Change search
Refine search result
1234567 51 - 100 of 2478
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Alemrajabi, Mahmoud
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemical Engineering.
    Forsberg, Kerstin
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemical Engineering.
    Rasmuson, Åke
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemical Engineering.
    Recovery of REE from an apatite concentrate in the nitrophosphate process of fertilizer production.2015Conference paper (Refereed)
  • 52.
    Alexakis, Alexandros Efraim
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Preparation and Testing of FDCA based Nanocomposites2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The project focuses on the use of diallyl 2,5-furanedicarboxylate (DAFDC) as a bio-based alternative for phthalic acid based thermosets. Initially, kinetic analysis, by means of Borchardt and Daniels method was performed to study the curing conditions. However, this model gave inaccurate results mainly due to different conditions apparent during Differential Scanning Calorimetry (DSC) measurement which were not able to be simulated in the experimental procedure that was followed. Nevertheless, by curing DAFDC with  of dicumyl peroxide (DCP), which comprise the matrix, and incorporating graphene oxide nanodots (GONDs) and carbon nanotubes (CNTs) in different weight amounts, in a staggered temperature and time fashion, nanocomposites based on DAFDC were produced. GONDs were oxidized from carbon nanospheres (CNs). The latter were produced from cellulose by adding a dialysis step in the protocol found in the literature 2.

    Through the characterization of the nanocomposites, it was concluded that the above protocol resulted in partially crosslinked materials which were further cured at elevated temperatures during Dynamical Mechanical Analysis (DMA). The fully crosslinked nanocomposites produced from this heating ramp exhibited enhanced properties. More specifically, the degradation temperature corresponding to  loss of mass, i.e. , seemed to be unaffected by the filler content and compared to the matrix it was enhanced by roughly  and  for GOND-filled and CNT-filled nanocomposites, respectively. Conductivity measurements gave an insight on the percolation threshold of the produced nanocomposites. On the one hand, CNT-filled nanocomposites exhibited a percolation threshold at  of CNT and their conductivity was increasing by increasing filler content. On the other hand, for GOND-filled nanocomposites, the filler content seemed to be lower than this threshold, since no electrical conductivity value could be monitored. The mechanical testing showed indications of enhanced properties of the fully cured nanocomposites compared to their partially cured analogues. However, due to the geometry and breaking of the cured samples during DMA, the mechanical properties could not be verified. Finally, the morphology of the nanocomposites was investigated by means of digital microscopy. Both sides of the samples were studied, since the side that was in contact with oxygen during curing, exhibited different morphological behavior than the side that was not in contact with oxygen. In particular, the side which was in contact with oxygen, showed a smoother surface than the side which was in contact with the mold.

    In conclusion, the possibility to produce a bio-based alternative of phthalic acid based thermosets was verified, giving the opportunity to eagerly investigate this monomer in different applications in the future.

  • 53.
    Alfrijat, Christopher
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Eriksson, Rasmus
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Analys och utvärdering av LED-belysning i Stockholms tunnelbana2019Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Trafikförvaltningen, responsible for public transport in Stockholm, has started a project to replace existing luminaires in the subway of Stockholm to LED lights. This thesis could be a basis for an upcoming procurement.

    In this report, various models of LED lights technical specifications will be evaluated based on the environmental requirements in Stockholm’s subway, where the existing luminaires will be replaced. For this environment, there is no standard regarding LED lights today. With the help of literature studies and tests, a groundwork for a specification could be made. The tests were only made on a selection of LED lights and their technical specifications were presented. All luminaires passed the EMC (electromagnetic compatibility) tests that were made in order to determine any interference with Stockholm’s public transport (SL) radio communication system.

    Environmental aspects and economical aspects of the implementation of LED lights has been taken into consideration.

  • 54.
    Ali pour, Nazanin
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Enebro, J.
    Strömberg, Emma
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Qualitative characterization of nanoclay particle emissions from PP nanocomposites after thermal degradation2015In: ICCM International Conferences on Composite Materials, International Committee on Composite Materials , 2015Conference paper (Refereed)
    Abstract [en]

    The use of nanomaterials in polymeric materials is a rapidly expanding field, and the polymer nanocomposites are being introduced into various markets. But there is still little known about the fate of nanocomposites and nanoparticles during service life and end-of-life of the materials. To avoid possible environmental, health and safety problems, simulating different scenarios for nanoparticles release from the polymer matrix plays a key role in commercialization of these advanced materials. The polymer/nanoclay nanocomposites show superior material properties in comparison with the pure polymers, such as improved mechanical properties, heat resistance, flame retardancy and decreased gas permeability. Polypropylene (PP) nanocomposites have attracted a considerable interest due to the material's low cost, low density and extensive production volumes. In this study, in order to obtain reliable results regarding the release of nanoclays from PP nanocomposites, homogenous composite with predetermined content of nanoclay was produced and characterized to obtain information regarding content, dispersion and size of the nanoclays in the matrix. The PP nanocomposite was degraded under controlled conditions and the surface morphology as well as oxidation of the material was characterized with scanning electron microscopy (SEM) and infrared spectroscopy during degradation. A prototype environmental chamber was designed in order to collect nano-sized particles in a controlled manner and subsequent characterization of the released or formed particles was performed with transmission electron microscopy (TEM) and the exposed nanocomposite was analysed with thermogravimetric analysis (TGA). 

  • 55.
    Alipour, Nazanin
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Vinneras, Bjorn
    SLU Swedish Univ Agr Sci, Dept Energy & Technol, POB 7032, SE-75007 Uppsala, Sweden..
    Gouanve, Fabrice
    Univ Lyon 1, Univ Lyon, Ingn Mat Polymeres, CNRS,UMR 5223, 15 Bd Andre Latarjet, F-69622 Villeurbanne, France..
    Espuche, Eliane
    Univ Lyon 1, Univ Lyon, Ingn Mat Polymeres, CNRS,UMR 5223, 15 Bd Andre Latarjet, F-69622 Villeurbanne, France..
    Hedenqvist, Mikael S.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Polymeric Materials.
    A Protein-Based Material from a New Approach Using Whole Defatted Larvae, and Its Interaction with Moisture2019In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 11, no 2, article id 287Article in journal (Refereed)
    Abstract [en]

    A protein-based material created from a new approach using whole defatted larvae of the Black Soldier fly is presented. The larvae turn organic waste into their own biomass with high content of protein and lipids, which can be used as animal feed or for material production. After removing the larva lipid and adding a plasticizer, the ground material was compression molded into plates/films. The lipid, rich in saturated fatty acids, can be used in applications such as lubricants. The amino acids present in the greatest amounts were the essential amino acids aspartic acid/asparagine and glutamic acid/glutamine. Infrared spectroscopy revealed that the protein material had a high amount of strongly hydrogen-bonded beta-sheets, indicative of a highly aggregated protein. To assess the moisture-protein material interactions, the moisture uptake was investigated. The moisture uptake followed a BET type III moisture sorption isotherm, which could be fitted to the Guggenheim, Anderson and de Boer (GAB) equation. GAB, in combination with cluster size analysis, revealed that the water clustered in the material already at a low moisture content and the cluster increased in size with increasing relative humidity. The clustering also led to a peak in moisture diffusivity at an intermediate moisture uptake.

  • 56.
    Aljure, Mauricio
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS).
    Becerra Garcia, Marley
    KTH, School of Electrical Engineering and Computer Science (EECS), Electromagnetic Engineering.
    Karlsson, Mattias
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Polymeric Materials.
    Erratum to: Aljure, M.; Becerra, M.; Karlsson, E.M. Streamer inception from ultra-sharp needles in mineral oil based nanofluids2018In: Energies, ISSN 1996-1073, E-ISSN 1996-1073, Vol. 11, no 11, article id 2900Article in journal (Refereed)
    Abstract [en]

    The authors wish to make the following corrections to their paper [1]: i. On pages 13 and 14, the numbering of references from 17 to 30 is incorrect. References 17 to 30 should be renumbered from the original order below: 17. Liu, Z.; Liu, Q.; Wang, Z.D.; Jarman, P.; Krause, C.; Smith, P.W.R.; Gyore, A. Partial discharge behaviour of transformer liquids and the influence of moisture content. In Proceedings of the 2014 IEEE 18th International Conference on Dielectric Liquids (ICDL), Bled, Slovenia, 29 June–3 July 2014. 18. Yamashita, H.; Yamazawa, K.; Wang, Y.S. The effect of tip curvature on the prebreakdown streamer structure in cyclohexane. IEEE Trans. Dielectr. Electr. Insul. 1998, 5, 396–401. 19. Dumitrescu, L.; Lesaint, O.; Bonifaci, N.; Denat, A.; Notingher, P. Study of streamer inception in cyclohexane with a sensitive charge measurement technique under impulse voltage. J. Electrostat. 2001, 53, 135–146. 20. Pourrahimi, A.M.; Hoang, T.A.; Liu, D.; Pallon, L.K.H.; Gubanski, S.; Olsson, R.T.; Gedde, U.W.; Hedenqvist, M.S. Highly efficient interfaces in nanocomposites based on polyethylene and ZnO nano/hierarchical particles: A novel approach toward ultralow electrical conductivity insulations. Adv. Mater. 2016, 28, 8651–8657. 21. Li, J.; Du, B.; Wang, F.; Yao, W.; Yao, S. The effect of nanoparticle surfactant polarization on trapping depth of vegetable insulating oil-based nanofluids. Phys. Lett. A 2016, 380, 604–608. 22. Aljure, M.; Becerra, M.; Pallon, L.K.H. Electrical conduction currents of a mineral oil-based nanofluid in needle-plane configuration. In Proceedings of the 2016 IEEE Conference on Electrical Insulation and Dielectric Phenomena (CEIDP), Toronto, ON, Canada, 16–19 October 2016; pp. 687–690. 23. Primo, V.A.; Garcia, B.; Albarracin, R. Improvement of transformer liquid insulation using nanodielectric fluids: A review. IEEE Electr. Insul. Mag. 2018, 34, 13–26. 24. Jin, H.; Andritsch, T.; Morshuis, P.H.F.; Smit, J.J. AC breakdown voltage and viscosity of mineral oil based SiO2 nanofluids. In Proceedings of the 2012 Annual Report Conference on Electrical Insulation and Dielectric Phenomena, Montreal, QC, Canada, 14–17 October 2012; pp. 902–905. 25. Jin, H.; Morshuis, P.; Mor, A.R.; Smit, J.J.; Andritsch, T. Partial discharge behavior of mineral oil based nanofluids. IEEE Trans. Dielectr. Electr. Insul. 2015, 22, 2747–2753. 26. Du, Y.; Lv, Y.; Li, C.; Chen, M.; Zhong, Y.; Zhou, J.; Li, X.; Zhou, Y. Effect of semiconductive nanoparticles on insulating performances of transformer oil. IEEE Trans. Dielectr. Electr. Insul. 2012, 19, 770–776. 27. Dung, N.V.; Høidalen, H.K.; Linhjell, D.; Lundgaard, L.E.; Unge, M. Effects of reduced pressure and additives on streamers in white oil in long point-plane gap. J. Phys. D Appl. Phys. 2013, 46, 255501. 28. McCool, J.I. Using the Weibull Distribution; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2012. 29. Lesaint, O.L.; Top, T.V. Streamer initiation in mineral oil. part I: Electrode surface effect under impulse voltage. IEEE Trans. Dielectr. Electr. Insul. 2002, 9, 84–91. 30. Becerra, M.; Frid, H.; Vázquez, P.A. Self-consistent modeling of laminar electrohydrodynamic plumes from ultra-sharp needles in cyclohexane. Phys. Fluids 2017, 29, 123605. to the following, corrected numbering: 17. Dumitrescu, L.; Lesaint, O.; Bonifaci, N.; Denat, A.; Notingher, P. Study of streamer inception in cyclohexane with a sensitive charge measurement technique under impulse voltage. J. Electrostat. 2001, 53, 135–146. 18. Liu, Z.; Liu, Q.; Wang, Z.D.; Jarman, P.; Krause, C.; Smith, P.W.R.; Gyore, A. Partial discharge behaviour of transformer liquids and the influence of moisture content. In Proceedings of the 2014 IEEE 18th International Conference on Dielectric Liquids (ICDL), Bled, Slovenia, 29 June–3 July 2014. 19. Yamashita, H.; Yamazawa, K.; Wang, Y.S. The effect of tip curvature on the prebreakdown streamer structure in cyclohexane. IEEE Trans. Dielectr. Electr. Insul. 1998, 5, 396–401. 20. Becerra, M.; Frid, H.; Vázquez, P.A. Self-consistent modeling of laminar electrohydrodynamic plumes from ultra-sharp needles in cyclohexane. Phys. Fluids 2017, 29, 123605. 21. Pourrahimi, A.M.; Hoang, T.A.; Liu, D.; Pallon, L.K.H.; Gubanski, S.; Olsson, R.T.; Gedde, U.W.; Hedenqvist, M.S. Highly efficient interfaces in nanocomposites based on polyethylene and ZnO nano/hierarchical particles: A novel approach toward ultralow electrical conductivity insulations. Adv. Mater. 2016, 28, 8651–8657. 22. Li, J.; Du, B.; Wang, F.; Yao, W.; Yao, S. The effect of nanoparticle surfactant polarization on trapping depth of vegetable insulating oil-based nanofluids. Phys. Lett. A 2016, 380, 604–608. 23. Aljure, M.; Becerra, M.; Pallon, L.K.H. Electrical conduction currents of a mineral oil-based nanofluid in needle-plane configuration. In Proceedings of the 2016 IEEE Conference on Electrical Insulation and Dielectric Phenomena (CEIDP), Toronto, ON, Canada, 16–19 October 2016; pp. 687–690. 24. Primo, V.A.; Garcia, B.; Albarracin, R. Improvement of transformer liquid insulation using nanodielectric fluids: A review. IEEE Electr. Insul. Mag. 2018, 34, 13–26. 25. Jin, H.; Andritsch, T.; Morshuis, P.H.F.; Smit, J.J. AC breakdown voltage and viscosity of mineral oil based SiO2 nanofluids. In Proceedings of the 2012 Annual Report Conference on Electrical Insulation and Dielectric Phenomena, Montreal, QC, Canada, 14–17 October 2012; pp. 902–905. 26. Jin, H.; Morshuis, P.; Mor, A.R.; Smit, J.J.; Andritsch, T. Partial discharge behavior of mineral oil based nanofluids. IEEE Trans. Dielectr. Electr. Insul. 2015, 22, 2747–2753. 27. Du, Y.; Lv, Y.; Li, C.; Chen, M.; Zhong, Y.; Zhou, J.; Li, X.; Zhou, Y. Effect of semiconductive nanoparticles on insulating performances of transformer oil. IEEE Trans. Dielectr. Electr. Insul. 2012, 19, 770–776. 28. Dung, N.V.; Høidalen, H.K.; Linhjell, D.; Lundgaard, L.E.; Unge, M. Effects of reduced pressure and additives on streamers in white oil in long point-plane gap. J. Phys. D Appl. Phys. 2013, 46, 255501. 29. McCool, J.I. Using the Weibull Distribution; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2012. 30. Lesaint, O.L.; Top, T.V. Streamer initiation in mineral oil. part I: Electrode surface effect under impulse voltage. IEEE Trans. Dielectr. Electr. Insul. 2002, 9, 84–91. ii. On the last paragraph of page 9, the last sentence should be changed from: However, the results in [11] also show the consistent increase in the initiation voltage of prebreakdown phenomena in both polarities, as reported in Figure 11. to the following, corrected version: However, the results in [26] also show the consistent increase in the initiation voltage of prebreakdown phenomena in both polarities, as reported in Figure 11. iii. On the last paragraph of page 10, the third sentence should be changed from: Even though the existing hypotheses of the dielectric effect of NPs [8–10] were proposed for blunter electrodes (where charge generation before streamer initiation is less important [30]), they should still apply under the experimental conditions here reported. to the following, corrected version: Even though the existing hypotheses of the dielectric effect of NPs [5,6,16] were proposed for blunter electrodes (where charge generation before streamer initiation is less important [30]), they should still apply under the experimental conditions here reported. The authors would like to apologize for any inconvenience caused to the readers by these changes. The changes do not affect the scientific results. The manuscript will be updated and the original will remain online on the article webpage, with a reference to this Correction.

  • 57.
    Aljure, Mauricio
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS).
    Becerra Garcia, Marley
    KTH, School of Electrical Engineering and Computer Science (EECS), Electromagnetic Engineering. ABB Corp Res, Vasteras, Sweden..
    Karlsson, Mattias E.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    On the injection and generation of charge carriers in mineral oil under high electric fields2019In: JOURNAL OF PHYSICS COMMUNICATIONS, ISSN 2399-6528, Vol. 3, no 3, article id UNSP 035019Article in journal (Refereed)
    Abstract [en]

    Charge injection and generation mechanisms under intense electric fields (up to 10(9)Vm(-1)) in mineral oil are assessed experimentally and numerically. For this, current-voltage characteristics under positive and negative polarities are measured in a needle-plane configuration using sharp needles (with tip radius R-tip <= 1.1 mu m). In addition, a state of the art electro-hydrodynamic (EHD) model is implemented to calculate the contribution of the different mechanisms on the high-field conduction currents in the liquid. In order to evaluate exclusively the contribution of field emission, experiments are also performed in vacuum. It is found that neither field emission nor field ionisation can explain the conduction currents measured in mineral oil. It is proposed that field molecular ionisation, as described by Zener tunnelling model for solids, and electron impact ionisation are the processes dominating the generation of excess electron-ion pairs in mineral oil under positive and negative polarity, respectively. It is also shown that Zener molecular ionisation alone grossly overestimates the measured currents when parameters previously suggested in the literature for mineral oil are used. Preliminary model parameters for these mechanisms that best fit the conduction currents measured in mineral oil are presented and discussed.

  • 58.
    Aljure, Mauricio
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS).
    Becerra Garcia, Marley
    KTH, School of Electrical Engineering and Computer Science (EECS), Electromagnetic Engineering.
    Karlsson, Mattias E.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Polymeric Materials.
    Streamer Inception from Ultra-Sharp Needles in Mineral Oil Based Nanofluids2018In: Energies, ISSN 1996-1073, E-ISSN 1996-1073, Vol. 11, no 8, article id 2064Article in journal (Refereed)
    Abstract [en]

    Positive and negative streamer inception voltages from ultra-sharp needle tips (with tip radii below 0.5 m) are measured in TiO2, SiO2, Al2O3, ZnO and C-60 nanofluids. The experiments are performed at several concentrations of nanoparticles dispersed in mineral oil. It is found that nanoparticles influence positive and negative streamers in different ways. TiO2, SiO2 and Al2O3 nanoparticles increase the positive streamer inception voltage only, whilst ZnO and C-60 nanoparticles augment the streamer inception voltages in both polarities. Using these results, the main hypotheses explaining the improvement in the dielectric strength of the host oil due to the presence of nanoparticles are analyzed. It is found that the water adsorption hypothesis of nanoparticles is consistent with the increments in the reported positive streamer inception voltages. It is also shown that the hypothesis of nanoparticles reducing the electron velocity by hopping transport mechanisms fails to explain the results obtained for negative streamers. Finally, the hypothesis of nanoparticles attaching electrons according to their charging characteristics is found to be consistent with the results hereby presented on negative streamers.

  • 59.
    Alkhatib, Husam
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Developing an Optimal Design for A Heart Container Operated Via Drone2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In the healthcare system when a patient is waiting for a donated heart, the choice of the transportation method is critical. Thus, the efficiency of this procedure relies on the traveling time, which could affect the ischemic time, which is the time that heart can be discharged outside the human body. For best patient outcome, the heart has to be transplanted within four hours from the donor to the recipient. By transporting the donated heart via Unmanned Aerial Vehicle (UAV, or drone), both the time and the cost required for the heart transportation will be minimized. This thesis intends to explore the specifications needed for the design and manufacture of a heart container and pick-up system for a drone, which will be able to transport a donated heart between hospitals.

  • 60.
    Alm, Tove L.
    et al.
    KTH, School of Biotechnology (BIO).
    von Feilitzen, Kalle
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO).
    Antibodypedia - The wiki of antibodies2015In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 26Article in journal (Other academic)
  • 61.
    Almandoz-Gil, Leire
    et al.
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Mol Geriatr, SE-75185 Uppsala, Sweden..
    Welander, Hedvig
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Mol Geriatr, SE-75185 Uppsala, Sweden..
    Ihse, Elisabeth
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Mol Geriatr, SE-75185 Uppsala, Sweden..
    Khoonsari, Payam Emami
    Uppsala Univ, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Musunuri, Sravani
    Uppsala Univ, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Lendel, Christofer
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry.
    Sigvardson, Jessica
    BioArctic AB, Warfvinges Vag 35, SE-11251 Stockholm, Sweden..
    Karlsson, Mikael
    Uppsala Univ, Dept Engn Sci, SE-75121 Uppsala, Sweden..
    Ingelsson, Martin
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Mol Geriatr, SE-75185 Uppsala, Sweden..
    Kultima, Kim
    Uppsala Univ, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Bergstrom, Joakim
    Uppsala Univ, Dept Publ Hlth & Caring Sci, Mol Geriatr, SE-75185 Uppsala, Sweden..
    Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote oligomerization of alpha-synuclein through different pathways (vol 110, pg 421, 2017)2018In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 117, p. 258-258Article in journal (Refereed)
  • 62.
    Alneberg, Johannes
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bioinformatic Methods in Metagenomics2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Microbial organisms are a vital part of our global ecosystem. Yet, our knowledge of them is still lacking. Direct sequencing of microbial communities, i.e. metagenomics, have enabled detailed studies of these microscopic organisms by inspection of their DNA sequences without the need to culture them. Furthermore, the development of modern high- throughput sequencing technologies have made this approach more powerful and cost-effective. Taken together, this has shifted the field of microbiology from previously being centered around microscopy and culturing studies, to largely consist of computational analyses of DNA sequences. One such computational analysis which is the main focus of this thesis, aims at reconstruction of the complete DNA sequence of an organism, i.e. its genome, directly from short metagenomic sequences.

    This thesis consists of an introduction to the subject followed by five papers. Paper I describes a large metagenomic data resource spanning the Baltic Sea microbial communities. This dataset is complemented with a web-interface allowing researchers to easily extract and visualize detailed information. Paper II introduces a bioinformatic method which is able to reconstruct genomes from metagenomic data. This method, which is termed CONCOCT, is applied on Baltic Sea metagenomics data in Paper III and Paper V. This enabled the reconstruction of a large number of genomes. Analysis of these genomes in Paper III led to the proposal of, and evidence for, a global brackish microbiome. Paper IV presents a comparison between genomes reconstructed from metagenomes with single-cell sequenced genomes. This further validated the technique presented in Paper II as it was found to produce larger and more complete genomes than single-cell sequencing.

  • 63.
    Alneberg, Johannes
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Bennke, Christin
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Beier, Sara
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Pinhassi, Jarone
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Jürgens, Klaus
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Ekman, Martin
    Department of Ecology, Environment and Plant Sciences, Stockholm University Science for Life Laboratory, Solna, Sweden.
    Ininbergs, Karolina
    Department of Ecology, Environment and Plant Sciences, Stockholm University Science for Life Laboratory, Solna, Sweden.
    Labrenz, Matthias
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Andersson, Anders F.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Recovering 2,032 Baltic Sea microbial genomes by optimized metagenomic binningManuscript (preprint) (Other academic)
    Abstract [en]

    Aquatic microorganism are key drivers of global biogeochemical cycles and form the basis of aquatic food webs. However, there is still much left to be learned about these organisms and their interaction within specific environments, such as the Baltic Sea. Crucial information for such an understanding can be found within the genome sequences of organisms within the microbial community.

    In this study, the previous set of Baltic Sea clusters, constructed by Hugert et al., is greatly expanded using a large set of metagenomic samples, spanning the environmental gradients of the Baltic Sea. In total, 124 samples were individually assembled and binned to obtain 2,032 Metagenome Assembled Genomes (MAGs), clustered into 353 prokaryotic and 14 eukaryotic species- level clusters. The prokaryotic genomes were widely distributed over the prokaryotic tree of life, representing 20 different phyla, while the eukaryotic genomes were mostly limited to the division of Chlorophyta. The large number of reconstructed genomes allowed us to identify key factors determining the quality of the genome reconstructions.

    The Baltic Sea is heavily influenced of human activities of which we might not see the full implications. The genomes reported within this study will greatly aid further studies in our strive for an understanding of the Baltic Sea microbial ecosystem.

  • 64.
    Alneberg, Johannes
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Karlsson, Christofer M. G.
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden..
    Divne, Anna-Maria
    Uppsala Univ, Dept Cell & Mol Biol, SciLifeLab, Uppsala, Sweden..
    Bergin, Claudia
    Uppsala Univ, Dept Cell & Mol Biol, SciLifeLab, Uppsala, Sweden..
    Homa, Felix
    Uppsala Univ, Dept Cell & Mol Biol, SciLifeLab, Uppsala, Sweden..
    Lindh, Markus V.
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden.;Lund Univ, Dept Biol, Lund, Sweden..
    Hugerth, Luisa
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ettema, Thijs J. G.
    Uppsala Univ, Dept Cell & Mol Biol, SciLifeLab, Uppsala, Sweden..
    Bertilsson, Stefan
    Uppsala Univ, Dept Ecol & Genet, Sci Life Lab, Limnol, Uppsala, Sweden..
    Andersson, Anders F.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Pinhassi, Jarone
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden..
    Genomes from uncultivated prokaryotes: a comparison of metagenome-assembled and single-amplified genomes2018In: Microbiome, ISSN 0026-2633, E-ISSN 2049-2618, Vol. 6, article id 173Article in journal (Refereed)
    Abstract [en]

    Background: Prokaryotes dominate the biosphere and regulate biogeochemical processes essential to all life. Yet, our knowledge about their biology is for the most part limited to the minority that has been successfully cultured. Molecular techniques now allow for obtaining genome sequences of uncultivated prokaryotic taxa, facilitating in-depth analyses that may ultimately improve our understanding of these key organisms. Results: We compared results from two culture-independent strategies for recovering bacterial genomes: single-amplified genomes and metagenome-assembled genomes. Single-amplified genomes were obtained from samples collected at an offshore station in the Baltic Sea Proper and compared to previously obtained metagenome-assembled genomes from a time series at the same station. Among 16 single-amplified genomes analyzed, seven were found to match metagenome-assembled genomes, affiliated with a diverse set of taxa. Notably, genome pairs between the two approaches were nearly identical (average 99.51% sequence identity; range 98.77-99.84%) across overlapping regions (30-80% of each genome). Within matching pairs, the single-amplified genomes were consistently smaller and less complete, whereas the genetic functional profiles were maintained. For the metagenome-assembled genomes, only on average 3.6% of the bases were estimated to be missing from the genomes due to wrongly binned contigs. Conclusions: The strong agreement between the single-amplified and metagenome-assembled genomes emphasizes that both methods generate accurate genome information from uncultivated bacteria. Importantly, this implies that the research questions and the available resources are allowed to determine the selection of genomics approach for microbiome studies.

  • 65.
    Alneberg, Johannes
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Karlsson, Christofer M.G.
    Centre for Ecology and Evolution in Microbial Model Systems, EEMiS, Linnaeus University, Barlastgatan 11, 391 82 Kalmar, Sweden.
    Divne, Anna-Maria
    Department of Cell and Molecular Biology, SciLifeLab, Uppsala University, Uppsala, Sweden .
    Bergin, Claudia
    Department of Cell and Molecular Biology, SciLifeLab, Uppsala University, Uppsala, Sweden .
    Homa, Felix
    Department of Cell and Molecular Biology, SciLifeLab, Uppsala University, Uppsala, Sweden .
    Lindh, Markus V.
    Centre for Ecology and Evolution in Microbial Model Systems, EEMiS, Linnaeus University, Barlastgatan 11, 391 82 Kalmar, Sweden.
    Hugerth, Luisa W.
    Karolinska Institutet, Science for Life Laboratory, Department of Molecular, Tumour and Cell Biology, Centre for Translational Microbiome Research, Solna, Sweden.
    Ettema, Thijs JG
    Department of Cell and Molecular Biology, SciLifeLab, Uppsala University, Uppsala, Sweden.
    Bertilsson, Stefan
    Department of Ecology and Genetics, Limnology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Andersson, Anders F.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Pinhassi, Jarone
    Centre for Ecology and Evolution in Microbial Model Systems, EEMiS, Linnaeus University, Barlastgatan 11, 391 82 Kalmar, Sweden.
    Genomes from uncultivated prokaryotes: a comparison of metagenome-assembled and single-amplified genomesManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Prokaryotes dominate the biosphere and regulate biogeochemical processes essential to all life. Yet, our knowledge about their biology is for the most part limited to the minority that has been successfully cultured. Molecular techniques now allow for obtaining genome sequences of uncultivated prokaryotic taxa, facilitating in-depth analyses that may ultimately improve our understanding of these key organisms.

    Results: We compared results from two culture-independent strategies for recovering bacterial genomes: single-amplified genomes and metagenome-assembled genomes. Single-amplified genomes were obtained from samples collected at an offshore station in the Baltic Sea Proper and compared to previously obtained metagenome-assembled genomes from a time series at the same station. Among 16 single-amplified genomes analyzed, seven were found to match metagenome-assembled genomes, affiliated with a diverse set of taxa. Notably, genome pairs between the two approaches were nearly identical (>98.7% identity) across overlapping regions (30-80% of each genome). Within matching pairs, the single-amplified genomes were consistently smaller and less complete, whereas the genetic functional profiles were maintained. For the metagenome-assembled genomes, only on average 3.6% of the bases were estimated to be missing from the genomes due to wrongly binned contigs; the metagenome assembly was found to cause incompleteness to a higher degree than the binning procedure.

    Conclusions: The strong agreement between the single-amplified and metagenome-assembled genomes emphasizes that both methods generate accurate genome information from uncultivated bacteria. Importantly, this implies that the research questions and the available resources are allowed to determine the selection of genomics approach for microbiome studies.

  • 66.
    Alneberg, Johannes
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sundh, John
    Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.
    Bennke, Christin
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Beier, Sara
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Lundin, Daniel
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Hugerth, Luisa
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).
    Pinhassi, Jarone
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Kisand, Veljo
    University of Tartu, Institute of Technology, Tartu, Estonia.
    Riemann, Lasse
    Section for Marine Biological Section, Department of Biology, University of Copenhagen, Helsingør, Denmark.
    Jürgens, Klaus
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Labrenz, Matthias
    Leibniz Institute for Baltic Sea Research, Warnemünde, Germany.
    Andersson, Anders F.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    BARM and BalticMicrobeDB, a reference metagenome and interface to meta-omic data for the Baltic SeaManuscript (preprint) (Other academic)
    Abstract [en]

    The Baltic Sea is one of the world’s largest brackish water bodies and is characterised by pronounced physicochemical gradients where microbes are the main biogeochemical catalysts. Meta-omic methods provide rich information on the composition of, and activities within microbial ecosystems, but are computationally heavy to perform. We here present the BAltic Sea Reference Metagenome (BARM), complete with annotated genes to facilitate further studies with much less computational effort. The assembly is constructed using 2.6 billion metagenomic reads from 81 water samples, spanning both spatial and temporal dimensions, and contains 6.8 million genes that have been annotated for function and taxonomy. The assembly is useful as a reference, facilitating taxonomic and functional annotation of additional samples by simply mapping their reads against the assembly. This capability is demonstrated by the successful mapping and annotation of 24 external samples. In addition, we present a public web interface, BalticMicrobeDB, for interactive exploratory analysis of the dataset.

  • 67.
    Alneberg, Johannes
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sundh, John
    Stockholm Univ, Sci Life Lab, Dept Biochem & Biophys, S-17165 Solna, Sweden..
    Bennke, Christin
    Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany..
    Beier, Sara
    Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany..
    Lundin, Daniel
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, S-39182 Kalmar, Sweden..
    Hugerth, Luisa W.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Mol Tumor & Cell Biol, Ctr Translat Microbiome Res, Sci Life Lab, S-17165 Solna, Sweden..
    Pinhassi, Jarone
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, S-39182 Kalmar, Sweden..
    Kisand, Veljo
    Univ Tartu, Inst Technol, EE-50411 Tartu, Estonia..
    Riemann, Lasse
    Univ Copenhagen, Sect Marine Biol Sect, Dept Biol, DK-3000 Helsingor, Denmark..
    Juergens, Klaus
    Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany..
    Labrenz, Matthias
    Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany..
    Andersson, Anders F.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    BARM and BalticMicrobeDB, a reference metagenome and interface to meta-omic data for the Baltic Sea2018In: Scientific Data, E-ISSN 2052-4463, Vol. 5, article id 180146Article in journal (Refereed)
    Abstract [en]

    The Baltic Sea is one of the world's largest brackish water bodies and is characterised by pronounced physicochemical gradients where microbes are the main biogeochemical catalysts. Meta-omic methods provide rich information on the composition of, and activities within, microbial ecosystems, but are computationally heavy to perform. We here present the Baltic Sea Reference Metagenome (BARM), complete with annotated genes to facilitate further studies with much less computational effort. The assembly is constructed using 2.6 billion metagenomic reads from 81 water samples, spanning both spatial and temporal dimensions, and contains 6.8 million genes that have been annotated for function and taxonomy. The assembly is useful as a reference, facilitating taxonomic and functional annotation of additional samples by simply mapping their reads against the assembly. This capability is demonstrated by the successful mapping and annotation of 24 external samples. In addition, we present a public web interface, BalticMicrobeDB, for interactive exploratory analysis of the dataset.

  • 68.
    Alsaeede, Mustafa
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Test and Evaluation of a Novel Passive Tool Used For Blood Dilution in Hematology Analyzers2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Executive Summary

    The Complete Blood Count (CBC) is considered one of the most commonly performed screening tests in medical diagnostics. The CBC is performed using a hematological analyzer, which counts the numbers and types of different cells within the blood. However, due to the high concentration of cells in the blood samples to be counted, the dilution process is considered an essential factor for obtaining accurate counting results. Below is an investigation for an invention of a unique method and device for blood sample dilution in hematology analyzers. As mentioned, before starting an analysis a hematology cell counter device must dilute a precise defined volume of a whole blood sample with a diluent reagent (in this study 20ml of a blood sample is diluted with 4,5ml of diluent reagent). This dilution process must be accurate and repeatable with a high precision to produce the target dilution ratio (here 1:200). Exclusive to almost all hematology analyzers today, shear values (SV) are used to obtain highly precise volumes. These SV components are however very costly and add a higher complexity to the systems. This thesis was therefore aimed as an experimental evaluation for a novel passive dilution tool called shearing block (SB), which could possibly then replace the SV and be used in the coming Haematology Analyzer Devices manufactured by Boule Medical AB. The SB has the advantages of being low cost, having a simple mechanism, being much more flexible for integration with any microfluidic system and also eliminates the need for complex control systems or equipment, thereby lowering the need for calibration and maintenance. If a SB could replace the SV with an equally precise accuracy on the 20ml blood volume it would be highly beneficial.

     

    The set hypothesis was that the dilution process via the SB, will only be affected by blood viscosity. Through changing the blood’s viscosity, via changing the hematocrit concentration (HCT) and blood sample temperature, this study aimed to conclude if this gave a significant effect on the blood sample dilution via the SB. This was achieved through two performed experiments both including the same control group (CG) along with a test group (TG). All tests were performed using the same blood sample, the same reference measuring device (Medonic M32) and experimental setup. The experimental setup included the control group, CG, (N=30) consisting of 20µl blood samples aspirated through an electronic pipette in room temperature condition being mixed with 4,5ml of diluent reagent that had been automatically dispensed by the Medonic M32 instrument. The 20µl blood together with the 4,5ml diluent resulted in the targeted 1:200 dilution ratio. The test group, TG, (where N=30 for each respective group) was diluted through the SB through a fully automated process for the targeted 1:200 dilution. All diluted blood samples were then analyzed on the Medonic M32 for all hematology parameters and the hemoglobin (HGB) parameter was used as an indicator to quantify the blood volume in the TG runs as compared to the CG reference runs. Two test groups (TG) were analyzed: the first investigating the effect of the HCT and the second of the sample temperature on the blood volume (before dilution) in the SB. The HCT concentration levels were tested at 15%, 27%, 33% and 58% with samples and test run and kept at a constant 25°C. The second test group investigated the effect of 15°C, 25°C, 35°C and 39°C on a blood sample with a constant HCT of 33%.

    The main aim of this experimental study was to validate the SB simulation. However, the experiments results, showed that the diluted blood volume via SB was strongly influenced by changes in hematocrit concentration and that the unwanted additional blood volume, was increasing directly proportionally with hematocrit concentration.  On the other hand, there seemed to be no apparent change in the blood volume on the SB diluted samples for the various temperature differences between 15-35°C. To conclude, the experiments results were not consistent with predictions of SB simulation model and there are two reasons that could explain that. Firstly, in the simulation the blood was approximated with a homogeneous fluid with a given viscosity. The second reason is the mismatch between the dilution process via the SB and the simulation (the simulation started with an idealized initial status, whereas the SB channel was prefilled by blood). This means that the simulation excluded any effect that may occur as a convection effect during blood flow inside the channel and whilst encountering diluent reagent. These two reasons explain why the results of the simulation was not consistent with that of the experiments, regarding the unwanted blood volume. Therefore, a new simulation is required. Recommendations for future actions: undoubtedly there are several optimizations that may increase the accuracy of the proposed SB design such as; removing the diluent's reservoir for eliminating the effect of bubbles, changing the geometrical angles or use a smaller diameter for the inlets and outlets of the microchannels to reduce the convection and diffusion effect, (which in turn would reduce the unwanted blood volume). Therefore, determining the best SB's microchannel structure to perform the dilution process with minimum unwanted blood volume remains a near future next step follow-up project.

  • 69. Altai, M.
    et al.
    Liu, Hao
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Ding, Haozhong
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Mitran, B.
    Edqvist, P. -H
    Tolmachev, V.
    Orlova, A.
    Gräslund, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Affibody-derived drug conjugates: Potent cytotoxic molecules for treatment of HER2 over-expressing tumors2018In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 288, p. 84-95Article in journal (Refereed)
    Abstract [en]

    Patients with HER2-positive tumors often suffer resistance to therapy, warranting development of novel treatment modalities. Affibody molecules are small affinity proteins which can be engineered to bind to desired targets. They have in recent years been found to allow precise targeting of cancer specific molecular signatures such as the HER2 receptor. In this study, we have investigated the potential of an affibody molecule targeting HER2, ZHER2:2891, conjugated with the cytotoxic maytansine derivate MC-DM1, for targeted cancer therapy. ZHER2:2891 was expressed as a monomer (ZHER2:2891), dimer ((ZHER2:2891)2) and dimer with an albumin binding domain (ABD) for half-life extension ((ZHER2:2891)2-ABD). All proteins had a unique C-terminal cysteine that could be used for efficient and site-specific conjugation with MC-DM1. The resulting affibody drug conjugates were potent cytotoxic molecules for human cells over-expressing HER2, with sub-nanomolar IC50-values similar to trastuzumab emtansine, and did not affect cells with low HER2 expression. A biodistribution study of a radiolabeled version of (ZHER2:2891)2-ABD-MC-DM1, showed that it was taken up by the tumor. The major site of off-target uptake was the kidneys and to some extent the liver. (ZHER2:2891)2-ABD-MC-DM1 was found to have a half-life in circulation of 14 h. The compound was tolerated well by mice at 8.5 mg/kg and was shown to extend survival of mice bearing HER2 over-expressing tumors. The findings in this study show that affibody molecules are a promising class of engineered affinity proteins to specifically deliver small molecular drugs to cancer cells and that such conjugates are potential candidates for clinical evaluation on HER2-overexpressing cancers. 

  • 70.
    Altai, M.
    et al.
    Uppsala Univ, Imuunol Genet & Pathol, Uppsala, Sweden..
    Liu, Hao
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Div Prot Technol, Stockholm, Sweden..
    Orlova, A.
    Div Mol Imaging, Dept Med Chem, Uppsala, Sweden..
    Tolmachev, V.
    Uppsala Univ, Imuunol Genet & Pathol, Uppsala, Sweden..
    Gräslund, Torbjörn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Div Prot Technol, Stockholm, Sweden..
    Improving of molecular design of a novel Affibody-fused HER2-recognising anticancer toxin using radionuclide-based techniques2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, p. S178-S178Article in journal (Other academic)
  • 71.
    Altai, M.
    et al.
    Immunology, Genetics and Pathology, Uppsala, SWEDEN, .
    Vorobyeva, A.
    Immunology, Genetics and Pathology, Uppsala, SWEDEN, .
    Westerlund, Kristina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Mitran, B.
    Div Mol Imaging, Uppsala, Sweden..
    Orlova, A.
    Div Mol Imaging, Uppsala, Sweden..
    Eriksson Karlström, Amelie
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Tolmachev, V.
    Immunology, Genetics and Pathology, Uppsala, SWEDEN, .
    A novel method for conjugation of PNA to antibodies for radionuclide based pretargeting: proof of principal2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S648-S648Article in journal (Other academic)
  • 72.
    Altai, Mohamed
    et al.
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.;Uppsala Univ, Dept Med Chem, S-75123 Uppsala, Sweden..
    Leitao, Charles Dahlsson
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Rinne, Sara S.
    Uppsala Univ, Dept Med Chem, S-75123 Uppsala, Sweden..
    Vorobyeva, Anzhelika
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Atterby, Christina
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Ståhl, Stefan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Tolmachev, Vladimir
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Löfblom, John
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Orlova, Anna
    Uppsala Univ, Dept Med Chem, S-75123 Uppsala, Sweden.;Uppsala Univ, Sci Life Lab, S-75237 Uppsala, Sweden..
    Influence of Molecular Design on the Targeting Properties of ABD-Fused Mono- and Bi-Valent Anti-HER3 Affibody Therapeutic Constructs2018In: CELLS, ISSN 2073-4409, Vol. 7, no 10, article id 164Article in journal (Refereed)
    Abstract [en]

    Overexpression of human epidermal growth factor receptor type 3 (HER3) is associated with tumour cell resistance to HER-targeted therapies. Monoclonal antibodies (mAbs) targeting HER3 are currently being investigated for treatment of various types of cancers. Cumulative evidence suggests that affibody molecules may be appropriate alternatives to mAbs. We previously reported a fusion construct (3A3) containing two HER3-targeting affibody molecules flanking an engineered albumin-binding domain (ABD 035) included for the extension of half-life in circulation. The 3A3 fusion protein (19.7 kDa) was shown to delay tumour growth in mice bearing HER3-expressing xenografts and was equipotent to the mAb seribantumab. Here, we have designed and explored a series of novel formats of anti-HER3 affibody molecules fused to the ABD in different orientations. All constructs inhibited heregulin-induced phosphorylation in HER3-expressing BxPC-3 and DU-145 cell lines. Biodistribution studies demonstrated extended the half-life of all ABD-fused constructs, although at different levels. The capacity of our ABD-fused proteins to accumulate in HER3-expressing tumours was demonstrated in nude mice bearing BxPC-3 xenografts. Formats where the ABD was located on the C-terminus of affibody binding domains (3A, 33A, and 3A3) provided the best tumour targeting properties in vivo. Further development of these promising candidates for treatment of HER3-overexpressing tumours is therefore justified.

  • 73. Altai, Mohamed
    et al.
    Liu, Hao
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Ding, Haozhong
    Mitran, Bogdan
    Edqvist, Per-Henrik
    Tolmachev, Vladimir
    Orlova, Anna
    Gräslund, Torbjorn
    Affibody-derived Drug Conjugates: Potent Cytotoxic Drugs ForTreatment Of HER2 Over-Expressing TumorsManuscript (preprint) (Other academic)
  • 74.
    Alvarez, Victor
    et al.
    KTH.
    Halldin, Peter
    KTH.
    Kleiven, Svein
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    The Influence of Neck Muscle Tonus and Posture on Brain Tissue Strain in Pedestrian Head Impacts2014In: 58th SAE Stapp Car Crash Conference, STAPP 2014, Vol. 58Article in journal (Refereed)
    Abstract [en]

    Pedestrians are one of the least protected groups in urban traffic and frequently suffer fatal head injuries. An important boundary condition for the head is the cervical spine, and it has previously been demonstrated that neck muscle activation is important for head kinematics during inertial loading. It has also been shown in a recent numerical study that a tensed neck musculature also has some influence on head kinematics during a pedestrian impact situation. The aim of this study was to analyze the influence on head kinematics and injury metrics during the isolated time of head impact by comparing a pedestrian with relaxed neck and a pedestrian with increased tonus. The human body Finite Element model THUMS Version 1.4 was connected to head and neck models developed at KTH and used in pedestrian-to-vehicle impact simulations with a generalized hood, so that the head would impact a surface with an identical impact response in all simulations. In order to isolate the influence of muscle tonus, the model was activated shortly before head impact so the head would have the same initial position prior to impact among different tonus. A symmetric and asymmetric muscle activation scheme that used high level of activation was used in order to create two extremes to investigate. It was found that for the muscle tones used in this study, the influence on the strain in the brain was very minor, in general about 1-14% change. A relatively large increase was observed in a secondary peak in maximum strains in only one of the simulated cases. 

  • 75.
    Alvarez, Victor S
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    Kleiven, Svein
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Neuronic Engineering.
    Effect of pediatric growth on cervical spine kinematics and deformations in automotive crashes2018In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 71, p. 76-83, article id S0021-9290(18)30075-7Article in journal (Refereed)
    Abstract [en]

    Finite element (FE) models are a powerful tool that can be used to understand injury mechanisms and develop better safety systems. This study aims to extend the understanding of pediatric spine biomechanics, where there is a paucity of studies available. A newly developed and continuously scalable FE model was validated and scaled to 1.5-, 3-, 6-, 10-, 14- and 18-year-old using a non-linear scaling technique, accounting for local topological changes. The oldest and youngest ages were also scaled using homogeneous geometric scaling. To study the effect of pediatric spinal growth on head kinematics and intervertebral disc strain, the models were exerted to 3.5 g acceleration pulse at the T1 vertebra to simulate frontal, rear and side impacts. It was shown that the head rotation increases with age, but is over predicted when geometrically scaling down from 18- to 1.5-year-old and under predicted when geometrically scaling up from 1.5- to 18-year-old. The strain in the disc, however, showed a clear decrease with age in side impact and for the upper cervical spine in rear impact, indicating a higher susceptibility for neck injury at younger ages. In the frontal impact, no clear age dependence could be seen, suggesting a large contribution from changed facet joint angles, and lower levels of strain, suggesting a lower risk of injury. The results also highlight the benefit of rearward facing children in a seat limiting head lateral motion.

  • 76.
    Amaral, Sarah da Costa
    et al.
    Univ Fed Parana, Sect Biol Sci, Postgrad Program Biochem Sci, BR-81531990 Curitiba, PR, Brazil..
    Barbieri, Shayla Fernanda
    Univ Fed Parana, Sect Biol Sci, Postgrad Program Biochem Sci, BR-81531990 Curitiba, PR, Brazil..
    Ruthes, Andrea C.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience. UF, GCREC, Dept Entomol & Nematol, Wimauma, FL USA..
    Bark, Juliana Mueller
    Univ Fed Parana, Sect Biol Sci, Postgrad Program Biochem Sci, BR-81531990 Curitiba, PR, Brazil..
    Brochado Winnischofer, Sheila Maria
    Univ Fed Parana, Sect Biol Sci, Postgrad Program Biochem Sci, BR-81531990 Curitiba, PR, Brazil.;Univ Fed Parana, Dept Biochem & Mol Biol, PB 19046, BR-81531980 Curitiba, PR, Brazil.;Univ Fed Parana, Postgrad Program Cellular & Mol Biol, BR-81531980 Curitiba, PR, Brazil..
    Meira Silveira, Joana Lea
    Univ Fed Parana, Sect Biol Sci, Postgrad Program Biochem Sci, BR-81531990 Curitiba, PR, Brazil.;Univ Fed Parana, Dept Biochem & Mol Biol, PB 19046, BR-81531980 Curitiba, PR, Brazil..
    Cytotoxic effect of crude and purified pectins from Campomanesia xanthocarpa Berg on human glioblastoma cells2019In: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 224, article id UNSP 115140Article in journal (Refereed)
    Abstract [en]

    A new source of pectin with a cytotoxic effect on glioblastoma cells is presented. A homogeneous GWP-FP-S fraction (M-w, of 29,170 g mol(-1)) was obtained by fractionating the crude pectin extract (GW) from Campomanesia xanthocarpa pulp. According to the monosaccharide composition, the GWP-FP-S was composed of galacturonic acid (58.8%), arabinose (28.5%), galactose (11.3%) and rhamnose (1.1%), comprising 57.7% of homogalacturonans (HG) and 42.0% of type I rhamnogalacturonans (RG-I). These structures were characterized by chromatographic and spectroscopic methods; GW and GWP-FP-S fractions were evaluated by MIT and crystal violet assays for their cytotoxic effects. Both fractions induced cytotoxicity (15.55-37.65%) with concomitant increase in the cellular ROS levels in human glioblastoma cells at 25-400 mu g mL(-)(1), after 48 h of treatment, whereas no cytotoxicity was observed for normal NIH 3T3 cells. This is the first report of in vitro bioactivity and the first investigation of the antitumor potential of gabiroba pectins.

  • 77. Ambort, D.
    et al.
    Johansson, M.E.V.
    Gustafsson, J. K.
    Nilsson, Harriet
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Structural Biotechnology.
    Ermund, A.
    Johansson, B.R.
    Koeck, Philip J. B.
    KTH, School of Technology and Health (STH), Structural Biotechnology (Closed 20130701).
    Hebert, Hans
    KTH, School of Technology and Health (STH), Structural Biotechnology (Closed 20130701).
    Hansson, G.C.
    Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 15, p. 5645-5650Article in journal (Refereed)
    Abstract [en]

    MUC2, the major colonic mucin, forms large polymers by N-terminal trimerization and C-terminal dimerization. Although the assembly process for MUC2 is established, it is not known how MUC2 is packed in the regulated secretory granulae of the goblet cell. When the N-terminal VWD1-D2-D'D3 domains (MUC2-N) were expressed in a goblet-like cell line, the protein was stored together with full-length MUC2. By mimicking the pH and calcium conditions of the secretory pathway we analyzed purified MUC2-N by gel filtration, density gradient centrifugation, and transmission electron microscopy. At pH 7.4 the MUC2-N trimer eluted as a single peak by gel filtration. At pH 6.2 with Ca2+ it formed large aggregates that did not enter the gel filtration column but were made visible after density gradient centrifugation. Electron microscopy studies revealed that the aggregates were composed of rings also observed in secretory granulae of colon tissue sections. TheMUC2-N aggregates were dissolved by removing Ca2+ and raising pH. After release from goblet cells, the unfolded full-length MUC2 formed stratified layers. These findings suggest a model for mucin packing in the granulae and the mechanism for mucin release, unfolding, and expansion.

  • 78.
    Aminzadeh, Selda
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Valorization of Kraft Lignin by Fractionation and Chemical Modifications for Different Applications2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Abstract

    Lignin is one of the most abundant biopolymers. Approximately 70 million tons of technical lignin is generated annually, but only little is used for products other than energy. The complexity of lignin hinders full utilization in high-value products and materials. In spite of the large recent progress of knowledge of lignin structure and biosynthesis, much is still not fully understood, including structural inhomogeneity. We made synthetic lignin at different pH’s and obtained structural differences that might explain the structural inhomogeneity of lignin.

    Technical lignins from the chemical pulping are available in large scale, but the processes result in alterations, such as oxidation and condensation. Therefore, to utilize technical lignin, modifications, such as fractionation and/or chemical modifications are necessary. Fractionation with ceramic membranes is one way to lower the polydispersity of lignin. The main advantage is their tolerance towards high temperature and harsh conditions. We demonstrated that low Mw lignin was extracted from industrially produced LignoBoost lignin aiming: i) to investigate the performance of the membrane over time; ii) to analyze the antioxidant properties of the low Mw lignin.

    Chemical modification can also improve the properties of lignin. By adding moieties, different properties can be obtained. Amination and methacrylation of kraft lignin were performed, as well as lignin-silica hybrid materials with potential for the adsorption were produced and investigated.

    Non-modified and methacrylated lignin were used to synthesize lignin-St-DVB porous microspheres to be utilized as a sorbent for organic pollutants. The possibility to substitute styrene with methacrylated lignin was evaluated, demonstrating that interaction between lignin and DVB, and porosity increased.

    Lignin has certain antibacterial properties. Un-modified and modified (aminated) lignin samples and sphere nanoparticles of lignin were tested for their effect against gram-positive and gram-negative bacteria’s and an injectable hydrogel was developed with encapsulated lignin for being used as an injectable gel for the open wounds. Results demonstrated promising antibacterial efficiency of lignins against gram-positive, more especially better inhibition with aminated lignins against gram-positive and negative bacterium.

     

     

    The full text will be freely available from 2019-11-22 11:08
  • 79.
    Aminzadeh, Selda
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Haghniaz, R.
    Ottenhall, A.
    Sevastyanova, Olena
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Lindström, E.
    Khademhosseini, A.
    Lignin based hydrogel for the antibacterial applicationManuscript (preprint) (Other academic)
  • 80.
    Amiri, Fatemeh
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Nouiser, Sara
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Optisk metod för glukosmätning: En studie för framtida icke-invasiva blodglukosmätningar2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Today there are currently living around 365 000 people with diabetes in Sweden. Measuring of blood sugar can be experienced as painful and difficult with blood glucose monitoring devices found in the market. Using lancets and test strip makes direct contact with blood which increases the risk of infection. To reduce these risks and difficulties a non-invasive method is required. This method can even provide an opportunity for healthy individuals to monitor their blood glucose and prevent the disease.This thesis presents the disease, sequelae and the problem around blood glucose monitoring. The work is based on an earlier study about optic measurement of glucose. By illumine a solution of saline and glucose, with infrared-light from a LED, absorption is carried out by the glucose. The amount of transmitted light is detected and processed by a photodetector which generates a current that is converted to a voltage and amplified. This report examines a modification of the circuit used in the previous study to establish a correlation between the glucose concentration and the output voltage by adding a transimpedance amplifier around the photodetector.The results corroborate that the modification with the transimpedance gives a better correlation between the measured output voltage and glucose concentration. The measurements were compiled and plotted to compare which circuit gave a better correlation between the measured output voltage and glucose concentration. The study showed that the modification with transimpedance amplifier gives a better correlation, though it is not enough for clinical use.

  • 81.
    Ammendrup, Katrin
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Framework for Wireless Acquisition of Surface EMG and Real-Time Control2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Muscle driven devices are controlled or powered with muscle activation. These devices open up the possibility of offering patients with limited muscle function to automatically control assistive devices - for instance exoskeletons - with input from their own muscles. This solution would help a number of patient groups suffering from common conditions, such as spinal cord injuries, stroke and cerebral palsy.

    To use muscle activation as input it is necessary to have a way to communicate with the mus- cles. Electromyography (EMG) is a technology used to gain information about muscle function and activation. It is performed by measuring and analyzing electrical signals conducted by the muscles during activation. Activation and activation level can be seen from analyzed EMG signal. EMG signals are frequently measured and analyzed afterwards, however, to use it as a controlling an assistive devices, real time analysis is necessary. In this thesis real time acquisi- tion and analysis of EMG was performed. The measured signal was used as an input to control a simple MATLAB computer game.

    The EMG of a muscle of the forearm, Brachioradialis, was measured with Myon Aktos sys- tem. The measured signal was written to a server as soon as the measurements were acquired. MATLAB was used to connect to the server and performing the signal analysis. The analysis was kept simple in order to limit delay.

    The result showed that it was possible to acquire real time signal with this method. The delay was negligible, both for the testing and for the game play.

    Showing that it is possible to play a game with muscle activation supports the idea of a motor that can be controlled automatically with muscle input. Future work should focus on understanding movement intent with respect to EMG and on analyzing multiple signals from different muscles at the same time.

  • 82.
    Anantha, Krishnan Hariramabadran
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Surface and Corrosion Science.
    Örnek, Cem
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Ejnermark, Sebastian
    Uddeholms AB, Res & Dev, SE-68385 Hagfors, Sweden..
    Thuvander, Anders
    Uddeholms AB, Res & Dev, SE-68385 Hagfors, Sweden..
    Medvedeva, Anna
    Uddeholms AB, Res & Dev, SE-68385 Hagfors, Sweden..
    Sjostrom, Johnny
    Uddeholms AB, Res & Dev, SE-68385 Hagfors, Sweden..
    Pan, Jinshan
    KTH, School of Industrial Engineering and Management (ITM), Materials Science and Engineering.
    Experimental and modelling study of the effect of tempering on the susceptibility to environment-assisted cracking of AISI 420 martensitic stainless steel2019In: Corrosion Science, ISSN 0010-938X, E-ISSN 1879-0496, Vol. 148, p. 83-93Article in journal (Refereed)
    Abstract [en]

    The resistance to environment-assisted cracking (EAC) of AISI 420 martensitic stainless steel (MSS) was investigated in 0.3 M NaCl solution (room temperature) at constant loads for 30 days. The steel tempered at 250 degrees C was superior to the 500 degrees C-temper, which showed corrosion pits favouring cracking. The fracture surface showed faceted grains, cleavage, striations, and inter- and transgranular cracks, suggesting a mixed stress corrosion cracking (SCC) and hydrogen embrittlement (HE) mechanism as the cause for EAC. Finite element modelling (FEM) indicated strain/stress localization at the mouth of deep pits and at the wall of shallow pits, displaying the favoured locations for pit-to-crack transition.

  • 83.
    Andersson, Annika
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Remnestål, Julia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nellgård, B.
    Vunk, Helian
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Kotol, David
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Edfors, Fredrik
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Ilag, L. L.
    Zetterberg, H.
    Blennow, K.
    Månberg, Anna
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Fredolini, Claudia
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Development of parallel reaction monitoring assays for cerebrospinal fluid proteins associated with Alzheimer's disease2019In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 494, p. 79-93Article in journal (Refereed)
    Abstract [en]

    Detailed knowledge of protein changes in cerebrospinal fluid (CSF) across healthy and diseased individuals would provide a better understanding of the onset and progression of neurodegenerative disorders. In this study, we selected 20 brain-enriched proteins previously identified in CSF by antibody suspension bead arrays (SBA) to be potentially biomarkers for Alzheimer's disease (AD) and verified these using an orthogonal approach. We examined the same set of 94 CSF samples from patients affected by AD (including preclinical and prodromal), mild cognitive impairment (MCI), non-AD dementia and healthy individuals, which had previously been analyzed by SBA. Twenty-eight parallel reaction monitoring (PRM) assays were developed and 13 of them could be validated for protein quantification. Antibody profiles were verified by PRM. For seven proteins, the antibody profiles were highly correlated with the PRM results (r > 0.7) and GAP43, VCAM1 and PSAP were identified as potential markers of preclinical AD. In conclusion, we demonstrate the usefulness of targeted mass spectrometry as a tool for the orthogonal verification of antibody profiling data, suggesting that these complementary methods can be successfully applied for comprehensive exploration of CSF protein levels in neurodegenerative disorders.

  • 84.
    Andersson, David
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Holgersson, Emanuel
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Optimering av ett 3D cellmanipulationssystem: Karakterisering av hur ultraljud påverkar temperatur i ett chip2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    A popular method for manipulation of cells is the use of ultrasound. Since the ultrasound usually affects the temperature in its surroundings, there is an interest in characterizing the temperature change in a chip mounted on a transducer that is supplying high frequency ultrasound. If it were possible to control the temperature in the chip by only controlling the voltage being supplied to the ultrasound transducer, the energy costs would be reduced due to not needing a high energy demanding cooling system to control the temperature. By varying the amplitude of the voltage being supplied to the transducer, the temperature in the chip was observed continuously. An IR camera was used to measure the temperature during cycles of heating and cooling. The result shows that there is a certain linearity between the voltage applied to the transducer and the temperature in the chip in certain intervals of voltage. Conduction of heat energy seems to be the lead reason of temperature change in the chip. It has been shown to be possible to control the temperature with a controller as simple as a proportional one, but if a faster pace of heating is desired, then the use of a more sophisticated one should suffice.

  • 85.
    Andersson, Jennie
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    T2 Mapping Compared to Standard MRI Assessment: An Assessment of the Knee Cartilage on Distal Femur2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Magnetic resonance imaging (MRI) has become the most important modality for assessment of pathological changes in the knee cartilage. The assessment of the cartilage is usually made by a set of anatomical MRI images with different sequences. Newer techniques, that map various in MRI parameters, have been developed and allows changes in an earlier stage of the disease. One of these techniques is T2 mapping. The goal of this thesis was to compare this newer technique, T2 mapping, with the standard MRI assessment for assessment of articular cartilage on distal femur in the knee. The purpose was to assess the cartilage with these two different methods and analyze its outcomes.

    Eight subjects were included in this study and scanned with a 3.0 T or 1.5 T MRI machine. A specific MRI knee protocol was used for the standard MRI assessment, and a multi-echo sequence was used for the T2 mapping. The T2 map was created and analyzed in the program IntelliSpace Portal.

    Both the standard MRI assessment and the T2 map showed changes in the knee cartilage. The result showed either indication for damage cartilage or healthy cartilage. The standard assessment showed cartilage lesion in three subjects and no lesion in five subjects. The same outcomes were with the T2 mapping. However, not all results were equal. The T2 mapping also showed higher values in the trochlea area where no indications for changes were found in the standard assessment.

    This study showed similar results for both the standard assessment and the T2 map. Both methods could identify damage and is, therefore, useful for assessment of the knee cartilage. The outcomes of the different methods differ, and the assessment is therefore made in different ways. The T2 mapping can be analyzed both visual and quantitative. The outcomes were both a color map of the knee but also results in graphs and values. The standard assessment is only assessed from grayscale images. The best outcomes from the T2 mapping was when it only was changes within the cartilage and not when the cartilage lesion was adjacent to an underlying bone lesion. Based on what was examined in this work, the best result was when T2 mapping was used together with the anatomical images used in the standard assessment.

    The conclusion is that the standard assessment is necessary when it comes to make a damage assessment and perform damage marking as for Episurf. The T2 mapping is, however, an interesting method and will be more useful with more applications in the future. It is therefore exciting to keep an eye on the technology and its development.

  • 86.
    Andersson, Joakim
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemical Engineering, Energy Processes.
    Grönkvist, Stefan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemical Engineering, Energy Processes.
    Large-scale storage of hydrogen2019In: International journal of hydrogen energy, ISSN 0360-3199, E-ISSN 1879-3487, Vol. 44, no 23, p. 11901-11919Article in journal (Refereed)
    Abstract [en]

    The large-scale storage of hydrogen plays a fundamental role in a potential future hydrogen economy. Although the storage of gaseous hydrogen in salt caverns already is used on a full industrial scale, the approach is not applicable in all regions due to varying geological conditions. Therefore, other storage methods are necessary. In this article, options for the large-scale storage of hydrogen are reviewed and compared based on fundamental thermodynamic and engineering aspects. The application of certain storage technologies, such as liquid hydrogen, methanol, ammonia, and dibenzyltoluene, is found to be advantageous in terms of storage density, cost of storage, and safety. The variable costs for these high-density storage technologies are largely associated with a high electricity demand for the storage process or with a high heat demand for the hydrogen release process. If hydrogen is produced via electrolysis and stored during times of low electricity prices in an industrial setting, these variable costs may be tolerable.

  • 87.
    Andersson, Julius
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    Engström, David
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Health Informatics and Logistics.
    A study in how to inject steganographic data into videos in a sturdy and non-intrusive manner2019Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    It is desirable for companies to be able to hide data inside videos to be able to find the source of any unauthorised sharing of a video. The hidden data (the payload) should damage the original data (the cover) by an as small amount as possible while also making it hard to remove the payload without also severely damaging the cover. It was determined that the most appropriate place to hide data in a video was in the visual information, so the cover is an image. Two injection methods were developed and three methods for attacking the payload. One injection method changes the pixel values of an image directly to hide the payload and the other transforms the image to cosine waves that represented the image and it then changes those cosine waves to hide the payload. Attacks were developed to test how hard it was to remove the hidden data. The methods for attacking the payload where to add and remove a random value to each pixel, to set all bits of a certain importance to 1 or to compress the image with JPEG. The result of the study was that the method that changed the image directly was significantly faster than the method that transformed the image and it had a capacity for a larger payload. The injection methods protected the payload differently well against the various attacks so which method that was the best in that regard depends on the type of attack.

  • 88.
    Andersson, Ken G.
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Persson, Jonas
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Ståhl, Stefan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Löfblom, John
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Autotransporter-Mediated Display of a Naive Affibody Library on the Outer Membrane of Escherichia coli2019In: Biotechnology Journal, ISSN 1860-6768, E-ISSN 1860-7314, Vol. 14, no 4, article id 1800359Article in journal (Refereed)
    Abstract [en]

    Development of new affinity proteins using combinatorial protein engineering is today established for generation of monoclonal antibodies and also essential for discovery of binders that are based on non-immunoglobulin proteins. Phage display is most frequently used, but yeast display is becoming increasingly popular, partly due to the option of utilizing fluorescence-activated cell sorting (FACS) for isolation of new candidates. Escherichia coli has several valuable properties for library applications and in particular the high transformation efficiency. The use of various autotransporters and intimins for secretion and anchoring on the outer membrane have shown promising results and particularly for directed evolution of different enzymes. Here, the authors report on display of a large naive affibody library on the outer membrane of E. coli using the autotransporter Adhesin Involved in Diffuse Adherence (AIDA-I). The expression cassette is first engineered by removing non-essential sequences, followed by introduction of an affibody library, comprising more than 10(9) variants, into the new display vector. The quality of the library and general performance of the method is assessed by FACS against five different targets, which resulted in a panel of binders with down to nanomolar affinities, suggesting that the method has potential as a complement to phage display for generation of affibody molecules.

  • 89.
    Andersson, Linn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Enskilda brunnars vattenkvalitet samt förekommande vattenreningstekniker2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 90.
    Andersson, Olle
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Predicting Patient Length Of Stay at Time of Admission Using Machine Learning2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This master thesis investigates the possibility of using machine learning methods to predict patient length of stay at the time of admission to a clinical ward from the emergency department. The main aim of this thesis is to provide a comparative analysis of different algorithms and to suggest a suitable model that can be used in a hospital prediction software. The results show that it is possible to achieve a balanced accuracy of 0.72 at the time of admission and of 0.75 at a later stage in the process. The suggested algorithm was Random Forest which combines good accuracy with effective training time, making it suitable for on-line use in a hospital. The study shows that there is a clear potential for the use of machine learning methods for predicting length of stay, but that further improvements have to be made before adaption into the healthcare.

  • 91. Andersson, Thord
    et al.
    Romu, Thobias
    Karlsson, Anette
    Norén, Bengt
    Forsgren, Mikael F
    Smedby, Örjan
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Image Processing and Visualization. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging. Linköping University.
    Kechagias, Stergios
    Almer, Sven
    Lundberg, Peter
    Borga, Magnus
    Leinhard, Olof Dahlqvist
    Consistent intensity inhomogeneity correction in water-fat MRI2015In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 42, no 2Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To quantitatively and qualitatively evaluate the water-signal performance of the consistent intensity inhomogeneity correction (CIIC) method to correct for intensity inhomogeneities

    METHODS: Water-fat volumes were acquired using 1.5 Tesla (T) and 3.0T symmetrically sampled 2-point Dixon three-dimensional MRI. Two datasets: (i) 10 muscle tissue regions of interest (ROIs) from 10 subjects acquired with both 1.5T and 3.0T whole-body MRI. (ii) Seven liver tissue ROIs from 36 patients imaged using 1.5T MRI at six time points after Gd-EOB-DTPA injection. The performance of CIIC was evaluated quantitatively by analyzing its impact on the dispersion and bias of the water image ROI intensities, and qualitatively using side-by-side image comparisons.

    RESULTS: CIIC significantly ( P1.5T≤2.3×10-4,P3.0T≤1.0×10-6) decreased the nonphysiological intensity variance while preserving the average intensity levels. The side-by-side comparisons showed improved intensity consistency ( Pint⁡≤10-6) while not introducing artifacts ( Part=0.024) nor changed appearances ( Papp≤10-6).

    CONCLUSION: CIIC improves the spatiotemporal intensity consistency in regions of a homogenous tissue type.

  • 92.
    Andreasson, Jörgen
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Organizational preconditions and supportive resources for Swedish healthcare managers.: Factors that contribute to or counteract changes2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Swedish Healthcare managers’ organizational preconditions and supportive resources are important for their ability to work with planned change in a sustainable way. This thesis further investigates these factors together with an output measure, healthcare process quality (HPQ).

    The overall aim was to investigate how healthcare managers’ organizational preconditions and support contribute to or counteract managers’ work with planned change in order to implement process development in a sustainable way. Specific aims were: to improve knowledge of managers’ views of and approaches to increasing their employees’ influence on and engagement in models for improving care processes (study I); to investigate relationships among managers’ organizational preconditions, support, and work to improve quality of care and HPQ over time (study II); to investigate whether managers’ coaching style, preconditions, implementation strategy, appraisal of change, and clinical autonomy are associated with HPQ (study III ); and to assess the influence of support from superiors, colleagues, external sources, subordinates, and private life on managers’ own health (study IV ).

    The data for Studies I – III came from five hospitals collected over a three-year period. The data were collected by means of interviews (Study I, qualitative analysis) and annual questionnaires (Studies II and III, quantitative and mixed-method analyses). The data for Study IV were based on questionnaires administered to first- and second-line managers in municipal care, twice during a two-year period.

    The results revealed that the healthcare managers were key actors in implementing planned change, but were dependent on their employees’ engagement in order to succeed. Managers’ appraisal of work with planned change became more positive with strong support from other managers, employees, and the organization as well as with long managerial experience. Support from private life and networks, as well as the managers’ attitudes towards their managerial role, predicted their own health. For new managers or managers with many employees, organizational support predicted their health-related sustainability. Managers practising a more distanced style of coaching (e.g., clearly delegating responsibility for implementation work to employees) were associated with better HPQ outcomes than were managers who were more involved in implementation. In conclusion, implementation of planned change are facilitated by, engaged managers, employees with knowledge of implementation work and of the healthcare system, as well as organizational structures that support the managers. Strong support from various sources as well as managerial experience are important for managers’ appraisal of work with planned change. Strong managerial support and a more delegated leadership style are both important factors related to higher estimated HPQ.

  • 93.
    Andreasson, Jörgen
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Ljungar, Erik
    Ahlstrom, Linda
    Hermansson, Jonas
    Dellve, Lotta
    Professional Bureaucracy and Health Care Managers’Planned Change Strategies: Governance in SwedishHealth Care2018In: Nordic Journal of Working Life Studies, ISSN 2245-0157, E-ISSN 2245-0157, Vol. 8, no 1, p. 23-41Article in journal (Refereed)
    Abstract [en]

    To increase efficiency and quality, process development has been implemented in many Swedish

    hospitals. These hospitals are usually organized as professional bureaucracies in which

    health care managers have limited decision control. The new governance principles has been

    implemented without removing bureaucratic elements. This study analyzes how managers implement

    planned change in these professional bureaucracies, considering if managers coaching

    style, organizational preconditions, implementation strategy, appraisal of change and clinic autonomy,

    is associated with health care process quality (HPQ). The study is based on interviews

    with health care managers and longitudinal assessments of HPQ. The results revealed significant

    differences between coaching style, organizational preconditions, and HPQ over time. The

    conclusion is that leadership and preconditions is of importance for the health care manager’s

    ability to work with planned change, as that the health care managers understand how management

    methods, governance principles, and professional bureaucracies work in practice.

  • 94. Andreo-Vidal, Andres
    et al.
    Sanchez-Amat, Antonio
    Campillo-Brocal, Jonatan C.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    The Pseudoalteromonas luteoviolacea L-amino Acid Oxidase with Antimicrobial Activity Is a Flavoenzyme2018In: Marine Drugs, ISSN 1660-3397, E-ISSN 1660-3397, Vol. 16, no 12, article id 499Article in journal (Refereed)
    Abstract [en]

    The marine environment is a rich source of antimicrobial compounds with promising pharmaceutical and biotechnological applications. The Pseudoalteromonas genus harbors one of the highest proportions of bacterial species producing antimicrobial molecules. For decades, the presence of proteins with L-amino acid oxidase (LAAO) and antimicrobial activity in Pseudoalteromonas luteoviolacea has been known. Here, we present for the first time the identification, cloning, characterization and phylogenetic analysis of Pl-LAAO, the enzyme responsible for both LAAO and antimicrobial activity in P. luteoviolacea strain CPMOR-2. Pl-LAAO is a flavoprotein of a broad substrate range, in which the hydrogen peroxide generated in the LAAO reaction is responsible for the antimicrobial activity. So far, no protein with a sequence similarity to Pl-LAAO has been cloned or characterized, with this being the first report on a flavin adenine dinucleotide (FAD)-containing LAAO with antimicrobial activity from a marine microorganism. Our results revealed that 20.4% of the sequenced Pseudoalteromonas strains (specifically, 66.6% of P. luteoviolacea strains) contain Pl-laao similar genes, which constitutes a well-defined phylogenetic group. In summary, this work provides insights into the biological significance of antimicrobial LAAOs in the Pseudoalteromonas genus and shows an effective approach for the detection of novel LAAOs, whose study may be useful for biotechnological applications.

  • 95.
    Andrieux, Sebastien
    et al.
    Univ Stuttgart, Inst Phys Chem, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.;Inst Charles Sadron UPR22 CNRS, 23 Rue Loess, F-67034 Strasbourg 2, France..
    Medina, Lilian
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Biocomposites. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Wallenberg Wood Science Center.
    Herbst, Michael
    Univ Stuttgart, Inst Phys Chem, Pfaffenwaldring 55, D-70569 Stuttgart, Germany..
    Berglund, Lars
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Biocomposites. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Wallenberg Wood Science Center.
    Stubenrauch, Cosima
    Univ Stuttgart, Inst Phys Chem, Pfaffenwaldring 55, D-70569 Stuttgart, Germany..
    Monodisperse highly ordered chitosan/cellulose nanocomposite foams2019In: Composites. Part A, Applied science and manufacturing, ISSN 1359-835X, E-ISSN 1878-5840, Vol. 125, article id UNSP 105516Article in journal (Refereed)
    Abstract [en]

    In solid foams, most physical properties are determined by the pore size and shape distributions and the organisation of the pores. For this reason, it is important to control the structure of porous materials. We recently tackled this issue with the help of microfluidic-aided foam templating, which allowed us to generate mono-disperse and highly ordered chitosan foams. However, the properties of foams also depend on the properties of the pore wall constituents. In case of chitosan-based foams, the foams have poor absolute mechanical properties, simply due to the fact that the solubility of chitosan in water is very low, so that the relative density of the freeze-dried foams becomes very small. Drawing inspiration from the field of nanocomposites, we incorporated cellulose nanofibres into the foamed chitosan solutions, with a view to strengthening the pore walls in the foam and thus the mechanical properties of the final foam. We report here how the cellulose nanofibres affect the structure of both the liquid foam template and the solid foam. The resulting nanocomposite foams have improved mechanical properties, which, however, are not proportional to the amount of cellulose nanofibres in the composites. One reason for this observation is the disturbance of the porous structure of the solid foams by the cellulose nanofibres.

  • 96.
    Andrén, Oliver C. J.
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    Ingverud, Tobias
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    Hult, Daniel
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    Håkansson, Joakim
    Bogestål, Yalda
    Caous, Josefin S.
    Blom, Kristina
    Zhang, Yuning
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Andersson, Therese
    Pedersen, Emma
    Björn, Camilla
    Löwenhielm, Peter
    Malkoch, Michael
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings2019In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 8, no 5Article in journal (Refereed)
    Abstract [en]

    Abstract A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged ?-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G? = 0.5?8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.

  • 97.
    Anette, Kniberg
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    Nokto, David
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems.
    A Benchmark of Prevalent Feature Selection Algorithms on a Diverse Set of Classification Problems2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Feature selection is the process of automatically selecting important features from data. It is an essential part of machine learning, artificial intelligence, data mining, and modelling in general. There are many feature selection algorithms available and the appropriate choice can be difficult. The aim of this thesis was to compare feature selection algorithms in order to provide an experimental basis for which algorithm to choose. The first phase involved assessing which algorithms are most common in the scientific community, through a systematic literature study in the two largest reference databases: Scopus and Web of Science. The second phase involved constructing and implementing a benchmark pipeline to compare 31 algorithms’ performance on 50 data sets.The selected features were used to construct classification models and their predictive performances were compared, as well as the runtime of the selection process. The results show a small overall superiority of embedded type algorithms, especially types that involve Decision Trees. However, there is no algorithm that is significantly superior in every case. The pipeline and data from the experiments can be used by practitioners in determining which algorithms to apply to their respective problems.

  • 98. Angiolini, L.
    et al.
    Valetti, S.
    Cohen, B.
    Feiler, Adam
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Surface and Corrosion Science. Nanologica AB, Södertälje, Sweden.
    Douhal, A.
    Fluorescence imaging of antibiotic clofazimine encapsulated within mesoporous silica particle carriers: Relevance to drug delivery and the effect on its release kinetics2018In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 20, no 17, p. 11899-11911Article in journal (Refereed)
    Abstract [en]

    We report on the encapsulation of the antibiotic clofazimine (CLZ) within the pores of mesoporous silica particles having hydrophilic (CBET value of 137) and more hydrophobic (CBET value of 94 after calcination at 600 °C) surfaces. We studied the effect of pH on the released amount of CLZ in aqueous solutions and observed a maximum at pH 4.1 in correlation with the solubility of the drug. Less release of the drug was observed from the more hydrophobic particles which was attributed to a difference in the affinity of the drug to the carrier particles. Fluorescence lifetime imaging microscopy, emission spectra, and fluorescence lifetimes of single drug loaded particles provided detailed understanding and new knowledge of the physical form of the encapsulated drug and the distribution within the particles. The distribution of CLZ within the particles was independent of the surface chemistry of the particles. The confirmation of CLZ molecules as monomers or aggregates was revealed by controlled removal of the drug with solvent. Additionally, the observed optical "halo effect" in the fluorescent images was interpreted in terms of specific quenching of high concentration of molecules. The emission lifetime experiments suggest stronger interaction of CLZ with the more hydrophobic particles, which is relevant to its release. The results reported in this work demonstrate that tuning the hydrophilicity/hydrophobicity of mesoporous silica particles can be used as a tool to control the release without impacting their loading ability.

  • 99.
    Anikeeva, Polina
    et al.
    MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.;MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA.;MIT, Res Lab Elect, Cambridge, MA 02139 USA.;MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA..
    Lundberg, Emma
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH). Stanford Univ, Dept Genet, Stanford, CA 94305 USA.;Chan Zuckerberg Biohub, San Francisco, CA USA..
    Zhuang, Xiaowei
    Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.;Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.;Howard Hughes Med Inst, Cambridge, MA USA..
    Voices in methods development2019In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 16, no 10, p. 945-951Article in journal (Other academic)
  • 100.
    Annelies, Nonneman
    et al.
    KU Leuven Univ Leuven, Dept Neurosci, Lab Neurobiol & Expt Neurol, Herestr 49, B-3000 Leuven, Belgium.;LBI, Herestr 49, B-3000 Leuven, Belgium.;Ctr Brain & Dis Res, VIB, Herestr 49, B-3000 Leuven, Belgium..
    Nathan, Criem
    Ctr Brain & Dis Res, VIB, Herestr 49, B-3000 Leuven, Belgium.;KU Leuven Univ Leuven, Dept Cardiovasc Sci, Ctr Mol & Vasc Biol, Herestr 49, B-3000 Leuven, Belgium.;KU Leuven Univ Leuven, Dept Human Genet, Herestr 49, B-3000 Leuven, Belgium..
    Lewandowski, Sebastian
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden..
    Rik, Nuyts
    KU Leuven Univ Leuven, Dept Neurosci, Lab Neurobiol & Expt Neurol, Herestr 49, B-3000 Leuven, Belgium.;LBI, Herestr 49, B-3000 Leuven, Belgium.;Ctr Brain & Dis Res, VIB, Herestr 49, B-3000 Leuven, Belgium..
    Dietmar, Thal R.
    KU Leuven Univ Leuven, Dept Neurosci, Lab Neuropathol, Herestr 49, B-3000 Leuven, Belgium.;Univ Hosp Leuven, Dept Neurol, Herestr 49, B-3000 Leuven, Belgium..
    Frank, Pfrieger W.
    Univ Strasbourg, CNRS UPR 3212, Inst Cellular & Integrat Neurosci, F-67084 Strasbourg, France..
    John, Ravits
    Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr, San Diego, CA 92093 USA..
    Philip, Van Damme
    KU Leuven Univ Leuven, Dept Neurosci, Lab Neurobiol & Expt Neurol, Herestr 49, B-3000 Leuven, Belgium.;LBI, Herestr 49, B-3000 Leuven, Belgium.;Ctr Brain & Dis Res, VIB, Herestr 49, B-3000 Leuven, Belgium.;Univ Hosp Leuven, Dept Neurol, Herestr 49, B-3000 Leuven, Belgium..
    An, Zwijsen
    Ctr Brain & Dis Res, VIB, Herestr 49, B-3000 Leuven, Belgium.;KU Leuven Univ Leuven, Dept Cardiovasc Sci, Ctr Mol & Vasc Biol, Herestr 49, B-3000 Leuven, Belgium.;KU Leuven Univ Leuven, Dept Human Genet, Herestr 49, B-3000 Leuven, Belgium..
    Ludo, Van Den Bosch
    KU Leuven Univ Leuven, Dept Neurosci, Lab Neurobiol & Expt Neurol, Herestr 49, B-3000 Leuven, Belgium.;LBI, Herestr 49, B-3000 Leuven, Belgium.;Ctr Brain & Dis Res, VIB, Herestr 49, B-3000 Leuven, Belgium..
    Wim, Robberecht
    KU Leuven Univ Leuven, Dept Neurosci, Lab Neurobiol & Expt Neurol, Herestr 49, B-3000 Leuven, Belgium.;LBI, Herestr 49, B-3000 Leuven, Belgium.;Ctr Brain & Dis Res, VIB, Herestr 49, B-3000 Leuven, Belgium.;Univ Hosp Leuven, Dept Neurol, Herestr 49, B-3000 Leuven, Belgium..
    Astrocyte-derived Jagged-1 mitigates deleterious Notch signaling in amyotrophic lateral sclerosis2018In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 119, p. 26-40Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a late-onset devastating degenerative disease mainly affecting motor neurons. Motor neuron degeneration is accompanied and aggravated by oligodendroglial pathology and the presence of reactive astrocytes and microglia. We studied the role of the Notch signaling pathway in ALS, as it is implicated in several processes that may contribute to this disease, including axonal retraction, microgliosis, astrocytosis, oligodendrocyte precursor cell proliferation and differentiation, and cell death. We observed abnormal activation of the Notch signaling pathway in the spinal cord of SOD1(G93A) mice, a well-established model for ALS, as well as in the spinal cord of patients with sporadic ALS (sALS). This increased activation was particularly evident in reactive GFAP-positive astrocytes. In addition, one of the main Notch ligands, Jagged-1, was ectopically expressed in reactive astrocytes in spinal cord from ALS mice and patients, but absent in resting astrocytes. Astrocyte-specific inactivation of Jagged-1 in presymptomatic SOD1(G93A) mice further exacerbated the activation of the Notch signaling pathway and aggravated the course of the disease in these animals without affecting disease onset. These data suggest that aberrant Notch signaling activation contributes to the pathogenesis of ALS, both in sALS patients and SOD1(G93A) mice, and that it is mitigated in part by the upregulation of astrocytic Jagged-1.

1234567 51 - 100 of 2478
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf