| 1. |
- Lu, Lu, 1984-, et al.
(författare)
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MEPicides : α,β-Unsaturated Fosmidomycin N-acyl Analogsas inhibitors that selectively target DXR from Plasmodium falciparum, the deadliest causative parasite of human Malaria
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Fosmidomycin and FR-9000098 have been confirmed to show parasiticidal activity against Plasmodium falciparum, targeting DXR involved in the MEP pathway. We designed a construct of PfDXR that has successfully been overexpressed in E. coli BL21(DE3) C43, and purified by IMAC and SEC, with the final yield of 1.2 mg/ 8 L culture. PfDXR was concentrated to 20 mg/ml, and co-crystallized with previously tested inhibitors in the FR-9000098 scaffold in the presence of Mn2+. Three FR-9000098 analogues with double-bonded Ca-Cband/or a phenyl ring with various lengths to N1, showed inhibitory activities with IC50s roughly 50 nM. Three crystals were in triclinic P1space group, with similar dimensions in the unit cell (51Å, 56Å, 86Å, 103°, 103°, 101°). All four complex structures have been crystallographically determined at resolutions in the range 1.86 Å, 2.45 Å, 2.13Å, 2.05 Å. Given the high similarity in structures, the initial phases were determined by rigid body refinement with search model PfDXR-FN3 complex, followed by restrained refinement in refmac5. Subsequently, the ligands and surrounding amino acid residues were manually rebuilt with theqdstools in O. the Ca-Cbbonds of the three ligands were altered from a single to double bond based on the structure of FR9000098. In addition, two ligands were extended at the Cdwith a phenyl group, and with the benzyl group connected by two carbons. N-terminal NADPH binding domains from four complexes undergo minor rigid body movement, and more details of conformational changes in the flap region are discussed.
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| 2. |
- Engberg, David L. J., et al.
(författare)
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Solid Solution and Segregation Effects in Arc-Deposited Ti1-xSixN Thin Films Resolved on the nanometer scale by 15N Isotopic Substitution in AtomP robe Tomography
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Nanostructured TiSiN is an important material in wear--‐resistant coatings for extending the lifetime of cutting tools. Yet, the understanding regarding the structure, phase composition, and bonding on the detailed nanometer scale, which determines the properties of TiSiN, is lacking. This limits our understanding of the growth phenomena and eventually a larger exploitation of the material. By substituting natN2 with 15N2 during reactive arc deposition of TiSiN thin films, atom probe tomography (APT) gives elemental sensitivity and sub-nanometer resolution, a finer scale than what can be obtained by commonly employed energy dispersive electron spectroscopy in scanning transmission electron microscopy. Using a combination of analytical transmission electron microscopy and APT we show that arc-deposited Ti0.92Si0.0815N and Ti0.81Si0.1915N exhibit Si segregation on the nanometer scale in the alloy films. APT composition maps and proximity histograms from domains with higher than average Ti content show that the TiN domains contain at least ~2 at. % Si for Ti0.92Si0.08N and ~5 at. % Si for Ti0.81Si0.19N, thus confirming the formation of solid solutions. The formation of relatively pure SiNy domains in the Ti0.81Si0.19N films is tied to pockets between microstructured, columnar features in the film. Finer SiNy enrichments seen in APT possibly correspond to tissue layers around TiN crystallites, thus effectively hindering growth of TiN crystallites, causing TiN renucleation and thus explaining the featherlike nanostructure within the columns of these films. For the stoichiometry of the TiN phase, we establish a global under stoichiometry, in accordance with the tendency for SiNy films to have tetrahedral bonding coordination towards a nominal Si3N4 composition.
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| 3. |
- Kindlund, Hanna, et al.
(författare)
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Microstructure and mechanical properties of : V0.5Mo0.5Nx(111)/Al2O3(0001) thin films
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We report results of growth, microstructure, and mechanical properties of V0.5Mo0.5Nx thin films deposited on Al2O3(0001) substrates by reactive magnetron sputtering. Sputtering is carried out in 5 mTorr Ar/N2 atmospheres and the growth temperatures Ts are varied between 100 and 900 °C. We find that the V0.5Mo0.5Nx/Al2O3(0001) alloy films are 111-oriented NaCl-structure. In-plane and out-of plane lattice parameters are found to decrease with increasing Ts and indicate that all alloy films are strained. V0.5Mo0.5Nx hardnesses and reduced elastic moduli increase with increasing Ts, and vary between 15-23 GPa, and 220-318 GPa, respectively. The wear resistance of the alloy films is also found to increase with increasing Ts. In addition, scanning electron micrographs of indents performed on V0.5Mo0.5Nx films show material pile-up around the indent edges and no evidence of crack arising from nanoindentation experiments. Coefficients of friction acquired at normal forces of 1000 μN are found to be of the order of 0.09.
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| 4. |
- Kindlund, Hanna, et al.
(författare)
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V0.5Mo0.5Nx/MgO(001) layers grown at 100-900 °C : composition, nanostructure, and mechanical properties
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- V0.5Mo0.5Nx/MgO(001) alloys with the B1-NaCl structure are grown by ultra-highvacuum reactive magnetron sputter deposition in 5 mTorr mixed Ar/N2 atmospheres at temperatures Ts which are varied from 100 and 900 °C. Alloy films grown at Ts ≤ 500 °C are polycrystalline with a strong 002 texture; layers grown at Ts ≤ 700 °C are epitaxial single-crystals. The N/Me ratio x ranges from 0.64±0.05 with Ts = 900 °C to 0.94±0.05 at 700 °C to 1.02±0.05 with Ts = 500 to 100 °C. The N loss at higher growth temperatures leads to a corresponding decrease in the relaxed lattice parameter ao from 4.212 Å with x = 1.02 to 4.175 Å with x = 0.94 to 4.121 Å with x = 0.64. V0.5Mo0.5Nx nanoindentation hardnesses H and elastic moduli E increase with increasing Ts from 17±3 GPa and 274±31 GPa at 100 °C to 26±1 GPa and 303±10 GPa at 900 °C. Films deposited at higher Ts also exhibit enhanced wear resistance. Scanning electron micrographs of nanoindents performed in single-crystal V0.5Mo0.5Nx films and films deposited at 100 and 300 °C reveal no evidence of cracking; instead they exhibit material pile-up around the indents characteristic of plastic flow in ductile materials. Valence band x-ray photoelectron spectroscopy analyses show an enhanced volume density of the shear sensitive d-t2g – d-t2g metallic states in V0.5Mo0.5Nx compared to VN and the density of these orbitals increases with increasing deposition temperature, i.e., the metallic states become more populated with the introduction of N vacancies.
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