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  • Hallén, Mattias
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Comminution control using reinforcement learning: Comparing control strategies for size reduction in mineral processing2018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In mineral processing the grinding comminution process is an integral part since it is often the bottleneck of the concentrating process, thus small improvements may lead to large savings. By implementing a Reinforcement Learning controller this thesis aims to investigate if it is possible to control the grinding process more efficiently compared to traditional control strategies. Based on a calibrated plant simulation we compare existing control strategies with Proximal Policy Optimization and show possible increase in profitability under certain conditions.

  • Karlsson, Patrik
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    BILINGUALISM AND INHIBITORY CONTROL: The relationship between hours of speaking a second language and inhibition2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In the globalized world of today the ability to speak more than one language, known asbilingualism, has become more common now than ever. There is research indicating thatlanguage processing accounts for the well debated „bilingual advantage‟ in inhibitory control.The process of speech production is supposed to make retrieved words more accessible forfuture retrieval through a consolidation process. When there is an association between thewords there will be a competition in retrieval during speech production; a competition that issolved by inhibitory control. The hypothesis tested in this study was that more hours ofspeaking second language (L2) could be associated with better performance on threeinhibition tests; the Flanker task, the Stroop task and the Simon task, when controlling for ageand fluid intelligence. The study contained 241 participants between 50-75 years old. Theresults were not in line with the hypothesis, except for one result that was significant in theopposite direction of the hypothesis; indicating that hours of speaking L2 was associated withworse performance on the Stroop test Alternative considerations concerning the results arepresented in the discussion.

    Keywords: Bilingualism, Inhibition, memory retrieval.

  • Boateng, Vanessa
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Hälsoskyddstillsyn på bostäder som hyrs ut till nyanlända2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of this study is to map the municipalities’ public health supervision regarding apartments which is rent to persons who have a residence permit (previous asylum seekers). Municipalities were selected by using statistics over numbers of residence permit which were obtained from the Swedish Migration Agency. To find out how the municipalities works with supervision on this type of apartments, a survey was sent to the concerned municipalities. The result of the study was that 8 of 64 municipalities operate supervision on this type of apartments. To operate this kind of public health supervision the municipalities can e.g. use The Public Health Agency of Sweden’s supervisory guidance as a tool. Even though there are supervisory guidance, which can be used to operate public health supervision, there were municipalities who considered it insufficient.Which may be due to the fact that The Public Health Agency of Sweden does not have a specific supervisory guidance for apartments which is rent to persons who have a residence permit (previous asylum seekers). To make public health supervision on this type of apartments more efficient, the municipalities should cooperate with stakeholders e.g. Social Services Department and the Swedish Migration Agency to easily find this type of apartments. To make the supervision more effective, one can look after the good examples like the eight municipalities, among other things like send out letter with a prebooked date and the aim of the supervision to the real estate owner, operate supervision in project form, using checklist when operating supervision.

  • Bernulf, Jonna
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Utvärdering av kalkbehandlad sulfidjord i Ersmark, Umeå2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Acid sulfate soils cover a relatively large area of Sweden, especially the coast along Gulf of Botnia. As these soils in contact with oxygen they start to oxidize and the sulphide is converted to sulphate, leading to a strong acidification. Today, these acid sulfate soils often end up on landfills, which is not a sustainable solution as it is both costly and there is a risk of leakage. A company based in Umea has developed a method for neutralizing acid sulphate soil with hope that it can be reused as plant soil, by adding sand and calcium as well as organic matter. At present, the process is only half-finished as the organic matter is not yet added. This study determined how the treatment worked so far, how much sulphide and neutralizing potential remains in the soil, as well as a number of metals and nutrients commonly and preferably found in plant soil. The treated sulfide soil was compared with a plant soil nearby, along with comparison of data from four different studies elsewhere on sulphide soil and results from samples taken before the sulphide soil was treated. Results show that pH value was higher than before the treatment and total sulfur content had decreased, but is still twice as high compared to the plant soil. Sulphide is still found in the soil, but also a fair amount of calcium carbonate, which shows that the reaction is not completed but that the soil has the potential to be further neutralized. Metal content in the treated sulfide soil is similar to the plant soil. The humus content is at 1.3 % and lower than recommended. Depending on area of use the humus content has to increase, more or less. Based on the results of the analyzes, the treated soil cannot be used as plant soil at the present time. This because of the organic matter that has not yet been added, and that there is still sulphide left in the soil.

  • Sukhin, V. S.
    et al.
    Danyliuk, S. V.
    Sukhina, O. N.
    Zadnepryanniy, A. V.
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hermelin, H.
    Tarján, M.
    The investigation of PD-L1 expression as a prognostic marker for uterine sarcoma2018In: Морфологія, ISSN 1997-9665, Vol. 12, no 2, p. 62-71Article in journal (Refereed)
    Abstract [en]

    Background: The uterine sarcoma is a rare tumor with the unpredictable, aggressive clinical behavior. Medical science relies on the development of reliable tumor markers, on the basis of which the optimal treatment program can be chosen, and will be also possible to make a prognosis. The hyperexpression of PD-L1 in many cases correlates with unfavorable prognosis of the disease and is an important prognostic biomarker for some types of tumors: melanoma, kidney cancer, non-small cell lung cancer. The role of PD-L1 expression, as a tumor marker in sarcoma, remains unclear. Objective. The investigation of PD-L1 expression as a prognostic tumor marker for uterine sarcoma.

    Methods: There have been selected 30 uterine sarcoma patients stage I-II (T1-2NxM0), for immunohistochemistry analyze of PD-L1 expression. Depending on the morphological tumor types all the patients were distributed: leiomyosarcoma (LMS) - 20.0%, endometrial stromal sarcoma (ESS) - 46.7%, undifferentiated sarcoma (HC) - 33.3%.

    Results: Our results showed that 73.3 % of patients with uterine sarcoma exhibited low expression level of PD-L1. The moderate level and overexpression of PD-L1 were observed in undifferentiated and endometrial stromal sarcoma - 13.3 and 6.7 %, respectively. At further follow-up of patients with PD-L1 expression, the relapse of the disease was detected in 50.0 % of cases.

    Conclusion: The PD-L1 expression in tumor tissue, regardless of its level, is considered to be an unfavorable prognostic factor for uterine sarcoma patients. In case of moderate expression level of PD-L1, so as at its overexpression, the tumor progression was detected in 83.3% of uterine sarcoma patients.

  • Sukhin, V. S.
    et al.
    Danyliuk, S. V.
    Sukhina, O. M.
    Sadniprjaniy, O. V.
    Lindquist, David
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hermelin, H.
    Tarján, M.
    Expression of mmp-9 as a prognostic factor of uterine sarcoma2018In: Reports of morphology, ISSN 1818-1295, Vol. 24, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Uterine sarcoma is a highly aggressive mesenchymal neoplasm with an extremely unfavorable prognosis. Up today there are still relevant issues concerning search for clinical-morphological and biomolecular criteria for prognosis relapse-free survival of uterine sarcoma patients. It is well-known, the increase of the expression level of MMP-9 in primary tumor or metastatic foci correlates with a low differentiation of tumor cells, high ability for invasiveness, high metastatic activity, and shortened life expectancy. It’s still unknown, whether it is possible to consider the expression of MMP-9 in uterine sarcoma cells as a convincing prognostic factor. For many types of epithelial malignant neoplasms, high metastatic rate is associated with an increase level of MMP-9 both in plasma and in tumor tissue. The purpose of this study is to investigate the features of MMP-9 expression in uterine sarcoma cells for development of the model for individual prediction of the disease course. The study of the surgical material of selected 54 cases of uterine sarcoma of stage I-II (according to FIGO criteria) with a known prognosis of the disease, which were distributed depending on the morphological type done: leiomyosarcoma (LMS) – 18 cases, endometrial stromal sarcoma (ESS) - 22 cases, undifferentiated sarcoma (US) – 14 (according to the classification of tumors of the uterus of the WHO). For histological examination, pieces of tissue were cut from different parts of the tumor nodes – central, peripheral, parts of the adjacent intact tissue of myometrium (total of 6-8 bits). The tumor cell phenotype was determined using low molecular weight cytokeratins (Cytokeratin PAN, AE1 / AE3), smooth muscle actin (Smooth Muscle Actin, 1A4), myogenin (Myogenin (F5D)), CD 10 and vimentin (Vimentin, V9). The histochemical label was evaluated in two parameters: the degree of prevalence and intensity of coloration. To assess the color intensity, a qualitative scale was used: 0 – no reaction, 1+ – weak cytoplasmic coloration to 30.0% of tumor cells, 2+ – moderate reaction, 30.0 to 60.0% of stained cells, 3+ – pronounced cytoplasmic reaction in 60,0-100,0% of tumor cells. Statistical processing of the data was performed using the “STATISTICA 10.0” program package. The conducted study has showed, the negative (0) and weak (1+) expression of matrix metalloproteinase-9 were observed in the most part of ESS and only partially in US. Despite the stage of the disease, with such a status of MMP-9, there was observed no signs of relapsed disease. The moderate (2+) and high (3+) expression of MMP-9 was detected in 44.5 % of uterine sarcoma, in the most part in LMS patients. However, if in LMS cases the progressive disease was observed only in one third of them (4 of 12 cases), in case of ESS and US, in all the patients with such tumors status there was observed relapsed disease. Such a reaction may be indicative for invasive and metastatic potential of ESS and US and cause of the hematogenous metastases.

  • Public defence: 2018-12-04 09:00 Betula, Byggnad 6M, Umeå
    Rawcliffe, Denise F. R.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    The regulation of incorrect splicing of ISCU in hereditary myopathy with lactic acidosis2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Patients suffering from hereditary myopathy with lactic acidosis (HML) can be found in the northern Swedish counties of Ångermanland and Västerbotten. HML is a rare autosomal recessive disease where patients display a low tolerance to exercise at an early age. Exercise can trigger symptoms such as palpitations, tachycardia, muscle cramps and dyspnoea. Extensive exercise or strict diets can result in myoglobinuria and life-threatening levels of lactic acid. The disease is caused by a nonsense G > C mutation (c.418 + 328G < C) in the last intron of the iron-sulphur (FeS) cluster assembly gene (ISCU), resulting in nonsense-mediated decay (NMD) of the transcript due to incorrect splicing. The ISCU protein is involved in the assembly of FeS clusters, which are essential cofactors for a wide range of proteins. Patient muscles display decreased levels of several FeS cluster proteins: mitochondrial aconitase in the tricarboxylic acid (TCA) cycle and Complex I, II (succinate dehydrogenase [SDH]) and III in the electron transport chain (ETC). The incorrect splicing of ISCU occurs to the highest extent in HML patient skeletal muscle, restricting the loss of ISCU protein to muscles, thereby preventing a more severe phenotype.

    We found that the incorrect splicing occurs to the highest extent in slow-fibre muscle, which may be caused by the serine/arginine-rich splicing factor (SRSF3) as it is expressed at higher levels in slow-fibre muscle compared to other muscles, and since it is able to activate the incorrect splicing of ISCU. Following muscle, there is a gradual decrease of the incorrect splicing in heart, brain, liver and kidney, which is negatively correlated with the levels of the splicing inhibitor polypyrimidine-tract binding protein 1 (PTBP1). Overexpression of PTBP1 in HML patient myoblasts resulted in a drastic decrease in the incorrect splicing, while a PTBP1 knockdown had the opposite effect. Our results suggest that PTBP1 acts as a dominant inhibitor of the incorrect splicing and is likely the main cause for the tissue-specific splicing of ISCU in HML. We also identified RBM39 and MBNL1 as activators of the incorrect splicing of ISCU, which, together with the low levels of PTBP1, could explain the high levels of incorrect splicing in muscle.

    Since almost 95% of all human gene transcripts are alternatively spliced, it is not surprising that a wide range of diseases are caused by mutations that affect splicing. Further knowledge of the function of splicing, such as tissue-specific splicing, can provide vital information for the development of therapies for diseases caused by splicing.

  • Hagner, Johan
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Recurrent Neural Networks for End-to-End Speech Recognition: A comparison of gated units in an acoustic model2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    End-to-end speech recognition is the problem of mapping raw audio signal all the way to text. In doing so the process is not explicitly divided into modules. e.g. [signal → phoneme, phoneme → word]. Recurrentneural networks equipped with specialised temporal based loss functions have recently demonstrated breakthrough results for the end-to-end problem.In this thesis we evaluate a number of neural network architectures for end-to-end learning. LSTM (Long Short Term Memory) is a specialised gated recurrent unit that preserves a signal within a neura lnetwork over period of time. GRU (Gated recurrent Unit) is a recently discovered refinement of LSTM with still unknown performance characteristics. It is reported that different architectures works better or worse depending on the problem at hand. We explore these characteristics for the end-to-end speech recognition problem. Specifically we evaluate various networks on the LibriSpeech corpus. All the audio is read in English by people from different parts of the world. The audio files are excerpts sourced from audio books. The LibriSpeech corpus is divided into both noisy and clean audio. The noisy audio is considered to be more challenging. This corpus is pre-segmented and thus contain ready sub sets for testing. These include both noisy and clean audio and we will evaluate the end-to-end models on both sets. The findings of our experiments shows that GRU can not perform on the same level as LSTM variants. Especially not when trained on noisy data where the GRU network stop improving after only a small part of the allotted training time.

  • Lippman, Sheri A.
    et al.
    Leddy, Anna M.
    Neilands, Torsten B.
    Ahern, Jennifer
    MacPhail, Catherine
    Wagner, Ryan G.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
    Peacock, Dean
    Twine, Rhian
    Goin, Dana E.
    Gómez-Olivé, F. Xavier
    Selin, Amanda
    Tollman, Stephen M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; INDEPTH Network, Accra, Ghana.
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
    Pettifor, Audrey
    Village community mobilization is associated with reduced HIV incidence in young South African women participating in the HPTN 068 study cohort2018In: Journal of the International AIDS Society, ISSN 1758-2652, E-ISSN 1758-2652, Vol. 21, no S7, article id e25182Article in journal (Refereed)
    Abstract [en]

    Introduction: Adolescent girls and young women (AGYW) in South Africa bear a disproportionate burden of HIV. Community mobilization (CM), defined as community members taking collective action to achieve a common goal related to health, equity and rights, has been associated with increased HIV testing and condom use and has been called a ‘critical enabler’ for addressing the HIV epidemic. However, limited research has examined whether CM is associated with HIV incidence among AGYW.

    Methods: We examine the association of CM with incident HIV among AGYW (ages 13 to 21) enrolled in the HPTN 068 cohort in the Agincourt Health and socio‐Demographic Surveillance System, South Africa. This analysis includes 2292 participants residing in 26 villages where cross‐sectional, population‐based surveys were conducted to measure CM among 18‐ to 35‐year‐old residents in 2012 and 2014. HPTN 068 participants completed up to five annual visits that included an HIV test (2011 to 2016). Household‐level data were collected from AGYW parents/guardians and census data is updated annually. Mean village‐level CM scores were created using a validated community mobilization measure with seven components (social cohesion, social control, critical consciousness, shared concerns, organizations and networks, leadership and collective action). We used pooled generalized estimating equation regression with a Poisson distribution to estimate risk ratios (RR) for the association of village‐level CM score and CM components with incident HIV infection, accounting for village‐level clustering and adjusting for key covariates.

    Results: There were 194 incident infections over the follow‐up period. For every additional standard deviation of village‐level CM there was 12% lower HIV incidence (RR: 0.88, 95% CI: 0.79, 0.98) after adjusting for individual, household and community characteristics. CM components associated with lower HIV incidence included critical consciousness (RR: 0.88; CI: 0.79, 0.97) and leadership (RR: 0.87; CI: 0.79, 0.95); while not statistically significant, social cohesion (RR: 0.91; CI: 0.81, 1.01), shared concerns (RR: 0.90; CI: 0.81, 1.00), and organizations and networks (RR: 0.91; CI: 0.79, 1.03) may also play a protective role.

    Conclusions: These results suggest that having strong community social resources will reduce AGYW's risk of HIV acquisition. Work to mobilize communities, focusing on building social cohesion, shared concerns, critical consciousness, and effective and accountable leadership, can fortify prevention programming for AGYW.

  • Rozman Grinberg, Inna
    et al.
    Lundin, Daniel
    Sahlin, Margareta
    Crona, Mikael
    Berggren, Gustav
    Hofer, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Sjöberg, Britt-Marie
    A glutaredoxin domain fused to the radical-generating subunit of ribonucleotide reductase (RNR) functions as an efficient RNR reductant2018In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 293, no 41, p. 15889-15900Article in journal (Refereed)
    Abstract [en]

    Class I ribonucleotide reductase (RNR) consists of a catalytic subunit (NrdA) and a radical-generating subunit (NrdB) that together catalyze reduction of ribonucleotides to their corresponding deoxyribonucleotides. NrdB from the firmicute Facklamia ignava is a unique fusion protein with N-terminal add-ons of a glutaredoxin (Grx) domain followed by an ATP-binding domain, the ATP cone. Grx, usually encoded separately from the RNR operon, is a known RNR reductant. We show that the fused Grx domain functions as an efficient reductant of the F. ignava class I RNR via the common dithiol mechanism and, interestingly, also via a monothiol mechanism, although less efficiently. To our knowledge, a Grx that uses both of these two reaction mechanisms has not previously been observed with a native substrate. The ATP cone is in most RNRs an N-terminal domain of the catalytic subunit. It is an allosteric on/off switch promoting ribonucleotide reduction in the presence of ATP and inhibiting RNR activity in the presence of dATP. We found that dATP bound to the ATP cone of F. ignava NrdB promotes formation of tetramers that cannot form active complexes with NrdA. The ATP cone bound two dATP molecules but only one ATP molecule. F. ignava NrdB contains the recently identified radical-generating cofactor MnIII/MnIV. We show that NrdA from F. ignava can form a catalytically competent RNR with the MnIII/MnIV-containing NrdB from the flavobacterium Leeuwenhoekiella blandensis. In conclusion, F. ignava NrdB is fused with a Grx functioning as an RNR reductant and an ATP cone serving as an on/off switch.

  • Eriksson, Rebecca
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Legionella i kyltorn: Enkätundersökning gällande kommuners och länsstyrelsers tillsyn på kyltorn och behovet av ökad prioritering2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    If cooling towers are poorly maintained there is a risk of microbial growth such as Legionella which in turn might spread via aerosols and infect humans. This may lead to an outbreak of legionnaires’ disease. The purpose of this study was to highlight the risks of Legionella and cooling towers along with investigating the legal responsibility of businesses and supervision authorities in this regard. The study also investigated whether business should be obligated to register their cooling towers at supervising authorities. The study was partly based on a survey which was sent to Sweden’s 290 municipalities and 21 county administration boards to investigate their knowledge regarding Legionella and cooling towers and if they had inventoried which of their facilities that uses cooling towers. The results of the survey showed that 16% of the municipalities and none of the county administration board had inventoried which of their facilities that uses cooling towers. Half of the municipalities do not have any knowledge if any of their facilities uses cooling towers. Moreover, 45% of the municipalities and 30% of the county administration boards consider that business should register their cooling towers. The results showed that many of Sweden’s municipalities and county administration boards have shortcomings in their knowledge and supervision. Legislation and priorities need to be assessed and regulatory guidance from the Public Health Agency of Sweden is necessary for future progress.

  • Biedenbach, Galina
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Business Administration.
    Boström, Gert-Olof
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Business Administration.
    A data-driven lab in the context of open data: opportunities and challenges for a sustainable business model2018Report (Other academic)
    Abstract [en]

    The report investigates theoretical and practical perspectives on sustainable business models in the context of open data. The main purposes of this report are (1) to investigate the opportunities and challenges for establishing a regional data-driven lab in the context of open data, and (2) to explore the possibility of developing a sustainable business model for a data-driven lab in Umeå (Västerbotten). The report examines conceptualizations of open data that initially emerged in the public sector and highlights the requirements open data are expected to comply with. The report identifies several types and categories of open data, which can be used to provide a variety of benefits for the public and private sectors, stimulate data-driven innovation, and enhance public value. In addition, the report acknowledges the barriers to the publishing and re-use of open data. The review of contextual conditions includes prominent examples of international, regional, and national initiatives for stimulating practical activities and policy-making in the context of open data. Furthermore, the report addresses different theoretical perspectives on how to conceptualize business models, ranging from presenting a company’s organization and its strategic view to emphasizing the elements required for creating, delivering, and capturing value in a specific context. The report elaborates upon the capacities of sustainable business models to achieve long-term success through business model innovation and to address environmental and social challenges while sustaining economic performance. Furthermore, the report emphasizes the importance of considering a complex ecosystem engaging diverse stakeholder groups and the open data lifecycle for developing a successful business model in the context of open data. The report reviews the business models used in the open data industry and discusses the important practical considerations for a data-driven lab. Overall, the report emphasizes the critical importance of creating the conditions that will enable the valuable resource of open data to be exploited and prioritizing the establishment of a regional data-driven lab by considering its potential to stimulate data-driven innovation and increase public value for society.

  • Ching, Rosanna C.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Schwann cell-like differentiated adipose stem cells promote neurite outgrowth via secreted exosomes and RNA transfer2018In: Stem Cell Research & Therapy, E-ISSN 1757-6512, Vol. 9, article id 266Article in journal (Refereed)
    Abstract [en]

    Background: Adipose derived stem cells can be stimulated to produce a growth factor rich secretome which enhances axon regeneration. In this study we investigated the importance of exosomes, extracellular vesicles released by many different cell types, including stem cells and endogenous nervous system Schwann cells (SCs), on neurite outgrowth.

    Methods: Adipose derived stem cells were differentiated towards a Schwann cell-like phenotype (dADSCs) by in vitro stimulation with a mix of factors (basic fibroblast growth factor, platelet derived growth factor-AA, neuregulin-1 and forskolin). Using a precipitation and low-speed centrifugation protocol the extracellular vesicles were isolated from the medium of the stem cells cultures and also from primary SCs. The conditioned media or concentrated vesicles were applied to neurons in vitro and computerised image analysis was used to assess neurite outgrowth. Total RNA was purified from the extracellular vesicles and investigated using qRT-PCR.

    Results: Application of exosomes derived from SCs significantly enhanced in vitro neurite outgrowth and this was replicated by the exosomes from dADSCs. qRT-PCR demonstrated that the exosomes contained mRNAs and miRNAs known to play a role in nerve regeneration and these molecules were up-regulated by the Schwann cell differentiation protocol. Transfer of fluorescently tagged exosomal RNA to neurons was detected and destruction of the RNA by UV-irradiation significantly reduced the dADSCs exosome effects on neurite outgrowth. In contrast, this process had no significant effect on the SCs-derived exosomes.

    Conclusions: In summary, this work suggests that stem cell-derived exosomes might be a useful adjunct to other novel therapeutic interventions in nerve repair.

  • Rodríguez, Maria Angels
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Parkkonen, Kimmo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Li, Zhenlin
    Domellöf, Fatima Pedrosa
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    The Cytoskeleton in the Extraocular Muscles of Desmin Knockout Mice2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 12, p. 4847-4855Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the effect of absence of desmin on the extraocular muscles (EOMs) with focus on the structure and composition of the cytoskeleton.

    Methods: The distribution of synemin, syncoilin, plectin, nestin, and dystrophin was evaluated on cross and longitudinal sections of EOMs and limb muscles from 1-year-old desmin knockout mice (desmin−/−) by immunofluorescence. General morphology was evaluated with hematoxylin and eosin while mitochondrial content and distribution were evaluated by succinate dehydrogenase (SDH) and modified Gomori trichrome stainings.

    Results: The muscle fibers of the EOMs in desmin−/− mice were remarkably well preserved in contrast to those in the severely affected soleus and the slightly affected gastrocnemius muscles. There were no signs of muscular pathology in the EOMs and all cytoskeletal proteins studied showed a correct location at sarcolemma and Z-discs. However, an increase of SDH staining and mitochondrial aggregates under the sarcolemma was detected.

    Conclusions: The structure of the EOMs was well preserved in the absence of desmin. We suggest that desmin is not necessary for correct synemin, syncoilin, plectin, and dystrophin location on the cytoskeleton of EOMs. However, it is needed to maintain an appropriate mitochondrial distribution in both EOMs and limb muscles.

  • Sandvig, Axel
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.
    Arnell, Kai
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Analysis of Codman microcerebrospinal fluid shunt2018In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 8, no 10, article id e01002Article in journal (Refereed)
    Abstract [en]

    Introduction: Ventriculo-peritoneal cerebrospinal fluid (CSF) shunt is the most common method of treating pediatric hydrocephalus. The Codman microadjustable valve (CMAV) is a CSF shunt constructed for children. The objective of the study was (a) to analyze complications after insertion of a CMAV shunt in hydrocephalic children, (b)to analyze complications after replacing a CMAV by an adult-type Codman Hakim adjustable valve shunt (CHAV), and to (c) analyze the in vitro characteristics of the CMAV shunt and correlate the findings with the clinical performance of the shunt.

    Methods: A retrospective study analyzed a cohort of hydrocephalic children who had received a CMAV shunt and later replaced by a CHAV shunt. We report on the complications that resulted from replacing the CMAV with the CHAV. We tested six CMAV shunts with or without an antisiphon device (ASD) in which opening pressure, resistance, sensitivity to abdominal pressure, ASD position dependency, and function were determined. The test results were correlated with the clinical performance of the shunt in the retrospective study.

    Results: Thirty-seven children (19 boys, 18 girls) were identified. Within the first month after shunt placement, a total of 10 patients (27%) developed complications including infections, hygromas, and shunt dysfunction. Shunt survival varied from 1week to 145 months. Over the 10-year follow-up period, 13 children had their shunts replaced, six of them with a CHAV without any further complications. A bench test of the CMAV was done to test whether the opening pressure was in agreement with the manufacturer's specifications. Our results were generally in agreement with specifications stated by the manufacturer.

    Conclusion: Replacing a CMAV with a CHAV was well tolerated by the patients. Bench test results were generally in agreement with manufacturers specifications. Replacing a CMAV with a CHAV in pediatric hydrocephalus patients can be accomplished safely.

  • Chahlafi, Zahra
    et al.
    Alvarez, Laura
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Cava, Felipe
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Berenguer, José
    The role of conserved proteins DrpA and DrpB in nitrate respiration of Thermus thermophilus2018In: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 20, no 10, p. 3851-3861Article in journal (Refereed)
    Abstract [en]

    In many Thermus thermophilus strains, nitrate respiration is encoded in mobile genetic regions, along with regulatory circuits that modulate its expression based on anoxia and nitrate presence. The oxygen‐responsive system has been identified as the product of the dnrST (dnr) operon located immediately upstream of the nar operon (narCGHJIKT), which encodes the nitrate reductase (NR) and nitrate/nitrite transporters. In contrast, the nature of the nitrate sensory system is not known. Here, we analyse the putative nitrate‐sensing role of the bicistronic drp operon (drpAB) present downstream of the nar operon in most denitrifying Thermus spp. Expression of drp was found to depend on the master regulator DnrT, whereas the absence of DrpA or DrpB increased the expression of both DnrS and DnrT and, concomitantly, of the NR. Absence of both proteins made expression from the dnr and nar operons independent of nitrate. Polyclonal antisera allowed us to identify DrpA as a periplasmic protein and DrpB as a membrane protein, with capacity to bind to the cytoplasmic membrane. Here, we propose a role for DrpA/DrpB as nitrate sensors during denitrification.

  • Albin, Irgens
    Umeå University, Faculty of Arts, Department of historical, philosophical and religious studies.
    Det Stora Vilddjuret och Yogan: En religionshistorisk studie av Aleister Crowleys yoga och hans påverkan på sentida efterföljare i Sverige2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Den här uppsatsen behandlar den brittiske tänkaren Aleister Crowley, hans tolkning avyoga, och hans tankars påverkan på moderna efterföljare av hans religion i Sverige.Uppsatsen behandlar frågorna om hur Crowleys syn på yoga utvecklats och hur denkan ses i svenska efterföljares tankar idag. Uppsatsen använder sig av litteraturstudierav Crowleys verk, samt intervjuer med medlemmar i ordern Ordo Templi OrientisSverige. Uppsatsen utmynnar i att Crowleys tankar om yoga kan ses i sin historiskakontext påverkad av bland annat orientalism och religionism, och att Crowleys tankarfortsätter påverka moderna utövare av yoga inom O.T.O.

  • Håkansson, Susanna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Roxbo, Sara
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Optimal fördelning av anställningsformer på SJ: Ett planeringsprogram baserat på villkorsprogrammering och kända schemakäggningsproblem2018Independent thesis Advanced level (degree of Master (One Year)), 300 HE creditsStudent thesis
    Abstract [sv]

    A big challenge for many companies, road haulers business among others, is how to make a schedule for all employees. Scheduling problems handles a big number of constraints which also increase the complexity of the problem.

     

    It is important to SJ that all train departures are staffed. SJ offers both permanent and temporary employments but during recruitment in connection to the summer they only hire temporary employees. It often happens that SJ hires a larger number of workers than needed, and as a consequence of this some of the employees does not get to work the number of hours the wishes and they might turn to other employers. Temporary employments can result in uncertainty for SJ as they can choose when to work. Due to this, SJ now wants to examine the possibility to hire permanent employees during the summer and they also want to examine how the distribution of employments should look like for different stations and time periods.

     

    Important constraints for scheduling and planning have been identified and formulated, and these have formed the basis to the optimization problem that is indented to be solved. A scheduling tool, EAPS, has been developed and with help from this minimal staff set and employment arrangements for boarders can be identified. EAPS ensure that each worker is free every other weekend, that no worker is assigned more shifts than allowed for the analyzed period and that they do not work more shifts in a row than allowed. EAPS ensure that all departures are covered by boarders at the same time as the number of workers are minimized.

  • Öhlund, Hanna
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Modelling of a solar project network for time improvement2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis is written for the Finnish company Wärtsilä and looks into the project processes of an EPC solar project and an EPC Engine power plant project to find similarities, by looking into both qualitative and quantitative aspects. This is done so that Wärtsilä may use the information gained from the engine power plant projects to further their solar projects by cutting down the total project time. These comparisons are done by collecting data from interviews and from constructing a project network for both projects, which is then remade into a linear program, solved, and then evaluated by sensitivity analysis and looking into the critical paths and slack times of both networks. This data is then used to present a recommendation to Wärtsilä on which activities should be prioritised when trying to improve the project time. These recommendations include looking into container usage, the installation process of posts and photovoltaic panels, as well as allocation of manpower for civil work.

  • Eriksson, Anna
    et al.
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Kristoffersson, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Skärmönstergenerering för 2D-cutting stock problem: Råmaterialsoptimering med fyra olika optimeringsmodeller för Olofsfors AB2018Independent thesis Advanced level (professional degree), 300 HE creditsStudent thesis
    Abstract [sv]

    Olofsfors AB beställer idag stålplåtar, remsor och stänger av stålleveran- törer för sin produktion av skop- och vägstål samt skogsband. Stålremsorna för produktion av skop- och vägstål beställs i dimensioner som är redo att skä- ras endimensionellt och vidarebehandlas till skopstålsdetaljer i fabriken. För att effektivisera produktionen i form av ekonomibesparingar och minskning av spill har Olofsfors AB köpt en ny maskin som kan behandla större plåtar och skära ut mindre remsor från dessa och de kan således göra ekonomiska besparingar tack vare billigare inköp.

    Företaget vill hitta en metod som minimerar spill av material vilket ska leda till ekonomiska besparingar. Syftet med projektet är att utveckla ett program som Olofsfors AB kan använda sig av i den dagliga verksamheten för att optimera materialanvändningen.

    Problemet att skära ut mindre bitar ur ett större råmaterial är vanligt i industrier och kallas Cutting stock problem. Vi har använt oss av en redan utvecklad modell bestående av en modifierad branch & bound-algoritm för att hitta möjliga mönster som kan skäras ut ur råmaterialet, implementerat den i MATLAB® samt förbättrat den. Vidare har det använts fyra olika optimeringsmodeller vilka lett till olika heltalsprogram som samtliga lösts med den inbyggda MATLAB®-metoden intlinprog, vilken använder sig av branch & bound som lösningsmetod.

    Resultatet gav ett för användaren lättanvänt program som ger förslag på en optimal dimension bland en mängd möjliga dimensioner på ett råmate- rial, utifrån årsvolym och dimensioner för remsor eller stänger. Föreslagen dimension är den dimension som resulterar i så låg materialförbrukning som möjligt. Utöver detta kan Olofsfors AB använda detta program för att hitta vilka mönster som ska skäras ut givet efterfrågan, samt använda utdata från programmet för att reda ut kapacitetsgräns i restbitslager och finna vilka lagerartiklar som är särskilt lämpliga att producera från restbitar.

  • Gavelin, Hanna
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Från fjäll till stad: En studie om bemanningsproblematiken av polisens ingripandeverksamhet i glesbygd2018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The Swedish Police Authority is an authority with objective to handle, investigate and prevent criminality in Sweden. The authority is divided into seven regions with corresponding police areas and local police areas. South Lapland in police area Västerbotten is a geographically big local police area with rural areas and long travelling distances characterizing the area. The number of incidents needing police resources is limited, the number of police workers is sometimes low, and a lot of work time is spent on transports, leading to conflicts in degree of service to the public, costs/resource allocation and working environment.

    The purpose of the study is to investigate possible improvements of the manning of the patrolling units in South Lapland by studying and comparing several manning scenarios. The scenarios were evaluated by the probability to handle incidents reached by the police through the public with priority 1, 2 and 3 within certain time references using the chosen scenario manning. A comparison with a Norwegian proposition of time limits for call outs of the Norwegian Police was also made. To study the problem, a model that simulates incidents based on processed statistics was created, to calculate the time consumption for patrols to handle incidents given the different scenarios. The scenarios have been analysed and internally compared to end up in conclusions of possible improvements of the manning of patrols in South Lapland.

    The study shows that the frequency of incidents reaching the police through the public in the different communities in South Lapland tend to correlate with the population in the communities. The distribution of incidents does not differ much when studying either day shift, evening shift, night shift, weekends or priority. The result shows that it seems to be preferable to have patrols in both west and east areas of South Lapland to increase the probability of decreasing the call out time. Lycksele, Storuman and Vilhelmina seem to be important cities for the manning planning due to their geographically strategic placement, together with the fact that these cities have the biggest population and incident frequency. Having one patrol in Lycksele, Storuman and Vilhelmina is shown to be the most preferable scenario studied, with 45% of the incidents handled within 30 minutes and 83% within one hour. This scenario is also the scenario closest to the Norwegian proposition of call out time limits. The result with three patrols in the area needs a lot of workers in relation to the incident frequency, which makes further studies of creative solutions to reach a well-balanced solution between service level, working environment and practical implementation as the next suggested step.

  • Public defence: 2018-12-07 09:00 Sal D, byggnad 1D, Tandläkarhögskolan, Umeå
    Isehed, Catrine
    Umeå University, Faculty of Medicine, Department of Odontology. Folktandvården Gävleborg AB, Region Gävleborg.
    Peri-implantitis: treatment and effects of enamel matrix derivative2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biological complications affecting osseointegrated dental implants are a growing treatment problem in clinical practice. Since the number of implant carriers has increased in recent decades, this is an urgent topic in dentistry. Peri-implantitis, inflammatory degradation of the implant-supporting jawbone, affects approximately 20% of all implant carriers and approximately 10% of all implants.

    Implant surfaces are colonised by microbes that may cause an inflammatory process in the soft tissue around the implant. In some sensitive individuals, the inflammatory response leads to disturbed jawbone remodelling, with increased recruitment and activity of bone-resorbing osteoclasts, which could ultimately lead to implant loss. The corresponding degradation of the bone supporting the teeth is denoted as periodontitis. The current view is that factors such as proinflammatory cytokines and prostaglandins, produced by leukocytes and cells of mesenchymal origin in the inflamed connective tissue, are responsible for local osteoclast recruitment and activation. Pro-inflammatory factors and tissue degradation products will leak into the exudate in the peri-implant sulci and the gingival pockets around the teeth. Analysis of the exudate could be of use for predicting and monitoring peri-implantitis, as well as identifying new targets for treatment.

    The standard treatment for peri-implantitis is surgery in combination with mechanical cleaning of the implant surface and optimisation of oral hygiene, with the goal of achieving infection control and pocket reduction. This treatment has a moderate effect on healing of the peri-implantitis lesion around the dental implant. The use of adjunctive bone grafts, membranes and antimicrobials has thus far not been shown to achieve a more successful outcome. Adjunctive treatment with enamel matrix derivative (EMD) during regenerative periodontal surgery contributes to wound healing and increased tissue support, but the adjunctive effect of EMD during surgical treatment of peri-implantitis remains unknown.

    The overall aim of this thesis was to investigate the outcome of a regenerative surgical treatment approach with and without adjunctive EMD treatment from the short- and long-term perspectives and to increase our knowledge of microbial flora and biomarkers in the peri-implant sulci before and after treatment. Furthermore, an additional aim of this work was to investigate whether EMD could directly affect osteoclast formation and activity.

    We performed a randomised controlled clinical trial of a surgical intervention for peri-implantitis with and without EMD. In multivariate modelling, an increased marginal bone level at the implant site 12 months after surgery was significantly associated with EMD, the number of osseous walls in the peri-implant bone defect and a gram-positive/aerobic microbial flora, whereas a reduced bone level was associated with a gram-negative/anaerobic microbial flora and the presence of bleeding and pus, with a cross-validated predictive capacity (Q2) of 36.4%. Similar trends were observed for bone level, pocket depth, plaque, pus and bleeding, but these associations were statistically non-significant in the univariate analysis. Five years after treatment, no significant differences in bone level changes were observed between groups, but fewer implants were lost to follow-up due to reinfections in the EMD-treated group.

    We used mass spectrometry to analyse the protein content in peri-implant crevicular fluid (PICF) before and up to 12 months after treatment. The total protein amount and diversity displayed decreasing trends 3, 6 and 12 months after treatment. Multivariate analysis of the PICF protein content revealed two major groups, cluster 2 and cluster 3, of which cluster 2 was associated with an increased risk of implant loss. EMD treatment was associated with cluster 3, which was in turn associated with increased implant survival.

    To test whether EMD affects osteoclast formation or bone resorption, we added purified EMD to RANKL-stimulated mouse bone marrow macrophage cultures in plastic dishes and counted the number of osteoclasts. We also cultured the cells on bone slices and measured the secretion of TRAP5b and the release of CTX-1 into the culture medium as biomarkers of osteoclast numbers and bone resorption, respectively, but no effect of EMD was observed.

    In conclusion, adjunctive EMD during surgical treatment of peri-implantitis changed the microbial flora to a less pathogenic microbiota, and similar changes in the inflammatory protein profile of PICF were observed; these effects were associated with implant survival. However, the trend toward a positive healing response after EMD treatment was not associated with a significant radiographic bone gain in this study and needs to be further explored. In addition, our finding that EMD did not affect osteoclast formation or bone resorption in vitro indicates that the effect of EMD on bone regeneration, as seen in periodontitis treatment, does not seem to depend on a direct inhibitory effect on osteoclast formation or bone resorption.

  • Public defence: 2018-11-30 09:00 Betula, målpunkt L, by 6M, plan 0, Umeå
    Toppe, Cecilia
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    End stage renal disease in type 1 diabetes: time trends and risk factors2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims: Sweden has a high incidence of type 1 diabetes (T1D) and the incidence is increasing worldwide. The incidence is now twice as high as when the registration of childhood onset T1D in Sweden started in 1977. One of the major risk factors for developing late complications such as renal failure (ESRD) is duration of T1D. With a disease onset early in life this could lead to young patients with serious complications. It is therefore of interest to follow these patients to see how the risk for complications develops over time. In the first study, time trends in onset of ESRD due to diabetes (type 1 and 2) and other causes of kidney failure were studied as well as the age at onset of ESRD. To follow up on this, the aim of the second study was to look at cumulative incidence in ESRD and analyse possible time trends and gender differences in a younger diabetes population with known T1D duration. An earlier study had shown a low incidence of ESRD and now 8 more years of follow up could be added. Besides genetics, metabolic control is a factor with strong impact on the future risk of complications. The social environment of the child and adolescent with diabetes influence the understanding and management of the disease and hence the blood glucose control. Social vulnerability and/or low education imposes even more stress on the individual which could negatively influence disease management. The aim of the third study was therefore to study the impact of socio-economic status (SES) on the risk of developing ESRD in the young diabetes population. The aim of the fourth study was to analyse time trends in the treatment choices once the patients develop ESRD, the survival and cause of death in treatment and how it has developed over time.

    Study population: In all studies, data from the Swedish Renal Register (SRR) were used. The data on the T1D patients with onset before the age of 15, used in studies II-IV, came from the Swedish Childhood Diabetes Register (SCDR).  In study II we also retrieved data from the Swedish National Diabetes Register (NDR) and the Diabetes Incidence Study in Sweden (DISS). All registers have national coverage. The diabetes registers were linked to the SRR to find the patients who had developed ESRD. In study III we used the linkage between the SCDR, the SRR and Longitudinal integration database for health insurance and labour market studies (LISA).

    Results: Even though the incidence of ESRD in Sweden remained stable, the incidence of ESRD due to T1D decreased over the studied years, 1991-2010. We did not see a concurrent change for T2D. The age when the T1D patients developed ESRD had increased by 3 years and this was not seen in patients with other causes of ESRD. For patients in the SCDR the increase in age was almost 6 years. The cumulative incidence of ERSD in Sweden due to T1D is still low, 5.6% at a maximum follow up of 38 years (median 23). The incidence of ESRD is decreasing when comparing onset of T1D in the 1970´s and 80´s to onset in the 90´s, even when adjusting for T1D duration. Once they had developed ESRD, the survival in renal replacement therapy (RRT) had also improved over the years. The longest survival was seen after receiving a kidney transplant which about 50% of the patients do.

    When analysing social risk factors for development of ESRD we found that the educational level of both parents, but especially the mothers, affected the child’s risk of developing ESRD. The strongest association of education however was seen in the T1D patients own education. There was also an increased risk of developing ESRD if any or both of the parents had received income support.

    Conclusion: The incidence of ESRD due to T1D is decreasing in Sweden and the age at onset of ESRD has increased by at least 3 years. There was a significant decrease in development of ESRD over time. The patients have a longer survival once in RRT today and many of them are transplanted, further improving their survival. Growing up in families with a lower SES increases the risk of later developing ESRD, a finding worthy of recognition in the clinical setting.

  • Public defence: 2018-11-30 10:00 N450, Naturvetarhuset, Umeå
    Hausmaninger, Thomas
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Mid- and near-infrared NICE-OHMS: techniques for ultra-sensitive detection of molecules in gas phase2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Noise-immune cavity-enhanced optical heterodyne molecular spectrometry (NICE-OHMS) is a technique for ultra-sensitive detection of molecular absorption and dispersion. For highest performance, the technique combines cavity enhancement (CE) with frequency modulation (FM); while the former increases the effective interaction length between the light and the analyte by several orders of magnitudes, the latter removes the in-coupling of 1/f noise and makes the signals background free. The combination of CE and FM also gives the technique an immunity to amplitude noise caused by the jitter of the laser frequency relative to the cavity resonance frequencies. All these properties make the technique suitable for ultra sensitive trace gas detection in the sub-parts-per-trillion (ppt) range. The aim of this thesis is to improve the performance of the NICE-OHMS technique and to increase its range of applications.

    The work in this thesis can be divided into three areas:Firstly, a mid-infrared (MIR)-NICE-OHMS instrumentation was developed. In a first realization an unprecedented white-noise equivalent absorption limit for Doppler broadened (Db) detection in the MIR of 3×10-9 cm-1Hz-1/2was demonstrated. This was subsequently improved to 2.4×10-10 cm-1Hz-1/2allowing for detection methane and its two main isotopologues (CH3D and 13CH4) at their natural abundance.Secondly, further development of an existing near-infrared NICE-OHMS system was performed. This resulted in an improved longtime stability and the first shot-noise limited NICE-OHMS system for Db detection with a noise equivalent absorption limit of 2.3×10-14 cm-1detected over 200 s. Thirdly, models and theoretical descriptions of NICE-OHMS signals under strong absorption conditions and from methane under high laser power were developed. It was experimentally verified that the models allow for a more accurate evaluation of NICE-OHMS signals under a wide range of conditions.

  • Public defence: 2018-11-30 13:00 HumlabX, Umeå Arts Campus
    Kuenen, Stoffel
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Aesthetics of being together2018Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Design deals with matters of aesthetics. Historically, aesthetics in industrial design refers to the designed artifact: aesthetics of objects. When designed artifacts include digital technologies, aesthetics in design refers to what happens between people and artifacts as well: aesthetics of interaction. Now that these artifacts increasingly mediate our social lives, what aesthetics in design quite obviously also refers to, is what happens between people.

    This dissertation proposes an aesthetic of being together, as a necessary addition to current notions of aesthetics in interaction design practice, when it engages with digital systems that are part of people’s social life. It does not answer the question what Aesthetics is in general, instead it examines the work that particular notions of aesthetics do in interaction design practice.

    The practice based design research assembled in this dissertation starts from current notions of aesthetics in interaction design to explore the social experiences that mediated interactions between groups of people offer. What I found, through designing digital systems, is that current notions of aesthetics in interaction design are not conducive to addressing the kind of social experience people have with such systems. On the contrary, current notions actually inhibit interaction design to approach any experiences that cannot in the first place be conceived of as useful in terms of instrumental task performance. Yet, being social is hardly like performing a task or using other people in that sense.

    An aesthetic of being together is a proposition of a different fundament for interaction design practice. In addition to referring to properties of things and qualities of interacting with things, it refers to the kind of relations that come to expression between people interacting with each other with these things. Consequently, interaction design needs to resolve basic issues in what it considers and brings to expression, i.e. people’s relations with things and people at the same time. This requires (re-) considering what the designed thing is, what interaction is about and what the role of design is in bringing those to expression.

    My work contributes to the field of interaction design research an example of how, through practice, fundamental issues can be addressed. By orienting one set of concepts, ways of working and objectives into a different design situation, tensions built up that exposed foundational issues with that frame of reference, while pointing to the different fundaments needed to enable design practice to engage such situations.

    The results of the practical experimentation led to the articulation of a series of structural mechanisms of mediating systems.  These mechanisms provide material handles for interaction designers on how experiences of being present with others take shape. They configure the relations of artifacts and people in different ways than current notions of aesthetics afford. This theoretical investigation is then synthesised in the form of a new logic of expression for interaction design practice: an aesthetic of being together.

  • Public defence: 2018-11-30 13:00 Sal B, 9 tr, byggnad 1D, Norrlands Universitetssjukhus, Umeå
    Lampa, Ewa
    Umeå University, Faculty of Medicine, Department of Odontology.
    Pain and disability in the jaw and neck regions after whiplash trauma: a short- and long-term perspective2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Whiplash trauma, a hyperextension-flexion trauma to the neck that is often related to a car accident, affects tens of thousands in Sweden every year. A significant proportion will develop long-term symptoms including neck pain and dysfunction – this is embraced as Whiplash associated disorders (WAD). Some individuals also develop pain and dysfunction in the orofacial region that is denoted as Temporomandibular disorder (TMD). TMD is common in the population with a prevalence of about 10% but the relation to whiplash trauma is still unclear. The limited number of prospective studies on TMD after whiplash trauma show diverging results, but it has been suggested that TMD develops over time and not in close proximity to the trauma. Prospective studies are needed to determine the course of jaw pain and disability after whiplash trauma.

    The general aim of this thesis was to evaluate the presence and course of pain and disability in the jaw and neck regions at the acute and chronic stages after whiplash trauma.

    This prospective cohort study included at baseline 176 cases with a recent whiplash trauma, and 116 age and gender matched controls without a history of neck trauma that were recruited from the general population. The cases had visited the emergency department at Umeå university hospital, Sweden, with neck pain within 72 hours following a car accident and had been diagnosed with neck distortion by a physician. The cases were examined within one month after the trauma (December 2010 to January 2016) and at a 2-year followup (December 2012 to January 2018). All participants completed questionnaires regarding pain and disability in the jaw and neck regions, physical symptoms (pain and non-pain items), and depression. At baseline, 80 of the cases and 80 of the controls also completed a 5-minute chewing capacity test. At the 2- year follow-up, 119 cases (68%) and 104 controls (90%) were re-examined with the same questionnaires.

    Compared to controls, within one month after a whiplash trauma cases reported significantly more pain in the jaw and neck regions with a positive correlation between the intensity of pain in these regions (Paper I). In the acute stage after trauma, cases, compared to controls, showed a reduced chewing capacity, and this was related to the severity of neck disability (Paper II). For cases, jaw and neck pain correlated positively to each other, to non-specific physical symptoms, and to depression at both the acute (Paper III) and chronic stages (Paper IV). About one third (34%) of the cases reported orofacial pain at baseline, and for a majority of these, the pain persisted at the 2-year follow-up (Paper IV).

    The presence of orofacial pain early after a whiplash trauma indicates involvement of central sensitization and spread of pain between the jaw and neck regions. The positive correlations between pain in the jaw and neck regions, and to psychosocial factors, underline the integration of these regions and the importance of a biopsychosocial perspective. The impaired jaw function shortly after a neck trauma further underlines the close sensorimotor relationship between the trigeminal and cervical regions. The finding that orofacial pain is common shortly after whiplash trauma, and often persists into the chronic stage, indicates that assessment in the acute stage should include both the neck and jaw regions. From this, it follows that multidisciplinary teams that entail both medical professions and dentists specialised in orofacial pain can be beneficial in the early assessment after whiplash trauma.

  • Public defence: 2018-11-30 09:00 E04, R-1, Norrlands Universitetssjukhus, byggnad 6E, Umeå
    Ling, Agnes
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Immune cell infiltration and prognosis in colorectal cancer2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Colorectal cancer (CRC) is globally the second most common form of cancer among women, and third in men. It is also one of the most common causes of cancer-related death in high-income countries. Surgical resection is the basis for curative therapy but still almost half of the patients die from metastatic disease. It is therefore imperative to strive on in the search for more efficient strategies to improve patient survival. The success scores for accurate prediction of patient prognosis remain discouraging and novel markers to identify high-risk patients are called for.

    The tumour immune response has proven critical to prognosis in CRC. A high amount of tumour infiltrating lymphocytes have in studies been found to significantly improve patient outcome. The opposite has been seen in patients with sparsely infiltrated tumours. Findings in this area have driven forth the design of the Immunoscore® system, which may be implemented in clinic as a complement to the TNM staging system. Ongoing research is also focusing on which immune evading mechanisms CRC might deploy in order to progress and metastasize.

    Aim: To study immune cell infiltration in relation to prognosis in CRC. More specifically the aim has been to investigate the prognostic importance of different subsets of immune cells infiltrating the tumour, not only according to quantity but also to intratumoural subsite (tumour invasive front, tumour centre and within the tumour epithelium). The tumour immune response was also evaluated in different molecular subgroups of CRC. Another part of this thesis concerns possible molecular mechanisms involved in tumour immune escape in CRC.

    Methods: CRC cases in the Colorectal Cancer in Umeå Study (CRUMS) were evaluated using immunohistochemistry, gene expression analyses as well as methylation analyses. Cytokine and chemokine expression was evaluated in CRC tumour tissues and one CRC cell line (Caco2) and derivatives using semi-quantitative real-time PCR. Methylation was analysed using methylation-specific pyrosequencing.

    Results: We found high quantities of both cytotoxic T cells (CTLs) as well as of regulatory T cells (Tregs) to associate with a better patient outcome. The infiltration of CTLs within the tumour epithelium provided the strongest prognostic information, whilst Tregs withheld the strongest association to prognosis at the tumour invasive front and tumour centre. We could further show that a high Th1 lymphocyte infiltration was strongly associated with a better prognosis in patients with CRC, independently of intratumoural subsite. Another finding was that the extent of Th1 infiltration and patient outcome differed in different molecular subgroups of CRC. We also found down-regulation of TAP1, a protein involved in antigen presentation by MHC class I, to be significantly associated with low infiltration of various subtypes of immune cells. Down-regulation of TAP1 was also correlated to poor prognosis in patients with early stages of CRC. Furthermore, we found TAP1 expression to be inversely correlated with methylation at sites close to the TAP1 promoter region.

    Conclusion: Tumour infiltrating T lymphocytes have a significant positive impact on prognosis in CRC patients. Different subsets of T lymphocytes vary in their dependency on intratumoural subsite, in to what extent they exert their prognostic influence. We moreover found varying Th1 lymphocyte infiltration rates as well as prognostic impact thereof, in different molecular subgroups of CRC. Our results also show down-regulation of TAP1 to be a mechanism of tumour immune escape in CRC. Further findings suggest methylation of the TAP1 gene to be a putative mechanism for TAP1 down-regulation.

  • Public defence: 2018-11-30 10:00 Hörsal E, Humanisthuset, Umeå
    Lind Pantzare, Anna
    Umeå University, Faculty of Social Sciences, Department of applied educational science, Departement of Educational Measurement.
    Dimensions of validity: studies of the Swedish national tests in mathematics2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main purpose for the Swedish national tests was from the beginning to provide exemplary assessments in a subject and support teachers when interpreting the syllabus. Today, their main purpose is to provide an important basis for teachers when grading their students. Although the results from tests do not entirely decides a student’s grade, they are to be taken into special account in the grading process. Given the increasing importance and raise of the stakes, quality issues in terms of validity and reliability is attracting greater attention. The main purpose of this thesis is to examine evidence demonstrating the validity for the Swedish national tests in upper secondary school mathematics and thereby identify potential threats to validity that may affect the interpretations of the test results and lead to invalid conclusions. The validation is made in relation to the purpose that the national tests should support fair and equal assessment and grading. More specifically, the focus was to investigate how differences connected to digital tools, different scorers and the standard setting process affect the results, and also investigate if subscores can be used when interpreting the results. A model visualized as a chain containing links associated with various aspects of validity, ranging from administration and scoring to interpretation and decision-making, is used as a framework for the validation.

    The thesis consists of four empirical studies presented in the form of papers and an introduction with summaries of the papers. Different parts of the validation chain are examined in the studies. The focus of the first study is the administration and impact of using advanced calculators when answering test items. These calculators are able to solve equations algebraically and therefore reduce the risk of a student making mistakes. Since the use of such calculators is allowed but not required and since they are quite expensive, there is an obvious threat to validity since the national tests are supposed to be fair and equal for all test takers. The results show that the advanced calculators were not used to a great extent and it was mainly those students who were high-achieving in mathematics that benefited the most. Therefore the conclusion was that the calculators did not affect the results.

    The second study was an inter-rater reliability study. In Sweden, teachers are responsible for scoring their own students’ national tests, without any training, monitoring or moderation. Therefore it was interesting to investigate the reliability of the scoring since there is a potential risk of bias against one’s own students. The analyses showed that the agreement between different raters, analyzed with percent-agreement and kappa, is rather high but some items have lower agreement. In general, items with several correct answers or items where different solution strategies are available are more difficult to score reliably.

    The cut scores set by a judgmental Angoff standard setting, the method used to define the cut scores for the national tests in mathematics, was in study three compared with a statistical linking procedure using an anchor test design in order to investigate if the cut scores for two test forms were equally demanding. The results indicate that there were no large differences between the test forms. However, one of the test taker groups was rather small which restricts the power of the analysis. The national tests do not include any anchor items and the study highlights the challenges of introducing equating, that is comparing the difficulty of different test forms, on a regular basis.

    In study four, the focus was on subscores and whether there was any value in reporting them in addition to the total score. The syllabus in mathematics has been competence-based since 2011 and the items in the national tests are categorized in relation to these competencies. The test grades are only connected to the total score via the cut scores but the result for each student is consolidated in a result profile based on those competencies. The subscore analysis shows that none of the subscores have added value and the tests would have to be up to four times longer in order to achieve any significant value.

    In conclusion, the studies indicate that several of the potential threats do not appear to be significant and the evidence suggests that the interpretations made and decisions taken have the potential to be valid. However, there is a need for further studies. In particular, there is a need to develop a procedure for equating that can be implemented on a regular basis.

  • Yoluk, Özge
    et al.
    KTH, Science for Life Laboratory, SciLifeLab.
    Lindahl, Erik
    KTH, Science for Life Laboratory, SciLifeLab.
    Andersson, Magnus
    Science for Life Laboratory; Theoretical and Computational Biophysics, Department of Theoretical Physics, KTH Royal Institute of Technology, Stockholm, Sweden.
    Conformational Gating Dynamics in the GluCl Anion-Selective Chloride Channel2015In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 6, no 8, p. 1459-1467Article in journal (Refereed)
    Abstract [en]

    Cys-loop receptors are central to propagation of signals in the nervous system. The gating of the membrane-spanning pore is triggered by structural rearrangements in the agonist-binding site, located some so A away from the pore. A sequential conformational change, propagating from the ligand-binding site to the pore, has been proposed to govern gating in all Cys-loop receptors. Here, we identify structural and dynamic components of the conformational gating in the eukaryotic glutamate-gated chloride channel (GluCl) by means of molecular dynamics (MD) simulations with and without the L-glutamate agonist bound. A significant increase in pore opening and accompanying hydration is observed in the presence of glutamate. Potential of mean force calculations reveal that the barrier for ion passage drops from 15 kcal/mol to 5-10 kcal/mol with the agonist bound. This appears to be explained by agonist binding that leads to significant changes in the intersubunit hydrogen-bonding pattern, which induce a slight tilt of the extracellular domain relative to the transmembrane domain in the simulations. This rearrangement is subtle, but correspond to the direction of the quaternary twist observed as a key difference between open and closed X-ray structures. While the full reversible gating is still a much slower process, the observed structural dynamics sheds new light on the early stages of how the agonist influences the extracellular domain, how the extracellular domain interacts with the transmembrane domain, and how changes in the transmembrane domain alter the free energy of ion passage.

  • Kimanius, Dari
    et al.
    Pettersson, Ingrid
    Schluckebier, Gerd
    Lindahl, Erik
    Andersson, Magnus
    Department of Theoretical Physics and Swedish e-Science Research Center, Science for Life Laboratory, KTH Royal Institute of Technology, Solna, Sweden.
    SAXS-Guided Metadynamics2015In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 11, no 7, p. 3491-3498Article in journal (Refereed)
    Abstract [en]

    The small-angle X-ray scattering (SAXS) methodology enables structural characterization of biological macromolecules in solution. However, because SAXS provides low-dimensional information, several potential structural configurations can reproduce the experimental scattering profile, which severely complicates the structural refinement process. Here, we present a bias-exchange metadynamics refinement protocol that incorporates SAXS data as collective variables and therefore tags all possible configurations with their corresponding free energies, which allows identification of a unique structural solution. The method has been implemented in PLUMED and combined with the GROMACS simulation package, and as a proof of principle, we explore the Trp-cage protein folding landscape.

  • Grønberg, Christina
    et al.
    Sitsel, Oleg
    Lindahl, Erik
    Gourdon, Pontus
    Andersson, Magnus
    Theoretical Physics and Swedish e-Science Research Center, Science for Life Laboratory, KTH Royal Institute of Technology, Solna, Sweden.
    Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport2016In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 111, no 11, p. 2417-2429Article in journal (Refereed)
    Abstract [en]

    Cu+-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu+-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu+ entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu+ delivery. Mutational analyses and simulations in the presence and absence of Cu+ predict that the ion-entry path involves two ion-binding sites: one transient Met148-Cys382 site and one intramembranous site formed by trigonal coordination to Cys384, Asn689, and Met717. The results reconcile earlier biochemical and x-ray absorption data and provide a molecular understanding of ion entry in Cu+-transporting P-type ATPases.

  • Figuero, Andrés
    et al.
    Rodriguez, Alvaro
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Sande, Jose
    Peña, Enrique
    Rabuñal, Juan R.
    Field measurements of angular motions of a vessel at berth: Inertial device application2018In: Control Engineering and Applied Informatics, ISSN 1454-8658, Vol. 20, no 3, p. 79-88Article in journal (Refereed)
    Abstract [en]

    The study and characterization of the oscillations of a moored vessel has a major importance in port operational efficiency, not only in the design of mooring and anchoring systems, but also in order to prevent the movement of the cargo, minimize ship and dock damage and optimizing the operations which have to take place while the ship is moored.The dynamic behavior of a vessel moored in waves has been mathematically described and interactions between ships and environmental loads such as waves, wind, currents and ice are commonly tested for different docks and mooring systems in scale models. However, field data studies of the behavior moored ships have not been properly addressed so far.This paper proposes a novel application of Inertial Measurement Units to estimate the angular movements (roll, pitch and yaw) of a moored vessel. The proposed technique has been validated in laboratory conditions and the behavior of the ship Urania Mella in the Outer Port of Punta Langosteira (A Coruña, Spain), has been analyzed, obtaining very promising results.

  • Linden, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Heijl, Anders
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Aspberg, Johan
    Andersson Geimer, Sabina
    Bengtsson, Boel
    Initial intraocular pressure reduction by mono‐ versus multi‐therapy in patients with open‐angle glaucoma: results from the Glaucoma Intensive Treatment Study2018In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 6, p. 567-572Article in journal (Refereed)
    Abstract [en]

    Purpose: To study newly diagnosed glaucoma patients given mono‐ or multi‐therapy regarding differences in initial intraocular pressure (IOP) reduction, target IOP levels reached and influence of untreated baseline IOP on IOP reduction.

    Methods: Patients newly diagnosed with manifest primary open‐angle glaucoma and included in the Glaucoma Intensive Treatment Study (GITS) were randomized to immediate intensive treatment with any of three different IOP‐lowering substances supplied in two bottles plus 360° laser trabeculoplasty or to conventional stepwise treatment starting with a single‐drug. Intraocular pressure reduction was analysed 1 month after initiation of treatment.

    Results: One hundred eighteen patients (143 eyes) received mono‐therapy and 122 patients (152 eyes) multi‐therapy. Median baseline IOP was 24.0 (min: 9.7, max: 56.0) mmHg in mono‐therapy eyes and 24.0 (min: 12.3, max: 48.5) mmHg in multi‐therapy eyes (p = 0.56). After 1 month in the two groups, respectively, values for median IOP reduction were 6.3 (range: −5.3–31.0) and 11.0 (range: 0.7–34.5) mmHg, and for mean relative decline 26.8 (range: −32.0–55.4) and 46.0 (range: 4.6–81.6) % (p = 0.000). A larger proportion of the multi‐therapy patients reached each target IOP level (p = 0.000). The higher the baseline IOP, the larger the observed pressure reduction, considering both absolute and relative figures. The effect was more pronounced in eyes with multi‐therapy than in those with mono‐therapy (p = 0.000). For every mmHg higher IOP at baseline, the IOP was reduced by an additional 0.56 (mono‐therapy) or 0.84 (multi‐therapy) mmHg.

    Conclusion: Intensive treatment led to considerably greater IOP reduction than mono‐therapy. Among patients with IOP ≥30 mmHg at diagnosis an IOP of <16 was reached in 2/3 of those with multi‐therapy but in none with mono‐therapy. The IOP reduction was highly dependent on the untreated IOP level.

  • Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, University College of London, Institute of Neurology, London, UK.
    The paper that wrote itself – A ghost story2018In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, no 9, p. 1509-1510Article in journal (Refereed)
  • Enetjärn, Albin
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Temporal och spatial variation för pH och relaterade parametrar i Bastuån, Jämtland2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Anthropogenic emissions of acidifying substances, mainly sulfur dioxide, during the second half of the 20th century caused a widespread acidification of many European freshwater environments. Even relatively remote areas, such as inland northern Sweden, experienced reduced pH-values, much due to low buffering capacity in the environment. Extensive liming has taken place in Sweden over the past fifty years to counteract negative effects on limnic ecosystems. Despite a general increase in pH over the last decades, problems with acidification still occur. However, this can be hard to separate from natural acidity due to a large landscape variability. This study aims at describing the temporal and spatial variation of pH and pH-related parameters in Bastuån, a 46 km2 watershed in Jämtland, Sweden, which is being investigated for future liming measures. Existing water chemistry data sets were analyzed and extended with an additional field study, sampling the twelve largest tributaries to Bastuån. Results show that pronounced high and low pH values has become increasingly rare while the average is basically unchanged between 1999 and 2017. Low pH is mainly associated with high discharge during snowmelt or rain events. Anthropogenic SO42- concentrations seems to contribute relatively little to pH-depressions while organic acids plays a more important role. Large water chemical variations in the tributaries indicate that several different biological and physical properties within the watershed regulates pH. However, any credible function that can predict pH using such properties remains to be found.

  • Alakpa, Enateri V.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Saeed, Anwer
    Chung, Peter
    Riehle, Mathis O.
    Gadegaard, Nikolaj
    Dalby, Matthew J.
    Cusack, Maggie
    The Prismatic Topography of Pinctada maxima Shell Retains Stem Cell Multipotency and Plasticity In Vitro2018In: Advanced Biosystems, ISSN 2366-7478, Vol. 2, no 6, article id 1800012Article in journal (Refereed)
    Abstract [en]

    The shell of the bivalve mollusc Pinctada maxima is composed of the calcium carbonate polymorphs calcite and aragonite (nacre). Mother-of-pearl, or nacre, induces vertebrate cells to undergo osteogenesis and has good osteointegrative qualities in vivo. The calcite counterpart, however, is less researched in terms of the response of vertebrate cells. This study shows that isolation of calcite surface topography from the inherent chemistry allows viable long-term culture of bone marrow derived mesenchymal stem cells (MSCs). Self-renewal is evident from the increased gene expression of the self-renewal markers CD63, CD166, and CD271 indicating that cells cultured on the calcite topography maintain their stem cell phenotype. MSCs also retain their multipotency and can undergo successful differentiation into osteoblasts and adipocytes. When directed to adipogenesis, MSCs cultured on prism replicas are more amenable to differentiation than MSCs cultured on tissue culture polystyrene indicating a higher degree of plasticity in MSCs growing on calcite P. maxima prismatic topography. The study highlights the potential of the calcite topography of P. maxima as a biomimetic design for supporting expansion of MSC populations in vitro, which is of fundamental importance if it meets the demands for autologous MSCs for therapeutic use.

  • Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart Centre, Umeå.
    Pugliese, Nicola Riccardo
    D'Agostino, Andreina
    Rosa, Gian Marco
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Heart Centre, Umeå.
    Perçuku, Luan
    Miccoli, Mario
    Galeotti, Gian Giacomo
    Fabiani, Iacopo
    Pedrinelli, Roberto
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart Centre, Umeå.
    Dini, Frank L.
    Echo- and B-Type Natriuretic Peptide-Guided Follow-Up versus Symptom-Guided Follow-Up: Comparison of the Outcome in Ambulatory Heart Failure Patients2018In: Cardiology Research and Practice, ISSN 2090-8016, E-ISSN 2090-0597, article id 3139861Article in journal (Refereed)
    Abstract [en]

    Recent European Society of Cardiology and American Heart Association/American College of Cardiology Guidelines did not recommend biomarker-guided therapy in the management of heart failure (HF) patients. Combination of echo- and B-type natriuretic peptide (BNP) may be an alternative approach in guiding ambulatory HF management. Our aim was to determine whether a therapy guided by echo markers of left ventricular filling pressure (LVFP), lung ultrasound (LUS) assessment of B-lines, and BNP improves outcomes of HF patients. Consecutive outpatients with LV ejection fraction (EF) <= 50% have been prospectively enrolled. In Group I (n=224), follow-up was guided by echo and BNP with the goal of achieving E-wave deceleration time (EDT) >= 150 ms, tissue Doppler index E/e' < 13, B-line numbers < 15, and BNP <= 125 pg/ml or decrease > 30%; in Group II (n=293), follow-up was clinically guided, while the remaining 277 patients (Group III) did not receive any dedicated follow-up. At 60 months, survival was 88% in Group I compared to 75% in Group II and 54% in Group III (chi(2) 53.5; p<0.0001). Survival curves exhibited statistically significant differences using Mantel-Cox analysis. The number needed to treat to spare one death was 7.9 (Group I versus Group II) and 3.8 (Group I versus Group III). At multivariate Cox regression analyses, major predictors of all-cause mortality were follow-up E/e' (HR: 1.05; p=0.0038) and BNP > 125 pg/ml or decrease <= 30% (HR: 4.90; p=0.0054), while BNP > 125 pg/ml or decrease <= 30% and B-line numbers >= 15 were associated with the combined end point of death and HF hospitalization. Evidence-based HF treatment guided by serum biomarkers and ultrasound with the goal of reducing elevated BNP and LVFP, and resolving pulmonary congestion was associated with better clinical outcomes and can be valuable in guiding ambulatory HF management.

  • Hakopuro, Janina
    Umeå University, Faculty of Arts, Department of language studies.
    Svecismer i sverigefinskan: En kvantitativ undersökning om ett urval av svenska ord som används i finska språket i Sverige2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this study is to investigate how people of varying ages, generations and genders use a selection of Swedish words that occurs in the Finnish language that is spoken in Sweden. The informants examined are originated from Finland or has at least one parent from Finland and speaks Finnish. In order to answer the aim and research questions for this study a quantitative method has been used and a survey with 277 replies has been accomplished. The result of the study shows that the Sweden Finns are using the investigated Sweden Finnish words. Some variations occurred due to age, generation and gender but despite these variations the words are overall used to a greater degree in relative to the investigated aspects.

  • Lindholm, Mark
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Aung, Kyaw Min
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Role of OmpA1 and OmpA2 in Aggregatibacter actinomycetemcomitans and Aggregatibacter aphrophilus serum resistance2019In: Journal of Oral Microbiology, ISSN 2000-2297, E-ISSN 2000-2297, Vol. 11, no 1, article id 1536192Article in journal (Refereed)
    Abstract [en]

    Aggregatibacter actinomycetemcomitans and Aggregatibacter aphrophilus belong to the HACEK group of fastidious Gram-negative organisms, a recognized cause of infective endocarditis. A. actinomycetemcomitans is also implicated in aggressive forms of periodontitis. We demonstrated that A. aphrophilus strains, as A. actinomycetemcomitans are ubiquitously serum resistant. Both species encode two Outer membrane protein A paralogues, here denoted OmpA1 and OmpA2. As their respective pangenomes contain several OmpA1 and OmpA2 alleles, they represent potential genotypic markers. A naturally competent strain of A. actinomycetemcomitans and A. aphrophilus, respectively were used to elucidate if OmpA1 and OmpA2 contribute to serum resistance. Whereas OmpA1 was critical for survival of A. actinomycetemcomitans D7SS in 50% normal human serum (NHS), serum resistant ompA1 mutants were fortuitously obtained, expressing enhanced levels of OmpA2. Similarly, OmpA1 rather than OmpA2 was a major contributor to serum resistance of A. aphrophilus HK83. Far-Western blot revealed that OmpA1AA, OmpA2AA, and OmpA1AP can bind to C4-binding protein, an inhibitor of classical and mannose-binding lectin (MBL) complement activation. Indeed, ompA1 mutants were susceptible to these pathways, but also to alternative complement activation. This may at least partly reflect a compromised outer membrane integrity but is also consistent with alternative mechanisms involved in OmpA-mediated serum resistance.

  • Rawcliffe, Denise F. R.
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Österman, Lennart
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Nordin, Angelica
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Holmberg, Monica
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    PTBP1 acts as a dominant repressor of the aberrant tissue-specific splicing of ISCU in hereditary myopathy with lactic acidosis2018In: Molecular Genetics & Genomic Medicine, ISSN 2324-9269Article in journal (Refereed)
    Abstract [en]

    Background: Hereditary myopathy with lactic acidosis (HML) is an autosomal recessive disease caused by an intron mutation in the iron-sulfur cluster assembly (ISCU) gene. The mutation results in aberrant splicing, where part of the intron is retained in the final mRNA transcript, giving rise to a truncated nonfunctional ISCU protein. Using an ISCU mini-gene system, we have previously shown that PTBP1 can act as a repressor of the mis-splicing of ISCU, where overexpression of PTBP1 resulted in a decrease of the incorrect splicing. In this study, we wanted to, in more detail, analyze the role of PTBP1 in the regulation of endogenous ISCU mis-splicing.

    Methods: Overexpression and knockdown of PTBP1 was performed in myoblasts from two HML patients and a healthy control. Quantification of ISCU mis-splicing was done by qRTPCR. Biotinylated ISCU RNA, representing wildtype and mutant intron sequence, was used in a pull-down assay with nuclear extracts from myoblasts. Levels of PTBP1 in human cell lines and mice tissues were analyzed by qRTPCR and western blot.

    Results: PTBP1 overexpression in HML patient myoblasts resulted in a substantial decrease of ISCU mis-splicing while knockdown of PTBP1 resulted in a drastic increase. The effect could be observed in both patient and control myoblasts. We could also show that PTBP1 interacts with both the mutant and wild-type ISCU intron sequence, but with a higher affinity to the mutant sequence. Furthermore, low levels of PTBP1 among examined mouse tissues correlated with high levels of incorrect splicing of ISCU.

    Conclusion: Our results show that PTBP1 acts as a dominant repressor of ISCU mis-splicing. We also show an inverse correlation between the levels of PTBP1 and ISCU mis-splicing, suggesting that the high level of mis-splicing in the skeletal muscle is primarily due to the low levels of PTBP1.

  • Seidegård, Jacob
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    RÄDSLAN FÖR ATT FÖRLORA ARBETET: Jämförande studie mellan Sverige, Danmark och Polen2018Independent thesis Advanced level (degree of Master (Two Years)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this study is to examine how different risk factors on the labour market affect an individuals’ perceived unemployment risk and how this perceived risk is affected depending on what country you work in. By comparing countries, a difference can be made on, depending on the countries labour policies and the state of their welfare, how they are affecting your perceived unemployment risk. The countries used in this study are Sweden, Denmark and Poland and the risk factors used are, gender, education level, competence and trade unions. The data for this study is taken from ISSPs surveys and the analysis method used is a bivariate and a multiple regression analysis. The result from the study show that there are differences between the countries perceived unemployment risk and how the risk factors affect this. But, because a lot of the results are non-significant, a general conclusion can’t be done because there is no certainty that the results exist outside of this study. But one thing is certain, that this is a much more complex field were general conclusions are hard to make and that the risk factors needs more and thorough studying and how the individuals perceived unemployment risk affects their mental health.

  • Sjödin, Tord
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    A Short and Unified Proof of Kummer's Test2018Other (Other academic)
    Abstract [en]

    Kummer’s test from 1835 states that the positive series ∑n=1an is convergent if and only if there is a sequence {Bn}1 of positive numbers such that Bn·an/an+1Bn+1 ≥ 1, for all sufficiently large n. We present an exact analysis and a short and unified proof of Kummer’s test. The test has been applied to differential equations and studied in mathematical philosophy.

  • Gümüscü, Ahmet
    et al.
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Nygren, Lennart
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Khoo, Evelyn
    Umeå University, Faculty of Social Sciences, Department of Social Work.
    Social work and the management of complexity in Swedish child welfare services2018In: Nordic Social Work Research, ISSN 2156-857X, E-ISSN 2156-8588Article in journal (Refereed)
    Abstract [en]

    This paper elucidates how Swedish child welfare social workers manage complexity co-occuring in the families with which they work and the organisational contexts of practice. Focus groups were held with social workers in three municipalities in Sweden who described work processes generally and in response to a fictitious vignette. The vignette was constructed as a complex family situation to explore how social workers approach complexity when faced with a family with complex needs. Findings showed that social workers are challenged in their everyday work where they are aware of the many needs in a family. They focus on immediate conditions for children while recognising that some problems are less amenable to being solved. However they try to manage complexities related to families as well as the structural conditions of work by sorting, prioritising and oscillating between a child focus and a family service orientation. This paper serves as a necessary reminder of the complexity of social work in the broader area of child welfare and raises further questions about the use of comparative typologies to explain social work practices.

  • Dam Roadley-Battin, Nikolaj
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Educational VR: An exploration of educational VR for professional users2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis explores Virtual Reality (VR) as a digital medium for teaching in a professional context. In collaboration with ABB, a pioneering technology leader, the thesis questions whether VR could be the future medium for training ABB service personnel. 

    The research discusses how you can design for VR, by drawing parallels to traditional mediums; Moreover, the research covers insights into the ABB education and VR explorations. 

    Three experience prototypes were designed as the final concept. These experience prototypes aim to highlight educational use cases through VR, covering collaborative work, safety guidelines and various utilities. The goal of the final experience prototypes is to engage potential users and designers in a dialog concerning VR as an educational medium of the future.

  • Pruchnicka, Joanna
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    A BETTER WAY TO LIVE WITH A CHRONIC CONDITION: Envisioning transition kit for women living with endometriosis2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This project explores the question of how to support women living with endometriosis in the transition into live with a chronic condition while maintaining the best possible quality of life.

    Design process was planned out and exercises in four steps - preparations and background research (outlining well-being perspective, desk research, research online via social media), design research (multiple surveys, interviews, reflections online, co-creation sessions, probing, interviews following probing with co-creation sessions, ideation sessions, analysis), explorations (creation of directions, analysis, initial concepts creation, feedback, synthesis, design proposal, feedback and evaluation sessions, design improvements) and final design proposal. Activities were aiming to repeatedly

    open up the scope of the project and then through the analysis of each phase narrow it down again following diamond shape.

    One important aspect of the process was to engage women living with endometriosis as well as their loved ones throughout the whole process and design together instead of designing for them. Of course, experts were consulted as well to make sure project is following standards of medical care, but the primary focus on the users was important since the product was shaped rather as a lifestyle change facilitator as well as data collection tool rather than a strictly medical solution.

    The outcome of the project is a flexible system VEA serving as a transition kit for women diagnosed with endometriosis, but also early detection screening tool and awareness platform for those who haven’t been diagnosed yet. Even though this might seem complicated I’ll try to explain why only this kind of a multifaceted approach can fully support women in their journey toward their best possible quality of life.

    VEA allows users to access Habit Nooks supporting them in introducing changes while guided by experts and supported by the community.

    Physical tracker allowing to track symptoms together with the Data Dashboard allow users to explore data patterns and make informed decisions. The system gives also an opportunity to get in touch with experts via calls or structured long-term programs.

    Beside the design proposal project was closed with a series of reflection touching on the bias in a medical field and how it might affect healthcare design, as well as designer’s experience of working on a project with a personal relevance. 

  • Kuklo, Piotr
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    The future of podcasting: Envisioning an audio stories community for listeners and creators, where they connect through similar interests and share inspiring content.2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This project explores the future of podcasting as a digital audio media format for stories. As podcasts continue to grow in popularity the medium becomes more and more influential amongst all age groups. Unfortunately, existing solutions do not give enough attention to all possible aspects of the medium. Podcasts carry an untapped potential as they are often treated similarly to music files. This project consists of a platform, Cast3, with two separate products directed to listeners and creators of audio stories. The platform gives users a possibility to connect with similar minded people around specific topics through clubs.

    Inspiration and Method

    To understand the needs of listeners and creators of the stories, I immersed myself with the storytelling world and conducted a thorough research with conversations with both users groups, opportunities evaluations and concepts testing. The insights gathered during the research brought the conclusion that both listeners and creators tend to want more involvement and have stronger community gathered around audio stories. That is why the project’s goal is to form an audio story community for listeners and creators, where they connect through similar interests and share inspiring content.

    Result

    The final outcome of the project consists of a platform Cast3 that has 2 separate products directed to listeners and creators of audio stories. The platform gives users a possibility to connect with similar minded people around specific topics through clubs. The clubs are the spaces where listeners can exchange information, discover new content through a word of mouth and bond with the creators through live shows. The creators’ needs are supported through specialised tools that help to record stories and help to learn more about the listeners. The users of the platform can interact with audio stories through a redefined media format called freecasting. The new format improves a listening experience and respond to presently existing needs of listeners as well as creators.

  • Kennedy, André
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Finance for all: Envisioning inclusive financial systems2018Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    One of the more pressing long-term concerns for parents of children with a neurodevelopmental disorder (NDD), such as autism, is financial management (Abbott & Marriott, 2012). Few of these people ever manage to attain a level of financial literacy that allows them to become fully independent. Value, in it’s current form, is just too abstract for many (Cheak-Zamora, et al. 2017). This problem is augmented by our financial institutions, who have neglected to offer these groups any form of accessible financial products, rendering any aspirations of becoming “financially independent” by these groups, as unattainable. This is detrimental to their well-being and sense of self. (Abbott & Marriott, 2012).

    With this in light, this thesis will firstly highlight the obstacles faced by these groups in achieving financial independence, secondly, it will present a new paradigm through which to look at value. A paradigm that understands that money isn’t about a number, but rather the complex social interactions that that govern our liberties as members of society. Finally, this thesis will present an example of a new breed of fiancial system, Olive. Making use of emerging distributed technologies, Olive presents a system that enables us to produce products that recognises the spectrum of needs and abilities our community contains.

  • Chien, Yi-Ting
    Umeå University, Faculty of Science and Technology, Umeå Institute of Design.
    Immersive Tour at Umeå’s Prison Hotel2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The overall purpose of this project is to develop an immersive storytelling experience that connects with both physical and social environment. To be specific, it focuses on the old prison in Umeå which was closed in 1981 and nowadays serves as a hotel. There are abundant historical materials related to the old prison preserved, and how might we transform such textual, historical information into relatively interactive experience. By collaborating with Hotell Gamla Fängelset ( Umeå’s Prison Hotel ), the result turns out to be an application in combination with augmented reality (AR), to build a guided tour that brings history to life at Umeå’s Prison Hotel. The tour not only demonstrates the plight of the prisoners, but also showcases the reform to humanized treatment over time, at the end linking back to the cozy hotel where the guests are staying. After users experience the tour application, it stimulates people’s imagination of the prisoners’ story and raises their awareness towards the cultural heritage that has always been forgotten.

  • Björklund Larsen, Lotta
    et al.
    Linköping University.
    Boll, Karen
    Copenhagen Business School.
    Brögger, Benedicte
    BI Norwegian Business School.
    Kettunen, Jaana
    University of Jyväskylä.
    Potka-Soininen, Tuulia
    University of Jyväskylä.
    Pellinen, Jukka
    University of Jyväskylä.
    Brehm Johansen, Mette
    Copenhagen Business School.
    Aziz, Kiran
    BI Norwegian Business School.
    Nordic Experiences of Co-Operative Compliance Programmes: Comparisons and Recommendations2018Report (Refereed)
    Abstract [en]

    For the last decade a major trend within tax administrations has been to shift from a roughly one size fits all approach—where close to all taxpayers experience a deterrence approach—to a more responsive and collaborative approach as in co-operative compliance programmes. Such programmes build on the idea that the participating corporations disclose relevant information including their tax risks and are transparent to the tax administrations and in return will tax administrations provide real-time predictability and clarity concerning taxation issues of relevance for the corporation. In brief, co-operative compliance builds on the slogan: “…certainty in exchange for transparency” (OECD 2016, 7). Co-operative compliance has increasingly become a core concern and way of organizing the relation between tax authorities and large corporate tax payers when it comes to securing tax compliance.

    This working paper is the result of research by Work Package 6 in EU’s Horizon 2020 funded programme FairTax that has been running for the four-year period 2015-2019. Our research in Work Package 6 addresses how proactive engagements with large corporate taxpayers have affected regulation of tax collection and administrative processes, changed relationships between stakeholders and tax administrations, and influenced tax compliance in the Nordic countries. The aim of this working paper is to provide a comparison of the experiences in four of the Nordic countries: Denmark, Finland, Norway and Sweden and to propose recommendations.

    The Nordic countries are considered similar and so were the co-operative compliance programmes that were implemented in each country, yet the outcomes were very different. We thus dealt with various case characteristics (Flyvbjerg 2006) where the outcomes hinged on a complexity of elements. We argue that the Swedish case is an extreme case due to its turbulent life and concomitantly with only a handful of participants that have very little activity. The Norwegian case, in contrast, is an example of a maximum variation case because of the much longer history of collaborative relationships and the outcome of the work with tax risk. The combination of a collaborative way of working and systematic risk management and monitoring may either reflect a most likely scenario of future tax administration—or perhaps the least likely. Lastly, we argue that the Danish and Finnish cases represent paradigmatic cases because both of these align largely with the standards set by the OECD and because they therefore present more ordinary or regular ways of working with co-operative compliance. Analyzing a wide variety of case characteristics means that our findings can be of general interest, beyond the Nordic countries.

  • Public defence: 2018-11-23 09:00 Stora hörsalen (KBE303), Umeå
    Fallah, Mahsa
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Plasminogen: a pleiotropic inflammatory regulator in radiation-induced wound formation and wound repair2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The plasminogen activator (PA) system plays important roles in many physiological and pathological processes, including inflammation and wound healing. Plasmin, the central component of the PA system, is a broad-spectrum serine protease that is derived from its inactive precursor form, plasminogen. The first aim of this thesis was to study the role of plasminogen in the formation of radiation-induced wounds, which are an inflammatory side effect of radiotherapy. The second aim was to investigate the molecular mechanisms behind the potentiating effect of plasminogen in the healing of radiation-induced wounds. The third aim was to explore the therapeutic potential of plasminogen in the healing of radiation-induced wounds.

    Radiation therapy in cancer patients is often limited by side effects such as radiation-induced skin damage (radiodermatitis). The mechanisms behind the formation of radiodermatitis are not fully elucidated, and there are no effective preventive therapies for clinical use. In this study, we show that irradiation of skin in WT (wild-type) mice induces plasminogen accumulation, which is followed by activation of TGF-β (transforming growth factor-beta) signaling and the development of inflammation that leads to skin damage. However, plasminogen-deficient mice and mice lacking PAs were mostly resistant to radiodermatitis. Moreover, treatment with a plasminogen inhibitor, tranexamic acid, decreases radiodermatitis in WT mice and prevented radiodermatitis in heterozygous mice. Thus, plasmin is required for the formation of radiodermatitis, and inhibition of plasminogen activation might be a novel treatment strategy to reduce or prevent radiodermatitis in patients undergoing radiotherapy.

    Wound healing consists of partially overlapping inflammatory, proliferation, and tissue remodeling phases, and failure to terminate inflammation leads to the formation of chronic wounds. Previous studies by our group have shown that plasminogen is transported to acute wounds by inflammatory cells where it potentiates inflammation and enhances wound healing. Here, we report that plasminogen-deficient mice, which have delayed wound healing, have extensive fibrin and neutrophil depositions in the wounded area long after re-epithelialization, indicating inefficient debridement and chronic inflammation. The delayed formation of granulation tissue suggests that fibroblast function is also impaired in the absence of plasminogen. Therefore, in addition to its role in the activation of inflammation, plasminogen is also crucial for the resolution of inflammation and the activation of the proliferation phase. Importantly, supplementation of plasminogen-deficient mice with human plasminogen leads to a restored healing capacity that is comparable to that in WT mice. Therefore, plasminogen might be an important future therapeutic agent for treatment of wounds.

    In radiation-induced wounds, inflammation often cannot resolve and the wounds become chronic and fibrotic. Currently, there is no gold standard for the treatment of radiation-induced wounds. In this study, we have shown that radiation-induced wounds treated with plasminogen healed faster than placebo-treated wounds, had diminished inflammation and granulation tissue formation, and had enhanced re-epithelialization and collagen maturation. Transcriptome analysis showed that plasminogen has a pleiotropic effect on gene expression during wound healing, influencing the expression of 33 genes out of the 84 genes studied. In particular, plasminogen decreased the expression of 11 pro-inflammatory genes early in the healing process. Later, plasminogen decreased WNT (Wingless/Integrated) and TGF-β signaling, as well as the expression of 5 growth factors and 13 factors involved in granulation tissue formation. From the genes downregulated by plasminogen, 19 genes are known to be involved in fibrosis. These results show that in radiation-induced wounds with excessive inflammation and tissue formation plasminogen is able to direct the healing process to a normal outcome without the risk for developing fibrosis. This makes plasminogen an attractive drug candidate for treating radiodermatitis in cancer patients. Taken together, our results indicate that plasminogen is a pleiotropic inflammatory regulator involved in radiation-induced wound formation as well as in wound repair.