Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy ...in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation, bypass signaling pathway activation and histological transformation. And the most common mechanism is T790M which accounts for approximately 50% of all subtypes. Many strategies have been explored to overcome the acquired resistance to EGFR TKI. Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones. While the combination of EGFR TKI and chemotherapy or other targeted agents has improved the survival benefit in EGFR TKI resistant patients, there are controversies within them. The next-generation EGFR TKI and immunotherapy represent two novel directions for overcoming acquired resistance and have achieved promising efficacy. Liquid biopsy provides surveillance of the EGFR mutation by disclosing the entire genetic landscape but tissue biopsy is still indispensable because of the considerable rate of false-negative plasma.
Metallic glasses boast high strength, but their low ductility has been a major concern. Here, taking a structural perspective and citing selected examples, we advocate purposely enhanced structural ...inhomogeneities, in an otherwise compositionally uniform and single-phase amorphous alloy, to promote distributed plastic flow. Four current tactics (the four R's) to improve deformability are highlighted, from the standpoint of structural, and consequentially mechanical, heterogeneities that can be tailored in the monolithic glassy state. Highly rejuvenated glass structures, coupled with restrained shear banding instability, lead to tensile ductility and necking, which is unusual for glasses at room temperature. Possibilities of strain hardening and strain rate hardening that are needed to stabilize uniform elongation are discussed. Innovative design and processing of amorphous metals, with internal structures tuned to facilitate flow, offer new possibilities in pushing the envelope of ductility accessible to these high-strength materials.
During the COVID‐19 lockdown (24 January–20 March) in China low air pollution levels were reported in the media as a consequence of reduced economic and social activities. Quantification of the ...pollution reduction is not straightforward due to effects of transport, meteorology, and chemistry. We have analyzed the NOx emission reductions calculated with an inverse algorithm applied to daily NO2 observations from TROPOMI onboard the Copernicus Sentinel‐5P satellite. This method allows the quantification of emission reductions per city and the analysis of emissions of maritime transport and of the energy sector separately. The reductions we found are 20–50% for cities, about 40% for power plants, and 15–40% for maritime transport depending on the region. The reduction in both emissions and concentrations shows a similar timeline consisting of a sharp reduction (34–50%) around the Spring festival and a slow recovery from mid‐February to mid‐March.
Plain Language Summary
During the COVID‐19 lockdown in China, air quality had strongly improved. Here we study what sources were reduced and how much the reduction per city was. We used TROPOMI observations of the Sentinel‐5P satellite, which monitors the Earth's atmosphere daily. We focused on observations of the pollutant “nitrogen dioxide,” an important precursor of air pollution in the atmosphere. With our novel methodology we are able to calculate the pollution back to the sources of the emissions, whether these are big cities, industrial regions, power plants, or busy shipping lanes. We applied this method to East China, where the 36 biggest Chinese cities are located. Almost all those cities showed strong emission reductions of 20–50% during the lockdown in February 2020. Besides urban China, we found an average emission reduction of 40% over coal power plants and a reduction in maritime transport by 15–40% depending on the region. The period of reduced emissions lasted until around the end of February, and the emissions slowly returned to normal during the month March 2020. Exception is the region Wuhan, the center of the COVID‐19 crisis, where emissions started to rebound since 8 April, the end of their lockdown period.
Key Points
NOx emissions derived from TROPOMI observations show reductions for individual Chinese cities of about 35% due to the COVID‐19 lockdown
Emissions of coal power plants and maritime transport show strong reductions (25–40%) during the lockdown
Urban emissions rebound in March to levels before the lockdown, while emissions of power plants and maritime transport take longer to recover
► In this paper, we synthesized Na0.74CoO2 as cathode for rechargeable sodium ion batteries. ► We examined its electrochemical performance. ► A reversible capacity of 107mAh/g with 0.1% capacity ...fading for the first 40 cycles was obtained. ► The deintercalation/intercalation reactions of Na ions from/into Na0.74CoO2 proceeded while Co3+/Co4+ redox.
P2-phase Na0.74CoO2 cathode material prepared by a solid-state method exhibits the specific discharge capacity of 107mAhg−1 at 0.1C with good cycling performance for rechargeable sodium ion batteries. The voltage polarization between charging and discharging at 0.1C rate is about 150–250mV and the coulombic efficiency in each cycle is about 89%. The expansion and compression in c-axis of the NaxCoO2 unit cell during the Na intercalation/deintercalation is revealed by ex situ XRD. XPS and in situ XAS data directly confirm that deintercalation/intercalation of Na ions from/into the layered structure proceeds with the Co3+/Co4+ redox reaction.
Wire + Arc Additive Manufacturing Williams, S. W.; Martina, F.; Addison, A. C. ...
Materials science and technology,
05/2016, Letnik:
32, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Depositing large components (>10 kg) in titanium, aluminium, steel and other metals is possible using Wire + Arc Additive Manufacturing. This technology adopts arc welding tools and wire as feedstock ...for additive manufacturing purposes. High deposition rates, low material and equipment costs, and good structural integrity make Wire+Arc Additive Manufacturing a suitable candidate for replacing the current method of manufacturing from solid billets or large forgings, especially with regards to low and medium complexity parts. A variety of components have been successfully manufactured with this process, including Ti-6Al-4V spars and landing gear assemblies, aluminium wing ribs, steel wind tunnel models and cones. Strategies on how to manage residual stress, improve mechanical properties and eliminate defects such as porosity are suggested. Finally, the benefits of non-destructive testing, online monitoring and in situ machining are discussed.
Superelastic conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of highly stretchable (up to 1320%) sheath-core ...conducting fibers created by wrapping carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber cores. The resulting structure exhibited distinct short- and long-period sheath buckling that occurred reversibly out of phase in the axial and belt directions, enabling a resistance change of less than 5% for a 1000% stretch. By including other rubber and carbon nanotube sheath layers, we demonstrated strain sensors generating an 860% capacitance change and electrically powered torsional muscles operating reversibly by a coupled tension-to-torsion actuation mechanism. Using theory, we quantitatively explain the complementary effects of an increase in muscle length and a large positive Poisson's ratio on torsional actuation and electronic properties.
It is a huge challenge in both classical and quantum physics to solve analytically the equation of motion in a strongly anharmonic confinement. For an isolated nanoring, we propose a continuous and ...bounded potential model, which patches up the disadvantages of the usual square-well and parabolic potentials. A fully nonlinear and nonperturbative approach is developed to solve analytically the equation of motion, from which various frequency shifts and dynamic displacements are exactly derived by an order-by-order self-consistent method. A series of new energy levels and new energy states are found, indicating an alternative magnetic response mechanism. In nominally identical rings, especially, we observe a diamagnetic-paramagnetic transition in the period-halving Φ
/2-current with Φ
the flux quantum and a large increase in the Φ
-current at least one order of magnitude, which explain well the experimental observations. This work opens a new way to solve the strong or weak nonlinear problems.
Stress, a prevalent experience in modern society, is a major risk factor for many psychiatric disorders. Although sensorimotor abnormalities are often present in these disorders, little is known ...about how stress affects the sensory cortex. Combining behavioral analyses with in vivo synaptic imaging, we show that stressful experiences lead to progressive, clustered loss of dendritic spines along the apical dendrites of layer (L) 5 pyramidal neurons (PNs) in the mouse barrel cortex, and such spine loss closely associates with deteriorated performance in a whisker-dependent texture discrimination task. Furthermore, the activity of parvalbumin-expressing inhibitory interneurons (PV+ INs) decreases in the stressed mouse due to reduced excitability of these neurons. Importantly, both behavioral defects and structural changes of L5 PNs are prevented by selective pharmacogenetic activation of PV+INs in the barrel cortex during stress. Finally, stressed mice raised under environmental enrichment (EE) maintain normal activation of PV+ INs, normal texture discrimination, and L5 PN spine dynamics similar to unstressed EE mice. Our findings suggest that the PV+ inhibitory circuit is crucial for normal synaptic dynamics in the mouse barrel cortex and sensory function. Pharmacological, pharmacogenetic and environmental approaches to prevent stress-induced maladaptive behaviors and synaptic malfunctions converge on the regulation of PV+ IN activity, pointing to a potential therapeutic target for stress-related disorders.
Aims
Mitochondrial fission is an essential dynamics that maintains mitochondrial morphology and function. This study seeks to determine the roles of mitochondrial fission in the filamentous ...entomopathogenic fungus Beauveria bassiana.
Material and methods
Three fission‐related genes (BbFis1, BbMdv1 and BbDnm1) were functionally characterized via protein intracellular localization and construction of gene disruption mutants.
Results
Mitochondrial localization was only observed for BbFis1 which interacts with BbMdv1, but BbMdv1 did not have interaction with BbDnm1. Single disruption mutant of three genes generated the elongated and enlarged mitochondria which could not be eliminated via the mitophagy. Three mutant strains displayed the reduced ATP synthesis and vegetative growth compared with the wild type. Three genes were involved in the early stage of conidiation and unnecessary for the late stage. However, all three genes significantly contribute to blastospore development under submerged condition, and the loss of BbMdv1 had the greatest effects compared with the losses of BbFis1 or BbDnm1. Finally, disruption of three genes significantly attenuated fungal virulence, but their mutations had different influences.
Conclusions
In addition to their consistent roles in mitochondrial division and mitophagy, three fission‐related genes perform divergent roles in the development and virulence of the entomopathogenic fungus B. bassiana.
Significance and Impact of the Study
This study shows that mitochondrial fission is associated with lifecycle of B. bassiana. These findings provide information for the manipulation of fungal physiology and facilitate the application of entomopathogenic fungi.
PDF
