Modeling for High-Frequency Spurious Responses in Incredible High-Performance Surface Acoustic Wave Devices.

To ensure that surface acoustic wave (SAW) filters fulfill the requirements of Carrier Aggregation (CA) applications, the development of modeling tools that can forecast and simulate high-frequency spurious responses has been necessary. This paper presents an advanced methodology for extending the coupling-of-modes (COM) model to obtain precise modeling of the high-frequency spurious responses of incredible high-performance surface acoustic wave (I.H.P. SAW) devices. The extended COM (ECOM) model is derived by modifying the conventional COM model and extending it accordingly. The parameters used in this model are determined through numerical fitting. For validation, firstly, the ECOM model is applied to a one-port synchronous I.H.P. SAW resonator, and the simulation and measurement results match. Then, the structural parameters of the ECOM model are varied, and the accuracy of the model after the structural parameters are varied is verified. It is demonstrated that this model can be applied to the design work of SAW filters. Finally, the ECOM model is applied to the design of the I.H.P. SAW filter based on a 42°YX-LiTaO3 (LT)/SiO2/AlN/Si structure. By using this method, the I.H.P. SAW filter's high-frequency spurious response can be predicted more accurately.

An Infrared Near-Sensor Reservoir Computing System Based on Large-Dynamic-Space Memristor with Tens of Thousands of States for Dynamic Gesture Perception.

To efficiently process the massive amount of sensor data, it is demanding to develop a new paradigm. Inspired by neurobiological systems, an infrared near-senor reservoir computing (RC) system, consisting of infrared sensors and memristors based on single-crystalline LiTaO3 and LiNbO3 (LN) thin film respectively, is demonstrated. The analog memristor is used as a reservoir in the RC system to process sensor signals with spatiotemporal characteristics. LN crystal structure stacked with oxygen octahedra provides favorable conditions for reliable Mott variable-range hopping conduction, which provides the memristor with tens of thousands of reservoir states within a large dynamic range. With the characteristics, the analog sensor signals with high data fidelity can be directly fed to the memristive reservoir, and the spatiotemporal features can be separated and mapped. The system demonstrated a dynamic gesture perception task, achieving an accuracy of 99.6%, which highlights the great application potential of the memristor in signal sensor processing and will advance the application of artificial intelligence in sensor systems. Crystal ion slicing techniques are used to fabricate a single-crystalline thin film for both the memristor and sensor, which opens up the possibility of realizing monolithic integration of a memristor-based near-sensor computing system.

Designed Structures of Interdigital Electrodes for Thin Film SAW Devices.

This paper studied the impact of the microstructure of interdigital electrodes on the performance of surface acoustic wave (SAW) resonators and proposed an innovative piston, dummy finger and tilt (PDT) structure, which was then applied to the GLONASS L3 band filters. Through the adoption of 3D finite element simulation (FEM), photolithography, and testing on an incredible high-performance surface acoustic wave (I.H.P. SAW) substrate, it is concluded that the total aperture length is 20T (T is period), resulting in a more optimal resonator performance; changing the width and length of the piston can suppress transverse modes spurious, but it does not enhance impedance ratio; to further improve the quality of the SAW resonator, the proposed PDT structure has been experimentally proven to not only effectively suppress transverse modes spurious but also possess a high impedance ratio. By utilizing a PDT structure within a "T + π" topology circuit, we successfully designed and manufactured a GLONASS L3 band filter with a bandwidth of 8 MHz and an insertion loss of 3.73 dB. The design of these resonators and filters can be applied to the construction of SAW filters in similar frequency bands such as BeiDou B2 band or GPS L2/L5 band.

Controllable modulation of the oxygen vacancy-induced adjustment of memristive behavior for direct differential operation with transistor-free memristor.

To achieve the goal of neuromorphic computing hardware implementation with extremely high efficiency, low power consumption, and high density, it is necessary to develop transistor-free memristors and implement differential operation without subtraction circuits. In this study, argon ion irradiation was used during the fabrication process of a single crystalline LiNbO3 (LN) thin film to controllably introduce oxygen vacancies (OVs) into the bottom surface, which realized the modulation of OVs based on the excellent environment provided by a single-crystalline thin film. The memristive behavior of memristors was then modulated by regulating the distribution of OVs, and the effect of OVs distributed near the bottom surface of the single crystalline LN thin film on the memristive behavior was analyzed. In this way, two transistor-free memristors with opposite memristive behavior directions were fabricated. Two transistor-free memristors exhibit excellent synaptic plasticity and reliable multilevel resistance states. Based on two transistor-free memristors, a novel differential pair was constructed. Hardware implementations of direct differential operation without subtraction circuits were achieved. This study provides a new pathway to develop a transistor-free memristor and achieve differential operation without subtraction circuits in neuromorphic computing, which will simplify the peripheral circuits, improve integration density, and reduce power consumption and latency.

Personalized demand-responsive biphasic microneedle patch for smart drug administration.

Many patients, especially those with chronic diseases, would benefit from personalized drugs that could modulate the treatment regimen. Tailored drug delivery via microneedle patches (MNPs) has emerged as a promising technology to address this problem. However, it is still difficult to modulate the treatment regimen in one MNP. Here, multiple treatment regimens were achieved by the same MNP functionalized with modifiable nanocontainers (NCs). The MNPs were biphasic in design, resulting in approximately a twice as high drug loading capacity than that of traditional dissolving MNPs. The drug-loaded NCs could have a zero-order release rate for at least 20 d in vitro. Furthermore, three model MNPs, Type-A (100% drug), Type-B (50% drug and 50% NCs) and Type-C (100% NCs) were generated to simulate various personalized dosing needs. In vivo application of these models could achieve effective therapeutic drug concentrations in the first 12 h and adjusted the duration of effective drug action from 24 h to 96 h and 144 h, respectively, with outstanding biocompatibility. These findings indicate that this device holds significant promise for personalized drug delivery.

BAW Resonator with an Optimized SiO2/Ta2O5 Reflector for 5G Applications.

In the present work, a lithium niobate (LN) 43°Y cut LN film is transferred onto a substrate with 11 layers of SiO2/Ta2O5 and solidly mounted resonators with a reflector are successfully fabricated with the multilayer structure. The design method and fabrication process are demonstrated. The finite element model and the Mason model are used. Scanning electron microscopy and atomic force microscopy are used to characterize film quality. An optimized design of a Bragg reflector to suppress the leakage of acoustic energy by thickness shear mode is proven to be effective. The influence of the reflector on parasitic modes and filter out-of-band suppression is analyzed. The resonator for 3.5 GHz shows an effective electromechanical coupling coefficient of 17.9%, and the figure of merit is 40.4, which is suitable for band pass filter on the N78 band with high rejection.

Wide Band BAW Filter Based on Single-Crystalline LiNbO3 Thin Film With Insulating Bragg Reflector.

Bulk acoustic wave (BAW) filter with large bandwidth is an urgent need in fifth-generation (5G) communication systems. In the present work, 43° Y-cut lithium niobate (LN) single-crystal film is prepared on multilayer oxide film, and bulk acoustic filter with oxide Bragg reflector (BR) is successfully achieved. The design method of the filter and the fabrication process are presented. Atomic force microscope (AFM) and scanning electron microscope (SEM) are used to characterize the quality of thin films. The results demonstrate the feasibility of transferring single-crystal film onto multilayer oxide, which is efficient for the confinement of acoustic energy. The resonator has effective electromechanical coupling coefficient of 14.6% and figure of merit (FOM) of 32.94. The filter with a compact size of 600 [Formula: see text] has a relative bandwidth of 10.3% at a center frequency of 3.128 GHz, which is promising for the application of 5G systems.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

A Solidly Mounted Resonator Fabricated by LiNbO3 Single-Crystalline Film on Flexible Polyimide Substrate.

A solidly mounted resonator on flexible polyimide (PI) substrate with high-effective coupling coefficient ( Kt2 ) of 14.06% is reported in this article. This high Kt2 is resulting from the LiNbO3 (LN) single-crystalline film and [SiO2/Mo]3 Bragg reflector. The quality of LN film fabricated by the crystal-ion-slicing (CIS) technique using benzocyclobutene (BCB) bonding layer was close to the bulk crystalline LN. The interfaces of the Al/LN/Al/[SiO2/Mo]3 Bragg reflector/BCB/PI multilayer are sharp, and the thickness of each layer is consistent with its design value. The resonant frequency and Kt2 keep stable when it is bent at different radii. These results demonstrate a feasible approach to realizing RF filters on flexible polymer substrates, which is an indispensable device for building integrated and multifunctional wireless flexible electronic systems.

Novel Method for the Quantitative Analysis of Protease Activity: The Casein Plate Method and Its Applications.

No simple methods are used for the quantitative analysis of the protease activity in colored food up till now. Thus, this study aims to establish a new and simple method for the quantitative detection of protease activity, especially in colored food. The detection accuracy, detection limit, and repeatability of the casein plate method were analyzed. Then, the application of the casein plate method in sample detection and recovery was further evaluated. The results showed that the casein plate method for the quantitative detection of protease activity has high accuracy, high precision, and low detection limit. The recoveries of eight kinds of colored samples were in the range of 92.26-97.84%, and the relative standard deviation (RSD) was in the range of 3.56-10.88%. The results of the casein plate method exhibited high accuracy. This indicated that the method was suitable for the detection of colored samples. The casein plate method for the quantitative detection of protease activity is simple. The newly constructed casein plate method has broad potential application value in food industry, especially for the detection of dark food.

Record-Low Subthreshold-Swing Negative-Capacitance 2D Field-Effect Transistors.

Power consumption is one of the most challenging bottlenecks for complementary metal-oxide-semiconductor integration. Negative-capacitance field-effect transistors (NC-FETs) offer a promising platform to break the thermionic limit defined by the Boltzmann tyranny and architect energy-efficient devices. However, it is a great challenge to achieving ultralow-subthreshold-swing (SS) (10 mV dec-1 ) and small-hysteresis NC-FETs simultaneously at room temperature, which has only been reported using the hafnium zirconium oxide system. Here, based on a ferroelectric LiNbO3 thin film with great spontaneous polarization, an ultralow-SS NC-FET with small hysteresis is designed. The LiNbO3 NC-FET platform exhibits a record-low SS of 4.97 mV dec-1 with great repeatability due to the superior capacitance matching characteristic as evidenced by the negative differential resistance phenomenon. By modulating the structure and operating parameters (such as channel length (Lch ), drain-sourse bias (Vds ), and gate bias (Vg )) of devices, an optimized SS from ≈40 to ≈10 mV dec-1 and hysteresis from ≈900 to ≈60 mV are achieved simultaneously. The results provide a new potential method for future highly integrated electronic and optical integrated energy-efficient devices.

Macromolecules and Antibody-Based Drugs.

Macromolecule drugs particularly antibody drugs are very powerful therapies developing rapidly in the recent 20 years, providing hopes for many patients diagnosed with "incurable" diseases in the past. They also provide more effective and less side effects for many afflicting diseases, and greatly improve the survival rate and life quality of patients. In the last two decades, the proportion of US Food and Drug Administration (FDA) approved macromolecules and antibody drugs are increasing quickly, especially after the discovery of immune checkpoints. To crown all, the 2017 Nobel prize in physiology or medicine was given to immunotherapy. In this chapter, we would like to summarize the current situation of macromolecule and antibody drugs, and what effort scientists and pharmaceutical industry have made to discover and manufacture better antibody drugs.

Engineering of self-rectifying filamentary resistive switching in LiNbO3 single crystalline thin film via strain doping.

The abilities to fabricate wafer scale single crystalline oxide thin films on metallic substrates and to locally engineer their resistive switching characteristics not only contribute to the fundamental investigations of the resistive switching mechanism but also promote the practical applications of resistive switching devices. Here, wafer scale LiNbO3 (LNO) single crystalline thin films are fabricated on Pt/SiO2/LNO substrates by ion slicing with wafer bonding. The lattice strain of the LNO single crystalline thin films can be tuned by He implantation as indicated by XRD measurements. After He implantation, the LNO single crystalline thin films show self-rectifying filamentary resistive switching behaviors, which is interpreted by a model that the local conductive filaments only connect/disconnect with the bottom interface while the top interface maintains the Schottky contact. Thanks to the homogeneous distribution of defects in single crystalline thin films, highly reproducible and uniform self-rectifying resistive switching with large on/off ratio over four order of magnitude was achieved. Multilevel resistive switching can be obtained by varying the compliance current or by using different magnitude of writing voltage.

Lighting Up Live Cells with Smart Genetically Encoded Fluorescence Probes from GMars Family.

As a special kind of delicate light-controllable genetically encoded optical device, reversibly photoswitchable fluorescent proteins (RSFPs) have been widely applied in many fields, especially various kinds of advanced nanoscopy approaches in recent years. However, there are still necessities for exploring novel RSFPs with specific biochemical or photophysical properties not only for bioimaging or biosensing applications but also for fluorescent protein (FP) mechanisms study and further knowledge-based molecular sensors or optical actuators' rational design and evolution. Besides previously reported GMars-Q and GMars-T variants, herein, we reported the development and applications of other RSFPs from GMars family, especially some featured RSFPs with desired optical properties. In the current work, in vitro FP purification, spectra measurements, and live-cell RESOLFT nanoscopy approaches were applied to characterize the basic properties and test the imaging performances of the selected RSFPs. As demonstrated, GMars variants such as GMars-A, GMars-G, or remarkable photofatigue-resistant GMars-L were found with beneficial properties to be capable of parallelized RESOLFT nanoscopy in living cells, while other featured GMars variants such as dark GMars-P may be a good candidate for further biosensor or actuator design and applications.

Investigation of the Temperature Fluctuation of Single-Phase Fluid Based Microchannel Heat Sink.

The temperature fluctuation in a single-phase microchannel heat sink (MCHS) is investigated using the integrated temperature sensors with deionized water as the coolant. Results show that the temperature fluctuation in single phase is not negligible. The causes of the temperature fluctuation are revealed based on both simulation and experiment. It is found that the inlet temperature fluctuation and the gas bubbles separated out from coolant are the main causes. The effect of the inlet temperature fluctuation is global, where the temperatures at different locations change simultaneously. Meanwhile, the gas bubble effect is localized where the temperature changes at different locations are not synchronized. In addition, the relation between temperature fluctuation and temperature gradient is established. The temperature fluctuation increases with the temperature gradient accordingly.

A Comprehensive Study of a Micro-Channel Heat Sink Using Integrated Thin-Film Temperature Sensors.

A micro-channel heat sink is a promising cooling method for high power integrated circuits (IC). However, the understanding of such a micro-channel device is not sufficient, because the tools for studying it are very limited. The details inside the micro-channels are not readily available. In this letter, a micro-channel heat sink is comprehensively studied using the integrated temperature sensors. The highly sensitive thin film temperature sensors can accurately monitor the temperature change in the micro-channel in real time. The outstanding heat dissipation performance of the micro-channel heat sink is proven in terms of maximum temperature, cooling speed and heat resistance. The temperature profile along the micro-channel is extracted, and even small temperature perturbations can be detected. The heat source formed temperature peak shifts towards the flow direction with the increasing flow rate. However, the temperature non-uniformity is independent of flow rate, but solely dependent on the heating power. Specific designs for minimizing the temperature non-uniformity are necessary. In addition, the experimental results from the integrated temperature sensors match the simulation results well. This can be used to directly verify the modeling results, helping to build a convincing simulation model. The integrated sensor could be a powerful tool for studying the micro-channel based heat sink.

Comparative medical characteristics of ZDF-T2DM rats during the course of development to late stage disease.

BACKGROUND: There are few reports on the comparative medical characteristics of type 2 diabetes models in late stage. An analysis of comparative medical characteristics of Zucker diabetic fatty type 2 diabetes mellitus (ZDF-T2DM) rats during the course of development to late stage disease was performed. METHODS: In this study, ZDF rats were fed with high-sugar and high-fat diets to raise the fasting blood glucose, and develop of type 2 diabetes. At the late stage of T2DM, the preliminary comparative medical characteristics of the T2DM model were analyzed through the detection of clinical indicators, histopathology, related cytokine levels, and insulin-related signaling molecule expression levels. RESULTS: In the T2DM group, the fasting blood glucose was higher than 6.8 mmol/L, the serum insulin, leptin, and adiponectin levels were significantly decreased, and glucose intolerance and insulin resistance were measured as clinical indicators. Regarding pathological indicators, a large number of pancreatic islet cells showed the reduction of insulin secretion, resulting in damaged glycogen synthesis and liver steatosis. At the molecular level, the insulin signal transduction pathway was inhibited by decreasing the insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), phosphatidylinositol 3 kinase (PI3K), and glycogen synthesis kinase 3ß (GSK-3ß) expression levels. CONCLUSION: The results show that the ZDF/T2DM rats have typical clinical, histopathological, and molecular characteristics of human T2DM and thus can be used as an effective model for T2DM drug development and treatment of advanced T2DM.

T7 RNA polymerase translocation is facilitated by a helix opening on the fingers domain that may also prevent backtracking.

Here, we studied the complete process of a viral T7 RNA polymerase (RNAP) translocation on DNA during transcription elongation by implementing extensive all-atom molecular dynamics (MD) simulations to construct a Markov state model (MSM). Our studies show that translocation proceeds in a Brownian motion, and the RNAP thermally transits among multiple metastable states. We observed non-synchronized backbone movements of the nucleic acid (NA) chains with the RNA translocation accomplished first, while the template DNA lagged. Notably, both the O-helix and Y-helix on the fingers domain play key roles in facilitating NA translocation through the helix opening. The helix opening allows a key residue Tyr639 to become inserted into the active site, which pushes the RNA-DNA hybrid forward. Another key residue, Phe644, coordinates the downstream template DNA motions by stacking and un-stacking with a transition nucleotide (TN) and its adjacent nucleotide. Moreover, the O-helix opening at pre-translocation (pre-trans) likely resists backtracking. To test this hypothesis, we computationally designed mutants of T7 RNAP by replacing the amino acids on the O-helix with counterpart residues from a mitochondrial RNAP that is capable of backtracking. The current experimental results support the hypothesis.

Plasma-Induced Nonvolatile Resistive Switching with Extremely Low SET Voltage in TiOxFy with AgF Nanoparticles.

Low power consumption is crucial for the application of resistive random access memory. In this work, we present the bipolar resistive switching in an Ag/TiOxFy/Ti/Pt stack with extremely low switch-on voltage of 0.07 V. Operating current as low as 10 nA was also obtained by conductive atomic force microscopy. The highly defective TiOxFy layer was fabricated by plasma treatment using helium, oxygen, and carbon tetrafluoride orderly. During the electroforming process, AgF nanoparticles were formed due to the diffusion of Ag+ which reacted with the adsorbed F- in the TiOxFy layer. These nanoparticles are of great importance to resistive switching performance because they are believed to be conductive phases and become part of the conducting path when the sample is switched to a low-resistance state.