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Towards realizing the future quantum internet1,2, a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive multi-node set-ups on large scales. Here we report the creation of memory-memory entanglement in a multi-node quantum network over a metropolitan area. We use three independent memory nodes, each of which is equipped with an atomic ensemble quantum memory3 that has telecom conversion, together with a photonic server where detection of a single photon heralds the success of entanglement generation. The memory nodes are maximally separated apart for 12.5 kilometres. We actively stabilize the phase variance owing to fibre links and control lasers. We demonstrate concurrent entanglement generation between any two memory nodes. The memory lifetime is longer than the round-trip communication time. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a stage of quantum internet research.
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Intermediary metabolism in cancer cells is regulated by diverse cell-autonomous processes, including signal transduction and gene expression patterns, arising from specific oncogenotypes and cell lineages. Although it is well established that metabolic reprogramming is a hallmark of cancer, we lack a full view of the diversity of metabolic programs in cancer cells and an unbiased assessment of the associations between metabolic pathway preferences and other cell-autonomous processes. Here, we quantified metabolic features, mostly from the 13C enrichment of molecules from central carbon metabolism, in over 80 non-small cell lung cancer (NSCLC) cell lines cultured under identical conditions. Because these cell lines were extensively annotated for oncogenotype, gene expression, protein expression, and therapeutic sensitivity, the resulting database enables the user to uncover new relationships between metabolism and these orthogonal processes.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral/metabolismo , Metaboloma/fisiologia , Biomarcadores Tumorais/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Regulação Neoplásica da Expressão Gênica/fisiologia , Glucose/metabolismo , Glutamina/metabolismo , Humanos , Redes e Vias Metabólicas/genética , Metabolômica/métodos , Neoplasias/metabolismoRESUMO
The perfluorocarbons tetrafluoromethane (CF4, PFC-14) and hexafluoroethane (C2F6, PFC-116) are potent greenhouse gases with near-permanent atmospheric lifetimes relative to human timescales and global warming potentials thousands of times that of CO2. Using long-term atmospheric observations from a Chinese network and an inverse modeling approach (top-down method), we determined that CF4 emissions in China increased from 4.7 (4.2-5.0, 68% uncertainty interval) Gg y-1 in 2012 to 8.3 (7.7-8.9) Gg y-1 in 2021, and C2F6 emissions in China increased from 0.74 (0.66-0.80) Gg y-1 in 2011 to 1.32 (1.24-1.40) Gg y-1 in 2021, both increasing by approximately 78%. Combined emissions of CF4 and C2F6 in China reached 78 Mt CO2-eq in 2021. The absolute increase in emissions of each substance in China between 2011-2012 and 2017-2020 was similar to (for CF4), or greater than (for C2F6), the respective absolute increase in global emissions over the same period. Substantial CF4 and C2F6 emissions were identified in the less-populated western regions of China, probably due to emissions from the expanding aluminum industry in these resource-intensive regions. It is likely that the aluminum industry dominates CF4 emissions in China, while the aluminum and semiconductor industries both contribute to C2F6 emissions. Based on atmospheric observations, this study validates the emission magnitudes reported in national bottom-up inventories and provides insights into detailed spatial distributions and emission sources beyond what is reported in national bottom-up inventories.
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Stereoconvergent reactions enable the transformation of mixed stereoisomers into well-defined, chiral productsâa crucial strategy for handling Z/E-mixed olefins, which are common but challenging substrates in organic synthesis. Herein, we report a stereoconvergent and highly enantioselective method for synthesizing Z-homoallylic alcohols via the nickel-catalyzed reductive coupling of Z/E-mixed 1,3-dienes with aldehydes. This process is enabled by an N-heterocyclic carbene ligand characterized by C2-symmetric backbone chirality and bulky 2,6-diisopropyl N-aryl substituents. Our method achieves excellent stereocontrol over both enantioselectivity and Z-selectivity in a single step, producing chiral Z-homoallylic alcohols that are valuable in natural products and pharmaceuticals.
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The PD-L1 protein on extracellular vesicles (EVs) is a promising biomarker for tumor immunotherapy. However, PD-L1+ EVs have various cell origins, so further analysis of the subpopulations is essential to help understand better their relationship with tumor immunotherapy. Different from the previous work which focus on the level of total PD-L1+ EVs expression, we, herein, report a dual-recognition mediated autocatalytic amplification (DRMAA) assay to detect the PD-L1 derived from tumors (EpCAM+), immune T cells (CD3+), and total (Lipids) EVs, respectively. The DRMAA assay employed proximity hybridization to construct a complete trigger sequence and then catalyzed the cross-hybridization of three hairpin probes, producing a three-way DNA junction (3-WJ) structure carrying the newly exposed trigger sequence. The 3-WJ complex subsequently initiated an autocatalytic amplification reaction and higher sensitivity than the traditional catalytic hairpin assembly assay was obtained. It was found that the EpCAM+ and PD-L1+ EVs were more effective than others in distinguishing lung cancer patients from healthy people. Surprisingly, the CD3+ and PD-L1+ EVs in lung cancer patients were also upregulated, indicating that immune cell-derived PD-L1+ EVs are also non-negligible marker in a tumor microenvironment. Our results suggested that the DRMAA assay would improve the study of subpopulations of PD-L1+ EVs to provide new insights for cancer immunotherapies.
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Antígeno B7-H1 , Vesículas Extracelulares , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Catálise , Molécula de Adesão da Célula Epitelial/metabolismo , Técnicas de Amplificação de Ácido Nucleico , Biomarcadores Tumorais , Hibridização de Ácido NucleicoRESUMO
Carbene transfer reactions have emerged as pivotal methodologies for the synthesis of complex molecular architectures. Heme protein-catalyzed carbene transfer reactions have shown promising results on model compounds. However, their limited substrate scope has hindered their application in natural product functionalization. Building upon the foundation of previously published work on a carbene transferase-myoglobin variant, this study employs computer-aided protein engineering to design myoglobin variants, using either docking or the deep learning-based LigandMPNN method. These variants were utilized as catalysts in carbene transfer reactions with a selection of monoterpene substrates featuring C-C double bonds, leading to seven target products. This cost-effective methodology broadens the substrate scope for heme protein-catalyzed reactions, thereby opening novel pathways for research in heme protein functionalities and offering fresh perspectives in the synthesis of bioactive molecules.
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Metano , Monoterpenos , Mioglobina , Mioglobina/química , Metano/química , Metano/análogos & derivados , Monoterpenos/química , Monoterpenos/metabolismo , Engenharia de Proteínas/métodos , Transferases/química , Transferases/metabolismo , Simulação de Acoplamento MolecularRESUMO
Light-induced heat has a non-negligible role in photocatalytic reactions. However, it is still challenging to design highly efficient catalysts that can make use of light and thermal energy synergistically. Herein, the study proposes a plasma super-photothermal S-scheme heterojunction core-shell nanoreactor based on manipulation of the driving factors, which consists of α-Fe2 O3 encapsulated by g-C3 N4 modified with gold quantum dots. α-Fe2 O3 can promote carrier spatial separation while also acting as a thermal core to radiate heat to the shell, while Au quantum dots transfer energetic electrons and heat to g-C3 N4 via surface plasmon resonance. Consequently, the catalytic activity of Au/α-Fe2 O3 @g-C3 N4 is significantly improved by internal and external double hot spots, and it shows an H2 evolution rate of 5762.35 µmol h-1 g-1 , and the selectivity of CO2 conversion to CH4 is 91.2%. This work provides an effective strategy to design new plasma photothermal catalysts for the solar-to-fuel transition.
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Low solar energy utilization efficiency and serious charge recombination remain major challenges for photocatalytic systems. Herein, a hollow core-shell Au/g-C3N4@Ag3PO4 photothermal nanoreactor is successfully prepared by a two-step deposition method. Benefit from efficient spectral utilization and fast charge separation induced by the unique hollow core-shell heterostructure, the H2 evolution rate of Au/g-C3N4@Ag3PO4 is 16.9 times that of the pristine g-C3N4, and the degradation efficiency of tetracycline is increased by 88.1%. The enhanced catalytic performance can be attributed to the ordered charge movement on the hollow core-shell structure and a local high-temperature environment, which effectively accelerates the carrier separation and chemical reaction kinetics. This work highlights the important role of the space confinement effect in photothermal catalysis and provides a promising strategy for the development of the next generation of highly efficient photothermal catalysts.
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BACKGROUND: Aurora kinase B (Aurora-B), a member of the chromosomal passenger complex (CPC), is involved in correcting kinetochore-microtubule (KT-MT) attachment errors and regulating sister chromatid condensation and cytoplasmic division during mitosis. SUMMARY: However, few reviews have discussed its mechanism in oocyte meiosis and the differences between its role in mitosis and meiosis. Therefore, in this review, we summarize the localization, recruitment, activation, and functions of Aurora-B in mitosis and oocyte meiosis. The accurate regulation of Aurora-B is essential for ensuring accurate chromosomal segregation and correct KT-MT attachments. Aurora-B regulates the stability of KT-MT attachments by competing with cyclin-dependent kinase 1 (CDK1) to control the phosphorylation of the SILK and RVSF motifs on kinetochore scaffold 1 and by competing with protein phosphatase 1 (PP1) to influence the phosphorylation of NDC80 which is the substrate of Aurora-B. In addition, Aurora-B regulates the spindle assembly checkpoint (SAC) by promoting the recruitment and activation of mitotic arrest deficient 2 (MAD2). KEY MESSAGES: This review provides a theoretical foundation for elucidating the mechanism of cell division and understanding oocyte chromosomal aneuploidy.
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Evidence suggests that neurometabolite alterations may be involved in the pathophysiology of autism spectrum disorders (ASDs). We performed a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies to examine the neurometabolite levels in the brains of patients with ASD. A systematic search of PubMed and Web of Science identified 54 studies for the meta-analysis. A random-effects meta-analysis demonstrated that compared with the healthy controls, patients with ASD had lower N-acetyl-aspartate-containing compound (NAA) and choline-containing compound (Cho) levels and NAA/(creatine-containing compound) Cr ratios in the gray matter and lower NAA and glutamate + glutamine (Glx) levels in the white matter. Furthermore, NAA and gamma-aminobutyric acid (GABA) levels, NAA/Cr ratios, and GABA/Cr ratios were significantly decreased in the frontal cortex of patients with ASD, whereas glutamate (Glu) levels were increased in the prefrontal cortex. Additionally, low NAA levels and GABA/Cr ratios in the temporal cortex, low NAA levels and NAA/Cr ratios in the parietal and dorsolateral prefrontal cortices, and low NAA levels in the cerebellum and occipital cortex were observed in patients with ASD. Meta-regression analysis revealed that age was positively associated with effect size in studies analyzing the levels of gray matter NAA and white matter Glx. Taken together, these results provide strong clinical evidence that neurometabolite alterations in specific brain regions are associated with ASD and age is a confounding factor for certain neurometabolite levels in patients with ASD.
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Transtorno do Espectro Autista , Humanos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Ácido Glutâmico , Ácido Aspártico , Colina , Ácido gama-AminobutíricoRESUMO
An efficient method for the first ene-reaction of 2-aryl-3H-indol-3-ones with allyltrimethylsilane has been developed for the first time. The reaction proceeded under the catalysis of Pd(OAc)2 and chiral phosphoric ligand L11 in the presence of Cu(CF3COO)2·XH2O, PivOH, and 5 Å molecular sieves in DMSO at 60 °C. The present methodology can avoid the impact of amine products generated by the reaction on the catalyst, and at the same time, the high catalytic activity of classical palladium catalysts still has catalytic ability for low electrophilic keto-imines. The desired products were furnished in excellent yields with good enantioselectivity.
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An efficient method for the synthesis of five-membered chiral propargylic amines from 2-aryl-3H-indol-3-one and alkynylsilanes has been developed. The reaction proceeded under the catalytic system of PtCl4, oxazoline-based ligand L11, Zn(CF3COO)2, and AcOH in DCE at 95 °C via in situ desilylation of TMS-alkynes. This methodology also highlights a new protocol for the in situ desilylation of alkynylsilanes. The reaction showed a broad substrate scope with good yields and enantioselectivity.
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1,1-Difluoroethane (HFC-152a) is a hydrofluorocarbon regulated by the Montreal Protocol, and its emissions in China are of concern as China will regulate HFC-152a in 2024. However, no observation-inferred top-down estimates were undertaken after 2017, and substantial gaps existed among previous estimates of China's HFC-152a emissions. Using the atmospheric observations and inverse modeling, this study reveals China's HFC-152a emissions of 9.4 ± 1.7 Gg/yr (gigagrams per year), 10.6 ± 1.8 Gg/yr, and 9.7 ± 1.5 Gg/yr in 2018, 2019, and 2020, respectively. In addition, we display an overall increasing trend during 2011-2020, which is in contrast to the decreasing and steady trend reported by the Emission Database for Global Atmospheric Research (EDGAR) and the Chinese government, respectively. Subsequently, we establish a comprehensive bottom-up emission inventory matching with top-down estimates and thus succeed in explaining the gaps among previous estimates. Furthermore, the contribution of China's emissions to global HFC-152a emission growth increased from 15% during 2001-2010 to >100% during 2011-2020. An emission projection based on our improved inventory shows that the Kigali Amendment (KA) would assist in avoiding 1535.6-4710.6 Gg (251.8-772.5 Tg CO2-eq) HFC-152a emissions during 2024-2100. Our findings indicate relatively accurate China's HFC-152a emissions and provide scientific support for addressing climate change and implementing the KA.
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Gases de Efeito Estufa , Ruanda , China , Mudança ClimáticaRESUMO
Hydrochlorofluorocarbons (HCFCs) are transitional substitutes for chlorofluorocarbons (CFCs). However, they still have the capacity to be ozone-depleting substances (ODSs). Therefore, they are scheduled to be phased out in China by 2030 under the Montreal Protocol. The emission estimates of HCFC-22 (CHClF2) and HCFC-142b (CH3CClF2) in China using atmospheric observations are lacking after 2017, making it hard to understand the effectiveness of the phase-out process of HCFCs in China. Here, we use flask and in situ measurements of HCFC-22 and HCFC-142b during 2018-2021 and inverse modeling to determine the emission magnitude and changes in China. It was determined that China's emissions were 172 ± 40, 154 ± 39, 160 ± 22, and 155 ± 33 Gg yr-1 of HCFC-22 and 8.3 ± 1.8, 7.8 ± 1.6, 7.4 ± 1.7, and 7.9 ± 1.7 Gg yr-1 of HCFC-142b from 2018 to 2021, respectively. Top-down estimates show that HCFC-22 emissions in China were stable, while HCFC-142b emissions were decreasing during 2013-2021, although both substances were in the stage of being phased out during 2013-2021. This study reveals that 46 and 39% of the global HCFC-22 and HCFC-142b emissions, respectively, cannot be traced to certain countries in 2020. We suggest that more studies on HCFC emissions around the world in the future are needed to better safeguard the ozone layer recovery and climate mitigation by ensuring compliance with the Montreal Protocol during HCFC phase-out processes.
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Global atmospheric emissions of perfluorocyclobutane (c-C4F8, PFC-318), a potent greenhouse gas, have increased rapidly in recent years. Combining atmospheric observations made at nine Chinese sites with a Lagrangian dispersion model-based Bayesian inversion technique, we show that PFC-318 emissions in China grew by approximately 70% from 2011 to 2020, rising from 0.65 (0.54-0.72) Gg year-1 in 2011 to 1.12 (1.05-1.19) Gg year-1 in 2020. The PFC-318 emission increase from China played a substantial role in the overall increase in global emissions during the study period, contributing 58% to the global total emission increase. This growth predominantly originated in eastern China. The regions with high emissions of PFC-318 in China overlap with areas densely populated with polytetrafluoroethylene (PTFE) factories, implying that fluoropolymer factories are important sources of PFC-318 emissions in China. Our investigation reveals an emission factor of approximately 3.02 g of byproduct PFC-318 emissions per kg of hydrochlorofluorocarbon-22 (HCFC-22) feedstock use in the production of tetrafluoroethylene (TFE) (for PTFE production) and hexafluoropropylene (HFP) if we assume all HCFC-22 produced for feedstock uses in China are pyrolyzed to produce PTFE and HFP. Further facility-level sampling and analysis are needed for a more precise evaluation of emissions from these factories.
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Poluentes Atmosféricos , Atmosfera , China , Poluentes Atmosféricos/análise , Atmosfera/química , Monitoramento Ambiental , Fluorocarbonos/análise , Teorema de Bayes , Politetrafluoretileno , CiclobutanosRESUMO
INTRODUCTION: This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs). METHODS: A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses. RESULTS: The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0-15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341-0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157-0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041-8.677, p = 0.042). CONCLUSION: The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14-15 Gy were recommended. Further studies are required to validate our findings.
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Hemangioma Cavernoso do Sistema Nervoso Central , Malformações Arteriovenosas Intracranianas , Radiocirurgia , Adulto , Feminino , Humanos , Tronco Encefálico/cirurgia , Seguimentos , Hemangioma Cavernoso do Sistema Nervoso Central/radioterapia , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemorragia/complicações , Hemorragia/cirurgia , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Resultado do Tratamento , MasculinoRESUMO
PURPOSE: Extracorporeal cardiopulmonary resuscitation (ECPR) might markedly increase the survival of selected patients with refractory cardiac arrest. But the application situation and indications remained unclear. MATERIALS AND METHODS: We respectively reviwed all adult patients who underwent ECPR from January 2017 to March 2021. Patient characteristics, initiation and management of ECMO, complications, and outcomes were collected and compared between the survivors and nonsurvivors. LASSO regression was used to screen risk factors. Multivariate logistic regression was performed with several parameters screened by LASSO regression. RESULTS: Data were reported from 42 ECMO centers covering 19 provinces of China. A total of 648 patients were included in the study, including 491 (75.8%) males. There were 11 ECPR centers in 2017, and the number increased to 42 in 2020. The number of patients received ECPR increased from 33 in 2017 to 274 in 2020, and the survival rate increased from 24.2% to 33.6%. Neurological complications, renal replacement therapy, epinephrine dosage after ECMO, recovery of spontaneous circulation before ECMO, lactate clearance and shockable rhythm were risk factors independently associated with outcomes of whole process. Sex, recovery of spontaneous circulation before ECMO, lactate, shockable rhythm and causes of arrest were pre-ECMO risk factors independently affecting outcomes. CONCLUSIONS: From January 2017 to March 2021, the numbers of ECPR centers and cases in mainland China increased gradually over time, as well as the survival rate. Pre-ECMO risk factors, especially recovery of spontaneous circulation before ECMO, shockable rhythm and lactate, are as important as post-ECMO management,. Neurological complications are vital risk factors after ECMO that deserved close attention. TRIAL REGISTRATION: NCT04158479, registered on 2019/11/08. https://clinicaltrials.gov/NCT04158479.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Humanos , Masculino , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , China/epidemiologia , Feminino , Estudos Retrospectivos , Reanimação Cardiopulmonar/métodos , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Parada Cardíaca/terapia , Parada Cardíaca/epidemiologia , Parada Cardíaca/mortalidade , Taxa de Sobrevida , IdosoRESUMO
We replicated and extended the findings of Yao et al. [(2018). Differential emotional processing in concrete and abstract words. Journal of Experimental Psychology: Learning, Memory, and Cognition, 44(7), 1064-1074] regarding the interaction of emotionality, concreteness, and imageability in word processing by measuring eye fixation times on target words during normal reading. A 3 (Emotion: negative, neutral, positive) × 2 (Concreteness: abstract, concrete) design was used with 22 items per condition, with each set of six target words matched across conditions in terms of word length and frequency. Abstract (e.g. shocking, reserved, fabulous) and concrete (e.g. massacre, calendar, treasure) target words appeared (separately) within contextually neutral, plausible sentences. Sixty-three participants each read all 132 experimental sentences while their eye movements were recorded. Analyses using Gamma generalised linear mixed models revealed significant effects of both Emotion and Concreteness on all fixation measures, indicating faster processing for emotional and concrete words. Additionally, there was a significant Emotion × Concreteness interaction which, critically, was modulated by Imageability in early fixation time measures. Emotion effects were significantly larger in higher-imageability abstract words than in lower-imageability ones, but remained unaffected by imageability in concrete words. These findings support the multimodal induction hypothesis and highlight the intricate interplay of these factors in the immediate stages of word processing during fluent reading.
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This study explores the important role of assessing force levels in accurately controlling upper limb movements in human-computer interfaces. It uses a new method that combines entropy to improve the recognition of force levels. This research aims to differentiate between different levels of isometric contraction forces using electroencephalogram (EEG) signal analysis. It integrates eight different entropy measures: power spectrum entropy (PSE), singular spectrum entropy (SSE), logarithmic energy entropy (LEE), approximation entropy (AE), sample entropy (SE), fuzzy entropy (FE), alignment entropy (PE), and envelope entropy (EE). The findings emphasize two important advances: first, including a wide range of entropy features significantly improves classification efficiency; second, the fusion entropy method shows exceptional accuracy in classifying isometric contraction forces. It achieves an accuracy rate of 91.73% in distinguishing between 15% and 60% maximum voluntary contraction (MVC) forces, along with 69.59% accuracy in identifying variations across 15%, 30%, 45%, and 60% MVC. These results illuminate the efficacy of employing fusion entropy in EEG signal analysis for isometric contraction detection, heralding new opportunities for advancing motor control and facilitating fine motor movements through sophisticated human-computer interface technologies.
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Eletroencefalografia , Contração Isométrica , Humanos , Entropia , Movimento , Reconhecimento PsicológicoRESUMO
The neural mechanisms of inner speech remain unclear despite its importance in a variety of cognitive processes and its implication in aberrant perceptions such as auditory verbal hallucinations. Previous research has proposed a corollary discharge model in which inner speech is a truncated form of overt speech, relying on speech production-related regions (e.g. left inferior frontal gyrus). This model does not fully capture the diverse phenomenology of inner speech and recent research suggesting alternative perception-related mechanisms of generation. Therefore, we present and test a framework in which inner speech can be generated by two separate mechanisms, depending on its phenomenological qualities: a corollary discharge mechanism relying on speech production regions and a perceptual simulation mechanism within speech perceptual regions. The results of the activation likelihood estimation meta-analysis examining inner speech studies support the idea that varieties of inner speech recruit different neural mechanisms.