SRY gene transferred by extracellular vesicles accelerates atherosclerosis by promotion of leucocyte adherence to endothelial cells

Abstract We set out to investigate whether and how SRY (sex-determining region, Y) DNAs in plasma EVs (extracellular vesicles) is involved in the pathogenesis of atherosclerosis. PCR and gene sequencing found the SRY gene fragment in plasma EVs from male, but not female, patients; EVs from male patients with CAD (coronary artery disease) had a higher SRY GCN (gene copy number) than healthy subjects. Additional studies found that leucocytes, the major source of plasma EVs, had higher SRY GCN and mRNA and protein expression in male CAD patients than controls. After incubation with EVs from SRY-transfected HEK (human embryonic kidney)-293 cells, monocytes (THP-1) and HUVECs (human umbilical vein endothelial cells), which do not endogenously express SRY protein, were found to express newly synthesized SRY protein. This resulted in an increase in the adherence factors CD11-a in THP-1 cells and ICAM-1 (intercellular adhesion molecule 1) in HUVECs. EMSA showed that SRY protein increased the promoter activity of CD11-a in THP-1 cells and ICAM-1 in HUVECs. There was an increase in THP-1 cells adherent to HUVECs after incubation with SRY-EVs. SRY DNAs transferred from EVs have pathophysiological significance in vivo; injection of SRY EVs into ApoE −/− (apolipoprotein-knockout) mice accelerated atherosclerosis. The SRY gene in plasma EVs transferred to vascular endothelial cells may play an important role in the pathogenesis of atherosclerosis; this mechanism provides a new approach to the understanding of inheritable CAD in men

Characterization of a Human Antibody Fragment Fab and Its Calcium Phosphate Nanoparticles that Inhibit Rabies Virus Infection with Vaccine

Recombinant antibody phage display technology has been used to mimic many aspects of the processes that govern the generation and selection of high-affinity natural human antibodies in the human immune system, especially for infectious disease prophylaxis. An anti-rabies virus immunized phage-display Fab library was constructed from peripheral blood lymphocytes from vaccinated volunteers. The immunized antibody library, with a diversity of 6.7×108, was used to select and produce antibodies that bound to rabies virus glycoprotein. After five rounds of immobilized fixed rabies virion panning, four unique DNA sequences were found in the higher binding clones, and only one, Fab094, showed neutralization activity. Fab094 components were analyzed by ELISA, immunoprecipitation and immunofluorescent staining. ELISA and immunofluorescence showed that Fab094 bound specifically to rabies virions. Immunoprecipitation and mass spectrometry showed that Fab094 reacted with rabies virus glycoprotein. To improve the penetration power of Fab094 antibodies, we developed Fab094 calcium phosphate nanoparticles (Fab094-CPNPs) and tested their efficacy. The rapid fluorescent focus inhibition test indicated that the neutralizing antibody titers of Fab094 and Fab094-CPNPs were reached at 200.17 IU/Kg and 246.12 IU/Kg, respectively. These findings were confirmed in vivo in a Kunming mouse challenge model. Our results demonstrate that human Fab094 and Fab094-CPNPs are efficacious candidate drugs to replace rabies immunoglobulin in post-exposure prophylaxis (PEP)

Study on the Pricing of Water Rights Transaction between Irrigation Water Users Based on Cooperative Game in China

China’s water rights transaction is still in the initial stage of development. There is no systematic pricing method for water rights transactions between farmers. This paper puts forward a pricing model of water rights transactions among farmers in water-deficient areas. The price of water rights transaction consists of cost price and earnings price. The earnings price is determined by studying the crop water production function, calculating the crop’s marginal benefit of the two parties, and combining the Cooperative Game Theory. Finally, the pricing model was applied to the water rights transactions among the farmers of Hetao Irrigation District of Bayannaoer City, Inner Mongolia Autonomous Region. Results showed that under the A4 trading strategy, the overall income increased without losing the interests of any farmer. The increasing income of the three farmer households N1, N2, and N3 after the alliance was 8.14 thousand dollars, 4.66 thousand dollars, and 20.33 thousand dollars, respectively, and the water rights transaction prices of N3 and N1, N2 were respectively 0.485 $/m3, 0.565$/m3. It is estimated that the model can provide a scientific basis for water rights trading between farmers and the efficient use of water resources

Study on Water Rights Allocation of Irrigation Water Users in Irrigation Districts of the Yellow River Basin

With the increasingly serious problems of water security and water shortage in the Yellow River Basin, the establishment of a fair and efficient water rights distribution system is an important way to improve water resource utilization efficiency and achieve high-quality development. In this paper, a double-level water rights allocation model of national canals–farmer households in irrigation districts is established. The Gini coefficient method is used to construct the water rights allocation model among farmer households based on the principle of fairness. Finally, the Wulanbuhe Irrigation Area in the Hetao Irrigation District is taken as an example. Results show that the allocated water rights of the national canals in the irrigation district are less than the current; for example, water rights of the Grazing team (4) canal are reduced by 73,000 m3 than before, in which water rights of farmer households 1, 2, 3, and 4 obtain compensation and 5, 6, 7, and 8 are cut by the water rights allocation model and the Gini coefficient is reduced from 0.1968 to 0.1289. The research has fully tapped the water-saving potential of irrigation districts, improved the fairness of initial water rights distribution, and can provide a scientific basis for the development of water rights allocation of irrigation water users in irrigation districts of the Yellow River Basin

Study on Water Rights Allocation of Irrigation Water Users in Irrigation Districts of the Yellow River Basin

With the increasingly serious problems of water security and water shortage in the Yellow River Basin, the establishment of a fair and efficient water rights distribution system is an important way to improve water resource utilization efficiency and achieve high-quality development. In this paper, a double-level water rights allocation model of national canals–farmer households in irrigation districts is established. The Gini coefficient method is used to construct the water rights allocation model among farmer households based on the principle of fairness. Finally, the Wulanbuhe Irrigation Area in the Hetao Irrigation District is taken as an example. Results show that the allocated water rights of the national canals in the irrigation district are less than the current; for example, water rights of the Grazing team (4) canal are reduced by 73,000 m3 than before, in which water rights of farmer households 1, 2, 3, and 4 obtain compensation and 5, 6, 7, and 8 are cut by the water rights allocation model and the Gini coefficient is reduced from 0.1968 to 0.1289. The research has fully tapped the water-saving potential of irrigation districts, improved the fairness of initial water rights distribution, and can provide a scientific basis for the development of water rights allocation of irrigation water users in irrigation districts of the Yellow River Basin

An Optimized Player Taxonomy Model for Mobile MMORPGs with Millions of Users

Massively multiplayer online role-playing games (MMORPGs) have great potential as sites for research within the social and human-computer interaction. In the MMORPGs, a stability player taxonomy model is very important for game design. It helps to balance different types of players and improve business strategy of the game. The players in mobile MMORPGs are also connected with social networks; many studies only use the player's own attributes statistics or questionnaire survey method to predict player taxonomy, so lots of social network relations' information will be lost. In this paper, by analyzing the impacts of player's social network, commercial operating data from mobile MMORPGs is used to establish our player taxonomy model (SN model). From the model results, social network-related information in mobile MMORPGs will be considered as important factors to pose this optimized player taxonomy model. As experimental results showed, compared with another player taxonomy model (RA model), our proposed player taxonomy model can achieve good results: classification is more stable

A new framework for a multi-site stochastic daily rainfall model: Coupling a univariate Markov chain model with a multi-site rainfall event model

Multi-site rainfall models are useful tools to provide synthetic realizations of spatially-correlated rainfall at multiple stations, which are of great importance for flood and drought risk assessment and climate change impact analysis. Therefore, a good preservation of various observed rainfall characteristics including rainfall time-series statistics and rainfall event characteristics at individual stations and the inter-site correlations of these rainfall characteristics is very crucial. To achieve this purpose, this study aims to develop a multi-site stochastic daily rainfall model by coupling a univariate Markov chain with a multi-site rainfall event model (MSDRM-MCREM), based on our previously-developed single-site SDRM-MCREM. The univariate Markov chain model in MSDRM-MCREM is used to generate spatially-correlated multi-site rainfall occurrence time series and extract simulated rainfall events for individual stations based on continuous wet days. The multi-site rainfall event model is then constructed using Vine copulas to simulate spatially-correlated rainfall event characteristics of those simulated rainfall events that occur simultaneously at multiple stations, including rainfall durations, rainfall depths and temporal patterns. Subsequently, this model was applied to the Changshangang River basin in Zhejiang Province, East China and its performance in reproducing rainfall characteristics and spatial correlations was evaluated for three cases, i.e. simulations for two, three and four stations. Results show that except for overestimation of light rainfall, MSDRM-MCREM can simultaneously well preserve rainfall time-series statistics (i.e. different rainfall percentiles, mean monthly rainfall, standard deviations and probabilities and mean values of wet days), extreme rainfall (i.e. exceedance probabilities of annual maximum 1-day, 3-day and 5-day rainfall) and rainfall event characteristics (i.e. cumulative probabilities of wet spell, dry spell and rainfall depth, temporal patterns and occurrence probabilities of rainfall types for different depth-based event classes) at individual stations. In addition, the spatial correlations of rainfall characteristics have also been well maintained, including rainfall occurrence time series and rainfall event characteristics in different groups, with the inter-site correlations of rainfall time series being slightly underestimated