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  • 1. Aaldering, L. J.
    et al.
    Poongavanam, V.
    Langkjær, N.
    Natarajan Arul, Murugan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Jørgensen, P. T.
    Wengel, J.
    Veedu, R. N.
    Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule2017In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 18, no 8, p. 755-763Article in journal (Refereed)
    Abstract [en]

    The thrombin-binding aptamer (TBA), which shows anticoagulant properties, is one of the most studied G-quadruplex-forming aptamers. In this study, we investigated the impact of different chemical modifications such as a three-carbon spacer (spacer-C3), unlocked nucleic acid (UNA) and 3′-amino-modified UNA (amino-UNA) on the structural dynamics and stability of TBA. All three modifications were incorporated at three different loop positions (T3, T7, T12) of the TBA G-quadruplex structure to result in a series of TBA variants and their stability was studied by thermal denaturation; folding was studied by circular dichroism spectroscopy and thrombin clotting time. The results showed that spacer-C3 introduction at the T7 loop position (TBA-SP7) significantly improved stability and thrombin clotting time while maintaining a similar binding affinity as TBA to thrombin. Detailed molecular modelling experiments provided novel insights into the experimental observations, further supporting the efficacy of TBA-SP7. The results of this study could provide valuable information for future designs of TBA analogues with superior thrombin inhibition properties. 

  • 2. Abahazi, Emese
    et al.
    Satorhelyi, Peter
    Erdelyi, Balazs
    Vertessy, Beata G.
    Land, Henrik
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    Paizs, Csaba
    Berglund, Per
    KTH, School of Biotechnology (BIO), Industrial Biotechnology.
    Poppe, Laszlo
    Covalently immobilized Trp60Cys mutant of omega‰-transaminase from Chromobacterium violaceum for kinetic resolution of racemic amines in batch and continuous-flow modes2018In: Biochemical engineering journal, ISSN 1369-703X, E-ISSN 1873-295X, Vol. 132, p. 270-278Article in journal (Refereed)
    Abstract [en]

    Covalent immobilization of an engineered omega-transaminase mutant Trp60Cys from Chromobacterium violaceum (CvTAW60C) was performed on bisepoxide-activated aminoalkyl resins. Activity of the various CvTAW60C preparations was evaluated in kinetic resolution of four racemic amines (rac-1a–d). The most active EA-G-CvTAW60C preparation (CvTAW60C attached to polymeric resin with ethylamine function activated with glycerol diglycidyl ether—EA-G) could perform the kinetic resolution of racemic 4-phenylbutan-2-amine (rac-1a) over 49% conversion up to 19 consecutive reaction cycles or in media containing up to 50% v/v DMSO as cosolvent in batch mode reactions. The immobilization process of CvTAW60C onto the EA-G resin filled in stainless steel bioreactors was also tested in flow-through mode. Kinetic resolution of three racemic amines containing aromatic moieties (rac-1a-c) was performed in continuous-flow mode resulting in easy-to-separate mixture of the corresponding ketone (2a–c) and the non-converted (R)-amine in high enantiopurity (ee(R)-1a-c ≥ 96%).

  • 3.
    Abdel Rehim, Abobakr
    KTH, School of Biotechnology (BIO).
    Elucidating CD3-gamma-epsilon and T-cell receptor-beta ectodomain interaction2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 4. Abdo, A. A.
    et al.
    Ackermann, M.
    Ajello, M.
    Baldini, L.
    Ballet, J.
    Barbiellini, G.
    Bastieri, D.
    Bechtol, K.
    Bellazzini, R.
    Berenji, B.
    Blandford, R. D.
    Bloom, E. D.
    Bonamente, E.
    Borgland, A. W.
    Bouvier, A.
    Bregeon, J.
    Brez, A.
    Brigida, M.
    Bruel, P.
    Burnett, T. H.
    Buson, S.
    Caliandro, G. A.
    Cameron, R. A.
    Caraveo, P. A.
    Carrigan, S.
    Casandjian, J. M.
    Cecchi, C.
    Celik, Oe.
    Chekhtman, A.
    Cheung, C. C.
    Chiang, J.
    Ciprini, S.
    Claus, R.
    Cohen-Tanugi, J.
    Conrad, J.
    Cutini, S.
    Dermer, C. D.
    de Angelis, A.
    de Palma, F.
    Digel, S. W.
    do Couto e Silva, E.
    Drell, P. S.
    Dubois, R.
    Dumora, D.
    Edmonds, Y.
    Farnier, C.
    Favuzzi, C.
    Fegan, S. J.
    Focke, W. B.
    Fortin, P.
    Frailis, M.
    Fukazawa, Y.
    Fusco, P.
    Gargano, F.
    Gasparrini, D.
    Gehrels, N.
    Germani, S.
    Giglietto, N.
    Giordano, F.
    Glanzman, T.
    Godfrey, G.
    Grove, J. E.
    Guillemot, L.
    Guiriec, S.
    Gustafsson, M.
    Hadasch, D.
    Harding, A. K.
    Horan, D.
    Hughes, R. E.
    Johnson, A. S.
    Johnson, W. N.
    Kamae, T.
    Katagiri, H.
    Kataoka, J.
    Kawai, N.
    Kerr, M.
    Knoedlseder, J.
    Kuss, M.
    Lande, J.
    Latronico, L.
    Garde, M. Llena
    Longo, F.
    Loparco, F.
    Lott, B.
    Lovellette, M. N.
    Lubrano, P.
    Makeev, A.
    Mazziotta, M. N.
    McEnery, J. E.
    Meurer, C.
    Michelson, P. F.
    Mitthumsiri, W.
    Mizuno, T.
    Monte, C.
    Monzani, M. E.
    Morselli, A.
    Moskalenko, I. V.
    Murgia, S.
    Nolan, P. L.
    Norris, J. P.
    Nuss, E.
    Ohsugi, T.
    Omodei, N.
    Orlando, E.
    Ormes, J. F.
    Paneque, D.
    Panetta, J. H.
    Parent, D.
    Pelassa, V.
    Pepe, M.
    Pesce-Rollins, M.
    Piron, F.
    Raino, S.
    Rando, R.
    Reimer, A.
    Reimer, O.
    Reposeur, T.
    Rodriguez, A. Y.
    Roth, M.
    Sadrozinski, H. F. -W
    Sander, A.
    Parkinson, P. M. Saz
    Scargle, J. D.
    Sellerholm, A.
    Sgro, C.
    Siskind, E. J.
    Smith, P. D.
    Spandre, G.
    Spinelli, P.
    Starck, J. -L
    Strickman, M. S.
    Suson, D. J.
    Takahashi, H.
    Tanaka, T.
    Thayer, J. B.
    Thayer, J. G.
    Torres, D. F.
    Uchiyama, Y.
    Usher, T. L.
    Vasileiou, V.
    Vilchez, N.
    Vitale, V.
    Waite, A. P.
    Wang, P.
    Winer, B. L.
    Wood, K. S.
    Ylinen, Tomi
    KTH, School of Engineering Sciences (SCI), Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Zaharijas, G.
    Ziegler, M.
    Constraints on cosmological dark matter annihilation from the Fermi-LAT isotropic diffuse gamma-ray measurement2010In: Journal of Cosmology and Astroparticle Physics, E-ISSN 1475-7516, Vol. 2010, no 04Article in journal (Refereed)
    Abstract [en]

    The first published Fermi large area telescope (Fermi-LAT) measurement of the isotropic diffuse gamma-ray emission is in good agreement with a single power law, and is not showing any signature of a dominant contribution from dark matter sources in the energy range from 20 to 100 GeV. We use the absolute size and spectral shape of this measured flux to derive cross section limits on three types of generic dark matter candidates: annihilating into quarks, charged leptons and monochromatic photons. Predicted gamma-ray fluxes from annihilating dark matter are strongly affected by the underlying distribution of dark matter, and by using different available results of matter structure formation we assess these uncertainties. We also quantify how the dark matter constraints depend on the assumed conventional backgrounds and on the Universe's transparency to high-energy gamma-rays. In reasonable background and dark matter structure scenarios (but not in all scenarios we consider) it is possible to exclude models proposed to explain the excess of electrons and positrons measured by the Fermi-LAT and PAMELA experiments. Derived limits also start to probe cross sections expected from thermally produced relics (e. g. in minimal supersymmetry models) annihilating predominantly into quarks. For the monochromatic gamma-ray signature, the current measurement constrains only dark matter scenarios with very strong signals.

  • 5.
    Abouzayed, Ayman
    et al.
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Tano, Hanna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Nagy, Abel
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Rinne, Sara S.
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Wadeea, Fadya
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
    Kumar, Sharmishtaa
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Westerlund, Kristina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Tolmachev, Vladimir
    Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden..
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH Royal Inst Technol, AlbaNova Univ Ctr, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden..
    Orlova, Anna
    Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Centrum Oncotheranost, Tomsk 634050, Russia.;Uppsala Univ, Sci Life Lab, S-75105 Uppsala, Sweden..
    Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer2020In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 12, no 10, article id 977Article in journal (Refereed)
    Abstract [en]

    The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated in vitro and in vivo. The labelled conjugate was stable in PBS and retained specificity and its antagonistic function against GRPR. The half-maximal inhibitory concentration (IC50) of In-nat-DOTA-ABD-RM26 in the presence of human serum albumin was 49 +/- 5 nM. [In-111]In-DOTA-ABD-RM26 had a significantly longer residence time in blood and in tumors (without a significant decrease of up to 144 h pi) than the parental RM26 peptide. We conclude that the ABD-RM26 conjugate can be used for GRPR-targeted therapy and delivery of cytotoxic drugs. However, the undesirable elevated activity uptake in kidneys abolishes its use for radionuclide therapy. This proof-of-principle study justified further optimization of the molecular design of the ABD-RM26 conjugate.

  • 6.
    Abrahamsson, Erik
    KTH, School of Biotechnology (BIO).
    Changing or improving the enantioselectivity of ω-transaminase towards (R)-amines, utilizing a semi-rational design approach2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis gives a brief insight on how protein engineering is made with ω-Transaminases - enzymes that are used to create chiral amines which are included in many pharmaceuticals, fine chemicals and agrochemicals - in order to find ω-Transaminase variants that have potential for scale up in industrial processes.

    Several ways to produce (S)-amines with ω-Transaminases exist today as most characterized ω-Transaminases are (S)-selective. The (R)-selective ω-Transaminases are in the other hand rare and in 2003, only 1 (R)-selective ω-Transaminases was known. In 2012, the group of Svedendahl Humble et al. to change the enantioselectivity for the substrate 2-aminotetralin from E = 3.9 (S) to E = 63 (R) by introducing two poiny mutations (F88A/A231F) in the active site of Chromobacterium violaceum ω-Transaminase.

    By using the same variant (F88A/A231F) as a starting template, two new residues in the active site were targeted for site directed mutagenesis that hopefully would give variatns with increased E-caalue for (R)-2-aminotetralin or with changed enantiopreference, frpm (S) to (R), for other stubstrates.

    This report covers most of the steps, starting from the rational design of the active site and ends up with screening and kinetics of the possible hits using one template substrate, 1-aminotetralin.

  • 7. Abrahamsson, T. R.
    et al.
    Jakobsson, H. E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björkstén, B.
    Engstrand, Lars
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, M. C.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 8. Abrahamsson, Thomas R.
    et al.
    Jakobsson, Hedvig E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björksten, Bengt
    Engstrand, Lars
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, Maria C.
    Gut microbiota diversity and atopic disease: Does breast-feeding play a role? Reply2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, no 1, p. 248-249Article in journal (Other academic)
  • 9. Abrahamsson, Thomas R.
    et al.
    Jakobsson, Hedvig E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björkstén, Bengt
    Engstrand, Lars
    Jenmalm, Maria C.
    Low diversity of the gut microbiota in infants with atopic eczema2012In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, no 2, p. 434-U244Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. OBJECTIVE: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. METHODS: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). RESULTS: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P= .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P= .02 and P= .01) and the phylum Proteobacteria at 12 months of age (P= .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R edgeR test: P= .008, q= 0.02). CONCLUSION: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.

  • 10.
    Abramczuk, Monika
    KTH, School of Biotechnology (BIO).
    Isolation and characterization of the first heart field progenitor cells2011Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 11. Acero Sanchez, Josep Ll.
    et al.
    Joda, Hamdi
    Henry, Olivier Y. F.
    Solnestam, Beata W.
    Kvastad, Linda
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sahlén, Pelin
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Laddach, Nadja
    Ramakrishnan, Dheeraj
    Riley, Ian
    Schwind, Carmen
    Latta, Daniel
    O'Sullivan, Ciara K.
    Electrochemical Genetic Profiling of Single Cancer Cells2017In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 89, no 6, p. 3378-3385Article in journal (Refereed)
    Abstract [en]

    Recent understandings in the development and spread of cancer have led to the realization of novel single cell analysis platforms focused on circulating tumor cells (CTCs). A simple, rapid, and inexpensive analytical platform capable of providing genetic information on these rare cells is highly desirable to support clinicians and researchers alike to either support the selection or adjustment of therapy or provide fundamental insights into cell function and cancer progression mechanisms. We report on the genetic profiling of single cancer cells, exploiting a combination of multiplex ligation-dependent probe amplification (MLPA) and electrochemical detection. Cells were isolated using laser capture and lysed, and the mRNA was extracted and transcribed into DNA. Seven markers were amplified by MLPA, which allows for the simultaneous amplification of multiple targets with a single primer pair, using MLPA probes containing unique barcode sequences. Capture probes complementary to each of these barcode sequences were immobilized on a printed circuit board (PCB) manufactured electrode array and exposed to single-stranded MLPA products and subsequently to a single stranded DNA reporter probe bearing a HRP molecule, followed by substrate addition and fast electrochemical pulse amperometric detection. We present asimple, rapid, flexible, and inexpensive approach for the simultaneous quantification of multiple breast cancer related mRNA markers, with single tumor cell sensitivity.

  • 12. Adhikari, Subash
    et al.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
    Baker, Mark S.
    A high-stringency blueprint of the human proteome2020In: Nature Communications, E-ISSN 2041-1723, Vol. 11, no 1, article id 5301Article in journal (Refereed)
    Abstract [en]

    The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases. The Human Proteome Project (HPP) was launched in 2010 to enhance accurate annotation of the genome-encoded proteome. Ten years later, the HPP releases its first blueprint of the human proteome, annotating 90% of all known proteins at high-stringency and discussing the implications of proteomics for precision medicine.

  • 13. Adiels, Martin
    et al.
    Mardinoglu, Adil
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
    Taskinen, Marja-Riitta
    Boren, Jan
    Kinetic Studies to Elucidate Impaired Metabolism of Triglyceride-rich Lipoproteins in Humans2015In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 6, article id 342Article, review/survey (Refereed)
    Abstract [en]

    To develop novel strategies for prevention and treatment of dyslipidemia, it is essential to understand the pathophysiology of dyslipoproteinemia in humans. Lipoprotein metabolism is a complex system in which abnormal concentrations of various lipoprotein particles can result from alterations in their rates of production, conversion, and/or catabolism. Traditional methods that measure plasma lipoprotein concentrations only provide static estimates of lipoprotein metabolism and hence limited mechanistic information. By contrast, the use of tracers labeled with stable isotopes and mathematical modeling, provides us with a powerful tool for probing lipid and lipoprotein kinetics in vivo and furthering our understanding of the pathogenesis of dyslipoproteinemia.

  • 14. Adler, Belinda
    et al.
    Boström, Tove
    KTH, School of Biotechnology (BIO), Proteomics.
    Ekström, Simon
    Hober, Sophia
    KTH, School of Biotechnology (BIO), Proteomics.
    Laurell, Thomas
    Miniaturized and Automated High-Throughput Verification of Proteins in the ISET Platform with MALDI MS2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 20, p. 8663-8669Article in journal (Refereed)
    Abstract [en]

    A major bottleneck in high-throughput protein production is the validation step, which is why parallel and automated sample processing methods are highly desirable. Also, a miniaturized sample preparation format is preferred, as the reduction of reagent volumes significantly decreases the analysis cost per sample. We have developed an automated and miniaturized protein sequence verification protocol for recombinant proteins utilizing peptide mass fingerprinting and MS/MS analysis. The integrated selective enrichment target (ISET) platform, previously developed in our group, with its dual functionality, being both a sample preparation platform and a MALDI target plate, is employed. All steps including immobilized metal ion affinity chromatography of protein on cobalt-loaded beads, tryptic digestion, and MALDI MS analysis are performed in an array format, without any sample transfers, on the same ISET chip. The automated configuration reduced the sample preparation time significantly. Starting with crude lysate, a full plate of 48 purified, digested samples prepared for MALDI-MS can be generated in 4 h, with only 30 min of operator involvement. This paper demonstrates the utility of the method by parallel analysis of 45 His-tagged human recombinant proteins.

  • 15.
    Admassu Deginet, Tebekew
    KTH, School of Biotechnology (BIO).
    Focusing plane-wave light by metallic nano-optic lens2011Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 16. Adori, Csaba
    et al.
    Barde, Swapnali
    Bogdanovic, Nenad
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Institutet, Sweden.
    Reinscheid, Rainer R.
    Kovacs, Gabor G.
    Hokfelt, Tomas
    Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons2015In: Frontiers in Neuroanatomy, E-ISSN 1662-5129, Vol. 9Article in journal (Refereed)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects. In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1) is, however, widely distributed in the brain. The anxiolytic and arousal promoting effects of NPS make the NPS NPSR1 system an interesting potential drug target in mood-related disorders. However, so far possible disease-related mechanisms involving NPS have only been studied in rodents. To validate the relevance of these animal studies for i.a. drug development, we have explored the distribution of NPS-expressing neurons in the human pons using in situ hybridization and stereological methods and we compared the distribution of NPS mRNA expressing neurons in the human and rat brain. The calculation revealed a total number of 22,317 +/- 2411 NPS mRNA-positive neurons in human, bilaterally. The majority of cells (84%) were located in the parabrachial area in human: in the extension of the medial and lateral parabrachial nuclei, in the Kolliker-Fuse nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS cells) in the pontine central gray matter both in human and rat, which has not been described previously even in rodents. We also examined the distribution of NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the microcellular tegmental nucleus region and in the periaqueductal gray. Our results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior. The reported interspecies differences must, however, be considered when looking for targets for new pharmacotherapeutical interventions.

  • 17. Adori, Csaba
    et al.
    Barde, Swapnali
    Vas, Szilvia
    Ebner, Karl
    Su, Jie
    Svensson, Camilla
    Mathé, Aleksander A.
    Singewald, Nicolas
    Reinscheid, Rainer R.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kultima, Kim
    Bagdy, Gyorgy
    Hökfelt, Tomas
    Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study2016In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, no 7, p. 3521-3546Article in journal (Refereed)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep.

  • 18.
    Adori, Csaba
    et al.
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Daraio, Teresa
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Kuiper, Raoul
    Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden..
    Barde, Swapnali
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Horvathova, Lubica
    Slovak Acad Sci, Biomed Res Ctr, Inst Expt Endocrinol, Bratislava, Slovakia..
    Yoshitake, Takashi
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
    Ihnatko, Robert
    Linköping Univ, Dept Clin Chem, S-58285 Linköping, Sweden.;Linköping Univ, Dept Clin & Expt Med, S-58285 Linköping, Sweden.;Georg August Univ Gottingen, Univ Med Ctr, Inst Pathol, Gottingen, Germany..
    Valladolid-Acebes, Ismael
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Vercruysse, Pauline
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Wellendorf, Ashley M.
    Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA..
    Gramignoli, Roberto
    Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden..
    Bozoky, Bela
    Karolinska Univ Hosp, Dept Clin Pathol Cytol, Huddinge, Sweden..
    Kehr, Jan
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
    Theodorsson, Elvar
    Linköping Univ, Dept Clin Chem, S-58285 Linköping, Sweden.;Linköping Univ, Dept Clin & Expt Med, S-58285 Linköping, Sweden..
    Cancelas, Jose A.
    Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.;Univ Cincinnati, Hoxworth Blood Ctr, Coll Med, Cincinnati, OH 45267 USA..
    Mravec, Boris
    Slovak Acad Sci, Biomed Res Ctr, Inst Expt Endocrinol, Bratislava, Slovakia.;Comenius Univ, Fac Med, Inst Physiol, Bratislava, Slovakia..
    Jorns, Carl
    Karolinska Univ Hosp Huddinge, PO Transplantat, S-14152 Stockholm, Sweden..
    Ellis, Ewa
    Karolinska Inst, Karolinska Univ Hosp, Dept Transplantat Surg, S-17177 Stockholm, Sweden.;Karolinska Inst, Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol CLINTEC, S-17177 Stockholm, Sweden..
    Mulder, Jan
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.;Royal Inst Technol, Sci Life Lab, S-10691 Stockholm, Sweden..
    Bark, Christina
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Hokfelt, Tomas
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging2021In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 30, article id eabg5733Article in journal (Refereed)
    Abstract [en]

    Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

  • 19. Adori, Csaba
    et al.
    Glueck, Laura
    Barde, Swapnali
    Yoshitake, Takashi
    Kovacs, Gabor G.
    Mulder, Jan
    Magloczky, Zsofia
    Havas, Laszlo
    Boelcskei, Kata
    Mitsios, Nicholas
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Szolcsanyi, Janos
    Kehr, Jan
    Ronnback, Annica
    Schwartz, Thue
    Rehfeld, Jens F.
    Harkany, Tibor
    Palkovits, Miklos
    Schulz, Stefan
    Hokfelt, Tomas
    Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer's disease2015In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 129, no 4, p. 541-563Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer's and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer's disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer's pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine beta-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 (-/-) mice and, unlike in Sstr1 (-/-) or Sstr4 (-/-) genotypes, they showed selective, global and progressive degeneration of their central noradrenergic projections. However, neuronal perikarya in the LC were found intact until late adulthood (< 8 months) in Sstr2 (-/-) mice. In contrast, the noradrenergic neurons in the superior cervical ganglion lacked SSTR2 and, as expected, the sympathetic innervation of the head region did not show any signs of degeneration. Our results indicate that SSTR2-mediated signaling is integral to the maintenance of central noradrenergic projections at the system level, and that early loss of somatostatin receptor 2 function may be associated with the selective vulnerability of the noradrenergic system in Alzheimer's disease.

  • 20.
    Adori, Monika
    et al.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Bhat, Sadam
    Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
    Gramignoli, Roberto
    Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Valladolid-Acebes, Ismael
    Department of Molecular Medicine and Surgery, The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
    Bengtsson, Tore
    Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Adori, Csaba
    Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hepatic Innervations and Nonalcoholic Fatty Liver Disease2023In: Seminars in liver disease (Print), ISSN 0272-8087, E-ISSN 1098-8971, Vol. 43, no 2, p. 149-162Article in journal (Refereed)
    Abstract [en]

    Abbreviations: VMN/PVN, hypothalamic ventromedial nucleus/paraventricular nucleus; VLM/VMM, ventrolateral medulla/ventromedial medulla; SMG/CG, superior mesenteric ganglion/caeliac ganglia; NTS, nucleus of the solitary tract; NG, nodose ganglion. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.

  • 21. Adriani, O.
    et al.
    Barbarino, G. C.
    Bazilevskaya, G. A.
    Bellotti, R.
    Boezio, M.
    Bogomolov, E. A.
    Bonechi, L.
    Bongi, M.
    Bonvicini, V.
    Borisov, S.
    Bottai, S.
    Bruno, A.
    Cafagna, F.
    Campana, D.
    Carbone, R.
    Carlson, Per
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Casolino, M.
    Castellini, G.
    Consiglio, L.
    De Pascale, M. P.
    De Santis, C.
    De Simone, N.
    Di Felice, V.
    Galper, A. M.
    Gillard, W.
    Grishantseva, L.
    Hofverberg, Petter
    KTH, School of Engineering Sciences (SCI), Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Jerse, G.
    Koldashov, S. V.
    Krutkov, S. Y.
    Kvashnin, A. N.
    Leonov, A.
    Malvezzi, V.
    Marcelli, L.
    Menn, W.
    Mikhailov, V. V.
    Mocchiutti, E.
    Monaco, A.
    Mori, N.
    Nikonov, N.
    Osteria, G.
    Papini, P.
    Pearce, Mark
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Picozza, P.
    Ricci, M.
    Ricciarini, S. B.
    Rossetto, L.
    Simon, M.
    Sparvoli, R.
    Spillantini, P.
    Stozhkov, Y. I.
    Vacchi, A.
    Vannuccini, E.
    Vasilyev, G.
    Voronov, S. A.
    Wu, Juan
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Yurkin, Y. T.
    Zampa, G.
    Zampa, N.
    Zverev, V. G.
    Marinucci, D.
    A statistical procedure for the identification of positrons in the PAMELA experiment2010In: Astroparticle physics, ISSN 0927-6505, E-ISSN 1873-2852, Vol. 34, no 1, p. 1-11Article in journal (Refereed)
    Abstract [en]

    The PAMELA satellite experiment has measured the cosmic-ray positron fraction between 1.5 GeV and 100 GeV. The need to reliably discriminate between the positron signal and proton background has required the development of an ad hoc analysis procedure. In this paper, a method for positron identification is described and its stability and capability to yield a correct background estimate is shown. The analysis includes new experimental data, the application of three different fitting techniques for the background sample and an estimate of systematic uncertainties due to possible inaccuracies in the background selection. The new experimental results confirm both solar modulation effects on cosmic-rays with low rigidities and an anomalous positron abundance above 10 GeV. (c) 2010 Elsevier B.V. All rights reserved.

  • 22. Adriani, O.
    et al.
    Barbarino, G. C.
    Bazilevskaya, G. A.
    Bellotti, R.
    Boezio, M.
    Bogomolov, E. A.
    Bongi, M.
    Bonvicini, V.
    Bottai, S.
    Bruno, A.
    Cafagna, F.
    Campana, D.
    Carlson, Per
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. ‎ AlbaNova Univ Ctr, Oskar Klein Ctr Cosmoparticle Phys, SE-10691 Stockholm, Sweden.
    Casolino, M.
    Castellini, G.
    De Santis, C.
    Di Felice, V.
    Galper, A. M.
    Karelin, A. V.
    Koldashov, S. V.
    Koldobskiy, S.
    Krutkov, S. Y.
    Kvashnin, A. N.
    Leonov, A.
    Malakhov, V.
    Marcelli, L.
    Martucci, M.
    Mayorov, A. G.
    Menn, W.
    Merge, M.
    Mikhailov, V. V.
    Mocchiutti, E.
    Monaco, A.
    Munini, R.
    Mori, N.
    Osteria, G.
    Panico, B.
    Papini, P.
    Pearce, Mark
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. ‎ AlbaNova Univ Ctr, Oskar Klein Ctr Cosmoparticle Phys, SE-10691 Stockholm, Sweden.
    Picozza, P.
    Ricci, M.
    Ricciarini, S. B.
    Simon, M.
    Sparvoli, R.
    Spillantini, P.
    Stozhkov, Y. I.
    Vacchi, A.
    Vannuccini, E.
    Vasilyev, G.
    Voronov, S. A.
    Yurkin, Y. T.
    Zampa, G.
    Zampa, N.
    Ten years of PAMELA in space2017In: La Rivista del nuovo cimento della Società italiana di fisica, ISSN 0393-697X, E-ISSN 1826-9850, Vol. 40, no 10, p. 473-522Article in journal (Refereed)
    Abstract [en]

    The PAMELA cosmic-ray detector was launched on June 15th 2006 on board the Russian Resurs-DK1 satellite, and during ten years of nearly continuous data-taking it has observed new interesting features in cosmic rays (CRs). In a decade of operation it has provided plenty of scientific data, covering different issues related to cosmic-ray physics. Its discoveries might change our basic vision of the mechanisms of production, acceleration and propagation of cosmic rays in the Galaxy. The antimatter measurements, focus of the experiment, have set strong constraints to the nature of Dark Matter. Search for signatures of more exotic processes (such as the ones involving Strange Quark Matter) was also pursued. Furthermore, the long-term operation of the instrument had allowed a constant monitoring of the solar activity during its maximum and a detailed and prolonged study of the solar modulation, improving the comprehension of the heliosphere mechanisms. PAMELA had also measured the radiation environment around the Earth, and it detected for the first time the presence of an antiproton radiation belt surrounding our planet. The operation of Resurs-DK1 was terminated in 2016. In this article we will review the main features of the PAMELA instrument and its constructing phases. The main part of the article will be dedicated to the summary of the most relevant PAMELA results over a decade of observation.

  • 23.
    Afkham, Heydar Maboudi
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Ek, Carl Henrik
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    Carlsson, Stefan
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    A topological framework for training latent variable models2014In: Proceedings - International Conference on Pattern Recognition, 2014, p. 2471-2476Conference paper (Refereed)
    Abstract [en]

    We discuss the properties of a class of latent variable models that assumes each labeled sample is associated with a set of different features, with no prior knowledge of which feature is the most relevant feature to be used. Deformable-Part Models (DPM) can be seen as good examples of such models. These models are usually considered to be expensive to train and very sensitive to the initialization. In this paper, we focus on the learning of such models by introducing a topological framework and show how it is possible to both reduce the learning complexity and produce more robust decision boundaries. We will also argue how our framework can be used for producing robust decision boundaries without exploiting the dataset bias or relying on accurate annotations. To experimentally evaluate our method and compare with previously published frameworks, we focus on the problem of image classification with object localization. In this problem, the correct location of the objects is unknown, during both training and testing stages, and is considered as a latent variable.

  • 24.
    Afkham, Heydar Maboudi
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Ek, Carl Henrik
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    Carlsson, Stefan
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    Gradual improvement of image descriptor quality2014In: ICPRAM 2014 - Proceedings of the 3rd International Conference on Pattern Recognition Applications and Methods, 2014, p. 233-238Conference paper (Refereed)
    Abstract [en]

    In this paper, we propose a framework for gradually improving the quality of an already existing image descriptor. The descriptor used in this paper (Afkham et al., 2013) uses the response of a series of discriminative components for summarizing each image. As we will show, this descriptor has an ideal form in which all categories become linearly separable. While, reaching this form is not feasible, we will argue how by replacing a small fraction of these components, it is possible to obtain a descriptor which is, on average, closer to this ideal form. To do so, we initially identify which components do not contribute to the quality of the descriptor and replace them with more robust components. Here, a joint feature selection method is used to find improved components. As our experiments show, this change directly reflects in the capability of the resulting descriptor in discriminating between different categories.

  • 25.
    Afkham, Heydar Maboudi
    et al.
    KTH, School of Computer Science and Communication (CSC).
    Qiu, Xuanbin
    KTH, School of Computer Science and Communication (CSC).
    The, Matthew
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Käll, Lukas
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uncertainty estimation of predictions of peptides' chromatographic retention times in shotgun proteomics2017In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 33, no 4, p. 508-513Article in journal (Refereed)
    Abstract [en]

    Motivation: Liquid chromatography is frequently used as a means to reduce the complexity of peptide-mixtures in shotgun proteomics. For such systems, the time when a peptide is released from a chromatography column and registered in the mass spectrometer is referred to as the peptide's retention time. Using heuristics or machine learning techniques, previous studies have demonstrated that it is possible to predict the retention time of a peptide from its amino acid sequence. In this paper, we are applying Gaussian Process Regression to the feature representation of a previously described predictor ELUDE. Using this framework, we demonstrate that it is possible to estimate the uncertainty of the prediction made by the model. Here we show how this uncertainty relates to the actual error of the prediction. Results: In our experiments, we observe a strong correlation between the estimated uncertainty provided by Gaussian Process Regression and the actual prediction error. This relation provides us with new means for assessment of the predictions. We demonstrate how a subset of the peptides can be selected with lower prediction error compared to the whole set. We also demonstrate how such predicted standard deviations can be used for designing adaptive windowing strategies.

  • 26.
    Afrasiabi, Roodabeh
    et al.
    KTH, School of Information and Communication Technology (ICT).
    Jokilaakso, Nima
    KTH, School of Biotechnology (BIO).
    Localized Functionalization and Integration with Microfluidics for Multiplexed Biomolecule Detection using Silicon Nanoribbon-FET SensorsManuscript (preprint) (Other academic)
    Abstract [en]

    Biological processes causing different medical conditions are seldom characterized by the simple presence or absence of a single biomarker molecule and it can be expected that biosensors with options for multiplexed detection of a panel of analytes will be required for the development of bed-side diagnostic/prognostic tools for personalized healthcare. One sensor technology with potential to be used for label-free detection of biomolecules is based on Silicon Nanoribbon Field-Effect Transistors (SiNR FET). In this study, the possibilities for multiplexed detection of biomolecules have been explored by the integration of a SiNR FET device with a microfluidic system, in combination with localized immobilization of receptor molecules using a microdispensing instrument. SiNR FET devices were fabricated using CMOS technology and integrated with a microfluidic delivery system composed of channels defined in an SU-8 layer, covered with a PDMS lid. Switching between buffer solutions of different pH was used to demonstrate that the microfluidic system could be used for controlled sample delivery. The shift in conductance of the sensing wire upon change of pH showed that the SiNR FET devices were functional. Protocols for surface functionalization and biomolecule immobilization were evaluated using model systems based on synthetic complementary DNA oligonucleotides and the protein A-derived Z domain and its interaction with immunoglobulin G. The study demonstrates that localized immobilization of biomolecules on silicon nanoribbons can be achieved, opening up for multiplexed detection of analytes and improved possibilities for referencing.

  • 27.
    Afrasiabi, Roodabeh
    et al.
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Material Physics, MF.
    Jokilaakso, Nima
    KTH, School of Biotechnology (BIO), Protein Technology.
    Schmidt, Torsten
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Material Physics, MF.
    Björk, P.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Protein Technology.
    Linnros, Jan
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Material Physics, MF.
    Effect of microwave-assisted silanization on sensing properties of silicon nanoribbon FETs2015In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 209, p. 586-595Article in journal (Refereed)
    Abstract [en]

    An important concern with using silicon nanoribbon field-effect transistors (SiNR FET) for ion-sensing is the pH-response of the gate oxide surface. Depending on the application of the FET sensor, this response has to be chemically manipulated. Thus in silicon oxide-gated pH-sensors with integrated sensor and reference FETS, a surface with high pH-sensitivity, compared to the bare gate oxide, is required in the sensor FETs (SEFET), whereas in the reference FETs (REFET) the surface has to be relatively pH-insensitive. In order to control the sensitivity and chemistry of the oxide surface of the nanoribbons, a silanization reagent with a functional group is often self-assembled on the SiNR surface. Choice of a silanization reaction that results in a self-assembled layer on a silicon oxide surface has been studied extensively over the past decades. However, the effect of various self-assembled layers such as monolayers or mixed layers on the electrical response of SiNR FETs in aqueous solution needs to be exploited further, especially for future integrated SEFET/REFET systems. In this work, we have performed a comprehensive study on 3-aminopropyltriethoxysilane (APTES) silanization of silicon oxide surfaces using microwave (MW) heating as a new biocompatible route to conventional methods. A set of complementary surface characterization techniques (ellipsometry, AFM and ATR-FTIR) was used to analyze the properties of the APTES layer deposited on the silicon surface. We have found that a uniform monolayer can be achieved within 10 min by heating the silanization solution to 75 degrees C using MW heating. Furthermore, electrical measurements suggest that little change in device performance is observed after exposure to MW irradiation. Real-time pH measurements indicate that a uniform APTES monolayer not only reduces the pH sensitivity of SiNR FET by passivating the surface silanol groups, but also makes the device less sensitive to cation concentration in the background electrolyte. Our silanization route proves promising for future chemical surface modification of on-chip REFETs.

  • 28.
    Afrasiabi, Roodabeh
    et al.
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Material Physics, MF.
    Jokilaakso, Nima
    KTH, School of Biotechnology (BIO), Protein Technology.
    Schmidt, Torsten
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Material Physics, MF.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Protein Technology.
    Linnros, Jan
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Material Physics, MF.
    Microwave-assisted silanization of SiNW-FET: characterization and effect on sensing propertiesManuscript (preprint) (Other academic)
  • 29.
    Afrasiabi, Roodabeh
    et al.
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics.
    Söderberg, Lovisa M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Jönsson, Håkan
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Björk, Per
    Acreo Swedish ICT AB, SE-164 40 Kista, Sweden.
    Svahn Andersson, Helene
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Linnros, Jan
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics.
    Integration of a Droplet-Based Microfluidic System and Silicon Nanoribbon FET Sensor2016In: Micromachines, E-ISSN 2072-666X, Vol. 7, no 8Article in journal (Refereed)
    Abstract [en]

    We present a novel microfluidic system that integrates droplet microfluidics with a silicon nanoribbon field-effect transistor (SiNR FET), and utilize this integrated system to sense differences in pH. The device allows for selective droplet transfer to a continuous water phase, actuated by dielectrophoresis, and subsequent detection of the pH level in the retrieved droplets by SiNR FETs on an electrical sensor chip. The integrated microfluidic system demonstrates a label-free detection method for droplet microfluidics, presenting an alternative to optical fluorescence detection. In this work, we were able to differentiate between droplet trains of one pH-unit difference. The pH-based detection method in our integrated system has the potential to be utilized in the detection of biochemical reactions that induce a pH-shift in the droplets.

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  • 30.
    Afshari, Delaram
    KTH, School of Biotechnology (BIO).
    Enhancement of the coagulation and antimicrobial activity of M. oliefera by mutagenesis2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 31. Agnarsdottir, Margret
    et al.
    Sooman, Linda
    Bolander, Asa
    Stromberg, Sara
    Rexhepaj, Elton
    Bergqvist, Michael
    Ponten, Fredrik
    Gallagher, William
    Lennartsson, Johan
    Ekman, Simon
    Uhlen, Mathias
    KTH, School of Biotechnology (BIO), Proteomics. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Hedstrand, Hakan
    SOX10 expression in superficial spreading and nodular malignant melanomas2010In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 20, no 6, p. 468-478Article in journal (Refereed)
    Abstract [en]

    SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P = 0.008). The staining intensity was also inversely correlated with T-stage (Spearman's rho = -0.261, P = 0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (rho = -0.173, P = 0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P <= 0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn. Melanoma Res 20:468-478

  • 32.
    Aguilar, Xavier
    et al.
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz). KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Schliephake, Michael
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz). KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Vahtras, Olav
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Gimenez, Judit
    Laure, Erwin
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz). KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Scalability analysis of Dalton, a molecular structure program2013In: Future generations computer systems, ISSN 0167-739X, E-ISSN 1872-7115, Vol. 29, no 8, p. 2197-2204Article in journal (Refereed)
    Abstract [en]

    Dalton is a molecular electronic structure program featuring common methods of computational chemistry that are based on pure quantum mechanics (QM) as well as hybrid quantum mechanics/molecular mechanics (QM/MM). It is specialized and has a leading position in calculation of molecular properties with a large world-wide user community (over 2000 licenses issued). In this paper, we present a performance characterization and optimization of Dalton. We also propose a solution to avoid the master/worker design of Dalton to become a performance bottleneck for larger process numbers. With these improvements we obtain speedups of 4x, increasing the parallel efficiency of the code and being able to run in it in a much bigger number of cores.

  • 33.
    Aguilar, Xavier
    et al.
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC.
    Schliephake, Michael
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC.
    Vahtras, Olav
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC.
    Gimenez, Judit
    Barcelona Supercomputing Center, Universitat Politecnica de Catalunya, Barcelona, Spain.
    Laure, Erwin
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC.
    Scaling Dalton, a molecular electronic structure program2011In: Seventh International Conference on e-Science, e-Science 2011, 5-8 December 2011, Stockholm, Sweden, IEEE conference proceedings, 2011, p. 256-262Conference paper (Refereed)
    Abstract [en]

    Dalton is a molecular electronic structure program featuring common methods of computational chemistry that are based on pure quantum mechanics (QM) as well as hybrid quantum mechanics/molecular mechanics (QM/MM). It is specialized and has a leading position in calculation of molecular properties with a large world-wide user community (over 2000 licenses issued). In this paper, we present a characterization and performance optimization of Dalton that increases the scalability and parallel efficiency of the application. We also propose asolution that helps to avoid the master/worker design of Daltonto become a performance bottleneck for larger process numbers and increase the parallel efficiency.

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  • 34. Ahlin, G.
    et al.
    Hilgendorf, C.
    Karlsson, J.
    Al-Khalili Szigyarto, Cristina
    KTH, School of Biotechnology (BIO), Proteomics.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    Artursson, P.
    Endogenous Gene and Protein Expression of Drug-Transporting Proteins in Cell Lines Routinely Used in Drug Discovery Programs2009In: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 37, no 12, p. 2275-2283Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the gene and protein expression profiles of important drug-transporting proteins in human cell lines commonly used for studies of drug transport mechanisms. Human cell lines used to transiently or stably express single transporters [HeLa, human embryonic kidney (HEK) 293] and leukemia cell lines used to study drug resistance by ATP-binding cassette transporters (HL-60, K562) were investigated and compared with organotypic cell lines (HepG2, Saos-2, Caco-2, and Caco-2 TC7). For gene expression studies, real-time polymerase chain reaction was used, whereas monospecific polyclonal antibodies were generated and used to investigate protein expression by immunohistochemistry. Thirty-six transporters were studied for gene expression, and nine were studied for protein expression. The antibodies were validated using expression patterns in human tissues. Finally, the function of one ubiquitously expressed transporter, MCT1/SLC16A1, was investigated using [C-14]lactic acid as a substrate. In general, the adherent cell lines (HeLa, HEK293) displayed low transporter expression, and the expression patterns were barely affected by transfection. The leukemia cell lines (K562, HL-60) and Saos-2 also had low endogenous transporter expression, whereas the organotypic cell lines (HepG2 and Caco-2) showed higher expression of some transporters. Comparison of gene and protein expression profiles gave poor correlations, but better agreement was obtained for antibodies with a good validation score, indicating that antibody quality was a significant variable. It is noteworthy that the monocarboxylic acid-transporting protein MCT1 was significantly expressed in all and was functional in most of the cell lines, indicating that MCT1 may be a confounding factor when the transport of small anionic drugs is investigated.

  • 35.
    Ahlquist, Mårten
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Fabrizi, G
    Cacchi, S
    Norrby, Per-Ola
    Technical University of Denmark.
    Palladium(0) alkyne complexes as active species: a DFT investigation2005In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, no 33, p. 4196-4198Article in journal (Refereed)
    Abstract [en]

    Alkynes have been found to be excellent ligands for Pd(0); the stability of a range of alkyne-Pd(0) complexes, and their reactivity in oxidative addition, have been investigated by DFT methods.

  • 36.
    Ahlquist, Mårten
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Fabrizi, Giancarlo
    Cacchi, Sandro
    Norrby, Per-Ola
    Technical Univeristy of Denmark.
    The mechanism of the phosphine-free palladium-catalyzed hydroarylation of alkynes2006In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 128, no 39, p. 12785-12793Article in journal (Refereed)
    Abstract [en]

    The mechanism of the Pd-catalyzed hydroarylation and hydrovinylation reaction of alkynes has been studied by a combination of experimental and theoretical methods (B3LYP), with an emphasis on the phosphine-free version. The regioselectivity of the hydroarylation and hydrovinylation shows unexpected differences, which could be attributed mainly to the higher steric demand of the cyclohexenyl group as compared to the phenyl group. Hydroarylation of alpha,beta-acetylenic carbonyl substrates yields a very unusual anti-Michael selectivity, which is shown to result from reaction of the nonconjugated double bond, leaving the conjugation intact. In all cases were the regioselectivities reproduced by the calculations.

  • 37.
    Ahlquist, Mårten
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Norrby, Per-Ola
    Department of Chemistry, University of Gothenburg, Sweden.
    Dispersion and Back-Donation Gives Tetracoordinate [Pd(PPh3)4]2011In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 50, no 49, p. 11794-11797Article in journal (Refereed)
    Abstract [en]

    18e R.I.P. The apparent compliance of [Pd(PPh3)4] ("tetrakis") with the 18-electron rule is not due to an electronic preference on the central metal. Pd is valence-saturated already by two ligands. Further ligand addition gives a minor energy gain, and is only possible due to strong back-bonding. Dispersion corrections are needed for properly describing the interactions between the ligands.

  • 38.
    Ahlquist, Mårten S. G.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry.
    Iridium catalyzed hydrogenation of CO2 under basic conditions-Mechanistic insight from theory2010In: Journal of Molecular Catalysis A: Chemical, ISSN 1381-1169, E-ISSN 1873-314X, Vol. 324, no 1-2, p. 3-8Article in journal (Refereed)
    Abstract [en]

    The iridium(III) catalyzed hydrogenation of carbon dioxide under basic conditions was studied with density functional theory. It was found that the insertion of CO2 into an Ir-H bond proceeds via a two-step mechanism. The rate-limiting step was calculated to be the regeneration of the iridium(III) trihydride intermediate, and the overall barrier for the reaction was calculated to 26.1 kcal mol(-1). The formation of the iridium trihydride proceeds via formation of a cationic Ir(H)(2)(H-2) complex at which the base abstracts a proton from the dihydrogen ligand. (C) 2010 Elsevier B.V. All rights reserved.

  • 39.
    Ahlquist, Mårten S. G.
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Norrby, Per-Ola
    Department of Chemistry, University of Gothenburg, Sweden.
    Dispersion and back-donation gives tetracoordinate Pd(PPh3)(4)2012In: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 243Article in journal (Other academic)
  • 40.
    Ahlquist, Mårten S. G.
    et al.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Wang, Ying
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Xue, Liqin
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Sanchez-de-Armas, Rocio
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Proton transfers in first row transition metal complexes2013In: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 245, p. 1381-INOR-Article in journal (Other academic)
  • 41. Ahlqvist, J.
    et al.
    Kumar, A.
    Sundstrom, H.
    Ledung, E.
    Hornsten, E. G.
    Enfors, Sven-Olof
    KTH, School of Biotechnology (BIO), Bioprocess Technology.
    Mattiasson, B.
    Affinity binding of inclusion bodies on supermacroporous monolithic cryogels using labeling with specific antibodies2006In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 122, no 2, p. 216-225Article in journal (Refereed)
    Abstract [en]

    A new chromatographic method based on affinity supermacroporous monolithic cryogels is developed for binding and analyzing inclusion bodies during fermentation. The work demonstrated that it is possible to bind specific IgG and IgY antibodies to the 15 and 17 amino acids at the terminus ends of a 33 kDa target protein aggregated as inclusion bodies. The antibody treated inclusion bodies from lysed fermentation broth can be specifically retained in protein A and pseudo-biospecific ligand sulfamethazine modified supermacroporous cryogels. The degree of binding of IgG and IgY treated inclusion bodies to the Protein A and sulfamethazine gels are investigated, as well as the influence of pH on the sulfamethazine ligand. Optimum binding of 78 and 72% was observed on both protein A and sulfamethazine modified cryogel columns, respectively, using IgG labeling of the inclusion bodies. The antibody treated inclusion bodies pass through unretained in the sulfamethazine supermacroporous gel at pH that does not favour the binding between the ligand on the gel and the antibodies on the surface of inclusion bodies. Also the unlabeled inclusion bodies went through the gel unretained, showing no non-specific binding or trapping within the gel. These findings may very well be the foundation for the building of a powerful analytical tool during fermentation of inclusion bodies as well as a convenient way to purify them from fermentation broth. These results also support our earlier findings [Kumar, A., Plieva, F.M., Galaev, I.Yu., Mattiasson, B.. 2003. Affinity fractionation of lymphocytes using a monolithic cyogel. J. Immunol. Methods 283, 185-194] with mammalian cells that were surface labeled with specific antibodies and recognized on protein A supermacroporous gels. A general binding and separation system can be established on antibody binding cryogel affinity matrices.

  • 42. Ahlstrand, David A.
    et al.
    Polukeev, Alexey V.
    Marcos, Rocio
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Ahlquist, Mårten S. G.
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Wendt, Ola F.
    Csp(3)-H Activation without Chelation Assistance in an Iridium Pincer Complex Forming Cyclometallated Products2017In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 23, no 8, p. 1748-1751Article in journal (Refereed)
    Abstract [en]

    Cyclometallation of 8-methylquinoline and 2-(dimethylamino)-pyridine in an iridium-based pincer complex is described. The C-H activation of 2-(dimethylamino) pyridine is not chelation assisted, which has not been described before for Csp(3)-H bonds in cyclometallation reactions. The mechanism of the cyclometallation of 2-(dimethylamino) pyridine was studied by DFT calculations and kinetic measurements.

  • 43. Ahmad, Yasmeen
    et al.
    Boisvert, Francois-Michel
    Lundberg, Emma
    KTH, School of Biotechnology (BIO), Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lamond, Angus I.
    Systematic Analysis of Protein Pools, Isoforms, and Modifications Affecting Turnover and Subcellular Localization2012In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 11, no 3Article in journal (Refereed)
    Abstract [en]

    In higher eukaryotes many genes encode protein isoforms whose properties and biological roles are often poorly characterized. Here we describe systematic approaches for detection of either distinct isoforms, or separate pools of the same isoform, with differential biological properties. Using information from ion intensities we have estimated protein abundance levels and using rates of change in stable isotope labeling with amino acids in cell culture isotope ratios we measured turnover rates and subcellular distribution for the HeLa cell proteome. Protein isoforms were detected using three data analysis strategies that evaluate differences between stable isotope labeling with amino acids in cell culture isotope ratios for specific groups of peptides within the total set of peptides assigned to a protein. The candidate approach compares stable isotope labeling with amino acids in cell culture isotope ratios for predicted isoform- specific peptides, with ratio values for peptides shared by all the isoforms. The rule of thirds approach compares the mean isotope ratio values for all peptides in each of three equal segments along the linear length of the protein, assessing differences between segment values. The three in a row approach compares mean isotope ratio values for each sequential group of three adjacent peptides, assessing differences with the mean value for all peptides assigned to the protein. Protein isoforms were also detected and their properties evaluated by fractionating cell extracts on one- dimensional SDS- PAGE prior to trypsin digestion and MS analysis and independently evaluating isotope ratio values for the same peptides isolated from different gel slices. The effect of protein phosphorylation on turnover rates was analyzed by comparing mean turnover values calculated for all peptides assigned to a protein, either including, or excluding, values for cognate phosphopeptides. Collectively, these experimental and analytical approaches provide a framework for expanding the func- tional annotation of the genome.

  • 44.
    Ahmadian, Afshin
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    AnderssonSvahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Massively parallel sequencing platforms using lab on a chip technologies2011In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 11, no 16, p. 2653-2655Article in journal (Refereed)
  • 45.
    Ahmadian, Afshin
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Ehn, M.
    Hober, Sophia
    KTH, School of Biotechnology (BIO), Proteomics.
    Pyrosequencing: History, biochemistry and future2006In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 363, no 02-jan, p. 83-94Article, review/survey (Refereed)
    Abstract [en]

    Background: Pyrosequencing is a DNA sequencing technology based on the sequencing-by-synthesis principle. Methods: The technique is built on a 4-enzyme real-time monitoring of DNA synthesis by bioluminescence using a cascade that upon nucleotide incorporation ends in a detectable light signal (bioluminescence). The detection system is based on the pyrophosphate released when a nucleotide is introduced in the DNA-strand. Thereby, the signal can be quantitatively connected to the number of bases added. Currently, the technique is limited to analysis of short DNA sequences exemplified by single-nucleotide polymorphism analysis and genotyping. Mutation detection and single-nucleotide polymorphisin genotyping require screening of large samples of materials and therefore the importance of high-throughput DNA analysis techniques is significant. In order to expand the field for pyrosequencing, the read length needs to be improved. Conclusions: Th pyrosequencing system is based on an enzymatic system. There are different current and future applications of this technique.

  • 46. Ahmadian, Afshin
    et al.
    Pettersson, Erik
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology.
    Method for amplification2005Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The invention refers to a method for multiplex amplification of at least one specific nucleic acid locus, comprising the steps of: providing at least one oligonucleotide probe pair that is designed so that the first and second probe of the pair anneal to a specific nucleic acid locus on a target molecule, in which pair the first probe has an extendable 3'-end, and a second probe has a 5'-end that is directly or indirectly labelled with a phosphate group; providing a target molecule comprising at least one specific nucleic acid locus; allowing the probe pair to anneal to the target molecule; allowing the 3'-end of the first probe to extend by influence of polymerase by adding a set of three different dNTPs; ligating the 3'-end of the extended first probe to the 5'-end of the second probe. Hereby, a method is provided which allows a high specificity for simultaneous amplification of several loci. Further, the invention involves a kit for use in the method of the invention.

  • 47.
    Ahmadian, Afshin
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology.
    Ren, Z P
    Williams, Cecilia
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Pontén, F
    Odeberg, Jacob
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Pontén, J
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology.
    Genetic instability in the 9q22.3 region is a late event in the development of squamous cell carcinoma.1998In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 17, no 14Article in journal (Refereed)
    Abstract [en]

    Squamous cell carcinoma (SCC) of the skin represents a group of neoplasms which is associated with exposure to UV light. Recently, we obtained data suggesting that invasive skin cancer and its precursors derive from one original neoplastic clone. Here, the analysis were extended by loss of heterozygosity (LOH) analysis in the chromosome 9q22.3 region. A total of 85 samples, taken from twenty-two sections of sun-exposed sites, corresponding to normal epidermis, morphological normal cells with positive immuno-staining for the p53 protein (p53 patches), dysplasias, cancer in situ (CIS) and squamous cell carcinomas (SCC) of the skin were analysed. Overall, about 70% of p53 patches had mutations in the p53 gene but not LOH in the p53 gene or 9q22.3 region. Approximately 70% of the dysplasias showed p53 mutations of which about 40% had LOH in the p53 region but not in the 9q22.3 region. In contrast, about 65% of SCC and CIS displayed LOH in the 9q22.3 region, as well as frequent (80%) mutations and/or LOH in the p53 gene. These findings strongly suggest that alterations in the p53 gene is an early event in the progression towards SCC, whereas malignant development involves LOH and alterations in at least one (or several) tumor suppressor genes located in chromosome 9q22.3.

  • 48. Ahmed, Engy
    et al.
    Hugerth, Luisa W.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Logue, Jürg Brendan
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bruchert, Volker
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Holmström, Sara J. M.
    Mineral Type Structures Soil Microbial Communities2017In: Geomicrobiology Journal, ISSN 0149-0451, E-ISSN 1521-0529, Vol. 34, no 6, p. 538-545Article in journal (Refereed)
    Abstract [en]

    Soil microorganisms living in close contact with minerals play key roles in the biogeochemical cycling of elements, soil formation, and plant nutrition. Yet, the composition of microbial communities inhabiting the mineralosphere (i.e., the soil surrounding minerals) is poorly understood. Here, we explored the composition of soil microbial communities associated with different types of minerals in various soil horizons. To this effect, a field experiment was set up in which mineral specimens of apatite, biotite, and oligoclase were buried in the organic, eluvial, and upper illuvial horizons of a podzol soil. After an incubation period of two years, the soil attached to the mineral surfaces was collected, and microbial communities were analyzed by means of Illumina MiSeq sequencing of the 16S (prokaryotic) and 18S (eukaryotic) ribosomal RNA genes. We found that both composition and diversity of bacterial, archaeal, and fungal communities varied across the different mineral surfaces, and that mineral type had a greater influence on structuring microbial assemblages than soil horizon. Thus, our findings emphasize the importance of mineral surfaces as ecological niches in soils.

  • 49.
    Ahrenstedt, Lage
    KTH, School of Biotechnology (BIO).
    Surface modification of cellulose materials: from wood pulps to artificial blood vessels2007Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    This thesis describes the improvement of two radically different cellulose materials, paper and artificial blood vessels, constructed from two diverse cellulose sources, wood pulp and Acetobacter xylinum. The improvement of both materials was possible due to the natural affinity of the hemicellulose xyloglucan for cellulose.

    Chemical and mechanical pulps were treated with xyloglucan in the wet-end prior to hand sheet formation or by spray application of dry hand sheets, loading a comparable amount of xyloglucan. The tensile strength increases for the wet-end treatment and spray application were 28% and 71% respectively for bleached soft wood, compared to untreated sheets (20.7 Nm/g). The corresponding strength increases for hand sheets made of thermo-mechanical pulp were 6% and 13% respectively compared to untreated sheets (42.4 Nm/g). The tendency for chemical pulp to be superior to mechanical pulp with respect to strength increase was valid even for tear strength and Scott-Bond. These results suggest, in agreement with other studies, that adhesion of xyloglucan to wood fibres is dependent on their degree of surface lignification.

    Also, a method was developed to increase the blood compatibility of artificial blood vessels constructed of bacterial cellulose. Xyloglucan was covalently linked to the endothelial cell adhesion motif (Arg-Gly-Asp). To obtain this, new solid-phase coupling chemistry was developed. Xyloglucan oligosaccharides (XGO) were transformed into XGO-succinamic acid via the corresponding XGO--NH2 derivative prior to coupling with the N-terminus of the solid-phase synthesised Gly-Arg-Gly-Asp-Ser peptide. The resin-bound glyco-peptide was then cleaved and enzymatically re-incorporated into high molecular weight xyloglucan. The glyco-peptide was further adsorbed onto bacterial cellulose scaffolds, increasing the adhesion and proliferation of endothelial cells and therefore blood compatibility.

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  • 50.
    Ahrenstedt, Lage
    et al.
    KTH, School of Biotechnology (BIO). KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Olksanen, Antti
    VTT Technical Research Centre of Finland.
    Salmien, Kristian
    VTT Technical Research Centre of Finland.
    Brumer, Harry
    KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Paper dry strength improvement by xyloglucan addition: Wet-end application, spray coating and synergism with borate2008In: Holzforschung, ISSN 0018-3830, E-ISSN 1437-434X, Vol. 62, no 1, p. 8-14Article in journal (Refereed)
    Abstract [en]

    The polysaccharide xyloglucan as a wet-end additive improves paper properties. In the present study, paper strength improvement was analysed for dry handsheets made from chemical, mechanical and recycled pulps coated with xyloglucan in a spray application. Results are compared with sheets made from the same pulps treated with xyloglucan in the wet-end. Kraft pulp handsheets of bleached hardwood and softwood showed significant improvements of tensile, tear and Z-strength by xyloglucan spray treatment versus wet-end application, whereas handsheets of de-inked and thermomechanical pulp were improved only slightly. In both wet-end and spray applications, the effect of xyloglucan addition was intimately related to the presence of non-cellulosic components on the fibre surface. Further strength improvements were obtained for chemical pulps by addition of borax to the spray solution, which were likely to be due to the formation of borate-mediated xyloglucan cross-links. Spray coating of xyloglucan, with or without borax, thus represents a potential new application of this polysaccharide to increase paper dry strength.

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