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  • 1. Alrifaiy, Ahmed
    et al.
    Borg, Johan
    Lindahl, Olof A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Department of Computer Science, Electrical and Space Engineering, Luleå University of Technology; CMTF, Centre for Biomedical Engineering and Physics, Luleå and Umeå, Sweden; Department of Engineering Sciences and Mathematics, Luleå University of Technology.
    Ramser, Kerstin
    A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy-first investigations of single biological cells2015In: Biomedical engineering online, ISSN 1475-925X, E-ISSN 1475-925X, Vol. 14, article id 36Article in journal (Refereed)
    Abstract [en]

    The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O-2 to an anoxic value of 0.0-0.5% O-2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 +/- 1 s and a fully developed deoxygenated spectrum was observed after 298 +/- 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 +/- 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 +/- 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 +/- 0.412 M Omega and 889.7 +/- 1.74 M Omega respectively.

  • 2.
    Anderson, Fredrick
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    β3-adrenergic antagonism alleviates weight loss associated with cancer cachexia2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Cancer induced cachexia (CIC) is a devastating wasting disorder affecting people with tumor diseases and is deemed responsible for approximately 20% of all cancer-related deaths. This syndrome is associated with atrophy of adipose tissue and skeletal muscle. No established treatment is available for CIC and the underlying mechanisms are unveiled. However, one proposed culprit is brown adipose tissue (BAT) and browning of white adipose tissue (WAT), which produces heat via activation uncoupling protein 1 (UCP1). The result is increased energy wasting. Β3-adrenergic receptor (ADRB3) signaling activates BAT and we hypothesized that treatment with a specific ADRB3 antagonist would mitigate energy wasting in CIC. Balb/ca nude mice implanted with the LuCAP32 human xenograft tumor was used as a model system for CIC. The mice were treated with the selective ADRB3-blocker SR59230A and the unselective ADRB1 and 2-blocker propranolol for 4 weeks. A vehicle (VEH) and non-tumor bearing (NTB) group was also used. Significant effects were seen on total body weight loss with SR-treatment compared to VEH. Similar effects were seen on the wasting of local WAT depots. When measuring body composition, we found moderate evidence that SR spares the wasting of lean mass. We were also able to show decreased gene expression of BAT-markers, as well as markers for lipolysis, in the subcutaneous WAT. This supports our main hypothesis. In conclusion, we can show that treatment with a selective ADRB3 antagonist alleviates the symptoms of CIC through decreased lipolysis and decreased browning of WAT. These findings add to the mechanistic understanding of the pathophysiology of CIC and could be a potential treatment strategy for this syndrome.

  • 3.
    Arndt, Anton
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Laboratory for Biomechanics and Motor Control.
    The evolution of running shoes2012Conference paper (Other academic)
  • 4.
    Arndt, Anton
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Laboratory for Biomechanics and Motor Control.
    Lundgren, Paul
    Liu, Anmin
    Nester, Christopher
    Maiwald, Christian
    Jones, Richard
    Lundberg, Arne
    The effect of a midfoot cut in the outer sole of a shoe on intrinsic foot kinematics during walking.2013In: Footwear Science, ISSN 1942-4280, Vol. 5, no 1, p. 63-69Article in journal (Refereed)
    Abstract [en]

    Modifications in shoe outer soles are frequently made with the intention of altering biomechanics of the foot inside the shoe. These modifications are however, generally based upon intuition with little or no scientific data for support. The purpose of this study was to quantify changes in intrinsic foot segmental kinematics between walking in a neutral shoe and a shoe modified with a clear cut forming a break underneath the midfoot, approximating the Lisfrancs joint.

    Five healthy male subjects participated in the study. Intracortical pins were inserted under sterile conditions and local anaesthetic in nine different bones of the foot and shank. The subjects performed 10 walking trials in both a neutral, standard, flatsoled, flexible walking shoe and in the same shoe with an approximately 1 cm deep cut aligned with the subjects’ Lisfrancs joint. Material tests showed that the cut reduced midfoot shoe bending stiffness by 23% to 38% and torsional stiffness by 23% to 28%. A helical axis approach was applied for calculating the 3D rotations about relevant joints.

    Kinematic trajectories in the sagittal, frontal, and transverse planes were normalised to the stance phase for seven selected joints to compare rotation patterns when wearing the two shoe conditions. Although one out of 21 ranges of motion (ROM) showed a significant difference, there is strong reason to regard this as the result of a type 1 error. Apart from this no differences in ROM occurred between the shoe conditions.

    The low subject number reduced the statistical power of the results. However, the study indicated that outer sole modifications that may be assumed to have clear effects upon foot kinematics, do not necessarily do so.

  • 5.
    Bass, Tarek
    KTH, School of Biotechnology (BIO), Protein Technology.
    Affibody molecules targeting HER3 for cancer therapy2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The development of targeted therapy has contributed tremendously to the treatment of patients with cancer. The use of highly specific affinity proteins to target cancer cells has become a standard in treatment strategies for several different cancers. In light of this, many cancer cell markers are investigated for their potential use in diagnostics and therapy. One such marker is the human epidermal growth factor receptor 3, HER3. It has been established as an important contributor to many cancer types. The function of HER3 is to relay cell growth signals from outside of the cell to the inside. Interfering with- and inhibit- ing the function of HER3 has emerged as an interesting strategy for cancer therapeutics. The studies presented in this thesis aim to target HER3 with small, engineered affinity domain proteins for therapeutic purposes. Monomeric affibody molecules have previously been engineered to bind and inhibit HER3 in vitro. Due to the relatively low expression of HER3, an increase in valency appears promising to strengthen the therapeutic potential. Affibody molecules targeting the receptor were thus linked to form bivalent and bispecific constructs and evaluated both in vitro and in vivo. In the first study of this thesis affibody molecules specific for HER3 and HER2 were fused to an albumin binding domain to form bivalent and bispecific construct. The constructs inhibited ligand-induced receptor phos- phorylation of both HER2 and HER3 more efficiently than monomeric affibody molecules. A second approach to enhance the potential of affibody molecules in tumor targeting is described in the second study, where monomeric HER3-binding affibody molecules were engineered to increase their affinity for HER3. The resulting variants showed a 20-fold in- creased affinity and higher capacity to inhibit cancer cell growth. Combining the findings of the first two studies, the third study describes the evaluation of a HER3-targeting bivalent affibody construct for potential application as a therapeutic. Here, the bivalent construct inhibited cancer cell growth in vitro and was found to slow down tumor growth in mice, while being well tolerated and showing no visible toxicity. The fourth study built upon these findings and compares a very similar bivalent construct to the clinically-investigated HER3-specific monoclonal antibody seribantumab. The affibody construct showed very comparable efficacy with the antibody in terms of decreasing tumor growth rate and ex- tending mouse survival. Collectively, these works describe for the first time the use of alternative affinity protein constructs with therapeutic potential targeting HER3.

  • 6.
    Bass, Tarek
    KTH, School of Biotechnology (BIO), Protein Technology.
    Evaluating the therapeutic potential of a dimeric HER3-binding affibody construct in comparison with a monoclonal antibody, seribantumab.Manuscript (preprint) (Other academic)
    Abstract [en]

    A number of monoclonal antibodies targeting HER3 are currently under clinical investigation as potential cancer therapeutics. We have earlier generated high affinity (low picomolar) affibody molecules targeting HER3. These are small, 58 amino acid, non-immunoglobulin based scaffold proteins that have proved suitable for tumor targeting applications, previously primarily for molecular imaging purposes. Our high affinity HER3-binding affibody molecule has demonstrated to have anti-proliferative capacity on HER3-positive tumor cells. When formatted as a bivalent construct, in which the two affibody moieties are flanking a small albumin-binding domain (ABD), we have recently demonstrated that tumor growth could be delayed in mice for HER3-positive xenografts. In this study, we have modified the construct further and reduced the size. In a comparative study, we evaluated safety, the capacity to delay tumor growth in mice with BxPC-3 xenografts, and mouse survival. Our novel construct was compared to the HER3-specific monoclonal antibody seribantumab (MM-121), presently in clinical development. They were found to be equally potent in their therapeutic effects and in their safety profile. We conclude that this format of bivalent HER3-binding affibody molecules seems promising for further evaluation as candidate therapeutics for treatment of HER3-overexpressing tumors.

  • 7. Bello, M. A.
    et al.
    Ruiz-León, Y.
    Sandoval-Sierra, J. V.
    Rezinciuc, Svetlana
    KTH, School of Biotechnology (BIO), Glycoscience.
    Diéguez-Uribeondo, J.
    Scanning electron microscopy (SEM) protocols for problematic plant, oomycete, and fungal samples2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, Vol. 2017, no 120, article id e55031Article in journal (Refereed)
    Abstract [en]

    Common problems in the processing of biological samples for observations with the scanning electron microscope (SEM) include cell collapse, treatment of samples from wet microenvironments and cell destruction. Using young floral tissues, oomycete cysts, and fungi spores (Agaricalesas examples, specific protocols to process delicate samples are described here that overcome some of the main challenges in sample treatment for image capture under the SEM. Floral meristems fixed with FAA (Formalin-Acetic-Alcohol) and processed with the Critical Point Dryer (CPD) did not display collapsed cellular walls or distorted organs. These results are crucial for the reconstruction of floral development. A similar CPD-based treatment of samples from wet microenvironments, such as the glutaraldehyde-fixed oomycete cysts, is optimal to test the differential growth of diagnostic characteristics (e.g., the cyst spines) on different types of substrates. Destruction of nurse cells attached to fungi spores was avoided after rehydration, dehydration, and the CPD treatment, an important step for further functional studies of these cells. The protocols detailed here represent low-cost and rapid alternatives for the acquisition of good-quality images to reconstruct growth processes and to study diagnostic characteristics.

  • 8. Bengtsson, Erik
    et al.
    Nerjovaj, Pashtrik
    Wangefjord, Sakarias
    Nodin, Björn
    Eberhard, Jakob
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Borgquist, Signe
    Jirström, Karin
    HMG-CoA reductase expression in primary colorectal cancer correlates with favourable clinicopathological characteristics and an improved clinical outcome2014In: Diagnostic Pathology, ISSN 1746-1596, E-ISSN 1746-1596, Vol. 9, no 1, p. 78-Article in journal (Refereed)
    Abstract [en]

    Background: An association between tumor-specific HMG-CoA reductase (HMGCR) expression and good prognosis has previously been demonstrated in breast and ovarian cancer. In this study, the expression, clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined. Findings: Immunohistochemical expression of HMGCR was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmo Diet and Cancer Study. Pearson's Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival (CSS) according to negative vs positive HMGCR expression. A total number of 535 (96.0%) tumours were suitable for analysis, of which 61 (11.4%) were HMGCR negative. Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis (p = 0.002), lack of vascular invasion (p = 0.043), microsatellite-instability (p = 0.033), expression of cyclin D1 (p = <0.001) and p21 (p = <0.001). Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort (HR = 1.79; 95% CI 1.20-2.66) and in Stage III-IV disease (HR = 1.71; 95% CI 1.09-2.68), but not after adjustment for established clinicopathological parameters. Conclusions: Findings from this prospective cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis. The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study. Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464.

  • 9.
    Bengtsson, Katarina
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, Faculty of Science & Engineering. LunaMicro AB, Linköping, Sweden.
    Christoffersson, Jonas
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Robinson, Nathaniel D
    Linköping University, Department of Physics, Chemistry and Biology, Surface Physics and Chemistry. Linköping University, Faculty of Science & Engineering. LunaMicro AB, Linköping, Sweden.
    A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices2018In: Microfluidics and Nanofluidics, ISSN 1613-4982, E-ISSN 1613-4990, Vol. 22, no 3, article id 27Article in journal (Refereed)
    Abstract [en]

    Recent advances in microfluidic devices put a high demand on small, robust and reliable pumps suitable for high-throughput applications. Here we demonstrate a compact, low-cost, directly attachable (clip-on) electroosmotic pump that couples with standard Luer connectors on a microfluidic device. The pump is easy to make and consists of a porous polycarbonate membrane and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) electrodes. The soft electrode and membrane materials make it possible to incorporate the pump into a standard syringe filter holder, which in turn can be attached to commercial chips. The pump is less than half the size of the microscope slide used for many commercial lab-on-a-chip devices, meaning that these pumps can be used to control fluid flow in individual reactors in highly parallelized chemistry and biology experiments. Flow rates at various electric current and device dimensions are reported. We demonstrate the feasibility and safety of the pump for biological experiments by exposing endothelial cells to oscillating shear stress (up to 5 dyn/cm2) and by controlling the movement of both micro- and macroparticles, generating steady or oscillatory flow rates up to ± 400 μL/min.

  • 10.
    Bernzen, Noel
    Halmstad University, School of Business, Engineering and Science.
    Noellator: Vinterrollator2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Idag är det en hög andel av äldre personer, främst kvinnor, som använder rollatorer. De blir allt fler med tiden, då genomsnittsåldern av befolkningen blir allt högre. För att öka livskvalitet för de äldre, är det rekommenderat att promenera utomhus så ofta som möjligt, exempelvis med hjälp av en rollator. Ett problem som uppstår är att ingen rollator är anpassad för användning under vintern. I detta examensarbete har ett rollator-koncept tagits fram, speciellt anpassat för ”fyra årstider”. Detta innebär att konceptet har allt som en vanligt rollator har men även tillbehör som är användarvänliga i vilket väder som helst, såväl vid snö- som isförhållanden. Det innebär en komplettering med specialdesignade tillbehör som är enkla att byta oberoende av väderslag. En årstidsoberoende rollator blir dyrare än en vanligt rollator, men samtidigt skapas ett hjälpmedel som gör det lättare för användaren att vara en del av samhället och förbättra sin hälsa, vilket faktiskt är såväl viktigt som aktuellt

  • 11. Brazalez, Astrid Algaba
    et al.
    Manholm, Lars
    Johansson, Martin
    Quevedo-Teruel, Oscar
    Miao, Jingwei
    KTH, School of Electrical Engineering and Computer Science (EECS), Electromagnetic Engineering.
    Investigation of a Ka-band Luneburg Lens Made of a Glide-Symmetric Holey Structure2017In: 2017 INTERNATIONAL SYMPOSIUM ON ANTENNAS AND PROPAGATION (ISAP 2017), IEEE , 2017Conference paper (Refereed)
    Abstract [en]

    A Ka-hand 2D flat-profiled Luneburg lens antenna implemented with a glide-symmetric holey structure is presented. The required refractive index for the lens design has been investigated via an analysis of the hole depth and the gap between the two metallic layers constituting the lens. The final unit cell is described and applied to create the complete metasurface Luneburg lens showing that a plane wave is obtained when feeding at an opposite arbitrary point with a discrete source.

  • 12. Carlsson, J
    et al.
    Gedda, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Grönvik, C
    Hartman, T
    Lindström, A
    Lindström, P
    Lundqvist, H
    Lövqvist, A
    Malmqvist, J
    Olsson, P
    Strategy for boron neutron capture therapy against tumor cells with over-expression of the epidermal growth factor-receptor.1994In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 30, no 1, p. 105-15Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Gliomas, squamous carcinomas and different adenocarcinomas from breast, colon and prostate might have an increased number of epidermal growth factor (EGF) receptors. The receptors are, in these cases, candidates for binding of receptor specific toxic conjugates that might inactivate cellular proliferation. The purpose of this study was to evaluate whether it is reasonable to try ligand-dextran based conjugates for therapy.

    METHODS AND MATERIALS: EGF or TGF alpha were conjugated to dextran and binding, internalization, retention and degradation of eight types of such conjugates were analyzed in EGF-receptor amplified glioma cells. The conjugates were labelled with radioactive nuclides to allow detection and two of the conjugates were carrying boron in the form of carboranyl amino acids or aminoalkyl-carboranes. Comparative binding tests, applying 125I-EGF, were made with cultured breast, colon and prostate adenocarcinoma, glioma and squamous carcinoma cells. Some introductory tests to label with 76Br for positron emission tomography and with 131I for radionuclide therapy were also made.

    RESULTS: The dextran part of the conjugates did not prevent receptor specific binding. The amount of receptor specific binding varied between the different types of conjugates and between the tested cell types. The dextran part improved intracellular retention and radioactive nuclides were retained for at least 20-24 h. The therapeutical effect improved when 131I was attached to EGF-dextran instead of native EGF.

    CONCLUSION: The improved cellular retention of the ligand-dextran conjugates is an important property since it gives extended exposure time when radionuclides are applied and flexibility in the choice of time for application of neutrons in boron neutron capture therapy (BNCT). It is possible that ligand-dextran mediated BNCT might allow, if the applied neutron fields covers rather wide areas around the primary tumor, locally spread cells that otherwise would escape treatment to be inactivated.

  • 13.
    Cedersund, G
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    Elimination of the initial value parameters when identifying a system close to a Hopf bifurcation.2006In: IEE Proceedings - Systems Biology, ISSN 1741-2471, E-ISSN 1741-248X, Vol. 153, no 6, p. 448-456Article in journal (Refereed)
    Abstract [en]

    One of the biggest problems when performing system identification of biological systems is that it is seldom possible to measure more than a small fraction of the total number of variables. If that is the case, the initial state, from where the simulation should start, has to be estimated along with the kinetic parameters appearing in the rate expressions. This is often done by introducing extra parameters, describing the initial state, and one way to eliminate them is by starting in a steady state. We report a generalisation of this approach to all systems starting on the centre manifold, close to a Hopf bifurcation. There exist biochemical systems where such data have already been collected, for example, of glycolysis in yeast. The initial value parameters are solved for in an optimisation sub-problem, for each step in the estimation of the other parameters. For systems starting in stationary oscillations, the sub-problem is solved in a straight-forward manner, without integration of the differential equations, and without the problem of local minima. This is possible because of a combination of a centre manifold and normal form reduction, which reveals the special structure of the Hopf bifurcation. The advantage of the method is demonstrated on the Brusselator.

  • 14.
    Cheddad, Abbas
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Nord, Christoffer
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Hörnblad, Andreas
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Prunskaite-Hyyryläinen, Renata
    Oulu Center for Cell-Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland.
    Eriksson, Maria
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Georgsson, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Vainio, Seppo
    Oulu Center for Cell-Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland.
    Ahlgren, Ulf
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
    Improving signal detection in emission optical projection tomography via single source multi-exposure image fusion2013In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 21, no 14, p. 16584-16604Article in journal (Refereed)
    Abstract [en]

    We demonstrate a technique to improve structural data obtained from Optical Projection Tomography (OPT) using Image Fusion (IF) and contrast normalization. This enables the visualization of molecular expression patterns in biological specimens with highly variable contrast values. In the approach, termed IF-OPT, different exposures are fused by assigning weighted contrasts to each. When applied to projection images from mouse organs and digital phantoms our results demonstrate the capability of IF-OPT to reveal high and low signal intensity details in challenging specimens. We further provide measurements to highlight the benefits of the new algorithm in comparison to other similar methods.

  • 15. Chen, Ye
    et al.
    Wang, Aiguo
    Ding, Huitong
    Que, Xia
    Li, Yabo
    An, Ning
    Jiang, Lili
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    A global learning with local preservation method for microarray data imputation2016In: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 77, p. 76-89Article in journal (Refereed)
    Abstract [en]

    Microarray data suffer from missing values for various reasons, including insufficient resolution, image noise, and experimental errors. Because missing values can hinder downstream analysis steps that require complete data as input, it is crucial to be able to estimate the missing values. In this study, we propose a Global Learning with Local Preservation method (GL2P) for imputation of missing values in microarray data. GL2P consists of two components: a local similarity measurement module and a global weighted imputation module. The former uses a local structure preservation scheme to exploit as much information as possible from the observable data, and the latter is responsible for estimating the missing values of a target gene by considering all of its neighbors rather than a subset of them. Furthermore, GL2P imputes the missing values in ascending order according to the rate of missing data for each target gene to fully utilize previously estimated values. To validate the proposed method, we conducted extensive experiments on six benchmarked microarray datasets. We compared GL2P with eight state-of-the-art imputation methods in terms of four performance metrics. The experimental results indicate that GL2P outperforms its competitors in terms of imputation accuracy and better preserves the structure of differentially expressed genes. In addition, GL2P is less sensitive to the number of neighbors than other local learning-based imputation. methods.

  • 16.
    Chudinova, Ekaterina
    et al.
    Tomsk Polytechnic University, Tomsk, Russia.
    Surmeneva, Maria
    Tomsk Polytechnic University, Tomsk, Russia.
    Koptyug, Andrey
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Quality Technology and Management, Mechanical Engineering and Mathematics.
    Skoglund, Per
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Quality Technology and Management, Mechanical Engineering and Mathematics.
    Sharanova, A
    Tomsk Polytechnic University, Tomsk, Russia.
    Loza, K
    University of Duisburg-Essen, Germany.
    Epple, M
    University of Duisburg-Essen, Germany.
    Surmenev, Roman
    Tomsk Polytechnic University, Tomsk, Russia.
    Hydroxyapatite coating and silver nanoparticles assemblies on additively manufactured Ti6Al4V scaffolds2015Conference paper (Other academic)
  • 17. Czub, Joanna
    et al.
    Banas, Dariusz
    Braziewicz, Janusz
    Buraczewska, Iwona
    Jaskola, Marian
    Kazmierczak, Urszula
    Korman, Andrzej
    Lankoff, Anna
    Lisowska, Halina
    Szeflinski, Zygmunt
    Wojewodzka, Maria
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
    Biological effects of mixed-ion beams. Part 1: Effect of irradiation of the CHO-K1 cells with a mixed-ion beam containing the carbon and oxygen ions2018In: Applied Radiation and Isotopes, ISSN 0969-8043, E-ISSN 1872-9800, Vol. 139, p. 304-309Article in journal (Refereed)
    Abstract [en]

    Carbon and oxygen ions were accelerated simultaneously to estimate the effect of irradiation of living cells with the two different ions. This mixed ion beam was used to irradiate the CHO-K1 cells, and a survival test was performed. The type of the effect of the mixed ion beam on the cells was determined with the isobologram method, whereby survival curves for irradiations with individual ion beams were also used. An additive effect of irradiation with the two ions was found.

  • 18.
    Danø, Sune
    et al.
    Copenhagen University.
    Madsen, Mads F
    Copenhagen University.
    Schmidt, Henning
    Chalmers Technical University.
    Cedersund, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Reduction of a biochemical model with preservation of its basic dynamic properties.2006In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, no 21, p. 4862-4877Article in journal (Refereed)
    Abstract [en]

    The complexity of full-scale metabolic models is a major obstacle for their effective use in computational systems biology. The aim of model reduction is to circumvent this problem by eliminating parts of a model that are unimportant for the properties of interest. The choice of reduction method is influenced both by the type of model complexity and by the objective of the reduction; therefore, no single method is superior in all cases. In this study we present a comparative study of two different methods applied to a 20D model of yeast glycolytic oscillations. Our objective is to obtain biochemically meaningful reduced models, which reproduce the dynamic properties of the 20D model. The first method uses lumping and subsequent constrained parameter optimization. The second method is a novel approach that eliminates variables not essential for the dynamics. The applications of the two methods result in models of eight (lumping), six (elimination) and three (lumping followed by elimination) dimensions. All models have similar dynamic properties and pin-point the same interactions as being crucial for generation of the oscillations. The advantage of the novel method is that it is algorithmic, and does not require input in the form of biochemical knowledge. The lumping approach, however, is better at preserving biochemical properties, as we show through extensive analyses of the models.

  • 19.
    Ebai, Tonge
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Parallel protein detection by solid-phase proximity ligation assay with real-time PCR or sequencing2015In: Current Protocol in Molecular Biology, ISSN 1934-3647, Vol. 109, no 20Article in journal (Refereed)
    Abstract [en]

    Proximity ligation assays are a group of protein detection techniques in which reagents with affinity for target proteins, typically antibodies, are coupled to short strands of DNA. DNA-modified affinity reagents are combined in assays constructed such that the coordinated binding of individual target molecules or complexes of interacting proteins by two or more of the reagents, followed by DNA ligation and/or polymerization reactions, gives rise to amplifiable DNA reporter strands. Proximity ligation assays have been shown to exhibit excellent sensitivity in single and multiplexed protein assays for individual or interacting proteins, both in solution and in situ. This unit describes procedures for developing solid-phase proximity ligation assays for soluble proteins using either real-time PCR or DNA sequencing as the readout. In addition, critical steps for assay optimization are discussed.

  • 20. Enroth, Stefan
    et al.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Gyllensten, Ulf
    Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations2016In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 12, p. 309-314Article in journal (Refereed)
    Abstract [en]

    The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.

  • 21.
    Eriksson, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Moreno, R
    Milenova, I. Yoanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Liljenfeldt, L
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Dieterich, L C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Christiansson, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Karlsson, H
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mangsbo, Sara M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Alemany, R
    Loskog, Angelica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Activation of myeloid and endothelial cells by CD40L gene therapy supports T-cell expansion and migration into the tumor microenvironment2017In: Gene Therapy, ISSN 0969-7128, E-ISSN 1476-5462, Vol. 24, no 2, p. 92-103Article in journal (Refereed)
    Abstract [en]

    CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate T-helper 1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer. Further, the CD40L mechanisms of action were elucidated in cancer models. The results demonstrated that the virus transferring TMZ-CD40L had oncolytic capacity in pancreatic cancer cells and could control tumor progression. TMZ-CD40L was a potent stimulator of human myeloid cells and T-cell responses. Further, CD40L-mediated stimulation increased tumor-infiltrating T cells in vivo, which may be due to a direct activation of endothelial cells to upregulate receptors for lymphocyte attachment and transmigration. In conclusion, CD40L-mediated gene therapy is an interesting concept for the treatment of tumors with high levels of M2 macrophages, such as pancreatic cancer, and an oncolytic virus as carrier of CD40L may further boost tumor killing and immune activation.

  • 22.
    Gao, Xiang
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Yang, Ting
    Liu, Ming
    Peleli, Maria
    Zollbrecht, Christa
    Weitzberg, Eddie
    Lundberg, Jon O.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlstrom, Mattias
    NADPH Oxidase in the Renal Microvasculature Is a Primary Target for Blood Pressure-Lowering Effects by Inorganic Nitrate and Nitrite2015In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 65, no 1, p. 161-+Article in journal (Refereed)
    Abstract [en]

    Renal oxidative stress and nitric oxide (NO) deficiency are key events in hypertension. Stimulation of a nitrate-nitrite-NO pathway with dietary nitrate reduces blood pressure, but the mechanisms or target organ are not clear. We investigated the hypothesis that inorganic nitrate and nitrite attenuate reactivity of renal microcirculation and blood pressure responses to angiotensin II (ANG II) by modulating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NO bioavailability. Nitrite in the physiological range (10(-7)-10(-5) mol/L) dilated isolated perfused renal afferent arterioles, which were associated with increased NO. Contractions to ANG II (34%) and simultaneous NO synthase inhibition (56%) were attenuated by nitrite (18% and 26%). In a model of oxidative stress (superoxide dismutase-1 knockouts), abnormal ANG II-mediated arteriolar contractions (90%) were normalized by nitrite (44%). Mechanistically, effects of nitrite were abolished by NO scavenger and xanthine oxidase inhibitor, but only partially attenuated by inhibiting soluble guanylyl cyclase. Inhibition of NADPH oxidase with apocynin attenuated ANG II-induced contractility (35%) similar to that of nitrite. In the presence of nitrite, no further effect of apocynin was observed, suggesting NADPH oxidase as a possible target. In preglomerular vascular smooth muscle cells and kidney cortex, nitrite reduced both basal and ANG II-induced NADPH oxidase activity. These effects of nitrite were also abolished by xanthine oxidase inhibition. Moreover, supplementation with dietary nitrate (10(-2) mol/L) reduced renal NADPH oxidase activity and attenuated ANG II-mediated arteriolar contractions and hypertension (99+/-2-146+/-2 mm Hg) compared with placebo (100+/-3-168+/-3 mm Hg). In conclusion, these novel findings position NADPH oxidase in the renal microvasculature as a prime target for blood pressure-lowering effects of inorganic nitrate and nitrite.

  • 23.
    Glas, Peter
    et al.
    Swedish School of Sport and Health Sciences, GIH.
    Mattsson, C. Mikael
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Physiological requirements of elite handball – measured with a combination of local positioning system and heart rate monitoring.2017Conference paper (Refereed)
    Abstract [en]

    For all athletes, it is important to adjust training plans and competition schedule according to each individual's specific traits and situation. This is crucial in team sports, where players, despite being involved in the same sport, and even on the same team, may have very different physiological capacities and, also have completed a wide variety of work in both training and match situations. A first step towards being able to carry out individualized training is to accurately measure the amount of stress (physiological burden) for each individual. The purpose of the study was to create a comprehensive picture of the physical requirements of elite handball matches, and further investigate how the relationship between work load and physical capacity impacts performance.

    Heart rate measurements have since decades been used to quantify the relative work, and GPS measurement as a tool for objective values has been available for outdoor sports for about ten years, but GPS is not possible to use indoors. We have used a new technology with a similar system for indoor use called Local Positioning System (LPS) (Kinexon Precision Technologies, Münich, Germany) to record and analyze the players’ motion during games, and we have combined that technology with data from accelerometry, gyroscope and heart rate measurements.

    So far, 42 handball matches have been measured and analyzed, ranging from juniors (9 games U21 men's national team) to seniors, men and women, and both in Sweden’s highest league and between national teams (Women: 8 national and 7 international games; Men: 14 national and 4 international games).

    A first "result" is that the categorization of motion patterns need to be adapted to each sport. For example, some moves that should be counted as accelerations in handball are not recognized by the system, simply because it has been adapted to the pattern of motion on the much larger soccer field. This is similarly important to realize when comparing results for handball’s physiological requirements reached using other technologies. In this presentation, we will in part discuss the future technological opportunities, and in part report descriptive results, including how fast and far the players move, as well as differences between men and women, between national and international games, and between juniors and seniors.

  • 24.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine.
    Turkina, Maria V
    Department of Clinical and Experimental Medicine, Linköpings universitet.
    Carlsson, Anders
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Gerdle, Björn
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Larsson, Britt
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Hellström, Fredrik
    Department of Occupational and Public Health Sciences, Högskolan i Gävle.
    Ghafouri, Bijar
    Division of Community Medicine, Department of Medical and Health Sciences, Linköpings universitet.
    Myosin light chain and calcium regulating protein differences in chronic musculoskeletal neck and shoulder pain2016In: Journal of Integrated Omnics, ISSN 2182-0287, Vol. 6, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Proteomic screening analysis has detected myosin light chain (MLC) as a protein implied to be involved in chronic musculoskeletal neck and shoulder pain. Several analyses of MLC proteins have stated a difference in phosphorylation being the determining factor for protein activation hence altered contrability of the muscle in i.e. senescence. In continuation of a previous publication, this study is an attempt to analyze the different MLC isoforms by mass spectrometry and immune-analyses in myalgic and healthy trapezius muscle. In the present study no differences in phosphorylation level between the corresponding individual proteins were detected using LC-MSMS and immunoblotting; instead we assigned different isoforms of regulatory MLCs. To further elucidate the contrability: calcium (Ca2+) regulatory proteins, sarco(endo)plasmic reticulum Ca2+ ATPase 1 (SERCA-1) and calsequestrine (CSQ) were analyzed by western blot. The analysis revealed a significantly increased abundance of SERCA-1 protein in the myalgic muscle and a significantly increased abundance of CSQ in healthy muscle. Myalgic muscle contraction patterns have in previous studies shown to differ from healthy muscle which may be connected to the Ca2+ availability in the muscle. Here we present the proteomic characterization of differences in Ca2+ regulating proteins and particularly regulatory MLCs in trapezius muscle of women with chronic musculoskeletal neck and shoulder pain.

  • 25.
    Hammond, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    A DNA-mediated search for optimal combinations of protein bindersManuscript (preprint) (Other academic)
  • 26.
    Hasmats, Johanna
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Analysis of genetic variations in cancer2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis is to apply recently developed technologies for genomic variation analyses, and to ensure quality of the generated information for use in preclinical cancer research.

    Faster access to a patients’ full genomic sequence for a lower cost makes it possible for end users such as clinicians and physicians to gain a more complete understanding of the disease status of a patient and adjust treatment accordingly. Correct biological interpretation is important in this context, and can only be provided through fast and simple access to relevant high quality data.

    Therefore, we here propose and validate new bioinformatic strategies for biomarker selection for prediction of response to cancer therapy. We initially explored the use of bioinformatic tools to select interesting targets for toxicity in carboplatin and paclitaxel on a smaller scale. From our findings we then further extended the analysis to the entire exome to look for biomarkers as targets for adverse effects from carboplatin and gemcitabine. To investigate any bias introduced by the methods used for targeting the exome, we analyzed the mutation profiles in cancer patients by comparing whole genome amplified DNA to unamplified DNA. In addition, we applied RNA-seq to the same patients to further validate the variations obtained by sequencing of DNA. The understanding of the human cancer genome is growing rapidly, thanks to methodological development of analysis tools. The next step is to implement these tools as a part of a chain from diagnosis of patients to genomic research to personalized treatment.

  • 27.
    Hellström, Fredrik
    et al.
    University of Gävle, Faculty of Health and Occupational Studies, Department of Occupational and Public Health Sciences, Occupational health science. University of Gävle, Centre for Musculoskeletal Research.
    Gouveia-Figueira, Sandra
    Department of Chemistry, Umeå University, Umeå; Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå.
    Nording, Malin
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå.
    Björklund, Martin
    University of Gävle, Faculty of Health and Occupational Studies, Department of Occupational and Public Health Sciences, Occupational health science. University of Gävle, Centre for Musculoskeletal Research. Department of Community Medicine and Rehabilitation, Umeå University, Umeå.
    Fowler, Christopher John
    Department of Community Medicine and Rehabilitation, Umeå universitet, Umeå.
    Association between plasma concentrations of linoleic acid-derived oxylipins and the perceived pain scores in an exploratory study in women with chronic neck pain2016In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, no 1, article id 103Article in journal (Refereed)
    Abstract [en]

    Background: Chronic musculoskeletal pain may be associated with changes in the balance of algogenic and anti-nociceptive compounds, and that such changes may be visible in plasma samples. We have undertaken an exploratory study to measure the levels of endocannabinoids, related N-acylethanolamines and oxylipins (primarily those derived from linoleic acid) in plasma samples from women with chronic neck pain (NP) and chronic widespread pain (CWP), and to investigate whether the observed levels are associated with the pain experienced by these women.

    Methods: Blood samples from 35 women with NP, 15 with CWP and 27 age-matched controls were analysed for the lipids using an ultra performance liquid chromatography coupled to tandem mass spectrometry method. Current pain ("NRSday") and the average pain during the last week ("NRSweek") were rated by the participants using a numerical rating scale.

    Results: There were no significant differences in the plasma concentrations of the fifteen lipids investigated between the pain subjects and the controls. However, significant correlations were seen for the NP group between the NRSday scores and the plasma concentrations of the linoleic acid derivatives 9- and 13- hydroxy-10E,12Zoctadecadienoic acid (Spearman's rho values 0.51 [P=0.0016]) and 0.53 [P=0.0011], respectively).

    Conclusions: The data obtained in this exploratory study are consistent with a model whereby the underlying inflammatory nature of the musculoskeletal disorders leads both to an increase in the NRSday scores and the hydroxy-10E,12Z-octadecadienoic acid levels, and these increases further influence the perceived pain of in the NP subjects.

  • 28.
    Hernandez, Frank J
    Biodonostia Research Institute, San Sebastian, Spain.
    Hernandez, Luiza I.
    Biodonostia Research Institute, San Sebastian, Spain.
    Ozalp, Veli C.
    Istanbul Kemerburgaz University, School of Medicine, Istanbul, Turkey.
    Nanocapsules in biomedicine: promises and challenges2015In: Advanced Theranostics Materials / [ed] Ashutosh Tiwari et al, John Wiley & Sons, 2015Chapter in book (Other academic)
  • 29.
    Hirvonen, M. Karoliina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Assay development for in situ detection of autophagy-related protein-protein interactions for characterization of colorectal cancer2015Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Every year, more than a million people are diagnosed with colorectal cancer (CRC) that develops in the large intestine. It is one of the most studied cancers in the world but still more knowledge about how this cancer develops and acts is needed in order to use more effective ways to treat CRC. Autophagy is a vital mechanism in cells that is also suggested to maintain cancer cell survival. In normal cells, it plays an important role by removing damaged cells and organelles as well as eliminating pathogens. Under metabolic stress this mechanism is induced to provide enough nutrients and energy for the cell to survive. Cancer cells are exposed to greater environmental stress than normal cells and therefore, cancer cells exhibit higher levels of autophagy suggesting it to be a crucial mechanism for their survival. Gaining a deeper understanding of this essential mechanism and its activation might provide new insights and improved treatments for the fight against colorectal cancer. In situ Proximity Ligation Assay (PLA) is a protein detection method that enables sensitive and specific detection of proteins and protein-protein interactions (PPIs) in cell lines and tissue samples. The method uses simultaneous recognition of two independent antigens on a protein or protein complex together with a rolling circle amplification (RCA) to form a rolling circle product (RCP) on top of the target. By using fluorescent oligonucleotides, RCP can be visualized and is seen as a bright spot that enables sensitive detection of the target at single-molecule resolution. The aim of this study was to develop assays to detect endogenous molecular events known to be biomarkers of autophagy in situ in order to study autophagy mechanism in CRC patient samples. We focused our research on two PPIs that were known to interact when autophagy is induced. The first investigated interaction was between microtubule-associated protein 1A/1B- light chain 3 (LC3) and sequestome-1 (SQSTM1), an interaction that occurs during autophagy initiation. The second interaction was between B-cell lymphoma 2 (Bcl-2) and Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) that takes place during hypoxia-induced autophagy. To study whether these PPIs can be used as a detection method to monitor autophagy, we used a well- established cell model based on serum starvation and CoCl2 - an hypoxic mimetic- treatment of the intestinal cancer cell line Caco-2 in comparison to normal culture condition. According to isPLA quantification, detection of both PPIs was distinctly higher in treated cells compared to untreated cells giving promising results and suggesting that they can be potentially used as suitable assays to monitor these biomarkers of autophagy. For development of an improved protein detection method that enables the study of several PPIs simultaneously in a tissue sample (In situ Multiplexing), we conjugated directly a short oligonucleotide strand to the primary antibodies. These formed proximity probes could later be used in in situ for multiplexing. 

  • 30.
    Hollmark, M
    et al.
    Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institutet and Stockholm University.
    Edgren, M
    Kundrát, P
    Lind, B
    A comparison of radiobiological models for light ion therapyManuscript (preprint) (Other academic)
  • 31.
    Jonsson, Amanda
    et al.
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Song, Zhiyang
    Department of Clinical Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Nilsson, David
    Acreo Swedish ICT AB, SE-601 17 Norrköping, Sweden.
    Meyerson, Björn A.
    Department of Clinical Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Simon, Daniel
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Linderoth, Bengt
    Department of Clinical Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Therapy using implanted organic bioelectronics2015In: Science Advances, ISSN 2375-2548, Vol. 1, no 4, article id e1500039Article in journal (Refereed)
    Abstract [en]

    Many drugs provide their therapeutic action only at specific sites in the body, but are administered in ways that cause the drug’s spread throughout the organism. This can lead to serious side effects. Local delivery from an implanted device may avoid these issues, especially if the delivery rate can be tuned according to the need of the patient. We turned to electronically and ionically conducting polymers to design a device that could be implanted and used for local electrically controlled delivery of therapeutics. The conducting polymers in our device allow electronic pulses to be transduced into biological signals, in the form of ionic and molecular fluxes, which provide a way of interfacing biology with electronics. Devices based on conducting polymers and polyelectrolytes have been demonstrated in controlled substance delivery to neural tissue, biosensing, and neural recording and stimulation. While providing proof of principle of bioelectronic integration, such demonstrations have been performed in vitro or in anesthetized animals. Here, we demonstrate the efficacy of an implantable organic electronic delivery device for the treatment of neuropathic pain in an animal model. Devices were implanted onto the spinal cord of rats, and 2 days after implantation, local delivery of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) was initiated. Highly localized delivery resulted in a significant decrease in pain response with low dosage and no observable side effects. This demonstration of organic bioelectronics-based therapy in awake animals illustrates a viable alternative to existing pain treatments, paving the way for future implantable bioelectronic therapeutics. Keywords

  • 32.
    Juntikka, Rickard
    et al.
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Lightweight Structures.
    Kleiven, Svein
    KTH, School of Technology and Health (STH), Neuronic Engineering (Closed 20130701).
    Hallström, Stefan
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Lightweight Structures.
    Optimization of single skin surfaces for head injury prevention - a comparison of optima calculated for global versus local injury thresholds2004In: International Journal of Crashworthiness, ISSN 1358-8265, E-ISSN 1754-2111, Vol. 9, no 4, p. 365-379Article in journal (Refereed)
    Abstract [en]

    This paper describes optimizations of material properties for a bonnet-like plate using finite element calculations and the Euro-NCAP pedestrian head impact test. Four different head models were used for the impact simulations, a Euro-NCAP dummy head, a Hybrid III dummy head and two biomechanical head models exhibiting different mechanical properties for the brain tissue. The objective function was to minimize the displacement of the bonnet plate while satisfying constraints on the head injury criterion (HIC), the resultant contact force and, for the human head models, the strain in the brain tissue. An investigation was also conducted of the kinematics of the head models during impact, evaluating the energy distribution and the apparent mass. The analysis gave at hand that optimization of the plate with respect to impact with the Euro-NCAP and Hybrid III head models reached substantially, different results compared to impact with the biomechanical head models. For the latter case, the stiffness of the brain tissue influenced which constraints were active in the final solution. The investigation of the kinematics at impact showed that a substantial portion of energy was confined within the brain during impact for the biomechanical head models. The apparent mass at impact coincided with the actual mass for the rigid dummy heads while for the human head models it was roughly the mass of the skull only.

  • 33.
    Kamali-Moghaddam, Masood
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Löf, Liza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Oliveir, Felipe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Wik, Lotta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Wu, Di
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Yan, Junhong
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Advanced Molecular Tools for Proteomic Analyses of Microvesicles2014In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 23, p. 102-102Article in journal (Other academic)
  • 34.
    Karlheden, Rebecka
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Asthma, asthma medication and training intensity in Swedish competitive athletes: An internet-based survey2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 35. Katchy, Anne
    et al.
    Williams, Cecilia
    Profiling of estrogen-regulated microRNAs in breast cancer cells.2014In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 84, article id e51285Article in journal (Refereed)
    Abstract [en]

    Estrogen plays vital roles in mammary gland development and breast cancer progression. It mediates its function by binding to and activating the estrogen receptors (ERs), ERα, and ERβ. ERα is frequently upregulated in breast cancer and drives the proliferation of breast cancer cells. The ERs function as transcription factors and regulate gene expression. Whereas ERα's regulation of protein-coding genes is well established, its regulation of noncoding microRNA (miRNA) is less explored. miRNAs play a major role in the post-transcriptional regulation of genes, inhibiting their translation or degrading their mRNA. miRNAs can function as oncogenes or tumor suppressors and are also promising biomarkers. Among the miRNA assays available, microarray and quantitative real-time polymerase chain reaction (qPCR) have been extensively used to detect and quantify miRNA levels. To identify miRNAs regulated by estrogen signaling in breast cancer, their expression in ERα-positive breast cancer cell lines were compared before and after estrogen-activation using both the µParaflo-microfluidic microarrays and Dual Labeled Probes-low density arrays. Results were validated using specific qPCR assays, applying both Cyanine dye-based and Dual Labeled Probes-based chemistry. Furthermore, a time-point assay was used to identify regulations over time. Advantages of the miRNA assay approach used in this study is that it enables a fast screening of mature miRNA regulations in numerous samples, even with limited sample amounts. The layout, including the specific conditions for cell culture and estrogen treatment, biological and technical replicates, and large-scale screening followed by in-depth confirmations using separate techniques, ensures a robust detection of miRNA regulations, and eliminates false positives and other artifacts. However, mutated or unknown miRNAs, or regulations at the primary and precursor transcript level, will not be detected. The method presented here represents a thorough investigation of estrogen-mediated miRNA regulation.

  • 36.
    Khorshidi, Mohammad Ali
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Live Single Cell Imaging and Analysis Using Microfluidic Devices2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Today many cell biological techniques study large cell populations where an average estimate of individual cells’ behavior is observed. On the other hand, single cell analysis is required for studying functional heterogeneities between cells within populations. This thesis presents work that combines the use of microfluidic devices, optical microscopy and automated image analysis to design various cell biological assays with single cell resolution including cell proliferation, clonal expansion, cell migration, cell-cell interaction and cell viability tracking. In fact, automated high throughput single cell techniques enable new studies in cell biology which are not possible with conventional techniques.

    In order to automatically track dynamic behavior of single cells, we developed a microwell based device as well as a droplet microfluidic platform. These high throughput microfluidic assays allow automated time-lapse imaging of encapsulated single cells in micro droplets or confined cells inside microwells. Algorithms for automatic quantification of cells in individual microwells and micro droplets are developed and used for the analysis of cell viability and clonal expansion. The automatic counting protocols include several image analysis steps, e.g. segmentation, feature extraction and classification. The automatic quantification results were evaluated by comparing with manual counting and revealed a high success rate. In combination these automatic cell counting protocols and our microfluidic platforms can provide statistical information to better understand behavior of cells at the individual level under various conditions or treatments in vitro exemplified by the analysis of function and regulation of immune cells. Thus, together these tools can be used for developing new cellular imaging assays with resolution at the single cell level.

    To automatically characterize transient migration behavior of natural killer (NK) cells compartmentalized in microwells, we developed a method for single cell tracking. Time-lapse imaging showed that the NK cells often exhibited periods of high motility, interrupted with periods of slow migration or complete arrest. These transient migration arrest periods (TMAPs) often overlapped with periods of conjugations between NK cells and target cells. Such conjugation periods sometimes led to cell-mediated killing of target cells. Analysis of cytotoxic response of NK cells revealed that a small sub-class of NK cells called serial killers was able to kill several target cells. In order to determine a starting time point for cell-cell interaction, a novel technique based on ultrasound was developed to aggregate NK and target cells into the center of the microwells. Therefore, these assays can be used to automatically and rapidly assess functional and migration behavior of cells to detect differences between health and disease or the influence of drugs.

    The work presented in this thesis gives good examples of how microfluidic devices combined with automated imaging and image analysis can be helpful to address cell biological questions where single cell resolution is necessary. 

  • 37.
    Kreiser, Julian
    et al.
    Visual Computing Group, Ulm University, Ulm, Germany.
    Freedman, Jacob
    Karolinska Institutet Stockholm, Stockholm, Sweden.
    Ropinski, Timo
    Visual Computing Group, Ulm University, Ulm, Germany.
    Visually Supporting Multiple Needle Placement in Irreversible Electroporation Interventions2018In: Computer Graphics Forum, Vol. 37, no 6, p. 59-71Article in journal (Refereed)
    Abstract [en]

    Irreversible electroporation (IRE) is a minimally invasive technique for small tumour ablation. Multiple needles are inserted around the planned treatment zone and, depending on the size, inside as well. An applied electric field triggers instant cell death around this zone. To ensure the correct application of IRE, certain criteria need to be fulfilled. The needles' placement in the tissue has to be parallel, at the same depth, and in a pattern which allows the electric field to effectively destroy the targeted lesions. As multiple needles need to synchronously fulfill these criteria, it is challenging for the surgeon to perform a successful IRE. Therefore, we propose a visualization which exploits intuitive visual coding to support the surgeon when conducting IREs. We consider two scenarios: first, to monitor IRE parameters while inserting needles during laparoscopic surgery; second, to validate IRE parameters in post‐placement scenarios using computed tomography. With the help of an easy to comprehend and lightweight visualization, surgeons are enabled to quickly visually detect what needs to be adjusted. We have evaluated our visualization together with surgeons to investigate the practical use for IRE liver ablations. A quantitative study shows the effectiveness compared to a single 3D view placement method.

  • 38.
    Kroon, Martin
    Royal Institute of Technology (KTH).
    Modeling of fibroblast-controlled strengthening and remodeling of uniaxially constrained collagen gels2010In: Journal of Biomechanical Engineering, ISSN 0148-0731, E-ISSN 1528-8951, Vol. 132, no 11, article id 111008Article in journal (Refereed)
    Abstract [en]

    A theoretical model for the remodeling of collagen gels is proposed. The collagen fabric is modeled as a network of collagen fibers, which in turn are composed of collagen fibrils. In the model, the strengthening of collagen fabric is accomplished by fibroblasts, which continuously recruit and attach more collagen fibrils to existing collagen fibers. The fibroblasts also accomplish a reorientation of collagen fibers. Fibroblasts are assumed to reorient collagen fibers toward the direction of maximum material stiffness. The proposed model is applied to experiments in which fibroblasts were inserted into a collagen gel. The model is able to predict the force-strain curves for the experimental collagen gels, and the final distribution of collagen fibers also agrees qualitatively with the experiments.

  • 39. Kumar, Abhinav
    et al.
    Bicer, Elif Melis
    Morgan, Anna Babin
    Pfeffer, Paul E.
    Monopoli, Marco
    Dawson, Kenneth A.
    Eriksson, Jonny
    Edwards, Katarina
    Lynham, Steven
    Arno, Matthew
    Behndig, Annelie F.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Somers, Graham
    Hassall, Dave
    Dailey, Lea Ann
    Forbes, Ben
    Mudway, Ian S.
    Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid2016In: Nanomedicine: Nanotechnology, Biology and Medicine, ISSN 1549-9634, E-ISSN 1549-9642, Vol. 12, no 4, p. 1033-1043Article in journal (Refereed)
    Abstract [en]

    When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semiquantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. From the Clinical Editor: Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics. (C) 2016 Published by Elsevier Inc.

  • 40.
    Kupferschmidt, Natalia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanologica AB, SE-11428 Stockholm, Sweden.
    Csikasz, Robert
    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Ballell, Lluis
    Diseases of the Developing World, GlaxoSmithKline, Madrid, Spanien.
    Bengtsson, Tore
    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Garcia-Bennett, Alfonso E.
    Stockholm Univ, Arrhenius Lab, MMK, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden.
    Large pore mesoporous silica induced weight loss in obese mice2013In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, no 9, p. 1353-1362Article in journal (Refereed)
    Abstract [en]

    Background: There is a need for medical treatments to curb the rising rate of obesity. Weight reduction is correlated with a decrease in associated risk factors and cholesterol levels in humans. Amorphous silica particles have been found to exert a hypocholesterolemic effect in humans, making them popular dietary additives. Aim: To investigate the effect of mesoporous silica, which possess sharp pore size distributions, on: weight loss, cholesterol, triglycerides and glucose blood levels in obese mice. Materials & methods: Mesoporous silicas with differing pore size were mixed in the high-fat diet of obese mice. Results: Animals receiving large pore mesoporous silica with a high-fat diet show a significant reduction in body weight and fat composition, with no observable negative effects. Conclusion: Pore size is an important parameter for reduction of body weight and body fat composition by mesoporous silica, demonstrating promising signs for the treatment of obesity.

  • 41.
    Kühnemund, Malte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Science for life laboratory.
    Wei, Qingshan
    Department of Bioengineering, University of California Los Angeles (UCLA).
    Darai, Eva
    Science for life laboratory, Stockholm University.
    Wang, Y
    Department of Bioengineering, University of California Los Angeles (UCLA).
    Hernandez-Neuta, Ivan
    Science for life laboratory, Stockholm University.
    Tseng, D
    Department of Bioengineering, University of California Los Angeles (UCLA).
    Ahlford, Annika
    Science for life laboratory, Stockholm University.
    Ozcan, Aydogan
    Department of Bioengineering, University of California Los Angeles (UCLA).
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Science for life laboratory, Stockholm University.
    In situ detection of KRAS point mutations and targeted DNA sequencing with a mobile phoneManuscript (preprint) (Other academic)
  • 42.
    Larsen, Christian
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Forchheimer, Robert
    Edman, Ludvig
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Tu, Deyu
    Design, fabrication and application of organic power converters: Driving light-emitting electrochemical cells from the AC mains2017In: Organic electronics, ISSN 1566-1199, E-ISSN 1878-5530, Vol. 45, p. 57-64Article in journal (Refereed)
    Abstract [en]

    The design, fabrication and operation of a range of functional power converter circuits, based on diode configured organic field-effect transistors as the rectifying unit and capable of transforming a high AC input voltage to a selectable DC voltage, are presented. The converter functionality is demonstrated by selecting and tuning its constituents so that it can effectively drive a low-voltage organic electronic device, a light-emitting electrochemical cell (LEC), when connected to high-voltage AC mains. It is established that the preferred converter circuit for this task comprises an organic full-wave rectifier and a regulation resistor but is void of a smoothing capacitor, and that such a circuit connected to the AC mains (230 V, 50 Hz) successfully can drive an LEC to bright luminance (360 cd m(-2)) and high efficiency (6.4 cd A(-1)).

  • 43.
    Larsson, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    An Analysis of XCR1 in GFAP+ Glial Cells Throughout the Brain and Brainstem using Karma mice2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 44. Liu, Anmin
    et al.
    Nester, Christopher
    Jones, Richard
    Lundgren, Paul
    Lundberg, Arne
    Arndt, Anton
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Laboratory for Biomechanics and Motor Control.
    Wolf, Peter
    The Effect of an Antipronation Foot Orthosis on Ankle and Subtalar Kinematics2012In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 44, no 12, p. 2384-91Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION/PURPOSE:

    The aim of this study was to describe the effect of an anti pronation foot orthosis on motion of the heel relative to the leg and explore the individual contributions of the ankle and subtalar joints to this effect.

    METHODS:

    Five subjects were investigated using invasive intracortical pins to track the movement of the tibia, talus and calcaneus during walking with and without a foot orthosis.

    RESULTS:

    The anti pronation foot orthosis produced small and unsystematic reductions in eversion and abduction of the heel relative to the leg at various times during stance. Changes in calcaneus-tibia motion were comparable to those described in the literature (1-3°). Changes at both the ankle and subtalar joints contributed to this orthotic effect. However, the nature and scale of changes was highly variable between subjects. Peak angular position, range of motion and angular velocity in frontal and transverse planes were affected to different degrees in different subjects. In some cases changes occurred mainly at the ankle, in other cases changes occurred mainly at the subtalar joint.

    CONCLUSION:

    The changes in ankle and subtalar kinematics in response to the foot orthosis contradict existing orthotic paradigms that assume that changes occur only at the subtalar joint. The kinematic changes due to the orthosis are indicative of a strong interaction between the often common function of the ankle and subtalar joints.

  • 45.
    Lundin, Anton
    et al.
    Halmstad University, School of Business, Engineering and Science.
    Johansson, Frida
    Halmstad University, School of Business, Engineering and Science.
    OutDoor Office: Ett alternativ till konventionella mötesplatser2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 46.
    Lundström, Claes
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Characterizing visual analytics in diagnostic imaging2011In: EuroVA 2011: International Workshop on Visual Analytics, 2011, p. 1-4Conference paper (Other academic)
    Abstract [en]

    Many necessary and desired improvements in healthcare are dependent on progress in medical imaging. As shown in this paper, the challenges targeted by visual analytics (VA) coincide with main challenges for radiologists' diagnostic work. Key prerequisites for VA in this application domain have been identified through analysis of a survey among 22 radiologists at a university hospital. Two major findings are that efficiency is perceived as the most challenging aspect of their diagnostic work and that an exploratory approach is necessary in everyday image review. The presented characterization constitutes a validated input for design of future VA research initiatives within medical imaging.

  • 47.
    Matar, Amal
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Couples Considering a Baby? Screen for the Future: Ethical and Implementation Aspects of Preconception Genetic Carrier Screening2016Licentiate thesis, comprehensive summary (Other academic)
  • 48.
    Matar, Amal
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Hansson, Mats G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Höglund, Anna T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Couple autonomy in preconception expanded carrier screeningManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Preconception Expanded Carrier Screening (ECS) is a genetic test offered to a general population or to couples who have no known risk of recessive and X-linked genetic diseases and are interested in becoming parents. A test may screen for carrier status of several autosomal recessive diseases at one go. Such a program has been piloted in the Netherlands and may become a reality in more European countries in the future. The ethical rationale for such tests is that they would enhance reproductive autonomy. The dominant conception of autonomy is individual-based. However, at the clinic, people deciding on preconception ECS will be counselled together and are expected to make a joint decision, as a couple. The aim of the present study was to develop an understanding of autonomous decisions made by couples in the context of reproductive technologies in general and of preconception ECS in particular. A further aim was to shed light on what occurs in reproductive clinics and to suggest concrete implications for the approach of healthcare professionals in those clinics. Discussion: Based on the shift in emphasis from individual autonomy to relational autonomy, a notion of couple autonomy was suggested and some features of this concept were outlined. First, that both partners are individually autonomous and that the decision is reached through a communicative process. In this process each partner should feel free to express his or her concerns and preferences, so no one partner dominates the discussion. Further, there should be adequate time for the couple to negotiate possible differences and conclude that the decision is right for them. The final decision should be reached through consensus of both partners without coercion, manipulation or miscommunication. Through concrete examples, the suggested notion of couple autonomy was applied to diverse clinical situations. Conclusions: A notion of couple autonomy can be fruitful for healthcare professionals by facilitating the ways in which close ones are vital for the decision-making concerning preconception ECS. A normative implication for healthcare staff is to allow the necessary

    2

    time for decision-making and to promote a dialogue that can increase the power of the weaker part in a relationship.

  • 49.
    Matar, Amal
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Hansson, Mats G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Höglund, Anna T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Values and value conflicts in implementation and use of preconception expanded carrier screening: an expert interview studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Ethical values and principles have been incorporated in most aspects of healthcare, such as policy-making, communication, medical research and health technology assessment. Preconception expanded carrier screening is a genetic test offered to a general population or to couples with no known risk of recessive genetic diseases and planning a pregnancy. A test screens for carrier status of several autosomal recessive diseases simultaneously.

    Aim: To examine values and value conflicts experts recounted in implementation and use of preconception expanded carrier screening in Sweden. Methods: We interviewed ten experts, directly associated with influencing health policy- making in Sweden, and members of two non-governmental and three governmental organizations. We employed systematizing expert interviews to access experts’ specialist knowledge. There were four female and six male informants, of which four were physicians, three bioethicists, a legal expert, a theologian and a political party representative in the parliament. We used thematic analysis to identify themes and sub-themes in the data.

    Results: The main values that emerged were Respect for persons, Solidarity, Human dignity, Do no harm, Health, Love and Trust. Concepts relating to autonomy, integrity and privacy were the most commonly mentioned among the participants, followed by notions of equality, justice and social care. The experts’ descriptions of values were concordant to those in bioethical literature.

    Conclusions: Experts highlighted values that are distinctive of welfare states, as Sweden. Certain values were deemed more substantive than others, judging by the extent and detail of inference; for example, respect for persons and solidarity.

  • 50.
    Matar, Amal
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Höglund, Anna T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hansson, M G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    “A perfect society”— Swedish policymakers’ ethical and social views on preconception expanded carrier screening2018In: Journal of Community Genetics, ISSN 1868-310X, E-ISSN 1868-6001Article in journal (Refereed)
    Abstract [en]

    To improve healthcare policymaking, commentators have recommended the use of evidence, health technology assessment, priority setting, and public engagement in the process of policymaking. Preconception expanded carrier screening, according to the World Health Organization’s definition, is a novel health technology and therefore warrants assessment, part of which involves evaluating ethical and social implications. We examined ten Swedish policymakers’ perspectives on ethical and social aspects of preconception expanded screening through in-depth expert interviewing, using a semi-structured questionnaire. Respondents were affiliated to governmental and non-governmental institutions that directly influence healthcare policymaking in Sweden. The interviews were recorded, transcribed verbatim, and analyzed via inductive thematic analysis method, which generated seven themes and several subthemes. Policymakers harbored concerns regarding the economics, Swedish and international political respects, implementation procedures, and societal effects, which included long-term ones. Moreover, participants detailed the role of public engagement, research, and responsibility in regard to preconception expanded carrier screening implementation. Since this is a qualitative study, with a small non-random sample, the results may not be generalizable to all policymakers in Sweden. However, the results give a profound insight into the process and interpretative knowledge of experts, in the Swedish milieu and the extent of readiness of Sweden to implement a preconception expanded carrier screening program.

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