management and software evolution.

LTEP: Long-Term Evolution Planning for Highly Variable Software Systems

Fractional-order systems are dynamic systems the mathematical description of which, and thus modelling, comprises fractional differential equations, that is, contains derivatives of non-integer order. Such fractional-order systems already proved useful in studying the various nonlinear, and even anomalous, behaviours in biology, material science, electrochemistry, and others. For instance, typical dynamic phenomena, calling for derivatives and integrals of fractional orders, can be of a chaotic, creeping, viscoelastic, and memory-containing type. So far both - the modelling and identification of physical plants to be controlled and the control systems to be designed and implemented - experienced limited benefits from the fractional-order systems theory, although the associated mathematical body has already reached certain maturity. The main scope for our collaborative research encompasses the analysis of the dynamics, including modelling and identification, and control design for the fractional-order systems with potential real-world examples. For reaching individual project targets and to comply with the overall program objectives, the solicited project will implement different practical measures and strengthen the academic relationship between the research groups at TUIlm (Technische Universität Ilmenau) in Germany and UIA (Universitetet i Agder) in Norway. The synergies expected from the complementary cooperative research work will increase visibility of both groups on national level and within the large international communities of control and systems engineering. It will also contribute to an enhanced education quality of the master and doctoral students at both institutions. The case studies on the fractional-order systems in control and mechatronic applications can also attract attention of various maritime, offshore, and construction industries, which are essential for the East- and West-Agder regions in Norway and local Thuringian industry in Germany.

Dynamics and Control of Fractional-Order Systems

Numerical modeling of reactive flow in deformable porous media as a multi-physics system continues to remain a challenging task. Beyond the coupling of fluid-structure interaction, which is currently a research topic of strong scientific interest by itself, multicomponent reactive transport is further involved. Typically, the time scales of the three coupled physical systems differ by orders of magnitude which is a considerable problem for numerical simulations and the indispensable resolution of all relevant time scales. Standard single-rate time discretization methods for multi-physics systems work with time steps that are allowed to vary in time but are constant over the involved subproblems. To exploit local time scale variations and ensure reliable simulations, one needs multirate (multiscale in time) methods that use different local time steps over the system's subproblems. 

The objective of this research project is to develop multirate schemes for reactive flow in deformable porous media with self-adaptive local time stepping based on a posteriori error control such that large-scale simulations become feasible. The developed schemes will work for a large range of discretization methods, including higher-order space-time methods.

Multirate Variational Time Stepping with Error Control for Reactive Flows in Deformable Porous Media (MATEROC)

This project seeks to bring together two different, but inter-connected research agendas that are being developed in parallel by the applicants at the GIGA in Hamburg and the University of Bergen. These agendas deal with a common preoccupation for the stability and the quality of democratic institutions, focusing on the apex of power, the elected chief executives, and the constitutional constraints on incumbents, particularly on the rules regulating their tenure: presidential term limits and presidential succession. While term limits are defined as the length and number of times a president may rule, succession rules define how transition from power from one president to the next occurs and who is allowed to succeed the incumbent. These rules are often negotiated and changed, or decided by fiat by an authoritarian president because, more often than not, incumbents seek to control the terms of their own retirement, first of all, by postponing the date of departure as long as possible (ideally, by removing term limits), and second, by controlling who will succeed them. As Baturo (2014) argues in his book “Democracy, Dictatorship, and Term Limits”, presidents who manipulate and extend their term limits tend to experience less orderly forms of succession. In fact, presidents without term limits have a higher risk of being the victims of a coup, assassination, or other forms of non-constitutional removals. This topic is highly relevant today when the world is experiencing a democratic backsliding. These new challenges to democracy often come from within the realm of civilian politics. Key to these processes are often incumbents' manipulation of both term limits and rules of succession. Combining the study of these two aspects of presidential regimes will allow us to explore better the mechanism and processes of democratic backsliding.

Presidents who die too soon and presidents who live too long. Term Limits and succession in Presidential regimes

Hjernen utgjør et enormt nettverk av nerveceller som er bundet sammen av aksoner. Aksoner er lange, tynne nervefibre som overfører informasjon fra cellekroppen til synapsene, hvor nervecellene kommuniserer med hverandre. Aksonet er altså nødvendig for å lede nervecellens signaler videre. Kunnskap om hvordan informasjon blir bearbeidet i aksonet, er derfor viktig for å forstå hvordan hjernen fungerer. Fordi aksonene er svært tynne - ofte mindre enn en tusendels millimeter tykke - er det teknisk uhyre vanskelig å analysere funksjonene deres i detalj. Mekanismene som kontrollerer signalprosesseringen i aksonene i hjernebarken, er derfor ennå ikke helt kjent.
Det nevrale nettverket i hjernebarken består av både stimulerende (eksitatoriske) og hemmende (inhibitoriske) nerveceller. I dette prosjektet ønsker jeg å studere aksonene til hemmende nerveceller i hjernen. Som deres navn tilsier, demper disse cellene aktiviteten i andre nerveceller, og dermed regulerer de hjernens nettverk. Feil og svikt i slike hemmende nerveceller kan ofte føre til epilepsi. Disse cellene har også en sentral rolle i informasjonsbearbeidingen i hjernen. De koordinerer hvordan informasjon, også den som hovedsakelig bearbeides av stimulerende hjerneceller, strømmer i det nevrale nettverket, både i tid og rom. Disse funksjonene avhenger av rask signalisering i aksonene til hemmende nerveceller. Målet med dette prosjektet er å avdekke mekanismen bak disse raske elektriske signalene. For å nå dette målet, vil vi bruke en kombinasjon av avanserte elektrofysiolgiske teknikker, bildeteknikker og datamodellering.
Den foreslåtte forskningsplanen vil kunne bidra vesentlig til forståelsen av hvordan hjernebarkens nettverk funksjonerer. Spesielt vil resultatene øke vår kunnskap om prinsippene som ligger til grunn for den raske informasjonsprosesseringen i nervesystemet. Resultatene våre vil også være viktige byggestener for å konstruere modeller av hjernens nettverk i datamaskiner.

This application aims to develop an ambitious and yet feasible collaborative project to analyze dendritic computation during rhythmic activities of the brain. A functional hallmark of the brain is its rhythmic activity. Brain rhythms are generated by the synchronized firing of many nerve cells in the network, and these oscillatory activities play a key role in neuronal coding and higher cognitive processes. To produce synchrony during rhythmic activities, nerve cells in the network translate synaptic inputs in their dendrites into action potential output in the axon with high temporal precision. But the mechanism underlying this temporally precise input-output operation is not well understood, because dendrites and axons of nerve cells in the mammalian brain are very thin and nearly inaccessible to functional analyses. Consequently, studying dendritic computation during neuronal network oscillations represents a long-standing technical challenge in neuroscience. To face this challenge, the Synaptic Signaling group at the University of Oslo and the Neurophysiology group in Heidelberg will take advantage of their complementary expertise to jointly address a question of their common interest: how is information processed in the dendrites of hippocampal neurons during neuronal network oscillations? To maintain a long-term collaboration, we will take the opportunity provided by the DAAD mobility grant to prepare a collaborative European Research Council (ERC) synergy grant. The collaboration is expected to produce a strong synergistic effect to accelerate our research of how neuronal oscillations organize the formation, storage and retrieval of memories at the subcellular level, which represents a key question at the frontier of neuroscience.

Further details are described in the project description found in the attachments.

In this project we want to use single-molecule tracking (SMT) to gain insight into the mechanisms of DNA repair by the real-time tracking and analysis of single DNA repair proteins in action. The main challenges in SMT of DNA-protein complexes are (1) having the DNA locked in a linear form in order to be able to track the protein that is moving along the DNA contour, (2) being able to detect the rather weak signal from one single protein labeled with a fluorescent reporter probe, and (3) perform a robust data acquisition and analysis in order to reliably obtain quantitative biological and biophysical results. 

Studies of single-molecule imaging of DNA repair proteins in action have so far been performed either using a constant flow of buffer to stretch the DNA substrate, or labeling of proteins using quantum dots and antibodies, to obtain high quantum efficiency and long-lived signals. Both these methods have severe fundamental drawbacks with respect to extracting relevant biophysical parameters.

Therefore, we have developed a new protocol combining DNA substrate trapping, protein labeling and data collection strategies which eliminates shortcomings of previous published studies. By trapping the ends of DNA we can optically track the protein while it is moving along the DNA. Overcoming the second challenge is achieved through a series of optimizations to reduce the noise and detect the signal. A unique combination of optical tweezers and high localization precision
microscopy meets the core needs of the single molecule experiments very well. There are no such instruments in Norway, and the setup at UBI (Bielefeld, Germany) is ideal for these kinds of experiments by combining the two research groups expertise in biology and optics, respectively.

Development of single-molecule tracking using fluorescence microscopy

The idea of policy styles has never been extensively examined in either comprehensive or comparable ways as regards urban or metropolitan planning and policy making including standard operating procedures for making and implementing policies and the specific norms underlying and legitimising these policies. It is thus timely to carry out comparative research on urban policies and governance arrangements in targeted political and socioeconomic contexts. We suggest exploring and comparing the evolution and reorientation of such arrangements, focusing particularly on the development of urban and metropolitan development strategies in Oslo, Hamburg and Hannover, while discussing the results in a broader European context. As such, this project will contribute to the following innovations:
a) Empirical knowledge on decision-making processes: New knowledge about policy styles and governance arrangements in urban and regional development processes can help lead to innovative approaches in decision-making related to shaping the built environment.
b) New theory development: Based on state-of-the-art research in urban and metropolitan development and governance arrangements, and informed by existing and emerging policy styles and forms of governance in the above German and Norwegian contexts.
c) Policy learning and innovation: A contribution to capacity-building for mutual learning in relation to policy styles and governance implications. In turn, this can help to facilitate policy experimentation and governance innovation.
d) New comparative research methodologies: By establishing a comparative framework for analyzing urban or metropolitan policy styles in different national and local contexts, the project further contributes to the development of innovative comparative research strategies and methodologies.
e) Advanced teaching materials: Based on the further development of theories of policy styles and through the advancement of comparative research methodology.

Urban Planning and Governance Styles. A Comparative Study of Oslo, Hamburg and Hannover

We propose a novel method for reaching ignition conditions in ICF without the build-up of any instabilities, by implementing relativistic concepts not previously used in this field. Instead of the usual adiabtic compression and heating of a spherical fuel pellet using an array of lasers, our project proposal is to use a linear configuration with a flat target and only two lasers. In this way, using RFD, we can heat the target by rapid light absorption through rapid ignition. The detonation front will then become "time-like", which makes simultaneous, whole volume ignition possible. Then there is no time for instabilities to occur. 

This method is based on the fundamental theories of Taub (1948), with the correction by Csernai in 1987. New relativistic fluid dynamics methods, developed in the field of ultra-relativistic heavy ion reactions at CERN provide spin-offs for Inertial Confinement Fusion. The time-like behavior of the detonation front is only possible using relativistic energies, and this behavior is well known in Relativistic Heavy Ion Collisions, but never before used in ICF.

In order to have uniform heating throughout the whole fuel volume, we "dope" the fuel target with golden nano-shells. The use of such Nano-Technology is also a completely novel concept in ICF.

We will also study heavy ion induced fusion, which is relevant for  FAIR in Darmstadt and FIAS in Frankfurt. The same rapid ignition and the uniform burning can be achieved by short accelerator bunch length focusing.

Volume Ignition in Pellet Fusion

The project aims at developing and implementing a numerical framework for the prediction of crack formation and growth due to material fatigue in engineering structures. Material fatigue is a crucial issue for the safe design of many engineering structures, and its prediction by numerical simulations is still a major challenge. This project will create a novel numerical framework for engineers to perform accurate fatigue life predictions with less effort than state-of-the-art FEM software. We focus on fatigue in thin-walled structures made of aluminum alloys and fiber reinforced composite. The numerical models are based on isogeometric analysis (IGA) for structural analysis and a phase-field description for modeling crack evolution. The developed models will be validated through experimental tests in the structural analysis laboratory of the Norwegian group. The two groups provide a perfectly complementary background and preliminary works for the objectives of this project. 
The project is planned for two years with regular research visits. These visits include short visits of for joint meetings (kick-off, mid-term, and final) and longer stays of the involved PhD and MSc students to closely work together with the other group. 
The purpose of the visits is:
- Bring together experts with complementary background and common vision.
- Establish personal relations between the groups, as fundament for an efficient collaboration.
- Give the young researchers the chance to get to know different environments and learn from internationally renowned experts in their fields. They will get a sound expertise in the theories, and practical experience in high-end numerical simulations and their experimental validation.
- Furthermore, it is envisaged that during or after completion of the project, a Master student might become a PhD student at the foreign partner's institution, which would strengthen even more the long-term perspective of this collaboration.

Isogeometric phase-field modeling of fatigue in slender structures

The free movement of people, goods, capital and services within the Schengen area is one of the major achievements of the European integration process and provides economic opportunities for businesses and residents in the Schengen area. "Schengen" not only stands as a symbol of the process of economic integration, but also for social cohesion and a common identity as European citizens. Those achievements are particularly important for border zones in the Schengen area. In the wake of tightening border controls and securitization measures, because of the contemporary migration crisis, the roles and functions of these borderlands are both challenged and changed, turning the former "zones of contact and co-operation" increasingly into "lines of separation". Even though the practical consequences of this "Schengen crisis" (Börzel/Risse 2017) can be observed (f.ex. the introduction of border controls and traffic jams on the German-Austrian or Swedish-Norwegian border), there is little knowledge to date on the social-economic effects that they have on companies and residents in the border regions where border enforcements take place. In our project, we aim to explore the effects of (changing) border enforcements and practices in selected border regions along the Swedish-Norwegian and German-Austrian border by adopting a comparative perspective. We conceptualise border regions as landscapes with a shared history and established traditions and practices of how to live along and across the border (Newman 2006, Perkmann 2003, Wagner/Lukowsk 2010). We will investigate if and how changing border enforcements would affect cross-border activities such as small-scale cross-border trade and logistics, commuting, and (shopping) tourism, but also the perceptions with regard to smuggling, human trafficking and irregular entries. In the collaborative Norwegian-German project, we will empirically work with field/participant observation and interviews from the two border regions.

Contesting Schengen: Effects of border enforcements on economic and social cohesion in European border spaces

We build on the anti-de Sitter/conformal field theory correspondence in theoretical physics. This conjecture gives a correspondence between gravitational dynamics (rooted in Einstein?s general relativity) and quantum field theory. By considering Einstein?s field equations for a time-dependent gravity configuration, we will find solutions which provide new information about the dual non-equilibrium quantum field theory at strong coupling.

The research will begin by taking Einstein's equations and deriving the partial differential equations in the special case at hand, in anti-de Sitter space-time. We would bring mathematics to bear on this problem by writing the problem as an initial boundary value problem. In particular we plan to write this as an hyperbolic problem by a conformal transformation of the 3-metric [1]. This is in principle possible to do in the case we are interested in. It leads to a first order hyperbolic system for which we will derive the eigenstructure of this system [2]. This leads to a form of the problem for which the theoretical and numerical knowledge of Prof. Klingenberg and Prof. Risebro can come to bear. Not only can the accuracy of the numerical method be proven, but also it will be possible to perform reliable numerical simulations yielding predictions for observables in the dual non-equilibrium quantum field theory that were not accessible for numerical study before, such as the entanglement entropy in steady state systems in three and more dimensions.

Numerical solutions of non-equilibrium quantum field theories via 
gauge/gravity duality

For the present project we take language complexity as a key to the study of LS-KS, whereby complexity is seen as one of three main parameters of what we call Transparent Language. Among features affecting complexity we will in particular focus on verb valence, and the lexical and structural constraints that valence frames enforce. In establishing LS-KS (Leichte Sprache-Klart Språk) corpora, we will partly make use of existing LS corpora. The project will study properties of LS-KS relative to those of the standard language, and on the other hand facilitate the derivation of corpora and instructive paradigms for the creation of LS-KS resource for both languages. We aim to create 3 resources:
(1) a dictionary for verbs comparing valence frames of a normal complexity with valence frames suitable for LS-KS
(2) an addition to the Open German WordNet using results from (1) A similar resource will be created for Norwegian.
(3) building an application that allows for the rephrasing of expressions building on standard Norwegian to KS Norwegian. A similar possibility will be explored for German.
In the process of creating (1)-(3), we will develop and make use of
(a) conversion procedures between LS and standard German valence frames
(b) conversion procedures between normal KS and standard Norwegian valence frames. All resources will be made public.

FRIMUF-Miljø- og utviklingsforskning

Predicting the Population Dynamics of Large Mammals

Tildelt: kr 0,74 mill.

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FRIMUF-Miljø- og utviklingsforskning

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