RESUMO
We aimed to utilize chaos game representation (CGR) for the investigation of microstate sequences and explore its potential as neurobiomarkers for psychiatric disorders. We applied our proposed method to a public dataset including 82 patients with first-episode psychosis (FEP) and 61 control subjects. Two time series were constructed: one using the microstate spacing distance in CGR and the other using complex numbers representing the microstate coordinates in CGR. Power spectral features of both time series and frequency matrix CGR (FCGR) were compared between groups and employed in a machine learning application. The four canonical microstates (A, B, C, and D) were identified using both shared and separate templates. Our results showed the microstate oscillatory pattern exhibited alterations in the FEP group. Using oscillatory features improved machine learning performance compared with classical features and FCGR. This study opens up new avenues for exploring the use of CGR in analyzing EEG microstate sequences. Features derived from microstate sequence CGR offer fine-grained neurobiomarkers for psychiatric disorders.
Assuntos
Transtornos Psicóticos , Humanos , Aprendizado de Máquina , Pacientes , Fatores de TempoAssuntos
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Mutagênese Insercional , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/enzimologia , Masculino , Taxa de Sobrevida , Tirosina Quinase 3 Semelhante a fms/metabolismoRESUMO
OBJECTIVE: The aim of this study was to investigate the effects of hyperbaric oxygen on the permeability of the blood-brain barrier in rats with global cerebral ischemia/reperfusion injury and explore possible mechanisms. METHODS: A rat model of global cerebral ischemia/reperfusion injury established via Pulsinelli four-vessel occlusion method and a total of 162 Wistar rats were randomly divided into three groups, including sham group, global cerebral ischemia/reperfusion group (IR group) and hyperbaric oxygen treated group (HBO group). Permeability of the blood-brain barrier of these rats were evaluated by Evans Blue staining. The expression of caveolin-1 and tight junction protein ZO-1 was examined by Immunohistochemistry staining and western-blotting. RESULTS: Successfully establishment of the rat model was verified by W:D ratio, and significantly increased Evans Blue level was found in IR group compared to control group, whereas hyperbaric treatment could result in decreased Evans Blue level in HBO group. Increased expression of caveolin-1 and tight junction protein ZO-1 were found in rats with hyperbaric oxygen exposure compared to those in IS group. CONCLUSIONS: Hyperbaric oxygen exposure improved the permeability of the blood-brain barrier in rats with global cerebral ischemia/reperfusion injury, and increased expression of caveolin-1 and tight junction protein ZO-1 were involved in the mechanisms.
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Barreira Hematoencefálica/patologia , Isquemia Encefálica/patologia , Isquemia Encefálica/terapia , Oxigenoterapia Hiperbárica , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapia , Animais , Isquemia Encefálica/metabolismo , Caveolina 1/metabolismo , Masculino , Permeabilidade , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
FMS-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in hematological malignancies. FLT3 internal tandem duplication (FLT3-ITD) mutations located in juxtamembrane domain (JMD) and tyrosine kinase domain 1 (TKD1) regions account for two-thirds of all FLT3 mutations. The outcome of patients remains unsatisfactory, with low survival rates. It is not yet known whether the different mutations within the FLT3 gene are all associated with patient outcome. In addition, the cause of FLT3-ITD in-frame duplication events remains unknown. Although there are some published studies investigating the FLT3-ITD mutation and its clinical implications in Chinese acute myeloid leukemia (AML) patients, sample sizes tend to be small and detailed molecular profiles of FLT3 mutations are lacking in these studies. In our study, 227 FLT3-ITD sequences were analyzed from 227 Chinese de novo AML patients. ITD were next classified into 3 types based on molecular profiles of insertion DNA sequences: DNA complete duplication (type I), DNA partial duplication (type II) and complete random sequence (type III). From the 154 patients, we confirmed that high ITD allelic ratio (≥.5) and allogeneic stem cell transplant treatment under CR1 are independent prognostic factors. We also presented evidence that ITD integration sites in the hinge region or beta1-sheet region are an unfavorable prognostic factor in adult AML patients with FLT3-ITD mutations. These findings may help to decipher the mechanisms of FLT3-ITD in-frame duplication events and stratify patients when considering different therapeutic combinations.
Assuntos
Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco/métodos , Sequências de Repetição em Tandem , Tirosina Quinase 3 Semelhante a fms/química , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , China , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Mutagênese Insercional , Prognóstico , Domínios Proteicos , Indução de Remissão , Tamanho da Amostra , Análise de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
Alveolar echinococcosis is a chronically progressive and potentially fatal disease. Patients with multiple giant alveolar echinococcosis have a poor prognosis when radical resection cannot be achieved, but curative resection can be limited by low future remnant liver volumes. In these cases, 2-stage liver resection may be a better choice: after a first-stage hepatectomy with partial resection, liver regeneration is allowed in the residual liver before proceeding to the second-stage hepatectomy. In this study, we therefore retrospectively reviewed and evaluated the safety and feasibility of two-stage hepatectomy in patients with multiple giant alveolar echinococcosis.We reviewed the data for all patients who underwent 2-stage hepatectomy for multiple giant alveolar echinococcosis between August 2013 and December 2015 at either the West China Hospital of Sichuan University or the Hospital of Ganzi Tibetan Autonomous Prefecture.We identified 7 patients in whom 2-stage hepatectomy was completed. During the first-stage hepatectomy, 4 patients underwent right-sided hepatectomy and the other 3 underwent left-sided hepatectomy. The second-stage hepatectomies were successfully performed 3 months after the first-stage procedures. All patients had follow-up durations of >1 year; there were no cases of operation-related mortality, and no patients experienced disease recurrence.Two-stage hepatectomy is safe and feasible for patients with multiple giant alveolar echinococcosis.
Assuntos
Equinococose Hepática/cirurgia , Hepatectomia/métodos , Adulto , China , Equinococose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
In this paper, a channel transmission communication system of expendable conductivity-temperature-depth is established in accordance to the operation characteristics of the transmission line to more accurately assess the characteristics of deep-sea abandoned profiler channel. The wrapping inductance is eliminated to maximum extent through the wrapping pattern of the underwater spool and the overwater spool and the calculation of the wrapping diameter. The feasibility of the proposed channel transmission communication system is verified through theoretical analysis and practical measurement of the transmission signal error rate in the amplitude shift keying (ASK) modulation. The proposed design provides a new research method for the channel assessment of complex abandoned measuring instrument and an important experiment evidence for the rapid development of the deep-sea abandoned measuring instrument.
RESUMO
OBJECTIVE: To explore the effects of testosterone synthesis in adult leydig cell (ALC) of male rats exposed by perfluorooctane sulfonate (PFOS) during pregnancy. METHODS: At gestations 12 day, the pregnant rats were exposed to PFOS (5 mg/kg, PFOS group) or 0.5% Tween (control group) by gavage, once a day for 8 consecutive days. On postnatal day (PND) 70, several indexes of male offspring rats were measured including body mass, testicular coefficient, sperm count, serum testosterone concentration. The mRNA levels of ALC associated with testosterone synthesis were detected by real-time quantitative RT-PCR. RESULTS: The result showed that sperm count and serum testosterone concentration decreased in male offspring rats of PFOS group (P < 0.05), and body mass was significantly lower (P < 0.001). The expression of steroidogenic acute regulatory factor (Star), scavenger receptor class B type 1 (Scarb1), Cyp11a1 (coding gene of cytochrome P450 side chain cleavage) and Hsd17b3 (coding gene of 17ß-hydroxysteroid dehydrogenase) were down regulated (P < 0.05), no significant statistical difference was observed on the mRNA level of insulin-like growth factor-1 (Igf1) and insulin-like factor 3 (Insl3). CONCLUSION: Gestational exposure to PFOS can inhibit the mRNA levels associated with testosterone synthesis, and decrease the ability of testosterone synthesis in ALC of male offspring rats.
Assuntos
Ácidos Alcanossulfônicos/efeitos adversos , Fluorocarbonos/efeitos adversos , Células Intersticiais do Testículo/patologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Testosterona/sangue , Animais , Feminino , Masculino , Gravidez , RNA Mensageiro , Ratos , Contagem de EspermatozoidesRESUMO
Activity and half-life play key roles in the application of GHRH analogues. The GHRH monomers produced in a solid synthesizer were incubated, respectively, in NH4OH solution and lyophilized to obtain their dimers. The activities, specificities, and receptor affinities of the GHRH dimers were evaluated in rGH release/inhibition, rACTH/LH/PRL release, pituitary homogenate binding, and fluorescent staining. Compared to hGHRH(1-44)NH2 (S), PP-hGHRH(1-44)-GGC-CGG-hGHRH(44-1)-PP (2D), P-hGHRH(1-44)-GGC-CGG-hGHRH(44-1)-P (2E), (1)P-hGHRH(2-44)-GGC-CGG-hGHRH(44-2)-(1)P (2F), or hGHRH(1-44)-GGC-CGG-hGHRH(44-1) (2Y) had potency of 104 ± 16.7%, 94 ± 32.6%, 114 ± 16.6%, or 122 ± 14.5% and similar specificities. The inhibition effect of GHIH on rGH stimulated by GHRH dimer was in dose-/time-dependent manner. The staining of FITC-labeled dimer showed cytomembrane distribution and the binding ranking was 2F>2D>2Y>2E>S. 2F presents the strongest activity and the highest affinity to pituitary cells. The dimer with (1)Pro-GHRH stimulates stronger rGH release than that with (1)Tyr-GHRH and the N-terminal single cyclic amino acid is required for the stimulation.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/análogos & derivados , Hormônio Liberador de Hormônio do Crescimento/química , Animais , Membrana Celular/metabolismo , Feminino , Corantes Fluorescentes/química , Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/síntese química , Hormônios/metabolismo , Humanos , Ligantes , Fragmentos de Peptídeos/química , Hipófise/metabolismo , Ligação Proteica , Multimerização Proteica , Estrutura Terciária de Proteína , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/químicaRESUMO
Lipid metabolism disorder is an important risk factor to obesity, hyperlipidemia and type 2 diabetes as well as other chronic metabolic disease. It is also a key target in preventing metabolic syndrome, chronic disease prevention. Plant polyphenol plays an important role in maintaining or improving lipid profile in a variety of ways. including regulating cholesterol absorption, inhibiting synthesis and secretion of triglyceride, and lowering plasma low density lipoprotein oxidation, etc. The purpose of this article is to review the lipid regulation effects of plant polyphenols and its related mechanisms.
Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/metabolismo , Polifenóis/farmacologia , Animais , Humanos , Doenças Metabólicas/tratamento farmacológicoRESUMO
OBJECTIVE: To analyze the chemical composition of essential oil from Thymus citriodorus and its toxic effect on liver cancer cells. METHODS: The essential oil from Thymus citriodorus leaves was extracted by steam distillation, and GC-MS was used for analyzing chemical composition. 35 components were identified which accounted for 95.44% of the total peak area. The main components were borneol (28.82%), thymol (14.43%), 3, 7-dimethyl-1, 6-octadiene-3-ol (8.26%), 1-methyl-4-[alpha-hydroxy-isopropyl] cyclohexene (8.23%) and terpenes camphor (5.1%), et. al. The toxic effects on HepG2 cells and expression of NF-kappabeta65 were measured by MTT assay and confocal laser scanning microscopy, respectively. RESULTS: The IC50 of HepG2 cells inhibition was 0.34%. The mean fluorescence intensity of NF-kappabeta65 expression was as follows: control group 323.25, 2(-10) concentration group 84.18, 2(-11) concentration group 197.93 and 2(-12) concentration group 261.43. CONCLUSION: The essential oil from Thymus citriodorus leaves has strong toxic effects. The induced apoptosis mechanism may be associated with the expression of NF-kappabeta65.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Thymus (Planta)/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Canfanos/análise , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Células Hep G2 , Humanos , Concentração Inibidora 50 , Neoplasias Hepáticas/patologia , NF-kappa B/metabolismo , Óleos Voláteis/isolamento & purificação , Folhas de Planta/química , Timol/análiseRESUMO
The cytotoxicities of two oxovanadium complexes, VOI [VO(satsc)(phen)] (satsc = salicylaldehyde thiosemicarbazone, phen = 1,10-phenanthroline) and VOII [VO(3,5-dibrsatsc)(phen)](3,5-dibrsatsc = 3,5-dibromosalicylaldehyde thiosemicarbazone), were studied by performing MTT assays on human hepatoma cell lines BEL-7402, HUH-7 and HepG2. The results showed that both the VOI and VOII complexes possess significant anti-proliferative effects. In addition, the anti-proliferative mechanism of the complexes was analyzed by cell cycle analysis and an apoptosis assay and by detecting the mitochondrial membrane potential (delta psi m). The experimental results showed that the complexes can cause a G0/G1 phase cell cycle arrest and can significantly decrease delta psi m, causing depolarization of the mitochondrial membrane. Notably, the two complexes induced apoptosis in BEL-7402 cells and displayed typical morphological apoptotic characteristics. The cytotoxicities of the VOII complex are significantly stronger than that of the VOI complex, suggesting that the cytotoxic effects of oxovanadium complexes may be associated with the electronic effects of the complexes.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Compostos Organometálicos/farmacologia , Vanádio/farmacologia , Animais , Anexina A5 , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corantes , Ensaios de Seleção de Medicamentos Antitumorais , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Fase G1/efeitos dos fármacos , Humanos , Neoplasias Hepáticas Experimentais/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia de Fluorescência , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Sais de Tetrazólio , TiazóisRESUMO
Natural product-inspired discovery of new drug leads plays a key role in drug development. Recently, small-molecule JAK inhibitors have been pursued for the development of anticancer therapeutics. However, most of these inhibitors reported up to now are multi-nitrogen polycyclic aromatic heterocycles. Undoubtedly, the discovery of new types of promising JAK-inhibitory leads is pivotal for JAK inhibitor-based anticancer drug development. Herein we report an unprecedented sesquiterpenoid-alkaloid named thespesilactam, containing a benzo[cd]indole scaffold, from the heartwood of the Portia tree, Thespesia populnea. Its 3-O-Me product, i.e. 8-hydroxy-5-isopropyl-3-methoxy-7-methylbenzo[cd]indol-2(1H)-one, named 3-O-methylthespesilactam, of which the structure was identified by NMR investigations and single-crystal X-ray diffraction analysis, was discovered as a new type of small-molecule anticancer pan-JAK inhibitor against A2058 human melanoma cells, and selective and potent inhibitor of JAK1 and TYK2.
Assuntos
Alcaloides/síntese química , Antineoplásicos/síntese química , Janus Quinases/antagonistas & inibidores , Sesquiterpenos/síntese química , Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Malvaceae , Melanoma , Fosforilação , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
One of the strategies to improve the outcome of anti-erbB2-mediated immunotherapy is to combine anti-erbB2 antibodies with T-cell-based adoptive immunotherapy, which can be achieved by expressing anti-erbB2 mAb on the surface of T cells. A single-chain variable fragment (scFv) from an anti-erbB2 mAb has been expressed on T cell surface to bind to erbB2-positive cells, and CD3ζ has been expressed as a fusion partner at C terminus of this scFv to transduce signals. T cells grafted with this chimeric scFv/CD3ζ were able to specifically attack target tumor cells with no MHC/Ag restriction. To test the effects of CD28 signal on cellular activation and antitumor effectiveness of chimeric scFv/CD3ζ-modified T cells, we constructed a recombinant anti-erbB2 scFv/Fc/CD28/CD3ζ gene in a retroviral vector. T cells expressing anti-erbB2 scFv/Fc/CD28/CD3ζ specifically lyzed erbB2-positive target tumor cells and secreted not only interferon-γ (IFN-γ) but also IL-2 after binding to their target cells. Our data indicate that CD3 and CD28 signaling can be delivered in one molecule, which is sufficient for complete T cell activation without exogenous B7/CD28 co-stimulation.
Assuntos
Neoplasias da Mama/terapia , Terapia Genética/métodos , Imunoterapia Adotiva/métodos , Linfoma de Células T/terapia , Receptor ErbB-2/imunologia , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Fusão Gênica Artificial , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Antígenos CD28/biossíntese , Antígenos CD28/genética , Antígenos CD28/imunologia , Complexo CD3/biossíntese , Complexo CD3/genética , Complexo CD3/imunologia , Linhagem Celular Tumoral , Humanos , Região Variável de Imunoglobulina/biossíntese , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Células Jurkat , Linfoma de Células T/genética , Linfoma de Células T/imunologia , Células MCF-7 , Camundongos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Transdução de Sinais , TransfecçãoRESUMO
A DFT-SOFM-RBFNN method is proposed to improve the accuracy of DFT calculations on Y-NO (Y = C, N, O, S) homolysis bond dissociation energies (BDE) by combining density functional theory (DFT) and artificial intelligence/machine learning methods, which consist of self-organizing feature mapping neural networks (SOFMNN) and radial basis function neural networks (RBFNN). A descriptor refinement step including SOFMNN clustering analysis and correlation analysis is implemented. The SOFMNN clustering analysis is applied to classify descriptors, and the representative descriptors in the groups are selected as neural network inputs according to their closeness to the experimental values through correlation analysis. Redundant descriptors and intuitively biased choices of descriptors can be avoided by this newly introduced step. Using RBFNN calculation with the selected descriptors, chemical accuracy (≤1 kcal·mol(-1)) is achieved for all 92 calculated organic Y-NO homolysis BDE calculated by DFT-B3LYP, and the mean absolute deviations (MADs) of the B3LYP/6-31G(d) and B3LYP/STO-3G methods are reduced from 4.45 and 10.53 kcal·mol(-1) to 0.15 and 0.18 kcal·mol(-1), respectively. The improved results for the minimal basis set STO-3G reach the same accuracy as those of 6-31G(d), and thus B3LYP calculation with the minimal basis set is recommended to be used for minimizing the computational cost and to expand the applications to large molecular systems. Further extrapolation tests are performed with six molecules (two containing Si-NO bonds and two containing fluorine), and the accuracy of the tests was within 1 kcal·mol(-1). This study shows that DFT-SOFM-RBFNN is an efficient and highly accurate method for Y-NO homolysis BDE. The method may be used as a tool to design new NO carrier molecules.
Assuntos
Modelos Químicos , Óxido Nítrico/química , Algoritmos , Análise por Conglomerados , Redes Neurais de Computação , Teoria Quântica , TermodinâmicaRESUMO
BACKGROUND: Serum testosterone levels have been found lower in acute ischemic stroke male patients. However, the exact mechanism remains unclear. In the present study, we measured serum testosterone levels, steroidogenesis- related genes and Leydig cells number in experimental transient cerebral ischemia male rats to elucidate the mechanism. METHODS: The middle cerebral arteries of adult male Sprague-Dawley rats were sutured for 120 minutes and then sacrificed after 24 hours. Blood was collected for measurement of serum testosterone, follicular stimulating hormone and estradiol levels, and testes were collected for measurement of steroidogenesis-related gene mRNA levels and number of Leydig cells. RESULTS: Serum testosterone levels in rats after cerebral ischemia were significantly lower (0.53 ± 0.16) ng/ml, n = 7, mean ± SE) compared with control ((2.33 ± 0.60) ng/ml, n = 7), while serum estradiol and follicular stimulating hormone levels did not change. The mRNA levels for luteinizing hormone receptor (Lhcgr), scavenger receptor class B member 1 (Scarb1), steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (Cyp11a1), 3ß-hydroxysteroid dehydrogenase 1 (HSD3ß1), 17α-hydroxylase/20-lyase (Cyp17a1) and membrane receptor c-kit (kit) were significantly downregulated by cerebral ischemia, while luteinizing hormone, Kit ligand (KitL), 17ß-hydrosteroid dehydrogenase 3 (HSD17ß3) and 5α-reductase (Srd5a1) were not affected. We also observed that, relative to control, the Leydig cell number did not change. CONCLUSIONS: These results indicate that transient cerebral ischemia in the brain results in lower expression levels of steroidogenesis-related genes and thus lower serum testosterone level. Transient cerebral ischemia did not lower the number of Leydig cells.
Assuntos
Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/metabolismo , Testículo/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Células Intersticiais do Testículo/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Testosterona/sangueRESUMO
The proper theoretical calculation method for nonlinear optical (NLO) properties is a key factor to design the excellent NLO materials. Yet it is a difficult task to obatin the accurate NLO property of large scale molecule. In present work, an effective intelligent computing method, as called extreme learning machine-neural network (ELM-NN), is proposed to predict accurately the first hyperpolarizability (ß(0)) of alkalides from low-accuracy first hyperpolarizability. Compared with neural network (NN) and genetic algorithm neural network (GANN), the root-mean-square deviations of the predicted values obtained by ELM-NN, GANN, and NN with their MP2 counterpart are 0.02, 0.08, and 0.17 a.u., respectively. It suggests that the predicted values obtained by ELM-NN are more accurate than those calculated by NN and GANN methods. Another excellent point of ELM-NN is the ability to obtain the high accuracy level calculated values with less computing cost. Experimental results show that the computing time of MP2 is 2.4-4 times of the computing time of ELM-NN. Thus, the proposed method is a potentially powerful tool in computational chemistry, and it may predict ß(0) of the large scale molecules, which is difficult to obtain by high-accuracy theoretical method due to dramatic increasing computational cost.
Assuntos
Metais Alcalinos/química , Redes Neurais de Computação , Teoria QuânticaRESUMO
We propose a generalized regression neural network (GRNN) approach based on grey relational analysis (GRA) and principal component analysis (PCA) (GP-GRNN) to improve the accuracy of density functional theory (DFT) calculation for homolysis bond dissociation energies (BDE) of Y-NO bond. As a demonstration, this combined quantum chemistry calculation with the GP-GRNN approach has been applied to evaluate the homolysis BDE of 92 Y-NO organic molecules. The results show that the ull-descriptor GRNN without GRA and PCA (F-GRNN) and with GRA (G-GRNN) approaches reduce the root-mean-square (RMS) of the calculated homolysis BDE of 92 organic molecules from 5.31 to 0.49 and 0.39 kcal mol(-1) for the B3LYP/6-31G (d) calculation. Then the newly developed GP-GRNN approach further reduces the RMS to 0.31 kcal mol(-1). Thus, the GP-GRNN correction on top of B3LYP/6-31G (d) can improve the accuracy of calculating the homolysis BDE in quantum chemistry and can predict homolysis BDE which cannot be obtained experimentally.
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Modelos Moleculares , Óxido Nítrico/química , Análise de Componente Principal , Teoria Quântica , TermodinâmicaRESUMO
Mitochondrial respiratory chain defects have been associated with various diseases and normal aging, particularly in tissues with high energy demands including skeletal muscle. Muscle-specific mitochondrial DNA (mtDNA) mutations have also been reported to accumulate with aging. Our understanding of the molecular processes mediating altered mitochondrial gene expression to dysfunction associated with mtDNA mutations in muscle would be greatly enhanced by our ability to transfer muscle mtDNA to established cell lines. Here, we report the successful generation of mouse cybrids carrying skeletal muscle mtDNA. Using this novel approach, we performed bioenergetic analysis of cells bearing mtDNA derived from young and old mouse skeletal muscles. A significant decrease in oxidative phosphorylation coupling and regulation capacity has been observed with cybrids carrying mtDNA from skeletal muscle of old mice. Our results also revealed decrease growth capacity and cell viability associated with the mtDNA derived from muscle of old mice. These findings indicate that a decline in mitochondrial function associated with compromised mtDNA quality during aging leads to a decrease in both the capacity and regulation of oxidative phosphorylation.
Assuntos
Envelhecimento/genética , DNA Mitocondrial/química , Mitocôndrias/metabolismo , Músculo Esquelético/química , Envelhecimento/metabolismo , Animais , Linhagem Celular , Proliferação de Células , Respiração Celular , Sobrevivência Celular , Células Híbridas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Fosforilação Oxidativa , Consumo de OxigênioRESUMO
Thrombin-like enzyme (TLE) plays a significant role in vessel injury hemostasis. A novel snake venom TLE (Agacutin) was purified from Agkistrodon Acutus snake venom. Structural analysis indicated that Agacutin is a heterodimer that has a MW of 29,402 Da, a pI value of 5.39, and optimum activity at 35 degrees C and pH 7.5. The N-terminal 15 amino acid sequences of Agacutin are DSSGWSSYEGHEYYV (small subunit) and DCSSGWSSYEEHQYY (large subunit). In vitro studies indicated that the coagulation activity of Agacutin was activated by Ca(+2) or inhibited by phenylmethanesulfonyl fluoride, but not influenced by heparin or hirudin. The arginine esterase activity and fibrinogen hydrolysis result showed that Agacutin only cleaves alpha-subunit and releases fibrinopeptide A. In vivo studies indicated that Agacutin iv (0.01-0.05 U/kg) shortened 30.2-49% of the rabbit blood clotting time, or ip (0.5-2.0 U/kg) shortened 29.7-73.1% of the mouse tail bleeding time. Agacutin does not influence APTT, platelet or euglobulin clotting time, and activate Factor II or XIII. It converts fibrinogen into the soluble fibrin that accelerates hemostasis at wound.
Assuntos
Agkistrodon/metabolismo , Venenos de Crotalídeos/química , Venenos de Crotalídeos/farmacologia , Hemostasia/efeitos dos fármacos , Trombina/química , Trombina/farmacologia , Sequência de Aminoácidos , Animais , Coagulação Sanguínea/efeitos dos fármacos , Cálcio/farmacologia , Venenos de Crotalídeos/isolamento & purificação , Venenos de Crotalídeos/metabolismo , Eletroforese em Gel de Poliacrilamida , Fibrinogênio/metabolismo , Heparina/farmacologia , Hirudinas/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Ponto Isoelétrico , Camundongos , Dados de Sequência Molecular , Coelhos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Temperatura , Trombina/isolamento & purificação , Trombina/metabolismoRESUMO
Support vector machines (SVMs), as a novel type of learning machine, has been very successful in pattern recognition and function estimation problems. In this paper we introduce least-squares (LS) SVMs to improve the calculation accuracy of density functional theory. As a demonstration, this combined quantum mechanical calculation with LS-SVM correction approach has been applied to evaluate the electronic excitation energies of 160 organic molecules. The newly introduced LS-SVM approach reduces the root-mean-square deviation of the calculated electronic excitation energies of 160 organic molecules from 0.32 to 0.11 eV for the B3LYP/6-31G(d) calculation. Thus, the LS-SVM correction on top of B3LYP/6-31G(d) is a better method to correct electronic excitation energies and can be used as the approximation of experimental results which are impossible to obtain experimentally.