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Scanning electron microscope measurement of width and shape of 10 nm patterned lines using a JMONSEL-modeled library
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Reproducible responses of geochemical and microbial successional patterns in the subsurface to carbon source amendment
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Structural variants identified using non-Mendelian inheritance patterns advance the mechanistic understanding of autism spectrum disorder
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Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues
There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens. • TSP1 (and not TSP2) may be considered as a target for antibody-based pharmacodelivery.
The effect of DNA damage on the pattern of immune-detectable DNA methylation in mouse embryonic fibroblasts
The methylation of cytosine at CpG dinucleotides (5meC) is an important epigenetic mechanism that governs genome stability and gene expression. Important ontological and pathological transitions are associated with marked global changes in detectable levels of methylation. We have previously found two pools of immune-detectable 5meC exist within cells, a pool that can be detected after acid treatment of fixed cells to denature chromatin and another large but variable pool that requires a further tryptic digestion step for complete epitope retrieval. The trypsin-sensitive pool has been shown to be largely associated with the heterochromatic fraction (by a heterochromatin marker, HP1-β) of the genome, and the size of this pool varies with the growth disposition of cells. Since DNA damage imposes large changes on chromatin structure the present study analyzed how such changes influences the faithful immunological detection of 5meC within mouse embryonic fibroblasts. DNA damage was induced by either UV-irradiation or doxorubicin treatment, each of which resulted in increased levels of immune-detectable 5meC at 24–48 h after treatment. There was a marked trypsin-sensitive pool of 5meC in these cells which was significantly increased after DNA damage. The increased levels of 5meC staining predominantly co-located with heterochromatic foci within nuclei, as assessed by HP1-β staining. The relative amount of masked 5meC after DNA damage was positively associated with increased levels of HP1-β. The methyl binding protein, MBD1, was a less reliable measure of changes in 5meC, with a significant fraction of 5meC not being marked by MBD1. The cyto-epigenetic approaches used here reveal dynamism in the levels and localization of immune-detectable 5meC within the nuclei of fibroblasts in response to DNA damage. - Highlights: • Immune-detectable 5meC within two pools retrieved after acid and trypsin after acid. • The size of the trypsin-sensitive pool varied in response to DNA damage. • This was associated with changes in the level of HP1-β within heterochromatic foci. • Epitope retrieval method detected remarkable dynamism in 5meC's level and location.
Some further considerations in powder diffraction pattern indexing with the dichotomy method
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Formation of dynamic topographic patterns during electron beam induced etching of diamond
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Accurate Calculation of CBED Patterns for 4D STEM Using Electron Densities Calculated by Density Functional Theory.
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Aromatic Ring Fluorination Patterns Modulate Inhibitory Potency of Fluorophenylhydroxamates Complexe
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Patterning, Transfer, and Tensile Testing of Covalent Organic Framework Films with Nanoscale Thickne
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Competing Intermolecular and Molecule–Surface Interactions: Dipole–Dipole-Driven Patterns in Mixed Carborane Self-Assembled Monolayers
Carboranedithiol isomers adsorbing with opposite orientations of their dipoles on surfaces are self-assembled together to form mixed monolayers where both lateral dipole–dipole and lateral thiol–thiolate (S–H···S) interactions provide enhanced stability over single-component monolayers. Here, we demonstrate the first instance of the ability to map individual isomers in a mixed monolayer using the model system carboranedithiols on Au{111}. The addition of methyl groups to one isomer provides both an enhanced dipole moment and extra apparent height for differentiation via scanning tunneling microscopy (STM). Associated computational investigations rationalize favorable interactions of mixed pairs and the associated stability changes that arise from these interactions. Both STM images and Monte Carlo simulations yield similarly structured mixed monolayers, where approximately 10% of the molecules have reversed dipole moment orientations but no direct chemical attachment to the surface, leading to homogeneous monolayers with no apparent phase separation. Deprotonating the thiols by depositing the molecules under basic conditions eliminates the lateral S–H···S interactions while accentuating the dipole–dipole forces. The molecular system investigated is composed of isomeric molecules with opposite orientations of dipoles and identical surface packing, which enables the mapping of individual molecules within the mixed monolayers and enables analyses of the contributions of the relatively weak lateral interactions to the overall stability of the assemblies.