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Graphene, a promising material with excellent properties, suffers from a major limitation in electronics due to its zero bandgap. The gas molecules adsorption has proven to be an effective approach for band regulation, which usually requires a harsh environment. Here, O2 - ions produced with triboelectric plasma are used for in situ regulation of graphene, and the switching ratio can reach 1010. The O2 - ions physical adsorption will reduce the Fermi-level (EF) of graphene. As the EF of graphene is lower than the lowest unoccupied molecular orbital (LUMO) level of O2-, the adsorption of O2 - changes from uniform physical adsorption to local chemical adsorption, thereby realizing the semiconductor properties of graphene. The local graphene bandgap is calculated to be 83.4 meV by the variable-temperature experiment. Furthermore, annealing treatment can restore to 1/10 of the initial conductance. The CâO bond formed by O2 - adsorption has low bond energy and is easy to desorb, while the CâO bond formed by adsorption on defects and edges has higher bond energy and is difficult to desorb. The study proposes a simple in situ method to investigate the microscopic process of O2 - adsorption on the graphene surface, demonstrating a new perspective for local energy band engineering of graphene.
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As a non-destructive, fast, and cost-effective technique, near-infrared (NIR) spectroscopy has been widely used to determine the content of bioactive components in tea. However, due to the similar chemical structures of various catechins in black tea, the NIR spectra of black tea severely overlap in certain bands, causing nonlinear relationships and reducing analytical accuracy. In addition, the number of NIR spectral wavelengths is much larger than that of the modeled samples, and the small-sample learning problem is rather typical. These issues make the use of NIRS to simultaneously determine black tea catechins challenging. To address the above problems, this study innovatively proposed a wavelength selection algorithm based on feature interval combination sensitivity segmentation (FIC-SS). This algorithm extracts wavelengths at both coarse-grained and fine-grained levels, achieving higher accuracy and stability in feature wavelength extraction. On this basis, the study built four simultaneous prediction models for catechins based on extreme learning machines (ELMs), utilizing their powerful nonlinear learning ability and simple model structure to achieve simultaneous and accurate prediction of catechins. The experimental results showed that for the full spectrum, the ELM model has better prediction performance than the partial least squares model for epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). For the feature wavelengths, our proposed FIC-SS-ELM model enjoys higher prediction performance than ELM models based on other wavelength selection algorithms; it can simultaneously and accurately predict the content of EC (Rp2 = 0.91, RMSEP = 0.019), ECG (Rp2 = 0.96, RMSEP = 0.11), EGC (Rp2 = 0.97, RMSEP = 0.15), and EGCG (Rp2 = 0.97, RMSEP = 0.35) in black tea. The results of this study provide a new method for the quantitative determination of the bioactive components of black tea.
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Algoritmos , Catequina , Espectroscopia de Luz Próxima ao Infravermelho , Chá , Catequina/análise , Catequina/química , Catequina/análogos & derivados , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Chá/química , Análise dos Mínimos Quadrados , Aprendizado de MáquinaRESUMO
Significant variations in leaf colours, pigment contents, and main taste compounds in young shoots from albino tea plants (Camellia sinensis) influence tea flavour. However, the seasonal metabolic pattern and molecular regulatory mechanism of these metabolites remain largely elusive. Herein, we conducted morphological, biochemical, metabolomic and transcriptomic analyses between an albino tea cultivar 'Zhonghuang 3' ('ZH3') and a green strain 'Tai cha 15' ('TC15') at four-time points (April 12, May 31, July 14, and August 17) to elucidate dynamic changes in these compounds and predict the relationships among transcription factors (TFs), target genes (TGs), and metabolite abundance. Generally, leaf colours and pigment contents were significantly lighter and lower, respectively, in 'ZH3' than in 'TC15' from spring to summer, but were subsequently similar. Compared to 'TC15', 'ZH3' had a lower and broader phenol/ammonia ratio as well as stable caffeine content and showed more significantly different metabolites and differentially expressed genes. The relationship between pigments, main taste compounds, and their biosynthetic genes, as well as TFs and their TGs, had genetic specificity. These results suggested that the biosynthesis of these compounds was probably both season- and variety-dependent. In total, 12 models of the TF-TG-metabolite regulatory network were proposed to uncover the biosynthetic and regulatory mechanisms of these metabolites in tea plants. A high correlation was observed between some structural genes and TFs with the accumulation of these metabolites. These findings provide novel insights into the regulatory mechanisms underlying accumulation of pigments and main taste compounds in tea plants.
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Camellia sinensis , Transcriptoma , Paladar , Camellia sinensis/genética , Camellia sinensis/metabolismo , Perfilação da Expressão Gênica , Folhas de Planta/metabolismo , Chá/química , Chá/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismoRESUMO
Two inorganic-organic hybrid complexes based on bi-capped Keggin-type cluster, {([CuII(2,2'-bpy)2]2[PMoVI8VV2VIV2O40(VIVO)2])[CuI(2,2'-bpy)]}â2H2O (1) and {[CuII(2,2'-bpy)2]2[SiMoVI8.5MoV2.5VIVO40(VIVO)2]}[CuI0.5(2,2'-bpy)(H2O)0.5] (2) (bpy = bipyridine), had been hydrothermally synthesized and structurally characterized by elemental analysis, FT-IR, TGA, PXRD and X-ray single-crystal diffraction analysis. Compound 1 consists of a novel 1-D chain structure constructed from [CuI(2,2'-bpy)]+ unit linking bi-supported POMs anion {[CuII(2,2'-bpy)2]2[PMoVI8VV2VIV2O40(VIVO)2]}-. Compound 2 is a bi-capped Keggin cluster bi-supported Cu-bpy complex. The main highlights of the two compounds are that Cu-bpy cations contain both CuI and CuII complexes. Furthermore, the fluorescence properties, the catalytic properties, and the photocatalytic performance of compounds 1 and 2 have been assessed, and the results show that both compounds are active for styrene epoxidation and degradation and adsorption of Methylene blue (MB), Rhodamine B (RhB) and mixed aqueous solutions.
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Mammalian mitochondrial NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the tricarboxylic acid cycle. It exists as the α2ßγ heterotetramer composed of the αß and αγ heterodimers. Different from the αγ heterodimer that can be allosterically activated by CIT and ADP, the αß heterodimer cannot be allosterically regulated by the activators; however, the molecular mechanism is unclear. We report here the crystal structures of the αß heterodimer of human NAD-IDH with the α subunit in apo form and in Ca2+-bound, NAD-bound, and NADH-bound forms. Structural analyses and comparisons reveal that the αß heterodimer has a similar yet more compact overall structure compared with the αγ heterodimer and contains a pseudo-allosteric site that is structurally different from the allosteric site. In particular, the ß3-α3 and ß12-α8 loops of the ß subunit at the pseudo-allosteric site adopt significantly different conformations from those of the γ subunit at the allosteric site and hence impede the binding of the activators, explaining why the αß heterodimer cannot be allosterically regulated by the activators. The structural data also show that NADH can compete with NAD to bind to the active site and inhibits the activity of the αß heterodimer. These findings together with the biochemical data reveal the molecular basis for the function of the αß heterodimer of human NAD-IDH.
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Isocitrato Desidrogenase/metabolismo , Isocitrato Desidrogenase/ultraestrutura , Regulação Alostérica , Sítio Alostérico , Catálise , Domínio Catalítico , Dimerização , Humanos , Cinética , NAD/metabolismo , Conformação ProteicaRESUMO
Aberrant activation of Wnt signaling plays a critical role in the development of colon cancer. BMI, a component of the polycomb repressive complex (PRC1), is upregulated in various types of cancer and contributes to epigenetic silencing of tumor suppressors. In this study, we showed that BMI1 is upregulated in colon cancer tissues and cell lines. Overexpression of BMI1 in primary epithelial colon cells promotes cellular growth and activates WNT pathway, while BMI1 silencing in colon cancer cells represses these effects. We also found that BMI1 binds to the promoter of IDAX, a Wnt antagonist, and decreases its transcription. Expression of IDAX is downregulated in colon cancer tissues and cell lines and negatively correlated with BMI1 in colon cancer tissues. Furthermore, Silencing of IDAX counteracts the effects of BMI1 suppression, while its overexpression reverses oncogenic effects of BMI1. Together, these findings indicate that BMI1-mediated IDAX epigenetic suppression is crucial for enhancement of colon carcinogenesis, suggesting that BMI1∖IDAX axis as a potential novel diagnostic and therapeutic target of colon cancer.
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Carcinogênese/genética , Neoplasias do Colo/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Complexo Repressor Polycomb 1/genética , Fatores de Transcrição/genética , Via de Sinalização Wnt , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Complexo Repressor Polycomb 1/antagonistas & inibidores , Complexo Repressor Polycomb 1/metabolismo , Cultura Primária de Células , Regiões Promotoras Genéticas , Ligação Proteica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Fourier transform spectrometers (FTS) based on piston-scanning MEMS mirrors have clear advantages of small size and low cost. However, the performance of this type of MEMS FTS is seriously limited by the difficulty of precisely controlling the tilt angle of the MEMS mirror plate during its piston scanning. This paper reports an integrated tilt angle sensing method, which is achieved via a mixed signal integrated optoelectronic position sensor (iOE-PS) that is bonded directly on the back of an electrothermally-actuated MEMS mirror. The iOE-PS integrates a laser diode, a band-gap reference, a quadrant photo-detector (QPDs), and the QPDs' readout circuits all on a single chip. The iOE-PS has been fabricated in a 180 nm CMOS process. Experimental results show that the iOE-PS has a linear response when the MEMS mirror plate moves vertically between 1.31 mm to 1.50 mm over the iOE-PS chip; the tilt angle can be measured up to at least 5° with a resolution of 0.0067°. The iOE-PS can greatly reduce the size and complexity of MEMS mirrors-enabled systems with integrated closed-loop control capability.
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Special AT-rich sequence-binding protein 1 (SATB1) functions as a 'genome organizer' in tumorigenesis. Our previous report showed that SATB1 forms a tetramer through its N-terminal ubiquitin like domain rather than the proposed PDZ domain. In the present study, we aim to illustrate whether this oligomerization is critical to its function as a global repressor of gene expression in vivo. Luciferase and GST pull-down assays demonstrated that disrupting SATB1's tetramerization not only affects the activities of promoters but also influences the recruitment of interaction partners. Furthermore, we developed stable cell lines that overexpressed either the SATB1 tetramer or STAB1 dimer (KWN-AAA) and monitored global gene expression. Gene expression profiling revealed that over 1000 genes were significantly upregulated or downregulated upon the overexpression of SATB1 or the SATB1 (KWN-AAA) mutant. These data implied that SATB1 might regulate gene expression through its different oligomerization state. In conclusion, we inferred that the oligomerization of SATB1 is pivotal to its function of different biological processes.
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Regulação da Expressão Gênica/fisiologia , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Multimerização Proteica/fisiologia , Células HeLa , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/genética , MutaçãoRESUMO
Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease characterized by a grim prognosis, in which various forms of cell death are significant contributors to its development. The objective of this study is to explore diagnostic biomarkers and molecular subtypes associated with PANoptosis in IPF, and to develop reliable diagnostic models based on PANoptosis-related mechanisms. The peripheral blood transcriptomic data of IPF from the Gene Expression Omnibus (GEO) database and PANoptosis-related genes from the GeneCards database were utilized to conduct differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), identifying PANoptosis-related differentially expressed genes (PDEGs). We yielded 9 PDEGs and employed machine learning algorithms to identify 3 key diagnostic biomarkers for PANoptosis in IPF: MMP9, FCMR, NIBAN3. Consensus clustering algorithm was applied to recognize two PANoptosis-related subtypes. Cluster 1 exhibited higher abundance of adaptive immune response cells and significant enrichment in DNA damage and repair-related pathways. Cluster 2 exhibited greater prevalence of innate immune response cells and predominant enhancement in pathways related to lipid cholesterol metabolism and vascular remodeling. Diagnostic models were developed with the aid of clinical decision-making and a novel approach to the diagnosis and treatment for IPF.
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Fibrose Pulmonar Idiopática , Aprendizado de Máquina , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/patologia , Humanos , Perfilação da Expressão Gênica/métodos , Transcriptoma , Biomarcadores , Redes Reguladoras de Genes , Bases de Dados GenéticasRESUMO
BACKGROUND: PANoptosis represents a newly identified form of programmed cell death that plays a significant role in the autoimmune diseases. Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies. Nevertheless, the specific biomarkers and molecular mechanisms responsible for the apoptotic characteristics of RA remain largely uninvestigated. METHODS: We utilized 8 synovial tissue RA datasets. We selected genes associated with PANoptosis from the GeneCard database. By employing the limma, WGCNA, and machine learning algorithms we identified core genes. We utilized consensus clustering analysis to identify distinct PANoptosis subtypes of RA. Boruta algorithm was employed to construct a PANoptosis signature score. The sensitivity of distinct subtypes to drug treatment was verified using an independent dataset. RESULTS: The SPP1 emerged as the significant gene, with its elevated expression in RA patients. We identified two PANoptosis RA subtypes. Cluster 1 showed high expression of Tregs, resting dendritic cells, and resting mast cells. Cluster 2 exhibited high expression of CD4 memory T cells and follicular helper T cells. Cluster 2 exhibited a higher degree of sensitivity towards immune checkpoint therapy. Employing the Boruta algorithm, a subtype score was devised for 37 PANoptosis genes, successfully discerning the subtypes (AUC = 0.794), wherein patients with elevated scores demonstrated enhanced responsiveness to Rituximab treatment. CONCLUSION: Our analysis revealed that SPP1 holds potential biomarker for the diagnosis of RA. Cluster 2 exhibited enhanced sensitivity to immune checkpoint therapy, higher PANoptosis scores, and improved responsiveness to drug treatment. This study offers potential implications in the realm of diagnosis and treatment.
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Artrite Reumatoide , Doenças Autoimunes , Humanos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Rituximab , Membrana Sinovial , Aprendizado de MáquinaRESUMO
Objective: To analyze the correlation between the expression of circFAT1 in serum and immune cells in patients with non-small cell lung cancer (NSCLC). Methods: A total of 96 patients with NSCLC admitted to our hospital from November 2019 to November 2022 were regarded as the study subjects. In the meantime, 96 volunteers who had physical examination in our hospital were regarded as the control group. The expression level of circFAT1 in serum was detected by real-time fluorescence quantitative PCR. NSCLC cancer tissue (NSCLC group) and paracancerous tissue (tissue ≥ 2cm away from the focus) (paracancerous group) were collected during the operation, the expression of CD4+, CD8+ and Foxp3+ in tissues was determined by immunohistochemistry; the expression level of circFAT1 mRNA in NSCLC tissue was analyzed using the Ualcan database. Spearman correlation was applied to analyze the correlation between the expression of circFAT1 and immune cells (CD4+, Foxp3+, CD8+). Results: The level of circFAT1 in NSCLC tissue was higher than that in normal tissue (P < 0.05). Compared with the control group, the expression level of circFAT1 in serum of NSCLC group was obviously higher (P < 0.05). The expression level of circFAT1 was related to lymph node metastasis, TNM stage and differentiation (P < 0.05). Compared with the paracancerous group, the positive expression rate of CD8+ in NSCLC group was obviously lower, and the positive expression rates of CD4+ and Foxp3+ were obviously higher (P < 0.05). The expression of CD4+, Foxp3+ and CD8+ in NSCLC patients' cancer tissue was related to lymph node metastasis, TNM stage and differentiation degree (P < 0.05). Spearman correlation analysis showed that circFAT1 was positively correlated with the expression of CD4+ and Foxp3+ and negatively correlated with the expression of CD8+ (P < 0.05). Conclusion: CircFAT1 is highly expressed in the serum of NSCLC patients and is closely related to immune cells.
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Reducing the high operation temperature of gas sensor to room temperature (RT) have attracted intense interests for its distinct preponderances, including energy-saving and super stability, which presents great prospects in commercial application. The exciting strategies for RT gas sensing, such as unique materials with activated surface or light activation, do not directly modulate the active ions for gas sensing, limiting the RT gas sensing performances. Here, an active-ion-gated strategy has been proposed for RT gas sensing with high performance and low power consumption, in which gas ions in triboelectric plasma are introduced into metal oxide semiconductor (MOS) film to act as both floating gate and active sensing ions. The active-ion-gated ZnO nanowires (NWs) array shows a sensitivity of 38.3% to 10 ppm acetone gas at RT, and the maximum power consumption is only 4.5 mW. At the same time, the gas sensor exhibits excellent selectivity to acetone. More importantly, the response (recovery) time of this sensor is as low as 11 s (25 s). It is found that OH-(H2O)4 ions in plasma are the key for realizing RT gas sensing ability, and an accompanied resistive switch is also observed. It is considered that the electron transfer between OH-(H2O)4 and ZnO NWs will forms a hydroxyl-like intermediate state (OH*) on the top of Zn2+, leading to the band bending of ZnO and activating the reactive O2 - ions on the oxygen vacancies. The active-ion-gated strategy proposed here present a novel exploration to achieving RT gas sensing performance of MOS by activating sensing properties at the scale of ions or atoms.
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Electrothermal actuation is one of the main actuation mechanisms and has been employed to make scanning microelectromechanical systems (MEMS) mirrors with large scan range, high fill factor, and low driving voltage, but there exist long-term drifting issues in electrothermal bimorph actuators whose causes are not well understood. In this paper, the stability of an Al / SiO 2 bimorph electrothermal MEMS mirror operated in both static and dynamic scan mode has been studied. Particularly, the angular drifts of the MEMS mirror plate were measured over 90 h at different temperatures in the range of 50 - 150 °C. The experiments show that the temporal drift of the mirror plate orientation largely depends on the temperature of the electrothermal bimorph actuators. Interestingly, it is found that the angular drift changes from falling to rising as the temperature increases. An optimal operating temperature between 75 °C to 100 °C for the MEMS mirror is identified. At this temperature, the MEMS mirror exhibited stable scanning with an angular drift of less than 0.0001 °/h.
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Human NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the oxidative decarboxylation of isocitrate in the citric acid cycle. In the α2ßγ heterotetramer of NAD-IDH, the γ subunit plays the regulatory role and the ß subunit the structural role. Previous biochemical data have shown that mammalian NAD-IDHs can be inhibited by NADH; however, the molecular mechanism is unclear. In this work, we show that the αß, αγ and α2ßγ enzymes of human NAD-IDH can be inhibited by NADH, and further determine the crystal structure of the αγ heterodimer bound with an Mg2+ and an NADH at the active site and an NADH at the allosteric site, which resembles that of the inactive αMgγ heterodimer. The NADH at the active site occupies the binding site for NAD+ and prevents the binding of the cofactor. The NADH at the allosteric site occupies the binding sites for ADP and citrate and blocks the binding of the activators. The biochemical data confirm that the NADH binding competes with the binding of NAD+ and the binding of citrate and ADP, and the two effects together contribute to the NADH inhibition on the activity. These findings provide insights into the inhibitory mechanisms of the αγ heterodimer by NADH.
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Isocitrato Desidrogenase/química , NAD/farmacologia , Multimerização Proteica/efeitos dos fármacos , Sítio Alostérico/efeitos dos fármacos , Domínio Catalítico , Humanos , Isocitrato Desidrogenase/metabolismo , Cinética , Modelos Moleculares , Estrutura Quaternária de ProteínaRESUMO
We present a novel circumferential-scan endoscopic optical coherence tomography (OCT) probe by using a circular array of six electrothermal microelectromechanical (MEMS) mirrors and six C-lenses. The MEMS mirrors have a 0.5 mm × 0.5 mm mirror plate and a chip size of 1.5 mm × 1.3 mm. Each MEMS mirror can scan up to 45° at a voltage of less than 12 V. Six of those mirrors have been successfully packaged to a probe head; full circumferential scans have been demonstrated. Furthermore, each scan unit is composed of a MEMS mirror and a C-lens and the six scan units can be designed with different focal lengths to adapt for lesions with uneven surfaces. Configured with a swept source OCT system, this MEMS array-based circumferential scanning probe has been applied to image a swine's small intestine wrapped on a 20 mm-diameter glass tube. The OCT imaging result shows that this new MEMS endoscopic OCT has promising applications in large tubular organs.
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Human NAD-dependent isocitrate dehydrogenase existing as the α2ßγ heterotetramer, catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the Krebs cycle, and is allosterically regulated by citrate, ADP and ATP. To explore the functional roles of the regulatory ß and γ subunits, we systematically characterized the enzymatic properties of the holoenzyme and the composing αß and αγ heterodimers in the absence and presence of regulators. The biochemical and mutagenesis data show that αß and αγ alone have considerable basal activity but the full activity of α2ßγ requires the assembly and cooperative function of both heterodimers. α2ßγ and αγ can be activated by citrate or/and ADP, whereas αß cannot. The binding of citrate or/and ADP decreases the S0.5,isocitrate and thus enhances the catalytic efficiencies of the enzymes, and the two activators can act independently or synergistically. Moreover, ATP can activate α2ßγ and αγ at low concentration and inhibit the enzymes at high concentration, but has only inhibitory effect on αß. Furthermore, the allosteric activation of α2ßγ is through the γ subunit not the ß subunit. These results demonstrate that the γ subunit plays regulatory role to activate the holoenzyme, and the ß subunit the structural role to facilitate the assembly of the holoenzyme.
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Isocitrato Desidrogenase/metabolismo , Multimerização Proteica , Difosfato de Adenosina/metabolismo , Regulação Alostérica , Sítio Alostérico , Ácido Cítrico/metabolismo , Humanos , Isocitrato Desidrogenase/química , Isocitrato Desidrogenase/genética , Ligação Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismoRESUMO
Micro-electro-mechanical system (MEMS) mirrors are widely used for optical modulation, attenuation, steering, switching and tracking. In most cases, MEMS mirrors are packaged in air, resulting in overshoot and ringing upon actuation. In this paper, an electrothermal bimorph MEMS mirror that does not generate overshoot in step response, even operating in air, is reported. This is achieved by properly designing the thermal response time and the mechanical resonance without using any open-loop or closed-loop control. Electrothermal and thermomechanical lumped-element models are established. According to the analysis, when setting the product of the thermal response time and the fundamental resonance frequency to be greater than Q/2π, the mechanical overshoot and oscillation caused by a step signal can be eliminated effectively. This method is verified experimentally with fabricated electrothermal bimorph MEMS mirrors.
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The aim of this study was to explore the chronergy of intravenous recombinant streptokinase (r-SK) in patients with acute myocardial infarction (AMI). A total of 114 patients were divided into two groups according to the time of AMI onset: the morning onset (6:01-12:00, n=53) and non-morning onset (12:01-06:00, n=61) groups. The recanalization rate was recorded, as well as anticoagulant and fibrinolytic indices. Statistical analysis was performed to evaluate the recanalization rate following thrombolysis, as well as the anticoagulant and fibrinolytic activities. The recanalization rates following thrombolysis in the morning onset and non-morning onset groups were 60.4 and 82.0%, respectively (P<0.05). The level of plasminogen activator inhibitor-1 (PAI-1) antigen was significantly higher in the morning onset group compared with that in the non-morning onset group (P<0.05). This indicated a resistance to r-SK thrombolysis in the morning at the early stage of AMI, which possibly correlates with increased PAI-1 antigen levels and activity.