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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 ERASME-Støtte til innovasjonsprosjekter i SMB-bedrifter i Europa fordelt på år

Midlene fra ERASME-Støtte til innovasjonsprosjekter i SMB-bedrifter i Europa fordelt på fylker

Midlene fra ERASME-Støtte til innovasjonsprosjekter i SMB-bedrifter i Europa fordelt på fagområde

Proposal (project outline) for the ERASME 6th call Closing date 30.10.2009. Fresh fish. Rapid tool to determine fish quality

EraSME FreshFish - Rapid tool to determine the freshness of fish

Målet med dette prosjektet var å bruke avanserte røntgenspredningsmetoder for å bedre forståelsen av nanostrukturerte materialer, med vekt på katalytiske anvendelser. Som det framgår av rapporteringen, har prosjektet vært vellykket og resultert i ny viten  og flere gode publikasjoner. Prosjektet har også bidratt til kompetansebygging på in-situ eksperiment med gasser og høy temperatur.
Lagring av karbondioksid blir for tiden heftig diskutert pga. at atmosfærisk karbondioksid er en viktig faktor for global  oppvarming. For å lagre karbondioksid, må gassen først fanges i en reversibel prosess slik at den kan transporteres bort for videre opplagring. Dette kan gjøres med litiumzirkonat, hvor Li2ZrO3 reagerer med CO2 og blir til Li2CO3 og ZrO2 når partialtrykk et av CO2 er høyt og temperaturen over ~500 grader C. Den reversible reaksjonen skjer når partialtrykket av CO2 er lavt og temperaturen er over 650 grader C. Vi ønsket å avbilde disse partiklene under oppvarming til 600 grader C, og også når gassen blir s kiftet fra vanlig luft til karbondioksid. Dette er eksperimentelt krevende siden partiklene er meget små (~100 nm), og de må være omgitt av gass for at reaksjonene skal kunne foregå. Vi løste utfordringen ved å bruke koherent røntgenavbildning ("ptychogra phy").  Vi plasserte Li2ZrO3-partikler på tynne silisiumnitrid-membraner som vi monterte i en koherent røntgenstråle ved synkrotronen i Sveits (Swiss Light Source). Vi klarte å avbilde litiumzirkonat-partiklene under varierende gass- og temperaturforhold,  hvilket er av stor vitenskapelig interesse. Resultatene er publisert i Applied Physics Letters (Høydalsvik et al, 2014). 
Et annet delarbeid handlet om å karakterisere nanostrukturer på overflater, nærmere bestemt en prøve med GaSb nanokjegler, ved hjel p av ellipsometri og GISAXS (grazing-incidence small-angle X-ray scattering). Ved å kombinere disse teknikkene kunne vi både regne ut midlere form på kjeglene og finne 2D pakke-mønster for kjeglene. Spesielt interessant var det å kunne konkludere fra begg e teknikkene at kjeglene har en viss tilt-vinkel i forhold til overflatenormalen. Arbeidet er akseptert for utgivelse i Thin Solid Films (Høydalsvik et al, 2013).
Fischer-Tropsch Syntese er en katalytisk prosess for å omdanne hydrogen og karbonmonoksid t il drivstoff. Ofte brukes kobolt-nanopartikler med diameter ~20 nm til dette, ettersom man oppnår et stort total overflateareal fra katalysator-partiklene, og dermed høyere katalyse-aktivitet. Det er eksperimentelt krevende å studere nanopartikler under i ndustrielle prosessbetingelser med høy temperatur og høyt gasstrykk. Vi har brukt in situ småvinkel-røntgenspredning (SAXS) for å følge utviklingen av formen på nanopartiklene i alumina mens prøven ble utsatt for realistiske katalyseforhold (10 bars trykk  og temperatur på 210 grader Celsius). Ved å sammenligne de målte småvinkel-spredningsmønstrene med teori og modeller, har vi funnet at partiklene kan anses å være "diffuse" ved at de har en kontinuerlig overgang i elektrontetthet mot omkringliggende mate riale. Fra dette kan vi konkludere at overflatestrukturen på partiklene endrer seg når syntesegassen blir ført inn. Det er sannsynlig at den observerte endringen av overflatestuktur er relatert til økt katalyse-aktivitet rett etter at syntesegass (hydroge n og karbonmonoksid) tilføres prøva. Dette åpner for bedret forståelse av hvordan syntesegassen påvirker overflaten til katalysepartiklene, som vil være nyttig for å konstruere mer effektive katalysatorer i framtiden. Resultatene ble presentert med foredr ag på Small-Angle Scattering konferansen (SAS-2012) i Sydney, og er publiser i Journal of Physical Chemistry C (Høydalsvik et al, 2014).
Ytterligere eksperimenter er gjennomført og publisert, delfinansiert med dette prosjektet, vi nevner spesielt:
- Sil kefibre under varierende relativ luftfuktighet har blitt studert med tomografi basert på koherent diffraksjon ("ptychography"). Det er kjent at det er porer inne i silkefibrene, og disse har vi avbildet ikke-destruktivt i 3D. Kvantitativ mapping av elektr ontettheten viser at proteinstrukturene i silkefibre, snarere enn porene, fylles under forhold med høy luftfuktighet. Arbeidet er publisert i Macromolecules (Esmaeili et al, 2013). 
- Groing av epitaksiell grafén ved industrielt realistiske (tilstrekkeli g lave) temperaturer er et vesentlig skritt for å kunne realisere elektronikk basert på grafén. Arbeidet er publisert i Carbon (Cooil et al, 2012). 
- Mesoporøse alumina substrat er viktig for en bedret forståelse av katalyse. Vi har demonstrert at alumi nafilmer med regulær porestruktur kan syntetiseres ved å bruke selv-organiserte blokk-kopolymere miceller. Arbeidet er publisert i Journal of Materials Chemistry A (Voss et al, 2014).

Vi konkluderer at prosjektet har vært meget vellykket og frambrakt n y viten gjennom en serie nyskapende eksperimenter.


This proposal is aiming at developing new techniques for studying functional materials such as catalysts at their working conditions. Rational design of catalyst nanomaterials and the ability to identify and observe the active sites while functioning have  been highlighted as key barriers for the future design of catalyst materials. While a wide range of techniques are routinely being used to characterise catalyst materials, only a limited few give direct information at reaction conditions relevant to indu strial processes (Weckhuysen 2009).

Recent advances in methods utilising synchrotron radiation open for unprecedented opportunities to study the electronic and structural properties of nanostructured catalysts and to actually "see" these catalysts workin g in a realistic environment. In this context, the proposed project is especially targeting methods development for in situ characterization of catalysts, with characterisation of bimetallic core-shell nanoparticles as chosen model system.

Towards nanoscale 3D imaging of working catalyst nanoparticles

The main goal of this project is to structurally and functionally characterize the molecular interactions underlying infection by the common gastric pathogen H. pylori. This will not only lead to a better understanding of the fundamental molecular recogni tion mechanisms, but also put us in a position to develop new tools for disease intervention. This project is part of a broader investigation by us, directed at the role of blood group antigens in pathogenesis, as the blood group of individuals has been s hown to correlate with the severity of disease in a number of bacterial infections. Understanding the underlying molecular recognition processes may eventually provide us with important leads towards patient-specific treatment and prevention strategies.

 This project is very challenging, as it deals with the structure determination of membrane proteins. Membrane protein structure determination has two major bottlenecks: the production of the protein sample in sufficient amounts and protein crystallization . In this case, protein production is a minor issue, at least for BabA, as 30% of the total protein content of H. pylori consists of BabA, its major blood group antigen binding adhesin. However, membrane protein crystallization is notoriously difficult an d membrane protein crystals are often of inferior quality, making extensive synchrotron use a necessity. This project will pave the way to the establishment of membrane protein crystallography in Norway.

Microbial recognition investigated by membrane protein crystallography

This proposal is a project aiming at strengthening the current upgrade of the Swiss-Norwegian Beamline B-station from a standard X-ray diffraction (XRD) and absorption spectroscopy (XAS) beamline to a state-of-the-art beamline for in situ/operando catalys is experiments. XAS and XRD are the techniques of choice for studying long- and short-range order in the solid state, respectively. Furthermore, with the availability of Raman spectroscopy, one is able to probe the scale between these two extremes. All th ree techiques have in common that they are very suitable for studying catalyst materials at relevant working conditions (in situ). Combining these techniques in situ provide a tool for studying a wide range of scientific problems that is much more powerfu l than the separate techniques. The combination can only be effected at a synchrotron (because XAS is only practical with synchrotron radiation which of course also makes XRD far superior to conventional lab sources). This combination will place SNBL at t he forefront  for characterising catalysts and other types of materials. Recently, we have invested in a dedicated reaction gas feeding system and a online mass spectrometer to be placed at the beamline (through the research based innovation centre InGap) . It is therefore highly relevant and to the interests of several large SNBL user groups in Norway and abroad to that a trained chemical engineering candidate can work closely with the beamline personnel and the users to make the dedicated in situ equipme nt readily available to the user community.

The project aims at designing and constructing several in situ cells for combining XRD, XAS and Raman spectroscopy. The cells and the in situ instrumentation will be applied to two selected systems: structured,  selective CO oxidation catalysts and NGL dehydrogenation catalysts. The cells and catalytic testing routines will be made available to the general users.

Multi-technique probing of catalytic reactions at real working conditions

DNA repair enzymes are important for maintaining genome stability of microorganisms during environmental stress. This project aims to identify the role of DNA repair enzymes in the radiation resistance mechanism of Deinococcus radiodurans (DEIRA) using a combination of molecular biology, biophysical techniques and synchrotron radiation experiments. The DNA glycosylases, 3-methyladenine DNA glycosylase (AlkA) and Endonuclease III (EndoIII), which are present in several copies in the genome of DEIRA, have b een selected as targets for this study. Proteins will be produced recombinantly in quantities necessary for interaction and structural studies. Protein complexes will be characterised through biophysical methods and structural studies will be carried out on stable complexes using Small Angle X-ray Scattering (SAXS) experiments and X-ray crystallography. In addition expression profiling experiments will be carried out to investigate the effect of X-ray irradiation on production of AlkA and EndoIII at RNA a nd protein levels. The project will benefit immensely from the long-standing collaboration investigating mechanisms of DNA repair between the Norwegian Structural Biology centre (NorStruct) at the University of Tromsø and the Macromolecular Crystallograph y (MX) group at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. NorStructs excellent infrastructure will provide a solid basis for this project, which can only be enhanced by the support and access to the state-of-the-art structura l biology facilities available at ESRF.

Functional and structural biology studies of DNA repair proteins from the radiation resistant bacterium Deinococcus radiodurans

One major unsolved problem for the introduction of hydrogen into the global energy system is effective storage of hydrogen. This proposal addresses novel materials for hydrogen storage and in particular aluminium-, magnesium- and boron-based metal hydride s. Materials with hydrogen contents higher than 6 mass% H will be studied with synchrotron X-ray diffraction. High-resolution X-ray diffraction is important for structural studies of new compounds and also for studies of morphological properties and effec ts of catalysts. In-situ diffraction studies will be carried out in order to understand absorption/desorption processes, effect of catalysts and to determine thermodynamical properties of novel hydrides. Combination with other techniques, for example comb ined EXAFS/diffraction and Raman spectroscopy/diffraction will be performed. In addition the combination with neutron diffraction will also be important. The project will accommodate work for 1 PhD student who will stay about 9 months at ESRF, probably at  SNBL, during the project period. The project will involve extensive national and international collaboration.

Novel materials for hydrogen storage studied by synchrotron X-ray diffraction

The goal of the present project is to utilize modern technology and interdisciplinary work to close a fundamental gap in the description of the medium sea ice. We will for the first time apply synchrotron-based X-ray computed micro-tomography (XMT) to obt ain a three-dimensional description of the sea-ice-matrix. 

XMT has earlier been successfully applied to the three-dimensional monitoring of snow, polar firn, and artificial ice samples. The synchrotron-based approach allows for a resolution of a few mik rometers, necessary to describe the sea ice microstructure properly.

Size distribution functions and the detailed morphology of ice, liquid and gas inclusions will be determined, to improve the understanding of the dynamic freezing process of sea ice and  the formation of permeable pore networks. 

Brine pocket migration is one important mechanism during morphological metamorphosis of brine pocket networks. Intermittent phase transitions during warming and cooling, leading to pore widening/coarsening and reshaping, is another important process. A temperature-gradient setup with XMT will be used to monitor the dynamics near the sea ice seawater interface, and the migration of brine pockets. In combination with thermal cycling experiments this will improve microphysical modelling of natural sea ice. 

Disregarding a few reported observations of salt crystals obtained by optical means, there is a lack in observations
of the locations of impurities in sea ice, necessary to develop fractionation theories. X-Ra y based
micro-spectroscopy at the LUCIA beamline of the Swiss Light Source (SLS) allows to study the chemical
composition (chemical environment (NEAXFS) and the ordering (EXAFS)) of inclusions. First tests of sea ice micro-spectroscopy are planned.


The present approach will contribute to basic resarch on the microscopic scale. It will also help to solve
macroscopic scientific problems related to the medium sea ice in polar regions.

Synchrotron-based X-ray studies of sea ice

Støtte til opphold ved SNBL

The project will perform a structure/function study at an atomic level where protein targets will be selected from the extremophilic ("being able to survive under extreme conditions") bacterias Deinococcus radiodurans and Vibrio salmonicida. The target se lection will be mainly based on results from the ongoing search for virulence factors from V. salmonicida, but also on homologous proteins from D. radiodurans when advantageous. The main objective of the project is to perform an in-depth study of proteins  essential for proliferation and virulence of V. salmonicida. The selected proteins will be produced using recombinant techniques and in quantities required for structural and functional studies. The homologous proteins from the two organisms will be subj ected to a biochemical and structural comparative study in order to highlight structural and functional features. A crucial aspect of the project is to benefit from a two-way exchange of personnel, techniques, ideas and general expertise between the Norwe gian Structural Biology Centre (NorStruct) and the Macromolecular Crystallography (MX) Group at the European Synchrotron Radiation Facility (ESRF). The rather unique competence of the MX group at the ESRF in data collection and structure determination on novel proteins will be an asset to NorStruct. In addition, the MX group is facing similar tasks as NorStruct in that both entities are handling a relatively large number of target proteins in a structural genomics approach. Transfer of technology and stra tegies for problem-solving will thus be useful for both research groups.

A comparative structure/function study at an atomic level

Comparing enzymes from the fish-pathogen Vibrio salmonicida and 
the radiation

The general aim of the project are structure studies of ferroic materials and is composed of three complementary parts.  Inorganic perovskites and perovskite-like materials comprizing nanosize epitaxial films and nanosize particles are the targets for two  of the subprojects.  A common critical parameter here is size and its impact on stability and electronic properties which determine several functions of both fundamental and technological importance.  The third subproject is related to organic ferroics.  Diffraction data of excellent quality have been obtained for two compounds, enabling detailed studies of the structural changes associated with the ferroic transformation.  Application of a three-beam interference technique is proposed for studies of the  structural dynamics during the transformation.

In all the three subprojects we will rely on synchrotron radiation under non-ambient conditions involving  temperature, pressure and electric field, in order to obtain a better understanding of important as pects of ferroic materials.

Structure studies of ferroic materials under non-ambient conditions.

One major unsolved problem for the introduction of hydrogen into the global energy system is the storage of hydrogen. The present proposal concerns metal hydrides based on complex hydrides, an important group of metal hydrides where improved hydrogen stor age properties are anticipated. The focus is on using high resolution X-ray synchrotron diffraction to understand kinetic, thermodynamic and morphological properties that must be overcome to develop complex hydrides into hydrogen storage materials of real  interest for the transportation sector.

High capacity hydrogen storage materials studied by X-ray synchrotron diffraction

Kryostat ved SNBL

Fysiske fenomener i leire er et prosjekt som omfatter eksperimentelle studier, simuleringer og teori forbundet med transport av vann inn i og ut av kompakte syntetiske leirestrukturer. Videre omfatter prosjektet studier av strukturer av sammensatte mesosk opiske leirepartikler i vann kontrollert av salter, og hvorledes disse strukturene oversettest til makroskopiske egenskaper som for eksempel elastisitet og flyt.

ERASME-Støtte til innovasjonsprosjekter i SMB-bedrifter i Europa

EraSME FreshFish - Rapid tool to determine the freshness of fish

Awarded: NOK 0.24 mill.

Summary

Funding scheme:

ERASME-Støtte til innovasjonsprosjekter i SMB-bedrifter i Europa

Thematic Areas and Topics