A small molecule, alpha-(trichloromethyl)-4-pyridineethanol (PETCM), was identified by high-throughput screening as an activator of caspase-3 in extracts of a panel of cancer cells. PETCM was used in combination with biochemical fractionation to identify a pathway that regulates mitochondria-initiated caspase activation. This pathway consists of tumor suppressor putative HLA-DR-associated proteins (PHAP) and oncoprotein prothymosin-alpha (ProT). PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation. PETCM relieved ProT inhibition and allowed apoptosome formation at a physiological concentration of deoxyadenosine triphosphate. Elimination of ProT expression by RNA interference sensitized cells to ultraviolet irradiation-induced apoptosis and negated the requirement of PETCM for caspase activation. Thus, this chemical-biological combinatory approach has revealed the regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis.
The mandatory Non-Destructive Testing (NDT) by the aerospace industry for both present and future generation hybrid aircraft using thick composite structures poses many challenges for traditional inspection techniques. Laser Ultrasonic Testing (LUT) deployed by a robot for inspection of modern aerospace composite components shows good promise. It is a non-contact method offering the possibility of fast scan times without the need for couplant. This paper presents the latest work-in-progress for the design and development of the system developed by the ACCURATe consortium. ACCURATe is an ongoing H2020 Clean Sky 2 part funded project to develop a laser ultrasound based NDT system prototype for fast and contactless testing of large carbon fibre reinforced polymer (CFRP) aircraft structures.
The approach is based on a non-contact laser generated and detected pulsed ultrasound technique with delivery of both the laser ultrasound excitation and detection pulses through flexible optical fibres. The backscattered light from the lasers is also collected into a fibre. The measurement head, which contains the two beam outputs and the light collection optics is raster scanned over the surface by a 6-axis robot arm. A balanced two wave mixing interferometer (B-TWM) is used for the demodulation of the ultrasonic waves.
The system has recently been used to scan a reference panel, and a scrap panel of fuselage, the latest test results are presented and show promising progress against the project objectives.
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