| 1. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Arrowsmith, CH, et al.
(författare)
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The promise and peril of chemical probes
- 2015
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Ingår i: Nature chemical biology. - : Springer Science and Business Media LLC. - 1552-4469 .- 1552-4450. ; 11:8, s. 536-541
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Ackloo, S, et al.
(författare)
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Target 2035 - an update on private sector contributions
- 2023
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Ingår i: RSC medicinal chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 14:6, s. 1002-1011
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Target 2035, an international federation of biomedical scientists from the public and private sectors, is leveraging ‘open’ principles to develop a pharmacological tool for every human protein.
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| 5. |
- Graslund, S, et al.
(författare)
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Protein production and purification
- 2008
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Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 5:2, s. 135-146
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Muller, S, et al.
(författare)
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Target 2035 - update on the quest for a probe for every protein
- 2022
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Ingår i: RSC medicinal chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 13:1, s. 13-21
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. Target 2035 aims to develop a pharmacological modulator for every protein in the human proteome to fill this gap.
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| 7. |
- Peacock, Christopher S, et al.
(författare)
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Comparative genomic analysis of three Leishmania species that cause diverse human disease.
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:7, s. 839-847
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Tidskriftsartikel (refereegranskat)abstract
- Leishmania parasites cause a broad spectrum of clinical disease. Here we report the sequencing of the genomes of two species of Leishmania: Leishmania infantum and Leishmania braziliensis. The comparison of these sequences with the published genome of Leishmania major reveals marked conservation of synteny and identifies only 200 genes with a differential distribution between the three species. L. braziliensis, contrary to Leishmania species examined so far, possesses components of a putative RNA-mediated interference pathway, telomere-associated transposable elements and spliced leader–associated SLACS retrotransposons. We show that pseudogene formation and gene loss are the principal forces shaping the different genomes. Genes that are differentially distributed between the species encode proteins implicated in host-pathogen interactions and parasite survival in the macrophage.
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| 8. |
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| 9. |
- Arrowsmith, C. D., et al.
(författare)
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Generating ultradense pair beams using 400 GeV/c protons
- 2021
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Ingår i: Physical Review Research. - : AMER PHYSICAL SOC. - 2643-1564. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- An experimental scheme is presented for generating low-divergence, ultradense, relativistic, electron-positron beams using 400 GeV/c protons available at facilities such as HiRadMat and AWAKE at CERN. Preliminary Monte Carlo and particle-in-cell simulations demonstrate the possibility of generating beams containing 10(13)-10(14) electron-positron pairs at sufficiently high densities to drive collisionless beam-plasma instabilities, which are expected to play an important role in magnetic field generation and the related radiation signatures of relativistic astrophysical phenomena. The pair beams are quasineutral, with size exceeding several skin depths in all dimensions, allowing the examination of the effect of competition between transverse and longitudinal instability modes on the growth of magnetic fields. Furthermore, the presented scheme allows for the possibility of controlling the relative density of hadrons to electron-positron pairs in the beam, making it possible to explore the parameter spaces for different astrophysical environments.
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| 10. |
- Arrowsmith, C. D., et al.
(författare)
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Inductively-coupled plasma discharge for use in high-energy-density science experiments
- 2023
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Ingår i: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- Inductively-coupled plasma discharges are well-suited as plasma sources for experiments in fundamental high-energy density science, which require large volume and stable plasmas. For example, experiments studying particle beam-plasma instabilities and the emergence of coherent macroscopic structures - which are key for modelling emission from collisionless shocks present in many astrophysical phenomena. A meter-length, table-top, inductive radio-frequency discharge has been constructed for use in a high-energy density science experiment at CERN which will study plasma instabilities of a relativistic electron-positron beam. In this case, a large volume is necessary for the beam to remain inside the plasma as it diverges to centimeter-scale diameters during the tens-of-centimeters of propagation needed for instabilities to develop. Langmuir probe measurements of the plasma parameters show that plasma can be stably sustained in the discharge with electron densities exceeding 1011 cm-3. The discharge has been assembled using commercially-available components, making it an accessible option for commissioning at a University laboratory.
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| 11. |
- Arrowsmith, C. D., et al.
(författare)
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Laboratory realization of relativistic pair-plasma beams
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Relativistic electron-positron plasmas are ubiquitous in extreme astrophysical environments such as black-hole and neutron-star magnetospheres, where accretion-powered jets and pulsar winds are expected to be enriched with electron-positron pairs. Their role in the dynamics of such environments is in many cases believed to be fundamental, but their behavior differs significantly from typical electron-ion plasmas due to the matter-antimatter symmetry of the charged components. So far, our experimental inability to produce large yields of positrons in quasi-neutral beams has restricted the understanding of electron-positron pair plasmas to simple numerical and analytical studies, which are rather limited. We present the first experimental results confirming the generation of high-density, quasi-neutral, relativistic electron-positron pair beams using the 440 GeV/c beam at CERN’s Super Proton Synchrotron (SPS) accelerator. Monte Carlo simulations agree well with the experimental data and show that the characteristic scales necessary for collective plasma behavior, such as the Debye length and the collisionless skin depth, are exceeded by the measured size of the produced pair beams. Our work opens up the possibility of directly probing the microphysics of pair plasmas beyond quasi-linear evolution into regimes that are challenging to simulate or measure via astronomical observations.
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| 12. |
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| 13. |
- Jonsson, Christina E., et al.
(författare)
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Stable oxygen and hydrogen isotopes in sub-Arctic lake wateras from northern Sweden
- 2009
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 376:1-2, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Lakes in sub-Arctic regions have the potential of retaining many different aspects of water isotope composition in their sediments which can be used for palaeoclimate reconstruction. It is therefore important to understand the modern isotope hydrology of these lakes. Here we discuss the significance of variations in water isotope composition of a series of lakes located in north-west Swedish Lapland. Climate in this region is forced by changes in the North Atlantic which renders it an interesting area for climate reconstructions. We compare δ18Olake and δ2Hlake collected between 2001 and 2006 and show that the lakes in this sub-Arctic region are currently mainly recharged by shallow groundwater and precipitation which undergoes little subsequent evaporation, and that the d18O and δ2H composition of input to the majority of the lakes varies on a seasonal basis between winter precipitation (and spring thaw) and summer precipitation. Seasonal variations in the isotopic composition of the lake waters are larger in lakes with short residence times (<6 months), which react faster to seasonal changes in the precipitation, compared to lakes with longer residence times (>6 months), which retain an isotopic signal closer to that of annual mean precipitation. Lake waters also show a range of isotope values between sites due to catchment elevation and timing of snow melt. The lake water data collected in this study was supported by isotope data from lake waters, streams and ground waters from1995 to 2000 reported in other studies.
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| 14. |
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| 15. |
- Sheng, Yi, et al.
(författare)
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Molecular basis of Pirh2-mediated p53 ubiquitylation
- 2008
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Ingår i: NATURE STRUCTURAL and MOLECULAR BIOLOGY. - : Springer Science and Business Media LLC. - 1545-9985 .- 1545-9993. ; 15:12, s. 1334-1342
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Tidskriftsartikel (refereegranskat)abstract
- Pirh2 (p53-induced RING-H2 domain protein; also known as Rchy1) is an E3 ubiquitin ligase involved in a negative-feedback loop with p53. Using NMR spectroscopy, we show that Pirh2 is a unique cysteine-rich protein comprising three modular domains. The protein binds nine zinc ions using a variety of zinc coordination schemes, including a RING domain and a left-handed beta-spiral in which three zinc ions align three consecutive small beta-sheets in an interleaved fashion. We show that Pirh2-p53 interaction is dependent on the C-terminal zinc binding module of Pirh2, which binds to the tetramerization domain of p53. As a result, Pirh2 preferentially ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting that Pirh2 regulates protein turnover of the transcriptionally active form of p53.
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| 16. |
- Vedadi, M, et al.
(författare)
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Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 103:43, s. 15835-15840
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Tidskriftsartikel (refereegranskat)abstract
- The 3D structures of human therapeutic targets are enabling for drug discovery. However, their purification and crystallization remain rate determining. In individual cases, ligands have been used to increase the success rate of protein purification and crystallization, but the broad applicability of this approach is unknown. We implemented two screening platforms, based on either fluorimetry or static light scattering, to measure the increase in protein thermal stability upon binding of a ligand without the need to monitor enzyme activity. In total, 221 different proteins from humans and human parasites were screened against one or both of two sorts of small-molecule libraries. The first library comprised different salts, pH conditions, and commonly found small molecules and was applicable to all proteins. The second comprised compounds specific for protein families of particular interest (e.g., protein kinases). In 20 cases, including nine unique human protein kinases, a small molecule was identified that stabilized the proteins and promoted structure determination. The methods are cost-effective, can be implemented in any laboratory, promise to increase the success rates of purifying and crystallizing human proteins significantly, and identify new ligands for these proteins.
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| 17. |
- Zhang, Rong guang, et al.
(författare)
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Structure of Escherichia coli ribose-5-phosphate isomerase : a ubiquitous enzyme of the pentose phosphate pathway and the Calvin cycle
- 2003
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Ingår i: Structure. - 0969-2126 .- 1878-4186. ; 11:1, s. 31-42
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Tidskriftsartikel (refereegranskat)abstract
- Ribose-5-phosphate isomerase A (RpiA; EC 5.3.1.6) interconverts ribose-5-phosphate and ribulose-5-phosphate. This enzyme plays essential roles in carbohydrate anabolism and catabolism; it is ubiquitous and highly conserved. The structure of RpiA from Escherichia coli was solved by multiwavelength anomalous diffraction (MAD) phasing, and refined to 1.5 A resolution (R factor 22.4%, R(free) 23.7%). RpiA exhibits an alpha/beta/(alpha/beta)/beta/alpha fold, some portions of which are similar to proteins of the alcohol dehydrogenase family. The two subunits of the dimer in the asymmetric unit have different conformations, representing the opening/closing of a cleft. Active site residues were identified in the cleft using sequence conservation, as well as the structure of a complex with the inhibitor arabinose-5-phosphate at 1.25 A resolution. A mechanism for acid-base catalysis is proposed.
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| 18. |
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