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  • 451.
    Teneberg, Susanne
    et al.
    Halmstad University, School of Information Technology. Institute of Medical Biochemistry, Göteborg University, P. O. Box 440, SE 405 30 Göteborg, Sweden.
    Leonardsson, I.
    Department of Clinical Microbiology and Immunology, Örebro Medical Centre Hospital, SE 701 85 Örebro, Sweden.
    Karlsson, H.
    Department of General Surgery, Örebro Medical Centre Hospital, SE 701 85 Örebro, Sweden.
    Jovall, P.-A.
    Department of Medical Microbiology, Dermatology, and Infection, University of Lund, SE 223 62 Lund, Sweden.
    Ångström, J.
    Institute of Medical Biochemistry, Göteborg University, P. O. Box 440, SE 405 30 Göteborg, Sweden.
    Danielsson, D.
    Institute of Medical Biochemistry, Göteborg University, P. O. Box 440, SE 405 30 Göteborg, Sweden.
    Näslund, I.
    Institute of Medical Biochemistry, Göteborg University, P. O. Box 440, SE 405 30 Göteborg, Sweden.
    Ljungh, A.
    Institute of Medical Biochemistry, Göteborg University, P. O. Box 440, SE 405 30 Göteborg, Sweden.
    Wadström, T.
    Institute of Medical Biochemistry, Göteborg University, P. O. Box 440, SE 405 30 Göteborg, Sweden.
    Karlsson, K.-A
    Institute of Medical Biochemistry, Göteborg University, P. O. Box 440, SE 405 30 Göteborg, Sweden.
    Lactotetraosylceramide, a novel glycosphingolipid receptor for Helicobacter pylori, present in human gastric epithelium2002In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 277, no 22, p. 19709-19719Article in journal (Refereed)
    Abstract [en]

    The binding of Helicobacterpylori to glycosphingolipids was examined by binding of 35S-labeled bacteria to glycosphingolipids on thin-layer chromatograms. In addition to previously reported binding specificities, a selective binding to a non-acid tetraglycosylceramide of human meconium was found. This H. pylori binding glycosphingolipid was isolated and, on the basis of mass spectrometry, proton NMR spectroscopy, and degradation studies, were identified as Galβ3GlcNAcβ3-Galβ4Glcβ1Cer (lactotetraosylceramide). When using non-acid glycosphingolipid preparations from human gastric epithelial cells, an identical binding of H. pylori to the tetraglycosylceramide interval was obtained in one of seven samples. Evidence for the presence of lactotetraosylceramide in the binding-active interval was obtained by proton NMR spectroscopy of intact glycosphingolipids and by gas chromatography-electron ionization mass spectrometry of permethylated tetrasaccharides obtained by ceramide glycanase hydrolysis. The lactotetraosylceramide binding property was detected in 65 of 74 H. pylori isolates (88%) Binding of H. pylori to lactotetraosylceramide on thin-layer chromatograms was inhibited by preincubation with lactotetraose but not with lactose. Removal of the terminal galactose of lactotetraosylceramide by galactosidase hydrolysis abolished the binding as did hydrazinolysis of the acetamido group of the N-acetylglucosamine. Therefore, Galβ3GlcNAc is an essential part of the binding epitope.

  • 452.
    Theurich, Melissa Ann
    et al.
    LMU - Ludwig-Maximilians-Universität Munich, Div. Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Munich, Germany.
    Davanzo, Riccardo
    Department of Mother and Child Health, ASM-Matera and Task Force on Breastfeeding, MOH, Rome, Italy.
    Busck-Rasmussen, Marianne
    Danish Committee for Health Education, Copenhagen, Denmark.
    Díaz-Gómez, N. Marta
    Instituto de Tecnologías Biomédicas (ITB) and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, Spain.
    Brennan, Christine
    Breastfeeding Promotion Foundation, Bern, Switzerland.
    Kylberg, Elisabeth
    University of Skövde, School of Health and Education. University of Skövde, Health and Education.
    Bærug, Anne
    Norwegian National Advisory Unit on Breastfeeding, Oslo, Norway.
    McHugh, Laura
    Health Service Executive, Ennis, Ireland.
    Weikert, Cornelia
    German Federal Institute for Risk Assessment, Department of Food Safety, Berlin, Germany.
    Abraham, Klaus
    German Federal Institute for Risk Assessment, Department of Food Safety, Berlin, Germany.
    Koletzko, Berthold
    LMU - Ludwig-Maximilians-Universität Munich, Div. Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Munich, Germany.
    Breastfeeding Rates and Programs in Europe: A Survey of 11 National Breastfeeding Committees and Representatives2018In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Among the world's regions, the WHO European Region has the lowest rates of exclusive breastfeeding at age 6 months with around 25%. Low rates and early cessation of breastfeeding have important adverse health consequences for women, infants and young children. Protecting, promoting and supporting breastfeeding are a public health priority.

    OBJECTIVES: National breastfeeding data and monitoring systems among selected European countries and the WHO European Region are compared. Mechanisms for the support, protection and promotion of breastfeeding are reviewed and successes and challenges in implementation of national programs are presented.

    METHODS: National representatives of national breastfeeding committees and initiatives in eleven European countries, including Belgium, Croatia, Denmark, Germany, Ireland, Italy, The Netherlands, Norway, Spain, Sweden and Switzerland, participated in a standardized survey. Results are evaluated and compared in a narrative review.

    RESULTS: Variation exists in Europe on breastfeeding rates, methodology for data collection and mechanisms for support, protection and promotion of breastfeeding. Directly after birth, between 56 and 98 % of infants in all countries were reported to receive any human milk, and at 6 months 38-71% and 13-39 % of infants to be breastfed or exclusively breastfed, respectively. National plans addressing breastfeeding promotion, protection and support exist in 6 of the 11 countries.

    CONCLUSIONS: National governments should commit to evidence-based breastfeeding monitoring and promotion activities, including financial and political support, to improve breastfeeding rates in the Europe. Renewed efforts for collaboration between countries in Europe, including a sustainable platform for information exchange, are needed.

  • 453.
    Tian, Haining
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Yu, Ze
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Inorganic Chemistry (closed 20110630).
    Hagfeldt, Anders
    Kloo, Lars
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Inorganic Chemistry (closed 20110630).
    Sun, Licheng
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Organic Redox Couples and Organic Counter Electrode for Efficient Organic Dye-Sensitized Solar Cells2011In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 133, no 24, p. 9413-9422Article in journal (Refereed)
    Abstract [en]

    A series of organic thiolate/disulfide redox couples have been synthesized and have been studied systematically in dye-sensitized solar cells (DSCs) on the basis of an organic dye (TH305). Photophysical, photoelectrochemical, and photovoltaic measurements were performed in order to get insights into the effects of different redox couples on the performance of DSCs. The polymeric, organic poly(3,4-ethylenedioxythiophene) (PEDOT) material has also been introduced as counter electrode in this kind of noniodine-containing DSCs showing a promising conversion efficiency of 6.0% under AM 1.5G, 100 mW.cm(-2) light illumination. Detailed studies using electrochemical impedance spectroscopy and linear-sweep voltammetry reveal that the reduction of disulfide species is more efficient on the PEDOT counter electrode surface than on the commonly used platinized conducting glass electrode. Both pure and solvated ionic-liquid electrolytes based on a thiolate anion have been studied in the DSCs. The pure and solvated ionic-liquid-based electrolytes containing an organic redox couple render efficiencies of 3.4% and 1.2% under 10 mW.cm(-2) light illumination, respectively.

  • 454. Tjarks, W
    et al.
    Gedda, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Silvander, M
    Mars, U
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Ghaneolhosseini, H
    Henssen, C
    Olsson, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sjoberg, S
    Carlsson, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Larsson, B
    Edwards, K
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Carboranyl phenantridinium analogues: Synthesis and biological evaluation.1997Conference paper (Other academic)
  • 455. Tjarks, W
    et al.
    Ghaneolhosseini, H
    Gedda, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Mars, U
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Olsson, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sjoberg, S
    Carlsson, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Larsson, B
    Carboranyl phenanthridinium analogues: synthesis and biological evaluation.1996In: Seventh International Symposium on Neutron Capture Therapy for Cancer, p. 74-Article, book review (Other academic)
  • 456. Tjarks, W
    et al.
    Malmquist, J
    Gedda, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sjoberg, S
    Carlsson, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Synthesis and initial biological evaluation of carborane-containing phenanthridinium derivatives.1996In: Cancer Neutron Capture Therapy for Cancer, Mishima Y, Plenum Press, New York , 1996, Vol. chapter 15, p. 121-Chapter in book (Other academic)
  • 457.
    Tjust, Anton
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Extraocular Muscles in Amyotrophic Lateral Sclerosis2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease of motor neurons characterized by muscle paralysis and death within 3-5 years of onset. However, due to unknown mechanisms, the extraocular muscles (EOMs) remain remarkably unaffected. The EOMs are highly specialized muscles that differ from other muscles in many respects, including innervation and satellite cells (SCs). Understanding whether these factors play a role in the relative sparing of EOMs in ALS could provide useful clues on how to slow down the progression of ALS in other muscles.

    The EOMs and limb muscles from terminal ALS patients and age-matched controls as well as the commonly used SOD1G93A ALS mouse model were studied with immunofluorescence. Antibodies against neurofilament and synaptophysin were used to identify nerves and neuromuscular junctions (NMJs); against Pax7, NCAM, MyoD, myogenin, Ki-67, dystrophin and laminin, to identify SCs and their progeny in EOMs and limb muscles. The proportion and fiber size of myofibers containing myosin heavy chain (MyHC) slow tonic and MyHC slow twitch were also determined in human EOMs.

    The abundance of SCs differed extensively along the length of control human EOMs, being twice as abundant in the anterior portion. Pax7-positive cells were also detected in non-traditional SC positions. EOMs from terminal ALS patients showed similar numbers of resting and activated SCs as the controls. In limb muscles of ALS patients, the number of resting and activated SCs ranged from low (similar to normal aged, sedentary individuals) to high numbers, especially in muscles with long duration of disease and varied between the upper and lower limbs. The EOMs maintained a high degree of innervation compared to hindlimb muscles of symptomatic SOD1G93A mice. MyHC slow tonic fibers were less abundant in ALS patients than in controls. The change seemed more pronounced in bulbar onset patients, and in this group of subjects only, there was a strong association between decline in MyHC slow tonic fibers and age of death. Notably, the decline in MyHC slow tonic fibers was unrelated to disease duration.

    Our data suggested that SCs play a minor role in the progression of ALS in general and in the sparing of the EOMs in particular. The generally preserved innervation in the EOMs of G93A mice may reflect distinct intrinsic properties relevant for sparing of the oculomotor system.  Even though the EOMs are relatively spared in ALS, MyHC slow tonic myofibers were selectively affected and this may reflect differences in innervation, as these fibers are multiply innervated.

  • 458. Treusch, Sebastian
    et al.
    Hamamichi, Shusei
    Goodman, Jessica L
    Matlack, Kent ES
    Chung, Chee Yeun
    Baru, Valeriya
    Shulman, Joshua M
    Parrado, Antonio
    Bevis, Brooke J
    Valastyan, Julie S
    Han, Haesun
    Lindhagen-Persson, Malin
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Reiman, Eric M
    Evans, Denis A
    Bennett, David A
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Dejager, Philip L
    Tanzi, Rudolph E
    Caldwell, Kim A
    Caldwell, Guy A
    Lindquist, Susan
    Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast2011In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 334, no 6060, p. 1241-1245Article in journal (Refereed)
    Abstract [en]

    Aβ (beta amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained using yeast as a model system.

  • 459.
    Trey, Stacy M.
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Netrval, Julia
    Berglund, Lars
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Johansson, Mats
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Electron-Beam-Initiated Polymerization of Poly(ethylene glycol)-Based Wood Impregnants2010In: ACS APPL MATER INTERFACES, ISSN 1944-8244, Vol. 2, no 11, p. 3352-3362Article in journal (Refereed)
    Abstract [en]

    The current study demonstrates that methacrylate and acrylate poly(ethylene glycol) (PEG) functional oligomers can be effectively impregnated into wood blocks and cured efficiently to high conversions without catalyst by e-beam radiation, allowing for less susceptibility to leaching, and favorable properties including higher Brinell hardness values. PEG based monomers were chosen because there is a long history of this water-soluble monomer being able to penetrate the cell wall, thus bulking it and decreasing the uptake of water which further protects the wood from fungal attack. Diacrylate dimethacrylate and dihydroxyl functional PEG of M-v, 550-575 of concentration 0-30, 60 and 100 wt % in water, were vacuum pressure impregnated into Scots Pine blocks of 15 x 25 x 50 mm in an effort to bulk the cell wall. The samples were then irradiated and compared with nonirradiated samples it was shown by IR, DSC that the acrylate polymers were fully cured to much higher conversions than can be reached with conventional methods Leaching studies indicated a much lower amount of oligomer loss from the cured to much higher conversions than can be reached with conventional methods functional PEG indication a high degree of fastening of the polymer in the wood. The Brinell hardness indicated a significant increase in hardness to hardwood levels in the modified samples compared to the samples of hydroxyl functional PEG and uncured vinyl PEC samples, which actually became softer than the untreated Scots Pine. By monitoring the dimensions of the sample it was found by weight percent gain calculations WPC %) that water helps to swell the wood structure and allow better access of the oligomers into the cell wall as this was not observed for methyl methacrylate which is well-cocumented to remain in the lumen. However dimensional stability of the viny ploymer modified blocks when placed in water was not observed to the same extent as PEG.

  • 460.
    Tryzell, Robert
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Multidetection and chemometrics in flow injection analysis1997Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An ideal method for the determination of ions in aqueous solutions should be fast, inexpensive, simple, reliable and require small sample volumes. Flow Injection Analysis (FIA) is in many respects such an ideal method but it is too often limited to the determination of one analyte at a time. In this thesis some system design aspects have been addressed. A new system for multianalyte determination has been developed which is based on the hyphenation of FIA with capillary electrophoresis (CE). Chemometrics have been used to optimise the design of this new system and further to optimise the design of a typical single analyte FIA manifold namely a gas diffusion manifold for the determination of ammonia.

    The second major theme in this work is the development of new signal evaluation methods for FIA and FIA-CE systems. By using a multivariate approach the simultaneous determination of ammonium and excess acid (sulphuric acid) in one single run has been made possible. For conventional two line or gas diffusion applications in FIA, peak area by triangulation was found to be the evaluation method of choice both for "normal" and extended analyte concentration ranges. For the FIA-CE system, which is based on electrokinetic injection, various evaluation methods, both univariate and multivariate, were critically examined and compared. The conductivity corrected peak area method is superior to the traditionally used evaluation principles such as peak height, peak area, standard addition and internal standard methods.

  • 461. Tu, Yaoquan
    et al.
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Implementing Quantum Mechanics into Molecular Mechanics-Combined QM/MM Modeling Methods2010In: Advances in Quantum Chemistry, ISSN 0065-3276, E-ISSN 2162-8815, Vol. 59, p. 1-15Article, review/survey (Refereed)
  • 462.
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
    Does Feed Containing Trans Fatty Acids Influence the Cholesterol and Oxycholesterols Levels in Chicken?2011In: Nutrition Focus Newsletter, Nutrition Society of Sri Lanka, no 3, p. 5-Article in journal (Other (popular science, discussion, etc.))
  • 463.
    Ulfenborg, Benjamin
    et al.
    University of Skövde, Skövde, Sweden.
    Klinga-Levan, Karin
    University of Skövde, Skövde, Sweden.
    Olsson, Björn
    University of Skövde, Skövde, Sweden.
    Genome-wide discovery of miRNAs using ensembles of machine learning algorithms and logistic regression2015In: International Journal of Data Mining and Bioinformatics, ISSN 1748-5673, Vol. 13, no 4, p. 338-359Article in journal (Refereed)
    Abstract [en]

    In silico prediction of novel miRNAs from genomic sequences remains a challenging problem. This study presents a genome-wide miRNA discovery software package called GenoScan and evaluates two hairpin classification methods. These methods, one ensemble-based and one using logistic regression were benchmarked along with 15 published methods. In addition, the sequence-folding step is addressed by investigating the impact of secondary structure prediction methods and the choice of input sequence length on prediction performance. Both the accuracy of secondary structure predictions and the miRNA prediction are evaluated. In the benchmark of hairpin classification methods, the regression model achieved highest classification accuracy. Of the structure prediction methods evaluated, ContextFold achieved the highest agreement between predicted and experimentally determined structures. However, both the choice of secondary structure prediction method and input sequence length had limited impact on hairpin classification performance.

  • 464.
    Ulfenborg, Benjamin
    et al.
    University of Skövde.
    Olsson, Björn
    University of Skövde, Skövde, Sweden.
    Biomarker discovery and partial least squares-driven exploratory analysis of cancer expression dataManuscript (preprint) (Other academic)
  • 465.
    Ullsten, Henrik
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymeric Materials.
    Processing and Development of Wheat Gluten Plastics2008Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

     Renewable packaging materials are of interest for a more sustainable environment. Wheat gluten is one of the most interesting candidates to replace petroleum-based oxygen-barrier polymers for packaging applications. The high amount of hydrogen bonds makes wheat gluten interesting as oxygen barrier films with sufficient elastomeric mechanical properties. Wheat gluten based materials are homogeneous, mechanically strong and relatively water insoluble compared with other biological materials. Several studies of wheat gluten films have been performed on solution cast films and a few studies have been executed on compression molding. Extrusion, without solvents, is the most common and fastest processing method for the production of packaging films. In order to develop wheat gluten films to commercially competitive material it is crucial to make the material extrudable.The temperature window for extrusion of glycerol-plasticized wheat gluten was increased by the use of salicylic acid, a known scorch retarder and radical scavenger. Small effects of shear-induced heating during extrusion at the higher temperatures suggested that the acid acted as a lubricant and viscosity reducer. The latter was suggested to originate primarily from the salicylic-acid-induced reduction in the degree of protein aggregation/crosslinking, as indicated by size-exclusion high-performance liquid chromatography and chemiluminescence. Electron paramagnetic resonance spectroscopy on extruded films indicated that the beneficial effect of salicylic acid was due to its radical scavenging effect. The complex shear modulus increased more slowly with increasing salicylic acid content above 110-120°C, indicating that the aggregation/crosslinking rate was slower with salicylic acid, i.e. that it did have a scorch-retarding effect, besides yielding a lower final degree/complexity of aggregation.Sodium hydroxide was used as an additive to be able to extrude gluten at alkaline conditions. The oxygen barrier, at dry conditions, was improved significantly with the addition of sodium hydroxide. Oxygen transmission rate measurements, tensile tests, protein solubility, glycerol migration, infrared spectroscopy and electrophoresis were used to assess the properties of the extrudate. It was observed that the extrudate with 3 wt.% sodium hydroxide had the most suitable combination of properties, low oxygen permeability, large strain at break and relatively small aging-induced changes in mechanical properties, the reason probably due to high protein aggregation and low plasticizer migration.As an alternative method to get alkaline conditions ammonium hydroxide was added. It resulted in a three times stronger film compared to the pure gluten glycerol material and had an oxygen barrier that can favorably be compared with these of oriented polyethylene terephtalat or Nylon 66.Several plasticizers were examined in a screening test where the extrusion properties were predicted in a plasticorder. The temperature and melt viscosity were recorded during the kneading. The most promising plasticizers were chosen to further studies with tensile tests. Glycerol was shown to be the most efficient plasticizer for thermoformed gluten films.In order to use wheat gluten as a packaging material, it is important to be able to seal it. Wheat gluten films, molded at 100–130°C, were sealed by impulse sealing at 120– 175°C. The lap-shear and peel strength of the sealed films were evaluated. The lapshear strength was greater than or similar to that of polyethylene film, although the peel strength was poorer.

  • 466.
    Unger, Maria
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Asplund, Lillemor
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Marsh, Göran
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
    Gustafsson, Örjan
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Characaterization of an abundant and novel methyl- and methoxy-substituted brominated diphenyl ether isolated from whale blubber2010In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 79, no 4, p. 408-413Article in journal (Refereed)
    Abstract [en]

    A previously unidentified yet abundant substituted polybrominated diphenyl ether (PBDE) was isolated from a northern bottlenose whale (Hyperoodon ampullatus) found dead in the Skagerrak, North Sea. A combination of gas chromatography, high and low resolution mass spectrometry and nuclear magnetic resonance spectroscopy (NMR) (1H, 1H–1H and 1H–13C) after isolation with preparative capillary gas chromatography (PCGC) lead to the identification of the unknown substance as 6-MeO-5-Me-2,2′,3,4′-tetrabromo diphenyl ether (6-MeO-5-Me-BDE42). To our knowledge this is only the second time PCGC has been used to isolate individual organohalogen compounds present in trace amounts for identification with NMR. The concentration of this novel bioaccumulated compound was estimated to be about 100 ng g−1 lipid, which was 2.5 times higher compared with the most abundant MeO-PBDE congeners.

  • 467.
    Uppgård, Lise-Lott
    Umeå University, Faculty of Science and Technology, Chemistry.
    Nonionic surfactants: A multivariate study2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis technical nonionic surfactants are studied using multivariate techniques. The surfactants studied were alkyl ethoxylates (AEOs) and alkyl polyglucosides (APGs).

    The aquatic toxicity of the surfactants towards two organisms, a shrimp and a rotifer, was examined. The specified effect was lethality, LC50, as indicated by immobilisation. In a comparative study, the LC50 values obtained were used to develop two different types of model. In the log P model the toxicity was correlated to log P alone, while in the multivariate model several physicochemical variables, including log P, were correlated to the toxicity. The multivariate model gave smaller prediction errors than the log P model.

    Further, the change in reactivity when a surfactant mixture was added to dissolving pulp under alkaline conditions was studied, using the amount of residual cellulose as a measure of the reactivity. Ten AEO/APG mixtures were tested, and the mixture with greatest potential was studied in more detail. An optimum in the amount of added surfactant was found that seems to coincide, according to surface tension measurements, with the CMC.

  • 468.
    Uppgård, Lise-Lott
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindgren, Åsa
    Akzo Nobel Surface Chemistry AB, Stenungsund, Sweden.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wold, Svante
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivariate quantitative structure-activity relationships for the aquatic toxicity of technical nonionic surfactants2000In: Journal of Surfactants and Detergents, ISSN 1097-3958 (Print) 1558-9293 (Online), Vol. 3, no 1, p. 33-41Article in journal (Refereed)
    Abstract [en]

    The aquatic toxicity of 36 technical nonionic surfactants (ethoxylated fatty alcohols) was examined toward two freshwater animal species, the fairy shrimp Thamnocephalus playtyurus and the rotifer Brachionus calyciflorus. Responses of the two species to the surfactants were generally similar. A multivariate-quantitative structure-activity relationship (M-QSAR) model was developed from the data. The M-QSAR model consisted of a partial least squares model with three components and explained 92.4% of the response variance and had a predictive capability of 89.1%. The most important physicochemical variables for the M-QSAR model were the number of carbon atoms in the longest chain of the surfactant hydrophobe (redC), the molecular hydrophobicity (log P), the number of carbon atoms in the hydrophobe (C), the hydrophilic-lipophilic balance according to Davis (Davis), the critical packing parameter with respect to whether the hydrophobe was branched or not (redCPP), and the critical micelle concentration. Surfactant toxicity tended to increase with increasing alkyl chain lengths.

  • 469.
    Uppgård, Lise-Lott
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wold, Svante
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivariate quantitative structure-activity relationships for the aquatic toxicity of alkyl polyglucosides2000In: Tenside Surfactants Detergents:, Vol. 37, no 2, p. 131-8Article in journal (Refereed)
    Abstract [en]

    The aquatic toxicity of 34 alkyl polyglucosides (APGs) towards two fresh-water species, Thamnocephalus platyurus and Brachionus calyciflorus were studied. The toxicity tests were performed using so-called toxkits, and for each surfactant the results are presented as (10)log (mean LC50) values. The toxicity data were combined with physico-chemical data for the APGs, and a Multivariate Quantitative Structure-Activity Relationship (M-QSAR) model was calculated. Partial Least Squares (PLS) regression was used to develop the M-QSAR model. The resulting linear M-QSAR model explained 93.6% of the variance in the biological response and had a predictability of 86.6% according to cross-validation. The physico-chemical properties with the strongest influences on the toxicity of the surfactants were the critical micelle concentration (c.m.c.), wetting, contact angle, and number of carbon atoms in their hydrophobic parts (C and redC).

  • 470.
    Velikyan, Irina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bulenga, Thomas N
    Selvaraju, Ram Kumar
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Espes, Daniel
    Rosenström, Ulrika
    Eriksson, Olof
    Dosimetry of [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 - impact on the feasibility of insulinoma internal radiotherapy.2015In: American journal of nuclear medicine and molecular imaging, ISSN 2160-8407, Vol. 5, no 2, p. 109-26Article in journal (Refereed)
    Abstract [en]

    [(68)Ga]-DO3A-VS-Cys(40)-Exendin-4 has been shown to be a promising imaging candidate for targeting glucagon like peptide-1 receptor (GLP-1R). In the light of radiotheranostics and personalized medicine the (177)Lu-labelled analogue is of paramount interest. In this study we have investigated the organ distribution of [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 in rat and calculated human dosimetry parameters in order to estimate the maximal acceptable administered radioactivity, and thus potential applicability of [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 for internal radiotherapy of insulinomas. Nine male and nine female Lewis rats were injected with [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 for ex vivo organ distribution study at nine time points. The estimation of human organ/total body absorbed and total effective doses was performed using Organ Level Internal Dose Assessment Code software (OLINDA/EXM 1.1). Six more rats (male: n = 3; female: n = 3) were scanned by single photon emission tomography and computed tomography (SPECT-CT). The renal function and potential cell dysfunction were monitored by creatinine ISTAT and glucose levels. The fine uptake structure of kidney and pancreas was investigated by ex vivo autoradiography. Blood clearance and washout from most of the organs was fast. The kidney was the dose-limiting organ with absorbed dose of 5.88 and 6.04 mGy/MBq, respectively for female and male. Pancreatic beta cells demonstrated radioactivity accumulation. Renal function and beta cell function remained unaffected by radiation. The absorbed dose of [(177)Lu]-DO3A-VS-Cys(40)-Exendin-4 to kidneys may limit the clinical application of the agent. However, hypothetically, kidney protection and peptidase inhibition may allow reduction of kidney absorbed dose and amplification of tumour absorbed doses.

  • 471. Venkatakrishnan, K.
    et al.
    Friberg, Lena E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Ouellet, D.
    Mettetal, J. T.
    Stein, A.
    Troconiz, I. F.
    Bruno, R.
    Mehrotra, N.
    Gobburu, J.
    Mould, D. R.
    Optimizing Oncology Therapeutics Through Quantitative Translational and Clinical Pharmacology: Challenges and Opportunities2015In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 97, no 1, p. 37-54Article in journal (Refereed)
    Abstract [en]

    Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety.

  • 472.
    Vestin, Jenny
    Mid Sweden University, Faculty of Science, Technology and Media, Department of Natural Sciences.
    Biogeochemical Interactions between Soil, Soil Solution and Stream Water2007Doctoral thesis, comprehensive summary (Other academic)
  • 473.
    Viklund, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    PREVALENCE OF HPV IN ANAL CARCINOMA AS REVEALED BY P16IMMUNOHISTOCHEMISTRY – A RETROSPECTIVE STUDY2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background

    Squamous cell carcinoma of the anus is often considered related to chronic infection of

    oncogene HPV types, primarily HPV16 and HPV18. P16 is a tumor suppressing protein

    involved in the cell cycle. This protein is normally inhibited by the pRB (retinoblastoma)

    protein, however HPV produces the protein E7 which binds to pRB and inactivates it.

    Overexpression of p16 therefore indicates HPV-infection.

    Purpose

    The purpose of this study was to determine the likelihood of HPV-infection being the cause of

    squamous cell carcinoma of the anus.

    Materials and methods

    The method used was immunohistochemistry using antibody towards p16-antigen. A

    pathologist evaluated the tissues and graded them depending on the percentage of cancer cells

    showing presence of p16. Tissues from 63 patients, 49 women, 14 men, were used.

    Results

    The results showed that 81 % of patients tested positive for p16. Cases showed positive

    results in 85.7 % for women versus 64.3 % for men. Mann-Whitney U-test showed a

    difference between genders with a two-tailed p value of 0.00386. Spearman’s rho test showed

    no statistical monotone correlation between degree of overexpression of p16 and patient age.

    Conclusion

    In conclusion this study has shown that HPV-infection in 81 % of cases was the cause of

    squamous cell carcinoma of the anus. The study further showed higher likelihood of

    HPV-infection being the cause of the disease among female patients. The study could not

    show patient age being a factor in likelihood of HPV-infection being the cause.

  • 474.
    Vikström, Anna C.
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
    Wilson, Kathryn M.
    Paulsson, Birgit
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
    Athanassiadis, Ioannis
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
    Grönberg, Henrik
    Adami, Hans-Olov
    Adolfsson, Jan
    Mucci, Lorelei A.
    Bälter, Katarina
    Törnqvist, Margareta
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
    Alcohol influence on acrylamide to glycidamide metabolism assessed with hemoglobin-adducts and questionnaire data2010In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 58, no 3, p. 820-824Article in journal (Refereed)
    Abstract [en]

    Our purpose was to investigate whether alcohol (ethanol) consumption could have an influence on the metabolism of acrylamide to glycidamide in humans exposed to acrylamide through food. We studied a subsample from a population-based case–control study of prostate cancer in Sweden (CAPS). Questionnaire data for alcohol intake estimates was compared to the ratio of hemoglobin-adduct levels for acrylamide and glycidamide, used as a measure of individual differences in metabolism. Data from 161 non-smoking men were processed with regard to the influence of alcohol on the metabolism of acrylamide to glycidamide. A negative, linear trend of glycidamide-adduct to acrylamide-adduct-level ratios with increasing alcohol intake was observed and the strongest association (p-value for trend = 0.02) was obtained in the group of men with the lowest adduct levels (⩽47 pmol/g globin) when alcohol intake was stratified by acrylamide-adduct levels. The observed trend is likely due to a competitive effect between ethanol and acrylamide as both are substrates for cytochrome P450 2E1. Our results, strongly indicating that ethanol influence metabolism of acrylamide to glycidamide, partly explain earlier observations of only low to moderate associations between questionnaire data on dietary acrylamide intake and hemoglobin-adduct levels.

  • 475.
    Waldenborg, Micael
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Echocardiographic measurements at Takotsubo cardiomyopathy: transient left ventricular dysfunction2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Takotsubo cardiomyopathy (TTC) is a disease characterized by transient left ventricular (LV) dysfunction and typical wall motion abnormalities in apical parts, without obvious signs of coronary influence. Due to its elusive natural cause and the lack of clarified pathology, further studies are needed. Thirteen patients presented with an episode of TTC, and referred to Örebro University Hospital (USÖ), were prospectively included and investigated by comparisons made at onset (acute phase) against at follow-up three months later (recovery phase). Including echocardiographic measurements, focused on biventricular systolic long-axis function and conventional diastolic function (DF) variables. Systolic improvement was shown, while most DF data were unchanged, suggesting that TTC is mainly a systolic disease affecting both ventricles.

    Diagnosis should include multidisciplinary engagement, as TTC associates both with emotional stress and pathological markers of physiological stress. In this thesis, such approach was offered to the aforementioned patients; to see if a common denominator could be found, thus, contributing to better handling. Emotional state was assessed, along with an array of cardiac investigations in addition to echocardiography. Acutely, imbalance in the autonomic cardiac control was shown, as well as a trend toward posttraumatic stress, but specific findings allowing conclusions on differential diagnosis could not be demonstrated.

    By adding another 15 TTC patients (i.e. 28 in total), through collaboration with observers from USA, a retrospective echocardiographic analysis could be done to further study DF; concluding that TTC associates with impairment of conventional DF variables which tends to parallel the systolic recovery, in contrary to the initial result but in line with other causesof LV dysfunction.

    Magnetic resonance imaging (MRI) is another method of choice at TTC. The USÖ patients had cardiac MRI, thus, a retrospective analysis was done to investigate the effect on LV geometry, both echocardiographic and by MRI; suggesting that TTC is consistently associated with increased LV mass, due to a local impact that seems to follow the change in LVconcentric wall motion.

  • 476.
    Wallménius, Katarina
    et al.
    Department of Medical Sciences, Section of Clinical Microbiology, Uppsala University.
    Barboutis, Christos
    Natural History Museum of Crete, University of Crete, Iraklion, Greece.
    Fransson, Thord
    Swedish Museum of Natural History, Department of.
    Jaenson, Thomas GT
    Medical Entomology Unit, Department of Organismal Biology, Uppsala University.
    Lindgren, Per-Eric
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University.
    Nyström, Fredrik
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University.
    Olsen, Björn
    Department of Medical Sciences, Section of Infectious Diseases, Uppsala University.
    Salanek, Erik
    Department of Medical Sciences, Section of Infectious Diseases, Uppsala University.
    Nilsson, Kenneth
    Department of Medical Sciences, Section of Clinical Microbiology, Uppsala University.
    Spotted fever Rickettsia species in Hyalomma and Ixodes ticks infesting migratory birds in the European Mediterranean area2014In: Parasites & Vectors, ISSN 1756-3305, E-ISSN 1756-3305, Vol. 7Article in journal (Refereed)
  • 477.
    Wallner, Fredrik K
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Spjut, Sara
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Boström, Dan
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics, Energy Technology and Thermal Process Chemistry.
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Synthesis and evaluation of 2-(2-fluoro-4-hydroxymethyl-5-methoxy-phenoxy)acetic acid as a linker in solid-phase synthesis monitored by gel-phase 19F NMR spectroscopy2007In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 5, p. 2464-2471Article in journal (Refereed)
    Abstract [en]

    Gel-phase 19F NMR spectroscopy is a useful monitoring technique for solid-phase organic chemistry due to the high information content it delivers and swift acquisition times, using standard NMR spectrometers. This paper describes the synthesis of the novel linker 2-(2-fluoro-4-hydroxymethyl-5-methoxy-phenoxy)acetic acid in 29% yield over seven steps, using nucleophilic aromatic substitutions on 2,4,5-trifluorobenzonitrile as key steps. Following standard solid-phase synthesis a peptide could be cleaved from the linker using 20% TFA in CH2Cl2 in 30 minutes, in contrast to a previously described monoalkoxy linker that requires 90% TFA in water at elevated temperature. A resin-bound peptide could be successfully glycosylated using only two equivalents of a thioglycoside donor, activated with N-iodosuccinimide and trifluoromethanesulfonic acid, and subsequent cleavage and deprotection gave the target glycopeptide. Direct glycosylation of the linker itself followed by mild acidic cleavage gave a fully protected hemiacetal for further chemical manipulation.

  • 478. Wang, Z.
    et al.
    Fu, Y.
    Kang, Zhengzhong
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology.
    Liu, X.
    Chen, N.
    Wang, Q.
    Tu, Yaoquan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology.
    Wang, L.
    Song, S.
    Ling, D.
    Song, H.
    Kong, X.
    Fan, C.
    Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton2017In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 139, no 44, p. 15784-15791Article in journal (Refereed)
    Abstract [en]

    DNA has proven of high utility to modulate the surface functionality of metal-organic frameworks (MOFs) for various biomedical applications. Nevertheless, current methods for preparing DNA-MOF nanoparticles rely on either inefficient covalent conjugation or specific modification of oligonucleotides. In this work, we report that unmodified oligonucleotides can be loaded on MOFs with high density (∼2500 strands/particle) via intrinsic, multivalent coordination between DNA backbone phosphate and unsaturated zirconium sites on MOFs. More significantly, surface-bound DNA can be efficiently released in either bulk solution or specific organelles in live cells when free phosphate ions are present. As a proof-of-concept for using this novel type of DNA-MOFs in immunotherapy, we prepared a construct of immunostimulatory DNA-MOFs (isMOFs) by intrinsically coordinating cytosine-phosphate-guanosine (CpG) oligonucleotides on biocompatible zirconium MOF nanoparticles, which was further armed by a protection shell of calcium phosphate (CaP) exoskeleton. We demonstrated that isMOFs exhibited high cellular uptake, organelle specificity, and spatiotemporal control of Toll-like receptors (TLR)-triggered immune responses. When isMOF reached endolysosomes via microtubule-mediated trafficking, the CaP exoskeleton dissolved in the acidic environment and in situ generated free phosphate ions. As a result, CpG was released from isMOFs and stimulated potent immunostimulation in living macrophage cells. Compared with naked CpG-MOF, isMOFs exhibited 83-fold up-regulation in stimulated secretion of cytokines. We thus expect this isMOF design with soluble CaP exoskeleton and an embedded sequential "protect-release" program provides a highly generic approach for intracellular delivery of therapeutic nucleic acids.

  • 479.
    Webb, Matthew J
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Palmgren, Pål
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Surface and Interface Science.
    Pal, Prabir
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Surface and Interface Science.
    Karis, Olof
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Surface and Interface Science.
    Grennberg, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    A simple method to produce almost perfect graphene on highly oriented pyrolytic graphite2011In: Carbon, ISSN 0008-6223, E-ISSN 1873-3891, Vol. 49, no 10, p. 3242-3249Article in journal (Refereed)
  • 480.
    Wei, Q
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Kullberg, EB
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Gedda, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Trastuzumab-conjugated boron-containing liposomes for tumor-celltargeting; development and cellular studies.2003In: Int J Oncol, Vol. 23, p. 1159-Article in journal (Refereed)
  • 481. Wergeland, Gro Janne H.
    et al.
    Fjermestad, Krister W.
    Marin, Carla E.
    Haugland, Bente Storm-Mowatt
    Silverman, Wendy K.
    Öst, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Haukeland University Hospital, Norway; University of Bergen, Norway; Karolinska Institutet, Sweden.
    Havik, Odd E.
    Heiervang, Einar R.
    Predictors of dropout from community clinic child CBT for anxiety disorders2015In: Journal of Anxiety Disorders, ISSN 0887-6185, E-ISSN 1873-7897, Vol. 31, p. 1-10Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate predictors of treatment dropout among 182 children (aged 8-15 years) participating in an effectiveness trial of manual-based 10-session individual and group cognitive behavior therapy (CBT) for anxiety disorders in community clinics. The dropout rate was 14.4%, with no significant difference between the two treatment conditions. We examined predictors for overall dropout (n=26), early (<= session 4, n = 15), and late dropout (>= session 5, n = 11). Overall dropout was predicted bylaw child and parent rated treatment credibility, and high parent self-rated internalizing symptoms. Low child rated treatment credibility predicted both early and late dropout. High parent self-rated internalizing symptoms predicted early dropout, whereas low parent rated treatment credibility predicted late dropout. These results highlight the importance of addressing treatment credibility, and to offer support for parents with internalizing symptoms, to help children and families remain in treatment.

  • 482.
    Westerberg, Per-Anton
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tivesten, Åsa
    Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Göteborg, Sweden.
    Karlsson, Magnus
    Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Orthopedic Surgery, Lund University, Skåne University Hospital, Sweden..
    Mellström, Dan
    Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden..
    Ohlsson, Claes
    Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden..
    Larsson, Tobias
    Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm,.
    Linde, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Klotho polymorphisms, FGF23 and mortality among elderly men (Swedish MrOs).Manuscript (preprint) (Other academic)
    Abstract [en]

     

    Westerberg, P-A and Kindmark, A contributed equally in preparation of the manuscript.

    Introduction. α-Klotho is the co receptor for Fibroblast growth factor(FGF)23and crucial for phosphate and vitamin D metabolism. Variants in the KLOTHO (KL) gene are associated with longevity and cardiovascular morbidities. Primary aim of this study is to examine if variations in  KL affect mortality risk in a cohort of elderly men. Secondary aims are to examine associations with serum levels of FGF23, phosphate and renal function.

    Methods and results. 27 single nucleotide polymorphisms (SNP) in KLOTHO were genotyped using single base primer extension mass array technique on samples from 2924 men, aged 69 to 81 years, included in Swedish MrOs. After in average 6.1 years of follow up 584 had died, 214 of cardiovascular cause.  After quality analyses and tagging of haplotypes 11 SNPs were analyzed for variation in  mortality risk, serum levels of FGF23, phosphate, calcium and renal function. There were no associations with mortality of all cause. One SNP, (rs398655), in proximity to the promoter, demonstrated an increased Hazard ratio (95% Confidence interval(CI)) of 53% (95% CI, 8-118%) for death due to CVD in heterozygotes compared to homozygotes. Analysis using a dominant model showed an association between SNPs in the 5’ end of the gene and eGFR, phosphate level and logFGF23 (P=0.01).

    Conclusion. KL polymorphisms are associated with variation in FGF23 and phosphate.

  • 483.
    Westerlund, Jessica
    Örebro University, School of Medical Sciences.
    Occupational exposure to trichloramine and trihalomethanes: adverse respiratory and ocular effects among Swedish indoor swimming pool workers2016Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Occupational exposure in swimming pool facilities related to disinfection by-products (DBPs) has been an issue for the last 15 years. Trichloramine (NCl3) and trihalomethanes (THMs) are DBPs formed in swimming pool water following a reaction between organic matter containing nitrogen or organic or inorganic matter, and chlorine. Due to its volatility, trichloramine can easily evaporate into the air and cause nausea and irritation of the eyes and upper airways. Symptoms are likely to be particularly pronounced in those suffering from asthma. Chloroform is the dominant THM in swimming pool atmospheres and is classified by the International Agency for Research on Cancer (IARC) as being possibly carcinogenic to humans. There are no adverse health effects reported among swimming pool employees due to occupational exposure levels of THMs found in the air at swimming pools.

    There is no OEL for trichloramine adapted in Sweden, but some reference values and recommendations based on stationary measurements at the pool side are available. In 2006, the World Health Organisation (WHO) recommended a reference value for trichloramine of 500 μg/m3. The Swedish OEL for chloroform is 10 000 μg/m3.

    This thesis describes research into the occupational exposure to airborne trichloramine and THMs in eight Swedish indoor swimming pool facilities and the investigation into the prevalence of adverse health effects, manifesting primarily as ocular and respiratory symptoms.

    Concentrations of trichloramine and chloroform in Swedish indoor swimming pool facilities were found to be in the same range or lower compared to previous studies in other countries. The trichloramine concentrations varied between <1 and 240 μg/m3 for the personal sampling and between <1 and 640 μg/m3 for the stationary sampling. Personal trichloramine levels in the high-exposure group were more than 60% higher compared to the corresponding stationary measurements. The exposed group had a higher frequency of self-reported ocular and nasal symptoms compared to the controls. A significant difference in the concentration of exhaled FENO over a work shift with an increase in the exposed group, indicated acute airway inflammation due to respiratory irritant agent exposure. Although a dose-response effect could not be established, the results indicate an elevated risk of occupational health problems in indoor swimming pools and calls for an OEL to be established, based on personal sampling.

  • 484.
    Westerlund, Kristina
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Honarvar, H.
    Tolmachev, V.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Protein Technology.
    Design, Preparation, and Characterization of PNA-Based Hybridization Probes for Affibody-Molecule-Mediated Pretargeting2015In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 26, no 8, p. 1724-1736Article in journal (Refereed)
    Abstract [en]

    In radioimmunotherapy, the contrast between tumor and normal tissue can be improved by using a pretargeting strategy with a primary targeting agent, which is conjugated to a recognition tag, and a secondary radiolabeled molecule binding specifically to the recognition tag. The secondary molecule is injected after the targeting agent has accumulated in the tumor and is designed to have a favorable biodistribution profile, with fast clearance from blood and low uptake in normal tissues. In this study, we have designed and evaluated two complementary peptide nucleic acid (PNA)-based probes for specific and high-affinity association in vivo. An anti-HER2 Affibody-PNA chimera, Z<inf>HER2:342</inf>-SR-HP1, was produced by a semisynthetic approach using sortase A catalyzed ligation of a recombinantly produced Affibody molecule to a PNA-based HP1-probe assembled using solid-phase chemistry. A complementary HP2 probe carrying a DOTA chelator and a tyrosine for dual radiolabeling was prepared by solid-phase synthesis. Circular dichroism (CD) spectroscopy and UV thermal melts showed that the probes can hybridize to form a structured duplex with a very high melting temperature (T<inf>m</inf>), both in HP1:HP2 and in Z<inf>HER2:342</inf>-SR-HP1:HP2 (T<inf>m</inf> = 86-88 °C), and the high binding affinity between Z<inf>HER2:342</inf>-SR-HP1 and HP2 was confirmed in a surface plasmon resonance (SPR)-based binding study. Following a moderately fast association (1.7 × 105 M-1 s-1), the dissociation of the probes was extremely slow and <5% dissociation was observed after 17 h. The equilibrium dissociation constant (K<inf>D</inf>) for Z<inf>HER2:342</inf>-SR-HP1:HP2 binding to HER2 was estimated by SPR to be 212 pM, suggesting that the conjugation to PNA does not impair Affibody binding to HER2. The biodistribution profiles of 111In- and 125I-labeled HP2 were measured in NMRI mice, showing very fast blood clearance rates and low accumulation of radioactivity in kidneys and other organs. The measured radioactivity in blood was 0.63 ± 0.15 and 0.41 ± 0.15%ID/g for 125I- and 111In-HP2, respectively, at 1 h p.i., and at 4 h p.i., the kidney accumulation of radioactivity was 0.17 ± 0.04%ID/g for 125I-HP2 and 3.83 ± 0.39%ID/g for 111In-HP2. Taken together, the results suggest that a PNA-based system has suitable biophysical and in vivo properties and is a promising approach for pretargeting of Affibody molecules.

  • 485.
    Wiberg, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Granstam, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ingvast, Sofie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Harkonen, T.
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Knip, M.
    Univ Helsinki, Childrens Hosp, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland.;Folkkhalsan Res Ctr, Helsinki, Finland.;Tampere Univ Hosp, Dept Pediat, Tampere, Finland..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Skog, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Characterization of human organ donors testing positive for type 1 diabetes-associated autoantibodies2015In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 182, no 3, p. 278-288Article in journal (Refereed)
    Abstract [en]

    In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within the Nordic Network for Islet Transplantation. One thousand and thirty organ donors have been screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA (33% of all non-diabetic donors) were studied in more detail, together with 32 matched controls. Mean age among the autoantibody-positive donors was 526 (range 21-74), family history of type 1 diabetes (T1D) was unknown, and no donor was genetically predisposed for T1D regarding the human leucocyte antigen (HLA) locus. Subjects were analysed for islet cell antibodies (ICA), insulin autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas morphology and clinical data were examined. Eight non-diabetic donors tested positive for two antibodies and one donor tested positive for four antibodies. No insulitis or other signs of a diabetic process were found in any of the donors. While inflammatory cells were present in all donors, subjects with high GADA titres had significantly higher CD45 cell numbers in exocrine tissue than controls. The extent of fibrosis was more pronounced in autoantibody-positive donors, even in subjects with lower GADA titres. Notably, it is possible that events not related directly to T1D (e.g. subclinical pancreatitis) may induce autoantibodies in some cases.

  • 486.
    Wiberg, Jörgen
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Mechanisms controlling DNA damage survival and mutation rates in budding yeast2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    All living organisms are made of cells, within which genetic information is stored on long strands of deoxyribonucleic acid (DNA). The DNA encodes thousands of different genes and provides the blueprint for all of the structures and activities occurring within the cell. The building blocks of DNA are the four deoxyribonucleotides, dATP, dGTP, dTTP, and dCTP, which are collectively referred to as dNTPs.

    The key enzyme in the production of dNTPs is ribonucleotide reductase (RNR). In the budding yeast Saccharomyces cerevisiae, the concentrations of the individual dNTPs are not equal and it is primarily RNR that maintains this balance. Maintenance of the dNTP pool balance is critical for accurate DNA replication and DNA repair since elevated and/or imbalanced dNTP concentrations increase the mutation rate and can ultimately lead to genomic instability and cancer. In response to DNA damage, the overall dNTP concentration in S. cerevisiae increases. Cell survival rates increase as a result of the elevated concentration of dNTPs, but the cells also suffer from a concomitant increase in mutation rates. When the replication machinery encounters DNA damage that it cannot bypass, the replication fork stalls and recruits specialized translesion synthesis (TLS) polymerases that bypass the damage so that replication can continue. We hypothesized that elevated dNTP levels in response to DNA damage may allow the TLS polymerases to more efficiently bypass DNA damage. To explore this possibility, we deleted all known TLS polymerases in a yeast strain in which we could artificially increase the dNTP concentrations. Surprisingly, even though all TLS polymerases had been deleted, elevated dNTP concentrations led to increased cell survival after DNA damage. These results suggest that replicative DNA polymerases may be involved in the bypass of certain DNA lesions under conditions of elevated dNTPs. We confirmed this hypothesis in vitro by demonstrating that high dNTP concentrations result in an increased efficiency in the bypass of certain DNA lesions by DNA polymerase epsilon, a replicative DNA polymerase not normally associated with TLS activity.

    We asked ourselves if it would be possible to create yeast strains with imbalanced dNTP concentrations in vivo, and, if so, would these imbalances be recognized by the checkpoint control mechanisms in the cell. To address these questions, we focused on the highly conserved loop2 of the allosteric specificity site of yeast Rnr1p. We introduced several mutations into RNR1-loop2 that resulted in changes in the amino acid sequence of the protein.

    Each of the rnr1-loop2 mutation strains obtained had different levels of individual dNTPs relative to the others. Interestingly, all of the imbalanced dNTP concentrations led to increased mutation rates, but these mutagenic imbalances did not activate the S-phase checkpoint unless one or several dNTPs were present at concentrations that were too low to sustain DNA replication. We were able to use these mutant yeast strains to successfully correlate amino acid substitutions within loop2 of Rnr1p to specific ratios of dNTP concentrations in the cells. We also demonstrated that specific imbalances between the individual dNTP levels result in unique mutation spectra. These mutation spectra suggest that the mutagenesis that results from imbalanced dNTP pools is due to a decrease in fidelity of the replicative DNA polymerases at specific DNA sequences where they are more likely to make a mistake. The mutant rnr1-loop2 strains that we have created with defined dNTP pool imbalances will be of great value for in vivo studies of polymerase fidelity, translesion synthesis by specialized DNA polymerases, and lesion recognition by the DNA repair machinery.

  • 487.
    Widenkvist, Erika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
    Quinlan, Ronald A.
    Dept of Applied Science.
    Holloway, Brian C.
    Luna Innovations Nano Works Division.
    Grennberg, Helena
    Dept of biochemistry and organic chemistry.
    Jansson, Ulf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
    Synthesis of Nanostructed Tungsten Oxide Thin Films2008In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 8, no 10, p. 3750-3753Article in journal (Refereed)
    Abstract [en]

    A facile and inexpensive method to produce thin films of nanostructured tungsten oxide is described. A nanocrystalline tungstite (WO3·H2O) film is spontaneously formed when a tungsten substrate is immersed in nitric acid at elevated temperatures. The resulting thin film is composed of plate-like tungstite crystals with edges preferentially directed out from the substrate surface. The tungstite can easily be transformed into WO3 by annealing. Patterned WO3·H2O/W structures can be obtained by a combination of lithographic techniques and etching. In this study, the effect of exposure time, acid concentration, and temperature on the microstructure of the films has been investigated. The potential of this inexpensive synthesis method to produce large-area coatings of nanostructured tungsten oxide as well as patterned films makes it interesting for several different applications, such as batteries, gas sensors, and photocatalysts.

  • 488.
    Xin, D. L.
    et al.
    Department of Surgery, University of Pennsylvania, USA.
    Hadrevi, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Elliott, M. E.
    Department of Neurosurgery, Thomas Jefferson University, USA.
    Amin, M
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadephia, USA.
    Harris, M. Y.
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, USA.
    Barr-Gillespie, A
    College of Health Professions, Pacific University, USA.
    Barbe, M. F.
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, USA.
    Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task2017In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 18, article id 36Article in journal (Refereed)
    Abstract [en]

    Background: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.

    Methods: Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.

    Results: TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.

    Conclusions: These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.

  • 489. Xu, Jing
    et al.
    Marsac, Remi
    Costa, Dominique
    Cheng, Wei
    Wu, Feng
    Boily, Jean-Francois
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hanna, Khalil
    Co-Binding of Pharmaceutical Compounds at Mineral Surfaces: Molecular Investigations of Dimer Formation at Goethite/Water Interfaces2017In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 51, no 15, p. 8343-8349Article in journal (Refereed)
    Abstract [en]

    The emergence of antibiotic and anti-inflammatory agents in aquatic and terrestrial systems is becoming a serious threat to human and animal health worldwide. Because pharmaceutical compounds rarely exist individually in nature, interactions between various compounds can have unforeseen effects on their binding to mineral surfaces. This work demonstrates this important possibility for the case of two typical antibiotic and anti-inflammatory agents (nalidixic acid (NA) and niflumic acid (NFA)) bound at goethite (alpha FeOOH) used as a model mineral surface. Our multidisciplinary study, which makes use of batch sorption experiments, vibration spectroscopy and periodic density functional theory calculations, reveals enhanced binding of the otherwise weakly bound NFA caused by unforeseen intermolecular interactions with mineral-bound NA. This enhancement is ascribed to the formation of a NFA NA dimer whose energetically favored formation (-0.5 eV compared to free molecules) is predominantly driven by van der Waals interactions. A parallel set of efforts also showed that no. cobinding occurred with sulfamethoxazole (SMX) because of the lack of molecular interactions with coexisting contaminants. As such, this article raises the importance of recognizing drug cobinding, and lack of cobinding, for predicting and developing policies on the fate of complex mixtures of antibiotics and anti-inflammatory agents in nature.

  • 490.
    Yang, Lingling
    et al.
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Di, Guohu
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Qi, Xia
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Qu, Mingli
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Wang, Yao
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Duan, Haoyun
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Danielson, Patrik
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Xie, Lixin
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Zhou, Qingjun
    State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.
    Substance P promotes diabetic corneal epithelial wound healing through molecular mechanisms mediated via the neurokinin-1 receptor.2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 12, p. 4262-4274Article in journal (Refereed)
    Abstract [en]

    Substance P (SP) is a neuropeptide, predominantly released from sensory nerve fibers, with a potentially protective role in diabetic corneal epithelial wound healing. However, the molecular mechanism remains unclear. We investigated the protective mechanism of SP against hyperglycemia-induced corneal epithelial wound healing defects, using type 1 diabetic mice and high glucose-treated corneal epithelial cells. Hyperglycemia induced delayed corneal epithelial wound healing, accompanied with attenuated corneal sensation, mitochondrial dysfunction, and impairments of Akt-, EGFR-, and Sirt1-activation, as well as decreased reactive oxygen species (ROS) scavenging capacity. However, SP application promoted the epithelial wound healing, the recovery of corneal sensation, the improvement of mitochondrial function, and the reactivation of Akt, EGFR and Sirt1, as well as increased ROS scavenging capacity, in both diabetic mouse corneal epithelium and high glucose-treated corneal epithelial cells. The promotion of SP on diabetic corneal epithelial healing was completely abolished by a NK-1 receptor antagonist. Moreover, the subconjunctival injection of NK-1 receptor antagonist also caused diabetic corneal pathological changes in normal mice. In conclusion, the results suggest that SP-NK-1 receptor signaling plays a critical role in the maintenance of corneal epithelium homeostasis, and that SP signaling through the NK-1 recssssseptor contributes to the promotion of diabetic corneal epithelial wound healing by rescued activation of Akt, EGFR, and Sirt1, improvement of mitochondrial function, and increased ROS scavenging capacity.

  • 491.
    Yang, Wenzhi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Widenkvist, Erika
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Inorganic Chemistry.
    Jansson, Ulf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Inorganic Chemistry.
    Grennberg, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry.
    Stirring-induced aggregation of graphene in suspension2011In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 35, no 4, p. 780-783Article in journal (Refereed)
    Abstract [en]

    Graphene in suspension undergoes stirring-induced aggregation that leads to reversible agglomeration and folding/scrolling, all of which affects the Raman spectra; the findings are of importance in all solution-based protocols for graphene preparation and processing.

  • 492. Yousefzadeh, Matthew J
    et al.
    Wyatt, David W
    Takata, Kei-Ichi
    Mu, Yunxiang
    Hensley, Sean C
    Tomida, Junya
    Bylund, Göran O
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Doublié, Sylvie
    Johansson, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ramsden, Dale A
    McBride, Kevin M
    Wood, Richard D
    Mechanism of suppression of chromosomal instability by DNA polymerase POLQ2014In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 10, p. e1004654-Article in journal (Refereed)
    Abstract [en]

    Although a defect in the DNA polymerase POLQ leads to ionizing radiation sensitivity in mammalian cells, the relevant enzymatic pathway has not been identified. Here we define the specific mechanism by which POLQ restricts harmful DNA instability. Our experiments show that Polq-null murine cells are selectively hypersensitive to DNA strand breaking agents, and that damage resistance requires the DNA polymerase activity of POLQ. Using a DNA break end joining assay in cells, we monitored repair of DNA ends with long 3' single-stranded overhangs. End joining events retaining much of the overhang were dependent on POLQ, and independent of Ku70. To analyze the repair function in more detail, we examined immunoglobulin class switch joining between DNA segments in antibody genes. POLQ participates in end joining of a DNA break during immunoglobulin class-switching, producing insertions of base pairs at the joins with homology to IgH switch-region sequences. Biochemical experiments with purified human POLQ protein revealed the mechanism generating the insertions during DNA end joining, relying on the unique ability of POLQ to extend DNA from minimally paired primers. DNA breaks at the IgH locus can sometimes join with breaks in Myc, creating a chromosome translocation. We found a marked increase in Myc/IgH translocations in Polq-defective mice, showing that POLQ suppresses genomic instability and genome rearrangements originating at DNA double-strand breaks. This work clearly defines a role and mechanism for mammalian POLQ in an alternative end joining pathway that suppresses the formation of chromosomal translocations. Our findings depart from the prevailing view that alternative end joining processes are generically translocation-prone.

  • 493.
    Yu, Ji-Guo
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bonnerud, Patrik
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Eriksson, Anders
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Stål, Per S.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Tegner, Yelverton
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Malm, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Effects of long term supplementation of anabolic androgen steroids on human skeletal muscle2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, article id e105330Article in journal (Refereed)
    Abstract [en]

    The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained morphological changes in human skeletal muscle, leading to physical performance enhancement.

  • 494.
    Zakrisson Mortensson, Elin
    et al.
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Öhlen, Malin
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Natural Science and Biomedicine.
    Samband mellan tandvårdsrädsla och temperament- vilken betydelse har kön och utländsk bakgrund?: En tvärsnittsstudie på ungdomar i nionde klass i Jönköpings kommun2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Summary

     

    Associations between dental fear and temperament - does sex or foreign origin have an impact? A cross-sectional study of youths in the ninth grade in Jönköping.

     

    Background: Dental fear is a common problem in dental care which can contribute to a poor oral health. Previous research shows certain correlations between dental fear and temperaments but varies. Objective: The aim of this study was to investigate the association between dental fear and temperament of youths in ninth grade. Method: The study is a cross-sectional study based on a stratified sample of youths in ninth grade. Two validated questionnaires containing self-reported questions about dental fear and temperament was distributed. Results: A total of 3 % was found to have dental fear. Significant correlation between DFS scores and shyness were observed. Women had significantly higher mean in DFS scores and emotionality, compared to men. Males had significantly higher mean in the temperament activity. No significant associations were found between dental fear and foreign or Swedish background. Youths with a Swedish background had higher mean in sociability. Conclusion: The prevalence of dental fear was 3 % of the young people. The women had a higher score of DFS and emotionality. The men reported higher degree of activity. Young people with foreign background had a lower degree of sociability. A significant association was found between DFS scores and shyness.

  • 495.
    Zamani, Akram
    University of Borås, School of Engineering.
    Superabsorbent Polymers from the Cell Wall of Zygomycetes Fungi2010Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The present thesis presents new renewable, antimicrobial and biodegradable superabsorbent polymers (SAPs), produced from the cell wall of zygomycetes fungi. The cell wall was characterized and chitosan, being one of the most important ingredients, was extracted, purified, and converted to SAP for use in disposable personal care products designed for absorption of different body fluids. The cell wall of zygomycetes fungi was characterized by subsequent hydrolysis with sulfuric and nitrous acids and analyses of the products. The main ingredients of the cell wall were found to be polyphosphates (4-20%) and copolymers of glucosamine and N-acetyl glucosamine, i.e. chitin and chitosan (45-85%). The proportion of each of these components was significantly affected by the fungal strain and also the cultivation conditions. Moreover, dual functions of dilute sulfuric acid in relation to chitosan, i.e. dissolution at high temperatures and precipitation at lowered temperatures, were discovered and thus used as a basis for development of a new method for extraction and purification of the fungal chitosan. Treatment of the cell wall with dilute sulfuric acid at room temperature resulted in considerable dissolution of the cell wall polyphosphates, while chitosan and chitin remained intact in the cell wall residue. Further treatment of this cell wall residue, with fresh acid at 120°C, resulted in dissolution of chitosan and its separation from the remaining chitin/chitosan of the cell wall skeleton which was not soluble in hot acid. Finally, the purified fungal chitosan (0.34 g/g cell wall) was recovered by precipitation at lowered temperatures and pH 8-10. The purity and the yield of fungal chitosan in the new method were significantly higher than that were obtained in the traditional acetic acid extraction method. As a reference to pure chitosan, SAP from shellfish chitosan, was produced by conversion of this biopolymer into water soluble carboxymethyl chitosan (CMCS), gelation of CMCS with glutaraldehyde in aqueous solutions (1-2%), and drying the resultant gel. Effects of carboxymethylation, gelation and drying conditions on the water binding capacity (WBC) of the final products, were investigated. Finally, choosing the best condition, a biological superabsorbent was produced from zygomycetes chitosan. The CMCS-based SAPs were able to absorb up to 200 g water/g SAP. The WBC of the best SAP in urine and saline solutions was 40 and 32 g/g respectively, which is comparable to the WBC of commercially acceptable SAPs under identical conditions (34-57 and 30-37 g/g respectively).

  • 496.
    Zamani, Akram
    et al.
    University of Borås, School of Engineering.
    Jeihanipour, Azam
    University of Borås, School of Engineering.
    Edebo, Lars
    Niklasson, Claes
    Taherzadeh, Mohammad J.
    University of Borås, School of Engineering.
    Determination of glucosamine and N-acetyl glucosamine in fungal cell walls2008In: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 56, no 18, p. 8314-8318Article in journal (Refereed)
    Abstract [en]

    A new method was developed to determine glucosamine (GlcN) and N-acetyl glucosamine (GlcNAc) in materials containing chitin and chitosan, such as fungal cell walls. It is based on two steps of hydrolysis with (i) concentrated sulfuric acid at low temperature and (ii) dilute sulfuric acid at high temperature, followed by one-step degradation with nitrous acid. In this process, chitin and chitosan are converted into anhydromannose and acetic acid. Anhydromannose represents the sum of GlcN and GlcNAc, whereas acetic acid is a marker for GlcNAc only. The method showed recovery of 90.1% of chitin and 85.7-92.4% of chitosan from commercial preparations. Furthermore, alkali insoluble material (AIM) from biomass of three strains of zygomycetes, Rhizopus oryzae, Mucor indicus, and Rhizomucor pusillus, was analyzed by this method. The glucosamine contents of AIM from R. oryzae and M. indicus were almost constant (41.7 +/- 2.2% and 42.0 +/- 1.7%, respectively), while in R. pusillus, it decreased from 40.0 to 30.0% during cultivation from 1 to 6 days. The GlcNAc content of AIM from R. oryzae and R. pusillus increased from 24.9 to 31.0% and from 36.3 to 50.8%, respectively, in 6 days, while it remained almost constant during the cultivation of M. indicus (23.5 +/- 0.8%).

  • 497.
    Zazzi, Åsa
    KTH, School of Chemical Science and Engineering (CHE), Chemistry.
    Chlorite: Geochemical properties, Dissolution kinetcis and Ni(II) sorption2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In Sweden, among other countries, a deep multi-barrier geological repository, KBS-3, is planned for the burial of nuclear waste. One of the barriers is identified as the grantic bedrock itself and in this environment chlorite is present at surfaces in fracture zones.

    This thesis is focused on characterisation of chlorite samples and studies of their dissolution and sorption behaviour, in order to verify chlorites capacity to retard possible radionuclide migration in the case of leaking canisters.

    Chlorite dissolution of has been studied in the pH interval 2-12, and as expected the dissolution is highest at acidic pH and at most alkaline pH, whereas dissolution is lowest at near neutral pH values. Chemical and physical properties of chlorites clearly influence the dissolution rates, and at steady-state dissolution rates in the interval 10-12 ‑ 10-13 mol g-1 s-1 was observed.

    Sorption studies were performed since Ni(II) is one of the important activation products in spent nuclear fuel and sorption data on minerals like chlorite are lacking. Ni(II) sorption onto chlorite was studied using batch technique as a function of; pH, concentration of Ni(II), ionic strength and solid concentrations. As expected, the sorption of Ni(II) onto chlorite was pH dependent, but not ionic strength dependent, with a sorption maximum at pH ~ 8, and with a Kd of ~ 103 cm3/g. This confirms that the Ni(II) sorption onto chlorite is primarily acting through surface complexation. The acid-base properties were determined by titrations and described by a non-electrostatical surface complexation model in FITEQL. Further, the sorption results were fit with a 2-pK NEM model and three surface complexes, Chl_OHNi2+, Chl_OHNi(OH)+ and Chl_OHNi(OH)2, gave the best fit using FITEQL.

  • 498.
    Zelenin, Sergey
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Käller, M.
    Nazarov, A.
    Brismar, H.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    High density custom microarrays formed by microcompartment amplification on glass surface2014In: 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014, Chemical and Biological Microsystems Society , 2014, p. 1027-1029Conference paper (Refereed)
    Abstract [en]

    Compartmentalization of a single DNA molecule is necessary for digital amplification. In the present study we have developed a microscale isothermal amplification using exponential rolling circle amplification (RCA). RCA was performed in PDMS microcompartments on a microarray glass, with a volume of less than 1 pL. Resulting amplicons were attached to the glass surface and formed a custom array with the density of spots above 2,5 × 105 per cm2. Our technology can be applied for digital amplification of DNA or RNA from a variety of complex biological samples in a microchip format.

  • 499. Zerbetto, Mirco
    et al.
    Polimeno, Antonino
    Kotsyubynskyy, Dmytro
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Ghalebani, Leila
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Kowalewski, Jozef
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Department of Physical Chemistry.
    Meirovitch, Eva
    Olsson, Ulrika
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    An integrated approach to NMR spin relaxation in flexible biomolecules: Application to β-D-glucopyranosyl-(1→6)-α-D-mannopyranosyl-OMe2009In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 131, no 23, p. p234501-Article in journal (Refereed)
    Abstract [en]

    The description of the reorientational dynamics of flexible molecules is a challenging task, in particular when the rates of internal and global motions are comparable. The commonly used simple mode-decoupling models are based on the assumption of statistical independence between these motions. This assumption is not valid when the time scale separation between their rates is small, a situation that was found to arise in oligosaccharides in the context of certain internal motions. To make possible the interpretation of NMR spin relaxation data from such molecules, we developed a comprehensive approach generally applicable to flexible rotators with one internal degree of freedom. This approach integrates a stochastic description of coupled global tumbling and internal torsional motion, quantum chemical calculations of the local potential and the local geometry at the site of the restricted torsion, and hydrodynamics-based calculations of the diffusive properties. The method is applied to the disaccharide -D-Glcp-(16)--D-[6-13C]-Manp-OMe dissolved in a DMSO-d6/D2O cryosolvent. The experimental NMR relaxation parameters, associated with the 13CH2 probe residing at the glycosidic linkage, include 13C T1 and T2 and 13C-{1H} nuclear Overhauser enhancement (NOE) as well as longitudinal and transverse dipole-dipole cross-correlated relaxation rates, acquired in the temperature range of 253–293 K. These data are predicted successfully by the new theory with only the H–C–H angle allowed to vary. Previous attempts to fit these data using mode-decoupling models failed.

  • 500.
    Zhou, Ye
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Andersson, Olof
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Lindberg, Peter
    Biacore AB, Rapsgatan 7, S-754 50, Uppsala, Sweden.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Protein Microarrays on Carboxymethylated Dextran Hydrogels: Immobilization, Characterization and Application2004In: Microchimica Acta, ISSN 0026-3672, E-ISSN 1436-5073, Vol. 147, no 1-2, p. 21-30Article in journal (Refereed)
    Abstract [en]

    Tetraoctadecylammonium bromide (TOAB, (CH3(CH2)17)4N+Br) has been used to print temporary hydrophobic barriers on carboxymethylated dextran (CMD) hydrogels to create a generic platform for protein microarray applications. The primary reason for printing temporary hydrophobic barriers is to prevent cross-contamination and overflow during microdrop dispensing. Equally important is to eliminate the risk for non-specific binding to the barriers during analyte exposure. This has been accomplished by introducing a regeneration step that removes the barriers after ligand immobilization. The overall fabrication process was characterized by microscopic wetting, atomic force microscopy, imaging ellipsometry, fluorescence microscopy, surface plasmon microscopy and biospecific interaction analysis. A series of model proteins including transferrin, Protein A, anti-myoglobin and bovine serum albumin was spotted into the TOAB-defined areas under different experimental conditions, e.g. at increased humidity and reduced substrate temperature or with glycerol as an additive in the protein solution. Much emphasis was devoted to studies aiming at exploring the homogeneity and activity of the immobilized proteins. The printed barriers were removed after protein immobilization using tert-n-butyl alcohol (TBA). TBA was found to be a very efficient agent as compared to previously used salt regeneration solutions, and the regeneration time could be reduced from 30 to 10 minutes. Finally, the potential of using the well established CMD hydrogel chemistry as a platform for protein microarrays was exploited using surface plasmon microscopy.

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