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- Aziz, Emad F., et al.
(author)
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Photoinduced formation of N-2 molecules in ammonium compounds
- 2007
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In: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 111:39, s. 9662-9669
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Journal article (peer-reviewed)abstract
- Via fluorescence yield (FY) and resonant inelastic scattering spectroscopy in the soft X-ray range we find that soft X-rays induce formation of N-2 molecules in solid NH4Cl and in related compounds. The nitrogen molecules form weak bonds in NH4Cl, so that a substantial fraction of the molecules remains in the sample. From measurements of the FY as a function of exposure and temperature, the rates for the photochemical processes are estimated. At elevated temperatures (363 K), several nitrogen atoms are removed from the sample per incoming photon. At lower temperatures (233 K), the rate is reduced to around 0.02 nitrogen atoms for each incoming photon. Virtually all these atoms form N-2 molecules which are bound in the sample. The generality and implications of these results are briefly discussed.
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- Liwing, Johan, et al.
(author)
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Improved survival in myeloma patients : starting to close in on the gap between elderly patients and a matched normal population
- 2014
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 164:5, s. 684-693
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Journal article (peer-reviewed)abstract
- The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n = 1638) diagnosed in a defined period and compared survival with a gender- and age-matched cohort Swedish population (n = 9 340 682). Median overall survival for non-high-dose treated patients was 2.8 years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4.9 years) compared to conventional treatment (2.3 years). Among non-high-dose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% and 63% have survived at 3 and 5 years as compared to 48% and 22% with conventional drugs and 88% and 79% in the matched cohort populations, respectively. The median overall survival in high-dose treated patients was 6.9 years. Of these patients, 84% survived at 3 years and 70% at 5 years as compared to 98% and 95% in the matched cohort population. Overall survival in the best non-high-dose treated outcome group is closing the gap with the matched cohort. Upfront use of new drugs is clearly better than waiting until later lines of treatment.
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- Barkefors, Irmeli, et al.
(author)
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Exocyst Complex Component 3-like 2 (EXOC3L2) Associates with the Exocyst Complex and Mediates Directional Migration of Endothelial Cells
- 2011
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:27, s. 24189-24199
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Journal article (peer-reviewed)abstract
- The exocyst is a protein complex that ensures spatial targeting of exocytotic vesicles to the plasma membrane. We present microarray data obtained from differentiating mouse embryonic stem cell cultures that identify an up-regulation of exocyst complex component 3-like 2 (exoc3l2) mRNA in sprouting blood vessels. Vascular expression of exoc3l2 is confirmed by qPCR analysis of different mouse tissues and immunofluorescence analyses of mouse brain sections. We detect an up-regulation of exoc3l2 mRNA synthesis in primary human endothelial cells in response to VEGFA, and this response is enhanced when the cells are grown on a three-dimensional collagen I matrix. Myc-tagged EXOC3L2 co-precipitates with the exocyst protein EXOC4, and immunofluorescence detection of EXOC3L2 shows partial subcellular colocalization with EXOC4 and EXOC7. Finally, we show that exoc3l2 silencing inhibits VEGF receptor 2 phosphorylation and VEGFA-directed migration of cultured endothelial cells.
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- de Oliveira, Kelin Gonçalves, et al.
(author)
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Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche
- 2024
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In: Acta Neuropathologica Communications. - : BioMed Central (BMC). - 2051-5960. ; 12:1
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Journal article (peer-reviewed)abstract
- Immunotherapies with antibody-drug-conjugates (ADC) and CAR-T cells, targeted at tumor surface antigens (surfaceome), currently revolutionize clinical oncology. However, target identification warrants a better understanding of the surfaceome and how it is modulated by the tumor microenvironment. Here, we decode the surfaceome and endocytome and its remodeling by hypoxic stress in glioblastoma (GBM), the most common and aggressive brain tumor in adults. We employed a comprehensive approach for global and dynamic profiling of the surfaceome and endocytosed (endocytome) proteins and their regulation by hypoxia in patient-derived GBM cultures. We found a heterogeneous surface-endocytome profile and a divergent response to hypoxia across GBM cultures. We provide a quantitative ranking of more than 600 surface resident and endocytosed proteins, and their regulation by hypoxia, serving as a resource to the cancer research community. As proof-of-concept, the established target antigen CD44 was identified as a commonly and abundantly expressed surface protein with high endocytic activity. Among hypoxia induced proteins, we reveal CXADR, CD47, CD81, BSG, and FXYD6 as potential targets of the stressed GBM niche. We could validate these findings by immunofluorescence analyses in patient tumors and by increased expression in the hypoxic core of GBM spheroids. Selected candidates were finally confronted by treatment studies, showing their high capacity for internalization and ADC delivery. Importantly, we highlight the limited correlation between transcriptomics and proteomics, emphasizing the critical role of membrane protein enrichment strategies and quantitative mass spectrometry. Our findings provide a comprehensive understanding of the surface-endocytome and its remodeling by hypoxia in GBM as a resource for exploration of targets for immunotherapeutic approaches in GBM.
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- Forsberg, Johan, et al.
(author)
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A versatile soft x-ray transmission system for time resolved in situ microscopy with chemical contrast
- 2009
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In: Ultramicroscopy. - : Elsevier BV. - 0304-3991 .- 1879-2723. ; 109:9, s. 1157-1163
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Journal article (peer-reviewed)abstract
- We present the design and operation of a versatile soft X-ray transmission system for time resolved in situ microscopy with chemical contrast. The utility of the setup is demonstrated by results from following a corrosion process of iron in saline environment, subjected to a controlled humid atmosphere. The system includes a transmission flow-cell reactor that allows for in situ microscopic probing with soft X-rays. We employ a full field technique by using a nearly collimated X-ray beam that produces an unmagnified projection of the transmitted soft X-rays (below 1.1 keV) which is magnified and recorded by an optical CCD camera. Time lapse series with chemical contrast allow us to follow and interpret the chemical processes in detail. The obtainable lateral resolution is a few mu m, sufficient to detect filiform corrosion on iron.
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10. |
- Forsberg, Johan, et al.
(author)
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Angular anisotropy in resonant inelastic soft X-ray scattering of liquid water
- 2009
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 79:13, s. 132203-
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Journal article (peer-reviewed)abstract
- Resonantly excited soft x-ray emission spectra of liquid water have been measured at two different angles relative to the polarization direction of the exciting radiation. The results demonstrate that the emission is much more isotropic than expected for the free water molecule but that the trends in the remaining anisotropy qualitatively agree. It is found that the two sharp oxygen peaks at high emission energy correspond to states of different symmetry.
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