Design and Applications of In-Situ Differential Scanning Electron Microscopy

Contrast enhancement in the scanning electron microscope (SEM) is usually achieved by either of the two techniques of black level suppression, and differential imaging. This paper is mainly concerned with the latter method. Differential imaging of SEM images is commonly accomplished by either using a selective electronic filtering circuit (time sensitive) on the video signals, or the post processing of a collected digitized image (application of special kernel operatives). A technique is described that is capable of generating true in-situ SEM differential video signals of local sample features. Characteristics of this method are enhanced sample feature-boundary sensitivity, suppression of large background signals, and the ability to perform critical pattern alignments prior to feature measurements. Results are presented on the application of the technique to the general field of electron microscopy, as well as to integrated circuit micro-metrology

Bird Community Responses to Rest-Rotation Grazing in Western Canada\u27s Grasslands

Western Canada’s native grasslands support high levels of avian diversity including both resident and migrant species. Many grassland specialist bird populations, however, are in serious decline due to widespread habitat loss resulting from agricultural conversion and adverse land management. As the primary use on remaining grasslands, cattle grazing largely determines the availability and quality of bird species’ habitat, depending on the timing, intensity, and frequency of livestock use. While adaptive multi-paddock grazing (AMP, a short duration, high-intensity grazing system that prioritises plant recovery between grazing events) is growing in popularity, comprehensive assessments of bird diversity in relation to AMP grazing practices are largely lacking. As part of a larger grazing management study, we examined how AMP grazing practices influence the taxonomic and phylogenetic diversity of bird species, compared to neighbouring (n-AMP) properties managed with more conventional grazing practices. In addition to the AMP/n-AMP contrast, we used rancher survey information to test for the influence of specific grazing practices over and above biophysical effects. Bird communities were surveyed at 309 point count locations across 38 ranches (set up as matched pairs) using visual and acoustic detection. Overall, we identified 96 bird species, of which 81 species were recorded on AMP-grazed ranches compared to 84 species on grasslands under n-AMP grazing, ranging from 10-32 species per ranch. We observed a considerable grazing management signal on species abundance and diversity including significant associations between some threatened species and n-AMP grazing. Moreover, AMP grazing, and specifically the use of higher rest-to-grazing ratios early in the growing season (prior to August 1), was associated with phylogenetically more clustered bird communities. Overall, this study highlights the potential of specialized rotational grazing systems to alter the composition and phylogenetic diversity of grassland bird communities. In conclusion, we stress the importance for prioritisation of strategic management plans to safeguard and restore North America’s grassland bird communities

Cancer-Associated Fibroblasts Suppress CD8⁺ T-cell Infiltration and Confer Resistance to Immune-Checkpoint Blockade

\ua92022 The Authors. Immune-checkpoint blockade (ICB) promotes antitumor immune responses and can result in durable patient benefit. However, response rates in breast cancer patients remain modest, stimulating efforts to discover novel treatment options. Cancer-associated fibroblasts (CAF) represent a major component of the breast tumor microenvironment and have known immunosuppressive functions in addition to their well-established roles in directly promoting tumor growth and metastasis. Here we utilized paired syngeneic mouse mammary carcinoma models to show that CAF abundance is associated with insensitivity to combination aCTLA4 and aPD-L1 ICB. CAF-rich tumors exhibited an immunologically cold tumor microenvironment, with transcriptomic, flow cytometric, and quantitative histopathologic analyses demonstrating a relationship between CAF density and a CD8+ T-cell–excluded tumor phenotype. The CAF receptor Endo180 (Mrc2) is predominantly expressed on myofibroblastic CAFs, and its genetic deletion depleted a subset of aSMA-expressing CAFs and impaired tumor progression in vivo. The addition of wild-type, but not Endo180-deficient, CAFs in coimplantation studies restricted CD8+ T-cell intratumoral infiltration, and tumors in Endo180 knockout mice exhibited increased CD8+ T-cell infiltration and enhanced sensitivity to ICB compared with tumors in wild-type mice. Clinically, in a trial of melanoma patients, high MRC2 mRNA levels in tumors were associated with a poor response to aPD-1 therapy, highlighting the potential benefits of therapeutically targeting a specific CAF subpopulation in breast and other CAF-rich cancers to improve clinical responses to immunotherapy

Effect of vitamin E on chemotherapy-induced mucositis and neutropenia in leukemic patients undergoing bone marrow transplantation

Aim: This study was conducted to investigate the effect of oral vitamin E on mucositis and neutropenia in patients with leukemia. Methods: This was a randomized double-blind placebo controlled clinical trial of 60 patients with leukemia (acute lymphoblastic, acute myelogenous leukemia and chronic myelogenous leukemia) who were consecutive recipients of allogenic bone marrow transplantation (BMT), randomly assigned to receive 400 mg vitamin E twice daily (supplemented group) or placebo (control). The incidence and severity of mucositis and the mean duration of neutropenia were compared. Results: The mean duration of neutropenia and the incidence of the mucositis between the two groups was the same (P = 1.0). The difference between the placebo group and mucositis grade 1 (P = 0.31), grade 2 (P = 0.25), grade 3 (P = 0.93) and grade 4 (P = 0.32) was not statistically significant. Moreover the variables of age, sex, BMI and underlying disease had no effect. Conclusion: In this study supplementation with oral vitamin E had no effect on mucositis and neutropenia in patients with leukemia who were recipients of allogenic BMT. More interventional trials are warranted. © 2007 The Authors; Journal Compilation © Blackwell Publishing Asia Pty Ltd

Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis

\ua9 2021, The Author(s). Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is hampered by the lack of specific markers defining these populations. Here we show that genetic deletion of the Endo180 (MRC2) receptor, predominantly expressed by a population of matrix-remodelling CAFs, profoundly limits tumour growth and metastasis; effects that can be recapitulated in 3D co-culture assays. This impairment results from a CAF-intrinsic contractility defect and reduced CAF viability, which coupled with the lack of phenotype in the normal mouse, demonstrates that upregulated Endo180 expression by a specific, potentially targetable CAF subset is required to generate a supportive tumour microenvironment. Further, characterisation of a tumour subline selected via serial in vivo passage for its ability to overcome these stromal defects provides important insight into, how tumour cells adapt to a non-activated stroma in the early stages of metastatic colonisation