Digitala Vetenskapliga Arkivet - Academic Archive On-line
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From Photon to Protein: Using X-ray Lasers for High-resolution Structure Determination with Single Proteins
No full textX-ray Free-Electron Lasers (XFELs) promise Single Particle Imaging (SPI) of biomolecules through “diffraction before destruction,” but present experiments involving single proteins are limited by weak scattering signals and significant background scattering. This background scattering comes primarily from the sample delivery, and poses a major challenge for small proteins. Recent progress in aerosol sample delivery has shown that the background scattering can be reduced by about 80% by replacing some of the carrier gas with helium. The first paper in this thesis was a large-scale simulation study of a 15 nm diameter GroEL protein, where the impact of reduced gas background on the resolution was investigated. In Paper II the feasibility of SPI is investigated using liquid sheet sample delivery with the same protein. I find that it is indeed possible to do SPI in solution but with demanding requirements: specifically, a large number of diffraction patterns and a high fluence, which currently only a nanofocus can deliver. The second half of this thesis focuses on my contribution to analysis performed on experimental data. Paper III is about work where I developed the initial scripts for data analysis of a Rayleigh-scattering microscope used to characterise the aerosol sample delivery system that is also used during SPI experiments. The final paper is about my contribution to an experiment where the liquid sheet sample delivery was used during an experiment. I end this thesis with an outlook where I provide my perspective on the computational and experimental improvements that can make the biggest impact on the future of SPI
Design of 3D spheroid models for drug-response studies of HER2-targeted radiopharmaceuticals.
No full textThe development of targeted radionuclide- and chemotherapeutics-based drugs requires in vitro models that reflect the structural and molecular complexity of solid tumors. Here, we present a high-throughput 3D cell culture platform for targeted drug response studies. The platform was based on agarose micro-dishes that generate 81 tumor spheroids. The platform was validated across eight human and murine cancer cell lines that overexpress receptors of the HER family. The high spheroid yield supports robust quantitative analysis of binding of radiolabeled compounds, while spheroid trapping in microwells enables medium exchange for precise drug exposure. Therefore, we evaluated targeted radionuclide therapy of EMT-HER2 spheroids using the HER2-specific affibody PEP48937 labelled with terbium-161. We demonstrated both HER2-specific binding to spheroids and receptor-specific therapeutic effects, including reduced spheroid proliferation over time and impaired cell migration. These results highlight the platform potential to accelerate the development of targeted cancer therapeutics for biomedicine
Toward a transparent life cycle assessment of photovoltaic systems : Addressing regulatory and methodological challenges
No full textPhotovoltaic (PV) systems are central to global decarbonization, but their assessed environmental impacts vary due to inconsistencies in life cycle assessment (LCA) methodologies. These differences hinder comparability and the development of a transparent sustainability framework. To address this issue, this review systematically synthesizes PV LCA studies across five continents. The analysis highlights variations in system boundaries, functional units, data quality, and regulatory frameworks, revealing that methodological coherence is strongly shaped by regional policy and data infrastructure. Europe, supported by stringent regulations and localized inventories, demonstrates high methodological alignment. In contrast, Africa and Latin America face major data gaps, with over 90 % of studies relying on non local inventories, creating uncertainty in the results. Building on these findings, this study proposes key harmonization strategies, including enhanced transparency, the adoption of standardized guidelines such as IEA PVPS Task 12, and the targeted development of regional life cycle inventory databases. These measures provide policymakers, industry, and researchers with a practical framework to strengthen the reliability and comparability of PV sustainability assessments, supporting solar energy’s role in a low carbon future. Future research should prioritize the expansion of localized datasets and the integration of dynamic LCA approaches to capture rapid technological evolution and circular economy principles
Nickel : Geochemistry, biochemistry and its role in chemical and biological evolutions
No full textNickel is a versatile element that plays critical roles in Earth's geological and biological evolution, from the depths of the magmatic mantle to the complexity of prebiotic chemistry. While it is not considered the sole catalyst for the origin of life, recent research suggests that Ni may have had a more profound role than traditionally recognized. This review synthesizes Ni isotope geochemistry, biology, and prebiotic chemistry, exploring how Ni isotope variations offer new insights into magmatic processes, hydrothermal systems, and the cycling of Ni through Earth's lithosphere and hydrosphere. We summarize the pathways of Ni in oceanic environments, highlighting its influence on biogeochemical cycles and microbial metabolisms that shape global ecosystems. Furthermore, we examine the essential roles of Ni in biological systems, focusing on its function as a catalytic metal in enzymes crucial for nitrogen and carbon cycling. Extending to the prebiotic world, we evaluate Ni's potential in catalyzing life's earliest chemical reactions, including the polymerization of amino acids and the fixation of CO2, possibly driven by unique metal-ligand interactions. Our comprehensive review positions Ni as a pivotal element across geological timescales and environments, underscoring its relevance to both planetary and biochemical processes
Olfaction and Memory Related Brain Connectivity : In Health and Parkinson’s Disease
No full textParkinson's Disease (PD) is among the most prevalent neurodegenerative diseases, primarily recognized for its motor symptoms. However, PD also encompasses debilitating non-motor symptoms (NMS), such as olfactory dysfunction and memory decline, both strongly associated with cognitive deficit. As the disease progresses, combined with long-term oral levodopa therapy, patients experience frequent and unpredictable motor fluctuations, marking the so called "complication phase". At this phase, device-aided Parkinson therapy (DAPT), which provides continuous dopaminergic stimulation, can effectively restore motor control. Despite its efficacy, some patients exhibit increased apathy and cognitive decline following DAPT, highlighting the need for new markers of cognitive decline in PD before DAPT selection. The objectives of this thesis are: (1) to explore dynamic functional connectivity (dFC) underlying olfaction and memory processes, with a particular emphasis on episodic odor memory, and (2) to map hippocampal dFC patterns during task-based and resting-state conditions and assess their implications for olfactory function and declarative memory in individuals with PD, awaiting evaluation for DAPT. By using independent component analysis and k-means clustering as main methodological approaches in this thesis, data analysis relied minimally on theoretical assumptions and was predominantly explorative and data-driven. Study I identified an overlapping neural network encompassing regions of the olfactory cortex engaged during passive smelling, odor encoding and odor recognition memory (ORM). A distinct ORM-related network involving the hippocampus exhibited delayed reactivity. Moreover, successful recognition of previously encoded odors was associated with neuronal suppression. Study II revealed that four hippocampal networks were sequentially activated during ORM. One network, incorporating regions of the dorsal attention network, showed shorter and less frequent activations, along with reduced asymmetric hippocampal activity (AHA), a pattern linked to impaired successful ORM in PD. Study III uncovered two resting-state hippocampal networks that distinguish individuals with PD from healthy controls. The first network, involving occipitoparietal regions and the cerebellum, exhibited shorter activations, whereas the second network, including regions of the central executive network, showed less frequent activations in PD. Individuals with PD who demonstrated reduced AHA within these networks, exhibited a general trend toward deficit in semantic odor memory and auditory-verbal memory. Taken together, ORM not only engages primary olfactory regions but also recruits higher-order cognitive areas such as the hippocampus. Individuals with PD exhibit shorter and less frequent activations of specific hippocampal networks, along with reduced AHA, both during episodic olfactory memory task and at rest. These hippocampal dFC patterns are associated with deficits in declarative odor memory and auditory-verbal memory, suggesting their potential as markers of cognitive decline in PD, particularly prior to the selection of DAPT. Nevertheless, longitudinal studies with larger, more diverse, and well-characterized cohorts are essential before these markers can be translated into clinical practice.Parkinsons sjukdom är en av de vanligaste neurodegenerativa sjukdomarna och är främst känd för sina motoriska symptom. Sjukdomen innefattar dock även inskränkande icke-motoriska symptom, som nedsatt luktsinne och minnesfunktion. Båda är nära relaterade till kognitiv svikt. I takt med sjukdomens progression och vid långtidsbehandling med oral levodopa, upplever patienter frekventa och oförutsägbara motoriska fluktuationer, vilket kännetecknar den så kallade "komplikationsfasen". Vid denna fas kan apparatassisterad behandling vid Parkinsons sjukdom, som ger kontinuerlig dopaminerg stimulering, effektivt återställa motorisk kontroll. Trots behandlingens effektivitet, uppvisar vissa patienter ökad apati och kognitiv försämring efter apparatassisterad behandling. Detta understryker behovet av nya markörer för kognitiv svikt vid Parkinsons sjukdom före valet av apparatassisterad behandling. Avhandlingens syften är: (1) att undersöka dynamisk funktionell konnektivitet (dFC) som ligger till grund för lukt- och minnesprocesser, med särskilt fokus på episodiskt luktminne och (2) att kartlägga hippocampala dFC-mönster under uppgiftsbaserade betingelser och vilotillstånd samt bedöma deras betydelse för luktfunktion och deklarativt minne hos individer med Parkinsons sjukdom inför utredning och val av apparatassisterad behandling. Användningen av oberoende komponentanalys och k-means klustring som centrala metodologiska angreppssätt innebar att dataanalysen i denna avhandling i begränsad grad baserades på teoretiska antaganden och i stället präglades av ett explorativt samt datadrivet förhållningssätt. Studie I identifierade ett överlappande neuralt nätverk som inkluderade områden i luktbarken vid passivt luktande, luktinlärning och luktigenkänning (ORM). Ett distinkt ORM-relaterat nätverk som inkluderade hippocampus uppvisade fördröjd reaktivitet. Utöver detta, framgångsrik luktigenkänning av tidigare inlärda dofter associerades med dämpad neuronal aktivitet. Studie II visade att fyra hippocampala nätverk aktiverades sekventiellt under ORM. Ett nätverk som inkluderade områden i det dorsala uppmärksamhetsnätverket uppvisade kortare och mindre frekventa aktiveringar samt reducerad asymmetrisk hippocampal aktivering (AHA), ett mönster kopplat till nedsatt ORM hos individer med Parkinsons sjukdom. Studie III identifierade två hippocampala vilonätverk som skilde individer med Parkinsons sjukdom från friska kontroller. Det första nätverket, omfattande områden i nackloben, hjässloben och lillhjärnan, uppvisade kortare aktiveringar, medan det andra nätverket, som inkluderade områden i det centrala exekutiva nätverket, uppvisade lägre aktiveringsfrekvens vid Parkinsons sjukdom. Individer med Parkinsons sjukdom som hade reducerad AHA inom dessa nätverk hade en generell tendens till nedsatt semantiskt luktminne och audioverbalt minne. Sammanfattningsvis engagerar ORM inte bara primära luktrelaterade områden utan även högre kognitiva områden som hippocampus. Individer med Parkinsons sjukdom uppvisar kortare och mindre frekventa aktiveringar i specifika hippocampala nätverk samt reducerad AHA, både under episodiska luktminnesuppgifter och i vila. De här hippocampala dFC-mönstren är associerade med nedsättningar i deklarativt luktminne och audioverbalt minne. Detta tyder på deras potential att fungera som markörer för kognitiv svikt vid Parkinsons sjukdom, särskilt före valet av apparatassisterad behandling. Longitudinella studier med större, mer heterogen och välkarakteriserade kohorter är dock nödvändiga innan dessa markörer är tillräckligt valida och reliabla för att implementeras kliniskt.Funding agencies: County Council of Östergötland, Lions Research Foundation against Endemic Diseases, Medical Research Council of Southeast Sweden (FORSS), The Swedish Parkinson Foundation, The Swedish Research Council</p
Successful Management of Two Consecutive Pregnancies With Maternal-Fetal Phenylketonuria : Lessons From Clinical Practice
No full textPhenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase (PAH), leading to the accumulation of phenylalanine (Phe) and an increased risk of developmental disorders. Treatment involves a Phe-restricted diet, amino acid supplements, and for a subset of patients, a tetrahydrobiopterin (BH4) chaperone. Managing PKU during pregnancy is challenging due to changing protein and energy needs, stricter Phe control, nausea, and unpalatable supplements. In rare cases of simultaneous maternal and fetal PKU, Phe tolerance may increase less throughout gestation, raising the demands on the patient and caregivers. There are few reports and no guidelines on the management of PKU during pregnancies in which both mother and fetus have PKU, hereafter referred to as maternal-fetal PKU (mfPKU). This report outlines our approach for successfully managing two consecutive mfPKU pregnancies. We emphasize a patient-centered approach, focusing on patient education and close collaboration with a multidisciplinary metabolic team. This involves regular monitoring of body weight, blood Phe levels, and calorie intake through an online food diary to tailor individual recommendations for natural protein restriction and amino acid supplements
Restoring landscapes to build common futures : Land redistribution and environmental action in rural Scotland
No full textEcosystem restoration is crucial for reversing environmental degradation, yet contemporary approaches often frame restoration as a technical, science-driven endeavour, neglecting the social and political processes through which communities mobilise for landscape revitalisation. This paper develops the concept of restorative commoning, which we define as a bottom-up creative process in which communities envision and enact new futures for their landscapes in pursuit of collective thriving. We ground this concept in an ethnographic study of Langholm in Scotland, where local residents organised a landmark community buyout of private land, establishing the Tarras Valley Nature Reserve. Through interviews, participant observations, and transect walks, we analyse how residents engaged with restoration not just as an ecological project but as a social, political, and affective act, redefining relationships with place, community, and ecosystems. Our findings reveal how restorative commoning emerges from grassroots mobilisation, historical solidarity, and supportive policy frameworks, particularly land tenure reforms that enable collective ownership. The Langholm case demonstrates that such ownership acts as a catalyst, transforming reactive resistance into proactive reimagination of landscapes. Beyond ecological outcomes, the process nurtures civic revitalisation, challenging dominant paradigms of privatisation and expert-led restoration. We argue that restorative commoning shifts restoration from a return to past conditions to a forward-looking, collective process of socio-ecological change. The study highlights the need for policies that create enabling conditions for community-led restoration, emphasising the interdependence of ecosystem health and social well-being. By centering local agency, affective ties to place, and democratic governance, restorative commoning offers a pathway for more inclusive and sustainable approaches to landscape revitalisation
EnergyFlow: Predictive trading platform for decentralized energy exchange
No full textThe integration of renewable energy sources (RES) into modern power grids has enabled decentralized energy generation at the community level, fostering peer-to-peer (P2P) energy trading among prosumers and microgrids. Accurate forecasting of household energy consumption and photovoltaic (PV) generation is critical for optimizing energy flows, enhancing grid reliability, and enabling cost-effective trading decisions. This paper presents an intelligent energy trading platform that integrates machine learning-based forecasting, battery-aware decision-making, and blockchain-enabled transactions to facilitate secure and efficient local energy exchange. Using historical smart meter and weather data from London households, multiple forecasting models including GRU, LSTM, Random Forest, and XGBoost were trained and evaluated. The GRU model achieved superior performance in predicting energy consumption, while Random Forest produced the most accurate PV generation forecasts. These predictions were combined with household battery levels to dynamically determine next-day operational roles: Buyer, Seller, Store, or Use Battery. Unlike conventional fixed-threshold approaches, the framework supports user-defined variable battery thresholds, allowing personalized energy management strategies. The proposed decision-making model achieved an accuracy of 90.72 % for one random block, and extended simulations across 29 different random household blocks confirmed its robustness with an average accuracy of 88.69 % (95 % CI: 87.9–89.6 %). In the trading phase, households participate in a decentralized energy trading platform powered by blockchain and smart contracts. Based on the next-day forecasts, a linear programming-based optimization algorithm matches buyer requests and seller offers to minimize the total system cost while ensuring fairness and efficient energy allocation. To assess its performance, the proposed optimization approach was compared against a greedy matching algorithm where sequential matching is done without a cost optimization and a grid baseline scenario where no storage/sharing of energy takes place. The optimized matching consistently achieved substantially lower trading costs across all households demonstrating superior efficiency, fairness, and scalability compared to the benchmark methods. All transactions are executed securely and transparently on the blockchain through Ethereum-based smart contracts, which automate energy trading, pricing, and settlement. A user-friendly web interface was developed to allow participants to monitor and interact seamlessly with the platform. Overall, this battery-aware, community-driven trading framework showcases how intelligent energy forecasting, cost-optimized decision-making, and blockchain-enabled trading can collectively enhance energy autonomy, cost savings, and renewable energy utilization at both the household and community levels.Fulltext license: CC BY</p
Student then, now and forward : Assessment narratives and student performativity in development and grade dialogues
No full textBetygs- och utvecklingssamtal är återkommande inslag i skolgången och är centrala för såväl skolans styrning som elevers syn på sig själva och sin förmåga. I avhandlingen studeras betygs- och utvecklingssamtal med elever som får betyg i årskurs 4–6. Syftet är att bidra med kunskap om det elever, lärare och vårdnadshavare gör genom samtalen och belysa betydelser detta kan ha för elever och skolan. Fokus är att förstå hur betygs- och utvecklingssamtal formar elever i ett skolsystem präglat av performativ styrning. Frågeställningarna rör hur berättelser formas och används, hur elever positioneras, hur nationell bedömningspolicy och lokala villkor kommer till uttryck samt hur föreställningar om elever konstrueras och förhandlas i relation till skolans bredare uppdrag. Avhandlingen utgår från en interaktionsorienterad narrativ ansats med perspektiv på positionering, policygörande och performativitet. Empirin består av ljudinspelningar från betygs- och utvecklingssamtal från fem skolor och analyseras genom en positioneringsanalys. I avhandlingen ingår tre artiklar som visar hur deltagarna (I) formar narrativ om elevers framtidsutsikter, (II) förhandlar förväntningar om elevers muntliga aktivitet och (III) gör betyg till en emotionell angelägenhet. Resultaten diskuteras genom begreppen individualisering och temporalitet som synliggör hur elevers förmåga, ansvar och utveckling förstås, förhandlas och värderas över tid. För att fördjupa diskussionen introduceras begreppen elevperformativitet och bedömningsberättelser. Elevperformativitet synliggör hur elever förväntas framställa sig själva som ansvarstagande och strategiska i linje med skolans mål och ideal. Bedömningsberättelser synliggör hur samtalets deltagare i samspel med bedömningspolicy formar berättelser om elever och deras prestationer. Avhandlingen visar hur betygs- och utvecklingssamtal fungerar som styrningsmekanismer som kan stabilisera, utmana eller omförhandla bedömningsberättelser om elever, som därigenom kan forma hur elever ser på sin förmåga och sig själva i skolan.Development and grade dialogues are recurring meetings, central for both educational governing and students’ perceptions of themselves and their abilities. This thesis examines development and grade dialogues with students who receive grades in Years 4–6. The aim is to contribute to knowledge about the actions of students, teachers and parents in these meetings and their implications for students and school. The focus is on how these dialogues shape students within a performativity-driven school system. The research questions address how narratives are formed, how students are positioned, how national assessment policies and local conditions interact, and how notions of students are constructed in relation to broader educational goals. The thesis uses an interaction-oriented narrative approach combined with perspectives on positioning, policy enactment and performativity. The data consists of audio recordings of development and grade dialogues in five schools, analysed through positioning analysis. The included articles show how participants (I) construct narratives about students’ paths, (II) negotiate expectations about students’ verbal participation and (III) construct grades as an emotional concern. The findings are discussed using the concepts of individualisation and temporality, illustrating how the students’ responsibility and progress are negotiated, understood and valued over time. The thesis also introduces the concepts of student performativity and assessment narratives. Student performativity refers to expectations for students to present themselves as responsible and strategic in line with school objectives. Assessment narratives demonstrate how participants, in interaction with assessment policies, form stories about students and their performance. The thesis demonstrates that development and grade dialogues function as mechanisms that can stabilise, challenge or negotiate assessment narratives, shaping how students understand themselves and their abilities in school.
