Publikationer från Umeå universitet
Not a member yet
55455 research outputs found
Sort by
Molecular mechanisms of SOD1-amyotrophic lateral sclerosis : innovative models of human disease
No full textMutations in superoxide dismutase 1 (SOD1) are linked to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder predominantly affecting upper and lower motor neurons leading to progressive paralysis and atrophy of skeletal muscles ultimately resulting in quadriplegia and fatal respiratory failure. The SOD1 protein is primarily responsible for defence against damaging superoxide free radicals. SOD1 loss of function was initially thought to play a role in ALS due to the discovery of disease- causing mutations in the SOD1 gene and the well-established link between oxidative stress and neurodegeneration. However, a reduction in SOD1 activity is not causative for ALS, although it is likely to play a modifying role. The major effect of SOD1 mutations in ALS is linked to the protein aggregation of misfolded SOD1 protein species, a process that has been termed toxic gain of function. While numerous genetic and molecular discoveries have deepened the understanding of ALS pathophysiology the precise mechanism of SOD1-ALS pathogenesis remains unclear. Established animal and cellular models of SOD1-associated ALS (SOD1- ALS) have relied upon overexpression systems, including in vivo transgenic mouse models and in vitro plasmid-based transfection cell models. In mouse models, the presence of numerous transgene copies resulting in overexpression of the mutant SOD1 protein has been advantageous to accelerate the neurodegenerative phenotype and examine late-stage ALS pathology. Furthermore, the utility of overexpression in vitro models of SOD1-ALS has enabled identification of key pathological features associated with SOD1 mutations and recapitulated the hallmark proteinopathies seen in ALS patients. However, the presence of non-physiological levels of SOD1 expression in these models makes it difficult to study the early disease process and hinders the discovery of early biomarkers for disease. The principal goal of this thesis was to develop and utilise new in vivo and in vitro models of SOD1-ALS. These models were used to elucidate early pathogenic mechanisms of ALS linked to loss or gain of function of the SOD1 protein, under conditions of endogenous levels of expression from single loci. Further, given the multistep nature of ALS pathogenesis, the goal of this work was to highlight temporal signatures of disease in SOD1-ALS mouse models and human induced pluripotent stem cell-derived motor neurons (iPSC-MNs). The SOD1-ALS genetically humanised mouse models developed in this thesis work led to the discovery of pre-symptomatic transcriptomic and metabolomic signatures of disease whilst dysregulated proteome degradation dynamics and alteration of axonal mitochondrial integrity was highlighted in SOD1-ALS patient derived iPSC-MNs. This thesis also describes the establishment of a custom-built semi-automated tool (Axon-OI) for analysing organelle interactions in iPSC-MN axons leveraging machine learning and live cell imaging to provide a unique resource to understand the impact of axonal transport disruptions in ALS pathogenesis. Collectively, the work described in this thesis establishes a novel foundation for future investigations into the early stages of ALS pathogenesis and identification of therapeutic targets for pre- symptomatic treatment of SOD1-ALS
Octree-Based Optimization for Large CAD Models in VR : Rendering Efficiency Under Resource Constraints
No full textIn world of complex and increasingly massive three-dimensional datasets, a demand for efficient techniques for storage and rendering has emerged. The data structure octree is a popular solution within this field, providing an efficient structure for managing the large amounts of information. One such three-dimensional dataset is large 3D triangle meshes, commonly found in complex CAD models. The purpose of this thesis was to identify advantages and obstacles of using octrees to partition and visualize complex CAD models, specifically in the resource-constrained environment of a VR device. A VR application was developed where a large CAD model's 3D triangle mesh underwent partitioning into an octree. The octree model was then further equipped with a Level of Detail system to adjust the mesh's detail level based on distance from the camera, enabling the total triangle count to be decreased while keeping its essential detail up close. View frustum culling was implemented to remove unnecessary information from the rendering process, culling any parts of the model outside of the field of view. These techniques along with an Out-of-Core system for storage at the local disk allowed freeing up memory otherwise used by mesh information that was not to be displayed at that moment. Testing the application and tracking its performance metrics, it was shown that the performance of the program was significantly increased, as frame rate was consistently higher for the octree model than for the original model. Some advantages that were identified with the octree structure was the ability to treat parts of the model as separate entities, which allowed for any specific part to effectively be culled or have its mesh complexity adjusted, and free up memory for any information not currently needed. Some obstacles with this approach included a lengthy construction time of the octree largely occupied by mesh simplification, as well as occasional performance issues relating to frequent reading and writing large amounts of data to the disk.
Psychosocial moderators of the effect of lifestyle interventions in primary prevention of cardiovascular disease : a scoping review
No full textBackground: Lifestyle modification plays a key role in prevention of cardiovascular disease (CVD), but often fails due to non-adherence to lifestyle recommendations. Previous research has highlighted the importance of psychosocial factors in non-adherence, though focused on secondary rather than primary prevention. The aim of this scoping review was to provide an overview of the moderating role of psychosocial factors on the effect of lifestyle interventions in primary CVD prevention. Methods: A literature search of scientific databases was performed to identify studies published in peer-reviewed journals, that evaluated lifestyle interventions in primary prevention in adult populations (18 years and older), with a composite CVD risk score or a CVD risk factor (diet, physical activity, smoking or alcohol) as outcome, and assessed the moderating effect of a psychosocial factor. Results: Thirty-five studies published between 2000 and 2025 were included in this review. Most were randomized controlled trials (RCT), included middle-aged participants, and investigated samples in which women were in majority. The outcomes differed, with fourteen studies reporting on physical activity, eleven on diet, six on body weight, two on smoking and one on alcohol. One study used a CVD risk score as the outcome. The studies included a broad array of psychological factors that were grouped into five categories: self-efficacy or motivation (n = 11), social support or relationship quality (n = 8), mental health (n = 6), personality or emotions (n = 6), and cognitive factors (n = 4). Sixteen (44%) of the studies did not use validated instruments in the assessment of the psychosocial factor. Conclusions: This review highlights the potential role of psychosocial factors on the effectiveness of lifestyle interventions. However, our ability to draw detailed conclusions or identify any general trends were limited by the heterogeneity amongst the studies in terms of study design, assessment of outcomes and moderators, and populations. Still, we identified a lack of RCTs (1) with long follow-up time, (2) with sufficient sample size, (3) using validated instruments to assess the psychosocial moderator, and (4) using interaction analyses to assess moderating effect.Trial registration: This scoping review was registered at Open Science Framework (osf.io) under https://doi.org/10.17605/OSF.IO/VEADK on December 19, 2023.</p
Four academics and a student : a multiethnographic study on joy acrossacademic life
No full textJoy is diffuse and challenging to define and demarcate. To highlight the individuality and collectiveunderstanding of joy, this paper considers joy in higher education at five points of life—the student, thedoctoral researcher, the early career lecturer, the established senior lecturer and the professor. Variousreports suggest that lecturers feel constrained, fearing that upsetting students could lead to formalcomplaints. Many are hesitant to intervene in classroom conflicts, worried about potential allegations ofabusive treatment, and feel unsupported by departmental leadership. Yet joy is experienced in highereducation. It is against this background that the focus of this paper considers the presence and natureof joy within higher education. Presented as a dialogue, the paper unites five voices across twocountries in a multiethnographic study to tease apart what it means to experience joy in higher educationsettings. Each participant examines joy in higher education through their personal lived experiences.This dialogue unfolds as an open exchange, moving both vertically and horizontally, as eachperspective deepens and broadens the individual and collective understandings of joy in highereducation
Cripping the co-design of pacing technologies for energy-limiting conditions
No full textPeople with energy-limiting conditions, such as chronic fatigue syndrome (ME/CFS) and Long COVID, need to limit their activity levels and balance exertion with rest and restorative activities. This practice is known as “pacing”. There is an opportunity for technology to help people with this process, but conducting research with this population can be difficult given their limited and unpredictable energy levels. This research explores how we can use crip theory to inform the development of co-design methods suitable for this cohort, and as an analytical lens to explore how these tools should be designed outside of normative and abelist assumptions about fatigue and productivity. This is done through a 5 week Asynchronous Remote Community study utilising various co-design techniques. These findings point to future designs of pacing technologies and contribute insights about developing more accessible approaches to conducting research with people with energy-limiting conditions
The React Compiler in Practice: Assessing Rendering Efficiency and Memory Consumption
No full textThe rapid growth of React-based web applications has renewed attention on rendering efficiency, yet manual optimization with React.memo, useMemo, and useCallback remains error-prone and hard to scale. React 19 introduces the experimental React Compiler ("React Forget"), which promises to inject memoization automatically at build time. This thesis offers an early, independent, and end-to-end evaluation of that compiler. A purpose-built chat benchmark-implemented in TypeScript and bundled with Vite-simulates realistic high-frequency user-interface updates. Two functionally identical variants are tested: a prop-drilling tree that pushes every message through nested wrappers and a flat tree that renders messages directly. Each variant is compiled with and without the React Compiler. Automated Playwright scripts record component-level render counts via \textless Profiler/\textgreater, while Chrome DevTools snapshots capture heap usage. Workloads range from 100 to 10000 messages, with controlled batch sizes and artificial per-message delays. The results show that the compiler cuts unnecessary re-renders by up to 2500\% in deeply nested components. Performance gains scale with workload: larger batches and heavier component graphs amplify the benefit. The trade-off is a consistent memory overhead of roughly 8–15\% (135 MB at 10000 messages), attributable to compiler-inserted caches. No statistically significant differences are observed between prop drilling and flat tree topologies in either performance or memory. The study concludes that the React Compiler delivers substantial automatic rendering time savings with modest memory cost, provided that the components obey the purity rules of React. It therefore represents a practical pathway toward declarative, zero-maintenance performance tuning for most modern web applications, while memory-constrained deployments and projects using unconventional patterns should evaluate adoption case-by-case
Teaching ideals and materiality during the establishment of the Swedish comprehensive school 1949–1972
No full textThis study examines inter-relations between school equipment and teaching ideals in relation to the Swedish comprehensive-school reform process that took place between 1949 and 1972. Experimental activities at two specific schools, marking the beginning and end of the reform period, are analysed. The study uses a sociomaterial perspective that sees human actors and material objects as intra-acting components of networks that make up what can be termed the social technology of teaching. The study identifies various forms of school equipment, and links these to the progressive ideals of the time. Dynamic relationships between the purpose of teaching and the use of teaching aids are explored, and it is argued that school equipment is introduced and disseminated in schools in order to teach specific topics. The overarching finding is that the relations between teaching ideals and materiality are entangled, and that the meaning of social technology for teaching is created through its usage. School buildings, classroom furniture, or teaching equipment alone have not provided a ready-made path to achieving teaching ideals
Evaluating Forest Recovery via Tree Species Richness in a Restored Tropical Rainforest of Uganda
No full textThis study investigates how tree species richness can be used to assess forest recovery in restored tropical rainforests in Kibale National Park, Uganda. Restoration projects in Kibale have enabled research opportunities concerning forest recovery. One study, which this study incorporates, investigated how tree communities in tropical rainforests recover after being actively restored. The datasets were collected in 2021, across different-aged restored forests. By using the recorded taxa richness and age of the forest, a linear regression was conducted, exploring how age can predict tree species richness. Species accumulation curves were used to explore how tree species richness differs between different-aged forests. The statistical analyses revealed a positive relationship between forest age and tree species richness, likely due to older forest developing characteristics which promote species accumulation, such as canopy cover. The species accumulation curves revealed that the younger and intermediate restored forests had a lower tree species richness, while the older restored and primary forest accumulated species at a similar rate, due to the development of forest characteristics that promote species accumulation. However, the community composition of trees in the restored forests was still significantly distinct from that of primary forests, suggesting that tree species richness alone is not a viable indicator for ecosystem recovery, and that long-term commitment is required. However, evidence of increased wildlife, such as chimpanzees, argues for active restoration being a successful strategy for forest recovery. For future research, this study may be improved by long-term monitoring, factoring in multiple variables and using site-specific methods
Postoperative complications and their risk factors in breast cancer patients treated with neoadjuvant chemotherapy
No full textIntroduction: Although neoadjuvant chemotherapy (NACT) has become established treatment of breast cancer, its impact on postoperative complications varies across studies. Furthermore, association between known risk factors and different kind of complications is unclear. We aimed to characterize the type, rate and risk factors of postoperative complications in a cohort of breast cancer patients treated with NACT. Materials and methods: A retrospective review of breast cancer patients treated with NACT in Helsinki University Hospital between 2020 and 2022 was performed. Complications were graded according to Clavien Dindo classification. Risk factors were identified for overall complications, chronic seroma (defined as a seroma requiring more than five needle aspirations) and hematoma or infection in a multivariable logistic regression model. Results: Out of 4432 patients, 377 met the inclusion criteria. Of these, 216 (57 %) had 314 postoperative complications, commonly seroma (n = 204, 65 %), wound or seroma infection (n = 42, 13 %) and problems with wound healing (n = 19, 6 %). In multivariable analyses, higher age (OR = 1.03, p = 0.003) and undergoing mastectomy (OR = 6.45, p < 0.001) and/or axillary lymph node dissection (ALND) (OR = 2.54, p < 0.001) were independent risk factors of overall complications. Hypertension increased the odds of chronic seroma (OR = 2.26, p = 0.035) and overweight increased the odds of hematoma or infection (OR = 1.06, p = 0.012). Conclusion: Postoperative complications were common yet in most cases treated in an outpatient setting. Patients with higher age and BMI, and those operated with mastectomy and/or ALND were in greater risk of developing postoperative complications. This study also identified that hypertension could have a role in the development of chronic seroma
Production of functional CD19 CAR T cells under hypoxic manufacturing conditions
No full textIntroduction: Chronic lymphocytic leukemia (CLL) has proven difficult to treat with chimeric antigen receptor (CAR) T cell therapy. CLL cells can negatively alter T cell fitness and induce a pseudohypoxic state. We hypothesized that production of CAR T cells under restricted oxygen conditions resembling physiological oxygen levels that can be encountered in tissues (i.e. 2% O2) could promote outgrowth of hypoxia-tolerant CAR T cells. Methods: We performed in vitro phenotypic and functional assessments of CD19-directed CAR T cells produced in either 21% (NorCAR) or 2% (HypCAR) O2 derived from healthy donors (HDs) or patients with CLL. Results: Production of HD-derived CAR T cells in 2% O2 promoted the enrichment of a naïve-like subset. HypCAR and NorCAR cells were functionally distinct; CD4+ HypCAR cells produced more IL-2 and tumor necrosis factor than CD4+ NorCAR cells. Production in 2% O2 was not detrimental to viability or proliferation upon cognate antigen-stimulation and led to increased activation. After chronic stimulation in hypoxia, HypCAR-product remained enriched in naïve-like cells, and demonstrated cytotoxic and cytokine production capacity. In CAR T cells derived from patients with CLL, NorCAR and HypCAR subsets were functionally and phenotypically comparable, but displayed different mitochondrial metabolism. Discussion: We demonstrated that production in 2% O2 is not detrimental, confers subtle but lasting functional and phenotypic changes in CAR T cells warranting further research on the impact of hypoxic production on CAR T cell functionality in hypoxic tumor microenvironments