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  • 201.
    Hildingsson, Victoria
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Clarström, Anders
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Kartläggning av fysioterapeutiska interventioner i multimodal smärtrehabilitering inom primärvården.: En enkätstudie.2018Independent thesis Advanced level (degree of Master (One Year)), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund:

    Långvarig smärta är ett stort folkhälsoproblem som innebär stora kostnader för

    samhället och självklart också stort lidande för individen. Multimodal smärtrehabilitering

    (MMR) innebär att olika yrkeskategorier arbetar gemensamt kring dessa patienter.

    Forskningen visar måttligt till starkt vetenskapligt stöd för MMR vid komplex

    smärtproblematik. Det finns kunskapsluckor kring vilken typ av fysioterapeutiska

    interventioner som används vid multimodal smärtrehabilitering.

    Syfte:

    Syftet med studien var att kartlägga fysioterapeuternas arbete inom ramen för

    multimodal smärtrehabilitering i primärvården.

    Metod:

    Enkätstudie av tvärsnittstyp med kvantitativ ansats baserad på en egenkonstruerad

    webbenkät. Populationen utgjordes av fysioterapeuter anslutna till Nationella Registret över

    Smärtrehabilitering (NRS) primärvård och resultatet bygger på de 23 fysioterapeuter som

    valde att svara på webbenkäten.

    Resultat:

    Resultaten baseras på svar från 71 % av de NRS-anslutna klinikerna.

    Sammanfattning av resultaten visade framför allt att råd/undervisning samt olika former av

    fysisk träning utgjorde grunden i fysioterapeutens arbete inom MMR-team i primärvården.

    Det framkommer att så gott som alla patienter träffade fysioterapeut under

    behandlingsperioden. Det var en klar övervikt mot gruppbehandling eller en kombination av

    grupp och individuell behandling gällande de fysioterapeutiska interventionerna.

    Behandlingsperioderna var för det mesta fyra till elva veckor där patienten träffade

    fysioterapeut oftast varje vecka eller flera gånger/vecka. I primärvårdens MMR-team var

    fysioterapeut, arbetsterapeut, KBT terapeut, läkare och rehabkoordinator de vanligast

    förekommande yrkeskategorierna i teamen.

    Slutsats:

    Fysioterapeuten har en central roll i primärvårdens MMR-team och använder sig

    primärt av evidensbaserade, aktiva interventioner.

  • 202. Hildén, Lars
    et al.
    Väljamäe, Priit
    Johansson, Gunnar
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för naturvetenskaplig biokemi.
    Surface character of pulp fibres studied using endoglucanases2005Inngår i: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 118, nr 4, s. 386-397Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The endoglucanase Cel5A from Trichoderma reesei and an endoglucanase from Aspergillus sp. (Novozym 476TM from Novozyme A/S) were evaluated as probes for the surface properties of soft- and hardwood chemical pulp fibres. The hydrolysis time curves were in accordance with a two-phase degradation model described by a biexponential function. The kinetic parameters corresponding to the amount of fast and slow degraded parts of the substrate correlated to tensile index, relative bonded area and z-strength of the paper. All paper properties showing a correlation with enzyme kinetic parameters were related to fibre–fibre interactions. Fluorescence labelling of the reducing end groups in pulp fibres followed by enzyme treatment indicated that the fast substrate class corresponds to the population of “loose” cellulose chain ends not tightly associated with the bulk cellulose. The correlation between the parameters of enzyme kinetics and mechanical properties of the paper produced from the corresponding pulp found in this study should allow a rapid evaluation of the raw fibre material used in paper making process.

  • 203.
    Hillgren, Mikael J
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Dahlgren, Markus K
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    To, Tam M
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Synthesis of [4-(2-Hydroxyphenyl)thiazol-2-yl]methanones as Potential Bioisosteres of Salicylidene Acylhydrazides2010Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 15, nr 9, s. 6019-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A focused library of [4-(2-hydroxyphenyl)thiazol-2-yl]methanones was prepared in a four-step synthesis with the aim to obtain potent inhibitors of type III secretion in Gram-negative bacteria. The compounds are potential bioisosteres of salicylidene acylhydrazides that are a known class of type III secretion inhibitors.

  • 204.
    Hofer, Per-Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Urbach-Wiethe disease1974Doktoravhandling, med artikler (Annet vitenskapelig)
  • 205.
    Hofström, Camilla
    et al.
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Altai, Mohamed
    Honarvar, H.
    Strand, J.
    Malmberg, J.
    Hosseinimehr, Seyed Jalal
    Orlova, Anna
    Gräslund, Torbjörn
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Tolmachev, Vladimir
    HAHAHA, HEHEHE,HIHIHI or HKHKHK: influence of position and composition of histidine containing tags on biodistribution of [99mTc(CO)3]+-labeled Affibody moleculesManuskript (preprint) (Annet vitenskapelig)
  • 206.
    Hofström, Camilla
    et al.
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Orlova, Anna
    Altai, Mohamed
    Wångsell, Fredrik
    Gräslund, Torbjörn
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Tolmachev, Vladimir
    Use of a HEHEHE Purification Tag Instead of a Hexahistidine Tag Improves Biodistribution of Affibody Molecules Site-Specifically Labeled with Tc-99m, In-111 and I-1252011Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 54, nr 11, s. 3817-3826Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Affibody molecules are a class of small (similar to 7 kDa) robust scaffold proteins suitable for radionuclide molecular imaging in vivo. The attachment of a hexahistidine (His(6))-tag to the Affibody molecule allows facile purification by immobilized metal ion affinity chromatography (IMAC) but leads to high accumulation of radioactivity in the liver. Earlier, we have demonstrated that replacement of the His(6)- tag with the negatively charged histidine-glutamate-histidine-glutamate-histidine-glutamate (HEHEHE)-tag permits purification of Affibody molecules by IMAC, enables labeling with [Tc-99m(CO)(3)](+), and provides low hepatic accumulation of radioactivity. In this study, we compared the biodistribution of cysteine-containing Affibody molecules site-specifically labeled with In-111, Tc-99m, and I-125 at the C-terminus, having a His(6)-tag at the N- or C-terminus or a HEHEHE-tag at the N-terminus. We show that the use of a HEHEHE-tag provides appreciable reduction of hepatic radioactivity, especially for radiometal labels. We hope that this information can also be useful for development of other scaffold protein-based imaging agents.

  • 207.
    Hofström, Camilla
    et al.
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Stadler, C.
    Vermet, E.
    Gräslund, Torbjörn
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Step-wise down regulationof the epidermal growth factor receptor by affinity-based intracellular redirectionManuskript (preprint) (Annet vitenskapelig)
  • 208.
    Holm, Patrik
    Karlstads universitet, Institutionen för kemi.
    Single-chain antibody construction and functional mapping of the monoclonal antibody TS1: Its interaction with the antigen and the anti-idiotype2005Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The aims of this study are to synthesize and produce a single-chain antibody (scFv) of the anti-cytokeratin 8 monoclonal IgG antibody TS1 and to functionally map amino acid residues important for the interaction with its antigen and the anti-idiotypic antibody TS1. The TS1 antibody has been shown to be effective in binding cytokeratin 8 (CK8) expressed in tumors in vivo and is proposed to be useful in immunotargeting and/or immunotherapy. The anti-idiotypic antibody TS1 can be used to regulate the tumor:non-tumor ratio. Mutagenesis of certain amino acid residues can be used to alter the affinity to improve the tumor:non-tumor ratio further.

    In the present study, the TS1 IgG was chemically modified to specify groups of residues important for interaction with both CK8 and TS1. If important residues were found in the CDRs, they were mutated in the TS1 scFv construct and the effect was studied using ELISA.

    The main conclusions drawn from this study are that the important amino acid residues in TS1 for the interaction with both CK8 and TS1 are mainly tyrosines, charged residues and a tryptophan. A central interacting interface was identified with the somewhat unusual participation of residues in the CDR 2 of the light chain. Mutations which resulted in increased affinity to both CK8 and TS1 were also identified.

  • 209.
    Holmboe, Michael
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    The bentonite barrier: microstructural aspects on colloid filtration and radiation effects on bentonite colloid stability2009Licentiatavhandling, med artikler (Annet vitenskapelig)
  • 210.
    Holmfeldt, Linda
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Mullighan, Charles G
    Generation of human acute lymphoblastic leukemia xenografts for use in oncology drug discovery2015Inngår i: Current protocols in pharmacology, ISSN 1934-8290, Vol. 68, s. 14.32.1-14.32.19Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The establishment of reproducible mouse models of acute lymphoblastic leukemia (ALL) is necessary to provide in vivo therapeutic test systems that recapitulate human ALL, and for amplification of limited amounts of primary tumor material. A popular assay is the primary xenograft model that utilizes immunocompromised mice. The protocol includes injection of primary patient tumor specimens into mice with subsequent serial passaging of the tumors by retransplants of cells harvested from the mouse bone marrow and spleen. The tumors generated are then used for genomic profiling, ex vivo compound testing, mechanistic studies and retransplantation. Detailed in this unit are procedures for the establishment and maintenance of primary ALL xenograft panels for use in basic research and translational studies.

  • 211.
    Holmström, Sara J M
    et al.
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för naturvetenskap, teknik och matematik.
    Rosling, A
    Finlay, R D
    van Hees, P A W
    Lundström, Ulla
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för naturvetenskap, teknik och matematik.
    Contribution of ectomycorrhizal fungi to biogeochemical processes during iron and calcium limitation: Meeting abstract2009Inngår i: GEOCHIMICA ET COSMOCHIMICA ACTA, Pergamon Press, 2009, s. A546-A546Konferansepaper (Fagfellevurdert)
  • 212. Honkanen, Juuso
    et al.
    Turunen, Mikael
    Freedman, Jonathan
    Saarakkala, Simo
    Grinstaff, Mark
    Ylärinne, Janne
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Jurvelin, Jukka
    Töyräs, Juha
    Cationic contrast agent diffusion differs between cartilage and meniscus2016Inngår i: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 44, nr 10, s. 2913-2921Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Contrast enhanced computed tomography (CECT) is a non-destructive imaging technique used for the assessment of composition and structure of articular cartilage and meniscus. Due to structural and compositional differences between these tissues, diffusion and distribution of contrast agents may differ in cartilage and meniscus. The aim of this study is to determine the diffusion kinematics of a novel iodine based cationic contrast agent (CA(2+)) in cartilage and meniscus. Cylindrical cartilage and meniscus samples (d = 6 mm, h ≈ 2 mm) were harvested from healthy bovine knee joints (n = 10), immersed in isotonic cationic contrast agent (20 mgI/mL), and imaged using a micro-CT scanner at 26 time points up to 48 h. Subsequently, normalized X-ray attenuation and contrast agent diffusion flux, as well as water, collagen and proteoglycan (PG) contents in the tissues were determined. The contrast agent distributions within cartilage and meniscus were different. In addition, the normalized attenuation and diffusion flux were higher (p < 0.05) in cartilage. Based on these results, diffusion kinematics vary between cartilage and meniscus. These tissue specific variations can affect the interpretation of CECT images and should be considered when cartilage and meniscus are assessed simultaneously.

  • 213. Huber, Stefan M.
    et al.
    Ertem, Mehmed Z.
    Aquilante, Francesco
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Kvantkemi.
    Gagliardi, Laura
    Tolman, William B.
    Cramer, Christopher J.
    Generating Cu-II-oxyl/Cu-III-oxo species from Cu-I-alpha-ketocarboxylate complexes and O-2: in silico studies on ligand effects and C-H-activation reactivity.2009Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 15, nr 19, s. 4886-4895Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A mechanism for the oxygenation of Cu-I complexes with alpha-keto-carboxylate ligands that is based on a combination of density functional theory and multireference second-order perturbation theory (CASSCF/CASPT2) calculations is elaborated. The reaction proceeds in a manner largely analogous to those of similar Fe-II-alpha-ketocarboxylate systems, that is, by initial attack of a coordinated oxygen molecule on a ketocarboxylate ligand with concomitant decarboxylation. Subsequently, two reactive intermediates may be generated, a Cu-peracid structure and a [CuO](+) species, both of which are capable of oxidizing a phenyl ring component of the supporting ligand. Hydroxylation by the [CuO](+) species is predicted to proceed with a smaller activation free energy. The effects of electronic and steric variations on the oxygenation mechanisms were studied by introducing substituents at several positions of the ligand backbone and by investigating various N-donor ligands. In general, more electron donation by the N-donor ligand leads to increased stabilization of the more Cu-II/Cu-III-like intermediates (oxygen adducts and [CuO](+) species) relative to the more Cu-I-like peracid intermediate. For all ligands investigated the [CuO](+) intermediates are best described as Cu-II-O center dot(-) species with triplet ground states. The reactivity of these compounds in C-H abstraction reactions decreases with more electron-donating N-donor ligands, which also increase the Cu-O bond strength, although the Cu-O bond is generally predicted to be rather weak (with a bond order of about 0.5). A comparison of several methods to obtain singlet energies for the reaction intermediates indicates that multireference second-order perturbation theory is likely more accurate for the initial oxygen adducts, but not necessarily for subsequent reaction intermediates.

  • 214.
    Hultén, Lillemor Mattsson
    et al.
    Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden.
    Ullström, Christina
    Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden.
    Krettek, Alexandra
    Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden.
    van Reyk, David
    Department of Health Sciences, University of Technology, Sydney, Australia.
    Marklund, Stefan L.
    Medical Biosciences, Clinical Chemistry, Umeå University Hospital, Umeå, Sweden.
    Dahlgren, Claes
    Phagocyte Research Laboratory, Department of Rheumatology and Inflammation Research, University of Göteborg, Göteborg, Sweden.
    Wiklund, Olov
    Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden.
    Human macrophages limit oxidation products in low density lipoprotein2005Inngår i: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 4, artikkel-id 6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study tested the hypothesis that human macrophages have the ability to modify oxidation products in LDL and oxidized LDL (oxLDL) via a cellular antioxidant defence system. While many studies have focused on macrophage LDL oxidation in atherosclerosis development, less attention has been given to the cellular antioxidant capacity of these cells. Compared to cell-free controls (6.2 +/- 0.7 nmol/mg LDL), macrophages reduced TBARS to 4.42 +/- 0.4 nmol/mg LDL after 24 h incubation with LDL (P = 0.022). After 2 h incubation with oxLDL, TBARS were 3.69 +/- 0.5 nmol/mg LDL in cell-free media, and 2.48 +/- 0.9 nmol/mg LDL in the presence of macrophages (P = 0.034). A reduction of lipid peroxides in LDL (33.7 +/- 6.6 nmol/mg LDL) was found in the presence of cells after 24 h compared to cell-free incubation (105.0 +/- 14.1 nmol/mg LDL) (P = 0.005). The levels of lipid peroxides in oxLDL were 137.9 +/- 59.9 nmol/mg LDL and in cell-free media 242 +/- 60.0 nmol/mg LDL (P = 0.012). Similar results were obtained for hydrogen peroxide. Reactive oxygen species were detected in LDL, acetylated LDL, and oxLDL by isoluminol-enhanced chemiluminescence (CL). Interestingly, oxLDL alone gives a high CL signal. Macrophages reduced the CL response in oxLDL by 45% (P = 0.0016). The increased levels of glutathione in oxLDL-treated macrophages were accompanied by enhanced catalase and glutathione peroxidase activities. Our results suggest that macrophages respond to oxidative stress by endogenous antioxidant activity, which is sufficient to decrease reactive oxygen species both in LDL and oxLDL. This may suggest that the antioxidant activity is insufficient during atherosclerosis development. Thus, macrophages may play a dual role in atherogenesis, i.e. both by promoting and limiting LDL-oxidation.

  • 215.
    Hägg, Daniel
    et al.
    Research Center for Endocrinology and Metabolism, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Sjöberg, Sara
    Research Center for Endocrinology and Metabolism, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Hultén, Lillemor Mattsson
    Wallenberg Laboratory for Cardiovascular Research, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Fagerberg, Björn
    Wallenberg Laboratory for Cardiovascular Research, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Wiklund, Olov
    Wallenberg Laboratory for Cardiovascular Research, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Rosengren, Annika
    Department of Acute and Cardiovascular Medicine, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
    Carlsson, Lena M. S.
    Research Center for Endocrinology and Metabolism, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Borén, Jan
    Wallenberg Laboratory for Cardiovascular Research, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Svensson, Per-Arne
    Research Center for Endocrinology and Metabolism, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden / Wallenberg Laboratory for Cardiovascular Research, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Krettek, Alexandra
    Wallenberg Laboratory for Cardiovascular Research, Department of Metabolism and Cardiovascular Research, Göteborg, Sweden.
    Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible IL-6-CD44 feedback loop?2007Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 190, nr 2, s. 291-297Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cell-adhesion molecule CD44 likely participates in atherosclerosis development. We have shown previously that pro-inflammatory cytokines affect CD44 expression. Therefore, this work examined the role of elevated CD44 levels in human macrophages. Macrophages from human atherosclerotic subjects (n=15) showed elevated levels of CD44 transcript and protein (1.5-fold) compared to matched controls (n=15) (P=0.050 and 0.044, respectively). To test whether genetic factors influence CD44 expression, two single nucleotide polymorphisms in the CD44 gene were analyzed but these were not associated with coronary artery disease. We also examined the potential connection between plasma cytokine levels and CD44 expression. In atherosclerotic subjects, elevated CD44 expression correlates (P=0.012) with enhanced macrophage IL-6 secretion (3.13+/-2.5 pg/mL versus 0.32+/-0.16 pg/mL in controls, P=0.021). Additionally, CD44-deficient mice exhibit less circulating IL-6 than wild-type controls (9.8+/-0.7 pg/mL versus 14.3+/-0.7 pg/mL; P=0.032). Furthermore, IL-6 augments CD44 expression in primary human macrophages after 24 h (P=0.038) and 48 h (P=0.015). Taken together, our data show an IL-6-CD44 feedback loop in macrophages. Such a positive feedback loop may aggravate atherosclerosis development.

  • 216.
    Hörnblad, Andreas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Imaging the pancreas: new aspects on lobular development and adult constitution2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The mouse pancreas is a mixed exocrine and endocrine glandconsisting of three lobular compartments: the splenic, duodenal and gastric lobes. During embryogenesis, the pancreas forms from two progenitor populations located on the dorsal and ventral side of the primitive gut tube. These anlagen are brought in close proximity as the gut elongates and rotates, and fuse to form a single organ. The splenic and duodenal lobes develop from the dorsal and ventral anlagen, respectively.

    In the adult pancreas, exocrine tissue secretes digestive enzymes intothe gut lumen to support nutrient uptake. The endocrine Islets of Langerhans are scattered throughout the exocrine tissue and aid in regulation of energy homeostasis through the secretion of hormones. One of the key players in energy homeostasis is the pancreatic ß-cell, which is the most abundant cell type of the islets. The β-cells regulates blood glucose levels through the action of insulin. Conditions where this regulation does not function properly are gathered under the common name of Diabetes mellitus.

    Type 1 diabetes (T1D) is characterized by insulin deficiency due to autoimmune destruction of the ß-cells. Using recently developed protocols for optical projection tomography (OPT) whole-organ imaging, we have revealed new spatial and quantitative aspects on ß-cell mass dynamics and immune infiltration during the course of T1D development in the non-obese diabetic (NOD) mouse model. We show that although immune infiltration appears to occur asynchronously throughout the organ, smaller islets, mainly located in the periphery of the organ, preferentially loose their ß-cells during early stages of disease progression. Larger islets appear more resistant to the autoimmune attack and our data indicate the existence of a compensatory proliferative capacity within these islets. We also report the appearance of structures resembling tertiary lymphoid organs (TLOs) in association with the remaining islets during later phases of T1D progression.

    OPT has already proven to be a useful tool for assessments of ß-cellmass in the adult mouse pancreas. However, as with other techniques, previous protocols have relied on a tedious degree of manual postivacquisition editing. To further refine OPT-based assessment of pancreatic ß-cell mass distribution in the murine pancreas, we implemented a computational statistical approach, Contrast-Limited Adaptive Histogram Normalisation (CLAHE), to the OPT projection data of pancreata from C57Bl/6 mice. This methodology provided increased islet detection sensitivity, improved islet morphology and diminished subjectivity in thresholding for reconstruction and quantification. Using this approach, we could report a substantially higher number of islets than previously described for this strain and provide evidence of significant differences in islet mass distribution between the pancreatic lobes. The gastric lobe stood out in particular and contained a 75% higher islet density as compared to the splenic lobe.

    Although the development of the early pancreatic buds has been relatively well studied, later morphogenetic events are less clear and information regarding the formation of the gastric lobe has largely been missing. Using OPT we have generated a quantitative three-dimensional road map of pancreatic morphogenesis in the mouse. We show that the gastric lobe forms as a perpendicular outgrowth fromthe stem of the dorsal pancreas at around embryonic day (e) 13.5, which grows into a mesenchymal domain overlaying the pyloric sphincter and proximal part of the glandular stomach. By analyzing mutant mice with aberrant spleen development, we further demonstrate that proper formation of the gastric lobe is dependent on the initial formation of the closely positioned spleen, indicating a close interplay between pancreatic and splenic mesenchyme during development. Additionally, we show that the expression profile of markers for pancreatic multipotent progenitors within the pancreas is heterogenous with regards to lobular origin. Altogether, our studies regarding the morphogenesis and adult constitution of the mouse pancreas recognize lobular heterogeneities that add important information for future interpretations of this organ.

  • 217.
    Iakovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Selection of transthyretin amyloid inhibitors2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Amyloidosis is a group of clinical disorders caused by the aggregation of specific proteins into abnormal extracellular deposits. Today, 31 different proteins have been linked to amyloid diseases including transthyretin-related amyloidosis (ATTR). ATTR occurs through the aggregation of either wild-type plasma protein transthyretin (TTR) or a mutated form. TTR is a homotetramer that under normal circumstances functions as a carrier of thyroxine and retinol binding protein. The aggregation cascade requires dissociation of the tetramer into monomers, and preventing this dissociation represents a potential mode of intervention. Interestingly, small molecules, referred as kinetic stabilizers, can bind to TTR’s thyroxine-binding site (TBS) and such molecules are currently being used as a therapeutic approach to impair tetramer dissociation.

    The efficacy of TTR stabilization is directly correlated to the binding affinity of the ligand to TBS. However, the binding of the ligand to TTR in vivo can be affected by other plasma components resulting in poor efficacy. Thus, the selectivity of ligands is an important parameter. We have designed an assay where the ability to stabilize TTR can be directly evaluated in plasma and we have investigated the stabilizing effect of nine potential TTR binders (Paper I). The results, surprisingly, revealed that the binding affinity of molecules has a poor correlation to its selectivity. However, the nature of protein-ligand complex formation can also be described by enthalpic (∆H) and entropic (∆S) energy contributions. ∆H represents the change in chemical bonds and frequently requires a higher order of orientation compared to the ∆S component, which mainly represents the hydrophobic effect via the exclusion of water. We hypothesized that ligands possessing high ΔH in binding to their co-partner would also be more specific in a complex environment such as plasma. By applying a thermodynamic analysis using isothermal titration calorimetry, we found that the selectivity in plasma correlates well with the ∆H contribution and might, therefore, be a better predictor for selectivity.

    Luteolin was found to be a highly selective stabilizer of TTR and was investigated further (Paper II). The ligand displayed a significant rescuing effect in both cell culture and animal models. However, luteolin undergoes rapid enzymatic degradation in the liver and this impairs its use as a potential therapeutic drug. To attempt to circumvent this issue, we modified the most exposed hydroxyl group thus rendering the molecule inert towards glucuronidation (Paper III). The substitutions resulted in higher stability in the face of hepatic degradation molecules, but they also affected the selectivity in a negative manner.

    The screening for new TTR stabilizers resulted in the discovery of tetrabromobisphenol A, which displayed a very high selectivity (Paper IV). This study also included a comparison with the drug Vyndaqel™ which currently is in clinically use, and showed how the dosage could be altered to acquire a better level of saturation and possibly also a better clinical effect.

    Taken together we present new molecules with the ability to stabilize TTR, and these can serve as scaffolds for the design of new drugs. We present a method to measure the efficacy of a TTR-stabilizing drugs in a complex matrix and as well as a way to adjust the dosage of existing drugs. We also show that the selectivity of a drug is affected by the relative proportion of ∆H and ∆S, and this is of interest for drug design in general.

  • 218.
    Ibrahem, Ismail
    et al.
    Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University.
    Rios, Ramon
    Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University.
    Vesely, Jan
    Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University.
    Hammar, Peter
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi.
    Eriksson, Lars
    Department of Structural Chemistry, Arrhenius Laboratory, Stockholm University.
    Himo, Fahmi
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi.
    Córdova, Armando
    Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University.
    Enantioselective Organocatalytic Hydrophosphination of α,β-Unsaturated Aldehydes2007Inngår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 46, nr 24, s. 4507-4510Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Keeping it simple: Optically active phosphine derivatives can be obtained in high yields and in up to 99% ee by using simple chiral amines to catalyze the hydrophosphination of α,β-unsaturated aldehydes (see scheme, green sphere = chiral group). The synthetic utility of this highly chemo- and enantioselective transformation was exemplified by the one-pot asymmetric synthesis of β-phosphine oxide acids.

  • 219.
    Ihse, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Two Types of Fibrils in ATTR Amyloidosis: Implications for Clinical Phenotype and Treatment Outcome2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Systemic amyloidoses are a group of lethal diseases where proteins aggregate into fibrillar structures, called amyloid fibrils, that deposits throughout the body. Transthyretin (TTR) causes one type of amyloidosis, in which the aggregates mainly infiltrate nervous and cardiac tissue. Almost a hundred different mutations in the TTR gene are known to trigger the disease, but wild-type (wt) TTR is also incorporated into the fibrils, and may alone form amyloid. Patients with the TTRV30M mutation show, for unknown reasons, two clinical phenotypes. Some have an early onset of disease without cardiomyopathy while others have a late onset and cardiomyopathy. It has previously been described that amyloid fibrils formed from TTRV30M can have two different compositions; either with truncated molecules beside full-length TTR (type A) or only-full-length molecules (type B).  In this thesis, the clinical importance of the two types of amyloid fibrils was investigated.

    We found that the fibril composition types are correlated to the two clinical phenotypes seen among TTRV30M patients, with type A fibrils present in late onset patients and type B fibrils in early onset patients.

    The only treatment for hereditary TTR amyloidosis has been liver transplantation, whereby the liver producing the mutant TTR is replaced by an organ only producing wt protein. However, in some patients, cardiac symptoms progress post-transplantationally. We demonstrated that the propensity to incorporate wtTTR differs between fibril types and tissue types in TTRV30M patients, with cardiac amyloid of type A having the highest tendency. This offers an explanation to why particularly cardiac amyloidosis develops after transplantation, and suggests which patients that are at risk for such development.

    By examining patients with other mutations than TTRV30M, we showed that, in contrast to the general belief, a fibril composition with truncated TTR is very common and might even be the general rule. This may explain why TTRV30M patients often have a better outcome after liver transplantation than patients with other mutations.

    In conclusion, this thesis has contributed with one piece to the puzzle of understanding the differences in clinical phenotype and treatment response between TTR amyloidosis patients, by demonstrating corresponding differences at a molecular level.

  • 220.
    Ihse, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Rapezzi, Claudio
    Cardiovascular Dept, University of Bologna, Italy.
    Merlini, Giampaolo
    Amyloid Research and Treatment Center, Scientific Institute Policlinico San Matteo, University of Pavia, Italy.
    Benson, Merrill D
    Dept of Pathology and Laboratory Medicine, Indiana University School of Medicine and Roudebush VA medical Center, Indianapolis, IN, USA.
    Ando, Yukio
    Dept of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
    Suhr, Ole B
    Dept of Public Health and Clinical Medicine, Umeå University.
    Leone, Ornella
    Pathology Department, S.Orsola-Malpighi Hospital, Bologna, Italy.
    Lorenzini, Massimiliano
    Cardiovascular Dept, University of Bologna, Italy.
    Quarta, Candida Cristina
    Cardiovascular Dept, University of Bologna, Italy.
    Obici, Laura
    Amyloid Research and Treatment Center, Scientific Institute Policlinico San Matteo, University of Pavia, Italy.
    Lavatelli, Francesca
    Amyloid Research and Treatment Center, Scientific Institute Policlinico San Matteo, University of Pavia, Italy.
    Liepnieks, Juris
    Dept of Pathology and Laboratory Medicine, Indiana University School of Medicine and Roudebush VA medical Center, Indianapolis, IN, USA.
    Ohshima, Toshinori
    Dept of Neurology, Graduate School of Medical Sciences, Kumamoto University, Japan.
    Jono, Hirofumi
    Dept of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan.
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Amyloid fibrils with fragmented ATTR may be the rule in non-Val30Met ATTR amyloidosisManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one composed of only intact ATTR (type B). Patients with type A fibrils have a late age of onset and signs of cardiomyopathy, while patients with type B fibrils have an early onset and much less myocardial involvement.

    The present study aimed to determine if the correlation between fibril type and clinical phenotype is true for familial amyloidosis in general. Cardiac and/or adipose tissue from 48 patients carrying 21 different non-TTRV30M mutations were examined, as well as 7 non-Swedish ATTRV30M patients. Fibril type was determined with western blotting and compared to the patients´ age of onset and degree of cardiomyopathy.

    Non-Swedish V30M patients showed the same correlation as described for Swedish V30M patients, with fibrils of only full-length ATTR (type B) linked to less myocardial involvement. In contrast, all patients with non-V30M mutations had a fibril composition with ATTR fragments (type A). Some of these patients had onset of disease at young age. The vast majority had increased thickness of left cardiac ventricle, but a few individuals had values within normal limits.

    This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis. It also suggests that fibrils composed of only full-length ATTR is an exception, perhaps only found among young ATTRV30M amyloidosis patients.

  • 221.
    Isaksson, Helena
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Clinical studies of RNA as a prognostic and diagnostic marker for disease2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Technologies for RNA detection are evolving rapidly and gives an op-portunity for discovery of new markers for early detection of complex diseases. Today in clinical work we rely on signs and symptoms in com-bination with the measurement of protein levels for diagnosis. The quick turnaround time of mRNA synthesis may provide an earlier diagnostic signal than protein-based biomarkers assays, in acute dramatic condi-tions such as acute mesenteric ischemia (AMI), for early detection of cancer, as prognostic tool in cancer treatment and as an aid in difficult diagnosis of unknown origin.

    The main goals of this thesis was to apply a whole genome approach to study different complex diseases to evaluate the applicability of RNA as a diagnostic or prognostic marker for disease, preferably from an easily accessible source such as peripheral blood. This was investigated in an animal model with induced AMI, a cohort of ovarian cancer patients and in a single-patient study of a girl with a severe inflammatory syn-drome.

    Through this thesis we have gained insight into how gene expression is regulated in ischemic intestinal tissue.

    We found that a peripheral blood test can distinguish between ovarian cancer patients with or without residual tumour mass after surgery with the help of expression analysis of six genes. We also found that gene expressions of three genes can predict overall survival in peripheral whole blood from ovarian cancer patients. And that gene expression profiles indeed can significantly distinguish between two groups of high and low risk ovarian cancer. In the single-patient study, we tried but failed to device a successful treatment before it was too late. Neverthe-less, the things we learned and the case studies that were published may serve as a diagnostic tool for clinicians facing similar syndromes.

  • 222.
    Itsenko, Oleksiy
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Blom, Elisabeth
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Kihlberg, Tor
    The Use of Lithium Amides in the Palladium-Mediated Synthesis of [Carbonyl-11C]Amides2007Inngår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, Vol. 2007, nr 26, s. 4337-4342Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Weakly nucleophilic amines were converted into the corresponding lithium amides and used in either one- or two-pot palladium mediated-reactions with [11C]carbon monoxide and aryl iodides. It was found that palladium acyl complexes may be prepared in a separate step and have sufficient lifetime to be used in a subsequent reaction with a nucleophile. This two-pot procedure was used for the labelling synthesis of eleven amides (nine of which are analogues of WAY-100635, a 5-HT1A radioligand) from weakly nucleophilic amines. The results were compared to a direct one-pot procedure using lithium amides. Both approaches extend the scope of palladium-mediated carbonylation using [11C]carbon monoxide and aryl iodides allowing use of weakly nucleophilic amines.

  • 223.
    Jain, Mayur V.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Los, Marek Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. BioApplications Ent., Winnipeg, MB, Canada; Department of Pathomorphology, Pomeranian Medical University, Szczecin, Poland.
    Spatiotemporal cytometry—Simultaneous analysis of DNA replication and damage2013Inngår i: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 83, nr 11, s. 975-976Artikkel i tidsskrift (Fagfellevurdert)
  • 224.
    Jansson, Emelie
    Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Gaskromatografisk metod för analys av GHB i urin2009Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    En metod för detektering och kvantifiering av gamma-hydroxysmörsyra (GHB) i urin med gaskromatografi (GC) är framtagen på Sahlgrenska universitetssjukhuset. Metoden är relativt unik då den inte kräver upparbetning i form av derivatisering, indunstning eller extraktion. Urinen surgörs med koncentrerad saltsyra och internstandard, gamma-valerolakton, tillsätts. GHB övergår då till laktonformen, gamma-butyrolakton (GBL). Därefter injiceras provet direkt på en GC-FID med en kapillärkolonn för glykoler och alkoholer. Detektion ner till 100 μmol/L är möjligt med en variationskoefficient mellan 6 och 12 %. Provsvar erhålls efter 6,5 minuter. Metoden är dock inte fullständig då en del frågetecken kvarstår. Bland annat bör det undersökas om andra föreningar, som kan förekomma i urin, kan eluera samtidigt som GHB. Om ja så bör vidare analyser genomföras för att separera GHB och den andra föreningen. Metoden kan däremot användas i nuläget som en screeninganalys för att snabbt få ett svar på om GHB finns närvarande eller inte. Verifiering kan sedan ske med GC-MS.

  • 225.
    Jansson-Löfmark, Rasmus
    et al.
    Sahlgrenska Academy at University of Gothenburg, Unit for Pharmacokinetics and drug metabolism, Göteborg, Sweden.
    Römsing, Susanne
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Albers, E.
    Sahlgrenska Academy at University of Gothenburg, Unit for Pharmacokinetics and drug metabolism, Göteborg, Sweden.
    Ashton, M.
    Sahlgrenska Academy at University of Gothenburg, Unit for Pharmacokinetics and drug metabolism, Göteborg, Sweden .
    Determination of eflornithine enantiomers in plasma by precolumn derivatization with o-phthalaldehyde-N-acetyl-l-cysteine and liquid chromatography with UV detection2010Inngår i: BMC Biomedical chromotography, ISSN 0269-3879, E-ISSN 1099-0801, Vol. 24, nr 7, s. 768-773Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A bioanalytical method for indirect determination of eflornithine enantiomers in 75 mu L human plasma has been developed and validated. L- and D-eflornithine were derivatized with o-phthalaldehyde and N-acetyl-L-cysteine to generate diastereomers which were separated on two serially connected Chromolith Performance columns (RP-18e 100 x 4.6 mm i.d.) by a isocratic flow followed by a gradient flow for elution of endogenous compounds. The diastereomers were detected with UV (340 nm). The between-day precisions for L- and D-eflornithine in plasma were 8.4 and 2.3% at 3 mu m, 4.0 and 5.1% at 400 mu m, and 2.0 and 3.7% at 1000 mu m. The lower limit of quantification was determined to be 1.5 mu m, at which precision was 14.9 and 9.9% for 1- and D-eflornithine, respectively.

  • 226.
    Jayaprakash, Kartheyaene
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Monocyte and Neutrophil Inflammatory Responses to the Periodontopathogen Porphyromonas gingivalis2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Periodontitis is one of the most common adult infections. Duing bacteremia in healthy individuals or patients with chronic periodontitis, a number of oral bacteria such as Porphyromonas gingivalis encounter inflammatory cells in the blood eg. platelets, neutrophils and monocytes. Although several studies have suggested an association between periodontitis and cardiovascular diseases, the infection and inflammatory mechanisms are poorly understood. Hence, the aim of this thesis was to elucidate the mechanisms that are involved in P. gingivalis interaction with blood leukocytes, in order to further understand the molecular pathogenesis that renders periodontitis as a risk factor for several systemic conditions. We have demonstrated that P. gingivalis induces ROS production in neutrophils, THP1 cells and in whole blood, through activation of pattern recognition receptors, such as toll-like receptors, nuclear oligomerizing domains and protease- activated receptors. Besides, we have also shown that monocytes secrete IL-1β and CXCL8 in response to P. gingivalis. Both these cytokines prime neutrophils, endothelial cells and other vascular cells in an autocrine and paracrine manner. P. gingivalis has a plethora of virulence factors of which gingipains are very unique. In addition to activating inflammatory signalling pathways in cells, gingipains also regulate CXCL8 and IL-1β, thereby curtailing the host defence strategies. We demonstrated that oxidized LDL, but not native LDL, induces IL-1β release and CD36 expression on THP1 cells. Furthermore, LDL mildly modifies P. gingivalis-induced inflammatory responses as well as CD36 expression in THP1 cells. We also observed that P. gingivalis is eliminated mainly by phagocytosis in neutrophils. In summary, these studies clarify the mechanisms of interaction between P. gingivalis and leukocytes, which can increase the understanding of the pathogenesis of periodontitis and associated systemic disorders.

  • 227.
    Jayaprakash, Kartheyaene
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Demirel, Isak
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Gunaltay, Sezin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Khalaf, Hazem
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för medicinska vetenskaper.
    PKC, ERK/p38 MAP kinases and NF-κB targeted signalling plays a crucial role in expression and release of IL-1β and CXCL8 in Porphyromonas gingivalis infected monocytesManuskript (preprint) (Annet vitenskapelig)
  • 228.
    Jayaprakash, Kartheyaene
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Demirel, Isak
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Khalaf, Hazem
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Bengtsson, Torbjörn
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Porphyromonas gingivalis induced release of reactive oxygen species and interleukin-1 beta and the effects of low density lipoproteins in monocytes and whole bloodManuskript (preprint) (Annet vitenskapelig)
  • 229.
    Jenkins, Samantha
    et al.
    Högskolan Väst, Institutionen för ingenjörsvetenskap.
    Kirk, Steven
    IV.
    Guevara-Garcia, Alfredo
    Ayers, Paul W.
    Echegaray, Eleonora
    Toro-Labbe, Alejandro
    The mechanics of charge-shift bonds: A perspective from the electronic stress tensor2011Inngår i: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 510, s. 18-20Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The mechanism of charge-shift bonding is discussed from the perspective of the electronic stress tensor. In charge-shift bonds, the tensile mode of the stress tensor (attraction of electrons to the nuclei) is stronger, relative to the compressive modes (attraction of electrons toward the bond axis) than in conventional covalent bonds. Similar bonding indicators based on the eigenvalues of the tensor of second derivatives of the electron density and bond metallicity measures also correlate with charge-shift binding. These indicators seem preferable to the electron-density Laplacian and the local energy density because they can distinguish between weak covalent bonds and charge-shift bonds. 

  • 230.
    Jenkins, Samantha
    et al.
    Högskolan Väst, Institutionen för ingenjörsvetenskap.
    Restrepo, A.
    Univ Antioquia, Inst Quim, Medellin 1226, Colombia.
    David, J.
    Univ Eafit, Dept Ciencias Basicas, Medellin 3300, Colombia.
    Yin, D. L.
    Kirk, S. R.
    Högskolan Väst, Institutionen för ingenjörsvetenskap.
    Spanning QTAIM topology phase diagrams of water isomers W4, W5 and W62011Inngår i: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 13, nr 24, s. 11644-11656Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Structural and chemical properties of the small water clusters W-4, W-5 and W-6 are investigated with the theory of atoms and molecules (QTAIM). For the W-4, W-5 and W-6 clusters, nine, fourteen and twenty-seven conformers, respectively, have been analyzed. For the W-4, W-5 and W-6 clusters one, two and three of these structures, respectively, have not been reported before. We then proceed to extend the W-4, W-5 and W-6 water cluster topology space using QTAIM; the Poincare-Hopf topological sum rules are applied to create rules to identify the spanning set of conformer topologies, this includes finding three, ten and eight new distinct topologies that satisfy the Poincare-Hopf relation for W-4, W-5 and W-6 respectively. The topological stability of degenerate solutions to the Poincare-Hopf relation is compared by evaluating the proximity to rupturing of critical points of the gradient vector field of the charge density. We introduce a QTAIM topology space to replace the inconsistent use of Euclidean geometry to determine whether a cluster is 1-, 2- or 3-D. We show from the topology of the charge density that the conformers of the W-4, W-5 clusters are more energetically stable in less compact, planar forms, conversely the conformers of W-6 are more energetically stable with compact 3-D topologies. Quantifying the degree of covalent character in the hydrogen bonding for the W-4, W-5 and W-6 clusters independently verifies this finding. Differences in simple rules for the number of hydrogen bonds obeying the Bernal-Fowler ice rules between W-4, W-5 and W-6 reflect the transition from 2-D to 3-D structures being more energetically stable. In addition, we identify a new class of O-O bonding interactions that are up to 48% longer than the inter-nuclear separation and appear to be failed hydrogen bonds.

  • 231.
    Jernberg, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Mechanisms behind growth of castration-resistant prostate cancer bone metastases2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: The first-line treatment for patients with advanced prostate cancer (PC) is androgen deprivation therapy. This therapy is initially effective, but after some time tumors relapse, predominantly within the bone, and are then termed castration-resistant prostate cancer (CRPC). The majority of CRPC tumors show androgen receptor (AR) activity despite castrate levels of circulating testosterone. AR activity could be caused by several mechanisms including; intratumoral androgen synthesis, AR amplification, AR mutations and expression of AR splice variants. The mechanisms controlling CRPC growth in the clinically most relevant metastatic site, the bone, are not fully identified. The purpose of this thesis was therefore to explore AR expression and possible mechanisms behind CRPC growth in PC bone metastases in order to find mechanisms that could be targeted for treatment and/or predict response to certain therapies.

    Materials and Methods: We have examined hormone-naïve and CRPC bone metastases samples obtained from patients at metastasis surgery, non-malignant and malignant prostate samples obtained from patients at radical prostatectomy, and PC cell lines cultured in vitro. Analysis has been performed using RT-PCR, whole-genome expression arrays, immunohistochemistry, western blotting, FISH, copy number assays and gene ontology analysis. Functional studies have been made by protein overexpression and knock-down in PC cells in vitro and effects studied by evaluation of cell viability, migration, and invasion.

    Results: We found that high nuclear AR immunostaining (presumed to reflect high AR activity) in bone metastases from CRPC patients was associated with a particularly poor prognosis, while no difference in AR staining was observed between hormone-naïve and CRPC metastases. Further, expression of AR splice variants (AR-V7, AR-V567es) was associated with a high nuclear AR immunostaining score and shown to be increased in CRPC compared to hormone-naïve bone metastases. High levels (levels in the upper quartile) of AR splice variants in CRPC bone metastases was related to disturbed cell cycle regulation and short patients survival. No differences in steroidogenic enzyme levels were detected between CRPC and hormone-naïve bone metastases. Higher levels of enzymes involved in late steps of androgen synthesis (adrenal gland steroid conversion) were observed in bone metastases than in non-malignant and/or malignant prostate tissue, while the enzyme levels in earlier steps (de novo steroidogenesis) were lower in bone metastases. A subgroup of metastases expressed very high levels of AKR1C3, indicating that this group may have an induced capacity of converting adrenal-gland derived steroids into more potent androgens. This was not associated to CRPC but merely with the advanced stage of metastasis. High protein levels of AR splice variants were found in bone metastases with low AKR1C3 levels, while metastases with high AKR1C3 levels primarily contained low AR variant levels. Furthermore, about half of the CRPC bone metastases showed androgen receptor gene amplification which was associated with co-amplification of YIPF6, and a gene expression pattern that pointed at decreased osteoclast activity, and consequently decreased bone resorption.

    Conclusions: The majority of CRPC bone metastases show high nuclear AR immunostaining that seems to be associated with a particularly unfavorable outcome after metastasis surgery. Subgroups of CRPC bone metastases could be identified according to presence of AR amplification and expression levels of AKR1C3 or AR splice variants, which might have clinical relevance for treatment of PC patients.

  • 232. Johansson, E. M. J.
    et al.
    Odelius, M.
    Gorgoi, M.
    Karis, Olof
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och materialvetenskap, Yt- och gränsskiktsvetenskap.
    Ovsyannikov, R.
    Schafers, S.
    Svensson, Svante
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och materialvetenskap, Yt- och gränsskiktsvetenskap.
    Siegbahn, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och materialvetenskap, Yt- och gränsskiktsvetenskap.
    Rensmo, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och materialvetenskap, Yt- och gränsskiktsvetenskap.
    Valence Electronic Structure Of Ruthenium Based Complexes Probed By Photoelectron Spectroscopy At High Kinetic Energy (Hike) And Modeled By Dft Calculations2008Inngår i: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 464, nr 4-6, s. 192-197Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The valence electronic structure of a series of molecular films containing ruthenium polypyridine complexes has been investigated by photoelectron spectroscopy (PES) at high kinetic energy (HIKE) using hard X-ray. The experiment shows the possibility to experimentally probe the metal contribution to the valence spectra in a bulk sensitive mode. Specifically to directly follow the Ru 4d contribution to the highest occupied molecular orbitals of such complexes. The experimental spectra are accurately modeled by DFT calculations only if a crystal structure environment is taken into account showing the importance of intermolecular interaction for modeling the electronic structure of such complexes.

  • 233.
    Johansson, Helene
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Extraction and Characterization of Hydrophobin from Trichoderma reesei2010Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Hydrophobins are a class of small proteins (7-15kDa) found in filamentous fungi and are among the most surface active proteins known today. Because of this they have received attention for different applications, e.g. for the food industry as an alternative in emulsions. The goal of this project was to culture and extract hydrophobins from Trichoderma reesei and characterize it. This was done from a freeze-dried culture of Trichoderma reesei, which was cultured on PDA-plates and in liquid medium with glucose as carbon source. Extraction was made by breaking the cells, mechanically and by sonication, and then by shaking a seperating funnel to create foam from the surface-active proteins. The foam was washed and freeze-dried and the total protein concentration of the freeze-dried substance was determined with Bradford assay and the hydrophpbin was characterized with SDS-PAGE. The culturing of the fungi was successful. The amount of foam created was, however, less than expected. The Bradford assay gave a total protein concentration of 7.5% in the freeze-dried substance, but the SDS-PAGE didn't give any results. The reason for this probably depends on the culturing and the extraction of the hydrophobin. T. reesei hydrophobin HFBI, expressed in glucose containing media, is bound to the mycelium of the fungi and the breaking of the mycelium might not have been enough to release all the protein, which also would explain the small amounts of foam. One way to improve this could be to grow the fungi on lactose instead. This will result in that T. reesei produces HFBII instead, which is mainly released to the surrounding. The conclusion of the project is that the method for culturing and extraction needs to be improved to obtain hydrophobin from T. reesei.

  • 234.
    Johansson, Johannes D.
    et al.
    ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology.
    Farzam, Parisa
    ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology.
    Mireles, Miguel
    ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology.
    Jiménez Valerio, Gabriela
    Bellvitge Biomedical Research Institute–IDIBELL.
    Martínez Lozano, Mar
    Bellvitge Biomedical Research Institute–IDIBELL.
    Casanovas, Oriol
    Bellvitge Biomedical Research Institute–IDIBELL.
    Durduran, Turgut
    ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Sciences and Technology.
    Optical investigation of antiangiogenic therapy in renal cell carcinoma2015Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Diffuse optical spectroscopy and diffuse correlation spectroscopy was used to monitor antiangiogenic therapy in renal cell carcinoma. The measurements allowed for hemodynamic characterization of the tumors and to monitor the initial antiangiogenic effect and relate it to final vessel density and tumor size.

  • 235.
    Jones, Iwan
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Hägglund, Anna-Carin
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Törnqvist, Gunilla
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Nord, Christoffer
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Ahlgren, Ulf
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Carlsson, Leif
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development2015Inngår i: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 8, nr 12, s. 1517-1529Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that is best characterised by neurodevelopmental deficits and the presence of benign tumours (called hamartomas) in affected organs. This multi-organ disorder results from inactivating point mutations in either the TSC1 or the TSC2 genes and consequent activation of the canonical mammalian target of rapamycin complex 1 signalling (mTORC1) pathway. Because lesions to the eye are central to TSC diagnosis, we report here the generation and characterisation of the first eye-specific TSC mouse model. We demonstrate that conditional ablation of Tsc1 in eye-committed progenitor cells leads to the accelerated differentiation and subsequent ectopic radial migration of retinal ganglion cells. This results in an increase in retinal ganglion cell apoptosis and consequent regionalised axonal loss within the optic nerve and topographical changes to the contra- and ipsilateral input within the dorsal lateral geniculate nucleus. Eyes from adult mice exhibit aberrant retinal architecture and display all the classic neuropathological hallmarks of TSC, including an increase in organ and cell size, ring heterotopias, hamartomas with retinal detachment, and lamination defects. Our results provide the first major insight into the molecular etiology of TSC within the developing eye and demonstrate a pivotal role for Tsc1 in regulating various aspects of visual-pathway development. Our novel mouse model therefore provides a valuable resource for future studies concerning the molecular mechanisms underlying TSC and also as a platform to evaluate new therapeutic approaches for the treatment of this multi-organ disorder.

  • 236.
    Jonsson, Hanna
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Säwén, Elin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Studies on the conformational flexibility of α-L-Rhap-(1→2)-α-L-Rhap-OMe using molecular simulation and 13C-site-specific labeling: a model for a commonly occurring disaccharide in bacterial polysaccharidesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Bacterial polysaccharides are comprised of a variety of monosaccharides, L-rhamnose (6-deoxy-Lmannose) being one of them. This sugar is often part of α-(1→2)- and/or α-(1→3)-linkages and wehave therefore studied the disaccharide α-L-Rhap-(1→2)-α-L-Rhap-OMe to obtain information onconformational preferences at this glycosidic linkage. The target disaccharide was synthesized with 13C site-specific labeling at C1' and at C2', i.e., in the terminal group. 2D 1H,13C-HSQC-HECADE and 1H,13C-J-HMBC NMR experiments, 1D 13C and 1H NMR spectra together with total line-shape analysis were used to extract conformationally dependent hetero- and homonuclear spin-spincoupling constants. This resulted in the determination of 2JC2',H1' , 3JC1',C1 , 3JC1',C3 , 3JC2',C2 , 2JC1',C2 ,1JC1',C2' , and 1JC1',H1' . These data together with previously determined JC,H and 1H,1H NOEs result in fourteen conformationally dependent NMR parameters that are available for analysis of glycosidiclinkage flexibility and conformational preferences. A molecular dynamics simulation of the disaccharide with explicit water molecules as solvent showed a major conformational state at ΦH =40° and ψH = –35°, consistent with experimental NMR data.

  • 237.
    Jonsson, Hanna
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    NMR analysis of conformationally dependent nJCH and nJCC in the trisaccharide α-L-Rhap-(1→2)[α-L-Rhap-(1→3)]-α-L-Rhap-OMe and a site-specifically labeled isotopologue thereofManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    An array of NMR spectroscopy experiments have been carried out to obtain conformationallydependent 1H,13C- and 13C,13C-spin-spin coupling constants in the trisaccharide a-L-Rhap-(1®2)[a-LRhap-(1®3)]-a-L-Rhap-OMe. The trisaccharide was synthesized with 13C site-specific labeling at C2'and C2'', i.e., in the rhamnosyl groups in order to alleviate 1H spectral overlap. Using both the naturalabundance compound and the 13C-labeled sample 2D 1H,13C-J-HMBC and 1H,13C-HSQC-HECADENMR experiments, total line-shape analysis of 1H NMR spectra and 1D 13C NMR experiments wereemployed to extract 3C,H J , 2C,H J , 3C,C J , and1C,C J . The 13C site-specific labeling facilitates straightforward determination of nC,C J as the splitting of the 13C natural abundance resonances. This studyresulted in seven conformationally dependent coupling constants for the trisaccharide and illustrates theuse of 13C site-specific labeling as a valuable tool that extends the 1D and 2D NMR methods in currentuse to attain both hetero- and homonuclear spin-spin coupling constants.

  • 238.
    Jonsson, K. Hanna M.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Weintraub, Andrej
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Structural determination of the O-antigenic polysaccharide from Escherichia coli O742009Inngår i: Carbohydrate Research, ISSN 0008-6215, E-ISSN 1873-426X, Vol. 344, nr 12, s. 1592-1595Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The structure of the O-antigen polysaccharide (PS) from Escherichia coli O74 has been determined. Component analysis, together with 1H and 13C NMR spectroscopy as well as 1H,15N-HSQC experiments were employed to elucidate the structure. Inter-residue correlations were determined by 1H,1H-NOESY and 1H,13C-heteronuclear multiple-bond correlation experiments. The PS is composed of tetrasaccharide repeating units with the following structure:

    Full-size image (5K)

    Cross-peaks of low intensity from an α-linked N-acetylglucosamine residue were present in the NMR spectra, and spectral analysis indicates that they originate from the penultimate residue in the polysaccharide. Consequently, the biological repeating unit has a 3-substituted N-acetyl-d-glucosamine residue at its reducing end. The 1H, 13C and 15N NMR chemical shifts of the α- and β-anomeric forms of d-Fucp3NAc are also reported. The repeating unit of the E. coli O74 O-antigen is identical to that of the capsular polysaccharide from E. coli K45.

  • 239.
    Jonsson, Petter
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Utveckling av en ny sportdryck för uthållighetsidrott2008Independent thesis Advanced level (degree of Magister), 20 poäng / 30 hpOppgave
    Abstract [en]

    The aim of this examination project work was to develop one new sports drink for consumption during prolonged exercise. Most existing sports drinks contain carbohydrates and electrolytes but the drink developed during this project work aimed to contain protein/amino acids and other substances that potentially may help the athlete to perform better compared with sports dinks containing only carbohydrates and electrolytes. Since it is unclear if whole proteins, oligopeptides or free amino acids are preferred, three different sports drink where developed.

    All three sports drinks contain 25 mmol Na+/l, 5.5 mmol K+/l, 240 mg caffeine (per serving), high molecular weight glucose polymer (7%), aromas, beta-carotene and other substances supposed to improve the taste of the drinks. The three drinks contain different sources of amino acids: 0.47% branched-chain amino acids (BCAA) in the BCAA-sports drink, 2% whey protein in the Whey protein-sports drink and 0.8% hydrolyzed casein (oligopeptides) in the Peptopro®-sports drink. The serving size of each sports drink is 0.75 l.

    As the drinks should taste well and be easy to drink during exercise blinded tasting tests were performed. During these tests prototypes and the final versions of all three sports drinks were compared to a placebo drink containing no amino acids or caffeine.

    The results from the taste-tests show that none of the test drinks or the placebo drink exhibited significantly better taste (p>0.05). However, the BCAA-sports drink, the Whey protein-sports drink and the placebo drink was shown to taste better than the Peptopro®-sports drink.

    To investigate the effects of the sports drinks on performance, two elite trained cyclists were supplemented with the test drinks and the placebo drink during interval-trials on a cycle ergometer equipped to measure power output during blinded tests. The power output was compared to the heart rate of each test participant. The placebo drinks contained 8% carbohydrates but no caffeine or amino acids. The results indicate that all three sports drinks either were considered equal, or improved the performance, as compared to the placebo drink. All drinks were considered to taste well during exercise. These findings indicate that the three sports drinks developed during this project work, improved performance and tasted well. However, it is desired to improve the taste of both the Peptopro®-sports drink and the Whey protein-sports drink. Alternative drinks containing no caffeine should be developed in order for the athlete to intake large quantities of the developed sports drinks during prolonged exercise

  • 240.
    Jonsson, Samuel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Rebecca
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    McGrath, Aleksandra M
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Novikova, Liudmila N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kingham, Paul J
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Effect of delayed peripheral nerve repair on nerve regeneration, Schwann cell function and target muscle recovery2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 2, artikkel-id e56484Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using retrograde labeling. Nerve tissue was also collected from the proximal and distal stumps and from the nerve graft, together with the medial gastrocnemius (MG) muscles. A dramatic decline in the number of regenerating motoneurons and myelinated axons in the distal nerve stump was observed in the 3- and 6-months delayed groups. After 3 months delay, the axonal number in the proximal stump increased 2-3 folds, accompanied by a smaller axonal area. RT-PCR of distal nerve segments revealed a decline in Schwann cells (SC) markers, most notably in the 3 and 6 month delayed repair samples. There was also a progressive increase in fibrosis and proteoglycan scar markers in the distal nerve with increased delayed repair time. The yield of SC isolated from the distal nerve segments progressively fell with increased delay in repair time but cultured SC from all groups proliferated at similar rates. MG muscle at 3- and 6-months delay repair showed a significant decline in weight (61% and 27% compared with contra-lateral side). Muscle fiber atrophy and changes to neuromuscular junctions were observed with increased delayed repair time suggestive of progressively impaired reinnervation. This study demonstrates that one of the main limiting factors for nerve regeneration after delayed repair is the distal stump. The critical time point after which the outcome of regeneration becomes too poor appears to be 3-months.

  • 241.
    Jourdain, Elsa
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Olsen, Björn
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Lundkvist, Ake
    Hubálek, Zdenek
    Sikutová, Silvie
    Waldenström, Jonas
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Karlsson, Malin
    Wahlström, Maria
    Jozan, Martine
    Falk, Kerstin I
    Surveillance for West Nile virus in wild birds from northern Europe.2011Inngår i: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 11, nr 1, s. 77-79Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A total of 1935 migratory birds from 104 different species were captured in southeastern Sweden in 2005-2006 and tested for antibodies against West Nile virus (WNV). Overall, 46 birds (2.4%; binomial confidence limits, 1.8-3.2) were positive by blocking-ELISA, but only 2 (0.10%; binomial confidence limits, 0.0-0.4) had antibodies detectable by both blocking-ELISA and WNV neutralization test. ELISA-positive birds included long- and short-distance migrants likely exposed to WNV while wintering in or migrating through areas enzootic for WNV. Exposure to a cross-reactive Flavivirus was suspected for short-distance migrants of the Turdidae family, but no cross-neutralization with tick-borne encephalitis and Usutu viruses was observed.

  • 242.
    Jönsson, Katarina
    Högskolan i Kalmar, Naturvetenskapliga institutionen.
    Investigation of Salt Limit Values and Product Safety in Seafood Products using Water Activity and Water Phase Salt Content2009Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
  • 243.
    Jönsson, Tove
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Distribution of Anthocyanin in Bilberries (Vaccinium myrtillus) and Effects of Heat Treatment on Antioxidant Capacity, Total Phenolic and Total Anthocyanin Content2010Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Anthocyanins are water-soluble pigments responsible for the red, violet and blue colours in plants. Anthocyanins belong to the flavonoid group and are the major antioxidant in bilberries (Vaccinium myrtillus), where the highest content can be found in the peel. Several health benefits of anthocyanins have been reported, like preventing cancer and diabetes and inhibit the oxidation of low density lipoprotein (LDL).

    The anthocyanins are degraded during heating and storage, thus the nutritional quality changes as berry products are produced. It has been reported earlier that the degradation products also might possess antioxidant activity, hence heating may be beneficial.

    The aim of this degree project work was to determine the distribution of anthocyanin in bilberries (Vaccinium myrtillus) and effects of heat treatment on antioxidant capacity, total phenolic and total anthocyanin content. The scavenging capacity was studied against both peroxyl radicals and the DPPH radical. Another part of this project was to develop new products that can stimulate the intake of berry based products.

    The bilberries used for determination of distribution of anthocyanins were peeled, which gave one fraction of peel and one fraction of pulp. The study showed that the peel contained 9 times more anthocyanins than the pulp. When the antioxidant capacity, total content of polyphenolic compounds and anthocyanins, was determined samples obtained in a juiceextractor were used. The bilberries were filtered through a juice-extractor which yielded one fraction of juice and one fraction of presscake. The heat treatments of samples were performed at 80ºC and 120 ºC for 10 and 30 min. The antioxidant capacity against peroxyl radicals increased after thermal treatment, but decreased for the DPPH radical. Thus it seems as the degradation products possess some antioxidant capacity. The content of polyphenols increased after thermal treatment. The anthocyanin content decreased after heating, except when heating at 80ºC for 10 min. The presscake possessed the highest antioxidant capacity and content of polyphenols and anthocyanins compared to the juice.

    The results indicate that heating of bilberry juice and presscake can be beneficial in regard to antioxidant capacity to scavenge peroxyl radicals and that a bilberry product in which the peel is included gives the product a higher content of antioxidants.

    The outcome of the product development was a mixture of bilberry pomace and corn flour that could be used to make an extruded snack and a bilberry jam with sugar distributed in domains, which was perceived as sweeter than a traditional bilberry jam without sugar domains but with equal total sugar concentration.

  • 244. Kakehashi, Rie
    et al.
    Karlsson, Göran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Fysikalisk kemi.
    Almgren, Mats
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Fysikalisk kemi.
    Stomatosomes, blastula vesicles and bilayer disks: morphological richness of structures formed in dilute aqueous mixtures of a cationic and an anionic surfactant2009Inngår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 331, nr 2, s. 484-493Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cryogenic transmission electron microscopy (cryoTEM) was used to study the structures formed in mixts. of sodium dodecylsulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) in dil. aq. solns. with 0-300 mM NaBr. The DTAB mole fraction, X, was in the range 0.2-0.4, limited at 25 DegC by pptn. of solid DTA-DS at X = 0.38 without salt to X = 0.25 at 300 mM NaBr. At a total surfactant concn. of 100 mM the samples sepd. into two liq. phases (the bottom phase birefringent) within a narrow (+-0.01 mol fraction units) compn. range. At the mid-point X varied from 0.32 without salt to 0.22 at 300 mM NaBr. Elemental anal. of C, S, O, and N in the sepd. phases of a sample with 100 mM NaBr and X = 0.26 showed the top phase to contain almost only SDS at a low concn., 14 mM, and the bottom phase 175 mM total surfactant, with X = 0.27 . Elemental anal. on samples without added salt gave erratic results, indicating problems in the phys. sepn. of the phases. The cryoTEM survey of the sepd. phases revealed similar problems. Without salt both phases showed similar structures, whereas the top phase in the sample with added salt was void of structures larger than small micelles. The cryoTEM survey revealed a variety of structures being simultaneously present in most samples. A general trend with increasing X was an evolution from globular micelles, over disks, bands, branched bands transforming into sparse webs, perforated bilayer structures, and finally smooth bilayers. Increasing salt and total surfactant concns. resulted in the emergence of structures with smaller mean curvature at lower X. Perforated bilayers were found in samples with 100 mM or less of added salt, and usually persisted to DTAB contents where ppts. appeared. The porous bilayers seemed to derive from sparse webs of band-like structures, and the hole size decreased with increasing X and salt concn. Two types of recurrent structures were noticed: blastula aggregates, seemingly an intermediate structure transforming crumpled bilayers into vesicles of similar size (diam. 400-500 ANG.), obsd. over a broad range of conditions, and at 100 mM total surfactant concn. and 50 mM added salt or more a type of regular disks with a diam. of 180 +- 30 ANG.

  • 245. Kalkunte, Satyan S.
    et al.
    Neubeck, Stefan
    Norris, Wendy E.
    Cheng, Shi-Bin
    Kostadinov, Stefan
    Vu Hoang, Dang
    Ahmed, Aftab
    von Eggeling, Ferdinand
    Shaikh, Zahir
    Padbury, James
    Berg, Goran
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Markert, Udo R.
    Sharma, Surendra
    Transthyretin is dysregulated in preeclampsia, and its native form prevents the onset of disease in a preclinical mouse model2013Inngår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 183, nr 5, s. 1425-1436Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother and fetus. Understanding its pathogenesis and causative biomarkers is likely to yield insights for prediction and treatment. Herein, we provide evidence that transthyretin, a transporter of thyroxine and retinol, is aggregated in preeclampsia and is present at reduced levels in sera of preeclamptic women, as detected by proteomic screen. We demonstrate that transthyretin aggregates form deposits in preeclampsia placental tissue and cause apoptosis. By using in vitro approaches and a humanized mouse model, we provide evidence for a causal link between dysregulated transthyretin and preeclampsia. Native transthyretin inhibits all preeclampsia-like features in the humanized mouse model, including new-onset proteinuria, increased blood pressure, glomerular endotheliosis, and production of anti-angiogenic factors. Our findings suggest that a focus on transthyretin structure and function is a novel strategy to understand and combat preeclampsia.

  • 246.
    Karlsson, Björn C. G.
    et al.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Rosengren, Annika M.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Näslund, Inga
    FOI.
    Andersson, Per Ola
    FOI.
    Nicholls, Ian A.
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Synthetic Human Serum Albumin Sudlow I Binding Site Mimics2010Inngår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 53, nr 22, s. 7932-7937Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here, we report the design, synthesis, and characterization of molecularly imprinted polymer (MIP) derived mimics of the human serum albumin (HSA) Sudlow I site-the binding site for the anticoagulant warfarin. MIP design was based upon a combination of experimental (H-1 NMR) and computational (molecular dynamics) methods, Two MIPs and corresponding nonimprinted reference polymers were synthesized and characterized (scanning electron microscopy; nitrogen sorption; and Fourier transform infrared spectroscopy). MIP-ligand recognition was examined using radioligand binding studies, where the largest number of selective sites was found in a warfarin-imprinted methacrylic acid ethylene dimethacrylate copolymer (MAA-MIP). The warfarin selectivity of this MIP was confirmed using radioligand displacement and zonal chromatographic studies. A direct comparison of MIP-warfarin binding characteristics with those of the HSA Sudlow I binding site was made, and similarities in site population (per gram polymer or protein) and affinities were observed. The warfarin selectivity of the MIP suggests its potential for use as a recognition element in a MIP-based warfarin sensor and even as a model to aid in understanding and steering blood-plasma protein-regulated transport processes or even for the development of warfarin sensors.

  • 247.
    Karlsson, Oskar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Rodosthenous, Rodosthenis S
    Jara, Calvin
    Brennan, Kasey J
    Wright, Robert O
    Baccarelli, Andrea A
    Wright, Rosalind J
    Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development.2016Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, artikkel-id 0Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Breastmilk has many documented beneficial effects on the developing human infant, but the components of breastmilk that influence these developmental pathways have not been fully elucidated. Increasing evidence suggests that non-coding RNAs encapsulated in extracellular vesicles (EVs) represent an important mechanism of communication between the mother and child. Long non-coding RNAs (lncRNAs) are of particular interest given their key role in gene expression and development. However, it is not known whether breastmilk EVs contain lncRNAs. We used qRT-PCR to determine whether EVs isolated from human breastmilk contain lncRNAs previously reported to be important for developmental processes. We detected 55 of the 87 screened lncRNAs in EVs from the 30 analyzed breastmilk samples, and CRNDE, DANCR GAS5, SRA1 and ZFAS1 were detected in >90% of the samples. GAS5, SNHG8 and ZFAS1 levels were highly correlated (Spearman's rho>0.9; P<0.0001), which may indicate that the loading of these lncRNAs into breastmilk EVs is regulated by the same pathways. The detected lncRNAs are important epigenetic regulators involved in processes such as immune cell regulation and metabolism. They may target a repertoire of recipient cells in offspring and could be essential for child development and health. Further experimental and epidemiological studies are warranted to determine the impact of breastmilk EV-encapsulated lnRNAs in mother to child signaling.

  • 248.
    Karlsson, Susanne
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap.
    Modin, Judit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    Becker, Hans-Christian
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap.
    Hammarström, Leif
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för biokemi och organisk kemi.
    How Close Can You Get?: Studies of Ultrafast Light-Induced Processes in Ruthenium-[60] Fullerene Dyads with Short Pyrazolino and Pyrrolidino Links2008Inngår i: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 47, nr 16, s. 7286-7294Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two pyrazoline- and one pyrrolidine-bridged Ru(II)bipyridine-[60]fullerene dyads have been prepared and studied by ultrafast time-resolved spectroscopy. A silver-assisted synthesis route, in which Ag(I) removes the chlorides from the precursor complex Ru(bpy)(2)Cl-2 facilitates successful coordination of the [60]fullerene-substituted third ligand. Upon light excitation of the ruthenium moiety, the emission was strongly quenched by the fullerene. The main quenching mechanism is an exceptionally fast direct energy transfer (k(obs) > , 1 x 10(12) s(-1) in the pyrazoline-bridged dyads), resulting in population of the lowest excited triplet state of fullerene. No evidence for electron transfer was found, despite the extraordinarily short donor-acceptor distance that could kinetically favor that process. The observations have implications on the ongoing development of devices built from Ru-polypyridyl complexes and nanostructured carbon, such as C-60 or nanotubes.

  • 249.
    Karlsson, Susanne
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fotokemi och molekylärvetenskap, Kemisk fysik.
    Streich, Daniel
    Johansson, Olof
    Anderlund, Magnus
    Becker, Hans-Christian
    Hammarström, Leif
    Double-pulse Excitation of a Mn2-Ru(II)-Naphthalenediimide Triad: Challenges for Accumulative Electron TransferManuskript (preprint) (Annet vitenskapelig)
  • 250. Kars, Mohammed
    et al.
    Fredrickson, Daniel C.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för oorganisk kemi och strukturkemi.
    Gomez-Herrero, A.
    Lidin, Sven
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK), Avdelningen för oorganisk kemi och strukturkemi.
    Rebbah, Allaoua
    Otero-Diaz, L. C.
    Structural study by X-ray diffraction and transmission electron microscopy of the misfit compound (SbS1-xSex)(1.16)(Nb1.036S2)(2)2010Inngår i: Materials research bulletin, ISSN 0025-5408, E-ISSN 1873-4227, Vol. 45, nr 8, s. 982-988Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the Sb-Nb-S-Se system, a new misfit layer compound (MSL) has been synthesized and its structure was determined by combining single crystal X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. It presents a composite crystal structure formed by (SbS1-xSex)slabs stacking alternately with double NbS2 layers and both can be treated as separate monoclinic subsystems. The (SbS1-xSex) slabs comprise a distorted, two-atom-thick layer with NaCl-type structure formed by an array of (SbX5) square pyramids joined by edges (X: S, Se); the NbS2 layers consist of (SbX5) trigonal prisms linked through edge-sharing to form sheets, just as in the 2H-NbS2 structure type. Both sublattices have the same lattice parameters a = 5.7672(19) angstrom, c = 17.618(6) angstrom and beta = 96.18(3)degrees, with incommensurability occurring along the b direction: b(1) = 3.3442(13) angstrom for the NbS2 subsystem and b(2) = 2.8755(13) angstrom for the (SbS1-xSex) subsystem. The occurrence of diffuse scattering intensity streaked along c* indicates that the (SbS1-xSex) subsystem is subjected to extended defects along the stacking direction.

2345678 201 - 250 of 510
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