Heightened international concerns relating to security and identity management have led to an increased interest in security applications, such as face recognition and baggage and passenger screening ...at airports. A common feature of many of these technologies is that a human operator is presented with an image and asked to decide whether the passenger or baggage corresponds to a person or item of interest. The human operator is a critical component in the performance of the system and it is of considerable interest to not only better understand the performance of human operators on such tasks, but to also design systems with a human operator in mind. This paper discusses a number of human factors issues which will have an impact on human operator performance in the operational environment, as well as highlighting the variables which must be considered when evaluating the performance of these technologies in scenario or operational trials based on Defence Science and Technology Organisation’s experience in such testing.
Short in-frame deletions in the second extracellular domain of the cytokine receptor gp130 are the leading cause of inflammatory hepatocellular adenomas (IHCAs). The deletions render gp130 ...constitutively active. In this study we investigate the intracellular signaling potential of one of the most potent constitutively active gp130 mutants (CAgp130) found in IHCAs.
Trafficking and signaling of CAgp130 were studied in stably transfected cell lines that allowed the inducible expression of CAgp130 fused to fluorescent proteins such as YFP and mCherry. In contrast to the predominantly highly glycosylated gp130 wild type (WTgp130), CAgp130 is preferentially found in the less glycosylated high-mannose form. Accordingly, the mutated receptor is retained intracellularly and therefore less prominently expressed at the cell surface. CAgp130 persistently activates Stat3 despite the presence of the feedback inhibitor SOCS3 but fails to activate Erk1/2. De novo synthesized CAgp130 signals already from the ER-Golgi compartment before having reached the plasma membrane. Cell surface expressed and endocytosed CAgp130 do not significantly contribute to signaling. As a consequence, Stat3 activation through CAgp130 cannot be inhibited by neutralizing gp130 antibodies but through overexpression of a dominant-negative Stat3 mutant.
CAgp130 and WTgp130 differ significantly with respect to glycosylation, trafficking and signaling. As a consequence of intracellular signaling pharmacological inhibition of CAgp130 will not be achieved by targeting the receptor extracellularly but by compounds that act from within the cell.
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