Multiscale correlative characterization of environmentally assisted crack initiation, propagation and failure in a high strength AA5083 H131 alloy

Environmentally assisted cracking in a high strength AA5083 H131 alloy has been investigated using a multiscale correlative characterization approach to understand the surface intergranular corrosion to environmentally assisted crack (EAC) transition. Time-lapse 3D synchrotron X-ray tomography was employed during slow strain testing of a sensitized AA5083 sample sensitized at 80 °C for 250 h. In addition, several of the specimens tested were pre-exposed to a chloride containing environment to induce corrosion sites which could act as ‘realistic’ stress raisers in the subsequent straining. Reconstructed volumes of the X-ray CT time-lapse series allowed us to track and follow crack propagation in the material during slow strain rate testing at high resolution \u3c5 µm. Volumes of interest from the test samples identified from the X-ray CT reconstructions were further analyzed post-mortem using electron microscopy and spectroscopy based techniques to study the presence and chemistry of secondary phases such as those based on Mg-Si, and their role in the initiation, propagation and/or arrest of crack tips/fronts

Membrane interactions of the globular domain and the hypervariable region of KRAS4b define its unique diffusion behavior.

The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable region side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here, we characterize RAS in live human and mouse cells using single-molecule-tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the protein's globular domain. To understand the altered mobility of an oncogenic KRAS4b, we used complementary experimental and molecular dynamics simulation approaches to reveal a detailed mechanism

Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission

The human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-1–associated myelopathy. HTLV-1 is transmitted to T cells through the virological synapse and by extracellular viral assemblies. Here, we uncovered an additional mechanism of virus transmission that is regulated by the HTLV-1–encoded p8 protein. We found that the p8 protein, known to anergize T cells, is also able to increase T-cell contact through lymphocyte function-associated antigen-1 clustering. In addition, p8 augments the number and length of cellular conduits among T cells and is transferred to neighboring T cells through these conduits. p8, by establishing a T-cell network, enhances the envelope-dependent transmission of HTLV-1. Thus, the ability of p8 to simultaneously anergize and cluster T cells, together with its induction of cellular conduits, secures virus propagation while avoiding the host's immune surveillance. This work identifies p8 as a viral target for the development of therapeutic strategies that may limit the expansion of infected cells in HTLV-1 carriers and decrease HTLV-1–associated morbidity