Change search
Refine search result
1234567 51 - 100 of 796
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • 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.
    Baumann, Martin J.
    et al.
    KTH, School of Biotechnology (BIO).
    Eklöf, Jens
    KTH, School of Biotechnology (BIO).
    Michel, G.
    Kallas, Åsa
    KTH.
    Teeri, Tuula
    KTH, School of Biotechnology (BIO).
    Czjzek, Mirjam
    KTH.
    Brumer, Harry
    KTH, School of Biotechnology (BIO), Glycoscience.
    Structural analysis of nasturtium NXG reveals the evolution of GH16 xyloglucanase activity from XETs: biological implications for cell wall metabolismManuscript (Other academic)
  • 52. Beatriz Badia, Mariana
    et al.
    Mans, Robert
    Lis, Alicia V.
    Ariel Tronconi, Marcos
    Lucia Arias, Cintia
    Maurino, Veronica Graciela
    Santiago Andreo, Carlos
    Fabiana Drincovich, Maria
    van Maris, Antonius J. A.
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    Gerrard Wheeler, Mariel Claudia
    Specific Arabidopsis thaliana malic enzyme isoforms can provide anaplerotic pyruvate carboxylation function in Saccharomyces cerevisiae2017In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 284, no 4, p. 654-665Article in journal (Refereed)
    Abstract [en]

    NAD(P)-malic enzyme (NAD(P)-ME) catalyzes the reversible oxidative decarboxylation of malate to pyruvate, CO2, and NAD(P)H and is present as a multigene family in Arabidopsis thaliana. The carboxylation reaction catalyzed by purified recombinant Arabidopsis NADP-ME proteins is faster than those reported for other animal or plant isoforms. In contrast, no carboxylation activity could be detected in vitro for the NAD-dependent counterparts. In order to further investigate their putative carboxylating role in vivo, Arabidopsis NAD(P)-ME isoforms, as well as the NADP-ME2del2 (with a decreased ability to carboxylate pyruvate) and NADP-ME2R115A (lacking fumarate activation) versions, were functionally expressed in the cytosol of pyruvate carboxylase-negative (Pyc(-)) Saccharomyces cerevisiae strains. The heterologous expression of NADP-ME1, NADP-ME2 (and its mutant proteins), and NADP-ME3 restored the growth of Pyc(-) S. cerevisiae on glucose, and this capacity was dependent on the availability of CO2. On the other hand, NADP-ME4, NAD-ME1, and NAD-ME2 could not rescue the Pyc(-) strains from C-4 auxotrophy. NADP-ME carboxylation activity could be measured in leaf crude extracts of knockout and over-expressing Arabidopsis lines with modified levels of NADP-ME, where this activity was correlated with the amount of NADP-ME2 transcript. These results indicate that specific A. thaliana NADP-ME isoforms are able to play an anaplerotic role in vivo and provide a basis for the study on the carboxylating activity of NADP-ME, which may contribute to the synthesis of C-4 compounds and redox shuttling in plant cells.

  • 53.
    Beaussant Törne, Karin
    KTH, School of Engineering Sciences (SCI), Applied Physics, Material Physics, MF.
    Investigation of corrosion properties of metals for degradable implant applications2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Degradable metallic implants are a new class of biomaterials with potentialto replace permanent materials in temporary applications to reduce therisk of long term adverse effects.This thesis focuses on in vitro testing of zinc and magnesium based metals.As new degradable metals are developed screening of new materials within vitro test methods is an attractive option to avoid unnecessary, time consumingand expensive animal studies. The influence of factors such as ioniccomposition of the test solution, buffer system, strain and alloy compositionwas investigated. By employing electrochemical in situ techniques such asimpedance spectroscopy it is possible to study the metal-solution interfaceand determine the properties of the corroding surface. Ex situ surface characterizationtechniques such as scanning electron microscopy and infraredspectroscopy were then used to complement the results of the electrochemicalmeasurements.The importance of appropriate selection of the test solution is highlightedin this work. Zinc was found to corrode in Ringer’s solution by a mechanismcloser to in vivo corrosion than in a phosphate buffered saline solution(PBS).Ringer’s solution is therefore the more appropriate test environment for longterm evaluation of zinc based metals.When evaluating the corrosion of Zn-Mg and Zn-Ag alloys in Ringer’ssolution selective dissolution was found to occur for both types of alloys. Localprecipitation and formation of a porous, less protective, layer of corrosionproducts was found for Zn-Mg alloys. The selective dissolution of Zn-Agalloy caused an enrichment of AgZn3 on the surface which may affect thebiocompatibility of the alloy.The use of HEPES to maintain the pH of the test solution increasedthe corrosion rate of magnesium due to formation of a less protective layerof corrosion products. Magnesium corrosion should therefore preferably bestudied in solutions where the pH is maintained by the biological buffer systemCO2/H2CO3.In addition to saline solutions human whole blood and plasma were evaluatedas more clinically relevant in vitro environments. They were found toproduce reproducible results and to be suitable for short term experiments.Formation of a corrosion product layer comprised of both organic and inorganicmaterial was detected on zinc in both plasma and whole blood.During anodic polarization the adsorption of organic species on the zincsurface was found to increase the surface coverage of Zn ions in whole blood.The increased surface coverage then allowed for precipitation of a protectivelayer of Zn5(PO4)3 and a subsequent decrease in corrosion rate at higherpotentials.When subjecting zinc samples to strain the organic/inorganic corrosionproduct formed in whole blood was observed by impedance spectroscopy toprevent micro cracking and premature failure.The cracking of magnesium alloy samples under applied strain was alsocharacterized by impedance. Changes in surface properties due to crack initiation

    Download full text (pdf)
    Kappa
  • 54. Beerenwinkel, N.
    et al.
    Greenman, C. D.
    Lagergren, Jens
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Computational Cancer Biology: An Evolutionary Perspective2016In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 12, no 2, article id e1004717Article in journal (Refereed)
  • 55.
    Berglund, Lisa
    KTH, School of Biotechnology (BIO), Proteomics.
    Selection of antigens for antibody-based proteomics2008Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

    The human genome is predicted to contain ~20,500 protein-coding genes. The encoded proteins are the key players in the body, but the functions and localizations of most proteins are still unknown. Antibody-based proteomics has great potential for exploration of the protein complement of the human genome, but there are antibodies only to a very limited set of proteins. The Human Proteome Resource (HPR) project was launched in August 2003, with the aim to generate high-quality specific antibodies towards the human proteome, and to use these antibodies for large-scale protein profiling in human tissues and cells.

    The goal of the work presented in this thesis was to evaluate if antigens can be selected, in a high-throughput manner, to enable generation of specific antibodies towards one protein from every human gene. A computationally intensive analysis of potential epitopes in the human proteome was performed and showed that it should be possible to find unique epitopes for most human proteins. The result from this analysis was implemented in a new web-based visualization tool for antigen selection. Predicted protein features important for antigen selection, such as transmembrane regions and signal peptides, are also displayed in the tool. The antigens used in HPR are named protein epitope signature tags (PrESTs). A genome-wide analysis combining different protein features revealed that it should be possible to select unique, 50 amino acids long PrESTs for ~80% of the human protein-coding genes.

    The PrESTs are transferred from the computer to the laboratory by design of PrEST-specific PCR primers. A study of the success rate in PCR cloning of the selected fragments demonstrated the importance of controlled GC-content in the primers for specific amplification. The PrEST protein is produced in bacteria and used for immunization and subsequent affinity purification of the resulting sera to generate mono-specific antibodies. The antibodies are tested for specificity and approved antibodies are used for tissue profiling in normal and cancer tissues. A large-scale analysis of the success rates for different PrESTs in the experimental pipeline of the HPR project showed that the total success rate from PrEST selection to an approved antibody is 31%, and that this rate is dependent on PrEST length. A second PrEST on a target protein is somewhat less likely to succeed in the HPR pipeline if the first PrEST is unsuccessful, but the analysis shows that it is valuable to select several PrESTs for each protein, to enable generation of at least two antibodies, which can be used to validate each other.

    Download full text (pdf)
    FULLTEXT01
  • 56.
    Berglund, Lisa
    et al.
    KTH, School of Biotechnology (BIO).
    Andrade, Jorge
    KTH, School of Biotechnology (BIO).
    Odeberg, Jacob
    KTH, School of Biotechnology (BIO).
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO).
    The epitope space of the human proteome2008In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 17, no 4, p. 606-613Article in journal (Refereed)
    Abstract [en]

    In the post-genome era, there is a great need for protein-specific affinity reagents to explore the human proteome. Antibodies are suitable as reagents, but generation of antibodies with low cross-reactivity to other human proteins requires careful selection of antigens. Here we show the results from a proteomewide effort to map linear epitopes based on uniqueness relative to the entire human proteome. The analysis was based on a sliding window sequence similarity search using short windows (8, 10, and 12 amino acid residues). A comparison of exact string matching (Hamming distance) and a heuristic method (BLAST) was performed, showing that the heuristic method combined with a grid strategy allows for whole proteome analysis with high accuracy and feasible run times. The analysis shows that it is possible to find unique antigens for a majority of the human proteins, with relatively strict rules involving low sequence identity of the possible linear epitopes. The implications for human antibody-based proteomics efforts are discussed.

  • 57.
    Berglund, Lisa
    et al.
    KTH, School of Biotechnology (BIO).
    Björling, Erik
    KTH, School of Biotechnology (BIO).
    Gry, Marcus
    KTH, School of Biotechnology (BIO).
    Asplund, Anna
    Uppsala Univ, Rudbeck laboratory.
    Al-Khalili Szigyarto, Cristina
    KTH, School of Biotechnology (BIO).
    Persson, Anja
    KTH, School of Biotechnology (BIO).
    Ottoson, Jenny
    KTH, School of Biotechnology (BIO).
    Wernérus, Henrik
    KTH, School of Biotechnology (BIO).
    Nilsson, Peter
    KTH, School of Biotechnology (BIO).
    Sivertsson, Åsa
    KTH, School of Biotechnology (BIO).
    Wester, Kenneth
    Uppsala Univ, Rudbeck laboratory.
    Kampf, Caroline
    Uppsala Univ, Rudbeck laboratory.
    Hober, Sophia
    KTH, School of Biotechnology (BIO).
    Pontén, Fredrik
    Uppsala Univ, Rudbeck laboratory.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO).
    Generation of validated antibodies towards the human proteomeArticle in journal (Other academic)
    Abstract [en]

    Here we show the results from a large effort to generate antibodies towards the human proteome. A high-throughput strategy was developed based on cloning and expression of antigens as recombitant protein epitope signature tags (PrESTs) Affinity purified polyclonal antibodies were generated, followed by validation by protein microarrays, Western blotting and microarray-based immunohistochemistry. PrESTs were selected based on sequence uniqueness relative the proteome and a bioinformatics analysis showed that unique antigens can be found for at least 85% of the proteome using this general strategy. The success rate from antigen selection to validated antibodies was 31%, and from protein to antibody 55%. Interestingly, membrane-bound and soluble proteins performed equally and PrEST lengths between 75 and 125 amino acids were found to give the highest yield of validated antibodies. Multiple antigens were selected for many genes and the results suggest that specific antibodies can be systematically generated to most human proteibs.

  • 58.
    Berglund, Lisa
    et al.
    KTH, School of Biotechnology (BIO).
    Björling, Erik
    KTH, School of Biotechnology (BIO).
    Jonasson, Kalle
    KTH, School of Biotechnology (BIO).
    Rockberg, Johan
    KTH, School of Biotechnology (BIO).
    Fagerberg, Linn
    KTH, School of Biotechnology (BIO).
    Al-Khalili Szigyarto, Cristina
    KTH, School of Biotechnology (BIO).
    Sivertsson, Åsa
    KTH, School of Biotechnology (BIO).
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO).
    A whole-genome bioinformatics approach to selection of antigens for systematic antibody generation2008In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 8, no 14, p. 2832-2839Article in journal (Refereed)
    Abstract [en]

    Here, we present an antigen selection strategy based on a whole-genome bioinformatics approach, which is facilitated by an interactive visualization tool displaying protein features from both public resources and in-house generated data. The web-based bioinformatics platform has been designed for selection of multiple, non-overlapping recombinant protein epitope signature tags by display of predicted information relevant for antigens, including domain- and epitope sized sequence similarities to other proteins, transmembrane regions and signal peptides. The visualization tool also displays shared and exclusive protein regions for genes with multiple splice variants. A genome-wide analysis demonstrates that antigens for approximately 80% of the human protein-coding genes can be selected with this strategy.

  • 59.
    Berglund, Lisa
    et al.
    KTH, School of Biotechnology (BIO), Proteomics.
    Björling, Erik
    KTH, School of Biotechnology (BIO), Proteomics.
    Oksvold, Per
    KTH, School of Biotechnology (BIO), Proteomics.
    Fagerberg, Linn
    KTH, School of Biotechnology (BIO), Proteomics.
    Al-Khalili Szigyarto, Cristina
    KTH, School of Biotechnology (BIO), Proteomics.
    Persson, Anja
    KTH, School of Biotechnology (BIO), Proteomics.
    Ottosson, Jenny
    KTH, School of Biotechnology (BIO), Proteomics.
    Wernérus, Henrik
    KTH, School of Biotechnology (BIO), Proteomics.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Lundberg, Emma
    KTH, School of Biotechnology (BIO), Proteomics.
    Sivertsson, Åsa
    KTH, School of Biotechnology (BIO), Proteomics.
    Hober, Sophia
    KTH, School of Biotechnology (BIO), Proteomics.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    et al.,
    A genecentric human protein atlas for expression profiles based on antibodies2008In: Molecular & Cellular Proteomics, ISSN 1535-9476, Vol. 7, no 10, p. 2019-2027Article in journal (Refereed)
    Abstract [en]

    An attractive path forward in proteomics is to experimentally annotate the human protein complement of the genome in a genecentric manner. Using antibodies, it might be possible to design protein-specific probes for a representative protein from every protein-coding gene and to subsequently use the antibodies for systematical analysis of cellular distribution and subcellular localization of proteins in normal and disease tissues. A new version (4.0) of the Human Protein Atlas has been developed in a genecentric manner with the inclusion of all human genes and splice variants predicted from genome efforts together with a visualization of each protein with characteristics such as predicted membrane regions, signal peptide, and protein domains and new plots showing the uniqueness (sequence similarity) of every fraction of each protein toward all other human proteins. The new version is based on tissue profiles generated from 6120 antibodies with more than five million immunohistochemistry-based images covering 5067 human genes, corresponding to similar to 25% of the human genome. Version 4.0 includes a putative list of members in various protein classes, both functional classes, such as kinases, transcription factors, G-protein-coupled receptors, etc., and project-related classes, such as candidate genes for cancer or cardiovascular diseases. The exact antigen sequence for the internally generated antibodies has also been released together with a visualization of the application-specific validation performed for each antibody, including a protein array assay, Western blot analysis, immunohistochemistry, and, for a large fraction, immunofluorescence-based confocal microscopy. New search functionalities have been added to allow complex queries regarding protein expression profiles, protein classes, and chromosome location. The new version of the protein atlas thus is a resource for many areas of biomedical research, including protein science and biomarker discovery.

  • 60.
    Berglund, Lisa
    et al.
    KTH, School of Biotechnology (BIO).
    Persson, Anja
    KTH, School of Biotechnology (BIO).
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO).
    Primer design for high-throughput PCR cloningArticle in journal (Other academic)
  • 61.
    Berglund, P.
    et al.
    University of Toronto, Canada.
    Stabile, M. R.
    Gold, M.
    Jones, J. B.
    Mitchinson, C.
    Bott, R. R.
    Graycar, T. P.
    Altering the specificity of subtilisin B. lentus by combining site-directed mutagenesis and chemical modification1996In: Bioorganic and Medicinal Chemistry Letters, ISSN 0960-894X, Vol. 6, no 21, p. 2507-2512Article in journal (Refereed)
    Abstract [en]

    The thiol side chain of the M222C mutant of the subtilisin from Bacillus lentus (SBL) has been chemically modified by methyl-, aminoethyl-, and sulfonatoethylthiosulfonate reagents. Introduction of charged residues into the active site of the enzyme reduced the catalytic efficiency with Suc-AAPF-pNA as the substrate, but resulted in better binding of sterically demanding boronic acid inhibitors.

  • 62.
    Berglund, Per
    KTH, School of Biotechnology (BIO), Biochemistry.
    BIO-AMINES: Searching for a Novel Approach to Biocatalytic Transaminations – a Vinnova Sponsored Project2009In: Book of abstracts, 2009Conference paper (Other academic)
  • 63.
    Berglund, Per
    KTH, School of Biotechnology (BIO), Biochemistry.
    Biocatalysis with Promiscuous Enzymes2007In: 2007 European BioPerspectives / [ed] Dechema, 2007Conference paper (Refereed)
  • 64.
    Berglund, Per
    KTH, School of Biotechnology (BIO), Biochemistry.
    Enzyme Catalytic Promiscuity and Rational Design2006In: Book of abstracts, 2006Conference paper (Refereed)
  • 65.
    Berglund, Per
    KTH, School of Biotechnology (BIO), Biochemistry.
    omega-Transaminases: Tailored for Chiral Amine Synthesis2010In: Biocat2010 / [ed] Ralf Grote, Garabed Antranikian, Hamburg, Germany: TuTech Verlag , 2010Conference paper (Refereed)
  • 66.
    Berglund, Per
    et al.
    KTH, School of Biotechnology (BIO), Biochemistry.
    Christiernin, M.
    Hedenström, E.
    Enantiorecognition of chiral acids by Candida rugosa lipase: Two substrate binding modes evidenced in an organic medium2001In: American Chemical Society Symposium Series (ACS), ISSN 0097-6156, E-ISSN 1947-5918, Vol. 776, p. 263-273Article in journal (Refereed)
    Abstract [en]

    We have identified the existence of different modes of binding the enantiomers of 2-methyl-branched carboxylic acids to a lipase active site by rational substrate engineering. Similar to hydrolysis, previously investigated, we have now evidence for differential binding modes in the Candida rugosa lipase-catalyzed esterifications in cyclohexane. The relevance of considering two different binding modes to understand lipase enantiorecognition is demonstrated by introducing bulky substituents on a chiral carboxylic acid which impose a different orientation of the substrate acyl chain in the active site of Candida rugosa lipase. With this substrate engineering approach based on molecular modeling it is thus possible to markedly alter the enantioselectivity of the lipase. Examples from hydrolysis and new results from esterifications in an organic solvent are presented and discussed.

  • 67.
    Berglund, Per
    et al.
    KTH, School of Biotechnology (BIO), Biochemistry.
    Hedenström, Erik
    Mid Sweden university.
    Preparation of 2-, 3-, and 4-methylcarboxylic acids and the corresponding alcohols of high enantiopurity by lipase-catalyzed esterification2001In: Enzymes in Nonaqueous Solvents: Methods and Protocols / [ed] Vulfson, E. N.; Halling, P. J.; Holland, H. L., Totowa: Humana Press , 2001, p. 307-317Chapter in book (Refereed)
  • 68.
    Berglund, Per
    et al.
    KTH, School of Biotechnology (BIO), Biochemistry.
    Holmquist, M.
    Hult, K.
    Reversed enantiopreference of Candida rugosa lipase supports different modes of binding enantiomers of a chiral acyl donor1998In: Journal of Molecular Catalysis - B Enzymatic, ISSN 13811177 (ISSN), Vol. 5, no 1-4, p. 283-287Article in journal (Refereed)
    Abstract [en]

    Molecular modelling identifies two different productive modes of binding the enantiomers of a 2-methyldecanoic acid ester to the active site of Candida rugosa lipase (CRL). The fast reacting S-enantiomer occupies the previously identified acyl-binding tunnel of the enzyme, whereas the R- enantiomer leaves the tunnel empty. The modelling suggested that if both enantiomers were forced to bind to the active site leaving the tunnel empty, the enzyme would reverse its enantiopreference to become R-enantioselective. To test this hypothesis, we designed a structural analogue to 2- methyldecanoic acid, 2-methyl-6-(2-thienyl)hexanoic acid, which was expected to be too bulky to fit its acyl moiety into the acyl-binding tunnel. The CRL- catalysed hydrolysis of the ethyl ester of this substrate resulted in the preferential conversion of the R-enantiomer as predicted by molecular modelling. This represents the first kinetic evidence supporting the existence of two different modes of binding the enantiomers of a 2- methyldecanoic acid ester to the active site of CRL. We have shown that a rational 3D based approach in combination with substrate engineering can be used to predict and control the stereochemical outcome of a lipase catalysed reaction.

  • 69.
    Berglund, Per
    et al.
    KTH, School of Biotechnology (BIO), Biochemistry.
    Hult, Karl
    KTH, School of Biotechnology (BIO), Biochemistry.
    Biocatalytic synthesis of enantiopure compounds using lipases: Chapter 212000In: Stereoselective Biocatalysis / [ed] Patel, R. N., New York: Marcel Dekker, 2000, p. 633-657Chapter in book (Refereed)
  • 70.
    Berglund, Per
    et al.
    KTH, School of Biotechnology (BIO), Biochemistry.
    Svedendahl, Maria
    KTH, School of Biotechnology (BIO), Biochemistry.
    Engelmark Cassimjee, Karim
    KTH, School of Biotechnology (BIO), Biochemistry.
    Branneby, Cecilia
    Cambrex Karlskoga AB.
    Abedi, Vahak
    AstraZeneca.
    Wells, Andrew
    AstraZeneca.
    Federsel, Hans-Jürgen
    AstraZeneca.
    Omega-Transaminases Redesigned for Chiral Amine Synthesis2011In: BIT Life Sciences’ 2nd Symposium on Enzymes & Biocatalysis, Dalian, China: BIT Life Sciences , 2011Conference paper (Refereed)
  • 71.
    Berglund, Per
    et al.
    Mid Sweden University.
    Vörde, Carin
    Hogberg, Hans-Erik
    Esterification of 2-methylalkanoic acids Catalysed by Lipase from Candida rugosa: Enantioselectivity as a Function of water Activity and Alcohol Chain Length1994In: Biocatalysis and Biotransformation, ISSN 1024-2422, E-ISSN 1029-2446, Vol. 9, no 1-4, p. 123-130Article in journal (Refereed)
  • 72.
    Bergström, Sofia
    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.
    Olofsson, Jennie
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Markaki, Ioanna
    Karolinska Institutet.
    Carvalho, Stephanie
    Institut du Cerveau et de la Moelle épinière, Sorbonne Université.
    Corvol, Jean-Christophe
    Institut du Cerveau et de la Moelle épinière, Sorbonne Université.
    Kultima, Kim
    Uppsala Universitet.
    Kilander, Lena
    Uppsala Universitet.
    Löwenmark, Malin
    Uppsala Universitet.
    Ingelsson, Martin
    Uppsala Universitet.
    Blennow, Kaj
    Sahlgrenska University Hospital, University of Gothenburg.
    Zetterberg, Henrik
    Sahlgrenska University Hospital, University of Gothenburg; Department of Neurodegenerative Disease, UCL Institute of Neurology, London; UK Dementia Research Institute at UCL, London.
    Nellgård, Bengt
    Sahlgrenska University Hospital, University of Gothenburg.
    Brosseron, Frederic
    Universitätsklinikum, Bonn; German Center for Neurodegenerative Diseases (DZNE), Bonn.
    Heneka, Michael
    Universitätsklinikum, Bonn.
    Bosch, Beatriz
    University of Barcelona.
    Sanches-Valle, Raquel
    University of Barcelona.
    Månberg, Anna
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Svenningsson, Per
    Karolinska Institutet.
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Multi-cohort protein profiling reveals higher levels of six brain-enriched proteins in Alzheimer’s disease patientsManuscript (preprint) (Other academic)
  • 73.
    Bernotat, Knut
    et al.
    KTH, Superseded Departments, Industrial Economics and Management.
    Sandberg, Thomas
    KTH, Superseded Departments, Industrial Economics and Management.
    Biomass fired small-scale CHP in Sweden and the Baltic States: a case study on the potential of clustered dwellings2004In: Biomass and Bioenergy, ISSN 0961-9534, E-ISSN 1873-2909, Vol. 27, no 6, p. 521-530Article in journal (Refereed)
    Abstract [en]

    Sweden as well as the three Baltic states has an abundant supply of biomass, mostly wood waste. Much of it goes into district heating (DH), which has expanded continuously since the first system started 50 years ago. DH now accounts for 43% of the heating consumption and a further expansion is possible in many directions. Firstly existing DH systems can be enlarged, secondly DH can be upgraded to combined heat and power (CHP) to a much larger extent, thirdly new DH (and CHP) systems can be implemented in many smaller places down to 1000 inhabitants or less. The last alternative, biomass and especially pellets fired small-scale cogeneration in combination with local heating networks, is the topic for this paper. It presents a method to estimate the potential for small-scale DH and CHP and results from a "test" area in southeast Sweden. The method estimates local heat demand using databases with individual and statistical property data. It identifies areas with clusters of buildings where the heat demand is enough to implement decentralized small DH networks if possible in combination with small-scale CHP. In the event for Swedish circumstances very sparsely populated test area of 36 x 48 km(2) with around 8000 inhabitants, the total heat consumption in residential buildings is estimated to 84 GWh. When we have identified the areas with clusters of buildings, we have set the minimum heat consumption in such an area to 500 MW h. The area size is varied in 250 m steps from 250 x 250 m(2) to 1000 x 1000 m(2). For the four area sizes, the method then identifies and locates 30, 38, 38,30, respectively, clustered areas with a potential for small-scale DH and CHP worth investing closer.

  • 74. Bessani, A.
    et al.
    Brandt, J.
    Bux, M.
    Cogo, V.
    Dimitrova, L.
    Dowling, Jim
    KTH, School of Information and Communication Technology (ICT), Software and Computer systems, SCS.
    Gholami, Ali
    KTH.
    Hakimzadeh, Kamal
    KTH, School of Information and Communication Technology (ICT), Software and Computer systems, SCS.
    Hummel, M.
    Ismail, Mahmoud
    KTH, School of Information and Communication Technology (ICT), Software and Computer systems, SCS.
    Laure, Erwin
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC. KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz).
    Leser, U.
    Litton, J. -E
    Martinez, R.
    Niazi, Salman
    KTH, School of Information and Communication Technology (ICT), Software and Computer systems, SCS.
    Reichel, J.
    Zimmermann, K.
    BiobankCloud: A platform for the secure storage, sharing, and processing of large biomedical data sets2016In: 1st International Workshop on Data Management and Analytics for Medicine and Healthcare, DMAH 2015 and Workshop on Big-Graphs Online Querying, Big-O(Q) 2015 held in conjunction with 41st International Conference on Very Large Data Bases, VLDB 2015, Springer, 2016, p. 89-105Conference paper (Refereed)
    Abstract [en]

    Biobanks store and catalog human biological material that is increasingly being digitized using next-generation sequencing (NGS). There is, however, a computational bottleneck, as existing software systems are not scalable and secure enough to store and process the incoming wave of genomic data from NGS machines. In the BiobankCloud project, we are building a Hadoop-based platform for the secure storage, sharing, and parallel processing of genomic data. We extended Hadoop to include support for multi-tenant studies, reduced storage requirements with erasure coding, and added support for extensible and consistent metadata. On top of Hadoop, we built a scalable scientific workflow engine featuring a proper workflow definition language focusing on simple integration and chaining of existing tools, adaptive scheduling on Apache Yarn, and support for iterative dataflows. Our platform also supports the secure sharing of data across different, distributed Hadoop clusters. The software is easily installed and comes with a user-friendly web interface for running, managing, and accessing data sets behind a secure 2-factor authentication. Initial tests have shown that the engine scales well to dozens of nodes. The entire system is open-source and includes pre-defined workflows for popular tasks in biomedical data analysis, such as variant identification, differential transcriptome analysis using RNA-Seq, and analysis of miRNA-Seq and ChIP-Seq data.

  • 75. Bessueille, Laurence
    et al.
    Bulone, Vincent
    KTH, School of Biotechnology (BIO), Glycoscience.
    A survey of cellulose biosynthesis in higher plants2008In: PLANT BIOTECHNOLOGY, ISSN 1342-4580, Vol. 25, no 3, p. 315-322Article in journal (Refereed)
    Abstract [en]

    Cellulose plays a central role in plant development and its biosynthesis represents one of the most important biochemical processes in plant biology. However, the corresponding molecular mechanisms are not well understood, despite the progress made in the past years in the identification of genes that code for the catalytic subunits of the cellulose synthases and other proteins potentially involved in cellulose formation. A major bottleneck is the high instability of the cellulose synthase complexes and their location in the plasma membrane. Additional efforts are currently being made to unravel the mechanisms of cellulose biosynthesis. Indeed, understanding how cellulose is formed and how its crystallinity is achieved is relevant not only for studying plant development, but also for improving the digestibility of the plant biomass, which is foreseen as an alternative to fossil fuels for the production of energy. This review summarizes the major unanswered questions related to the process of cellulose biosynthesis, and describes the recent progress that has been made in the area through the combination of biochemical approaches and molecular genetics.

  • 76.
    Bi, Ran
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Wood Chemistry and Pulp Technology. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Lignocellulose Degradation by Soil Micro-organisms2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Lignocellulosic biomass is a sustainable resource with abundant reserves. Compared to petroleum ‐ based products, the biomass ‐ derived polymers and chemicals give better environmental profiles. A lot of research interest is focused on understanding the lignocellulose structures.

    Lignin, among the three major wood components, represents most difficulty for microbial degradation because of its complex structure and because cross ‐ linking to hemicellulose makes wood such a compact structure. Nevertheless, wood is naturally degraded by wood ‐ degrading micro ‐ organisms and modified and partly degraded residual of lignin goes into soil. Therefore soil serves as a good environment in which to search for special lignin ‐ degraders. In this thesis, different types of lignin have been used as sole carbon sources to screen for lignin ‐ degrading soil micro ‐ organisms. Eleven aerobic and three anaerobic microbe strains have been isolated and identified as able to grow on lignin. The lignin degradation patterns of selected strains have been studied and these partly include an endwise cleavage of  β‐ O ‐ 4 bonds in lignin and is more complex than simple hydrolytic degradation.

    As lignin exists in wood covalently bonded to hemicellulose, one isolated microbe strain, Phoma herbarum, has also been studied with regards to its ability to degrade covalent lignin polysaccharide networks (LCC). The results show that its culture filtrate can attack lignin ‐ polysaccharide networks in a manner different from that of the commercial enzyme product, Gammanase, possibly by selective cleavage of phenyl glucoside bonds. The effects on LCC of Phoma herbarum also enhance polymer extractability. Hot ‐ water extraction of a culture filtrate of Phoma herbarum ‐ treated fiberized spruce wood material gave an amount of extracted galactoglucomannan more than that given by the Gammanase ‐ treated material and non ‐ enzyme ‐ treated material.

    Over millions of years of natural evolution, micro ‐ organisms on the one hand develop so that they can degrade all wood components to get energy for growth, while plants on the other hand also continuously develop to defend from microbial attack. Compared with lignin and cellulose, hemicelluloses as major components of plant cell walls, are much more easily degraded, but hemicelluloses differ from cellulose in that they are acetylated to different extents. The biological functions of acetylation are not completely understood, but it is suggested is that one function is to decrease the microbial degradability of cell walls. By cultivation of soil micro ‐ organisms using mannans acetylated to deffernent degrees as sole carbon source on agar plates, we were able to see significant trends where the resistance towards microbial degradation of glucomannan and galactomannan increased with increasing degree of acetylation. Possible mechanisms and the technological significance of this are discussed. Tailoring the degree of acetylation of polysaccharide materials might slow down the biodegradation, making it possible to design a material with a degradation rate suited to its application.

    Download full text (pdf)
    Thesis
  • 77.
    Bjervås, Jens
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Simulation of dry matter loss in biomass storage2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Material degradation and a decrease of fuel quality are common phenomena when storing biomass. A magnitude of 7.8% has been reported to degrade over five months when storing spruce wood chips in the winter in Central Europe. This thesis presents a theoretical study of biomass storage. It includes investigations of bio-chemical, chemical and physical processes that occur during storage of chipped woody biomass. These processes lead to degradation caused by micro-activity, chemical oxidation reactions and physical transformation of water. Micro-activity was modeled with Monod kinetics which are Michaelis-Menten type of expressions. The rate expressions were complemented with dependency functions describing the impact of oxygen, moisture and temperature. The woody biomass was divided into three fractions. These fractions represent how hard different components of the wood are to degrade by microorganisms. Chemical oxidation was modeled as a first order rate expression with respect to the active components of the wood. Two different cases have been simulated during the project. Firstly, an isolated system with an initial oxygen concentration of air was considered. This case displayed a temperature increase of approximately 2˚C and a material degradation less than 1%. The second case considered an isolated system with an endless depot of oxygen. This case resulted in degradation losses around 0.45-0.95% in the temperature range between 65-80˚C during approximately 300 days of storage. The temperature increased slowly due to chemical oxidation.

    Download full text (pdf)
    fulltext
  • 78.
    Bjällmark, Anna
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering.
    Larsson, Matilda
    KTH, School of Technology and Health (STH), Medical Engineering.
    Lind, Britta
    KTH, School of Technology and Health (STH), Medical Engineering.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Winter, Reidar
    Westholm, Carl
    Jacobsen, Per
    Velocity tracking - a novel method for quantitative analysis of longitudinal myocardial function2007In: Journal of the American Society of Echocardiography, ISSN 0894-7317, E-ISSN 1097-6795, Vol. 20, no 7, p. 847-856Article in journal (Refereed)
    Abstract [en]

    Doppler tissue imaging is a method for quantitative analysis of longitudinal myocardial velocity. Commercially available ultrasound systems can only present velocity information using a color Dopplerbased overlapping continuous color scale. The analysis is time-consuming and does not allow for simultaneous analysis in different projections. We have developed a new method, velocity tracking, using a stepwise color coding of the regional longitudinal myocardial velocity. The velocity data from 3 apical projections are presented as static and dynamic bull's-eye plots to give a 3-dimensional understanding of the function of the left ventricle. The static bull's-eye plot can display peak systolic velocity, late diastofic tissue velocity, or the sum of peak systolic velocity and early diastolic tissue velocity. Conversely, the dynamic bull's-eye plot displays how the myocardial velocities change over one heart cycle. Velocity tracking allows for a fast, simple, and hituitive visual analysis of the regional longitudinal contraction pattern of the left ventricle with a great potential to identify characteristic pathologic patterns.

  • 79.
    Björk, Sara
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Jönsson, Håkan
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Nano Biotechnology.
    Microfluidics for cell factory and bioprocess development2019In: Current Opinion in Biotechnology, ISSN 0958-1669, E-ISSN 1879-0429, Vol. 55, p. 95-102Article in journal (Refereed)
    Abstract [en]

    Bioindustry is expanding to an increasing variety of food, chemical and pharmaceutical products, each requiring rapid development of a dedicated cell factory and bioprocess. Microfluidic tools are, together with tools from synthetic biology and metabolic modeling, being employed in cell factory and bioprocess development to speed up development and address new products. Recent examples of microfluidics for bioprocess development range from integrated devices for DNA assembly and transformation, to high throughput screening of cell factory libraries, and micron scale bioreactors for process optimization. These improvements act to improve the biotechnological engineering cycle with tools for building, testing and evaluating cell factories and bioprocesses by increasing throughput, parallelization and automation.

  • 80. Björlenius, Berndt
    Avloppsreningsverket-hur fungerar det?2005In: Läkemedel och miljö / [ed] Apoteket AB, Stockholm: Apoteket AB , 2005Chapter in book (Other academic)
  • 81.
    Björlenius, Berndt
    Stockholm Water Co..
    Avloppsverkens förmåga att ta hand om läkemdelsrester och andra farliga ämnen. Rapport 57942008Report (Refereed)
  • 82.
    Björlenius, Berndt
    Stockholm Water Company.
    En jämförelse av olika reningsmetoder för avskiljning av läkemedelsrester: Resultat från Stockholm Vattens projekt 2009In: Den Nordiske / Foredrag, Skanderborg: Dansk Vand- og Spildevandsforening , 2009Conference paper (Refereed)
  • 83.
    Björlenius, Berndt
    Stockholm Water Company.
    Läkemedelsrester i Stockholms vattenmiljö-förekomst, förebyggande åtgärder och rening av avloppsvatten2010Report (Refereed)
  • 84.
    Björlenius, Berndt
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology.
    Pharmaceuticals – improved removal from municipal wastewater and their occurrence in the Baltic Sea2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pharmaceutical residues are found in the environment due to extensive use in human and veterinary medicine. The active pharmaceutical ingredients (APIs) have a potential impact in non-target organisms. Municipal wastewater treatment plants (WWTPs) are not designed to remove APIs.

    In this thesis, two related matters are addressed 1) evaluation of advanced treatment to remove APIs from municipal wastewater and 2) the prevalence and degradation of APIs in the Baltic Sea.

    A stationary pilot plant with nanofiltration (NF) and a mobile pilot plant with activated carbon and ozonation were designed to study the removal of APIs at four WWTPs. By NF, removal reached 90%, but the retentate needed further treatment. A predictive model of the rejection of APIs by NF was developed based on the variables: polarizability, globularity, ratio hydrophobic to polar water accessible surface and charge. The pilot plants with granular and powdered activated carbon (GAC) and (PAC) removed more than 95% of the APIs. Screening of activated carbon products was essential, because of a broad variation in adsorption capacity. Recirculation of PAC or longer contact time, increased the removal of APIs. Ozonation with 5-7 g/m3 ozone resulted in 87-95% removal of APIs. Elevated activity and transcription of biomarkers indicated presence of xenobiotics in regular effluent. Chemical analysis of APIs, together with analysis of biomarkers, were valuable and showed that GAC-filtration and ozonation can be implemented to remove APIs in WWTPs, with decreased biomarker responses.

    Sampling of the Baltic Sea showed presence of APIs in 41 out of 43 locations. A developed grey box model predicted concentration and half-life of carbamazepine in the Baltic Sea to be 1.8 ng/L and 1300 d respectively.

    In conclusion, APIs were removed to 95% by GAC or PAC treatment. The additional treatment resulted in lower biomarker responses than today and some APIs were shown to be widespread in the aquatic environment.

    Download full text (pdf)
    fulltext
  • 85.
    Björling, Erik
    KTH, School of Biotechnology (BIO).
    Databases for antibody-based proteomics2008Doctoral thesis, comprehensive summary (Other scientific)
    Abstract [en]

    Humans are believed to have ~20,500 protein-coding genes andmuch effort has over the last years been put into the characterizationand localization of the encoded proteins in order to understand theirfunctions. One such effort is the Human Proteome Resource (HPR)project, started in Sweden 2003 with the aim to generate specificantibodies to each human protein and to use those antibodies toanalyze the human proteome by screening human tissues and cells.The work reported in this thesis deals with structuring of data fromantibody-based proteomics assays, with focus on the importance ofaggregating and presenting data in a way that is easy to apprehend.The goals were to model and build databases for collecting, searchingand analyzing data coming out of the large-scale HPR project and tomake all collected data publicly available. A public website, theHuman Protein Atlas, was developed giving all end-users in thescientific community access to the HPR database with proteinexpression data. In 2008, the Human Protein Atlas was released in its4th version containing more than 6000 antibodies, covering more than25% of the human proteins. All the collected protein expression datais searchable on the public website. End-users can query for proteinsthat show high expression in one tissue and no expression in anotherand possibly find tissue specific biomarkers. Queries can also beconstructed to find proteins with different expression levels in normalvs. cancer tissues. The proteins found by such a query could identifypotential biomarkers for cancer that could be used as diagnosticmarkers and maybe even be involved in cancer therapy in the future.Validation of antibodies is important in order to get reliable resultsfrom different assays. It has been noted that some antibodies arereliable in certain assays but not in others and therefore anotherpublicly available database, the Antibodypedia, has been createdwhere any antibody producer can submit their binders together withthe validation data in order for end users to purchase the bestantibody for their protein target and their intended assay.

    Download full text (pdf)
    FULLTEXT02
  • 86.
    Björling, Erik
    et al.
    KTH, School of Biotechnology (BIO), Proteomics.
    Lindskog, Cecilia
    Uppsala Univ, Rudbeck Lab.
    Oksvold, Per
    KTH, School of Biotechnology (BIO), Proteomics.
    Linné, Jerker
    Uppsala Univ, Rudbeck Lab.
    Kampf, Caroline
    Uppsala Univ, Rudbeck Lab.
    Hober, Sophia
    KTH, School of Biotechnology (BIO), Proteomics.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO).
    Pontén, Fredrik
    Uppsala Univ, Rudbeck Lab.
    A web-based tool for in silico biomarker discovery based on tissue-specific protein profiles in normal and cancer tissues2008In: Molecular & Cellular Proteomics, ISSN 1535-9476, Vol. 7, no 5, p. 825-844Article in journal (Refereed)
    Abstract [en]

    Here we report the development of a publicly available Web-based analysis tool for exploring proteins expressed in a tissue- or cancer-specific manner. The search queries are based on the human tissue profiles in normal and cancer cells in the Human Protein Atlas portal and rely on the individual annotation performed by pathologists of images representing immunohistochemically stained tissue sections. Approximately 1.8 million images representing more than 3000 antibodies directed toward human proteins were used in the study. The search tool allows for the systematic exploration of the protein atlas to discover potential protein biomarkers. Such biomarkers include tissue-specific markers, cell type-specific markers, tumor type-specific markers, markers of malignancy, and prognostic or predictive markers of cancers. Here we show examples of database queries to generate sets of candidate biomarker proteins for several of these different categories. Expression profiles of candidate proteins can then subsequently be validated by examination of the underlying high resolution images. The present study shows examples of search strategies revealing several potential protein biomarkers, including proteins specifically expressed in normal cells and in cancer cells from specified tumor types. The lists of candidate proteins can be used as a starting point for further validation in larger patient cohorts using both immunological approaches and technologies utilizing more classical proteomics tools.

  • 87.
    Björling, Erik
    et al.
    KTH, School of Biotechnology (BIO), Proteomics.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    Antibodypedia: a portal for sharing antibody and antigen validation data2008In: Molecular & Cellular Proteomics, ISSN 1535-9476, Vol. 7, no 10, p. 2028-2037Article in journal (Refereed)
    Abstract [en]

    Antibodies are useful tools to characterize the components of the human proteome and to validate potential protein biomarkers discovered through various clinical proteomics efforts. The lack of validation results across various applications for most antibodies often makes it necessary to perform cumbersome investigations to ensure specificity of a particular antibody in a certain application. A need therefore exists for a standardized system for sharing validation data about publicly available antibodies and to allow antibody providers as well as users to contribute and edit experimental evidence data, including data also on the antigen. Here we describe a new publicly available portal called Antibodypedia, which has been developed to allow sharing of information regarding validation of antibodies in which providers can submit their own validation results and reliability scores. We report standardized validation criteria and submission rules for applications such as Western blots, protein arrays, immunohistochemistry, and immunofluorescence. The contributor is expected to provide experimental evidence and a validation score for each antibody, and the users can subsequently provide feedback and comments on the use of the antibody. The database thus provides a virtual resource of publicly available antibodies toward human proteins with accompanying experimental evidence supporting an individual validation score for each antibody in an application-specific manner.

  • 88. Björn, N.
    et al.
    Sigurgeirsson, B.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. School of Engineering and Natural Sciences, University of Iceland, Reykjavík, Iceland.
    Svedberg, A.
    Pradhananga, Sailendra
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brandén, E.
    Koyi, H.
    Lewensohn, R.
    de Petris, L.
    Apellániz-Ruiz, M.
    Rodríguez-Antona, C.
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology.
    Gréen, H.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Clinical Pharmacology, Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia2019In: Pharmacogenomics JournalArticle in journal (Refereed)
    Abstract [en]

    Chemotherapy-induced myelosuppression, including thrombocytopenia, is a recurrent problem during cancer treatments that may require dose alterations or cessations that could affect the antitumor effect of the treatment. To identify genetic markers associated with treatment-induced thrombocytopenia, we whole-exome sequenced 215 non-small cell lung cancer patients homogeneously treated with gemcitabine/carboplatin. The decrease in platelets (defined as nadir/baseline) was used to assess treatment-induced thrombocytopenia. Association between germline genetic variants and thrombocytopenia was analyzed at single-nucleotide variant (SNV) (based on the optimal false discovery rate, the severity of predicted consequence, and effect), gene, and pathway levels. These analyses identified 130 SNVs/INDELs and 25 genes associated with thrombocytopenia (P-value < 0.002). Twenty-three SNVs were validated in an independent genome-wide association study (GWAS). The top associations include rs34491125 in JMJD1C (P-value = 9.07 × 10−5), the validated variants rs10491684 in DOCK8 (P-value = 1.95 × 10−4), rs6118 in SERPINA5 (P-value = 5.83 × 10−4), and rs5877 in SERPINC1 (P-value = 1.07 × 10−3), and the genes CAPZA2 (P-value = 4.03 × 10−4) and SERPINC1 (P-value = 1.55 × 10−3). The SNVs in the top-scoring pathway “Factors involved in megakaryocyte development and platelet production” (P-value = 3.34 × 10−4) were used to construct weighted genetic risk score (wGRS) and logistic regression models that predict thrombocytopenia. The wGRS predict which patients are at high or low toxicity risk levels, for CTCAE (odds ratio (OR) = 22.35, P-value = 1.55 × 10−8), and decrease (OR = 66.82, P-value = 5.92 × 10−9). The logistic regression models predict CTCAE grades 3–4 (receiver operator characteristics (ROC) area under the curve (AUC) = 0.79), and large decrease (ROC AUC = 0.86). We identified and validated genetic variations within hematopoiesis-related pathways that provide a solid foundation for future studies using genetic markers for predicting chemotherapy-induced thrombocytopenia and personalizing treatments.

  • 89.
    Bollok, Monika
    et al.
    KTH, School of Biotechnology (BIO).
    Henriksson, Hongbin
    KTH, School of Biotechnology (BIO).
    Kallas, Åsa
    KTH, School of Biotechnology (BIO).
    Jahic, Mehmedalija
    KTH, School of Biotechnology (BIO).
    Teeri, Tuula T.
    KTH, School of Biotechnology (BIO).
    Enfors, Sven-Olof
    KTH, School of Biotechnology (BIO).
    Production of poplar xyloglucan endotransglycosylase using the methylotrophic yeast Pichia pastoris2005In: Applied Biochemistry and Biotechnology, ISSN 0273-2289, Vol. 126, p. 61-77Article in journal (Refereed)
    Abstract [en]

    The gene XET16A encoding the enzyme xyloglucan endotransglycosylase (XET) from hybrid aspen (Populus tremula x tremuloides Mich) was transformed into Pichia pastoris GS115 and the enzyme was secreted to the medium. The influence of process conditions on the XET production, activity, and proteolytic degradation were examined. Inactivation of XET occurred in the foam, but could be decreased significantly by using an efficient antifoam. Rich medium (yeast extract plus peptone) was needed for product accumulation, but not for growth. The proteolytic degradation of the enzyme in the medium was substantially decreased by also adding yeast extract and peptone to the glycerol medium before induction with methanol. Decreasing the fermentation pH from 5.0 to 4.0 further reduced the proteolysis. The specific activity was further improved by production at 15 degrees C instead of 22 degrees C. In this way a XET production of 54 mg/L active enzyme could be achieved in the process with a specific activity of 18 Unit/mg protein after a downstream process including centrifugation, micro- and ultrafiltration, and ion exchange chromatography.

  • 90.
    Bondesson, Laban
    KTH, School of Biotechnology (BIO).
    Microscopic views of drug solubility2006Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    The development of computational models for predicting drug solubility has increased drastically during the last decades. Nevertheless these models still have diffculties to estimate the aqueous solubility as accurate as desired. In this thesis di erent aspects that are known to have a large impact on the aqueous solubility of a molecule have been studied in detail using various theoretical methods with intension to provide microscopic view on drug solubility. The rst aspect studied is the hydrogen bond energies. Eight drug molecules have been calculated using density functional theory and the validity of additive model that has often been used in solubility models is examined. The impact of hydrogen bonds in Infrared and Raman spectra of three commonly used drug molecules has also been demonstrated. The calculated spectra are found to be in good agreement with the experimental data. Another aspect that is important in solubility models is the volume that a molecule occupies when it is dissolved in water. The volume term and its impact on the solvation energy has therefore also been calculated using three di erent methods. It was shown that the calculated volume di ered signi cantly dependent on which method that had been used, especially for larger molecules.

    Most of the solubility models assume the solute molecule to be in the bulk of the solvent. The molecular behavior at the water/gas interface has been investigated to see how it di ers from bulk. It was seen that the concentration close to the interface was almost three times higher than in the bulk. The increase in concentration close to the surface depends on the larger gap between the interface energy and the gas phase energy than between the bulk energy and the gas phase energy.

    Download full text (pdf)
    FULLTEXT01
  • 91.
    Boström, Karin
    KTH, School of Chemical Science and Engineering (CHE).
    Tillförsel av jäst till SSF i industriell skala2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Användning av etanol som drivmedel och en efterfråga på gröna kemikalier driver utvecklingen av bioetanol framåt. Etanolpiloten, SEKAB, i Örnsköldsvik är en av få anläggningar i världen med kompetens och kunskap att producera bioetanol baserat på lignocellulosa. På senare tid har det dock uppstått problem vid etanolframställningen på grund av att en del jästodlingar blivit kontaminerade av bakterier vilket lett till ett sämre utbyte av biomassa och etanol. Det huvudsakliga syftet med detta examensarbete var att ta reda på orsaken till dessa misslyckade jästodlingar.

     

    Examensarbetet delades upp i två huvudsakliga problemområden. Förutom orsaken till de kontaminerade odlingarna studerades även funktionen hos en ny jäststam, Saccaromyces cerevisiae torrjäst, i syfte att undersöka om det finns bättre alternativ till den jäststam som används i etanopiloten i nuläget.

     

    En specialstudie av rengöringen av odlingstankar och ledningar i etanolpiloten utfördes i syfte att kartlägga var i utrustningen som infektionsrisken är som störst. Försöken påvisade att det huvudsakliga problemet kan lokaliseras till den största jästodlingstanken. Där befinner sig jästen under en längre tid i en miljö som är gynnsam för tillväxt av både jäst och bakterier. En annan orsak till de infekterade odlingarna är att rengöringen av utrustningen inte har skett på rätt sätt, samt att temperaturen hos tvättkemikalierna har varit för låg. En viktig slutsats är därför att bättre rutiner vid hanteringen av jästodlingsutrustningen samt att större noggrannhet i samband med rengöringen bör eftersträvas.

     

    En bidragande orsak till de infekterade odlingarna kan också härröra från uppodlingsprocessen av ympjäst som i dagens läge sker på laboratorium. Genom att använda en stam av S. cerevisiae som köps in i frystorkad form kan flera steg i jästodlingsprocessen elimineras. Det både förkortar odlingsprocessen och minskar infektionsrisken. S. cerevisiae torrjäst undersöktes både i laboratorium och i etanolpiloten. Tre olika odlingsskalor användes, skakflaskor (250 ml), labfermentorer (3 l) och pilotskala (10m3). Försöken påvisar höga utbyten av både biomassa och etanol. För att kunna hålla nere produktionskostnaderna för etanolframställningen är det viktigt att jästen som används går att odla på det hydrolysat som produceras vid förbehandlingen av råvaran. Försök i pilotskala visar på lovande resultat vid uppodling av S. cerevisiae torrjäst när hela 70 % av sockerkällan kommer från hydrolysat. Ytterligare utvärdering och optimering av odlingsprocessen samt en ekonomisk jämförelse mellan de tillgängliga jäststammarna krävs dock innan S. cerevisiae torrjäst eventuellt kan användas kontinuerligt i pilotskala. 

    Download full text (pdf)
    fulltext
  • 92. Bourbeillon, Julie
    et al.
    Orchard, Sandra
    Benhar, Itai
    Borrebaeck, Carl
    de Daruvar, Antoine
    Duebel, Stefan
    Frank, Ronald
    Gibson, Frank
    Gloriam, David
    Haslam, Niall
    Hiltker, Tara
    Humphrey-Smith, Ian
    Hust, Michael
    Juncker, David
    Koegl, Manfred
    Konthur, Zoltan
    Korn, Bernhard
    Krobitsch, Sylvia
    Muyldermans, Serge
    Nygren, Per-Åke
    KTH, School of Biotechnology (BIO), Molecular Biotechnology. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Palcy, Sandrine
    Polic, Bojan
    Rodriguez, Henry
    Sawyer, Alan
    Schlapshy, Martin
    Snyder, Michael
    Stoevesandt, Oda
    Taussig, Michael J.
    Templin, Markus
    Uhlén, Matthias
    KTH, School of Biotechnology (BIO), Proteomics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    van der Maarel, Silvere
    Wingren, Christer
    Hermjakob, Henning
    Sherman, David
    Minimum information about a protein affinity reagent (MIAPAR)2010In: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 28, no 7, p. 650-653Article in journal (Other academic)
  • 93. Bracher, Jasmine M.
    et al.
    Martinez-Rodriguez, Oscar A.
    Dekker, Wijb JC
    Verhoeven, Maarten D.
    van Maris, Antonius
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology.
    Pronk, Jack T.
    Reassessment of requirements for anaerobic xylose fermentation by engineered, non-evolved Saccharomyces cerevisiae strains2019In: FEMS yeast research (Print), ISSN 1567-1356, E-ISSN 1567-1364, Vol. 19, no 1, article id foy104Article in journal (Refereed)
    Abstract [en]

    Expression of a heterologous xylose isomerase, deletion of the GRE3 aldose-reductase gene and overexpression of genes encoding xylulokinase (XKS1) and non-oxidative pentose-phosphate-pathway enzymes (RKI1, RPE1, TAL1, TKL1) enables aerobic growth of Saccharomyces cerevisiae on d-xylose. However, literature reports differ on whether anaerobic growth on d-xylose requires additional mutations. Here, CRISPR-Cas9-assisted reconstruction and physiological analysis confirmed an early report that this basic set of genetic modifications suffices to enable anaerobic growth on d-xylose in the CEN.PK genetic background. Strains that additionally carried overexpression cassettes for the transaldolase and transketolase paralogs NQM1 and TKL2 only exhibited anaerobic growth on d-xylose after a 7-10 day lag phase. This extended lag phase was eliminated by increasing inoculum concentrations from 0.02 to 0.2 g biomass L-1. Alternatively, a long lag phase could be prevented by sparging low-inoculum-density bioreactor cultures with a CO2/N-2-mixture, thus mimicking initial CO2 concentrations in high-inoculum-density, nitrogen-sparged cultures, or by using l-aspartate instead of ammonium as nitrogen source. This study resolves apparent contradictions in the literature on the genetic interventions required for anaerobic growth of CEN.PK-derived strains on d-xylose. Additionally, it indicates the potential relevance of CO2 availability and anaplerotic carboxylation reactions for anaerobic growth of engineered S. cerevisiae strains on d-xylose.

  • 94.
    Branneby, Cecilia
    et al.
    Cambrex Karlskoga AB.
    Svedendahl, Maria
    KTH, School of Biotechnology (BIO), Biochemistry.
    Hult, Karl
    KTH, School of Biotechnology (BIO), Biochemistry.
    Berglund, Per
    KTH, School of Biotechnology (BIO), Biochemistry.
    Lipase-Catalyzed Aldol and Michael-Type Reactions2006Conference paper (Refereed)
  • 95.
    Branneby, Cecilia
    et al.
    Cambrex Karlskoga AB.
    Svedendahl, Maria
    KTH, School of Biotechnology (BIO), Biochemistry.
    Hult, Karl
    KTH, School of Biotechnology (BIO), Biochemistry.
    Berglund, Per
    KTH, School of Biotechnology (BIO), Biochemistry.
    Lipase-Catalyzed Aldol and Michael-Type Reactions2005In: Book of abstracts, 2005Conference paper (Refereed)
  • 96.
    Brechmann, Nils Arnold
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology. AdBIOPRO, VINNOVA Competence Centre for Advanced BioProduction by Continuous Processing, Stockholm, Sweden.
    Eriksson, Per-Olov
    Eriksson, Kristofer
    Oscarsson, Sven
    Buijs, Jos
    Shokri, Atefeh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology. AdBIOPRO, VINNOVA Competence Centre for Advanced BioProduction by Continuous Processing, Stockholm, Sweden.
    Hjälm, Göran
    Chotteau, Véronique
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology. AdBIOPRO, VINNOVA Competence Centre for Advanced BioProduction by Continuous Processing, Stockholm, Sweden.
    Pilot-scale process for magnetic bead purification of antibodies directly from non-clarified CHO cell culture2019In: Biotechnology progress (Print), ISSN 8756-7938, E-ISSN 1520-6033Article in journal (Refereed)
    Abstract [en]

    High capacity magnetic protein A agarose beads, LOABeads PrtA, were used in the development

    of a new process for affinity purification of monoclonal antibodies (mAbs) from non-clarified

    CHO cell broth using a pilot-scale magnetic separator. The LOABeads had a maximum binding

    capacity of 65 mg/mL and an adsorption capacity of 25–42 mg IgG/mL bead in suspension for an

    IgG concentration of 1 to 8 g/L. Pilot-scale separation was initially tested in a mAb capture step

    from 26 L clarified harvest. Small-scale experiments showed that similar mAb adsorptions were

    obtained in cell broth containing 40 Å~ 106 cells/mL as in clarified supernatant. Two pilot-scale

    purification runs were then performed on non-clarified cell broth from fed-batch runs of 16 L,

    where a rapid mAb adsorption ≥96.6% was observed after 1 h. This process using 1 L of magnetic beads had an overall mAb yield of 86% and 16 times concentration factor. After this single protein

    A capture step, the mAb purity was similar to the one obtained by column chromatography, while

    the host cell protein content was very low, <10 ppm. Our results showed that this magnetic bead

    mAb purification process, using a dedicated pilot-scale separation device, was a highly efficient

    single step, which directly connected the culture to the downstream process without cell clarification.

    Purification of mAb directly from non-clarified cell broth without cell separation can provide

    significant savings in terms of resources, operation time, and equipment, compared to legacy procedure of cell separation followed by column chromatography step.

    Download full text (pdf)
    fulltext
  • 97. Brennan, Donal J.
    et al.
    Laursen, Henriette
    O'Connor, Darran P.
    Borgquist, Signe
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    Gallagher, William M.
    Ponten, Fredrik
    Millikan, Robert C.
    Ryden, Lisa
    Jirström, Karin
    Tumor-specific HMG-CoA reductase expression in primary premenopausal breast cancer predicts response to tamoxifen2011In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 13, no 1, p. R12-Article in journal (Refereed)
    Abstract [en]

    Introduction: We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. Methods: HMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response. Results: HMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as patients with ER-positive or HMG-CoAR-positive tumors (P = 0.035). Stratification according to ER and HMG-CoAR status demonstrated that ER-positive/HMG-CoAR-positive tumors had an improved RFS compared with ER-positive/HMG-CoAR-negative tumors in the treatment arm (P = 0.033); this effect was lost in the control arm (P = 0.138), however, suggesting that HMG-CoAR predicts tamoxifen response. Conclusions: HMG CoAR expression is a predictor of response to tamoxifen in both ER-positive and ER-negative disease. Premenopausal patients with tumors that express ER or HMG-CoAR respond to adjuvant tamoxifen.

  • 98.
    Brumer, Harry
    et al.
    KTH, Superseded Departments, Biotechnology.
    Zhou, Qi
    KTH, Superseded Departments, Biotechnology.
    Baumann, Martin J.
    KTH, Superseded Departments, Biotechnology.
    Carlsson, Kjell
    KTH, Superseded Departments, Biotechnology.
    Teeri, Tuula
    KTH, Superseded Departments, Biotechnology.
    Activation of crystalline cellulose surfaces though the chemoenzymatic modification of xyloglucan2004In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 126, no 18, p. 5715-1721Article in journal (Refereed)
    Abstract [en]

    Cellulose constitutes an important raw material for many industries. However, the superb load-bearing properties of cellulose are accompanied by poor chemical reactivity. The hydroxyl groups on cellulose surfaces can be reacted but usually not without loss of fiber integrity and strength. Here, we describe a novel chemoenzymatic approach for the efficient incorporation of chemical functionality onto cellulose surfaces. The modification is brought about by using a transglycosylating enzyme, xyloglucan endotranglycosylase, to join chemically modified xyloglucan oligosaccharides to xyloglucan, which has a naturally high affinity to cellulose. Binding of the chemically modified hemicellulose molecules can thus be used to attach a wide variety of chemical moieties without disruption of the individual fiber or fiber matrix.

  • 99.
    Bäcklund, Emma
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Growth rate control of periplasmic product retention in Escherichia coli2008Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    The recombinant product is secreted to the periplasm in many processes where E. coli is used as host. One drawback with secretion is the undesired leakage of the periplasmic products to the medium.

    The aim of this work was to find strategies to influence the periplasmic retention of recombinant products. We have focused on the role of the specific growth rate, a parameter that is usually controlled in industrial bioprocesses. The hypothesis was that the stability of the outer membrane in E. coli is gained from a certain combination of specific phospholipids and fatty acids on one side and the amount and specificity of the outer membrane proteins on the other side, and that the specific growth rate influences this structure and therefore can be used to control the periplasmic retention.

    We found that is possible to control the periplasmic retention by the growth rate. The leakage of the product increased as the growth rate increased. It was however also found that a higher growth rate resulted in increased productivity. This resulted in equal amounts of product inside the cells regardless of growth rate.

    We also showed that the growth rate influenced the outer membrane composition with respect to OmpF and LamB while OmpA was largely unaffected. The total amount of outer membrane proteins decreased as the growth rate increased. There were further reductions in outer membrane protein accumulation when the recombinant product was secreted to the periplasm. The lowered amount of outer membrane proteins may have contributed to the reduced ability for the cell to retain the product in the periplasm.

    The traditional way to control the growth rate is through a feed of substrate in a fed-batch process. In this work we used strains with a set of mutations in the phosphotransferase system (PTS) with a reduced uptake rate of glucose to investigate if these strains could be used for growth rate control in batch cultivations without the use of fed-batch control equipment. The hypothesis was that the lowering of the growth rate on cell level would result in the establishment of fed-batch similar conditions.

    This study showed that it is possible to control the growth rate in batch cultivations by using mutant strains with a decreased level of substrate uptake rate. The mutants also produced equivalent amounts of acetic acid as the wild type did in fed-batch cultivation with the same growth rate. The oxygen consumption rates were also comparable. A higher cell density was reached with one of the mutants than with the wild type in batch cultivations. It is possible to control the growth rate by the use of the mutants in small-scale batch cultivations without fed-batch control equipment.

    Download full text (pdf)
    FULLTEXT01
  • 100.
    Bäcklund, Emma
    et al.
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Markland, Katrin
    KTH, School of Biotechnology (BIO).
    Larsson, Gen
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Fedbatch design for periplasmic product retention in Escherichia coli2008In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 135, no 4, p. 358-365Article in journal (Refereed)
    Abstract [en]

    The feed profile of glucose during fedbatch cultivation could be used to influence the retention of the periplasmic product ZZ-cutinase. An increased feed rate led to a higher production rate but also to an increased specific leakage, which reduced the periplasmic retention. Three growth rates: 0.3, 0.2 and 0.1 h-1 where studied and resulted in 20, 9 and 6%, respectively, of the total ZZ-cutinase accumulating in the medium. It was also shown that leakage during fedbatch production of a Fab fragment was also influenced by the feed rate in a similar manner to ZZ-cutinase. If intracellular product accumulation is desired the advantage of a high productivity, resulting from a high substrate feed rate, is diminished because of a reduced product retention. Biochemical analysis revealed that the growth rate, resulting from a glucose limited feed, influenced the outer membrane protein compositions with respect to OmpF and LamB, whilst OmpA was largely unaffected. As the feed rate increased the amount of total outer membrane protein decreased. When ZZ-cutinase was produced there were further reductions in outer membrane protein accumulation, by 82, 100 and 22% for OmpF, LamB and OmpA, respectively, and the total reduction was almost 60% with a high product formation rate. We suggest that the reduced titre of the outer membrane proteins, OmpF and LamB, may have contributed to a reduced ability for the cell to retain recombinant protein secreted to the periplasm.

1234567 51 - 100 of 796
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • 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