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  • 1.
    Vastesson, Alexander
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Micro-Structuring of New Materials Combined with Electronic Polymers for Interfaces with Cells2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Materials based on novel Off-Stoichiometry Thiol-Ene polymers, abbreviated OSTE, show promising properties as materials forlow cost and scalable manufacturing of micro- and nanosystems such as lab-on-chip devices. The OSTE materials have tunablemechanical properties, offer possibility for low temperature bonding to many surfaces via tunable surface chemistry, and can beused in soft lithography. Unlike the commonly used elastomer poly(dimethylsiloxane), PDMS, the OSTE materials have lowpermeability for gasses, are resistant to common solvents and can be more permanently surface modified.In this master’s thesis project, the OSTE materials have been evaluated with focus on compatibility with cells, possibility fornanostructuring using soft lithography and the use of OSTE as a flexible support for conducting polymers.Results from cell seeding studies with HEP G2 cells suggest that cells can proliferate on a low thiol off-stoichiometry OSTEmaterial for at least five days. The biocompatibility for this type of OSTE material may be similar to poly(styrene). However, highlevels of free thiol monomers in the material decrease cell viability considerably.By using soft lithography techniques it is possible to fabricate OSTE nanochannels with at least the dimensions of 400 nm x 15nm. Combined with the advantages of using the OSTE materials, such as low temperature bonding and possibility for stablesurface modifications, a candidate construction material for future development of systems for DNA analysis is at hand.OSTE can serve as a flexible support for an adsorbed film of a conducting polymer with the possibility for future applicationssuch as electronic interfaces in microsystems. In this project, a film of PEDOT:PSS with the electrical resistance of ~5 kΩ wascreated by adsorption to an flexible OSTE material. Furthermore, results suggest that it is possible to further optimize theconductivity and water resistance of PEDOT:PSS films on OSTE.

  • 2.
    Ronquist, Gunnar
    et al.
    Avdelningen för klinisk kemi, institutionen för medicinska vetenskaper, Uppsala universitet, Uppsala, Sverige.
    Lötvall, Jan
    Krefting Research Center, Göteborgs universitet, Göteborg, Sverige.
    Gabrielsson, Susanne
    Enheten för translationell immunologi, medicinkliniken, Karolinska universitetssjukhuset; Karolinska institutet, Stockholm, Sverige.
    Mincheva-Nilsson, Lucia
    Avdelningen för klinisk immunologi, institutionen för klinisk mikrobiologi, Umeå universitet, Umeå, Sverige.
    Svanvik, Joar
    Transplantationscentrum Sahlgrenska universitetssjukhuset, Göteborg, Sverige.
    Telemo, Esbjörn
    Avdelningen för reumatologi och inflammationsforskning, Göteborgs universitet, Göteborg, Sverige.
    Waldenström, Anders
    Institutionen för folkhälsa och klinisk medicin, Umeå universitet, Umeå, Sverige.
    Exosomen – intercellulär signalbärare med framtids­potential [Exosomes - intercellular signal carriers with a future potential]: Kan ge nya diagnostiska och terapeutiska möjligheter [May provide new diagnostic and therapeutic opportunities]2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 46, no 110, 2050-2052 p.Article in journal (Other academic)
    Abstract [en]

    Small vesicles were first described in prostatic and seminal fluids more than 30 years ago [5]. They were called prostasomes and are members of the same family now called exosomes. All cells in the body can release extracellular vesicles that function as intercellular messengers. The smallest of these, exosomes, are produced by almost all types of cells in the body and exist in all body fluids. Exosomal signalling takes place in two different ways: either with a cargo of functional proteins and/or by transfection of functional RNA molecules from one cell to the cytoplasm of another, or by ligand-receptor mediated interactions between molecules of the exosome membrane and the cellular membrane of the target cell. The importance of exosomes both in health and disease is rapidly acknowledged and clinical applications in diagnosticts and therapy are under development. The content of proteins and nucleic acids of exosomes will soon be used as bio markers for different diseases such as cancer and cardiac disease. Clinical tests are ongoing where exosomes are used as natural vectors for cancer specific peptides in the treatment of cancer. Exosomes will most probably soon be used in therapy by using them as natural vectors for new  RNA based therapies and also for follow up of therapy.

  • 3.
    Bergström, Simon
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    Ivarsson, Oscar
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    Automation of a Data Analysis Pipeline for High-content Screening Data2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    High-content screening is a part of the drug discovery pipeline dealing with the identification of substances that affect cells in a desired manner. Biological assays with a large set of compounds are developed and screened and the output is generated with a multidimensional structure. Data analysis is performed manually by an expert with a set of tools and this is considered to be too time consuming and unmanageable when the amount of data grows large. This thesis therefore investigates and proposes a way of automating the data analysis phase through a set of machine learning algorithms. The resulting implementation is a cloud based application that can support the user with the selection of which features that are relevant for further analysis. It also provides techniques for automated processing of the dataset and training of classification models which can be utilised for predicting sample labels. An investigation of the workflow for analysing data was conducted before this thesis. It resulted in a pipeline that maps the different tools and software to what goal they fulfil and which purpose they have for the user. This pipeline was then compared with a similar pipeline but with the implemented application included. This comparison demonstrates clear advantages in contrast to previous methodologies in that the application will provide support to work in a more automated way of performing data analysis.

  • 4.
    Onengut-Gumuscu, Suna
    et al.
    Center for Public Health Genomics, Univ Department of Medicine, Division of Endocrinology, University of Virginia, Charlottesville, Virginia, USA.
    Chen, Wei-Min
    Center for Public Health Genomics, Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia, USA.
    Burren, Oliver
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Cooper, Nick J
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Quinlan, Aaron R
    Center for Public Health Genomics, Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia, USA.
    Mychaleckyj, Josyf C
    Center for Public Health Genomics, Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, Virginia, USA.
    Farber, Emily
    Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
    Bonnie, Jessica K
    Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
    Szpak, Michal
    Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
    Schofield, Ellen
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Achuthan, Premanand
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Guo, Hui
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Fortune, Mary D
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Stevens, Helen
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Walker, Neil M
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Ward, Lucas D
    Department of Computer Science, Massachusetts Institute of Technology (MIT), Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
    Kundaje, Anshul
    Department of Computer Science, Massachusetts Institute of Technology (MIT), Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA / Department of Genetics, Stanford University, Stanford, California, USA / Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
    Kellis, Manolis
    Department of Computer Science, Massachusetts Institute of Technology (MIT), Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
    Daly, Mark J
    Broad Institute of MIT and Harvard, Cambridge, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
    Barrett, Jeffrey C
    Wellcome Trust Sanger Institute, Hinxton, UK.
    Cooper, Jason D
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Deloukas, Panos
    Wellcome Trust Sanger Institute, Hinxton, UK.
    Todd, John A
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
    Wallace, Chris
    Juvenile Diabetes Research Foundation (JDRF)/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Addenbrooke's Hospital, Medical Research Council (MRC) Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, UK.
    Concannon, Patrick
    Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
    Rich, Stephen S
    Center for Public Health Genomics, University of Virginia, Department of Public Health Sciences, Division of Biostatistics and Epidemiology, Charlottesville, Virginia, USA.
    Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.2015In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 4, 381-386 p.Article in journal (Refereed)
    Abstract [en]

    Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.

  • 5.
    Gustavsson, Frida
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Validation study: HemoCue Hb 201 + as a tool in comparative physiological field studies on avian blood2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Haemoglobin concentration is becoming a widely popular parameter to use to assess physiological condition within a broad range of species. Assessments of large populations would preferable be done in field to receive quick results and avoid confounding factors associated with transport of blood. A validation study is here performed to see how well the point-of-care device HemoCue Hb 201 + can assess haemoglobin concentration on avian blood. Nucleated erythrocytes have previously been pointed out as something that makes it problematic to apply HemoCue Hb 201 +, designed for human blood, on avian blood. Here it is shown that HemoCue Hb 201 + accurately can estimate haemoglobin concentration for chicken-, tinamou-, and ostrich blood. However, manipulation of ostrich cells, to yield a larger mean corspuscular volume, results in HemoCue Hb 201 + overestimating haemoglobin concentration. A large mean corpuscular volume could therefore be something that impair accuracy in values retrieved with HemoCue Hb 201 +. This study shows that HemoCue Hb 201 + seems possible to apply on avian blood to some extent, but highlights the importance of validation studies when applying this device on new species. 

  • 6.
    Ödling, Sara
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Is there a correlation between the nutrient content and variation in the HvNAM-2 gene in Hordeum vulgare?2015Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Barley is one of the most important cereal crops in the world and a better understanding of the factors that regulates the nutrient content in the grain is of high interest. The industrial breeding during the last century has led to bigger yield but possibly a decrease in nutrient content. In wheat, the NAM-B1 gene is a well-studied gene that affects the grain protein and micronutrient content. Two orthologue genes in barley HvNAM-1 and HvNAM-2 are candidate genes to play a similar role in the barley senescence process.

    I have looked for a correlation between the diversity in the HvNAM-2 gene and nutrient content in 37 Nordic barley accessions. The samples were sequenced and then aligned and analyzed for variation. I found three haplotypes which were compared in nutrient content and in micronutrient content. No significant difference between the haplotypes was found, which can be due to small sample size or that no correlation exists between the grain protein content and the HvNAM-2 gene variation. Significant correlation was however found between the nitrogen content and the micronutrient contents that indicate that the pathways of all the nutrients’ mobilizations are tightly coupled. For future research a bigger number of accessions, preferably at least 100, need to be analyzed to be able to give any conclusions. The molecular mechanisms in the cells during senescence also need further investigation.

  • 7.
    Nadhom, Hama
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Protein Microparticles for Printable Bioelectronics2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In biosensors, printing involves the transfer of materials, proteins or cells to a substrate. It offers many capabilities thatcan be utilized in many applications, including rapid deposition and patterning of proteins or other biomolecules.However, issues such as stability when using biomaterials are very common. Using proteins, enzymes, as biomaterialink require immobilizations and modifications due to changing in the structural conformation of the enzymes, whichleads to changes in the properties of the enzyme such as enzymatic activity, during the printing procedures andrequirements such as solvent solutions. In this project, an innovative approach for the fabrication of proteinmicroparticles based on cross-linking interchange reaction is presented to increase the stability in different solvents.The idea is to decrease the contact area between the enzymes and the surrounding environment and also preventconformation changes by using protein microparticles as an immobilization technique for the enzymes. The theory isbased on using a cross-linking reagent trigging the formation of intermolecular bonds between adjacent proteinmolecules leading to assembly of protein molecules within a CaCO3 template into a microparticle structure. TheCaCO3 template is removed by changing the solution pH to 5.0, leaving behind pure highly homogenous proteinmicroparticles with a size of 2.4 ± 0.2 μm, according to SEM images, regardless of the incubation solvents. Theenzyme model used is Horse Radish Peroxidase (HRP) with Bovine Serum Albumin (BSA) and Glutaraldehyde (GL)as a cross-linking reagent. Furthermore, a comparison between the enzymatic activity of the free HRP and the BSAHRPprotein microparticles in buffer and different solvents are obtained using Michaelis-Menten Kinetics bymeasuring the absorption of the blue product produced by the enzyme-substrate interaction using a multichannelspectrophotometer with a wavelength of 355 nm. 3,3’,5,5’-tetramethylbenzidine (TMB) was used as substrate. As aresult, the free HRP show an enzymatic activity variation up to ± 50 % after the incubation in the different solventswhile the protein microparticles show much less variation which indicate a stability improvement. Moreover, printingthe microparticles require high microparticle concentration due to contact area decreasing. However, usingmicroparticles as a bioink material prevent leakage/diffusion problem that occurs when using free protein instead.

  • 8.
    Micael, Karlberg
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Soft sensor application on lactate controlled fed-batch cultivation for monoclonal antibody production2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Monoclonal antibody producing cells are of great interest and used frequently in the field of biomedical research, diagnostics and therapy with increasing need for better systems to more efficiently produce antibodies at a lower costs. In this project three fed-batch cultivations of hybridoma cells (HB-8696) were cultured in a stirred tank reactor with the use of a soft sensor to monitor the lactate concentration and as well as a dielectric probe for biomass measurements. In addition, a protocol for growing the inoculum was also successfully produced and a previous batch cultivation was also analyzed which gave crucial information about stoichiometrically relation in the feed medium which was used in the fed-batch cultivations. The BioSenz Analyzer was used for on-line lactate concentration monitoring and was later used to control the feed profile to avoid overflow metabolism in two of the three fed-batch cultivations. However, nothing conclusive could be said about the lactate controller as of yet which needs further research.

  • 9.
    Klarbring, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Physics. Linköping University, Faculty of Science & Engineering.
    A first-principles non-equilibrium molecular dynamicsstudy of oxygen diffusion in Sm-doped ceria2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Solid oxide fuel cells are considered as one of the main alternatives for future sources of clean energy. To further improve their performance, theoretical methods able to describe the diffusion process in candidate electrolyte materials at finite temperatures are needed. The method of choice for simulating systems at finite temperature is molecular dynamics. However, if the forces are calculated directly from the Schrödinger equation (first-principles molecular dynamics) the computational expense is too high to allow long enough simulations to properly capture the diffusion process in most materials.

    This thesis introduces a method to deal with this problem using an external force field to speed up the diffusion process in the simulation. The method is applied to study the diffusion of oxygen ions in Sm-doped ceria, which has showed promise in its use as an electrolyte. Good agreement with experimental data is demonstrated, indicating high potential for future applications of the method.

  • 10.
    Björklund, Sam
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Characterization of Inosine triphosphate pyrophosphatase, an important protein involved in purine metabolism2015Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    The enzyme inosine triphosphate pyrophosphatase (ITPase) is responsible for controlling the levels of the by-products guanosine monophosphate (GMP) and adenosine monophosphate (AMP) through their precursor inosine monophosphate (IMP). ). Human ITPase consists of a 194-amino acid homodimer which relies upon either an Mg2+ ion or a Mn2+ ion for catalytic activity, and orthologs of this protein have been found in many different organisms.

    The purpose of this project was to try out methods learned throughout the education and to use this knowledge to gather new data about the human protein inosine triphosphate pyrophosphatase (ITPase). The protein was expressed in BL21/DE3 cells from a pre-made vector. Experiments performed during this project include secondary- and tertiary stability measurements, tryptophan fluorescence spectra, binding curve and thermic stability to ITPase with ANS and methotrexate.

    The Tm-value of human ITPase was examined with Trp-Fluorescence, ANS-fluorescence and Near-UV and Far-UV circular dichroism (CD). The stability of ITPase monitored by Near-UV as well as Far-UV coincides, indicating that secondary- and tertiary-unfolding occur simultaneously without any intermediates.

    The results of Trp-fluorescence showed that the tryptophans were already exposed and thus it did not yield a reliable result. The binding properties of ANS and MTX to ITPase were also examined.

  • 11. Oliynyk, Igor
    et al.
    Varelogianni, Georgia
    Roomans, Godfried M
    Johannesson, Marie
    Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia.2010In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 118, no 12, 982-990 p.Article in journal (Refereed)
    Abstract [en]

    The lantibiotic duramycin (Moli1901, Lancovutide) has been suggested as a drug of choice in the treatment for cystic fibrosis (CF). It has been proposed that duramycin may stimulate chloride secretion through Ca²(+) -activated Cl⁻ channels (CaCC). We investigated whether duramycin exhibited any effect on Cl⁻ efflux and intracellular Ca²(+) concentration ([Ca²(+)](i)) in CF and non-CF epithelial cells. Duramycin did stimulate Cl⁻ efflux from CF bronchial epithelial cells (CFBE) in a narrow concentration range (around 1 μM). However, 100 and 250 μM of duramycin inhibited Cl⁻ efflux from CFBE cells. An inhibitor of the CF transmembrane conductance regulator (CFTR(inh)₋₁₇₂) and a blocker of the capacitative Ca²(+) entry, gadolinium chloride, inhibited the duramycin-induced Cl⁻ efflux. No effect on Cl⁻ efflux was observed in non-CF human bronchial epithelial cells (16HBE), human airway submucosal gland cell line, human pancreatic epithelial cells, CF airway submucosal gland epithelial cells, and CF pancreatic cells. The [Ca²(+)](i) was increased by 3 μM duramycin in 16HBE cells, but decreased after 1, and 3 μM of duramycin in CFBE cells. The results suggest that the mechanism responsible for the stimulation of Cl⁻ efflux by duramycin is mainly related to unspecific changes of the cell membrane or its components rather than to effects on CaCC.

  • 12. Varelogianni, Georgia
    et al.
    Hussain, Rashida
    Strid, Hilja
    Oliynyk, Igor
    Roomans, Godfried M
    Johannesson, Marie
    The effect of ambroxol on chloride transport, CFTR and ENaC in cystic fibrosis airway epithelial cells.2013In: Cell Biology International, ISSN 1065-6995, E-ISSN 1095-8355, Vol. 37, no 11, 1149-1156 p.Article in journal (Refereed)
    Abstract [en]

    Ambroxol, a mucokinetic anti-inflammatory drug, has been used for treatment of cystic fibrosis (CF). The respiratory epithelium is covered by the airway surface liquid (ASL), the thickness and composition of which is determined by Cl(-) efflux via the cystic fibrosis transmembrane conductance regulator (CFTR) and Na(+) influx via the epithelial Na(+) channel (ENaC). In cells expressing wt-CFTR, ambroxol increased the Cl(-) conductance, but not the bicarbonate conductance of the CFTR channels. We investigated whether treatment with ambroxol enhances chloride transport and/or CFTR and ENaC expression in CF airway epithelial cells (CFBE) cells. CFBE cells were treated with 100 µM ambroxol for 2, 4 or 8 h. mRNA expression for CFTR and ENaC subunits was analysed by real-time polymerase chain reaction (RT-PCR); protein expression was measured by Western blot. The effect of ambroxol on Cl(-) transport was measured by Cl(-) efflux measurements with a fluorescent chloride probe. Ambroxol significantly stimulated Cl(-) efflux from CFBE cells (a sixfold increase after 8 h treatment), and enhanced the expression of the mRNA of CFTR and α-ENaC, and of the CFTR protein. No significant difference was observed in β-ENaC after exposure to ambroxol, whereas mRNA expression of γ-ENaC was reduced. No significant effects of ambroxol on the ENaC subunits were observed by Western blot. Ambroxol did not significantly affect the intracellular Ca(2+) concentration. Upregulation of CFTR and enhanced Cl(-) efflux after ambroxol treatment should promote transepithelial ion and water transport, which may improve hydration of the mucus, and therefore be beneficial to CF-patients.

  • 13.
    Moritz, Matilda S. M.
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology. Maastricht University, Netherlands.
    Verbruggen, Sanne E. L.
    Maastricht University, Netherlands.
    Post, Mark J.
    Maastricht University, Netherlands.
    Alternatives for large-scale production of cultured beef: A review2015In: JOURNAL OF INTEGRATIVE AGRICULTURE, ISSN 2095-3119, Vol. 14, no 2, 208-216 p.Article, review/survey (Refereed)
    Abstract [en]

    Cultured beef is a method where stem cells from skeletal muscle of cows are cultured in vitro to gain edible muscle tissue. For large-scale production of cultured beef, the culture technique needs to become more efficient than todays 2-dimensional (2D) standard technique that was used to make the first cultured hamburger. Options for efficient large-scale production of stem cells are to culture cells on microcarriers, either in suspension or in a packed bed bioreactor, or to culture aggregated cells in suspension. We discuss the pros and cons of these systems as well as the possibilities to use the systems for tissue culture. Either of the production systems needs to be optimized to achieve an efficient production of cultured beef. It is anticipated that the optimization of large-scale cell culture as performed for other stem cells can be translated into successful protocols for bovine satellite cells resulting in resource and cost efficient cultured beef.

  • 14.
    Lundberg, Peter
    et al.
    Department of Biochemistry, University of Sydney, Australia.
    Roy, Sushmita
    Frick Laboratories, Princeton University, USA.
    Kuchel, Philip W
    Department of Biochemistry, University of Sydney, Australia.
    Immobilization Methods for NMR Studies of Cellular Metabolism: A Practical Guide1994In: ImmunoMethods, ISSN 1058-6687, Vol. 4, no 2, 163-178 p.Article in journal (Refereed)
    Abstract [en]

    Nuclear magnetic resonance (NMR) can be used in a nondestructive manner to study cellular metabolism in intact cell samples such as a suspension of cells. However, many different cell types require a well-regulated medium that includes a buffered pH, as well as a continuous supply of oxygen. A series of methods that have been used for the maintenance of the extracellular conditions involves the immobilization of cells, followed by perfusion of the immobilized cell sample. NMR studies can then be performed for extended periods of time, as well as under sterile conditions. We discuss methodology, with perfused erythrocytes and thymocytes as specific examples.

  • 15.
    Saint-Leger, A.
    et al.
    Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France; Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, Lyon, France.
    Koelblen, M.
    Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, Lyon, France.
    Civitelli, Livia
    Bah, A.
    Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, Lyon, France; Institute of Biochemistry (IBC), Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich, Switzerland.
    Djerbi, N.
    Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France.
    Giraud-Panis, M.-J.
    Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France; Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, Lyon, France.
    Londono-Vallejo, A.
    Telomeres and Cancer Lab., UMR3244, Institut Curie, Paris, France.
    Ascenzioni, F.
    Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Biologia e Biotecnologie Charles Darwin, Sapienza Università di Roma, Rome, Italy.
    Gilson, E.
    Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France; Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, Lyon, France; Department of Medical Genetics, Archet 2 Hospital, CHU of Nice, Nice, France.
    The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres2014In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 13, no 15, 2469-2479 p.Article in journal (Refereed)
    Abstract [en]

    The stability of mammalian telomeres depends upon TRF2, which prevents inappropriate repair and checkpoint activation. By using a plasmid integration assay in yeasts carrying humanized telomeres, we demonstrated that TRF2 possesses the intrinsic property to both stimulate initial homologous recombination events and to prevent their resolution via its basic N-terminal domain. In human cells, we further showed that this TRF2 domain prevents telomere shortening mediated by the resolvase-associated protein SLX4 as well as GEN1 and MUS81, 2 different types of endonucleases with resolvase activities. We propose that various types of resolvase activities are kept in check by the basic N-terminal domain of TRF2 in order to favor an accurate repair of the stalled forks that occur during telomere replication. © 2014 Landes Bioscience.

  • 16.
    Lundell, Christian
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    Water simulation for cell based sandbox games2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis work presents a new algorithm for simulating fluid based on the Navier-Stokes equations. The algorithm is designed for cell based sandbox games where interactivity and performance are the main priorities. The algorithm enforces mass conservation conservatively instead of enforcing a divergence free velocity field. A global scale pressure model that simulates hydrostatic pressure is used where the pressure propagates between neighboring cells. A prefix sum algorithm is used to only compute work areas that contain fluid.

  • 17.
    Tuvhag, Ellinor
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Undersökning av koppars effekt som antibakteriellt agens i tyg2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this study was to test the antibacterial effect of thin copper treads woven into a polyester fabric. The investigation was done by inoculation of Staphylococcus aureus strain ATCC 6538 to the fabric and evaluation of the number of viable cells post exposure by viable count. The issue to be answered was whether the copper fabric had a bactericide or bacteriostatic effect? The fabric is still in prototype stage, and if proven to have antibacterial properties the aim is to use it to prevent bacterial growth in wounds and other vulnerable locations in clinical care. Copper is an essential trace element, but also has antimicrobial properties through a wide range of mechanisms where cell membrane damage is one of the more important. Methods used for inoculation was the absorption method, where a nutrient broth containing S. aureus was pipetted on to the fabric specimens, and the transfer method where the fabric specimens were pressed onto an agar plate that had previously been spread with peptone salt solution containing S. aureus. Total number of bacteria per fabric specimen after short contact (<1 min) and incubation (18-24 h at 37±2°C) was calculated. Incubation showed significant difference in total number of bacteria between the copper fabric and negative control in three of four tests. Short contact showed a tendency of antibacterial effect. The conclusion was that the copper fabric harmed and killed bacteria during incubation but that more records would be needed to be sure about the effects of short contact on bacteria.

  • 18.
    Walldén, Johan
    Linköping University, Department of Electrical Engineering, Electronic Devices. Linköping University, The Institute of Technology.
    Radiation Induced Effects in Electronic Devices and Radiation Hardening By Design Techniques2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim with this thesis has been to make a survey of radiation hardened electronics, explaining why and how radiation affects electronics and what can be done to harden it.

    The effects radiation have on electronics in general and in specific commonly used devices are explained qualitatively. The effects are divided into Displacement Damage (DD), Total Ionizing Dose (TID) and Single Event Effects (SEEs). The devices explained are MOSFETs, Silicon On Insulator (SOI) transistors, 3D-transistors, Power transistors, Optocouplers, Field Programmable Gate Arrays (FPGAs), three dimensional circuits (3D-ICs) and Flash memories.

    Different radiation hardening by design (RHBD) techniques used to reduce or to remove the negative effects radiation induces in electronics are also explained. The techniques are Annular transistors, Enclosed source/drain transistors, Guard rings, Triple Modular Redundancy (TMR), Dual Interlocked Storage Cells (DICE), Guard gates, Temporal filtering,Multiple drive, Charge dissipation, Differential Charge Cancellation (DCC), Scrubbing, Lockstep, EDAC codes and Watchdog timers.

  • 19.
    Jonsson, Emil
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, The Institute of Technology.
    Modeling and Simulation of Cells2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this thesis is to create a computer program that simulates the motionof cells in a developing embryo. The resulting simulator is to be used by in the CellLineage project (Robert Forchheimer et al.) as an input to their genetic model, themeta-Boolean model [18]. This genetic model is not the focus of this work. Sincethe simulated system is highly complex, with fluids and deforming soft bodies, itis unfeasible to simulate the system in a physically realistic manner while keepingexecution time to reasonable values. Therefore some physical realism is sacrificedin favor of simulation stability and execution speed.The resulting simulator, Cell-Lab, uses Position Based Dynamics (PBD) [17] toimplement a number of different models for the cell’s mechanical properties. PBDis well suited for this purpose since it, while not taking excessively long time toexecute, guarantees an unconditionally stable simulation. The simulator includesa hard eggshell surrounding the cells. Cells can be split during the simulation,emulating mitosis. There is also the possibility to simulate cell adhesion usinga cadherin like mechanism. To control when and how cells are split and fetchinformation about the current state of the simulation there is an interface to beused by external applications. The meta-Boolean model can be implemented insuch an application

  • 20.
    Wali, Naveen
    et al.
    Linköping University, Department of Electrical Engineering, Electronics System. Linköping University, The Institute of Technology.
    Radhakrishnan, Balamurali
    Linköping University, Department of Electrical Engineering, Electronics System. Linköping University, The Institute of Technology.
    Design of a Time-to-Digital Converter for an All-Digital Phase Locked Loop for the 2-GHz Band2013Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    An all-digital phase locked loop for WiGig systems was implemented. The developedall-digital phase locked loop has a targeted frequency range of 2.1-GHz to2.5-GHz. The all-digital phase locked loop replaces the traditional charge pumpbased analog phase locked loop. The digital nature of the all-digital phase lockedloop system makes it superior to the analog counterpart.There are four main partswhich constitutes the all-digital phase locked loop. The time-to-digital converteris one of the important block in all-digital phase locked loop.

    Several time-to-digital converter architectures were studied and simulated. TheVernier delay based architecture and inverter delay based architecture was designedand evaluated. There architectures provided certain short comings whilethe pseudo-differential time-to-digital converter architecture was chosen, becauseof it’s less occupation of area. Since there exists a relationship between the sizeof the delay cells and it’s time resolution, the pseudo-differential time-to-digitalconverter severed it’s purpose.

    The whole time-to-digital converter system was tested on a 1 V power supply,reference frequency 54-MHz which is also the reference clock Fref , and a feedbackfrequency Fckv 2.1-GHz. The power consumption was found to be around 2.78mW without dynamic clock gating. When the clock gating or bypassing is done,the power consumption is expected to be reduced considerably. The measuredtime-to-digital converter resolution is around 7 ps to 9 ps with a load variation of15 fF. The inherent delay was also found to be 5 ps. The total output noise powerwas found to be -128 dBm.

  • 21.
    Kalldin, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Lamination of Organic Solar Modules2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    As the Worlds energy demand is increasing we need more of our energy to be generated from resources that affect the climate as little as possible. Solar power could be the solution if there were solar panels with a less energy demanding production than the established silicon based solar modules.

    Printable organic solar cells will enable a cheap production process, thus they are mainly made out of polymers in solution. However, to be able to decrease the total cost of the solar modules the commonly used indium tin oxide (ITO) for the transparent electrode needs to be replaced by a less expensive material. If the cheap, high conductive and transparent polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) could replace ITO the cost of organic solar modules would significantly decrease.

    For PEDOT:PSS to be able to replace ITO there are requirements that have to be met. The transparent electrode needs to be apart from transparent, highly conductive, have a low contact resistance to the other materials in the organic solar cell and be printable.

    In this study it has been shown that the PEDOT:PSS film with Zonyl and Diethylene Glycol (DEG) as an secondary dopant, is capable of laminating to thin films made out of PEDOT:PSS, metal or a polymer fullerene blend. The contact resistances between two PEDOT:PSS films and PEDOT:PSS film and a metal film proved to be low. When laminating to a metal film an interlayer of Silver Nano Wires (AgNW) was needed to achieve a low contact resistance.

  • 22.
    Håkman, Jonna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Vitamin C as a modifier of mammalian epigenetics: implications for adaptive immunity2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Ascorbic acid (AA), in popular speech vitamin C, is a commonly known nutrient. It is involved in several biological processes and deficiency can lead to scurvy. Recent publications have shown the impact of AA on epigenetic regulation in mice. Addition of AA, via enzymatic activity, enhances the generation of 5-hydroxymethylcytosine (5hmC), which is an intermediate in active demethylation of DNA.

    The role of AA on epigenetic changes in humans has to our knowledge never been studied. In this study, naïve CD4+ T cells from blood donors were used as a model system to investigate AAs possible role in methylation changes in the immune system. By using dot-blot assay, hydroxymethylated DNA immunoprecipitation (hmeDIP) and qPCR, changes in methylation executed by AA could be detected.

    A confirmation of AAs impact on epigenetic changes in mice was observed. AA enhanced the levels of 5hmC compared to untreated cells. The Jurkat cell line, a human T lymphocyte cell line, showed an opposite result. Treatment with AA decreased the levels of 5hmC compared to untreated cells. When comparing this result with the results obtained in human naïve T cells, the same observation was made. The difference between mouse and human in the ability of producing and metabolize AA could be a reason for this opposite result.

    Since AA had the ability to modify epigenetic changes in primary human CD4+ T cells, the results suggest that AA may have a function in the human immune system.

  • 23.
    Li, Wei
    et al.
    Linköping University, Department of Clinical and Experimental Medicine.
    Yuan, Xi-Ming
    Linköping University, Department of Clinical and Experimental Medicine.
    Olsson, AG
    Brunk, UT
    Uptake of oxidized LDL by macrophages results in partial lysosomal enzyme inactivation and relocation.1998In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 18, 177-184 p.Article in journal (Other academic)
    Abstract [en]

    he cytotoxicity of oxidized LDL (oxLDL) to several types of artery wall cells might contribute to atherosclerosis by causing cell death, presumably by both apoptosis and necrosis. After its uptake into macrophage lysosomes by receptor-mediated endocytosis, oxLDL is poorly degraded, resulting in ceroid-containing foam cells. We studied the influence ofoxLDL on lysosomal enzyme activity and, in particular, on lysosomal membrane stability and the modulation of these cellular characteristics by HDL and vitamin E (vit-E). Unexposed cells and cells exposed to acetylated LDL (AcLDL) were used as controls. The lysosomal marker enzymes cathepsin L and N-acetyl-beta-glucosaminidase (NAbetaGase) were biochemically assayed in J-774 cells after fractionation. Lysosomal integrity in living cells was assayed by the acridine orange (AO) relocation test. Cathepsin D was immunocytochemically demonstrated in J-774 cells and human monocyte-derived macrophages. We found that the total activities of NAbetaGase and cathepsin L were significantly decreased, whereas their relative cytosolic activities were enhanced, after oxLDL exposure. Labilization of the lysosomal membranes was further proven by decreased lysosomal AO uptake and relocation to the cytosol of cathepsin D, as estimated by light and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The results indicate that endocytosed oxLDL not only partially inactivates lysosomal enzymes but also destabilizes the acidic vacuolar compartment, causing relocation of lysosomal enzymes to the cytosol. Exposure to AcLDL resulted in its uptake with enlargement of the lysosomal apparatus, but the stability of the lysosomal membranes was not changed.

  • 24. Garner, B
    et al.
    Li, Wei
    Linköping University, Department of Clinical and Experimental Medicine.
    Roberg, K
    Brunk, UT
    On the cytoprotective role of ferritin in macrophages and its ability to enhance lysosomal stability.1997In: Free radical research, ISSN 1071-5762, Vol. 27, 487-500 p.Article in journal (Other academic)
    Abstract [en]

    Macrophages have a great capacity to take up (e.g. by endocytosis and phagocytosis) exogenous sources of iron which could potentially become cytotoxic, particularly following the intralysosomal formation of low-molecular weight, redox active iron, and under conditions of oxidative stress. Following autophagocytosis of endogenous ferritin/apoferritin, these compounds may serve as chelators of such lysosomal iron and counteract the occurrence of iron-mediated intralysosomal oxidative reactions. Such redox-reactions have been shown to lead to destabilisation of lysosomal membranes and result in leakage of damaging lysosomal contents to the cytosol. In this study we have shown: (i) human monocyte-derived macrophages to accumulate ferritin in response to iron exposure; (ii) iron to destabilise macrophage secondary lysosomes when the cells are exposed to H2O2; and (iii) endocytosed apoferritin to act as a stabiliser of the acidic vacuolar compartment of iron-loaded macrophages. While the endogenous ferritin accumulation which was induced by iron exposure was not sufficient to protect cells from the damaging effects of H2O2, exogenously added apoferritin, as well as the potent iron chelator desferrioxamine, afforded significant protection. It is suggested that intralysosomal formation of haemosiderin, from partially degraded ferritin, is a protective strategy to suppress intralysosomal iron-catalysed redox reactions. However, under conditions of severe macrophage lysosomal iron-overload, induction of ferritin synthesis is not enough to completely prevent the enhanced cytotoxic effects of H2O2.

  • 25.
    Zandén, Adam
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Utvärdering av solceller och vindkraft2012Independent thesis Basic level (university diploma), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    According to the evaluations that have been made of the three different solar cell types (polycrystalline, monocrystalline and thin film) and the various models from Sino Sun, PPAM and Schüco the conclusion is that the most expensive solar cell, is not always the best. The differences between Sino Sun and PPAM are so small and along with the price off the last mentioned solar cell which means that Sino Sun’s solar cells are the best choice of solar cell technology that Egen El AB has to offer.

    The different wind power alternatives on Kullen in the city of Katrineholm come in many shapes and method of fabrication. The results have shown that ETC is not a great wind power solution but Svarta Sara, one av Egen El AB’s flagship, is according to the output power effectiveness.

  • 26.
    Ovrén, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Knockdown of the ERK pathway using siRNA in cultured chicken cardiomyocytes2014Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The ancient South American birds called tinamous (Tinamidae) have the smallest hearts known among birds and their cardiomyocytes have previously been shown to express significantly lower levels of the mitogen-activated protein kinase ERK compared to the more modern chicken (Gallus gallus). ERK is a well-known mediator of growth signalling in the heart, especially in hypertrophy. The aim of this project was to assess the effect of ERK knockdown on proliferation in cultured chicken cardiomyocytes. By transfecting these cells with a lipoplexed siRNA, ERK mRNA levels were knocked down to approximately half (45%, SD: 27%) compared to cells transfected with a negative control siRNA. The knockdown was coupled with a decreased proliferative response to insulin-like growth factor 1 (IGF-1) and foetal bovine serum (FBS). In conclusion, the ERK pathway was confirmed to be instrumental also in proliferative signalling. The results also support the notion that ERK itself is the rate-limiting step of this MAPK cascade. The low native expression of ERK in tinamou cardiomyocytes is expected to impose a strict limit on proliferative growth in response to various stimuli in these hearts. The genetic changes leading to higher expression levels, and with it the potential for larger hearts, in modern birds would have led to greatly increased evolutionary fitness by way of an increased aerobic scope and the ability to sustain flight. 

  • 27.
    Ragavan, Rengarajan
    Linköping University, Department of Electrical Engineering, Electronic Devices. Linköping University, The Institute of Technology.
    Reconfigurable FSM for Ultra-Low Power Wireless Sensor Network Nodes2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Wireless sensor networks (WSN) play an important role in today’s monitoring and controlsystems like environmental monitoring, military surveillance, industrial sensing and control, smarthome systems and tracking systems. As the application of WSN grows by leaps and bounds, there is anincreasing demand in placing a larger number of sensors and controllers to meet the requirements. Theincreased number of sensors necessitates flexibility in the functioning of nodes. Nodes in wirelesssensor networks should be capable of being dynamically reconfigured to perform various tasks is theneed of the hour.In order to achieve flexibility in node functionality, it is common to adopt reconfigurablearchitecture for WSN nodes. FPGA-based architectures are popular reconfigurable architectures bywhich WSN nodes can be programmed to take up different roles across time. Area and power are themajor overheads in FPGA based architectures, where interconnect consumes more power and area thanlogic cells. The contemporary WSN standard requires longer battery life and micro size nodes for easyplacement and maintenance-free operation for years together.Three solutions have been studied and evaluated to approach this problem: 1) Homogenousembedded FPGA platform, 2) Power gated reconfigurable finite state machines and 3) Pass transistorlogic (PTL) based reconfigurable finite state machines. Embedded FPGA is a CMOS 65nm customdeveloped small homogenous FPGA which holds the functionality of the WSN nodes and it will bedynamically reconfigured from time to time to change the functionality of the node. In Power gatedreconfigurable FSM architecture, the functionality of the node is expressed in the form of finite statemachines, which will be implemented in a LUT based power gated design. In PTL based reconfigurablefinite state machine architecture, the finite state machines are completely realized using PTL basedcustom designed sets of library components. Low power configuration memory is used to dynamicallyreconfigure the design with various FSMs at different times.

  • 28.
    Varelogianni, Georgia
    et al.
    Uppsala University, Sweden.
    Oliynyk, Igor
    Uppsala University, Sweden.
    Roomans, Godfried M
    Uppsala University, Sweden.
    Johanssesson, Marie
    Uppsala University, Sweden.
    The effect of N-acetylcysteine on chloride efflux from airway epithelial cells2010In: Cell Biology International, ISSN 1065-6995, E-ISSN 1095-8355, Vol. 34, no 3, 245-252 p.Article in journal (Refereed)
    Abstract [en]

    Defective chloride transport in epithelial cells increases mucus viscosity and leads to recurrent infections with high oxidative stress in patients with CF (cystic fibrosis). NAC (N-acetylcysteine) is a well known mucolytic and antioxidant drug, and an indirect precursor of glutathione. Since GSNO (S-nitrosoglutathione) previously has been shown to be able to promote Cl- efflux from CF airway epithelial cells, it was investigated whether NAC also could stimulate Cl- efflux from CF and non-CF epithelial cells and through which mechanisms. CFBE (CF bronchial epithelial cells) and normal bronchial epithelial cells (16HBE) were treated with 1 mM, 5 mM, 10 mM or 15 mM NAC for 4 h at 37 degrees C. The effect of NAC on Cl- transport was measured by Cl- efflux measurements and by X-ray microanalysis. Cl- efflux from CFBE cells was stimulated by NAC in a dose-dependent manner, with 10 mM NAC causing a significant increase in Cl- efflux with nearly 80% in CFBE cells. The intracellular Cl- concentration in CFBE cells was significantly decreased up to 60% after 4 h treatment with 10 mM NAC. Moreover immunocytochemistry and Western blot experiments revealed expression of CFTR channel on CFBE cells after treatment with 10 mM NAC. The stimulation of Cl- efflux by NAC in CF airway epithelial cells may improve hydration of the mucus and thereby be beneficial for CF patients.

  • 29.
    Oliynyk, Igor
    et al.
    Uppsala University, Sweden.
    Varelogianni, Georgia
    Uppsala University, Sweden.
    Schalling, Martin
    Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
    Stenkvist Asplund, Monika
    Uppsala University, Sweden.
    Roomans, Godfres M
    Uppsala University, Sweden.
    Johannesson, Marie
    Uppsala University, Sweden.
    Azithromycin increases chloride efflux from cystic fibrosis airway epithelial cells2009In: Experimental Lung Research, ISSN 0190-2148, E-ISSN 1521-0499, Vol. 35, no 3, 210-221 p.Article in journal (Refereed)
    Abstract [en]

    It was investigated whether azithromycin (AZM) stimulates chloride (Cl-) efflux from cystic fibrosis (CF) and non-CF airway epithelial cells, possibly secondary to up-regulation of the multidrug resistance protein (MDR). CF and non-CF human airway epithelial cell lines (CFBE and 16HBE) were treated with 0.4, 4, and 40 microg/mL AZM for 4 days. Cl- efflux was explored in the presence or absence of specific inhibitors of CFTR and alternative Cl- channels. Six CF patients received AZM (500 mg daily) for 6 months. The percentage of predicted forced vital capacity (FVC%), forced expiratory volume (FEV1%), and the number of acute exacerbations were compared before and after treatment. Nasal biopsies were taken before and after treatment, and mRNA expression of MDR and CFTR was determined by in situ hybridization. A significant dose-dependent increase of Cl- efflux from CFBE cells (but not from 16HBE cells) was observed after AZM treatment. A CFTR inhibitor significantly reduced AZM-stimulated Cl- efflux from CFBE cells. A significant improvement in FEV1%, and fewer exacerbations were observed. AZM treatment did not affect mRNA expression of MDR and CFTR. The stimulation of Cl- efflux could be part of the explanation for the clinical improvement seen among the patients.

  • 30.
    Ottosson, Markus
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Bränsleceller i fyrar - en alternativ energiförsörjning av fasta nautiska navigationshjälpmedel2005Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Rapporten utreder bränslecellsteknikens lämplighet som energikälla till sjö- märken i allmänhet och fyrar i synnerhet.

    Ingående tekniker, såväl rörande bränsleceller som fyrar, presenteras i två introducerande kapitel. Vidare utreds problematiken kring lagring och hantering av vätgas. Slutsatser från de inledande delarna leder fram till ett systemförslag. Avslutningsvis presenteras en en kortfattad ekonomisk analys.

    Rapporten visar att tekniken i sig är lämplig. Sjöfartsverkets krav vad gäller tillförlitlighet och livslängd uppfylls i exempelsystemet. Utbyggnadsmöjligheterna är goda, vilket öppnar för nya funktioner hos fristående fyrar.

    Det är dock i dagsläget svårt att ekonomiskt konkurrera med bentliga lösningar. Huvudproblemet är när det gäller bränslecellerna är gasförsörjningen. Gastransporter är en högst oönskad verksamhet, vilket gör att den enda attraktiva lösningen blir lokalt producerad vätgas genom elektrolys. Där för erforderlig apparatur är kostsam och adderar systemkomplexitet.

  • 31.
    Bark, Fredrik
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Beläggningsanalys av motorprovningen vid Volvo Aero Corporation2005Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This is a result of a Master’s thesis initiated by the Engine Testing Department (ETD), at Volvo Aero Corporation in Trollhättan, Sweden. The ETD performs a variety of testings, encompassing delivery testing of complete engines as well as engine components. The engine tests are accomplished in a special made area called test cell, TC.

    At the present time the ETD has to make a decision, if it is possible to shut down one of the test cells and transfer those engines to another test cell. The ETD has no knowledge of flow capacity of the different test cells and whether this transfer is possible to do or not. The principal purpose of this study is to identify those variables that have an effect on an engine test and from that build a load model. The model is supposed to give information about what resources is needed concerning as time and manpower, to test a quantity of different engines.

    The study also includes an economic estimation of the consequences of the shut down. The ETD has to raise the standards for faster throughput time and today they do not calculate their own throughput time at all. Another purpose in this study is to manage how to calculate the throughput time, to meet the new increasing demands.

    The load model is now developed and consists of those variables that effect the lead time of testing an engine. The idea is that the model updates inputs from old engine tests and uses the data to estimate the time for future engine tests. Those results give the ETD information about approximately resources for future engine tests. The input to the model transforms from another program called TCDB, Test Cells Database, which is used to register data by engine tests. It is of vital importance that TCDB is used and filled in correctly in order to establish a correct result in the model. The model is simple, easy to use and it gives the user an opportunity to adjust times changes and the frequency of faults which sometimes arises in engine tests. The user is able to experiment within the model to see how different effects influence the final coating results.

    When the model is calculating the engine volume for the year 2005, with the existing input, it requires resources for about 2100 hours excluding maintenance. Since the ETD estimates the number test cell hours to 1400 hours per year, the result gives a shift work at about 1,5 shifts. 1,5 shifts means that the ETD has to increase their shifts from one to two shifts to settle the prognosticated engine unit of volume.

    The economic consequences of shutting down a test cell contribute to saving XX 2 SEK in the year of 2005 and approximately XX SEK yearly from year 2006 and forward. The difference between the years depends in a certain extend, on that some of the fixed costs can not be eliminated directly because of the contact agreements.

    A routine has been initiated which makes it possible to measure the throughput time. How ever, it must improve to be more effective to give a straightforward knowledge about the throughput time. Suggestions on how this should be done have been given in this study.

  • 32.
    Fakhraee Seyedabad, Ali
    Linköping University, Department of Computer and Information Science, Database and information techniques. Linköping University, The Institute of Technology.
    Using Semi-supervised Clustering for Neurons Classification2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    We wish to understand brain; discover its sophisticated ways of calculations to invent improved computational methods. To decipher any complex system, first its components should be understood. Brain comprises neurons.

    Neurobiologists use morphologic properties like “somatic perimeter”, “axonal length”, and “number of dendrites” to classify neurons. They have discerned two types of neurons: “interneurons” and “pyramidal cells”, and have a consensus about five classes of interneurons: PV, 2/3, Martinotti, Chandelier, and NPY. They still need a more refined classification of interneurons because they suppose its known classes may contain subclasses or new classes may arise. This is a difficult process because of the great number and diversity of interneurons and lack of objective indices to classify them.

    Machine learning—automatic learning from data—can overcome the mentioned difficulties, but it needs a data set to learn from. To meet this demand neurobiologists compiled a data set from measuring 67 morphologic properties of 220 interneurons of mouse brains; they also labeled some of the samples—i.e. added their opinion about the sample’s classes.

    This project aimed to use machine learning to determine the true number of classes within the data set, classes of the unlabeled samples, and the accuracy of the available class labels. We used K-means, seeded K-means, and constrained K-means, and clustering validity techniques to achieve our objectives. Our results indicate that: the data set contains seven classes; seeded K-means outperforms K-means and constrained K-means; chandelier and 2/3 are the most consistent classes, whereas PV and Martinotti are the least consistent ones.

  • 33.
    Waqar, Azeem
    et al.
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Zafar, Muhammad Ammar
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Simulation and Optimization of Frequency Reuse in OFDMA Networks2011Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Efficient radio resource management is an important aspect when it comes to achieving high bit rates in technologies such as the 3GPP Long Term Evolution (LTE). This thesis aims at understanding existing frequency reuse schemes in OFDMA networks, and to develop an algorithm for frequency allocation for irregular cellular layouts. Previous work done in this field mostly covers schemes for regular cells, whereas in real life cellular layouts are mostly irregular. A comparison of the existing allocation schemes for the users near the boundary of the cells, also known as edge users, with our scheme is presented.

    Reuse-1, Fractional frequency reuse-3 with random frequency allocation (FFR3-RFA) (for edge users) and our algorithmic frequency allocation (FFR3-AFA) scheme are simulated and compared. FFR3-AFA algorithm assigns a frequency sub-band to a cell by considering the frequency allocations in the neighbor cell edges and the overlap area between those neighboring cells. Static simulations were performed with one user per base station and constant downlink traffic of 100 Kbits/sec, so that all the resources are utilized and there is maximum interference. This way, the difference between the frequency reuse schemes is much more evident. The throughput for our calculation is the ratio of the total successful packets sent in the network and the total packets sent in the network. Small scenarios are considered with different downlink data rates and the results show that FFR3-AFA has better performance than the other two techniques. There is also room for improvement in the algorithm by introducing other factors into the equation other than overlap area, such as user throughput.

  • 34.
    Chen, Juan
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    PWM DC/DC Converter2008Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This report is the result of a Master Thesis work done at Seaward Electronics Inc. in Beijing, China from June to December in 2007. The main goal for this thesis is to verify and improve the performance of Honey-PWM DC-DC converter, which has been fabricated by a standard 0.6um CMOS processes.

    The project was started with studying of Buck converter structure. After the understanding of the converter structure, the project goes in to the analyses phase for each sub-cells, including the theory, functionality and implementation methods. In the end, the report presents the results from both of the schematic simulation and test on silicon. All the design works are supported by EDA tool of Cadence.

  • 35.
    Nuhanovic, Ezmir
    et al.
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Oksanen, Mika
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Solar cells and wind power for a susntainable, economic and environmental friendly development2007Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Möjligheterna att använda förnybara, sol- och vindenergi, att driva luftvärmepumpar har studerats. En typisk luftvärmepump drar 1,8kW effekt som högst under de kallaste perioderna. Studien visar att Sverige är ganska solfattig under tiden då värmepumpen behövs som mest. Investeringen i solel är mycket dyr. En kWh solel kostar cirka 4 - 5 kronor, räknat på 25års drift. Solel, som energikälla rekommenderas inte för att driva värmepumpar.

    Vindkraft å andra sidan kan vara ekonomisk hållbar under vissa förhållanden. I motsats till solstrålning har vinden olika hastigheter vid olika höjder och olika lägen. Småskalig vindkraft vid bra läge kan vara ekonomisk hållbar medan vid ett vindfattigt läge kan vindkraft inte bära sina kostnader. Rapporten visar vidare kostnadskalkyler för småskalig sol och vind elproduktion. Vidare jämförs prisnivån i Sverige med Tyskland, som är ledande inom solel. Lagstiftning och regelverk för installation av vindkraft berörs också.

  • 36.
    Lind, Liza
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Non-coding RNA in T cell activation and function2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    For a long time research has focused on the protein-coding mRNA, but there is a complex world of non-coding RNAs regulating the human body that we yet know very little about. Non-coding RNAs (ncRNAs) are involved in modulation of different cell processes including proliferation, differentiation and apoptosis. In the current study the role of ncRNAs in T cell activation and function was investigated. T cells are important mediators of immune responses, for example upon viral infections. The T helper cells (TH or CD4+ cells) are involved in orchestrating immune processes like aiding the activation of macrophages and enhancement of B cell function. The TH1 cell subtype is generally pro-inflammatory and IFNγ-secreting. There are regulatory T (Treg) cells that are involved in downregulation of TH1 cells, to decrease or terminate the immune response. It has been shown that upon repeated stimulation TH1 cells can switch into a Treg-like IL10-secreting anti-inflammatory phenotype.

    In the IL10-secreting Treg-like cells the microRNA 150 (miR-150) was found upregulated compared to IFNγ-secreting TH1 cells. Thus, miR-150 was believed to be a candidate in key regulation of the switch between the two phenotypes. Predicted target genes of miR-150 were identified using mRNA arrays investigating down-regulated genes in the IL10-secreting Treg-like subpopulation. In this thesis predicted targets of miR-150 were investigated using luciferase assays. Unfortunately no targets were identified.

    Upon isolation of IFNγ-secreting TH1 cells and Treg-like IL10-secreting cells, it was found that the ncRNA 886 (nc886) was upregulated in these activated cells, compared to resting TH cells. This indicates that nc886 has an important role in T cell activation. Nc886 has been shown to inhibit PKR activation in other cell types. The effect of nc886 on protein kinase R (PKR) was therefore investigated. PKR shuts down translation upon activation in response to viral double-stranded RNA or cellular stress. We showed that in an activated T cell phenotype nc886 is affecting PKR upon activation by dsRNA from HIV or synthetic origin. The PKR activation pattern is reversed in a resting T cell phenotype.

  • 37.
    Johansson, Malin
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
    Investigation of hPin1 mediated phosphorylation dependency in degradation control of c-Myc oncoprotein2012Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Cancer is the main cause of death in economically developed countries and the second leading cause of death in developing countries. Along with today’s knowledge that more than two hundred different diseases lie in the category of this prognosis there is an urge for more detailed and case-specific treatments to replace the dramatic actions of available radiation- and chemotherapy, which in many cases do not make a difference between healthy and cancer cells.

    The transcription factor and onco-protein c-Myc has, after being extensively studied during the past decades, become a prognostic marker for almost all cancer forms known. Still, many questions remain regarding how c-Myc interacts with its many different target proteins involved in cell-cycle regulation, proliferation and apoptosis. Current cell biology states that one of the regulating proteins, hPin1, interacts with c-Myc in a phosphorylation-dependent manner which appears to direct the correct timing of c-Myc activation and degradation through the ubiquitin/proteasome-pathway. The critical phosphorylation sites, T58 and S62, are located in the Myc-Box-I (MBI) region, a highly conserved sequence strongly coupled to aggressive tumourigenesis by hotspot mutations. Interestingly, preliminary results in the Sunnerhagen group suggested that MBI alone did not bind hPin1, suggesting hPin1 targeting a site distal from the residues to be phosphorylated.

    In this thesis, results from Surface Plasmon Resonance (SPR) and Nuclear Magnetic Resonance (NMR) show that the docking WW-domain of hPin1 binds unphosphorylated c-Myc at a region distal from the phosphorylation site, including residues 13-34. Furthermore, SPR experiments revealed that hPin1 binds unphosphorylated c-Myc with apparently greater affinity and with much slower kinetics than phosphorylated c-Myc. Thus, hPin1 recognition and interaction with c-Myc appears not to be dependent on phosphorylation of c-Myc prior binding. The newly identified binding region of c-Myc, located N-terminal of MBI, may further increase the understanding of protein degradation control and c-Myc function.

    The studies presented in this thesis provide a brick in the puzzle of c-Myc and hPin1 coupled oncogenesis for further development of new therapeutic strategies.

  • 38.
    Abdul Aziz Hasan Ali, Aamir
    et al.
    Linköping University, Department of Science and Technology, Communications and Transport Systems. Linköping University, The Institute of Technology.
    Shahzad, Muhammad Adil
    Linköping University, Department of Science and Technology, Communications and Transport Systems. Linköping University, The Institute of Technology.
    A Joint Subcarrier/Power allocation Scheme for OFDMA-based Cellular Networks2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The assignment of this master thesis consists of initiating power, subcarrier allocation in a dynamic FFR based scheme designed for multi-cell OFDMA networks and to enhance the throughput of all center users in bandwidth hungry borrower cells (overloaded cells) which was previously degraded by original FFR3 scheme as a result of partitioning of system bandwidth into center and edge bands respectively. The method uses band borrowing to compensate center user’s throughput loss in a semi and fully overloaded system. The scheme uses dynamic programming method (0/1 knapsack problem) to bargain an edge band on various power levels and tends to check the best combination (power and sub-carrier) which the system can utilize while still maintaining acceptable throughput loss for the users at the edge of the neighboring cell (lender cell).

    The algorithm consists of generating a borrowing request to neighboring cells for utilizing their edge bands by the overloaded borrower cell if their average center user throughput reaches below a minimum threshold value set in the system. The borrowing method uses 0/1 knapsack problem to capture an edge band based on limiting factors of total cost in average throughput losses by neighbors (Ci) and Un (tolerable mean user edge user throughput loss by lending cell). While solving knapsack problem the lender (neighbors) will check Ci and Un before granting the right to use its edge band. The later stage requires reducing subcarrier power level in order to utilize the lenders edge band using "soft borrower" mode. The borrowed sub-carriers will be activated take power from the original center band sub-carriers of the overloaded cell by taking into account the interference between the lender and the borrower. In case of negative (0) reply from the lender cell after the first request, multiple requests are generated at reduce power level at every step to order to acquire more bands. If a neighbor has band borrowing requests from multiple overloaded base stations, the band will be granted to the one which gives minimal loss in terms of throughput to the lender cell.

    The simulation results are analyzed w.r.t reuse-1 and FFR3 scheme of a multi cell regular and irregular scenarios comprising of lightly to heavily overloaded cells with various subcarrier allocation patterns. An overhead and time assessment is also presented between borrower and lender cells. Simulation results show an increase of 60% in center user’s throughput w.r.t original FFR3 scheme with an acceptable loss of 18% at the edges in complex overloaded scenarios while the overall system throughout increases by 35%.

  • 39.
    Patra, Hirak
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics.
    Cell selective response to gold nanoparticles: Cellular specificity of gold nanoparticles2007In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, Vol. 3, no 2, 111-119 p.Article in journal (Refereed)
    Abstract [en]

    Gold nanoparticles (GNPs) are considered a potential probe to detect cancer. The present article investigates whether GNPs, even in the absence of any specific functionalization, induce any cell specific response. We report GNP-induced death response in human carcinoma lung cell line A549. In contrast, the two other cell lines tested, BHK21 (baby hamster kidney) and HepG2 (human hepatocellular liver carcinoma), remained unaffected by GNP treatment. The specificity of the induction of the death response in A549 cells implies that GNPs do not universally target all cell types. Flow-cytometric studies indicated that the response was dose dependent and had a threshold effect (in A549). Gradual increase in GNP concentration induces a proportional cleavage of poly(ADP-ribose) polymerase. The programmed nature of the death response is implied, because such cleavage follows activation of caspases. Notably, at higher GNP concentration there was an asymmetric accumulation of GNPs in the periphery outside the cell nucleus of the A549 cells. This was confirmed by confocal microscopy, a green scattering (possibly, surface-enhanced Raman effect) appearing on selective z-slices of the image.

  • 40.
    Spetz, Anna-Lena
    et al.
    Karolinska Institute, Sweden.
    Patterson, Bruce K.
    Northwestern University Medical School, Chicago, USA.
    Lore, Karin
    Karolinska Institute, Sweden.
    Andersson, Jan
    Karolinska Institute, Sweden.
    Holmgren, Lars
    Karolinska Institute, Sweden.
    Functional gene transfer of HIV DNA by an HIV receptor-independent mechanism1999In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 163, no 2, 736-742 p.Article in journal (Refereed)
    Abstract [en]

    HIV-1 enters target cells mainly via binding to CD4 and its coreceptors. The presence of HIV-1 in CD4(-) cells suggests, however, that there exist other mechanisms for viral entry, Here it is reported that HIV-1 DNA may be transferred from one cell to another by uptake of apoptotic bodies in a CD4-independent way. This was investigated by coculturing CD4(-), chemokine receptor CCR5(-) and CXCR4(-) human fetal fibroblasts with apoptotic HIV-1-infected HuT78 cells or apoptotic PBMC isolated from HIV-1-infected patients. After 2 wk of coculture, fibroblasts contained HIV-1 DNA and expressed HIV-1 proteins p24 and gp120, Transfer of HIV-1 DNA was verified by coculturing fibroblasts with apoptotic bodies derived from cells infected with a defective HIV-1 virus. These cells contain one integrated copy of a reverse transcriptase (RT)-negative HIV-1 strain (8E5/LAV RT- cells) and consequently cannot produce free virus, Intracellular HIV-1 gag DNA was detected in both fibroblasts and dendritic cells after coculture with apoptotic 8E5/LAV RT- cells. Transfer of viral DNA after uptake of apoptotic bodies mag explain HIV-1 infection of CD4(-) cells in vivo and furthermore may be relevant for Ag presentation.

  • 41.
    Joshi, Raoul
    et al.
    Linköping University, Department of Electrical Engineering, Communication Systems. Linköping University, The Institute of Technology.
    Sundström, Per
    Linköping University, Department of Electrical Engineering, Communication Systems. Linköping University, The Institute of Technology.
    WCDMA Cell Load Control in a High-speed Train Scenario: Development of Proactive Load Control Strategies2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Load control design is one of the major cornerstones of radio resource management in today's UMTS networks. A WCDMA cell's ability to utilize available spectrum efficiently, maintain system stability and deliver minimum quality of service (QoS) requirements to in-cell users builds on the algorithms employed to manage the load. Admission control (AC) and congestion control (CC) are the two foremost techniques used for regulating the load, and differing environments will place varying requirements on the AC and CC schemes to optimize the QoS for the entire radio network. This thesis studies a real-life situation where cells are put under strenuous conditions, investigates the degrading effects a high-speed train has on the cell's ability to maintain acceptable levels of QoS, and proposes methods for mitigating these effects.

    The scenario is studied with regard to voice traffic where the limiting radio resource is downlink power. CC schemes that take levels of fairness into account between on-board train users and outdoor users are proposed and evaluated through simulation. Methods to anticipatorily adapt radio resource management (RRM) in a cell to prepare for a train is proposed and evaluated through simulation. A method to detect a high-speed train in a cell, and the users on it, is outlined and motivated but not simulated.

    Simulation results are promising but not conclusive. The suggested CC schemes show a surprising tendency towards an increase in congestion avoidance performance. Proactive RRM shows a significant increase in QoS for on-board users. No negative effects to users in the macro environment is noticed, with regard to the studied metrics.

  • 42.
    Christoffersson, Jonas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Distribution of Sca-1+ cardiac progenitor cells in the healthy and the post-MI heart2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The myocardial infarction (MI) is one of the leading causes of death in the world today. Accumulated atherosclerotic plaque occluding cardiac blood vessels results in a lack of oxygen supply to parts of the heart, and consequentially the death cardiomyocytes. The damaged area is replaced by scar tissue because of the heart’s insufficient regenerative capability, and the contraction property of the post-MI heart is therefore compromised. The recent findings of an endogenous cardiac progenitor cell (CPC) population gives hope for the establishment of new methods for medical treatments of the post-MI heart. Compared to other stem/progenitor cell sources, the CPCs are committed to a cardiac fate which places them in the forefront of interesting cell sources for regenerative treatments. In this thesis, the distribution of stem cell antigen 1 (Sca-1) positive CPCs in the healthy mouse myocardium, as well as the healthy and post-MI rat left ventricle was determined and compared to the total amount of nuclei. An immunohistochemistry protocol for the detection of Sca-1+ cells was established, and the number of Sca-1+ cells and the total number of nuclei in the different mouse and rat tissue samples were counted using laser scanning cytometry (LSC). The results could conclude a significantly higher distribution of Sca-1+ cells in the mouse atrium compared to the mouse ventricle, and a significantly higher distribution of Sca-1+ cells in the 8 days post-MI rat left ventricle compared to the healthy rat left ventricle. Furthermore, a heterogeneous distribution within the 8 days post-MI rat left ventricle was observed.

  • 43.
    Shamsudin, Nebil
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    A Device for Measurement of Capillary Refilling Time2012Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    The main objective of this project is to design, construct and validate a portable prototype of a device that is capable of performing a test to accurately measure Capillary Refilling Time (CRT), and to analyze the results with defined parameters; force, area, pressure (compression) and time. This prototype is dedicated to study and evaluate CRT readouts for different pressure values, collected from healthy subjects.The presented prototype of this study is capable of producing skin compressing and to measure the refilling time of capillaries following this compression. This prototype introduces accuracy, mechanical reproducibility and controlling options for the applied pressure and compression time. The presented prototype is non-invasive, portable and it can be used to conduct more CRT tests and other capillary refilling studies.CRT measurement is done by calculating time interval starting from the first point when the applied pressure is released; ending with the recording point at the time when the concentration of red blood cells has reached the level of its pre-occlusion values.Based on the calculated CRT values and the number of iterations of the test in CRT tables, one can observe that given the same applied pressure value, CRT values do not significantly vary when the test is repetitively conducted on the same subject and on the same site.

  • 44.
    Graflund, Marianne
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Sorbe, B.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Karlsson, M.
    Department of Pathology, Örebro University Hospital, Örebro.
    Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma: Correlation with clinical outcome2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 3, 290-298 p.Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.

  • 45.
    Graflund, Marianne
    et al.
    Department of Gynecologic Oncology, Medical Center Hospital, Örebro, Sweden.
    Sorbe, B.
    Department of Gynecologic Oncology, Medical Center Hospital, Örebro, Sweden.
    Hussein, A.
    Department of Pathology, Medical Center Hospital, Örebro, Sweden.
    Bryne, M.
    Department of Pathology, Institute of Cancer Research, the Norwegian Radium Hospital, Oslo, Norway.
    Karlsson, M.
    Department of Pathology, Medical Center Hospital, Örebro, Sweden.
    The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 1, 32-41 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate the prognostic importance of clinical and histopathologic factors, including malignancy grading systems (MGS), partial index (PI), invasive front grading (IFG), and microvessel density. A complete geographic series of 172 early stage (FIGO I–II) cervical carcinomas treated by Wertheim-Meigs surgery during the period 1965–1990 was studied. The patients were followed up for at least 10 years. Significant prognostic factors for disease-free survival were lymph node status (P < 0.0000001), radical surgical margins (P = 0.00003), and tumor size (P = 0.008). In a multivariate Cox analysis it was shown that lymph node status was the single most important prognostic factor with regard to disease-free survival. The total MGS and the PI scores were highly significantly (P = 0.0001) associated with pelvic lymph node metastases and disease-free survival rate in squamous cell carcinomas. The MGS and the PI systems were superior to the IFG system in predicting lymph node metastases. The total IFG score was also a statistically highly significant (P = 0.003) prognostic factor with regard to disease-free survival in both univariate and multivariate analyses. Microvessel density was a nonsignificant prognostic factor. There was a highly significant (P = 0.002) association between vascular space invasion of tumor cells and the presence of lymph node metastases. In conclusion, histopathologic malignancy grading systems provide valuable prognostic information in patients with early stage squamous cell carcinomas of the uterine cervix.

  • 46.
    Graflund, Marianne
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Sorbe, Bengt
    Department of Gynecological Oncology, Örebro University Hospital, Örebro.
    Karlsson, Mats
    Department of Pathology, Örebro University Hospital, Örebro.
    MIB-1, p53, bcl-2 and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas: Correlation with clinical outcomeManuscript (preprint) (Other academic)
    Abstract [en]

    A complete series of 40 cervical carcinomas with pelvic lymph node rnetastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamouscarcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 twnors (30%) were moderately differentiated, and 27 tumors (67 .5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymphnode metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and mu!tivariate proportional hazard Cox analyses.

  • 47.
    Svensson, Ingvar L
    et al.
    Department of Mechanical Engineering/Component Technology, Jönköping University, Sweden.
    Millberg, Adam
    Department of Mechanical Engineering/Component Technology, Jönköping University, Sweden.
    Diószegi, Attila
    Department of Mechanical Engineering/Component Technology, Jönköping University, Sweden.
    A study of eutectic inoculation in grey iron by addition of Fe-Si-Ca-Al-, Sr, Ba, Zr, Ti, RE and C2003In: International Journal of Cast Metals Research, ISSN 1364-0461, Vol. 16, no 1-3, 29-34 p.Article in journal (Refereed)
    Abstract [en]

    The interest to improve the mechanical properties and decrease shrinkage or expansion defects in grey cast irons, the inoculation is an important issue for component manufactures. The inoculation, growth of graphite and eutectic structure, are related to those demands. The paper will show a study of the effect of some inoculants on the graphite nucleation and eutectic microstructure in grey cast iron. The procedure to achieve this was to study the influence of inoculants and cooling rate on the eutectic microstructure. Six inoculants were chosen with a base of Fe-Si-Ca-Al with additions of Sr, Ba, Zr, Ti, RE and C at different proportions. Two of the inoculants were investigated at three different levels of additions. The inoculants gave eutectics with great variety of microstructure. The experimental equipment was designed to produce cast samples under controlled thermal conditions and equipped with thermocouples. To study the influence of cooling rate on the eutectic nucleation, the mould was equipped with three different cooling conditions. In order to measure the eutectic cell size the samples were colour etched. The measurements were made near the thermocouples to relate the eutectic cell size and cells/area with the cooling curves. The microstructure, cell-size and cooling curves were used to model the nucleation behaviour of the investigated compositions and solidification behaviour. The investigation showed that the type and amount of inoculation influenced the number of potent nuclei of graphite eutectic and the fading followed Lifshitz-Slyosov-Wagner (LSW) theory of ripening.

  • 48.
    Dussarrat, Johann
    et al.
    Linköping University, Department of Electrical Engineering, Electronic Devices. Linköping University, The Institute of Technology.
    Balondrade, Gael
    Linköping University, Department of Electrical Engineering, Electronic Devices. Linköping University, The Institute of Technology.
    Design of a Test Bench for Battery Management2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The report deals with energy conservation, mainly in the field of portable energy, which is asubject that today raises questions around the world. This report describes the design and theimplementation of a Battery Management System on the platform NI ELVIS II+ managed bythe software Labview. The first aim has been on finding information about the design of theBattery Management System that corresponds to the choice of the battery itself. The systemwas designed completely independent with different charging methods, simulations ofdischarge, and its own cell balancing, as a 3 cells battery pack was used. The battery chosenwas the lithium-ion technology that has the most promising battery chemistry and is the fastestgrowing. Several experimentations and simulations have been done, with and without cellbalancing that permited to highlight that the cell balancing is mandatory in a Batterymanagement System. Furthermore, a simulation of use of the battery in an Electrical Vehiclewas made, which can lead to conclude that the Lithium-Ion battery must be manageddifferently to be used in the application of an Electrical Vehicle.

  • 49.
    Ronoh, Kennedy
    et al.
    Linköping University, Department of Science and Technology, Communications and Transport Systems. Linköping University, The Institute of Technology.
    Mengistie, Awoke
    Linköping University, Department of Science and Technology, Communications and Transport Systems. Linköping University, The Institute of Technology.
    Load Balancing in Heterogeneous LTE-A Networks2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    LTE-A is the latest cellular network technology. One feature of LTE-A is the use ofheterogeneous networks (HetNets) which consist of macro-cells and low power nodes(LPNs). One of the objectives of heterogeneous networks is to increase capacity especially inhotspot areas where there is high density of users. Due to their low transmit power, very fewusers associate with LPNs and this will result in load imbalance between LPNs and macrocells.Load balancing is therefore key issue in HetNets so as to maximize cell splitting gainsand ensure even user experiences. Cell range extension (CRE) is a technique that can be usedto achieve load balancing in HetNets. Under CRE, an offset is added to LPNs during cellselection so as to expand the range of LPNs and offload more users from macro-cells toLPNs. CRE usually involves the use of uniform offsets. The use of uniform offsets results insome degree of load balancing in a HetNet which is not optimal. This arises because differentLPNs require different offsets due to varying conditions such as user distribution andpropagation environment in different hotspots. The use of cell-specific offsets is necessary forimproving the level of load balancing in HetNets. In this thesis a heuristic load balancingalgorithm that is used to assign cell-specific offsets to LPNs is designed. The algorithm makesuse of a range optimization framework which applies the concept of cell load coupling. Ourresults show that the use of the cell-specific offsets results in not only a high degree of loadbalancing as measured by Jain’s fairness index but also more even user experiences in termsof throughput.

  • 50.
    Loogna, Peter
    et al.
    Department of Surgery, Örebro Medical Centre Hospital, Örebro, Sweden.
    Franzén, Lennart
    Department of Pathology, Örebro Medical Centre Hospital, Örebro, Sweden.
    Sipponen, Pentti
    Department of Pathology, Jorvi Hospital, Espoo, Finland.
    Domellöf, Lennart
    Department of Surgery, Örebro Medical Centre Hospital, Örebro, Sweden.
    Helicobacter pylori, N-methyl-N'-nitro-N'-nitrosoguanidine, and bile modulate gastric cell kinetics in experimental cancer2001In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 439, no 5, 653-660 p.Article in journal (Refereed)
    Abstract [en]

    Helicobacter pylori infection is a risk factor for gastric cancer. How the bacterium contributes to this process is still unclear. We present a new Wistar rat model that was used to evaluate the effect of H. pylori on early preneoplastic events as judged from epithelial cell turnover and histopathological changes. One hundred and four rats were colonized with H. pylori and exposed MNNG (N-methyl-N'-nitro-N'-nitrosoguanidine) and/or taurocholic acid. Inflammation, goblet cell-like metaplasia, atrophy, dysplasia, and adenocarcinoma were scored in a blinded manner. Apoptotic cells were counted after staining with terminal uridine deoxynucleotidyl nick end labeling, and epithelial cell proliferation was determined by means of the Ki-67 labeling index. No early tumor enhancement with H. pylori could be found in ordinary histology. However, H. pylori significantly enhanced the epithelial cell proliferation compared with the control group, and the combination with taurocholic acid appeared to have a synergistic effect. MNNG significantly increased the normal gastric epithelial apoptosis. This increase was reduced in antral mucosa with H. pylori infection. The findings suggest that H. pylori, especially when combined with bile. has an influence on cell kinetics, contributing to the development of gastric cancer. The reduced apoptosis of MNNG also observed in infected animals indicates a dual function of H. pylori.

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