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- Hultquist, Gunnar, et al.
(författare)
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Water Corrodes Copper
- 2009
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Ingår i: Catalysis Letters. - : Springer Science and Business Media LLC. - 1011-372X .- 1572-879X. ; 132:3-4, s. 311-316
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Tidskriftsartikel (refereegranskat)abstract
- According to a current concept, copper canisters of thickness 0.05 m will be safe for nuclear waste containment for 100,000 years. We show that more than 1 m copper thickness might be required for 100,000 years durability based on water exposures of copper for 20 h, 7 weeks, 15 years, and 333 years. An observed evolution of hydrogen which involves heterogeneous catalysis of molecular hydrogen, first principles simulations, thermodynamic considerations and corrosion product characterization provide further evidence that water corrodes copper resulting in the formation of a copper hydroxide. These findings cast additional doubt on copper for nuclear waste containment and other important applications.
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| 3. |
- Hyrenius-Wittsten, Axel, et al.
(författare)
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De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3 ITD, FLT3 N676K, and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Further, also subclonal FLT3 N676K mutations accelerate disease, possibly by providing stimulatory factors. Herein, we show that one such factor, MIF, promotes survival of mouse KMT2A-MLLT3 leukemia initiating cells. We identify acquired de novo mutations in Braf, Cbl, Kras, and Ptpn11 in KMT2A-MLLT3 leukemia cells that favored clonal expansion. During clonal evolution, we observe serial genetic changes at the Kras G12D locus, consistent with a strong selective advantage of additional Kras G12D . KMT2A-MLLT3 leukemias with signaling mutations enforce Myc and Myb transcriptional modules. Our results provide new insight into the biology of KMT2A-R leukemia with subclonal signaling mutations and highlight the importance of activated signaling as a contributing driver.
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| 5. |
- Siddle, A., et al.
(författare)
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Investigation of the initial reaction of the alloy Co86Cr14 and its constituent metals with oxygen using secondary ion mass spectrometry
- 2002
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Ingår i: Surface and Interface Analysis. - : Wiley. - 0142-2421 .- 1096-9918. ; 33:11-okt, s. 807-814
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Tidskriftsartikel (refereegranskat)abstract
- The initial oxidation of Co86Cr14 and its constituent metals is investigated using an in situ dynamic secondary ion mass spectrometry (SIMS) technique. Simultaneous analysis and controlled formation of oxidation products, rather than just analysis, allows the oxidation to be studied at the very early stages of the process, i.e. when the oxidation product is of submonolayer extent. The technique, initiated by Hultquist(5-7) for the study of pure metals in various in situ environments, involves exposing a sputter-cleaned sample to various partial pressures of oxygen in the SIMS chamber and achieving an equilibrium between the formation and removal of the reaction products under the normal dynamic SIMS conditions. Here, the study is extended to give some insight into the interpretation of the SIMS data obtained by this method, and to determine a model for the oxidation of materials. An empirical model is derived for the oxidation of cobalt. A theoretical model is also derived based on the Langmuir model, but allowing for the more energetic nature of ion bombardment and oxide removal. The theoretical and empirical models are indistinguishable at low oxygen pressures. The cobalt component in the alloy Co86Cr14 behaves in a similar way to that of the pure metal, which suggests that the cobalt oxidizes independently of the chromium in the alloy.
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- Wallner, Fredrik K., et al.
(författare)
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Correlation and cluster analysis of immunomodulatory drugs based on cytokine profiles
- 2018
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Ingår i: Pharmacological Research. - : Elsevier. - 1043-6618 .- 1096-1186. ; 128, s. 244-251
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Tidskriftsartikel (refereegranskat)abstract
- Drug discovery is a constant struggle to overcome hurdles posed by the complexity of biological systems. One of these hurdles is to find and understand the molecular target and the biological mechanism of action. Although the molecular target has been determined, the true biological effect may be unforeseen also for well-established drugs. Hence, there is a need for novel ways to increase the knowledge of the biological effects of drugs in the developmental process. In this study, we have determined cytokine profiles for 26 non-biological immunomodulatory drugs or drug candidates and used these profiles to cluster the compounds according to their effect in a preclinical ex vivo culture model of arthritis. This allows for prediction of functions and drug target of a novel drug candidate based on profiles obtained in this study. Results from the study showed that the JAK inhibitors tofacitinib and ruxolitinib formed a robust cluster and were found to have a distinct cytokine profile compared to the other drugs. Another robust cluster included the calcineurin inhibitors cyclosporine A and tacrolimus and the protein kinase inhibitors fostamatinib disodium and sotrastaurin acetate, which caused a strong overall inhibition of the cytokine production. The results of this methodology indicate that cytokine profiles can be used to provide a fingerprint-like identification of a drug as a tool to benchmark novel drugs and to improve descriptions of mode of action.
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