Data-driven fault detection and root cause analysis methods become attractive in modern industrial production that can guarantee the safety and stability of process operation. If process monitoring ...technology is implemented for fault detection, and the root cause of faults is analyzed timely, it is beneficial to maintain and improve the quality of coming batches. In this paper, a framework of fault detection and root cause analysis is proposed to address the aforementioned issue, particularly for a batch process. First, a new algorithm, termed kernel entropy component analysis (KECA)–DISSIM that combines KECA and dissimilarity analysis (DISSIM), is proposed for the batch process monitoring purpose. The KECA can extract nonlinear characteristics of the batch process effectively based on nonlinear mapping with the Renyi quadratic entropy. Then, dissimilarity indices between normal reference datasets and testing datasets can be calculated. If the testing dataset is detected as the non-normal batch by KECA–DISSIM, a novel root cause analysis named comparative Granger causality analysis is introduced for root cause analysis. The testing dataset is decomposed into a series of data slices via the moving window along the time domain. A series of causality values for each pair of variables are obtained by performing Granger causality analysis on these time slices. Lastly, the case studies based on a typical seven-variable nonlinear numerical process and a benchmark fed-batch penicillin fermentation process are studied to illustrate the practicality and effectiveness of the proposed framework.
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IJS, KILJ, NUK, PNG, UL, UM
Our goal in this work was to illustrate the Epstein-Barr virus (EBV)-modulated global biochemical profile and provide a novel metabolism-related target to improve the therapeutic regimen of ...nasopharyngeal carcinoma (NPC). We used a metabolomics approach to investigate EBV-modulated metabolic changes, and found that the exogenous overexpression of the EBV-encoded latent membrane protein 1 (LMP1) significantly increased glycolysis. The deregulation of several glycolytic genes, including hexokinase 2 (HK2), was determined to be responsible for the reprogramming of LMP1-mediated glucose metabolism in NPC cells. The upregulation of HK2 elevated aerobic glycolysis and facilitated proliferation by blocking apoptosis. More importantly, HK2 was positively correlated with LMP1 in NPC biopsies, and high HK2 levels were significantly associated with poor overall survival of NPC patients following radiation therapy. Knockdown of HK2 effectively enhanced the sensitivity of LMP1-overexpressing NPC cells to irradiation. Finally, c-Myc was demonstrated to be required for LMP1-induced upregulation of HK2. The LMP1-mediated attenuation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis resulted in the stabilization of c-Myc. These findings indicate a close relationship between EBV and glycolysis in NPC. Notably, LMP1 is the key regulator of the reprogramming of EBV-mediated glycolysis in NPC cells. Given the importance of EBV-mediated deregulation of glycolysis, anti-glycolytic therapy might represent a worthwhile avenue of exploration in the treatment of EBV-related cancers.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ZnO, MgO, and GeO2 nanowires were successfully synthesized by simply heating the desired metal powder to a temperature above its melting point in a flow of mixed gases (20 percent O2, 80 percent Ar, ...with the total flow rate of 120 sccm). Transmission electron microscopy observations show that as-synthesized products are exclusively nanowires, structurally uniform and single crystalline. The same technique was used to fabricate arrays of ZnO nanowires on silicon substrates, which would be of particular interest for direct integration in the current silicon-technology-based optoelectronic devices. Based on our experimental results, a metal self-catalytic growth mechanism was proposed and described conceptually. Because of the absence of impurities such as transition metal or noble metal throughout the whole growth process, the intrinsic properties of the resulting metal oxide nanowires could be expressed and utilized. And with in-depth understanding of the growth mechanism, our method could be efficient and controllable in extension to many other low-melting-point metals, such as Al, In, and Sn, for the synthesis of corresponding metal oxide nanostructures
A flexible and elastic carbon coil (see figure) has been fabricated using a continuous yarn of carbon nanotube arrays. The processed yarn is both elastic and pliable and can be freely manipulated and ...molded to any desired shape that is retained after heat treatment. Owing to their highly ordered macroscopic structures, the good electrical and thermal conductivity of the nanotube components, and their good mechanical properties, these carbon nanostructures may find extensive use in a wide range of applications.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Syngas is a valuable chemical intermediate for producing commodity chemicals, such as olefins, methanol, liquid fuels, etc. The chemical looping route for syngas production presents an attractive ...alternative to state-of-the-art technology, such as partial oxidation, autothermal reforming, and steam methane reforming. Out of the several chemical looping configurations, the co-current moving-bed reactor with iron titanium composite metal oxide particles has demonstrated a high-purity syngas production. In this study, an alternative reactor configuration (indirect chemical looping system) is proposed to the co-current moving-bed reactor system (direct chemical looping system) to enhance the syngas yield. The indirect chemical looping system consists of a fuel reactor and a syngas generation reactor, both operated in countercurrent mode, with respect to the gas–solid flow, as opposed to just one co-current fuel reactor in the direct chemical looping system. This unique gas–solid contact pattern in the indirect chemical looping system aids in greater utilization of CO2 and H2O and improves the thermodynamic performance for syngas production. Thermodynamic simulations in Aspen Plus software are performed for system analysis and comparison under isothermal and autothermal conditions. Isothermal analysis at several different temperatures and pressures, with and without co-injection of CO2/H2O, is conducted to explain the behavior of the proposed system. Autothermal operation of the system under different pressures is also evaluated to determine the maximum syngas yield within the constraints of a practical system for syngas production to further produce liquid fuels via Fischer–Tropsch synthesis. The results from these simulations are compared against the direct chemical looping system to highlight the difference in thermodynamic constraints between the two processes. The oxidation behavior of reduced Fe2O3–MgAl2O4 with CO2 and H2O is experimentally tested at different pressures and temperatures to gain an understanding for the syngas generation reactor in the indirect chemical looping system.
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IJS, KILJ, NUK, PNG, UL, UM
Macrophages are essential regulators of inflammation and bone loss. Receptor activator of nuclear factor-κβ ligand (RANKL), a pro-inflammatory cytokine, is responsible for macrophage differentiation ...to osteoclasts and bone loss. We recently showed that 14-3-3ζ-knockout (YwhazKO) rats exhibit increased bone loss in the inflammatory arthritis model. 14-3-3ζ is a cytosolic adaptor protein that actively participates in many signaling transductions. However, the role of 14-3-3ζ in RANKL signaling or bone remodeling is unknown. We investigated how 14-3-3ζ affects osteoclast activity by evaluating its role in RANKL signaling. We utilized 14-3-3ζ-deficient primary bone marrow–derived macrophages obtained from wildtype and YwhazKO animals and RAW264.7 cells generated using CRISPR-Cas9. Our results showed that 14-3-3ζ-deficient macrophages, upon RANKL stimulation, have bigger and stronger tartrate-resistant acid phosphatase–positive multinucleated cells and increased bone resorption activity. The presence of 14-3-3ζ suppressed RANKL-induced MAPK and AKT phosphorylation, transcription factors (NFATC1 and p65) nuclear translocation, and subsequently, gene induction (Rank, Acp5, and Ctsk). Mechanistically, 14-3-3ζ interacts with TRAF6, an essential component of the RANKL receptor complex. Upon RANKL stimulation, 14-3-3ζ–TRAF6 interaction was increased, while RANK–TRAF6 interaction was decreased. Importantly, 14-3-3ζ supported TRAF6 ubiquitination and degradation by the proteasomal pathway, thus dampening the downstream RANKL signaling. Together, we show that 14-3-3ζ regulates TRAF6 levels to suppress inflammatory RANKL signaling and osteoclast activity. To the best of our knowledge, this is the first report on 14-3-3ζ regulation of RANKL signaling and osteoclast activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell's responses to starvation and other stresses is ...amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells, and potentially providing a new route for pharmacological intervention.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective
The purpose of this study is to examine the associations of BMI with testing positive for severe acute respiratory coronavirus 2 (SARS‐CoV‐2) and risk of adverse outcomes in a cohort of ...Veterans Affairs enrollees.
Method
Adjusted relative risks/hazard ratios (HRs) were calculated for the associations between BMI category (underweight, normal weight, overweight, class 1 obesity, class 2 obesity, and class 3 obesity) and testing positive for SARS‐CoV‐2 or experiencing hospitalization, intensive care unit admission, mechanical ventilation, and death among those testing positive.
Results
Higher BMI categories were associated with higher risk of a positive SARS‐CoV‐2 test compared with the normal weight category (class 3 obesity adjusted relative risk: 1.34, 95% CI: 1.28‐1.42). Among 25,952 patients who tested positive for SARS‐CoV‐2, class 3 obesity was associated with higher risk of mechanical ventilation (adjusted HR aHR: 1.77, 95% CI: 1.35‐2.32) and mortality (aHR: 1.42, 95% CI: 1.12‐1.78) compared with normal weight individuals. These associations were present primarily in patients younger than 65 and were attenuated or absent in older age groups (interaction P < 0.05).
Conclusion
Veterans Affairs enrollees with higher BMI were more likely to test positive for SARS‐CoV‐2 and were more likely to be mechanically ventilated or die if infected with SARS‐CoV‐2. Higher BMI contributed relatively more to the risk of death in those younger than 65 years of age as compared with other age categories.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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