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  • 1.
    Markwardt, Niklas
    et al.
    Laser-Forschungslabor, LIFE-Zentrum, Klinikum der Universität München, Munich, Germany.
    Haj-Hosseini, Neda
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Hollnburger, Bastian
    Laser-Forschungslabor, LIFE-Zentrum, Klinikum der Universität München, Munich, Germany.
    Stepp, Herbert
    Laser-Forschungslabor, LIFE-Zentrum, Klinikum der Universität München, Munich, Germany.
    Zelenkov, Petr
    Burdenko Neurosurgery Institute, Moscow, Russia.
    Rühm, Adrian
    Laser-Forschungslabor, LIFE-Zentrum, Klinikum der Universität München, Munich, Germany.
    405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence-guided stereotactic biopsy of brain tumors2016In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 9, no 9, 901-912 p.Article in journal (Refereed)
    Abstract [en]

    Fluorescence diagnosis may be used to improve the safety and reliability of stereotactic brain tumor biopsies using biopsy needles with integrated fiber optics. Based on 5-aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence, vital tumor tissue can be localized in vivo during the excision procedure to reduce the number of necessary samples for a reliable diagnosis. In this study, the practical suitability of two different PpIX excitation wavelengths (405 nm, 633 nm) was investigated on optical phantoms. Violet excitation at 405 nm provides a 50-fold higher sensitivity for the bulk tumor; this factor increases up to 100 with decreasing fluorescent volume as shown by ray tracing simulations. Red excitation at 633 nm, however, is noticeably superior with regard to blood layers obscuring the fluorescence. Experimental results on the signal attenuation through blood layers of well-defined thicknesses could be confirmed by ray tracing simulations. Typical interstitial fiber probe measurements were mimicked on agarose-gel phantoms. Even in direct contact, blood layers of 20-40 µm between probe and tissue must be expected, obscuring 405-nm-excited PpIX fluorescence almost completely, but reducing the 633-nm-excited signal only by 25.5%. Thus, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of high-grade gliomas in stereotactic biopsy. PpIX signal attenuation through clinically relevant blood layers for 405 nm (violet) and 633 nm (red) excitation.

  • 2.
    Lindström, Tom
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering. Colorado State University, CO 80523 USA; US National Institute Heatlh, MD USA; University of Exeter, England.
    Tildesley, Michael
    US National Institute Heatlh, MD USA; University of Nottingham, England.
    Webb, Colleen
    Colorado State University, CO 80523 USA; US National Institute Heatlh, MD USA.
    A Bayesian Ensemble Approach for Epidemiological Projections2015In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 11, no 4, e1004187- p.Article in journal (Refereed)
    Abstract [en]

    Mathematical models are powerful tools for epidemiology and can be used to compare control actions. However, different models and model parameterizations may provide different prediction of outcomes. In other fields of research, ensemble modeling has been used to combine multiple projections. We explore the possibility of applying such methods to epidemiology by adapting Bayesian techniques developed for climate forecasting. We exemplify the implementation with single model ensembles based on different parameterizations of the Warwick model run for the 2001 United Kingdom foot and mouth disease outbreak and compare the efficacy of different control actions. This allows us to investigate the effect that discrepancy among projections based on different modeling assumptions has on the ensemble prediction. A sensitivity analysis showed that the choice of prior can have a pronounced effect on the posterior estimates of quantities of interest, in particular for ensembles with large discrepancy among projections. However, by using a hierarchical extension of the method we show that prior sensitivity can be circumvented. We further extend the method to include a priori beliefs about different modeling assumptions and demonstrate that the effect of this can have different consequences depending on the discrepancy among projections. We propose that the method is a promising analytical tool for ensemble modeling of disease outbreaks.

  • 3.
    Hult, Peter
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Arts and Sciences.
    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.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    A bioacoustic method for timing of the different phases of the breathing cycle and monitoring of breathing frequency.2000In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 22, no 6, 425-433 p.Article in journal (Refereed)
    Abstract [en]

    It is well known that the flow of air through the trachea during respiration causes vibrations in the tissue near the trachea, which propagate to the surface of the body and can be picked up by a microphone placed on the throat over the trachea. Since the vibrations are a direct result of the airflow, accurate timing of inspiration and expiration is possible. This paper presents a signal analysis solution for automated monitoring of breathing and calculation of the breathing frequency. The signal analysis approach uses tracheal sound variables in the time and frequency domains, as well as the characteristics of the disturbances that can be used to discriminate tracheal sound from noise. One problem associated with the bioacoustic method is its sensitivity for acoustic disturbances, because the microphone tends to pick up all vibrations, independent of their origin. A signal processing method was developed that makes the bioacoustic method clinically useful in a broad variety of situations, for example in intensive care and during certain heart examinations, where information about both the precise timing and the phases of breathing is crucial.

  • 4.
    Hult, Peter
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Ask, Per
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Wranne, Bengt
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    A bioacoustic method for timing of the different phases of the breathing cycle and monitoring of breathing frequency2000In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 22, no 6, 425-433 p.Article in journal (Refereed)
    Abstract [en]

    It is well known that the flow of air through the trachea during respiration causes vibrations in the tissue near the trachea, which propagate to the surface of the body and can be picked up by a microphone placed on the throat over the trachea. Since the vibrations are a direct result of the airflow, accurate timing of inspiration and expiration is possible. This paper presents a signal analysis solution for automated monitoring of breathing and calculation of the breathing frequency. The signal analysis approach uses tracheal sound variables in the time and frequency domains, as well as the characteristics of the disturbances that can be used to discriminate tracheal sound from noise. One problem associated with the bioacoustic method is its sensitivity for acoustic disturbances, because the microphone tends to pick up all vibrations, independent of their origin. A signal processing method was developed that makes the bioacoustic method clinically useful in a broad variety of situations, for example in intensive care and during certain heart examinations, where information about both the precise timing and the phases of breathing is crucial.

  • 5.
    Azahar Ali, Md.
    et al.
    CSIR, India; Indian Institute Technology Hyderabad, India.
    Srivastava, Saurabh
    CSIR, India; Delhi Technology University, India.
    Agrawal, Ved V.
    CSIR, India.
    Willander, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    John, Renu
    Indian Institute Technology Hyderabad, India.
    Malhotra, Bansi D.
    Delhi Technology University, India.
    A biofunctionalized quantum dot-nickel oxide nanorod based smart platform for lipid detection2016In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 4, no 15, 2706-2714 p.Article in journal (Refereed)
    Abstract [en]

    A reagent-free, low-cost and sensitive immunosensor has been fabricated using anti-apolipoprotein B (AAB) conjugated L-cysteine in situ capped cadmium sulfide quantum dots (CysCdS QDs) bound to nickel oxide nanorods (nNiO) for detection of low density lipoprotein (LDL) molecules in human serum samples. The structural and morphological properties of AAB conjugated CysCdS QDs and nNiO have been investigated using electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and UV-visible techniques. In this immunosensor, the synthesized NiO nanorods act as mediators that allow the direct electron transfer due to their channeling effect resulting in a mediator-free biosensor. This mediator-free CysCdS-NiO based immunosensor shows improved characteristics such as a good sensitivity of 32.08 mu A (mg dl(-1))(-1) cm(-2) compared to that based on nNiO (1.42 mA (mg dl(-1))(-1) cm(-2)) alone for detection of lipid (LDL) molecules over a wide concentration range, 5-120 mg dl(-1) (0.015-0.36 mu M). The kinetic analysis yields an association constant (K-a) of 3.24 kM(-1) s(-1), indicating that the antibody conjugated CysCdS-NiO platform has a strong affinity towards lipid molecules. The excellent electron transport properties of the CysCdS-NiO nanocomposite in this immunosensor reveal that it provides an efficient platform for routine quantification of LDL molecules in real samples.

  • 6.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Lagali, Neil S
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    Merrett, Kimberley
    University of Ottawa Eye Institute.
    Jackson, W Bruce
    University of Ottawa Eye Institute.
    Munger, Rejean
    University of Ottawa Eye Institute.
    Liu, Yuwen
    CooperVision Inc, Pleasanton, USA .
    Polarek, James W
    FibroGen Inc, San Francisco.
    Söderqvist, Monica
    Synsam Opticians, Linköping.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study2010In: Science translational medicine, ISSN 1946-6234, Vol. 2, no 46, 46-61 p.Article in journal (Refereed)
    Abstract [en]

    Corneas from human donors are used to replace damaged tissue and treat corneal blindness, but there is a severe worldwide shortage of donor corneas. We conducted a phase 1 clinical study in which biosynthetic mimics of corneal extracellular matrix were implanted to replace the pathologic anterior cornea of 10 patients who had significant vision loss, with the aim of facilitating endogenous tissue regeneration without the use of human donor tissue. The biosynthetic implants remained stably integrated and avascular for 24 months after surgery, without the need for long-term use of the steroid immunosuppression that is required for traditional allotransplantation. Corneal reepithelialization occurred in all patients, although a delay in epithelial closure as a result of the overlying retaining sutures led to early, localized implant thinning and fibrosis in some patients. The tear film was restored, and stromal cells were recruited into the implant in all patients. Nerve regeneration was also observed and touch sensitivity was restored, both to an equal or to a greater degree than is seen with human donor tissue. Vision at 24 months improved from preoperative values in six patients. With further optimization, biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage.

  • 7.
    La Fleur, Linnea
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Johansson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    A CD44(high)/EGFR(low) Subpopulation within Head and Neck Cancer Cell Lines Shows an Epithelial-Mesenchymal Transition Phenotype and Resistance to Treatment2012In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 9Article in journal (Refereed)
    Abstract [en]

    Mortality in head and neck squamous cell carcinoma (HNSCC) is high due to emergence of therapy resistance which results in local and regional recurrences that may have their origin in resistant cancer stem cells (CSCs) or cells with an epithelial-mesenchymal transition (EMT) phenotype. In the present study, we investigate the possibility of using the cell surface expression of CD44 and epidermal growth factor receptor (EGFR), both of which have been used as stem cell markers, to identify subpopulations within HNSCC cell lines that differ with respect to phenotype and treatment sensitivity. Three subpopulations, consisting of CD44(high)/EGFR(low), CD44(high)/EGFR(high) and CD44(low) cells, respectively, were collected by fluorescence-activated cell sorting. The CD44(high)/EGFR(low) population showed a spindle-shaped EMT-like morphology, while the CD44(low) population was dominated by cobblestone-shaped cells. The CD44(high)/EGFR(low) population was enriched with cells in G0/G1 and showed a relatively low proliferation rate and a high plating efficiency. Using a real time PCR array, 27 genes, of which 14 were related to an EMT phenotype and two with stemness, were found to be differentially expressed in CD44(high)/EGFR(low) cells in comparison to CD44(low) cells. Moreover, CD44(high)/EGFR(low) cells showed a low sensitivity to radiation, cisplatin, cetuximab and gefitinib, and a high sensitivity to dasatinib relative to its CD44(high)/EGFR(high) and CD44(low) counterparts. In conclusion, our results show that the combination of CD44 (high) and EGFR (low) cell surface expression can be used to identify a treatment resistant subpopulation with an EMT phenotype in HNSCC cell lines.

  • 8.
    Edberg, Andreas
    et al.
    Central Hospital, Karlstad.
    Jurstrand, Margaretha
    University Hospital, Örebro.
    Johansson, Eva
    Central Hospital, Karlstad.
    Wikander, Elisabeth
    Central Hospital, Karlstad.
    Höög, Anna
    Central Hospital, Karlstad.
    Ahlqvist, Thomas
    Central Hospital, Karlstad.
    Falk, Lars
    Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Linköping University, Faculty of Health Sciences.
    Skov Jensen, Jørgen
    Statens Serum Institute, Denmark.
    Fredlund, Hans
    University Hospital, Örebro.
    A comparative study of three different PCR assays for detection of Mycoplasma genitalium in urogenital specimens from men and women2008In: Journal of Medical Microbiology, ISSN 0022-2615, Vol. 57, 304-309 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare conventional 16S rRNA gene PCR, real-time 16S rRNA gene PCR and real-time Mycoplasma genitalium adhesin protein (MgPa) gene PCR as detection methods for M. genitalium infection. The study also determined the prevalence of M. genitalium in male and female patients attending a sexually transmitted infections clinic in a rural area in the west of Sweden. First void urine (FVU) and/or urethral swabs were collected from 381 men, and FVU and/or cervical swabs and/or urethral swabs were collected from 298 women. A total of 213 specimens were used in the PCR comparative study: 98 consecutively sampled specimens from patients enrolled in the prevalence study, 36 consecutively sampled specimens from patients with symptoms of urethritis and 79 specimens from patients positive for M. genitalium by real-time MgPa gene PCR in the prevalence study. A true-positive M. genitalium DNA specimen was defined as either a specimen positive in any two PCR assays or a specimen whose PCR product was verified by DNA sequencing. The prevalence of M. genitalium infection in men and women was 27/381 (7.1 %) and 23/298 (7.7 %), respectively. In the PCR comparative study, M. genitalium DNA was detected in 61/76 (80.3 %) of true-positive specimens by conventional 16S rRNA gene PCR, in 52/76 (68.4 %) by real-time 16S rRNA gene PCR and in 74/76 (97.4 %) by real-time MgPa gene PCR. Real-time MgPa gene PCR thus had higher sensitivity compared with conventional 16S rRNA gene PCR and had considerably increased sensitivity compared with real-time 16S rRNA gene PCR for detection of M. genitalium DNA. Real-time MgPa gene PCR is well suited for the clinical diagnosis of M. genitalium.

  • 9.
    Nordigården, Amanda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Tang, Yanjuan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Halvarsson, Camilla
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
    A comparative study of various FLT3-ITDs in relation to function and signalingManuscript (preprint) (Other academic)
    Abstract [en]

    Internal tandem duplications (ITD) in the FMS like tyrosine kinase (FLT3) receptor are one of the most common classes of mutations in acute myeloid leukemia (AML), which presence indicates a poor prognosis. Lengths of FLT3-ITD mutations found in patients can vary from 3 up to hundreds of nucleotides and may be located either in the juxtamembrane domain or the tyrosine kinase-1 domain (TKD1). There are contradicting opinions whether the length of the ITD has an impact on the clinical situation and whether tyrosines duplicated are of any significance for oncogenic signaling. Considering the substantial differences in lengths as well as the variability of start and end points of ITDs, we have performed a study of various FLT3-ITD mutations isolated from AML-patients. The ITD region from leukemic blasts of nine AML patients were sequenced and cloned by PCR into the human wildtype FLT3 cDNA, inserted to a retroviral GFP-containing vector. The hematopoietic progenitor cell line FDC-P1 was used to elucidate the impact of the different ITDs on growth, survival, signal transduction, and resistance to the FLT3-targeting inhibitor PKC412. Interestingly, the shortest and the longest ITDs were two of the three mutations that lead to the poorest survival of cells upon cytokine-deprivation, indicating that ITD size may not influence the transforming potential of cells. Furthermore one ITD that starts and ends relatively 3´ positioned, and comprises the 5´-part of the TKD1 showed both a survival advantage in starvation experiments and a significantly higher proliferation potential in comparison to several other mutations. Two other ITDs spanning this region, but with more 5´localized starting points, displayed less sensitivity to PKC412 treatment. However, this was not associated to STAT5 activity and MCL-1 upregulation as suggested by previous report. Taken together, this study suggests that different FLT3-ITD mutations may induce distinct signaling and response towards FLT3 targeting drugs, dependent of FLT3-ITD composition and not length.

  • 10.
    Svärd, Anna
    et al.
    Rheumatology Clinic, Falun Hospital, Falun.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Söderlin, Maria K.
    Spenshult Rheumatology Centre, Oskarström, Sweden.
    Reckner-Olsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    A Comparison Between IgG- and IgA-class Antibodies to Cyclic Citrullinated Peptides and to Modified Citrullinated Vimentin in Early Rheumatoid Arthritis and Very Early Arthritis2011In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 38, no 7, 1265-1272 p.Article in journal (Refereed)
    Abstract [en]

    Objective. Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis. less thanbrgreater than less thanbrgreater thanMethods. Two Swedish arthritis populations were examined: 215 patients with early RA (andlt;= 12 months duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (andlt;= 3 months duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. less thanbrgreater than less thanbrgreater thanResults were related to disease course, smoking habits, and shared epitope status. Results. In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive. less thanbrgreater than less thanbrgreater thanConclusion. The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.

  • 11.
    Eriksson, Jens
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Rorsman, N
    Zirath, H
    Henry, Anne
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials.
    Magnusson, Björn
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials.
    Ellison, A
    Janzén, Erik
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Semiconductor Materials.
    A comparison of MESFETs on different 4H-Silicon carbide semi-insulating substrates2003In: Materials Science Forum Vols. 433-434, 2003, Vol. 433-4, 737-739 p.Conference paper (Refereed)
    Abstract [en]

    DC and RF measurements for MESFET devices fabricated on three different 4H-SiC Semi-Insulating (SI) substrates are compared in this paper and the epilayers were grown simultaneously for all three wafers. The different wafers were processed during the same batch run. The MESFETs processed on the high-purity wafers showed less light sensitivity than those processed on the Vanadium doped wafer.

  • 12.
    Lesen, Eva
    et al.
    Nordic School for Public Health.
    Sandstrom, Tatiana Z
    Nordic School for Public Health.
    Carlsten, Anders
    Medical Prod Agency.
    Jönsson, Anna K
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
    Mardby, Ann-Charlotte
    University of Gothenburg.
    Andersson Sundell, Karolina
    Nordic School for Public Health.
    A comparison of two methods for estimating refill adherence to statins in Sweden: the RARE project2011In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 20, no 10, 1073-1079 p.Article in journal (Refereed)
    Abstract [en]

    Purpose To analyse and compare refill adherence to statins estimated with two different methods with a focus on sensitivity to definitions. less thanbrgreater than less thanbrgreater thanMethods Individuals aged 18-85 years who filled a statin prescription for the first time in 1.5 years during 1 January-30 June 2007 were followed until emigration or death or until 2 years after their first statin purchase. The data were collected via linkage between the Swedish Prescribed Drug Register, the National Patient Register and the Total Population Register. Days supply was estimated based on amount dispensed and prescribed dosage. Refill adherence was estimated with the continuous measure of medication acquisition (CMA) and the maximum gap method (cut-off 45days). The impact of altering definitions, for example, regarding hospitalisations, length of observation period and management of overlapping supply, was analysed. less thanbrgreater than less thanbrgreater thanResults The study included 36661 individuals (mean age 64 years, 47% women). The median proportion of days with statins was 95%, and 76% were classified as adherent with a cut-off at andgt;= 80% with CMA. With the maximum gap method, 65% were adherent. Disregarding hospitalisations did not alter the results. Emigration or death at least one year after statin initiation was associated with a lower adherence with both methods, and a shorter observation period and adding overlapping supply to the subsequent prescription increased the adherence estimates. less thanbrgreater than less thanbrgreater thanConclusions The choice of method and definitions, particularly regarding the management of overlapping supplies and the length of observation period, has a substantial impact on estimates of refill adherence to statins.

  • 13. Hilding, D.
    et al.
    Torstenfelt, Bo
    Linköping University, The Institute of Technology. Linköping University, Department of Management and Engineering, Solid Mechanics .
    Klarbring, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Management and Engineering, Mechanics .
    A computational methodology for shape optimization of structures in frictionless contact2001In: Computer Methods in Applied Mechanics and Engineering, ISSN 0045-7825, Vol. 190, no 31, 4043-4060 p.Article in journal (Refereed)
    Abstract [en]

    This paper presents a computational methodology for shape optimization of structures in frictionless contact, which provides a basis for developing user-friendly and efficient shape optimization software. For evaluation it has been implemented as a subsystem of a general finite element software. The overall design and main principles of operation of this software are outlined. The parts connected to shape optimization are described in more detail. The key building blocks are: analytic sensitivity analysis, an adaptive finite element method, an accurate contact solver, and a sequential convex programing optimization algorithm. Results for three model application examples are presented, in which the contact pressure and the effective stress are optimized. cr 2001 Elsevier Science B.V. All rights reserved.

  • 14.
    Kleinstaeuber, Maria
    et al.
    University of Marburg, Germany.
    Frank, Ina
    Johannes Gutenberg University of Mainz, Germany.
    Weise, Cornelia
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research. University of Marburg, Germany.
    A confirmatory factor analytic validation of the Tinnitus Handicap Inventory2015In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 78, no 3, 277-284 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Because the postulated three-factor structure of the internationally widely used Tinnitus Handicap Inventory (THI) has not been confirmed yet by a confirmatory factor analytic approach this was the central aim of the current study. Methods: From a clinical setting, N = 373 patients with chronic tinnitus completed the THI and further questionnaires assessing tinnitus-related and psychological variables. In order to analyze the psychometric properties of the THI, confirmatory factor analysis (CFA) and correlational analyses were conducted. Results: CFA provided a statistically significant support for a better fit of the data to the hypothesized three-factor structure (RMSEA = .049, WRMR = 1.062, CFI = .965, TLI = .961) than to a general factor model (RMSEA = .062, WRMR = 1.258, CFI = .942, TLI = .937). The calculation of Cronbachs alpha as indicator of internal consistency revealed satisfactory values (.80-.91) with the exception of the catastrophic subscale (.65). High positive correlations of the THI and its subscales with other measures of tinnitus distress, anxiety, and depression, high negative correlations with tinnitus acceptance, moderate positive correlations with anxiety sensitivity, sleeping difficulties, tinnitus loudness, and small correlations with the Big Five personality dimensions confirmed construct validity. Conclusion: Results show that the THI is a highly reliable and valid measure of tinnitus-related handicap. In contrast to results of previous exploratory analyses the current findings speak for a three-factor in contrast to a unifactorial structure. Future research is needed to replicate this result in different tinnitus populations.

  • 15.
    Larsson, Jan-Åke
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, The Institute of Technology.
    A contextual extension of Spekkens toy model2012In: AIP Conference Proceedings, ISSN 0094-243X, Vol. 1424Article in journal (Refereed)
    Abstract [en]

    Quantum systems show contextuality. More precisely, it is impossible to reproduce the quantum-mechanical predictions using a non-contextual realist model, i.e., a model where the outcome of one measurement is independent of the choice of compatible measurements performed in the measurement context. There has been several attempts to quantify the amount of contextuality for specific quantum systems, for example, in the number of rays needed in a KS proof, or the number of terms in certain inequalities, or in the violation, noise sensitivity, and other measures. This paper is about another approach: to use a simple contextual model that reproduces the quantum-mechanical contextual behaviour, but not necessarily all quantum predictions. The amount of contextuality can then be quantified in terms of additional resources needed as compared with a similar model without contextuality. In this case the contextual model needs to keep track of the context used, so the appropriate measure would be memory. Another way to view this is as a memory requirement to be able to reproduce quantum contextuality in a realist model. The model we will use can be viewed as an extension of Spekkens toy model [Phys. Rev. A 75, 032110 (2007)], and the relation is studied in some detail. To reproduce the quantum predictions for the Peres-Mermin square, the memory requirement is more than one bit in addition to the memory used for the individual outcomes in the corresponding noncontextual model.

  • 16.
    Levin, Lars-Åke
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Sobocinski, Piotr Doliwa
    Department of Clinical Sciences, Danderyd Hospital, Division of cardiovascular medicine, Karolinska Institutet, Stockholm, Sweden.
    Kull, Viveka Frykman
    Department of Clinical Sciences, Danderyd Hospital, Division of cardiovascular medicine, Karolinska Institutet, Stockholm, Sweden.
    Friberg, Leif
    Department of Clinical Sciences, Danderyd Hospital, Division of cardiovascular medicine, Karolinska Institutet, Stockholm, Sweden.
    Rosenqvist, Mårten
    Department of Clinical Sciences, Danderyd Hospital, Division of cardiovascular medicine, Karolinska Institutet, Stockholm, Sweden.
    Davidson, Thomas
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    A cost-effectiveness analysis of screening for silent atrial fibrillation after ischaemic stroke.2015In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 17, no 2, 207-14 p.Article in journal (Refereed)
    Abstract [en]

    AIMS: The purpose of this study was to estimate the cost-effectiveness of two screening methods for detection of silent AF, intermittent electrocardiogram (ECG) recordings using a handheld recording device, at regular time intervals for 30 days, and short-term 24 h continuous Holter ECG, in comparison with a no-screening alternative in 75-year-old patients with a recent ischaemic stroke.

    METHODS AND RESULTS: The long-term (20-year) costs and effects of all alternatives were estimated with a decision analytic model combining the result of a clinical study and epidemiological data from Sweden. The structure of a cost-effectiveness analysis was used in this study. The short-term decision tree model analysed the screening procedure until the onset of anticoagulant treatment. The second part of the decision model followed a Markov design, simulating the patients' health states for 20 years. Continuous 24 h ECG recording was inferior to intermittent ECG in terms of cost-effectiveness, due to both lower sensitivity and higher costs. The base-case analysis compared intermittent ECG screening with no screening of patients with recent stroke. The implementation of the screening programme on 1000 patients resulted over a 20-year period in 11 avoided strokes and the gain of 29 life-years, or 23 quality-adjusted life years, and cost savings of €55 400.

    CONCLUSION: Screening of silent AF by intermittent ECG recordings in patients with a recent ischaemic stroke is a cost-effective use of health care resources saving costs and lives and improving the quality of life.

  • 17.
    Öberg, Per
    Linköping University, Department of Electrical Engineering, Vehicular Systems. Linköping University, The Institute of Technology.
    A DAE Formulation for Multi-Zone Thermodynamic Models and its Application to CVCP Engines2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the automotive area there are ever increasing demands from legislators and customers on low emissions and good fuel economy. In the process of developing and investigating new technologies, that can meet these demands, modeling and simulation have become important as standard engineering tools. To improve the modeling process new concepts and tools are also being developed.

    A formulation of a differential algebraic equation (DAE) that can be used for simulation of multi-zone in-cylinder models is extended and analyzed. Special emphasis is placed on the separation between thermodynamic state equations and the thermodynamic properties. This enables implementations with easy reuse of model components and analysis of simulation results in a structured manner which gives the possibility to use the formulation in a large number of applications. The introduction and depletion of zones are handled and it is shown that the DAE formulation has a unique solution as long as the gas model fulfills a number of basic criteria. Further, an example setup is used to validate that energy, mass, and volume are preserved when using the formulation in computer simulations. In other words, the numerical solution obeys the thermodynamic state equation and the first law of thermodynamics, and the results are consistent and converge as tolerances are tightened. As example applications, the DAE formulation is used to simulate spark ignited SI and Diesel engines as well as simple control volumes and 1-dimensional pipes. It is thus shown that the DAE formulation is able to adapt to the different requirements of the SI and Diesel engine models.

    An interesting application is the SI engine with continuously variable cam phasing (CVCP), which is a technology that reduces the fuel consumption. It influences the amount of air and residual gases in the engine in a non trivial manner and this SI application is used to evaluate three control oriented models for cylinder air charge and residual mass fraction for a CVCP-engine both for static and transient conditions. The models are: a simple generalized flow restriction model created with physical insight and two variants of a model that is based on an energy balance at intake valve closing (IVC). The two latter models require measurement of cylinder pressure and one also requires an air mass flow measurement. Using the SI model as reference it is shown that transients in cam positions have a large impact on air charge and residual mass fraction, and the ability of the models to capture these effects is evaluated. The main advantages of the generalized flow restriction model are that it is simple and does not require measurement of the cylinder pressure but it is also the model with the largest errors for static operating points and highest sensitivity in transients. The two models that use an energy balance at IVC both handle the transient cycles well. They are, however, sensitive to the temperature at IVC. For static cycles it is therefore advantageous to use the model with air mass flow measurement since it is less sensitive to input data. During transients however, if the external measurement is delayed, it is better to use the model that does not require the air mass flow.

    The conclusion is that the DAE formulation is a flexible, robust, tool, and that it is well suited for multi-zone in-cylinder models as well as models for manifolds and pipes outside the cylinder.

    List of papers
    1. Control Oriented Modeling of the Gas Exchange Process in Variable Cam Timing Engines
    Open this publication in new window or tab >>Control Oriented Modeling of the Gas Exchange Process in Variable Cam Timing Engines
    2006 (English)In: SAE Technical Paper 2006-01-0660, SAE , 2006Conference paper, Published paper (Refereed)
    Abstract [en]

    Variable cam timing engines pose new questions for engine control system designers. The cam timing directly influences cylinder air charge and residual mass fraction. Three models that predict residual mass fraction are investigated for a turbocharged dual independent Variable Cam Timing (VCT) engine. The three models (Fox et. al. 1993, Ponti et. al. 2002, and Mladek et. al. 2000) that all have real time capabilities are evaluated and validated against data from a crank angle based reference model. None of these models have previously been validated to cover this engine type. It is shown that all three models can be extended to dual independent VCT engines and that they also give a good description of the residual gas fraction. However, it is shown that the two most advanced models, based on a thermodynamic energy balance, are very sensitive to the model inputs and proper care must therefore be taken when these models are used

    Place, publisher, year, edition, pages
    SAE, 2006
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-18306 (URN)
    Available from: 2009-05-18 Created: 2009-05-18 Last updated: 2009-10-14Bibliographically approved
    2. Control Oriented Gas Exchange Models for CVCP Engines and their Transient Sensitivity
    Open this publication in new window or tab >>Control Oriented Gas Exchange Models for CVCP Engines and their Transient Sensitivity
    2007 (English)In: Oil & gas science and technology, ISSN 1294-4475, Vol. 62, no 4, 573-584 p.Article in journal (Refereed) Published
    Abstract [en]

    The paper analyzes a set of control oriented models for the gas exchange phase in engines with continuously variable cam phasing (CVCP). These models describe the mass flow of fresh gases and the residual gases caught in the cylinder during the gas exchange phase. Simulations with CVCP transients are also performed to analyze the models performance during transients.

    Place, publisher, year, edition, pages
    IFP, 2007
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-18307 (URN)10.2516/ogst:2007041 (DOI)
    Available from: 2009-05-18 Created: 2009-05-18 Last updated: 2009-05-18Bibliographically approved
  • 18.
    Carvalho Bittencourt, André
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Saarinen, Kari
    ABB Corporate Research, Västerås, Sweden.
    Sander Tavallaey, Shiva
    ABB Corporate Research, Västerås, Sweden.
    Gunnarsson, Svante
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Norrlöf, Mikael
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology. ABB Robotics, Västerås, Sweden.
    A data-driven approach to diagnostics of repetitive processes in the distribution domain: Applications to gearbox diagnosticsin industrial robots and rotating machines2014In: Mechatronics (Oxford), ISSN 0957-4158, Vol. 24, no 8, 1032-1041 p.Article in journal (Refereed)
    Abstract [en]

    This paper presents a data-driven approach to diagnostics of systems that operate in a repetitive manner. Considering that data batches collected from a repetitive operation will be similar unless in the presence of an abnormality, a condition change is inferred by comparing the monitored data against an available nominal batch. The method proposed considers the comparison of data in the distribution domain, which reveals information of the data amplitude. This is achieved with the use of kernel density estimates and the Kullback–Leibler distance. To decrease sensitivity to disturbances while increasing sensitivity to faults, the use of a weighting vector is suggested which is chosen based on a labeled dataset. The framework is simple to implement and can be used without process interruption, in a batch manner. The approach is demonstrated with successful experimental and simulation applications to wear diagnostics in an industrial robot gearbox and for diagnostics of gear faults in a rotating machine.

  • 19.
    Carvalho Bittencourt, André
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Saarinen, Kari
    ABB Corporate Research.
    Sander Tavallaey, Shiva
    ABB Corporate Research.
    Gunnarsson, Svante
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    A Data-Driven Method for Monitoring of Repetitive Systems: Applications to Robust Wear Monitoring of a Robot Joint2013Report (Other academic)
    Abstract [en]

    This paper presents a method for monitoring of systems that operate in a repetitive manner. Considering that data batches collected from a repetitive operation will be similar unless in the presence of an abnormality, a condition change is inferred by comparing the monitored data against a nominal batch. The method proposed considers the comparison of data in the distribution domain, which reveals information of the data amplitude. This is achieved with the use of kernel density estimates and the Kullback-Leibler distance. To decrease sensitivity to unknown disturbances while increasing sensitivity to faults, the use of a weighting vector is suggested which is chosen based on a labeled dataset. The framework is simple to implement and can be used without process interruption, in a batch manner. The method was developed with interests in industrial robotics where a repetitive behavior is commonly found. The problem of wear monitoring in a robot joint is studied based on data collected from a test-cycle. Real data from accelerated wear tests and simulations are considered. Promising results are achieved where the method output shows a clear response to the wear increases.

  • 20.
    Carvalho Bittencourt, André
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Saarinen, Kari
    ABB Corporate Research Västerås, Sweden.
    Sander-Tavallaey, Shiva
    ABB Corporate Research Västerås, Sweden.
    A Data-driven Method for Monitoring Systems that Operate Repetitively: Applications to Robust Wear Monitoring inan Industrial Robot Joint2011Manuscript (preprint) (Other academic)
    Abstract [en]

    This paper presents a method for condition monitoring of systems that operate in a repetitive manner. A data driven method is proposed that considers changes in the distribution of data samples obtained from multiple executions of one or several tasks. This is made possible with the use of kernel density estimators and the Kullback-Leibler distance measure between distributions. To increase robustness to unknown disturbances and sensitivity to faults, the use of a weighting function is suggested which can considerably improve detection performance. The method is very simple to implement, it does not require knowledge about the monitored system and can be used without process interruption, in a batch manner. The method is illustrated with applications to robust wear monitoring in a robot joint. Interesting properties of the application are presented through a real case study and simulations. The achieved results show that robust wear monitoring in industrial robot joints is made possible with the proposed method.

  • 21.
    Carvalho Bittencourt, André
    et al.
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Saarinen, Kari
    ABB Corporate Research Västerås, Sweden.
    Sander-Tavallaey, Shiva
    ABB Corporate Research Västerås, Sweden.
    A Data-Driven Method for Monitoring Systems that Operate Repetitively: Applications to Robust Wear Monitoring inan Industrial Robot Joint2011Report (Other academic)
    Abstract [en]

    This paper presents a method for condition monitoring of systems that operate in a repetitive manner. A data driven method is proposed that considers changes in the distribution of data samples obtained from multiple executions of one or several tasks. This is made possible with the use of kernel density estimators and the Kullback-Leibler distance measure between distributions. To increase robustness to unknown disturbances and sensitivity to faults, the use of a weighting function is suggested which can considerably improve detection performance. The method is very simple to implement, it does not require knowledge about the monitored system and can be used without process interruption, in a batch manner. The method is illustrated with applications to robust wear monitoring in a robot joint. Interesting properties of the application are presented through a real case study and simulations. The achieved results show that robust wear monitoring in industrial robot joints is made possible with the proposed method.

  • 22.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Olsson, Anders
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Toss, Göran
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults2002In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 147, no 1, 49-57 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.

    DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.

    RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.

    CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.

  • 23.
    Korishe, Abdulah
    Linköping University, Department of Electrical Engineering, Electronics System.
    A Driver Circuit for Body-Coupled Communication2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The main concept of Body-Coupled Communication (BCC) is to transmit the electrical information through the human body as a communication medium by means of capacitive coupling. Nowadays the current research of wireless body area network are expanding more with the new ideas and topologies for better result in respect to the low power and area, security, reliability and sensitivity since it is first introduced by the Zimmerman in 1995. In contrast with the other existing wireless communication technology such as WiFi, Bluetooth and Zigbee, the BCC is going to increase the number of applications as well as solves the problem with the cell based communication system depending upon the frequency allocation. In addition, this promising technology has been standardized by a task group named IEEE 802.15.6 addressing a reliable and feasible system for low power in-body and on-body nodes that serves a variety of medical and non medical applications.

    The entire BAN project is divided into three major parts consisting of application layer, digital baseband and analog front end (AFE) transceiver. In the thesis work a strong driver circuit for BCC is implemented as an analog front end transmitter (Tx). The primary purpose of the study is to transmit a strong signal as the signal is attenuated by the body around 60 dB. The Driver circuit is cascaded of two single-stage inverter and an identical inverter with drain resistor. The entire driver circuit is designed with ST65 nm CMOS technology with 1.2 V supply operated at 10 MHz frequency, has a driving capability of 6 mA which is the basic requirement. The performance of the transmitter is compared with the other architecture by integrating different analysis such as corner analysis, noise analysis and eye diagram. The cycle to cycle jitter is 0.87% which is well below to the maximum point and the power supply rejection ratio (PSRR) is 65 dB indicates the good emission of supply noise. In addition, the transmitter does not require a filter to emit the noise because the body acts like a low pass filter.

    In conclusion the findings of the thesis work is quite healthy compared to the previous work. Finally, there is some point to improve for the driver circuit in respect to the power consumption, propagation delay and leakage power in the future.   

  • 24.
    Andersson, Thord
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Läthén, Gunnar
    Linköping University, Department of Science and Technology, Digital Media. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lenz, Reiner
    Linköping University, Department of Science and Technology, Digital Media. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    A Fast Optimization Method for Level Set Segmentation2009In: Image Analysis: 16th Scandinavian Conference, SCIA 2009, Oslo, Norway, June 15-18, 2009. Proceedings / [ed] A.-B. Salberg, J.Y. Hardeberg, and R. Jenssen, Springer Berlin/Heidelberg, 2009, 400-409 p.Conference paper (Refereed)
    Abstract [en]

    Level set methods are a popular way to solve the image segmentation problem in computer image analysis. A contour is implicitly represented by the zero level of a signed distance function, and evolved according to a motion equation in order to minimize a cost function. This function defines the objective of the segmentation problem and also includes regularization constraints. Gradient descent search is the de facto method used to solve this optimization problem. Basic gradient descent methods, however, are sensitive for local optima and often display slow convergence. Traditionally, the cost functions have been modified to avoid these problems. In this work, we instead propose using a modified gradient descent search based on resilient propagation (Rprop), a method commonly used in the machine learning community. Our results show faster convergence and less sensitivity to local optima, compared to traditional gradient descent.

  • 25.
    Gokulakrishnan, P
    et al.
    Queens University, Canada.
    Lawrence, David
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    McLellan, PJ
    Queens University, Canada.
    Grandmaison, EW
    Queens University, Canada.
    A functional-PCA approach for analyzing and reducing complex chemical mechanisms2006In: Computers and Chemical Engineering, ISSN 0098-1354, Vol. 30, no 07-Jun, 1093-1101 p.Article in journal (Refereed)
    Abstract [en]

    In industrial reactive flow systems such as furnaces and gas turbines, there are considerable variations in the temperature and concentrations of species along different spatial directions. Functional principal component analysis (fPCA) can be used to study the temporal (or spatial) evolution of reactions in a reactive flow system, and to develop simplified kinetic models to describe this behaviour. A comprehensive kinetic mechanism for CO oxidation is used to demonstrate application of fPCA to identify important reactions as a function of time. In conventional PCA, the eigenvalue-eigenvector decomposition specifically transforms the variations associated with the time (or spatial directions) and species into loadings that represent only the reactions. However, fPCA produces functional loading vectors (xi) over bar (1)(t) which are functions of time or distance, whose elements are referred to as functional loadings. The functional loading vectors are the eigenfunctions of the covariance matrix associated with the sensitivity trajectories. The functional loadings are used to identify reactions playing a significant role, possibly as a function of time, and are used to develop a reduced kinetic scheme from a detailed kinetic mechanism.

  • 26.
    Bernardi, R. E.
    et al.
    Heidelberg University, Germany.
    Zohsel, K.
    Heidelberg University, Germany.
    Hirth, N.
    Heidelberg University, Germany.
    Treutlein, J.
    Heidelberg University, Germany.
    Heilig, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Social and Affective Neuroscience (CSAN). Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
    Laucht, M.
    Heidelberg University, Germany.
    Spanagel, R.
    Heidelberg University, Germany.
    Sommer, W. H.
    Heidelberg University, Germany.
    A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology2016In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 6, no e861Article in journal (Refereed)
    Abstract [en]

    It has been proposed that vulnerability to nicotine addiction is moderated by variation at the mu-opioid receptor locus (OPRM1), but results from human studies vary and prospective studies based on genotype are lacking. We have developed a humanized mouse model of the most common functional OPRM1 polymorphism rs1799971_A4G (A118G). Here we use this model system together with a cohort of German youth to examine the role of the OPRM1 A118G variation on nicotine reward. Nicotine reinforcement was examined in the humanized mouse model using i.v. self-administration. Male (n = 17) and female (n = 26) mice homozygous either for the major human A allele (AA) or the minor G allele (GG) underwent eight daily 2 h sessions of nicotine self-administration. Furthermore, male (n = 104) and female (n = 118) subjects homozygous for the A allele or carrying the G allele from the Mannheim Study of Children at Risk were evaluated for pleasurable and unpleasant experiences during their initial smoking experience. A significant sex-by-genotype effect was observed for nicotine self-administration. Male 118GG mice demonstrated higher nicotine intake than male 118AA mice, suggesting increased nicotine reinforcement. In contrast, there was no genotype effect in female mice. Human male G allele carriers reported increased pleasurable effects from their first smoking experience, as compared to male homozygous A, female G and female homozygous A allele carriers. The 118G allele appears to confer greater sensitivity to nicotine reinforcement in males, but not females.

  • 27.
    Blad, Anton
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Electrical Engineering, Electronics System.
    Johansson, Håkan
    Linköping University, The Institute of Technology. Linköping University, Department of Electrical Engineering, Electronics System.
    Löwenborg, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Electrical Engineering, Electronics System.
    A General Formulation of Analog-to-Digital Converters Using Parallel Sigma-Delta Modulators and Modulation Sequences2006In: Asia Pacific Conference on Circuits and Systems,2006, IEEE , 2006Conference paper (Refereed)
    Abstract [en]

    A formulation based on multirate theory is introduced for analog-to-digital converters using parallel sigma-delta modulators in conjunction with modulation sequences. It is shown how the formulation can be used to analyze a system's sensitivity to channel mismatch errors by means of circulant and pseudo-circulant matrices. It is demonstrated how the time-interleaved-modulated (TIM), Hadamard-modulated (HM) and frequency-band decomposition (FBD) converters can be viewed as special cases of this more general description, and it is shown why the TIM and HM ADCs are sensitive to channel mismatch errors, whereas the FBD ADCs are not.

  • 28.
    Neely, G Gregory
    et al.
    Austrian Academy of Science.
    Hess, Andreas
    University of Erlangen Nurnberg.
    Costigan, Michael
    Harvard University.
    Keene, Alex C
    NYU.
    Goulas, Spyros
    Austrian Academy of Science.
    Langeslag, Michiel
    Innsbruck Medical University.
    Griffin, Robert S
    Massachusetts General Hospital.
    Belfer, Inna
    University of Pittsburgh.
    Dai, Feng
    University of Pittsburgh.
    Smith, Shad B
    University N Carolina.
    Diatchenko, Luda
    University N Carolina.
    Gupta, Vaijayanti
    Strand Life Science Pvt Ltd.
    Xia, Cui-Ping
    Austrian Academy Science.
    Amann, Sabina
    Austrian Academy of Science.
    Kreitz, Silke
    University of Erlangen Nurnberg.
    Heindl-Erdmann, Cornelia
    University of Erlangen Nurnberg.
    Wolz, Susanne
    University of Erlangen Nurnberg.
    Ly, Cindy V
    Strand Life Science Pvt Ltd.
    Sarangi, Rinku
    Strand Life Science Pvt Ltd.
    Dan, Debasis
    Strand Life Science Pvt Ltd.
    Novatchkova, Maria
    Austrian Academy of Science.
    Rosenzweig, Mark
    Brandeis University.
    Gibson, Dustin G
    University N Carolina.
    Truong, Darwin
    Austrian Academy of Science.
    Schramek, Daniel
    Austrian Academy of Science.
    Zoranovic, Tamara
    Austrian Academy of Science.
    Cronin, Shane J F
    Austrian Academy of Science.
    Angjeli, Belinda
    Austrian Academy of Science.
    Brune, Kay
    University of Erlangen Nurnberg.
    Dietzl, Georg
    Stanford University.
    Maixner, William
    University N Carolina.
    Meixner, Arabella
    Austrian Academy of Science.
    Thomas, Winston
    Deltagen Inc.
    Pospisilik, J Andrew
    Max Planck Institute.
    Alenius, Mattias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Developmental Biology, IKE.
    Kress, Michaela
    Innsbruck Medical University.
    Subramaniam, Sai
    Strand Life Science Pvt Ltd.
    Garrity, Paul A
    Brandeis University.
    Bellen, Hugo J
    Baylor College of Medicine.
    Woolf, Clifford J
    Harvard University.
    Penninger, Josef M
    Austrian Academy of Science.
    A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene2010In: CELL, ISSN 0092-8674, Vol. 143, no 4, 628-638 p.Article in journal (Refereed)
    Abstract [en]

    Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the alpha 2 delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (alpha 2 delta 3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha 2 delta 3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha 2 delta 3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha 2 delta 3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.

  • 29.
    Lundgren, Jan
    et al.
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Peterson, Anders
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    A Heuristic for the Bilevel Origin–Destination Matrix Estimation Problem2008In: Transportation Research Part B: Methodological, ISSN 0191-2615, Vol. 42, no 4, 339-354 p.Article in journal (Refereed)
    Abstract [en]

    In this paper we consider the estimation of an origin–destination (OD) matrix, given a target OD-matrix and traffic counts on a subset of the links in the network. We use a general nonlinear bilevel minimization formulation of the problem, where the lower level problem is to assign a given OD-matrix onto the network according to the user equilibrium principle. After reformulating the problem to a single level problem, the objective function includes implicitly given link flow variables, corresponding to the given OD-matrix. We propose a descent heuristic to solve the problem, which is an adaptation of the wellknown projected gradient method. In order to compute a search direction we have to approximate the Jacobian matrix representing the derivatives of the link flows with respect to a change in the OD-flows, and we propose to do this by solving a set of quadratic programs with linear constraints only. If the objective function is differentiable at the current point, the Jacobian is exact and we obtain a gradient. Numerical experiments are presented which indicate that the solution approach can be applied in practice to medium to large size networks.

  • 30.
    Berggren, Karl
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    A high sensitivity imaging detector for the study of the formation of (anti)hydrogen2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    AEGIS (Antimatter Experiment, Gravity, Interferometry and Spectroscopy) isan experiment under development at CERN which will measure earth's gravitationalforce on antimatter. This will be done by creating a horizontal pulsedbeam of low energy antihydrogen, an atom consisting of an antiproton anda positron. The experiment will measure the vertical de ection of the beamthrough which it is possible to calculate the gravitational constant for antimatter.To characterise the production process in the current state of the experimentit is necessary to develop an imaging detector for single excited hydrogenatoms. This thesis covers the design phase of that detector and includes studiesand tests of detector components. Following literature studies, tests and havingdiscarded several potential designs, a baseline design was chosen. The suggesteddetector will contain a set of ionising rings followed by an electron multiplyingmicrochannel plate, a light emitting phosphor screen, a lens system and nallya CCD camera for readout. The detector will be able to detect single hydrogenatoms, measure their time of ight as well as being able to image electronplasmas and measure the time of ight of the initial particles in such a plasma.Tests were made to determine the behaviour of microchannel plates at the lowtemperatures used in the experiment. Especially, the resistance and multiplicationfactor of the microchannel plates have been measured at temperaturesdown to 14 K.

  • 31.
    Sekretaryova, Alina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Beni, Valerio
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Eriksson, Mats
    Linköping University, Department of Physics, Chemistry and Biology, Chemical and Optical Sensor Systems. Linköping University, The Institute of Technology.
    Turner, Anthony
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Vagin, Mikhail Y
    Linköping University, Department of Physics, Chemistry and Biology, Chemical and Optical Sensor Systems. Linköping University, The Institute of Technology.
    A highly sensitive and self-powered cholesterol biosensor2014In: 24th Anniversary World Congress on Biosensors – Biosensors 2014, Elsevier, 2014Conference paper (Other academic)
    Abstract [en]

    Blood cholesterol is a very important parameter for the assessment of atherosclerosis and other lipid disorders. The total cholesterol concentration in human blood should be less than 5.17 mM. Concentrations in the range 5.17 – 6.18 mM are considered borderline high risk and levels above 6.21 mM, high risk. Cholesterol determination with high accuracy is therefore necessary in order to differentiate these levels for medical screening or diagnosis. Several attempts to develop highly sensitive cholesterol biosensors have been described, but, to the best of our knowledge, this is the first report of a self-powered cholesterol biosensor, i.e. a device delivering the analytical information from the current output of the energy of the biocatalytic conversion of cholesterol, without any external power source. This is particularly relevant to the development of inexpensive screening devices based on printed electronics.

     

    We present two complementary bioelectrocatalytic platforms suitable for the fabrication of a self-powered biosensor. Both are based on cholesterol oxidase (ChOx) immobilisation in a sol-gel matrix, as illustrated in Fig. 1 [1]. Mediated biocatalytic cholesterol oxidation [2] was used as the anodic reaction and electrocatalytic reduction of hydrogen peroxide on Prussian Blue (PB) as the cathodic reaction. Due to a synergistic effect in the self-powered cholesterol biosensor, the analytical parameters of the overall device exceeded those of the individual component half-cells, yielding a sensitivity of 0.19 A M-1 cm-2 and a dynamic range that embraces the free cholesterol concentrations found in human blood.

     

    Thus, we have demonstrated the novel concept of highly sensitive cholesterol determination using the first self-powered cholesterol biosensor. This configuration is particularly promising for incorporation in emerging plastic- and paper-based analytical instruments for decentralised diagnostics and mobile health.

     

  • 32.
    Hassanli, Kourosh
    et al.
    Isfahan University of Technology, Iran.
    Masoud Sayedi, Sayed
    Isfahan University of Technology, Iran.
    Dehghani, Rasoul
    Isfahan University of Technology, Iran.
    Jalili, Armin
    Linköping University, Department of Electrical Engineering, Integrated Circuits and Systems. Linköping University, Faculty of Science & Engineering.
    Wikner, Jacob
    Linköping University, Department of Electrical Engineering, Integrated Circuits and Systems. Linköping University, Faculty of Science & Engineering.
    A highly sensitive, low-power, and wide dynamic range CMOS digital pixel sensor2015In: Sensors and Actuators A-Physical, ISSN 0924-4247, E-ISSN 1873-3069, Vol. 236, 82-91 p.Article in journal (Refereed)
    Abstract [en]

    This paper proposes a new pixel-level light-to-frequency converter (LFC) that operates at a low supply voltage, and also offers low power consumption, low area, wide dynamic range, and high sensitivity. By using the proposed LFC, a digital pixel sensor (DPS) based on a pulse-frequency-modulation (PFM) scheme has been designed and fabricated. The prototype chip, including an array of 16 x 16 DPS with pixel size of 23 x 23 mu m(2) and 33.5% fill factor, was fabricated in a standard 180-nm CMOS technology. Experimental results show that the pixel operates with maintained output characteristics at supply voltages down to 1 V. The pixel sensor achieves an overall dynamic range of more than 142 dB and consumes 103 nW per pixel at a supply voltage of 1V at room light intensity. The sensitivity of the LFC is very high at the lower end of the light intensity compared to the higher end which enables the ability to capture clear images. (C) 2015 Elsevier B.V. All rights reserved.

  • 33.
    Ali Kamyabi, Mohammad
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Hajari, Nasim
    University of Zanjan, Iran .
    Turner, Anthony
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Tiwari, Ashutosh
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    A high-performance glucose biosensor using covalently immobilised glucose oxidase on a poly(2,6-diaminopyridine)/carbon nanotube electrode2013In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 116, 801-808 p.Article in journal (Refereed)
    Abstract [en]

    A highly-sensitive glucose biosensor amenable to ultra-miniaturisation was fabricated by immobilisation of glucose oxidase (GOx), onto a poly(2,6-diaminopyridine)/multi-walled carbon nanotube/glassy carbon electrode (poly(2,6-DP)/MWNT/GCE). Cyclic voltammetry was used for both the electrochemical synthesis of poly-(2,6-DP) on the surface of a MWNT-modified GC electrode, and characterisation of the polymers deposited on the GC electrode. The synergistic effect of the high active surface area of both the conducting polymer, i.e., poly-(2,6-DP) and MWNT gave rise to a remarkable improvement in the electrocatalytic properties of the biosensor. The transfer coefficient (alpha), heterogeneous electron transfer rate constant and Michaelis-Menten constant were calculated to be 0.6, 4 s(-1) and 0.20 mM at pH 7.4, respectively. The GOx/poly(2,6-DP)/MWNT/GC bioelectrode exhibited two linear responses to glucose in the concentration ranging from 0.42 mu M to 8.0 mM with a correlation coefficient of 0.95, sensitivity of 52.0 mu AmM-1 cm(-2), repeatability of 1.6% and long-term stability, which could make it a promising bioelectrode for precise detection of glucose in the biological samples. (C) 2013 Elsevier B.V. All rights reserved.

  • 34.
    Timpka, Toomas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    Angbratt, Marianne
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Hermansson, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Bolme, P
    Häger, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Valter, L
    A high-precision protocol for identification of preschool children at risk for persisting obesity2007In: PLoS ONE, ISSN 1932-6203, Vol. 2, no 6Article in journal (Refereed)
    Abstract [en]

    Background: Recent studies suggest that adolescent adiposity is established already in preadolescence. Earlier studies have confirmed a strong tracking of obesity from adolescence to adulthood. Our aim was to examine the diagnostic accuracy of a population-derived protocol for identification of preschool children at risk for obesity in preadolescence. Methodology/Principal Findings: We analysed data obtained for child health surveillance up to age 5 from 5778 children born in a swedish county in 1991. The basic data set included age, sex, and weight and height measurements from the regular checkups between ages 1.5 and 5. Data not routinely collected in the child health centre setting were disregarded. The children were at age 10 randomly assigned to protocol derivation and validation cohorts and assessed for obesity according to IOTF criteria. The accuracy of predicting obesity in the validation cohort was measured using decision precision, specificity, and sensitivity. The decision protocol selected 1.4% of preschool children as being at obesity risk. The precision of the protocol at age 10 was 82% for girls and 80% for boys, and the specificity was 100% for both boys and girls, The sensitivity was higher for girls (41 %) than for boys (21%). The relative risk for obesity at age 10 estimated by the odds ratio for individuals selected by the protocol compared to non-selected peers was 212.6 (95% confidence interval 56.6 to 798.4) for girls and 120.3 (95% Cl 24.5 to 589.91for boys. Conclusion/Significance: A simple and inexpensive decision protocol based on BMI values proved to have high precision and specificity for identification of preschool children at risk for obesity persisting into adolescence, while the sersitivity was low especially for boys. Implementation and further evaluations of the protocol in chlid health centre settings are warranted. © 2007 Timpka et al.

  • 35.
    Dizdar (Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Smeds, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Årstrand, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    A high-sensitivity fluorometric high-performance liquid chromatographic method for determination of glutathione and other thiols in cultured melanoma cells, microdialysis samples from melanoma tissue, and blood plasma.1991In: Melanoma Research, ISSN 0960-8931, Vol. 1, no 1, 33-42 p.Article in journal (Refereed)
    Abstract [en]

    A high-performance liquid chromatographic method with fluorometric detection is described which is suitable for determination of glutathione in small samples. Reduced glutathione (GSH) and total glutathione obtained as GSH after reduction with glutathione reductase is derivatized with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) and subjected to chromatography. The detection limit for the GSH-DACM derivative was 5-10 fmol/injection, and analytical recovery was quantitative. The method is suitable for determination of both reduced and total glutathione in samples from microdialysis of melanoma tumours, and cysteine can be quantified in the same chromatogram. Application is shown also for glutathione determinations in cultured melanoma cells, melanoma homogenates and plasma.

  • 36.
    Gharehbaghi, Arash
    et al.
    Malardalen University, Sweden.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Science & Engineering.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Janerot-Sjoberg, Birgitta
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; KTH Royal Institute Technology, Sweden.
    Ekman, Inger
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Linden, Maria
    Malardalen University, Sweden.
    Babic, Ankica
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Science & Engineering. University of Bergen, Norway.
    A Hybrid Model for Diagnosing Sever Aortic Stenosis in Asymptomatic Patients using Phonocardiogram2015In: WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, 2015, VOLS 1 AND 2, Springer, 2015, Vol. 51, 1006-1009 p.Conference paper (Refereed)
    Abstract [en]

    This study presents a screening algorithm for severe aortic stenosis (AS), based on a processing method for phonocardiographic (PCG) signal. The processing method employs a hybrid model, constituted of a hidden Markov model and support vector machine. The method benefits from a preprocessing phase for an enhanced learning. The performance of the method is statistically evaluated using PCG signals recorded from 50 individuals who were referred to the echocardiography lab at Linkoping University hospital. All the individuals were diagnosed as having a degree of AS, from mild to severe, according to the echocardiographic measurements. The patient group consists of 26 individuals with severe AS, and the rest of the 24 patients comprise the control group. Performance of the method is statistically evaluated using repeated random sub sampling. Results showed a 95% confidence interval of (80.5%-82.8%)/(77.8%-80.8%) for the accuracy/sensitivity, exhibiting an acceptable performance to be used as decision support system in the primary healthcare center.

  • 37.
    Dannetun, Helen
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics . Linköping University, The Institute of Technology.
    Petersson, L.-G.
    Söderberg, D.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics . Linköping University, The Institute of Technology.
    A hydrogen-sensitive Pd-MOS structure working over a wide pressure range1984In: Applied Surface Science, ISSN 0169-4332, E-ISSN 1873-5584, Vol. 17, 259- p.Article in journal (Refereed)
    Abstract [en]

    A Pd-MOS structure has been developed which has proven to be sensitive to hydrogen both in air at atmospheric pressures and in UHV. The ability to work over a wide pressure range makes it an interesting component in, e.g., the study of catalytic reactions involving hydrogen on metal surfaces. Here we demonstrate the hydrogen sensitivity of such a structure over a pressure range of 5x10-11 to 2 Torr.

  • 38.
    Bajuri, M. N.
    et al.
    University of Oxford, England; University of Teknol Malaysia, Malaysia.
    Isaksson, Hanna
    Lund University, Sweden.
    Eliasson, Pernilla T.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Thompson, Mark S.
    University of Oxford, England.
    A hyperelastic fibre-reinforced continuum model of healing tendons with distributed collagen fibre orientations2016In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 15, no 6, 1457-1466 p.Article in journal (Refereed)
    Abstract [en]

    The healing process of ruptured tendons is problematic due to scar tissue formation and deteriorated material properties, and in some cases, it may take nearly a year to complete. Mechanical loading has been shown to positively influence tendon healing; however, the mechanisms remain unclear. Computational mechanobiology methods employed extensively to model bone healing have achieved high fidelity. This study aimed to investigate whether an established hyperelastic fibre-reinforced continuum model introduced by Gasser, Ogden and Holzapfel (GOH) can be used to capture the mechanical behaviour of the Achilles tendon under loading during discrete timepoints of the healing process and to assess the models sensitivity to its microstructural parameters. Curve fitting of the GOH model against experimental tensile testing data of rat Achilles tendons at four timepoints during the tendon repair was used and achieved excellent fits (0.9903 amp;lt; R-2 amp;lt; 0.9986). A parametric sensitivity study using a three-level central composite design, which is a fractional factorial design method, showed that the collagen-fibre-related parameters in the GOH model-kappa, k(1) and k(2)-had almost equal influence on the fitting. This study demonstrates that the GOH hyperelastic fibre-reinforced model is capable of describing the mechanical behaviour of healing tendons and that further experiments should focus on establishing the structural and material parameters of collagen fibres in the healing tissue.

  • 39.
    Zhang, Juankun
    et al.
    Tianjin University Science and Technology, Coll Biotechnol, Minist Educ, Key Lab Ind Microbiol, Tianjin, Peoples R China.
    Dong, Shanmu
    Tianjin University Science and Technology.
    Lu, Jinhui
    Tianjin University Science and Technology.
    Turner, Anthony P. F.
    Cranfield University, UK.
    Fan, Qingjie
    Lanlike Elect Chemistry High Tech Ltd, Tianjin, Peoples R China.
    Jia, Shiru
    Tianjin University Science and Technology.
    Yang, Hongjiang
    Tianjin University Science and Technology.
    Qiao, Changsheng
    Tianjin University Science and Technology.
    Zhou, Hao
    Tianjin University Science and Technology.
    He, Guowei
    TEDA Int Cardiovasc Hospital, Tianjin, Peoples R China.
    A Label Free Electrochemical Nanobiosensor Study2009In: Analytical Letters, ISSN 0003-2719, E-ISSN 1532-236X, Vol. 42, no 17, 2905-2913 p.Article in journal (Refereed)
    Abstract [en]

    Nano-porous silicon (PS) is an attractive material for incorporation into biosensors, because it has a large surface area combined with the ability to generate both optical and electrical signals. In this paper, we describe a label-free nanobiosensor for bovine serum albumin (BSA). Nano-porous silicon produced in our laboratory was functionalized prior to immobilization of anti-BSA antibody on the surface. Reaction with BSA in phosphate buffered saline (PBS) buffer resulted in an impedance change which was inversely proportional to the concentration of the analyte. The system PBS buffer/antigen-antibody/PS constitutes an electrolyte-insulator-semiconductor (EIS) structure, thus furnishing an impedance EIS nanobiosensor. The linear range of the sensor was 0-0.27mgmL-1 and the sensitivity was less than 10 mu g mL-1.

  • 40.
    Hassanli, Kourosh
    et al.
    Isfahan University of Technology, Iran.
    Masoud Sayedi, Sayed
    Isfahan University of Technology, Iran.
    Dehghani, Rasoul
    Isfahan University of Technology, Iran.
    Jalili, Armin
    Linköping University, Department of Electrical Engineering, Integrated Circuits and Systems. Linköping University, Faculty of Science & Engineering.
    Wikner, Jacob
    Linköping University, Department of Electrical Engineering, Integrated Circuits and Systems. Linköping University, Faculty of Science & Engineering.
    A low-power wide tuning-range CMOS current-controlled oscillator2016In: Integration, ISSN 0167-9260, E-ISSN 1872-7522, Vol. 55, 57-66 p.Article in journal (Refereed)
    Abstract [en]

    This paper presents a low-power, small-size, wide tuning-range, and low supply voltage CMOS current controlled oscillator (CCO) for current converter applications. The proposed oscillator is designed and fabricated in a standard 180-nm, single-poly, six-metal CMOS technology. Experimental results show that the oscillation frequency of the CCO is tunable from 30 Hz to 970 MHz by adjusting the control current in the range of 100 fA to 10 mu A, giving an overall dynamic range of over 160 dB. The operation of the circuit is nearly independent of the power supply voltage and the circuit operates at supply voltages as low as 800 my. Also, at this voltage, with control currents in the range of sub-nano-amperes, the power consumption is about 30 nW. These features are promising in sensory and biomedical applications. The chip area is only 8.8 x 11.5 mu m(2). (C) 2016 Elsevier B.V. All rights reserved.

  • 41.
    Sowdamini Nakka, Sravya
    et al.
    PEAS Institut, Linköping, Sweden.
    Johansson, Jessica
    Örebro University, Sweden.
    Shahzad, Fasial
    PEAS Institut, Linköping, Sweden.
    Hanning, Anders
    Episentec AB, Sollentuna, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institut, Linköping.
    A methachromatic-based experimental model for identification of bowel as the focus of an acute inflammation2013In: Open Journal of Gastroenterology, ISSN 2163-9450, E-ISSN 2163-9469, Vol. 3, no 1, 42-48 p.Article in journal (Refereed)
    Abstract [en]

    Diarrhea is the most common symptom of acute inflammation in gastrointestinal tract and the patients are isolated in order to inhibit transmission and to conduct investigations. Yet there is no standard test to distinguish gastrointestinal infection from more generalized diseases at admittance which might cause delay in therapy. Hepatocyte growth factor (HGF) is produced upon injury by mesenchymal cells. On the contrary to chronic inflammation, HGF produced in the course of acute inflammation is biologically active and shows binding affinity to heparan sulphate proteoglycan (HSPG) and dextran sulphate (DS). Based on this phenomenon, an agarose gel containing DS was prepared and immobilized on loops to investigate the feces samples for the presence or absence of growth factors such as HGF with affinity to DS. The study is conducted as a clinical evaluation of an experimental model to distinguish acute infectious gastroenteritis from other causes of diarrhea. 656 fecal samples gathered consequently from patients seeking for bowel disturbances and healthy were tested by the test and the medical reports were investigated. Upon interaction with DS, methylene blue changes color to pink. This phenomenon was inhibited by HGF and converted by addition of anti-HGF antibodies to the samples. The test distinguished acute infectious gastroenteritis with high sensitivity and specificity (96% and 92% respectively) from other causes of diarrhea. We introduce a metachromatic experimental model that might distinguish acute inflammation in alimentary tract from other causes of diarrhea. This model might be used in developing rapid diagnostic tests.

  • 42.
    Ingeström, Victor
    et al.
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    Hansson, John
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    A Method for Estimating Soot Load in a DPF using an RF-based Sensor2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The European emission standard is an EU directive which describes what emission limits car manufactures are required to meet. In order to meet these requirements car manufacturers use different techniques and components. In a modern diesel automobile a Diesel Particulate Filter (DPF) is used to gather soot from the exhausts. As soot accumulates in the DPF, the back pressure increases and the capability to hold more soot decreases. Therefore the DPF continuously needs to get rid of the stored soot. The soot is removed through a process called regeneration. In order to optimize when to perform regeneration, it is vital to know the amount of soot in the filter.

    A method for estimating the soot mass in a DPF using a radio frequency-based sensor has been developed. The sensor that has been studied is the Accusolve soot sensor from General Electric. A parameter study has been performed to evaluate the parameters that affects the sensor’s output. Parameters that have been studied include positioning of the sensor, temperature in the DPF, flow rate through the DPF and distribution of soot in the DPF. Different models for estimation of soot mass in the DPF has been developed and analyzed.

    An uncertainty caused by removing the coaxial cable connectors when weighing the DPF has been identified and methods for minimizing this uncertainty has been presented. Results show that the sensor output is sensitive to temperature, soot distribution and position, and also show some sensitivity to the flow rate. An ARX model, with only one state, is proposed to estimate the soot mass in the DPF, since it gives the best prediction of soot mass and showed good resistance to bias errors and noise in all the input signals.

  • 43.
    Redhe, Marcus
    et al.
    Linköping University, Department of Management and Engineering, Solid Mechanics. Linköping University, The Institute of Technology.
    Nilsson, Larsgunnar
    Linköping University, Department of Management and Engineering, Solid Mechanics. Linköping University, The Institute of Technology.
    A method to determine structural sensitivities in vehicle crashworthiness design2002In: International Journal of Crashworthiness, ISSN 1358-8265, Vol. 7, no 2, 179-190 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this work is to determine when a linear surface approximation in the Response Surface Methodology can be utilised to calculate parameter sensitivities of a vehicle exposed to impact loading. Linear surface approximations are less costly than quadratic surfaces due to a lower number of function evaluations. However, the linear surface approximation error is often larger. Two structural impact problems are studied: one simple rail structure with two design variables and one vehicle model with ten design variables. The study has shown that linear surface approximations can be used to determine the order of sensitivity. However, the absolute magnitudes of the sensitivities are not reliable. This can be used if the normalised root mean square error is smaller than 10%.

  • 44.
    Sahlén, Viktoria
    et al.
    Linköping University, Department of Management and Engineering, Logistics & Quality Management.
    Daberius, Jessica
    Linköping University, Department of Management and Engineering, Logistics & Quality Management.
    A model based on total cost and manufacturer performance to evaluate a product as well as possible cost reductions2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Omega Pharma is a distributer of over the counter products, selling thousands of products produced at more than 200 manufacturers and sold in most European countries. The company was founded in Belgium in 1987 and has since then had a high market focus and expanded through acquisitions of brands and products. The company has in recent years started working towards centralization and supplier base management. A project team has been set up to work strategically by choosing key manufacturers and by reducing the supplier base. A first step in this is to look more closely at products with a low turnover and that are not strategically important in order to evaluate if the product is profitable and which products that could be moved to other manufacturers or cancelled from the portfolio. Therefore the purpose of the study is to:

    Create an evaluation model based on revenue, total cost and manufacturer performance to evaluate a product and if cost reductions can be achieved by ending the production of the product or moving the product to a different manufacturer.

    A four step approach for analyzing total cost was followed in order to, in a structured way, create the model and identify the relevant elements related to revenue, total cost and manufacturer performance that were to be present in the model. The four steps were:

    1. In a first step elements and costs were identified that might be relevant for the model. This was done based on previous research, holding interviews at the company and reviewing documents.
    2. The second step was to adapt the elements to the model.
    3. In the third step, it was decided how the elements and costs that were to be in the model would be calculated and presented as well as looking into how the model would be built.
    4. The fourth step consisted of doing test runs and a sensitivity analysis to test the robustness of the model.

    The result handed over to the company is in the form of the evaluation model created based on the above stated purpose. Within the model, there are 4 manufacturer performance parameters and 1 for revenue. When it comes to costs, the amount varies depending on the case analyzed. To evaluate product profitability there are 7 cost elements containing 20 identified costs. When evaluating moving a product to another manufacturer there are the same costs, however an additional element for transfer is added containing 5 costs. For the situation ending a production, there are 2 costs. In order to facilitate the use of the model, estimations were done to the costs to the extent possible. From test runs the model was further adapted to the company as it was identified what values connected to a product where possible for the user to find in the system and in what units of measure. The sensitivity analyses showed that none of the estimated values would, if the estimation was not accurate, affect the evaluation of the product. They could however affect the cost element of that cost.

  • 45.
    Larsson, Jonas
    et al.
    Linköping University, Department of Computer and Information Science.
    Fritzson, Peter
    Linköping University, Department of Computer and Information Science.
    A Modelica-based Format for Flexible Code Generation and Causal Model Transformation2006Conference paper (Refereed)
    Abstract [en]

     The equation-based modeling language Modelica offers the possibility to extract a differential algebraic equation system (DAE). The DAE in turn can be used in numerical simulation, optimization, sensitivity analysis, diagnosis and more. For each of these categories, there exist software tools that all require slightly different input data, sometimes in symbolic form. Through examples, this paper briefly outlines a Modelica based format which can be used as input to the final code generation. This could yield a modular Modelica compiler in which the creation of diverse code generators is encouraged, which in turn widens the application area for Modelica. However, no formal definition of the format is presented here.. The paper also briefly addresses the issue of possible model causal adaptation needed at the equation level to make the model fit into target application with a causal usage context and how to automate the inclusion of these changes for seamless translation.

  • 46.
    Stenkula, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    A molecular approach to insulin signalling and caveolae in primary adipocytes2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The prevalence of type II diabetes is increasing at an alarming rate due to the western world lifestyle. Type II diabetes is characterized by an insulin resistance distinguished by impaired glucose uptake in adipose and muscle tissues. The molecular mechanisms behind the insulin recistance and also the knowledge considering normal insulin signalling in fat cells, especially in humans, are still unclear.

    Insulin receptor substrate (IRS) is known to be important for medating the insulin-induced signal from the insulin receptor into the cell. We developed and optimized a method for transfection of primary human adipocytes by electroporation. By recombinant expression of proteins, we found a proper IRS to be crucial for both mitogenic and metabolic signalling in human adipocytes. In human, but not rat, primary adipocytes we found IRS1 to be located at the plasma membrane in non-insulin stimulated cells. Insulin stimulation resulted in a two-fold increase of the amount of IRS1 at the plasma membrane in human cells, compared with a 12-fold increase in rat cells. By recombinant expression of IRS1 we found the species difference between human and rat IRS1 to depend on the IRS proteins and not on properties of the host cell.

    The adipocytes function as an energy store, critical for maintaining the energy balance, and obesity strongly correlates with insulin resistance. The insulin sensitivity of the adipocytes with regard to the size of the cells was examined by separating small and large cells from the same subject. We found no increase of the GLUT4 translocation to the plasma membrane following insulin stimulation in the large cells, whereas there was a two-fold increase in the small cells. This finding supports the idea of a causal relationship between the enlarged fat cells and reduced insulin sensitivity found in obese subjects.

    The insulin receptor is located and functional in a specific membrane structure, the caveola. The morphology of the caveola and the localization of the caveolar marker proteins caveolin-1 and -2 were examined. Caveolae were shown to be connected to the exterior by a narrow neck. Caveolin was found to be located at the neck region of caveolae, which imply importance of caveolin for maintaining and sequestering caveolae to the plasma membrane.

    In conclusion, the transfection technique proved to be highly useful for molecular biological studies of insulin signal transduction and morphology in primary adipocytes.

    List of papers
    1. Expression of a mutant IRS inhibits metabolic and mitogenic signalling of insulin in human adipocytes
    Open this publication in new window or tab >>Expression of a mutant IRS inhibits metabolic and mitogenic signalling of insulin in human adipocytes
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    2004 (English)In: Molecular and Cellular Endocrinology, ISSN 0303-7207, Vol. 221, no 1-2, 1-8 p.Article in journal (Refereed) Published
    Abstract [en]

    Adipose tissue is a primary target of insulin, but knowledge about insulin signalling in human adipocytes is limited. We developed an electroporation technique for transfection of primary human adipocytes with a transfection efficiency of 15% ± 5 (mean ± S.D.). Human adipocytes were co-transfected with a mutant of IRS-3 (all four potential PI3-kinase binding motifs mutated: IRS-3F4) and HA-tagged protein kinase B (HA-PKB/Akt). HA-PKB/Akt was immunoprecipitated from cell lysates with anti-HA antibodies, resolved with SDS-PAGE, and immunoblotted with phospho-specific antibodies. We found that IRS-3F4 blocked insulin stimulation of HA-PKB/Akt phosphorylation and in further analyses also translocation of recombinant HA-tagged glucose transporter to the plasma membrane. IRS-3F4 also blocked insulin-induced activation of the transcription factor Elk-1. Our results demonstrate the critical importance of IRS for metabolic as well as mitogenic signalling by insulin. This method for transfection of primary human adipocytes will be useful for studying insulin signalling in human adipocytes with molecular biological techniques.

    Keyword
    Insulin, Transfection, Human, Adipocytes, Protein kinase B, Elk-1
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14538 (URN)10.1016/j.mce.2004.04.011 (DOI)000222854100001 ()
    Available from: 2007-06-01 Created: 2007-06-01 Last updated: 2013-10-22Bibliographically approved
    2. Cell surface orifices of caveolae and localization of caveolin to the necks of caveolae in adipocytes
    Open this publication in new window or tab >>Cell surface orifices of caveolae and localization of caveolin to the necks of caveolae in adipocytes
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    2003 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 14, no 10, 3967-3976 p.Article in journal (Refereed) Published
    Abstract [en]

    Caveolae are noncoated invaginations of the plasma membrane that form in the presence of the protein caveolin. Caveolae are found in most cells, but are especially abundant in adipocytes. By high-resolution electron microscopy of plasma membrane sheets the detailed structure of individual caveolae of primary rat adipocytes was examined. Caveolin-1 and -2 binding was restricted to the membrane proximal region, such as the ducts or necks attaching the caveolar bulb to the membrane. This was confirmed by transfection with myc-tagged caveolin-1 and -2. Essentially the same results were obtained with human fibroblasts. Hence caveolin does not form the caveolar bulb in these cells, but rather the neck and may thus act to retain the caveolar constituents, indicating how caveolin participates in the formation of caveolae. Caveolae, randomly distributed over the plasma membrane, were very heterogeneous, varying in size between 25 and 150 nm. There was about one million caveolae in an adipocyte, which increased the surface area of the plasma membrane by 50%. Half of the caveolae, those larger than 50 nm, had access to the outside of the cell via ducts and 20-nm orifices at the cell surface. The rest of the caveolae, those smaller than 50 nm, were not open to the cell exterior. Cholesterol depletion destroyed both caveolae and the cell surface orifices.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14539 (URN)10.1091/mbc.E03-01-0050 (DOI)
    Available from: 2007-06-01 Created: 2007-06-01 Last updated: 2013-09-10
    3. Human, but not rat, IRS1 targets to the plasma membrane in both human and rat primary adipocytes
    Open this publication in new window or tab >>Human, but not rat, IRS1 targets to the plasma membrane in both human and rat primary adipocytes
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    2007 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, Vol. 363, no 3, 840-845 p.Article in journal (Refereed) Published
    Abstract [en]

    Adipocytes are primary targets for insulin control of metabolism. The activated insulin receptor phosphorylates insulin receptor substrate-1 (IRS1), which acts as a docking protein for downstream signal mediators. In the absence of insulin stimulation, IRS1 in rat adipocytes is intracellular but in human adipocytes IRS1 is constitutively targeted to the plasma membrane. Stimulation of adipocytes with insulin increased the amount of IRS1 at the plasma membrane 2-fold in human adipocytes, but >10-fold in rat adipocytes, with the same final amount of IRS1 at the plasma membrane in cells from both species. Cross-transfection of rat adipocytes with human IRS1, or human adipocytes with rat IRS1, demonstrated that the species difference was due to the IRS1 protein and not the cellular milieus or posttranslational modifications. Chimeric IRS1, consisting of the conserved N-terminus of rat IRS1 with the variable C-terminal of human IRS1, did not target the plasma membrane, indicating that subtle sequence differences direct human IRS1 to the plasma membrane.

    Keyword
    Insulin receptor substrate; Human; Rat; Insulin; Plasma membrane; Signaling; Transfection; Caveolae
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14540 (URN)10.1016/j.bbrc.2007.09.065 (DOI)
    Available from: 2007-06-01 Created: 2007-06-01 Last updated: 2013-09-10
    4. Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual
    Open this publication in new window or tab >>Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual
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    2007 (English)In: Diabetologia, ISSN 0012-186X, Vol. 50, no 8, 1716-1722 p.Article in journal (Refereed) Published
    Abstract [en]

    Aims/hypothesis: Several studies have suggested that large fat cells are less responsive to insulin than small fat cells. However, in these studies, large fat cells from obese individuals were compared with smaller fat cells from leaner participants, in effect making it impossible to draw conclusions about whether there is a causal relationship between fat cell size and insulin sensitivity. We hypothesised that small fat cells might be more insulin-responsive than large adipocytes when obtained from the same individual.

    Materials and methods: We developed a method of sorting isolated primary human fat cells by using nylon filters of two different pore sizes. The cells were stained to visualise DNA, which allowed discrimination from artefacts such as lipid droplets. The sorted cells were left to recover overnight, since we had previously demonstrated that this is necessary for correct assessment of insulin response.

    Results: We found similar amounts of the insulin receptor (IR), IRS-1 and GLUT4 when we compared small and large adipocytes from the same volunteer by immunoblotting experiments using the same total cell volume from both cell populations. Activation of IR, IRS-1 and Akt1 (also known as protein kinase B) by insulin was similar in the two cell populations. However, immunofluorescence confocal microscopy of plasma membrane sheets did not reveal any increase in the amount of GLUT4 in the plasma membrane following insulin stimulation in the large fat cells, whereas we saw a twofold increase in the amount of GLUT4 in the small fat cells.

    Conclusions/interpretation: Our results support a causal relationship between the accumulation of large fat cells in obese individuals and reduced insulin responsiveness.

    Keyword
    Adipocyte, GLUT4, Human, Insulin, Insulin receptor, Insulin resistance, IRS-1, Primary fat cell
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14541 (URN)10.1007/s00125-007-0713-1 (DOI)
    Available from: 2007-06-01 Created: 2007-06-01 Last updated: 2013-09-10Bibliographically approved
  • 47.
    Tahmasebi, Amir M.
    et al.
    Queen's University, Kingston, Canada.
    Abolmaesumi, Purang
    Queen's University, Kingston, Canada.
    Geng, Xiujuan
    National Institute on Drug Abuse, NIH, USA.
    Morosan, Patricia
    Institute of Medicine, Research Center Juelich, Germany.
    Amunts, Katrin
    Brain Imaging Center West, Germany.
    Christensen, Gary E.
    University of Iowa, USA.
    Johnsrude, Ingrid
    Queen's University, Kingston, Canada.
    A new approach for creating customizable cytoarchitectonic probabilistic maps wtihout a template2009In: Medical Image Computing and Computer-Assisted Intervention – MICCAI 2009: 12th International Conference London, UK September 20-24, 2009 Proceedings, Part II / [ed] Guang-Zhong Yang, David Hawkes, Daniel Rueckert, Alison Noble, Chris Taylor, Springer, 2009, 795-802 p.Chapter in book (Refereed)
    Abstract [en]

    We present a novel technique for creating template-free probabilistic maps of the cytoarchitectonic areas using a groupwise registration. We use the technique to transform 10 human post-mortem structural MR data sets, together with their corresponding cytoarchitectonic information, to a common space. We have targeted the cytoarchitectonically defined subregions of the primary auditory cortex. Thanks to the template-free groupwise registration, the created maps are not macroanatomically biased towards a specific geometry/topology. The advantage of the groupwise versus pairwise registration in avoiding such anatomical bias is better revealed in studies with small number of subjects and a high degree of variability among the individuals such as the post-mortem data. A leave-one-out cross-validation method was used to compare the sensitivity, specificity and positive predictive value of the proposed and published maps. We observe a significant improvement in localization of cytoarchitectonically defined subregions in primary auditory cortex using the proposed maps. The proposed maps can be tailored to any subject space by registering the subject image to the average of the groupwise-registered post-mortem images.

  • 48.
    Eriksson, Olle
    Linköping University, Department of Mathematics, Statistics. Linköping University, Faculty of Arts and Sciences.
    A new program for fast emission calculations based on the COPERT III modelManuscript (Other academic)
    Abstract [en]

    Emissions from road traffic are hard to measure and therefore usually estimated in models. In this paper the construction of the widely used COPERT III model is examined, and the model is rewritten in mathematical notation. The original COPERT III software is easily handled but is not suitable as an emissiondata generating tool for fast calculations over a broad variety of driving conditions, which is required for sensitivity analysis. An alternative program has been developed to meet the desired properties of such a tool. The construction of the alternative program is discussed together with its new abilities and restrictions. Some differences between the results from the original COPERT III software and the alternative program are analyzed and discussed.

  • 49.
    Klarbring, Anders
    et al.
    Linköping University, Department of Management and Engineering, Mechanics. Linköping University, The Institute of Technology.
    Strömberg, Niclas
    Department of Mechanical Engineering, Jönköping University.
    A note on the min-max formulation of stiffness optimization including non-zero prescribed displacements2012In: Structural and multidisciplinary optimization (Print), ISSN 1615-147X, E-ISSN 1615-1488, Vol. 45, no 1, 147-149 p.Article in journal (Refereed)
    Abstract [en]

    The present theoretical note shows how a natural objective function in stiffness optimization, including both prescribed forces and non-zero prescribed displacements, is the equilibrium potential energy. It also shows how the resulting problem has a saddle point character that may be utilized when calculating sensitivities.

  • 50.
    Gharehbaghi, Arash
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Janerot Sjöberg, Birgitta
    Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden; School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.
    Per, Ask
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    A novel method for discrimination between innocent and pathological heart murmurs2015In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 37, no 7, 674-682 p.Article in journal (Refereed)
    Abstract [en]

    This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM.

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