The solar transition region （TR） is the temperature regime from roughly 0.02 MK to 0.8 MK in the solar atmosphere. It is the transition layer from the collisional and partially ionized chromosphere ...to the collisionless and fully ionized corona. The TR plays an important role in the mass and energy transport in both the quiet solar atmosphere and solar eruptions. Most of the TR emission lines fall into the spectral range of far ultraviolet and extreme ultraviolet （~400/~-1600/~）. Imaging and spec- troscopic observations in this spectral range are the most important ways to obtain information about the physics of the TR. Static solar atmosphere models predict a very thin TR. However, recent high- resolution observations indicate that the TR is highly dynamic and inhomogeneous. I will summarize some major findings about the TR made through imaging and spectroscopic observations in the past 20 years. These existing observations have demonstrated that the TR may be the key to understanding coronal heating and origin of the solar wind. Future exploration of the solar TR may need to focus on the upper TR, since the plasma in this temperature regime （0.1 MK-0.8 MK） has not been routinely imaged before. High-resolution imaging and spectroscopic observations of the upper TR will not only allow us to track the mass and energy from the lower atmosphere to the corona, but also help us to understand the initiation and heating mechanisms of coronal mass ejections and solar flares.
Proximate cloud computing enables computationally intensive applications on mobile devices, providing a rich user experience. However, remote resource bottlenecks limit the scalability of offloading, ...requiring optimization of the offloading decision and resource utilization. To this end, in this paper, we leverage the variability in capabilities of mobile devices and user preferences. Our system utility metric is a measure of quality of experience (QoE) based on task completion time and energy consumption of a mobile device. We propose a heuristic offloading decision algorithm (HODA), which is semidistributed and jointly optimizes the offloading decision, and communication and computation resources to maximize system utility. Our main contribution is to reduce the problem to a submodular maximization problem and prove its NP-hardness by decomposing it into two subproblems: 1) optimization of communication and computation resources solved by quasiconvex and convex optimization and 2) offloading decision solved by submodular set function optimization. HODA reduces the complexity of finding the local optimum to O(K 3 ), where K is the number of mobile users. Simulation results show that HODA performs within 5% of the optimal on average. Compared with other solutions, HODA's performance is significantly superior as the number of users increases.
The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we ...report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) from the full-length spike (S) protein that is stable in the prefusion conformation. NVX-CoV2373 S form 27.2-nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicit high titer anti-S IgG that blocks hACE2 receptor binding, neutralize virus, and protects against SARS-CoV-2 challenge with no evidence of vaccine-associated enhanced respiratory disease. NVX-CoV2373 also elicits multifunctional CD4
and CD8
T cells, CD4
follicular helper T cells (Tfh), and antigen-specific germinal center (GC) B cells in the spleen. In baboons, low-dose levels of NVX-CoV2373 with Matrix-M was also highly immunogenic and elicited high titer anti-S antibodies and functional antibodies that block S-protein binding to hACE2 and neutralize virus infection and antigen-specific T cells. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2373 with Matrix-M (NCT04368988).
•Full-length SARS-CoV-2 prefusion spike with Matrix-M™ (NVX-CoV2373) vaccine.•Induced hACE2 receptor blocking and neutralizing antibodies in macaques.•Vaccine protected against SARS-CoV-2 replication ...in the nose and lungs.•Absence of pulmonary pathology in NVX-CoV2373 vaccinated macaques.
There is an urgent need for a safe and protective vaccine to control the global spread of SARS-CoV-2 and prevent COVID-19. Here, we report the immunogenicity and protective efficacy of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length SARS-CoV-2 spike (S) glycoprotein stabilized in the prefusion conformation. Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M™ adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. Following intranasal and intratracheal challenge with SARS-CoV-2, immunized macaques were protected against upper and lower infection and pulmonary disease. These results support ongoing phase 1/2 clinical studies of the safety and immunogenicity of NVX-CoV2327 vaccine (NCT04368988).
A novel severe acute respiratory syndrome human coronavirus (SARS HCoV) was identified from respiratory illness patients (named SARS-CoV-2 by ICTV) in December 2019 and has recently emerged as a ...serious threat to world public health. However, no approved drugs have been found to effectively inhibit the virus. Since it has been reported that HIV protease inhibitors can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose six approved anti-HIV drugs and investigated their binding interactions with 3CLpro to evaluate their potential to become clinical drugs for the new coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection. The molecular docking results indicate that the 3CLpro of SARS-CoV-2 has a higher binding affinity for all the studied inhibitors than does SARS-CoV-1. Two docking complexes (indinavir and darunavir) with high docking scores were further subjected to MM-PBSA binding free energy calculations to detail the molecular interactions between these two protease inhibitors and SARS HCoV 3CLpro. Our results show that, among the inhibitors tested, darunavir has the highest binding affinity with SARS-CoV-2 and SARS-CoV-1 3CLpro, indicating that it may have the potential to be used as an anti-COVID-19 clinical drug. The mechanism behind the increased binding affinity of HIV protease inhibitors toward SARS-CoV-2 3CLpro (as compared to SARS-CoV-1) was investigated by MD simulations. Our study provides insight into the possible role of structural flexibility during interactions between SARS HCoV 3CLpro and inhibitors and sheds light on structure-based design of anti-COVID-19 drugs targeting SARS-CoV-2 3CLpro.
A novel severe acute respiratory syndrome human coronavirus (SARS HCoV) was identified from respiratory illness patients (named SARS-CoV-2 by ICTV) in December 2019 and has recently emerged as a serious threat to world public health.
Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, ...deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in
C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.
Plant pathogens are the main threat for profitable agricultural productivity. Currently, chemical-based pesticides are thought to be an effective and reliable agricultural management measure for ...controlling pests. Chemical pesticides are highly effective and convenient to use but they are a potential threat for the environment and all kinds of life on earth. Therefore, the use of biological control agents for the management of plant pathogens is considered as a safer and sustainable strategy for safe and profitable agricultural productivity. Bacillus-based biocontrol agents play a fundamental role in the field of biopesticides. Many Bacillus species have proved to be effective against a broad range of plant pathogens. They have been reported as plant growth promoter, systemic resistance inducer, and used for production of a broad range of antimicrobial compounds (lipopeptides, antibiotics and enzymes) and competitors for growth factors (space and nutrients) with other pathogenic microorganisms through colonization. The aim of this article is to present the biocontrol potential of Bacillus species in relation with their antagonizing attributes against plant pathogens. These attributes include production of lipopeptides, antibiotics and enzymes as well as plant growth promotion and systemic induced resistance.
ABSTRACT Recent observations by the Interface Region Imaging Spectrograph (IRIS) have revealed pockets of hot gas (∼2-8 × 104 K) potentially resulting from magnetic reconnection in the partially ...ionized lower solar atmosphere (IRIS bombs; IBs). Using joint observations between IRIS and the Chinese New Vacuum Solar Telescope, we have identified 10 IBs. We find that 3 are unambiguously and 3 others are possibly connected to Ellerman bombs (EBs), which show intense brightening of the extended wings without leaving an obvious signature in the core. These bombs generally reveal the following distinct properties: (1) the O iv 1401.156 and 1399.774 lines are absent or very weak; (2) the Mn i 2795.640 line manifests as an absorption feature superimposed on the greatly enhanced Mg ii k line wing; (3) the Mg ii k and h lines show intense brightening in the wings and no dramatic enhancement in the cores; (4) chromospheric absorption lines such as Ni ii 1393.330 and 1335.203 are very strong; and (5) the 1700 images obtained with the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory reveal intense and compact brightenings. These properties support the formation of these bombs in the photosphere, demonstrating that EBs can be heated much more efficiently than previously thought. We also demonstrate that the Mg ii k and h lines can be used to investigate EBs similarly to , which opens a promising new window for EB studies. The remaining four IBs obviously have no connection to EBs and they do not have the properties mentioned above, suggesting a higher formation layer, possibly in the chromosphere.
The aim of this study was to investigate the differences in main characteristics, reporting and methodological quality between prospectively registered and nonregistered systematic reviews.
PubMed ...was searched to identify systematic reviews of randomized controlled trials published in 2015 in English. After title and abstract screening, potentially relevant reviews were divided into three groups: registered non-Cochrane reviews, Cochrane reviews, and nonregistered reviews. For each group, random number tables were generated in Microsoft Excel, and the first 50 eligible studies from each group were randomly selected. Data of interest from systematic reviews were extracted. Regression analyses were conducted to explore the association between total Revised Assessment of Multiple Systematic Review (R-AMSTAR) or Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) scores and the selected characteristics of systematic reviews.
The conducting and reporting of literature search in registered reviews were superior to nonregistered reviews. Differences in 9 of the 11 R-AMSTAR items were statistically significant between registered and nonregistered reviews. The total R-AMSTAR score of registered reviews was higher than nonregistered reviews mean difference (MD) = 4.82, 95% confidence interval (CI): 3.70, 5.94. Sensitivity analysis by excluding the registration-related item presented similar result (MD = 4.34, 95% CI: 3.28, 5.40). Total PRISMA scores of registered reviews were significantly higher than nonregistered reviews (all reviews: MD = 1.47, 95% CI: 0.64-2.30; non-Cochrane reviews: MD = 1.49, 95% CI: 0.56-2.42). However, the difference in the total PRISMA score was no longer statistically significant after excluding the item related to registration (item 5). Regression analyses showed similar results.
Prospective registration may at least indirectly improve the overall methodological quality of systematic reviews, although its impact on the overall reporting quality was not significant.
Superionic states are phases of matter that can simultaneously exhibit some of the properties of a liquid and of a solid. For example, in superionic ice, hydrogen atoms can move freely while oxygen ...atoms are fixed in their sublattice. ‘Superionicity’ has attracted much attention in both fundamental science and applications. Helium is the most inert element in nature and it is generally considered to be unreactive. Here, we use ab initio calculations to show that He and H2O can form stable compounds within a large pressure range that can exist even close to ambient pressure. Surprisingly, we find that they can form two previously unknown types of superionic state under high pressure and high temperature. In the first of these phases, the helium atoms exhibit liquid behaviour within a fixed ice-lattice framework. In the second phase, both helium and hydrogen atoms move in a liquid-like fashion within a fixed oxygen sublattice. As the He–O interaction is weaker than the H–O interaction, the helium atoms in these superionic states have larger diffusion coefficients and lower ‘melting’ temperatures than those of hydrogen, although helium is heavier than hydrogen. The insertion of helium atoms substantially decreases the pressure at which superionic states may be formed, compared to those in pure ice.
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