Additional file 3: of Physical basis of the ‘magnification rule’ for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer

Figure S3. Scatter-plot of HER2 DAB-precipitates width and color intensity. For scoring intensities 1+ and 2+ (grey), width and intensity show a linear correlation (r = 0.73, dashed lined). Scoring category 3+ shows saturated intensity (n = 1200 measurements in 40 cases per scoring category). (JPEG 585 kb

Additional file 1: of Physical basis of the ‘magnification rule’ for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer

Figure S1. Example photomicrographs of HER2-IHC. Images depict scoring categories 1+, 2+ and 3+ at magnifications reflecting different microscope objectives (2.5× - 63×. Inserts: Magnified details, 4× additional magnification). Note that the linear DAB-precipitates in categories 1+ and 2+ are not perceivable at low power magnification (2.5×, 5×). (TIFF 47314 kb

Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease

Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington’s disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit <b>7d</b>, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay