An Integrated Dual-Functional Nanotool Capable of Studying Single-Cell Epigenetics and Programmable Gene Regulation

Single-cell epigenetics is envisioned to decipher manifold epigenetic phenomena and to contribute to our accurate knowledge about basic epigenetic mechanisms. Engineered nanopipette technology has gained momentum in single-cell studies; however, solutions to epigenetic questions remain unachieved. This study addresses the challenge by exploring N6-methyladenine (m⁶A)-bearing deoxyribozyme (DNAzyme) confined within a nanopipette for profiling a representative m⁶A-modifying enzyme, fat mass and obesity-associated protein (FTO). Electroosmotic intracellular extraction of FTO could remove the m⁶A and cause DNAzyme cleavage, leading to the altered ionic current signal. Because the cleavage can release a DNA sequence, we simultaneously program it as an antisense strand against FTO-mRNA, intracellular injection of which has been shown to induce early stage apoptosis. This nanotool thus features the dual functions of studying single-cell epigenetics and programmable gene regulation.     

含时滞的参数不确定主动悬架离散系统鲁棒控制

针对主动悬架存在传输时滞和参数不确定性的控制问题,设计了含时滞的参数不确定鲁棒控制器。首先,运用线性分式变换方法推导出含时滞的参数不确定主动悬架状态空间方程,采用零阶保持器取值处理和双线性变换,建立主动悬架离散控制系统模型。其次,以车身垂向加速度为车辆悬架系统的最优化输出目标,采用Lyapunov泛函方法,推导出系统渐进稳定的鲁棒控制器充分条件,得到满足最优H_∞性能指标约束的反馈控制律,再通过求解线性矩阵不等式获得控制器参数。最后,进行数值算例仿真,结果表明,相较于只考虑时滞的控制器,含时滞的参数不确定鲁棒控制器具有更好的控制效果和鲁棒性,且受采样周期与不确定参数的耦合影响较小。     

Interfacial deformation of confined photocurable fluid for fabrication of shape-imprinted microspheres

This study presents a simple route to fabricate shape imprinted microspheres and their application toward multiplex immunoassay. Specifically, a photocurable fluid (polyethylene glycol diacrylate, [PEGDA]) confined in a micromold results in drop formation due to mold swelling and capillarity upon addition of immiscible wetting fluid; during this formation, part of the photocurable fluid is entrapped at the swollen open end, thereby producing polymeric microspheres with controlled imprinted shapes on their surface upon photopolymerization. This approach is able to produce highly uniform microspheres with different imprinted shapes depending on mold geometry in a consistent manner; their size can also be tuned by varying mold dimensions. Furthermore, we impart amine-reactive functional groups to the microsphere, which allows them to be functionalized efficiently. Lastly, we conjugate different capture antibodies on microspheres with different imprinted shapes, and these microspheres were demonstrated to be shape-encoded suspension arrays for multiplex immunoassays. This technique provides high selectivity and a simple decoding method for biosensing applications.     

Measure-transmission metric and stability of structured population models

In Gwiazda, et al. (2012) a framework for studying cell differentiation processes based on measure-valued solutions of transport equations was introduced. Under application of the so-called measure-transmission conditions it enabled to describe processes involving both discrete and continuous transitions. This framework, however, admits solutions which lack continuity with respect to initial data. In this paper, we modify the framework from Gwiazda, et al. (2012) by replacing the flat metric, known also as bounded Lipschitz distance, by a new Wasserstein-type metric. We prove, that the new metric provides stability of solutions with respect to perturbations of initial data while preserving their continuity in time. The stability result is important for numerical applications.     

CIMS下基于成组单元的无能力约束的生产批量计划的新方法

CIMS中基于成组单元的生产批量计划问题是确定属于M个族的N种不同的项目在给定的计划范围T内的每一个时间段上的批量,使得在T内项目总的调整费用（族调整费用和项目调整费用之和）和库存保管费用以及生产费用之和最小（GTLS）本文基于GTLS问题的性质,从一个新的角度即从调整变量出发,运用遗传算法（GA）随机搜索进行求解．对GTLS构造了两阶段启发式算法（Heuristic）,通过仿真实验,测试6个问题表明,GTLS／GA比GTLS／Heuristic平均改善5％以内．     

(E)-3-Arylidene-4-diazopyrrolidine-2,5-diones conveniently elaborated into cytotoxic compounds bearing primary sulfonamide and Michael acceptor moieties

The earlier described (E)-3-arylidene-4-diazopyrrolidine-2,5-diones have been elaborated into two distinct series of compounds both bearing a primary sulfonamide moiety and an electrophilic ‘Michael acceptor’ motif. These compounds demonstrated cytotoxicity against colorectal cancer cell line HCT 116.     

Biocompatible and noncytotoxic nucleoside-based AIEgens sensor for lighting-up nucleic acids

Aggregation-induced emission luminogens (AIEgens) have been used in biomacromolecules detection. Herein, TPE-dC and TPE-dU acted as the nucleoside-based AIEgens sensors in the first case, which can be used to detect ctDNA and rRNA in vitro and light up the nucleus in vivo depending on the intermolecular binding affinity. This AIE process enables the quantitative analysis or visualization of nucleic acids in solution or gels state, respectively. Furthermore, confocal laser scanning microscopy (CLSM) images of L929 cells stained with TPE-dC or TPE-dU clearly shows that nucleoside-based AIEgens bio-probes can pass the cell membranes to reach the cell nucleus, without cytotoxicity at the imaging condition (incubation time > 12 h, and 10 μmol/L of concentration). Since the nucleus is rich in DNA/RNA, fluorescence turn-on mode has a great potential in nucleus imaging and clinical diagnosis.     

Sheath-assisted focusing of microparticles on lab-on-a-chip platforms

Lab-on-a-chip (LOC) technologies can take advantage of sheath flows for particle/cell focusing before sensing or sorting. The integration of focusing with other microscale manipulation techniques (e.g., sorting) creates a trade-off between the throughput of the device and its performance. Therefore, exploring the effective parameters for cells/particles focusing enables us to improve the desired output of LOC devices. A common configuration for sheath-assisted focusing is Y junctions, which are parametrically studied in this paper. First, a computational model was developed and validated by comparing it with our experimental results. Using COMSOL Multiphysics modeling, the effects of multiple parameters were studied. These parameters include the sheath flow ratio (sheath flow over total flow), width ratio (width of the sheath inlet over the total width), junction angles, and particle size on the focusing width and the distribution of the particles within the focusing region. Then, the numerical data were used to develop two generalized linear models to predict the focusing width of the particles and the standard deviation of the position of the particles. The results showed that the focusing width is greatly impacted by the sheath flow rate ratio. Further, the standard deviation of the position of the particles, which represents the concentration of the particles, is mostly dependent on the flow rate ratio, width ratio, and particle size. Our results provide a better understanding of how the device geometrical and operational factors affect the position of the particles in the development of high-performance on-chip sensing and sorting of both cells and particles.     

Inertial microfluidics: Recent advances

Inertial microfluidics has attracted significant attentions in last decade due to its superior advantages of high throughput, label- and external field-free operation, simplicity, and low cost. A wide variety of channel geometry designs were demonstrated for focusing, concentrating, isolating, or separating of various bioparticles such as blood components, circulating tumor cells, bacteria, and microalgae. In this review, we first briefly introduce the physics of inertial migration and Dean flow for allowing the readers with diverse backgrounds to have a better understanding of the fundamental mechanisms of inertial microfluidics. Then, we present a comprehensive review of the recent advances and applications of inertial microfluidic devices according to different channel geometries ranging from straight channels, curved channels to contraction-expansion-array channels. Finally, the challenges and future perspective of inertial microfluidics are discussed. Owing to its superior benefit for particle manipulation, the inertial microfluidics will play a more important role in biology and medicine applications.     

基于安全文化视角的实验安全管理机制研究

良好的安全文化可引导人树立安全理念,提升安全素养。结合实验室安全管理的要素,从安全物质文化、安全制度文化、安全行为文化和安全精神文化4个层面,探索安全文化与实验室管理共融机制。