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  • 1.
    AbdElKhalek, Y. M.
    et al.
    KTH, Skolan för elektroteknik och datavetenskap (EECS).
    Awad, M. I.
    Abd El Munim, H. E.
    Maged, S. A.
    Trajectory-based fast ball detection and tracking for an autonomous industrial robot system2021Ingår i: International Journal of Intelligent Systems Technologies and Applications, ISSN 1740-8865, E-ISSN 1740-8873, Vol. 20, nr 2, s. 126-145Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autonomising industrial robots is the main goal in this paper; imagine humanoid robots that have several degrees of freedom (DOF) mechanisms as their arms. What if the humanoid's arms could be programmed to be responsive to their surrounding environment, without any hard-coding assigned? This paper presents the idea of an autonomous system, where the system observes the surrounding environment and takes action on its observation. The application here is that of rebuffing an object that is thrown towards a robotic arm's workspace. This application mimics the idea of high dynamic responsiveness of a robot's arm. This paper will present a trajectory generation framework for rebuffing incoming flying objects. The framework bases its assumptions on inputs acquired through image processing and object detection. After extensive testing, it can be said that the proposed framework managed to fulfil the real-time system requirements for this application, with an 80% successful rebuffing rate. 

  • 2. Adhikari, Subash
    et al.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Baker, Mark S.
    A high-stringency blueprint of the human proteome2020Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 11, nr 1, artikel-id 5301Artikel i tidskrift (Refereegranskat)
    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.

  • 3.
    Adlerz, Ellen
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Sortase A coupling of the recombinant partial silk proteins 4Rep-Srt and G-/G5-CT to understand the structure of silk fiber2023Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Spindelsilke är ett intressant material på grund av dess biokompatibilitet och därav användning som biomaterial. Det är jämförbart med konstgjorda material när det gäller styrka och elasticitet, och i kombination med biokompatibiliteten, är spindelsilke eftertraktat inom det medicinska området. Sju olika spindeltrådar produceras av hjulspindeln och en kan användas som säkerhetslina vid flykt, och är därav mycket stark och töjbar. Säkerhetslinan består av två proteiner, så kallade stora ampullkörtel spidroiner 1 och 2 (MaSp1 & 2) eftersom de produceras i den stora ampullkörteln i spindeln. Dessa två proteiner är i sin tur sammansatta av tre delar, en repetitiv region i mitten och två icke-repetitiva regioner vid proteinets terminaler, N- och C-terminal domänerna. Att använda spindlar som huvudsakliga producenter av spindeltråd inom forskning är problematiskt och har fått forskare att vända sig till rekombinant produktion för uttryck av proteiner, mestadels i E. coli. Proteinstorleken är en begränsning vid produktion i E. coli, så forskare har uppfunnit ett mindre protein än MaSp som endast består av en mindre del av den repetitiva regionen och C-terminal domänen, så kallad 4RepCT. 4RepCT kan fortfarande bilda spindeltråd under fysiologiskt tillstånd och är biokompatibel. 4RepCT kan funktionaliseras med biomolekyler som kan ändra dess funktion, till exempel genom ett celladhesions motiv från fibronektin, som gör att 4RepCT kan binda till celler. I detta projekt siktar vi på att producera 4Rep-Srt och G-/G5-CT separat innan de kopplas med enzymet Sortase A. Sortase A känner igen en Sortase-tagg (LPXTG) på C-terminalen av ett protein (4Rep-Srt i detta projekt) och kopplar det till annat protein som har 1-5 glyciner på N-terminalen (G-/G5-CT i detta projekt). När proteinerna produceras separat kan G-/G5-CT uttryckas med 13C och 15N före kopplingen, och ge information om vilken del av 4Rep-G-/G5-CT-proteinet som är G-/G5-CT. Genom att känna till proteinets struktur, kan även dess egenskaper och funktioner förstås för att bättre bistå konstruktionen av proteiner för att erhålla biomolekyler med önskade funktioner.

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  • 4. 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, Skolan för bioteknologi (BIO), Proteomik. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Hedstrand, Hakan
    SOX10 expression in superficial spreading and nodular malignant melanomas2010Ingår i: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 20, nr 6, s. 468-478Artikel i tidskrift (Refereegranskat)
    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

  • 5. Agostinho, Ana
    et al.
    Manneberg, Otto
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    van Schendel, Robin
    Hernandez-Hernandez, Abrahan
    Kouznetsova, Anna
    Blom, Hans
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Cellens fysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Höög, Christer
    High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation2016Ingår i: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 17, nr 6, s. 901-913Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.

  • 6.
    Ahlgren, Kajsa
    et al.
    Chalmers Univ Technol, Dept Phys, Div Nanobiophys, SE-41296 Gothenburg, Sweden..
    Olsson, Christoffer
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Medicinteknik och hälsosystem, Medicinsk avbildning.
    Ermilova, Inna
    Chalmers Univ Technol, Dept Phys, Div Nanobiophys, SE-41296 Gothenburg, Sweden..
    Swenson, Jan
    Chalmers Univ Technol, Dept Phys, Div Nanobiophys, SE-41296 Gothenburg, Sweden..
    New insights into the protein stabilizing effects of trehalose by comparing with sucrose2023Ingår i: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 25, nr 32, s. 21215-21226Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Disaccharides are well known to be efficient stabilizers of proteins, for example in the case of lyophilization or cryopreservation. However, although all disaccharides seem to exhibit bioprotective and stabilizing properties, it is clear that trehalose is generally superior compared to other disaccharides. The aim of this study was to understand this by comparing how the structural and dynamical properties of aqueous trehalose and sucrose solutions influence the protein myoglobin (Mb). The structural studies were based on neutron and X-ray diffraction in combination with empirical potential structure refinement (EPSR) modeling, whereas the dynamical studies were based on quasielastic neutron scattering (QENS) and molecular dynamics (MD) simulations. The results show that the overall differences in the structure and dynamics of the two systems are small, but nevertheless there are some important differences which may explain the superior stabilizing effects of trehalose. It was found that in both systems the protein is preferentially hydrated by water, but that this effect is more pronounced for trehalose, i.e. trehalose forms less hydrogen bonds to the protein surface than sucrose. Furthermore, the rotational motion around dihedrals between the two glucose rings of trehalose is slower than in the case of the dihedrals between the glucose and fructose rings of sucrose. This leads to a less perturbed protein structure in the case of trehalose. The observations indicate that an aqueous environment closest to the protein molecules is beneficial for an efficient bioprotective solution.

  • 7.
    Ahrenstedt, Lage
    KTH, Skolan för bioteknologi (BIO).
    Surface modification of cellulose materials: from wood pulps to artificial blood vessels2007Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    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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  • 8.
    Akhras, Michael S.
    KTH, Skolan för bioteknologi (BIO).
    Nucleic Acid Based Pathogen Diagnostics2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Patogena organismer smittas till värd organismen genom alla möjliga kontaktnätverk och skapar en mångfald olika sjukdomstillstånd. Dock är det fortfarande vanligt förekommande behandlingsbara infektiösa sjukdomar som orsakar den största hälsoförlusten, sett från ett globalt perspektiv. Bill och Melinda Gates Stiftelsen samarbetade med RAND kooperation för att forma “The Global Health Diagnostics Forum”. Deras mål var att etablera och analysera matematiska modeller för vilka effekter en ny diagnostisk metod utrustat för fältarbete skulle ha i utvecklingsländer. Resultaten var häpnadsveckande, med potentiellt miljoner av liv som skulle kunna räddas på en årlig basis.

    Den etablerade standarden för diagnostik av patogena bakterier har länge varit kultiveringsmedia baserad. Miljö specialiserade biologer har estimerat att mindre än 1 % av alla bakterie arter går att kultivera. Dock erbjuder genetiska analyser potentialen att kunna identifiera alla mikrober från alla de biologiska rikena. Nukleinsyrebaserade diagnostiska metoder har märkbart förbättrats över de senaste årtionden. Nya tekniker erbjuder utökad sensitivitet, selektivitet, sänkta kostnader och parallella analyser av patient prover. Dock är de flesta metoderna begränsade till standardiserade laboratoriemiljöer. För att konstruera en väl fungerande diagnostisk fältutrustning för användning i problem områden, behöver världsledande tekniker identifieras och kombineras.

    Fokuseringsområdet för denna doktorsavhandling har varit att utveckla och utföra nukleinsyrebaserade metoder för patogen diagnostik. Metoder och experimentella utförande applicerades på två distinkta system i) sökning av antibiotika resistens relaterade mutationer i den patogena bakterien Neisseria gonorrhoeae och ii) genotypning av det cancer orsakande Humana Papillomaviruset (HPV). Den första delen av studien inriktade sig mot utveckling av snabba, direkta och multiplexa Pyrosekvenserings baserade nukleinsyreanalyser. Med förbättrad provprepareringsmetodologi kunde vi detektera multipla HPV infektioner med högre sensitivitet än vad tidigare beskrivits med liknande metodologi. Den andra delen av studien fokuserades på multiplexa nukleinsyre amplifikationer med “Molecular Inversion Probe” tekniken med sista steg Pyrosekvenserings analys. “PathogenMip assay” erbjuder ett komplett detektionsprotokoll för alla kända patogena organismer. Vi introducerar även den nya “Connector Inversion Probe”, en “Padlock Probe” kapabel att genomföra kompletta gap fyllningar för multiplex nukleinsyre amplifiering.

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  • 9.
    Akkuratov, Evgeny E.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    The Biophysics of Na+,K+-ATPase in neuronal health and disease2020Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Na+,K+-ATPas är ett av de viktigaste proteinerna i däggdjurscellen. Det skapar natrium- och kaliumgradienter som är grundläggande för den elektriska potentialen över cellmembranet och för natriumberoende sekundär aktiv transport. Det har dessutom en roll som receptor som genom att binda hjärtstimulerande steroider, varav den mest kända är ouabain, startar olika signalvägar i cellen som bl.a. reglerar genaktivering, prolifiering och apoptos. Det har visats att flera allvarliga neurologiska sjukdomar är kopplade till mutationer i Na+,K+-ATPas gener. Trots att Na+,K+-ATPas upptäcktes redan 1957, av Dansken Jens Skou, är vår kunskap om enzymets funktion ännu inte komplett. I studierna i denna avhandling har vi lärt oss mer om Na+,K+-ATPas funktion inom hälsa och sjukdomar. I studie I påvisade vi en ouabainberoende reglering av NMDA-receptorn – en grundläggande receptor i nervsystemet – via bindning till Na+,K+-ATPas. Detta visar att Na+,K+- ATPas fungerar som en regulator genom att direkt interagera med andra proteiner. I studie II undersökte vi en annan sida av Na+,K+-ATPas funktion – hur bindning av ouabain till Na+,K+-ATPas aktiverar flera signal-kaskader – genom att titta på cellens fosfoproteoms-status. Vi kunde på så sätt få en mer heltäckande bild av ouabain-styrda kaskader, och karakterisera dem. I studie III fokuserade vi på Na+,K+-ATPas roll i svårartad epileptisk encefalopati orsakad av en mutation i ATP1A1-genen. Vi utförde en molekylär och cellulär studie för att beskriva hur en mutation påverkar proteinets struktur och funktion, och fann att mutationen omvandlar jonpumpen till en ospecifik läckkanal. I studie IV genomförde vi en translationell studie för den vanligaste mutationen vid dystoni parkinsonism med snabb debut. Vi studerade hur mutationen påverkar vi nervsystemet på protein-, cell-, och organismnivå och fann att frånvaro av ultralångsam efterhyperpolarisering skulle kunna förklara patienters problem med gången. I pågående studie visade vi att Na+,K+-ATPas kan oligomerisera och att detta startas av bindning till ouabain. I denna studie utvecklade vi en fluorescensmärkning av Na+,K+-ATPas, och oligomeriseringen studerades med fluorescenstekniker med en-molekylkänslighet. Sammanfattningsvis har vi använt biofysikaliska och molekylära metoder för att studera olika aspekter av Na+,K+-ATPas funktion och nått insikter som kan vara till hjälp, inte bara för att beskriva grundläggande molekylära funktioner men även för att hitta botemedel mot sjukdommar kopplade till mutationer i Na+,K+-ATPas.

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  • 10.
    Akkuratov, Evgeny E.
    et al.
    St Petersburg State Univ, Inst Translat Biomed, St Petersburg, Russia.
    Gelfand, Mikhail S.
    Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Moscow, Russia.;Russian Acad Sci, Inst Informat Transmiss Problems, Moscow, Russia.;Natl Res Univ, Higher Sch Econ, Fac Comp Sci, Moscow, Russia.;MM Lomonosov Moscow State Univ, Dept Bioengn & Bioinformat, Moscow, Russia..
    Khrameeva, Ekaterina E.
    Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Moscow, Russia.;Russian Acad Sci, Inst Informat Transmiss Problems, Moscow, Russia..
    Neanderthal and Denisovan ancestry in Papuans: A functional study2018Ingår i: Journal of Bioinformatics and Computational Biology, ISSN 0219-7200, E-ISSN 1757-6334, Vol. 16, nr 2, artikel-id 1840011Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sequencing of complete nuclear genomes of Neanderthal and Denisovan stimulated studies about their relationship with modern humans demonstrating, in particular, that DNA alleles from both Neanderthal and Denisovan genomes are present in genomes of modern humans. The Papuan genome is a unique object because it contains both Neanderthal and Denisovan alleles. Here, we have shown that the Papuan genomes contain different gene functional groups inherited from each of the ancient people. The Papuan genomes demonstrate a relative prevalence of Neanderthal alleles in genes responsible for the regulation of transcription and neurogenesis. The enrichment of specific functional groups with Denisovan alleles is less pronounced; these groups are responsible for bone and tissue remodeling. This analysis shows that introgression of alleles from Neanderthals and Denisovans to Papuans occurred independently and retention of these alleles may carry specific adaptive advantages.

  • 11.
    Aktay, Serhat
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Computational Pipeline for Analyses of Genome-Wide Nascent Transcription from PRO-seq Data2023Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Celler har en rad olika sätt att försvara sig mot stress för att överleva, främst genom att reglera transkriptionen av gener. En metod för att undersöka hur cellens transkription förändras vid cellulär stress är precision run-on sequencing (PRO-seq). PRO-seq utnyttjar biotinkopplade nukleotider som förhindrar RNA polymeras från att inkorporera fler nukloetider efter den biotinkopplade. De olika RNA fragmenten med biotinkopplad nukleotid kan sedan separeras från all annan RNA i cellen och sedan sekvenseras. Målet med detta examensarbete är att förenkla analysen av sekvenserad PRO-seq data genom att utveckla en dataanalys-pipeline som gör denna typ av analys mer tillgänglig. Denna pipeline består av fem shell skript och tre R skript som skapar ett genomindex, laddar ned eller läser in experimentdata, anpassar data till genomet och producerar .bed och .bigWig filer för vidare analys. Genom att använda polymerasprofilen av nysyntetiserat RNA kan programmet vidare kartlägga funktionella genomregioner och analysera förändringen av genuttryck. I detta arbete användes data från värmechockade Homo sapiens, Canis lupis familiaris, Mus musculus, och Drosophila melanogaster celler. Denna analys ger en metod att studera genlängd, kartlägga funktionella genomregioner, kvantifiera mängden transkriberande RNA polymeras samt identifiera tidigare oidentifierade gener och genetiska förstärkare. Analysen visade att nyttjande av dubbelriktad transkription för att studera cellstress fungerar något bättre i däggdjur än insekter samt att gener som kodar för olika chaperoner var upreglerade i samtliga organismer. Denna pipeline är ett användarvänligt och standardiserat verktyg som hanterar storskaligt data och automatiserar analysen.

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  • 12.
    Albertsson, Ann-Christine
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Edlund, Ulrica
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Wood hydrolysates: From fractions to products2015Ingår i: Abstracts of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 249Artikel i tidskrift (Övrigt vetenskapligt)
  • 13.
    Albertsson, Ann-Christine
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Voepel, Jens
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Edlund, Ulrica
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi.
    Dahlman, Olof
    Soderqvist-Lindblad, Margaretha
    Design of Renewable Hydrogel Release Systems from Fiberboard Mill Wastewater2010Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 11, nr 5, s. 1406-1411Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A new route for the design of renewable hydrogels is presented. The soluble waste from masonite production was isolated, fractionized, and upgraded. The resulting hemicellulose rich fraction was alkenyl-functionalized and used in the preparation of covalently cross-linked hydrogels capable of sustained release of incorporated agents. Said hydrogels showed a Fickian diffusion-based release of incorporated bovine serum albumin. Also, a method for the coating of seeds with hydrogel was developed. The sustained release of incorporated growth retardant agents from the hydrogel coating on rape seeds was shown to enable the temporary inhibition of germination.

  • 14.
    Alexeyenko, Andrey
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lee, Woojoo
    Pernemalm, Maria
    Guegan, Justin
    Dessen, Philippe
    Lazar, Vladimir
    Lehtio, Janne
    Pawitan, Yudi
    Network enrichment analysis: extension of gene-set enrichment analysis to gene networks2012Ingår i: BMC Bioinformatics, E-ISSN 1471-2105, Vol. 13, s. 226-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Gene-set enrichment analyses (GEA or GSEA) are commonly used for biological characterization of an experimental gene-set. This is done by finding known functional categories, such as pathways or Gene Ontology terms, that are over-represented in the experimental set; the assessment is based on an overlap statistic. Rich biological information in terms of gene interaction network is now widely available, but this topological information is not used by GEA, so there is a need for methods that exploit this type of information in high-throughput data analysis. Results: We developed a method of network enrichment analysis (NEA) that extends the overlap statistic in GEA to network links between genes in the experimental set and those in the functional categories. For the crucial step in statistical inference, we developed a fast network randomization algorithm in order to obtain the distribution of any network statistic under the null hypothesis of no association between an experimental gene-set and a functional category. We illustrate the NEA method using gene and protein expression data from a lung cancer study. Conclusions: The results indicate that the NEA method is more powerful than the traditional GEA, primarily because the relationships between gene sets were more strongly captured by network connectivity rather than by simple overlaps.

  • 15.
    Alexeyenko, Andrey
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schmitt, Thomas
    Tjärnberg, Andreas
    Stockholm University, Science for Life Laboratory.
    Guala, Dmitri
    Stockholm University, Science for Life Laboratory.
    Frings, Oliver
    Stockholm University, Science for Life Laboratory.
    Sonnhammer, Erik L. L.
    Stockholm University, Science for Life Laboratory.
    Comparative interactomics with Funcoup 2.02012Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 40, nr D1, s. D821-D828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    FunCoup (http://FunCoup.sbc.su.se) is a database that maintains and visualizes global gene/protein networks of functional coupling that have been constructed by Bayesian integration of diverse high-throughput data. FunCoup achieves high coverage by orthology-based integration of data sources from different model organisms and from different platforms. We here present release 2.0 in which the data sources have been updated and the methodology has been refined. It contains a new data type Genetic Interaction, and three new species: chicken, dog and zebra fish. As FunCoup extensively transfers functional coupling information between species, the new input datasets have considerably improved both coverage and quality of the networks. The number of high-confidence network links has increased dramatically. For instance, the human network has more than eight times as many links above confidence 0.5 as the previous release. FunCoup provides facilities for analysing the conservation of subnetworks in multiple species. We here explain how to do comparative interactomics on the FunCoup website.

  • 16. Allerbring, Eva B.
    et al.
    Duru, Adil D.
    Chadderton, Jesseka
    Markov, Natalia
    Uchtenhagen, Hannes
    Popov, Alexander
    Madhurantakam, Chaithanya
    Sandalova, Tatyana
    Turner, Stephen J.
    Nygren, Per-Åke
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Achour, Adnane
    Structural and thermodynamic basis underlying in vivo reestablishment of T-cell recognition of a viral escape mutant2015Ingår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 68, nr 2, s. 151-151Artikel i tidskrift (Övrigt vetenskapligt)
  • 17.
    Alm, Tove
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Introducing the Affinity Binder Knockdown Initiative-A public-private partnership for validation of affinity reagents2016Ingår i: EuPA Open Proteomics, E-ISSN 2212-9685, Vol. 10, s. 56-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The newly launched Affinity Binder Knockdown Initiative encourages antibody suppliers and users to join this public-private partnership, which uses crowdsourcing to collect characterization data on antibodies. Researchers are asked to share validation data from experiments where gene-editing techniques (such as siRNA or CRISPR) have been used to verify antibody binding. The initiative is launched under the aegis of Antibodypedia, a database designed to allow comparisons and scoring of publicly available antibodies towards human protein targets. What is known about an antibody is the foundation of the scoring and ranking system in Antibodypedia.

  • 18.
    Alm, Tove
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    von Feilitzen, Kalle
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sivertsson, Åsa
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    A Chromosome-Centric Analysis of Antibodies Directed toward the Human Proteome Using Antibodypedia2014Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, nr 3, s. 1669-1676Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibodies are crucial for the study of human proteins and have been defined as one of the three pillars in the human chromosome-centric Human Proteome Project (CHPP). In this article the chromosome-centric structure has been used to analyze the availability of antibodies as judged by the presence within the portal Antibodypedia, a database designed to allow comparisons and scoring of publicly available antibodies toward human protein targets. This public database displays antibody data from more than one million antibodies toward human protein targets. A summary of the content in this knowledge resource reveals that there exist more than 10 antibodies to over 70% of all the putative human genes, evenly distributed over the 24 human chromosomes. The analysis also shows that at present, less than 10% of the putative human protein-coding genes (n = 1882) predicted from the genome sequence lack antibodies, suggesting that focused efforts from the antibody-based and mass spectrometry-based proteomic communities should be encouraged to pursue the analysis of these missing proteins. We show that Antibodypedia may be used to track the development of available and validated antibodies to the individual chromosomes, and thus the database is an attractive tool to identify proteins with no or few antibodies yet generated.

  • 19.
    Alm, Tove
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Yderland, Louise
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilvebrant, Johan
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Halldin, Anneli
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Hober, Sophia
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    A small bispecific protein selected for orthogonal affinity purification2010Ingår i: BIOTECHNOL J, ISSN 1860-6768, Vol. 5, nr 6, s. 605-617Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A novel protein domain with dual affinity has been created by randomization and selection. The small alkali-stabilized albumin-binding domain (ABD(star)), used as scaffold to construct the library, has affinity to human serum albumin (HSA) and is constituted of 46 amino acids of which 11 were randomized. To achieve a dual binder, the binding site of the inherent HSA affinity was untouched and the randomization was made on the opposite side of the molecule. Despite its small size and randomization of almost a quarter of its amino acids, a bifunctional molecule, ABDz1, with ability to bind to both HSA and the Z(2) domain/protein A was successfully selected using phage display. Moreover, the newly selected variant showed improved affinity for HSA compared to the parental molecule. This novel protein domain has been characterized regarding secondary structure and affinity to the two different ligands. The possibility for affinity purification on two different matrices has been investigated using the two ligands, the HSA matrix and the protein A-based, MabSelect SuRe matrix, and the new protein domain was purified to homogeneity. Furthermore, gene fusions between the new domain and three different target proteins with different characteristics were made. To take advantage of both affinities, a purification strategy referred to as orthogonal affinity purification using two different matrices was created. Successful purification of all three versions was efficiently carried out using this strategy.

  • 20.
    Almquist, Ann-Charlotte
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Fäldt, Jenny
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Yart, A.
    Chevet, Y.
    Sauvard, D.
    Lieutier, F.
    Borg-Karlson, Anna Karin
    KTH, Skolan för kemivetenskap (CHE), Kemi.
    Host selection in Tomicus piniperda L.: Composition of monoterpene hydrocarbons in relation to attack frequency in the shoot feeding phase2006Ingår i: Zeitschrift fur Naturforschung - Section C Journal of Biosciences, ISSN 0939-5075, Vol. 61, nr 5-6, s. 439-444Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate the host selection capacity of the pine shoot beetle, Tomicus piniperda, in the shoot-feeding phase and analyze the chiral and non-chiral host volatiles by means of GC-MS and 2D-GC in five Pinus species originating from France (Pinus sylvestris, P. halepensis, P. nigra laricio, P. pinaster maritima, P. pinaster mesogeensis). Dominating monoterpenes were (-)-α-pinene, (+)-α-pinene, (-)-β-pinene and (+)-3-carene. The amounts of the enantiomers varied considerably within and among the species. In a principal component analysis-plot, based on the absolute amounts of 18 monoterpene hydrocarbons, separation of the pine species into two groups was obtained. P. halepensis and P. sylvestris were grouped according to the amount of (+)-α-pinene and (+)-3-carene, while P. nigra laricio, P. pinaster maritima and P. pinaster mesogeensis were grouped according to (-)-α-pinene and (-)-β-pinene. P. nigra laricio was the species most attacked and P. halepensis the one least attacked by T. piniperda.

  • 21.
    Alneberg, Johannes
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bjarnason, Brynjar Smári
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    de Bruijn, Ino
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Bioinformatics Infrastructure for Life Sciences (BILS), Sweden.
    Schirmer, Melanie
    Quick, Joshua
    Ijaz, Umer Z.
    Lahti, Leo
    Loman, Nicholas J.
    Andersson, Anders F.
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Quince, Christopher
    Binning metagenomic contigs by coverage and composition2014Ingår i: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 11, nr 11, s. 1144-1146Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Shotgun sequencing enables the reconstruction of genomes from complex microbial communities, but because assembly does not reconstruct entire genomes, it is necessary to bin genome fragments. Here we present CONCOCT, a new algorithm that combines sequence composition and coverage across multiple samples, to automatically cluster contigs into genomes. We demonstrate high recall and precision on artificial as well as real human gut metagenome data sets.

  • 22. Altai, M.
    et al.
    Wallberg, H.
    Honarvar, H.
    Strand, J.
    Orlova, A.
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Varasteh, Z.
    Sandström, M.
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Tolmachev, V.
    Re-188-Z(HER2: V2), a promising targeting agent against HER2-expressing tumors: in vitro and in vivo assessment2013Ingår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, s. S119-S119Artikel i tidskrift (Övrigt vetenskapligt)
  • 23. Altai, Mohamed
    et al.
    Strand, Joanna
    Rosik, Daniel
    Selvaraju, Ram Kumar
    Eriksson Karlström, Amelie
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Orlova, Anna
    Tolmachev, Vladimir
    Influence of Nuclides and Chelators on Imaging Using Affibody Molecules: Comparative Evaluation of Recombinant Affibody Molecules Site-Specifically Labeled with Ga-68 and In-111 via Maleimido Derivatives of DOTA and NODAGA2013Ingår i: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 24, nr 6, s. 1102-1109Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more of personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use should increase sensitivity of HER2 imaging. The chemical nature of the generator-produced positron-emitting radionuclide Ga-68 of radionuclides and chelators influences the biodistribution of Affibody molecules, providing an opportunity to further increase the imaging contrast. The aim of the study was to compare maleimido derivatives of DOTA and NODAGA for site-specific labeling of a recombinant Z(HER2:2395) HER2-binding Affibody molecule with Ga-68. DOTA and NODAGA were site-specifically conjugated to the Z(HER2:2395) Affibody molecule having a C-terminal cysteine and labeled with Ga-68 and In-111. All labeled conjugates retained specificity to HER2 in vitro. Most of the cell-associated activity was membrane-bound with a minor difference in internalization rate. All variants demonstrated specific targeting of xenografts and a high tumor uptake. The xenografts were dearly visualized using all conjugates. The influence of chelator on the biodistribution and targeting properties was much less pronounced for Ga-68 than for In-111. The tumor uptake of Ga-68-NODAGA-Z(HER2:2395) and Ga-68-NODAGA-Z(HER2:2395) and tumor-to-blood ratios at 2 h p.i. did not differ significantly. However, the tumor-to-liver ratio was significantly higher for Ga-68-NODAGA- Z(HER2:2395) (8 +/- 2 vs 5.0 +/- 0.3) offering the advantage of better liver metastases visualization. In conclusion, influence of chelators on biodistribution of Affibody molecules depends on the radionuclides and reoptimization of labeling chemistry is required when a radionuclide label is changed.

  • 24. Altai, Mohamed
    et al.
    Wållberg, Helena
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Orlova, Anna
    Rosestedt, Maria
    Hosseinimehr, Seyed Jalal
    Tolmachev, Vladimir
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
    Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of Tc-99m-labeled recombinant Affibody molecules2012Ingår i: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 42, nr 5, s. 1975-1985Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Affibody molecules constitute a novel class of molecular display selected affinity proteins based on non-immunoglobulin scaffold. Preclinical investigations and pilot clinical data have demonstrated that Affibody molecules provide high contrast imaging of tumor-associated molecular targets shortly after injection. The use of cysteine-containing peptide-based chelators at the C-terminus of recombinant Affibody molecules enabled site-specific labeling with the radionuclide Tc-99m. Earlier studies have demonstrated that position, composition and the order of amino acids in peptide-based chelators influence labeling stability, cellular processing and biodistribution of Affibody molecules. To investigate the influence of the amino acid order, a series of anti-HER2 Affibody molecules, containing GSGC, GEGC and GKGC chelators have been prepared and characterized. The affinity to HER2, cellular processing of Tc-99m-labeled Affibody molecules and their biodistribution were investigated. These properties were compared with that of the previously studied Tc-99m-labeled Affibody molecules containing GGSC, GGEC and GGKC chelators. All variants displayed picomolar affinities to HER2. The substitution of a single amino acid in the chelator had an appreciable influence on the cellular processing of Tc-99m. The biodistribution of all Tc-99m-labeled Affibody molecules was in general comparable, with the main difference in uptake and retention of radioactivity in excretory organs. The hepatic accumulation of radioactivity was higher for the lysine-containing chelators and the renal retention of Tc-99m was significantly affected by the amino acid composition of chelators. The order of amino acids influenced renal uptake of some conjugates at 1 h after injection, but the difference decreased at later time points. Such information can be helpful for the development of other scaffold protein-based imaging and therapeutic radiolabeled conjugates.

  • 25.
    Ampomah, Osei Yaw
    et al.
    University of Tromso.
    Jensen, John Beck
    University of Tromso.
    Bhuvaneswari, T V
    University of Tromso.
    Lack of trehalose catabolism in Sinorhizobium species increases their nodulation competitiveness on certain host genotypes2008Ingår i: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 179, nr 2, s. 495-504Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of host and bacterial genotypes in determining the competitiveness of trehalose utilization mutants of Sinorhizobium meliloti and Sinorhizobium medicae was investigated here. Trehalose utilization mutants of S. meliloti and S. medicae were obtained by mutagenesis of their trehalose utilization gene thuB. The mutant strains and the wild type were coinoculated on three cultivars of alfalfa (Medicago sativa) and two cultivars of Medicago truncatula and assessed for competitiveness in root colonization, and nodule occupancy. The thuB mutants formed more nodules than their parent strains on two of the three alfalfa lines tested and on one of the two M. truncatula lines tested. They were not more competitive on the other alfalfa and M. truncatula lines. Their competitiveness for nodule occupancy did not correlate positively with their ability to colonize these roots but correlated with the extent of thuB induction in the infection threads. Induction of thuB was shown to be dependent on the concentration of trehalose in the environment. These results suggest a direct role for host trehalose metabolism in early plant-symbiont interactions and show that the ability to manage host-induced stresses during infection, rather than the ability to colonize the root, is critical for competitive nodulation.

  • 26.
    An, Junxue
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Yt- och korrosionsvetenskap.
    Dédinaité, Andra
    KTH, Skolan för kemivetenskap (CHE), Kemi, Yt- och korrosionsvetenskap.
    Nilsson, Anki
    Holgersson, Jan
    Claesson, Per M.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Yt- och korrosionsvetenskap.
    Comparison of a Brush-with-Anchor and a Train-of-Brushes Mucin on Poly(methyl methacrylate) Surfaces: Adsorption, Surface Forces, and Friction2014Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 15, nr 4, s. 1515-1525Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Interfacial properties of two types of mucins have been investigated at the aqueous solution/poly(methyl methacrylate) (PMMA) interface. One is commercially available bovine submaxillary mucin, BSM, which consists of alternating glycosylated and nonglycosylated regions. The other one is a recombinant mucin-type fusion protein, PSGL-1/mIgG(2b), consisting of a glycosylated mucin part fused to the Fc part of an immunoglobulin. PSGL-1/mIgG(2b) is mainly expressed as a (timer upon production. A quartz crystal microbalance with dissipation was used to study the adsorption of the mucins to PMMA surfaces. The mass of the adsorbed mucin layers, including the adsorbed mucin and water trapped in the layer, was found to be significantly higher for PSGL-1/mIgG(2b) than for BSM. Atomic force microscopy with colloidal probe was employed to study interactions and frictional forces between mucin-coated PMMA surfaces. Purely repulsive forces of steric origin were Observed between PSGL-1/mIgG(2b) mucin layers, whereas a small adhesion was detected between BSM layers and attributed to bridging. Both mucin layers reduced the friction force between PMMA surfaces in aqueous solution. The reduction was, however, significantly more pronounced for PSGL-1/mIgG(2b). The effective friction coefficient between PSGL-1/mIgG(2b)-coated PMMA surfaces is as low as 0.02 at low loads, increasing to 0.24 at the highest load explored, 50 nN. In contrast, a friction coefficient of around 0.7 was obtained between BSM-coated PMMA surfaces. The large differences in interfacial properties for the two mucins are discussed in relation to their structural differences.

  • 27. Anderbrant, Olle
    et al.
    Matteson, Donald S.
    Unelius, C. Rikard
    Pharazyn, Philip S.
    Santangelo, Ellen M.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Organisk kemi.
    Schlyter, Fredrik
    Birgersson, Goran
    Pheromone of the elm bark beetle Scolytus laevis (Coleoptera Scolytidae): stereoisomers of 4-methyl-3-heptanol reduce interspecific competition2010Ingår i: Chemoecology, ISSN 0937-7409, E-ISSN 1423-0445, Vol. 20, nr 3, s. 179-187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stereoisomers of 4-methyl-3-heptanol (MH) are pheromone components of several Scolytus bark beetles. The elm bark beetle Scolytus laevis (Coleoptera: Scolytidae) has in previous studies been caught in traps baited with commercial MH containing all four stereoisomers, but the lure has been considered a weak attractant. In this study, we addressed the question whether stereospecific responses by S. laevis to stereoisomers of MH might contribute to its niche separation from other sympatric Scolytus species. Using GC-MS, we analyzed extracts of hindguts and abdomens from male and female S. laevis and the sympatric S. triarmatus. We also tested all four MH-stereoisomers individually and in combinations in the field to determine their role for S. laevis. All four stereoisomers were synthesized via a boronic ester method with 1,2-dicyclohexylethanediol as chiral director. In addition, the (3S,4R)-stereoisomer of MH was prepared through enantioselective, lipase-mediated transesterification of a mixture of the four stereoisomers of MH. Females of both species contained small amounts of syn-MH, and males contained trace amounts of anti-MH. The anti stereoisomer (3R,4S)-MH was attractive to male and female S. laevis, whereas the syn stereoisomer (3S,4S)-MH acted as an inhibitor or deterrent and reduced the catch when added to the attractive isomer. The syn isomer is the main aggregation pheromone component of the larger and sympatric S. scolytus and possibly also of S. triarmatus. The avoidance response of S. laevis to the (3S,4S)-stereoisomer may reduce interspecific competition for host trees.

  • 28.
    Andersen, Malin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Engström, Pär
    Lithwick, Stuart
    Arenillas, David
    Eriksson, Per
    Lenhard, Boris
    Wasserman, Wyeth
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    In silico detection of sequence variations modifying transcriptional regulation2008Ingår i: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 4, nr 1, s. e5-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN ( regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation.

  • 29.
    Andersen, Malin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Lenhard, Boris
    Whatling, Carl
    Eriksson, Per
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Alternative promoter usage of the membrane glycoprotein CD362006Ingår i: BMC Molecular Biology, E-ISSN 1471-2199, Vol. 7, s. 8-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation.

    Results: We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters.

    Conclusion: Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

  • 30.
    Anderson, Mattias
    KTH, Skolan för bioteknologi (BIO), Industriell bioteknologi.
    Amine Transaminases in Multi-Step One-Pot Reactions2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Amine transaminases are enzymes that catalyze the mild and selective formation of primary amines, which are useful building blocks for biologically active compounds and natural products. In order to make the production of these kinds of compounds more efficient from both a practical and an environmental point of view, amine transaminases were incorporated into multi-step one-pot reactions. With this kind of methodology there is no need for isolation of intermediates, and thus unnecessary work-up steps can be omitted and formation of waste is prevented. Amine transaminases were successfully combined with other enzymes for multi-step synthesis of valuable products: With ketoreductases all four diastereomers of a 1,3-amino alcohol could be obtained, and the use of a lipase allowed for the synthesis of natural products in the form of capsaicinoids. Amine transaminases were also successfully combined with metal catalysts based on palladium or copper. This methodology allowed for the amination of alcohols and the synthesis of chiral amines such as the pharmaceutical compound Rivastigmine. These examples show that the use of amine transaminases in multi-step one-pot reactions is possible, and hopefully this concept can be further developed and applied to make industrial processes more sustainable and efficient in the future.

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  • 31.
    Andersson, Alma
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Bergenstråhle, Joseph
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Asp, Michaela
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bergenstrahle, Ludvig
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Jurek, Aleksandra
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fernandez Navarro, Jose
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Single-cell and spatial transcriptomics enables probabilistic inference of cell type topography2020Ingår i: Communications Biology, E-ISSN 2399-3642, Vol. 3, nr 1, artikel-id 565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The field of spatial transcriptomics is rapidly expanding, and with it the repertoire of available technologies. However, several of the transcriptome-wide spatial assays do not operate on a single cell level, but rather produce data comprised of contributions from a – potentially heterogeneous – mixture of cells. Still, these techniques are attractive to use when examining complex tissue specimens with diverse cell populations, where complete expression profiles are required to properly capture their richness. Motivated by an interest to put gene expression into context and delineate the spatial arrangement of cell types within a tissue, we here present a model-based probabilistic method that uses single cell data to deconvolve the cell mixtures in spatial data. To illustrate the capacity of our method, we use data from different experimental platforms and spatially map cell types from the mouse brain and developmental heart, which arrange as expected.

  • 32. Andersson, E.
    et al.
    Stenrup, Michael
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi.
    Eland, J.H.D.
    Hedin, L.
    Berglund, M.
    Karlsson, L.
    Larson, Åsa
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi.
    Ågren, Hans
    KTH, Skolan för bioteknologi (BIO), Teoretisk kemi.
    Rubensson, Jan Erik
    Feifel, Raimund
    Single-photon core-valence double ionization of molecular oxygen2008Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics, ISSN 1050-2947, E-ISSN 1094-1622, Vol. 78, nr 2, s. 023409-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Single-photon core-valence double ionization of molecular oxygen has been studied using a magnetic bottle time-of-flight electron coincidence spectrometer. The K-1 V-1 double ionization electron spectrum of O2 is reported and is assigned with the aid of ab initio calculations. A direct comparison of the core-valence double ionization electron spectra with the conventional valence band photoelectron spectrum is made. The lowest core-valence double ionization energy is found to be 571.6 eV and is associated with a Π3 dicationic state.

  • 33.
    Andersson, Helene
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    van den Berg, A.
    Microfabrication and microfluidics for tissue engineering: state of the art and future opportunities2004Ingår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 4, nr 2, s. 98-103Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    An introductory overview of the use of microfluidic devices for tissue engineering is presented. After a brief description of the background of tissue engineering, different application areas of microfluidic devices are examined. Among these are methods for patterning cells, topographical control over cells and tissues, and bioreactors. Examples where microfluidic devices have been employed are presented such as basal lamina, vascular tissue, liver, bone, cartilage and neurons. It is concluded that until today, microfluidic devices have not been used extensively in tissue engineering. Major contributions are expected in two areas. The first is growth of complex tissue, where microfluidic structures ensure a steady blood supply, thereby circumventing the well-known problem of providing larger tissue structures with a continuous flow of oxygen and nutrition, and withdrawal of waste products. The second, and probably more important function of microfluidics, combined with micro/nanotechnology, lies in the development of in vitro physiological systems for studying fundamental biological phenomena.

  • 34.
    Andersson, Helene
    et al.
    KTH, Tidigare Institutioner (före 2005), Signaler, sensorer och system.
    van den Berg, A.
    Microtechnologies and nanotechnologies for single-cell analysis2004Ingår i: Current Opinion in Biotechnology, ISSN 0958-1669, E-ISSN 1879-0429, Vol. 15, nr 1, s. 44-49Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Many efforts are currently underway to try and mimic the properties of single cells with the aim of designing chips that are as efficient as cells. However, cells are nature's nanotechnology engineering at the scale of atoms and molecules, and it might be better to envision a microchip that utilizes a single cell as an experimentation platform. A novel, so-called laboratory-in-a-cell concept has been described, where advantage is taken of micro-and nanotechnological tools to enable precise control of the biochemical cellular environment; these tools also offer the possibility to analyse the composition of single cells. Methods for single-cell handling and analysis are being developed and will be required for this concept to progress further.

  • 35.
    Andersson, Jessica
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Kemi.
    Effect of triclosan on the growth of an oomycete pathogen by mass spectrometry-based comparative proteomics2023Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Oomyceten Saprolegnia parasitica är en opportunistisk parasit som infekterar fiskägg, samt ung och vuxen fisk. Infektionen orsakar en sjukdom som kallas saprolegniasis, och syns som fläckar på värden. Detta är ett allvarligt problem i fiskodlingar eftersom förhållandena med hög populationstäthet samt en ökad risk för stress och skador skapar en miljö där parasiten kan frodas. Vattenbruket bidrar till nästan hälften av livsmedelsfiskindustrin, men en stor del av den odlade fisken går förlorad på grund av saprolegniasis. Andra alternativ har både använts och undersökts, men de har visat sig vara ineffektiva eller hade negativa effekter på hälsa och miljö. Före detta projekt hade labbgruppen utfört en studie, där man hittade FDA-godkända läkemedel som kunde återanvändas för att rikta in sig på förutspådda essentiella proteiner i organismen. Triklosan visade sig ha lägst MIC100 på 4 µg/ml och är den utvalda inhibitorn för projektet, som är en masspektrometribaserad, storskalig, och jämförande proteomikstudie, vilken jämför prover av S. parasitica odlad med och utan triclosan som inhibitor.

    Proverna odlades i flytande media och undersöktes med mikroskopi, vilket visade en hög grad av förgrening av hyferna i de behandlade proverna medan de i kontrollen var långa och släta. Detta följdes av SDS-PAGE, proteinfragmentering i gel med trypsin och analys med masspektrometri. Resulterande rådata analyserades sedan med hjälp av flera program online, som detekterade totalt 1478 olika proteiner. 515 av dessa valdes ut och annoterades funktionellt, vilket genererade information om vilka biologiska processer de är involverade i. Proteinerna delades in i 11 olika kategorier av biologiska processer och proteinerna inom dessa jämfördes mellan de behandlade och obehandlade proverna. De huvudsakliga grupperna som upptäcktes skilja mellan behandlade och obehandlade var tyrosinkinasliknande (TKL) proteinkinaser, Ca2+/kalmodulinberoende proteinkinaser (CAMK) och aminopeptidaser. Proteinerna kategoriserades också i olika superfamiljer, av vilka superfamiljen NADB_Rossmann, superfamiljen AdoMet_MTases och superfamiljen PknB_PASTA_kin hade de högsta antalen proteiner i den behandlade/obehandlade gruppen, men inga i den andra. Proteinerna i dessa superfamiljer undersöktes ytterligare.

  • 36.
    Andersson, Ken G.
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Combinatorial Protein Engineering Of Affibody Molecules Using E. Coli Display And Rational Design Of Affibody-Based Tracers For Medical Imaging2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Directed evolution is today an established strategy for generation of new affinity proteins. This thesis describes the development of a cell-display method using Escherichia coli for directed evolution of Affibody molecules. Further, the thesis describes rational design of Affibody-based tracers, intended for future patient stratification using medical imaging. Fusing recombinant proteins to various autotransporters is a promising approach for efficient surface display on the surface of E. coli, as well as for construction of high-complexity libraries. In paper I, we successfully engineered an expression vector for display of Affibody molecules using the autotransporter AIDA-I. In paper II, a large Affibody library of 2.3x109 variants was constructed and screening using FACS resulted in new specific binders in the nanomolar range. In paper III, we demonstrated Sortase-mediated secretion and conjugation of binders directly from the E. coli surface. 

    The three following studies describe rational design of Affibody-based tracers against two cancer-associated targets for molecular imaging. First, anti-HER3 Affibody molecules were labelled with 111In, and SPECT imaging showed that the conjugates specifically targeted HER3-expressing xenografts. Furthermore, labeling with 68Ga for PET imaging showed that tumor uptake correlated with HER3 expression, suggesting that the tracers have potential for patient stratification. The last study describes the development and investigation of anti-EGFR Affibody-based imaging agents. Labeled with 89Zr, the Affibody tracer demonstrated higher tumor uptake at 3 h post injection than the anti-EGFR antibody cetuximab at 48 h post injection. 

    In conclusion, this thesis describes new tools and knowledge that will hopefully contribute to the development of affinity proteins for biotechnology, therapy and medical imaging in the future. 

     

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    20170831 Avhandling Kappa Ken Andersson
  • 37.
    Andersson, Ken G.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Persson, Jonas
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi. Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden.
    Ståhl, Stefan
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Autotransporter-mediated display of a naïve Affibody library on the outer membrane of E. coliManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Development of new affinity proteins using combinatorial protein engineering is today established for generation of monoclonal antibodies and also essential for discovery of binders that are based on non-immunoglobulin proteins. Phage display is the most frequently used method, but yeast display is becoming increasingly popular, partly due to the option of utilizing fluorescence-activated cell sorting (FACS) for isolation of new candidates. Escherichia coli have several properties that are valuable for library applications and then in particular the high transformation efficiency. Although the first studies on display of recombinant peptides and proteins on E. coli were reported over 25 years ago, the method is still not fully established for directed evolution of affinity proteins. More recently, the use of various autotransporters and intimins for secretion and anchoring on the outer membrane have shown promising results and in particular for directed evolution of different enzymes. Here, we report on display of a large naïve Affibody library on the outer membrane of E. coli using the autotransporter AIDA-I. The expression cassette was first engineered by removing non-essential sequences, followed by introduction of an Affibody library, comprising more than 109 variants, into the new display vector. Selections by FACS against five different target molecules resulted in a panel of binders with down to nanomolar affinities.

  • 38.
    Andersson, Ken G.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Sjöstrand, Nanna
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi.
    Löfblom, John
    KTH, Skolan för bioteknologi (BIO), Proteinteknologi. KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Coupled release and site-specific conjugation of Affibody molecules from the surface of E. coli using Sortase AManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Combinatorial protein engineering using libraries displayed on various microorganisms is a powerful method forgeneration of new affinity proteins. Successful efforts often result in broad panels of isolated binders, which are thentypically subcloned, produced, purified and characterized in various assays. Many such assays also require conjugation tofor example reporters or other functional molecules and the downstream production and modification thus tends to be verylaborious and limits the number of candidates that can be screened. Staphylococcal sortase A is a natural transpeptidasethat catalyzes the ligation between a LPXTG motif and N-terminal glycines and is today used in a variety of applicationsfor site-specific conjugation of different molecules to recombinant proteins. We have previously developed a surfacedisplay method for combinatorial protein engineering of Affibody molecules on the outer membrane of E. coli usingautodisplay. Here, we introduced a sortase-A recognition motif into the displayed recombinant proteins and evaluatedsortase-mediated release and specific conjugation of various reporters to Affibody molecules. The approach has potentialto significantly increase the flexibility and throughput of downstream characterization of affinity proteins after directedevolution using cell display and FACS.

  • 39.
    Andersson, Robert
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemiteknik.
    Boutonnet, Magali
    KTH, Skolan för kemivetenskap (CHE), Kemiteknik, Kemisk teknologi.
    Järås, Sven
    KTH, Skolan för kemivetenskap (CHE), Kemiteknik.
    On-line gas chromatographic analysis of higher alcohol synthesis products from syngas2012Ingår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1247, s. 134-145Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An on-line gas chromatographic (GC) system has been developed for rapid and accurate product analysis in catalytic conversion of syngas (a mixture of H-2 and CO) to alcohols, so called "higher alcohol synthesis (HAS)". Conversion of syngas to higher alcohols is an interesting second step in the route of converting coal, natural gas and possibly biomass to liquid alcohol fuel and chemicals. The presented GC system and method are developed for analysis of the products formed from syngas using alkali promoted MoS2 catalysts, however it is not limited to these types of catalysts. During higher alcohol synthesis not only the wanted short alcohols (similar to C-2-C-5) are produced, but also a great number of other products in smaller or greater amounts, they are mainly short hydrocarbons (olefins, paraffins, branched, non-branched), aldehydes, esters and ketones as well as CO2, H2O. Trace amounts of sulfur-containing compounds can also be found in the product effluent when sulfur-containing catalysts are used and/or sulfur-containing syngas is feed. In the presented GC system, most of them can be separated and analyzed within 60 min without the use of cryogenic cooling. Previously, product analysis in "higher alcohol synthesis" has in most cases been carried out partly on-line and partly off-line, where the light gases (gases at room temp) are analyzed on-line and liquid products (liquid at room temp) are collected in a trap for later analysis off-line. This method suffers from many drawbacks compared to a complete on-line GC system. In this paper an on-line system using an Agilent 7890 gas chromatograph equipped with two flame ionization detectors (FID) and a thermal conductivity detector (TCD), together with an Agilent 6890 with sulfur chemiluminescence dual plasma detector (SCD) is presented. A two-dimensional GC system with Deans switch (heart-cut) and two capillary columns (HP-FFAP and HP-Al2O3) was used for analysis of the organic products on the FIDs. Light inorganic gases (H-2, CO, CO2, N-2) and methane were separated on packed columns and quantified with the TCD. The "sulfur GC" was optimized for on-line trace level sulfur analysis in hydrocarbon matrices and used to understand to which degree sulfur is released from the catalyst and incorporated into the liquid product, and if so in which form. The method provides excellent quantitative measurements with a carbon material balance near 99.5% (carbon in/carbon out) for individual measurement points.

  • 40.
    Andersson Svahn, Helene
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik. University of Twente, Netherlands .
    Van Den Berg, A.
    Single cells or large populations?2007Ingår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 7, nr 5, s. 544-546Artikel i tidskrift (Refereegranskat)
  • 41.
    Andre, Sabine
    et al.
    Univ Munich, Inst Physiol Chem, Tierarztliche Fak, D-80539 Munich, Germany..
    Lahmann, Martina
    Univ Bangor, Sch Chem, Bangor LL57 2UW, Gwynedd, Wales..
    Gabius, Hans-Joachim
    Univ Munich, Inst Physiol Chem, Tierarztliche Fak, D-80539 Munich, Germany..
    Oscarson, Stefan
    Univ Coll Dublin, Ctr Synth & Chem Biol, Dublin 4, Ireland..
    Glycocluster Design for Improved Avidity and Selectivity in Blocking Human Lectin/Plant Toxin Binding to Glycoproteins and Cells2010Ingår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 7, nr 6, s. 2270-2279Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Blocking lectin/toxin binding to human cells by suitable inhibitors can therapeutically protect them from harmful effects. Clustered design of ligand presentation holds the promise of affinity increase relative to the free sugar and inherent selectivity among lectin targets. Using first a solid-phase assay with a glycoprotein presenting N-glycans as lectin-reactive probe, we assessed the inhibitory potency of bi- to tetravalent clusters on a plant toxin and three human adhesion/growth-regulatory lectins. Enhanced avidity relative to the free sugar was detected together with lectin-type selectivity. These effects were confirmed on the level of cells in vitro, also for two leguminous lectins. The lack of toxicity in cell proliferation assays excluded concerns to further work on these compounds. The given cluster design and the strategic combination of the two assay systems of increasing biorelevance will thus be helpful to take the next steps in drug development, e.g. tailoring the sugar headgroup.

  • 42.
    Andén, Olivia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Genteknologi.
    Structural basis of modulation by pH and calcium in a ligand-gated ion channel2021Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Pentameriska ligandstyrda jonkanaler (pLGICs) är avgörande för omvandlingen av kemisk till elektrisk signalöverföring i djurs nervsystem. Dysfunktion i dessa kanaler har visat sig vara kopplad till flera sjukdomar inklusive epilepsi, schizofreni, Alzheimers och autism, vilket gör dem till en måltavla för en mängd olika läkemedel. Att studera eukaryota kanaler är dock mycket utmanande, så upptäckten av prokaryota homologer, som är mycket lättare att studera, har därmed bidragit mycket till förståelsen för struktur och funktion hos proteiner i denna familj. I detta projekt producerades och renades en prokaryotisk pLGIC kallad DeCLIC från Escherichia coli. Strukturell bestämning av kanalen genomfördes med användning av kryo-elektronmikroskopi vid lågt pH och i närvaro av kalcium. En elektrontäthet med 3.4 Å upplösning uppnåddes och jämfördes med tidigare bestämda strukturer vid olika förhållanden i ett försök att bestämma hur proteinets struktur moduleras av kalcium och pH. Resultaten visar flera skillnader i kanalens konformation i närvaro och frånvaro av kalcium såväl som vid olika pH-värden. Dessutom antyder analys av den bestämda elektrontätheten ett möjligt intermediärt tillstånd vid lågt pH i närvaro av kalcium.

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    fulltext
  • 43. Andõn, F. T.
    et al.
    Kapralov, A. A.
    Yanamala, N.
    Feng, W.
    Baygan, Arjang
    Karolinska Institutet.
    Chambers, B. J.
    Hultenby, K.
    Ye, Fei
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Material- och nanofysik, Funktionella material, FNM.
    Toprak, Muhammet S.
    KTH, Skolan för informations- och kommunikationsteknik (ICT), Material- och nanofysik, Funktionella material, FNM.
    Brandner, B. D.
    Fornara, Andrea
    Institute for Surface Chemistry, Stockholm.
    Klein-Seetharaman, J.
    Kotchey, G. P.
    Star, A.
    Shvedova, Anna A.
    West Virginia University, USA.
    Fadeel, B.
    Kagan, V. E.
    Biodegradation of Single-Walled Carbon Nanotubes by Eosinophil Peroxidase2013Ingår i: Small, ISSN 1613-6810, E-ISSN 1613-6829, Vol. 9, nr 16, s. 2721-2729Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Eosinophil peroxidase (EPO) is one of the major oxidant-producing enzymes during inflammatory states in the human lung. The degradation of single-walled carbon nanotubes (SWCNTs) upon incubation with human EPO and H2O 2 is reported. Biodegradation of SWCNTs is higher in the presence of NaBr, but neither EPO alone nor H2O2 alone caused the degradation of nanotubes. Molecular modeling reveals two binding sites for SWCNTs on EPO, one located at the proximal side (same side as the catalytic site) and the other on the distal side of EPO. The oxidized groups on SWCNTs in both cases are stabilized by electrostatic interactions with positively charged residues. Biodegradation of SWCNTs can also be executed in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. Biodegradation is proven by a range of methods including transmission electron microscopy, UV-visible-NIR spectroscopy, Raman spectroscopy, and confocal Raman imaging. Thus, human EPO (in vitro) and ex vivo activated eosinophils mediate biodegradation of SWCNTs: an observation that is relevant to pulmonary responses to these materials. Human eosinophil peroxidase (EPO) is able to degrade SWCNTs in vitro in the presence of H2O2. EPO is one of the major oxidant-generating enzymes present in human lungs during inflammatory states. The biodegradation of SWCNTs is evidenced also in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. These results are relevant to potential respiratory exposure to carbon nanotubes.

  • 44.
    Aniander, Gustav
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Improved candidate screening through tailored co-culture assays and precise tuning of protein expression2024Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Det biologiska läkemedelsfältet är i snabb tillväxt. De senaste tio åren har antalet godkända biologiska läkemedel mer än fördubblats. Den höga kostnaden för behandlingar med biologiska läkemedel är dock ett stort hinder som måste överkommas för att öka tillgängligheten till nya, effektiva behandlingar. Mycket av kostnaden kan attribueras till den långa utvecklingstiden för dem. Som en följd av detta har intresset för förbättringar av biologiska läkemedel och deras framställningsprocess även det ökat kraftigt. Eftersom kostnaderna ökar desto längre in i processen en läkemedelskandidat tar sig är förbättringar av tidiga tester av läkemedelskandidater en god kandidat till att minska de stora kostnaderna för läkemedelsutveckling.

    I artikel I visar vi ett nytt sätt för att rikta läkemedel mot tumörmikromiljön (TME) och möjliggöra TMEriktad CD40-aktivering. Detta är av intresse då CD40- agonister har visat stor potential för immunaktivering, men lidit av bieffekter som uppkommit av systemisk immunaktivering. Den lokaliserade immunaktiveringen uppnås genom ett fuserat affinitetsprotein benämnt AffiMab, där en affibody riktat mot trombocytrelaterad tillväxtfaktor beta (PDGFRβ) fuserats till den tunga kedjan av en CD40-agonistisk monoklonal antikropp (mAb). Vi visar PDGFRβ-beroende aktivering i ett flertal av aktiveringsanalyser, vilket visar att tillvägagångssättet meriterar fortsatt forskning.

    Som en påbyggnad till arbetssättet för utvärdering i artikel I avser vi att generera en in vitro platform för utvärdering av immune cell engagers i artikel II. Att utvärdera kandidater för aktivering som är on-target off tumor är essentiellt, då sådan aktivering leder till bieffekter som begränsar doseringen av läkemedlet. För att utvärdera detta konstruerar vi en serie plasmider som efter transfektion leder till olika uttrycksnivåer att ett målprotein på cellytan, en så kallad target density panel. Vi uppnår detta genom att använda oss av hårnålsbildande element i den otranslaterade 5’ regionen av mRNAt benämnda regulatoriska element (RgEs). Genom att använda oss av olika RgEs kan vi visa att olika målproteinsdensiteter kan genereras samt validera dem i aktiveringsanalyser med AffiMaben som utvecklades i artikel I. Den uniforma bakgrunden på cellytorna som följd av att alla nivåer av målprotein uttrycks i samma cellinje samt plattformens reglerbarhet genom användande av olika RgEs är egenskaper som gör att plattformen är intressant för vidare forskning.

    Slutligen konstruerar vi en förbättrad sekvens för translationinitieringssstället (TIS) och testar den i artikel III. Med grund i tidigare studier kring vilken inverkan olika nukleotider i sekvensen har på effektiviteten hos en TIS konstruerar vi en ny sekvens, TISNOV. Denna sekvens uppvisar ökad titer och kvalitet för rekombinant produktion av IgG1 och IgG4 i transienta och stabila miljöer. Det är av fortsatt intresse att forska djupare kring andra sekvenser av TIS samt deras användning för att förbättra uttrycket av svåruttryckta proteiner såsom bispecifiker.

    Sammanfattningsvis har denna avhandling fokuserat på olika tillvägagångssätt för att förbättra och påskynda utveckling av nya biologiska läkemedel, såsom nya arbetssätt, nya analysplattformar, och strategier för genmanipulation.

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    GAniander_Lic
  • 45.
    Aniander, Gustav
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Mirazadeh, Kiavash
    Xbrane Biopharma Retzius väg 8 171 65 Solna.
    Thalén, Niklas
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Volk, Anna-Luisa
    Xbrane Biopharma Retzius väg 8 171 65 Solna.
    Samuelson, Patrik
    Rockberg, Johan
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Enhanced titer and quality of IgGs through alterations at the translation initiation sequenceManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Enhancing recombinant expression in mammalian cells remains an important and valuable goal. Much work has been done to develop cell lines, growth conditions, and expression vectors. However, some parts of the expression vector have been comparatively neglected in this quest for improvement. One such part is the translation initiation site (TIS) sequence, which drives translation initiation by increasing ribosomal recognition of the start codon. Using earlier work on what nucleotides could be exchanged for increased expression, we here present a novel TIS sequence. This TIS sequence increased titer in transient settings 4-fold while yielding 13-33 % increase in titer in final selected stable clones. This increase also comes with an increase in quality through reduction in non-paired chains, shift in charged species distribution, whilst maintaining the glycosylation profile. This increase in both titer and quality in transient and stable settings showing that TIS sequence engineering is of great interest for optimizing recombinant production in mammalian cells.

  • 46.
    Ansari, Farhan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.
    Berglund, Lars A.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.
    Toward Semistructural Cellulose Nanocomposites: The Need for Scalable Processing and Interface Tailoring2018Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, nr 7, s. 2341-2350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cellulose nanocomposites can be considered for semistructural load-bearing applications where modulus and strength requirements exceed 10 GPa and 100 MPa, respectively. Such properties are higher than for most neat polymers but typical for molded short glass fiber composites. The research challenge for polymer matrix biocomposites is to develop processing concepts that allow high cellulose nanofibril (CNF) content, nanostructural control in the form of well-dispersed CNF, the use of suitable polymer matrices, as well as molecular scale interface tailoring to address moisture effects. From a practical point of view, the processing concept needs to be scalable so that large-scale industrial processing is feasible. The vast majority of cellulose nanocomposite studies elaborate on materials with low nanocellulose content. An important reason is the challenge to prevent CNF agglomeration at high CNF content. Research activities are therefore needed on concepts with the potential for rapid processing with controlled nanostructure, including well-dispersed fibrils at high CNF content so that favorable properties are obtained. This perspective discusses processing strategies, agglomeration problems, opportunities, and effects from interface tailoring. Specifically, preformed CNF mats can be used to design nanostructured biocomposites with high CNF content. Because very few composite materials combine functional and structural properties, CNF materials are an exception in this sense. The suggested processing concept could include functional components (inorganic clays, carbon nanotubes, magnetic nanoparticles, among others). In functional three-phase systems, CNF networks are combined with functional components (nanoparticles or fibril coatings) together with a ductile polymer matrix. Such materials can have functional properties (optical, magnetic, electric, etc.) in combination with mechanical performance, and the comparably low cost of nanocellulose may facilitate the use of large nanocomposite structures in industrial applications.

  • 47.
    Ansari, Farhan
    et al.
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Biokompositer. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.
    Salajkova, Michaela
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Biokompositer. KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Träkemi och massateknologi.
    Zhou, Qi
    KTH, Skolan för bioteknologi (BIO), Glykovetenskap. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.
    Lars, Berglund
    KTH, Skolan för kemivetenskap (CHE), Fiber- och polymerteknologi, Biokompositer. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.
    Strong surface treatment effects on reinforcement efficiency in biocomposites based on cellulose nanocrystals in poly(vinyl acetate) matrix2015Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 16, nr 12, s. 3916-3924Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this work, the problem to disperse cellulose nanocrystals (CNC) in hydrophobic polymer matrices has been addressed through application of an environmentally friendly chemical modification approach inspired by clay chemistry. The objective is to compare the effects of unmodified CNC and modified CNC (modCNC) reinforcement, where degree of CNC dispersion is of interest. Hydrophobic functionalization made it possible to disperse wood-based modCNC in organic solvent and cast well-dispersed nanocomposite films of poly(vinyl acetate) (PVAc) with 1-20 wt % CNC. Composite films were studied by infrared spectroscopy (FT-IR), UV-vis spectroscopy, dynamic mechanical thermal analysis (DMTA), tensile testing, and field-emission scanning electron microscopy (FE-SEM). Strongly increased mechanical properties were observed for modCNC nanocomposites. The reinforcement efficiency was much lower in unmodified CNC composites, and specific mechanisms causing the differences are discussed.

  • 48.
    Apostolov, Rossen
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Centra, Parallelldatorcentrum, PDC.
    Yonezawa, Yasushige
    Standley, Daron M
    Kikugawa, Gota
    Takano, Yu
    Nakamura, Haruki
    Membrane attachment facilitates ligand access to the active site in monoamine oxidase A2009Ingår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 48, nr 25, s. 5864-5873Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Monoamine oxidase membrane enzymes are responsible for the catalytic breakdown of extra- and intracellular neurotransmitters and are targets for the development of central nervous system drugs. We analyzed the dynamics of rat MAOA by performing multiple independent molecular dynamics simulations of membrane-bound and membrane-free forms to clarify the relationship between the mechanics of the enzyme and its function, with particular emphasis on the significance of membrane attachment. Principal component analysis of the simulation trajectories as well as correlations in the fluctuations of the residues pointed to the existence of three domains that define the global dynamics of the protein. Interdomain anticorrelated movements in the membrane-bound system facilitated the relaxation of interactions between residues surrounding the substrate cavity and induced conformational changes which expanded the active site cavity and opened putative pathways for substrate uptake and product release. Such events were less pronounced in the membrane-free system due to differences in the nature of the dominant modes of motion. The presence of the lipid environment is suggested to assist in decoupling the interdomain motions, consistent with the observed reduction in enzyme activity under membrane-free conditions. Our results are also in accordance with mutational analysis which shows that modifications of interdomain hinge residues decrease the activity of rat MAOA in solution.

  • 49. Araujo, Rafael B.
    et al.
    Chakraborty, Sudip
    Ahuja, Rajeev
    KTH, Skolan för industriell teknik och management (ITM), Materialvetenskap, Tillämpad materialfysik. Uppsala University, Sweden .
    Unveiling the charge migration mechanism in Na2O2: implications for sodium-air batteries2015Ingår i: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 17, nr 12, s. 8203-8209Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Metal-air batteries have become promising candidates for modern energy storage due to their high theoretical energy density in comparison to other storage devices. The lower overpotential of Na compared with Li makes Na-air batteries more efficient in terms of battery lifetime. Additionally, the abundance of Na over Li is another advantage for Na batteries compared to Li batteries. Na2O2 is one of the main products of sodium-air battery reactions. The efficiency of air cells is always related to the charge transport mechanisms in the formed product. To unveil these diffusion mechanisms in one of the main products of the cell reaction Na-O-2 we systematically investigate the mobility of charge carriers as well as the electronic structural properties of sodium peroxide. The framework of the density functional theory based on hybrid functional approach is used to study the mobility of charge carriers and intrinsic defects in Na2O2. Our calculations reveal that the formation of small electron and hole polarons is preferentially occurring over the delocalized state in the crystal structure of Na2O2. The migration of these small polarons displays activation energies of about 0.92 eV and 0.32 eV for the electron and hole polarons respectively, while the analysis of the charged sodium vacancy mobility reveals an activation energy of about 0.5 eV. These results suggest that the charge transport in sodium peroxide would mainly occur through the diffusion of hole polarons.

  • 50.
    Arend, Giordana Demaman
    et al.
    Univ Fed Santa Catarina, Dept Chem & Food Engn, Florianopolis, SC, Brazil..
    Soares, Lenilton Santos
    Univ Fed Santa Catarina, Dept Chem & Food Engn, Florianopolis, SC, Brazil..
    Camelo-Silva, Callebe
    Univ Fed Santa Catarina, Dept Chem & Food Engn, Florianopolis, SC, Brazil..
    Ribeiro Sanches, Marcio Augusto
    State Univ Sao Paulo, Food Engn & Technol Dept, Sao Jose Do Rio Preto, SP, Brazil..
    Penha, Frederico M.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Kemiteknik, Resursåtervinning.
    Diaz-De-Cerio, Elixabet
    Univ Granada, Dept Nutr & Food Sci, Campus Cartuja, E-18071 Granada, Spain..
    Verardo, Vito
    Univ Granada, Dept Nutr & Food Sci, Campus Cartuja, E-18071 Granada, Spain..
    Prudencio, Elane Schwinden
    Univ Fed Santa Catarina, Dept Food Sci & Technol, Florianopolis, SC, Brazil..
    Segura-Carretero, Antonio
    Univ Granada, Dept Analyt Chem, Granada, Spain.;Univ Granada, Funct Food Res & Dev Ctr CIDAF, Granada, Spain..
    Tischer, Bruna
    Univ Fed Rio Grande do Sul, Inst Food Sci & Technol, Dept Food Technol, Porto Alegre, Brazil..
    Cunha Petrus, Jose Carlos
    Univ Fed Santa Catarina, Dept Chem & Food Engn, Florianopolis, SC, Brazil..
    Verruck, Silvani
    Univ Fed Santa Catarina, Dept Food Sci & Technol, Florianopolis, SC, Brazil..
    Rezzadori, Katia
    Univ Fed Santa Catarina, Dept Food Sci & Technol, Florianopolis, SC, Brazil..
    Is nanofiltration an efficient technology to recover and stabilize phenolic compounds from guava (Psidium guajava) leaves extract?2022Ingår i: Food Bioscience, ISSN 2212-4292, E-ISSN 2212-4306, Vol. 50, artikel-id 101997Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Guava leaves (Psidium guajava) are popularly known due to their effects antidiabetic, antihypertensive, anti-inflammatory, antidiarrheal, and functional properties. Processes for the concentration of these extracts are necessary since their pharmacological effects are dose-dependent. In this work, guava leaves aqueous extract (GE) concentration was carried out in nanofiltration (NF) equipment. Process performance was evaluated in terms of permeate flux, flux decline modeling, and extract quality (compounds characterization, total phenolic content and antioxidant activity). NF allowed an increase in phenolic compounds next to 20-times, retention coefficients of total phenolic compounds (99%) and enhanced antioxidant capacity (an increase of 4 and 9-fold for ABTS and DPPH, respectively) compared to the initial GE. Forty-two phenolic compounds were identified, being catechin (594.56 mg mL-1) and vescalagin (295.39 mg mL-1) the main compounds. All phenolics pre-sented a significant increase (p < 0.05) after the concentration suggesting that NF is efficient for the recovery and concentration of bioactive compounds and poses as an alternative to obtain functional products and improve added value in agro-industrial residues.

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