Background
Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the ...pathogenesis of CRS with nasal polyps (CRSwNP).
Methods
The expression of autophagic proteins microtubule‐associated protein 1 light chain 3B (LC3B)‐II, autophagy‐related proteins (Atg), and Beclin 1, substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules cysteine‐aspartic protease‐3 and cysteine‐aspartic protease‐8, and poly‐ADP‐ribose polymerase in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting. Autophagic vacuoles were observed with transmission electron microscopy. BEAS‐2B cells and NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some experiments, cultured NECs were transfected with small interfering RNA targeting p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting and flow cytometry.
Results
Although autophagic protein expression and autophagic vacuole formation were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in NECs, there was also an up‐regulation of substrate proteins and apoptotic signaling molecules. IFN‐γ, but not IL‐4, IL‐13, or IL‐17A, simultaneously enhanced LC3B‐II and p62 levels as well as cell apoptosis in BEAS‐2B cells and/or normal NECs. Bafilomycin A1 up‐regulated the levels of LC3B‐II and p62 in polyp NECs and IFN‐γ‐treated normal NECs. IFN‐γ‐induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN‐γ‐treated NECs. IFN‐γ protein levels were increased in both eosinophilic and noneosinophilic CRSwNP.
Conclusions
IFN‐γ induces activated but insufficient autophagy and thus contributes to a degree to p62‐dependent apoptosis of NECs in CRSwNP.
Convolutional neural networks (CNNs) are quickly becoming an attractive solution for autonomous vehicles, military weapons, and space exploration. Thanks to their reconfiguration ability, design ...flexibility, and low power consumption, field-programmable gate arrays (FPGAs) have become a promising candidate for CNN accelerators. However, FPGAs have been proven to be susceptible to radiation-induced single-event upsets (SEUs). One goal of this article is to analyze the impact of quantization on the reliability of CNNs in FPGAs. Therefore, we performed quantization on ZynqNet without affecting its classification accuracy. Meanwhile, we implemented the triple modular redundancy (TMR) version of ZynqNet and we also evaluated the effects of SEUs on these CNNs through both fault injections and neutron exposures. Fault injection results show that TMRed ZynqNet reduces the soft error rate (SER) by 33.59% with a circuit area increase of 111.92% when compared with the standard ZynqNet. The experimental results demonstrate that the quantized ZynqNet reduces the SER by 71.36% with a circuit area reduction of 44.76% when compared with the standard ZynqNet. These results confirm that quantization does contribute to SER reduction of the neural networks. In addition, the operating system on the processing system (PS) side was also found to be highly sensitive to SEUs, and, thus, mitigation techniques should be applied.
In order to improve the prediction accuracy of the roughing force prediction model, a cuckoo-random forest algorithm is proposed in this paper to quickly solve the set value of rolling force based on ...the standard random forest algorithm. The experimental results show that the prediction accuracy of the cuckoo-random forest algorithm is higher than that of traditional models, and it can effectively predict the set value of rough rolling force.
Large-scale, highly integrated and low-power-consuming hardware is becoming progressively more important for realizing optical neural networks (ONNs) capable of advanced optical computing. ...Traditional experimental implementations need N
units such as Mach-Zehnder interferometers (MZIs) for an input dimension N to realize typical computing operations (convolutions and matrix multiplication), resulting in limited scalability and consuming excessive power. Here, we propose the integrated diffractive optical network for implementing parallel Fourier transforms, convolution operations and application-specific optical computing using two ultracompact diffractive cells (Fourier transform operation) and only N MZIs. The footprint and energy consumption scales linearly with the input data dimension, instead of the quadratic scaling in the traditional ONN framework. A ~10-fold reduction in both footprint and energy consumption, as well as equal high accuracy with previous MZI-based ONNs was experimentally achieved for computations performed on the MNIST and Fashion-MNIST datasets. The integrated diffractive optical network (IDNN) chip demonstrates a promising avenue towards scalable and low-power-consumption optical computational chips for optical-artificial-intelligence.
Abstract
Zank et al. developed models describing the transport of low-frequency incompressible and nearly incompressible turbulence in inhomogeneous flows. The formalism was based on expressing the ...fluctuating variables in terms of the Elsässar variables and then taking “moments” subject to various closure hypotheses. The turbulence transport models are different according to whether the plasma beta regime is large, of order unity, or small. Here, we show explicitly that the three sets of turbulence transport models admit a conservation representation that resembles the well-known WKB transport equation for Alfvén wave energy density after introducing appropriate definitions of the “pressure” associated with the turbulent fluctuations. This includes introducing a distinct turbulent pressure tensor for 3D incompressible turbulence (the large plasma beta limit) and pressure tensors for quasi-2D and slab turbulence (the plasma beta order-unity or small regimes) that generalize the form of the WKB pressure tensor. Various limits of the different turbulent pressure tensors are discussed. However, the analogy between the conservation form of the turbulence transport models and the WKB model is not close for multiple reasons, including that the turbulence models express fully nonlinear physical processes unlike the strictly linear WKB description. The analysis presented here both serves as a check on the validity and correctness of the turbulence transport models and also provides greater transparency of the energy dissipation term and the “turbulent pressure” in our models, which is important for many practical applications.
The increasing severity of droughts/floods and worsening air quality from increasing aerosols in Asia monsoon regions are the two gravest threats facing over 60% of the world population living in ...Asian monsoon regions. These dual threats have fueled a large body of research in the last decade on the roles of aerosols in impacting Asian monsoon weather and climate. This paper provides a comprehensive review of studies on Asian aerosols, monsoons, and their interactions. The Asian monsoon region is a primary source of emissions of diverse species of aerosols from both anthropogenic and natural origins. The distributions of aerosol loading are strongly influenced by distinct weather and climatic regimes, which are, in turn, modulated by aerosol effects. On a continental scale, aerosols reduce surface insolation and weaken the land‐ocean thermal contrast, thus inhibiting the development of monsoons. Locally, aerosol radiative effects alter the thermodynamic stability and convective potential of the lower atmosphere leading to reduced temperatures, increased atmospheric stability, and weakened wind and atmospheric circulations. The atmospheric thermodynamic state, which determines the formation of clouds, convection, and precipitation, may also be altered by aerosols serving as cloud condensation nuclei or ice nuclei. Absorbing aerosols such as black carbon and desert dust in Asian monsoon regions may also induce dynamical feedback processes, leading to a strengthening of the early monsoon and affecting the subsequent evolution of the monsoon. Many mechanisms have been put forth regarding how aerosols modulate the amplitude, frequency, intensity, and phase of different monsoon climate variables. A wide range of theoretical, observational, and modeling findings on the Asian monsoon, aerosols, and their interactions are synthesized. A new paradigm is proposed on investigating aerosol‐monsoon interactions, in which natural aerosols such as desert dust, black carbon from biomass burning, and biogenic aerosols from vegetation are considered integral components of an intrinsic aerosol‐monsoon climate system, subject to external forcing of global warming, anthropogenic aerosols, and land use and change. Future research on aerosol‐monsoon interactions calls for an integrated approach and international collaborations based on long‐term sustained observations, process measurements, and improved models, as well as using observations to constrain model simulations and projections.
Key Points
The fast‐developing Asia has suffered severe air pollution problem
Aerosol affects the Asian monsoon
Aerosol‐monsoon interactions dictate the climate change in the region
Doxorubicin (DOX) is an anthracycline chemotherapy drug used in the treatment of various types of cancer. However, short-term and long-term cardiotoxicity limits the clinical application of DOX. ...Currently, dexrazoxane is the only approved treatment by the United States Food and Drug Administration to prevent DOX-induced cardiotoxicity. However, a recent study found that pre-treatment with dexrazoxane could not fully improve myocardial toxicity of DOX. Therefore, further targeted cardioprotective prophylaxis and treatment strategies are an urgent requirement for cancer patients receiving DOX treatment to reduce the occurrence of cardiotoxicity. Accumulating evidence manifested that Sirtuin 1 (SIRT1) could play a crucially protective role in heart diseases. Recently, numerous studies have concentrated on the role of SIRT1 in DOX-induced cardiotoxicity, which might be related to the activity and deacetylation of SIRT1 downstream targets. Therefore, the aim of this review was to summarize the recent advances related to the protective effects, mechanisms, and deficiencies in clinical application of SIRT1 in DOX-induced cardiotoxicity. Also, the pharmaceutical preparations that activate SIRT1 and affect DOX-induced cardiotoxicity have been listed in this review.
Cytokine storm syndrome (CSS) is a critical clinical condition induced by a cascade of cytokine activation, characterized by overwhelming systemic inflammation, hyperferritinaemia, haemodynamic ...instability and multiple organ failure (MOF). At the end of 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in Wuhan, China, and rapidly developed into a global pandemic. More and more evidence shows that there is a dramatic increase of inflammatory cytokines in patients with COVID‐19, suggesting the existence of cytokine storm in some critical illness patients. Here, we summarize the pathogenesis, clinical manifestation of CSS, and highlight the current understanding about the recognition and potential therapeutic options of CSS in COVID‐19.
Summary Objective To determine whether autophagy contributes to the pathogenesis of degenerative disc disease (DDD) or retards the intervertebral disc (IVD) degeneration, and investigate the possible ...relationship between compression-induced autophagy and intracellular reactive oxygen species (ROS) in nucleus pulposus (NP) cells in vitro. Methods The autophagosome and autophagy-related markers were used to explore the role of autophagy in rat NP cells under compressive stress, which were measured directly by electronic microscopy, monodansylcadaverine (MDC) staining, immunofluorescence, western blot, and indirectly by analyzing the impact of pharmacological inhibitors of autophagy such as 3-methyladenine (3-MA) and chloroquine (CQ). And the relationship between autophagy and apoptosis was investigated by Annexin-V/propidium iodide (PI)-fluorescein staining. In addition, ROS were measured to determine whether these factors are responsible for the development of compression-induced autophagy. Results Our results indicated that rat NP cells activated autophagy in response to the same strong apoptotic stimuli that triggered apoptosis by compression. Autophagy and apoptosis were interconnected and coordinated in rat NP cells exposed to compression stimuli. Compression-induced autophagy was closely related to intracellular ROS production. Conclusions Enhanced degradation of damaged components of NP cells by autophagy may be a crucial survival response against mechanical overload, and extensive autophagy may trigger autophagic cell death. Regulating autophagy and reducing the generation of intracellular ROS may retard IVD degeneration.
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