| 1. |
- Burza, Matthias, et al.
(författare)
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Dispersion and monochromatization of x-rays using a beryllium prism
- 2015
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Ingår i: Optics Express. - 1094-4087. ; 23:2, s. 620-627
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate experimentally and numerically that an x-ray prism made of beryllium can be used to disperse and monochromatize x-rays. A polished beryllium cuboid was employed as refractive and dispersive optics. The results of a proof-of-principle experiment and methods of performance optimization are presented. The spatial separation of undulator harmonics and their subsequent selection using a slit are described. A numerical study, assuming realistic beam and beamline parameters, suggests that undulator harmonics can be spatially separated in the range from 3 keV to beyond 20 keV, while maintaining throughput above 50%. Refractive optics is particularly suitable for low-repetition-rate sources such as free-electron lasers and other LINAC-based short-pulse sources. (C) 2015 Optical Society of America
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| 2. |
- Enquist, Henrik, et al.
(författare)
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FemtoMAX - An X-ray beamline for structural dynamics at the short-pulse facility of MAX IV
- 2018
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 25:2, s. 570-579
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Tidskriftsartikel (refereegranskat)abstract
- The FemtoMAX beamline facilitates studies of the structural dynamics of materials. Such studies are of fundamental importance for key scientific problems related to programming materials using light, enabling new storage media and new manufacturing techniques, obtaining sustainable energy by mimicking photosynthesis, and gleaning insights into chemical and biological functional dynamics. The FemtoMAX beamline utilizes the MAX IV linear accelerator as an electron source. The photon bursts have a pulse length of 100fs, which is on the timescale of molecular vibrations, and have wavelengths matching interatomic distances (Å). The uniqueness of the beamline has called for special beamline components. This paper presents the beamline design including ultrasensitive X-ray beam-position monitors based on thin Ce:YAG screens, efficient harmonic separators and novel timing tools.The FemtoMAX beamline facilitates studies of the structural dynamics of materials on the femtosecond timescale. The first commissioning results are presented.
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| 3. |
- Levinsen, Mette, et al.
(författare)
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Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity
- 2015
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Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 75:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMTIA) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However, since TPMTIA had lower blood counts at initiation of HD-MTX compared with TPMTHA patients (median WBC 2.8 vs. 3.3 x 10(9)/L, P = 0.01; median ANC 1.4 vs. 1.7 x 10(9)/L, P = 0.02), TPMTIA continued to have lower WBC and ANC levels compared with TPMTHA during all 28 days after HD-MTX [relative difference 9 % (95 % CI 2-17), P = 0.02 and 21 % (95 % CI 6-39), P = 0.005]. Still, the fractional decrease in WBC and ANC levels after HD-MTX did not differ between TPMTIA and TPMTHA patients (P = 0.47; P = 0.38). The degree of leukopenia, neutropenia, thrombocytopenia and rise in aminotransferases were all significantly related to 6MP dose (P < 0.001 for all analyses). For both TPMTIA and TPMTHA patients, dose of 6MP prior to HD-MTX should be guided by pre-HD-MTX blood counts, but not by TPMT activity.
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| 4. |
- Malik, Leila, et al.
(författare)
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Self-assembly of designed coiled coil peptides studied by small-angle X-ray scattering and analytical ultracentrifugation
- 2013
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Ingår i: Journal of Peptide Science. - : Wiley. - 1099-1387 .- 1075-2617. ; 19:5, s. 283-292
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Tidskriftsartikel (refereegranskat)abstract
- alpha-Helical coiled coil structures, which are noncovalently associated heptad repeat peptide sequences, are ubiquitous in nature. Similar amphipathic repeat sequences have also been found in helix-containing proteins and have played a central role in de novo design of proteins. In addition, they are promising tools for the construction of nanomaterials. Small-angle X-ray scattering (SAXS) has emerged as a new biophysical technique for elucidation of protein topology. Here, we describe a systematic study of the self-assembly of a small ensemble of coiled coil sequences using SAXS and analytical ultracentrifugation (AUC), which was correlated with molecular dynamics simulations. Our results show that even minor sequence changes have an effect on the folding topology and the self-assembly and that these differences can be observed by a combination of AUC, SAXS, and circular dichroism spectroscopy. A small difference in these methods was observed, as SAXS for one peptide and revealed the presence of a population of longer aggregates, which was not observed by AUC. Copyright (c) 2013 European Peptide Society and John Wiley & Sons, Ltd.
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| 5. |
- Munch, Henrik K, et al.
(författare)
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Construction of Insulin 18-mer Nanoassemblies Driven by Coordination to Iron(II) and Zinc(II) Ions at Distinct Sites.
- 2016
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Ingår i: Angewandte Chemie (International edition). - : Wiley. - 1521-3773. ; 55:7, s. 2378-2381
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Tidskriftsartikel (refereegranskat)abstract
- Controlled self-assembly (SA) of proteins offers the possibility to tune their properties or to create new materials. Herein, we present the synthesis of a modified human insulin (HI) with two distinct metal-ion binding sites, one native, the other abiotic, enabling hierarchical SA through coordination with two different metal ions. Selective attachment of an abiotic 2,2'-bipyridine (bipy) ligand to HI, yielding HI-bipy, enabled Zn(II) -binding hexamers to SA into trimers of hexamers, [[HI-bipy]6 ]3 , driven by octahedral coordination to a Fe(II) ion. The structures were studied in solution by small-angle X-ray scattering and on surfaces with AFM. The abiotic metal ligand had a higher affinity for Fe(II) than Zn(II) ions, enabling control of the hexamer formation with Zn(II) and the formation of trimers of hexamers with Fe(II) ions. This precise control of protein SA to give oligomers of oligomers provides nanoscale structures with potential applications in nanomedicine.
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| 6. |
- Nygaard, Jesper, et al.
(författare)
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Metal Ion Controlled Self-Assembly of a Chemically Reengineered Protein Drug Studied by Small-Angle X-ray Scattering
- 2012
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 28:33, s. 12159-12170
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Tidskriftsartikel (refereegranskat)abstract
- Precise control of the oligomeric state of proteins is of central importance for biological function and for the properties of biopharmaceutical drugs. Here, the self-assembly of 2,2'-bipyridine conjugated monomeric insulin analogues, induced through coordination to divalent metal ions, was studied. This protein drug system was designed to form non-native homo-oligomers through selective coordination of two divalent metal ions, Fe(II) and Zn(II), respectively. The insulin type chosen for this study is a variant designed for a reduced tendency toward native dimer formation at physiological concentrations. A small-angle X-ray scattering analysis of the bipyridine-modified insulin system confirmed an organization into a novel well-ordered structure based on insulin trimers, as induced by the addition of Fe(II). In contrast, unmodified monomeric insulin formed larger and more randomly structured assemblies upon addition of Fe(II). The addition of Zn(II), on the other hand, led to the formation of small quantities of insulin hexamers for both the bipyridine-modified and the unmodified monomeric insulin. Interestingly, the location of the bipyridine-modification significantly affects the tendency to hexamer formation as compared to the unmodified insulin. Our study shows how combining a structural study and chemical design can be used to obtain molecular understanding and control of the self-assembly of a protein drug. This knowledge may eventually be employed to develop an optimized in vivo drug release profile.
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| 7. |
- Rosenberg, Louise C., et al.
(författare)
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The Transcriptional Activity of Neurog3 Affects Migration and Differentiation of Ectopic Endocrine Cells in Chicken Endoderm
- 2010
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Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 239:7, s. 1950-1966
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Tidskriftsartikel (refereegranskat)abstract
- Neurog3 is expressed transiently in pancreatic endocrine progenitors where it is responsible for activating a transcription factor cascade which eventually defines the mature endocrine cells. However, the mechanism by which Neurog3 regulates different aspects of the endocrine differentiation program is less clear. In this report we used in ovo electroporation to investigate how manipulation of Neurog3 protein activity affected migration, differentiation and fate determination. We found that changes in the onset of Neurog3 expression only had minor effect on differentiation. However increasing the transcriptional activity of Neurog3 by fusing it to VP16 or co-electroporating with Ep300 caused the electroporated cells to migrate rather than differentiate. In contrast, reducing the transcriptional activity of Neurog3 by deleting parts of the activation domain, by fusing Neurog3 to the engrailed repressor domain, or co-electroporating with Hdac1 greatly increased the proportion of glucagon expressing cells. Developmental Dynamics 239:1950-1966, 2010. (C) 2010 Wiley-Liss, Inc.
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| 8. |
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