Publikationer från Uppsala Universitet
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New way of treatment- Norepinephrine a potential treatment?
No full textType 1 diabetes is an autoimmune condition where the immune system targets the insulin cells, mainly beta cells, resulting in the destruction of these insulin-producing cells. There is no treatment for type 1 diabetes. Since factors such as genetic predisposition can be a major influence in the progression of type 1 diabetes. The main goal of this study is to understand the effect of norepinephrine (NE) on the autoreactive CD8+ T cells. NE is a commonly known catecholamine present in the microenvironment of type 1 diabetes individuals. The effect of the NE was studied in vitro using live imaging performed by a confocal microscope, and analysis was carried out using IMARIS. Naïve CD8+ T cells are known to be motile and scan for antigens presented by APCs to interact with them to become activated. These CD8+ T cells become activated, becoming cytotoxic, causing beta cell destruction. To study the effect, it had on type 1 diabetes, the Ins2-OVA mouse model was used. This mouse model was used because of the beta cells presenting Ovalbumin (OVA) membrane-bound OVA in pancreatic β-cells where the ovalbumin (OVA) gene is expressed under the control of the rat insulin II promoter (Ins2). The OT-1 T cells specifically target these OVA-expressing beta cells, enabling us to study further about type 1 diabetes. Most of the studies were performed in vitro, where we visualized the effects of NE on T1D induced islets harvested after day 6, and also OT-1 T cells from day 6, as well as day 8 OT-1 T cell culture. Since we know that activated OT-1 T cells expressed adrenergic receptors thus we hypothesized that is how NE affected the OT-1 T cell motility. We also used qPCR to study the OT-1 T cell gene expression from day 0 to day 8 after stimulating these cells with OVA, which showed cytotoxic potential. We investigated the effects of two norepinephrine (NE) antagonists, phentolamine and propranolol. Phentolamine was used to block NE's effects, while propranolol was used to assess the phenotypic changes of OT-1 T cells. Treatment with NE increased early activation markers, whereas propranolol treatment led to a significant decrease, indicating promising results.
Multispecies Ethnography and Artful Methods
No full textMultispecies Ethnography and Artful Methods explores the potential of multimodal art practices in doing qualitative research beyond the human. Through artful endeavours such as creative writing, photography, filmmaking, drawing and poetry, the volume aims to overcome the shortcomings of conventional, anthropocentric and logocentric methods in multispecies research. To move beyond the limitations of language and linguistic communication, the contributors build on the long tradition of visual and sensory anthropology while also engaging in and consciously reflecting on innovative, creative and artistic methods. Taking a multispecies and more-than-human perspective – ranging from snow and trees to animals and an AI oracle – the volume investigates ways to touch, speak, listen, feel, walk with and reach across different species. This book and accompanying multimedia website advance the frontier of publishing artful expressions of academic research by highlighting how creative practices can be the very core of data collection, analysis and the communication of research. As such, the artful pieces are not ‘just’ illustrations of textual representations, but are practised as part of an iterative process of data collection and analysis. The contributions by well-established scholars, early career researchers and postgraduates who carry out new, cutting-edge research offer an engaging range of analytical, methodological and empiric orientations, while conversing at the intersection of multispecies ethnography and artful methods
Multiscale Monte Carlo dosimetry of gold-nanoparticle dose enhancement in I-125 brachytherapy
No full textGold nanoparticles (AuNPs) have emerged as potent radiosensitizers in low-energy radiotherapy due to their high atomic number and biocompatibility. In this work, utilizing a three-stage multiscale Monte-Carlo workflow, in conjunction with the established framework TOPAS/TOPAS-nBio and the TOPAS-Clustered-DNA-Damage C++ extension, the physical downstream effects of 15 nm AuNPs under I-125 isotope brachytherapy irradiation are quantified. Stage 1 transports 109 histories through a realistic well geometry to generate a valid phase-space for subsequent stages. Stage 2 propagates those particles into a single-cell geometry model with a variety of tested internalization fractions, and two model approaches. The complete internalization (42 120 AuNPs) raised the mean dose by 24.8% to the cytoplasm (dose-enhancement factor, DEF = 1.248 ± 0.008) and 13.1% to the nucleus (DEF = 1.131 ± 0.012). Another model reproduced the same per-particle effiency but with half the gold load. Stage 3 scores the strand break DNA damage spectra using up to 7 ns of radiation stage time. The raw single and double strand break counts increased in proportion to the extra doses (SSB 12.5 ± 0.8%, DSB 21.0 ± 4.9%, BD 12.1 ± 1.4%), but normalizing to DNA dose (per Gy), the AuNP to control ratios vanished within the uncertainty band across the simulation times. Thus, under the current cell and nanoparticle geometries, AuNPs provide up to a robust 13-25% physical dose boost, but no independent biochemical radiosensitization effect was detectable with present statistics. This study validates the integration of state-of-the-art Monte Carlo codes across varying length scales while simultaneously delivering benchmark DEF values for kilovoltage AuNP-augmented brachytherapy. To conclusively determine any radiosensitization effect, future work should (i) bridge the gap between DNA and nanoparticle geometry, (ii) explore additional chemical simulation times into the higher orders, (iii) increase particle histories and apply variance-reduction techniques to establish statistical precision
Patient-reported outcome measures and satisfaction after laminectomy for degenerative cervical myelopathy in octogenarians : an observational study from the national Swedish spine registry
No full textBackground Global demographics show a steady increase in the number of octogenarians. Consequently, the number of degenerative spine procedures in the elderly has significantly increased. This study aims to describe patient satisfaction, the patient-reported health-related quality-of-life, and complications, following posterior cervical laminectomy for degenerative cervical myelopathy (DCM) in octogenarians based on the national Swedish experience. Methods The national Swedish spine registry, Swespine was reviewed between January 2006 and December 2020 for patients who underwent laminectomy for DCM. Complication rates, patient satisfaction, and Patient-Reported Outcome Measures (PROMs) one year after surgery, were analyzed and compared between propensity score matched octogenarian (>= 80) and younger adult cohorts (< 80 years). Results A total of 1,382 patients, 162 octogenarians, and 1,220 younger patients were identified. At one-year after surgery there were no significant difference in patient satisfaction rate or in any of the other PROMS (Eq. 5D, NRS neck pain, NRS arm pain, EQ-VAS, Neck Disability Index (NDI), the European Myelopathy Score (EMS). Complication rates were also comparable, 8.0% in octogenarians (n = 13) and 11% in younger adults (n = 51), respectively. The length of hospital stay was significantly longer in the octogenarian group, with a mean hospitalization of 5.08 days (SD +/- 4.86) compared to 3.76 days (SD +/- 3.93) in the younger adult cohort (p < 0.001). Conclusions Octogenarians undergoing cervical spine surgery for DCM experience outcomes comparable to younger adults in terms of satisfaction, pain relief, and quality of life, indicating that age alone should not hinder surgical treatment. Level of evidence IV, Retrospective observational cohort study
Are We All in the Same Boat? : Germany and Hungary's Migration and Asylum Discourse (2015-2016), between Securitisation, Europeanisation, and Divergent Legitimation Strategies
No full textThis thesis aims to contribute to academic research on asylum and migration discourse analysis, reflecting on member states’ employment of discursive approaches to address refugee crises, with a specific focus on Germany and Hungary, two EU countries that exhibited notably different responses to the asylum crisis during Europe’s Refugee Crisis (2015-2016). Employing political discourse analysis, this study examines the language used by high-level leaders of the two EU member states to legitimate policy directions, highlighting their contrasting reactions to asylum issues through the dual perspectives of securitisation and Europeanisation. This contrast also informs an analysis of their alignment or resistance to European legal standards within the Common European Asylum System (CEAS) and their interpretations of the EU asylum framework and its core values. Based on a corpus of political discourse, this analysis sheds light on how national discourses on asylum reflect broader EU dynamics, including EU principles of solidarity and national sovereignty, in shaping asylum policies
HPV testing alone as a test of cure after treatment with cervical loop excision: : a retrospective register-based cohort study
No full textBackground Women treated with cervical loop electrosurgical excision procedure require follow-up to detect residual or recurrent HSIL+, defined as high-grade squamous intraepithelial lesions, adenocarcinoma in situ or cervical cancer. Currently, co-testing with cytology and human papillomavirus (HPV) analysis is usually recommended. This study investigates whether HPV testing alone is comparable to co-testing in detecting HSIL + up to three years after treatment. Recurrence rates of HSIL + are also presented, with follow-up extending up to 18 years. Methods This retrospective cohort study included all 3,540 women treated with a cervical excision in Uppsala County between 1 January 2005 and 31 December 2019. Women with cancer identified in the cone biopsy were excluded. The main outcome was HSIL + detected within three years of follow-up. Sensitivity, specificity and negative predictive value were calculated for the 1,938 women who had a co-testing result as part of their test of cure. Thus, the analysis for the main outcome could finally be performed on 1,938 out of the total number of 3,540 women. Additionally, long-term data on recurrence and time to HSIL+, along with a separate analysis of results prior to cervical cancer diagnosis, were collected for the whole cohort of 3,399 women. Results The sensitivity and negative predictive value for detecting HSIL + were 69% and 97% for HPV alone, and 74% and 98% for co-testing, respectively. These differences were not statistically significant. Specificity was higher for HPV alone than for co-testing. The negative predictive value of HPV testing for excluding cervical cancer (n = 5) within three years was 100%. Recurrence rate of HSIL + in the three-year follow up was 8%, and the total recurrence rate of HSIL + with a mean follow-up of nine years was 10%. Mean time to recurrence was 28 months. None of 19 cervical cancer cases identified in the long-term follow-up had a co-testing result showing negative HPV but positive cytology. Conclusions HPV testing alone, as a single test, is comparable to co-testing in detecting HSIL + up to three years after treatment independently of margin status, and demonstrates a higher specificity. Cytology plays a very limited role in the test of cure analysis and could therefore be omitted
Hemocyte diversity in crustaceans
No full textCrustaceans is a diverse and ecologically significant invertebrate group, in which circulating hemocytes act as the main immune defense cells, also participating in blood clotting and wound repair. As a result, considerable research has focused on understanding hemocyte function in crustaceans, with species such as crayfish and shrimp being commonly studied models. Traditionally, hemocytes have been categorized based on their morphology, particularly the presence and type of cytoplasmic granules. Based on these features, they have typically been classified into hyaline, semigranular, and granular types. However, recent techniques such as single-cell RNA sequencing have revealed new molecular markers for different hemocyte populations, indicating that the traditional classification is too simplistic. These new findings suggest the existence of additional hemocyte types with distinct, specialized functions. In this review, we present a brief historical perspective and highlight recent progress in understanding the traits and roles of various hemocyte types
VAT and intra-group services : Right of deduction, the open market value principle and transfer pricing adjustments
No full textThis thesis explores how intra-group services are assessed within the framework of EU VAT law, with a particular focus on the right to deduct input VAT, the application of the open market value principle, and the treatment of transfer pricing adjustments (“TP-adjustments”). Central to the analysis is the role of the principle of VAT neutrality, which serves as a legal benchmark for ensuring that the VAT system remains fair and efficient. The analysis is based on recent developments in EU case law, specifically the CJEU case C-527/23 (Weatherford Atlas GIP) and the pending cases C-808/23 (Högkullen) and C-732/23 (Arcomet Towercranes). These cases raise important interpretative questions about how intra-group transactions should be treated under VAT rules, particularly when pricing deviates from market conditions or when post-transaction TP-adjustments occur. The findings show that while the right to deduct input VAT is recognised for intra-group services, its application is highly dependent on documented and verifiable links between the costs and the taxable business activities. The use of the open market value as a corrective tool for determining the taxable base is limited to specific situations where there is a risk of tax avoidance, particularly when full deduction rights are not granted. Furthermore, TP-adjustments may only influence VAT obligations when they reflect actual consideration for a service, backed by mutual agreements and documentation. In conclusion, the thesis argues that a careful balance between formal compliance and economic reality is required to uphold VAT neutrality in intra-group settings. This calls for both businesses and tax authorities to ensure that VAT treatment of intra-group services accurately reflects their real economic substance
Balancing Cybersecurity and Data Protection : Proportionality at the Crossroads between Digital Operational Resilience and Data Protection
No full textStructural stability of chromophore-grafted Ubiquitin mutants in vacuum
No full textStructural biology is witnessing a transformative era with gas-phase techniques such as native mass spectrometry (MS), ion mobility, and single-particle imaging (SPI) emerging as critical tools for studying biomolecular assemblies like protein capsids in their native states. SPI with X-ray free-electron lasers has the potential to allow for capturing atomic-resolution structures of proteins without crystallization. However, determining particle orientation during exposure remains a major challenge, compounded by the heterogeneity of the protein complexes. Gas-phase F & ouml;rster resonance energy transfer (FRET) offers a promising solution to assess alignment-induced structural perturbations, providing insights into the stability of the tertiary structure under various activation methods. This study employs molecular dynamics (MD) simulations to explore chromophore integration's effect on ubiquitin's structure and alignment properties in vacuum. Ubiquitin serves as an ideal model due to its small size, well-characterized properties, and computational simplicity. By investigating chromophore placement, we identified optimal sites for monitoring gas-phase denaturation and unfolding processes, advancing SPI applications and a broader understanding of protein stability in the gas phase