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Gene therapy is a potentially curative medicine for many currently untreatable diseases, and recombinant adeno-associated virus (rAAV) is the most successful gene delivery vehicle for in vivo applications

Age-associated B cells (ABC) accumulate with age and are associated with autoimmunity and chronic infection. However, their contributions to acute infection in the aged and their developmental pathways are unclear. We find that the response against influenza A virus infection in aged mice is dominated by a Fas

With the development of Web 2.0, social media such as Twitter and Sina Weibo have become an essential platform for disseminating hot events. Simultaneously, due to the free policy of microblogging services, users can post user-generated content freely on microblogging platforms. Accordingly, more and more hot events on microblogging platforms have been labeled as spammers. Spammers will not only hurt the healthy development of social media but also introduce many economic and social problems. Therefore, the government and enterprises must distinguish whether a hot event on microblogging platforms is a spammer or is a naturally-developing event. In this paper, we focus on the hot event list on Sina Weibo and collect the relevant microblogs of each hot event to study the detecting methods of spammers. Notably, we develop an integral feature set consisting of user profile, user behavior, and user relationships to reflect various factors affecting the detection of spammers. Then, we employ typical machine learning methods to conduct extensive experiments on detecting spammers. We use a real data set crawled from the most prominent Chinese microblogging platform, Sina Weibo, and evaluate the performance of 10 machine learning models with five sampling methods. The results in terms of various metrics show that the Random Forest model and the over-sampling method achieve the best accuracy in detecting spammers and non-spammers.

Age-associated B cells (ABC) accumulate with age and are associated with autoimmunity and chronic infection. However, their contributions to acute infection in the aged and their developmental pathways are unclear. We find that the response against influenza A virus infection in aged mice is dominated by a Fas+GL7- effector B cell population we call infection-induced-ABC (iABC). Most iABC express IgM and include antibody-secreting cells in the spleen, lung and bone marrow. We find that in response to influenza, IgD+CD21-CD23-ABC are the precursors of iABC. These IgD+ABC develop in germ free mice, so are independent of foreign antigen recognition, suggesting they arise from an intrinsic age-associated developmental program. The response of ABC to influenza infection, resulting in iABC, is T cell independent and requires both extrinsic TLR7 and TLR9 signals. In response to influenza infection, IgD+ABC can induce a faster recovery of weight and higher total anti-influenza IgG and IgM titers that can neutralize virus. Immunization with whole inactivated virus also generates iABC in aged mice. Thus, in unimmunized aged mice, whose other B and T cell responses have waned, IgD+ABC are likely the naïve B cells with the potential to become Ab-secreting cells and to provide protection from infection in the aged.

Previously, we discovered that influenza-generated CD4 effectors must recognize cognate Ag at a defined effector checkpoint to become memory cells. Ag recognition was also required for efficient protection against lethal influenza infection. To extend these findings, we investigated if vaccine-generated effectors would have the same requirement. We compared live infection with influenza to an inactivated whole influenza vaccine. Live infection provided strong, long-lasting Ag presentation that persisted through the effector phase. It stimulated effector generation, long-lived CD4 memory generation, and robust generation of Ab-producing B cells. In contrast, immunization with an inactivated virus vaccine, even when enhanced by additional Ag-pulsed APC, presented Ag for 3 d or less and generated few CD4 memory cells or long-lived Ab-producing B cells. To test if checkpoint Ag addition would enhance this vaccine response, we immunized mice with inactivated vaccine and injected Ag-pulsed activated APC at the predicted effector checkpoint to provide Ag presentation to the effector CD4 T cells. This enhanced generation of CD4 memory, especially tissue-resident memory in the lung, long-lived bone marrow Ab-secreting cells, and influenza-specific IgG Ab. All responses increased as we increased the density of peptide Ag on the APC to high levels. This suggests that CD4 effectors induced by inactivated vaccine require high levels of cognate Ag recognition at the effector checkpoint to most efficiently become memory cells. Thus, we suggest that nonlive vaccines will need to provide high levels of Ag recognition throughout the effector checkpoint to optimize CD4 memory generation.

To evaluate the effectiveness of the Traditional Chinese Medicine tonifying-kidney and regulating-liver therapy on diminished ovarian reserve (DOR).The literature was comprehensively searched up to August 2019 using four Chinese and three English electronic databases to extract randomized clinical trials (RCTs) comparing Traditional Chinese Medicine tonifying-kidney and regulating-liver prescriptions (combined with hormone therapy or not) with Western Medicine. Data quality evaluation was conducted using the Cochrane risk of bias tool. Meta-analysis was conducted using Revman 5.3 software with effect estimates presented as mean difference (MD), risk ratio (RR), and 95% confidence interval (CI).A total of nine RCTs with 512 participants were extracted and eligible for Meta-analysis. There were no significant differences between Chinese medicine and Western Medicine on basal serum follicle-stimulating hormone (FSH) level (MD 0.11, 95% CI －0.52 to 0.74, 392 participants, seven trials), anti-Müllerian hormone level (MD 0.48, 95% CI －0.62 to 1.58, 95 participants, two trials), and the FSH and luteinizing hormone ratio (MD 0.01, 95% CI －0.95 to 0.96, 115 participants, two trials). Chinese medicine was more effective at improving Traditional Chinese Medicine symptom scores (TCMSS) (MD －2.39, 95% CI －3.83 to －0.94, 160 participants, three trials), effective rate of TCMSS (RR 1.18, 95% CI 1.02 to 1.36, 160 participants, three trials), antral follicle count (AFC) (MD 0.55, 95% CI 0.05 to 1.04, 155 participants, three trials), and FSH levels at 3 months post-treatment (MD -4.77, 95% CI －6.09 to －3.45, 137 participants, two trials).Compared with Western Medicine, tonifying-kidney and regulating-liver therapy is more effective at relieving symptoms and improving AFC and FSH at 3 months post-treatment.

Based on the entropy TOPSIS model and clustering method, this article builds a multi-functional evaluation index system for land use based on 21 indicators from the perspective of “production-life-ecology”, evaluates the multifunctionality of land use, and analyzes its spatial differences in Baise, Guangxi, China. The results show that the multifunctional level of land use in Baise is still at a poor level, and the ecology function are better utilized. There are big differences in the spatial distribution of multifunctional land use among counties in Baise, and the overall spatial distribution pattern is “slightly stronger in the south than in the north”. Multifunctional land use in Baise is greatly affected by production function factors. It is recommended to accelerate industrial transformation and upgrading, and give full play to the different ecology, resource, location or policy advantages of each county to improve the level of land production functions, and pay attention to green development, the common development of each function and the regional coordinated development.

Summary Conventionally, methods of coupling reservoirs and surface networks are categorized into implicit and explicit approaches. The term "implicit coupling" indicates that the two simulators solve unknowns together, simultaneously, or iteratively, whereas "explicit coupling" indicates that the two simulators solve unknowns sequentially and exchange their boundary conditions at the last coupled time tn. The explicit approach is straightforward to implement in existing reservoir and surface-network models and is widely used. Explicit coupling does have drawbacks, however, because well rate and pressure oscillations are often observed. In this paper, a new semi-implicit method for coupled simulation is presented. This technique stabilizes and improves the accuracy of the coupled model. The "semi-implicit coupling" overcomes the problems found in explicit-coupling methods without requiring the complexity of a fully implicit coupled model. The new approach predicts inflow-performance-relationship (IPR) curves at the next coupled time tn+1 by simultaneously conducting well tests for all wells in the reservoir before actually taking the required timestep. All wells first flow simultaneously to the next coupled time tn+1 with the well rates unchanged from the last coupled timestep. The timestep is rewound, and all well rates are reduced by a uniform fraction and then simultaneously flow again to tn+1. By extrapolating the resulting well pressures, the well's shut-in pressures at time tn+1 are determined, and thus, straight-line IPRs are produced. The new IPR curves approximate better each well's drainage region at tn+1 and each well's shut-in pressure at tn+1 which helps to stabilize the explicitly coupled model. The new coupling technique normally does not require iteration between the reservoir and surface network and normally has the stability and accuracy characteristics of an implicitly coupled approach. Because the well tests already account for individual well-drainage regions, an explicit knowledge of the well-drainage region is not required. Because of the stabilized IPR, the approach also was found to reduce the overall computational time compared with explicit coupling. Applications of the new approach are presented that show significant improvements surpassing explicit coupling in both stability and accuracy.

Conventionally, methods of coupling reservoirs and surface networks are categorized into implicit and explicit approaches. The term implicit coupling indicates the two simulators solve unknowns together, simultaneously or iteratively. While explicit coupling indicates the two simulators solve unknowns sequentially and exchange their boundary conditions at the last coupled time tn. The explicit approach is straightforward to implement in existing reservoir and surface network models and is widely used. Explicit coupling does have drawbacks, however; as well rate and pressure oscillations are often observed. In this paper, a new semi-implicit method for coupled simulation is presented. This technique stabilizes and improves the accuracy of the coupled model. The semi-implicit coupling overcomes the problems found in explicit coupling methods without requiring the complexity of a fully implicit coupled model. The new approach predicts inflow performance relationship (IPR) curves at the next coupled time tn+1 by simultaneously conducting well tests for all wells in the reservoir before actually taking the required timestep. All wells first simultaneously flow to the next coupled time tn+1 with the well rates unchanged from the last coupled timestep. The timestep is rewound, and all well rates are reduced by a uniform fraction and then simultaneously flow again to tn+1. By extrapolating the resulting well pressures, the well’s shut-in pressures at time tn+1 are determined and thus straight line IPRs are produced. The new IPR curves better approximates each well’s drainage region at tn+1 and each well’s shut-in pressure at tn+1 which helps to stabilize the explicitly coupled model. The new coupling technique normally does not require iteration between the reservoir and surface network and normally has the stability and accuracy characteristics of an implicitly coupled approach. Since the well tests already account for individual well drainage regions, explicit knowledge of the well drainage region is not required. Due to the stabilized IPR, the approach has also been found to reduce the overall computational time when compared with explicit coupling. Applications of the new approach are presented which show significant improvements over explicit coupling in both stability and accuracy.

Japan National Oil Corporation (JNOC) is conducting a survey on underground gas storage (UGS) using inert gas as cushion gas, which makes good use of assets of depleted gas or gas condensate reservoirs. Since the Japanese regulation for a heating value of city gas is extremely strict, a heating value and hence composition of gas withdrawn from those reservoirs must be carefully predicted to properly design UGS projects. JNOC has developed an UGS simulator, which can rigorously evaluate a heating value of withdrawn gas taking into consideration all the major phenomena that possibly affect composition of withdrawn gas. A conventional cubic equation of state (EOS) based 3-D compositional simulator and a PVT simulator were improved to construct the UGS simulator equipped with the functions for calculating physical phenomena: a) molecular diffusion and velocity dependent dispersion, b) three-phase flash including dissolution of gaseous components into water and vaporization of water, c) adsorption of gaseous components onto a rock surface and d) turbulence and Klinkenberg effects. In addition, new functions of MPFA (Multi-Point Flux Approximation) and TVD (Total Variation Diminishing) scheme with local grid refinement in a corner point geometry were incorporated into the simulator to rigorously calculate a fluid flux with permeability tensors and to reduce numerical dispersion, respectively. Furthermore, functions to calculate temperature distributions both in a reservoir and wellbore were added to examine the effect of cooling caused by gas injection and adiabatic expansion on fluid flow and gas composition. Each function newly developed for the UGS simulator was then validated through test runs using laboratory test data. Field scale simulations for hypothetical reservoirs were also conducted to confirm the simulator's performance as well as to examine the effect of cushion gas volume, working gas volume, reservoir heterogeneity and in situ gas composition on withdrawn gas composition. This paper describes the development and validation of the UGS simulator followed by the results of field scale simulation runs.