Rapid screening of acetylcholinesterase active contaminants in water: A solid phase microextraction-based ligand fishing approach.

Effect-directed analysis (EDA) has been increasingly used for screening toxic contaminants in the environment, but conventional EDA procedures are often time-consuming and labor-extensive. This challenges the use of EDA for toxicant identification in the scenarios when quick answers are demanded. Herein, a solid phase microextraction ligand fishing (SPME-LF) strategy has been proposed as a rapid EDA approach for identifying acetylcholinesterase (AChE) active compounds in water. The feasibility of ligand fishing techniques for screening AChE active chemicals from environmental mixtures was first verified by a membrane separation method. Then, SPME fibers were prepared through self-assembly of boronic acid groups with AChE via co-bonding and applied for SPME-LF. As AChE coated SPME fibers selectively enriched AChE-active compounds from water, comparing sorbing compounds by the SPME fibers with and without AChE coating can quickly distinguish AChE toxicants in mixtures. Compared with conventional EDA, SPME-LF does not require repeating sample separations and bioassays, endowing SPME-LF with the merits of low-cost, labor-saving, and user-friendly. It is believed that cost-efficient and easy-to-use SPME-LF strategy can potentially be a rapid EDA method for screening receptor-specific toxicants in aquatic environment, especially applicable in time-sensitive screening.

Disrupted mitochondrial response to nutrients is a presymptomatic event in the cortex of the APP SAA knock-in mouse model of Alzheimer's disease.

Introduction: Reduced brain energy metabolism, mTOR dysregulation, and extracellular amyloid-ß oligomer (xcAßO) buildup characterize AD; how they collectively promote neurodegeneration is poorly understood. We previously reported that xcAßOs inhibit N utrient-induced M itochondrial A ctivity (NiMA) in cultured neurons. We now report NiMA disruption in vivo . Methods: Brain energy metabolism and oxygen consumption were recorded in APP SAA/+ mice using two-photon fluorescence lifetime imaging and multiparametric photoacoustic microscopy. Results: NiMA is inhibited in APP SAA/+ mice before other defects are detected in these amyloid-ß-producing animals that do not overexpress APP or contain foreign DNA inserts into genomic DNA. GSK3ß signals through mTORC1 to regulate NiMA independently of mitochondrial biogenesis. Inhibition of GSK3ß with lithium or TWS119 stimulates NiMA in cultured human neurons, and mitochondrial activity and oxygen consumption in APP SAA mice. Conclusion: NiMA disruption in vivo occurs before histopathological changes and cognitive decline in APP SAA mice, and may represent an early stage in human AD.

Laser Machined Fiber-based Microprobe: Application in Microscale Electroporation.

Microscale electroporation devices are mostly restricted to in vitro experiments (i.e., microchannel and microcapillary). Novel fiber-based microprobes can enable in vivo microscale electroporation and arbitrarily select the cell groups of interest to electroporate. We developed a flexible, fiber-based microscale electroporation device through a thermal drawing process and femtosecond laser micromachining techniques. The fiber consists of four copper electrodes (80 µm), one microfluidic channel (30 µm), and has an overall diameter of 400 µm. The dimensions of the exposed electrodes and channel were customizable through a delicate femtosecond laser setup. The feasibility of the fiber probe was validated through numerical simulations and in vitro experiments. Successful reversible and irreversible microscale electroporation was observed in a 3D collagen scaffold (seeded with U251 human glioma cells) using fluorescent staining. The ablation regions were estimated by performing the covariance error ellipse method and compared with the numerical simulations. The computational and experimental results of the working fiber-based microprobe suggest the feasibility of in vivo microscale electroporation in space-sensitive areas, such as the deep brain.

Spatially expandable fiber-based probes as a multifunctional deep brain interface.

Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio. However, with single implantation, the physical properties of these devices limit their access to one, small brain region. To overcome this limitation, we developed a platform that provides three-dimensional coverage of brain tissue through multisite multifunctional fiber-based neural probes guided in a helical scaffold. Chronic recordings from the spatially expandable fiber probes demonstrate the ability of these fiber probes capturing brain activities with a single-unit resolution for long observation times. Furthermore, using Thy1-ChR2-YFP mice we demonstrate the application of our probes in simultaneous recording and optical/chemical modulation of brain activities across distant regions. Similarly, varying electrographic brain activities from different brain regions were detected by our customizable probes in a mouse model of epilepsy, suggesting the potential of using these probes for the investigation of brain disorders such as epilepsy. Ultimately, this technique enables three-dimensional manipulation and mapping of brain activities across distant regions in the deep brain with minimal tissue damage, which can bring new insights for deciphering complex brain functions and dynamics in the near future.

Multi-Frequency Based Direction-of-Arrival Estimation for 2q-Level Nested Radar & Sonar Arrays.

Direction finding is a hot research area in radar and sonar systems. In the case of q ≥ 2, the 2qth-order cumulant based direction of arrival (DOA) estimation algorithm for the 2q-level nested array can achieve high resolution performance. A virtual 2qth-order difference co-array, which contains O(N2q) virtual sensors in the form of a uniform linear array (ULA), is yielded and the Gaussian noise is eliminated. However, some virtual elements are separated by the holes among the 2qth-order difference co-array and cannot be fully used. Even though the application of the multi-frequency method for minimum frequency separation (MFMFS) can fill the holes with low computation complexity, it requires that the number of frequencies must increase with the number of holes. In addition, the signal spectra have to be proportional for all frequencies, which is hard to satisfy when the number of holes is large. Aiming at this, we further propose a multi-frequency method for a minimum number of frequencies (MFMNF) and discuss the best frequency choice under two specific situations. Simulation results verify that, compared with the MFMFS method, the proposed MFMNF method can use only one frequency to fill all the holes while achieving a longer virtual array and the DOA estimation performance is, therefore, improved.

A polarized digital shearing speckle pattern interferometry system based on temporal wavelet transformation.

Digital shearing speckle pattern interferometry (DSSPI) has been recognized as a practical tool in testing strain. The DSSPI system which is based on temporal analysis is attractive because of its ability to measure strain dynamically. In this paper, such a DSSPI system with Wollaston prism has been built. The principles and system arrangement are described and the preliminary experimental result of the displacement-derivative test of an aluminum plate is shown with the wavelet transformation method and the Fourier transformation method. The simulations have been conducted with the finite element method. The comparison of the results shows that quantitative measurement of displacement-derivative has been realized.

Continual mechanical vibration trajectory tracking based on electro-optical heterodyne interferometry.

Vibration is one of the confused problems in many fields. To give a comprehensive analysis of vibration, an electro-optical heterodyne interferometry with temporal intensity analysis method that can track the trajectory of the vibration dynamically has been built in this paper. The carrier frequency is introduced by the electrically controlled electro-optical frequency shifter. The trajectory is obtained by using temporal evolution of the light intensity in heterodyne interferometry. The instantaneous displacement of the vibration is extracted with spectral analysis technique. No target mirror and moving parts are required in our self-developed system. The principle and system configuration are described. The simulations and the preliminary experiments have been performed and the results show that this trajectory tracking system is high-efficiency, low-cost, jamproof, robust, precise and simple.

Adaptive pulse oximeter with dual-wavelength based on wavelet transforms.

Pulse oximeter is widely used in the monitoring of blood oxygen in clinic for its convenience and efficiency. However, synchronizing light source flashing with data collecting is required, otherwise the separation of the data from different LEDs will fail. More importantly, synchronous acquisition makes the pulse oximetry system vulnerable. Meanwhile, the pulse waveform extraction is a crucial procedure in the measurement. Hence, in this paper, an asynchronous acquisition pulse oximetry system based on wavelet transform has been built. PhotoPlethysmoGraph (PPG) and photoelectric detection technology are applied in our homemade system. The adaptive soft-threshold de-noising is realized by Stein's Unbiased Risk Estimate (SURE). The principle and system configuration are described. The preliminary experiment results from wavelet transforms and Fourier transforms are compared. The results show that our homemade system is adaptive, accurate, robust and simple.