A review on continuous-flow microfluidic PCR in droplets : advances, challenges and future

Significant advances have been made in developing microfluidic polymerase chain reaction (PCR) devices in the last two decades. More recently, microfluidic microdroplet technology has been exploited to perform PCR in droplets because of its unique features. For example, it can prevent crossover contamination and PCR inhibition, is suitable for single-cell and single molecule analyses, and has the potential for system integration and automation. This review will therefore focus on recent developments on droplet-based continuous-flow microfluidic PCR, and the major research challenges. This paper will also discuss a new way of on-chip flow control and a rational design simulation tool, which are required to underpin fully integrated and automated droplet-based microfluidic systems. We will conclude with a scientific speculation of future autonomous scientific discoveries enabled by microfluidic microdroplet technologies

Topological invariants, zero mode edge states and finite size effect for a generalized non-reciprocal Su-Schrieffer-Heeger model

Intriguing issues in one-dimensional non-reciprocal topological systems include the breakdown of usual bulk-edge correspondence and the occurrence of half-integer topological invariants. In order to understand these unusual topological properties, we investigate the topological phase diagrams and the zero-mode edge states of a generalized non-reciprocal Su-Schrieffer-Heeger model, based on some analytical results. Meanwhile, we provide a concise geometrical interpretation of the bulk topological invariants in terms of two independent winding numbers and also give an alternative interpretation related to the linking properties of curves in three-dimensional space. For the system under the open boundary condition, we construct analytically the wavefunctions of zero-mode edge states by properly considering a hidden symmetry of the system and the normalization condition with the use of biorthogonal eigenvectors. Our analytical results directly give the phase boundary for the existence of zero-mode edge states and unveil clearly the evolution behavior of edge states. In comparison with results via exact diagonalization of finite-size systems, we find our analytical results agree with the numerical results very well.Comment: 13 pages, 9 figure

Quantification of the influence of drugs on zebrafish larvae swimming kinematics and energetics

The use of zebrafish larvae has aroused wide interest in the medical field for its potential role in the development of new therapies. The larvae grow extremely quickly and the embryos are nearly transparent which allows easy examination of its internal structures using fluorescent imaging techniques. Medical treatment of zebrafish larvae can directly influence its swimming behaviours. These behaviour changes are related to functional changes of central nervous system and transformations of the zebrafish body such as muscle mechanical power and force variation, which cannot be measured directly by pure experiment observation. To quantify the influence of drugs on zebrafish larvae swimming behaviours and energetics, we have developed a novel methodology to exploit intravital changes based on observed zebrafish locomotion. Specifically, by using an in-house MATLAB code to process the recorded live zebrafish swimming video, the kinematic locomotion equation of a 3D zebrafish larvae was obtained, and a customised Computational Fluid Dynamics tool was used to solve the fluid flow around the fish model which was geometrically the same as experimentally tested zebrafish. The developed methodology was firstly verified against experiment, and further applied to quantify the fish internal body force, torque and power consumption associated with a group of normal zebrafish larvae vs. those immersed in acetic acid and two neuroactive drugs. As indicated by our results, zebrafish larvae immersed in 0.01% acetic acid display approximately 30% higher hydrodynamic power and 10% higher cost of transport than control group. In addition, 500 μM diphenylhydantoin significantly decreases the locomotion activity for approximately 50% lower hydrodynamic power, whereas 100 mg/L yohimbine has not caused any significant influences on 5 dpf zebrafish larvae locomotion. The approach has potential to evaluate the influence of drugs on the aquatic animal’s behaviour changes and thus support the development of new analgesic and neuroactive drugs

Thermal Stability of Ultrafine Grained CuCrZr Alloy Produced by Continuous Extrusion

The Cu-0.36Cr-0.15Zr alloy was prepared by solid solution, continuous extrusion and cold deformation. The microstructural evolution, microhardness and the thermal analysis were examined for the alloy after annealing treatment at different temperatures ranging from 300 oC to 700 oC. Experimental results show that the microstructure of the alloy remains stable after annealed below 500 oC due to the pinning effect of dislocations from the nanoscale precipitates. However, recrystallization and grain growth took place after a 600 oC annealing treatment when the precipitates grew up and lose inhibition of movement of dislocations and grain boundaries. Meanwhile, the higher dislocation density and finer grains introduced by continuous extrusion accelerate the recrystallization process compared with that prepared by the traditional rolling process

Role of IL-33 and ST2 signalling pathway in multiple sclerosis: expression by oligodendrocytes and inhibition of myelination in central nervous system

Recent research findings have provided convincing evidence indicating a role for Interleukin-33 (IL-33) signalling pathway in a number of central nervous system (CNS) diseases including multiple sclerosis (MS) and Alzheimer’s disease. However, the exact function of IL-33 molecule within the CNS under normal and pathological conditions is currently unknown. In this study, we have mapped cellular expression of IL-33 and its receptor ST2 by immunohistochemistry in the brain tissues of MS patients and appropriate controls; and investigated the functional significance of these findings in vitro using a myelinating culture system. Our results demonstrate that IL-33 is expressed by neurons, astrocytes and microglia as well as oligodendrocytes, while ST2 is expressed in the lesions by oligodendrocytes and within and around axons. Furthermore, the expression levels and patterns of IL-33 and ST2 in the lesions of acute and chronic MS patient brain samples are enhanced compared with the healthy brain tissues. Finally, our data using rat myelinating co-cultures suggest that IL-33 may play an important role in MS development by inhibiting CNS myelination

Interleukin-16 inhibits sodium channel function and GluA1 phosphorylation via CD4- and CD9-independent mechanisms to reduce hippocampal neuronal excitability and synaptic activity

Interleukin 16 (IL-16) is a cytokine that is primarily associated with CD4+ T cell function, but also exists as a multi-domain PDZ protein expressed within cerebellar and hippocampal neurons. We have previously shown that lymphocyte-derived IL-16 is neuroprotective against excitotoxicity, but evidence of how it affects neuronal function is limited. Here, we have investigated whether IL-16 modulates neuronal excitability and synaptic activity in mouse primary hippocampal cultures. Application of recombinant IL-16 impairs both glutamate-induced increases in intracellular Ca2+ and sEPSC frequency and amplitude in a CD4- and CD9-independent manner. We examined the mechanisms underlying these effects, with rIL-16 reducing GluA1 S831 phosphorylation and inhibiting Na+ channel function. Taken together, these data suggest that IL-16 reduces neuronal excitability and synaptic activity via multiple mechanisms and adds further evidence that alternative receptors may exist for IL-16