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Sökning: WFRF:(Johansson Roger) > (2010-2014) > Naturvetenskap

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1.
  • Gad, Helge, et al. (författare)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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2.
  • Wilson, Christopher, 1974, et al. (författare)
  • Observation of the dynamical Casimir effect in a superconducting circuit
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 479:7373, s. 376-9
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the most surprising predictions of modern quantum theory is that the vacuum of space is not empty. In fact, quantum theory predicts that it teems with virtual particles flitting in and out of existence. Although initially a curiosity, it was quickly realized that these vacuum fluctuations had measurable consequences-for instance, producing the Lamb shift of atomic spectra and modifying the magnetic moment of the electron. This type of renormalization due to vacuum fluctuations is now central to our understanding of nature. However, these effects provide indirect evidence for the existence of vacuum fluctuations. From early on, it was discussed whether it might be possible to more directly observe the virtual particles that compose the quantum vacuum. Forty years ago, it was suggested that a mirror undergoing relativistic motion could convert virtual photons into directly observable real photons. The phenomenon, later termed the dynamical Casimir effect, has not been demonstrated previously. Here we observe the dynamical Casimir effect in a superconducting circuit consisting of a coplanar transmission line with a tunable electrical length. The rate of change of the electrical length can be made very fast (a substantial fraction of the speed of light) by modulating the inductance of a superconducting quantum interference device at high frequencies (>10 gigahertz). In addition to observing the creation of real photons, we detect two-mode squeezing in the emitted radiation, which is a signature of the quantum character of the generation process.
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3.
  • Menzel, Carolin, et al. (författare)
  • Molecular structure of citric acid cross-linked starch films
  • 2013
  • Ingår i: Carbohydrate Polymers. - Amsterdam : Elsevier. - 0144-8617 .- 1879-1344. ; 96:2, s. 270-276
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of citric acid (CA) on starch films has been examined. A new method to detect cross-linkingof starch by CA in solution-cast films by molecular weight measurements is described. Furthermore, wemanaged to distinguished between free, mono- and di-esterified CA and quantify di-ester content withinstarch films by using a modification in the method of complexometric titration with copper(II)-sulfate.Cross-linking of starch by CA occurred at low temperature, 70◦C, which we assumed is so far the lowesttemperature reported where cross-linking reaction occurred. This is essential for starch coating applica-tions within paper industry since no high temperatures for curing will be required. However, curing at150◦C and high CA concentrations, 30 pph, increased cross-linking reaction. Furthermore, the physicalproperties like water solubility, gel content and glass transition temperature, were highly reflected bychanges in the molecular structure i.e. cross-linking and hydrolysis, as well as CA content and curingtemperature.
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4.
  • Müller, Christian, et al. (författare)
  • Functionalisation of recombinant spider silk with conjugated polyelectrolytes
  • 2011
  • Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry. - 0959-9428 .- 1364-5501. ; 21:9, s. 2909-2915
  • Tidskriftsartikel (refereegranskat)abstract
    • Conjugated polyelectrolytes are demonstrated to permit facile staining of recombinant spider silk fibres. We find that the polyelectrolyte concentration and pH of the staining solution as well as the incubation temperature strongly influence the efficiency of this self-assembly process, which appears to be principally mediated through favourable electrostatic interactions. Thus, depending on the choice of staining conditions as well as the polyelectrolyte, electrically conductive or photoluminescent recombinant silk fibres could be produced. In addition, staining of natural Bombyx mori silk is established, which emphasises the versatility of the here advanced approach to functionalise silk-based materials.
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5.
  • Ayatolahi, Fatemeh, 1984, et al. (författare)
  • A study of the impact of single bit-flip and double bit-flip errors on program execution
  • 2013
  • Ingår i: Lect. Notes Comput. Sci.. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783642407925 ; , s. 265-276
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents the results of an extensive experimental study of bit-flip errors in instruction set architecture registers and main memory locations. Comprising more than two million fault injection experiments conducted with thirteen benchmark programs, the study provides insights on whether it is necessary to consider double bit-flip errors in dependability benchmarking experiments. The results show that the proportion of silent data corruptions in the program output, is almost the same for single and double bit errors. In addition, we present detailed statistics about the error sensitivity of different target registers and memory locations, including bit positions within registers and memory words. These show that the error sensitivity varies significantly between different bit positions and registers. An important observation is that injections in certain bit positions always have the same impact regardless of when the error is injected.
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6.
  • Callaghan, Terry V., et al. (författare)
  • Changing snow cover and its impacts
  • 2011
  • Ingår i: Snow, Water, Ice and Permafrost in the Arctic (SWIPA). - Oslo : Arctic Monitoring and Assessment Programme. - 9788279710714 ; , s. 4:1-4:58
  • Bokkapitel (refereegranskat)
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7.
  • Johnson, Magnus, et al. (författare)
  • Mechanisms of the CO2 Insertion into (PCP) Palladium Allyl and Methyl sigma-Bonds. A Kinetic and Computational Study
  • 2010
  • Ingår i: Organometallics. - : American Chemical Society (ACS). - 0276-7333 .- 1520-6041. ; 29:16, s. 3521-3529
  • Tidskriftsartikel (refereegranskat)abstract
    • The reaction of the sigma-bonded (PCP)Pd-Me complex (PCP = 2,6-bis[(di-tert-butylphosphino)methyl]phenyl) with CO2 is first-order in palladium and first-order in CO, with a rate constant k(s) = 8.9 +/- 0.8 M-1 s(-1) at 353 K. Activation parameters are Delta H double dagger = 73 7 kJ/mol and Delta S double dagger = 118 +/- 19 J/K mol. Based on this and theoretical calculations we propose an S(E)2 mechanism where the coordinated methyl group attacks a completely noncoordinated carbon dioxide molecule in a bimolecular reaction. The PCPPd-crotyl complex was synthesized in an 65:35 E:Z mixture, and it was shown to react with CO, to give the complex PCPPd-O(CO)CH(CH3)CHCH2 as a single isomer, where the former gamma-carbon has been carboxylated. Theoretical calculations again suggest an S(E)2 mechanism with a noncoordinated carbon dioxide reacting with the terminal carbon on the allyl group, forming an eta(2)-bonded olefin complex as an intermediate. The rearrangement of this intermediate to the O-bonded product is concluded to be rate determining. The crystal structure of PCPPd-O(CO)C(CH3)(2)CHCH2 is reported and as well as the solubility of carbon dioxide in benzene-d(6) at different pressures and temperatures.
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8.
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9.
  • Weinstein, John N., et al. (författare)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Forskningsöversikt (refereegranskat)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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10.
  • Canbäck, Björn, et al. (författare)
  • The Littorina sequence database (LSD) - an online resource for genomic data.
  • 2012
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 12, s. 142-148
  • Tidskriftsartikel (refereegranskat)abstract
    • We present an interactive, searchable expressed sequence tag database for the periwinkle snail Littorina saxatilis, an upcoming model species in evolutionary biology. The database is the result of a hybrid assembly between Sanger and 454 sequences, 1290 and 147 491 sequences respectively. Normalized and non-normalized cDNA was obtained from different ecotypes of L. saxatilis collected in the UK and Sweden. The Littorina sequence database (LSD) contains 26 537 different contigs, of which 2453 showed similarity with annotated proteins in UniProt. Querying the LSD permits the selection of the taxonomic origin of blast hits for each contig, and the search can be restricted to particular taxonomic groups. The database allows access to UniProt annotations, blast output, protein family domains (PFAM) and Gene Ontology. The database will allow users to search for genetic markers and identifying candidate genes or genes for expression analyses. It is open for additional deposition of sequence information for L. saxatilis and other species of the genus Littorina. The LSD is available at http://mbio-serv2.mbioekol.lu.se/Littorina/.
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