mTOR Signaling, Translational Control, and the Circadian Clock

Almost all cellular processes are regulated by the approximately 24 h rhythms that are endogenously driven by the circadian clock. mRNA translation, as the most energy consuming step in gene expression, is temporally controlled by circadian rhythms. Recent research has uncovered key mechanisms of translational control that are orchestrated by circadian rhythmicity and in turn feed back to the clock machinery to maintain robustness and accuracy of circadian timekeeping. Here I review recent progress in our understanding of translation control mechanisms in the circadian clock, focusing on a role for the mammalian/mechanistic target of rapamycin (mTOR) signaling pathway in modulating entrainment, synchronization and autonomous oscillation of circadian clocks. I also discuss the relevance of circadian mTOR functions in disease

An Automated Data Fusion-Based Gear Faults Classification Framework in Rotating Machines

The feasibility and usefulness of frequency domain fusion of data from multiple vibration sensors installed on typical industrial rotating machines, based on coherent composite spectrum (CCS) as well as poly-coherent composite spectrum (pCCS) techniques, have been well-iterated by earlier studies. However, all previous endeavours have been limited to rotor faults, thereby raising questions about the proficiency of the approach for classifying faults related to other critical rotating machine components such as gearboxes. Besides the restriction in scope of the founding CCS and pCCS studies on rotor-related faults, their diagnosis approach was manually implemented, which could be unrealistic when faced with routine condition monitoring of multi-component industrial rotating machines, which often entails high-frequency sampling at multiple locations. In order to alleviate these challenges, this paper introduced an automated framework that encompassed feature generation through CCS, data dimensionality reduction through principal component analysis (PCA), and faults classification using artificial neural network (ANN). The outcomes of the automated approach are a set of visualised decision maps representing individually simulated scenarios, which simplifies and illustrates the decision rules of the faults characterisation framework. Additionally, the proposed approach minimises diagnosis-related downtime by allowing asset operators to easily identify anomalies at their incipient stages without necessarily possessing vibration monitoring expertise. Building upon the encouraging results obtained from the preceding part of this approach that was limited to well-known rotor-related faults, the proposed framework was significantly extended to include experimental and open-source gear fault data. The results show that in addition to early established rotor-related faults classification, the approach described here can also effectively and automatically classify gearbox faults, thereby improving the robustness

Development of a Dynamical Egress Behavioural Model under Building Fire Emergency

Building fire accidents, as a continuing menace to the society, not only incur enormous property damage but also pose significant threats to human lives. More recently, driven by the rapid population growth, an increasing number of large-capacity buildings are being built to meet the growing residence demands in many major cities globally, such as Sydney, Hong Kong, London, etc. These modern buildings usually have complex architectural layouts, high-density occupancy settings, which are often filled with a variety of flammable materials and items (i.e., electrical devices, flammable cladding panels etc.). For such reasons, in case of fire accidents, occupants of these buildings are likely to suffer from an extended evacuation time. Moreover, in some extreme cases, occupants may have to escape through a smoke-filled environment. Thus, having well-planned evacuation strategies and fire safety systems in place is critical for upholding life safety. Over the last few decades, due to the rapid development in computing power and modelling techniques, various numerical simulation models have been developed and applied to investigate the building evacuation dynamics under fire emergencies. Most of these numerical models can provide a series of estimations regarding building evacuation performance, such as predicting building evacuation time, visualising evacuation dynamics, identifying high-density areas within the building etc. Nevertheless, the behavioural variations of evacuees are usually overlooked in a significant proportion of such simulations. Noticeably, evacuees frequently adjust their egress behaviours based on their internal psychological state (i.e., the variation of stress) and external stimulus from their surrounding environments (i.e., dynamical fire effluents, such as high-temperature smoke). Evidence suggests that evacuees are likely to shift from a low-stress state to a high-stress state and increase their moving speed when escaping from a high-temperature and smoke-filled environment. Besides, competitive behaviours can even be triggered under certain extremely stressful conditions, which can cause clogging at exits or even stampede accidents. Without considering such behavioural aspects of evacuees, the predicted evacuation performance might be misinterpreted based on unreliable results; thereby, misleading building fire safety designs and emergency precautions. Therefore, to achieve a more realistic simulation of building fire evacuation processes, this research aims to advance in modelling of human dynamical behaviour responses of each evacuee and integrating it into building fire evacuation analysis. A dynamical egress behaviour-based evacuation model that considering the evacuee’s competitive/cooperative egress movements and their psychological stress variation is developed. Furthermore, a fire hazard-integrated evacuation simulation framework is established by coupling with the fire dynamics simulator (i.e., FDS). By means of tracking dynamical interactions between evacuees and the evolutionary fire dynamics within the building space, evacuees’ local fire risks and stress levels under the impacts of locally encountered fire hazards (i.e., radiation, temperature, toxic gas, and visibility) can be effectively quantified. In this study, the developed simulation tool can provide a further in-depth building fire safety assessment. Thus, it contributes to performance-based fire safety engineering in designs and real applications, including reducing budgets and risks of participating in evacuation drills, supporting emergency evacuation strategy planning, mitigating fire risks by identifying risk-prone areas associated with building fire circumstances (e.g., putting preventative measures in place beforehand to intervene or mitigate safety risks, such as mass panic, stampede, stress evoked behaviours)

Identifying the orbital angular momentum of light based on atomic ensembles

We propose a scheme to distinguish the orbital angular momentum state of the Laguerre-Gaussian (LG) beam based on the electromagnetically induced transparency modulated by a microwave field in atomic ensembles. We show that the transverse phase variation of a probe beam with the LG mode can be mapped into the spatial intensity distribution due to the change of atomic coherence caused by the microwave. The proposal may provide a useful tool for studying higher-dimensional quantum information based on atomic ensembles.Comment: 4 pages, 4 figure

A 5.8 GHz DSRC Digitally Controlled CMOS RF-SoC Transceiver for China ETC

This paper presents a 5.8 GHz dedicated short range communication (DSRC) CMOS RF-SoC transceiver with digitally controlled RF architecture for China electronic toll collection (ETC) system. The operation of key RF blocks, such as ASK modulator, power amplifier, LNA, and mixer, are directly controlled by digital baseband. Compared with state-of-the-art designs in literature, this work demonstrates remarkable advantages in design simplicity, Tx output peak power, adjacent channel power ratio (ACPR), dynamic range, occupied bandwidth (OBW), bit error rate (BER), and so on

Nutrient co‐limitation in the subtropical Northwest Pacific

Nutrients limiting phytoplankton growth in the ocean are a critical control on ocean productivity and can underpin predicted responses to climate change. The extensive western subtropical North Pacific is assumed to be under strong nitrogen limitation, but this is not well supported by experimental evidence. Here, we report the results of 14 factorial nitrogen–phosphorus–iron addition experiments through the Philippine Sea, which demonstrate a gradient from nitrogen limitation in the north to nitrogen–iron co-limitation in the south. While nitrogen limited sites responded weakly to nutrient supply, co-limited sites bloomed with up to ~60-fold increases in chlorophyll a biomass that was dominated by initially undetectable diatoms. The transition in limiting nutrients and phytoplankton growth capacity was driven by a gradient in deep water nutrient supply, which was undetectable in surface concentration fields. We hypothesize that this large-scale phytoplankton response gradient is both climate sensitive and potentially important for regulating the distribution of predatory fish

A new double-antigen sandwich test based on the light-initiated chemiluminescent assay for detecting anti-hepatitis C virus antibodies with high sensitivity and specificity

ObjectivesThe aim of this study was to evaluate the performance of a new double-antigen sandwich test that is based on the light-initiated chemiluminescent assay (LiCA®) for detecting anti-hepatitis C virus antibodies (anti-HCV) in comparison to Architect®.MethodsAnalytical characteristics and diagnostic performance were tested using seroconversion panels and large pools of clinical samples. Positive results were validated by the strip immunoblot assay (RIBA) and HCV RNA.ResultsRepeatability and within-lab imprecision of LiCA® anti-HCV were 1.31%–3.27%. The C5–C95 interval was −5.44%–5.03% away from C50. LiCA® detected seroconversion in an average of 28.9 days and showed a mean of 3.7 (p = 0.0056) days earlier than Architect®. In a pool of 239 samples with known HCV genotypes 1 to 6, both assays correctly detected all subjects. In 16,305 clinical patient sera, LiCA® detected 4 false-negative (0.25‰) and 14 false-positive (0.86‰) anti-HCV cases, while Architect® recorded 6 false-negative (0.37‰) and 138 false-positive (8.46‰) subjects, respectively. Compared to Architect®, LiCA® presented a significantly better performance in specificity (99.91% vs. 99.14%, n = 16,018, p < 0.0001), positive predictive value (95.29% vs. 67.06%, n = 419, p < 0.0001), and overall accuracy (99.89% vs. 99.12%, n = 16,305, p < 0.0001), while no significant difference in sensitivity (98.61% vs. 97.91%, n = 287, p = 0.5217) and negative predictive value (99.98% vs. 99.96%, n = 15,886, p = 0.3021) was seen. An S/Co value of 3.28 was predicted to be the threshold with a positivity ≥95% for the LiCA® anti-HCV assay.ConclusionLiCA® anti-HCV is a precise and fully automatic chemiluminescent assay with superior sensitivity and specificity. The assay can be used as a valuable tool to supplement the diagnosis of HCV infection

Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling

SummaryProtein synthesis is critical for circadian clock function, but little is known of how translational regulation controls the master pacemaker in mammals, the suprachiasmatic nucleus (SCN). Here we demonstrate that the pivotal translational repressor, the eukaryotic translational initiation factor 4E binding protein 1 (4E-BP1), is rhythmically regulated via the mechanistic target of rapamycin (mTOR) signaling in the SCN and preferentially represses vasoactive intestinal peptide (Vip) mRNA translation. Knockout (KO) of Eif4ebp1 (gene encoding 4E-BP1) leads to upregulation of VIP and higher amplitude of molecular rhythms in the SCN. Consequently, the 4E-BP1 null mice exhibit accelerated re-entrainment to a shifted light/dark cycle and are more resistant to the rhythm-disruptive effects of constant light. Conversely, in Mtor+/− mice VIP expression is decreased and susceptibility to the effects of constant light is increased. These results reveal a key role for mTOR/4E-BP1-mediated translational control in regulating entrainment and synchrony of the master clock

Case Report: ALK rearranged locally advanced lung adenocarcinoma showing inconsistent radiographic findings and pathological responses during neoadjuvant alectinib therapy

Alectinib has been approved as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung carcinoma. Oncologists are also exploring the possibility of applying alectinib in the perioperative period. Here, we present a patient with locally advanced lung adenocarcinoma associated with EML4-ALK fusion mutation, who received neoadjuvant chemotherapy and alectinib treatment, and then underwent thoracoscopic left lower lung lobectomy. The patient initially received eight chemotherapy cycles and achieved partial remission. After eight cycles of chemotherapy, the lymph nodes in the hilar region again enlarged. The patient was then switched to 4 months of alectinib therapy, but no significant lesion changes were detected on imaging during this period. This raised the question of whether the patient developed alectinib resistance. The pathological findings of the postoperative lung lobe specimens indicated extensive necrosis in the tumor area with no residual tumor cells and massive chronic inflammatory cell infiltration around the tumor area, confirming inconsistency between the imaging findings and pathological results. Multi-point tumor specimen sampling was postoperatively performed. Tumor immune-related gene expression was detected in the sample with the help of the PanCancer IO360™ panel based on the nCounter platform. This is a rare case of a patient who was treated with neoadjuvant alectinib and had paradoxical radiographic findings and pathological responses. The possibility that intratumoral immune heterogeneity was responsible for this phenomenon has been discussed. Based on the findings, it is argued that the pathological response should be an important basis for assessing the effectiveness of neoadjuvant alectinib therapy