Publikationer från Uppsala Universitet
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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
Firm ownership and pollution
No full textWe provide a theoretical micro foundation for how much pollution (negative externalities) a firm will internalize based on the ownership distribution of its shareholders. Small shareholders, compared to large ones, want the firm to spend more on avoiding pollution since they suffer less profit loss for the same environmental benefit. In particular, if a shareholder holds a share of 1/N, where N is the population in society, that shareholder's preferences align with a social planner's. Three theoretical predictions arise. First, small shareholders will systematically vote for a greener corporate profile. Second, firms with a smaller weighted-median shareholder will pollute less. Third, countries with concentrated corporate wealth holdings and/or more individualized firm ownership will pollute more. This implies that standard models of externalities in environmental economics and macroeconomics containing representative agents are either internally inconsistent or not fully specified
Near Infrared Spectroscopy Versus Stump Pressure in Detecting Cerebral Ischemia During Carotid Endarterectomy : A Prospective Multicenter Observational Study
No full textBackground: Determining the need for shunt use during carotid endarterectomy (CEA) under general anesthesia (GA) can be based on different methods, and one of the most common is stump pressure (SP). Previous studies have found favorable results of near infrared spectroscopy (NIRS). Methods: Patients undergoing CEA in 2 swedish hospitals were prospectively included. SP, rSO2 at different timepoints as well as neurological symptoms during surgery were reported for all patients. Receiver operating curve (ROC) analysis was used to determine the optimal cutoff points for SP and rSO2. Results: A total of 293 patients underwent CEA under local anesthesia (LA) and 66 under GA in 2 hospitals. Thirty two patients operated under LA had neurological symptoms. A relative change in ipsilateral rSO2 <-9% had a negative predictive value (NPV) of 99% in detecting neurological symptoms during clamping. Patients who developed neurological symptoms during clamping had lower Delta rSO2 (-14% +/- 6% vs.-4 +/- 5%, P < 0.001) and lower SP (36 +/- 21 mm Hg vs. 56 +/- 19 mm Hg, P <0.001) compared to those who did not. A Delta rSO2 of <-9% had a sensitivity of 91% (95% confidence interval (CI): 75-98%) and a specificity of 82% (95% CI: 77-87%) in predicting cerebral ischemia, whereas a SP < 50 mm Hg had a sensitivity of 78% (95% CI: 58- 91%) and a specificity of 60% (95% CI: 54-67%). Conclusion: This study found that NIRS could reduce unnecessary shunting while still having a higher sensitivity compared to SP. Additionally, it can also monitor shunt patency
Sväljfunktion vid strålbehandlad huvud-halscancer : En retrospektiv journalgranskning med fokus på munhåla och svalg
No full textDe två vanligaste tumörlokalisationerna vid huvud- och halscancer är i munhåla och orofarynx med 500 fall vardera per år. Hypofarynxcancer är mer sällsynt med cirka 50 fall per år. En vanlig behandlingsmetod vid cancer i munhåla och svalg är strålbehandling. Syftet med studien är att bredda kunskapen om strålbehandlingens långsiktiga effekter i munhåla och svalg. Detta är en retrospektiv longitudinell journalstudie som granskar sväljfunktion utifrån bedömningsmaterialet functional oral intake scale, FOIS, nutritionssätt samt kommunikationsförmåga hos 91 personer med orofaryngeal cancer. Studien, som inkluder har även undersökt hur länge patienterna har kontakt med onkologrelaterad sjukvård, samt hur många som har erbjudits logopedkontakt och hur länge de följdes av logoped. Resultatet visar att sväljfunktionen påverkas i hög grad av strålbehandlingen och att patientens kommunikationsförmåga påverkas i viss grad. Vid strålavslut hade 90,1 % av deltagarna en sväljpåverkan som klassificerades som dysfagi (sväljsvårigheter). Behov av näringsdryck var störst vid strålavslut. Gastrostomi förekom hos 21,9 %, varav 10 % av dessa klarade att tränas ur sin gastrostomi. Röstpåverkan rapporterades hos 17,5 % och talpåverkan rapporterades hos 31,8 %. Logopedkontakt erbjöds hos 55 % av deltagarna. Vid sista journalanteckning hade 40 % återfått en funktionell sväljförmåga där störst återhämtning sågs i tungbasgruppen. Studiens resultat förbättrar förutsättningarna för rehabilitering vid orofaryngeal dysfagi vid cancer i munhåla och svalg.The two most common tumour localizations in head and neck cancer patients are in the oral cavity and oropharynx, with 500 cases each per year. Hypopharynx cancer is rarer with approximately 60 cases per year. Radiotherapy is often used as a treatment for cancer in the oral cavity and pharynx. The aim of this study is to broaden the knowledge of the long-term effects of radiation treatment in the oral cavity and pharynx. This is a retrospective longitudinal study that examines swallowing function through the functional oral intake scale (FOIS), nutritional intake and communication in 91 people with oropharyngeal cancer. This study also investigated the duration of the participants´contact with oncology-related healthcare, as well as to what extent the patients were offered therapy with a speech language pathologist (SLP) and for how long. The result of the study shows that the swallowing function is affected to a high degree by radiotherapy and communication is affected to a certain extent. At the termination of radiotherapy, 90,1 % participants had affected swallowing, which was classified as dysphagia (swallowing difficulties). The need for nutritional drink was the greatest at the end of the radiotherapy. Gastrostomy was reported in 21,9 % participants, 10 % of these participants were successfully weaned from their gastrostomy. Voice function was reported affected in 17,5 % participants and speech function was reported affected in 38,8 % participants. Therapy with SLP was offered to 55 % of the participants. Between the time period 25 to 60 months 40 % of the participants had regained their swallowing function, and the greatest recovery was seen in the participants who had cancer in the base of the tongue. The result of the study will contribute to improving the conditions for rehabilitation for patients due to oropharyngeal dysphagia in cancer of the oral cavity and pharynx after radiotherapy. Svälj- och röstfunktion samt nutritionsstatus efter strålbehandlad larynxcancer: En långtidsuppföljningSväljfunktion och nutritionsstatus efter strålbehandlad tonsillcancer: En långtidsuppföljnin
Vegetation change in dry grasslands in Northeast Germany over two decades : A resurvey
No full textSemi-natural dry grasslands in Central Europe harbor many rare and specialized species and face threats due to altered management practices and environmental change. However, more studies on vegetation change and management effects in dry grasslands are needed, especially with consideration of non-vascular taxa. Here we used a resurvey approach to analyze vegetation change in dry grasslands on loamy and sandy soils (Festuco-Brometea, Trifolio-Geranietea sanguinei and Koelerio-Corynephoretea canescentis) in Brandenburg, Northeastern Germany. We surveyed 157 plots (10m2) at each of two time points, 1993-1997, and 20-25 years later, 2017-2018. We recorded a total of 362 vascular plants and 84 non-vascular taxa. Species richness per plot remained stable across surveys. We detected, on average, 32.2 and 21.9 species per plot in dry grasslands on loamy and sandy soils, respectively, including 3.25 and 4.8 non-vascular taxa and 7.6 and 2.2 endangered species according to the regional Red List. We found evidence for vegetation homogenization and a reduction in Shannon diversity and Shannon evenness in the recent survey, suggesting early signs of biodiversity decline. Analyses of mean ecological indicator values and plant traits, as well as of winner and loser species, revealed that changes in vegetation composition were accompanied by an increase in competitive, mesophytic species and a decline in disturbance-tolerant specialists. We further show that the highest diversity in dry grasslands on loamy soils was associated with intermediate levels of grazing. Our findings highlight the conservation significance of dry grasslands and suggest intermediate grazing pressure as a suitable management strategy
Evaluating the impact of age and treatment on neuroinflammation-related proteins in mouse models of proteinopathies
No full textNeuroinflammation plays a key role in Alzheimer's disease (AD), but the actions of microglial mediators may vary across stages of amyloid-beta (A beta) pathology. While drugs targeting brain immune responses are advancing to clinical trials, biomarkers to monitor their effects are lacking. This study investigated proteins expressed by activated microglia in three mouse models of A beta pathology and alpha-synuclein, both during disease progression and after treatment, to evaluate their potential as in vivo biomarkers. Immunofluorescent staining was performed on cortical sections from AppNL-G-F, tg-ArcSwe, and wild-type (WT) mice. TREM2, Axl, galectin-3, A beta, and cytokines were measured by immunoassays in brain homogenates from WT, AppNL-G-F, tg-ArcSwe, and tg-UppSwe mice across four age groups and from mice subjected to three treatment strategies targeting A beta (beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor NB-360 and antibody RmAb158) or alpha-synuclein (antibody RmAb38E2). TREM2 and Axl colocalized with Iba1 and A beta in AppNL-G-F and tg-ArcSwe mice, with age-dependent increases observed in both models but not in tg-UppSwe. The lectin galectin-3 increased with age across all genotypes, including WT. A beta correlated with elevated TREM2, Axl, and Galectin-3. Two months of BACE1-inhibition reduced TREM2, Axl, and galectin-3 in tg-ArcSwe mice and TREM2 and Axl in AppNL-G-F mice. In summary, microglial TREM2, Axl, and galectin-3 are promising biomarkers for tracking AD-related neuroinflammation. Microglial interactions with A beta likely influence the outcomes of A beta-targeting therapies, and characterizing their dynamic states will inform the development of diagnostic tools and treatments relying on microglial activation to alleviate pathologies associated with neurodegenerative diseases
Pea protein isolates adsorption on phospholipid bilayer interfaces : a quartz crystal microbalance and neutron reflectometry study
No full textLegumin and vicilin, the main storage proteins from peas, are increasingly employed as functional ingredients for food. The purpose of this work was to better understand the interactions between these proteins and selected lipids, due to their potential consequences on interfacial functionality of protein preparations. Legumin and vicilin isolates were obtained after isoelectric precipitation followed by further purification using size exclusion chromatography. The interactions were studied using DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine): DOPE (1,2-dioleoyl-sn-glycero-3 phosphoethanolamine) as mixed supported lipid bilayers, using quartz crystal microbalance with dissipation monitoring (QCM-D) and complementary neutron reflectometry (NR) experiments. This approach, fundamental in nature, allowed to observe interactions at the molecular level in the presence of phospholipids interfaces. QCM-D data suggested that legumin did not show any significant affinity for the investigated lipid interface. On the contrary there were changes in the bilayer with vicilin injection. NR experiments also supported these observations, and modeling of the experimental data also suggested a structural reorganization of the bilayer after vicilin injection and rinsing. This unique fundamental study of legumin and vicilin leads to the hypothesis that vicilin forms complexes with phospholipids bilayers which can be dispersed and removed by rinsing. All together, this study adds to the current debate on the importance of endogenous and non-endogenous phospholipids presence in affecting surface functionality of pea protein isolates
Dynamic fractures in rock-like materials analyzed by high-speed photography and a dynamic phase-field finite element model
No full textA so-called hydrostatic-spectral-deviatoric decomposition is integrated into dynamic phase-field finite element models to study its effectiveness in the prediction of crack paths and crack tip velocities in brittle materials under dynamic mixed-mode compressive loading conditions. The study focuses on dynamic experiments, including drop tower tests conducted using gypsum plaster specimens with embedded flaws and holes. The hydrostatic-spectral-deviatoric decomposition method enables a split in tensile and compressive strain energy density contributions, crucial for capturing the complex fracture behavior in brittle materials under compressive loads that traditional models struggle to simulate effectively. Numerical simulations were conducted in parallel with experiments, utilizing a unified set of material parameters derived from prior work on the same material under quasi-static conditions. This approach ensured consistency between the dynamic and quasi-static cases. Numerical results demonstrated a good level of agreement with experiments, replicating key aspects of fracture evolution, including initiation and propagation of primary and secondary cracks as well as the temporal progression of crack tip velocities. This enhanced modeling approach offers a deeper understanding of dynamic fracture mechanisms in brittle materials and demonstrates its potential for advancing fracture simulations in applications involving dynamic, mixed-mode loading scenarios
Disrupting tree continuity through clearcut forestry can alter the climate sensitivity of future tree growth in northern Sweden
No full textDisrupting tree continuity through clearcut forestry is a widespread management practice across the boreal biome. However, concerns remain that forests regenerated after clearcutting may be more sensitive to climatic fluctuations. We examined how clearcutting affects tree growth responses to weather variability, focusing particularly on the extreme 2018 drought. We collected tree-ring width data from forests in northern Sweden that either were clearcut similar to 60 years prior to the study or never had been clearcut but exposed to past selective logging. We tested whether growth responses to interannual weather variations variables differed between these forest types and assessed how the differences were mediated by soil organic matter, soil temperature stability, and variations in tree age, size, and early growth rates. Forests regenerated after clearcutting showed greater responsive to interannual variation in weather, being more negatively affected by increasing temperature but more positively affected by precipitation. During the 2018 drought, clearcut forests exhibited a mean growth reduction of 19 %, compared to 11 % in non-clearcut forests. The higher drought resistance in non-clearcut forests was primarily associated with greater mean tree age and slower early growth rate. However, as these variables are strongly correlated with clearcutting history, their independent mediation effects are difficult to interpret. Our results suggest that clearcut forestry may increase the sensitivity of regenerating forests to climatic variability. Further research is needed to disentangle the underlying mechanisms and to determine how forest management practices can promote greater climatic resilience in boreal ecosystems
Preliminary insights into the Bronze-to-Iron Age human demographic history of Pella (Jordan) using an ancient DNA approach
No full textIn recent times, the genetic analysis of ancient human remains has contributed significantly to the study of the human past, especially in the subjects of admixture, migrations and social organisation. By utilising distinct methods and source materials, genomic research is adding considerable value to conclusions reached by other disciplines, such as archaeology and history. However, the geographical region of the Levant has only very recently been the subject of genomic research, and the region of Jordan rarely at all, due to poor environmental conditions that hinder DNA preservation and limited access to archaeological excavations and therefore sampling of ancient remains. My Master’s thesis project aimed at generating genome-wide data for 16 Bronze and Iron Age skeletal human remains excavated in the archaeological site of Pella, a multi-period site located in the North Jordan Valley that hasn’t yet been sampled for DNA studies. I also aimed at analysing the resulting data in context with genomic data from the wider region of the Levant, by means of several standard population genetics tests. Additionally, genomic results were interpreted making use of historical and bio-archaeological records specific to the site of Pella. Through an initial assessment of the sequencing data, only six libraries were selected to be included in genome-wide analyses. Surprisingly, the performed tests show two very distinct genomic profiles among the six libraries: four of them have the expected Neolithic-to-Iron Age Levantine profile, while the other two show affinity with ancient and present-day East Asian populations. These results suggest that human mobility in Bronze-to-Iron Age Eurasia could have happened over distances much longer than previously thought. Further target enrichment will provide more power to either reinforce of reject these preliminary results