The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for maintaining cellular energy homeostasis. Activation of AMPK by salicylate and the thienopyridone A-769662 is critically dependent on phosphorylation of Ser108 in the β1 regulatory subunit. Here, we show a possible role for Ser108 phosphorylation in cell cycle regulation and promotion of pro-survival pathways in response to energy stress. We identify the autophagy initiator Unc-51-like kinase 1 (ULK1) as a β1-Ser108 kinase in cells. Cellular β1-Ser108 phosphorylation by ULK1 was dependent on AMPK β-subunit myristoylation, metabolic stress associated with elevated AMP/ATP ratio, and the intrinsic energy sensing capacity of AMPK; features consistent with an AMP-induced myristoyl switch mechanism. We further demonstrate cellular AMPK signaling independent of activation loop Thr172 phosphorylation, providing potential insight into physiological roles for Ser108 phosphorylation. These findings uncover new mechanisms by which AMPK could potentially maintain cellular energy homeostasis independently of Thr172 phosphorylation

Mapping SEARCH capabilities to Spirit AeroSystems NDE and automation demand for composites

Newly engineered and complex materials and processes such as composite and additive manufacturing are becoming an indispensable part of today's manufacturing economy owing to their potential to reduce material waste and carbon emissions whilst enhancing mechanical performance. To quantify and validate the high quality of manufacturing processes, and ensure safe in-service operation for these components, Non-Destructive Evaluation (NDE) sensor technologies, and their corresponding data acquisition and signal processing routines should evolve to better suit these new materials and processes. Besides, deployment of automated robotic systems has seen an increasing demand in the past decade as the repeatability, consistency, and speed of NDE scans offered through automation can boost the manufacturing throughput significantly. The large volumes of data generated through such automated NDE approaches require new intelligent algorithms for signal interpretation to sustain and match the pace of automated NDE. The Centre for Ultrasonic Engineering (CUE) has been supporting Spirit AeroSystems through a Royal Academy of Engineering Research Chair to drive the research and innovation in three distinct themes of a) sensor technology, b) automation and robotic sensor deployment, and c) data interpretation through machine learning. This presentation will provide an overview of different NDE challenges in manufacturing of composites at Spirit AeroSystems and discuss the approaches undertaken to tackle these by the team at CUE. This includes proposing a roadmap inspired by the current research efforts for future of NDE in aerospace composite manufacturing

Complex relationships among personality traits, job characteristics, and work behaviors

The aim of the study was to investigate the additive, mediating, and moderating effects of personality traits and job characteristics on work behaviors. Job applicants (N = 161) completed personality questionnaires measuring extraversion, neuroticism, achievement motivation, and experience seeking. One and a half years later, supervisors rated the applicants' job performance, and the job incumbents completed questionnaires about skill variety, autonomy, and feedback, work stress, job satisfaction, work self-efficacy, and propensity to leave. LISREL was used to test 15 hypotheses. Perceived feedback mediated the relationship between achievement motivation and job performance. Extraversion predicted work self-efficacy and job satisfaction. Work stress mediated the relationship between neuroticism and job satisfaction. Job satisfaction and experience seeking were related to propensity to leave. Autonomy, skill variety, and feedback were related to job satisfaction

Schools out : Adam Smith and pre-disciplinary international political economy

In this article, I argue that invocations of Adam Smith in international political economy (IPE) often reveal the influence therein of a disciplinary ontological disaggregation of economic and non-economic rationality, which I claim is obscured by the tendency to map its complex intellectual contours in terms of competing schools. I trace the origins of the disciplinary characterisation of Smith as the founder of IPE's liberal tradition to invocations of his thought by centrally important figures in the perceived Austrian, Chicago and German historical schools of economics, and reflect upon the significance to IPE of the reiteration of this portrayal by apparent members of its so-called American and British schools. I additionally contrast these interpretations to those put forward by scholars who seek to interpret IPE and Smith's contribution to it in pre-disciplinary terms, which I claim reflects a distinct ontology to that attributed to the British school of IPE with which their work is often associated. I therefore contend that reflection upon invocations of Smith's thought in IPE problematises the longstanding tendency to map its intellectual terrain in terms of competing schools, reveals that the disciplinary ontological consensus that informs this tendency impacts upon articulations of its core concerns and suggests that a pre-disciplinary approach offers an alternative lens through which such concerns might be more effectively framed