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Heat dissipation is a natural consequence of operating any electronic system. In nearly all computing systems, such heat is usually minimized by design and cooling. Here, we show that the temporal dynamics of internally produced heat in electronic devices can be engineered to both encode information within a single device and process information across multiple devices. In our demonstration, electronic NbOx Mott neurons, integrated on a flexible organic substrate, exhibit 18 biomimetic neuronal behaviours and frequency-based nociception within a single component by exploiting both the thermal dynamics of the Mott transition and the dynamical thermal interactions with the organic substrate. Further, multiple interconnected Mott neurons spatiotemporally communicate purely via heat, which we use for graph optimization by consuming over 106 times less energy when compared with the best digital processors. Thus, exploiting natural thermal processes in computing can lead to functionally dense, energy-efficient and radically novel mixed-physics computing primitives.
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The RNA modification N6-methyladenosine (m6A) regulates the interaction between RNA and various RNA binding proteins within the nucleus and other subcellular compartments and has recently been shown to be involved in experience-dependent plasticity, learning, and memory. Using m6A RNA-sequencing, we have discovered a distinct population of learning-related m6A- modified RNAs at the synapse, which includes the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1). RNA immunoprecipitation and mass spectrometry revealed 12 new synapse-specific learning-induced m6A readers in the mPFC of male C57/BL6 mice, with m6A-modified Malat1 binding to a subset of these, including CYFIP2 and DPYSL2. In addition, a cell type- and synapse-specific, and state-dependent, reduction of m6A on Malat1 impairs fear-extinction memory; an effect that likely occurs through a disruption in the interaction between Malat1 and DPYSL2 and an associated decrease in dendritic spine formation. These findings highlight the critical role of m6A in regulating the functional state of RNA during the consolidation of fear-extinction memory, and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.SIGNIFICANCE STATEMENT We have discovered that learning-induced m6A-modified RNA (including the long noncoding RNA, Malat1) accumulates in the synaptic compartment. We have identified several new m6A readers that are associated with fear extinction learning and demonstrate a causal relationship between m6A-modified Malat1 and the formation of fear-extinction memory. These findings highlight the role of m6A in regulating the functional state of an RNA during memory formation and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.
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Miedo , ARN Largo no Codificante , Animales , Masculino , Ratones , Extinción Psicológica , Miedo/fisiología , Aprendizaje/fisiología , ARN Largo no Codificante/metabolismo , Sinapsis/metabolismoRESUMEN
NbOx-based Mott memristors exhibit fast threshold switching behaviors, making them suitable for spike generators in neuromorphic computing and stochastic clock generators in security devices. In these applications, a high output spike amplitude is necessary for threshold level control and accurate signal detection. Here, we propose a materialwise solution to obtain the high amplitude spikes by inserting Au nanodots into the NbOx device. The Au nanodots enable increasing the threshold voltage by modulating the oxygen contents at the electrode-oxide interface, providing a higher ON current compared to nanodot-free NbOx devices. Also, the reduction of the local switching region volume decreases the thermal capacitance of the system, allowing the maximum spike amplitude generation. Consequently, the Au nanodot incorporation increases the spike amplitude of the NbOx device by 6 times, without any additional external circuit elements. The results are systematically supported by both a numerical model and a finite-element-method-based multiphysics model.
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BACKGROUND: Computational analysis of complex diseases involving multiple organs requires the integration of multiple different models into a unified model. Different models are often constructed in heterogeneous formats. Thus, the integration of the models requires a standard language format that can effectively represent essential biological information. However, the previously introduced formats have limitations that prevent from adequately representing essential biological information, particularly specifications of bio-molecules and biological contexts. RESULTS: We defined an XML-based markup language called context-oriented directed association markup language (CODA-ML), which better represents essential biological information. The CODA-ML has two major strengths in designating molecular specifications and biological contexts. It can cover heterogeneous entity types involved in biological events (e.g. gene/protein, compound, cellular function, disease). Molecular types of entities can have molecular specifications which include detailed information of a molecule from isoforms to modifications, enabling high-resolution representation of molecules. In addition, it can distinguish biological events that vary depending on different biological contexts such as cell types or disease conditions. Especially representation of inter-cellular events as well as intra-cellular events is available. These two major strengths can resolve contradictory associations when different models are integrated into one unified model, which improves the accuracy of the model. CONCLUSIONS: With the CODA-ML, diverse models such as signaling pathways, metabolic pathways, and gene regulatory pathways can be represented in a unified language format. Heterogeneous entity types can be covered by the CODA-ML, thus it enables detailed description for the mechanisms of diseases or drugs from multiple perspectives (e.g., molecule, function or disease). The CODA-ML is expected to help integrate different models into one systemic model in an efficient and effective. The unified model can be used to perform computational analysis not only for cancer but also for other complex diseases involving multiple organs beyond a single cell.
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Conocimiento , Fisiología , Programas Informáticos , Humanos , Lenguaje , Modelos BiológicosRESUMEN
Artificial intelligence (AI) is often considered a black box because it provides optimal answers without clear insight into its decision-making process. To address this black box problem, explainable artificial intelligence (XAI) has emerged, which provides an explanation and interpretation of its decisions, thereby promoting the trustworthiness of AI systems. Here, a memristive XAI hardware framework is presented. This framework incorporates three distinct types of memristors (Mott memristor, valence change memristor, and charge trap memristor), each responsible for performing three essential functions (perturbation, analog multiplication, and integration) required for the XAI hardware implementation. Three memristor arrays with high robustness are fabricated and the image recognition of 3 × 3 testing patterns and their explanation map generation are experimentally demonstrated. Then, a software-based extended system based on the characteristics of this hardware is built, simulating a large-scale image recognition task. The proposed system can perform the XAI operations with only 4.32% of the energy compared to conventional digital systems, enlightening its strong potential for the XAI accelerator.
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Insects can efficiently perform object motion detection via a specialized neural circuit, called an elementary motion detector (EMD). In contrast, conventional machine vision systems require significant computational resources for dynamic motion processing. Here, a fully memristive EMD (M-EMD) is presented that implements the Hassenstein-Reichardt (HR) correlator, a biological model of the EMD. The M-EMD consists of a simple Wye (Y) configuration, including a static resistor, a dynamic memristor, and a Mott memristor. The resistor and dynamic memristor introduce different signal delays, enabling spatio-temporal signal integration in the subsequent Mott memristor, resulting in a direction-selective response. In addition, a neuromorphic system is developed employing the M-EMDs to predict a lane-changing maneuver by vehicles on the road. The system achieved a high accuracy (> 87%) in predicting future lane-changing maneuvers on the Next Generation Simulation (NGSIM) dataset while reducing the computational cost by 92.9% compared to the conventional neuromorphic system without the M-EMD, suggesting its strong potential for edge-level computing.
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Identifying molecular targets of a drug is an essential process for drug discovery and development. The recent in-silico approaches are usually based on the structure information of chemicals and proteins. However, 3D structure information is hard to obtain and machine-learning methods using 2D structure suffer from data imbalance problem. Here, we present a reverse tracking method from genes to target proteins using drug-perturbed gene transcriptional profiles and multilayer molecular networks. We scored how well the protein explains gene expression changes perturbed by a drug. We validated the protein scores of our method in predicting known targets of drugs. Our method performs better than other methods using the gene transcriptional profiles and shows the ability to suggest the molecular mechanism of drugs. Furthermore, our method has the potential to predict targets for objects that do not have rigid structural information, such as coronavirus.
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Aprendizaje Automático , Transcriptoma , Transcriptoma/genética , Descubrimiento de Drogas/métodos , Proteínas/química , Redes Reguladoras de GenesRESUMEN
This paper reviews the currently used pretreatment methods for microplastics (MPs) analysis in soil and freshwater sediments, primarily sample processing, pretreatment, and characterization methods for MPs analysis. In addition, analytical tools (e.g., lab instruments), MPs characteristics, and MPs quantity, are included in this review. Prior to pretreatment, soil and sediment samples are typically processed using sieving and drying methods, and a sample quantity of <50 g was mostly used for the pretreatment. Density separation was commonly performed before organic matter removal. Sodium chloride (NaCl) and zinc chloride (ZnCl2) were most often used for density separation, and hydrogen peroxide (H2O2) oxidation was most frequently used to remove organic matter. Although advantages of each pretreatment method have been investigated, it is still challenging to determine a universal pretreatment method due to sample variability (e.g., sample characteristics). Furthermore, it is highly required to establish standard pretreatment methods that can be used for various environmental matrices, including air, water, and wastes as well as soil and sediment.
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Energy-based computing is a promising approach for addressing the rising demand for solving NP-hard problems across diverse domains, including logistics, artificial intelligence, cryptography, and optimization. Probabilistic computing utilizing pbits, which can be manufactured using the semiconductor process and seamlessly integrated with conventional processing units, stands out as an efficient candidate to meet these demands. Here, we propose a novel pbit unit using an NbOx volatile memristor-based oscillator capable of generating probabilistic bits in a self-clocking manner. The noise-induced metal-insulator transition causes the probabilistic behavior, which can be effectively modeled using a multi-noise-induced stochastic process around the metal-insulator transition temperature. We demonstrate a memristive Boltzmann machine based on our proposed pbit and validate its feasibility by solving NP-hard problems. Furthermore, we propose a streamlined operation methodology that considers the autocorrelation of individual bits, enabling energy-efficient and high-performance probabilistic computing.
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Discovering new bioactivities and identifying active compounds of food materials are major fields of study in food science. However, the process commonly requires extensive experiments and can be technically challenging. In the current study, we employed network biology and cheminformatic approaches to predict new target diseases, active components, and related molecular mechanisms of propolis. Applying UHPLC-MS/MS analysis results of propolis to Context-Oriented Directed Associations (CODA) and Combination-Oriented Natural Product Database with Unified Terminology (COCONUT) systems indicated atopic dermatitis as a novel target disease. Experimental validation using cell- and human tissue-based models confirmed the therapeutic potential of propolis against atopic dermatitis. Moreover, we were able to find the major contributing compounds as well as their combinatorial effects responsible for the bioactivity of propolis. The CODA/COCONUT system also provided compound-associated genes explaining the underlying molecular mechanism of propolis. These results highlight the potential use of big data-driven network biological approaches to aid in analyzing the impact of food constituents at a systematic level.
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Ascomicetos , Dermatitis Atópica , Própolis , Humanos , Própolis/farmacología , Quimioinformática , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem , CocosRESUMEN
In silico profiling is used in identification of active compounds and guide rational use of traditional medicines. Previous studies on Ethiopian indigenous aloes focused on documentation of phytochemical compositions and traditional uses. In this study, ADMET and drug-likeness properties of phytochemicals from Ethiopian indigenous aloes were evaluated, and pharmacophore-based profiling was done using Discovery Studio to predict therapeutic targets. The targets were examined using KEGG pathway, gene ontology and network analysis. Using random-walk with restart algorithm, network propagation was performed in CODA network to find diseases associated with the targets. As a result, 82 human targets were predicted and found to be involved in several molecular functions and biological processes. The targets also were linked to various cancers and diseases of immune system, metabolism, neurological system, musculoskeletal system, digestive system, hematologic, infectious, mouth and dental, and congenital disorder of metabolism. 207 KEGG pathways were enriched with the targets, and the main pathways were metabolism of steroid hormone biosynthesis, lipid and atherosclerosis, chemical carcinogenesis, and pathways in cancer. In conclusion, in silico target fishing and network analysis revealed therapeutic activities of the phytochemicals, demonstrating that Ethiopian indigenous aloes exhibit polypharmacology effects on numerous genes and signaling pathways linked to many diseases.
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Aloe , Medicamentos Herbarios Chinos , Humanos , Farmacóforo , Transducción de Señal , Fitoquímicos/farmacología , Fitoquímicos/química , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
A memristive stateful neural network allowing complete Boolean in-memory computing attracts high interest in future electronics. Various Boolean logic gates and functions demonstrated so far confirm their practical potential as an emerging computing device. However, spatio-temporal efficiency of the stateful logic is still too limited to replace conventional computing technologies. This study proposes a ternary-state memristor device (simply a ternary memristor) for application to ternary stateful logic. The ternary-state implementable memristor device is developed with bilayered tantalum oxide by precisely controlling the oxygen content in each oxide layer. The device can operate 157 ternary logic gates in one operational clock, which allows an experimental demonstration of a functionally complete three-valued Lukasiewicz logic system. An optimized logic cascading strategy with possible ternary gates is ≈20% more efficient than conventional binary stateful logic, suggesting it can be beneficial for higher performance in-memory computing.
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Valence change-type resistance switching behaviors in oxides can be understood by well-established physical models describing the field-driven oxygen vacancy distribution change. In those models, electroformed residual oxygen vacancy filaments are crucial as they work as an electric field concentrator and limit the oxygen vacancy movement along the vertical direction. Therefore, their movement outward by diffusion is negligible. However, this situation may not be applicable in the electroforming-free system, where the field-driven movement is less prominent, and the isotropic oxygen vacancy diffusion by concentration gradient is more significant, which has not been given much consideration in the conventional model. Here, we propose a modified physical model that considers the change in the oxygen vacancies' charged state depending on their concentrations and the resulting change in diffusivity during switching to interpret the electroforming-free device behaviors. The model suggests formation of an hourglass-shaped filament constituting a lower concentration of oxygen vacancies due to the fluid oxygen diffusion in the thin oxide. Consequently, the proposed model can explain the electroforming-free device behaviors, including the retention failure mechanism, and suggest an optimized filament configuration for improved retention characteristics. The proposed model can plausibly explain both the electroformed and the electroforming-free devices. Therefore, it can be a standard model for valence change memristors.
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The intrinsic stochasticity of the memristor can be used to generate true random numbers, essential for non-decryptable hardware-based security devices. Here, we propose a novel and advanced method to generate true random numbers utilizing the stochastic oscillation behavior of a NbOx mott memristor, exhibiting self-clocking, fast and variation tolerant characteristics. The random number generation rate of the device can be at least 40 kb s-1, which is the fastest record compared with previous volatile memristor-based TRNG devices. Also, its dimensionless operating principle provides high tolerance against both ambient temperature variation and device-to-device variation, enabling robust security hardware applicable in harsh environments.