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Heart failure is associated with a significant mortality rate, and an elevated prevalence of this condition has been noted among hypertensive patients. The identification of predictive factors for heart failure progression in hypertensive individuals is crucial for early intervention and improved patient outcomes. In this study, we aimed to identify these predictive factors by utilizing medical diagnosis records for hypertension patients from the MIMIC-IV database. In particular, we employed only diagnostic history prior to hypertension to enable patients to anticipate the onset of heart failure at the moment of hypertension diagnosis. In the methodology, chi-square tests and XGBoost modeling were applied to examine age-specific predictive factors across four groups: AL (all ages), G1 (0 to 65 years), G2 (65 to 80 years), and G3 (over 80 years). As a result, the chi-square tests identified 34, 28, 20, and 10 predictive factors for the AL, G1, G2, and G3 groups, respectively. Meanwhile, the XGBoost modeling uncovered 19, 21, 27, and 33 predictive factors for these respective groups. Ultimately, our findings reveal 21 overall predictive factors, encompassing conditions such as atrial fibrillation, the use of anticoagulants, kidney failure, obstructive pulmonary disease, and anemia. These factors were assessed through a comprehensive review of the existing literature. We anticipate that the results will offer valuable insights for the risk assessment of heart failure in hypertensive patients.
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We present the fabrication of 4 K-scale electrochemical random-access memory (ECRAM) cross-point arrays for analog neural network training accelerator and an electrical characteristic of an 8 × 8 ECRAM array with a 100% yield, showing excellent switching characteristics, low cycle-to-cycle, and device-to-device variations. Leveraging the advances of the ECRAM array, we showcase its efficacy in neural network training using the Tiki-Taka version 2 algorithm (TTv2) tailored for non-ideal analog memory devices. Through an experimental study using ECRAM devices, we investigate the influence of retention characteristics on the training performance of TTv2, revealing that the relative location of the retention convergence point critically determines the available weight range and, consequently, affects the training accuracy. We propose a retention-aware zero-shifting technique designed to optimize neural network training performance, particularly in scenarios involving cross-point devices with limited retention times. This technique ensures robust and efficient analog neural network training despite the practical constraints posed by analog cross-point devices.
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Cave crickets (Rhaphidophoridae) are insects of an ancient and wingless lineage within Orthoptera that are distributed worldwide except in Antarctica, and each subfamily has a high level of endemicity. Here, we show the comprehensive phylogeny of cave crickets using multi-gene datasets from mitochondrial and nuclear loci, including all extant subfamilies for the first time. We reveal phylogenetic relationships between subfamilies, including the sister relationship between Anoplophilinae and Gammarotettiginae, based on which we suggest new synapomorphies. Through biogeographic analyses based on divergence time estimations and ancestral range reconstruction, we propose novel hypotheses regarding the biogeographic history of cave crickets. We suggest that Gammarotettiginae in California originated from the Asian lineage when Asia and the Americas were connected by the Bering land bridge, and the opening of the western interior seaway affected the division of Ceuthophilinae from Tropidischiinae in North America. We estimate that Rhaphidophoridae originated at 138 Mya throughout Pangea. We further hypothesize that the loss of wings in Rhaphidophoridae could be the result of their adaptation to low temperatures in the Mesozoic era.
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Ortópteros , Animales , Filogenia , Asia , América del Norte , Regiones AntárticasRESUMEN
Parkinson's disease (PD) is a complex neurodegenerative disorder with an unclear etiology. Despite significant research efforts, developing disease-modifying treatments for PD remains a major unmet medical need. Notably, drug repositioning is becoming an increasingly attractive direction in drug discovery, and computational approaches offer a relatively quick and resource-saving method for identifying testable hypotheses that promote drug repositioning. We used an artificial intelligence (AI)-based drug repositioning strategy to screen an extensive compound library and identify potential therapeutic agents for PD. Our AI-driven analysis revealed that efavirenz and nevirapine, approved for treating human immunodeficiency virus infection, had distinct profiles, suggesting their potential effects on PD pathophysiology. Among these, efavirenz attenuated α-synuclein (α-syn) propagation and associated neuroinflammation in the brain of preformed α-syn fibrils-injected A53T α-syn Tg mice and α-syn propagation and associated behavioral changes in the C. elegans BiFC model. Through in-depth molecular investigations, we found that efavirenz can modulate cholesterol metabolism and mitigate α-syn propagation, a key pathological feature implicated in PD progression by regulating CYP46A1. This study opens new avenues for further investigation into the mechanisms underlying PD pathology and the exploration of additional drug candidates using advanced computational methodologies.
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Alquinos , Inteligencia Artificial , Benzoxazinas , Ciclopropanos , Reposicionamiento de Medicamentos , Enfermedad de Parkinson , alfa-Sinucleína , Ciclopropanos/farmacología , Ciclopropanos/uso terapéutico , Alquinos/farmacología , Benzoxazinas/farmacología , Reposicionamiento de Medicamentos/métodos , Animales , alfa-Sinucleína/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Ratones , Caenorhabditis elegans/efectos de los fármacos , Ratones Transgénicos , Humanos , Nevirapina/farmacología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BLRESUMEN
BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad and continuous spectrum of liver diseases ranging from fatty liver to steatohepatitis. The intricate interactions of genetic, epigenetic, and environmental factors in the development and progression of MASLD remain elusive. Here, we aimed to achieve an integrative understanding of the genomic and transcriptomic alterations throughout the progression of MASLD. APPROACH AND RESULTS: RNA-Seq profiling (n = 146) and whole-exome sequencing (n = 132) of MASLD liver tissue samples identified 3 transcriptomic subtypes (G1-G3) of MASLD, which were characterized by stepwise pathological and molecular progression of the disease. Macrophage-driven inflammatory activities were identified as a key feature for differentiating these subtypes. This subtype-discriminating macrophage interplay was significantly associated with both the expression and genetic variation of the dsDNA sensor IFI16 (rs6940, A>T, T779S), establishing it as a fundamental molecular factor in MASLD progression. The in vitro dsDNA-IFI16 binding experiments and structural modeling revealed that the IFI16 variant exhibited increased stability and stronger dsDNA binding affinity compared to the wild-type. Further downstream investigation suggested that the IFI16 variant exacerbated DNA sensing-mediated inflammatory signals through mitochondrial dysfunction-related signaling of the IFI16-PYCARD-CASP1 pathway. CONCLUSIONS: This study unveils a comprehensive understanding of MASLD progression through transcriptomic classification, highlighting the crucial roles of IFI16 variants. Targeting the IFI16-PYCARD-CASP1 pathway may pave the way for the development of novel diagnostics and therapeutics for MASLD.
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New systems for agrochemical delivery in plants will foster precise agricultural practices and provide new tools to study plants and design crop traits, as standard spray methods suffer from elevated loss and limited access to remote plant tissues. Silk-based microneedles can circumvent these limitations by deploying a known amount of payloads directly in plants' deep tissues. However, plant response to microneedles' application and microneedles' efficacy in deploying physiologically relevant biomolecules are unknown. Here, it is shown that gene expression associated with Arabidopsis thaliana wounding response decreases within 24 h post microneedles' application. Additionally, microinjection of gibberellic acid (GA3 ) in A. thaliana mutant ft-10 provides a more effective and efficient mean than spray to activate GA3 pathways, accelerating bolting and inhibiting flower formation. Microneedle efficacy in delivering GA3 is also observed in several monocot and dicot crop species, i.e., tomato (Solanum lycopersicum), lettuce (Lactuca sativa), spinach (Spinacia oleracea), rice (Oryza Sativa), maize (Zea mays), barley (Hordeum vulgare), and soybean (Glycine max). The wide range of plants that can be successfully targeted with microinjectors opens the doors to their use in plant science and agriculture.
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Plantas , SedaRESUMEN
BACKGROUND: Subarachnoid hemorrhage (SAH) is a fatal disease, with early brain injury (EBI) occurring within 72 h of SAH injury contributes to its poor prognosis. EBI is a complicated phenomenon involving multiple mechanisms. Although neuroinflammation has been shown to be important prognosis factor of EBI, whether neuroinflammation spreads throughout the cerebrum and the extent of its depth in the cerebral cortex remain unknown. Knowing how inflammation spreads throughout the cerebrum is also important to determine if anti-inflammatory agents are a future therapeutic strategy for EBI. METHODS: In this study, we induced SAH in mice by injecting hematoma into prechiasmatic cistern and created models of mild to severe SAH. In sections of the mouse cerebrum, we investigated neuroinflammation and neuronal cell death in the cortex distal to the hematoma injection site, from anterior to posterior region 24 h after SAH injury. RESULTS: Neuroinflammation caused by SAH spread to all layers of the cerebral cortex from the anterior to the posterior part of the cerebrum via the invasion of activated microglia, and neuronal cell death increased in correlation with neuroinflammation. This trend increased with the severity of the disease. CONCLUSIONS: Neuroinflammation caused by SAH had spread throughout the cerebrum, causing neuronal cell death. Considering that the cerebral cortex is responsible for long-term memory and movement, suppressing neuroinflammation in all layers of the cerebral cortex may improve the prognosis of patients with SAH.
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College students are at a high risk of mental health problems due to continuous exposure to considerable stress as they transition into adulthood. It is necessary to reflect on young people's needs and provide brief, personalized support interventions via mobile applications. This study aimed to (1) describe the co-design development process of a behavioral activation (BA) mobile health application called MEndorphins to help youth manage stress; and (2) evaluate the ease of use and quality of the application and its effects on psychological distress. College students aged 18-25 in South Korea participated as co-designers throughout the MEndorphins development process, which involved prototyping workshops. Thirty-five students also evaluated the application's ease of use and quality, as well as its effects on psychological distress, using a self-reported online questionnaire. In the pilot evaluation, ease of use scored 74.21 out of 100 and quality 3.72 out of 5. There were statistically significant decreases in depression, anxiety, and stress after using MEndorphins (p ≤ 0.001 for depression and anxiety, p = 0.001 for stress) for 7 days. In this developed BA based mobile application, participants could monitor their mood, plan stress self-management strategies, and gain motivation by sharing experiences.
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BACKGROUND: Obstructive Sleep Apnoea (OSA) often co-occurs with cardiometabolic and pulmonary diseases. This study is to apply genetic analysis methods to explain the associations between OSA and related phenotypes. METHODS: In the Hispanic Community Healthy Study/Study of Latinos, we estimated genetic correlations ρg between the respiratory event index (REI) and 54 anthropometric, glycemic, cardiometabolic, and pulmonary phenotypes. We used summary statistics from published genome-wide association studies to construct Polygenic Risk Scores (PRSs) representing the genetic basis of each correlated phenotype (ρg>0.2 and p-value<0.05), and of OSA. We studied the association of the PRSs of the correlated phenotypes with both REI and OSA (REI≥5), and the association of OSA PRS with the correlated phenotypes. Causal relationships were tested using Mendelian Randomization (MR) analysis. FINDINGS: The dataset included 11,155 participants, 31.03% with OSA. 22 phenotypes were genetically correlated with REI. 10 PRSs covering obesity and fat distribution (BMI, WHR, WHRadjBMI), blood pressure (DBP, PP, MAP), glycaemic control (fasting insulin, HbA1c, HOMA-B) and insomnia were associated with REI and/or OSA. OSA PRS was associated with BMI, WHR, DBP and glycaemic traits (fasting insulin, HbA1c, HOMA-B and HOMA-IR). MR analysis identified robust causal effects of BMI and WHR on OSA, and probable causal effects of DBP, PP, and HbA1c on OSA/REI. INTERPRETATION: There are shared genetic underpinnings of anthropometric, blood pressure, and glycaemic phenotypes with OSA, with evidence for causal relationships between some phenotypes. FUNDING: Described in Acknowledgments.
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Enfermedades Cardiovasculares , Apnea Obstructiva del Sueño , Glucemia , Índice de Masa Corporal , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/genética , Estudio de Asociación del Genoma Completo , Hemoglobina Glucada , Humanos , Insulina/genética , Fenotipo , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/genéticaRESUMEN
Spin Hall nano-oscillators (SHNOs) exploiting current-driven magnetization auto-oscillation have recently received much attention because of their potential for neuromorphic computing. Widespread applications of neuromorphic devices with SHNOs require an energy-efficient method of tuning oscillation frequency over broad ranges and storing trained frequencies in SHNOs without the need for additional memory circuitry. While the voltage-driven frequency tuning of SHNOs has been demonstrated, it was volatile and limited to megahertz ranges. Here, we show that the frequency of SHNOs is controlled up to 2.1 GHz by an electric field of 1.25 MV/cm. The large frequency tuning is attributed to the voltage-controlled magnetic anisotropy (VCMA) in a perpendicularly magnetized Ta/Pt/[Co/Ni]n/Co/AlOx structure. Moreover, the non-volatile VCMA effect enables cumulative control of the frequency using repetitive voltage pulses which mimic the potentiation and depression functions of biological synapses. Our results suggest that the voltage-driven frequency tuning of SHNOs facilitates the development of energy-efficient neuromorphic devices.
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All solid materials are created via nucleation. In this evolutionary process, nuclei form in solution or at interfaces, expand by monomeric growth and oriented attachment, and undergo phase transformation. Nucleation determines the location and size of nuclei, whereas growth controls the size, shape, and aggregation of newly formed nanoparticles. These physical properties of nanoparticles can affect their functionalities, reactivities, and porosities, as well as their fate and transport. Recent advances in nanoscale analytical technologies allow in situ real-time observations, enabling us to uncover the molecular nature of nuclei and the critical controlling factors for nucleation and growth. Although a single theory cannot yet fully explain such evolving processes, we have started to better understand how both classical andnonclassical theories can work together, and we have begun to recognize the importance of connecting these theories. This review discusses the recent convergence of knowledge about the nucleation and growth of nanoparticles.
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NanopartículasRESUMEN
The deficiency and excess of vitamin D cause various diseases, necessitating continuous management; but it is not easy to accurately measure the serum vitamin D level in the body using a non-invasive method. The aim of this study is to investigate the correlation between vitamin D levels, body information obtained by an InBody scan, and blood parameters obtained during health checkups, to determine the optimum frequency of vitamin D quantification in the skin and to propose a vitamin D measurement method based on impedance. We assessed body composition, arm impedance, and blood vitamin D concentrations to determine the correlation between each element using multiple machine learning analyses and an algorithm which predicted the concentration of vitamin D in the body using the impedance value developed. Body fat percentage obtained from the InBody device and blood parameters albumin and lactate dehydrogenase correlated with vitamin D level. An impedance measurement frequency of 21.1 Hz was reflected in the blood vitamin D concentration at optimum levels, and a confidence level of about 75% for vitamin D in the body was confirmed. These data demonstrate that the concentration of vitamin D in the body can be predicted using impedance measurement values. This method can be used for predicting and monitoring vitamin D-related diseases and may be incorporated in wearable health measurement devices.
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Técnicas Biosensibles , Vitamina D , Algoritmos , Composición Corporal , Impedancia EléctricaRESUMEN
How does vaccination against foot-and-mouth disease (FMD) affect pregnant cows? Vaccination is the most effective method of preventing the spread of FMD, but it is linked to sporadic side effects, such as abortion and premature birth, which result in economic loss. In this study, ruminoreticular temperature and body activity were measured before and after FMD vaccination using a ruminoreticular biocapsule sensor in Hanwoo cows at different stages of pregnancy. Compared to the unvaccinated groups, the ruminoreticular temperature increased 12 h after vaccination in the vaccinated groups. This increase in temperature is significantly correlated to vaccination. Compared to the nonpregnant and early pregnancy groups, the ruminoreticular temperature of the late pregnancy group increased sharply by more than 40 °C. Moreover, in nonpregnant and early pregnancy groups, a rapid increase in body activity was observed after FMD vaccinations. Of the 73 pregnant vaccinated cows in the study, a total of five cases had side effects (four abortions and one premature birth). Therefore, changes in the ruminoreticular temperature and activity in pregnant cows can be used as raw data to further clarify the association of FMD vaccination with the loss of a fetus and possibly predict abortion, miscarriage, and premature birth following FMD vaccination.
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Angelica polymorpha Maxim. (APM) is used in traditional medicine to treat chronic gastritis, rheumatic pain, and duodenal bulbar ulcers. However, it is not known whether APM has epidermis-associated biological activities. Here, we investigated the effects of APM flower absolute (APMFAb) on responses associated with skin wound healing and whitening using epidermal cells. APMFAb was obtained by solvent extraction and its composition was analyzed by GC/MS. Water-soluble tetrazolium salt, 5-bromo-2'-deoxyuridine incorporation, Boyden chamber, sprouting, and enzyme-linked immunosorbent assays and immunoblotting were used to examine the effects of APMFAb on HaCaT keratinocytes and B16BL6 melanoma cells. APMFAb contained five compounds and induced keratinocyte migration, proliferation, and type IV collagen synthesis. APMFAb also induced the phosphorylations of ERK1/2, JNK, p38 mitogen-activated protein kinase, and AKT in keratinocytes. In addition, APMFAb decreased serum-induced B16BL6 cell proliferation and inhibited tyrosinase expression, melanin contents, and microphthalmia-associated transcription factor expression in α-melanocyte-stimulating hormone-stimulated B16BL6 cells. These findings demonstrate that APMFAb has beneficial effects on skin wound healing by promoting the proliferation, migration, and collagen synthesis of keratinocytes and on skin whitening by inhibiting melanin synthesis in melanoma cells. Therefore, we suggest that APMFAb has potential use as a wound healing and skin whitening agent.
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Angelica/metabolismo , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Flores/metabolismo , Humanos , Queratinocitos/efectos de los fármacos , Melaninas/biosíntesis , Melaninas/metabolismo , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismoRESUMEN
The adaptive response of bones to mechanical loading is essential for musculoskeletal development. Despite the importance of collagen in bone mineralization, little is known about how cyclic strain influences physicochemical responses of collagen, especially at the early stage of mineralization when the levels of strain are higher than those in mature bones. The findings in this study show that, without any cell-mediated activity, cyclic strain increases nucleation rates of calcium phosphate (CaP) nanocrystals in highly-organized collagen matrices. The cyclic strain enhances the transport of mineralization fluids with nucleation precursors into the matrix, thus forming more CaP nanocrystals and increasing the elastic modulus of the collagen matrix. The results also suggest that the multiscale spatial distribution of nanocrystals in the fibrous collagen network determines tissue-level mechanical properties more critically than the total mineral content. By linking nano- and micro-scale observations with tissue-level mechanical properties, we provide new insights into designing better biomaterials.
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Matriz Ósea , Calcificación Fisiológica , Huesos , Colágeno , MineralesRESUMEN
Unveiling the effects of an environmental abundant anion "sulfate" on the formation of calcium carbonate (CaCO3) is essential to understand the formation mechanisms of biominerals like corals and brachiopod shells, as well as the scale formation in desalination systems. However, it was experimentally challenging to elucidate the sulfate-CaCO3 interactions at the explicit first step of CaCO3 formation: nucleation. In addition, there is limited quantitative information on the precise control of nucleation kinetics. Here, heterogeneous CaCO3 nucleation is monitored in real time as a function of sulfate concentrations (0-10 mM Na2SO4) using synchrotron-based grazing incidence X-ray scattering techniques. The results showed that sulfate can be incorporated in the nuclei, resulting in a nearly 90% decrease in the CaCO3 nucleation rate, causing a 120% increase in the CaCO3 nucleus size, and inhibiting the vaterite-to-calcite phase transformation. Moreover, this work quantitatively relates sulfate concentrations to the effective interfacial energies of CaCO3 and finds a non-linear trend, suggesting that CaCO3 heterogeneous nucleation is more sensitive at a low sulfate concentration. This study can be readily extended to study other additives and obtain quantitative relationships between additive concentrations and CaCO3 interfacial energies, a key step toward achieving natural and engineered controls on CaCO3 nucleation.
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Vaccination against foot-and-mouth disease is the most common method for preventing the spread of the disease; the negative effects include miscarriage, early embryo death, lower milk production, and decreased growth of fattening cattle. Therefore, in this study, we analyze the side effects of vaccination by determining the acute immune response and ovulation rate after vaccinating cows for foot-and-mouth disease. The test axis was synchronized with ovulation using 100 Hanwoo (Bos taurus coreanae) cows from the Gyeongsangbuk-do Livestock Research Institute; only individuals with estrus confirmed by ovarian ultrasound were used for the test. All test axes were artificially inseminated 21 days after the previous estrus date. The control group was administered 0.9% normal saline, the negative control was injected intramuscularly with lipopolysaccharide (LPS; 0.5 µg/kg), and the test group was administered a foot-and-mouth disease virus vaccine (FMDV vaccine; bioaftogen, O and A serotypes, inactivated vaccine) 2, 9, and 16 days before artificial insemination. White blood cells and neutrophils increased significantly 1 day after vaccination, and body temperature in the rumen increased for 16 h after vaccination. Ovulation was detected 1 day after artificial fertilization by ovarian ultrasound. The ovulation rates were as follows: control 89%, LPS 60%, FMDV vaccine (-2 d) 50%, FMDV vaccine (-9 d) 75%, and FMDV vaccine (-16 d) 75%. In particular, the FMDV vaccine (-2 d) test group confirmed that ovulation was delayed for 4 days after artificial insemination. In addition, it was confirmed that it took 9 days after inoculation for the plasma contents of haptoglobin and serum amyloid A to recover to the normal range as the main acute immune response factors. The conception rate of the FMDV vaccine (-2 d) group was 20%, which was significantly lower than that of the other test groups.
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When thickness-dependent carrier mobility is coupled with Thomas-Fermi screening and interlayer resistance effects in two-dimensional (2D) multilayer materials, a conducting channel migrates from the bottom surface to the top surface under electrostatic bias conditions. However, various factors including (i) insufficient carrier density, (ii) atomically thin material thickness, and (iii) numerous oxide traps/defects considerably limit our deep understanding of the carrier transport mechanism in 2D multilayer materials. Herein, we report the restricted conducting channel migration in 2D multilayer ReS2 after a constant voltage stress of gate dielectrics is applied. At a given gate bias condition, a gradual increase in the drain bias enables a sensitive change in the interlayer resistance of ReS2, leading to a modification of the shape of the transconductance curves, and consequently, demonstrates the conducting channel migration along the thickness of ReS2 before the stress. Meanwhile, this distinct conduction feature disappears after stress, indicating the formation of additional oxide trap sites inside the gate dielectrics that degrade the carrier mobility and eventually restrict the channel migration. Our theoretical and experimental study based on the resistor network model and Thomas-Fermi charge screening theory provides further insights into the origins of channel migration and restriction in 2D multilayer devices.
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Recently, drone shows have impressed many people through a convergence of technology and art. However, these demonstrations have limited operating hours based on the battery life. Thus, it is important to minimize the unnecessary transition time between scenes without collision to increase operating time. This paper proposes a fast and energy-efficient scene transition algorithm that minimizes the transition times between scenes. This algorithm reduces the maximum drone movement distance to increase the operating time and exploits a multilayer method to avoid collisions between drones. In addition, a swarming flight system including robust communication and position estimation is presented as a concrete experimental system. The proposed algorithm was verified using the swarming flight system at a drone show performed with 100 drones.
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Hot carrier injection (HCI), occurring when the horizontal electric field is strongly applied, usually affects the degradation of nanoelectronic devices. In addition, metal contacts play a significant role in nanoelectronic devices. In this study, Schottky contacts in multilayer tungsten diselenide (WSe2) field-effect transistors (FETs) by hot carrier injection (HCI), occurring when a high drain voltage is applied, is investigated. A small number of hot carriers with high energy reduces the Schottky barrier height and improves the performance of FETs effectively rather than damaging the channel. Thermal annealing at the end of the fabrication process increases device performance by causing interfacial reactions of the source/drain electrodes. HCI causes a significant enhancement in the local asymmetry, especially in the subthreshold region. The subthreshold swing (SS) of the thermally annealed FETs is significantly improved from 9.66 to 0.562 V dec-1 through the energy of HCI generated by a strong horizontal electric field. In addition, the contact resistances (RSD), also called series resistances, extracted by a four-probe measurement and a Y-function method were also improved by decreasing to a 10th through the energy of HCI. To understand the asymmetrical characteristics of the channel after the stress, we performed electrical analysis, electrostatic force microscopy (EFM), and Raman spectroscopy.