Abstract
Most triple-negative breast cancer (TNBC) patients fail to respond to T cell-mediated immunotherapies. Unfortunately, the molecular determinants are still poorly understood. Breast cancer is ...the disease genetically linked to a deficiency in autophagy. Here, we show that autophagy defects in TNBC cells inhibit T cell-mediated tumour killing in vitro and in vivo. Mechanistically, we identify Tenascin-C as a candidate for autophagy deficiency-mediated immunosuppression, in which Tenascin-C is Lys63-ubiquitinated by Skp2, particularly at Lys942 and Lys1882, thus promoting its recognition by p62 and leading to its selective autophagic degradation. High Tenascin-C expression is associated with poor prognosis and inversely correlated with LC3B expression and CD8
+
T cells in TNBC patients. More importantly, inhibition of Tenascin-C in autophagy-impaired TNBC cells sensitizes T cell-mediated tumour killing and improves antitumour effects of single anti-PD1/PDL1 therapy. Our results provide a potential strategy for targeting TNBC with the combination of Tenascin-C blockade and immune checkpoint inhibitors.
Amorphous iron phosphate (FePO4) has attracted enormous attention as a promising cathode material for sodium‐ion batteries (SIBs) because of its high theoretical specific capacity and superior ...electrochemical reversibility. Nevertheless, the low rate performance and rapid capacity decline seriously hamper its implementation in SIBs. Herein, we demonstrate a sagacious multi‐step templating approach to skillfully craft amorphous FePO4 yolk–shell nanospheres with mesoporous nanoyolks supported inside the robust porous outer nanoshells. Their unique architecture and large surface area enable these amorphous FePO4 yolk–shell nanospheres to manifest remarkable sodium storage properties with high reversible capacity, outstanding rate performance, and ultralong cycle life.
FePO4 nanospheres consisting of mesoporous nanoyolks supported inside robust porous nanoshells are synthesized by a judicious multi‐step templating strategy using carbon nanospheres as the starting material. Their architecture and composition allow these hierarchical FePO4 yolk–shell nanospheres to manifest excellent sodium storage performance as a cathode material for sodium‐ion batteries.
The objectives of the study were to (1) investigate the potential of using monopolar psychophysical detection thresholds for estimating spatial selectivity of neural excitation with cochlear implants ...and to (2) examine the effect of site removal on speech recognition based on the threshold measure. Detection thresholds were measured in Cochlear Nucleus® device users using monopolar stimulation for pulse trains that were of (a) low rate and long duration, (b) high rate and short duration, and (c) high rate and long duration. Spatial selectivity of neural excitation was estimated by a forward-masking paradigm, where the probe threshold elevation in the presence of a forward masker was measured as a function of masker-probe separation. The strength of the correlation between the monopolar thresholds and the slopes of the masking patterns systematically reduced as neural response of the threshold stimulus involved interpulse interactions (refractoriness and sub-threshold adaptation), and spike-rate adaptation. Detection threshold for the low-rate stimulus most strongly correlated with the spread of forward masking patterns and the correlation reduced for long and high rate pulse trains. The low-rate thresholds were then measured for all electrodes across the array for each subject. Subsequently, speech recognition was tested with experimental maps that deactivated five stimulation sites with the highest thresholds and five randomly chosen ones. Performance with deactivating the high-threshold sites was better than performance with the subjects' clinical map used every day with all electrodes active, in both quiet and background noise. Performance with random deactivation was on average poorer than that with the clinical map but the difference was not significant. These results suggested that the monopolar low-rate thresholds are related to the spatial neural excitation patterns in cochlear implant users and can be used to select sites for more optimal speech recognition performance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oscillations threaten the stability of a power system. Timely detecting oscillations can improve operators' situational awareness of system stability and enable remedial reactions. To detect ...oscillations during their early stages, this paper proposes a cross-coherence method using multiple-channel phasor measurement unit (PMU) data. Oscillations are related to the peaks in coherence spectra and can be detected by visual inspection and setting up a threshold. Using simulation data, it is shown that the proposed coherence method can detect oscillations even under low signal-to-noise ratios. Three algorithms for estimating coherence spectra are implemented and evaluated. Their performances are compared using Monte Carlo methods. Based on the comparison, this paper makes some recommendations for proper use of the algorithms.
Sulfide oxidation reaction (SOR) is one central step of electrochemical desulfurization and sulfur‐based batteries. However, the electrochemical performance of desulfurization and sulfur batteries ...has been severely hindered by sulfur passivation. Here, a discovery of sulfophobic phenomenon of electrocatalysts having weak interaction to sulfur species is reported. A self‐cleaning NiS2 electrode is developed to avoid the long‐perplexing passivation issue of solid sulfur during the SOR. Furthermore, sulfur‐vacancies are engineered into NiS2 lattice to synthesize v‐NiS2 for the hydrogen evolution reaction (HER). The resultant lattice expansion and electron redistribution can adjust the adsorbed hydrogen to reach a nearly thermos‐neutral state, enabling high catalytic activity for the HER. By coupling the HER and SOR, efficient desulfurization and simultaneous hydrogen production is demonstrated. Bifunctional NiS2 enables such a one‐stone‐kills‐two‐birds strategy to realize continuous electrochemical desulfurization with superior energy efficiency (1.05 gsulfur Wh−1). As a general design principle, sulfophobic electrocatalysts can improve the properties of lithium–sulfur batteries by minimizing the passivation of S8 during charge. In brief, interfacial interaction between electrocatalysts and sulfur species are systematically investigated and a sulfophobic strategy to significantly enhance the electrochemical performance of the SOR is offered.
Sulfide oxidation reactions for desulfurization and sulfur batteries are severely hindered by sulfur passivation. The discovery of sulfophobic phenomenon of NiS2 is reported for the first time. Furthermore, bifunctional NiS2 enables such a one‐stone‐kills‐two‐birds strategy to realize efficient desulfurization and simultaneous hydrogen production with ultralow energy consumption.
Sodium (Na)‐ion batteries (NIBs) are considered promising alternative candidates to the well‐commercialized lithium‐ion batteries, especially for applications in large‐scale energy storage systems. ...The electrochemical performance of NIBs such as the cyclability, rate capability, and voltage profiles are strongly dependent on the structural and morphological evolution, phase transformation, sodium‐ion diffusion, and electrode/electrolyte interface reconstruction during charge–discharge cycling. Therefore, in‐depth understanding of the structure and kinetics of electrode materials and the electrode/electrolyte interfaces is essential for optimizing current NIB systems and exploring new materials for NIBs. Recently, rapid progress and development in spectroscopic, microscopic, and scattering techniques have provided extensive insight into the nature of structural evolution, morphological changes of electrode materials, and electrode/electrolyte interface in NIBs. In this review, a comprehensive overview of both static (ex situ) and real‐time (in situ or in operando) techniques for studying the NIBs is provided. Special focus is placed on how these techniques are applied to the fundamental investigation of NIB systems and what important results are obtained.
Advanced characterization techniques are applied for a fundamental investigation of sodium‐ion batteries (NIBs) from different perspectives at various dimensions and scales during an electrochemical process. By summarizing the comprehensive overview of both static (ex situ) and real‐time (in situ or in operando) techniques, it is hoped that this review is helpful for scientists in the research field of NIBs.
Accurate estimation of the dynamic states of a synchronous machine (e.g., rotor's angle and speed) is essential in monitoring and controlling transient stability of a power system. It is well known ...that the covariance matrixes of process noise (Q) and measurement noise (R) have a significant impact on the Kalman filter's performance in estimating dynamic states. The conventional ad-hoc approaches for estimating the covariance matrixes are not adequate in achieving the best filtering performance. To address this problem, this paper proposes an adaptive filtering approach to adaptively estimate Q and R based on innovation and residual to improve the dynamic state estimation accuracy of the extended Kalman filter (EKF). It is shown through the simulation on the two-area model that the proposed estimation method is more robust against the initial errors in Q and R than the conventional method in estimating the dynamic states of a synchronous machine.
The past decades have witnessed an increasing interest in developing advanced polymerization techniques subjected to external fields. Various physical modulations, such as temperature, light, ...electricity, magnetic field, ultrasound, and microwave irradiation, are noninvasive means, having superb but distinct abilities to regulate polymerizations in terms of process intensification and spatial and temporal controls. Gas as an emerging regulator plays a distinctive role in controlling polymerization and resembles a physical regulator in some cases. This review provides a systematic overview of seven types of external-field-regulated polymerizations, ranging from chain-growth to step-growth polymerization. A detailed account of the relevant mechanism and kinetics is provided to better understand the role of each external field in polymerization. In addition, given the crucial role of modeling and simulation in mechanisms and kinetics investigation, an overview of model construction and typical numerical methods used in this field as well as highlights of the interaction between experiment and simulation toward kinetics in the existing systems are given. At the end, limitations and future perspectives for this field are critically discussed. This state-of-the-art research progress not only provides the fundamental principles underlying external-field-regulated polymerizations but also stimulates new development of advanced polymerization methods.
Oxygen‐redox of layer‐structured metal‐oxide cathodes has drawn great attention as an effective approach to break through the bottleneck of their capacity limit. However, reversible oxygen‐redox can ...only be obtained in the high‐voltage region (usually over 3.5 V) in current metal‐oxide cathodes. Here, we realize reversible oxygen‐redox in a wide voltage range of 1.5–4.5 V in a P2‐layered Na0.7Mg0.2Fe0.2Mn0.6□0.2O2 cathode material, where intrinsic vacancies are located in transition‐metal (TM) sites and Mg‐ions are located in Na sites. Mg‐ions in the Na layer serve as “pillars” to stabilize the layered structure during electrochemical cycling, especially in the high‐voltage region. Intrinsic vacancies in the TM layer create the local configurations of “□–O–□”, “Na–O–□” and “Mg–O–□” to trigger oxygen‐redox in the whole voltage range of charge–discharge. Time‐resolved techniques demonstrate that the P2 phase is well maintained in a wide potential window range of 1.5–4.5 V even at 10 C. It is revealed that charge compensation from Mn‐ and O‐ions contributes to the whole voltage range of 1.5–4.5 V, while the redox of Fe‐ions only contributes to the high‐voltage region of 3.0–4.5 V. The orphaned electrons in the nonbonding 2p orbitals of O that point toward TM‐vacancy sites are responsible for reversible oxygen‐redox, and Mg‐ions in Na sites suppress oxygen release effectively.
Na0.7Mg0.2Fe0.2Mn0.6□0.2O2 with native transitional metal (TM) vacancies is designed as a novel cathode material for sodium‐ion batteries. The TM vacancies lead to nonbonding O 2p orbitals in this material, pointing toward these vacancies triggering reversible whole‐voltage‐range oxygen redox during charge and discharge processes. This work provides new ideals for design of cathode materials in anionic redox chemistry.
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