Aberration-corrected Z-contrast (HAADF) STEM offers significant advantages for materials research due to its superior resolution and sensitivity, which allows observation of atomic-scale phenomena with unprecedented detail. ORNL's 300 kV VG Microscopes' HB603U STEM with Nion aberration corrector has a subAngstrom probe size [1] and routinely allows us to image single heavy atoms inside the materials and on their surfaces, providing the ideal experimental input for the concurrent first-principles calculations. These abilities proved necessary for elucidating the mechanism of stabilization of La-doped γ-Al 2 O 3 by dopant single atoms [2]. Combination of STEM and simultaneously acquired EELS assisted in the explanation of the drastic difference in stability between Cr/ γ-Al 2 O 3 and Cr/η-Al 2 O 3 catalytic systems, which was traced back to minor differences in vacancies' distribution in the bulk of the support [3]. Another promising avenue of research lies in the field of bimetallic catalysts. Z-contrast STEM is invaluable as the atomic structure and ultimately distribution of different metal atoms within catalytic particles can be revealed.We conducted a systematic STEM study of the prospective catalyst system (Pt, Ru)/MgO prepared from bimetallic cluster precursors of different stoichiometries [4]. For all cases, we observe regular monolayerlike metal particles on the surface, which have similar structure but varying sizes ( Fig.1 (a), (b)). On the MgO (110) surface, the particles are aligned closely with support lattice (Fig. 1(c)). Away from step defects, particles are not fixed rigidly to the surface, but travel easily under the beam, changing the outline and shedding and absorbing single atoms; however, the structural pattern stays the same.Density functional theory calculations have been used to determine the structure of possible particles on MgO (110). We find that regular monolayer-like structures can be formed by Pt, with metal atoms bonded to surface oxygen, from small isolated clusters (Fig 2(a)) to continuous (Fig 2(b)) or semicontinuous (Fig. 2(c))layers. The binding energy of the particles to the flat surface of the substrate is fairly low, in full agreement with experimentally observed mobility. We analyze the dependence of binding energy on cluster composition (addition of Ru), as well as the influence of surface defects such as steps and vacancies on cluster structure and mobility. Implications for the catalytic activity of the (Pt, Ru)/MgO system will also be discussed References:[1] P. D. Nellist et al.
Given the success of both targeted and immunotherapies against cancer, there is increasing utility for identifying targeted agents that also promote anti-tumor immunity. EphA2 is a receptor tyrosine kinase that contributes to tumor growth and metastasis and has been identified as a viable target for many solid cancers. Investigating EphA2's impact on the host immune system may advance our understanding of tumor immune evasion and the consequences of targeting EphA2 on the tumor microenvironment. Here, we examine how tumor-specific EphA2 affects the activation and infiltration of immune cell populations and the cytokine and chemokine milieu in non-small cell lung cancer (NSCLC). Effects of EphA2 overexpression in murine NSCLC cells were evaluated in both in vitro cell viability assays and in vivo tumor models. Tumor immune infiltrate was assessed by flow cytometry. Cytokine and chemokine expression was evaluated using NanoString technology and qRT-PCR. Although EphA2 overexpression in NSCLC cells did not display proliferative advantage in vitro, it conferred a growth advantage in vivo. Analysis of lung tumor infiltrate revealed decreased natural killer and T cells in the EphA2-overexpressing tumors, as well as increased myeloid populations, including tumor-associated macrophages (TAMs). T cell activation, particularly in CD8 T cells, was decreased, while PD-1 expression was increased. These changes were accompanied by increased monocyte-attracting chemokines, specifically CCL2, CCL7, CCL8, and CCL12, and immunosuppressive proteins TGF-β and arginase 1. Our studies suggest EphA2 on tumor cells recruits monocytes and promotes their differentiation into TAMs that likely inhibit activation and infiltration of cytotoxic lymphocytes, promoting tumor immune escape.Further studies are needed to determine the molecular mechanisms by which EphA2 affects the recruitment of these cell types and to test the function of these myeloid cells.
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