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  • André, Tomas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Benchmarking Physical Properties of Water Models2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

        Water is a fundamental part of life as we know it, and by that also a fundamental for biology, chemistry, and parts of physics. Understanding how water behaves and interacts is key in many fields of all these three branches of science. Numerical simulation using molecular dynamics can aid in building insight in the behavior and interactions of water. In this thesis molecular dynamics is used to simulate common rigid 3 point water models to see how well they replicate certain physical and chemical properties as functions of temperature. This is done with molecular dynamics program GROMACS which offers a complete set of tools to run simulations and analyze results. Everything has been automated to work with a python script and a file of input parameters. Most of the models follow the same trends and are valid within a limited temperature range.

  • Yu, Qian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Shuai, Hongyan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ahooghalandari, Parvin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Gylfe, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Tengholm, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Glucose controls glucagon secretion by directly modulating cAMP in alpha cells2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 7, p. 1212-1224Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis

    Glucagon is critical for normal glucose homeostasis and aberrant secretion of the hormone aggravates dysregulated glucose control in diabetes. However, the mechanisms by which glucose controls glucagon secretion from pancreatic alpha cells remain elusive. The aim of this study was to investigate the role of the intracellular messenger cAMP in alpha-cell-intrinsic glucose regulation of glucagon release.

    Methods

    Subplasmalemmal cAMP and Ca2+ concentrations were recorded in isolated and islet-located alpha cells using fluorescent reporters and total internal reflection microscopy. Glucagon secretion from mouse islets was measured using ELISA.

    Results

    Glucose induced Ca2+-independent alterations of the subplasmalemmal cAMP concentration in alpha cells that correlated with changes in glucagon release. Glucose-lowering-induced stimulation of glucagon secretion thus corresponded to an elevation in cAMP that was independent of paracrine signalling from insulin or somatostatin. Imposed cAMP elevations stimulated glucagon secretion and abolished inhibition by glucose elevation, while protein kinase A inhibition mimicked glucose suppression of glucagon release.

    Conclusions/interpretation

    Glucose concentrations in the hypoglycaemic range control glucagon secretion by directly modulating the cAMP concentration in alpha cells independently of paracrine influences. These findings define a novel mechanism for glucose regulation of glucagon release that underlies recovery from hypoglycaemia and may be disturbed in diabetes.

  • Public defence: 2019-09-04 13:00 Lindahlsalen, Uppsala
    Wang, Mi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Gene regulatory evolution in flycatchers: statistical approaches for the analysis of allele-specific expression2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Understanding the molecular mechanisms underlying evolutionary changes in gene expression is a major research topic in biology. While a powerful approach to study this is the analysis of allele-specific expression (ASE), most of previously published methods can only be applied to lab organisms. In this thesis, to enable the analysis of ASE in natural organisms, I developed two methods for ASE detection. The first one was Bayesian negative binomial approach, and the second one was Read-backed Phasing-based ASE approach. Both methods performed well in simulations and comparisons. By applying those methods, I found that ASE was prevalent in natural flycatcher species. Combining the analyses of differential gene expression and ASE, I found a widespread cis-trans compensation and a critical role of tissue-specific regulatory mechanism during gene expression evolution. Moreover, for cis-regulatory sequences, there was a larger proportion of slightly deleterious mutations and weaker signatures of positive selection for genes with ASE than genes without ASE. For coding sequence, no such difference was observed. These results indicated that the evolution of gene expression and coding sequences could be uncoupled and occurred independently.

    List of papers
    1. Bayesian Inference of Allele-Specific Gene Expression Indicates Abundant Cis-Regulatory Variation in Natural Flycatcher Populations
    Open this publication in new window or tab >>Bayesian Inference of Allele-Specific Gene Expression Indicates Abundant Cis-Regulatory Variation in Natural Flycatcher Populations
    2017 (English)In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, no 5, p. 1266-1279Article in journal (Refereed) Published
    Abstract [en]

    Polymorphism in cis-regulatory sequences can lead to different levels of expression for the two alleles of a gene, providing a starting point for the evolution of gene expression. Little is known about the genome-wide abundance of genetic variation in gene regulation in natural populations but analysis of allele-specific expression (ASE) provides a means for investigating such variation. We performed RNA-seq of multiple tissues from population samples of two closely related flycatcher species and developed a Bayesian algorithm that maximizes data usage by borrowing information from the whole data set and combines several SNPs per transcript to detect ASE. Of 2,576 transcripts analyzed in collared flycatcher, ASE was detected in 185 (7.2%) and a similar frequency was seen in the pied flycatcher. Transcripts with statistically significant ASE commonly showed the major allele in > 90% of the reads, reflecting that power was highest when expression was heavily biased toward one of the alleles. This would suggest that the observed frequencies of ASE likely are underestimates. The proportion of ASE transcripts varied among tissues, being lowest in testis and highest in muscle. Individuals often showed ASE of particular transcripts in more than one tissue (73.4%), consistent with a genetic basis for regulation of gene expression. The results suggest that genetic variation in regulatory sequences commonly affects gene expression in natural populations and that it provides a seedbed for phenotypic evolution via divergence in gene expression.

    Place, publisher, year, edition, pages
    OXFORD UNIV PRESS, 2017
    Keywords
    ASE, gene expression evolution, regulatory sequences, RNA-seq
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-333414 (URN)10.1093/gbe/evx080 (DOI)000406760400013 ()28453623 (PubMedID)
    Funder
    Swedish Research Council, 2010-5650, 2013-8271EU, European Research Council, AdG 249976Knut and Alice Wallenberg Foundation
    Available from: 2017-11-15 Created: 2017-11-15 Last updated: 2019-06-11Bibliographically approved
    2. RPASE: Individual-based allele-specific expression detection without prior knowledge of haplotype phase
    Open this publication in new window or tab >>RPASE: Individual-based allele-specific expression detection without prior knowledge of haplotype phase
    2018 (English)In: Molecular Ecology Resources, ISSN 1755-098X, E-ISSN 1755-0998, Vol. 18, no 6, p. 1247-1262Article in journal (Refereed) Published
    Abstract [en]

    Variation in gene expression is believed to make a significant contribution to phenotypic diversity and divergence. The analysis of allele-specific expression (ASE) can reveal important insights into gene expression regulation. We developed a novel method called RPASE (Read-backed Phasing-based ASE detection) to test for genes that show ASE. With mapped RNA-seq data from a single individual and a list of SNPs from the same individual as the only input, RPASE is capable of aggregating information across multiple dependent SNPs and producing individual-based gene-level tests for ASE. RPASE performs well in simulations and comparisons. We applied RPASE to multiple bird species and found a potentially rich landscape of ASE.

    Keywords
    allele-specific expression, gene expression evolution, regulatory variation, RNA-seq
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-369587 (URN)10.1111/1755-0998.12909 (DOI)000449535600007 ()29858523 (PubMedID)
    Funder
    Swedish Research CouncilKnut and Alice Wallenberg Foundation
    Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2019-06-11Bibliographically approved
    3. Gene regulatory evolution in natural flycatcher populations is highly tissue-specific and shows distinctive patterns in the testis
    Open this publication in new window or tab >>Gene regulatory evolution in natural flycatcher populations is highly tissue-specific and shows distinctive patterns in the testis
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-384395 (URN)
    Available from: 2019-06-04 Created: 2019-06-04 Last updated: 2019-06-11
    4. Cis-regulatory variation and allele-specific expression in the collared flycatcher (Ficedula albicollis) genome
    Open this publication in new window or tab >>Cis-regulatory variation and allele-specific expression in the collared flycatcher (Ficedula albicollis) genome
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-384392 (URN)
    Available from: 2019-06-04 Created: 2019-06-04 Last updated: 2019-06-11
  • Törlén, Johan
    et al.
    Karolinska Univ Hosp, Cell Therapy & Allogene Stem Cell Transplantat, Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Gaballa, Ahmed
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Remberger, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Uppsala Univ Hosp, Clin Res & Dev Unit, Uppsala, Sweden.
    Mörk, Lisa-Mari
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Sundberg, Berit
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Mattsson, Jonas
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden;Karolinska Univ Hosp, Dept Immunol & Transfus Med, Stockholm, Sweden.
    Uhlin, Michael
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden;Karolinska Univ Hosp, Dept Immunol & Transfus Med, Stockholm, Sweden;Royal Inst Technol, Dept Appl Phys, Stockholm, Sweden.
    Effect of Graft-versus-Host Disease Prophylaxis Regimens on T and B Cell Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation2019In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 25, no 6, p. 1260-1268Article in journal (Refereed)
    Abstract [en]

    Lymphocyte reconstitution is pivotal for successful long-term outcome after allogeneic hematopoietic stem cell transplantation (HSCT), and conditioning regimen and post-transplantation immunosuppression are risk factors for prolonged immunodeficiency. Nevertheless, the effects of different immunosuppressive protocols on lymphocyte output and replicative capacity have not been investigated. Here we assessed T cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and T cell telomere length (TL) as proxy markers for immune reconstitution in patients in a prospective randomized trial comparing graft-versus-host disease (GVHD) prophylaxis after transplantation (cyclosporine/methotrexate versus tacrolimus/sirolimus; n=200). Results showed that medians of TREC, KREC, and TL were not significantly different between the prophylaxis groups at any assessment time point during follow-up (24 months), but the kinetics of TREC, KREC, and TL were significantly influenced by other transplantation-related factors. Older recipient age, the use of antithymocyte globulin before graft infusion, and use of peripheral blood stem cell grafts were associated with lower TREC levels, whereas acute GVHD transiently affected KREC levels. Patients with lymphocyte excision circle levels above the median at <= 6 months post-transplantation had reduced transplantation-related mortality and superior 5-year overall survival (P<.05). We noticed significant T cell telomere shortening in the patient population as a whole during follow-up. Our results suggest that lymphocyte reconstitution after transplantation is not altered by different immunosuppressive protocols. This study has been registered at ClinicalTrials.gov (identifier: NCT00993343). (C) 2019 American Society for Blood and Marrow Transplantation.

  • Hochman, Assaf
    et al.
    Tel Aviv Univ, Porter Sch Environm & Earth Sci, Dept Geophys, IL-69978 Tel Aviv, Israel;Tel Aviv Univ, Porter Sch Environm & Earth Sci, Dept Geog & Human Environm, IL-69978 Tel Aviv, Israel;Tel Aviv Univ, Porter Sch Environm & Earth Sci, Porter Sch Environm Studies, IL-69978 Tel Aviv, Israel.
    Alpert, Pinhas
    Tel Aviv Univ, Porter Sch Environm & Earth Sci, Dept Geophys, IL-69978 Tel Aviv, Israel.
    Harpaz, Tzvi
    Tel Aviv Univ, Porter Sch Environm & Earth Sci, Dept Geophys, IL-69978 Tel Aviv, Israel;Tel Aviv Univ, Porter Sch Environm & Earth Sci, Dept Geog & Human Environm, IL-69978 Tel Aviv, Israel.
    Saaroni, Hadas
    Tel Aviv Univ, Porter Sch Environm & Earth Sci, Dept Geophys, IL-69978 Tel Aviv, Israel;Tel Aviv Univ, Porter Sch Environm & Earth Sci, Porter Sch Environm Studies, IL-69978 Tel Aviv, Israel.
    Messori, Gabriele
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL. Stockholm Univ, Dept Meteorol, Stockholm, Sweden;Stockholm Univ, Bolin Ctr Climate Res, Stockholm, Sweden.
    A new dynamical systems perspective on atmospheric predictability: Eastern Mediterranean weather regimes as a case study2019In: Science Advances, E-ISSN 2375-2548, Vol. 5, no 6, article id eaau0936Article in journal (Refereed)
    Abstract [en]

    The atmosphere is a chaotic system displaying recurrent large-scale configurations. Recent developments in dynamical systems theory allow us to describe these configurations in terms of the local dimension-a proxy for the active number of degrees of freedom-and persistence in phase space, which can be interpreted as persistence in time. These properties provide information on the intrinsic predictability of an atmospheric state. Here, this technique is applied to atmospheric configurations in the eastern Mediterranean, grouped into synoptic classifications (SCs). It is shown that local dimension and persistence, derived from reanalysis and CMIP5 models' daily sea-level pressure fields, can serve as an extremely informative qualitative method for evaluating the predictability of the different SCs. These metrics, combined with the SC transitional probability approach, may be a valuable complement to operational weather forecasts and effective tools for climate model evaluation. This new perspective can be extended to other geographical regions.

  • Peolsson, Anneli
    et al.
    Linkoping Univ, Dept Med & Hlth Sci, Physiotherapy, Linkoping, Sweden.
    Peterson, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Linkoping Univ, Dept Med & Hlth Sci, Physiotherapy, Linkoping, Sweden.
    Hermansen, Anna
    Linkoping Univ, Dept Med & Hlth Sci, Physiotherapy, Linkoping, Sweden.
    Ludvigsson, Maria Landen
    Linkoping Univ, Dept Med & Hlth Sci, Physiotherapy, Linkoping, Sweden;Reg Council Ostergotland, Rehab Vast, Dept Rehabil, Linkoping, Sweden;Reg Council Ostergotland, Rehab Vast, Dept Med & Hlth Sci, Linkoping, Sweden.
    Dedering, Åsa
    Univ Hosp, Allied Hlth Profess Funct Occupat Therapy & Physi, Stockholm, Sweden;Karolinska Inst, Div Physiotherapy, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
    Löfgren, Hakan
    Ryhov Hosp, Neuroorthoped Ctr, Jonkoping, Sweden.
    Physiotherapy after anterior cervical spine surgery for cervical disc disease: study protocol of a prospective randomised study to compare internet-based neck-specific exercise with prescribed physical activity2019In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 2, article id e027387Article in journal (Refereed)
    Abstract [en]

    Introduction Patients suffering from remaining disability after anterior cervical decompression and fusion (ACDF) surgery for cervical disc disease may be prescribed physical activity (PPA) or neck-specific exercises (NSEs). Currently, we lack data for the success of either approach. There is also a knowledge gap concerning the use of internet-based care for cervical disc disease. The scarcity of these data, and the high proportion of patients with various degrees of incapacity following ACDF, warrant increased efforts to investigate and improve cost-effective rehabilitation. The objective is to compare the effectiveness of a structured, internet-based NSE programme, versus PPA following ACDF surgery. Methods and analysis This is a prospective, randomised, multicentre study that includes 140 patients with remaining disability (>= 30% on the Neck Disability Index, NDI) following ACDF for radiculopathy due to cervical disc disease. Patient recruitment occurs following attendance at routine clinical appointments, scheduled at 3 months postsurgery. Patients are then randomised to one of two groups (70 patients/group) for a 3-month treatment programme/period of either internet-based NSE or PPA. Questionnaires on background data, pain and discomfort, physical and mental capacity, satisfaction with care, and health and workplace factors are completed, along with physical measures of neck-related function conducted by independent test leaders blinded to randomisation. Measures are collected at inclusion, after the 3-month treatments (end of treatment) and at a 2-year follow-up. Radiography will be completed at the 2-year follow-up. Preoperative data will be collected from the Swedish Spine Registry. Data on healthcare consumption, drug use and sick leave will be requested from the relevant national registers. Ethical considerations This study was approved by the Regional Ethical Review Board in Linkoping Ref. 2016/283-31 and 2017/91-32. The scientists are independent with no commercial ties. Patients are recruited after providing written informed consent. Patient data are presented at group level such that no connection to any individual can be made. All data are anonymised when reported, and subject to the Swedish Official Secrets Health Acts. The test leaders are independent and blinded for randomisation. Exercises, both general and neck-specific, have been used extensively in clinical practice and we anticipate no harm from their implementation other than a risk of muscle soreness. Both randomisation groups will receive care that is expected to relieve pain, although the group receiving NSE is expected to demonstrate a greater and more cost-effective improvement versu s the PPA group. Any significant harm or unintended effects in each group will be collected by the test leaders. All questionnaires and test materials are coded by the research group, with code lists stored in locked, fireproof file cabinets, housed at the university in a room with controlled (card-based) access. Only individuals in receipt of a unique website address posted by the researchers can access the programme; patients can neither communicate with each other nor with caregivers via the programme. Study participation might lead to improved rehabilitation versus non-participation, and might therefore be of benefit. The results of this study should also contribute to more effective and flexible rehabilitation, shorter waiting times, lower costs and the possibility to implement our findings on a wider level. Dissemination If effective, the protocols used in this study can be implemented in existing healthcare structures. The results of the study will be presented in scientific journals and popular science magazines of relevance to health. The findings will also be presented at local, regional, national and international conferences and meetings, as well as in the education of university students and at public lectures. Information about the results will be communicated to the general population in cooperation with patient organisations and the media.

  • Prost, Stefan
    et al.
    Swedish Museum Nat Hist, Dept Biodivers & Genet, Frescativaegen 40, S-10401 Stockholm, Sweden;Univ Calif Berkeley, Dept Integrat Biol, 3040 Valley Life Sci Bldg, Berkeley, CA 94720 USA.
    Armstrong, Ellie E.
    Stanford Univ, Dept Biol, 371 Serra Mall, Stanford, CA 94305 USA.
    Nylander, Johan
    Swedish Museum Nat Hist, Dept Biodivers & Genet, Frescativaegen 40, S-10401 Stockholm, Sweden.
    Thomas, Gregg W. C.
    Indiana Univ, Dept Biol, 1001 E Third St, Bloomington, IN 47405 USA;Indiana Univ, Sch Informat Comp & Engn, 1001 E Third St, Bloomington, IN 47405 USA.
    Suh, Alexander
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Petersen, Bent
    Univ Copenhagen, Nat Hist Museum Denmark, Oster Voldgade 5-7, DK-1353 Copenhagen, Denmark;Asian Inst Med Sci & Technol, Fac Appl Sci, Ctr Excellence Omics Driven Computat Biodiscovery, Jalan Bedong Semeling, Bedong 08100, Kedah, Malaysia.
    Dalen, Love
    Swedish Museum Nat Hist, Dept Biodivers & Genet, Frescativaegen 40, S-10401 Stockholm, Sweden.
    Benz, Brett W.
    Amer Museum Nat Hist, Dept Ornithol, Cent Pk West, New York, NY 10024 USA.
    Blom, Mozes P. K.
    Swedish Museum Nat Hist, Dept Biodivers & Genet, Frescativaegen 40, S-10401 Stockholm, Sweden.
    Palkopoulou, Eleftheria
    Swedish Museum Nat Hist, Dept Biodivers & Genet, Frescativaegen 40, S-10401 Stockholm, Sweden.
    Ericson, Per G. P.
    Swedish Museum Nat Hist, Dept Biodivers & Genet, Frescativaegen 40, S-10401 Stockholm, Sweden.
    Irestedt, Martin
    Swedish Museum Nat Hist, Dept Biodivers & Genet, Frescativaegen 40, S-10401 Stockholm, Sweden.
    Comparative analyses identify genomic features potentially involved in the evolution of birds-of-paradise2019In: GigaScience, ISSN 2047-217X, E-ISSN 2047-217X, Vol. 8, no 5, article id giz003Article in journal (Refereed)
    Abstract [en]

    The diverse array of phenotypes and courtship displays exhibited by birds-of-paradise have long fascinated scientists and nonscientists alike. Remarkably, almost nothing is known about the genomics of this iconic radiation. There are 41 species in 16 genera currently recognized within the birds-of-paradise family (Paradisaeidae), most of which are endemic to the island of New Guinea. In this study, we sequenced genomes of representatives from all five major clades within this family to characterize genomic changes that may have played a role in the evolution of the group's extensive phenotypic diversity. We found genes important for coloration, morphology, and feather and eye development to be under positive selection. In birds-of-paradise with complex lekking systems and strong sexual dimorphism, the core birds-of-paradise, we found Gene Ontology categories for "startle response" and "olfactory receptor activity" to be enriched among the gene families expanding significantly faster compared to the other birds in our study. Furthermore, we found novel families of retrovirus-like retrotransposons active in all three de novo genomes since the early diversification of the birds-of-paradise group, which might have played a role in the evolution of this fascinating group of birds.

  • Wright, Alison E.
    et al.
    Univ Sheffield, Dept Anim & Plant Sci, Sheffield, S Yorkshire, England.
    Rogers, Thea F.
    Univ Sheffield, Dept Anim & Plant Sci, Sheffield, S Yorkshire, England.
    Fumagalli, Matteo
    Imperial Coll London, Dept Life Sci, London, England.
    Cooney, Christopher R.
    Univ Sheffield, Dept Anim & Plant Sci, Sheffield, S Yorkshire, England.
    Mank, Judith E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. UCL, Dept Genet Evolut & Environm, London, England; Univ British Columbia, Dept Zool, Vancouver, BC, Canada.
    Phenotypic sexual dimorphism is associated with genomic signatures of resolved sexual conflict2019In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 28, no 11, p. 2860-2871Article in journal (Refereed)
    Abstract [en]

    Intralocus sexual conflict, where an allele benefits one sex at the expense of the other, has an important role in shaping genetic diversity of populations through balancing selection. However, the potential for mating systems to exert balancing selection through sexual conflict on the genome remains unclear. Furthermore, the nature and potential for resolution of sexual conflict across the genome has been hotly debated. To address this, we analysed de novo transcriptomes from six avian species, chosen to reflect the full range of sexual dimorphism and mating systems. Our analyses combine expression and population genomic statistics across reproductive and somatic tissue, with measures of sperm competition and promiscuity. Our results reveal that balancing selection is weakest in the gonad, consistent with the resolution of sexual conflict and evolutionary theory that phenotypic sex differences are associated with lower levels of ongoing conflict. We also demonstrate a clear link between variation in sexual conflict and levels of genetic variation across phylogenetic space in a comparative framework. Our observations suggest that this conflict is short-lived, and is resolved via the decoupling of male and female gene expression patterns, with important implications for the role of sexual selection in adaptive potential and role of dimorphism in facilitating sex-specific fitness optima.

  • Orellana, Cecilia
    et al.
    Karolinska Inst, Inst Environm Med, Unit Occupat Med, Stockholm, Sweden.
    Kreshpaj, Bertina
    Karolinska Inst, Inst Environm Med, Unit Occupat Med, Stockholm, Sweden.
    Johansson, Gun
    Karolinska Inst, Inst Environm Med, Unit Occupat Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden.
    Burström, Bo
    Karolinska Inst, Equ & Hlth Policy Res Grp, Dept Publ Hlth Sci, Stockholm, Sweden.
    Kjellberg, Katarina
    Karolinska Inst, Inst Environm Med, Unit Occupat Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden.
    Hemmingsson, Tomas
    Karolinska Inst, Inst Environm Med, Unit Occupat Med, Stockholm, Sweden;Stockholm Univ, Dept Publ Hlth Sci, Stockholm, Sweden.
    Axen, Magnus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Business Studies.
    Davis, Letitia
    Massachusetts Dept Publ Hlth, Occupat Hlth Surveillance Program, Boston, MA USA.
    Wegman, David
    Univ Massachusetts, Lowell, MA USA.
    Bodin, Theo
    Karolinska Inst, Inst Environm Med, Unit Occupat Med, Stockholm, Sweden;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden.
    Precarious employment, business performance and occupational injuries: a study protocol of a register-based Swedish project2019In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 2, article id e026091Article in journal (Refereed)
    Abstract [en]

    Introduction There is uncertainty regarding the trends in occupational injuries (OIs) in Sweden due to a significant and increasing problem with under-reporting to injury registers. Under-reporting, in general, is likely to be exacerbated by the rise in precarious employment (PE), a set of unfavourable employment characteristics that would benefit from formal definition and study. PE and global trends are believed also to affect companies and their commitment to health and safety. The present study attempts to bridge these knowledge gaps and presents a study protocol for planned studies, with three main objectives: first, to review the literature for definitions of PE emphasising those that are multidimensional and operationalise components in routinely collected register data; second, to estimate the under-reporting of OI in Swedish registers and third, using results from the first objective, to conduct large, register-based prospective studies, designed to measure effect sizes and interactions between PE, business performance and OI. Methods and analysis First, a scientific literature review will be conducted, including scientific databases and grey literature. Second, data from two major OI registers will be used to estimate the magnitude of under-reporting using capture-recapture methodology. Finally, all residents aged 18-65 in Sweden with any registered income during 2003-2015 will be included. Data sources encompass Swedish population and labour market registers with linkage to both the main OI register with national coverage and hospital records. Trends in PE and OI will be explored, together with risk of OI associated with PE and business performance. Ethics and dissemination The project has been approved by the Regional Ethics Committee, Stockholm (dnr: 2016/2325-31; 2017/2173-32). Dissemination of study results will include a series of peer-reviewed papers, at least one PhD thesis and one report in Swedish, engaging relevant stakeholders. Results will be presented in national and international conferences and through press releases to mass media.

  • Launonen, Antti P.
    et al.
    Tampere Univ Hosp, Tampere, Finland.
    Fjalestad, Tore
    Oslo Univ Hosp, Oslo, Norway.
    Laitinen, Minna K.
    Tampere Univ Hosp, Tampere, Finland.
    Lahdeoja, Tuomas
    Helsinki Univ Hosp, Helsinki, Finland.
    Ekholm, Carl
    Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Wagle, Tone
    Oslo Univ Hosp, Oslo, Norway.
    Mattila, Ville M.
    Tampere Univ Hosp, Tampere, Finland.
    Sumrein, Bakir O.
    Tampere Univ Hosp, Tampere, Finland.
    Paloneva, Juha
    Jyvaskyla Cent Hosp, Jyvaskyla, Finland.
    Lehtimaki, Kaisa
    Turku Univ Hosp, Turku, Finland.
    Thillemann, Theis
    Aarhus Univ Hosp, Aarhus, Denmark.
    Berg, Hans
    Karolinska Univ Hosp, Stockholm, Sweden.
    Wolf, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nordic Innovative Trials to Evaluate osteoPorotic Fractures (NITEP) Collaboration: The Nordic DeltaCon Trial protocol-non-operative treatment versus reversed total shoulder arthroplasty in patients 65 years of age and older with a displaced proximal humerus fracture: a prospective, randomised controlled trial2019In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 1, article id e024916Article in journal (Refereed)
    Abstract [en]

    Introduction The proximal humerus fracture (PHF) is one of the most common fractures in the elderly. The majority of PHFs are treated non-operatively, while 15%-33% of patients undergo surgical treatment. Recent randomised controlled trial (RCT) and meta-analyses have shown that there is no difference in outcome between non-operative treatment and locking plate or hemi-arthroplasty. During the past decade, reverse total shoulder arthroplasty (RTSA) has gained popularity in the treatment of PHF, although there is a lack of RCTs comparing RTSA to non-operative treatment. Methods This is a prospective, single-blinded, randomised, controlled, multicentre and multinational trial comparing RTSA with non-operative treatment in displaced proximal humeral fractures in patients 65-85 years. The primary outcome in this study is QuickDASH-score measured at 2 years. Secondary outcomes include visual analogue scale for pain, grip strength, Oxford shoulder score, Constant score and the number of reoperations and complications. The hypothesis of the trial is that operative treatment with RTSA produces better outcome after 2 and 5 years measured with QuickDASH. Ethics and dissemination In this protocol, we describe the design, method and management of the Nordic DeltaCon trial. The ethical approval for the trial has been given by the Regional Committee for Medical and Health Research Ethics, Norway. There have been several examples in orthopaedics of innovations that result in failure after medium-term follow-ups. In order to prevent such failures and to increase our knowledge of RSTA, we feel a large-scale study of the effects of the surgery on the outcome that focuses on the complications and reoperations is warranted. After the trial 2-year follow-up, the results will be disseminated in a major orthopaedic publication.

  • Shen, Qiujin
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Polom, Karol
    Univ Siena, Dept Gen Surg & Surg Oncol, Siena, Italy;Gdansk Med Univ, Dept Surg Oncol, Gdansk, Poland.
    Williams, Coralie
    Ariana Pharmaceut, Paris, France.
    de Oliveira, Felipe Marques Souza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Guergova-Kuras, Mariana
    Ariana Pharmaceut, Paris, France.
    Lisacek, Frederique
    Swiss Inst Bioinformat, Proteome Informat Grp, Geneva, Switzerland;Univ Geneva, Comp Sci Dept, Geneva, Switzerland;Univ Geneva, Sect Biol, Geneva, Switzerland.
    Karlsson, Niclas G.
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden.
    Roviello, Franco
    Univ Siena, Dept Gen Surg & Surg Oncol, Siena, Italy.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A targeted proteomics approach reveals a serum protein signature as diagnostic biomarker for resectable gastric cancer2019In: EBioMedicine, E-ISSN 2352-3964, Vol. 44, p. 322-333Article in journal (Refereed)
    Abstract [en]

    Background: Gastric cancer (GC) is the third leading cause of cancer death. Early detection is a key factor to reduce its mortality. Methods: We retrospectively collected pre- and postoperative serum samples as well as tumour tissues and adjacent normal tissues from 100 GC patients. Serum samples from non-cancerous patients were served as controls (n = 50). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure levels of over 300 proteins. Alteration of each protein was analysed by univariate analysis. Elastic-net logistic regression was performed to select serum proteins into the diagnostic model. Findings: We identified 19 serum proteins (CEACAM5, CA9, MSLN, CCL20, SCF, TGF-alpha, MMP-1, MMP-10, IGF-1, CDCPI, PPIA, DDAH-1, HMOX-1, FLI1, IL-7, ZBTB-17, APBB1IP, KAZALD-1, and ADAMTS-15) that together distinguish GC cases from controls with a diagnostic sensitivity of 93%, specificity of 100%, and area under receiver operating characteristic curve (AUC) of 0.99 (95% CI: 0.98-1). Moreover, the 19-serum protein signature pro-vided an increased diagnostic capacity in patients at TNMI-II stage (sensitivity 89%, specificity 100%, AUC 0.99) and in patients with high miaosatellite instability (MSI) (91%. 98%, and 0.99) compared to individual proteins. These promising results will inspire a large-scale independent cohort study to be pursued for validating the proposed protein signature. Interpretation: Based on targeted proteomics and elastic-net logistic regression, we identified a 19-serum protein signature which could contribute to clinical GC diagnosis, especially for patients at early stage and those with high MSI. (C) 2019 The Authors. Published by Elsevier B.V.

  • Wågberg, Felix
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Industrial Engineering & Management.
    Deliberate and Emergent Strategies for Digital Twin Utilization: A PLM-Principal’s Perspective2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The industry has during the past decades been changing towardsdigitalization at a rapid pace, adapting new frameworks and digitalsolutions, with the thrive to improve efficiency, and output quality.This thesis covers how a hyped industry concept, digital twin, incontext of smart manufacturing, could be applied in this changingclimate. Focus is put on what strategies a Product LifecycleManagement (PLM) principal could adapt when approaching theutilization of digital twins, in a customer setting. The research project, using a qualitative exploration format,incorporated a thorough review of journal articles and standards,interconnected with conducted interviews with industry experts, inorder to develop two strategies on how to approach the conceptof digital twins. The two-part strategies were formed on the basis of Mintzberg(1978) emergent and deliberate strategies. The former, consisted ofIDEF0 function modeling diagramming, where a digital twin businessprocess was portrayed, based on the literature review and interviewdata. The latter, approached the digital twin application challenge ina theoretical manner, based on the concept’s high risk anduncertainty, incorporating organizational structure theory andinnovation theory. The two strategies showed two different pathsto approach the digital twin phenomena and how to, boththeoretically and practically, adapt digital twins in a customer setting.

  • Cicek, Diana
    et al.
    Edin, Max
    Larsson, Alfred
    Petrovic, Alex
    Åberg, Anna
    An Investigation of Aspects Affecting Availability and Grading of High-risk Antibiotics in Sweden: Group 12019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This thesis examined 39 antibiotics that, according to Folkhälsomyndigheten, were most likely to be affected by availability problems on the Swedish market. The aim was to investigate possible factors affecting the availability of the antibiotics, to grade the antibiotics based on these factors and, if possible, identify some pattern or general trend. A grading system for assessing the risk of availability problems for each antibiotic was created based on a number of factors, such as number of market authorization holders, number of active pharmaceuticalingredient manufacturers and risk of natural disasters in the countries where the antibiotic is produced. Each antibiotic got a final value based on all the factors, which was then compiled in a final table. The results were evaluated and discussed, both in general and for the specific antibiotics. In the discussion, relevant information that was not included in the grading system,such as isolated incidents at manufacturing sites, was taken into account. The information was successfully gathered and used to grade the antibiotics, but no pattern or general trends were identified.

  • Laustsen, Christoffer
    et al.
    Aarhus Univ, MR Res Ctr, Dept Clin Med, Aarhus, Denmark.
    Lipso, Kasper
    Univ Copenhagen, Danish Res Ctr Magnet Resonance, Hosp Hvidovre, Hvidovre, Denmark;Tech Univ Denmark, Dept Elect Engn, Lyngby, Denmark.
    Ostergaard, Jakob Appel
    Aarhus Univ Hosp, Dept Endocrinol & Internal Med, Aarhus, Denmark.
    Nielsen, Per Mose
    Aarhus Univ, MR Res Ctr, Dept Clin Med, Aarhus, Denmark.
    Bertelsen, Lotte Bonde
    Aarhus Univ, MR Res Ctr, Dept Clin Med, Aarhus, Denmark.
    Flyvbjerg, Allan
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Univ Copenhagen, Copenhagen, Denmark.
    Pedersen, Michael
    Aarhus Univ, MR Res Ctr, Dept Clin Med, Aarhus, Denmark.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ardenkjaer-Larsen, Jan Henrik
    Univ Copenhagen, Danish Res Ctr Magnet Resonance, Hosp Hvidovre, Hvidovre, Denmark;Tech Univ Denmark, Dept Elect Engn, Lyngby, Denmark;GE Healthcare, Copenhagen, Denmark.
    High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes2019In: TOMOGRAPHY, ISSN 2379-1381, Vol. 5, no 2, p. 239-247Article in journal (Refereed)
    Abstract [en]

    Intrarenal hypoxia develops within a few days after the onset of insulinopenic diabetes in an experimental animal model (ie, a model of type-1 diabetes). Although diabetes-induced hypoxia results in increased renal lactate formation, mitochondrial function is well maintained, a condition commonly referred to as pseudohypoxia. However, the metabolic effects of significantly elevated lactate levels remain unclear. We therefore investigated in diabetic animals the response to acute intrarenal hypoxia in the presence of high renal lactate formation to delineate mechanistic pathways and compare these findings to healthy control animals. Hyperpolarized C-13-MRI and blood oxygenation level-dependent 1H-MRI was used to investigate the renal metabolism of [1-C-13] pyruvate and oxygenation following acutely altered oxygen content in the breathing gas in a streptozotocin rat model of type-1 diabetes with and without insulin treatment and compared with healthy control rats. The lactate signal in the diabetic kidney was reduced by 12%-16% during hypoxia in diabetic rats irrespective of insulin supplementation. In contrast, healthy controls displayed the well-known Pasteur effect manifested as a 10% increased lactate signal following reduction of oxygen in the inspired air. Reduced expression of the monocarboxyl transporter-4 may account for altered response to hypoxia in diabetes with a high intrarenal pyruvate-to-lactate conversion. Reduced intrarenal lactate formation in response to hypoxia in diabetes shows the existence of a different metabolic phenotype, which is independent of insulin, as insulin supplementation was unable to affect the pyruvate-to-lactate conversion in the diabetic kidney.

  • Asresu, Yohannes
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media.
    Defining fake news for algorithmic deception detection purposes2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • Capone, Isaac
    et al.
    Univ Oxford, Dept Mat, Parks Rd, Oxford OX1 3PH, England.
    Hurlbutt, Kevin
    Univ Oxford, Dept Mat, Parks Rd, Oxford OX1 3PH, England.
    Naylor, Andrew J.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Xiao, Albert W.
    Univ Oxford, Dept Mat, Parks Rd, Oxford OX1 3PH, England.
    Pasta, Mauro
    Univ Oxford, Dept Mat, Parks Rd, Oxford OX1 3PH, England.
    Effect of the Particle-Size Distribution on the Electrochemical Performance of a Red Phosphorus-Carbon Composite Anode for Sodium-Ion Batteries2019In: Energy & Fuels, ISSN 0887-0624, E-ISSN 1520-5029, Vol. 33, no 5, p. 4651-4658Article in journal (Refereed)
    Abstract [en]

    Red phosphorus (RP) is a promising candidate as an anode for sodium-ion batteries because of its low potential and high specific capacity. It has two main disadvantages. First, it experiences 490% volumetric expansion during sodiation, which leads to particle pulverization and substantial reduction of the cycle life. Second, it has an extremely low electronic conductivity of 10(-14) S cm(-1). Both issues can be addressed by ball milling RP with a carbon matrix to form a composite of electronically conductive carbon and small RP particles, less susceptible to pulverization. Through this procedure, however, the resulting particle-size distribution of the RP particles is difficult to determine because of the presence of the carbon particles. Here, we quantify the relationship between the RP particle-size distribution and its cycle life for the first time by separating the ball-milling process into two steps. The RP is first wet-milled to reduce the particle size, and then the particle-size distribution is measured via dynamic light scattering. This is followed by a dry-milling step to produce RP-graphite composites. We found that wet milling breaks apart the largest RP particles in the range of 2-10 mu m, decreases the Dv90 from 1.85 to 1.26 mu m, and significantly increases the cycle life of the RP. Photoelectron spectroscopy and transmission electron microscopy confirm the successful formation of a carbon coating, with longer milling times leading to more uniform carbon coatings. The RP with a Dv90 of 0.79 mu m mixed with graphite for 48 h delivered 1354 mA h g(-1) with high coulombic efficiency (>99%) and cyclability (88% capacity retention after 100 cycles). These results are an important step in the development of cyclable, high-capacity anodes for sodium-ion batteries.

  • Motiani, P.
    et al.
    Univ Turku, Turku PET Ctr, POB 52, FIN-20521 Turku, Finland.
    Teuho, J.
    Univ Turku, Turku PET Ctr, POB 52, FIN-20521 Turku, Finland;Turku Univ Hosp, Dept Med Phys, Turku, Finland.
    Saari, T.
    Univ Turku, Turku PET Ctr, POB 52, FIN-20521 Turku, Finland.
    Virtanen, K. A.
    Univ Turku, Turku PET Ctr, POB 52, FIN-20521 Turku, Finland;Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Honkala, S. M.
    Univ Turku, Turku PET Ctr, POB 52, FIN-20521 Turku, Finland.
    Middelbeek, R. J.
    Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA;Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
    Goodyear, L. J.
    Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA.
    Eskola, O.
    Univ Turku, Turku PET Ctr, POB 52, FIN-20521 Turku, Finland.
    Andersson, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Löyttyniemi, E.
    Univ Turku, Dept Biostat, Turku, Finland.
    Hannukainen, J. C.
    Univ Turku, Turku PET Ctr, POB 52, FIN-20521 Turku, Finland.
    Nuutila, P.
    Univ Turku, Turku PET Ctr, POB 52, FIN-20521 Turku, Finland;Turku Univ Hosp, Turku PET Ctr, Dept Endocrinol, Turku, Finland.
    Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity2019In: OASE : tijdschrift voor architectuur, ISSN 2451-8476, E-ISSN 2055-2238, Vol. 5, no 3, p. 258-272Article in journal (Refereed)
    Abstract [en]

    Introduction New strategies for weight loss and weight maintenance in humans are needed. Human brown adipose tissue (BAT) can stimulate energy expenditure and may be a potential therapeutic target for obesity and type 2 diabetes. However, whether exercise training is an efficient stimulus to activate and recruit BAT remains to be explored. This study aimed to evaluate whether regular exercise training affects cold-stimulated BAT metabolism and, if so, whether this was associated with changes in plasma metabolites. Methods Healthy sedentary men (n = 11; aged 31 [SD 7] years; body mass index 23 [0.9] kg m(-2); VO2 max 39 [7.6] mL min(-1) kg(-1)) participated in a 6-week exercise training intervention. Fasting BAT and neck muscle glucose uptake (GU) were measured using quantitative [F-18]fluorodeoxyglucose positron emission tomography-magnetic resonance imaging three times: (1) before training at room temperature and (2) before and (3) after the training period during cold stimulation. Cervico-thoracic BAT mass was measured using MRI signal fat fraction maps. Plasma metabolites were analysed using nuclear magnetic resonance spectroscopy. Results Cold exposure increased supraclavicular BAT GU by threefold (p < 0.001), energy expenditure by 59% (p < 0.001) and plasma fatty acids (p < 0.01). Exercise training had no effect on cold-induced GU in BAT or neck muscles. Training increased aerobic capacity (p = 0.01) and decreased visceral fat (p = 0.02) and cervico-thoracic BAT mass (p = 0.003). Additionally, training decreased very low-density lipoprotein particle size (p = 0.04), triglycerides within chylomicrons (p = 0.04) and small high-density lipoprotein (p = 0.04). Conclusions Although exercise training plays an important role for metabolic health, its beneficial effects on whole body metabolism through physiological adaptations seem to be independent of BAT activation in young, sedentary men.

  • Jarnulf, Therese
    et al.
    Univ Gavle, Fac Hlth & Occupat Studies, Kungsbacksvagen 47, S-80176 Gavle, Sweden.
    Skytt, Bernice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Gavle, Fac Hlth & Occupat Studies, Kungsbacksvagen 47, S-80176 Gavle, Sweden.
    Mårtensson, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Gavle, Fac Hlth & Occupat Studies, Kungsbacksvagen 47, S-80176 Gavle, Sweden.
    Engström, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Gavle, Fac Hlth & Occupat Studies, Kungsbacksvagen 47, S-80176 Gavle, Sweden;Lishui Univ, Med & Hlth Coll, Nursing Dept, 1 Xueyuan Rd, Lishui 323000, Zhejiang, Peoples R China.
    District nurses experiences of precepting district nurse students at the postgraduate level2019In: Nurse Education in Practice, ISSN 1471-5953, E-ISSN 1873-5223, Vol. 37, p. 75-80Article in journal (Refereed)
    Abstract [en]

    District nurses are preceptors of district nurse students at the postgraduate level. These district nurse students are already registered nurses who have graduated and are now studying to become district nurses; this training is at the postgraduate level. As preceptors at the postgraduate level, district nurses play an important role in helping these students to achieve the learning outcomes of the clinical practice part of their education. However, there is a lack of studies on precepting at this level. Thus, the aim was to describe district nurses' experiences of precepting district nurse students at the postgraduate level. The study was descriptive in design and used a qualitative approach. Purposive sampling was used and nine district nurses from seven primary health care units in Sweden were interviewed. Data were analysed using qualitative content analysis. An overall theme "Fluctuating between transferring knowledge and striving for reflective learning" and two subthemes emerged. The preceptors' views on precepting and performance varied depending on the situation. The conclusions is that given the current learning outcomes for clinical practice education at the postgraduate level, district nurses need to be more influenced by preception focused on reflective learning.

  • Lingaiah, Shilpa
    et al.
    Univ Oulu, Med Res Ctr, PEDEGO Res Unit, Dept Obstet & Gynaecol, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland.
    Morin-Papunen, Laure
    Univ Oulu, Med Res Ctr, PEDEGO Res Unit, Dept Obstet & Gynaecol, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland.
    Piltonen, Terhi
    Univ Oulu, Med Res Ctr, PEDEGO Res Unit, Dept Obstet & Gynaecol, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Stener-Victorin, Elisabet
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Tapanainen, Juha S.
    Univ Oulu, Med Res Ctr, PEDEGO Res Unit, Dept Obstet & Gynaecol, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland;Univ Helsinki, Dept Obstet & Gynaecol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Serum retinol-binding protein 4 levels in polycystic ovary syndrome2019In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 8, no 6, p. 709-717Article in journal (Refereed)
    Abstract [en]

    Objective: Serum levels of retinol-binding protein 4 (RBP4), an adipokine thought to affect systemic insulin sensitivity, were compared between women with polycystic ovary syndrome (PCOS) and non-PCOS controls to evaluate the association of RBP4 with clinical, hormonal and metabolic parameters of PCOS. Subjects and methods: Serum RBP4 levels were analysed in 278 women with PCOS (age range 18-57 years) and 191 non-PCOS controls (age 20-53 years) by enzyme-linked immunosorbent assay. Results: Serum levels of RBP4 were increased in women with PCOS compared with control women in the whole population (45.1 +/- 24.0 (S.D.) vs 33.5 +/- 18.3 mg/L, P < 0.001). Age-stratified analysis showed that serum RBP4 levels were increased in women with PCOS aged <= 30 years compared with controls (47.7 +/- 23.5 vs 27.1 +/- 10.4 mg/L, P < 0.001), whereas no significant differences were seen in the other age groups. No significant correlations of RBP4 were seen with either steroids or indices of insulin resistance. Conclusions: Although serum RBP4 levels were increased in younger women with PCOS compared with age-matched non-PCOS controls, RBP4 does not seem to be a good marker of insulin resistance or other metabolic derangements in women with PCOS.

  • Blomquist, Olivia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Identifiering av processmognad i en kundtjänst2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Maturity models can help organizations understand their processes and thereby improve them.  The Capability Maturity Model (CMM) is a framework with five index-based levels that describes key elements in an effective software process. By identifying a level of process maturity, the model's guidelines can be followed for improvement in process performance.

    The aim of the study has been to study the performance of a customer service process and identify its process maturity, in order to find proposals for process improvements. By measuring the current performance with the help of combination of methods the process has been compared with CMM's two first levels. The study is based on the questions (1) How does the process perform today? (2) Which level of maturity in relation to CMM does the process have? and (3) How can the processes maturity be improved?

    Data has been collected through questionnaires from which the mean values have been compared with the company’s specified goals. Causes of process variation have been studied with the help of regression analyses, employee surveys, interviews with leaders and participatory observations. The performance and maturity of the process has been analysed using CMM's guidelines and the quality tool capability analysis.

    The study shows (1) that the process varies considerably and that there are assignable causes of variation in the process. The process is not consistent with the target values. The target values ​​have not been updated in recent years and therefore do not match the actual process capability. There are no well-defined routines to manage the process. (2) The Capability Index is estimated to 0.7 which places the process on the first level of CMM. This would indicate that the process is as unstable and uncontrolled. (3) In order to develop from the first level of CMM, process management principles and target values should be implemented. Control parameters should be implemented in the process both from an organizational perspective and as a customer perspective in order to create the conditions for a more stable process. The organization itself should also implement process work, new goals and routines for improvement work in the daily work.

  • Bimpisidis, Zisis
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    König, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Stagkourakis, Stefanos
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
    Zell, Vivien
    Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
    Vlcek, Bianca
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Dumas, Sylvie
    Oramacell, 8 Rue Gregoire Tours, F-75006 Paris, France.
    Giros, Bruno
    INSERM, UMRS 1130, F-75005 Paris, France;CNRS, Unite Mixte Rech 8246, F-75005 Paris, France;Univ Paris 06, Sorbonne Univ, Neurosci Paris Seine, F-75005 Paris, France;Douglas Mental Hlth Univ Inst, 6875 LaSalle Blvd, Verdun, PQ H4H 1R3, Canada;McGill Univ, Dept Psychiat, Montreal, PQ, Canada.
    Broberger, Christian
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
    Hnasko, Thomas S.
    Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA;Res Serv VA San Diego Healthcare Syst, La Jolla, CA 92161 USA.
    Wallén-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    The NeuroD6 Subtype of VTA Neurons Contributes to Psychostimulant Sensitization and Behavioral Reinforcement2019In: eNeuro, E-ISSN 2373-2822, Vol. 6, no 3, article id e0066-19.2019Article in journal (Refereed)
    Abstract [en]

    Reward-related behavior is complex and its dysfunction correlated with neuropsychiatric illness. Dopamine (DA) neurons of the ventral tegmental area (VTA) have long been associated with different aspects of reward function, but it remains to be disentangled how distinct VTA DA neurons contribute to the full range of behaviors ascribed to the VTA. Here, a recently identified subtype of VTA neurons molecularly defined by NeuroD6 (NEX1M) was addressed. Among all VTA DA neurons, less than 15% were identified as positive for NeuroD6. In addition to dopaminergic markers, sparse NeuroD6 neurons expressed the vesicular glutamate transporter 2 (Vglut2) gene. To achieve manipulation of NeuroD6 VTA neurons, NeuroD6(NEX)-Cre-driven mouse genetics and optogenetics were implemented. First, expression of vesicular monoamine transporter 2 (VMAT2) was ablated to disrupt dopaminergic function in NeuroD6 VTA neurons. Comparing Vmat2(Cre)(lox/lox;NEX-) conditional knock-out (cKO) mice with littermate controls, it was evident that baseline locomotion, preference for sugar and ethanol, and place preference upon amphetamine-induced and cocaine-induced conditioning were similar between genotypes. However, locomotion upon repeated psychostimulant administration was significantly elevated above control levels in cKO mice. Second, optogenetic activation of NEX-Cre VTA neurons was shown to induce DA release and glutamatergic postsynaptic currents within the nucleus accumbens. Third, optogenetic stimulation of NEX-Cre VTA neurons in vivo induced significant place preference behavior, while stimulation of VTA neurons defined by Calretinin failed to cause a similar response. The results show that NeuroD6 VTA neurons exert distinct regulation over specific aspects of reward-related behavior, findings that contribute to the current understanding of VTA neurocircuitry.

  • VANTARAKI, CHRISTINA
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
    Counteraction of urea-induced protein denaturation by Trimethylamine N-oxide2019Student paper other, 10 HE creditsStudent thesis
    Abstract [en]

    A common consequence of protein denaturation is the loss of biological activity. Natural osmolytes such as Trimethylamine N-oxide (TMAO) contribute to protein folding, whereas other osmolytes such as urea act as an agent in the denaturation of proteins. Many studies have shown that denaturation of proteins could occur for certain concentrations of urea, however, this effect could be prevented with the presence of Trimethylamine N-oxide (TMAO) molecules. The aim of the present study is to find out the mechanism of TMAO as a protein stabilizer against urea. Firstly, Molecular Dynamics simulations were carried out for 1, 8, 27 and 64 TMAO molecules. The time-average location of the TMAO molecules during the simulation was studied by the partial density. These simulations examine if TMAO is amphiphilic molecule, i.e contains both hydrophobic and hydrophilic parts. However, these results might not be representative due to bad statistics. Secondly, an experiment ran at BESSY II at Helmholtz-Zentrum Berlin using X-ray Photoelectron Spectroscopy in liquids. In this experiment, Lauryldimethylamine oxide(LDAO) was used instead of Trimethylamine N-oxide (TMAO) due to some practical reasons. The behaviour of urea and LDAO molecule was studied when these molecules were in different and same solutions. The purpose of this experiment is to find out the mechanism of LDAO against urea. Finally, LDAO interacts with urea and a possible mechanism between them is suggested.

    A common consequence of protein denaturation is the loss of biological activity. Natural osmolytes such as Trimethylamine N-oxide (TMAO) contribute to protein folding, whereas other osmolytes such as urea act as an agent in the denaturation of proteins. Many studies have shown that denaturation of proteins could occur for certain concentrations of urea, however, this effect could be prevented with the presence of the Trimethylamine N-oxide (TMAO) molecules. The aim of the present study is to find out the mechanism of TMAO as a protein stabilizer against urea. Firstly, Molecular Dynamics simulations were carried out for 1, 8, 27 and 64 TMAO molecules. The time-average location of TMAO molecules during the simulation was studied by the partial density. These simulations examine if TMAO is amphiphilic molecule, i.e contains both hydrophobic and hydrophilic parts. However, these results might not be representative due to bad statistics. Secondly, an experiment ran at BESSY II at Helmholtz-Zentrum Berlin using X-ray Photoelectron Spectroscopy in liquids. In this experiment, Lauryldimethylamine oxide (LDAO) was used instead of Trimethylamine N-oxide (TMAO) due to some practical reasons. The behaviour of urea and LDAO molecule was studied when these molecules were in different and same solutions. The purpose of this experiment is to find out the mechanism of LDAO against urea. Finally, LDAO interacts with urea and a possible mechanism between them is suggested.

  • Grau, Andrea
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Industrial Engineering & Management.
    Wanner, Patrick
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Industrial Engineering & Management.
    Managing supply chain sustainability risks of antibiotics: A case study within Sweden2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Antimicrobial resistance (AMR) has been classified as one of the phenomena that belongs to the current top threats to human health. AMR is the process where bacteria become resistant to the antimicrobial drug and renders the antibiotic ineffective. This phenomenon is increasing exponentially due to misuse and overuse of antibiotics and is responsible for 700,000 annual deaths globally. If the contributing factors to AMR remain persistent, the estimated amount of annual deaths will increase to the exorbitant figure of 10 million by 2050. The inappropriate waste discharge from antibiotic manufacturing plants is the third major cause contributing to AMR. For this reason, environmental sustainability within the pharmaceutical industry is tightly linked to human health, and therefore, the importance of environmental risk management becomes crucial. Pharmaceutical supply chains are extremely complex, fragmented, and rigid due to the highly regulated environment and global distribution of the chains. Constant availability is sometimes compromised, and this leads to national shortages of antibiotics, which increase AMR. Therefore, supply chain sustainability risks (SCSRs) need to be thoroughly assessed and managed. The thesis aims to identify the sustainability risks that threaten the constant supply of antibiotics and further provide a comprehensive and sufficient framework on how to assess and manage SCSRs within the pharmaceutical industry. This research is based on the review of existing literature, followed by an empirical study that included a case study of two specific antibiotics relevant to the Swedish market. The analysis of publicly available databases, together with the qualitative interviews, revealed that the most susceptible node of the supply chain resides in the primary manufacturing stage. The most relevant SCSRs have been identified, and an adapted framework is suggested. The role of regulatory agencies has been demonstrated to be fundamental to achieve change concerning environmental progress. Further research needs to be implemented for the validation of the suggested framework within a practical context.

  • Alinder, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Observational Astronomy.
    Space Situational Awareness with the Swedish Allsky Meteor Network2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis investigates the use of the Swedish Allsky Meteor Network (SAMN) for observing, identifying, and determining the orbits of satellites. The overall goal of this project is to determine the feasibility of using such a network for Space Situational Awareness (SSA) purposes, which requires identification and monitoring of objects in orbit. This thesis is a collaboration with the Swedish Defense Research Agency (FOI) to support their efforts in SSA.

    Within the frame of this project, the author developed software that can take data of observations of an object collected from the all-sky cameras of SAMN and do an Initial Orbit Determination (IOD) of the object. An algorithm that improves the results of the IOD was developed and integrated into the software. The software can also identify the object if it is in a database that the program has access to or, if it could not be identified, make an approximate prediction of when and where the object will be visible again the next time it flies over. A program that analyses the stability of the results of the IOD was also developed. This measures the spread in results of the IOD when a small amount of artificial noise is added to one or more of the observed coordinates in the sky. It was found that using multiple cameras at different locations greatly improves the stability of the solutions.

    Gauss' method was used for doing the IODs. The advantages and disadvantages of using this method are discussed, and ultimately other methods, such as the Gooding method or Double R iteration, are recommended for future works. This is mostly because Gauss' method has a singularity when all three lines of sight from observer to object lie in the same plane, which makes the results unreliable.

    The software was tested on a number of observations, both synthetic and real, and the results were compared against known data from public databases. It was found that these techniques can, with some changes, be used for doing IOD and satellite identification, but that doing very accurate position determination required for full orbit determination is not feasible.

  • Di Martino, Maria Letizia
    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.
    Ek, Viktor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hardt, Wolf-Dietrich
    Swiss Fed Inst Technol, Inst Microbiol, Zurich, Switzerland.
    Eriksson, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sellin, Mikael E.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Barcoded Consortium Infections Resolve Cell Type-Dependent Salmonella enterica Serovar Typhimurium Entry Mechanisms2019In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 10, no 3, article id e00603-19Article in journal (Refereed)
    Abstract [en]

    Bacterial host cell invasion mechanisms depend on the bacterium's virulence factors and the properties of the target cell. The enteropathogen Salmonella enterica serovar Typhimurium (S. Tm) invades epithelial cell types in the gut mucosa and a variety of immune cell types at later infection stages. The molecular mechanism(s) of host cell entry has, however, been studied predominantly in epithelial cell lines. S. Tm uses a type three secretion system (TTSS-1) to translocate effectors into the host cell cytosol, thereby sparking actin ruffle-dependent entry. The ruffles also fuel cooperative invasion by bystander bacteria. In addition, several TTSS-1-independent entry mechanisms exist, involving alternative S. Tm virulence factors, or the passive uptake of bacteria by phagocytosis. However, it remains ill-defined how S. Tm invasion mechanisms vary between host cells. Here, we developed an internally controlled and scalable method to map S. Tm invasion mechanisms across host cell types and conditions. The method relies on host cell infections with consortia of chromosomally tagged wild-type and mutant S. Tm strains, where the abundance of each strain can be quantified by qPCR or amplicon sequencing. Using this methodology, we quantified cooccurring TTSS-1-dependent, cooperative, and TTSS-1-independent invasion events in epithelial, monocyte, and macrophage cells. We found S. Tm invasion of epithelial cells and monocytes to proceed by a similar MOI-dependent mix of TTSS-1-dependent and cooperative mechanisms. TTSS-1-independent entry was more frequent in macrophages. Still, TTSS-1-dependent invasion dominated during the first minutes of interaction also with this cell type. Finally, the combined action of the SopB/SopE/SopE2 effectors was sufficient to explain TTSS-1-dependent invasion across both epithelial and phagocytic cells. IMPORTANCE Salmonella enterica serovar Typhimurium (S. Tm) is a widespread and broad-host-spectrum enteropathogen with the capacity to invade diverse cell types. Still, the molecular basis for the host cell invasion process has largely been inferred from studies of a few selected cell lines. Our work resolves the mechanisms that Salmonellae employ to invade prototypical host cell types, i.e., human epithelial, monocyte, and macrophage cells, at a previously unattainable level of temporal and quantitative precision. This highlights efficient bacterium-driven entry into innate immune cells and uncovers a type III secretion system effector module that dominates active bacterial invasion of not only epithelial cells but also monocytes and macrophages. The results are derived from a generalizable method, where we combine barcoding of the bacterial chromosome with mixed consortium infections of cultured host cells. The application of this methodology across bacterial species and infection models will provide a scalable means to address host-pathogen interactions in diverse contexts.

  • Hanna, Holst
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Polypharmacy and inappropriate medicines  among participants in the MedBridge study2019Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Introduction: Polypharmacy and inappropriate medication are common issues in elderly patients. Older people are more likely to suffer from adverse drug reactions and other drug-related problems due to the increased presence of multimorbidity, inappropriate polypharmacy, age related impairments in the hepatic metabolism and renal clearance of medication and enhanced pharmacodynamic sensitivity to specific drugs.

    Aim: The aim of this study was to analyze, compare and describe medication use in the MedBridge study population, in total and for different patient groups.

    Materials and Methods: Medication data from approximately 700 patients from Uppsala University Hospital and the hospital of Enköping was extracted from the medical record system and stored in an electronic data capture system. This data was joined together with the collected data from the other 1939 study participants and exported to Microsoft excel for analyses.

    Results: The mean value of prescribed medicines was 9.2. Women had significantly higher (p<0.05) number of prescribed medicines. Participants aged 85 or older had the highest number of prescribed medicines and participant between 65-74 had the least prescribed medicines. The mean value was significantly higher (p<0.05) for women aged 85 years or older and women between 75-85 years compared with women aged 65- 74. In this population 461 patients (17.4%) used at least one inappropriate medicine. Of all the women 18.8% used at least one inappropriate medicine and 15.7% of all the men. Women aged 85 years or older used the most inappropriate medicines and men between 65-74 used the least. Women aged 85 or older used significantly (p<0.05) higher amount of inappropriate medicines than women aged 65-74 years did.

    Conclusion: In conclusion, this report shows that many of our elderly haves’ polypharmacy and that women are using more medicines than men and more inappropriate medicines than men. It also indicates that the older you get, the more medicines you use.

  • Bergström, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Risk factors and stroke-preventing medications among patients admitted for stroke: – a substudy within the MedBridge trial2019Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
  • Garcia-Pichel, Ferran
    et al.
    Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA;Arizona State Univ, Biodesign Inst, Ctr Fundamental & Appl Microbi, Tempe, AZ 85287 USA.
    Lombard, Jonathan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Soule, Tanya
    Purdue Univ, Dept Biol, Ft Wayne, IN USA.
    Dunaj, Sean
    Purdue Univ, Dept Biol, Ft Wayne, IN USA.
    Wu, Steven H.
    Arizona State Univ, Biodesign Inst, Ctr Personalized Diagnost, Tempe, AZ USA;BioConsortia Inc, Davis, CA USA.
    Wojciechowski, Martin F.
    Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA.
    Timing the Evolutionary Advent of Cyanobacteria and the Later Great Oxidation Event Using Gene Phylogenies of a Sunscreen2019In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 10, no 3, article id e00561-19Article in journal (Refereed)
    Abstract [en]

    The biosynthesis of the unique cyanobacterial (oxyphotobacterial) indole-phenolic UVA sunscreen, scytonemin, is coded for in a conserved operon that contains both core metabolic genes and accessory, aromatic amino acid biosynthesis genes dedicated to supplying scytonemin's precursors. Comparative genomics shows conservation of this operon in many, but not all, cyanobacterial lineages. Phylogenetic analyses of the operon's aromatic amino acid genes indicate that five of them were recruited into the operon after duplication events of their respective house-keeping cyanobacterial cognates. We combined the fossil record of cyanobacteria and relaxed molecular clock models to obtain multiple estimates of these duplication events, setting a minimum age for the evolutionary advent of scytonemin at 2.1 +/- 0.3 billion years. The same analyses were used to estimate the advent of cyanobacteria as a group (and thus the appearance of oxygenic photosynthesis), at 3.6 +/- 0.2 billion years before present. Post hoc interpretation of 16S rRNA-based Bayesian analyses was consistent with these estimates. Because of physiological constraints on the use of UVA sunscreens in general, and the biochemical constraints of scytonemin in particular, scytonemin's age must postdate the time when Earth's atmosphere turned oxic, known as the Great Oxidation Event (GOE). Indeed, our biological estimate is in agreement with independent geochemical estimates for the GOE. The difference between the estimated ages of oxygenic photosynthesis and the GOE indicates the long span (on the order of a billion years) of the era of "oxygen oases," when oxygen was available locally but not globally. IMPORTANCE The advent of cyanobacteria, with their invention of oxygenic photosynthesis, and the Great Oxidation Event are arguably among the most important events in the evolutionary history of life on Earth. Oxygen is a significant toxicant to all life, but its accumulation in the atmosphere also enabled the successful development and proliferation of many aerobic organisms, especially metazoans. The currently favored dating of the Great Oxidation Event is based on the geochemical rock record. Similarly, the advent of cyanobacteria is also often drawn from the same estimates because in older rocks paleontological evidence is scarce or has been discredited. Efforts to obtain molecular evolutionary alternatives have offered widely divergent estimates. Our analyses provide a novel means to circumvent these limitations and allow us to estimate the large time gap between the two events.

  • Daskalakis, Kosmas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece.
    Tsoli, Marina
    Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece.
    Angelousi, Anna
    Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece.
    Kassi, Evanthia
    Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece;Univ Athens, Med Sch, Dept Biol Chem, Athens, Greece.
    Alexandraki, Krystallenia, I
    Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece.
    Kolomodi, Denise
    Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece.
    Kaltsas, Gregory
    Univ Athens, Laiko Hosp, Endocrine Unit, Dept Propaupaed Internal Med 1, Athens, Greece;Univ Warwick, Univ Hosp, Warwick Med Sch, Clin Sci Res Labs, Coventry, W Midlands, England;Coventry Univ, Fac Hlth & Life Sci, Ctr Appl Biol & Exercise Sci, Coventry, W Midlands, England.
    Koumarianou, Anna
    Univ Athens, Haematol Oncol Unit, Dept Internal Med 4, Attikon Univ Gen Hosp, Athens, Greece.
    Anti-tumour activity of everolimus and sunitinib in neuroendocrine neoplasms2019In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 8, no 6, p. 641-653Article in journal (Refereed)
    Abstract [en]

    Comparisons between everolimus and sunitinib regarding their efficacy and safety in neuroendocrine neoplasms (NENs) are scarce. We retrospectively analysed the clinicopathological characteristics and outcomes in 92 patients with well-differentiated (WD) NEN of different origin (57 pancreatic NENs (PanNENs)), treated with molecular targeted therapy (MTT) with everolimus or sunitinib, first- (73: 19) or second-line (sequential; 12: 22) for progressive disease. Disease control rates (DCR: partial response or stable disease) at first-line were higher in all patients treated with everolimus than sunitinib (64/73 vs 12/19, P = 0.012). In PanNENs, DCR at first-line everolimus was 36/42 versus 9/15 with sunitinib (P = 0.062). Progression-free survival (PFS) at first-line everolimus was longer than sunitinib (31 months (95% CI: 23.1-38.9) vs 9 months (95% CI: 0-18.5); log-rank P < 0.0001) in the whole cohort and the subset of PanNENs (log-rank P < 0.0001). Median PFS at second-line MTT was 12 months with everolimus (95% CI: 4.1-19.9) vs 13 months with sunitinib (95% CI: 9.3-16.7; log-rank P = 0.951). Treatment with sunitinib (HR: 3.47; 95% CI: 1.5-8.3; P value: 0.005), KI67 > 20% (HR: 6.38; 95% CI: 1.3-31.3; P = 0.022) and prior chemotherapy (HR: 2.71; 95% CI: 1.2-6.3; P = 0.021) were negative predictors for PFS at first line in multivariable and also confirmed at multi-state modelling analyses. Side effect (SE) analysis indicated events of serious toxicities (Grades 3 and 4: n = 13/85 for everolimus and n = 4/41 for sunitinib). Discontinuation rate due to SEs was 20/85 for everolimus versus 4/41 for sunitinib (P = 0.065). No additive toxicity of second-line MTT was confirmed. Based on these findings, and until reliable predictors of response become available, everolimus may be preferable to sunitinib when initiating MTT in progressive NENs.

  • Ridolfi, Elena
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL. CNDS, Ctr Nat Hazards & Disaster Sci, S-75236 Uppsala, Sweden.
    Di Francesco, Silvia
    Niccolo Cusano Univ, I-00166 Rome, Italy.
    Pandolfo, Claudia
    Ctr Funz Reg Umbria CFD, I-06034 Foligno, Italy.
    Berni, Nicola
    Ctr Funz Reg Umbria CFD, I-06034 Foligno, Italy.
    Biscarini, Chiara
    Univ Foreigners Perugia, UNESCO Chair Water Resources Management & Culture, I-06123 Perugia, Italy.
    Manciola, Piergiorgio
    Univ Perugia, Dept Civil & Environm Engn, I-06125 Perugia, Italy.
    Coping with Extreme Events: Effect of Different Reservoir Operation Strategies on Flood Inundation Maps2019In: Water, ISSN 2073-4441, E-ISSN 2073-4441, Vol. 11, no 5, article id 982Article in journal (Refereed)
    Abstract [en]

    The need of addressing residual flood risk associated with structural protection measures, such as levee systems and flood-control reservoirs, has fostered actions aimed at increasing flood risk awareness. Structural measures have lowered risk perception by inducing a false sense of safety. As a result, these structures contribute to an underestimation of the residual risk. We analyze the effect of different reservoir operations, such as coping with drought versus coping with flood events, on flood inundation patterns. First, a hydrological model simulates different scenarios, which represent the dam regulation strategies. Each regulation strategy is the combination of an opening of the outlet gate and of the initial water level in the reservoir. Second, the corresponding outputs of the dam in terms of maximum discharge values are estimated. Then, in turn, each output of the dam is used as an upstream boundary condition of a hydraulic model used to simulate the flood propagation and the inundation processes in the river reach. The hydraulic model is thus used to determine the effect, in terms of inundated areas, of each dam regulation scenario. Finally, the ensemble of all flood inundation maps is built to define the areas more prone to be flooded. The test site is the Casanuova dam (Umbria, central Italy) which aims at: (i) mitigating floods occurring at the Chiascio River, one of the main tributaries of Tiber River, while (ii) providing water supply for irrigation. Because of these two competitive interests, the understanding of different scenarios generated by the dam operations offers an unique support to flood mitigation strategies. Results can lead to draw interesting remarks for a wide number of case studies.

  • Knopp, Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gudmundsdottir, Jonina S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Nilsson, Tobias
    Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
    Konig, Finja
    Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
    Warsi, Omar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rajer, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Adelroth, Pia
    Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
    Andersson, Dan I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    De Novo Emergence of Peptides That Confer Antibiotic Resistance2019In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 10, no 3, article id e00837-19Article in journal (Refereed)
    Abstract [en]

    The origin of novel genes and beneficial functions is of fundamental interest in evolutionary biology. New genes can originate from different mechanisms, including horizontal gene transfer, duplication-divergence, and de novo from non-coding DNA sequences. Comparative genomics has generated strong evidence for de novo emergence of genes in various organisms, but experimental demonstration of this process has been limited to localized randomization in preexisting structural scaffolds. This bypasses the basic requirement of de novo gene emergence, i.e., lack of an ancestral gene. We constructed highly diverse plasmid libraries encoding randomly generated open reading frames and expressed them in Escherichia coli to identify short peptides that could confer a beneficial and selectable phenotype in vivo (in a living cell). Selections on antibiotic-containing agar plates resulted in the identification of three peptides that increased aminoglycoside resistance up to 48-fold. Combining genetic and functional analyses, we show that the peptides are highly hydrophobic, and by inserting into the membrane, they reduce membrane potential, decrease aminoglycoside uptake, and thereby confer high-level resistance. This study demonstrates that randomized DNA sequences can encode peptides that confer selective benefits and illustrates how expression of random sequences could spark the origination of new genes. In addition, our results also show that this question can be addressed experimentally by expression of highly diverse sequence libraries and subsequent selection for specific functions, such as resistance to toxic compounds, the ability to rescue auxotrophic/temperature-sensitive mutants, and growth on normally nonused carbon sources, allowing the exploration of many different phenotypes. IMPORTANCE De novo gene origination from nonfunctional DNA sequences was long assumed to be implausible. However, recent studies have shown that large fractions of genomic noncoding DNA are transcribed and translated, potentially generating new genes. Experimental validation of this process so far has been limited to comparative genomics, in vitro selections, or partial randomizations. Here, we describe selection of novel peptides in vivo using fully random synthetic expression libraries. The peptides confer aminoglycoside resistance by inserting into the bacterial membrane and thereby partly reducing membrane potential and decreasing drug uptake. Our results show that beneficial peptides can be selected from random sequence pools in vivo and support the idea that expression of noncoding sequences could spark the origination of new genes.

  • Libard, Sylwia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Alzheimer's disease neuropathological change and loss of matrix/neuropil in patients with idiopathic Normal Pressure Hydrocephalus, a model of Alzheimer's disease2019In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 7, article id 98Article in journal (Refereed)
    Abstract [en]

    Here, we assessed unique brain tissue samples, obtained from living subjects with idiopathic Normal Pressure Hydrocephalus (iNPH). Our cohort of 95 subjects with age ranging from 75 to 79 years, displayed a high prevalence of beta-amyloid (A beta) and hyperphosphorylated t (HPt) pathology (63 and 61%, respectively) in a frontal cortex biopsy obtained during shunt operation. These lesions, i.e., Alzheimer's Disease Neuropathologic Change (ADNC), increased within 5 years and were more frequent in females. The extent of HPt pathology was sparse, primarily seen as neurites and stained dots. Noteworthy, concomitant pathology was seen in 49% of the whole cohort, indicating a severity of ADNC corresponding to a low/intermediate level following the current recommendations. This observation is predictable as based on previous publications a substantial number of subjects with iNPH over time develop AD. Thus, iNPH can be considered as a model of AD. We noted a surprisingly remarkable neuronal preservation assessing Neuronal Nuclei (NeuN) in parallel with a substantial depletion of matrix/neuropil. This finding is intriguing as it suggests that loss of matrix/neuropil might be one of the first lesion of ADNC but also a hallmark lesion of iNPH. The latter observation is in line with the enlarged ventricles, a cardinal feature of iNPH. Furthermore, a positive correlation was observed between the extent of A beta and NeuN but only in females indicating a neuronal preservation even when A beta pathology is present. The assessment of a surgical biopsy as described here is certainly informative and thus it is surprising that a neuropathologic assessment in the setting of iNPH, while inserting a shunt, is seldom performed. Here, we observed ADNC and surprisingly remarkable neuronal preservation in a substantial number of iNPH subjects. Thus, these subjects allow us to observe the natural course of the disease and give us an opportunity for intervention at the earliest stages of AD, prior to severe neuronal damage.

  • Irkhina, A.
    et al.
    Helmholtz Zentrum Berlin Mat & Energie, Dept Struct & Dynam Energy Mat, D-14109 Berlin, Germany.
    Levcenko, S.
    Helmholtz Zentrum Berlin Mat & Energie, Dept Struct & Dynam Energy Mat, D-14109 Berlin, Germany.
    Xie, Ling
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Leifer, Klaus
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Unold, T.
    Helmholtz Zentrum Berlin Mat & Energie, Dept Struct & Dynam Energy Mat, D-14109 Berlin, Germany.
    Radiative emission from Cu2ZnSnS4/ZnSn core/shell nanocrystals2019In: Journal of Materials Chemistry C, ISSN 2050-7526, E-ISSN 2050-7534, Vol. 7, no 20, p. 6129-6133Article in journal (Refereed)
    Abstract [en]

    Kesterite Cu2ZnSnS4 (CZTS) nanocrystals so far have been found to luminesce neither at room temperature nor at low temperature. Here a core-shell architecture for kesterite CZTS nanocrystals is demonstrated by applying a ZnSn-alloy shell overcoating approach. These CZTS/ZnSn nanocrystals show luminescence emission at 1.05 eV, which is red-shifted by about 0.4 eV from the absorption onset and is attributed to a radiative transition involving a deep defect. Temperature-dependent photoluminescence measurements within a range of 20-200 K indicate the presence of a competing nonradiative channel with an activation energy of 50-60 meV.

  • Goncalves, Leticia C. P.
    et al.
    TU Wien, Inst Appl Synthet Chem, Getreidemarkt 9 163, A-1060 Vienna, Austria.
    Mansouri, Hamid R.
    TU Wien, Inst Appl Synthet Chem, Getreidemarkt 9 163, A-1060 Vienna, Austria.
    PourMehdi, Shads
    TU Wien, Inst Appl Synthet Chem, Getreidemarkt 9 163, A-1060 Vienna, Austria.
    Abdellah, Mohamed
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry. Department of Chemistry, Qena Faculty of Science, South Valley University, 83523 Qena, Egypt.
    Fadiga, Bruna S.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry. Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-03178200 Sao Paulo, Brazil.
    Bastos, Erick L.
    Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-03178200 Sao Paulo, Brazil.
    Sá, Jacinto
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry. Polish Acad Sci, Inst Phys Chem, PL-01224 Warsaw, Poland.
    Mihovilovic, Marko D.
    TU Wien, Inst Appl Synthet Chem, Getreidemarkt 9 163, A-1060 Vienna, Austria.
    Rudroffe, Florian
    TU Wien, Inst Appl Synthet Chem, Getreidemarkt 9 163, A-1060 Vienna, Austria.
    Boosting photobioredox catalysis by morpholine electron donors under aerobic conditions2019In: Catalysis Science & Technology, ISSN 2044-4753, E-ISSN 2044-4761, Vol. 9, no 10, p. 2682-2688Article in journal (Refereed)
    Abstract [en]

    Light-driven reduction of flavins, e.g. FAD or FMN, by sacrificial electron donors emerged as a convenient method to promote biocatalytic transformations. However, flavin activation has been restricted to oxygen-free conditions to prevent enzyme deactivation caused by reactive oxygen species (ROS). Herein, we show that the photoreduction of FMN by morpholines, including 3-(N-morpholino)propanesulfonic acid (MOPS), lessens the deactivation of the enoate reductase XenB from Pseudomonas sp. during the stereoselective asymmetric enzymatic reduction of a model ,-unsaturated diketone under aerobic conditions, leading to a 91% GC-yield and a stereoselectivity greater than 94%. The kinetic stability of the thermolabile XenB was increased by more than 20-fold in MOPS buffer compared to that in Tris-HCl buffer, and a pronounced positive effect on the transition midpoint temperature was observed. The reactive form of the FMN photocatalyst is stabilized by the formation of a (3)[FMN--MOPS+] ensemble, which reduces the formation of hydrogen peroxide and other ROS in the presence of oxygen. These results contribute to broaden the application of photobiocatalytic transformations using flavin-dependent reductases.

  • Tedeblad, Ida
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Economics.
    The liberalized painkiller market: A study assessing the efficiency of increased access of painkillers in Sweden after 20092019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this study is to estimate the efficiency of increased access made on the non- prescriptive drug market, explicitly the painkiller market. In 2009 the Swedish government chose to cease the monopoly on the pharmacy market and also allowed regular stores to sell some non-prescriptive drugs. To assess the efficiency of these two reforms, I will investigate how the access of painkillers has changed for the individual and if this could have an impact on health. I will use a fixed effects model, including county- and year fixed effects, with the access per 100,000 people as explanatory variable and estimate the effect of outcomes such as sales, intoxication, asthma, ADHD prescriptions and doctors visits. This study finds no effect of increased access on consumption or health, although the access of painkillers has unambiguously increased after 2009.

  • Forsberg, Isabella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kvalité och säkerhet vid iordningställande av parenterala läkemedel2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Introduktion: Det finns många fördelar med parenteral administrering, exempelvis ger det hög biotillgänglighet och snabb systemisk insättning. Men eftersom kroppens naturliga försvarsbarriärer förbigås kan kontaminerade parenterala läkemedel leda till allvarlig patientskada eller i värsta fall död. För att undvika detta är det viktigt att personalen som iordningställer de parenterala läkemedlen arbetar aseptiskt.

    Syfte: Att utreda skillnader i säkerhet och kvalité vid iordningställande av parenterala läkemedel när det utförs av sjuksköterskor jämfört med farmaceuter.

    Metod: En observationsmall utformades innehållande sex olika parametrar som ansågs mäta säkerhet och kvalité vid iordningställande av parenterala läkemedel. Observationsmallen användes för observation av sjuksköterskor och farmaceuter när de iordningställde parenterala läkemedel på fyra olika avdelningar på Akademiska sjukhuset. Statistisk analys utfördes med Pearson´s Chi2-test. P-värden under 0,05 ansågs vara signifikanta.

    Resultat: Totalt observerades 276 iordningställanden av parenterala läkemedel utförda av 14 sjuksköterskor och 3 farmaceuter. Farmaceuterna utförde fem av de sex parametrarna signifikant fler gånger (p<0,0001) än sjuksköterskorna, med ett genomsnitt på 31,2 procentenheter högre. Det fanns även signifikanta skillnader inom samma yrke.

    Slutsats: Dessa resultat tyder på att kvalitén och säkerheten är beroende av vilken personal som iordningställer. Vad dessa skillnader beror på kan inte fastställas utifrån denna undersökning. Att farmaceuter fick bättre resultat kan bero på deras breda läkemedelskunskaper, men det går inte att utesluta andra anledningar. Andra faktorer som kan spelat in är de olika typerna av arbetssätt samt vilken typ av avdelning de arbetade på. För att säkerställa dessa resultat bör en mer omfattande studie genomföras med fler observerad personal.

  • Wagner-Golbs, Antje
    et al.
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Neuber, Sebastian
    Biocrates Life Sci AG, Eduard Bodem Gasse 8, A-6020 Innsbruck, Austria.
    Kamlage, Beate
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Christiansen, Nicole
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Bethan, Bianca
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Rennefahrt, Ulrike
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Schatz, Philipp
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Effects of Long-Term Storage at -80 degrees C on the Human Plasma Metabolome2019In: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 9, no 5, article id 99Article in journal (Refereed)
    Abstract [en]

    High-quality biological samples are required for the favorable outcome of research studies, and valid data sets are crucial for successful biomarker identification. Prolonged storage of biospecimens may have an artificial effect on compound levels. In order to investigate the potential effects of long-term storage on the metabolome, human ethylenediaminetetraacetic acid (EDTA) plasma samples stored for up to 16 years were analyzed by gas and liquid chromatography-tandem mass spectrometry-based metabolomics. Only 2% of 231 tested plasma metabolites were altered in the first seven years of storage. However, upon longer storage periods of up to 16 years and more time differences of few years significantly affected up to 26% of the investigated metabolites when analyzed within subject age groups. Ontology classes that were most affected included complex lipids, fatty acids, energy metabolism molecules, and amino acids. In conclusion, the human plasma metabolome is adequately stable to long-term storage at -80 degrees C for up to seven years but significant changes occur upon longer storage. However, other biospecimens may display different sensitivities to long-term storage. Therefore, in retrospective studies on EDTA plasma samples, analysis is best performed within the first seven years of storage.

  • Wellhagen, Gustaf J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Kjellsson, Maria C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    A Bounded Integer Model for Rating and Composite Scale Data2019In: AAPS Journal, ISSN 1550-7416, E-ISSN 1550-7416, Vol. 21, no 4, article id 74Article in journal (Refereed)
    Abstract [en]

    Rating and composite scales are commonly used to assess treatment efficacy. The two main strategies for modelling such endpoints are to treat them as a continuous or an ordered categorical variable (CV or OC). Both strategies have disadvantages, including making assumptions that violate the integer nature of the data (CV) and requiring many parameters for scales with many response categories (OC). We present a method, called the bounded integer (BI) model, which utilises the probit function with fixed cut-offs to estimate the probability of a certain score through a latent variable. This method was successfully implemented to describe six data sets from four different therapeutic areas: Parkinson's disease, Alzheimer's disease, schizophrenia, and neuropathic pain. Five scales were investigated, ranging from 11 to 181 categories. The fit (likelihood) was better for the BI model than for corresponding OC or CV models (ΔAIC range 11-1555) in all cases but one (ΔAIC -63), while the number of parameters was the same or lower. Markovian elements were successfully implemented within the method. The performance in external validation, assessed through cross-validation, was also in favour of the new model (ΔOFV range 22-1694) except in one case (ΔOFV -70). A residual for diagnostic purposes is discussed. This study shows that the BI model respects the integer nature of data and is parsimonious in terms of number of estimated parameters.

  • N.Ekdahl, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mohlin, Camilla
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Univ Tokyo, Dept Bioengn, Tokyo, Japan.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity2019In: Science and Technology of Advanced Materials, ISSN 1468-6996, E-ISSN 1878-5514, Vol. 20, no 1, p. 688-698Article, review/survey (Refereed)
    Abstract [en]

    In this review article, we focus on activation of the soluble components of the innate immune system triggered by nonbiological compounds and stress variances in activation due to the difference in size between nanoparticles (NPs) and larger particles or bulk material of the same chemical and physical composition. We then discuss the impact of the so-called protein corona which is formed on the surface of NPs when they come in contact with blood or other body fluids. For example, NPs which bind inert proteins, proteins which are prone to activate the contact system (e.g., factor XII), which may lead to clotting and fibrin formation or the complement system (e.g., IgG or C3), which may result in inflammation and vascular damage. Furthermore, we describe a whole blood model which we have developed to monitor activation and interaction between different components of innate immunity: blood protein cascade systems, platelets, leukocytes, cytokine generation, which are induced by NPs. Finally, we describe our own studies on innate immunity system activation induced by three fundamentally different species of NPs (two types of engineered NPs and diesel NPs) as demonstrator of the utility of an initial determination of the composition of the protein corona formed on NPs exposed to ethylenediaminetetraacetic acid (EDTA) plasma and subsequent analysis in our whole blood model. [GRAPHICS] .

  • Dawkins, Elena
    et al.
    Stockholm Environm Inst, Stockholm, Sweden;KTH, Dept Sustainable Dev Environm Sci & Engn, Stockholm, Sweden.
    Andre, Karin
    Stockholm Environm Inst, Stockholm, Sweden.
    Axelsson, Katarina
    Stockholm Environm Inst, Stockholm, Sweden.
    Benoist, Lise
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology.
    Swartling, Asa Gerger
    Stockholm Environm Inst, Stockholm, Sweden.
    Persson, Asa
    Stockholm Environm Inst, Stockholm, Sweden.
    Advancing sustainable consumption at the local government level: A literature review2019In: Journal of Cleaner Production, ISSN 0959-6526, E-ISSN 1879-1786, Vol. 231, p. 1450-1462Article, review/survey (Refereed)
    Abstract [en]

    The consumption of goods and services can be a driver of environmental and social impacts around the world. Understanding the role that the different levels of government can play in incentivising sustainable consumption is therefore critical. Using systematic review techniques, this paper reviews the latest evidence on the importance, effectiveness, successes and failures of local government in advancing sustainable consumption. We find that there is little focus on sustainable consumption in its entirety or whether it is being achieved at the local government level. Important consumption categories like food, procurement, water, waste prevention, clothing, other consumables or services are understudied. Evaluation of the outcome of sustainable consumption interventions was limited, and the assessment that was completed gave mixed results. The most popular policy instruments were of the less coercive administrative and informative type. Multiple barriers to the success of an intervention were identified, the top ones being funding; staff capacity, knowledge or data; lack of flexibility and lock-in to the status quo; lack of guidance or political will; administrative burdens; and lack of regulatory powers or tools. Sustainable consumption interventions by local government were most effective when they had strong leadership, good stakeholder engagement, participatory approaches and extensive consultations. (C) 2019 The Authors. Published by Elsevier Ltd.

  • Qian, Zhao
    et al.
    Shandong Univ, Key Lab Liquid Solid Struct Evolut & Proc Mat, Minist Educ, Shenzhen 518057, Peoples R China;Shandong Univ, Shenzhen Inst, Shenzhen 518057, Peoples R China.
    Jiang, Guanzhong
    Shandong Univ, Key Lab Liquid Solid Struct Evolut & Proc Mat, Minist Educ, Shenzhen 518057, Peoples R China;Shandong Univ, Shenzhen Inst, Shenzhen 518057, Peoples R China.
    Ren, Yingying
    Shandong Univ, Key Lab Liquid Solid Struct Evolut & Proc Mat, Minist Educ, Shenzhen 518057, Peoples R China;Shandong Univ, Shenzhen Inst, Shenzhen 518057, Peoples R China.
    Nie, Xi
    Shandong Univ, Key Lab Liquid Solid Struct Evolut & Proc Mat, Minist Educ, Shenzhen 518057, Peoples R China;Shandong Univ, Shenzhen Inst, Shenzhen 518057, Peoples R China.
    Ahuja, Rajeev
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
    Atomistic Modeling of Various Doped Mg2NiH4 as Conversion Electrode Materials for Lithium Storage2019In: Crystals, ISSN 2073-4352, Vol. 9, no 5, article id 254Article in journal (Refereed)
    Abstract [en]

    In this work, we have compared the potential applications of nine different elements doped Mg2NiH4 as conversion-type electrode materials in Li-ion batteries by means of state-of-the-art Density functional theory calculations. The electrochemical properties, such as specific capacity, volume change and average voltage, as well as the atomic and electronic structures of different doped systems have been investigated. The Na doping can improve the electrochemical capacity of the pristine material. Si and Ti doping can reduce the band gap and benefit the electronic conductivity of electrode materials. All of the nine doping elements can help to reduce the average voltage of negative electrodes and lead to reasonable volume changes. According to the computational screening, the Na, Si and Ti doping elements are thought to be promising to enhance the comprehensive properties of pure material. This theoretical study is proposed to encourage and expedite the development of metal-hydrides based lithium-storage materials.

  • Victor, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Binnmyr, Jonas
    Karolinska Inst, Dept Clin Neurosci, Therapeut Immune Design Unit, Stockholm, Sweden.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rask-Andersen, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Elfman, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Levels of horse allergen Equ c 4 in dander and saliva from ten horse breeds2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 5, p. 701-711Article in journal (Refereed)
    Abstract [en]

    Background: Horses are an important source of allergens, but the distribution of horse allergens is poorly understood. Five horse allergens have been identified, Equ c 1-4 and 6. Equ c 4 seems to be an important allergen, with an IgE-binding frequency of 77% in horse-sensitized individuals.0000 Objectives: The aim of this study was to investigate levels of horse allergen Equ c 4 in dander, saliva and urine from ten horse breeds. Method: The study population included 170 horses (87 mares, 27 stallions, 56 geldings) from ten breeds. Horse dander, saliva and urine samples were collected. Levels of horse allergen Equ c 4 were quantified using a two-site sandwich ELISA (mAb 103 and 14G4) and were expressed as Equ c 4 U/mu g protein. Results: The horse allergen Equ c 4 was present in all dander and saliva samples from ten horse breeds, with high within-breed and inter-breed variations; GM values were 639 Equ c 4 U/mu g protein (range 5-15 264) for dander and 39.5 (4-263) for saliva. Equ c 4 was found in 19/21 urine samples. Adjusted for age, sex and changes over time, no differences between breeds could be seen in dander, while in saliva the North Swedish horse showed lower levels of Equ c 4 than any other breed. The levels of Equ c 4 protein in dander and saliva were significantly higher in samples from stallions compared to mares and geldings, independent of breed. Conclusions and Clinical Relevance: The results show a high variability in allergen levels of Equ c 4 in dander and saliva both within and between breeds. Significantly higher levels were found in stallions compared to mares and geldings, independent of breed. Results suggest that none of the horse breeds studied can be recommended for individuals allergic to Equ c 4.

  • Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab. Antaros Med AB, Molndal, Sweden.
    GPR44 as a Target for Imaging Pancreatic Beta-Cell Mass2019In: Current Diabetes Reports, ISSN 1534-4827, E-ISSN 1539-0829, Vol. 19, no 8, article id 49Article, review/survey (Refereed)
    Abstract [en]

    Purpose of Review Quantitative markers for beta-cell mass (BCM) in human pancreas are currently lacking. Medical imaging using positron emission tomography (PET) markers for beta-cell restricted targets may provide an accurate and non-invasive measurement of BCM, to assist diagnosis and treatment of metabolic disease. GPR44 was recently discovered as a putative marker for beta cells and this review summarizes the developments so far. Recent Findings Several small molecule binders targeting GPR44 have been radiolabeled for PET imaging and evaluated in vitro and in small and large animal models. C-11-AZ12204657 and C-11-MK-7246 displayed a dose-dependent and GPR44-mediated binding to beta cells both in vitro and in vivo, with negligible uptake in exocrine pancreas. Summary GPR44 represents an attractive target for visualization of BCM. Further progress in radioligand development including clinical testing is expected to clarify the role of GPR44 as a surrogate marker for BCM in humans.

  • Lindblad, Peter
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Fuente, David
    Univ Politecn Valencia, Inst Aplicac Tecnol Informac & Comunicac Avanzada, Valencia, Spain.
    Borbe, Friederike
    KSD Innovat GmbH, Werksstr 15, D-45527 Hattingen, Germany.
    Cicchi, Bernardo
    CNR, Ist Valorizzaz Legno & Specie Arboree, Via Madonna Piano 10, I-50019 Florence, Italy.
    Conejero, J. Alberto
    Univ Politecn Valencia, Inst Univ Matemat Pura & Aplicada, Valencia, Spain.
    Couto, Narciso
    Univ Sheffield, Dept Chem & Biol Engn, ChELSI Inst, Sheffield, S Yorkshire, England.
    Celesnik, Helena
    Univ Ljubljana, Fac Chem & Chem Technol, Vecna Pot 113, SI-1000 Ljubljana, Slovenia.
    Diano, Marcello M.
    Business Innovat Ctr, Sci Ctr, M2M Engn Sas, Via Coroglio, Naples, Italy.
    Dolinar, Marko
    Univ Ljubljana, Fac Chem & Chem Technol, Vecna Pot 113, SI-1000 Ljubljana, Slovenia.
    Esposito, Serena
    Business Innovat Ctr, Sci Ctr, M2M Engn Sas, Via Coroglio, Naples, Italy.
    Evans, Caroline
    Univ Sheffield, Dept Chem & Biol Engn, ChELSI Inst, Sheffield, S Yorkshire, England.
    Ferreira, Eunice A.
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IBMC, Porto, Portugal;Univ Porto, ICBAS, Porto, Portugal.
    Keller, Joseph
    Ruhr Univ Bochum, Fac Biol & Biotechnol, Plant Biochem, D-44780 Bochum, Germany.
    Khanna, Namita
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Kind, Gabriel
    Univ Appl Sci, Biotechnol & Chem, Technikumpl 17, DE-09648 Mittweida, Germany.
    Landels, Andrew
    Univ Sheffield, Dept Chem & Biol Engn, ChELSI Inst, Sheffield, S Yorkshire, England;Plymouth Marine Lab, Prospect Pl, Plymouth PL1 3DH, Devon, England.
    Lemus, Lenin
    Univ Politecn Valencia, Inst Aplicac Tecnol Informac & Comunicac Avanzada, Valencia, Spain.
    Noirel, Josselin
    Conservatoire Natl Arts & Metiers, LGBA, F-75003 Paris, France.
    Ocklenburg, Sarah
    KSD Innovat GmbH, Werksstr 15, D-45527 Hattingen, Germany.
    Oliveira, Paulo
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IBMC, Porto, Portugal.
    Pacheco, Catarina C.
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IBMC, Porto, Portugal.
    Parker, Jennifer L.
    Univ Sheffield, Dept Chem & Biol Engn, ChELSI Inst, Sheffield, S Yorkshire, England.
    Pereira, Jose
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IBMC, Porto, Portugal.
    Khoa Pham, T.
    Univ Sheffield, Dept Chem & Biol Engn, ChELSI Inst, Sheffield, S Yorkshire, England.
    Pinto, Filipe
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IBMC, Porto, Portugal.
    Rexroth, Sascha
    Ruhr Univ Bochum, Fac Biol & Biotechnol, Plant Biochem, D-44780 Bochum, Germany.
    Roegner, Matthias
    Ruhr Univ Bochum, Fac Biol & Biotechnol, Plant Biochem, D-44780 Bochum, Germany.
    Schmitz, Hans-Juergen
    KSD Innovat GmbH, Werksstr 15, D-45527 Hattingen, Germany.
    Silva Benavides, Ana Margarita
    Univ Costa Rica, Escuela Biol, San Jose 11501, Costa Rica;Univ Costa Rica, Ctr Invest Ciencias Mar & Limnol CIMAR, San Jose 11501, Costa Rica.
    Siurana, Maria
    Univ Politecn Valencia, Inst Univ Matemat Pura & Aplicada, Valencia, Spain.
    Tamagnini, Paula
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IBMC, Porto, Portugal;Univ Porto, Dept Biol, Fac Ciencias, Porto, Portugal.
    Touloupakis, Eleftherios
    CNR, Ist Ric Ecosistemi Terr, Via Madonna Piano 10, I-50019 Sesto Fiorentino, Italy.
    Torzillo, Giuseppe
    CNR, Ist Valorizzaz Legno & Specie Arboree, Via Madonna Piano 10, I-50019 Florence, Italy.
    Urchueguia, Javier F.
    Univ Politecn Valencia, Inst Aplicac Tecnol Informac & Comunicac Avanzada, Valencia, Spain.
    Wegelius, Adam
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Wiegand, Katrin
    Ruhr Univ Bochum, Fac Biol & Biotechnol, Plant Biochem, D-44780 Bochum, Germany.
    Wright, Phillip C.
    Univ Sheffield, Dept Chem & Biol Engn, ChELSI Inst, Sheffield, S Yorkshire, England;Newcastle Univ, Fac Sci Agr & Engn, Fac Off, Sch Chem Engn & Adv Mat, Newcastle, NSW NE1 7RU, Australia.
    Wutschel, Mathias
    KSD Innovat GmbH, Werksstr 15, D-45527 Hattingen, Germany.
    Wuenschiers, Roebbe
    Univ Appl Sci, Biotechnol & Chem, Technikumpl 17, DE-09648 Mittweida, Germany.
    CyanoFactory, a European consortium to develop technologies needed to advance cyanobacteria as chassis for production of chemicals and fuels2019In: Algal Research, ISSN 2211-9264, Vol. 41, article id 101510Article, review/survey (Refereed)
    Abstract [en]

    CyanoFactory, Design, construction and demonstration of solar biofuel production using novel (photo) synthetic cell factories, was an R&D project developed in response to the European Commission FP7-ENERGY-2012-1 call "Future Emerging Technologies" and the need for significant advances in both new science and technologies to convert solar energy into a fuel. CyanoFactory was an example of "purpose driven" research and development with identified scientific goals and creation of new technologies. The present overview highlights significant outcomes of the project, three years after its successful completion. The scientific progress of CyanoFactory involved: (i) development of a ToolBox for cyanobacterial synthetic biology; (ii) construction of DataWarehouse/Bioinformatics web-based capacities and functions; (iii) improvement of chassis growth, functionality and robustness; (iv) introduction of custom designed genetic constructs into cyanobacteria, (v) improvement of photosynthetic efficiency towards hydrogen production; (vi) biosafety mechanisms; (vii) analyses of the designed cyanobacterial cells to identify bottlenecks with suggestions on further improvements; (viii) metabolic modelling of engineered cells; (ix) development of an efficient laboratory scale photobioreactor unit; and (x) the assembly and experimental performance assessment of a larger (1350 L) outdoor flat panel photobioreactor system during two seasons. CyanoFactory - Custom design and purpose construction of microbial cells for the production of desired products using synthetic biology - aimed to go beyond conventional paths to pursue innovative and high impact goals. CyanoFactory brought together ten leading European partners (universities, research organizations and enterprises) with a common goal - to develop the future technologies in Synthetic biology and Advanced photobioreactors.

  • Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Div Prevent Med, Brigham & Womens Hosp, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Ahluwalia, Tarunveer S.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark.
    Editorial: The Role of Genetic and Lifestyle Factors in Metabolic Diseases2019In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 10, article id 475Article in journal (Other academic)
  • Eriksson, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mohlin, Camilla
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    N. Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.
    The Human Platelet as an Innate Immune Cell: Interactions Between Activated Platelets and the Complement System2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 1590Article, review/survey (Refereed)
    Abstract [en]

    Platelets play an essential role in maintaining homeostasis in the circulatory system after an injury by forming a platelet thrombus, but they also occupy a central node in the intravascular innate immune system. This concept is supported by their extensive interactions with immune cells and the cascade systems of the blood. In this review we discuss the close relationship between platelets and the complement system and the role of these interactions during thromboinflammation. Platelets are protected from complement-mediated damage by soluble and membrane-expressed complement regulators, but they bind several complement components on their surfaces and trigger complement activation in the fluid phase. Furthermore, localized complement activation may enhance the procoagulant responses of platelets through the generation of procoagulant microparticles by insertion of sublytic amounts of C5b9 into the platelet membrane. We also highlight the role of post-translational protein modifications in regulating the complement system and the critical role of platelets in driving these reactions. In particular, modification of disulfide bonds by thiol isomerases and protein phosphorylation by extracellular kinases have emerged as important mechanisms to fine-tune complement activity in the platelet microenvironment. Lastly, we describe disorders with perturbed complement activation where part of the clinical presentation includes uncontrolled platelet activation that results in thrombocytopenia, and illustrate how complement-targeting drugs are alleviating the prothrombotic phenotype in these patients. Based on these clinical observations, we discuss the role of limited complement activation in enhancing platelet activation and consider how these drugs may provide opportunities for further dissecting the complex interactions between complement and platelets.

  • Nakayama, Kimiko
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History.
    The Histography of Eco City Tokyo: A Neoliberal Sustainable Urban City?2019Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Trend of Sustainability is applied to city planning and try to achieve the sustainable development of a city and a town that is generous to people, environment and vitalise the economy at the same time. Initiatives for sustainable city planning in Japan is organized by the national Government, so called, FutureCity Initiative. This initiative enables to local city and representative to participate and act for reducing greenhouse gas (GHG) within a city and aim sustainable development. Chiyoda city is one of the cities elected as an Eco-Model City’s FutureCity project. One of their approaches is to cooperate with local businesses group in Otemachi, Marunouchi, Yurakucho district (OMY district) to solve the environmental and social issues and contribute for their city to be sustainable. This thesis focuses on this OMY district that support a huge part of Japanese economy and aim to be the world most sustainable urban city to lead a sustainable earth in the future. When business leaders become main actors of sustainable city making, their business and economic knowledge and the interest to sustainability would be combined and influence the definition and understanding of ‘sustainability.’ It is important to acknowledge that the process of meaning making for sustainability, from a business perspective in capitalism and neoliberal society, has been influenced by historical factors that human beings has been prioritising economic growth and ideology of capitalism and affect the environment and vice versa. This also have impact on the structure of Tokyo including infrastructure, transportation, lifestyle, human behaviour in the future. In this circumstance, will it actually make the city sustainable for its environment, society and economy?

  • Lejonklo, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Friction and wear study of lean powder metallurgy steel in a lubricated sliding contact2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A fairly new technology used to produce metallic components is powder metallurgy (PM). Among the advantages with this technique are decreased cost of production for complex-shaped parts, new alloys are made possible, reduced end processing, less material loss, and vibrational damping effects. The downside is the number of pores created which can alter the tribological properties of the material.

    The focus of this report is to investigate how lean PM steel behaves under tribological contacts.  Friction and wear will be investigated using a pin-on-disc setup to mimic the sliding part of a gear tooth mesh.

    Previous studies show that the amount of wear, and if the wear increases or decreases with increased density is dependent on the degree of porosity and the pore size. This means that the wear might be minimized by optimizing the number of pores in the material and their shape and size.

    The result of this study shows that the friction coefficient decreases with increasing density. The wear coefficient show signs of the same correlations but further tests are needed. The main wear comes from adhesive wear, with signs of abrasive wear. The amount of abrasive wear seems to increase with an increase in density, supporting previous studies claiming that pores can trap wear debris and decrease the number of abrasive particles in the contact.

  • Persson, Tove
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Bergmark, Linnea
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Uttalet är toppen… av ett isberg: En kvalitativ studie om klasslärare, speciallärare och specialpedagogers arbete med elever som har en språkstörning.2019Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Diagnosen språkstörning hos barn är något som ofta försummas på de svenska skolorna och okunskapen kring ämnet, trots att diagnosen är så pass vanlig, är fortfarande väldigt stor. Studien belyser hur arbetet kring elever med språkstörning ser ut idag på skolor runt om i Mellansverige och även hur pedagoger reflekterar kring arbetet med dessa elever. Studien genomsyras av Lev Vygotskijs sociokulturella teori som även den svenska läroplanen lutar sig på idag. I studien utfördes sju kvalitativa intervjuer med lärare, speciallärare och en specialpedagog som arbetar med elever och lärare i årskurserna F-6 i olika kommuner i Mellansverige. Intervjumaterialet analyserades med färgteman och utgjorde resultatet. Resultatet visar att bildstöd, struktur och samarbete mellan lärare, speciallärare och specialpedagog är viktigt för ett optimalt lärande för elever med diagnostiserad språkstörning. Resultatet visar även en upplevd okunskap hos klasslärare om elever med diagnostiserad språkstörning som i sin tur kan leda till dåliga förutsättningar för elever med diagnostiserad språkstörning.

  • Rees, Rhianna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History.
    Seaweed is Sexy: The consumption and utilisation of seaweed throughout British history and the marketing that surrounds it2019Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Damp, rotting, smelly, rising from the depths, washed up on shorelines. Seaweed (or Macroalgae) has transitioned over time in its position and uses within the British Isles; as discussed in the thesis it has undergone an evolution from its historical use as a source of food in times of desperation, to the superfood it is lauded as today. Other applications, from medicinal to agricultural, have contributed to a narrative of seaweed’s identity over the centuries, to the appeal of seaweed as a food source in the present day. There is an increased interest in seaweed, especially for culinary purposes, in the British Isles. Research by chefs, cookbooks and innovative product ranges also frame the current attitudes in the use of seaweed in common everyday foods. The case study shows the challenges and opportunities in the current revitalised seaweed market, identifying marketing analysis approaches useful for changing the attitudes toward seaweed in the British Isles. Based on interviews with companies marketing seaweed, and a focus on Seagreens®, I draw on advertising theory and consultancy tools (such as SWOT, AGCC, ELM and DAGMAR) to analyse the current seaweed market defining what I call a ‘consumer triad’ of potential consumers. Findings indicate many possibilities for future USP endorsements depending on the target market, from health-orientated to sustainably farmed. Seaweed interest appears to be more knowledge than consumer driven, so the question instead surrounds the prospect of knowledge sharing in an integrated online manner. Meanwhile, challenges in farming, labelling and conservation within the EU hamper advancements in the field, with the balance shifting to invested interest in Blue Economy models and IMTA systems.