Anti-Inflammatory Effect for Atherosclerosis Progression by Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitor in a Normoglycemic Rabbit Model.

BACKGROUND AND OBJECTIVES: We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model. METHODS: Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment. RESULTS: Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase⁺ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1⁺ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4/nuclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment. CONCLUSIONS: These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.

Synergistic protective effects of a statin and an angiotensin receptor blocker for initiation and progression of atherosclerosis.

AIM: Although the atheroprotective effects of statins and angiotensin II receptor blockers (ARBs) are well-established, little is known about their additive effects, especially during the early period of atherosclerosis. The aim of this study was to investigate whether combination of a statin and an ARB exerts synergistic anti-atherosclerotic effects, and to elucidate the mechanisms of combined effects. METHODS: Atherosclerotic plaques were developed in arteries of 23 rabbits using a high-cholesterol diet (HCD) and intra-arterial balloon inflation. Rabbits received one of five different treatment strategies for 4 weeks: positive control [n = 5, HCD]; negative control [n = 3, regular chow diet]; statin [n = 5, HCD and rosuvastatin 10 mg]; ARB [n = 5, HCD and olmesartan 20 mg]; and combination [n = 5, HCD and statin+ARB]. RESULTS: Histological analysis demonstrated that development of atherosclerotic plaques was inhibited more in combination group than in statin group (P = 0.001). Although macrophage infiltration identified by RAM11 staining was not significantly different between combination and individual treatment groups (31.76±4.84% [combination] vs. 38.11±6.53% [statin; P = 0.35] or 35.14±2.87% [ARB; P = 0.62]), the relative proportion of pro-inflammatory M1-macrophages was significantly lower in combination group than in ARB group (3.20±0.47% vs. 5.20±0.78%, P = 0.02). Furthermore, M2-macrophage polarization was higher in combination group than in statin group (17.70±3.04% vs. 7.86±0.68%, P = 0.001). CONCLUSION: Combination treatment with a statin and an ARB produced synergistic protective effects for atherosclerosis initiation and progression, which may be attributed to modulation of macrophage characteristics in the early period of atherosclerosis.

Author Correction: A frequency reconfigurable dipole antenna with solid-state plasma in silicon.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

A frequency reconfigurable dipole antenna with solid-state plasma in silicon.

A frequency reconfigurable dipole antenna based on a silicon radiator is presented. The silicon radiator is activated with the aid of highly dense solid-state plasma by injecting carriers into the intrinsic region of p-i-n diodes. The fabrication and design guideline of the reconfigurable dipole antenna with this plasma radiator are described. When the plasma radiator is activated or deactivated, the length of the dipole arm changes, which means that the operating frequency of the dipole antenna is reconfigurable. When all the channels in the plasma radiator are activated, the operating frequency is tuned from 6.3 GHz to 4.9 GHz. The measured tunable bandwidth of our fabricated dipole antenna is approximately 31%, which is a practical value in comparison to conventional frequency reconfigurable antennas whose tunable bandwidth is in a range from 20% to 50%. To further support the validity of our results, we provide the well-matched simulation results from an antenna simulation. These results demonstrate that silicon with its commercial technology, which has not attracted attention in comparison to a metal antennas, is a promising tunable material for a frequency reconfigurable antenna. This plasma-based reconfigurable antenna has great potential for use in the dynamic communication environment.

Low-Temperature Fabrication of Robust, Transparent, and Flexible Thin-Film Transistors with a Nanolaminated Insulator.

The lack of reliable, transparent, and flexible electrodes and insulators for applications in thin-film transistors (TFTs) makes it difficult to commercialize transparent, flexible TFTs (TF-TFTs). More specifically, conventional high process temperatures and the brittleness of these elements have been hurdles in developing flexible substrates vulnerable to heat. Here, we propose electrode and insulator fabrication techniques considering process temperature, transmittance, flexibility, and environmental stability. A transparent and flexible indium tin oxide (ITO)/Ag/ITO (IAI) electrode and an Al2O3/MgO (AM)-laminated insulator were optimized at the low temperature of 70 °C for the fabrication of TF-TFTs on a polyethylene terephthalate (PET) substrate. The optimized IAI electrode with a sheet resistance of 7 Ω/sq exhibited the luminous transmittance of 85.17% and maintained its electrical conductivity after exposure to damp heat conditions because of an environmentally stable ITO capping layer. In addition, the electrical conductivity of IAI was maintained after 10 000 bending cycles with a tensile strain of 3% because of the ductile Ag film. In the metal/insulator/metal structure, the insulating and mechanical properties of the optimized AM-laminated film deposited at 70 °C were significantly improved because of the highly dense nanolaminate system, compared to those of the Al2O3 film deposited at 70 °C. In addition, the amorphous indium-gallium-zinc oxide (a-IGZO) was used as the active channel for TF-TFTs because of its excellent chemical stability. In the environmental stability test, the ITO, a-IGZO, and AM-laminated films showed the excellent environmental stability. Therefore, our IGZO-based TFT with IAI electrodes and the 70 °C AM-laminated insulator was fabricated to evaluate robustness, transparency, flexibility, and process temperature, resulting in transfer characteristics comparable to those of an IGZO-based TFT with a 150 °C Al2O3 insulator.

Metallic Ti3C2Tx MXene Gas Sensors with Ultrahigh Signal-to-Noise Ratio.

Achieving high sensitivity in solid-state gas sensors can allow the precise detection of chemical agents. In particular, detection of volatile organic compounds (VOCs) at the parts per billion (ppb) level is critical for the early diagnosis of diseases. To obtain high sensitivity, two requirements need to be simultaneously satisfied: (i) low electrical noise and (ii) strong signal, which existing sensor materials cannot meet. Here, we demonstrate that 2D metal carbide MXenes, which possess high metallic conductivity for low noise and a fully functionalized surface for a strong signal, greatly outperform the sensitivity of conventional semiconductor channel materials. Ti3C2Tx MXene gas sensors exhibited a very low limit of detection of 50-100 ppb for VOC gases at room temperature. Also, the extremely low noise led to a signal-to-noise ratio 2 orders of magnitude higher than that of other 2D materials, surpassing the best sensors known. Our results provide insight in utilizing highly functionalized metallic sensing channels for developing highly sensitive sensors.

Nano-electromechanical Switch Based on a Physical Unclonable Function for Highly Robust and Stable Performance in Harsh Environments.

A physical unclonable function (PUF) device using a nano-electromechanical (NEM) switch was demonstrated. The most important feature of the NEM-switch-based PUF is its use of stiction. Stiction is one of the chronic problems associated with micro- and nano-electromechanical system (MEMS/NEMS) devices; however, here, it was utilized to intentionally implement a PUF for hardware-based security. The stiction is caused by capillary and van der Waals forces, producing strong adhesion, which can be utilized to design a highly robust and stable PUF. The probability that stiction will occur on either of two gates in the NEM switch is the same, and consequently, the occurrence of the stiction is random and unique, which is critical to its PUF performance. This uniqueness was evaluated by measuring the interchip Hamming distance (interchip HD), which characterizes how different responses are made when the same challenge is applied. Uniformity was also evaluated by the proportion of "1" or "0" in the response bit-string. The reliability of the proposed PUF device was assessed by stress tests under harsh environments such as high temperature, high dose radiation, and microwaves.

Reconfigurable Yagi-Uda antenna based on a silicon reflector with a solid-state plasma.

This paper describes the fabrication and characterization of a reconfigurable Yagi-Uda antenna based on a silicon reflector with a solid-state plasma. The silicon reflector, composed of serially connected p-i-n diodes, forms a highly dense solid-state plasma by injecting electrons and holes into the intrinsic region. When this plasma silicon reflector is turned on, the front-realized gain of the antenna increases by more than 2 dBi beyond 5.3 GHz. To achieve the large gain increment, the structure of the antenna is carefully designed with the aid of semiconductor device simulation and antenna simulation. By using an aluminum nitride (AlN) substrate with high thermal conductivity, self-heating effects from the high forward current in the p-i-n diode are efficiently suppressed. By comparing the antenna simulation data and the measurement data, we estimated the conductivity of the plasma silicon reflector in the on-state to be between 104 and 105 S/m. With these figures, silicon material with its technology is an attractive tunable material for a reconfigurable antenna, which has attracted substantial interest from many areas, such as internet of things (IoT) applications, wireless network security, cognitive radio, and mobile and satellite communications as well as from multiple-input-multiple-output (MIMO) systems.

Highly stable 2D material (2DM) field-effect transistors (FETs) with wafer-scale multidyad encapsulation.

Field-effect transistors (FETs) composed of 2D materials (2DMs) such as transition-metal dichalcogenide (TMD) materials show unstable electrical characteristics in ambient air due to the high sensitivity of 2DMs to water adsorbates. In this work, in order to demonstrate the long-term retention of electrical characteristics of a TMD FET, a multidyad encapsulation method was applied to a MoS2 FET and thereby its durability was warranted for one month. It was well known that the multidyad encapsulation method was effective to mitigate high sensitivity to ambient air in light-emitting diodes (LEDs) composed of organic materials. However, there was no attempt to check the feasibility of such a multidyad encapsulation method for 2DM FETs. It is timely to investigate the water vapor transmission ratio (WVTR) required for long-term stability of 2DM FETs. The 2DM FETs were fabricated with MoS2 flakes by both an exfoliation method, that is desirable to attain high quality film, and a chemical vapor deposition (CVD) method, that is applicable to fabrication for a large-sized substrate. In order to eliminate other unwanted variables, the MoS2 FETs composed of exfoliated flakes were primarily investigated to assure the effectiveness of the encapsulation method. The encapsulation method uses multiple dyads comprised of a polymer layer by spin coating and an Al2O3 layer deposited by atomic layer deposition (ALD). The proposed method shows wafer-scale uniformity, high transparency, and protective barrier properties against adsorbates (WVTR of 8 × 10-6 g m-2 day-1) over one month.

Physically Transient Memory on a Rapidly Dissoluble Paper for Security Application.

We report the transient memory device by means of a water soluble SSG (solid sodium with glycerine) paper. This material has a hydroscopic property hence it can be soluble in water. In terms of physical security of memory devices, prompt abrogation of a memory device which stored a large number of data is crucial when it is stolen because all of things have identified information in the memory device. By utilizing the SSG paper as a substrate, we fabricated a disposable resistive random access memory (RRAM) which has good data retention of longer than 106 seconds and cycling endurance of 300 cycles. This memory device is dissolved within 10 seconds thus it can never be recovered or replicated. By employing direct printing but not lithography technology to aim low cost and disposable applications, the memory capacity tends to be limited less than kilo-bits. However, unlike high memory capacity demand for consumer electronics, the proposed device is targeting for security applications. With this regards, the sub-kilobit memory capacity should find the applications such as one-time usable personal identification, authentication code storage, cryptography key, and smart delivery tag. This aspect is attractive for security and protection system against unauthorized accessibility.

Electrothermal Annealing (ETA) Method to Enhance the Electrical Performance of Amorphous-Oxide-Semiconductor (AOS) Thin-Film Transistors (TFTs).

An electro-thermal annealing (ETA) method, which uses an electrical pulse of less than 100 ns, was developed to improve the electrical performance of array-level amorphous-oxide-semiconductor (AOS) thin-film transistors (TFTs). The practicality of the ETA method was experimentally demonstrated with transparent amorphous In-Ga-Zn-O (a-IGZO) TFTs. The overall electrical performance metrics were boosted by the proposed method: up to 205% for the trans-conductance (gm), 158% for the linear current (Ilinear), and 206% for the subthreshold swing (SS). The performance enhancement were interpreted by X-ray photoelectron microscopy (XPS), showing a reduction of oxygen vacancies in a-IGZO after the ETA. Furthermore, by virtue of the extremely short operation time (80 ns) of ETA, which neither provokes a delay of the mandatory TFTs operation such as addressing operation for the display refresh nor demands extra physical treatment, the semipermanent use of displays can be realized.

Controllable electrical and physical breakdown of poly-crystalline silicon nanowires by thermally assisted electromigration.

The importance of poly-crystalline silicon (poly-Si) in semiconductor manufacturing is rapidly increasing due to its highly controllable conductivity and excellent, uniform deposition quality. With the continuing miniaturization of electronic components, low dimensional structures such as 1-dimensional nanowires (NWs) have attracted a great deal of attention. But such components have a much higher current density than 2- or 3-dimensional films, and high current can degrade device lifetime and lead to breakdown problems. Here, we report on the electrical and thermal characteristics of poly-Si NWs, which can also be used to control electrical and physical breakdown under high current density. This work reports a controllable catastrophic change of poly-Si NWs by thermally-assisted electromigration and underlying mechanisms. It also reports the direct and real time observation of these catastrophic changes of poly-Si nanowires for the first time, using scanning electron microscopy.

Spontaneous Low-Frequency Cerebral Hemodynamics Oscillations in Restless Legs Syndrome with Periodic Limb Movements During Sleep: A Near-Infrared Spectroscopy Study.

BACKGROUND AND PURPOSE: Periodic limb movements (PLM) during sleep (PLMS) are associated with cortical and cardiovascular activation. Changes in cerebral hemodynamics caused by cortical activity can be measured using near-infrared spectroscopy (NIRS). We investigated oscillatory components of cerebral hemodynamics during PLM and different sleep stages in restless legs syndrome (RLS) patients with PLMS. METHODS: Four female RLS patients with PLMS, and four age- and sex-matched normal controls were included. PLM and sleep stages were scored using polysomnography, while the spontaneous cerebral hemodynamics was measured by NIRS. The phase and amplitude of the cerebral oxyhemoglobin concentration [HbO] and the deoxyhemoglobin concentration [Hb] low-frequency oscillations (LFOs) were evaluated during each sleep stage [waking, light sleep (LS; stages N1 and N2), slow-wave sleep (stage N3), and rapid eye movement (REM) sleep]. In RLS patients with PLMS, the cerebral hemodynamics during LS was divided into LS with and without PLM. RESULTS: The cerebral hemodynamics activity varied among the different sleep stages. There were changes in phase differences between [HbO] and [Hb] LFOs during the different sleep stages in the normal controls but not in the RLS patients with PLMS. The [HbO] and [Hb] LFO amplitudes were higher in the patient group than in controls during both LS with PLM and REM sleep. CONCLUSIONS: The present study has demonstrated the presence of cerebral hemodynamics disturbances in RLS patients with PLMS, which may contribute to an increased risk of cerebrovascular events.

Intraoperative combined color and fluorescent images-based sentinel node mapping in the porcine lung: comparison of indocyanine green with or without albumin premixing.

OBJECTIVES: We developed a multimodal optical imaging system for intraoperative visualization of sentinel lymph nodes (SLNs). This study is to validate our system by showing SLNs in the lung through combined optical color and fluorescent image with indocyanine green (ICG) and ICG with human serum albumin (HSA). METHODS: Identical ICG concentrations of ICG only or ICG:HSA was injected into the rat footpad and porcine lung. Absolute amounts of the fluorescents were scaled on the basis of animal weights. The entire procedures were recorded using color and near-infrared (NIR) charge-coupled device (CCD) cameras simultaneously, and the 2 images were merged by real-time image processing software. All fluorescence intensity signals to background ratio (SBR) and retention rates at SLN for both fluorescents were estimated and compared. RESULTS: This newly developed intraoperative color and fluorescence optical imaging system successfully visualized the SLNs in animal experiments. The SLNs were identified 100% for both rat and pig under in vivo conditions. Real-time image processing software overcame the low signal of NIR fluorescence images. ICG and ICG:HSA provided no significantly different SBR in the SLN images for both rat thigh and pig lung. CONCLUSIONS: The intraoperative optical imaging system enabled real-time image-guided surgery during SLN mapping in lung in an animal model. The ICG retention rate was similar to ICG:HSA. ICG alone can be useful for SLN imaging during lung cancer surgery.

Catching the right wave: evaluating wave energy resources and potential compatibility with existing marine and coastal uses.

Many hope that ocean waves will be a source for clean, safe, reliable and affordable energy, yet wave energy conversion facilities may affect marine ecosystems through a variety of mechanisms, including competition with other human uses. We developed a decision-support tool to assist siting wave energy facilities, which allows the user to balance the need for profitability of the facilities with the need to minimize conflicts with other ocean uses. Our wave energy model quantifies harvestable wave energy and evaluates the net present value (NPV) of a wave energy facility based on a capital investment analysis. The model has a flexible framework and can be easily applied to wave energy projects at local, regional, and global scales. We applied the model and compatibility analysis on the west coast of Vancouver Island, British Columbia, Canada to provide information for ongoing marine spatial planning, including potential wave energy projects. In particular, we conducted a spatial overlap analysis with a variety of existing uses and ecological characteristics, and a quantitative compatibility analysis with commercial fisheries data. We found that wave power and harvestable wave energy gradually increase offshore as wave conditions intensify. However, areas with high economic potential for wave energy facilities were closer to cable landing points because of the cost of bringing energy ashore and thus in nearshore areas that support a number of different human uses. We show that the maximum combined economic benefit from wave energy and other uses is likely to be realized if wave energy facilities are sited in areas that maximize wave energy NPV and minimize conflict with existing ocean uses. Our tools will help decision-makers explore alternative locations for wave energy facilities by mapping expected wave energy NPV and helping to identify sites that provide maximal returns yet avoid spatial competition with existing ocean uses.

Depth-dependent cerebral hemodynamic responses following direct cortical electrical stimulation (DCES) revealed by in vivo dual-optical imaging techniques.

We studied depth-dependent cerebral hemodynamic responses of rat brain following direct cortical electrical stimulation (DCES) in vivo with optical recording of intrinsic signal (ORIS) and near-infrared spectroscopy (NIRS). ORIS is used to visualize the immediate hemodynamic changes in cortical areas following the stimulation, whereas NIRS measures the hemodynamic changes originating from subcortical areas. We found strong hemodynamic changes in relation to DCES both in ORIS and NIRS data. In particular, the signals originating from cortical areas exhibited a tri-phasic response, whereas those originating from subcortical regions exhibited multi-phasic responses. In addition, NIRS signals from two different sets of source-detector separation were compared and analyzed to investigate the causality of perfusion, which demonstrated downstream propagation, indicating that the upper brain region reacted faster than the deep region.

Policosanol content and composition in perilla seeds.

Policosanols, long-chain alcohols, have many beneficial physiological activities. Contents and compositions in perilla seeds (Perilla frutescens) produced in Korea and China were determined. Waxy materials were extracted from perilla seeds using hot hexane. Yield of the waxy materials from perilla seeds was 72.1 mg/100 g of dry weight. Contents and compositions of the waxy materials and policosanols were identified and quantified by TLC, HPLC, and GC. Major components of the waxy materials from Korean and Chinese perilla seeds were policosanols (25.5 and 34.8%, respectively), hydrocarbons (18.8 and 10.5%), wax esters, steryl esters and aldehydes (53.0 and 49.8%), acids (1.7 and 2.1%), and triacylglycerols (1.0 and 2.9%), determined by HPLC. For comparison, waxy materials of sesame seeds were also analyzed. Yield of the waxy materials from sesame seeds were 8.6 mg/100 g. Less than 5% policosanols were detected in the waxy materials extracted from sesame seeds produced in Korea and China. Wax esters or steryl esters accounted for 93-95% of the sesame waxy materials. Policosanols in the perilla seeds were composed of 67-68% octacosanol, 16-17% hexacosanol, 6-9% triacontanol, and others.