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  • 1.
    Akan, Pelin
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Alexeyenko, Andrey
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Costea, Paul Igor
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hedberg, Lilia
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Werne Solnestam, Beata
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundin, Sverker
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hallman, Jimmie
    Lundberg, Emma
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Comprehensive analysis of the genome transcriptome and proteome landscapes of three tumor cell lines2012In: Genome Medicine, ISSN 1756-994X, Vol. 4, 86- p.Article in journal (Refereed)
    Abstract [en]

    We here present a comparative genome, transcriptome and functional network analysis of three human cancer cell lines (A431, U251MG and U2OS), and investigate their relation to protein expression. Gene copy numbers significantly influenced corresponding transcript levels; their effect on protein levels was less pronounced. We focused on genes with altered mRNA and/or protein levels to identify those active in tumor maintenance. We provide comprehensive information for the three genomes and demonstrate the advantage of integrative analysis for identifying tumor-related genes amidst numerous background mutations by relating genomic variation to expression/protein abundance data and use gene networks to reveal implicated pathways.

  • 2. Altai, M.
    et al.
    Tsourma, M.
    Mitran, B.
    Honarvar, H.
    Perols, Anna
    KTH, School of Biotechnology (BIO), Protein Technology.
    Robillard, M.
    Rossin, R.
    ten Hoeve, W.
    Sandstrom, M.
    Orlova, A.
    Karlström, Amelie Eriksson
    KTH, School of Biotechnology (BIO), Protein Technology.
    Tolmachev, V.
    Affibody-based bioorthogonal chemistry-mediated radionuclide pretargeting: proof-of-principle.2015In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 42, S246-S246 p.Article in journal (Refereed)
  • 3.
    Ask, Per
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    EDWALL, G
    Tibbling, Lita
    ESOPHAGEAL PH MEASUREMENTS USING AN ANTIMONY ELECTRODE1980In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 18, no 1Article in journal (Refereed)
  • 4.
    Ask, Per
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Öberg, Åke
    Linköping University, Department of Biomedical Engineering.
    Tibbling, Lita
    ESOPHAGEAL MANOMETRY - DETERMINATION OF BANDWIDTH REQUIREMENTS BY SIGNAL ANALYSIS1980In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 25, no 5Article in journal (Refereed)
  • 5. Bourbeillon, Julie
    et al.
    Orchard, Sandra
    Benhar, Itai
    Borrebaeck, Carl
    de Daruvar, Antoine
    Duebel, Stefan
    Frank, Ronald
    Gibson, Frank
    Gloriam, David
    Haslam, Niall
    Hiltker, Tara
    Humphrey-Smith, Ian
    Hust, Michael
    Juncker, David
    Koegl, Manfred
    Konthur, Zoltan
    Korn, Bernhard
    Krobitsch, Sylvia
    Muyldermans, Serge
    Nygren, Per-Åke
    KTH, School of Biotechnology (BIO), Molecular Biotechnology. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Palcy, Sandrine
    Polic, Bojan
    Rodriguez, Henry
    Sawyer, Alan
    Schlapshy, Martin
    Snyder, Michael
    Stoevesandt, Oda
    Taussig, Michael J.
    Templin, Markus
    Uhlén, Matthias
    KTH, School of Biotechnology (BIO), Proteomics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    van der Maarel, Silvere
    Wingren, Christer
    Hermjakob, Henning
    Sherman, David
    Minimum information about a protein affinity reagent (MIAPAR)2010In: Nature Biotechnology, ISSN 1087-0156, Vol. 28, no 7, 650-653 p.Article in journal (Other academic)
  • 6.
    Charpentier, Emmanuelle
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Department of Regulation in Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany; Hannover Medical School, Hannover, Germany.
    CRISPR-Cas9: how research on a bacterial RNA-guided mechanism opened new perspectives in biotechnology and biomedicine2015In: EMBO Molecular Medicine, ISSN 1757-4676, E-ISSN 1757-4684, Vol. 7, no 4, 363-365 p.Article in journal (Refereed)
  • 7.
    Chudinova, Ekaterina
    et al.
    Tomsk Polytechnic University, Tomsk, Russia.
    Surmeneva, Maria
    Tomsk Polytechnic University, Tomsk, Russia.
    Koptioug, Andrei
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Quality Technology and Management, Mechanical Engineering and Mathematics.
    Skoglund, Per
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Quality Technology and Management, Mechanical Engineering and Mathematics.
    Surmenev, Roman
    Tomsk Polytechnic University, Tomsk, Russia.
    Additive manufactured Ti6Al4V scaffolds with the RF-magnetron sputter deposited hydroxyapatite coating2016In: Journal of Physics: Conference Series, Institute of Physics Publishing (IOPP), 2016, Vol. 669, 012004Conference paper (Refereed)
    Abstract [en]

    Present paper reports on the results of surface modification of the additively manufactured porous Ti6Al4V scaffolds. Radio frequency (RF) magnetron sputtering was used to modify the surface of the alloy via deposition of the biocompatible hydroxyapatite (HA) coating. The surface morphology, chemical and phase composition of the HA-coated alloy were studied. It was revealed that RF magnetron sputtering allows preparing a homogeneous HA coating onto the entire surface of scaffolds.

  • 8.
    Chudinova, Ekaterina
    et al.
    Tomsk Polytechnic University, Tomsk, Russia.
    Surmeneva, Maria
    Tomsk Polytechnic University, Tomsk, Russia.
    Koptyug, Andrey
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Quality Technology and Management, Mechanical Engineering and Mathematics.
    Selezneva, Irina
    Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Puschino.
    Skoglund, Per
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Quality Technology and Management, Mechanical Engineering and Mathematics.
    Syrtanov, M
    Tomsk Polytechnic University, Tomsk, Russia.
    Surmenev, Roman
    Tomsk Polytechnic University, Tomsk, Russia.
    In Vitro Assessment of Hydroxyapatite Coating on the Surface of Additive Manufactured Ti6Al4V Scaffolds2017In: Materials Science Forum, ISSN 0255-5476, E-ISSN 1662-9752, Vol. 879, 2444-2449 p.Article in journal (Refereed)
    Abstract [en]

    Custom orthopedic and dental implants may be fabricated by additive manufacturing (AM), for example using electron beam melting technology. This study is focused on the modification of the surface of Ti6Al4V alloy coin-like scaffolds fabricated via AM technology (EBM®) by radio frequency (RF) magnetron sputter deposition of hydroxyapatite (HA) coating. The scaffolds with HA coating were characterized by Scanning Electron microscopy, X-ray diffraction. HA coating showed a nanocrystalline structure with the crystallites of an average size of 32±9 nm. The ability of the surface to support adhesion and the proliferation of human mesenchymal stem cells was studied using biological short-term tests in vitro. In according to in vitro assessment, thin HA coating stimulated the attachment and proliferation of cells. Human mesenchymal stem cells cultured on the HA-coated scaffold also formed mineralized nodules.

  • 9.
    Fleetwood, Filippa
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Klint, Susanne
    Hanze, Martin
    KTH, School of Biotechnology (BIO), Protein Technology.
    Gunneriusson, Elin
    Frejd, Fredrik
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Löfblom, John
    KTH, School of Biotechnology (BIO), Protein Technology.
    Simultaneous targeting of two ligand-binding sites on VEGFR2 using biparatopic Affibody molecules results in dramatically improved affinity2014In: Scientific Reports, ISSN 2045-2322, Vol. 4, 7518- p.Article in journal (Refereed)
    Abstract [en]

    Angiogenesis plays an important role in cancer and ophthalmic disorders such as age-related macular degeneration and diabetic retinopathy. The vascular endothelial growth factor (VEGF) family and corresponding receptors are regulators of angiogenesis and have been much investigated as therapeutic targets. The aim of this work was to generate antagonistic VEGFR2-specific affinity proteins having adjustable pharmacokinetic properties allowing for either therapy or molecular imaging. Two antagonistic Affibody molecules that were cross-reactive for human and murine VEGFR2 were selected by phage and bacterial display. Surprisingly, although both binders independently blocked VEGF-A binding, competition assays revealed interaction with non-overlapping epitopes on the receptor. Biparatopic molecules, comprising the two Affibody domains, were hence engineered to potentially increase affinity even further through avidity. Moreover, an albumin-binding domain was included for half-life extension in future in vivo experiments. The best-performing of the biparatopic constructs demonstrated up to 180-fold slower dissociation than the monomers. The new Affibody constructs were also able to specifically target VEGFR2 on human cells, while simultaneously binding to albumin, as well as inhibit VEGF-induced signaling. In summary, we have generated small antagonistic biparatopic Affibody molecules with high affinity for VEGFR2, which have potential for both future therapeutic and diagnostic purposes in angiogenesis-related diseases.

  • 10.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Brohede, Ulrika
    Sandvik AB, Stockholm.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Co-loading of bisphosphonates and antibiotics to a biomimetic hydroxyapatite coating2011In: Biotechnology letters, ISSN 0141-5492, E-ISSN 1573-6776, Vol. 33, no 6, 1265-1268 p.Article in journal (Refereed)
    Abstract [en]

    We have incorporated bisphosphonates and antibiotics simultaneously into a biomimetic hydroxyapatite implant coating aiming to use the interaction between drug-molecules and hydroxyapatite to enable local release of the two different substances to obtain a dual biological effect. A sustained release over for 43 h of antibiotics (cephalothin) was achieved without negative interference from the presence of the bisphosphonate (clodronate) which, in turn, successfully bonded to the coating surface. To our knowledge, this is the first study that indicates the possibility to simultaneously incorporate both antibiotics and bisphosphonates to an implant coating, a strategy that is believed to improve implant stability and reduce implant-related infections.

  • 11. Garousi, J.
    et al.
    Anderson, Ken
    KTH, School of Biotechnology (BIO), Protein Technology.
    Dam, J. H.
    Olsen, B. B.
    Orlova, A.
    Buijs, J.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Thisgaard, H.
    Tolmachev, V.
    The use of radiocobalt as a label improves PET imaging of EGFR using DOTA-conjugated affibody molecules2015In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 42, S244-S244 p.Article in journal (Refereed)
  • 12.
    Ghareh Baghi, Ghareh Baghi
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Assessment of Valvular Aortic Stenosis by Signal Analysis of the Phonocardiogram2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aortic stenosis (AS) is one of the most prevalent valvular heart diseases in elderly people. According to the recommendations of both the American Heart Association and the European Society of Cardiology, severity assessment of AS is primarily based on echocardiographic findings. The experience of the investigator here play important roles in the accuracy of the assessment, and therefore in the disease management. However, access to the expert physicians could be limited, especially in rural health care centers of developing countries.

    This thesis aims to develop processing algorithms tailored for phonocardiographic signal with the intension to obtain a noninvasive diagnostic tool for AS assessment and severity grading. The algorithms employ a phonocardiogram as input signal and perform analysis for screening and diagnostics. Such a decision support system, which we call “the intelligent phonocardiography”, can be widely used in primary healthcare centers.

    The main contribution of the thesis is to present innovative models for the phonocardiographic analysis by taking the segmental characteristics of the signal into consideration. Three novel methodologies are described, based on the presented models, to perform robust classification. In the first attempt, a novel pattern recognition framework is presented for screening of AS-related murmurs. The framework offers a hybrid model for classifying cyclic time series in general, but is tailored to detect the murmurs as a special case study. The time growing neural network is another method that we use to classify short time signals with abrupt frequency transition. The idea of the growing frames is extended to the cyclic signals with stochastic properties for the screening purposes. Finally, a combined statistical and artificial intelligent classifier is proposed for grading the severity of AS.

    The study suggests comprehensive statistical validations not only for the evaluation and representation of systolic murmurs but also for setting the methodology design parameters, which can be considered as one of the significant features of the study. The resulting methodologies can be implemented by using web and mobile technologies to be utilized in distributed healthcare system.

  • 13.
    Gillman, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Muradrasoli, Shaman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Soderstrom, Hanna
    Holmberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Latorre-Margalef, Neus
    Tolf, Conny
    Waldenstrom, Jonas
    Gunnarsson, Gunnar
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards2015In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 81, no 7, 2378-2383 p.Article in journal (Refereed)
    Abstract [en]

    Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.

  • 14.
    Gu, Gucci Jijuan
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Friedman, Mikaela
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ren, Ping
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Torn, Carina
    Fex, Malin
    Hampe, Christiane S.
    Lernmark, Ake
    Landegren, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Elevated Serum GAD65 and GAD65-GADA Immune Complexes in Stiff Person Syndrome2015In: Scientific Reports, ISSN 2045-2322, Vol. 5, 11196Article in journal (Refereed)
    Abstract [en]

    Glutamic acid decarboxylase 65 (GAD65) and autoantibodies specific for GAD65 (GADA) are associated with autoimmune diseases including Stiff Person Syndrome (SPS) and Type 1 diabetes (T1D). GADA is recognized as a biomarker of value for clinical diagnosis and prognostication in these diseases. Nonetheless, it remains medically interesting to develop sensitive and specific assays to detect GAD65 preceding GADA emergence, and to monitor GADA-GAD65 immune complexes in blood samples. In the present study, we developed a highly sensitive proximity ligation assay to measure serum GAD65. This novel assay allowed detection of as little as 0.65 pg/ml GAD65. We were also able to detect immune complexes involving GAD65 and GADA. Both free GAD65 and GAD65-GADA levels were significantly higher in serum samples from SPS patients compared to healthy controls. The proximity ligation assays applied for detection of GAD65 and its immune complexes may thus enable improved diagnosis and better understanding of SPS.

  • 15.
    Hofström, Camilla
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Engineering of Affibody molecules for Radionuclide Molecular Imaging and Intracellular Targeting2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Affibody molecules are small (7 kDa) affinity proteins of non-immunoglobulin origin that have been generated to specifically interact with a large number of clinically important molecular targets.

    In this thesis, Affibody molecules have been employed as tracers for radionuclide molecular imaging of HER2- and IGF-1R-expressing tumors, paper I-IV, and for surface knock-down of EGFR, paper V. In paper I, a tag with the amino acid sequence HEHEHE was fused to the N-terminus of a HER2-specific Affibody molecule, (ZHER2), and was shown to enable facile IMAC purification and efficient tri-carbonyl 99mTc-labeling. In vivo evaluation of radioactivity uptake in different organs showed an improved biodistribution, including a 10-fold lower radioactivity uptake in liver, compared to the same construct with a H6-tag. In paper II, it was further shown that an N-terminally placed HEHEHE-tag on ZHER2 provided lower unspecific uptake of radioactivity in liver compared to its H6-tagged counterpart even when radiolabeling was at the C-terminus using alternative chemistries to attach 99mTc, 111In or 125I. In paper III, the H6-tag’s composition and position was varied with regards to charge, hydrophobicity and its C- or N-terminal placement on ZHER2. Among the ten variants investigated, it was found that an N-terminal HEHEHE-tag provided the most favorable overall biodistribution profile and that introduction of hydrophobic and positively charged amino acids provoked liver uptake of radioactivity. In paper IV, the HEHEHE-tag was shown to enable IMAC purification and tri-carbonyl 99mTc-labeling of an IGF-1R-specific Affibody molecule and improved its overall biodistribution when compared to the same construct with a H6-tag. In paper V, the aim was to develop an intracellular receptor-entrapment system to reduce the surface levels of EGFR. An EGFR-specific Affibody molecule was expressed as a fusion to different mutants of an intracellular transport protein in SKOV-3 cells, resulting in a collection of cell lines with 50%, 60%, 80% and 96% reduced surface level of EGFR. Analysis of the proliferation rate of these cell lines showed that a modest reduction (15%) in proliferation occurs between 60% and 80% reduction of the surface level of EGFR.

  • 16.
    Hudson, Elton P.
    et al.
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Nikoshkov, Andrej
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Rockberg, Johan
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101).
    Automated Solid-Phase Subcloning Based on Beads Brought into Proximity by Magnetic Force2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 5, e37429- p.Article in journal (Refereed)
    Abstract [en]

    In the fields of proteomics, metabolic engineering and synthetic biology there is a need for high-throughput and reliable cloning methods to facilitate construction of expression vectors and genetic pathways. Here, we describe a new approach for solid-phase cloning in which both the vector and the gene are immobilized to separate paramagnetic beads and brought into proximity by magnetic force. Ligation events were directly evaluated using fluorescent-based microscopy and flow cytometry. The highest ligation efficiencies were obtained when gene- and vector-coated beads were brought into close contact by application of a magnet during the ligation step. An automated procedure was developed using a laboratory workstation to transfer genes into various expression vectors and more than 95% correct clones were obtained in a number of various applications. The method presented here is suitable for efficient subcloning in an automated manner to rapidly generate a large number of gene constructs in various vectors intended for high throughput applications.

  • 17. HULTEN, J
    et al.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    A DEVICE FOR BLADDER PRESSURE MONITORING DURING TRANS-URETHRAL RESECTION1984In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, no 82, 75-80 p.Article in journal (Refereed)
  • 18. JOHANSSON, KE
    et al.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    EDWALL, G
    Tibbling, Lita
    A PORTABLE UNIT FOR 24-HOUR ESOPHAGEAL PH MONITORING WITH ANTIMONY ELECTRODES1981In: ACTA CHIRURGICA SCANDINAVICA, ISSN 0001-5482, no 506Article in journal (Refereed)
  • 19.
    Johansson, Staffan
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Eklund, Anders
    Umeå University.
    Malm, Jan
    Umeå University.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    A MEMS-based passive hydrocephalus shunt with adaptive flow characteristics2013Conference paper (Refereed)
    Abstract [en]

    This paper reports a novel MEMS valve with adaptive flow characteristics for improved treatment of hydrocephalus, a disease that is characterized by elevated pressure in the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord. In contrast to conventional valves with two ports, the valve presented here features a third port, called compensation port, which utilizes hydrostatic pressure to adapt CSF drainage based on body position. A prototype has been fabricated using standard MEMS manufacturing processes and the experimental evaluation successfully showed that the flow rate was adjustable with a varying hydrostatic pressure on the compensation port. Extracted data shows that flow rate was at near ideal values at both standing and laying body position showing an effective adaptation to body position. This is the first passive hydrocephalus valve intended for body position dependent CSF pressure regulation.

  • 20.
    Johansson, Staffan
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    A MEMS-based passive air flow regulator for handheld breath diagnostics2014In: Sensors and Actuators A-Physical, ISSN 0924-4247, Vol. 215, 65-70 p.Article in journal (Refereed)
    Abstract [en]

    This paper reports on a passive MEMS-based flow regulator designed to maintain a steady flow during asthma diagnostics. A prototype consisting of six in-plane moving pistons that restrict the flow through six flow orifices has been fabricated from three wafers using standard silicon micromachining. The in-plane design enables relatively large flows and tuning of the flow and pressure range to specific application requirements by changing a wafer thickness. In particular, for FENO asthma monitoring, regulatory guidelines specifies that measurements should be made at steady flow of approximately 50 ml/s and within a pressure range of 1–2 kPa. Experimental evaluation of the prototype shows that the flow rate is controlled within a dynamic pressure range of 770 Pa compared to only 430 Pa for a dummy structure and that it can be achieved on a chip measuring only 2 mm × 2 mm × 4 mm. The evaluation also showed that condensation of exhaled air that expectedly occurs in the flow regulator at room temperature can be eliminated by local heating of the device to 40◦C.

  • 21.
    Kaczmarzyk, Danuta
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. Georg-August-University, Germany.
    Hudson, Elton P.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Fulda, Martin
    Arabidopsis acyl-acyl carrier protein synthetase AAE15 with medium chain fatty acid specificity is functional in cyanobacteria2016In: AMB Express, ISSN 2191-0855, E-ISSN 2191-0855, Vol. 6, no 1, 1-9 p., 7Article in journal (Refereed)
    Abstract [en]

    Cyanobacteria are potential hosts for the biosynthesis of oleochemical compounds. The metabolic precursors for such compounds are fatty acids and their derivatives, which require chemical activation to become substrates in further conversion steps. We characterized the acyl activating enzyme AAE15 of Arabidopsis encoded by At4g14070, which is a homologue of a cyanobacterial acyl-ACP synthetase (AAS). We expressed AAE15 in insect cells and demonstrated its AAS activity with medium chain fatty acid (C10-C14) substrates in vitro. Furthermore, we used AAE15 to complement a Synechocystis aas deletion mutant and showed that the new strain preferentially incorporates supplied medium chain fatty acids into internal lipid molecules. Based on this data we propose that AAE15 can be utilized in metabolic engineering strategies for cyanobacteria that aim to produce compounds based on medium chain fatty acids.

  • 22.
    Klavins, Maris
    et al.
    University of Latvia, Latvia.
    Burlakovs, Juris
    University of Latvia, Latvia.
    Ozola, Ruta
    University of Latvia, Latvia.
    Muter, Olga
    University of Latvia, Latvia.
    Composite clay sorbents for immobilisation of biomolecules and cells2015In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 208, no supplement, S56- p.Article in journal (Refereed)
  • 23.
    Kroll, Jens
    et al.
    Westfälische Wilhelms-Universität Münster, Germany.
    Klinter, Stefan
    Westfälische Wilhelms-Universität Münster, Germany.
    Schneider, Cornelia
    Westfälische Wilhelms-Universität Münster, Germany.
    Voß, Isabella
    Westfälische Wilhelms-Universität Münster, Germany.
    Steinbüchel, Alexander
    Westfälische Wilhelms-Universität Münster, Germany.
    Plasmid addiction systems: Perspectives and applications in biotechnology2010In: Microbial Biotechnology, ISSN 1751-7907, Vol. 3, no 6, 634-657 p.Article, review/survey (Refereed)
    Abstract [en]

    Biotechnical production processes often operate with plasmid-based expression systems in well-established prokaryotic and eukaryotic hosts such as Escherichia coli or Saccharomyces cerevisiae, respectively. Genetically engineered organisms produce important chemicals, biopolymers, biofuels and high-value proteins like insulin. In those bioprocesses plasmids in recombinant hosts have an essential impact on productivity. Plasmid-free cells lead to losses in the entire product recovery and decrease the profitability of the whole process. Use of antibiotics in industrial fermentations is not an applicable option to maintain plasmid stability. Especially in pharmaceutical or GMP-based fermentation processes, deployed antibiotics must be inactivated and removed. Several plasmid addiction systems (PAS) were described in the literature. However, not every system has reached a full applicable state. This review compares most known addiction systems and is focusing on biotechnical applications.

  • 24.
    Kroon, Martin
    et al.
    Royal Institute of Technology.
    Holzapfel, Gerhard
    Graz University of Technology, Austria.
    A model for saccular cerebral aneurysm growth by collagen fibre remodelling2007In: Journal of Theoretical Biology, ISSN 0022-5193, E-ISSN 1095-8541, Vol. 247, 775-787 p.Article in journal (Refereed)
    Abstract [en]

    The first structural model for saccular cerebral aneurysm growth is proposed. It is assumed that the development of the aneurysm isaccompanied by a loss of the media, and that only collagen fibres provide load-bearing capacity to the aneurysm wall. The aneurysm ismodelled as an axisymmetric multi-layered membrane, exposed to an inflation pressure. Each layer is characterized by an orientationangle, which changes between different layers. The collagen fibres and fibroblasts within a specific layer are perfectly aligned. The growthand the morphological changes of the aneurysm are accomplished by the turnover of collagen. Fibroblasts are responsible for collagenproduction, and the related deformations are assumed to govern the collagen production rate. There are four key parameters in themodel: a normalized pressure, the number of layers in the wall, an exponent in the collagen mass production rate law, and the pre-stretchunder which the collagen is deposited. The influence of the model parameters on the aneurysmal response is investigated, and a stabilityanalysis is performed. The model is able to predict clinical observations and mechanical test results, for example, in terms of predictedaneurysm size, shape, wall stress and wall thickness.

  • 25.
    Kupferschmidt, Natalia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Rahman Qazi, Khaleda
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Kemi, Cecilia
    Vallhov, Helen
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Garcia-Bennett, Alfonso E
    Stockholm Univ, Dept Mat & Environm Chem, Stockholm, Sweden.
    Gabrielsson, Susanne
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Scheynius, Annika
    Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
    Mesoporous silica particles potentiate antigen specific T cell responses2014In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, no 12, 1835-1846 p.Article in journal (Refereed)
  • 26.
    Lantz, Jonas
    et al.
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Gårdhagen, Roland
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wren, Joakim
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Heating in a Stenosed Coronary Artery With Pulsating Flow and Non-Newtonian Viscosity2009In: ASME 2008 Summer Bioengineering Conference: Parts A and B, The American Society of Mechanical Engineers (ASME) , 2009, no PART A, 331-332 p.Conference paper (Refereed)
    Abstract [en]

    Cardiovascular disease is the most prevalent cause of death in the developed countries and most deaths are due to coronary atherosclerosis [1]. During the development of atherosclerosis, several stages can be distinguished including vulnerable plaque. This group of plaque has an inclination for erosion and rupture and is therefore of particular interest. Due to the inflammatory response of vulnerable plaque including an increased metabolism and thereby a locally increased temperature, it is possible to detect such warm cores by intracoronally temperature measurement under some prerequisitions. Temperature differences up to 2.2 K on the surface of carotid plaques have been measured [2], but the relation between plaque vulnerability, inflammatory response, temperature increase and possibility to detection by means of temperature measurement is far from fully perceived.

  • 27.
    Loyd, Dan
    et al.
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Wranne, Bengt
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Doppler prediction of transvalvular gradient and stenotic orifice area.1988In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 61, no 11, 958-959 p.Article in journal (Refereed)
  • 28.
    Loyd, Dan
    et al.
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    BARCLAY, SA
    XIONG, Changsheng
    ANDERSSON, Gunnar
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Wranne, Bengt
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    ECHOCARDIOGRAPHIC ASSESSMENT OF HEART-VALVE REGURGITANT FLOW USING THE FLOW CONVERGENCE METHOD1991In: PROCEEDINGS OF THE ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 13, PTS 1-5, 1991, 191-192 p.Conference paper (Refereed)
  • 29.
    Lundberg, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Optimization of the multiplexed Proximity Ligation Assay for detection of blood-based biomarkers2014Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The Proximity Ligation Assay (PLA) is a relatively new method which utilizes the strength of both immunoassays and DNA detection. PLA has the capacity of high multiplexing due to the high specificity achieved with both dual protein-binding and dual primer binding during detection with Real-Time PCR. We developed a multiplexed PLA protocol that can measure 28 biomarkers in human EDTA plasma. The method was tested on 46 individuals diagnosed with colorectal cancer and 48 age matched healthy controls. The results are very promising as we re-discover the most well-known biomarkers for colorectal cancer and also find some potential new markers (significance tested with students T-test with p<0.05). Further improvements of the protocol are needed to decrease the variation.

  • 30.
    Lundin, Sigrid
    Karolinska Institutet .
    A yeast three-hybrid (Y3H) screen to evolve BirA biotin ligase variants with histone biotinylation activity2015Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 31.
    McKee, Lauren S.
    et al.
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Brumer, Harry
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center. Univ British Columbia, Canada.
    Growth of Chitinophaga pinensis on Plant Cell Wall Glycans and Characterisation of a Glycoside Hydrolase Family 27 beta-L-Arabinopyranosidase Implicated in Arabinogalactan Utilisation2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, e0139932Article in journal (Refereed)
    Abstract [en]

    The genome of the soil bacterium Chitinophaga pinensis encodes a diverse array of carbohydrate active enzymes, including nearly 200 representatives from over 50 glycoside hydrolase (GH) families, the enzymology of which is essentially unexplored. In light of this genetic potential, we reveal that C. pinensis has a broader saprophytic capacity to thrive on plant cell wall polysaccharides than previously reported, and specifically that secretion of beta-L-arabinopyranosidase activity is induced during growth on arabinogalactan. We subsequently correlated this activity with the product of the Cpin_5740 gene, which encodes the sole member of glycoside hydrolase family 27 (GH27) in C. pinensis, CpArap27. Historically, GH27 is most commonly associated with alpha-D-galactopyranosidase and alpha-D-N-acetylgalactosaminidase activity. A new phylogenetic analysis of GH27 highlighted the likely importance of several conserved secondary structural features in determining substrate specificity and provides a predictive framework for identifying enzymes with the less common beta-L-arabinopyranosidase activity.

  • 32.
    Nielsen, Jens
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Global regulation of yeast metabolism2015In: Yeast, ISSN 0749-503X, E-ISSN 1097-0061, Vol. 32, S33-S33 p.Article in journal (Other academic)
    Abstract [en]

    The yeast Saccharomyces cerevisiae is widely used for production of fuels, chemicals, pharmaceuticals andmaterials. Through metabolic engineering of this yeast a number of novel new industrial processes have beendeveloped over the last 10 years. Besides its wide industrial use, S. cerevisiae serves as an eukaryal modelorganism, and many systems biology tools have therefore been developed for this organism. Despite ourextensive knowledge of yeast metabolism and its regulation we are still facing challenges when we want tointegrate this information into mathematical models. In this presentation examples of studies on global regulationof yeast metabolism will be provided. This will include analysis of how yeast rewire its metabolism at the globallevel when exposed to various types of stress and how global regulators like Snf1 and Sir2 controls yeastmetabolism

  • 33.
    Nielsen, Jens
    KTH, School of Biotechnology (BIO), Gene Technology.
    Mathematical modeling of yeast: a driver for innovation in biotechnology and human medicine2015In: Yeast, ISSN 0749-503X, E-ISSN 1097-0061, Vol. 32, S50-S51 p.Article in journal (Other academic)
    Abstract [en]

    Saccharomyces cerevisiae is the most studied organism and is for this reason used widely as a model organismfor studying molecular mechanisms of relevance for human disease. Thus, several Nobel Prizes have been givento yeast researchers. Among many other discoveries studies of yeast resulted in identification of cyclins andcyclin dependent kinases that play a central role in the cell cycle of eukaryal cells and mapping of the proteinsecretory pathway in eukaryal cells. This yeast is also used for production of fuels, chemicals, pharmaceuticalsand materials, and the annual revenue derived from processes based on S. cerevisiae fermentations by farexceeds 200 billion EURO. Furthermore. through metabolic engineering of this yeast a number of novel newindustrial processes are under development resulting in an even more important role of this cell factory in thefuture. In order to advance our fundamental understanding of this important organism, but in human healthresearch and industrial biotechnology, it is important to advance our ability to integrate novel experimental datain quantitative framework. Mathematical models represent an excellent scaffold for this as they allowreconciliation of data and at the same time enable generation of novel hypothesis concerning specific molecularprocesses. Furthermore, in the field of industrial biotechnology mathematical models may be used for advancingmetabolic engineering, which will result in a reduction in development costs and hereby advance towards biosustainable production of fuels and chemicals

  • 34.
    Nilvebrant, Johan
    KTH, School of Biotechnology (BIO), Proteomics.
    An albumin-binding domain as a scaffold for bispecific affinity proteins2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Protein engineering and in vitro selection systems are powerful methods to generate binding proteins. In nature, antibodies are the primary affinity proteins and their usefulness has led to a widespread use both in basic and applied research. By means of combinatorial protein engineering and protein library technology, smaller antibody fragments or alternative non-immunoglobulin protein scaffolds can be engineered for various functions based on molecular recognition. In this thesis, a 46 amino acid small albumin-binding domain derived from streptococcal protein G was evaluated as a scaffold for the generation of affinity proteins. Using protein engineering, the albumin binding has been complemented with a new binding interface localized to the opposite surface of this three-helical bundle domain. By using in vitro selection from a combinatorial library, bispecific protein domains with ability to recognize several different target proteins were generated. In paper I, a bispecific albumin-binding domain was selected by phage display and utilized as a purification tag for highly efficient affinity purification of fusion proteins. The results in paper II show how protein engineering, in vitro display and multi-parameter fluorescence-activated cell sorting can be used to accomplish the challenging task of incorporating two high affinity binding-sites, for albumin and tumor necrosis factor-alpha, into this new bispecific protein scaffold. Moreover, the native ability of this domain to bind serum albumin provides a useful characteristic that can be used to extend the plasma half-lives of proteins fused to it or potentially of the domain itself. When combined with a second targeting ability, a new molecular format with potential use in therapeutic applications is provided. The engineered binding proteins generated against the epidermal growth factor receptors 2 and 3 in papers III and IV are aimed in this direction. Over-expression of these receptors is associated with the development and progression of various cancers, and both are well-validated targets for therapy. Small bispecific binding proteins based on the albumin-binding domain could potentially contribute to this field. The new alternative protein scaffold described in this thesis is one of the smallest structured affinity proteins reported. The bispecific nature, with an inherent ability of the same domain to bind to serum albumin, is unique for this scaffold. These non-immunoglobulin binding proteins may provide several advantages as compared to antibodies in several applications, particularly when a small size and an extended half-life are of key importance. 

  • 35.
    Nilvebrant, Johan
    et al.
    KTH, School of Biotechnology (BIO), Proteomics.
    Kuku, Gamze
    Björkelund, Hanna
    Nestor, Marika
    Selection and in vitro characterization of human CD44v6-binding antibody fragments2012In: Biotechnology and applied biochemistry, ISSN 0885-4513, E-ISSN 1470-8744, Vol. 59, no 5, 367-380 p.Article in journal (Refereed)
    Abstract [en]

    The cluster of differentiation (CD) 44v6 antigen has been suggested to be involved in tumor formation, invasion, and metastasis formation, and has been observed in a majority of primary and metastatic squamous cell carcinomas of the head and neck. Probes specifically binding to this region may be utilized as tools for the challenging tasks of early detection and targeted treatments of small residual disease. In this project, an epitope-guided phage display selection of human fragment antigen-binding (Fab) fragments with affinity to the v6 sequence was performed. A selected set of Fab fragments was shown to specifically recognize increasingly complex forms of the target sequence, both in the form of a short synthetic or recombinant peptide and in the context of a purified extracellular domain of CD44. The binding was independent of known v6-sequence variation and posttranslational modifications that are common in the CD44 protein family. Furthermore, real-time interaction measurements on antibody fragments labeled with 125I showed specific and high-affinity binding to the antigen present on cultured head and neck squamous cell carcinoma cells. There was no cross-reactivity toward cells that lack the target protein. As hypothesized, characterization of the interaction between Fab fragments and the targets using the mathematical tool Interaction Map revealed more heterogeneous interactions on cells than with pure proteins analyzed by surface plasmon resonance. One main candidate Fab fragment with optimal affinity for all forms of the target sequence was identified. The flexible recombinant source of the Fab fragments might aid the development of tailored molecules adapted for therapeutic or diagnostic applications in the future.

  • 36.
    Nyman, Erika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Rakar, Jonathan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Exogenous hyaluronic acid induces accelerated re-epithelialization and altered protein expression in adult human skin wounds in vivoManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Hyaluronic acid, a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to play an important role in ideal scarless fetal wound healing. This study aimed to investigate the effect of exogenous hyaluronic acid intradermal during deep dermal wound healing. Study parameters were erythema, re-epithelialization, and protein expression examined by using a previously described, minimally invasive in vivo human wound model in combination with tissue viability imaging, histology, and proteomics.

    Methods

    Standardized deep dermal wounds were created in the ventral forearm in ten healthy volunteers using blood collection lancets. The wound sites were injected with hyaluronic acid or saline solution, prior to wounding, or were left untreated. To quantify changes in red blood cell concentration as a measurement of inflammation, the study sites were photographed daily for two weeks using a tissue viability imaging system. At 24 hours and after 14 days, biopsy specimens were taken for histology and proteomics analysis.

    Results

    The inflammatory response was not affected by the injection of hyaluronic acid, as measured by tissue viability imaging. Hyaluronic acid significantly induced (p < 0.05) accelerated reepithelialization at 24 hours, and wounds treated with hyaluronic acid showed an altered protein expression.

    Conclusion

    The results from the present study are in concordance with  previous in vitro findings and suggest that exogenous hyaluronic acid has a  positive effect on the healing process of cutaneous wounds. We conclude that hyaluronic acid injected intradermally induces accelerated re-epithelialization and alters protein expression in vivo in human deep dermal skin wounds.

  • 37. Ohlson, Sten
    et al.
    Zopf, David
    Weak affinity chromatography1993In: Handbook of affinity chromatography / [ed] Toni Kline, New York: Marcel Dekker, 1993, 1, 299-314 p.Chapter in book (Other academic)
  • 38.
    Ohlsson, Sandra
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Evaluation and development of reagents and improved protocol for flow cytometry readout using in situ PLA2011Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The diagnosis of cancer today is obsolete, depending upon pattern recognition and non-quantifiable data. The time consuming diagnosis is often performed on biopsies, fixed using non standardised procedures, and leaves room for dubious results. The diagnosis is also invasive, exposing patients to risk of infections and discomfort due to the need of tissue samples. The knowledge about changes in protein expression levels related to cancer can instead be utilized to generate a new diagnostic tool. By adapting the in situ proximity ligation assay (in situ PLA) to cells in solution, it is possible to detect proteins, or protein interactions, within cells without the need for tissue samples. Since the method is both highly sensitive and specific, it delivers reliable results. In this report, the in situ PLA method for cells in solution is combined with flow cytometry readout. Hence, a new and less invasive diagnostic tool for cancer, delivering highly accurate high throughput single cell analysis, may be on the rise.

  • 39. POPE, CE
    et al.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    DEBLAN, H
    WINGATE, DL
    MEASUREMENT OF INSTANTANEOUS FLOW VELOCITY IN THE HUMAN GASTROINTESTINAL-TRACT1988In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 95, no 3Article in journal (Refereed)
  • 40.
    Rattfält, Linda
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology. Biomedical Engineering, Örebro County Council, Örebro, Sweden.
    Ahlström, Christer
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology. Biomedical Engineering, Örebro County Council, Örebro, Sweden.
    Eneling, Martin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Ragnemalm, Bengt
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Hult, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements. Biomedical Engineering, Örebro County Council, Örebro, Sweden.
    Lindén, M.
    Intelligent Sensor Systems, Mälardalen University, Västerås, Sweden.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology. Biomedical Engineering, Örebro County Council, Örebro, Sweden.
    A platform for physiological signals including an intelligent stethoscope2009In: 4th European Conference of the International Federation for Medical and Biological Engineering: ECIFMBE 2008 23–27 November 2008 Antwerp, Belgium / [ed] Jos Sloten, Pascal Verdonck, Marc Nyssen, Jens Haueisen, Springer Berlin/Heidelberg, 2009, Vol. 22, 1038-1041 p.Chapter in book (Refereed)
    Abstract [en]

    We have developed a physiological signal platform where presently phonocardiographic (PCG) and electrocardiographic (ECG) signals can be acquired and on which our signal analysis techniques can be implemented. The platform can also be used to store patient data, to enable comparison over time and invoke distance consultation if necessary. Our studies so far indicate that with our signal analysis techniques of heart sounds we are able to separate normal subject from those with aortic stenosis and mitral insufficiency. Further we are able to identify the third heart sound. The platform is being tested in a primary health care setting.

  • 41.
    Renner, Johan
    et al.
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Gårdhagen, Roland
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Karlsson, Matts
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Subject Specific In-Vivo CFD Estimated Aortic WSS: Comparison Between Manual and Automated Segmentation Methods2009In: ASME 2008 Summer Bioengineering Conference: Parts A and B, The American Society of Mechanical Engineers (ASME) , 2009, no PART A, 425-426 p.Conference paper (Refereed)
    Abstract [en]

    When making computational fluid dynamics (CFD) based estimations of wall shear stress (WSS) in the human aorta, medical image converting processes to 3D geometries are important as the result is strongly dependent on the quality of the geometry [1]. The image interpretation process or segmentation can be more or less automated; however in clinical work today the gold standard is to manually interpret the medical image information. This combined magnetic resonance imaging (MRI) and CFD method aims to estimate WSS in human arteries in-vivo as WSS is strongly linked to atherosclerosis [2]. More or less automated segmentation has been used in previous studies but normally based on a stack of 2D individually segmented slices which is combined into a 3D model [3]. The aim of this work is to compare manual 2D and automatic 3D segmentations.

  • 42.
    Samuelsson, Johanna
    Linköping University, Department of Medical and Health Sciences.
    Visualization of Regional Liver Function with Hepatobiliary Contrast Agent Gd-EOB-DTPA2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Liver biopsy is a very common, but invasive procedure for diagnosing liver disease. However, such a biopsy may result in severe complications and in some cases even death. Therefore, it would be highly desirable to develop a non-invasive method which would provide the same amount of information on staging of the disease and also the location of pathologies. This thesis describes the implementation of such a non-invasive method for visualizing and quantifying liver function by the combination of MRI (Magnetic Resonance Imaging), image reconstruction, and image analysis, and pharmacokinetic modeling. The first attempt involved automatic segmentation, functional clustering (k-means) and classification (kNN) of in-data (liver, spleen and blood vessel segments) in the pharmacokinetic model. However, after implementing and analyzing this method some important issues were identified and the image segmentation method was therefore revised. The segmentation method that was subsequently developed involved a semi-automatic procedure, based on a modified image forest transform (IFT). The data were then simulated and optimized using a pharmacokinetic model describing the pharmacokinetics of the liver specific contrast agent Gd-EOB-DTPA in the human body. The output from the modeling procedure was then further analyzed, using a least-squares method, in order to assess liver function by estimating the fractions of hepatocytes, extracellular extravascular space (EES) and blood plasma in each voxel of the image. The result were in fair agreement with literature values, although further analyses and developments will be required in order to validate and also to confirm the accuracy of the method.

  • 43.
    Sjöstedt, Evelina
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Fagerberg, Linn
    Hallstrom, Bjorn M.
    Haggmark, Anna
    Mitsios, Nicholas
    Nilsson, Peter
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hokfelt, Tomas
    Uhlen, Mathias
    Mulder, Jan
    Defining the Human Brain Proteome Using Transcriptomics and Antibody-Based Profiling with a Focus on the Cerebral Cortex2015In: PLoS ONE, ISSN 1932-6203, Vol. 10, no 6, e0130028Article in journal (Refereed)
    Abstract [en]

    The mammalian brain is a complex organ composed of many specialized cells, harboring sets of both common, widely distributed, as well as specialized and discretely localized proteins. Here we focus on the human brain, utilizing transcriptomics and public available Human Protein Atlas (HPA) data to analyze brain-enriched (frontal cortex) polyadenylated messenger RNA and long non-coding RNA and generate a genome-wide draft of global and cellular expression patterns of the brain. Based on transcriptomics analysis of altogether 27 tissues, we have estimated that approximately 3% (n=571) of all protein coding genes and 13% (n=87) of the long non-coding genes expressed in the human brain are enriched, having at least five times higher expression levels in brain as compared to any of the other analyzed peripheral tissues. Based on gene ontology analysis and detailed annotation using antibody-based tissue micro array analysis of the corresponding proteins, we found the majority of brain-enriched protein coding genes to be expressed in astrocytes, oligodendrocytes or in neurons with molecular properties linked to synaptic transmission and brain development. Detailed analysis of the transcripts and the genetic landscape of brainenriched coding and non-coding genes revealed brain-enriched splice variants. Several clusters of neighboring brain-enriched genes were also identified, suggesting regulation of gene expression on the chromatin level. This multi-angle approach uncovered the brainenriched transcriptome and linked genes to cell types and functions, providing novel insights into the molecular foundation of this highly specialized organ.

  • 44.
    Skiöld, Sara
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Naslund, Ingemar
    Brehwens, Karl
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Andersson, Arja
    Wersall, Peter
    Lidbrink, Elisabet
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Radiation-induced stress response in peripheral blood of breast cancer patients differs between patients with severe acute skin reactions and patients with no side effects to radiotherapy2013In: Mutation research. Genetic toxicology and environmental mutagenesis, ISSN 1383-5718, Vol. 756, no 1-2, 152-157 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to compare the radiation-induced oxidative stress response in blood samples from breast cancer patients that developed severe acute skin reactions during the radiotherapy, with the response in blood samples from patients with no side effects. Peripheral blood was collected from 12 breast cancer patients showing no early skin reactions after radiotherapy (RTOG grade 0) and from 14 breast cancer patients who developed acute severe skin reactions (RTOG grade 3-4). Whole blood was irradiated with 0, 5 and 2000 mGy gamma-radiation and serum was isolated. The biomarker for oxidative stress, 8-oxo-dG, was analyzed in the serum by a modified ELISA. While a significant radiation-induced increase of serum 8-oxo-dG levels was observed in serum of the RTOG 0 patients, no increase was seen in serum of the RTOG 3-4 patients. The radiation induced increase in serum 8-oxo-dG levels after 5 mGy did not differ significantly from the increase observed for 2000 mGy in the RTOG 3-4 cohort, thus no dose response relation was observed. A receiver operating characteristic (ROC) value of 0.97 was obtained from the radiation-induced increase in 8-oxo-dG indicating that the assay could be used to identify patients with severe acute adverse reactions to radiotherapy. The results show that samples of whole blood from patients, classified as highly radiosensitive (RTOG 3-4) based on their skin reactions to radiotherapy, differ significantly in their oxidative stress response to ionizing radiation compared to samples of whole blood from patients with no skin reactions (RTOG 0). Extracellular 8-oxo-dG is primarily a biomarker of nucleotide damage and the results indicate that the patients with severe acute skin reactions differ in their cellular response to ionizing radiation at the level of induction of oxidative stress or at the level of repair or both.

  • 45. Spånberg, Anders
    et al.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    ENGBERG, Anders
    TERIO, Hikki
    URODYNAMIC ASSESSMENT OF OBSTRUCTION - SHOULD IT BE EVALUATED ACCORDING TO GRIFFITHS OR SCHAFER MODEL1987In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, no 105Article in journal (Refereed)
  • 46.
    Tian, Bo
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Qiu, Zhen
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Ma, Jing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    de la Torre, Teresa Zardán Gómez
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Johansson, Christer
    Acreo Swedish ICT AB, Arvid Hedvalls Backe 4, SE-41133 Gothenburg, Sweden..
    Svedlindh, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Strömberg, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Attomolar Zika virus oligonucleotide detection based on loop-mediated isothermal amplification and AC susceptometry2016In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 86, 420-425 p.Article in journal (Refereed)
    Abstract [en]

    Because of the serological cross-reactivity among the flaviviruses, molecular detection methods, such as reverse-transcription polymerase chain reaction (RT-PCR), play an important role in the recent Zika outbreak. However, due to the limited sensitivity, the detection window of RT-PCR for Zika viremia is only about one week after symptom onset. By combining loop-mediated isothermal amplification (LAMP) and AC susceptometry, we demonstrate a rapid and homogeneous detection system for the Zika virus oligonucleotide. Streptavidin-magnetic nanoparticles (streptavidin-MNPs) are premixed with LAMP reagents including the analyte and biotinylated primers, and their hydrodynamic volumes are dramatically increased after a successful LAMP reaction. Analyzed by a portable AC susceptometer, the changes of the hydrodynamic volume are probed as Brownian relaxation frequency shifts, which can be used to quantify the Zika virus oligonucleotide. The proposed detection system can recognize 1 aM synthetic Zika virus oligonucleotide in 20% serum with a total assay time of 27 min, which can hopefully widen the detection window for Zika viremia and is therefore promising in worldwide Zika fever control.

  • 47. Tibbling, Lita
    et al.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Öberg, Åke
    Linköping University, Department of Biomedical Engineering.
    ACCURACY AND VALIDITY OF ESOPHAGEAL MANOMETRY SYSTEMS1980In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 25, no 5Article in journal (Refereed)
  • 48.
    Turner, Anthony
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Torrens del Valle, M.
    Beni, Valerio
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Ortiz, M.
    O'Sullivan, Ciara
    Universitat Rovira i Virgili, Tarragona, Spain.
    Development of alternative for carbon surface functionalisation with diazonium derivative andits application on DNA and protein detections2013In: Doctoral Days, 2013, Tarragona, Spain: Universitat Rovira i Virgili , 2013Conference paper (Other academic)
  • 49.
    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.

  • 50.
    Wikman, Maria
    et al.
    KTH, School of Biotechnology (BIO).
    Friedman, Mikaela
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Pinitkiatisakul, S.
    Andersson, Christin
    KTH, School of Biotechnology (BIO).
    Hemphill, A.
    Lovgren-Bengtsson, K.
    Lunden, A.
    Ståhl, Stefan
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    General strategies for efficient adjuvant incorporation of recombinant subunit immunogens2005In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 23, no 17-18, 2331-2335 p.Article in journal (Refereed)
    Abstract [en]

    We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptides or lipid tags to improve their capacity to be incorporated into an adjuvant formulation, e.g., immunostimulating complexes (iscoms). Recently, we also explored the strong interaction between biotin and streptavidin to achieve iscom association of recombinant immunogens. Plasmodium falciparum, Toxoplasma gondii and Neospora caninum antigens have served as model immunogens in the different studies. Generated fusion proteins have been found to be successfully incorporated into iscoms and high-titer antigen-specific antibody responses have been obtained upon immunization of mice. We believe that the different concepts presented, utilizing either hydrophobic peptide or lipid tags, or the recently explored biotin-streptavidin principle, offer convenient methods to achieve efficient adjuvant incorporation of recombinant immunogens.

12 1 - 50 of 54
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