Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

© 2017 The Author(s). Background: Multiple iterations of chimeric antigen receptors (CARs) have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined. Methods: We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo. Results: During in vitro culture period, the percentages and absolute numbers of T cells expressing the CARs containing a hinge domain continuously increased, mainly through the promotion of CD4+ CAR T cell expansion, regardless of the single-chain variable fragment (scFv). In vitro migration assay showed that the hinges enhanced CAR T cells migratory capacity. The T cells expressing anti-CD19 CARs with or without a hinge had similar antitumor capacities in vivo, whereas the T cells expressing anti-mesothelin CARs containing a hinge domain showed enhanced antitumor activities. Conclusions: Hence, our results demonstrate that a hinge contributes to CAR T cell expansion and is capable of increasing the antitumor efficacy of some specific CAR T cells. Our results suggest potential novel strategies in CAR vector design.Link_to_subscribed_fulltex

FWAlgaeDB, an integrated genome database of freshwater algae

Algal genomics research contributes to a deeper understanding of algal evolution and provides useful genomics inferences correlated with various functions. Published algal genome sequences are very limited owing to genome assembly challenges. Because genome data of freshwater algae are rapidly increasing with the recent boom in next-generation sequencing and bioinformatics, an interface to store, interlink, and display these data is needed. To provide a substantial genomic resource specifically for freshwater algae, we developed the Freshwater Algae Database (FWAlgaeDB), a user-friendly, constantly updated online repository for integrating genomic data and annotation information. This database, which includes information on 204 freshwater algae, allows easy access to gene repertoires and gene clusters of interest and facilitates potential applications. Three functional modules are integrated into FWAlgaeDB: a Basic Local Alignment Search Tool tool for similarity analyses, a Search tool for rapid data retrieval, and a Download function for data downloads. This database tool is freely available at http://www.fwalagedb.com/#/home. To demonstrate the utility of FWAlgaeDB, we also individually mapped metagenomic sequencing reads of 10 water samples to FWAlgaeDB and Nt algae databases we constructed to obtain taxonomic composition information. According to the mapping results, FWAlgaeDB may be a better choice for identifying algal species in freshwater samples, with fewer potential false positives because of its focus on freshwater algal species. FWAlgaeDB can therefore serve as an open-access, sustained platform to provide genomic data and molecular analysis tools specifically for freshwater algae

A Direct Position Determination Method under Unknown Multi-Perturbation with Moving Distributed Arrays

Distributed array manifold perturbation, which includes synchronization errors, amplitude-phase errors, and path attenuation, has seriously degraded the accuracy of existing direct position determination (DPD) methods. In this paper, a DPD method under unknown multi-perturbation with moving distributed coprime arrays is advocated for. Firstly, by means of array position interchange, the integrated signals received from distributed arrays can be fused, which contributes to multi-position fusion. Subsequently, by resorting to the orthogonality between the noise subspace and steering vector received via distributed arrays, a quadratic optimization problem is constructed. Finally, we realize multi-parameter decoupling and achieve localization regardless of unknown perturbations. The superiority of the advocated method is substantiated from simulation examples

Partial Dictionary Based Off-Grid DOA Estimation Using Combined Coprime and Nested Array

A partial dictionary based direction of arrival (DOA) estimation method which addresses the off-grid problem and exploits combined coprime and nested array (CCNA) is proposed. Compared to general coprime array, CCNA yields two sparse coprime subarrays in the coarray domain by adding a third subarray in the physical-array domain. To ensure the DOA estimation performance, the subarray with larger aperture is chosen, and the cyclic phase ambiguity caused by the sparse subarray allows partial dictionary covering arbitrary cycle to represent the whole atoms, and then, the off-grid sparse reconstruction method is developed to amend the grid mismatch. After the sparse recovery and off-grid compensation, ambiguous DOA estimations can be eliminated by substituting the estimations into the whole virtual array. Multiple simulations verify that the proposed algorithm outperforms the other state-of-the-art methods in terms of DOA estimation accuracy and angular resolution

A Direct Position Determination Method under Unknown Multi-Perturbation with Moving Distributed Arrays

Distributed array manifold perturbation, which includes synchronization errors, amplitude-phase errors, and path attenuation, has seriously degraded the accuracy of existing direct position determination (DPD) methods. In this paper, a DPD method under unknown multi-perturbation with moving distributed coprime arrays is advocated for. Firstly, by means of array position interchange, the integrated signals received from distributed arrays can be fused, which contributes to multi-position fusion. Subsequently, by resorting to the orthogonality between the noise subspace and steering vector received via distributed arrays, a quadratic optimization problem is constructed. Finally, we realize multi-parameter decoupling and achieve localization regardless of unknown perturbations. The superiority of the advocated method is substantiated from simulation examples

The Potential for PE Microplastics to Affect the Removal of Carbamazepine Medical Pollutants from Aqueous Environments by Multiwalled Carbon Nanotubes

Microplastics are ubiquitous in aquatic environments and interact with other kinds of pollutants, which affects the migration, transformation, and fate of those other pollutants. In this study, we employ carbamazepine (CBZ) as the contaminant to study the influence of polyethylene (PE) microplastics on the adsorption of CBZ pollutants by multiwalled carbon nanotubes (MCNTs) in aqueous solution. The adsorption capacity of CBZ by MCNTs in the presence of PE microplastics was obviously lower than that by MCNTs alone. The influencing factors, including the dose of microplastics, pH, and CBZ solution concentration, on the adsorption of CBZ by MCNTs and MCNTs−PE were thoroughly investigated. The adsorption rate of CBZ by MCNTs decreased from 97.4% to 90.6% as the PE microplastics dose increased from 2 g/L to 20 g/L. This decrease occurred because the MCNTs were coated on the surface of the PE microplastics, which further decreased the effective adsorption area of the MCNTs. This research provides a framework for revealing the effect of microplastics on the adsorption of pollutants by carbon materials in aqueous environments

Carbon Dioxide Emission Equivalent Analysis of Water Resource Behaviors: Determination and Application of CEEA Function Table

To achieve the global temperature control target under the background of climate warming, it is necessary to establish a systematic carbon dioxide (CO2) emission accounting method system in the field of water resources as soon as possible. In this study, the carbon dioxide emission equivalent analysis (CEEA) method for different water resource behaviors (WRBs) is proposed from four dimensions of development, allocation, utilization, and protection, and a function table of CEEA (FT-CEEA) for WRBs is constructed. The FT-CEEA includes CEEA formulae for 16 aspects in four categories of water resource development, allocation, utilization, and protection. The CEEA method is applied to 31 provinces in China. The results reveal that: (1) There are significant spatial differences in the carbon dioxide emission equivalent (CEE) of WRBs in different provinces of China under the influence of various factors such as water supply structure and natural conditions. (2) Reservoir storage, tap water allocation, and wastewater treatment are the main contributors to CEE in the categories of water resource development, allocation, and protection behaviors, respectively. (3) The water resource utilization behavior category has the most significant CO2 emission and absorption effects, and industrial and domestic water utilization behaviors are the main sources of emission effects. (4) The overall CO2 emission effect of WRBs is greater than the absorption effect. Measures such as increasing the proportion of hydroelectric power generation, improving ecological water security capacity, and strengthening the level of wastewater treatment and reclaimed water reuse are effective ways to promote the goal of carbon neutrality in the field of water resources

Yellow River Basin Management under Pressure. The Present State, Restoration and Protection: Lessons from a Special Issue

Ecological protection and high-quality development in the basin of the Yellow River, known as China’s “Mother River” and “the cradle of Chinese civilization”, have been receiving increasing attention because of the important role they play in China’s economic and social development, and its cultural heritage [...