Property Optimization for TWIP Steels – Effect of Pre-deformation Temperature on Fatigue Properties

The current work investigates the impact of pre-deformation temperatures on the microstructure evolution and the subsequent cyclic stress-strain response of high-manganese steel showing twinning-induced plasticity (TWIP) at room temperature (RT). Deformation at low temperatures increases the hardening rate at low to medium degrees of deformation through concurrent martensitic transformation. In contrast, high temperatures promote dislocation slip. Thus, employing pre-treatments at temperatures below and above RT leads to the evolution of considerably different microstructures. Low-cycle fatigue experiments revealed distinct differences for the pre-treated TWIP steels

Separation of VUV/UV photons and reactive particles in the effluent of a He/O2 atmospheric pressure plasma jet

Cold atmospheric pressure plasmas can be used for treatment of living tissues or for inactivation of bacteria or biological macromolecules. The treatment is usually characterized by a combined effect of UV and VUV radiation, reactive species, and ions. This combination is usually beneficial for the effectiveness of the treatment but it makes the study of fundamental interaction mechanisms very difficult. Here we report on an effective separation of VUV/UV photons and heavy reactive species in the effluent of a micro scale atmospheric pressure plasma jet ($\mu$-APPJ). The separation is realized by an additional flow of helium gas under well-defined flow conditions, which deflects heavy particles in the effluent without affecting the VUV and UV photons. Both components of the effluent, the photons and the reactive species, can be used separately or in combination for sample treatment. The results of treatment of a model plasma polymer film and vegetative Bacillus subtilis and Escherichia coli cells are shown and discussed. A simple model of the He gas flow and reaction kinetics of oxygen atoms in the gas phase and at the surface is used to provide a better understanding of the processes in the plasma effluent. The new jet modification, called X-Jet for its appearance, will simplify the investigation of interaction mechanisms of atmospheric pressure plasmas with biological samples.Comment: 10 pages, 7 figures, submitted to Journal of Physics D: Applied Physic

Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity

Prosurvival Bcl-2–like proteins, like Bcl-w, are thought to function on organelles such as the mitochondrion and to be targeted to them by their hydrophobic COOH-terminal domain. We unexpectedly found, however, that the membrane association of Bcl-w was enhanced during apoptosis. In healthy cells, Bcl-w was loosely attached to the mitochondrial membrane, but it was converted into an integral membrane protein by cytotoxic signals that induce binding of BH3-only proteins, such as Bim, or by the addition of BH3 peptides to lysates. As the structure of Bcl-w has revealed that its COOH-terminal domain occupies the hydrophobic groove where BH3 ligands bind, displacement of that domain by a BH3 ligand would displace the hydrophobic COOH-terminal residues, allowing their insertion into the membrane. To determine whether BH3 ligation is sufficient to induce the enhanced membrane affinity, or to render Bcl-w proapoptotic, we mimicked their complex by tethering the Bim BH3 domain to the NH2 terminus of Bcl-w. The chimera indeed bound avidly to membranes, in a fashion requiring the COOH-terminal domain, but neither promoted nor inhibited apoptosis. These results suggest that ligation of a proapoptotic BH3-only protein alters the conformation of Bcl-w, enhances membrane association, and neutralizes its survival function

Effects of Benzopyrene-7,8-Diol-9,10-Epoxide (BPDE) In Vitro and of Maternal Smoking In Vivo on Micronuclei Frequencies in Fetal Cord Blood

Up to 20% of pregnant women smoke and there is indirect evidence that certain tobacco-specific metabolites can cross the placental barrier and are genotoxic to the fetus. The presence of micronuclei results from chromosome damage and reflects the degree of underlying genetic instability. Fetal blood was obtained from the cord blood of 143 newborns (102 from nonsmoking mothers and 41 from mothers smoking >10 cigarettes/d during pregnancy). The micronucleus assay was performed following the guidelines established by the Human MicroNucleus project with modifications. To test the micronucleus assay, we evaluated the effect of a range of benzopyrene-7,8-diol-9,10-epoxide concentrations (from 3.125 nM to 4 microM) on cord blood from nonsmoking mothers. This validation showed that the number of micronuclei and apoptotic cells increased with benzopyrene-7,8-diol-9,10-epoxide dose (p < 0.0001 and p = 0.001, respectively); the minimal detectable effect was induced by 12.5 nM benzopyrene-7,8-diol-9,10-epoxide. In our sample, the number of MN was significantly higher in the 41 cord blood samples from mothers who smoked during pregnancy [smokers: 4 (1; 10.5); nonsmokers: 3 (0; 8); p = 0.016]. Therefore, the data reported herein support the hypothesis that tobacco compounds are able to induce chromosomal losses and breaks that are detectable as an increased number of micronuclei

A common framework for approaches to extreme event attribution

The extent to which a given extreme weather or climate event is attributable to anthropogenic climate change is a question of considerable public interest. From a scientific perspective, the question can be framed in various ways, and the answer depends very much on the framing. One such framing is a risk-based approach, which answers the question probabilistically, in terms of a change in likelihood of a class of event similar to the one in question, and natural variability is treated as noise. A rather different framing is a storyline approach, which examines the role of the various factors contributing to the event as it unfolded, including the anomalous aspects of natural variability, and answers the question deterministically. It is argued that these two apparently irreconcilable approaches can be viewed within a common framework, where the most useful level of conditioning will depend on the question being asked and the uncertainties involved

Eph/Ephrin Profiling in Human Breast Cancer Reveals Significant Associations between Expression Level and Clinical Outcome

Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs) and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated eph and ephrin expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA) and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between ephA2, ephA4, ephA7, ephB4, and ephB6 and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between ephrin ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment