1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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2. |
- Andersson, C David, et al.
(författare)
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Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
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Tidskriftsartikel (refereegranskat)abstract
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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3. |
- Beecken, Jörg, 1982, et al.
(författare)
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Performance assessment of state-of-the-art and novel methods for remote compliance monitoring of sulfur emissions from shipping
- 2023
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Ingår i: Atmospheric Measurement Techniques. - 1867-1381 .- 1867-8548. ; 16:23, s. 5883-5895
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Tidskriftsartikel (refereegranskat)abstract
- The fuel sulfur content (FSC) of ocean-going and inland vessels was measured simultaneously by eight different state-of-the-art and novel monitoring systems during a 6-week campaign at the Elbe River, at a distance of about 10 km to the port of Hamburg, Germany. Both stationary and airborne systems on unoccupied aerial vehicles (UAVs) were operated by four participating partners in a side-by-side measurement setup to measure the emission factors of the same emission sources. A novel laser spectrometer, with significantly better-precision specifications as compared with the other instruments, was used for the first time for emission monitoring regarding the International Convention for the Prevention of Pollution from Ships (MARPOL) Annex VI regulations. The comparison took place in the North Sea sulfur emission control area (SECA), where the allowed FSC is limited to 0.10 %Sm/m. The unit %Sm/m relates to the percentage of mass sulfur per mass combusted fuel. In total, 966 plumes that originated from 436 different vessels were analysed in this study. At the same time, fuel samples obtained from 34 different vessels and bunker delivery notes (BDNs) from five frequently monitored vessels were used as a reference to assess the uncertainties of the different systems. Seven of the eight measurement systems tended to underestimate the FSC found from fuel samples and BDNs. A possible relation between underestimation and high relative humidities (above 80 %) was observed. The lowest systematic deviations were observed for the airborne systems and the novel laser spectrometer. The two UAV-borne systems showed total uncertainties of 0.07 %Sm/m and 0.09 %Sm/m (confidence level: 95 %). The novel laser spectrometer showed the lowest total uncertainty of 0.05 %Sm/m compared with other stationary sniffer systems, whose total uncertainties range from 0.08 %Sm/m to 0.09 %Sm/m. It was concluded that non-compliant vessels, with an actual FSC of the combusted fuel above 0.15 %Sm/m to 0.19 %Sm/m, can be detected by the compared systems with 95 % confidence.
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4. |
- Kraus, Stefan, et al.
(författare)
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Planet Formation Imager (PFI) : Science vision and key requirements
- 2016
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Ingår i: Optical and Infrared Interferometry and Imaging V. - : SPIE. - 9781510601932 ; 9907
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Konferensbidrag (refereegranskat)abstract
- The Planet Formation Imager (PFI) project aims to provide a strong scientific vision for ground-based optical astronomy beyond the upcoming generation of Extremely Large Telescopes. We make the case that a breakthrough in angular resolution imaging capabilities is required in order to unravel the processes involved in planet formation. PFI will be optimised to provide a complete census of the protoplanet population at all stellocentric radii and over the age range from 0.1 to ∼100 Myr. Within this age period, planetary systems undergo dramatic changes and the final architecture of planetary systems is determined. Our goal is to study the planetary birth on the natural spatial scale where the material is assembled, which is the "Hill Sphere" of the forming planet, and to characterise the protoplanetary cores by measuring their masses and physical properties. Our science working group has investigated the observational characteristics of these young protoplanets as well as the migration mechanisms that might alter the system architecture. We simulated the imprints that the planets leave in the disk and study how PFI could revolutionise areas ranging from exoplanet to extragalactic science. In this contribution we outline the key science drivers of PFI and discuss the requirements that will guide the technology choices, the site selection, and potential science/technology tradeoffs.
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5. |
- Lehtiö, Lari, et al.
(författare)
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Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
- 2009
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Ingår i: Journal of medicinal chemistry. - : American Chemical Society (ACS). - 1520-4804 .- 0022-2623. ; 52:9, s. 3108-11
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Tidskriftsartikel (refereegranskat)abstract
- Poly(ADP-ribose) polymerases (PARPs) activate DNA repair mechanisms upon stress- and cytotoxin-induced DNA damage, and inhibition of PARP activity is a lead in cancer drug therapy. We present a structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors. Of these, KU0058948 is the strongest inhibitor of PARP-3 activity. The presented crystal structures highlight key features for potent inhibitor binding and suggest routes for creating isoenzyme-specific PARP inhibitors.
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6. |
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7. |
- Lindgren, Anders E. G., et al.
(författare)
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Chemical Probes to Study ADP-Ribosylation : Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3
- 2013
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:23, s. 9556-9568
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Tidskriftsartikel (refereegranskat)abstract
- The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of SS compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.
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8. |
- Lindgren, Anders E. G., et al.
(författare)
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PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3
- 2013
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:8, s. 1698-1703
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Tidskriftsartikel (refereegranskat)abstract
- Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12, members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.
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9. |
- Martinsson, Bengt, et al.
(författare)
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Comparison between CARIBIC Aerosol Samples Analysed by Accelerator-Based Methods and Optical Particle Counter Measurements
- 2014
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 7:8, s. 2581-2596
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Tidskriftsartikel (refereegranskat)abstract
- Inter-comparison of results from two kinds of aerosol systems in the CARIBIC (Civil Aircraft for the Regular Investigation of the atmosphere Based on a Instrument Container) passenger aircraft based observatory, operating during intercontinental flights at 9-12 km altitude, is presented. Aerosol from the lowermost stratosphere (LMS), the extra-tropical upper troposphere (UT) and the tropical mid troposphere (MT) were investigated. Aerosol particle volume concentration measured with an optical particle counter (OPC) is compared with analytical results of the sum of masses of all major and several minor constituents from aerosol samples collected with an impactor. Analyses were undertaken with the following accelerator-based methods: particle-induced X-ray emission (PIXE) and particle elastic scattering analysis (PESA). Data from 48 flights during 1 year are used, leading to a total of 106 individual comparisons. The ratios of the particle volume from the OPC and the total mass from the analyses were in 84% within a relatively narrow interval. Data points outside this interval are connected with inlet-related effects in clouds, large variability in aerosol composition, particle size distribution effects and some cases of non-ideal sampling. Overall, the comparison of these two CARIBIC measurements based on vastly different methods show good agreement, implying that the chemical and size information can be combined in studies of the MT/UT/LMS aerosol.
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10. |
- Van Roy, Ward, et al.
(författare)
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International maritime regulation decreases sulfur dioxide but increases nitrogen oxide emissions in the North and Baltic Sea
- 2023
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Ingår i: Communications Earth and Environment. - 2662-4435. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Sulfur dioxide and nitrogen oxide emissions from shipping have been regulated internationally for more than fifteen years. Emissions reduction from shipping provides benefits for human health and the environment, but the effectiveness of regulations in reducing ship emissions is less well understood. Here, we examine how the establishment of European Emission Control Areas and other international maritime regulations in the North and Baltic Seas affect sulfur dioxide and nitrogen oxide emissions in the region. We combine and analyze more than 110,000 ship plume measurements, inspection results, and satellite data from 2018 to 2022. We find that compliance rates for sulfur emissions are higher near ports than in open waters. However, the regulations did not affect the concentration of nitrogen oxide emissions, which increased in the past three years. These findings highlight the need for enhanced emission regulations that improve air quality.
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11. |
- Weigelt, Johan
(författare)
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Development of new NMR techniques and the structure of the N-terminal domain of Escherichia coli DnaB helicas
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New techniques applicable in biomolecular nuclear magnetic resonance (NMR) spectroscopy were developed. The three-dimensional structure of the N-terminal domain of Escherichia coli DnaB helicase was determined at atomic resolution using heteronuclear multidimensional NMR techniques. Homonuclear semi-selective decoupling during acquisition improves the resolution of an NMR experiment and presents a convenient way of suppressing zero-quantum cross peaks in NOESY and ROESY experiments. The decoupling pulses can, however, result in decoupling sidebands due to the modulation of the effective magnetic field by the decoupling pulses. Two methods for the suppression of the decoupling sidebands were devised. Spin-state selective filters for the separation of doublet components into different subspectra were developed. The filters are versatile building blocks for NMR pulse sequences and can be used in a straightforward manner for the measurement of one-bond coupling constants and relaxation interference effects as well as for the design of TROSY type experiments. A single scan, sensitivity enhanced TROSY experiment with pulsed field gradients for coherence order selection was developed. Since the modified TROSY pulse sequence requires only a single scan (two FIDs per complex data point) it represents a sequence element suitable for inclusion in more complex NMR experiments. DnaB helicase is the primary replicatory helicase in Escherichia coli. Native DnaB is a hexamer of identical 52.3 kDa subunits. Each subunit is comprised of two domains. The structurally well-defined core of the N-terminal domain of DnaB was determined by NMR to comprise residues 24 to 136 by resonance assignments of the flexible residues in two DnaB fragments of different length, DnaB(1-142) and DnaB(1-161). A third construct, DnaB(24-136), was subsequently overexpressed and isotopically enriched for structure determination. The three-dimensional structure was calculated using the program DYANA and energy minimised using the program OPAL. The final 20 conformers had a root mean square deviation relative to the mean structure of 0.51 A for the backbone heavy atoms of residues 29-134. An estimate of the rotational correlation time of DnaB(24-136) and ultracentrifugation data indicated partial self-aggregation of DnaB(24-136) into dimers. Chemical shift changes of amide (15N-1H) groups were measured as a function of protein concentration and identified the dimerisation interface. The dissociation constant was estimated to be in the mM range. A model of the dimer was built based on the identification of the interaction surface and intermolecular nuclear Overhauser effects (NOEs), and is in agreement with residual dipolar couplings. An association-dissociation equilibrium for the N-terminal domain of DnaB has been proposed earlier from electron microscopy data and is thought to be of importance in the functional DnaB hexamer. Interestingly, DnaB(24-136) is structurally related to the primary dimerisation domain of Escherichia coli gyrase A, which may indicate functional similarities.
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