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1.
  • Andersson, Gerhard, et al. (författare)
  • Internet-based psychodynamic versus cognitive behavioral guided self-help for generalized anxiety disorder : A randomized controlled trial
  • 2012
  • Ingår i: Psychotherapy and Psychosomatics. - Basel, Switzerland : Karger. - 0033-3190 .- 1423-0348. ; 81:6, s. 344-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Guided Internet-based cognitive behavior therapy (ICBT) has been tested in many trials and found to be effective in the treatment of anxiety and mood disorders. Generalized anxiety disorder (GAD) has also been treated with ICBT, but there are no controlled trials on guided Internet-based psychodynamic treatment (IPDT). Since there is preliminary support for psychodynamic treatment for GAD, we decided to test if a psychodynamically informed self-help treatment could be delivered via the Internet. The aim of the study was to investigate the efficacy of IPDT for GAD and to compare against ICBT and a waiting list control group.Method: A randomized controlled superiority trial with individuals diagnosed with GAD comparing guided ICBT (n = 27) and IPDT (n = 27) against a no treatment waiting list control group (n = 27). The primary outcome measure was the Penn State Worry Questionnaire.Results: While there were no significant between-group differences immediately after treatment on the main outcome measure, both IPDT and ICBT resulted in improvements with moderate to large within-group effect sizes at 3 and 18 months follow-up on the primary measure in the completer analyses. The differences against the control group, although smaller, were still significant for both PDT and CBT when conforming to the criteria of clinically significant improvement. The active treatments did not differ significantly. There was a significant group by time interaction regarding GAD symptoms, but not immediately after treatment.Conclusions: IPDT and ICBT both led to modest symptom reduction in GAD, and more research is needed.Copyright (C) 2012 S. Karger AG, Basel
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2.
  • Angserud, Jenny, et al. (författare)
  • On a wear test for rock drill inserts
  • 2013
  • Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 301:1-2, s. 109-115
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work wear of cemented carbide rock drill inserts is evaluated by using a rotating rock cylinder as counter surface. The influence on wear rate and degradation mechanisms from varying dry and wet conditions, cemented carbide grade, abrasive particle type and size as well as load is studied. The used abrasive media are alumina and silica.Test results show high repeatability and the three tested cemented carbide grades can be differentiated, even though their relative difference in sample hardness is modest. The loads used, 100–200 N, are sufficiently high to cause fracture and wear of the granite rock. The degraded microstructure of inserts tested under wet and dry conditions as well as with added silica particles is similar to field worn inserts. Hence, the same wear mechanisms occur and the test successfully mimics rock drill wear. Typical insert wear includes cracking and fragmentation of WC grains, depletion of Co binder phase and adhered material originating from the rock.Tests under dry conditions always cause less measured wear than tests under wet conditions.Addition of alumina particles, which are harder than the used cemented carbide samples, causes a significant wear rate increase but does not provide wear similar to rock drilling.
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3.
  • Buttner, Frank, et al. (författare)
  • Cyclic B-Tetra- and Pentapeptides: Synthesis through On-Resin Cyclization and Confomrational Studies by X-Ray, NMR and CD Spectroscopy and Theoretical Calculations
  • 2005
  • Ingår i: Chem. Eur. J.. - : Wiley. ; 11, s. 6145-6158
  • Tidskriftsartikel (refereegranskat)abstract
    • The solution-phase synthesis of the simplest cyclic B-tetrapeptide, cyclo(B-Ala)4 (4), as well as the solidphase syntheses through side chain anchoring and on-resin cyclization of the cyclic B3-tetrapeptide cyclo-(B3hPhe-B3hLeu-B3hLys-B3hGln-) (14) and the first cyclic B3-pentapeptide cyclo- (B3hVal-B3hPhe-B3Leu- B3hLys-B3hLys-) (19) are reported. Extensive computational as well as spectroscopic studies, including X-ray and NMR spectroscopy, were undertaken to determine the preferred conformations of these unnatural oligomers in solution and in the solid state. cyclo(B-Ala)4 (4) with no chiral side chains is shown to exist as a mixture of rapidly interchanging conformers in solution, whereas inclusion of chiral side chains in the cyclo-B3-tetrapetpride causes stabilizaton of one dominating conformer. The cyclic B3-pentapeptide on the other hand shows larger conformational freedom. The X-ray structure of achiral cyclo(B-Ala)4 (4) displays a Ci-symmetrical 16-membered ring with adjacent C=O and N-H atoms pointing pair wise up and down with respect to the ring plane. CD spectorscopic examinations of all cyclic B-peptides were undertaken and revealed results valuable as starting point for further structural investigations of these entities.
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5.
  • Darenberg, Jessica, et al. (författare)
  • Molecular and clinical characteristics of invasive group A streptococcal infection in Sweden
  • 2007
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 45:4, s. 8-450
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The incidence and severity of invasive group A streptococcal infection demonstrate great variability over time, which at least, in part, seems to be related to group A streptococcal type distribution among the human population. Methods. An enhanced surveillance study of invasive group A streptococcal infection (746 isolates) was performed in Sweden from April 2002 through December 2004. Noninvasive isolates from either the throat or skin (773 isolates) were collected in parallel for comparison. Clinical and epidemiological data were obtained from 88% of patients with invasive disease and were related to isolate characteristics, including T type, emm sequence type, and the presence of 9 superantigen genes, as well as pulsed-field gel electrophoresis pattern comparisons of selected isolates. Results. The annual incidence was 3.0 cases per 100,000 population. Among the patients with invasive disease, 11% developed streptococcal toxic shock syndrome, and 9.5% developed necrotizing fasciitis. The overall case-fatality rate was 14.5%, and 39% of the patients with streptococcal toxic shock syndrome died (P < .001). The T3/13/B3264 cluster accounted for 33% of invasive and 25% of noninvasive isolates. Among this most prevalent type cluster, emm types 89 and 81 dominated. Combined results from pulsed-field gel electrophoresis, emm typing, and superantigen gene profiling identified subgroups within specific emm types that are significantly more prone to cause invasive disease than were other isolates of the same type. Conclusions. This study revealed a changing epidemiology of invasive group A streptococcal infection in Sweden, with emergence of new emm types that were previously not described. The results also suggest that some clones may be particularly prone to cause invasive disease.
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6.
  • El Miri, Nassima, et al. (författare)
  • A comprehensive investigation on modified cellulose nanocrystals and their films properties
  • 2022
  • Ingår i: International Journal of Biological Macromolecules. - : Elsevier B.V.. - 0141-8130 .- 1879-0003. ; 219, s. 998-1008
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, we aimed to tune cellulose nanocrystals (CNCs) properties by introducing different functional groups (aldehyde, carboxyl, silane, and ammonium groups) on the surface through different chemical modifications. These functional groups were obtained by combining: the periodate oxidation with TEMPO-oxidation, aminosylation or cationization. CNCs produced and their films were characterized to elucidate their performances. The results showed that the properties of obtained CNCs varied depending on the grafted functionalities on the surface. The results reveal that after each modification a colloidal stability is preserved. Interestingly, Periodate oxidation of cellulose nanocrystals results in film components that interact through intra- and intermolecular hemiacetals and lead to films with a tensile strength of 116 MPa compared to the pristine CNCs, in contrast the subsequent modifications led to lower tensile strength. Of note, remarkable thermal stability has been achieved after modifications reaching a maximum of 280 °C. The oxygen barrier properties of the films after modifications varied between 0.48 and 0.54 cm3μm/(m2d*kPa) at 50 % RH. 
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7.
  • Eriksson, Anna, et al. (författare)
  • Cleavage of antigen-bound immunoglobulin G by SpeB contributes to streptococcal persistence in opsonizing blood.
  • 2003
  • Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 71:1, s. 211-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Group A streptococci (GAS) express a superantigen, SpeB, having cysteine protease activity. SpeB exhibits several properties that might contribute to virulence, the most recently discovered being the ability to cleave immunoglobulin G (IgG) in a manner similar to that of papain. In the present study, we confirmed this latter finding and found that the irreversible inhibition of SpeB protease activity completely abolishes IgG cleavage. SpeB cleavage of IgG was not species restricted since SpeB cleaved both human, rabbit, and mouse IgG. In order to investigate the nature of the SpeB cleavage of IgG, antibodies were immobilized prior to exposure to SpeB, either by unspecific binding of the Fc to GAS surface proteins or by antigen-specific binding. Analysis of the IgG molecules by SDS-PAGE showed that SpeB could cleave antigen-bound antibodies, while the IgG bound to IgG-binding proteins was protected from cleavage. In a phagocytosis assay using whole blood, the M49 GAS strain NZ131 showed a significantly higher survival than its isogenic speB mutant. Furthermore, the addition of extracellular supernatant derived from an overnight culture of native NZ131 increased the survival of its isogenic speB derivative. This indicates that SpeB's ability to cleave off the Fc part of antigen-bound IgG contributes to GAS escape from opsonophagocytosis while not interfering with the formation of a host-like coat by unspecific IgG binding.
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9.
  • Franco, Irene, et al. (författare)
  • Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type
  • 2019
  • Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of somatic mutation patterns, based on both types and genomic distribution of variants, can shed light on specific processes active in different human tissues and their effect on the transition to cancer. Results: To analyze somatic mutation patterns, we compile a comprehensive genetic atlas of somatic mutations in healthy human cells. High-confidence variants are obtained from newly generated and publicly available whole genome DNA sequencing data from single non-cancer cells, clonally expanded in vitro. To enable a well-controlled comparison of different cell types, we obtain single genome data (92% mean coverage) from multi-organ biopsies from the same donors. These data show multiple cell types that are protected from mutagens and display a stereotyped mutation profile, despite their origin from different tissues. Conversely, the same tissue harbors cells with distinct mutation profiles associated to different differentiation states. Analyses of mutation rate in the coding and non-coding portions of the genome identify a cell type bearing a unique mutation pattern characterized by mutation enrichment in active chromatin, regulatory, and transcribed regions. Conclusions: Our analysis of normal cells from healthy donors identifies a somatic mutation landscape that enhances the risk of tumor transformation in a specific cell population from the kidney proximal tubule. This unique pattern is characterized by high rate of mutation accumulation during adult life and specific targeting of expressed genes and regulatory regions.
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10.
  • Gericke, Martin, et al. (författare)
  • The European Polysaccharide Network of Excellence (EPNOE) research roadmap 2040: Advanced strategies for exploiting the vast potential of polysaccharides as renewable bioresources
  • 2024
  • Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 326
  • Tidskriftsartikel (refereegranskat)abstract
    • Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.
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11.
  • Joelsson, Tove, et al. (författare)
  • High strength paper from high yield pulps by means of hot-pressing
  • 2020
  • Ingår i: Nordic Pulp & Paper Research Journal. - : De Gruyter Open Ltd. - 0283-2631 .- 2000-0669. ; 35:2, s. 195-204
  • Tidskriftsartikel (refereegranskat)abstract
    • The hypothesis is that it should be possible to modify papermaking conditions in line with the softening properties of high yield pulp fibres and achieve similar strength properties to conventional chemical pulp based paper. We therefore investigated the rheological and physical properties of high yield pulp based papers during hot-pressing. Our results confirm that increased temperature combined with sufficient pressure enables permanent densification by softening of lignin, producing very high tensile strength. This treatment also significantly improved the wet tensile strength in comparison to bleached kraft pulp without using wet strength agents. The high yield pulps used here were spruce based thermomechanical pulp, chemi-thermomechanical pulp, and high temperature chemi-thermomechanical pulp, and birch-aspen based neutral sulphite semi chemical pulp, with spruce-pine based bleached kraft pulp as reference. Rapid Köhten sheets of 150 g/m 2 150\hspace{0.1667em}\text{g}/{\text{m}^{2}} and 50 % dryness were hot-pressed in a cylinder-press at 20-200 °C, 7 MPa, and 1 m/min. The mechanical properties showed great improvements in these high yield pulp papers, with tensile index increased to 75 kNm/kg and compression strength index to 45 kNm/kg; levels close to and better than bleached kraft. Wet strength increased to 16 Nm/g compared to 5 Nm/g for bleached kraft. 
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13.
  • Joelsson, Tove, et al. (författare)
  • Improving paper wet strength via increased lignin content and hot-pressing temperature
  • 2020
  • Ingår i: TAPPI Journal. - 0734-1415. ; 19:10, s. 487-499
  • Tidskriftsartikel (refereegranskat)abstract
    • It is known that the strength properties of wood-based paper materials can be enhanced via hot-pressing techniques. Today, there is a desire not only for a change from fossil-based packaging materials to new sustainable bio-based materials, but also for more effective and eco-friendly solutions for improving the dry and wet strength of paper and board. Against this background, hot pressing of paper made from high yield pulp (HYP), rich in lignin, becomes highly interesting. This study investigated the influence of pressing temperature and native lignin content on the properties of paper produced by means of hot pressing. Kraft pulps of varied lignin content (kappa numbers: 25, 50, 80) were produced at pilot scale from the same batch by varying the cooking time. We then studied the effect of lignin content by evaluating the physical properties of Rapid When sheets after hot pressing in the temperature range of 20 degrees C-200 degrees C with a constant nip pressure of 7 MPa. The pilot-scale cooked pulps were compared with reference samples of mill-produced northern bleached softwood kraft (NBSK) pulp and mill-produced chemithermomechanical pulp (CTMP). Generally, the results demonstrated that lignin content had a significant effect on both dry and wet tensile index. All of the pilot cooked pulps with increased lignin content had a higher tensile index than the reference NBSK pulp. To obtain high tensile index, both dry and wet, the pressing temperature should be set high, preferably at least 200 degrees C; that is, well above the glass transition temperature (Tg) for lignin. Moreover, the lignin content should preferably also be high. All kraft pulps investigated in this study showed a linear relationship between wet strength and lignin content.
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14.
  • Joelsson, Tove, et al. (författare)
  • The impact of sulfonation and hot-pressing of low-energy high temperature chemi-thermomecanical pulp
  • 2022
  • Ingår i: Holzforschung. - : Walter de Gruyter. - 0018-3830 .- 1437-434X. ; 76:5, s. 463-472
  • Tidskriftsartikel (refereegranskat)abstract
    • Hot-pressing high yield pulp-based paper, well above softening temperature of lignin, increases paper density and paper strength. It has been investigated whether improved paper strength can be achieved and if lower pressing temperatures can be used in combination with increased sulfonation of HTCTMP (high temperature chemi-thermomechanical pulp).Moist paper sheets from low-energy Norway Spruce HTCTMP were hot-pressed up to 270°C. Sulfite charges from 25 to 120 kg/bdt were used during impregnation, preheating, and refining at 180°C with an electric energy demand of 370–500 kWh/bdt to a shive content of 1%. The pulps were mixed with 20% bleached unrefined kraft pulp to ensure that the sheet formation would not be hampered by the coarseness of the pulps. A tensile index of 70 kNm/kg was reached with highest sulfite dosage at only 150°C in pressing temperature which can be compared to 60 kNm/kg for the corresponding market CTMP. To obtain high wet strength, the highest temperature was required, while the sulfite charge was found to be of minor importance. This study has shown that it is possible to obtain strong and wet-stable paper products from HTCTMP, having a yield of 94-96% and a low energy demand at reduced pressing temperature.
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15.
  • Joelsson, Tove, et al. (författare)
  • Unique steel belt press technology for high strength papers from high yield pulp
  • 2021
  • Ingår i: SN Applied Sciences. - : Springer. - 2523-3963 .- 2523-3971. ; 3:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The dry strength properties of hot-pressed moist paper improved as stiff high-yield pulp fibers soften and the sheet density increased. Very high wet strength was also achieved without adding strengthening agents. This research focuses on a new hot-pressing methodology based on a steel belt-based pilot cylinder press with infrared heating. The heated steel belt transports the moist paper into the cylinder nip with two adjacent steel rollers with adjustable nip pressure. The temperature ranges up to 300 °C, maximum speed is 5 m/min, maximum pulling force from the steel belt is 70 kN and the line load in the two press nips is 15 kN/m each. High peak pressures are possible due to the hard press nip between steel rolls and steel belt, allowing a good heat transfer to the paper. The long dwell time allows strained drying of the paper which results to high density and high wet strength. Paper samples from high-yield pulps were tested at different nip pressures, temperatures and machine speeds while the dry content was kept constant at about 63%. High nip pressure showed the largest effect on densification and dry strength. While high temperature and long dwell time seem to be most important in achieving high wet strength.
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16.
  • Kaszowska, Marta, et al. (författare)
  • Studies on the interactions between glycosylated beta(3)-peptides and the lectin Vicia villosa by saturation transfer difference NMR spectroscopy
  • 2009
  • Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 344:18, s. 2577-2580
  • Tidskriftsartikel (refereegranskat)abstract
    • Saturation transfer difference (STD) NMR spectroscopy was used to study the interaction of the lectin Vicia villosa (VVLB4) with alpha-D-GalNAc glycosylated beta(3)-peptides. The data were compared to those obtained with the monosaccharides D-Gal, D-GalNAc, and D-Glc as well as with those obtained with the Tn antigen alpha-glycopeptide (D-GalNAc-alpha-O-Ser/Thr), molecule naturally recognized by V. villosa. Evidence that the lectin also recognizes glycosylated beta(3)-peptides and has close contact with both the sugar and amino acid moieties was obtained.
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17.
  • Maripuu, Linda, et al. (författare)
  • Dynamics of the immune response against extracellular products of group A streptococci during infection
  • 2007
  • Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 14:1, s. 44-51
  • Tidskriftsartikel (refereegranskat)abstract
    • The immune response against the infecting group A streptococcus (GAS) extracellular products (EP) was determined in acute- and convalescent-phase sera from 75 patients with different clinical manifestations of GAS infection. All EP elicited a high proliferative response in human peripheral blood mononuclear cells. In patients with bacteremia, low neutralization in acute-phase sera was associated with development of streptococcal toxic shock syndrome. Lack of neutralization in acute-phase sera was more common in patients infected with the T1emm1 serotype. The majority of patients did not develop the ability to neutralize the mitogenic activity of their infecting isolate despite a significant increase in enzyme-linked immunosorbent assay titer in early convalescent-phase sera. In patients with the ability to neutralize GAS EP, the immune response remained high over at least 3 years. In contrast, the neutralization capacity conferred by intravenous immunoglobulin and/or plasma treatment disappeared within 3 months.
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18.
  • Maripuu, Linda, et al. (författare)
  • Superantigen gene profile diversity among clinical group A streptococcal isolates.
  • 2008
  • Ingår i: FEMS Immunology and Medical Microbiology. - 0928-8244 .- 1574-695X. ; 54:2, s. 236-44
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examines the diversity of superantigen gene profiles between and within emm-genotypes of 92 clinical group A streptococcal isolates (30 STSS, 24 sepsis, 25 erysipelas, and 12 tonsillitis) collected in Sweden between 1986 and 2001. The emm-genotype and the distribution of smeZ, speG, speJ, speA, speC, speH, speI, speK/L, speL/M, speM, and ssa genes, and the smeZ allelic variant were determined using PCR and DNA sequencing. Forty-five emm1 isolates revealed 10 superantigen gene profiles. One profile dominated and was identified in 22 isolates collected over 14 years. The results indicate that a selective advantage maintained this genotype in circulation. The superantigen content among the emm1 isolates ranged from three to seven, with smeZ-1, speG, and speA present in all but one profile. The 47 isolates of 27 other emm-genotypes exhibited 29 superantigen gene profiles. Thus, the distribution of superantigen genes was highly variable within isolates regardless of emm-genotype. Two novel emm1 subtypes and 14 novel smeZ allelic variants were identified. The 22 smeZ alleles were generally linked to the emm-genotype. The results of the investigation show that superantigen gene profiling is useful for tracking spread of clones in the community.
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19.
  • Nordin, Tommy, et al. (författare)
  • Industrially Relevant In-situ Production Of High Yield Pulp Based Nanocellulose Materials Optimized To Improve Strength In Packaging And Printing Papers : A Comparison Between CMC And MFC As The Anionic Component In Layer-by-Layer Technology
  • 2018
  • Ingår i: IMPC 2018. - Trondheim, Norway.
  • Konferensbidrag (refereegranskat)abstract
    • A key issue in papermaking is to understand how to improve strength without losing other important quality measures, like paper bulk. This must of course also be done in a cost efficient way. The trials described in this paper show some different aspects related to the replacement of the expensive anionic component CMC (carboxymethylcellulose) often used in Layer-by-Layer technology together with cationic starch in order to improve strength properties as z-strength and tensile strength of typical chemi-thermomechanical pulp (CTMP) often used as dominating component in industrial scale paper board production. The replacement for CMC investigated here is a MFC (micro-fibrillated cellulose) as the anionic component and paper sheets has been produced on an experimental paper machine at MoRe Research AB. This MFC is a commercially available product and it has not been treated in ways of increasing charge density. The trials were performed at a small pilot scale experimental paper machine (XPM) at MoRe Research in Örnsköldsvik, Sweden. This XPM is equipped with a unique setup to perform Layer-by-Layer-tests under very well controlled conditions. The general conclusion is that it could, with further developments, be feasible to replace CMC with MFC to improve bonding in typical CTMP based paper sheets.
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20.
  • Norgren, Anna S., et al. (författare)
  • Biomolecular Recognition of Glycosylated β3-Peptides by GalNAc Specific Lectins
  • 2007
  • Ingår i: Journal of Molecular Recognition. - : Wiley. - 0952-3499 .- 1099-1352. ; 20:2, s. 132-138
  • Tidskriftsartikel (refereegranskat)abstract
    • The molecular recognition of a novel kind of hybrid conjugates, composed of artificial biomimetic β-peptide oligomers with an O-linked natural N-acetyl-galactosamine (the Tn-antigen) residue, by four different GalNAc specific lectins was investigated using surface plasmon biosensor technology. The influence of the peptide and the glycosyl moiety on the recognition was studied using two glycosylated β3-heptapeptides, a glycosylated α-heptapeptide, two β-amino acid containing dipeptides, and monomeric αGalNAc-O-Thr. Although all four lectins displayed a decreased affinity for the carbohydrate residue when attached to a peptide, as compared to the monomeric Tn-antigen, the peptide part was found to have distinct effects on the binding kinetics - indicating that varying degrees of protein-peptide interactions occurred in the recognition process. Likewise, the lectins did not discriminate between β3-peptides and the α-peptide, but the β- linkage of the galactose had a detrimental effect for at least two of the lectins.
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21.
  • Norgren, Anna S., 1978- (författare)
  • Conformational Stability!? : Synthesis and Conformational Studies of Unnatural Backbone Modified Peptides
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The beauty of the wide functionality of proteins and peptides in Nature is determined by their ability to adopt three-dimensional structures. This thesis describes artificial molecules developed to mimic secondary structures similar to those found crucial for biological activities.In the first part of this thesis, we focused on post-translational modifications of a class of unnatural oligomers known as β-peptides. Through the design and synthesis of a glycosylated β3-peptide, the first such hybrid conjugate was reported. In this first report, a rather unstable 314-helical structure was found. Subsequently, a collection of six new glycosylated β3-peptides was synthesized with the aim to optimize the helical stability in water.The ability of natural proteins, i.e. lectins, to recognize the carbohydrate residue on these unnatural peptide backbones was investigated through a biomolecular recognition study.The second part of this thesis concerns the design of conformationally homogeneous scaffolds, which could be of importance for biomedical applications. In paper V, four- and five-membered cyclic all-β3-peptides were investigated for this purpose. In a subsequent paper, a completely different strategy was employed; herein, the ability of a single β2-amino acid to restrict the conformational freedom of a cyclic α-peptide was studied. In the third part of this thesis, we synthesized and investigated the folding propensities of novel backbone modified oligomers, i.e. β-peptoids (N-substituted β-Ala) with α-chiral side chains.The collective results of these studies have established the procedures required for synthesis of glycosylated β-peptides and deepened our understanding of the factors governing folding among such oligomers. Moreover, it was established that β-amino acids can be a useful tool to increase conformational stability of cyclic peptides.
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22.
  • Norgren, Anna S., et al. (författare)
  • Design and synthesis of glycosylated b 3-peptides capable of folding into the 314-helical conformation in water
  • 2008
  • Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 73:14, s. 5272-5278
  • Tidskriftsartikel (refereegranskat)abstract
    • Herein, we describe the synthesis of seven glycosylated adopt stable 3 novel class of functionalized foldamers in which a natural post-translational modification is attached to an unnatural peptidomimetic backbone. Conformational studies by CD spectroscopic measurements were performed in methanol and in water (pH 7). Additionally, the influence of temperature, pH, and concentration on the ability of glycosylated were investigated. The first NMR-derived solution state structure of a glycosylated water is also presented.
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24.
  • Norgren, Anna S., et al. (författare)
  • Glycosylated Foldamers : Synthesis of Carbohydrate-modified β3hSer and Incorporation into β-Peptides
  • 2007
  • Ingår i: Journal of Peptide Science. - : Wiley. - 1075-2617 .- 1099-1387. ; 13:11, s. 717-727
  • Tidskriftsartikel (refereegranskat)abstract
    • Fmoc-protected β3hserine (β3hSer) was prepared and O-linked to suitably protected N-acetylgalactosamine (GalNAc) and N-acetylglucosamine (GlcNAc) derivatives. Glycosylation of β3hSer was made by two independent routes: either by direct glycosyl linkage to the β3hSer, or linkage to natural L-Ser and then utilizing the carbohydrate moiety as a protecting group in an Arndt–Eistert homologation. Both procedures gave the novel glycosylated β3-amino acids Fmoc-β3hSer(α-D-GalNAc(Ac)3)-OH (1a), its β-anomer (1b), and Fmoc-β3hSer(β-D-GlcNAc(Ac)3)-OH (2), which were utilized in the solid-phase peptide synthesis of four glycosylated dipeptides (3a–d) and two heptapeptides (4a–b). The preparation of β-amino acids bearing common post-translational modifiers represents an important step towards functionalized foldamers with broad applications in biomedical research.
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26.
  • Norgren, Anna S., et al. (författare)
  • β2-Amino Acids in the Design of Conformationally Homogeneous cyclo-Peptide Scaffolds
  • 2006
  • Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 71:18, s. 6814-6821
  • Tidskriftsartikel (refereegranskat)abstract
    • Herein, we report studies on the influence of chiral, beta(2)-amino acids in the design of conformationally homogeneous cyclic tetrapeptide scaffolds. The cyclic alpha-tetrapeptide cyclo(-Phe-D-Pro-Lys-Phe-) (1) and its four mixed analogues, having one of the alpha-Phe replaced by either an (S)-or an (R)-beta(2)hPhe residue (i.e., cyclo(-(R)-beta(2)hPhe-D-Pro-Lys-Phe) (2a), cyclo(-(S)-beta(2)hPhe-D-Pro-Lys-Phe-) (2b), cyclo(-Phe-D-Pro-Lys-(R)-beta(2)hPhe-) (3a), and cyclo(- Phe- D- Pro- Lys-( R)-, 2hPhe-) ( 3b)), were all synthesized through solidphase procedures followed by solution- phase cyclization. Initially, all five cyclo- peptides were analyzed by H-1 NMR spectroscopic studies in different solvents and at variable temperatures. Subsequently, a detailed 2D NMR spectroscopic analysis of three of the mixed peptides in water was performed, and the information thus extracted was used as restraints in a computational study on the peptides' conformational preference. An X- ray crystallographic study on the side chain- protected (Boc) 2a revealed the solid- state structure of this peptide. The results presented herein, together with previous literature data on beta(3)-amino acid residues, conclusively demonstrate the potential of beta-amino acids in the design of conformationally homogeneous cyclic peptides that are homologous to peptides with known applications in biomedicinal chemistry and as molecular receptors.
  •  
27.
  • Norgren, Anna, et al. (författare)
  • Synthesis and circular dichroism spectroscopic investigations of oligomeric β-peptoids with α-chiral side chains
  • 2006
  • Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 8:20, s. 4533-4536
  • Tidskriftsartikel (refereegranskat)abstract
    • Biomimetic oligomers are of large interest both as targets for combinatorial and parallel synthetic efforts and as foldamers. For example, shorter peptoid derivatives of beta-peptides, i.e., oligo-N-substituted beta-Ala, have been described as potential lead structures. Herein, we describe a solid-phase synthetic route to beta-peptoids with alpha-chiral aromatic N-substituents up to 11 residues long. Furthermore, the folding propensities of these oligomers were investigated by circular dichroism (CD) spectroscopy.
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28.
  • Norgren, Claes, et al. (författare)
  • Näringspolitikens effekter : brister i informationen om statliga satsningar
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Det går idag inte att veta om viktiga delar av de insatser som staten riktar till näringslivet får effekt. Detta beror på att de aktörer som har hand om insatserna inte är skyldiga att lämna ut uppgifter om vilka företag som fått ta del av insatser. Enligt Riksrevisionen bör det systematiskt samlas in och sammanställas uppgifter om alla företag som har fått ta del av någon typ av insats från staten.Redan 2009 konstaterades att bristen på information gjorde det svårt, och ibland omöjligt, att följa upp och utvärdera vissa näringspolitiska insatser riktade till enskilda företag. Regeringen gav 2010 Myndigheten för tillväxtpolitiska utvärderingar och analyser (Tillväxtanalys) i uppdrag att upprätta en databas över företag som fått del av näringspolitiska satsningar. Vid avrapporteringen 2012 konstaterades att det fanns problem med att samla in information från företagen med hänvisning till affärssekretess och arbetsbörda.Riksrevisionen gör bedömningen att denna brist i information måste lösas. Riksrevisionen rekommenderar därför regeringen att tillsammans med Tillväxtanalys utreda möjligheterna att, exempelvis inom regelverket för den officiella statistiken, införa en lagreglerad uppgiftsskyldighet som möjliggör uppföljning och utvärdering av näringspolitiska insatser. Rekommendationer riktas även till de granskade statliga bolagen och de av staten ensamt bildade stiftelserna.
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29.
  • Norgren, Jakob, et al. (författare)
  • APOE-Genotype and Insulin Modulate Estimated Effect of Dietary Macronutrients on Cognitive Performance : Panel Analyses in Nondiabetic Older Adults at Risk of Dementia
  • 2023
  • Ingår i: Journal of Nutrition. - : Elsevier. - 0022-3166 .- 1541-6100. ; 153:12, s. 3506-3520
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The apolipoprotein E gene (APOE e-2/3/4, combined as 6 different genotypes: e-22/23/24/33/34/44) and insulin status modulate dementia risk and play a role in the metabolism of macronutrients.Objectives: We aimed to examine APOE-genotype and fasting insulin as effect modifiers of the slopes between dietary macronutrients and cognitive performance among older adults at risk of dementia. Methods: Panel analyses-with diet and cognition measured at baseline and follow-up at years 1 and 2-were performed in a sub-sample from the FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) trial (n = 676, 60-77 y, 46% fe -males, all nondiabetics). The associations between macronutrients (3-d food records, z-scores) and global cognition (modified Neuropsy-chological Test Battery, z-score) were analyzed in mixed regression models adjusted for confounders selected a priori. After a gradient was implied by the point estimates in categorical APOE analyses, we investigated a continuous APOE variable [APOE-gradient, coded-1 (for e-23), -0.5 (e-24), 0 (e-33), 1 (e-34), 2 (e-44)] as an effect-modifier.Results: At increasing levels of the APOE-gradient, a relatively more favorable slope between diet and cognition was observed for a lower carbohydrate/fat ratio [p = -0.040, 95% confidence interval (CI): -0.074, -0.006; P = 0.020 for interaction diet x APOE-gradient), and higher protein (p = 0.075, 95% CI: 0.042, 0.109; P = 9.4 x 10-6). Insulin concentration (log-linear) modulated the association between the car-bohydrate/fat ratio and cognition by a quadratic interaction (p = -0.016, P = 0.039). Coherent findings for exploratory predictors (fiber, fat subtypes, composite score, metabolic biomarkers) were compatible with published hypotheses of differential dietary adaptation by APOE, with cognition among e-33 being relatively independent of dietary parameters-implying metabolic flexibility. Antagonistic slopes to cognition for e-23 (positive) compared with e-34 and e-44 (negative) were found for a Higher-carbohydrates-fiber-Lower-fat-protein composite score, even as within-subjects effects. Conclusions: APOE-based precision nutrition appears conceptually promising, but replications in wider samples are warranted, as well as support from trials. Both relative hyper-and hypoinsulinemia might modulate the effect of diet on cognition.
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30.
  • Norgren, Jakob, et al. (författare)
  • Capillary blood tests may overestimate ketosis : triangulation between three different measures of beta-hydroxybutyrate
  • 2020
  • Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 318:2, s. e184-E188
  • Tidskriftsartikel (refereegranskat)abstract
    • The ketone body beta-hydroxybutyrate (BHB), assessed by a point-of-care meter in venous whole blood (BHBv), was used as the main outcome in a study on nutritional ketosis in healthy older adults. Two other BHB measures were also used in the study for validation and exploratory purposes, and here we report findings on correlation and agreement between those three methods. Ketosis in the range of 0-1.5 mmol/L was induced in 15 healthy volunteers by intake of medium-chain fatty acids after a 12-h fast. BHBv was assessed at 12 time points for 4 h. The same point-of-care meter was also used to test capillary blood (BHBc) at three time points, and a laboratory test determined total ketones (TK) in plasma (BHBp + acetoacetate) at four time points. A total of 180 cases included simultaneous data on BHBv, BHBc, BHBp, and TK. TK correlated with BHBp (Pearson's r = 0.99), BHBv (r = 0.91), and BHBc (r = 0.91), all P < 0.0001. BHBv and BHBp had good agreement in absolute values. However, the slope between BHBc and BHBv, measured with the same device, was in the range of 0.64-0.78 in different regression models, indicating substantially higher BHB concentrations in capillary versus venous blood. We conclude that all three methods are valid to detect relative changes in ketosis, but our results highlight the importance of method considerations and the possible need to adjust cutoffs, e.g., in the management of ketoacidosis and in the evaluation and comparison of dietary interventions.
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31.
  • Norgren, Jakob, et al. (författare)
  • Ketosis After Intake of Coconut Oil and Caprylic Acid-With and Without Glucose : A Cross-Over Study in Healthy Older Adults
  • 2020
  • Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Medium-chain-triglycerides (MCT), formed by fatty acids with a length of 6-12 carbon atoms (C6-C12), constitute about two thirds of coconut oil (Coc). MCT have specific metabolic properties which has led them to be described as ketogenic even in the absence of carbohydrate restriction. This effect has mainly been demonstrated for caprylic acid (C8), which constitutes about 6-8% of coconut oil. Our aim was to quantify ketosis and blood glucose after intake of Coc and C8, with and without glucose intake. Sunflower oil (Suf) was used as control, expected to not break fasting ketosis, nor induce supply-driven ketosis. Method: In a 6-arm cross-over design, 15 healthy volunteers-age 65-73, 53% women-were tested once a week. After a 12-h fast, ketones were measured during 4 h after intake of coffee with cream, in combination with each of the intervention arms in a randomized order: 1. Suf (30 g); 2. C8 (20 g) + Suf (10 g); 3. C8 (20 g) + Suf (10 g) + Glucose (50 g); 4. Coc (30 g); 5. Coc (30 g) + Glucose (50 g); 6. C8 (20 g) + Coc (30 g). The primary outcome was absolute blood levels of the ketone beta-hydroxybutyrate, area under the curve (AUC). ANOVA for repeated measures was performed to compare arms. Results: beta-hydroxybutyrate, AUC/time (mean +/- SD), for arms were 1: 0.18 +/- 0.11; 2: 0.45 +/- 0.19; 3: 0.28 +/- 0.12; 4: 0.22 +/- 0.12; 5: 0.08 +/- 0.04; 6: 0.45 +/- 0.20 (mmol/L). Differences were significant (all p <= 0.02), except for arm 2 vs. 6, and 4 vs. 1 & 3. Blood glucose was stable in arm 1, 2, 4, & 6, at levels slightly below baseline (p <= 0.05) at all timepoints hours 1-4 after intake. Conclusions: C8 had a higher ketogenic effect than the other components. Coc was not significantly different from Suf, or C8 with glucose. In addition, we report that a 16-h non-carbohydrate window contributed to a mild ketosis, while blood glucose remained stable. Our results suggest that time-restricted feeding regarding carbohydrates may optimize ketosis from intake of MCT.
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32.
  • Norgren, Jakob, et al. (författare)
  • Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF : Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults
  • 2021
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: β-hydroxybutyrate (BHB) can upregulate brain-derived neurotrophic factor (BDNF) in mice, but little is known about the associations between BHB and BDNF in humans. The primary aim here was to investigate whether ketosis (i.e., raised BHB levels), induced by a ketogenic supplement, influences serum levels of mature BDNF (mBDNF) and its precursor proBDNF in healthy older adults. A secondary aim was to determine the intra-individual stability (repeatability) of those biomarkers, measured as intra-class correlation coefficients (ICC).Method: Three of the arms in a 6-arm randomized cross-over trial were used for the current sub-study. Fifteen healthy volunteers, 65–75 y, 53% women, were tested once a week. Test oils, mixed in coffee and cream, were ingested after a 12-h fast. Labeled by their level of ketosis, the arms provided: sunflower oil (lowK); coconut oil (midK); caprylic acid + coconut oil (highK). Repeated blood samples were collected for 4 h after ingestion. Serum BDNF levels were analyzed for changes from baseline to 1, 2 and 4 h to compare the arms. Individual associations between BHB and BDNF were analyzed cross-sectionally and for a delayed response (changes in BHB 0–2 h to changes in BDNF at 0–4 h). ICC estimates were calculated from baseline levels from the three study days.Results: proBDNF increased more in highK vs. lowK between 0 and 4 h (z-score: β = 0.25, 95% CI 0.07–0.44; p = 0.007). Individual change in BHB 0–2 h, predicted change in proBDNF 0–4 h, (β = 0.40, CI 0.12–0.67; p = 0.006). Change in mBDNF was lower in highK vs. lowK at 0–2 h (β = −0.88, CI −1.37 to −0.40; p < 0.001) and cumulatively 0–4 h (β = −1.01, CI −1.75 to −0.27; p = 0.01), but this could not be predicted by BHB levels. ICC was 0.96 (95% CI 0.92–0.99) for proBDNF, and 0.72 (CI 0.47–0.89) for mBDNF.Conclusions: The findings support a link between changes in peripheral BHB and proBDNF in healthy older adults. For mBDNF, changes differed between arms but independent to BHB levels. Replication is warranted due to the small sample. Excellent repeatability encourages future investigations on proBDNF as a predictor of brain health.Clinical Trial Registration: ClinicalTrials.gov, NCT03904433.
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33.
  • Norrby-Teglund, Anna, et al. (författare)
  • Correlation between serum TNF alpha and IL6 levels and severity of group A streptococcal infections
  • 1995
  • Ingår i: Scandinavian Journal of Infectious Diseases. - 0036-5548 .- 1651-1980. ; 27:2, s. 125-130
  • Tidskriftsartikel (refereegranskat)abstract
    • The multiorgan failure syndrome caused by group A streptococci (GAS) designated streptococcal toxic shock syndrome (STSS) is believed to be mediated by cytokines induced by superantigens. In order to study the relationship between superantigen production, cytokine levels in patient sera, and clinical GAS manifestation we examined acute-phase sera and strains from 25 patients with GAS bacteremia. The patients had various disease manifestations, including STSS (44%), erysipelas (28%), septicemia (24%), wound infections (16%), and pneumonia (12%). Serotype T1M1 dominated, representing 56% of the isolates, but also strains of other serotypes were identified. The strains were found to produce the streptococcal pyrogenic exotoxins (Spe) A, B, and F, as determined by immuno-blot analyses. There was no difference in amounts of toxin produced between strains isolated from patients with different manifestations of disease. Levels of TNF alpha, IL1 alpha, IL6, IL8, and IFN gamma in acute-phase sera were determined by use of ELISA and RIA assays. The analyses showed higher levels of IL6 in sera from patients with STSS than in sera from patients with bacteremia without shock. TNF alpha was elevated in sera from patients with STSS, as compared to sera from patients with uncomplicated pharyngotonsillitis. No increase in the levels of IL1 alpha, IL8, and IFN gamma could be found in the patient sera and there was no difference in the level of those cytokines between the various patient categories.
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34.
  • Pettersson, Gunilla, et al. (författare)
  • Manufacturing of paper with high wetstrength from CTMP and high yield NSK by combining sizing and wet strength additives with hot-pressing
  • 2022
  • Ingår i: Proceedings of the International Mechanical Pulping Conference. ; , s. 109-113
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • In this work we have investigated the potention to maximize wet strength of papers made from lignin rich pulps by combining wet strength chemicals in with hotpressing. We have earlier shown that it is possible to increase density, dry and wet-strength of lignin rich paper sheets by hotpressing utilizing the softening properties of lignin. This work indi-cated that it was possible to achieve synergistic effects when using wet strength agents.
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35.
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36.
  • Samuelsson, Tove, et al. (författare)
  • Development of strong and water resistant packaging materials from high yield pulps – fundamental aspects
  • 2018
  • Ingår i: IMPC 2018. - Trondheim, Norway.
  • Konferensbidrag (refereegranskat)abstract
    • This work is focused on fundamental aspects of the densification of paper sheets during hot-pressing under conditions where the lignin in the fibre walls is softened. In this study light microscope and scanning electron microscope (SEM) techniques were used to reveal the mechanisms in the fibre network structure within the paper sheets that arises due to densification and the impact of lignin. UV and staining methods and spectrometric observations of the ultrastructure of cross section of paper sheets and fibre surfaces will highlight the changes that occur in the fibre structures. This study improves the understanding of how fibres collapse and how internal fibre-fibre bonds in lignin-rich mechanical pulp affect the physical properties of the final paper sheet. To demonstrate this, paper sheets from five different pulps containing different concentration of natural lignin were produced. Handsheets of 150 g/m2 were prepared in a Rapid Köthen (RK) laboratory sheet former, where the sheets were press-dried at 100 kPa and ca 90oC to a dry content of 45-50% d.c. After 24 hours in room temperature the hand sheets were hot-pressed in a temperature interval from 20 – 200oC at a constant pressure in a cylinder-press at a speed of 1 m/min. The results show that remarkable improvements on paper sheets, based lignin-rich pulps, can be achieved in terms of increased tensile index (up to 85 kNm/kg), compression strength, SCT, (up to 38 kNm/kg) and wet strength (up to 10 kNm/kg), which depends on the densification of the fibre structure at high temperature and pressure in the load nip. It is concluded that this to a major extent is related to that the lignin rich fibres are compressed at high enough temperature to both softened and develop tacky surfaces so that the fibres are locked into their positions within the highly densified sheets. The SEM evaluation shows how the surface structure get dense at pressing at 200oC for the CTMP based paper sheets. The light microscopy studies of the sheet cross sections reveal how the fibres collapse in the case of CTMP based sheets while fibres from bleached kraft pulp based sheets are quite well collapsed already at room temperature.
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37.
  • Sendi, Parham, et al. (författare)
  • Bacterial phenotype variants in group B streptococcal toxic shock syndrome
  • 2009
  • Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 15:2, s. 223-232
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes.
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38.
  • Shoja, Siamak, 1980, et al. (författare)
  • Microstructure investigation of textured CVD alumina coatings
  • 2020
  • Ingår i: International Journal of Refractory Metals and Hard Materials. - : Elsevier BV. - 0263-4368 .- 2213-3917. ; 87
  • Tidskriftsartikel (refereegranskat)abstract
    • This study concerns the interfacial microstructure and texture development in three textured CVD alpha-Al2O3 coatings using X-ray diffraction, transmission Kikuchi diffraction, scanning transmission electron microscopy and energy dispersive X-ray analysis. It is well known that the performance of these types of coatings relies on the degree and type of texture. The aim of this work is to study the microstructure of three different CVD alpha-Al2O3 layers when deposited onto a Ti(C,N,O) bonding layer. The coatings were deposited onto cemented carbide/cobalt substrates (WC/Co). It was observed that grain boundary diffusion of W and Co occurred through the TiN and Ti(C,N) layers to the bonding layer/alpha-Al2O3 interface. This may disturb the alumina layer nucleation and early growth. Interfacial porosity was observed at the bonding layer/alpha-Al2O3 interface. The number of voids that were detected in the (0001) and (01 (1) over bar0)-textured coatings was similar when H2S was not used during the initial deposition step. When H2S was present during the nucleation step deposition of the alpha-Al2O3 more voids were introduced at the interface for the (0001)-textured samples. The alumina grain morphology developed from small (similar to 100 nm) equiaxed grains at the start of the alumina coating to larger (several microns) columnar grains at the top of the coating. The inner part of the alumina coatings had a more random orientation. The texture changed either: (i) gradually over several grains, or (ii) more abruptly from one grain to another; from more random orientations to the desired texture. The desired texture develops earlier when using H2S at the start for the (0001)-textured coatings, while the (01 (1) over bar0)-texture development benefits from the absence of H2S. Thus, in this study, H2S promotes (0001) texture and interfacial void formation.
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39.
  • Stenlund, Patrik, et al. (författare)
  • Bone response to a novel Ti-Ta-Nb-Zr alloy
  • 2015
  • Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 20, s. 165-175
  • Tidskriftsartikel (refereegranskat)abstract
    • Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al-4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation.
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40.
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41.
  • Strand, Anders, et al. (författare)
  • Selective froth flotation of pitch components from spruce TMP process water
  • 2012
  • Ingår i: Appita journal. - 1038-6807. ; 65:4, s. 337-346
  • Tidskriftsartikel (refereegranskat)abstract
    • Selective removal of dissolved and colloidal pitch components from an unbleached thermomechanical pulp (TMP)pressate by addition of a cationic foaming agent, dodecyltrimethylammonium chloride (DoTAC), and subsequent frothflotation was assessed. The experiments were conducted with varying pH, temperature, and concentrations of DoTACand calcium. The concentrations of pitch components, lignans, and dissolved polysaccharides were determinedbefore and after flotation.All pitch components were removed more efficiently by flotation at pH 5 and 3.5 than by flotation at pH 7.6. Resinand fatty acids were removed to a higher degree than neutral pitch substances at all the tested pH levels. Most of thewater-soluble uronic acids and galactoglucomannans stayed in the TMP water after flotation.Froth flotation with DoTAC was an effective way of selectively removing colloidal and dissolved pitch. Removal of pitch,especially of resin acids, at an early stage should be beneficial to the overall papermaking process.
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42.
  • Stratmann, Svea, 1989-, et al. (författare)
  • Genomic characterization of relapsed acute myeloid leukemia reveals novel putative therapeutic targets
  • 2021
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:3, s. 900-912
  • Tidskriftsartikel (refereegranskat)abstract
    • Relapse is the leading cause of death of adult and pediatric patients with acute myeloid leukemia (AML). Numerous studies have helped to elucidate the complex mutational landscape at diagnosis of AML, leading to improved risk stratification and new therapeutic options. However, multi-whole-genome studies of adult and pediatric AML at relapse are necessary for further advances. To this end, we performed whole-genome and whole-exome sequencing analyses of longitudinal diagnosis, relapse, and/or primary resistant specimens from 48 adult and 25 pediatric patients with AML. We identified mutations recurrently gained at relapse in ARID1A and CSF1R, both of which represent potentially actionable therapeutic alternatives. Further, we report specific differences in the mutational spectrum between adult vs pediatric relapsed AML, with MGA and H3F3A p.Lys28Met mutations recurrently found at relapse in adults, whereas internal tandem duplications in UBTF were identified solely in children. Finally, our study revealed recurrent mutations in IKZF1, KANSL1, and NIPBL at relapse. All of the mentioned genes have either never been reported at diagnosis in de novo AML or have been reported at low frequency, suggesting important roles for these alterations predominantly in disease progression and/or resistance to therapy. Our findings shed further light on the complexity of relapsed AML and identified previously unappreciated alterations that may lead to improved outcomes through personalized medicine.
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43.
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44.
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45.
  • Stratmann, Svea, 1989-, et al. (författare)
  • Transcriptomic analysis reveals proinflammatory signatures associated with acute myeloid leukemia progression
  • 2022
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 152-164
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous studies have been performed over the last decade to exploit the complexity of genomic and transcriptomic lesions driving the initiation of acute myeloid leukemia (AML). These studies have helped improve risk classification and treatment options. Detailed molecular characterization of longitudinal AML samples is sparse, however; meanwhile, relapse and therapy resistance represent the main challenges in AML care. To this end, we performed transcriptome-wide RNA sequencing of longitudinal diagnosis, relapse, and/or primary resistant samples from 47 adult and 23 pediatric AML patients with known mutational background. Gene expression analysis revealed the association of short event-free survival with overexpression of GLI2 and IL1R1, as well as downregulation of ST18. Moreover, CR1 downregulation and DPEP1 upregulation were associated with AML relapse both in adults and children. Finally, machine learning–based and network-based analysis identified overexpressed CD6 and downregulated INSR as highly copredictive genes depicting important relapse-associated characteristics among adult patients with AML. Our findings highlight the importance of a tumor-promoting inflammatory environment in leukemia progression, as indicated by several of the herein identified differentially expressed genes. Together, this knowledge provides the foundation for novel personalized drug targets and has the potential to maximize the benefit of current treatments to improve cure rates in AML. ß 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
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46.
  • Svedberg, Anna, et al. (författare)
  • Cellulose replaces plastic in future packaging materials : Formation of cellulose-based foams with reinforcement of cellulose nanocrystals for porous architecture and thermal insulation
  • 2019
  • Ingår i: EPNOE2019 Book of Abstracts. ; , s. 232-
  • Konferensbidrag (refereegranskat)abstract
    • This paper deals with the production of reinforced and highly porous cellulose/nanocellulosebased foams with excellent mechanical properties, aiming to replace fossil based materials for barrier against air, water and thermal insulation. A lab concept has been developed to produce porous solid foams via convective drying of wet foams. The ambition has been to produce solid foams of low density, in the same regions as expandable polystyrene (EPS) and polypropylene (EPP). Foams have been produced by varying the pulp fiber source and by varying the added amount of foaming agent and stabilizing/reinforcement agents. The wet foams have been characterized by the foam ability, foam stability, drainage capacity and drying behavior. The dried solid foams have been characterized both mechanically and structurally but also with respect to barrier properties and thermal insulation.The results demonstrate that cellulosic foams reinforced with cellulosic nanocrystals can be produced with superior foam stability and excellent mechanical properties, in densities similar to foamed materials based on EPS and EPP. The choice of pulp fiber and reinforcement agent, along with the foaming technology, is decisive for the foam stability, processability and mechanical properties of the solid foam. During the presentation, our experience on this will be highlighted.
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47.
  • Zasadowski, Dariusz, 1980- (författare)
  • REMOVAL OF LIPOPHILIC EXTRACTIVES AND MANGANESE IONS FROM SPRUCE TMP WATER BY FLOTATION
  • 2012
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Dissolved and Colloidal substances (DisCo) and metals are released from wood during thermomechanical pulp (TMP) production. The mechanical treatment causes that these components have a tendency to accumulate in process waters, as the water circulation systems in integrated paper mills are being closed. Disturbances such as pitch depositions on the paper machine (pitch problems), specks in the paper, decreased wet and dry strength, interference with cationic process chemicals, and impaired sheet brightness and friction properties appear in the presence of DisCo substances. The presence of transition metal ions such as manganese results in higher consumption of bleaching chemicals (hydrogen peroxide) and lowers the optical quality of the final product, and addition of complexing agents, such as EDTA or DTPA, to prevent this is needed. The never ending trends to decrease water consumption and increase process efficiency in pulp and paper production stress that it is very important both to know the effects of wood substances on pulping and papermaking and to be able to remove them in an efficient way.Carried out investigations presented in this thesis show that the lipophilic extractives can be removed from TMP press water to high extent. A 90% decrease in turbidity and a 91% removal of lipophilic extractives from TMP press water can be obtained by addition of a cationic surfactant as foaming agent during flotation. Additionally, fibres located in TMP press water are not removed with the foam fraction but purified. A retained concentration of hydrophilic extractives in the process water indicates that the flotation is selective. Moreover, by introduction of a new recoverable surface active complexing agent, a chelating surfactant, manganese ions in the form of chelates can be successfully removed from the pulp fibres and separated from the process water in the same flotation process.iiiThe findings presented above indicate new possibilities for internal water cleaning and decreased emissions to water if flotation technology is applied in an integrated mechanical pulp mill.
  •  
48.
  •  
49.
  • Zasadowski, Darius, et al. (författare)
  • Selective purification of bleached spruce TMP process water by induced air flotation (IAF)
  • 2014
  • Ingår i: Holzforschung. - : Walter de Gruyter GmbH. - 0018-3830 .- 1437-434X. ; 68:2, s. 157-165
  • Tidskriftsartikel (refereegranskat)abstract
    • The environmentally benign closure of water systems in paper mills leads to the problem of accumulation of dissolved and colloidal wood substances (DCS) in process water. Notably, pitch affects the pulp and paper production negatively and increases the demand for additional treatment of the process water. In the present article, the purification of thermomechanical pulping process water from the alkaline peroxide bleaching stage has been investigated, with the induced air flotation (IAF) in focus. The following parameters were considered concerning the IAF efficiency to remove detrimental substances: concentration of cationic foaming agent, pH value, calcium concentration, and temperature. The amounts and characteristics of residual DCS were determined by gas chromatography and turbidity measurements. Residual concentrations of the foaming agent dodecyltrimetylammonium chloride were determined by electrospray ionization mass spectrometry. Up to 90% of pitch was removed, whereas hemicelluloses, which are important in preventing pitch problems, remained in the waters. Up to 70% of the pectic acids accounted for the high cationic demand of the process waters were removed by optimization of the IAF parameters. The presented separation process gives new opportunities to a selective purification of the process waters.
  •  
50.
  • Ås, Joel, et al. (författare)
  • Whole genome case-control study of central nervous system toxicity due to antimicrobial drugs
  • 2024
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 19:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A genetic predisposition to central nervous system (CNS) toxicity induced by antimicrobial drugs (antibiotics, antivirals, antifungals, and antiparasitic drugs) has been suspected. Whole genome sequencing of 66 cases and 833 controls was performed to investigate whether antimicrobial drug-induced CNS toxicity was associated with genetic variation. The primary objective was to test whether antimicrobial-induced CNS toxicity was associated with seventeen efflux transporters at the blood-brain barrier. In this study, variants or structural elements in efflux transporters were not significantly associated with CNS toxicity. Secondary objectives were to test whether antimicrobial-induced CNS toxicity was associated with genes over the whole genome, with HLA, or with structural genetic variation. Uncommon variants in and close to three genes were significantly associated with CNS toxicity according to a sequence kernel association test combined with an optimal unified test (SKAT-O). These genes were LCP1 (q = 0.013), RETSAT (q = 0.013) and SFMBT2 (q = 0.035). Two variants were driving the LCP1 association: rs6561297 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]) and the regulatory variant rs10492451 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]). No common genetic variant, HLA-type or structural variation was associated with CNS toxicity. In conclusion, CNS toxicity due to antimicrobial drugs was associated with uncommon variants in LCP1, RETSAT and SFMBT2.
  •  
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