Natural gas hydrate is one of the most potential carbon energy resources because of its tremendous reserves. Gas and water permeability of natural gas hydrate-bearing sediments (HBS) directly affects ...gas recovery from hydrate reservoirs and gas production efficiency. In this paper, we review the permeability of HBS with respect to its relevant factors and development in characterization. Hydrate morphology and distribution inherently affect the permeability, and are identified in both coarse- and fine-grained sediments. Measurement and estimation methods of permeability are discussed in four aspects: theoretical analysis and numerical simulation, laboratory experiment, and filed test. Research challenges to this subject are comprehensively discussed, and future prospects of research are addressed. We suggest that future research should focus on understanding hydrate formation and dissociation mechanism and their effect on the permeability in fine-grained sediments, obtaining reliable measurement results of the permeability, bridging the gap of permeability between laboratory samples and natural sediments, and highlighting multi-scale analysis on the permeability with appropriate parameters as well as developing models for safe and economically feasible gas production from HBS eventually.
•A comprehensive review of permeability in natural gas hydrate-bearing sediments is presented.•Hydrate morphology and pore habit as well as their effects on permeability are reviewed.•Research challenges and prospects for permeability of hydrate sediments are discussed.
Highlights • The multi-channel fully convolutional networks is designed. • We segment liver tumors from multiphase contrast-enhanced CT images. • We train one network for each phase of CT images and ...fuse their high-layer features together. • This method can make full use of the characteristics of different enhancement phases of CT images. • The results showed our model provided greater accuracy and robustness than previous methods.
The gravity-retaining wall is a common retaining structure in geotechnical engineering. The inertial load acting on the retaining wall itself (the horizontal seismic action) under earthquake ...conditions is one of the major loadings to be elaborately considered for the design of gravity-retaining walls. The horizontal seismic action of the retaining walls under seismic loading is dominated by the combination of the mass distribution of the wall body and the acceleration distribution along wall height. The mass distribution can be calculated by the wall geometry and density of the wall body. By contrast, due to the whipping effect, horizontal seismic acceleration along wall height often shows obvious amplification in relation to ground acceleration. Such a distribution of acceleration amplification is of great importance to comprehend the safe design of retaining walls. Nonvertical retaining walls, such as inclined and reclined retaining walls, are often used in practical engineering, and their dynamic responses under seismic actions will be different from those of vertical walls. This paper focused on the examination of the influence of the wall-back inclination angle of retaining walls on the dynamic acceleration distribution along wall height due to seismic actions. Dynamic responses of vertical, inclined, and reclined gravity retaining walls under various earthquake loads were tested on a shaking table system. Seismic acceleration time-history curves were recorded under different seismic waves and intensities. The influence of the wall-back inclination angle of retaining walls on the seismic effect was thus analyzed. The tested results showed that the wall-back inclination angle of retaining walls has a significant influence on the seismic dynamic response. The amplification coefficients of peak acceleration of the gravity retaining wall follow the order of the reclined type > the vertical type > the inclined type. Based on the experimental results, the amplification coefficient of peak acceleration was statistically analyzed under the commonly used risk level in engineering seismic design. A formula for the calculation of the horizontal earthquake action distribution coefficient along wall height was proposed involving the effect of the wall-back inclination angle, which might improve the existing calculation method of retaining wall design. The results of this work would guide the earthquake resistance dynamic design of retaining walls.
LY01008 was a biosimilar of Avastin® developed by Shandong Boan Biotechnology. To support the clinical trial and marketing application of LY01008 as a biosimilar, a series of non-clinical ...pharmacodynamics (PD), pharmacokinetics (PK), and toxicological studies have been conducted. The PD study results showed that LY01008 had similar pharmacodynamic effects with Avastin in VEGF (vascular endothelial growth factor) binding activity, inhibitory effect on angiogenesis and vascular permeability, and anti-tumor activities in nude mouse models alone or combined with chemotherapeutic agents. PK study showed that LY01008 had similar PK parameters with Avastin at the same doses, and the relative bioavailability of LY01008 was 111.4%. The maximum tolerated dose of LY01008 in the single-dose toxicity study of cynomolgus monkeys was greater than 258 mg/kg. LY01008 had no effects on central nervous system, cardiovascular system and respiratory system in cynomolgus monkeys. LY01008 had no hemolytic effect in vitro and no local irritation in cynomolgus monkeys. The immunogenicity of LY01008 was no higher than that of Avastin in cynomolgus monkeys. In the one-month multiple-dose toxicity study in cynomolgus monkeys, the toxicokinetics profiles of LY01008 was similar with Avastin, the characteristics of the toxic reactions were the same and the extent was similar between LY01008 and Avastin, and no new toxic reactions were observed on LY01008. In conclusion, LY01008 had a good safety profile, and was biosimilar with Avastin in the comparative studies of pharmacodynamics, pharmacokinetics, toxicokinetics and toxicology, which supported the clinical trial and marketing application of LY01008 as a biosimilar of Avastin.
Accurate segmentation of specific organ from computed tomography (CT) scans is a basic and crucial task for accurate diagnosis and treatment. To avoid time-consuming manual optimization and to help ...physicians distinguish diseases, an automatic organ segmentation framework is presented. The framework utilized convolution neural networks (CNN) to classify pixels. To reduce the redundant inputs, the simple linear iterative clustering (SLIC) of super-pixels and the support vector machine (SVM) classifier are introduced. To establish the perfect boundary of organs in one-pixel-level, the pixels need to be classified step-by-step. First, the SLIC is used to cut an image into grids and extract respective digital signatures. Next, the signature is classified by the SVM, and the rough edges are acquired. Finally, a precise boundary is obtained by the CNN, which is based on patches around each pixel-point. The framework is applied to abdominal CT scans of livers and high-resolution computed tomography (HRCT) scans of lungs. The experimental CT scans are derived from two public datasets (Sliver 07 and a Chinese local dataset). Experimental results show that the proposed method can precisely and efficiently detect the organs. This method consumes 38 s/slice for liver segmentation. The Dice coefficient of the liver segmentation results reaches to 97.43%. For lung segmentation, the Dice coefficient is 97.93%. This finding demonstrates that the proposed framework is a favorable method for lung segmentation of HRCT scans.
The dissociation of natural gas hydrate in the seabed during hydrate production can lead to substantial weakening in soil mechanic properties, which in turn results in the deformation and even ...destruction of the seafloor sediments, thereby posing a potential threat to the safety of the undersea engineering infrastructures. A better understanding of the effect of soil mechanical weakening on seabed deformation will benefit the prediction and/or determination of geological conditions for safer hydrate production. In this work, a three-dimensional model of the submarine geological body was established and engineering properties of hydrate reservoir under different degrees of hydrate dissociation were determined. Such model and engineering parameters were applied for simulation calculation on examining the effect of hydrate dissociation degree on soil subsidence using FLAC3D software. The simulation results show that the subsidence of sediments is centrally distributed within the dissociation area and the subsidence of hydrate-bearing sediment’s top surface is much more severe than that of the overlying layer. Subsidence on the horizontal section above the hydrate reservoir presents an essentially symmetric dish-like subsidence trough, with the greatest subsidence in the centre and approximately constant subsidence beyond the trough range. The radius of the subsidence trough increases with the increase of the degree of dissociation, and the increasing extent in the early dissociation stage (lower dissociation degree) is greater than in the middle and the later stage (higher dissociation degree). As the degree of hydrate dissociation increases, subsidence of both the overlying layer and the HBS increases. Especially when the decomposition exceeds a certain threshold, the seafloor subsidence increases rapidly. The simulation results in this work are of guiding significance for deformation monitoring and infrastructure deformation prevention in practical hydrate production projects.
Recurrence is still a major obstacle to the successful treatment of gliomas. Understanding the underlying mechanisms of recurrence may help for developing new drugs to combat gliomas recurrence. This ...study provides a strategy to discover new drugs for recurrent gliomas based on drug perturbation induced gene expression changes.
The RNA-seq data of 511 low grade gliomas primary tumor samples (LGG-P), 18 low grade gliomas recurrent tumor samples (LGG-R), 155 glioblastoma multiforme primary tumor samples (GBM-P), and 13 glioblastoma multiforme recurrent tumor samples (GBM-R) were downloaded from TCGA database. DESeq2, key driver analysis and weighted gene correlation network analysis (WGCNA) were conducted to identify differentially expressed genes (DEGs), key driver genes and coexpression networks between LGG-P
LGG-R, GBM-P
GBM-R pairs. Then, the CREEDS database was used to find potential drugs that could reverse the DEGs and key drivers.
We identified 75 upregulated and 130 downregulated genes between LGG-P and LGG-R samples, which were mainly enriched in human papillomavirus (HPV) infection, PI3K-Akt signaling pathway, Wnt signaling pathway, and ECM-receptor interaction. A total of 262 key driver genes were obtained with frizzled class receptor 8 (
), guanine nucleotide-binding protein subunit gamma-12 (
), and G protein subunit β2 (
) as the top hub genes. By screening the CREEDS database, we got 4 drugs (Paclitaxel, 6-benzyladenine, Erlotinib, Cidofovir) that could downregulate the expression of up-regulated genes and 5 drugs (Fenofibrate, Oxaliplatin, Bilirubin, Nutlins, Valproic acid) that could upregulate the expression of down-regulated genes. These drugs may have a potential in combating recurrence of gliomas.
We proposed a time-saving strategy based on drug perturbation induced gene expression changes to find new drugs that may have a potential to treat recurrent gliomas.
The dissociation of natural gas hydrate in the process of exploitation will weaken the mechanical properties of the surrounding soil, which will lead to the deformation and destruction of the seabed ...sediment, thus posing a potential threat to the safety of the undersea engineering infrastructures. In this paper, the finite difference method is used to simulate the vertical deformation of seabed sediments, and examine the effect of thickness ratio of the overlying layer to the HBS upon soil settlement via an established three-dimensional model of submarine hydrate mining. The main research results are as follows: The maximum settlement occurred at the top surface of HBS dissociation centre and the settlement decreased significantly from the mining well to the surrounding and from HBS to the overlying layer. The range of settlement trough on the top of HBS is far less than the overlaying layers. The thickness ratio of the overlying layer to the HBS will have a great influence on the distribution of sedimentation and deformation of seafloor sediments caused by hydrate dissociation. The deformation and the range of the settlement trough both decrease with the increasing thickness ratio of overlying layer to HBS. The research results will provide a strong theoretical reference for the stability of seabed and mining platform during hydrate mining.
•Thermostable PV-sVLPs were produced in large quantity.•PV-sVLPs were characterized by electron microscopy.•PV-sVLPs had significant D antigen content.•PV-sVLPs could induce strong humoral and ...cellular immune responses in mice.
Poliovirus (PV) is a pathogen that causes poliomyelitis, which may lead to paralysis and fatality. Inactivated PV vaccines (IPVs) and live-attenuated oral PV vaccines (OPVs) are currently used to defend against PV worldwide. Vaccines must be developed in a PV-free environment given the biosafety issues associated with OPV and IPV production and to eradicate PV globally. In this study, PV1, PV2, and PV3 virus-like particles with enhanced thermostability (PV-sVLPs) were produced in large quantities by using a baculovirus expression vector system (BEVS). Mice immunized with PV-sVLPs generated antibodies with strong PV-neutralizing response. In addition, splenocytes collected from immunized mice expressed high levels of IFN-γ, IL-2, GM-CSF, IL-5, and IL-10 upon PV-sVLPs stimulation. These data suggest that PV-sVLPs can serve as vaccines against PV infection.
The Enterovirus A71 (EV-A71) subgenogroup C4 is prevalent in China. EV-A71 causes hand, foot and mouth disease (HFMD) in children and may lead to severe neurological diseases. The development of ...antiviral and protective vaccines against EV-A71 is significantly hindered by the lack of suitable animal models to recapitulate human neurological symptoms. In this study, GZ-CII, a highly virulent EV-A71 subgenogroup C4 strain, was isolated from hospitalized children with HFMD. Intraperitoneal infections of GZ-CII resulted in progressive neurological disease in mice as old as 14 days. Administration of an inactivated EV-A71 vaccine or an anti-EV-A71 immune serum protected the mice against the GZ-CII infection. This demonstrated that a mouse model with EV-A71 GZ-CII could be used to evaluate potential vaccine candidates and therapeutics for subgenogroup C4. Comparing the genome sequence of GZ-CII with that of the avirulent EV-A71 subgenogroup C4 strain revealed unique mutations in GZ-CII. When mutation VP2-K149I was introduced into the nonpathogenic EV-A71 subgenogroup C4 strain, the variant similar to GZ-CII significantly increased viral replication and virulence in mice. These results indicated that the VP2-K149I mutation played an important role in enhancing the virulence of the EV-A71 subgenogroup C4 strain in mice, and that mice infected with the GZ-CII strain are a promising model for evaluating vaccines and therapeutics against the EV-A71 subgenogroup C4.
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•GZ-CII, an EV-A71 subgenogroup C4 strain, was highly virulent in mice.•Intraperitoneal infection of GZ-CII in 14-day-old mice resulted in progressive neural pathological diseases and even death.•VP2-K149I mutation enhanced the virulence of EV-A71 subgenogroup C4 strains in mice.
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