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An Fe­10Cr­4Al alloy containing reactive elements developed for application in high-temperature liquid lead environments was analyzed after exposure in 600 and 750°C lead with dissolved oxygen for 1,000­2,000 h. Atom probe tomography, transmission electron microscopy, and X-ray scattering were all used to study the protective oxide formed on the surface. Exposure at 750°C resulted in a 2-µm thick oxide, whereas the 600°C exposure resulted in a 100-nm thick oxide. Both oxides were layered, with an Fe­Al spinel on top, and an alumina layer toward the metal. In the 600°C exposed material, there was a Cr-rich oxide layer between the spinel and the alumina. Metallic lead particles were found in the inner and middle parts of the oxide, related to pores. The combination of the experimental techniques, focusing on atom probe tomography, and the interpretations that can be done, are discussed in detail.

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We summarize the findings from an interlaboratory study conducted between ten international research groups and investigate the use of the commonly used maximum separation distance and local concentration thresholding methods for solute clustering quantification. The study objectives are: to bring clarity to the range of applicability of the methods; identify existing and/or needed modifications; and interpretation of past published data. Participants collected experimental data from a proton-irradiated 304 stainless steel and analyzed Cu-rich and Ni-Si rich clusters. The datasets were also analyzed by one researcher to clarify variability originating from different operators. The Cu distribution fulfills the ideal requirements of the maximum separation method (MSM), namely a dilute matrix Cu concentration and concentrated Cu clusters. This enabled a relatively tight distribution of the cluster number density among the participants. By contrast, the group analysis of the Ni-Si rich clusters by the MSM was complicated by a high Ni matrix concentration and by the presence of Si-decorated dislocations, leading to larger variability among researchers. While local concentration filtering could, in principle, tighten the results, the cluster identification step inevitably maintained a high scatter. Recommendations regarding reporting, selection of analysis method, and expected variability when interpreting published data are discussed.

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Radiation induced clustering affects the mechanical properties, that is the ductile to brittle transition temperature (DBTT), of reactor pressure vessel (RPV) steel of nuclear power plants. The combination of low Cu and high Ni used in some RPV welds is known to further enhance the DBTT shift during long time operation. In this study, RPV weld samples containing 0.04 at% Cu and 1.6 at% Ni were irradiated to 2.0 and 6.4×1023 n/m2 in the Halden test reactor. Atom probe tomography (APT) was applied to study clustering of Ni, Mn, Si, and Cu. As the clusters are in the nanometer-range, APT is a very suitable technique for this type of study. From APT analyses information about size distribution, number density, and composition of the clusters can be obtained. However, the quantification of these attributes is not trivial. The maximum separation method (MSM) has been used to characterize the clusters and a detailed study about the influence of the choice of MSM cluster parameters, primarily on the cluster number density, has been undertaken.

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OBJECTIVE: Evaluate changes in active and passive function with onabotulinumtoxinA + standard of care within goal-oriented rehabilitation programmes in adults with focal post-stroke spasticity. METHODS: Prospective, 24-week double-blind study with an open-label extension. Subjects were randomized to onabotulinumtoxinA + standard of care or placebo + standard of care, at baseline and at 12 weeks, if judged appropriate, with follow-up to 52 weeks. The primary endpoint was the number of patients achieving their principal active functional goal at 24 weeks (or 10 weeks after an optional second injection). Secondary endpoints included achievement of a different active or a passive goal at this timepoint. RESULTS: The intent-to-treat population comprised 273 patients. The proportion of patients achieving their principal active functional goal and secondary active functional goal with onabotulinumtoxinA + standard of care was not statistically different from placebo + standard of care. Significantly more patients achieved their secondary passive goal with onabotulinumtoxinA + standard of care (60.0%) vs. placebo + standard of care (38.6%) (odds ratio, 2.46; 95% confidence interval, 1.18-5.14) as well as higher Goal Attainment Scaling levels for upper limb and ankle flexor subgroups. CONCLUSIONS: Addition of onabotulinumtoxinA to standard of care as part of goal-oriented rehabilitation in post-stroke spasticity patients significantly increased passive goal achievement and was associated with higher levels of active function.

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An automated platform for development of high producing cell lines for biopharmaceutical production has been established in order to increase throughput and reduce development costs. The concept is based on the Cello robotic system (The Automation Partnership) and covers screening for colonies and expansion of static cultures. In this study, the glutamine synthetase expression system (Lonza Biologics) for production of therapeutic monoclonal antibodies in Chinese hamster ovary cells was used for evaluation of the automation approach. It is shown that the automated procedure is capable of producing cell lines of equal quality to the traditionally generated cell lines in terms of colony detection following transfection and distribution of IgG titer in the screening steps. In a generic fed-batch evaluation in stirred tank bioreactors, IgG titers of 4.7 and 5.0 g/L were obtained for best expressing cell lines. We have estimated that the number of completed cell line development projects can be increased up to three times using the automated process without increasing manual workload, compared to the manual process. Correlation between IgG titers obtained in early screens and titers achieved in fed-batch cultures in shake flasks was found to be poor. This further implies the benefits of utilizing a high throughput system capable of screening and expanding a high number of transfectants. Two concentrations, 56 and 75 muM, of selection agent, methionine sulphoximine (MSX), were applied to evaluate the impact on the number of colonies obtained post transfection. When applying selection medium containing 75 muM MSX, fewer low producing transfectants were obtained, compared to cell lines selected with 56 muM MSX, but an equal number of high producing cell lines were found. By using the higher MSX concentration, the number of cell line development projects run in parallel could be increased and thereby increasing the overall capacity of the automated platform process.

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The in vivo mechanisms of action of most vaccine adjuvants are poorly understood. In this study, we present data in mice that reveal a series of critical interactions between the cholera toxin (CT) adjuvant and the dendritic cells (DC) of the splenic marginal zone (MZ) that lead to effective priming of an immune response. For the first time, we have followed adjuvant targeting of MZ DC in vivo. We used CT-conjugated OVA and found that the Ag selectively accumulated in MZ DC following i.v. injections. The uptake of Ag into DC was GM1 ganglioside receptor dependent and mediated by the B subunit of CT (CTB). The targeted MZ DC were quite unique in their phenotype: CD11c(+), CD8alpha(-), CD11b(-), B220(-), and expressing intermediate or low levels of MHC class II and DEC205. Whereas CTB only delivered the Ag to MZ DC, the ADP-ribosyltransferase activity of CT was required for the maturation and migration of DC to the T cell zone, where these cells distinctly up-regulated CD86, but not CD80. This interaction appeared to instruct Ag-specific CD4(+) T cells to move into the B cell follicle and strongly support germinal center formations. These events may explain why CT-conjugated Ag is substantially more immunogenic than Ag admixed with soluble CT and why CTB-conjugated Ag can tolerize immune responses when given orally or at other mucosal sites.

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