Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase

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Incorporation of Obstacle Hardening into Local Approach to Cleavage Fracture to Predict Temperature Effects in the Ductile to Brittle Transition Regime

Ductile-to-brittle-transition refers to observable change in fracture mode with decreasing temperature—from slow ductile crack growth to rapid cleavage. It is exhibited by body-centred cubic metals and presents a challenge for integrity assessment of structural components made of such metals. Local approaches to cleavage fracture, based on Weibull stress as a cleavage crack-driving force, have been shown to predict fracture toughness at very low temperatures. However, they are ineffective in the transition regime without the recalibration of Weibull stress parameters, which requires further testing and thus diminishes their predictive capability. We propose new Weibull stress formulation with thinning function based on obstacle hardening model, which modifies the number of cleavage-initiating features with temperature. Our model is implemented as a post-processor of finite element analysis results. It is applied to analyses of standard compact tension specimens of typical reactor pressure vessel steel, for which deformation and fracture toughness properties in the transition regime are available. It is shown that the new Weibull stress is independent of temperature, and of Weibull shape parameter, within the experimental error. It accurately predicts the fracture toughness at any temperature in the transition regime without relying upon empirical fits for the first time.     

Assessment of PI-RADS v2 categories ≥ 3 for diagnosis of clinically significant prostate cancer

Abdominal Radiology - To assess the diagnostic accuracy of PI-RADS v2 categories ≥ 3 to detect clinically significant prostate cancer (csPCa) against histopathology of...     

Immunocytochemical detection of milk proteins in tracheal aspirates of ventilated infants: a pilot study

In this study, we evaluated immunocytochemical staining for milk proteins (alpha-lactalbumin and beta-lactoglobulin) in tracheal aspirates of mechanically ventilated infants, and assessed whether this staining technique supported a clinical diagnosis of aspiration in infants receiving orogastric feedings. All newborns requiring mechanical ventilation in the neonatal intensive care unit of a major tertiary care hospital were potential subjects for this study. Tracheal aspirates were obtained prior to the introduction of enteral feeding and at various time points thereafter in newborns requiring mechanical ventilation. Cells were obtained and processed for immunocytochemical staining of alpha-lactalbumin and beta-lactoglobulin. In total, 88 specimens recovered from 34 infants were adequate for staining. Alveolar macrophages recovered from most of the infants who were never fed (true negative controls) did not display immunoreactivity for milk proteins: 4/34 or 12% of infants' aspirates demonstrated presence of milk proteins before enteral feeding was commenced. Tracheal aspirates obtained from 12 infants after introduction of enteral feedings appeared to support clinical and radiological findings suggestive of aspiration events, with positive immunostaining on several occasions. These observations support our work in a murine model and demonstrate that immunocytochemical staining of tracheal aspirates for milk proteins may enhance the ability to diagnose pulmonary aspiration. Further studies are needed to define the clinical significance of our findings and the effects of single and repeated aspiration events on respiratory status.