GFAP hyperpalmitoylation exacerbates astrogliosis and neurodegenerative pathology in PPT1-deficient mice.

The homeostasis of protein palmitoylation and depalmitoylation is essential for proper physiological functions in various tissues, in particular the central nervous system (CNS). The dysfunction of PPT1 (PPT1-KI, infantile neuronal ceroid lipofuscinosis [INCL] mouse model), which catalyze the depalmitoylation process, results in serious neurodegeneration accompanied by severe astrogliosis in the brain. Endeavoring to determine critical factors that might account for the pathogenesis in CNS by palm-proteomics, glial fibrillary acidic protein (GFAP) was spotted, indicating that GFAP is probably palmitoylated. Questions concerning if GFAP is indeed palmitoylated in vivo and how palmitoylation of GFAP might participate in neural pathology remain unexplored and are waiting to be investigated. Here we show that GFAP is readily palmitoylated in vitro and in vivo; specifically, cysteine-291 is the unique palmitoylated residue in GFAP. Interestingly, it was found that palmitoylated GFAP promotes astrocyte proliferation in vitro. Furthermore, we showed that PPT1 depalmitoylates GFAP, and the level of palmitoylated GFAP is overwhelmingly up-regulated in PPT1-knockin mice, which lead us to speculate that the elevated level of palmitoylated GFAP might accelerate astrocyte proliferation in vivo and ultimately led to astrogliosis in INCL. Indeed, blocking palmitoylation by mutating cysteine-291 into alanine in GFAP attenuate astrogliosis, and remarkably, the concurrent neurodegenerative pathology in PPT1-knockin mice. Together, these findings demonstrate that hyperpalmitoylated GFAP plays critical roles in regulating the pathogenesis of astrogliosis and neurodegeneration in the CNS, and most importantly, pinpointing that cysteine-291 in GFAP might be a valuable pharmaceutical target for treating INCL and other potential neurodegenerative diseases.

Sensitivity-Bandwidth Optimization of PMUT with Acoustical Matching Using Finite Element Method.

A new model in finite element method to study round-trip performance of piezoelectric micromachined ultrasonic transducers (pMUTs) is established. Most studies on the performance of pMUT are based only on the transmission sensibility, but the reception capacity is as much important as the transmission one, and is quite different from this latter. In this work, the round-trip sensitivity of pMUT is defined as the product of the frequency response of transmitted far field pressure to source voltage excitation and that of reception output to return wave pressure. Based on this sensitivity characteristic, firstly, a multi-parameter optimization for a cavity pMUT is performed using the sensitivity-bandwidth product parameter SBW as criterion. The radii of the electrode and the piezoelectric layer, the thicknesses of the piezoelectric layer and the vibration diaphragm are adjusted to maximize the performance. Secondly, an acoustic matching method is proposed and applied to pMUTs for the first time. As a result, the round-trip sensitivity can be evaluated and the pulse-echo response of wide-band excitation can be simulated, giving the most quantitative and intuitive feedback for pMUT design. The optimization enhances the sensitivity-bandwidth product by 52% when the top electrode and piezoelectric layer are both etched to 75% radius of the cavity beneath; the introduction of an acoustic matching layer shows significant bandwidth expansion in both the transmitting and receiving process.

Development of Broadband High-Frequency Piezoelectric Micromachined Ultrasonic Transducer Array.

Piezoelectric micromachined ultrasonic transducers (PMUT) are promising elements to fabricate a two-dimensional (2D) array with a pitch small enough (approximately half wavelength) to form and receive arbitrary acoustic beams for medical imaging. However, PMUT arrays have so far failed to combine the wide, high-frequency bandwidth needed to achieve a high axial resolution. In this paper, a polydimethylsiloxane (PDMS) backing structure is introduced into the PMUTs to improve the device bandwidth while keeping a sub-wavelength (λ) pitch. We implement this backing on a 16 × 8 array with 75 µm pitch (3λ/4) with a 15 MHz working frequency. Adding the backing nearly doubles the bandwidth to 92% (-6 dB) and has little influence on the impulse response sensitivity. By widening the transducer bandwidth, this backing may enable using PMUT ultrasonic arrays for high-resolution 3D imaging.

3D FEM Analysis of High-Frequency AlN-Based PMUT Arrays on Cavity SOI.

This paper presents three-dimensional (3D) models of high-frequency piezoelectric micromachined ultrasonic transducers (PMUTs) based on the finite element method (FEM). These models are verified with fabricated aluminum nitride (AlN)-based PMUT arrays. The 3D numerical model consists of a sandwiched piezoelectric structure, a silicon passive layer, and a silicon substrate with a cavity. Two types of parameters are simulated with periodic boundary conditions: (1) the resonant frequencies and mode shapes of PMUT, and (2) the electrical impedance and acoustic field of PMUT loaded with air and water. The resonant frequencies and mode shapes of an electrically connected PMUT array are obtained with a laser Doppler vibrometer (LDV). The first resonant frequency difference between 3D FEM simulation and the measurement for a 16-MHz PMUT is reasonably within 6%, which is just one-third of that between the analytical method and the measurement. The electrical impedance of the PMUT array measured in air and water is consistent with the simulation results. The 3D model is suitable for predicting electrical and acoustic performance and, thus, optimizing the structure of high-frequency PMUTs. It also has good potential to analyze the transmission and reception performances of a PMUT array for future compact ultrasonic systems.

High-mobility InSnZnO Thin Film Transistors via Introducing Water Vapor Sputtering Gas.

There is always a doubt that introducing water during oxide growing has a positive or negative effect on the properties of oxide films and devices. Herein, a comparison experiment on the condition of keeping the same oxygen atom flux in the sputtering chamber is designed to examine the influences of H2O on In-Sn-Zn-O (ITZO) films and their transistors. In comparison to no-water films, numerous unstable hydrogen-related defects are induced on with-water films at the as-deposited state. Paradoxically, this induction triggers an ordered enhancement in the microstructure of the films during conventional annealing, characterized by a reduction in H-related and vacancy (Vo) defects as well as an increase in film packing density and the M-O network ordering. Ultimately, the no-water thin-film transistors (TFTs) exhibit nonswitching behavior, whereas 5 sccm-water TFT demonstrates excellent electrical performance with a remarkable saturation field-effect mobility (µFE) of 122.10 ± 5.00 cm2·V-1·s-1, a low threshold (Vth) of -2.30 ± 0.40 V, a steep sub-threshold swing (SS) of 0.18 V·dec-1, a high output current (Ion) of 1420 µA, and a small threshold voltage shift ΔVth of -0.77 V in the negative bias stability test (3600 s).

Low-Noise Low-Power Ultrasound AFE With Continuous TGC Built in Both TIA and Beamformer.

This article presents a low-noise high-power-efficiency analog front-end (AFE) for capacitive-micromachined-ultrasonic transducers (CMUT). Implemented in 28-nm CMOS technology, the proposed AFE features three-stage continuous time-gain compensation (TGC) embedded in both trans-impedance amplifiers (TIAs) and an analog beamformer to provide a large compensation range with no extra power-consumption cost. The use of noise cancellation and capacitive feedback optimizes the noise performance of TIAs. The first stage of the TGC is built in the TIA by adjusting the positive and negative resistance loads, which are composed of voltage-controlled transistor arrays. An all-pass passive network is used as the delay unit of the analog beamformer, meanwhile achieving the second TGC stage. Phase shift for all frequency components in the ultrasound pass-band is manifested as a delay to the echoes. The third stage of the TGC is merged with a summing unit, which is a closed-loop amplifier with variable resistance feedback. The design takes into account the ability to handle large signals and power consumption, with TIA and beamforming operating at voltages of 2.5 V and 0.9 V, respectively. Experimental results show that the proposed AFE achieves a 2.11 pA/√Hz input-referred noise (IRN) at the 5 MHz center frequency of the echoes while consuming only 1.02 mW/channel. A total exponential TGC range of 60 dB with continuous ranges of 12 dB, 24 dB, and 24 dB assigned to three stages has been verified for this work.

Low-Temperature-Crystallized Ga2O3 Thin Films and Their TFT-Type Solar-Blind Photodetectors.

Crystalline Ga2O3 (c-Ga2O3) is a promising candidate for next-generation solar-blind photodetectors (SBPDs) but is suffering from high processing temperatures. Herein, seed-induced engineering is proposed via adopting Zn as an induced metal for crystallizing Ga2O3, lowering the processing temperature by 200 °C. After annealing, the Zn/Ga2O3 consists of an inner Ga2O3 layer of a monoclinic crystalline phase, top ZnO crystals coming from Zn oxidation, and a thin corundum Ga2O3 layer between them, which implies a "seed-induced" crystallization mechanism besides the nonequilibrium chaotic state caused by the traditional electron transfer one. As a result, the tailored c-Ga2O3 thin-film transistor-type SBPD with enhanced packing density and finite oxygen deficiency demonstrates a satisfactory responsivity of 8.6 A/W and also an ultrahigh UVC/visible rejection ratio (R254/R450) of 2 × 105. The seed-induced engineering forecasts its potential application in crystalline Ga2O3 SBPDs under a relatively low processing temperature.

A 619-pixel machine vision enhancement chip based on two-dimensional semiconductors.

The rapid development of machine vision applications demands hardware that can sense and process visual information in a single monolithic unit to avoid redundant data transfer. Here, we design and demonstrate a monolithic vision enhancement chip with light-sensing, memory, digital-to-analog conversion, and processing functions by implementing a 619-pixel with 8582 transistors and physical dimensions of 10 mm by 10 mm based on a wafer-scale two-dimensional (2D) monolayer molybdenum disulfide (MoS2). The light-sensing function with analog MoS2 transistor circuits offers low noise and high photosensitivity. Furthermore, we adopt a MoS2 analog processing circuit to dynamically adjust the photocurrent of individual imaging sensor, which yields a high dynamic light-sensing range greater than 90 decibels. The vision chip allows the applications for contrast enhancement and noise reduction of image processing. This large-scale monolithic chip based on 2D semiconductors shows multiple functions with light sensing, memory, and processing for artificial machine vision applications, exhibiting the potentials of 2D semiconductors for future electronics.

An artificial neural network chip based on two-dimensional semiconductor.

Recently, research on two-dimensional (2D) semiconductors has begun to translate from the fundamental investigation into rudimentary functional circuits. In this work, we unveil the first functional MoS2 artificial neural network (ANN) chip, including multiply-and-accumulate (MAC), memory and activation function circuits. Such MoS2 ANN chip is realized through fabricating 818 field-effect transistors (FETs) on a wafer-scale and high-homogeneity MoS2 film, with a gate-last process to realize top gate structured FETs. A 62-level simulation program with integrated circuit emphasis (SPICE) model is utilized to design and optimize our analog ANN circuits. To demonstrate a practical application, a tactile digit sensing recognition was demonstrated based on our ANN circuits. After training, the digit recognition rate exceeds 97%. Our work not only demonstrates the protentional of 2D semiconductors in wafer-scale integrated circuits, but also paves the way for its future application in AI computation.

A two-stage modification method using 1,4-α-glucan branching enzyme lowers the in vitro digestibility of corn starch.

Samples of granular corn starch were treated with 1,4-α-glucan branching enzyme (GBE) for 20 h using three different methods. These GBE modification methods all increased glycosidic linkage ratio, cyclic glucan content, and proportion of short chains while reducing weight mean molecular weight. The in vitro digestion rates of the modified starches were suppressed. Among these methods, a novel two-stage modification method comprising a 10-h GBE treatment, gelatinization, and a second 10-h GBE treatment, produced samples with the lowest in vitro digestibility. The rapidly digestible starch content was 34.2% lower than that of the control and 18.0% lower than that of the product of one-stage modification with the same duration. Fine structure characterization showed that more cluster structures were proved during the two-stage modification. This two-stage method suppressed the digestibility of corn starch and increased the substrate concentration, showing great potential for the industrial processing of slowly-digestible starchy foods.

Identifying the Potential Substrates of the Depalmitoylation Enzyme Acyl-protein Thioesterase 1.

BACKGROUND: The homeostasis of palmitoylation and depalmitoylation is involved in various cellular processes, the disruption of which induces severe physiological consequences. Acyl-protein thioesterase (APT) and palmitoyl-protein thioesterases (PPT) catalyze the depalmitoylation process. The natural mutation in human PPT1 caused neurodegenerative disease, yet the understanding of APT1 remains to be elucidated. While the deletion of APT1 in mice turned out to be potentially embryonically lethal, the decoding of its function strictly relied on the identification of its substrates. OBJECTIVE: To determine the potential substrates of APT1 by using the generated human APT1 knockout cell line. METHODS: The combined techniques of palmitoyl-protein enrichment and massspectrometry were used to analyze the different proteins. Palmitoyl-proteins both in HEK293T and APT1-KO cells were extracted by resin-assisted capture (RAC) and data independent acquisition (DIA) quantitative method of proteomics for data collection. RESULTS: In total, 382 proteins were identified. The gene ontology classification segregated these proteins into diverse biological pathways e.g. endoplasmic reticulum process and ubiquitin-mediated proteolysis. A few potential substrates were selected for verification; indeed, major proteins were palmitoylated. Importantly, their levels of palmitoylation were clearly changed in APT1-KO cells. Interestingly, the proliferation of APT1-KO cells escalated dramatically as compared to that of the WT cells, which could be rescued by APT1 overexpression. CONCLUSION: Our study provides a large scale of potential substrates of APT1, thus facilitating the understanding of its intervened molecular functions.

Modification by α-d-glucan branching enzyme lowers the in vitro digestibility of starch from different sources.

Granular corn starch, waxy corn starch, potato starch and tapioca starch were modified using the α-d-glucan branching enzyme (1,4-α-d-glucan:1,4-α-d-glucan 6-α-d-(1,4-α-d-glucano)-transferase, GBE, EC 2.4.1.18) from Geobacillus thermoglucosidans. The GBE-catalyzed modification caused a time-dependent increase in the ratios of α-1,6 linkages to total glycosidic linkages, as well as reductions in the average chain length and relative crystallinity. These modifications lowered the in vitro digestibility of the starch. Modification with GBE caused varying degrees of change in the in vitro digestibility of starches obtained from different sources. The highest slowly digestible starch (SDS) and resistant starch (RS) contents were found in modified tapioca starch. After modification of tapioca starch with GBE for 10h, the ratio of α-1,6 linkages to total glycosidic linkages was increased by 11.5%, while its relative crystallinity was decreased by 22.9%. Meanwhile, the SDS and RS contents of tapioca starch were increased by 47.3% and 13.5%, respectively. These results demonstrate that the digestibility of starch can be lowered through GBE modification, which may aid the development of modified starches that are digested more slowly.

Pasting and thermal properties of waxy corn starch modified by 1,4-α-glucan branching enzyme.

Waxy corn starch was modified with the 1,4-α-glucan branching enzyme (GBE) from Geobacillus thermoglucosidans STB02. Incubating waxy corn starch with GBE increased the number of α-1,6 branch points and reduced the average chain length. Enzymatic modification also decreased the breakdown and setback values of Brabender viscosity curves, indicating that the modified starch had higher paste stability. Preheating the starch at 65°C for 30min before incubation with GBE could promote enzymatic modification of starch. Linear regression was used to describe the relationships between starch structure and its pasting and thermal properties. The setback value showed a negative linear correlation with the α-1,6 branch point content (R2=0.9824) and a positive linear correlation with the average chain length (R2=0.8954). Meanwhile, the gelatinization enthalpy was also linearly correlated to the α-1,6 branch point content (R2=0.9326) and the average chain length (R2=0.8567). These insights provide a useful reference for food processors.

Maltooligosaccharide-forming amylase: Characteristics, preparation, and application.

As member of glycosyl hydrolase family 13, maltooligosaccharide-forming amylases (MFAses) are specific and interesting because of their capacity to hydrolyze starch into functional maltooligosaccharides, which are usually composed of 2-10 α-d-glucopyranosyl units linked by α-1,4 glycosidic linkages. MFAses have been extensively studied during recent decades, and have shown promise in various industrial applications. This review begins by introducing the potential uses of maltooligosaccharides. Then it describes the progress in the identification, assay, action pattern, structure, and modification of MFAses. The review continues with tips concerning the preparation of MFAses, which aim to improve MFAse production to meet the needs of industry. Finally, the industrial uses of MFAses are described, focusing on the production of maltooligosaccharides and application in the bread industry. Recent progress has demonstrated that the MFAses are poised to become important industrial catalysts.