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The paper presents the results of the research on the impact of process parameters of high-pressure, cold-chamber die casting of an industrial casting made of aluminium alloy on the casting properties assessed macroscopically by measuring the casting average density and microscopically through the characteristics of the casting microstructure. The analysis covers the influence of three selected velocity settings of the pressing plunger, which determine the filling time, and three values of the compression pressure setting characteristic of the third phase of the casting process. The cooling and solidification simulations of the casting were performed using the ProCAST software. During the simulation tests, the impact of the filling rate of the alloy into the die cavity on the cooling rate and the alloy solidification path at selected points were determined. The conducted research allowed linking the process parameters with the parameters of the casting structure with different wall thicknesses. Metallographic examinations of the castings were carried out using a light microscopy, SEM, and EDS analysis. The fraction of the phases α(Al), the size of dendritic cells, and the size of silicon particles, in the cross-sections of the castings with wall thickness of 3, 6, and 11 mm, respectively, were determined.

A methodological approach to perceptual learning was used to allow both early blind subjects (experimental group) and blindfolded sighted subjects (control group) to experience optical information and spatial phenomena, on the basis of visuo-tactile information transmitted by a 64-taxel pneumatic sensory substitution device. The learning process allowed the subjects to develop abilities in spatial localisation, shape recognition (with generalisation to different points of view), and monocular depth cue interpretation. During the training phase, early blind people initially experienced more difficulties than blindfolded sighted subjects (having previous perceptual experience of perspective) with interpreting and using monocular depth cues. The amelioration of the performance for all blind subjects during training sessions and the quite similar level of performance reached by two groups in the final navigation tasks suggested that early blind people were able to develop and apply cognitive understanding of depth cues. Both groups showed generalisation of the learning from the initial phases to cue identification in the maze, and subjectively experienced shapes facing them. Subjects' performance depended not only on their perceptual experience but also on their previous spatial competencies.

SummaryCaspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X2-D-X3 motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection.

SummarySelective autophagy of bacterial pathogens represents a host innate immune mechanism. Selective autophagy has been characterized on the basis of distinct cargo receptors but the mechanisms by which different cargo receptors are targeted for autophagic degradation remain unclear. In this study we identified a highly conserved Tectonin domain-containing protein, Tecpr1, as an Atg5 binding partner that colocalized with Atg5 at Shigella-containing phagophores. Tecpr1 activity is necessary for efficient autophagic targeting of bacteria, but has no effect on rapamycin- or starvation-induced canonical autophagy. Tecpr1 interacts with WIPI-2, a yeast Atg18 homolog and PI(3)P-interacting protein required for phagophore formation, and they colocalize to phagophores. Although Tecpr1-deficient mice appear normal, Tecpr1-deficient MEFs were defective for selective autophagy and supported increased intracellular multiplication of Shigella. Further, depolarized mitochondria and misfolded protein aggregates accumulated in the Tecpr1-knockout MEFs. Thus, we identify a Tecpr1-dependent pathway as important in targeting bacterial pathogens for selective autophagy.