A road map for reliable power electronics for more electric aircraft

The gradual evolution from hydro-pneumatic to electrical disposition of power in aircraft has placed stringent requirements on the reliability of power electronic components in current and future aerospace applications. This paper examines the prevalent state-of-the-art in power electronics and provides an analytical overview of power electronics in More Electric Aircraft (MEA) vis-à-vis the generation and distribution of power within these aircraft. The types of power devices currently employed for multiple conversion topologies are analysed and weighed according to their respective reliability characteristics. Beginning with an in-depth review of failure modes in the currently available devices, the paper highlights the salient emerging state-of-the-art Wide Band Gap (WBG) technologies such as Gallium Nitride (GaN) and Silicon Carbide (SiC) and draws an extensive comparison with their Silicon counterparts. A comprehensive examination of techniques employed for the estimation of the reliability of WBG power devices has revealed a number of areas that merit due consideration. For instance, the physics-based models that have been developed to assess the operational lifetime of silicon-based devices for given failure modes require revamping in light of the new materials and the unique electrical and physical characteristics the WBG devices possess. Similarly, the condition monitoring techniques, with respect to the primary and secondary parameters, require further investigation to determine highly representative feature vectors that best describe the degradation within these devices. More significantly, optimisation of the proposed techniques for the health assessment of these devices needs to be pursued through the optimal use of vital parameters. Keeping these critical findings in perspective, a road map highlighting various avenues for power electronics optimisation in MEA is put forth to apprise the aerospace fraternity of its growing significance

Global profiling of co- and post-translationally N-myristoylated proteomes in human cells

Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development and progression of a range of human diseases. Here, we report the global N-myristoylated proteome in human cells determined using quantitative chemical proteomics combined with potent and specific human N-myristoyltransferase (NMT) inhibition. Global quantification of N-myristoylation during normal growth or apoptosis allowed the identification of >100 N-myristoylated proteins, >95% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for >70 substrates simultaneously across the proteome. Small-molecule inhibition through a conserved substrate-binding pocket is also demonstrated by solving the crystal structures of inhibitor-bound NMT1 and NMT2. The presented data substantially expand the known repertoire of co- and post-translational N-myristoylation in addition to validating tools for the pharmacological inhibition of NMT in living cells

Integrins α2β1 and α11β1 regulate the survival of mesenchymal stem cells on collagen I

Although mesenchymal stem cells (MSCs) are the natural source for bone regeneration, the exact mechanisms governing MSC crosstalk with collagen I have not yet been uncovered. Cell adhesion to collagen I is mostly mediated by three integrin receptors – α1β1, α2β1 and α11β1. Using human MSC (hMSC), we show that α11 subunit exhibited the highest basal expression levels but on osteogenic stimulation, both α2 and α11 integrins were significantly upregulated. To elucidate the possible roles of collagen-binding integrins, we applied short hairpin RNA (shRNA)-mediated knockdown in hMSC and found that α2 or α11 deficiency, but not α1, results in a tremendous reduction of hMSC numbers owing to mitochondrial leakage accompanied by Bcl-2-associated X protein upregulation. In order to clarify the signaling conveyed by the collagen-binding integrins in hMSC, we analyzed the activation of focal adhesion kinase, extracellular signal-regulated protein kinase and serine/threonine protein kinase B (PKB/Akt) kinases and detected significantly reduced Akt phosphorylation only in α2- and α11-shRNA hMSC. Finally, experiments with hMSC from osteoporotic patients revealed a significant downregulation of α2 integrin concomitant with an augmented mitochondrial permeability. In conclusion, our study describes for the first time that disturbance of α2β1- or α11β1-mediated interactions to collagen I results in the cell death of MSCs and urges for further investigations examining the impact of MSCs in bone conditions with abnormal collagen I

The <i>N</i>-myristoylome of <i>Trypanosoma cruzi</i>

Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an essential and druggable target in Trypanosoma cruzi, the causative agent of Chagas’ disease. Here we have employed whole cell labelling with azidomyristic acid and click chemistry to identify N-myristoylated proteins in different life cycle stages of the parasite. Only minor differences in fluorescent-labelling were observed between the dividing forms (the insect epimastigote and mammalian amastigote stages) and the non-dividing trypomastigote stage. Using a combination of label-free and stable isotope labelling of cells in culture (SILAC) based proteomic strategies in the presence and absence of the NMT inhibitor DDD85646, we identified 56 proteins enriched in at least two out of the three experimental approaches. Of these, 6 were likely to be false positives, with the remaining 50 commencing with amino acids MG at the N-terminus in one or more of the T. cruzi genomes. Most of these are proteins of unknown function (32), with the remainder (18) implicated in a diverse range of critical cellular and metabolic functions such as intracellular transport, cell signalling and protein turnover. In summary, we have established that 0.43–0.46% of the proteome is N-myristoylated in T. cruzi approaching that of other eukaryotic organisms (0.5–1.7%)

Targeting N-myristoylation for therapy of B-cell lymphomas

N-myristoyltransferases (NMTs) target many signaling proteins to membranes. Here the authors show an NMT inhibitor named PCLX-001 selectively kills lymphoma cells by shutting down their main survival signaling pathway and offers an additional treatment strategy for lymphoma patients

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

A Component Level Digital Twin Model for Power Converter Health Monitoring

The proliferation of Power Electronic Converters (PECs) has had a pervasive affect in a variety of industries including the power generation, automotive and aerospace sectors, where their use brings reliability to the forefront, especially in applications where safety critical and harsh environments are experienced. Continuous improvements in the power density and efficiency through extensive research into new semiconductor technologies, passive components, circuit topologies and control methodologies has seen the performance of PECs improve indubitably. However, the manifestation of stresses occurring from significant heating due to high currents and switching frequencies; which over time can cause degradation in the performance of PEC components is still a real concern. This paper outlines a methodology for monitoring the degradation of PECs over the operational lifetime by utilizing a component level, physics based Digital Twin (DT). As well as providing a methodology for the real time comparison of parameters to realize the onset of faults subjected to operational stresses, the DT also provides a novel method of training a classifier by simulating the faults within the PEC, a process that in reality, would be difficult to achieve from a physical device. Feature extraction is via Wavelet Scattering and classification is provided using a Support Vector Machine (SVM) approach. The overall approach is one that is novel and expandable to a wide range of PEC topologies and will be beneficial to the optimization and maintenance of PECs in a variety of platforms

Enhanced online identification of battery models exploiting data richness

The online model parameter identification is essential to ensure the accuracy and dependability of other battery management system (BMS) tasks in the case of battery degradation and operational environment change. Traditional recursive least squares (RLS) algorithms have always been dependent on persistently exciting data, which limits their ability to operate online when this cannot be guaranteed. This paper proposed a modified RLS method that selects the data richest point for parameter identification. In this model, Fisher information matrix and Cramer-Rao bound are utilised to evaluate the data richness. The final algorithms solve the operational limitations of RLS algorithms, enabling a reliable online model parameter identification under real-world dynamic conditions. The identified model parameters from the single cycle dynamic stress test (DST) of an NCM battery are verified by terminal voltage and state of charge (SoC) estimation with the Root Mean Square Error (RMSE) 0.0332 and 0.0131, respectively