56 research outputs found

    Mitochondrial permeabilization engages NF-kappa B-dependent anti-tumour activity under caspase deficiency

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    Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-ÎşB activity through the downregulation of inhibitor of apoptosis proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-ÎşB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies

    Analytical modeling and experimental verification of a S-shaped vibration energy harvester

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    During the last decade, significant research effort has been spent on simple Cantilever Piezoelectric Vibration Energy Harvesters (PVEHs). These types of harvesters have their maximum efficiency in a very narrow bandwidth around their natural frequency and are therefore unfit for being used in presence of random or wide spectrum excitation. In this study, a periodic substructure for multi-frequency energy harvesting with single piezoelectric patch is proposed. This system is able to harvest energy from several modes (the lower ones) and, through proper design, these modes may be obtained in a narrow frequency band. The substructure is designed through an analytical model that allows to place modes exactly where required and tests are carried out to validate the proposed analytical model. The results confirm the validity of the proposed model that could be exploited to determine solutions for further improving both the bandwidth and overall efficiency of the harvester by helping of nonlinearity phenomena

    Fatigue behavior of duplex-treated samples coated with Cr(C,N) film

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    The effect of a Cr(C,N) PVD coating on the fatigue behavior of 42CrMo4 steel grade was investigated both in a quenched and tempered condition and after nitriding treatment. The latter, so-called “duplex process”, combines a nitriding pre-treatment in order to obtain a hard and stiff substrate and a PVD coating in order to reduce the friction coefficient and improve the wear resistance of tools and mechanical components. Prior to fatigue testing, the surface modifications were characterized by means of X-ray diffraction (XRD), residual stress distribution, Vickers nano-hardness measurements and scanning electron microscopy (SEM) analysis. For the quenched and tempered steels, the PVD coating acts as a high compressive residual stressed zone able to increase the fatigue resistance of the coated component. On the contrary, for the duplex-treated samples, a limited increase in the fatigue limit was detected with respect to uncoated nitrided samples. This result was interpreted by means of the residual stress gradient which does not show high differences for nitrided coated and uncoated samples
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