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Herein, we report effective, C-type lectin mannose receptor (MR)-selective, in vivo dendritic cell (DC)-targeting lipid nanoparticles (LNPs) of a novel lipid-containing mannose-mimicking di-shikimoyl- and guanidine head group and two n-hexadecyl hydrophobic tails (DSG). Subcutaneous administration of LNPs of the DSG/p-CMV-GFP complex showed a significant expression of green fluorescence protein in the CD11c+ DCs of the neighboring lymph nodes compared to the control LNPs of the BBG/p-CMV-GFP complex. Mannose receptor-facilitated in vivo DC-targeted vaccination (s.c.) with the electrostatic complex of LNPs of DSG/pCMV-MART1 stimulated long-lasting (270 days post B16F10 tumor challenge) antimelanoma immunity under prophylactic conditions. Remarkably, under therapeutic settings, vaccination (s.c.) with LNPs of the DSG/pCMV-MART1 complex significantly delayed melanoma growth and improved the survival of mice with melanoma. These findings demonstrate that this nonviral delivery system offers a resilient and potential approach to deliver DNA vaccines encoding tumor antigens to DCs in vivo with high efficacy.  相似文献   
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The observation of the immunomodulatory effects of opioid drugs opened the discussion about possible mechanisms of action and led researchers to consider the presence of opioid receptors (OR) in cells of the immune system. To date, numerous studies analyzing the expression of OR subtypes in animal and human immune cells have been performed. Some of them confirmed the expression of OR at both the mRNA and protein level, while others did not detect the receptor mRNA either. Although this topic remains controversial, further studies are constantly being published. The most recent articles suggested that the expression level of OR in human peripheral blood lymphocytes could help to evaluate the success of methadone maintenance therapy in former opioid addicts, or could serve as a biomarker for chronic pain diagnosis. However, the applicability of these findings to clinical practice needs to be verified by further investigations.  相似文献   
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Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.  相似文献   
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基于GA-BP的汽车风振噪声声品质预测模型   总被引:1,自引:1,他引:0  
目前对于汽车风振噪声的优化研究主要以声压级(Sound pressure level,SPL)作为单一评价指标,既不能全面反映噪声的物理属性,也无法考虑人耳对噪声的主观认知过程。为准确评价风振噪声,引入声品质,运用大涡模拟(Large eddy simulation,LES)对风振噪声进行数值仿真,根据实车道路试验判断仿真的准确性;对仿真结果进行声品质客观评价与主观评价,综合声品质客观评价参数与声品质主观评价试验结果建立BP神经网络预测模型;利用遗传算法(Genetic algorithm,GA),进一步对BP神经网络的结构参数进行优化,建立GA-BP声品质预测模型。研究结果表明,GA-BP声品质预测模型在训练速度和预测精度上都优于BP神经网络预测模型。预测模型基于声品质主客观评价结果,其预测值可以代替传统的声压级评价指标,为风振噪声提供更为准确合理的评价。  相似文献   
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杨春燕  宾冬梅  黎新 《电信科学》2021,37(2):144-153
提出了一种基于实用拜占庭容错(PBFT)算法的区块链技术,首先对传统的实用拜占庭容错算法原理进行了阐述,该传统算法包含前期、需求、预准备、准备、确认、答复6个阶段,但传统算法具有实时性差、缺乏惩罚机制、带宽高的缺点。针对出现的这些问题,又对传统算法进行了改进,具体涉及记账节点、共识过程以及视图切换过程。通过测试进一步证明了该改进算法的实用性,并将该算法应用于电网企业中,构建的虚拟仓库实现了联储联备,降低了库存资金的耗费,并且提高了电网企业库存管理的效率。  相似文献   
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This paper develops a novel approach to the parameterisation of high temperature exchange membrane fuel cells (HTPEMFC) with limited and non-invasive measurements. The proposed method allows an effective identification of electrochemical parameters for three-dimensional fuel cell models by combining computational simulation tools and genetic algorithms. To avoid each evaluation undertaken by the optimisation method involving a complete computational simulation of the 3D model, a strategy has been designed that, thanks to an iterative process, makes it possible to decouple the fluid dynamic resolution from the electrochemistry one.Two electrochemical models have been incorporated into these tools to describe the behaviour of the catalyst layer, Butler-Volmer and spherical aggregate. For each one, a case study has been carried out to validate the results by comparing them with empirical data in the first model and with data generated by numerical simulation in the second. Results show that, from a set of measured operating conditions, it is possible to identify a unique set of electrochemical parameters that fits the 3D model to the target polarisation curve. The extension of this framework can be used to systematically estimate any model parameter in order to reduce the uncertainty in 3D simulation predictions.  相似文献   
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Under the circumstance of perceptual consumption, it is still challenging to grasp consumer's emotions and demands due to the large search space, diversified preferences, and easy fatigue of consumers. To reduce user fatigue and enlarge search space, a novel method was presented to design and optimize the pattern of yarn-dyed plaid fabric using the isolation niche genetic algorithm and rough set theory. Each pattern was encoded as a chromosome based on the real number code. The population was initialized and evolved using INGA to maintain the diversity. The rough set theory was adopted as the fitness function of isolation niche genetic algorithm to extract the consumer's demands. After multiple evolutions, a large set of practical patterns of the yarn-dyed plaid fabric are obtained. Experiments were carried out by 24 testers of different ages and genders. The results prove that the proposed method based on the isolation niche genetic algorithm and rough set theory is feasible and effective, supplying references to the designer.  相似文献   
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