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  • Wild, de, Marc Noël
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    A VIEW INTO FUTURE POTENTIAL ICE THROW POLICIES AND THEIR EFFECT ON THE YIELD OF A VIRTUAL WIND FARM2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    There is a growth of wind power development in icing climates, in which ice accumulation on objects takes place. This leads to specific challenges including ice throw, the detachment of ice from wind turbine blades. The lack of understanding of the ice throw phenomenon among authorities leads to the fact that there is no coherence in the applied ice throw mitigation policies in various countries and regions, which can cause safety- and financial hazards for wind farms in icing climates.

    This research focusses on ice throw risk mitigation methods and their effect on a wind farms yield. Qualitative research is applied, interviewing six experts in the field of cold climate wind power development. The participants are from academic, public and private research institutions in five countries. The qualitative research focusses on policies that are plausible but non-preferred, as well as preference suggestions from the experts on how to treat the ice throw risks. The non-preferred policies involve shutting down wind farms during icing periods and conditionally allowed operation with applied heating systems. These policy scenarios are applied to a virtual wind farm near Slagnäs, Sweden, in order to indicate the impact on the yield and underline the impact that these policies would have on the turnover of a wind farm in a sever icing climate.

    The non-preferred policies have a significant impact on the Slagnäs wind farms yield with 2,28% annual yield losses in case of 200 annual icing hours. Apart from the impact on yield, the policies might not reduce the danger of ice throw significantly, as from a standing still turbine, detached ice can still travel a horizontal distance of up to one time the turbine height. Therefore, policies should according to the interviewed experts not focus on limitations, however focus on understanding risks and taking appropriate action for risk mitigation. International guidelines are the best tool to create a deeper understanding of ice throw risk assessments and their limitations, as well as an understanding of risk mitigation methods. In this case, the risk assessment process shall be standardised, however the risk mitigation methods shall be site specific.

  • Public defence: 2017-09-29 10:00 Hambergsalen, Uppsala
    Rasmusson, Kristina
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Modeling of geohydrological processes in geological CO2 storage – with focus on residual trapping2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Geological storage of carbon dioxide (CO2) in deep saline aquifers is one approach to mitigate release from large point sources to the atmosphere. Understanding of in-situ processes providing trapping is important to the development of realistic models and the planning of future storage projects. This thesis covers both field- and pore-scale numerical modeling studies of such geohydrological processes, with focus on residual trapping. The setting is a CO2-injection experiment at the Heletz test site, conducted within the frame of the EU FP7 MUSTANG and TRUST projects.

    The objectives of the thesis are to develop and analyze alternative experimental characterization test sequences for determining in-situ residual CO2 saturation (Sgr), as well as to analyze the impact of the injection strategy on trapping, the effect of model assumptions (coupled wellbore-reservoir flow, geological heterogeneity, trapping model) on the predicted trapping, and to develop a pore-network model (PNM) for simulating and analyzing pore-scale mechanisms.

    The results include a comparison of alternative characterization test sequences for estimating Sgr. The estimates were retrieved through parameter estimation. The effect on the estimate of including various data sets was determined. A new method, using withdrawal and an indicator-tracer, for obtaining a residual zone in-situ was also introduced.

    Simulations were made of the CO2 partitioning between layers in a multi-layered formation, and parameters influencing this were identified. The results showed the importance of accounting for coupled wellbore-reservoir flow in simulations of such scenarios.

    Simulations also showed that adding chase-fluid stages after a conventional CO2 injection enhances the (residual and dissolution) trapping. Including geological heterogeneity generally decreased the estimated trapping. The choice of trapping model may largely effect the quantity of the predicted residual trapping (although most of them produced similar results). The use of an appropriate trapping model and description of geological heterogeneity for a site when simulating CO2 sequestration is vital, as different assumptions may give significant discrepancies in predicted trapping.

    The result also includes a PNM code, for multiphase quasi-static flow and trapping in porous materials. It was used to investigate trapping and obtain an estimated trapping (IR) curve for Heletz sandstone.

    List of papers
    1. Analysis of alternative push-pull-test-designs for determining in situ residual trapping of carbon dioxide
    Open this publication in new window or tab >>Analysis of alternative push-pull-test-designs for determining in situ residual trapping of carbon dioxide
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    2014 (English)In: International Journal of Greenhouse Gas Control, ISSN 1750-5836, Vol. 27, 155-168 p.Article in journal (Refereed) Published
    Abstract [en]

    Carbon dioxide storage in deep saline aquifers is a promising technique to reduce direct emissions of greenhouse gas to the atmosphere. To ensure safe storage the in situ trapping mechanisms, residual trapping being one of them, need to be characterized. This study aims to compare three alternative single-well carbon dioxide push-pull test sequences for their ability to quantify residual gas trapping. The three tests are based on the proposed test sequence by Zhang et al. (2011) for estimating residual gas saturation. A new alternative way to create residual gas conditions in situ incorporating withdrawal and a novel indicator-tracer approach has been investigated. Further the value of additional pressure measurements from a nearby passive observation well was evaluated. The iTOUGH2 simulator with the EOS7C module was used for sensitivity analysis and parameter estimation. Results show that the indicator-tracer approach could be used to create residual conditions without increasing estimation uncertainty of S-gr. Additional pressure measurements from a passive observation well would reduce the uncertainty in the S-gr estimate. The findings of the study can be used to develop field experiments for site characterization.

    Keyword
    CO2, CCS, Site characterization, Field test, Residual saturation, Single-well test
    National Category
    Energy Systems
    Identifiers
    urn:nbn:se:uu:diva-232013 (URN)10.1016/j.ijggc.2014.05.008 (DOI)000340319600012 ()
    Available from: 2014-09-12 Created: 2014-09-12 Last updated: 2017-08-15Bibliographically approved
    2. Distribution of injected CO2 in a stratified saline reservoir accounting for coupled wellbore-reservoir flow
    Open this publication in new window or tab >>Distribution of injected CO2 in a stratified saline reservoir accounting for coupled wellbore-reservoir flow
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    2015 (English)In: Greenhouse Gases: Science and Technology, E-ISSN 2152-3878, Vol. 5, no 4, 419-436 p.Article in journal (Refereed) Published
    Abstract [en]

    Geological storage in sedimentary basins is considered a viable technology in mitigating atmospheric CO2 emissions. Alternating high and low permeability strata are common in these basins. The distribution of injected CO2 among such layers affects e.g. CO2 storage efficiency, capacity and plume footprint. A numerical study on the distribution of injected CO2 into a multi-layered reservoir, accounting for coupled wellbore-reservoir flow, was carried out using the T2Well/ECO2N code. A site-specific case as well as a more general case were considered. Properties and processes governing the distribution of sequestrated CO2 were identified and the potential to operationally modify the distribution was investigated. The distribution of CO2 was seen to differ from that of injected water, i.e. it was not proportional to the transmissivity of the layers. The results indicate that caution should be taken when performing numerical simulations of CO2 injection into layered formations. Ignoring coupled wellbore-reservoir flow and instead adopting a simple boundary condition at the injection well, such as an inflow rate proportional to the transmissivity of each layer, may result in significant underestimation of the proportion of CO2 ending up in the shallower layers, as not all relevant processes are accounted for. This discrepancy has been thoroughly investigated and quantified for several CO2 sequestration scenarios.

    Keyword
    CCS, flow distribution, geological storage, layered formation, wellbore model
    National Category
    Oceanography, Hydrology, Water Resources
    Identifiers
    urn:nbn:se:uu:diva-263036 (URN)10.1002/ghg.1477 (DOI)000360356800007 ()
    Funder
    EU, FP7, Seventh Framework Programme, 227286EU, FP7, Seventh Framework Programme, 309067
    Available from: 2015-09-30 Created: 2015-09-24 Last updated: 2017-08-15Bibliographically approved
    3. A simulation study of the effect of trapping model, geological heterogeneity and injection strategies on CO2 trapping
    Open this publication in new window or tab >>A simulation study of the effect of trapping model, geological heterogeneity and injection strategies on CO2 trapping
    2016 (English)In: International Journal of Greenhouse Gas Control, ISSN 1750-5836, E-ISSN 1878-0148, Vol. 52, 52-72 p.Article in journal (Refereed) Published
    Abstract [en]

    Industrial CO2 emissions to the atmosphere can be reduced through geological storage, where the gas is injected into the subsurface and trapped by several mechanisms. Residual and solubility trapping are two important processes providing trapping, and their effectiveness ultimately determines the feasibility of geological storage. By means of numerical modeling, a systematic analysis was made concerning the factors potentially affecting trapping, to guide the planned injection experiments at the Heletz test injection site. The effect of enhanced-trapping injection strategies along with the role of geological heterogeneity and the choice of trapping model (TM) were evaluated. The results showed that adding chase-fluid stages to a conventional CO2 injection enhanced the trapping. Taking into account the geological heterogeneity decreased trapping, as this retarded the buoyant migration, resulting in less imbibition and residual trapping. The choice of TM was significant, with the simplified Land TM producing the highest trapping, and the Aissaoui TM the lowest. The results stress the importance of using an appropriate TM as well as heterogeneity model for the site in question for any predictive modeling of CO2 sequestration, as different assumptions may lead to significant discrepancies in the predicted trapping.

    Keyword
    CCS, Capillary trapping, Hysteresis, Injection strategies, Residual trapping, Solubility trapping
    National Category
    Earth and Related Environmental Sciences
    Identifiers
    urn:nbn:se:uu:diva-303260 (URN)10.1016/j.ijggc.2016.06.020 (DOI)000381728300006 ()
    Funder
    EU, FP7, Seventh Framework Programme, 227286; 309067
    Available from: 2016-09-16 Created: 2016-09-15 Last updated: 2017-08-15Bibliographically approved
    4. Residual trapping of carbon dioxide during geological storage – insight gained through a pore-network modeling approach
    Open this publication in new window or tab >>Residual trapping of carbon dioxide during geological storage – insight gained through a pore-network modeling approach
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    (English)In: Article in journal (Other academic) Submitted
    National Category
    Earth and Related Environmental Sciences
    Identifiers
    urn:nbn:se:uu:diva-327991 (URN)
    Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2017-08-15
  • Alsharari, Zayed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Dietary Intake, Fatty Acid Biomarkers, and Abdominal Obesity: Population-Based Observational Studies2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to investigate the associations between fatty acid (FA) biomarkers, carbohydrate intake, and abdominal obesity (AO) and related anthropometric measures in a population-based cohort of men and women in Stockholm County. The overall hypothesis was that dietary fat quality assessed by serum and adipose tissue FA composition, and dietary intake of especially carbohydrates is associated with AO. FA composition was assessed by liquid gas chromatography, and AO was measured as waist circumference (WC), waist hip ratio (WHR) and sagittal abdominal diameter (SAD). Dietary intake was assessed by 7-day food records.

    Papers I, II, III, and IV were all observational studies based on a Swedish population in Stockholm County (n=5460). A sub-cohort of only men (n=301) was included in Papers II, III, and IV.

    In Paper I, serum proportions of the polyunsaturated FA (PUFA), linoleic acid (LA) (18:2n6), was inversely associated with AO in both men and women, whereas a positive association was observed between the saturated FA (SFA), palmitic acid (PA) (16:0) and AO measures. These findings support recent interventional studies suggesting that a higher relative intake of PUFA (LA) from vegetable oils as compared with 16:0 is associated with decreased abdominal adiposity.

    In Paper II, we investigated whether biomarkers of dietary fat quality were related to the corresponding FA intake from fat-rich foods reported in a short food frequency questionnaire (FFQ). Serum proportions of the long-chain n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) were higher among men with higher total fish intake. Serum LA was higher among men who reported a consumption of more than 5 g/d of margarine. Absolute agreement between intakes assessed with FFQ of 60YO and 7-day food record of "Kost och Metabola syndromet"/"Diet and the Metabolic syndrome" (KOMET) was highest for alcohol, total fish, and eggs. Weighted Kappa statistics revealed the strongest agreement for alcohol, margarine, and fruits.

    In Paper III, carbohydrate intake was inversely associated with 16:0 in serum phospholipids (PL). Disaccharide and alcohol intake was positively and non-linearly associated with palmitoleic acid (16:1) and stearoyl-CoA-desaturase (SCD) activity in PL. Alcohol was consistently associated with higher SFA and monounsaturated FA (MUFA).

    Results of Paper IV indicated that total carbohydrate intake was inversely associated with measures of AO and central fat distribution, WHR and SAD, respectively. Likewise, monosaccharide intake was associated with lower AO. In contrast, alcohol intake was associated with AO prevalence and all anthropometric measurements.

    In conclusion, serum SFA (palmitic acid) was positively associated with AO, whereas n-6 PUFA (linoleic acid) was associated with lower AO. High intake of total carbohydrate and monosaccharides were associated with lower AO. Overall, these results support a beneficial role on adiposity of diets that are higher in polyunsaturated fat (vegetable oils) and total carbohydrates compared with saturated fat.

    List of papers
    1. Serum Fatty Acids, Desaturase Activities and Abdominal Obesity - A Population-Based Study of 60-Year Old Men and Women
    Open this publication in new window or tab >>Serum Fatty Acids, Desaturase Activities and Abdominal Obesity - A Population-Based Study of 60-Year Old Men and Women
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    2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, e0170684Article in journal (Refereed) Published
    Abstract [en]

    Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA- desaturase and Delta 6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, alpha-linolenic acid, docohexaenoic acid, and Delta 5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the contrary was true for linoleic acid. Further trials should examine the potential role of linoleic acid and its main dietary source, vegetable oils, in abdominal obesity prevention.

    Place, publisher, year, edition, pages
    PUBLIC LIBRARY SCIENCE, 2017
    National Category
    Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-319131 (URN)10.1371/journal.pone.0170684 (DOI)000396176100074 ()28125662 (PubMedID)
    Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2017-08-08Bibliographically approved
    2. Comparison of a 21-item food questionnaire with a 7-day dietary registration andbiomarkers of fat intake in a Swedish cohort of 60-year-old adults.
    Open this publication in new window or tab >>Comparison of a 21-item food questionnaire with a 7-day dietary registration andbiomarkers of fat intake in a Swedish cohort of 60-year-old adults.
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Purpose. To evaluate a 21-item food frequency questionnaire (FFQ) in men participating in a

    large cohort of Swedish 60-year-old adults (60YO).

    Methods. A self-reported FFQ (including 21 qualitative and semi-quantitative questions) was completed by >2000 men as part of a detailed baseline examination. A subsample of 301 men was included in a subsequent study in which detailed dietary habits were determined by a 7-day food record. Spearman rank correlations (r) and weighted Kappa (Kw) statistics were used to compare food intake categories in FFQ and 7-day food record. Furthermore, fatty acid (FA) composition in serum cholesteryl esters, assessed concurrent with the FFQ completion, was used to evaluate intakes of specific fat-rich foods from the FFQ.

    Results. We found good agreement between FFQ and food records for the reported intake of

    alcohol (r=0.72, Kw=0.51), margarine (r=0.60, Kw=0.33), and fruit (r=0.49, Kw=0.31), reasonably good agreement for total fish (r=0.25, Kw=0.23), and egg (r=0.35, Kw=0.28), but poor agreement for other food groups such as bread, cheese, vegetables and cookies. In addition, serum proportions of long-chain n-3 polyunsaturated FAs and pentadecanoic acid were significantly higher in men with greater intakes of fish and cheese, respectively.

    Conclusion. In this evaluation of a short FFQ against 7-d food records and serum biomarkers of fat intake we found that the FFQ reasonably well reflected the intake of certain food groups (e.g. alcohol, fish, and margarine), but performed less accurate for other food groups. Firm and overall

    conclusions on validity are confined by the time-lag between the test and the reference method.

    Keyword
    validation, food frequency questionnaire, biomarkers of fat intake
    National Category
    Medical and Health Sciences
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-327199 (URN)
    Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2017-08-08
    3. Association between carbohydrate intake and fatty acids in the de novo lipogenic pathwayin serum phospholipids and adipose tissue among 63-year old men
    Open this publication in new window or tab >>Association between carbohydrate intake and fatty acids in the de novo lipogenic pathwayin serum phospholipids and adipose tissue among 63-year old men
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Background: Fatty acid composition in blood and adipose tissue is useful to reflect dietary fat

    quality, although the utility of even-chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) has been debated. Since SFA also can be produced via de novo lipogenesis (DNL), and desaturated to MUFA, it has been proposed that these fatty acids may reflect carbohydrate-induced DNL. We aimed to test the hypothesis that high carbohydrate intake, especially sugars, is related to SFA and MUFA in serum and adipose tissue.

    Methods: Validated 7-day food records were collected and fatty acid composition in serum phospholipids (PL) and adipose tissue (AT) were measured in 63-year-old men (n=299). Stearoyl-CoA desaturate (SCD) activities in AT and PL were estimated by the palmitoleic acid (16:1) to palmitic acid (16:0) ratio. Associations of dietary carbohydrate, disaccharides,  monosaccharides, carbohydrate-to-fiber ratio, and alcohol with the sum of even-chain SFA, 16:0, 16:1, and SCD activity were assessed using linear regression models with and without adjustment for BMI. Non-linear trends were evaluated using restricted cubic splines. In a subsample (n=81) with RNA measured in AT biopsies, associations of dietary carbohydrate and alcohol with SCD gene expression were assessed using linear regression models.

    Results: In BMI-adjusted models, intake of carbohydrates was inversely associated with palmitic acid in PL (P=0.005). Disaccharide intake was non-linearly associated with 16:1 and SCD activity in PL (P for nonlinear trend ≤0.02), with the lowest values observed in the mid tertile. Alcohol intake was linearly associated with 16:0 in PL (P<0.001) and with 16:1 (P<0.001) and SCD activity (P ≤0.005) in AT. Alcohol intake was non-linear associated (P≤0.02) with 16:1 and SCD activity in PL; with initially stable levels at lower intakes that rapidly increased at intakes above median. In the subsample, we found no associations between carbohydrate intake and SCD gene expression (P ≥0.08).

    Conclusion: In this Swedish population, we found no evidence to suggest that higher carbohydrate intake or sugar-rich foods or beverages is reflected by higher SFA in PL and AT.

    Instead, alcohol was consistently associated with higher SFA and MUFA.

    Keyword
    fatty acid, saturated fatty acids, carbohydrate, phospholipid
    National Category
    Medical and Health Sciences
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-327205 (URN)
    Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2017-08-08
    4. CarbohydrateIntake and Abdominal Obesity in Swedish Men
    Open this publication in new window or tab >>CarbohydrateIntake and Abdominal Obesity in Swedish Men
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    ABSTRACT

    Background/Objectives: Associations between carbohydrates, particularly simple sugar and starch, and abdominal anthropometric measures appears controversial. However, the role of dietary carbohydrate intake in obesity and abdominal obesity has been debated, and few studies have been conducted in Nordic populations. We aim to examine the associations between carbohydrate quantity and quality, and anthropometric measures in Swedish men.

    Subjects/Methods: A cross-sectional investigation of 301 63-year-old men was conducted. Six men were excluded due to missing data on dietary intake and anthropometric measures, leaving 295 men for the present study. Healthy men were recruited from the Swedish 60YO cohort of men and women who had a health screening between 1997 to 1999. Carbohydrate and alcohol intake were assessed by a 7-days food record. The examination included anthropometric measurements (e. g., weight, BMI, WC, WHR, and SAD), fasting blood samples, and a comprehensive questionnaire. Spearman rank correlation and linear regression models were performed to assess relations between dietary intakes and anthropometric measures. Intakes of macronutrients were energy-adjusted according to the residual method. Logistic regression models were used to calculate odds ratios (OR) and 95% CI for abdominal obesity per intake tertiles.

    Results: Intakes of carbohydrate, monosaccharide, fibers, and fruits and vegetables correlated negatively with anthropometric measures of overall obesity (BMI) and AO (WC, WHR, and SAD). Total carbohydrate intake was significantly inversely associated with WHR and SAD. Likewise, monosaccharide intake was significantly associated with lower BMI, WC, WHR, and SAD. In contrast, alcohol intake was significantly associated with weight, BMI, WC, and SAD (Table 4). Alcohol intake was associated with AO (P for linear trend 0.002). Men in the highest tertile of alcohol intake were almost three times as likely to have AO compared to the men in the lowest tertile of intake, OR (95% CI): 2.93 (1.40-6.16). There was no evidence of non-linear association between the macronutrients and AO.

    Conclusion: In this Swedish population of older men, higher intakes of total carbohydrates and monosaccharides were associated a more favorable body fat distribution and lower abdominal adiposity. Men with higher alcohol intake were more likely to have AO as compared with a lower intake.

    Keyword
    carbohydrate intake, abdominal obesity, anthropometric measures.
    National Category
    Medical and Health Sciences
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-327277 (URN)
    Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-08-08
  • Hellström-Lindahl, Ewa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Åberg, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Ericsson, Cecilia
    AstraZeneca R&D, SE-43150 Molndal, Sweden..
    O'Mahony, Gavin
    AstraZeneca R&D, SE-43150 Molndal, Sweden..
    Johnström, Peter
    Karolinska Inst, Karolinska Univ Hosp, AstraZeneca PET Sci Ctr, Personalised Healthcare & Biomarkers, SE-17176 Stockholm, Sweden..
    Skrtic, Stanko
    AstraZeneca R&D, SE-43150 Molndal, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, SE-41345 Gothenburg, Sweden..
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
    Toward molecular imaging of the free fatty acid receptor 12017In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 54, no 7, 663-668 p.Article in journal (Refereed)
    Abstract [en]

    Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling. In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([H-3]AZ1, [H-3]AZ2 and [H-3]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma. [H-3]AZ1 showed improved specificity to FFAR1, with decreased off-target binding compared to [H-3]AZ2 and [H-3]TAK-875, while retaining high affinity in the nanomolar range. FFAR1 density in human islets was approximately 50% higher than in exocrine tissue. AZ1 is a suitable lead compound for PET labeling for molecular imaging of FFAR1 in humans, due to high affinity and reduced off-target binding.

  • Aaboud, M.
    et al.
    Bergeås, Elin Kuutmann
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Gradin, P.O. Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Madsen, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Öhman, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Rangel-Smith, Camilla
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    Precision measurement and interpretation of inclusive W+, W- and Z/gamma* production cross sections with the ATLAS detector2017In: European Physical Journal C, ISSN 1434-6044, E-ISSN 1434-6052, Vol. 77, no 6, 367Article in journal (Refereed)
    Abstract [en]

    High-precision measurements by the ATLAS Collaboration are presented of inclusive W+ -> l(+) nu, W- -> l(-) (nu) over bar and Z/gamma* -> ll (l = e, mu) Drell-Yan production cross sections at the LHC. The data were collected in proton-proton collisions at root s = 7 TeV with an integrated luminosity of 4.6 fb(-1). Differential W+ and W- cross sections are measured in a lepton pseudorapidity range vertical bar eta(l)vertical bar < 2.5. Differential Z/gamma* cross sections are measured as a function of the absolute dilepton rapidity, for vertical bar y(ll)vertical bar < 3.6, for three intervals of dilepton mass, m(ll), extending from 46 to 150 GeV. The integrated and differential electron- and muon-channel cross sections are combined and compared to theoretical predictions using recent sets of parton distribution functions. The data, together with the final inclusive e(+/-) p scattering cross-section data from H1 and ZEUS, are interpreted in a next-to-next-to-leading-order QCD analysis, and a new set of parton distribution functions, ATLAS-epWZ16, is obtained. The ratio of strange-to-light sea-quark densities in the proton is determined more accurately than in previous determinations based on collider data only, and is established to be close to unity in the sensitivity range of the data. A new measurement of the CKM matrix element vertical bar V-cs vertical bar is also provided.

  • Aaboud, M.
    et al.
    Bergeås, Elin Kuutmann
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Bokan, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Brenner, Richard
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    De Bruin, Pedro Sales
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ekelöf, Tord
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ellert, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Ferrari, Arnaud
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Gradin, P.O. Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Madsen, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Mårtensson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Öhman, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Rangel-Smith, Camilla
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, High Energy Physics.
    Zwalinski, L.
    Measurement of jet fragmentation in Pb plus Pb and pp collisions at root s(NN)=2.76 TeV with the ATLAS detector at the LHC2017In: European Physical Journal C, ISSN 1434-6044, E-ISSN 1434-6052, Vol. 77, no 6, 379Article in journal (Refereed)
    Abstract [en]

    The distributions of transverse momentum and longitudinal momentum fraction of charged particles in jets are measured in Pb+Pb and pp collisions with the ATLAS detector at the LHC. The distributions are measured as a function of jet transverse momentum and rapidity. The analysis utilises an integrated luminosity of 0.14 nb(-1) of Pb+Pb data and 4.0 pb(-1) of pp data collected in 2011 and 2013, respectively, at the same centre-of-mass energy of 2.76 TeV per colliding nucleon pair. The distributions measured in pp collisions are used as a reference for those measured in Pb+Pb collisions in order to evaluate the impact on the internal structure of jets from the jet energy loss of fast partons propagating through the hot, dense medium created in heavy-ion collisions. Modest but significant centrality-dependent modifications of fragmentation functions in Pb+Pb collisions with respect to those in pp collisions are seen. No significant dependence of modifications on jet p(T) and rapidity selections is observed except for the fragments with the highest transverse momenta for which some reduction of yields is observed for more forward jets.

  • Golts, Alexandr
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Uppsala Centre for Russian and Eurasian Studies.
    Voennaja reforma i rossijskij militarizm2017Book (Other (popular science, discussion, etc.))
  • Laumann, Sebastian
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History.
    Tandhälsan i Västergarns Schakt 272017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The mass grave in Västergarn, Gotland, Sweden is located between two medieval churches and thought to be a bone depot from when one of the churches expanded their wall in more recent time. The bone depot is problematic in a way because it could contain individuals from a wide time frame, making it hard to ask certain questions regarding how the individuals lived and died. Also conducting individual studies of the skeletons is hard since the osteological material is highly fragmented and the individual graves has been disturbed post burial. Therefore this osteological study will not focus on studying the health of the people individual by individual, but rather examine the permanent teeth of this material and then apply statistics to study the overall oral health of Västergarns mass grave. Enquiries regarding tooth health and how people experienced their life because of it, are questions that I will be trying to answer in this study. A deeper and thorough investigation regarding certain teeth conditions such as dental calculus, caries, enamel hypoplasia as well as mechanical damage will be conducted. There will also be comparisons between other historic locations in Sweden such as Uppsala, Skara and the older cemetery and its ruin in Västergarn. Last but not least a discussion regarding the difficulty of examining a diverse material with different timeframes.

  • Ask, Simon
    et al.
    Lindh, Rickard
    Design och konstruktion av roterande LiDAR-system för 360 graders objektdetektering2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Although laser rangefinder technologies have been around for decades in military, cartography, building, industrial and research applications it is only in recent years that more generally applicable and cheaper consumer grade laser range finder sensors have become available. This project investigates the possibilities and limitations of creating a mobile 360 degree, two-dimensional obstacle detection system using off-the-shelf available electronic components.

    Using a Lidar Lite 3 from Garmin Ltd., an Arduino compatible microcontroller based on Atmel 328P, a Raspberry Pi 3 from The Raspberry Pi Foundation and an electronic speed controlled brushless DC motor driving the rotation, it is shown how range data measurements can be collected, communicated, processed and displayed at measurement rates between 500 and 1000 Hz. At 5 Hz update rate of a complete 360-degree data set, this translates to a worst case angular resolution of 2.5 degrees at ranges reaching 10 meters depending on target reflectivity. Configured for these faster measurement rates, at static measurements of a white painted wall, the measurements show a standard deviation of 0.06 m at a five-meter range, going up to 0.19 m at a range of 10 meters.

    A modular and mobile prototype was designed and built. The modularity allowed testing and verification of two configurations. Configuration A uses a slip ring for power and data transfer to the rotating sensor. Configuration B allows the laser range finder to be stationary and instead rotates a first surface aluminum mirror positioned at 45 degrees above the sensor.

    The measurement results show that increasing range has a notable adversely effect on the number of successful readings in a setting demanding faster measurement rates of above 500 Hz. The number of successful readings decreases at ranges above 5 meters, and this decrease of successful readings is more pronounced in the configuration using a mirror to reflect the measurement. The mirror reflected version does on the other hand allow an electromechanically simpler, more silent and durable system.

    Using a density based clustering algorithm it is shown how person sized objects in the point cloud data can be robustly detected at ranges up to 5 meters. 

  • Rylander, Andrea
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Cloud computing: Knowledge expectation and reality: Cloud computing: Knowledge expectation and reality2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    As today’s digitalized society constantly evolves, more and more companies andorganizations are transitioning over to using cloud computing solutions. Althoughcloud computing is not a new technology, the field has rapidly grown in the last fewyears alone. The Information Technology department at Uppsala University is one ofthe many institutions that has taken the step forward and has developed a privatecloud system in cooperation with Hewlett-Packard to extend the already extensiveresources the department has to offer their employees. The purpose of this thesiswas to investigate how familiar the employees at the Information Technologydepartment are with the concept of cloud computing and what expectations theymight have on the system. This was done by conducting semi-structured interviews,which were then transcribed and analysed carefully.The results were promising, showing that the respondents knew quite a lot about theconcept of cloud computing and that their expectations of the system are not too farfrom the reality of the system.

  • Al-Hayali, Anas
    et al.
    Thelin, Hampus
    Brandpåverkan och dimensionering av bärande delar2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this bachelor thesis is to describe how structural design for fire is done. The aim is to produce a report that step by step describes how the design is performed. Structural design for steel and glulam beams with and without fire protection are performed to see what the differences are when fire protection is used and when it’s not. The glulam beams are also inspected in the computer software SPFiT 2.0, to see how efficient such software is.  For glulam beams, the differences between structures with and without fire protection depend on how long the fire lasts. In protected structures, no carbonization occurs at the beginning, while carbonization starts directly for unprotected. If the design is exposed to fire for a long time, the differences are not so great.  For steel beams, the differences between protected and unprotected constructions are clearer. The steel temperature determines the load capacity and if the structure is not protected the temperature will rise very fast. However if the design is protected the steel temperature can be kept lower much longer.  SPFiT 2.0 turns out to be very effective as it saves a lot of time when performing structural design for fire. The results from SPFiT 2.0 correspond with the results from hand calculations.  The report is structured in four parts. The first part is generally about how fire occurs and how it is spread. It also includes various laws and regulations that are important for designers to follow.  The second part deals with wood in structural parts and investigates what happens to the material when it is exposed to fire and what protection methods are available. Here the design process for wood constructions is described step by step.  The third part is about steel in structural parts and investigates what happens to the material when it is exposed to fire and what protection methods are available. Here the design process for steel constructions is described step by step.  In the fourth part of the report, the results from calculations of glulam beams in three different cases are compared with the results from the software SPFiT 2.0.

  • Nilsson, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology.
    Nyttovärdering av nationellElektronisk Remiss2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The purpose of this thesis is to evaluate the benefits of the service Elektronisk remiss.Elektronisk remiss is a service that enables an exchange of medicalreferrals on a national level. The evaluation presents a number of recommendationsfor future work with Elektronisk remiss for Region Uppsala and otherstakeholders of the national electronic referral service. The benefits has beenevaluated with the use of the 5-model. The benefits that are examinedconsists of thoughts, ideas and feelings that the stakeholders have towards Elektroniskremiss. The information has been collected from semi-structuredinterviews together with the stakeholders. The interviews had the purpose to analyzewhat effects, positive and negative, that occurs with a nationalreferral system. The evaluation has not examined the economic benefits ofElektronisk remiss. The qualitative data can be the basis for future decisionswith the investment. The result of the 5 model shows the correlation betweenchange, effect and benefit. The change is that referrals will be handledelectronically on a national level, the effects are the findings from the interviews andthese are either direct or indirect and the benefit is the value in whichthe effect will result in. The correlation between change, effect and benefit isdisplayed in a 5-table that gives an overview of the effects and the benefits.The results of this study shows that the qualitative benefits of the investment ispositive and that Elektronisk remiss saves a lot of time in the process ofhandling referrals.

  • Grapensparr, Liza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Auxiliary Cells for the Vascularization and Function of Endogenous and Transplanted Islets of Langerhans2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 diabetes develops through the progressive destruction of the insulin-producing beta-cells. Regeneration or replacement of beta-cells is therefore needed to restore normal glucose homeostasis. Presently, normoglycemia can be achieved by the transplantation of whole pancreas or isolated islets of Langerhans. Islet transplantation can be performed through a simple laparoscopic procedure, but the long-term graft survival is low due to poor revascularization and early cell death.

    This thesis examined the possibility of using different auxiliary cells (Schwann cells, endothelial progenitor cells, and neural crest stem cells) to improve the engraftment and function of endogenous and transplanted islets.

    Co-transplantation of Schwann cells with islets improved islet graft function early after transplantation, and caused an increased islet mass at one month posttransplantation. However, the vascular densities of these grafts were decreased, which also related to an impaired graft function.

    Islet grafts containing endothelial progenitor cells had a superior vascular density, with functional chimeric blood vessels and substantially higher blood perfusion and oxygen tension than control transplants.

    By culturing and transplanting islets together with neural crest stem cells it was found that islets exposed to these cells had a higher beta-cell proliferation compared with control islets. At one month posttransplantation, the grafts with neural crest stem cells also had a superior vascular- and neural density.

    The potential of intracardially injected neural crest stem cells to home to the pancreas and ameliorate hyperglycemia in diabetic mice was investigated. During a three-week period after such cell treatment blood glucose concentrations decreased, but were not fully normalized. Neural crest stem cells were present in more than 10% of the pancreatic islets at two days postinjection, at which time the beta-cell proliferation was markedly increased when compared with islets of saline-treated diabetic animals. Three weeks later, a doubled beta-cell mass was observed in animals receiving neural crest stem cells.

    In summary, islets can easily be transplanted together with different auxiliary cells. Some of these cells provide the possibility of improving vascular- and neural engraftment, as well as beta-cell growth and survival. Systemic administration of neural crest stem cells holds the potential of regenerating the endogenous beta-cells.

    List of papers
    1. Influence of islet and peri-islet Schwann cells on vascularity and beta-cell function in endogenous and transplanted islets
    Open this publication in new window or tab >>Influence of islet and peri-islet Schwann cells on vascularity and beta-cell function in endogenous and transplanted islets
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-327312 (URN)
    Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2017-08-09
    2. Bioengineering with Endothelial Progenitor Cells Improves the Vascular Engraftment of Transplanted Human Islets
    Open this publication in new window or tab >>Bioengineering with Endothelial Progenitor Cells Improves the Vascular Engraftment of Transplanted Human Islets
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-327311 (URN)
    Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2017-08-09
    3. Co-transplantation of Human Pancreatic Islets With Post-migratory Neural Crest Stem Cells Increases beta-Cell Proliferation and Vascular And Neural Regrowth
    Open this publication in new window or tab >>Co-transplantation of Human Pancreatic Islets With Post-migratory Neural Crest Stem Cells Increases beta-Cell Proliferation and Vascular And Neural Regrowth
    Show others...
    2015 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 100, no 4, E583-E590 p.Article in journal (Refereed) Published
    Abstract [en]

    Context: Neural crest stem cells (NCSCs) are capable of substantially improving murine islet function by promoting beta-cell proliferation. Objective: The present study aimed to investigate the potential of NCSCs to stimulate human beta-cell proliferation, and improve neural and vascular engraftment of human islets. Design, Setting, and Subjects: Human pancreatic islets from 18 brain-dead cadaveric donors (age range, 19-78 y) were obtained through the Nordic Network for Clinical Islet Transplantation. beta-cell proliferation and graft function was investigated at our experimental laboratory. Intervention and Main Outcome Measures: Human islets were transplanted, either alone or together with spheres of NCSCs. beta-cell proliferation, as well as islet neuralandvascular densities, were assessed by immunohistochemistry. Graft blood perfusion and oxygen tension were measured using laser-Doppler flowmetry and Clark microelectrodes, respectively. Results: Two days posttransplantation, the number of Ki67-positive beta-cells was doubled in human islets that had been exposed to NCSCs. Similar findings were obtained in vitro, as well as with EdU as proliferation marker. Four weeks posttransplantation, NCSC-exposed human islet grafts had much higher neural and vascular densities. The newly formed blood vessels were also functional, given that these human islets had a substantially higher blood perfusion and oxygen tension when compared with control transplants. Conclusion: We conclude that exposure to NCSCs stimulates human beta-cell proliferation, andthat these cells improve both the neural and vascular engraftment of transplanted human islets. NCSCs are a promising cellular therapy for translation into clinical use.

    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-253267 (URN)10.1210/jc.2014-4070 (DOI)000353361500009 ()25668197 (PubMedID)
    Available from: 2015-05-25 Created: 2015-05-25 Last updated: 2017-08-09Bibliographically approved
    4. Systemic neural crest stem cell treatment alleviates experimental type 1 diabetes by cellular homing to the damaged islets, inducing beta-cell regeneration
    Open this publication in new window or tab >>Systemic neural crest stem cell treatment alleviates experimental type 1 diabetes by cellular homing to the damaged islets, inducing beta-cell regeneration
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-327313 (URN)
    Available from: 2017-08-09 Created: 2017-08-09 Last updated: 2017-08-09
  • Kjellgren, Peter
    et al.
    Spanoudakis, Nikolas
    Sales opportunities for solar collectors in industries: A market analysis of two different markets2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

     The intensifying environmental problems demand nations to take immediate action.

    The industry sector alone accounts for 54 % of the global energy demand (year

    2012) and the most common way for industries to get heat for its production, is still

    today by fossil-fuel boilers.

    One promising renewable energy source, which has great potential in replacing

    fossil-fuel boilers, is solar thermal energy. In order to meet all climate goals, the

    Paris agreement for example, renewable energy resources like solar thermal energy

    will become crucial.

    Absolicon Solar AB is a Swedish manufacturing company, whose main product is

    the solar collector T160. The T160 is a heat water producing collector, which is

    suitable for integrating in industrial heat water processes for temperatures up to 160

    °C. One of the challenges the company faces, is to find suitable markets and

    customers to sell its product to.

    Two promising markets that Absolicon want to explore and eventually enter are the

    Food and Beverage market in Spain, and the District Heating market in Denmark.

    This study aims to give Absolicon a better understanding of these two markets of

    interest, in order for Absolicon to enter and direct the right value proposition of its

    product to the right customers. Thus two qualitative market researches were

    conducted, one for each market. Based on the results of the market researches, two

    business strategies were proposed respectively. Finally, a comparative study is

    carried out and relative conclusions are drawn.

  • Broiles, Thomas W.
    et al.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA..
    Burch, J. L.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA..
    Chae, K.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA..
    Clark, G.
    Johns Hopkins Univ, Appl Phys Lab, 11100 Johns Hopkins Rd, Laurel, MD 20723 USA..
    Cravens, T. E.
    Univ Kansas, Dept Phys & Astron, 1450 Jayhawk Blvd, Lawrence, KS 66045 USA..
    Eriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Swedish Institute of Space Physics, Uppsala Division.
    Fuselier, S. A.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA.;Univ Texas San Antonio, Dept Phys & Astron, San Antonio, TX 78249 USA..
    Frahm, R. A.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA..
    Gasc, S.
    Univ Bern, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland..
    Goldstein, R.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA..
    Henri, P.
    CNRS, LPC2E, F-45071 Orleans, France..
    Koenders, C.
    Tech Univ Carolo Wilhelmina Braunschweig, Inst Geophys & Extraterr Phys, Mendelssohnstr 3, D-38106 Braunschweig, Germany..
    Livadiotis, G.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA..
    Mandt, K. E.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA.;Univ Texas San Antonio, Dept Phys & Astron, San Antonio, TX 78249 USA..
    Mokashi, P.
    Southwest Res Inst, Div Space Sci & Engn, 6220 Culebra Rd, San Antonio, TX 78238 USA..
    Nemeth, Z.
    Wigner Res Ctr Phys, H-1121 Budapest, Hungary..
    Odelstad, Elias
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Space Plasma Physics. Univ Kansas, Dept Phys & Astron, 1450 Jayhawk Blvd, Lawrence, KS 66045 USA..
    Rubin, M.
    Univ Bern, Phys Inst, Sidlerstr 5, CH-3012 Bern, Switzerland..
    Samara, M.
    Goddard Space Flight Ctr, Heliophys Div, 8800 Greenbelt Rd, Greenbelt, MD 20771 USA..
    Statistical analysis of suprathermal electron drivers at 67P/Churyumov-Gerasimenko2016In: Monthly notices of the Royal Astronomical Society, ISSN 0035-8711, E-ISSN 1365-2966, Vol. 462, S312-S322 p.Article in journal (Refereed)
    Abstract [en]

    We use observations from the Ion and Electron Sensor (IES) on board the Rosetta spacecraft to study the relationship between the cometary suprathermal electrons and the drivers that affect their density and temperature. We fit the IES electron observations with the summation of two kappa distributions, which we characterize as a dense and warm population (similar to 10 cm(-3) and similar to 16 eV) and a rarefied and hot population (similar to 0.01 cm(-3) and similar to 43 eV). The parameters of our fitting technique determine the populations' density, temperature, and invariant kappa index. We focus our analysis on the warm population to determine its origin by comparing the density and temperature with the neutral density and magnetic field strength. We find that the warm electron population is actually two separate sub-populations: electron distributions with temperatures above 8.6 eV and electron distributions with temperatures below 8.6 eV. The two sub-populations have different relationships between their density and temperature. Moreover, the two sub-populations are affected by different drivers. The hotter sub-population temperature is strongly correlated with neutral density, while the cooler sub-population is unaffected by neutral density and is only weakly correlated with magnetic field strength. We suggest that the population with temperatures above 8.6 eV is being heated by lower hybrid waves driven by counterstreaming solar wind protons and newly formed, cometary ions created in localized, dense neutral streams. To the best of our knowledge, this represents the first observations of cometary electrons heated through wave-particle interactions.

  • Beth, A.
    et al.
    Imperial Coll London, Dept Phys, Prince Consort Rd, London SW7 2AZ, England..
    Altwegg, K.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland..
    Balsiger, H.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland..
    Berthelier, J. -J
    Calmonte, U.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland..
    Combi, M. R.
    Univ Michigan, Dept Atmospher Ocean & Space Sci, 2455 Hayward, Ann Arbor, MI 48109 USA..
    De Keyser, J.
    Royal Belgian Inst Space Aeron, BIRA, IASB, Ringlaan 3, B-1180 Brussels, Belgium..
    Dhooghe, F.
    Royal Belgian Inst Space Aeron, BIRA, IASB, Ringlaan 3, B-1180 Brussels, Belgium..
    Fiethe, B.
    TU Braunschweig, Inst Comp & Network Engn IDA, Hans Sommer Str 66, D-38106 Braunschweig, Germany..
    Fuselier, S. A.
    Univ Texas San Antonio, Dept Phys & Astron, San Antonio, TX 78228 USA.;Southwest Res Inst San Antonio, San Antonio, TX 78228 USA..
    Galand, M.
    Imperial Coll London, Dept Phys, Prince Consort Rd, London SW7 2AZ, England..
    Gasc, S.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland..
    Gombosi, T. I.
    Univ Michigan, Dept Atmospher Ocean & Space Sci, 2455 Hayward, Ann Arbor, MI 48109 USA..
    Hansen, K. C.
    Univ Michigan, Dept Atmospher Ocean & Space Sci, 2455 Hayward, Ann Arbor, MI 48109 USA..
    Hassig, M.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland.;Univ Texas San Antonio, Dept Phys & Astron, San Antonio, TX 78228 USA..
    Heritier, K. L.
    Imperial Coll London, Dept Phys, Prince Consort Rd, London SW7 2AZ, England..
    Kopp, E.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland..
    Le Roy, L.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland..
    Mandt, K. E.
    Univ Texas San Antonio, Dept Phys & Astron, San Antonio, TX 78228 USA.;Southwest Res Inst San Antonio, San Antonio, TX 78228 USA..
    Peroy, S.
    Imperial Coll London, Dept Phys, Prince Consort Rd, London SW7 2AZ, England..
    Rubin, M.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland..
    Semon, T.
    Univ Bern, Phys Inst, CH-3012 Bern, Switzerland..
    Tzou, C. -Y
    Vigren, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Swedish Institute of Space Physics, Uppsala Division.
    First in situ detection of the cometary ammonium ion NH4+ (protonated ammonia NH3) in the coma of 67P/C-G near perihelion2016In: Monthly notices of the Royal Astronomical Society, ISSN 0035-8711, E-ISSN 1365-2966, Vol. 462, S562-S572 p.Article in journal (Refereed)
    Abstract [en]

    In this paper, we report the first in situ detection of the ammonium ion NH4+ at 67P/Churyumov-Gerasimenko (67P/C-G) in a cometary coma, using the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA)/Double Focusing Mass Spectrometer (DFMS). Unlike neutral and ion spectrometers onboard previous cometary missions, the ROSINA/DFMS spectrometer, when operated in ion mode, offers the capability to distinguish NH4+ from H2O+ in a cometary coma. We present here the ion data analysis of mass-to-charge ratios 18 and 19 at high spectral resolution and compare the results with an ionospheric model to put these results into context. The model confirms that the ammonium ion NH4+ is one of the most abundant ion species, as predicted, in the coma near perihelion.

  • Malmsten, Silva
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History.
    Palats som klass- och genusmarkör: Inomaristokratiska spänningar i 1800-talets Stockholm2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    During the second half of the 19th Century the influence and power of the Stockholm aristocracy had decreased significantly amidst the emergence of the modern society. Therefore, it was important for them to position themselves toward the surrounding society more symbolically. The bourgeoisie, on the other hand, had strengthened economically and advanced in the societal elite. The ongoing industrialization of the 19th Century created a bourgeois class with improved acquisition power that in an analogical manner aimed at manifesting its recently achieved social position. The time scope of the study includes class dislocations and changes in which the economically strengthened bourgeoisie occupy new spaces alongside the old aristocracy in the city.

    The study examines how class and gender defined power settings and cultural codes are reflected in the architecture of the period, as regards interior and construction plan among the new-aristocratic bourgeoisie and the older aristocracy respectively.

    The palaces of the Stockholm city core are analyzed and compared and will exemplify the two ideal positions.

  • Langwagen, Simon
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History, Conservation.
    Bjurfors bruk: Lämningar med guldkant2016Student paper second term, 180 HE creditsStudent thesis
    Abstract [en]

    During the 17th century, a handful of brassworks were founded in Sweden as a result of a royal decree. These brassworks are today mainly to be found in the swedish midlands, in a region called Bergslagen. Although a small industry, it was a big and heavy player in the swedish economy, and its goods were exported all over Europe.

    Even though it is an important part of Swedish industrial history, the brassworks of the Stuart era are badly recorded, and many of the industrial sites are long gone. The national archives sits on huge quantities of information, and yet it is seldomly used for research purposes.

    This study focuses on the brassworks at Bjurfors, and lists its historical devlopment in the region. The individual workshops are mainly described by its appearances and functions. Finally i rise the discussion concerning the situation of today , and the problems in preserving the ruins for the future

  • Mårtenson, Helene
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History.
    Konsten att skapa hållbart samspel mellan människor och natur: Hållbarhet och empowerment i Marjetica Potrcs "On-Site" projekt2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this paper is to examine how the Slovene artist Marjetica Potrc works with sustainability and empowerment in her “On-Site” projects. An analysis of various indicators of sustainability in the projects clarifies what the projects have in common. Balance in the relationships between people and nature stand out as a major theme in the projects. The artist works with tools such as “participatory design” where all participants are of equal importance, and “relational objects” with which the participants negotiate and transform the common space. The theory of “relational aesthetics” by Nicolas Bourriaud is applicable to the relational qualities of the projects, and the concept that all parts in the works functions as “forms” could be used here. Nature can be read as “form” together with the rest of the participants, on a “stage” of action in the projects. In all the projects one or more solutions are presented. By creating ideal prototypes of reality, where everyone, including nature, is empowered to participate on equal grounds, a solution is presented for a sustainable lifestyle.

  • Johansson, Frida
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History, Conservation.
    Från slott till koja: En studie av det svenska murteglets historia2017Independent thesis Basic level (degree of Bachelor), 180 HE creditsStudent thesis
    Abstract [en]

    The complete history of Swedish bricks has not yet been fully compiled. This paper is written with the intention to assemble the historic puzzle which can tell the story of how bricks have been used, who has used them and how their appearance has changed over the course of time. To do this, extensive literature studies have been made, with sources stretching over a period of 2000 years. Bits of each source have been taken to create a chronological picture of its history. The results showed that catholic monks took the knowledge of brick working to Sweden in the 12th century. Soon, the royal power and the church started using brick as well. Despite this, bricks did not get its biggest breakthrough until the 18th century, when a new church law made children learn how to read. Instruction books got released and were read by a fairly large portion of the Swedish population. In the 1870s, the brickyard industry got mechanized, which made the branch sensitive to changes in the country’s economy. From this, the conclusion is drawn that literacy rate and industrial revolution led to the two biggest blooms in the history of bricks. Ironically, the industrial revolution also lead to the descent of the brick industry, partly because of the economic sensitivity, partly because the concrete was allowed to take over.

  • Colfach, Peder
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History, Conservation.
    3D Laserskanning: Verktyg för antikvarisk dokumentation2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This study aims to figure out if there is any heritage aspect when documenting heritage buildings with 3D laser scanning in Sweden. The paper is based on three case studies of two privately owned and one public building where the purpose for 3D scanning has had different goals. In simple words this paper aims to describe what laser scanning is and how you work with the laser scanning in the field.  Through comparing results from prior studies on the matter, this study also aims to describe the advantages that come from using 3D laser scanning on heritage buildings. This study finally wants to bring up the subject and discuss the terms and uses of fulfilling a building heritage documentation that suites our time.

  • Stengård, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History, Conservation.
    Påverkare och Påverkade: En diskursanalys av relationen mellan Sida och Kulturarv utan Gränser utifrån deras arbete i Bosnien och Hercegovina 1996-20082017Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis examines two things, first the relationship between the aid agency Swedish International Development Co-operation Agency (Sida) and the Swedish foundation Cultural Heritage without Borders (CHwB) by examine the discourses that occur in the communication between them. The second aim is to see what part the two organizations play in the construction of the cultural heritage during the reconstruction process after the war in Bosnia and Herzegovina. The material for the survey consisted of documents related to project applications such as applications them self’s, decisions and reports. To analyze my material, I use Ashworth and Tunbridge's model describing the process behind the construction of cultural heritage. To see the relationship between CHwB and Sida, I have used Norman Fairclough's critical discourse analysis to visualize the discourses CHwB and Sida operates within and how they are influenced by other discourses but also by the social practice. For more than 10 years, Sida is CHwB's main financier during the foundation's work with restoration of buildings, development of competence and institution building to re-build and strengthen the cultural heritage sector in Bosnia and Herzegovina. The starting point is that the relationship between Sida and CHwB was fundamentally uneven because the foundation was financially dependent on Sida. The result of the survey shows that, due to its financial advantage, Sida completely transformed CHwB during the reviewed time-period. From focusing on working for the conservation and protection of cultural heritage, the Foundation's focus is shifting towards focusing on working with cultural heritage as a resource for further social and economic development

  • Myrstener, Pella
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Art History.
    Konsten att tävla i konst: en undersökning av tävlingar i offentlig konst i Sverige 1937-19702017Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    This thesis analyses the public art competitions arranged by the Public Art Agency Sweden (Statens konstråd) 1937-1970 and the discussions about public art competitions in within the art field of the 1940’s, -50’ and -60’s. The main material for this analysis has been the protocols of the Public Art Agency and the annual paper of the Swedish Artists' National Organization (Konstnärernas riksorganisation). The theoretical and methodological framework is based on Pierre Bourdieu’s understanding of the art field, and institutions as agents within that field. I also use Foucauldian discourse theory as another theoretical tool to understand the power relations between these institutions in the art field. My aim has been to understand why there were competitions for public art commissions – the purposes, the processes, the discussions and how these factors change over the decades.

    The purpose for public art competition can be understood through the ideology of the Swedish welfare state and the cultural policy of the Social Democratic government in the 1930’s. The public art competitions could support the Swedish artists economically, but was also a way for the Swedish Government, through the Public Art Agency, to control and guarantee that the public artworks were of high artistic quality. This idea of artistic quality became more and more dominant as a purpose for the competitions through the 1950’s and 1960’s. 

    The artists active in the Swedish Artists' National Organization found the competitions to be of great importance and the competitions were much discussed in the organisations annual paper. Many of the artists that discussed the artist competitions were of the same generation born in the 1910’s or 1920’s and were working with public art commissions to a great extent. For them, the public art competitions gave recognition and a possible income.

    My analysis also shows that the public art competitions were also connected to the concept of modernism. The status of the competitions changed along with the changing concept of modernism. The competition was at its highest status in the 1930’s and 1940’s, when many artists were engaged in public art commissions. It became less popular among young artists in the 1960’s, when the art field was more politically radical and critical against authorities. 

  • Hörnström, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The effect of low temperature and transportation time on Clostridium difficile viability2016Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Anaerobe opportunist Clostridium difficile causes the majority of hospital-acquired antibiotic-associated diarrhea. Infections can be severe because of its ability to withstand many antibiotics, to sporulate and to produce toxins (A, B and binary).

        In Sundsvall Hospital C. difficile is detected with real-time PCR, which targets the sequences of toxin B, binary toxin and a regulatory gene deletion seen in the virulent ribotype 027. All positive samples are stored frozen for one month, available for further analysis or outbreak investigation. The aim of this study was to investigate if temperature and transportation time may affect the viability of C. difficile, and the PCR-result.

        Frozen feces samples were cultivated, identified with MALDI-TOF and analyzed with real-time PCR after at least one month of storage. To simulate the effect of transportation time, samples were stored at 4-8°C for three and seven days before cultivation and identification. Controls were cultivated after freezing for comparison.

        Ninety percent of the frozen samples contained viable C. difficile. Discrepancies between PCR-results were found for two of the oldest samples collected (six months), which turned negative. Fresh samples showed lower amount of viable C. difficile after three days (50 %) than after seven days (60 %) of storage, perhaps because of competition with other bacteria and sporulation. The frozen control group contained a higher viable amount, 75 %. The results indicate that C. difficile tolerates to be stored at low temperatures as practiced today at the laboratory. Transportation time seem to affect the outcome of cultivation, but not the PCR-result.

  • Andersson, Vidar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Evaluation of CellaVision DM1200 Vet and its ability to differentiate feline leukocytes compared to manual differential count and Advia 21202016Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Leukocyte differential count in peripheral blood smear has, ever since the method was developed more than 100 years ago, been one of the most frequently used diagnostics tool in the routine hematology laboratory. The manual differential count of leukocytes using a microscope is still the standard method in most small and medium sized laboratories. Even though the method does not require any expensive instruments it comes at a high cost due to it being labor intensive and time consuming. In recent years the rapid technical advancements has led to the development of automatic or semi-automatic methods in which the leukocytes are differentiated. In this study a method comparison was made between manual leukocyte differential counts, CellaVision DM1200 Vet and Advia 2120 when analyzing 106 fresh, feline blood samples. The general agreement between results was good, especially for the most common leukocytes, such as neutrophils and lymphocytes. Results for eosinophils and monocytes had moderate agreement. The confidence intervals were generally wider when CellaVision DM1200 Vet was compared with Advia 2120, than when CellaVision DM1200 Vet was compared to the manual differential count. Despite the fact that Advia 2120 and CellaVision DM1200 Vet are both faster and often show comparable results to the manual differential count, the light microscopy will remain the gold standard for difficult samples, where there is suspicion of inflammation (band neutrophils), intracellular microorganisms, reactive lymphocytes or if the sample contains a high degree of smudge cells or artifacts. 

  • Bohjort, Emelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Method verification for homocysteine and a sustainability study on glucose, homocysteine and lactate in different sampling tubes2016Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The pre-analytical phase is known for being the most important step in the laboratory process to reach reliable test results. If handling, transport or preparation of the sample is performed incorrectly the results can deviate from the true value. Today, sampling tubes contains various additives to stabilize concentration levels. The aim of this study was to test a new sampling tube containing fluoride/citrate for glucose, lactate and homocysteine. It was also of interest to evaluate the stability of those three analytes in lithium-heparin, sodium-fluoride/potassium oxalate and fluoride/citrate tubes. To perform the sustainability study, a method verification was done for homocysteine in plasma. The study was performed in a hospital laboratory on the routine instrument Roche Cobas 6000 analyzer. Blood was drawn from 20 patients and was analyzed at the hospital laboratory in Gävle. The blood samples were transported frozen to the laboratory in Hudiksvall and were used in the method verification. For the sustainability study, blood was drawn from 10 healthy volunteers in lithium-heparin, sodium-fluoride/potassium oxalate and fluoride/citrate tubes. The method verification was approved. The results showed that glucose was stable for up to 72 hours in Vacuette Glycaemia tube with fluoride/citrate and this tube also gave more accurate results. Lactate and homocysteine were also stable in fluoride/citrate, but needs further studies. All three analytes were more stable if the sample tubes were centrifuged as soon as possible after blood collection. Fluoride/citrate tubes were stable without centrifugation directly.

  • Andrén, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Induction of HPV-16 Late Gene Expression Through Use of Small Molecule Drugs2016Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Cervical cancer is the second most common cancer in women worldwide. The principal cause of cervical cancer is infection with human papillomavirus (HPV). HPV-16 is a high-risk virus and it is responsible for a high portion of all HPV-caused cancers. The HPV-16 genome consists of early and late genes. The virus initially infects basal cells of the cervix epithelium and in these cells early genes are expressed, whilst late genes, L1 and L2, are only expressed in the upper cell layers of the epithelium. Proteins encoded by the late genes are highly immunogenic, thus it is speculated that expression of the late genes earlier in the virus life cycle could lead to clearance of the virus due to interference of the immune system.

        The aim of this study was to treat reporter cell lines with three different small molecule drugs to see if they had the ability to induce HPV-16 late gene expression. The reporter cell lines used in this study had been previously created by transfecting HeLa-cells with plasmids representing the HPV-16 genome. In these plasmids, L1 is replaced with a CAT reporter gene that encodes the CAT protein, which can be easily quantified using a sandwich ELISA.

        Upon treating the reporter cell lines with TPA, a significant induction of late gene expression was detected. Furthermore, treatment with valproic acid showed some induction of late gene expression. In conclusion, TPA and valproic acid was deemed to have potential to act as a candidate drugs for treatment of HPV infections. 

  • Guðjónsdóttir, Erla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Evaluation of a Viscosity/Elasticity Assay (ReoRox®) for Assessment of Platelet Storage Lesion and Fibrinogen Dependent Coagulation2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The impact storage has on function of platelet concentrates is not completely known, although some factors have been discovered and measures have been taken to counteract them, such as adding platelet additive solution. There are several methods for analysing platelet function. In this study, the aim was to analyse change of platelet function in platelet concentrates over time and to see what effect fibrogen has on the coagulation. A technique using free oscillation rheometry (FOR), ReoRox®, was used to analyse function in platelet concentrates, both over time and after addition of fibrinogen. The platelets were analyzed at a concentration of 800 x109 Ptl/L and activated with thrombin receptor antigen peptide (TRAP). For fibrinogen efect analysis, four different concentrations were used, 10 g/L, 2,25 g/L, 1,0 g/L and 0,1 g/L. The results showed no statistically significant change in the function over time. However an increase in elasticity and decrease in the decline of elasticity could be seen. While analysing the platelets with fibrinogen it showed that up to 2,25 g/L the aggregation increased, while it decreased significantly at 10 g/L. In conclusion, the platelet concentrates retained a good clotting function from day one to day seven of storage, while the clot became stronger and fibrinolysis decreased. Fibrinogen proved important for coagulation, however a too high concentration inhibits coagulation.

  • Sundström, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nanoparticle size-dependent activation of the hemostasis and the innate immune system.2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Nanoparticles are small particles with a size range of 10-1000 nm. They exist all around us, in make-up, dust and even food. They can enter our bloodstream through different pathways such as inhalation and cause thrombosis and multiple organ failure. They can be modified to act as drug deliverers and can treat even hard to reach places because of their small size. Studies have shown that the activation of the coagulation system and complement system is dependent on the size of the nanoparticle. This study’s main focus was to determine if there was a difference in the degree of activation on hemostasis and innate immunity by using four different nanoparticle sizes. The Chandler loop model makes it possible for blood to incubate with the nanoparticles and still be circulating in 37oC similar to the situation in the body. ELISA was thereafter performed on the plasma to determine the concentration of thrombin- antithrombin complex (TAT), C3a and Terminal Complement Complex (TCC). The most activating particles size on the complements system was 260 nm and for the coagulation system it was the 75 nm. FXII assay was performed and the results collaborated with the findings from the ELISA that the smallest particle sizes are most activating on the coagulation system. Taken together, smaller nanoparticle sizes are activating the coagulation system while the bigger nanoparticle sizes are more activating on the complement system. To confirm these results additional research should be performed to statistically confirm the importance of these findings. 

  • Norman, Albin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Co-localization of CYP4F22 and CERS3 in HeLa and HEKn cells could point towards metabolic pathway interactions2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The skin is the largest organ in the body. Its function is to protect the body from potential harm and to maintain homeostasis. The epidermis is the outermost layer of the skin. Stratum corneum is the outermost layer of the epidermis, composed of corneocytes and surrounding lipids. The lipids are produced by different enzymes that all play a role in the formation and function of the skin permeability barrier. Mutations in genes coding for these enzymes can lead to barrier dysfunction and could cause autosomal recessive congenital ichthyosis (ARCI). Nine genes have been identified as ARCI-causative and two of them are CYP4F22 and CERS3.

     

    The purpose of this project was to study co-localization of CYP4F22 with CERS3 and also mutated CYP4F22 enzymes, by transfecting plasmids into HeLa and HaCaT cells and performing PLA on HEKn cells. Co-localization could indicate potential interactions and by studying these more in the future, novel treatment strategies can be developed for ARCI patients.

     

    Transfection attempts showed a low transfection grade of wild type genes in both HeLa and HaCaT cells. Tendencies towards co-localization was seen in both cell types and some HeLa cells showed strong correlation after image analysis. Transfection of mutated genes failed, unfortunately. PLA showed co-localization in normal keratinocytes. The obtained results indicated a co-localization, but results need to be confirmed by immunoprecipitation and immunoblotting in the future. 

  • Molin, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Evaluation of different centrifugation settings using BD Microtainer® tubes2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In order to keep the turnaround time it is desirable to have few centrifugal programs and be able to centrifuge microtainer tubes together with vacutainer tubes. BD has launched a new type of microtainer tube that got a lower g-force than the older one on the same centrifugation program. The aims was to compare this program and three other, more powerful, programs and compare the impact on some common analytes and serum indices, especially on hemolysis. Three test parts was performed using venous samples taken from healthy individuals, 1) transfer of whole blood from serum tube to microtainer tubes, a clinical chemistry analysis; 2) whole blood from plasma tube to microtainer tubes, a clinical chemistry analysis and 3) whole blood from plasma tube to microtainer tubes for platelet count analysis. All tubes were examined for gel formation. The result showed a significant variance between some settings for some analytes but foremost at 899g and at 2000g, both in 10 min. The platelet count was below the threshold limit at 2000g. No tube had insufficient formation of the gel. The setting of 2000g was found suitable for microtainer tubes. These results correspond with the recommended settings from BD. Further studies are needed with more analytes and test subjects and a simulated transport time for plasma, because of the increased risk for hemolysis, to confirm if the same setting can be used for microtainer tubes (899g) as for the older microtainer tube and vacutainer tube (1300g).

  • Johansson, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jämförelse av två diffusionskapacitetsmetoder: en pilotstudie2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Pulmonary function testing is an important part when it comes to evaluating patients with or at risk for lung diseases. Measurement of the diffusing capacity with carbon monoxide (DLCO) of the lung is a very important parameter and reflects how well the gas exchange work. Traditionally the DLCO have been measured by the single breath (SB) method which requires a forcefully inhalation and a 10 second breath-hold. Not all patients are able to perform the method due to illness or related problems therefore it would be favourable if the ward could change to an easier method called intrabreath (IB). The IB method is not depending on a breath-holding manoeuvre, which should make it easier to perform. Eleven volunteers participated in the study. They all performed both DLCO techniques, starting with the SB followed by IB. The DLCO, when determined with the IB technique, had an excellent correlation to the SB technique. However, the IB systematically showed a lower value for DLCO, and can therefore not use the same references as SB. Before the ward can change from the SB- to the IB- method there are needs for further studies. New studies should include more volunteers so more trustworthy reference values can be made, they should also include sick patients as a check-up for the new reference values. For the moment the ward have to stay with the SB method.

  • Carls, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Optimization of pyrosequencing method for copy number analysis of CYP2D62017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    CYP2D6, a member of the cytochrome P450 enzyme system, has a central role in drug metabolism, it metabolizes 25 % of clinically used drugs. The gene that codes for the enzyme displays a high degree of polymorphism, which effects enzyme functions to various degrees. Aside from smaller mutations like SNPs, alleles may also feature duplications or deletion of the whole gene. Due to the clinical relevance of these mutations, a simple and precise method for genotyping is needed. In this study, a method based on pyrosequencing for copy number analysis was evaluated, wherein the copy number was determined by relative quantification to a reference gene CYP2D8P. During evaluation of the method, several adjustments were tried for optimization, including adjustments of annealing temperature and primer concentration. The results showed a difficulty in distinguishing between copy numbers using the method, as well as a high coefficient of variation. Therefore, further optimization is required before the method could be implemented into clinical practice.

  • Mutema Jonsson, Carla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Evaluation of Flow Cytometric Methods Used in Analysis of Immune Cells in Patients with Malignant Lymphoma.2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Malignant lymphomas are a group of cancerous diseases that develop from lymphocytes and primarily affect lymph nodes. Being the sixth most common cancer type in Sweden, lymphoma is a societal problem that needs to be tackled by improving care and treatment of patients. This study was designed to examine the blood cell composition in lymphoma patients and well as determine whether the use of cryopreserved cells affected the analysis outcome. An evaluation of the methods used was also performed. Frozen peripheral blood from lymphoma patients as well as fresh and frozen blood from healthy controls was used. The cells of interest were monocytes, granulocytes, Treg, NKT, iNKT, B and T cells plus the dendritic cell activation protein CCR7. Three immunophenotyping methods were used. Method one was used in staining surface cell markers while the other two were for both surface and intracellular staining using two distinctive kits. The results showed no significant difference in immune cell composition between patients and blood donors. Limited patient samples and the lack of female blood donors could explain the unexpected result. A substantial difference in Treg cells was observed in fresh and frozen tested samples as well as T cell outcomes in method one compared to the other two methods. There were fewer Treg cells in frozen samples, which probably was due to cryopreservation while the lack of fixation in method one led to the loss of CD4+ T cells. Overall, the methods used were adequate but definitely require some improvements. 

  • Grund, Olof
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Modification of a transient EPR and photoluminescence detection setup2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Climate change has given rise to higher demand of renewable energy. Conventional non-organic solar cells are still seen the most on the market but the last 10-20 years there has been an exponential increase in research about organic solar cells. The research demands measurements done on increasing fast time scales as insights about the topic and technology develops. Here is presented configurations done at the Isaak spectrometer at Freie Universit\"{a}t Berlin. The spectrometer is used for studying charge transport in organic solar cells as well as hybrid solar cells made from organic and inorganic semiconductors. One important feature for the time response is the Q factor property of the resonator in which the sample is placed. The Q factor describes the rate of energy loss relative to the stored energy of the resonator. The Q factor dependency over different temperature was studied in order to gain vital knowledge about the time response of the setup. Further new equipment was been installed at the setup and programmed in FSC2. This in order to increase the sensitivity of the optical setup, secure the personnel from possible dangerous excitation laser and in order to do more automated measurements. As the optical path was modified by installing a new optical fiber a new calibration had to be done. Finally, in order to try the functionality of the new equipment an automated energy dependency measurement was done on the polymer MEH-PPV and the polymer:fullerene blend MEH-PPV:PCBM. The automatic process of measuring was successful. 

  • Kåhre, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Experimental competition analysis of EHEC O157:H7 and commensal Enterobacteriaceae isolates from calves, selected by MALDI-TOF subtyping2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Escherichia coli are bacteria found in bowels of warm blooded animals. Most subspecies are harmless and part of the normal gut flora. However, E. coli have the ability to exchange genetic material with other bacteria, and some E. coli have acquired genes coding for virulence factors. VTEC, E. coli with the ability to produce verotoxin are commonly found in cattle, but certain types can cause severe disease in humans, known as enterohaemorrhagic E. coli, EHEC.

        In this study, isolates of E. coli and other bacteria in the family Enterobacteriaceae from calves were subtyped and clustered using MALDI-TOF. Ten strains were selected for experimental competition analysis against E. coli MG1655.

        The aim of the study was to identify strains of bacteria with the potential to outcompete VTEC in the cattle host and decrease the risk of human infections.

        Three of the bacterial strains were able to outcompete the laboratory strain, and in future studies these strains can be analysed when competing against VTEC. The rest of the strains were outcompeted. Four known strains of VTEC were analysed competing the laboratory strain, showing weak ability to compete. Finally, a highly pathogenic strain of VTEC was analysed against Escherichia coli Nissle 1917, known for its ability to outcompete many strains of bacteria. Nissle could not outcompete the tested VTEC strain under the tested conditions.

        In conclusion the majority of the bacterial strains isolated from calves were identified as E. coli and three of the isolates showed good ability to compete against the laboratory strain.

  • Isaksson, Amanda
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Optimization of PCR protocols used for genotyping transgenic mice & Evaluation of a method for co-detecting mRNA and protein2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of the current study was divided into two separate goals, (i) optimization of a number of PCR-based protocols employed for genotyping transgenic mouse lines and (ii) evaluating a protocol for co-detection of mRNA and its correlated protein in the mouse midbrain.

    The optimization was performed on PCR protocols for genotyping the following transgenic mouse lines; Dat-Cre, Vglut2-Lox, Vglut2-Cre and Vmat2-Lox. Also, two different polymerases were evaluated parallel to each other – KAPA and Maxima Hot Start. One of the main findings from the PCR optimizations were that for the Vglut2-Lox protocol. By decreasing the annealing temp and increasing the MgCl2 the bands appeared brighter. 

    For the second part of the project, in-situ hybridization (ISH) was used to detect the mRNA expression with a `non-radioactive in situ hybridization´ protocol, using digoxigenin or fluorescein labelled riboprobes (mRNA probes). To detect the correlated protein a basic immunohistochemistry (IHC) protocol with the use of primary and secondary antibodies was implemented. The combined protocol was tested with Nd6 and Grp markers. Before testing to combined the protocols the ISH protocol was performed alone with riboprobes for Girk2, Lpl and Fst. The combined protocol detected mRNA and protein for both the control marker Th and the Nd6 marker.

    In conclusions, the optimized PCR protocols were optimal when used with the Maxima Hot Start polymerase and the new combined ISH and IHC protocol worked for markers Th and Nd6.

  • Svedin, Nellie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Screening Swedish bees for pahogens shines new light on the parasite Gregarine2017Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    are under pressure from habitat loss, environmental stress and pathogens including viruses. Research have shown viral infections to be one of the major causes of colony losses. The purpose of this study was to screen three viruses; Deformed wing virus, Slow bee paralysis virus and Acute bee paralysis virus but also three parasites; Nosema spp., Crithidia spp., and Gregarine spp. due to their mortality and the lack of knowledge regarding some of the pathogens’ habitat and hosts. During the years of 2015 and 2016 three bee species were collected in a number of 156 samples including honeybees, bumblebees and solitary bees equally divided. Extraction of RNA and DNA was done using only the abdomen which was homogenised by the use of MixerMill and later extracted on a QIAcube. Real-time qPCR was used in this study as a qualitative screening method. DWV was detected primarily in honeybees, infecting as much as 70 %. The parasite known to have bumblebees as its host, namely Crithidia spp. was detected in 23 % of the honeybees collected, 15 % of the bumblebees and 2 % of the solitary bees. According to the results; Crithidia spp. is no longer a specific parasite found in bumblebees but have broaden its host spectrum to both honeybees and solitary bees. Furthermore, the parasite detected in most samples was Gregarine spp. and was detected in 50 % out of the bees collected suggesting that this parasite is common in Swedish bees.

  • Östlund, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Evaluating the Congo red staining method with the aim to solve problematics in the work process and optimize amyloidosis diagnostics2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Some diagnostic methods have been used for a very long time. Congo red stain saw the light of day in 1883, and quickly became important in many fields of use. Nowadays we recognize the importance of Congo red in diagnose of amyloid diseases. However, the technique and experience needed throughout the process from a suspected case to the diagnose is of greate importance. When diagnostic difficulties appeared in a few patient cases at the local hospital in Gävle, Sweden, a solution was needed. A delayed diagnose could have a potential devastating outcome seen in the perspective of the patient. Therefore it is crucial to have both sensitive and specific diagnostic methods that are optimized against the sought pathogenesis. This study aspired to find the solution to the difficulties in diagnostic work, brought to light by a pathology doctor at the hospital. Several different methodical procedures are used throughout the process, and were evaluated with focus lying on the thickness of the tissue, the staining method and the microscopes used in diagnostics. Different thickness of the tissue was cut and stained. The results demonstrated the importance of proper techniques and methods in preparing the tissue, and the tools to analyse it with. The thickness of tissue and the lightsource in the microscope played a cruicial role in diagnostics. Additionally it showed the importance to continue to raise the quality of work and make progress in the diagnostic and scientific field, possibly by finding new applications for old methods.

  • Ask, Alexandra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    REPLICATING THE TUMOUR MICROENVIRONMENT:CHEMOSENSITIVITY TESTING IN FIBROBLAST COCULTURES2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • Farhat, Leila
    Optimization and standardization of a novel method combining capillary electrophoresis and immunoblotting for the detection of the lectin pathway proteins.2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The complement system is a part of the innate immunity. Its function is to eliminate pathogens, by proteins interacting directly with pathogen surfaces and promoting a pro-inflammatory and anti-microbial environment. Related to the lectin pathway of the complement system are ten known proteins, with component properties and disease association still unclear. The aim of this study was to evaluate the instrument WES for the detection of seven proteins associated to the lectin pathway. The novel instrument introduces an automated technique based on capillary electrophoresis and immunoblotting. Trials were performed on donor plasma using instrument associated kits. For the evaluation, these kits were combined with assorted primary and secondary antibodies from several species, as well as antibodies in biotinylated form. The high protein content of plasma caused many artefacts, affecting separation and displaying unspecific binding of both primary and secondary antibodies. Biotinylated antibodies coupled with the kit streptavidin-horseradish peroxidase showed the best results for further trials. Several issues remain to be solved in the optimization, including determining the unspecificity of biotinylated primary antibodies, best antibody concentrations and optimal sample preparation and dilution.

  • Thulin, Satu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The presence of haemoglobin variants in Sweden – Detection by capillary zone electrophoresis.2017Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Haemoglobin A1c is besides glucose the most requested analysis for diagnosing diabetes due to its ability to predict diseases that occur due a high blood sugar. The analysis has some limitations when a haemoglobin variant is present as they may cause falsely low or high results.

    In this study, we used whole blood from routine requested haemoglobin A1c samples for screening for haemoglobin variants with Capillarys 3 TERA. The samples with haemoglobin variants was then analysed with Cobas c501, Roche and Afinion, Alere for comparison of the methods.

    The aim of this study was to investigate the presence of haemoglobin variants in the county of Uppsala by screening over 3000 haemoglobin A1c samples. Samples with known haemoglobin variant was analysed as above to compare the results with those found in our county to study the possibility to identify the haemoglobin variants with Capillarys 3 TERA.

    The presence of haemoglobin variants in the county of Uppsala was approximately 0.5%. Correlation between Cobas c501 and Capillarys 3 TERA was strong for samples with haemoglobin F (r = 0.988) and for the samples with haemoglobin variants the correlations coefficient was 0.94. Correlation coefficients between Afinion and Capillarys 3 TERA for samples with haemoglobin F was 0.987 and for the haemoglobin variant 0.937.

    The presence of haemoglobin variants in the county of Uppsala is still low. Capillarys 3 TERA is capable to separate the most common variants and despite the good correlation every haemoglobin variant needs to be handled separately and the results should be answered with a comment that there is a possibility that the haemoglobin variant is giving an incorrect result.

  • Rognås, Viktor
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Stenberg, Hanna
    Customer Based Business Development: Strategic Challenges for a Small Research-Based Spin-Off Enterprise2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The biotechnology industry is one of the fastest growing sectors of the western economy. The biotech industry is helping the world by creating significant societal and economic value in various sectors. However, as a result of the fast development of the biotech industry, the environment is constantly changing and doing so at a high pace. Hence, biotech companies are forced to always stay competitive and improve their business in order not to be outrivaled.

    XYZ is a family-owned chemical company based in Europe. The company’s main business is polysaccharide chemistry but specializes in fluorescent dextran derivatives for which XYZ offer different goods and services. Dextran is a polysaccharide that has been widely used as a research tool in various scientific fields. XYZ has been struggling with stagnating sales and wants to grow their business and find new customers.

    The purpose of this master thesis is to suggest ways of business development for XYZ through customer and market understanding. Assessment of the company’s current strategy, market and customers will aid in understanding the company’s value proposition and identify opportunities for business development. Data were collected mainly through qualitative unstructured interviews.

    In conclusion, based on the empirical results we recommend to assess the value propositions that the company is currently offering to customers. This should be done before reaching out to new customers. Further, this project aims to describe the factors a small research-based enterprise should consider when designing a business strategy.

  • Public defence: 2017-10-10 09:15 C4:301 BMC, Uppsala
    Balliu, Aleksandra
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Exploring molecular interactions between polypeptide conjugates and protein targets: Manipulating affinity by chemical modifications2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis molecular interactions between polypeptide conjugates and protein targets were investigated. Polypeptides were derivatized with small organic molecules, peptides and oligonucleotides. New strategies were developed with the aim to increase affinities for proteins of biological interest.

    A 42-residue polypeptide (4-C15L8) conjugated to a small organic molecule 3,5-bis[[bis(2-pyridylmethyl)amino]methyl]benzoic acid (PP1), was shown to bind glycogen phosphorylase a (GPa) in the presence of zinc ions. Under the assumption that hydrophobic interactions dominated the binding energy, the hydrophobic residues of 4-C15L8-PP1 were systematically replaced in order to study their contribution to the affinity enhancement. The replacement of the Nle, Ile and Leu residues by Ala amino acids reduced affinities. The introduction of non-natural L-2-aminooctanoic acid (Aoc) residues into the peptide sequence enhanced the binding affinity for GPa. A decreased KD of 27nM was obtained when Nle5, Ile9 and Leu12 were replaced by Aoc residues, in comparison to the KD value of 280nM obtained for the unmodified 4-C15L8-PP1. It is evident that there are non-obvious hydrophobic binding sites on the surfaces of proteins that could be identified by introducing the more hydrophobic and conformationally flexible Aoc residues. The downsizing of the 42-mer peptide to an 11-mer and the incorporation of three Aoc residues gave rise to a KD of 550 nM, comparable to that of  4-C15L8-PP1 suggesting that bioactive peptides can be downsized by the introduction of Aoc.

    Aiming to improve in vivo stability, the affinity for human serum albumin (HSA) of hydrophobic, positively and negatively charged polypeptide-PP1 conjugates was evaluated. Increased hydrophobicity due to the introduction of Aoc residues did not significantly increase the affinity for HSA. No binding was observed in the case of the most negatively charged polypeptides whereas the slightly negatively and positively charged polypeptides conjugated to PP1 bound HSA with affinities that increased with the positive charge. It was found that polypeptide-PP1 conjugates target the zinc binding site of the HSA. Affinity enhancement was obtained due to the incorporation of PP1 and increased by charge to charge interactions between the positively charged amino acids of the polypeptide and the negatively charged residues of HSA, in close proximity to the HSA zinc binding site. The survival times of the peptide-PP1 conjugates in human serum were extended as a result of binding to HSA. Zn2+ ion chelating agents can be incorporated in potential peptide therapeutics with a short plasma half-life, without increasing their molecular weights.

    List of papers
    1. Exploring Non-obvious Hydrophobic Binding Pockets on Protein Surfaces: Increasing Affinities in Peptide–Protein Interactions
    Open this publication in new window or tab >>Exploring Non-obvious Hydrophobic Binding Pockets on Protein Surfaces: Increasing Affinities in Peptide–Protein Interactions
    2017 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 18, no 14, 1396-1407 p.Article in journal (Refereed) Published
    Keyword
    affinity enhancement, aminooctanoic acid, hydrophobic amino acids, peptide conjugation, peptides
    National Category
    Natural Sciences Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-326803 (URN)10.1002/cbic.201700048 (DOI)
    Available from: 2017-07-31 Created: 2017-07-31 Last updated: 2017-08-03
    2. Conjugation of a Dipicolyl Chelate to Polypeptide Conjugates Increases Binding Affinities for Human Serum Albumin and Survival Times in Human Serum
    Open this publication in new window or tab >>Conjugation of a Dipicolyl Chelate to Polypeptide Conjugates Increases Binding Affinities for Human Serum Albumin and Survival Times in Human Serum
    2017 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 18, no 14, 1408-1414 p.Article in journal (Refereed) Published
    Keyword
    affinity, biosensor, human serum albumin, peptides, zinc-binding site
    National Category
    Natural Sciences Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-326838 (URN)10.1002/cbic.201700049 (DOI)
    Available from: 2017-07-31 Created: 2017-07-31 Last updated: 2017-08-03
  • Söderlund, Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Clinical and Immunological Studies in Chronic Myeloid Leukaemia2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic myeloid leukaemia (CML) is characterised by the constitutively active tyrosine kinase BCR-ABL. Standard treatment with tyrosine kinase inhibitors (TKI) in the chronic phase (CP) of CML conveys excellent long-term prognosis but is associated with side effects and costs. Treatment free remission (TFR) is possible in a proportion of patients discontinuing treatment after obtaining deep treatment responses but it is not fully known how to select the right patients for stopping attempts. Treatment of accelerated phase (AP) and blast crisis (BC) is more complicated and the prognosis more dismal. In this thesis, we have studied factors of importance for outcome in CML patients with focus on immunological factors and clinical management.

    In a cohort of 32 newly diagnosed CP-CML patients, evidence of active immune escape mechanisms were found. These declined with the course of TKI treatment and at the same time, effector lymphocyte responses were elicited. These anti-leukaemia immune responses might help in the long-term control of CML. Multiple plasma protein markers were also measured with three multiplex platforms in a smaller cohort of patients (n=14). Inflammatory cytokines and other plasma proteins were affected by TKI treatment and multiplexing seems useful for finding potential biomarkers with biologic or prognostic significance in CML.

    Patients progressing to AP/BC were studied in a population-based material from the Swedish CML register. Approximately 4% of TKI-treated CP-CML patients transformed to AP/BC within 2 years of diagnosis. Monitoring of treatment responses was suboptimal in 1/3 of these patients and the median survival was 1.4 years after diagnosis of AP/BC. Thus, minimising the risk of disease progression through strict adherence to guidelines for monitoring and treatment is essential.

    In a cohort of patients (n=50) discontinuing TKI treatment within a large European trial, musculoskeletal pain was reported by 30% of patients, starting within 1- 6 weeks of TKI discontinuation and spontaneously resolving over time in most cases. Patients (n=56) were also evaluated with a multiplex platform with a total of 162 inflammation- and cancer-related plasma proteins. No predictive protein biomarkers for successful TKI discontinuation could be found. However, profound effects of TKI-treatment were seen and plasma proteomics could be useful for understanding effects of long-term TKI-treatment.

    List of papers
    1. Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome?
    Open this publication in new window or tab >>Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome?
    Show others...
    2014 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 25, 2821-2823 p.Article in journal (Refereed) Published
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:uu:diva-233785 (URN)10.1200/JCO.2014.55.6910 (DOI)000341562600033 ()25071107 (PubMedID)
    Available from: 2014-10-10 Created: 2014-10-10 Last updated: 2017-08-05Bibliographically approved
    2. The Tyrosine Kinase Inhibitors Imatinib and Dasatinib Reduce Myeloid Suppressor Cells and Release Effector Lymphocyte Responses
    Open this publication in new window or tab >>The Tyrosine Kinase Inhibitors Imatinib and Dasatinib Reduce Myeloid Suppressor Cells and Release Effector Lymphocyte Responses
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    2015 (English)In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 14, no 5, 1181-1191 p.Article in journal (Refereed) Published
    Abstract [en]

    Immune escape mechanisms promote tumor progression and are hurdles of cancer immunotherapy. Removing immunosuppressive cells before treatment can enhance efficacy. Tyrosine kinase inhibitors (TKI) may be of interest to combine with immunotherapy, as it has been shown that the inhibitor sunitinib reduces myeloid suppressor cells in patients with renal cell carcinoma and dasatinib promotes expansion of natural killer-like lymphocytes in chronic myeloid leukemia (CML). In this study, the capacity of dasatinib and imatinib to reduce myeloid suppressor cells and to induce immunomodulation in vivo was investigated ex vivo. Samples from CML patients treated with imatinib (n = 18) or dasatinib (n = 14) within a Nordic clinical trial (clinicalTrials.gov identifier: NCT00852566) were investigated for the presence of CD11b(+)CD14(-)CD33(+) myeloid cells and inhibitorymolecules (arginase I, myeloperoxidase, IL10) as well as the presence of natural killer cells, T cells (naive/memory), and stimulatory cytokines (IL12, IFN gamma, MIG, IP10). Both imatinib and dasatinib decreased the presence of CD11b(+)CD14(-)CD33(+) myeloid cells as well as the inhibitory molecules and the remaining myeloid suppressor cells had an increased CD40 expression. Monocytes also increased CD40 after therapy. Moreover, increased levels of CD40, IL12, natural killer cells, and experienced T cells were noted after TKI initiation. The presence of experienced T cells was correlated to a higher IFNg and MIG plasma concentration. Taken together, the results demonstrate that both imatinib and dasatinib tilted the immunosuppressive CML tumor milieu towards promoting immune stimulation. Hence, imatinib and dasatinib may be of interest to combine with cancer immunotherapy. 

    National Category
    Hematology Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-269778 (URN)10.1158/1535-7163.MCT-14-0849 (DOI)000358053000010 ()25761894 (PubMedID)
    Available from: 2015-12-18 Created: 2015-12-18 Last updated: 2017-08-05Bibliographically approved
    3. Plasma proteomics in CML patients before and after initiation of tyrosine kinase inhibitor therapy reveals induced Th1 immunity and loss of angiogenic stimuli
    Open this publication in new window or tab >>Plasma proteomics in CML patients before and after initiation of tyrosine kinase inhibitor therapy reveals induced Th1 immunity and loss of angiogenic stimuli
    Show others...
    2016 (English)In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 50, 95-103 p.Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND AND AIMS: The simultaneous measurement of many proteins is now possible using multiplex assays. In this pilot study we investigated a total of 124 proteins in plasma from chronic myeloid leukemia (CML) patients with the purpose of identifying proteins that are differently expressed at diagnosis and after tyrosine kinase inhibitor (TKI) treatment initiation.

    METHODS: Samples were taken from 14 CML patients at diagnosis and after three months of TKI treatment (imatinib or dasatinib). Samples were analyzed by Mesoscale Discovery, Myriad RBM MAP technology and Olink Proseek.

    RESULTS: Multiple plasma proteins were differentially expressed before and after initiation of TKI therapy. Protein patterns demonstrated a possible shift towards Th1-immunity and reduced angiogenic stimuli. Further, some plasma proteins were identified that can be of potential interest to study further for biologic, prognostic or therapeutic significance such as E-selectin, uPAR, growth hormone and carbonic anhydrase IX.

    CONCLUSIONS: Plasma proteomics seems feasible and useful in CML patients, both for studying patterns of protein expression and for identifying single proteins differentially expressed before and after treatment. Plasma proteomics may be useful to map disease activity and biological processes. Hence, plasma proteomics can be used to understand drug mechanisms and treatment responses in CML.

    Keyword
    Proteomics, Chronic myeloid leukemia, Tyrosine kinase inhibitor, Th1, Angiogenesis
    National Category
    Cancer and Oncology Hematology
    Identifiers
    urn:nbn:se:uu:diva-310831 (URN)10.1016/j.leukres.2016.09.019 (DOI)000388315500015 ()27710869 (PubMedID)
    Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2017-08-05Bibliographically approved
    4. Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era: a report from the Swedish CML register
    Open this publication in new window or tab >>Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era: a report from the Swedish CML register
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    2017 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 98, no 1, 57-66 p.Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment.

    METHODS: Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment.

    RESULTS: The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively.

    CONCLUSION: In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression.

    National Category
    Hematology
    Identifiers
    urn:nbn:se:uu:diva-310827 (URN)10.1111/ejh.12785 (DOI)000393166600009 ()27428357 (PubMedID)
    Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2017-08-05Bibliographically approved
    5. Proximity extension assay-based plasma proteomics cannot predict relapse in chronic myeloid leukaemia patients stopping treatment with tyrosine kinase inhibitors (TKI) but reveal profound effects of long-term TKI treatment on plasma protein profiles
    Open this publication in new window or tab >>Proximity extension assay-based plasma proteomics cannot predict relapse in chronic myeloid leukaemia patients stopping treatment with tyrosine kinase inhibitors (TKI) but reveal profound effects of long-term TKI treatment on plasma protein profiles
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Hematology
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-327172 (URN)
    Available from: 2017-08-05 Created: 2017-08-05 Last updated: 2017-08-05
  • Han, Shangfeng
    et al.
    China Univ Petr, Sch Business Adm, Beijing .
    Zhang, Baosheng
    China Univ Petr, Sch Business Adm, Beijing .
    Sun, Xiaoyang
    China Univ Petr, Sch Business Adm, Beijing .
    Han, Song
    China Univ Petr, Sch Business Adm, Beijing .
    Höök, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Natural Resources and Sustainable Development.
    China's Energy Transition in the Power and Transport Sectors from a Substitution Perspective2017In: Energies, ISSN 1996-1073, E-ISSN 1996-1073, Vol. 10, no 5, 600Article in journal (Refereed)
    Abstract [en]

    Facing heavy air pollution, China needs to transition to a clean and sustainable energy system, especially in the power and transport sectors, which contribute the highest greenhouse gas (GHG) emissions. The core of an energy transition is energy substitution and energy technology improvement. In this paper, we forecast the levelized cost of electricity (LCOE) for power generation in 2030 in China. Cost-emission effectiveness of the substitution between new energy vehicles and conventional vehicles is also calculated in this study. The results indicate that solar photovoltaic (PV) and wind power will be cost comparative in the future. New energy vehicles are more expensive than conventional vehicles due to their higher manufacturer suggested retail price (MSRP). The cost-emission effectiveness of the substitution between new energy vehicles and conventional vehicles would be $96.7/ton or $114.8/ton. Gasoline prices, taxes, and vehicle insurance will be good directions for policy implementation after the ending of subsidies.

  • Wallberg, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Schoening, Caspar
    Inst Bee Res, Hohen Neuendorf, Germany..
    Webster, Matthew Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hasselmann, Martin
    Univ Hohenheim, Stuttgart, Germany..
    Two extended haplotype blocks are associated with adaptation to high altitude habitats in East African honey bees2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 5, e1006792Article in journal (Refereed)
    Abstract [en]

    Understanding the genetic basis of adaption is a central task in biology. Populations of the honey bee Apis mellifera that inhabit the mountain forests of East Africa differ in behavior and morphology from those inhabiting the surrounding lowland savannahs, which likely reflects adaptation to these habitats. We performed whole genome sequencing on 39 samples of highland and lowland bees from two pairs of populations to determine their evolutionary affinities and identify the genetic basis of these putative adaptations. We find that in general, levels of genetic differentiation between highland and lowland populations are very low, consistent with them being a single panmictic population. However, we identify two loci on chromosomes 7 and 9, each several hundred kilobases in length, which exhibit near fixation for different haplotypes between highland and lowland populations. The highland haplotypes at these loci are extremely rare in samples from the rest of the world. Patterns of segregation of genetic variants suggest that recombination between haplotypes at each locus is suppressed, indicating that they comprise independent structural variants. The haplotype on chromosome 7 harbors nearly all octopamine receptor genes in the honey bee genome. These have a role in learning and foraging behavior in honey bees and are strong candidates for adaptation to highland habitats. Molecular analysis of a putative breakpoint indicates that it may disrupt the coding sequence of one of these genes. Divergence between the highland and lowland haplotypes at both loci is extremely high suggesting that they are ancient balanced polymorphisms that greatly predate divergence between the extant honey bee subspecies.

  • Burman, August
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History, Classical archaeology and ancient history.
    Morgantina under och efter det andra puniska kriget: Den sista fria grekisk-sicilianska stadens fall2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The ancient city of Morgantina in Sicily was an important city during the Hellenistic age and probably member of a koinon (a union) under the leadership of Syracuse. Much research has been done on the city of Morgantina, but as far as I know, no study has had the aim to show what role Morgantina played in the Second Punic War. Therefore, this essay focuses on Morgantina during and after the Second Punic War (218–201 BCE). The main questions presented in this essay are what happened to the city after the war and what was the aftermath of the war? What happened to the people in the town and why were some houses abandoned and others not? To answer these questions archaeological evidence (numismatic material and buildings) as well as ancient historians’ narrations have been used (the historians used are Diodorus Siculus, Livy, Cicero and Strabo). The study argues that Morgantina might have been the last important free Greek town in Sicily (and possibly the very last) and that the city probably did not fight actively for either side, but might have provided Rome with grain and therefore taken Rome’s side.

  • Risemark Eriksson, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Environmental stress of electrical machine winding insulation2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The conducting winding of an electrical machine is insulated in order to prevent any short circuits to occur within the machine. This insulation is during its lifetime exposed to several environmental stresses and therefore plays an important role in the life length of the machine. Accelerated stress tests are used to investigate what design and material is most suitable for a good endurance of a product. In this master thesis, new accelerated test methods for the insulation system in an electrical machine are developed and evaluated. The study resulted in four stress tests that simulate the thermal stress, the thermomechanical stress and the ambient stress from direct oil cooling.

    Three diagnosis tests and a material analysis were used in order to evaluate how these accelerated stress test methods affected the insulation. The diagnosis tests showed no clear sign of deterioration of the insulation in terms of change in electrical characteristics. However, the material analysis indicated deterioration of the insulation, such as cracks and oxidation of the material. These changes show that the test methods are capable to affect the insulation, but will need more time to cause a breakdown, since a stator of this kind is expected to have a very long life length. Therefore, in future work on this topic, these test methods should continue for a longer time and it would likely be interesting to look into other diagnosis tests.

  • Stigenius, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Signals and Systems Group.
    Map Engine with Route and Slope Prediction for Autonomous Vehicles in Offroad Applications2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    With an imminent future of fully autonomous heavy duty vehicles in offroad applications, the need for advanced control system will increase accordingly.

    By implementing a raster map with tiles and pixels, to which a vehicle can record slope and position data while driving, it is possible to map earth's surface. By adding a heat parameter to every pixel, i.e. the number of passings through it historically, it is possible in future visits of the same are to generate a route prediction made up by the "hottest" pixels. By fetching the slope values in the hottest pixels, it is possible to generate a slope horizon that can be utilized by control systems, e.g. when planning gear shifts in hilly offroad terrain.

    To mange the incrementally growing map, a memory management system was implemented. It buffers the relevant map data from the database, i.e. the vehicles closest surroundings, which is then used for route prediction and horizon generation. As the vehicle moves into other areas, new data is read from the database, and the recently passed area is written back to the database, however updated from the recent passing.

    The system is implemented so that it runs through another application in the telematics electrical controller unit (ECU) in a Scania vehicle. The ECU contains a GNSS module from which the vehicle fetches satellite positioning data. Slope data is fetched from a slope sensor mounted on the truck.

    Due to implications during testing and debugging of the resulting application developed and implemented during this thesis project, the application's performance couldn't be assessed properly. However, it is concluded that the background the application is built on is reliable, although tweaks to get the application fit for usage in offroad terrain had to be made. Mainly, the horizon length and map building techniques should not be the same as in similar applications for onroad driving.