Nanovaccine-Mediated Cell Selective Delivery of Neoantigens Potentiating Adoptive Dendritic Cell Transfer for Personalized Immunization

Neoantigen vaccines and adoptive dendritic cell (DC) transfer are major clinical approaches to initiate personalized immunity in cancer patients. However, the immunization efficacy is largely limited by the in vivo trajectory including neoantigens’ access to resident DCs and DCs’ access to lymph nodes (LNs). Herein, an innovative strategy is proposed to improve personalized immunization through neoantigen-loaded nanovaccines synergized with adoptive DC transfer. It is found that it enables selective delivery of neoantigens to resident DCs and macrophages by coating cancer cell membranes onto neoantigen-loaded nanoparticles. In addition, the nanovaccines promote the secretion of chemokine C-C motif ligand 2 (CCL2), CCL3, and C-X-C motif ligand 10 from macrophages, thus potentiating the access of transferred DCs to LNs. This immunization strategy enables coordinated delivery of identified neoantigens and autologous tumor lysate-derived undefined antigens, leading to initiation of antitumor T cell immunity in a personalized manner. It significantly inhibits tumor growth in prophylactic and established mouse tumor models. The findings provide a new vision for potentiating adoptive cell transfer by nanovaccines, which may open the door to a transformative possibility for improving personalized immunization.     

Fixed mesh front‐tracking methodology for finite element simulations

A direct front‐tracking method using an Eulerian–Lagrangian formulation is developed in two space dimensions. The front‐tracking method is general in that it can track any type of interface once its local velocity is specified or has been determined by calculation. The method uses marker points to describe the interface position and tracks the interface evolution on a fixed finite‐element mesh, including growth, contraction, splitting and merging. Interfacial conditions are applied directly at the interface position. The method is applied to three scenarios that involve different interface conditions and are based on energy and mass diffusion. The three calculations are for the dendritic solidification of a pure substance, the cellular growth of an alloy, and the Ostwald ripening of silica particles in silicon. Numerical results show that very complicated interface morphologies and topological changes can be simulated properly and efficiently. Copyright © 2004 John Wiley & Sons, Ltd.     

Structure of rapidly solidified aluminum alloys

This paper is a summary of an extensive research program carried out by the authors on the structure of rapidly solidified aluminum alloys; and a comparison with the work of others also involved in this field. The paper discusses the changes in the dendritic and non-dendritic structure of the matrix at cooling rates from 10^–3 to 10¹⁰ K/s and discusses the hetergeneity of the structure caused by interdendritic-segretion during solidification.     

Synthesis and aqueous solution behaviors of sodium sulfonate‐terminated dendritic poly(ester‐amine)

Sodium sulfonate‐terminated dendritic poly(ester‐amine) (SPEA) was synthesized by sulfonation of acrylic double bond‐terminated dendritic poly(ester‐amine) (APEA) with sodium hydrogen sulfite (NaHSO₃) in mixture of diglycol and 2‐butanone under normal pressure. The structure of SPEA was characterized by IR, ¹H‐NMR, and elemental analysis. SPEA was water‐soluble. 1.0–40.0% (mass) SPEA aqueous solutions appeared as dilatant fluid. When pH value varied from 1.5 to 12.0, the viscosity of 1–5% (mass) SPEA aqueous solutions changed very small, and the electric conductivity almost kept stable within pH 3.0–10.0. The relationship between the viscosity and the concentration of SPEA water solutions was similar to that of NaCl water solutions. The surface tension of SPEA water solutions was lower than that of polyethylene glycol 2000 water solutions with the same concentration. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.     

凝固速率对定向凝固合金DZ22枝晶臂间距和枝晶偏析的影响

采用新研制的超高梯度定向凝固装置，研究了不同凝固速率下定向凝固高温合金ＤＺ２２枝晶臂间距和枝晶偏析。结果表明，冷运速率增大，枝晶臂间距显著细化，枝晶偏析被强烈抑制。当冷运速率为５２．４Ｋ．ｓ＾－１时，一次、二次枝晶臂间距λ１和λ２分别为２８．８和８．４μｍ，Ｎｂ，Ｔｉ，Ａｌ，Ｃｒ，Ｃｏ，Ｗ等元素的偏析比均趋近于１。     

基于危险理论和DCA的WSNs入侵检测系统模型

针对无线传感器网络(WSNs)由于自身特点易于遭到入侵且传统被动的安全机制无法完全应对这一问题,对人工免疫系统(AIS)进行研究,设计一种新的入侵检测系统(IDS)模型。模型采用危险理论和适用于WSNs的改良树突状细胞算法(DCA),可使节点之间彼此分工合作共同识别入侵,加强了网络的鲁棒性。仿真结果显示:与早期的自我—非我(SNS)模型相比,研究的模型在检测能力和能耗上均有很好的表现。     

树突细胞算法在线分析组件的研究

原始树突状细胞算法（DCA）的离线分析过程,将会导致时间差异,从而产生假警报,增加了虚警率,也会导致攻击的成功发生,这对一个人侵检测系统来说是致命的。因此,文中的目的就是在不影响检测精度的前提下提高检测速度。于是文中提出了分片思想的在线分析组件与DCA相集成的方法,即根据抗原采样数量或者时间将一系列已处理的信息分割成为更小的部分,使得每个分片独立地进行实时的、周期性的分析,这样在每个分片内的入侵攻击就能及时地被识别出来。文中给出了DCA在线分析模块的伪代码描述,并且将其应用于SYN端口扫描的检测实验中。结果表明,DCA在线分析模块在不影响检测精度的前提下有效地提高了检测速度。     

树枝形分子等增韧改性环氧树脂研究进展

简要介绍了两种环氧树脂增韧改性新方法,重点介绍了树枝形分子的基本概念和结构与性能特点,综述了国内外树枝形分子改性环氧树脂的研究进展,并进行了展望。     

某矿区变电站进线段防雷改造措施及仿真分析

介绍了某矿区110kV变电站线路防雷措施的基本情况,分析了该变电站35kV进线段遭受雷击的原因,即线路绝缘水平遭人为提高后与站内绝缘水平等级不匹配和进线段杆塔接地电阻过高,并提出了相应的采用加装绝缘子保护间隙配合避雷器进行差异性保护和采用树枝状接地装置的改造措施。ATPEMTP仿真分析结果验证了改造措施的可行性。