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In machine learning, multiple instance learning is a method evolved from supervised learning algorithms, which defines a "bag" as a collection of multiple examples with a wide range of applications. In this paper, we propose a novel deep multiple instance learning model for medical image analysis, called triple-kernel gated attention-based multiple instance learning with contrastive learning. It can be used to overcome the limitations of the existing multiple instance learning approaches to medical image analysis. Our model consists of four steps. i) Extracting the representations by a simple convolutional neural network using contrastive learning for training. ii) Using three different kernel functions to obtain the importance of each instance from the entire image and forming an attention map. iii) Based on the attention map, aggregating the entire image together by attention-based MIL pooling. iv) Feeding the results into the classifier for prediction. The results on different datasets demonstrate that the proposed model outperforms state-of-the-art methods on binary and weakly supervised classification tasks. It can provide more efficient classification results for various disease models and additional explanatory information.
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The DNA sensing pathway triggers innate immune responses against DNA virus infection, and NF-κB signaling plays a critical role in establishing innate immunity. We report here that the herpes simplex virus 1 (HSV-1) ubiquitin-specific protease (UL36USP), which is a deubiquitinase (DUB), antagonizes NF-κB activation, depending on its DUB activity. In this study, ectopically expressed UL36USP blocked promoter activation of beta interferon (IFN-ß) and NF-κB induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). UL36USP restricted NF-κB activation mediated by overexpression of STING, TANK-binding kinase 1, IκB kinase α (IKKα), and IKKß, but not p65. UL36USP was also shown to inhibit IFN-stimulatory DNA-induced IFN-ß and NF-κB activation under conditions of HSV-1 infection. Furthermore, UL36USP was demonstrated to deubiquitinate IκBα and restrict its degradation and, finally, abrogate NF-κB activation. More importantly, the recombinant HSV-1 lacking UL36USP DUB activity, denoted as C40A mutant HSV-1, failed to cleave polyubiquitin chains on IκBα. For the first time, UL36USP was shown to dampen NF-κB activation in the DNA sensing signal pathway to evade host antiviral innate immunity.IMPORTANCE It has been reported that double-stranded-DNA-mediated NF-κB activation is critical for host antiviral responses. Viruses have established various strategies to evade the innate immune system. The N terminus of the HSV-1 UL36 gene-encoded protein contains the DUB domain and is conserved across all herpesviruses. This study demonstrates that UL36USP abrogates NF-κB activation by cleaving polyubiquitin chains from IκBα and therefore restricts proteasome-dependent degradation of IκBα and that DUB activity is indispensable for this process. This study expands our understanding of the mechanisms utilized by HSV-1 to evade the host antiviral innate immune defense induced by NF-κB signaling.
Assuntos
Herpesvirus Humano 1/fisiologia , NF-kappa B/metabolismo , Proteínas Virais/fisiologia , Animais , Chlorocebus aethiops , Células HEK293 , Humanos , Interferon beta/fisiologia , Proteólise , Transdução de Sinais , Ubiquitinação , Células VeroRESUMO
All-solid-state lithium batteries are promising candidates for next-generation energy storage systems. Their performance critically depends on the capacity and cycling stability of the cathodic layer. Cells with a garnet Li7La3Zr2O12 (LLZO) electrolyte can show high areal storage capacity. However, they commonly suffer from performance degradation during cycling. For fully inorganic cells based on LiCoO2 (LCO) as cathode active material and LLZO, the electrochemically induced interface amorphization has been identified as an origin of the performance degradation. This study shows that the amorphized interface can be recrystallized by thermal recovery (annealing) with nearly full restoration of the cell performance. The structural and chemical changes at the LCO/LLZO heterointerface associated with degradation and recovery were analyzed in detail and justified by thermodynamic modeling. Based on this comprehensive understanding, this work demonstrates a facile way to recover more than 80% of the initial storage capacity through a thermal recovery (annealing) step. The thermal recovery can be potentially used for cost-efficient recycling of ceramic all-solid-state batteries.
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Marine environments wherein long-term microbial oxygen consumption exceeds oxygen replenishment can be associated with oxygen minimum zones (OMZ). The Bay of Bengal OMZ (BOB-OMZ) is one of the most intense OMZs globally. To assess the contribution of bacterial oxygen consumption to oxygen loss in BOB-OMZ, we measured bacterial production (BP), temperature, salinity, and dissolved oxygen (DO) in the whole water column. We then compared the estimated bacterial oxygen demand (BOD) with diapycnal oxygen supply (DOS) at depths of 50-200 m in the southern BOB in January 2020. The average BP was 3.53 ± 3.15 µmol C m-3 h-1 in the upper 200 m of four stations, which was lower than those reported in other tropical waters. The vertical distribution of BP differed between the open ocean and nearshore areas. In the open ocean, temperature and DO were the most important predictors for BP in the whole water column. In the nearshore areas, when DO increased sharply from the suboxic state, extremely high BP occurred at 200 m. The average estimated BOD/DOS could reach up to 153% at depths of 50-200 m, indicating advection and anticyclonic eddies probably are important DO replenishment pathways in the BOB.
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The garnet-type Li7La3Zr2O12 (LLZO) ceramic solid electrolyte combines high Li-ion conductivity at room temperature with high chemical stability. Several all-solid-state Li batteries featuring the LLZO electrolyte and the LiCoO2 (LCO) or LiCoO2-LLZO composite cathode were demonstrated. However, all batteries exhibit rapid capacity fading during cycling, which is often attributed to the formation of cracks due to volume expansion and the contraction of LCO. Excluding the possibility of mechanical failure due to crack formation between the LiCoO2/LLZO interface, a detailed investigation of the LiCoO2/LLZO interface before and after cycling clearly demonstrated cation diffusion between LiCoO2 and the LLZO. This electrochemically driven cation diffusion during cycling causes the formation of an amorphous secondary phase interlayer with high impedance, leading to the observed capacity fading. Furthermore, thermodynamic analysis using density functional theory confirms the possibility of low- or non-conducting secondary phases forming during cycling and offers an additional explanation for the observed capacity fading. Understanding the presented degradation paves the way to increase the cycling stability of garnet-based all-solid-state Li batteries.
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Garnet-based Li-ion conductors are one of the most promising oxide-ceramic solid electrolytes for next-generation Li batteries. However, they undergo a Li+ /H+ exchange (LHX) reaction with most protic solvents used in component manufacturing routes and even with moisture in ambient air. These protonated garnets show a lower Li-ionic conductivity, and even if only the surface is protonated, this degraded layer hinders the Li-ion exchange with, for example, a metallic Li anode. Furthermore, the resulting unstable surface properties during the processing in air lead to challenges with respect to reproducibility of the final component performance, limiting their commercial applicability. However, in recent years, the knowledge about the underlying chemical mechanisms has led to the development of mitigation strategies and enabled a push of this promising material class towards sustainable and scalable fabrication routes. This Minireview covers the following four aspects, which are relevant for a comprehensive understanding of these developments: (1) reports of LHX phenomenon in garnets exposed to air and solvents; (2) recent understandings of the fundamentals and properties of LHX; (3) strategies to prevent LHX and to recover garnets; and (4) sustainable application of LHX for material processing and energy-related devices.
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Internal solitary waves (ISWs) can cause strong vertical and horizontal currents and turbulent mixing in the ocean. These processes affect sediment and pollutant transport, acoustic transmissions and man-made structures in the shallow and deep oceans. Previous studies of the role of ISWs in suspending seafloor sediments and forming marine nepheloid layers were mainly conducted in shallow-water environments. In summer 2017, we observed at least four thick (70-140 m) benthic nepheloid layers (BNLs) at water depths between 956 and 1545 m over continental slopes in the northern South China Sea. We found there was a good correlation between the timing of the ISW packet and variations of the deepwater suspended sediment concentration (SSC). At a depth of 956 m, when the ISW arrived, the near-bottom SSC rapidly increased by two orders of magnitude to 0.62 mg/l at 8 m above the bottom. At two much deeper stations, the ISW-induced horizontal velocity reached 59.6-79.3 cm/s, which was one order of magnitude more than the seafloor contour currents velocity. The SSC, 10 m above the sea floor, rapidly increased to 0.10 mg/l (depth of 1545 m) and 1.25 mg/l (depth of 1252 m). In this study, we found that ISWs could suspend much more sediments on deepwater areas than previously thought. Specifically, we estimated that ISWs could induce and suspend 78.7 Mt/yr of sediment from shelf to deep-sea areas of the northern South China Sea. The total amount of sediment resuspended by shoaling ISWs was 2.7 times that of river-derived sediment reaching the northern South China Sea. This accounted for 6.1% of the global river-discharged sediment (16.4% of that from Asian rivers) transported to the sea.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.