Following wood pyrolysis, tar ball aerosols were laboratory generated from
wood tar separated into polar and nonpolar phases. Chemical information of
fresh tar balls was obtained from a ...high-resolution time-of-flight aerosol
mass spectrometer (HR-ToF-AMS) and single-particle laser desorption/resonance
enhanced multiphoton ionization mass spectrometry (SP-LD-REMPI-MS). Their
continuous refractive index (RI) between 365 and 425 nm was retrieved using
a broadband cavity enhanced spectroscopy (BBCES). Dynamic changes in the
optical and chemical properties for the nonpolar tar ball aerosols in
NOx-dependent photochemical process were investigated in an
oxidation flow reactor (OFR). Distinct differences in the chemical
composition of the fresh polar and nonpolar tar aerosols were identified.
Nonpolar tar aerosols contain predominantly high-molecular weight
unsubstituted and alkyl-substituted polycylic aromatic hydrocarbons (PAHs),
while polar tar aerosols consist of a high number of oxidized aromatic
substances (e.g., methoxy-phenols, benzenediol) with higher O : C ratios
and carbon oxidation states. Fresh tar balls have light absorption
characteristics similar to atmospheric brown carbon (BrC) aerosol with higher
absorption efficiency towards the UV wavelengths. The average retrieved RI is
1.661+0.020i and 1.635+0.003i for the nonpolar and polar tar aerosols,
respectively, with an absorption Ångström exponent (AAE) between 5.7
and 7.8 in the detected wavelength range. The RI fits a volume mixing rule
for internally mixed nonpolar/polar tar balls. The RI of the tar ball
aerosols decreased with increasing wavelength under photochemical oxidation.
Photolysis by UV light (254 nm), without strong oxidants in the system,
slightly decreased the RI and increased the oxidation state of the tar balls.
Oxidation under varying OH exposure levels and in the absence of
NOx diminished the absorption (bleaching) and increased the
O : C ratio of the tar balls. The photobleaching via OH radical initiated
oxidation is mainly attributed to decomposition of chromophoric aromatics,
nitrogen-containing organics, and high-molecular weight components in the
aged particles. Photolysis of nitrous oxide (N2O) was used to
simulate NOx-dependent photochemical aging of tar balls in
the OFR. Under high-NOx conditions with similar OH exposure,
photochemical aging led to the formation of organic nitrates, and increased
both oxidation degree and light absorption for the aged tar ball aerosols.
These observations suggest that secondary organic nitrate formation
counteracts the bleaching by OH radical photooxidation to eventually regain
some absorption of the aged tar ball aerosols. The atmospheric implication
and climate effects from tar balls upon various oxidation processes are
briefly discussed.
SARS-CoV-2 variants of interest and concern will continue to emerge for the duration of the COVID-19 pandemic. To map mutations in the receptor-binding domain (RBD) of the spike protein that affect ...binding to angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, we applied in vitro evolution to affinity-mature the RBD. Multiple rounds of random mutagenic libraries of the RBD were sorted against decreasing concentrations of ACE2, resulting in the selection of higher affinity RBD binders. We found that mutations present in more transmissible viruses (S477N, E484K and N501Y) were preferentially selected in our high-throughput screen. Evolved RBD mutants include prominently the amino acid substitutions found in the RBDs of B.1.620, B.1.1.7 (Alpha), B1.351 (Beta) and P.1 (Gamma) variants. Moreover, the incidence of RBD mutations in the population as presented in the GISAID database (April 2021) is positively correlated with increased binding affinity to ACE2. Further in vitro evolution increased binding by 1,000-fold and identified mutations that may be more infectious if they evolve in the circulating viral population, for example, Q498R is epistatic to N501Y. We show that our high-affinity variant RBD-62 can be used as a drug to inhibit infection with SARS-CoV-2 and variants Alpha, Beta and Gamma in vitro. In a model of SARS-CoV-2 challenge in hamster, RBD-62 significantly reduced clinical disease when administered before or after infection. A 2.9 Å cryo-electron microscopy structure of the high-affinity complex of RBD-62 and ACE2, including all rapidly spreading mutations, provides a structural basis for future drug and vaccine development and for in silico evaluation of known antibodies.
Salvia-Nelumbinis naturalis (SNN) formula is a traditional Chinese medicine prescription, and has been confirmed to be effective in treating non-alcoholic steatohepatitis (NASH), but the underlying ...mechanisms are still unknown. Here we showed that 4-week SNN administration alleviated methionine-choline-deficiency (MCD) diet-induced hepatic steatosis and inflammation as well as serum levels of alanine transaminase (ALT) increase in C57BL/6 mice. Fecal 16S rDNA sequencing indicated that SNN altered the structure of gut microbiota and partially reversed the gut dysbiosis. Simultaneously, we analyzed the fecal BA profile using liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQMS) -based metabolomics, and found that SNN modulated fecal BA profile, predominantly increased the microbiomes related BA species (e.g. nordeoxycholic acid) which in turn, activated farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling pathway in the colon but not the ileum. The activation of intestinal FXR-FGF15 signaling was accompanied by increase of liver protein kinase B (PKB/Akt) phosphorylation, and decrease of p-65 subunit of NF-κB phosphorylation, resulting in less liver CD68 positive macrophages, and inflammatory cytokine IL-1β and TNF-α expression. Our results established the link between SNN treatment, gut microbiota, BA profile and NASH, which might shed light into the mechanisms behind the beneficial effects of SNN on NASH, thus provide evidence for the clinical application of SNN.
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•SNN improves hepatic steatosis and inflammation in MCD-diet-induced NASH mice.•SNN modulates gut microbiota and BA components (e.g. norDCA), and the responded microbiomes and BAs are correlated.•Activation of the colonic FXR-FGF15 pathway upon gut microbiome and BA interaction may contribute to the effects of SNN on NASH.
The hybrid cloud extends the private cloud model by using both local and remote resources. The private cloud will rely on the resources leased from public cloud providers for the execution of private ...cloud applications. The paper presents optimal scheduling across public and private clouds in complex hybrid cloud environment. The contributions of this paper have three aspects. 1) The proposed hybrid cloud scheduling policy considers the benefits of private cloud applications and public cloud provider, it can adapt to the changes in the system to find the scheduling optimization. The scheduling optimization is decomposed and conducted across the private cloud and public cloud. 2) Secondly, The paper describes negotiations in hybrid cloud marketplace and gives an example to explain how these rules are resolved by the cloud marketplace. 3) Thirdly, the paper proposes an optimal scheduling algorithm across public and private clouds. The paper also describes negotiations in hybrid cloud marketplace and gives an example to explain how these rules are resolved by the cloud marketplace. In the simulations, the profit of public cloud provider and resource utilization of the proposed algorithm are better than other related works.
The scale of big data has shown an explosive growth, which makes the processing of big data put forward higher requirements on data centers, and a single data center can no longer meet the needs of ...big data processing. To deal with this situation, a geographically distributed cloud system needs to be built. However, in the geographically distributed cloud system, each data center is distributed in different geographic locations, which makes the data placement operations in the geographically distributed cloud system lead to greater overhead. To solve this problem, this paper proposes a data placement strategy. This strategy comprehensively considers the data transmission latency, bandwidth cost, cloud server storage capacity, and load capacity during the data placement process, and formulates a data placement problem that minimizes the energy consumption of data transmission. Then the minimum set cover method based on Lagrangian relaxation is used to solve this problem and obtain the optimal data placement scheme. On the other hand, in a geographically distributed cloud data center, the execution progress of the job submitted by the user will be affected by the straggler task. To solve this problem, this paper proposes a speculative execution strategy for the geographically distributed cloud system. This strategy performs different speculative execution operations according to the state of the cluster load, and then calculates the load capacity of the nodes in the cluster. The node with the strongest load capacity in the cluster is used to perform speculative execution operations. Experimental results show that the proposed data placement strategy can effectively improve the performance of the energy consumption, the data storage cost, the network transmission cost and the data transmission time. The proposed speculative execution strategy can effectively improve the performance of the job completion time, cluster throughput and QoS satisfaction rate.
With the growth of energy consumption and environmental protection concerns, it is of enormous economic and environmental values for the development of stranded gas. As a means for exploitation and ...transportation of stranded gas to market, a novel small-scale liquefaction process adopting single nitrogen expansion with carbon dioxide pre-cooling is put up with in this paper. Taking unit energy consumption as the target function, Aspen HYSYS is employed to simulate and optimize the process to achieve the liquefaction rate of 0.77 with unit energy consumption of 9.90 kW/kmol/h. Furthermore, the adaptability of this process under different pressure, temperature and compositions of feed gas is studied. Based on the optimization results, the exergy losses of main equipment in the process are evaluated and analyzed in details. With compact device, safety operation, simple capability, this liquefaction process proves to be suitable for the development of small gas reserves, satellite distribution fields of gas or coalbed methane fields.
•A novel small-scale liquefaction process used in stranded gas is designed.•The adaptability of this process under different pressure, temperature and compositions of feed gas is studied.•The exergy analysis of main equipment in the process is analyzed.
The ultimate displacement of the D-Bolt is more affected by the displacing angle α than the rebar bolt. Display omitted
•An approach was developed to apply pull-and-shear loading to rockbolt.•The ...performance of rebar and D-Bolt was examined in the laboratory.•The displacement capacity of D-Bolt depends on the displacing angle.•The displacing angle is different from the loading angle.
The performance of two types of rock bolts, fully encapsulated rebar and D-Bolt, under combined pull and shear loading were studied in the laboratory. A new test approach was developed to apply the pull and shear loads to the rock bolt at the same time so that the bolt is displaced in a direction different from the bolt axis. Five displacing angles between 0° (pure pull) and 90° (pure shear) were employed in the tests. The test results show that the linear elastic stiffness of both the D-Bolt and the rebar bolt is mobilised quickly after a small displacement. When the displacing angle is larger than 40°, grout crushing may occur underneath the bolt shank, resulting in reduction in the stiffness of the bolt. The ultimate load of the bolts remains approximately constant no matter what the displacing angle is for both the D-Bolt and the rebar bolt. The displacement capacity of the D-Bolt, however, is dependent on the displacing angle. The ultimate displacement of a 1-m long D-Bolt section varies from 140mm under pure pull (0°) to approximately 70mm when the displacing angle is larger than 40°. The ultimate displacement of the rebar slightly increases from 29mm under pure pull to 53mm under pure shear. In general, the displacement capacity of the D-Bolt is larger than that of the rebar bolt. It is approximately 3.5 times the rebar under pure pull and 50% higher than rebar under pure shear. The test results show that the displacing angle of the bolt is larger than its loading angle, which is also confirmed by the analytical solutions.
Nighttime oxidation of biogenic volatile organic compounds (BVOCs) by nitrate radicals (NO3·) represents one of the most important interactions between anthropogenic and natural emissions, leading to ...substantial secondary organic aerosol (SOA) formation. The direct climatic effect of such SOA cannot be quantified because its optical properties and atmospheric fate are poorly understood. In this study, we generated SOA from the NO3· oxidation of a series BVOCs including isoprene, monoterpenes, and sesquiterpenes. The SOA were subjected to comprehensive online and offline chemical composition analysis using high-resolution mass spectrometry and optical properties measurements using a novel broadband (315–650 nm) cavity-enhanced spectrometer, which covers the wavelength range needed to understand the potential contribution of the SOA to direct radiative forcing. The SOA contained a significant fraction of oxygenated organic nitrates (ONs), consisting of monomers and oligomers that are responsible for the detected light absorption in the 315–400 nm range. The SOA created from β-pinene and α-humulene was further photochemically aged in an oxidation flow reactor. The SOA has an atmospheric photochemical bleaching lifetime of >6.2 h, indicating that some of the ONs in the SOA may serve as atmosphere-stable nitrogen oxide sinks or reservoirs and will absorb and scatter incoming solar radiation during the daytime.
Fructose, especially industrial fructose (sucrose and high fructose corn syrup) is commonly used in all kinds of beverages and processed foods. Liver is the primary organ for fructose metabolism, ...recent studies suggest that excessive fructose intake is a driving force in non-alcoholic fatty liver disease (NAFLD). Dietary fructose metabolism begins at the intestine, along with its metabolites, may influence gut barrier and microbiota community, and contribute to increased nutrient absorption and lipogenic substrates overflow to the liver. Overwhelming fructose and the gut microbiota-derived fructose metabolites (e.g., acetate, butyric acid, butyrate and propionate) trigger the
de novo
lipogenesis in the liver, and result in lipid accumulation and hepatic steatosis. Fructose also reprograms the metabolic phenotype of liver cells (hepatocytes, macrophages, NK cells, etc.), and induces the occurrence of inflammation in the liver. Besides, there is endogenous fructose production that expands the fructose pool. Considering the close association of fructose metabolism and NAFLD, the drug development that focuses on blocking the absorption and metabolism of fructose might be promising strategies for NAFLD. Here we provide a systematic discussion of the underlying mechanisms of dietary fructose in contributing to the development and progression of NAFLD, and suggest the possible targets to prevent the pathogenetic process.
Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for ...cancer therapy in clinical trials. mAb targeting PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung cancer, or Merkel cell carcinoma by the FDA. However, the high cost of the antibody can limit its application. In our study, targeting PD-L1 peptide (TPP-1), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods. Using a T-cell activation assay and mixed lymphocyte reaction, TPP-1 was verified to interfere with the interaction of PD-1/PD-L1. To examine the inhibitory effect of TPP-1 on tumor growth
, a xenograft mouse model using H460 cells was established. The growth rate of tumor masses in TPP-1 or PD-L1 antibody-treated mice was 56% or 71% lower than that in control peptide-treated mice, respectively, indicating that TPP-1 inhibits, or at least retards, tumor growth. IHC of the tumors showed that IFNγ and granzyme B expression increased in the TPP-1 or PD-L1 antibody-treated groups, indicating that TPP-1 attenuates the inhibitory effect of PD-L1 on T cells and that T cells may get reactivated. On the basis of our data, TPP-1 peptide could work as an alternative to antibodies for tumor immunotherapy.
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