RESUMO
It has long been assumed that lifespan and healthspan correlate strongly, yet the two can be clearly dissociated1-6. Although there has been a global increase in human life expectancy, increasing longevity is rarely accompanied by an extended healthspan4,7. Thus, understanding the origin of healthy behaviours in old people remains an important and challenging task. Here we report a conserved epigenetic mechanism underlying healthy ageing. Through genome-wide RNA-interference-based screening of genes that regulate behavioural deterioration in ageing Caenorhabditis elegans, we identify 59 genes as potential modulators of the rate of age-related behavioural deterioration. Among these modulators, we found that a neuronal epigenetic reader, BAZ-2, and a neuronal histone 3 lysine 9 methyltransferase, SET-6, accelerate behavioural deterioration in C. elegans by reducing mitochondrial function, repressing the expression of nuclear-encoded mitochondrial proteins. This mechanism is conserved in cultured mouse neurons and human cells. Examination of human databases8,9 shows that expression of the human orthologues of these C. elegans regulators, BAZ2B and EHMT1, in the frontal cortex increases with age and correlates positively with the progression of Alzheimer's disease. Furthermore, ablation of Baz2b, the mouse orthologue of BAZ-2, attenuates age-dependent body-weight gain and prevents cognitive decline in ageing mice. Thus our genome-wide RNA-interference screen in C. elegans has unravelled conserved epigenetic negative regulators of ageing, suggesting possible ways to achieve healthy ageing.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Epigênese Genética , Envelhecimento Saudável/genética , Histona-Lisina N-Metiltransferase/metabolismo , Fatores Genéricos de Transcrição/metabolismo , Envelhecimento/genética , Animais , Proteínas de Caenorhabditis elegans/genética , Cognição , Disfunção Cognitiva , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/genética , Histonas/química , Histonas/metabolismo , Humanos , Longevidade/genética , Lisina/metabolismo , Masculino , Memória , Metilação , Camundongos , Mitocôndrias/metabolismo , Neurônios/metabolismo , Proteínas/genética , Interferência de RNA , Aprendizagem Espacial , Fatores Genéricos de Transcrição/deficiência , Fatores Genéricos de Transcrição/genéticaRESUMO
Grain size is one of the important traits in wheat breeding programs aimed at improving yield, and cytokinins, mainly involved in cell division, have a positive impact on grain size. Here, we identified a novel wheat gene TaMADS-GS encoding type I MADS-box transcription factor, which regulates the cytokinins signalling pathway during early stages of grain development to modulate grain size and weight in wheat. TaMADS-GS is exclusively expressed in grains at early stage of seed development and its knockout leads to delayed endosperm cellularization, smaller grain size and lower grain weight. TaMADS-GS protein interacts with the Polycomb Repressive Complex 2 (PRC2) and leads to repression of genes encoding cytokinin oxidase/dehydrogenases (CKXs) stimulating cytokinins inactivation by mediating accumulation of the histone H3 trimethylation at lysine 27 (H3K27me3). Through the screening of a large wheat germplasm collection, an elite allele of the TaMADS-GS exhibits higher ability to repress expression of genes inactivating cytokinins and a positive correlation with grain size and weight, thus representing a novel marker for breeding programs in wheat. Overall, these findings support the relevance of TaMADS-GS as a key regulator of wheat grain size and weight.
Assuntos
Endosperma , Fatores de Transcrição , Fatores de Transcrição/genética , Endosperma/metabolismo , Triticum/metabolismo , Melhoramento Vegetal , Grão Comestível , Citocininas/metabolismo , Regulação da Expressão Gênica de Plantas/genéticaRESUMO
In wheat (Triticum aestivum L.), breeding efforts have focused intensively on improving grain yield and quality. For quality, the content and composition of seed storage proteins (SSPs) determine the elasticity of wheat dough and flour processing quality. Moreover, starch levels in seeds are associated with yield. However, little is known about the mechanisms that coordinate SSP and starch accumulation in wheat. In this study, we explored the role of the endosperm-specific NAC transcription factor TaNAC019 in coordinating SSP and starch accumulation. TaNAC019 binds to the promoters of TaGlu-1 loci, encoding high molecular weight glutenin (HMW-GS), and of starch metabolism genes. Triple knock-out mutants of all three TaNAC019 homoeologs exhibited reduced transcript levels for all SSP types and genes involved in starch metabolism, leading to lower gluten and starch contents, and in flour processing quality parameters. TaNAC019 directly activated the expression of HMW-GS genes by binding to a specific motif in their promoters and interacting with the TaGlu-1 regulator TaGAMyb. TaNAC019 also indirectly regulated the expression of TaSPA, an ortholog of maize Opaque2 that activates SSP accumulation. Therefore, TaNAC019 regulation of starch- and SSP-related genes has key roles in wheat grain quality. Finally, we identified an elite allele (TaNAC019-BI) associated with flour processing quality, providing a candidate gene for breeding wheat with improved quality.
Assuntos
Endosperma/metabolismo , Proteínas de Plantas/metabolismo , Amido/metabolismo , Fatores de Transcrição/metabolismo , Alelos , Endosperma/genética , Glutens/genética , Glutens/metabolismo , Proteínas de Plantas/genética , Amido/genética , Fatores de Transcrição/genética , Triticum/genética , Triticum/metabolismoRESUMO
KEY MESSAGE: This study precisely mapped and validated a quantitative trait locus (QTL) located on chromosome 4B for flag leaf angle in wheat. Flag leaf angle (FLANG) is closely related to crop architecture and yield. We previously identified the quantitative trait locus (QTL) QFLANG-4B for FLANG on chromosome 4B, located within a 14-cM interval flanked by the markers Xbarc20 and Xzyh357, using a mapping population of recombinant inbred lines (RILs) derived from a cross between Nongda3331 (ND3331) and Zang1817. In this study, we fine-mapped QFLANG-4B and validated its associated genetic effect. We developed a BC3F3 population using ND3331 as the recurrent parent through marker-assisted selection, as well as near-isogenic lines (NILs) by selfing BC3F3 plants carrying different heterozygous segments for the QFLANG-4B region. We obtained eight recombinant types for QFLANG-4B, narrowing its location down to a 5.3-Mb region. This region contained 76 predicted genes, 7 of which we considered to be likely candidate genes for QFLANG-4B. Marker and phenotypic analyses of individual plants from the secondary mapping populations and their progeny revealed that the FLANG of the ND3331 allele is significantly higher than that of the Zang1817 allele in multiple environments. These results not only provide a basis for the map-based cloning of QFLANG-4B, but also indicate that QFLANG-4B has great potential for marker-assisted selection in wheat breeding programs designed to improve plant architecture and yield.
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Mapeamento Cromossômico , Folhas de Planta , Locos de Características Quantitativas , Triticum , Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Genes de Plantas , Ligação Genética , Marcadores Genéticos , Fenótipo , Melhoramento Vegetal , Folhas de Planta/anatomia & histologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Triticum/genética , Triticum/crescimento & desenvolvimento , Triticum/anatomia & histologiaRESUMO
Antibacterial theranostic nanoplatforms, which integrate diagnostic and therapeutic properties, exhibit gigantic application prospects in precision medicine. However, traditional theranostic nanoplatforms usually present an always-on signal output, which leads to poor specificity or selectivity in the treatment of bacterial infections. To address this challenge, stimuli-actuated turn-on nanoplatforms are developed for simultaneous activation of diagnostic signals (e.g., fluorescent, photoacoustic, magnetic signals) and initiation of antibacterial treatment. Specifically, by combining the infection microenvironment-responsive activation of visual signals and antibacterial activity, these theranostic nanoplatforms exert both higher accurate diagnosis rates and more effective treatment effects. In this review, the imaging and treatment strategies that are commonly used in the clinic are first briefly introduced. Next, the recent progress of stimuli-actuated turn-on theranostic nanoplatforms for treating bacterial infectious diseases is summarized in detail. Finally, current bottlenecks and future opportunities of antibacterial theranostic nanoplatforms are also outlined and discussed.
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Neoplasias , Medicina de Precisão , Humanos , Nanomedicina Teranóstica/métodos , Diagnóstico por Imagem , Neoplasias/tratamento farmacológico , Microambiente TumoralRESUMO
KEY MESSAGE: We identified ten QTLs controlling SDS-SV trait in a RIL population derived from ND3331 and Zang1817. Pinb-D1p is an elite allele from Tibetan semiwild wheat for good end-use quality. Gluten strength is an important factor for wheat processing and end-product quality and is commonly characterized using the sodium dodecyl sulfate-sedimentation volume (SDS-SV) test. The objective of this study was to identify quantitative trait loci (QTLs) associated with wheat SDS-SV traits using a recombinant inbred line (RIL) population derived from common wheat line NongDa3331 (ND3331) and Tibetan semi-wild wheat accession Zang1817. We detected 10 QTLs controlling SDS-SV on chromosomes 1A, 1B, 3A, 4A, 4B, 5A, 5D, 6B and 7A, with individual QTLs explaining 2.02% to 15.53% of the phenotypic variation. They included four major QTLs, Qsdss-1A, Qsdss-1B.1, Qsdss-1B.2, and Qsdss-5D, whose effects on SDS-SV were due to the Glu-A1 locus encoding the high-molecular-weight glutenin subunit 1Ax1, the 1B/1R translocation, 1Bx7 + 1By8 at the Glu-B1 locus, and the hardness-controlling loci Pina-D1 and Pinb-D1, respectively. We developed KASP markers for the Glu-A1, Glu-B1, and Pinb-D1 loci. Importantly, we showed for the first time that the hardness allele Pinb-D1p positively affects SDS-SV, making it a good candidate for wheat quality improvement. These results broaden our understanding of the genetic characterization of SDS-SV, and the QTLs identified are potential target regions for fine-mapping and marker-assisted selection in wheat breeding programs.
Assuntos
Melhoramento Vegetal , Triticum , Triticum/genética , Locos de Características Quantitativas , Alelos , FenótipoRESUMO
A one-dimensional (1D) unsteady and viscous flow model that is derived from the momentum and mass conservation equations is described, and to enhance this physics-based model, a machine learning approach is used to determine the unknown modeling parameters. Specifically, an idealized larynx model is constructed and ten cases of three-dimensional (3D) fluid-structure interaction (FSI) simulations are performed. The flow data are then extracted to train the 1D flow model using a sparse identification approach for nonlinear dynamical systems. As a result of training, we obtain the analytical expressions for the entrance effect and pressure loss in the glottis, which are then incorporated in the flow model to conveniently handle different glottal shapes due to vocal fold vibration. We apply the enhanced 1D flow model in the FSI simulation of both idealized vocal fold geometries and subject-specific anatomical geometries reconstructed from the magnetic resonance imaging images of rabbits' larynges. The 1D flow model is evaluated in both of these setups and shown to have robust performance. Therefore, it provides a fast simulation tool that is superior to the previous 1D models.
Assuntos
Vibração , Prega Vocal , Animais , Glote , Aprendizado de Máquina , Modelos Biológicos , Fonação , CoelhosRESUMO
BACKGROUND: Drug resistance to 5-fluorouracil (5-FU) and recurrence after chemotherapy in colorectal cancer remain a challenge to be resolved for the improvement of patient outcomes. It is recognized that a variety of secretory proteins released from the tumor cells exposed to chemo-drugs into the tumor microenvironment (TME) contributed to the cell-to-cell communication, and altered the drug sensitivity. One of these important factors is osteopontin (OPN), which exists in several functional forms from alternative splicing and post-translational processing. In colon cancer cells, increased total OPN expression was observed during the progression of tumors, however, the exact role and regulation of the OPN splicing isoforms was not well understood. METHODS: We assayed precisely the abundance of major OPN splicing isoforms under 5-FU treatments in colon cancer cell lines with different sensitivities to 5-FU, and also evaluated the effects of the condition medium from OPN splicing isoforms overexpressed cells on cell functions. The methods of nuclear calcium reporter assays and ChIP (chromatin immunoprecipitation) assays were used to investigate the molecular mechanism underlining the production of OPN isoforms. RESULTS: We discovered that OPNc was a most increased splicing isoform to a significant abundance following 5-FU treatment of colon cancer cells. OPNc as a secretory protein in the conditioned medium exerted a more potent effect to promote cell survival in 5-FU than other OPN isoforms. The kinetic response of nuclear calcium signals could be used to indicate an immediate effect of the conditioned medium containing OPNc and other isoforms. Methyl-CpG binding protein 2 (MeCP2) was identified to regulate the splicing of opn gene, where the phosphorylation of MeCP2 at S421 site, possibly by calmodulin dependent protein kinase II (CaMKII) was required. CONCLUSIONS: The results demonstrated that the production of OPNc was highly controlled under epigenetic regulations, where MeCP2 and the activation of nuclear calcium signaling were involved. It was also suggested that OPNc could transmit the stress signal of cells upon chemotherapy in TME and promoted the survival of adjacent colon cancer cells.
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BACKGROUND: Na+/H+ exchanger regulatory factor 1 (NHERF1) is an important scaffold protein participates in the modulation of a variety of intracellular signal pathways. NHERF1 was able to enhance the effects of chemo-drugs in breast and cervical cancer cells. Anaplastic lymphoma kinase (ALK) fusion mutations are validated molecules targeted therapy in lung cancers, where crizotinib can be used as the specific inhibitor to suppress tumor progression. However, due to the less frequent occurrence of ALK mutations and the complexity for factors to determine drug responses, the genes that could alter crizotinib sensitivity are unclear. METHODS: Both ALK-translocated and ALK-negative lung adenocarcinoma specimens in tissue sections were collected for immunohistochemistry. The possible mechanisms of NHERF1 and its role in the cell sensitivity to crizotinib were investigated using an ALK-positive and crizotinib-sensitive lung adenocarcinoma cell line H3122. Either a NHERF1 overexpression vector or agents for NHERF1 knockdown was used for crizotinib sensitivity measures, in association with cell viability and apoptosis assays. RESULTS: The expression level of NHERF1 in ALK-translocated NSCLC was significantly higher than that in other lung cancer tissues. NHERF1 expression in ALK positive lung cancer cells was regulated by ALK activities, and was in return able to alter the sensitivity to crizotinib. The function of NHERF1 to influence crizotinib sensitivity was depending on its subcellular distribution in cytosol instead of its nucleus localized form. CONCLUSION: Ectopically overexpressed NHERF1 could be a functional protein for consideration to suppress lung cancers. The determination of NHERF1 levels in ALK positive NSCLC tissues might be useful to predict crizotinib resistance, especially by distinguishing cytosolic or nuclear localized NHERF1 for the overexpressed molecules.
Assuntos
Quinase do Linfoma Anaplásico/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Crizotinibe/farmacologia , Neoplasias Pulmonares/metabolismo , Fosfoproteínas/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Regulação para Cima , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citosol/metabolismo , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Fosfoproteínas/genética , Trocadores de Sódio-Hidrogênio/genéticaRESUMO
A new technique involving large-volume (10 m3) samples of seawater was used to determine the abundance of microplastics (MPs) in the water column in the West Pacific Ocean and the East Indian Ocean. Compared to the conventional sampling methods based on smaller volumes of water, the new data yielded abundance values for the deep-water column that were at least 1-2 orders of magnitude lower. The data suggested that limited bulk volumes currently used for surface sampling are insufficient to obtain accurate estimates of MP abundance in deep water. Size distribution data indicated that the lateral movement of MPs into the water column contributed to their movement from the surface to the bottom. This study provides a reliable dataset for the water column to enable a better understanding of the transport and fate of plastic contamination in the deep-ocean ecosystem.
Assuntos
Microplásticos , Poluentes Químicos da Água , Ecossistema , Monitoramento Ambiental , Oceano Índico , Oceano Pacífico , Plásticos , Poluentes Químicos da Água/análiseRESUMO
Raspberry ketone is a primary aroma component of the red raspberry. The glycosylation of this compound is a potential approach used to improve its pharmaceutical properties. In this work, raspberry ketone glycosides are produced in bacteria for the first time. Bacillus licheniformis PI15, an organic solvent-tolerant glycosyltransferase-producing strain, was isolated from chemically polluted soil. The cloning and heterologous expression of a glycosyltransferase, which was designated PI-GT1, in Escherichia coli BL21 resulted in the expression of an active and soluble protein that accounted for 15% of the total cell protein content. Purified PI-GT1 was highly active and stable over a broad pH range (6.0-10.0) and showed excellent pH stability. PI-GT1 maintained almost 60% of its maximal activity after 3 H of incubation at 20-40 °C and demonstrated optimal activity at 30 °C. Additionally, PI-GT1 displayed high stability and activity in the presence of hydrophilic solvents with log P ≤ -0.2 and retained more than 80% of its activity after 3 H of treatment. Supplementation with 10% DMSO markedly improved the glycosylation of raspberry ketone, resulting in a value 26 times higher than that in aqueous solution. The organic solvent-tolerant PI-GT1 may have potential uses in industrial chemical and pharmaceutical synthesis applications.
Assuntos
Bacillus licheniformis/enzimologia , Butanonas/metabolismo , Dimetil Sulfóxido/metabolismo , Glicosídeos/biossíntese , Glicosiltransferases/metabolismo , Butanonas/química , Dimetil Sulfóxido/química , Glicosídeos/química , Glicosilação , Concentração de Íons de Hidrogênio , Solventes/química , Solventes/metabolismoRESUMO
We present a novel reduced-order glottal airflow model that can be coupled with the three-dimensional (3D) solid mechanics model of the vocal fold tissue to simulate the fluid-structure interaction (FSI) during voice production. This type of hybrid FSI models have potential applications in the estimation of the tissue properties that are unknown due to patient variations and/or neuromuscular activities. In this work, the flow is simplified to a one-dimensional (1D) momentum equation-based model incorporating the entrance effect and energy loss in the glottis. The performance of the flow model is assessed using a simplified yet 3D vocal fold configuration. We use the immersed-boundary method-based 3D FSI simulation as a benchmark to evaluate the momentum-based model as well as the Bernoulli-based 1D flow models. The results show that the new model has significantly better performance than the Bernoulli models in terms of prediction about the vocal fold vibration frequency, amplitude, and phase delay. Furthermore, the comparison results are consistent for different medial thicknesses of the vocal fold, subglottal pressures, and tissue material behaviors, indicating that the new model has better robustness than previous reduced-order models.
Assuntos
Vibração , Prega Vocal , Simulação por Computador , Glote , FonaçãoRESUMO
BACKGROUND: Increased cell mobility is a signature when tumor cells undergo epithelial-to-mesenchymal transition. TGF-ß is a key stimulating factor to promote the transcription of a variety of downstream genes to accelerate cancer progression and metastasis, including osteopontin (OPN) which exists in several functional forms as different splicing variants. In non-small cell lung cancer cells, although increased total OPN expression was observed under various EMT conditions, the exact constitution and the underlining mechanism towards the generation of such OPN splicing isoforms was poorly understood. METHODS: We investigated the possible mechanisms of osteopontin splicing variant and its role in EMT and cancer metastasis using NSCLC cell line and cell and molecular biology techniques. RESULTS: In this study, we determined that OPNc, an exon 4 excluded shorter form of Opn gene products, appeared to be more potent to promote cell invasion. The expression of OPNc was selectively increased to higher abundance during EMT following TGF-ß induction. The switching from OPNa to OPNc could be enhanced by RUNX2 (a transcription factor that recognizes the Opn gene promoter) overexpression, but appeared to be strictly in a HDAC dependent manner in A549 cells. The results suggested the increase of minor splicing variant of OPNc required both (1) the enhanced transcription from its coding gene driven by specific transcription factors; and (2) the simultaneous modulation or fluctuation of the coupled splicing process that depends to selective classed of epigenetic regulators, predominately HDAC family members. CONCLUSION: Our study not only emphasized the importance of splicing variant for its role in EMT and cancer metastasis, but also helped to understand the possible mechanisms of the epigenetic controls for defining the levels and kinetic of gene splicing isoforms and their generations.
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Biofilm is a biological complex caused by bacteria attachment to the substrates and their subsequent reproduction and secretion. This phenomenon reduces heat transfer efficiency and causes significant losses in treated sewage heat-recovering systems. This paper describes a physical approach to inhibit bacteria settlement and biofilm formation by Bacillus subtilis, which is the dominant species in treated sewage. Here, micro-patterned surfaces with different characteristics (stripe and cube) and dimensions (1-100 µm) were fabricated as surfaces of interest. Model sewage was prepared and a rotating coupon device was used to form the biofilms. Precision balance, scanning electron microscopy, and confocal laser scanning microscopy (CLSM) were employed to investigate the inhibitory effects and the mechanisms of the biofilm-surface interactions. The results have shown that surfaces with small pattern sizes (1 and 2 µm) all reduced biofilm formation significantly. Interestingly, the CLSM images showed that the surfaces do not play a role in "killing" the bacteria. These findings are useful for future development of new process surfaces on which bacteria settlement and biofilm formation can be inhibited or minimized.
Assuntos
Bacillus subtilis/crescimento & desenvolvimento , Biofilmes/crescimento & desenvolvimento , Bacillus subtilis/ultraestrutura , Microscopia Confocal , Microscopia Eletrônica de Varredura , Microtecnologia , Propriedades de SuperfícieRESUMO
When developing high-fidelity computational model of vocal fold vibration for voice production of individuals, one would run into typical issues of unknown model parameters and model validation of individual-specific characteristics of phonation. In the current study, the evoked rabbit phonation is adopted to explore some of these issues. In particular, the mechanical properties of the rabbit's vocal fold tissue are unknown for individual subjects. In the model, we couple a 3D vocal fold model that is based on the magnetic resonance (MR) scan of the rabbit larynx and a simple one-dimensional (1D) model for the glottal airflow to perform fast simulations of the vocal fold dynamics. This hybrid three-dimensional (3D)/1D model is then used along with the experimental measurement of each individual subject for determination of the vocal fold properties. The vibration frequency and deformation amplitude from the final model are matched reasonably well for individual subjects. The modeling and validation approaches adopted here could be useful for future development of subject-specific computational models of vocal fold vibration.
Assuntos
Modelos Biológicos , Fonação , Animais , Elasticidade , Estudos de Viabilidade , Masculino , Coelhos , Vibração , Prega Vocal/citologia , Prega Vocal/fisiologiaRESUMO
Closed-loop neural stimulation has been an effective treatment for epilepsy patients. Currently, most closed-loop neural stimulation strategies are designed based on accurate neural models. However, the uncertainty and complexity of the neural system make it difficult to build an accurate neural model, which poses a significant challenge to the design of the controller. This paper proposes an Adaptive Fuzzy Iterative Learning Control (AFILC) framework for closed-loop neural stimulation, which can realize neuromodulation with no model or model uncertainty. Recognizing the periodic characteristics of neural stimulation and neuronal firing, Iterative Learning Control (ILC) is employed as the primary controller. Furthermore, a fuzzy optimization module is established to update the internal parameters of the ILC controller in real-time. This module enhances the anti-interference ability of the control system and reduces the influence of initial controller parameters on the control process. The efficacy of this strategy is evaluated using a neural computational model. The simulation results validate the capability of the AFILC strategy to suppress epileptic states. Compared with ILC-based closed-loop neurostimulation schemes, the AFILC-based neurostimulation strategy has faster convergence speed and stronger anti-interference ability. Moreover, the control algorithm is implemented based on a digital signal processor, and the hardware-in-the-loop experimental platform is implemented. The experimental results show that the control method has good control performance and computational efficiency, which provides the possibility for future application in clinical research.
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Brain-inspired structured neural circuits are the cornerstones of both computational and perceived intelligence. Real-time simulations of large-scale high-dimensional neural populations with complex nonlinearities pose a significant challenge. Taking advantage of distributed computations using embedded multi-cores, we propose an ARM-based scalable multi-hierarchy parallel computing platform (EmPaas) for neural population simulations. EmPaas is constructed using 340 ARM Cortex-M4 microprocessors to achieve high-speed and high-accuracy parallel computing. The tree-two-dimensional grid-like hybrid topology completes the overall construction, reducing communication strain and power consumption. As an instance of embedded computing, the optimized model for a biologically plausible basal ganglia-thalamus (BG-TH) network is deployed into this platform to verify the performance. At an operating frequency of 168 MHz, the BG-TH network consisting of 4000 Izhikevich neurons is simulated in the platform for 3000 ms with a power consumption of 56.565 mW per core and an actual time of 2748.57 ms, which shows the parallel computing approach significantly improves computational efficiency. EmPaas can meet the requirement of real-time performance with the maximum amount of 2000 Izhikevich neurons loaded in each Extended Community Unit (ECUnit), which provides a new practical method for research in large-scale brain network simulation and brain-inspired computing.
Assuntos
Sistemas Computacionais , Redes Neurais de Computação , Simulação por Computador , Neurônios/fisiologia , EncéfaloRESUMO
A continuous chemical-free green approach was investigated for the comprehensive reutilization of all components in herbal extraction residues (HERs), taking Glycyrrhiza uralensis residue (GUR) as an example. The GUR structural changes induced by mechanical extrusion which improve the specific surface area and enzyme accessibility of GUR. With 3 % pretreated GUR loading of high-tolerance Penicillium oxalicum G2. The reducing sugar yield of 11.45 g/L was achieved, along with an 81.06 % in situ enzymatic hydrolysis. Finally, 8.23 g/L bioethanol (0.40 g/g total sugar) was produced from GUR hydrolysates after 24 h fermentation of Pichia stipitis G32. The amount of functional medicinal ingredients extracted from GUR after hydrolysis (39.63 mg/g) was 37.69 % greater than that of un-pretreated GUR. In total, 1.49 g flavonoids, 294.36 U cellulase, and 14.13 g ethanol could be produced from 100 g GUR using this process, illustrating that this green and efficient process has the potential for industrial production.
Assuntos
Celulase , Etanol , Flavonoides , Glycyrrhiza uralensis , Celulase/metabolismo , Etanol/metabolismo , Glycyrrhiza uralensis/química , Hidrólise , Penicillium/metabolismo , Fermentação , Pichia/metabolismo , Biotecnologia/métodosRESUMO
Human vocal folds experience flow-induced vibrations during phonation. In previous computational models, the vocal fold dynamics has been treated with linear elasticity theory in which both the strain and the displacement of the tissue are assumed to be infinitesimal (referred to as model I). The effect of the nonlinear strain, or geometric nonlinearity, caused by finite displacements is yet not clear. In this work, a two-dimensional model is used to study the effect of geometric nonlinearity (referred to as model II) on the vocal fold and the airflow. The result shows that even though the deformation is under 1 mm, i.e., less than 10% of the size of the vocal fold, the geometric nonlinear effect is still significant. Specifically, model I underpredicts the gap width, the flow rate, and the impact stress on the medial surfaces as compared to model II. The study further shows that the differences are caused by the contact mechanics and, more importantly, the fluid-structure interaction that magnifies the error from the small-displacement assumption. The results suggest that using the large-displacement formulation in a computational model would be more appropriate for accurate simulations of the vocal fold dynamics.
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Simulação por Computador , Fenômenos Mecânicos , Prega Vocal , Humanos , Estresse Mecânico , VibraçãoRESUMO
The constant updating of lupus drug treatment guidelines has led to a question. How can the efficacy of treatment be more effectively monitored? Systemic lupus erythematosus (SLE) is a complex autoimmune disease that often presents clinically with multi-organ involvement, and approximately 30% of patients with SLE develop lupus nephritis (LN). Therefore, it is important to better track disease progression and drug efficacy. Now, kidney biopsy is still the gold standard for diagnosing and guiding the treatment of LN, but it is invasive and expensive. If simple, non-invasive and effective biomarkers can be found, drug intervention and prognosis can be better monitored and targeted. In this review, we focus on LN and explore biomarkers related to LN therapeutics, providing clinicians with more possibilities to track the therapeutic effect of drugs, improve treatment options and assess patient outcomes.