Neuromorphic devices that mimic a human brain have attracted significant attention in the field of next-generation semiconductors. The human brain can efficiently process information with low power ...consumption. Several energy efficient artificial synapses have been reported; however, the energy consumption of these synapses is significantly higher than that of the human brain (10 fJ). In this study, we propose the use of double oxide semiconductors for obtaining synaptic transistors with ultra-low energy consumption. The synaptic transistor comprising InZnO (IZO) and InGaZnO (IGZO) exhibits a high mobility and positive turn-on voltage, which are required for ultra-low energy consumption. SiO 2 deposited at 200 °C by plasma enhanced atomic layer deposition is used as an electric double layer gate insulator. The IZO/IGZO synaptic transistor consumed an ultra-low energy of 0.269 fJ (gate voltage: 3.5 V, 1 ms and drain voltage: 3 mV). Furthermore, the synaptic transistor exhibits various synaptic plasticity features under the brain-like energy conditions, including excitatory post-synaptic current, paired-pulse facilitation, potentiation, and depression. All of the operations of the devices were performed under ambient conditions (25 °C, humidity 50%), in the dark probe station. The IZO/IGZO synaptic transistor exhibits similar energy efficiency to a human brain, and this strategy is expected to be utilized for the fabrication of various ultra-low energy consuming synaptic transistors.
The simultaneous infection with a tripledemic—simultaneous infection with influenza A pH1N1 virus (Flu), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus ...(RSV)—necessitates the development of accurate and fast multiplex diagnostic tests. The coronavirus disease 2019 (COVID-19) pandemic has emphasized the importance of virus detection. Field-effect transistor (FET)-based immuno-biosensors have a short detection time and do not require labeling or polymerase chain reaction. This study demonstrates the rapid, sensitive detection of influenza A pH1N1, SARS-CoV-2, and RSV using a multiplex immunosensor based on a dual-gate oxide semiconductor thin-film transistor (TFT), a type of FET. The dual-gate oxide TFT was modified by adjusting both top and bottom gate insulators to improve capacitive coupling to approximately 120-fold amplification, exhibiting a high pH sensitivity of about 10 V/pH. The dual-gate oxide TFT-based immunosensor detected the target proteins (hemagglutinin (HA) protein of Flu, spike 1 (S1) protein of SARS-CoV-2, and fusion protein of RSV) of each virus, with a limit of detection of approximately 1 fg/mL. Cultured viruses in phosphate-buffered saline or artificial saliva and clinical nasopharynx samples were detected in 1-μL sample volumes within 60 s. This promising diagnosis could be potentially as point-of-care tests to facilitate a prompt response to future pandemics with high sensitivity and multiplexed detection without pretreatment.
Fluorescent proteins contain an internal chromophore constituted of amino acids or an external chromophore covalently bonded to the protein. To increase their fluorescence intensities, many research ...groups have attempted to mutate amino acids within or near the chromophore. Recently, a new type of fluorescent protein, called UnaG, in which the ligand binds to the protein through many noncovalent interactions was discovered. Later, a series of mutants of the UnaG protein were introduced, which include eUnaG with valine 2 mutated to leucine emitting significantly stronger fluorescence than the wild type and V2T mutant, in which valine 2 is mutated to threonine, emitting weaker fluorescence than the wild type. Interestingly, the single mutation sites of both eUnaG and V2T mutants are distant from the fluorophore, bilirubin, which renders the mechanism of such fluorescence enhancement or reduction unclear. To elucidate the origin of fluorescence intensity changes induced by the single mutations, we carried out extensive analyses on MD simulations for the original UnaG, eUnaG and V2T, and found that the bilirubin ligand bound to eUnaG is conformationally more rigid than the wild-type, particularly in the skeletal dihedral angles, possibly resulting in the increase of quantum yield through a reduction of non-radiative decay. On the other hand, the bilirubin bound to the V2T appears to be flexible than that in the UnaG. Furthermore, examining the structural correlations between the ligand and proteins, we found evidence that the bilirubin ligand is encapsulated in different environments composed of protein residues and water molecules that increase or decrease the stability of the ligand. The changed protein stability affects the mobility and confinement of water molecules captured between bilirubin and the protein. Since the flexible ligand contains multiple hydrogen bond (H-bond) donors and acceptors, the H-bonding structure and dynamics of bound water molecules are highly correlated with the rigidity of the bound ligand. Our results suggest that, to understand the fluorescence properties of protein mutants, especially the ones with noncovalently bound fluorophores with internal rotations, the interaction network among protein residues, ligand, and water molecules within the binding cavity should be investigated rather than focusing on the local structure near the fluorescing moiety. Our in-depth simulation study may offer a foundation for the design principles for engineering this new class of fluorescent proteins.
As the application of oxide semiconductor thin-film transistors (oxide TFTs) expands, higher electrical properties are required. Hydrogen (H) is a crucial element related to both the mobility and ...stability of oxide TFTs. Appropriate H incorporation induces enhanced characteristics; however, excessive H degrades TFTs. In this letter, we suggest inserting an interfacial layer (IL) deposited via plasma-enhanced atomic layer deposition of several cycles to control H at the atomic-scale. As the number of IL deposition cycles increase from 0 to 10 cy, both mobility and stability improve. Furthermore, TFT with IL of 15 cy lost its on/off characteristic. Considering the analysis results, it was confirmed that the control of H concentration through IL can effectively improve the electrical characteristics of oxide TFTs. The oxide TFT with IL of 10 cy and optimized incorporation of H exhibits a high mobility of 50.12 cm2/V.s with great stability.
Summary Background Capecitabine plus oxaliplatin (CapeOX) is one of the reference doublet cytotoxic chemotherapy treatments for patients with metastatic colorectal cancer. We aimed to compare the ...efficacy and safety of CapeOX with that of S-1 plus oxaliplatin (SOX), a promising alternative treatment for patients with metastatic colorectal cancer. Methods In this open-label, multicentre, randomised phase 3 trial, we randomly assigned patients (1:1) from 11 institutions in South Korea to receive either CapeOX (capecitabine 1000 mg/m2 twice daily on days 1–14 and oxaliplatin 130 mg/m2 on day 1) or SOX (S-1 40 mg/m2 twice daily on days 1–14 and oxaliplatin 130 mg/m2 on day 1). Treatment was repeated every 3 weeks and continued for as many as nine cycles of oxaliplatin-containing chemotherapy, except in instances of disease progression, unacceptable toxicity, or a patient's refusal. Maintenance chemotherapy with S-1 or capecitabine was allowed after discontinuation of oxaliplatin. Randomisation was done with a computer-generated sequence (stratified by primary sites, previous adjuvant or neoadjuvant treatment, and the presence of measurable lesions). The primary endpoint was to show non-inferiority of SOX relative to CapeOX in terms of progression-free survival (PFS). The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00677443. Findings Between May 14, 2008, and Sept 23, 2009, we randomly assigned 168 patients to receive SOX and 172 to receive CapeOX. Median PFS was 8·5 months (95% CI 7·6–9·3) in the SOX group and 6·7 months (6·2–7·1) in the CapeOX group (hazard ratio, 0·79 95% CI 0·60–1·04; pnon-inferiority <0·0001, plog-rank =0·09). The upper limit of the CI was below the predefined margin of 1·43, showing the non-inferiority of SOX to CapeOX. We recorded a higher incidence of grade 3–4 neutropenia (49 29% vs 24 15%), thrombocytopenia (37 22% vs 11 7%), and diarrhoea (16 10% vs seven 4%) in the SOX group than in the CapeOX group. The frequency of any grade of hand-foot syndrome was greater in the CapeOX group than it was in the SOX group (51 31% vs 23 14%). Interpretation The SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer. Further investigation is needed to explore its potential when used together with other targeted agents or as adjuvant chemotherapy. Funding Korea Healthcare Technology Research and Development Project, Ministry of Health and Welfare, South Korea.
Top-gate self-aligned structured oxide thin-film transistors (TFTs) are suitable for the backplanes of high-end displays because of their low parasitic capacitances. The gate insulator (GI) ...deposition process should be carefully designed to manufacture a highly stable, high-mobility oxide TFT, particularly for a top-gate structure. In this study, a nanometer-thick Al2O3 layer via plasma-enhanced atomic layer deposition (PE-ALD) is deposited on the top-gate bottom-contact structured oxide TFT as the interface tailoring layer, which can also act as the hydrogen barrier to modulate carrier generation from hydrogen incorporation into the active layer of the TFT during the following process such as postannealing. Al-doped InSnZnO (Al/ITZO) with an Al/In/Sn/Zn atomic ratio composition of 1.7:24.3:40:34 was used for high mobility oxide semiconductors, and an Al2O3/Si3N4 bilayer was used for the GI. The degradation issue due to the excellent barrier characteristics of Al2O3 and Si3N4 can be minimized. An oxide TFT fabricated without the interface tailoring layer exhibits conductor-like characteristics owing to the excessive carrier generation by hydrogen incorporation. However, TFTs with additional interface layers exhibit reasonable characteristics and distinct trends in electrical characteristics depending on the thicknesses of the interface layers. The optimized devices exhibit an average turn-on voltage (V on) of −0.31 V with 33.63 cm2/(V s) of high mobility and 0.09 V/dec of subthreshold swing value. The interfaces between the active layer and hydrogen barriers were investigated using a high-resolution transmission electron microscope, contact angle measurement, and secondary ion mass spectroscopy to reveal the origin of the trends in properties between the devices. The top-gate device with a hydrogen barrier using the four-cycle deposition exhibits optimum electrical characteristics of both high mobility and good stability with only a 0.04 V shift of V on under positive-bias temperature stress (PBTS). We realize a high-end, self-aligned TFT with high mobility 34.7 cm2/(V s) and negligible V on shift of −0.06 V under PBTS by applying a subnanometer hydrogen barrier.
We present a piezoresistive high-G accelerometer that achieves 1% cross-axis sensitivity, 200kG shock endurance, and 90% fabrication yield. The special features and advances in the accelerometer are ...as follows. Firstly, the cross-symmetric structure of the accelerometer is effective in reducing cross-axis sensitivity. Secondly, the piezoresistors implanted on the elastic beam surface at a low doping level result in a high gauge factor and sensitivity with excellent shock endurance. Thirdly, the cross-symmetric structure, generating both tensile and compressive stresses on the elastic beam surface, forms a piezoresistor bridge interconnection on a single side of the accelerometer; thus, simplifying the fabrication process as well as the wiring and packaging process with a high yield of 90%. Experimental characteristics of the fabricated accelerometer show a detection range of up to 200 kG, a resonant frequency of 577.04±13.62 kHz, a prime-axis sensitivity of 1.01±0.11 μV/G, a cross-axis sensitivity ratio of 0.98±0.62%, and a linearity of 99.99±0.08% over the detection range. The fabricated accelerometer shows only a 1.35% variation of prime-axis sensitivities at 20 kG before and after a shock of 200 kG, indicating its performance stability and repeatability. Therefore, the accelerometer demonstrates strong potential for high-G impact monitoring applications in the fields of defense, aerospace, marine, automotive, construction, etc.
Power distribution systems should meet demands such as high reliability, efficiency, and penetration of renewable energy generators (REGs) in a smart grid. In general, power distribution systems are ...radial in nature. One-way power flow is the advantage of a radial system. However, the introduction of REGs causes bidirectional power flow. Furthermore, there are limits to improvements in reliability and efficiency in a radial system. Therefore, the upgrading of primary feeders from a radial to a loop configuration has been considered in the Korea Smart Distribution Project. An advanced power distribution system (APDS), in which primary feeders operate in a loop configuration, has been explored in this paper. First, the design scheme of a conventional power distribution system configuration that adopts distribution automation is introduced. Subsequently, an upgrading scheme of loop configuration using normally opened tie switches and a tie switch selection algorithm for loss minimization are described. Finally, the advantages of the upgraded configuration are reported through case studies. It is observed that the APDS configuration can integrate more REGs from the viewpoint of voltage regulation. An advanced distribution system allowing greater use of REGs will be a major contribution to smart grid implementation.
The Arg/N-degron pathway, which is involved in the degradation of proteins bearing an N-terminal signal peptide, is connected to p62/SQSTM1-mediated autophagy. However, the impact of the molecular ...link between the N-degron and autophagy pathways is largely unknown in the context of systemic inflammation. Here, we show that chemical mimetics of the N-degron Nt-Arg pathway (p62 ligands) decreased mortality in sepsis and inhibited pathological inflammation by activating mitophagy and immunometabolic remodeling. The p62 ligands alleviated systemic inflammation in a mouse model of lipopolysaccharide (LPS)-induced septic shock and in the cecal ligation and puncture model of sepsis. In macrophages, the p62 ligand attenuated the production of proinflammatory cytokines and chemokines in response to various innate immune stimuli. Mechanistically, the p62 ligand augmented LPS-induced mitophagy and inhibited the production of mitochondrial reactive oxygen species in macrophages. The p62 ligand-mediated anti-inflammatory, antioxidative, and mitophagy-activating effects depended on p62. In parallel, the p62 ligand significantly downregulated the LPS-induced upregulation of aerobic glycolysis and lactate production. Together, our findings demonstrate that p62 ligands play a critical role in the regulation of inflammatory responses by orchestrating mitophagy and immunometabolic remodeling.
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