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Mdivi-1, Mitochondrial DIVIsion inhibitor 1, has been widely employed in research under the assumption that it exclusively influences mitochondrial fusion, but effects other than mitochondrial dynamics have been underinvestigated. This paper provides transcriptome and DNA methylome-wide analysis for Mdivi-1 treated SH-SY5Y human neuroblastoma cells using RNA sequencing (RNA-seq) and methyl capture sequencing (MC-seq) methods. Gene ontology analysis of RNA sequences revealed that p53 transcriptional gene network and DNA replication initiation-related genes were significantly up and down-regulated, respectively, showing the correlation with the arrest cell cycle in the G1 phase. MC-seq, a powerful sequencing method for capturing DNA methylation status in CpG sites, revealed that although Mdivi-1 does not induce dramatic DNA methylation change, the subtle alterations were concentrated within the CpG island. Integrative analysis of both sequencing data disclosed that the p53 transcriptional network was activated while the Parkinson's disease pathway was halted. Next, we investigated several changes in mitochondria in response to Mdivi-1. Copy number and transcription of mitochondrial DNA were suppressed. ROS levels increased, and elevated ROS triggered mitochondrial retrograde signaling rather than inducing direct DNA damage. In this study, we could better understand the molecular network of Mdivi-1 by analyzing DNA methylation and mRNA transcription in the nucleus and further investigating various changes in mitochondria, providing inspiration for studying nuclear-mitochondrial communications.
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Dinaminas , Neuroblastoma , Humanos , Dinaminas/metabolismo , Dinâmica Mitocondrial , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Quinazolinonas/farmacologiaRESUMO
In addition to regulating cholesterol synthesis, statins have neuroprotective effects. Apoptosis of retinal ganglion cells (RGCs) causes a gradual loss of visual function in glaucoma. This study aimed to investigate the neuroprotective effect of statins on the RGC apoptosis induced by activated Müller glia. Primary Müller cells and RGCs were cultured from the retina of C57BL6 mice. Müller cells were activated with GSK101, a transient receptor potential vanilloid 4 (TRPV4) agonist, and tumor necrosis factor-alpha (TNF-α) released to the medium was measured using an enzyme-linked immunosorbent assay. Cells were pretreated with simvastatin or lovastatin before GSK101. RGCs were treated with conditioned media from Müller glia cultures, and apoptosis was determined using flow cytometry. TRPV4 activation through GSK101 treatment induced gliosis of Müller cells, and the conditioned media from activated Müller cells was potent to induce RGC apoptosis. Statins suppress both gliosis in Müller cells and subsequent RGC apoptosis. TNF-α release to the media was increased in GSK101-treated Müller cells, and TNF-α in the conditioned media was the critical factor causing RGC apoptosis. The increase in TRPV4-mediated TNF-α expression occurred through the nuclear factor kappa-light chain enhancer of activated B cell pathway activation, which was inhibited by statins. Herein, we showed that statins can modulate gliosis and TNF-α expression in Müller cells, protecting RGCs. These data further support the neuroprotective effect of statins, promoting them as a potential treatment for glaucoma.
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Antineoplásicos , Glaucoma , Inibidores de Hidroximetilglutaril-CoA Redutases , Fármacos Neuroprotetores , Animais , Camundongos , Antineoplásicos/farmacologia , Apoptose , Meios de Cultivo Condicionados/farmacologia , Células Ependimogliais/metabolismo , Glaucoma/tratamento farmacológico , Glaucoma/patologia , Gliose/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Canais de Cátion TRPV/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Mesenchymal stromal cells (MSCs) are increasingly combined with biomaterials to enhance their therapeutic properties, including their immunosuppressive function. However, clinical trials utilizing MSCs with or without biomaterials have shown limited success, potentially due to their functional heterogeneity across different donors and among different subpopulations of cells. Here, we evaluated the immunosuppressive capacity, as measured by the ability to reduce T-cell proliferation and activation, of interferon-gamma (IFN-γ)-licensed MSCs from multiple donors on fibrin and collagen hydrogels, the two most commonly utilized biomaterials in combination with MSCs in clinical trials worldwide according to ClinicalTrials.gov Variations in the immunosuppressive capacity between IFN-γ-licensed MSC donors on the biomaterials correlated with the magnitude of indoleamine-2,3-dioxygenase activity. Immunosuppressive capacity of the IFN-γ-licensed MSCs depended on the αV/α5 integrins when cultured on fibrin and on the α2/ß1 integrins when cultured on collagen. While all tested MSCs were nearly 100% positive for these integrins, sorted MSCs that expressed higher levels of αV/α5 integrins demonstrated greater immunosuppressive capacity with IFN-γ licensing than MSCs that expressed lower levels of these integrins on fibrin. These findings were equivalent for MSCs sorted based on the α2/ß1 integrins on collagen. These results demonstrate the importance of integrin engagement to IFN-γ licensed MSC immunosuppressive capacity and that IFN-γ-licensed MSC subpopulations of varying immunosuppressive capacity can be identified by the magnitude of integrin expression specific to each biomaterial.
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Colágeno/metabolismo , Fibrina/metabolismo , Terapia de Imunossupressão , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Integrina alfa2beta1/metabolismo , Interferon gama/farmacologia , Células-Tronco Mesenquimais/citologia , Antivirais/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Colágeno/química , Fibrina/química , Humanos , Hidrogéis/química , Hidrogéis/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismoRESUMO
PURPOSE: The objectives of this study were to assess the utility of dynamic contrast-enhanced magnetic resonance (MR) imaging in quantifying parenchymal perfusional changes after embolization and to characterize the association between pharmacokinetic (PK) parameters and final microwave ablation volume. MATERIALS AND METHODS: PK parameters from dynamic contrast-enhanced MR imaging were used to quantify perfusional changes in the liver after transarterial embolization of the right or left lobe in a swine liver model (n = 5). Each animal subject subsequently underwent microwave ablation (60 W for 5 minutes) of the embolized and nonembolized liver lobes. Changes in PK parameters from dynamic contrast-enhanced MR imaging were correlated with their respective final microwave ablation volumes in each liver lobe. RESULTS: Microwave ablation volumes of embolized liver lobes were significantly larger than those of nonembolized liver lobes (28.0 mL ± 6.2 vs 15.1 mL ± 5.2, P < .001). PK perfusion parameters were significantly lower in embolized liver lobes than in nonembolized liver lobes (Ktrans = 0.69 min-1 ± 0.15 vs 1.52 min-1 ± 0.37, P < .001; kep = 0.69 min-1 ± 0.19 vs 1.54 min-1 ± 0.42, P < .001). There was a moderate but significant correlation between normalized kep and ablation volume, with each unit increase in normalized kep corresponding to a 9.8-mL decrease in ablation volume (P = .035). CONCLUSIONS: PK-derived parameters from dynamic contrast-enhanced MR imaging can be used to quantify perfusional changes after transarterial embolization and are directly inversely correlated with final ablation volume.
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Embolização Terapêutica , Fígado , Suínos , Animais , Fígado/diagnóstico por imagem , Fígado/cirurgia , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Perfusão , Embolização Terapêutica/efeitos adversosRESUMO
PURPOSE: To investigate longitudinal changes in optic nerve head (ONH) superficial vessel density (VD), macular VD, circumpapillary retinal nerve fiber layer (RNFL) thickness, and macular ganglion cell-inner plexiform layer (GCIPL) thickness, and their associations with future VF defects in unaffected hemifields of primary open angle glaucoma (POAG) eyes with baseline VF defect confined to a single hemifield. METHODS: This retrospective observational study included 61 POAG eyes with VF defect confined to a single hemifield monitored over a mean follow-up time of 2.7 years. Development of VF defect in opposite hemifield was defined based the Early Manifest Glaucoma Trail criteria. Each eye was classified into either "conversion" or "no conversion" groups according to development of VF defect in the unaffected hemifield. The rates of longitudinal changes in VD and structure parameters in each hemiretina were compared between the two groups. A Cox proportional hazard model was used to identify potential risk factors for VF conversion in the unaffected hemifield. RESULTS: Among 61 eyes, 17 eyes (27.9%) were classified as "conversion" and 44 eyes (72.1%) were classified as "non-conversion" groups. The conversion group exhibited significantly greater rates of both VD and structural changes in both hemiretinas. In Cox proportional hazard model, greater rate of change in GCIPL thickness, ONH superficial VD, and macular VD of both hemiretinas and greater rate of change in RNFL thickness of the unaffected hemiretina were identified as risk factors for VF conversion in the unaffected hemifield. CONCLUSIONS: Monitoring progressive changes in VD and structural parameters effectively predict future VF defect in the opposite hemifields of POAG eyes with single-hemifield defects.
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Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Campos Visuais , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Células Ganglionares da Retina , Pressão Intraocular , Tomografia de Coerência Óptica , Fibras Nervosas , Glaucoma/complicações , Testes de Campo VisualRESUMO
Red blood cell (RBC) transfusion and albumin administration can affect kidney function. We aimed to evaluate the association between intraoperative 20% albumin administration and acute kidney injury (AKI), along with the duration of hospitalization and 30-day mortality in patients undergoing major abdominal surgery with RBC transfusion. This retrospective study included 2408 patients who received transfusions during major abdominal surgery. Patients were categorized into albumin (n = 842) or no-albumin (n = 1566) groups. We applied inverse probability of treatment weighting (IPTW), propensity score (PS) matching (PSM), and PS covariate adjustment to assess the effect of albumin administration on the outcomes. In the unadjusted cohort, albumin administration was significantly associated with increased risk of AKI, prolonged hospitalization, and higher 30-day mortality. However, there was no significant association between albumin administration and AKI after adjustment (OR 1.26, 95% CI 0.90-1.76 for the IPTW; OR 1.03, 95% CI 0.72-1.48 for the PSM; and OR 1.04, 95% CI 0.76-1.43 for the PS covariate adjustment methods). While albumin exposure remained associated with prolonged hospitalization after adjustment, it did not affect 30-day mortality. Our findings suggest that hyper-oncotic albumin can be safely administered to patients who are at risk of developing AKI due to RBC transfusion.
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Injúria Renal Aguda , Transfusão de Sangue , Humanos , Estudos Retrospectivos , Transfusão de Eritrócitos/efeitos adversos , Injúria Renal Aguda/etiologia , Fatores de RiscoRESUMO
BACKGROUND: To compare the surgical outcomes and postoperative complications with and without Ologen collagen matrix augmentation during XEN gel stent implantation. METHODS: We retrospectively analyzed patients who underwent XEN gel stent implantation with an ab externo technique. The amount of intraocular pressure (IOP) reduction, percentage of postoperative complications and additional management, and surgical success defined as IOP reduction greater than 20% compared with the preoperative IOP measurement were compared between Ologen-augmented and non-augmented groups. Groups of patients who underwent XEN gel stent implantation alone and combined with phacoemulsification were analyzed separately. RESULTS: A total 103 eyes of 103 participants were included. Of those, 72 eyes underwent standalone XEN gel stent implantation: 42 eyes with Ologen augmentation (Oloxen group) and 30 eyes without Ologen augmentation (Xen group). Thirty-one eyes underwent XEN gel stent implantation with phacoemulsification: 19 eyes with Ologen augmentation (Phaco-Oloxen group) and 12 eyes without Ologen augmentation (PhacoXen group). The surgical success rate at six months postoperatively was not different between the Oloxen and Xen groups (56.4% vs 43.3%, P > 0.05) or between the Phaco-Oloxen group and PhacoXen group (57.9% vs 41.7%, P > 0.05). The prevalence of postoperative hypotony, 5-fluorouracil injections, use of anti-glaucoma medications, bleb needling, and additional glaucoma surgeries was not different between the Oloxen and Xen groups or between the Phaco-Oloxen and PhacoXen groups when assessed six months postoperatively. CONCLUSIONS: All groups showed significant IOP reduction after XEN gel stent implantation, but there was no significant difference between the Ologen collagen matrix augmented and non-augmented groups in surgical outcomes.
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Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto , Humanos , Colágeno , Glaucoma de Ângulo Aberto/cirurgia , Pressão Intraocular , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
A trajectory tracking control for quadcopter unmanned aerial vehicle (UAV) based on a nonlinear robust backstepping algorithm and extended state/disturbance observer (ESDO) is presented in this paper. To obtain robust attitude stabilization and superior performance of three-dimension position tracking control, the construction of the proposed algorithm can be separated into three parts. First, a mathematical model of UAV negatively influenced by exogenous disturbances is established. Following, an extended state/disturbance observer using a general second-order model is designed to approximate undesirable influences of perturbations on the UAVs dynamics. Finally, a nonlinear robust controller is constructed by an integration of the nominal backstepping technique with ESDO to enhance the performance of attitude and position control mode. Robust stability of the closed-loop disturbed system is obtained and guaranteed through the Lyapunov theorem without precise knowledge of the upper bound condition of perturbations. Lastly, a numerical simulation is carried out and compared with other previous controllers to demonstrate the great advantage and effectiveness of the proposed control method.
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We characterized Müller cell gliosis induced by the activation of transient receptor potential vanilloid-type 4 (TRPV4) and assessed whether statins could modulate the gliosis. The human Müller cell line, MIO-M1, was used to analyze the gliosis caused by glaucomatous stimulation. To induce Müller gliosis in MIO-M1 cells, GSK101 was used to activate TRPV4, and Müller gliosis was evaluated by analyzing vimentin, nestin, and glial fibrillary acidic protein (GFAP) expression. The expression level of TNF-α was determined by ELISA. To evaluate the GSK101 activation of the NF-κB pathway, p65 phosphorylation was measured by Western blotting, and the nuclear translocation of p65 and IκBα phosphorylation were assessed by immunostaining. To assess the effect of statins on MIO-M1 gliosis, cells were pretreated for 24 h with statins before GSK101 treatment. Vimentin, nestin, and GFAP expression were upregulated by GSK101, while statins effectively inhibited them. The expression of TNF-α was increased by GSK101. The phosphorylation and nuclear translocation of p65 and IκBα phosphorylation, which occurs prior to p65 activation, were induced. Statins suppressed the GSK101-mediated phosphorylation of IκBα and p65 translocation. Statins can mitigate gliosis in the human Müller cell line. Because TRPV4 activation in Müller cells reflects glaucoma pathophysiology, statins may have the potential to prevent RGC death.
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Glaucoma , Inibidores de Hidroximetilglutaril-CoA Redutases , Células Ependimogliais/metabolismo , Glaucoma/metabolismo , Gliose/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidor de NF-kappaB alfa/metabolismo , Nestina/metabolismo , Canais de Cátion TRPV/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Vimentina/metabolismoRESUMO
Background and Objectives: The relation of dietary n-6 fatty acid to metabolic syndrome has not been examined and clearly defined. To improve health in the general population, this study was to investigate the role of n-3 and n-6 fatty acids in the reduction in metabolic syndrome and to observe changes in the effects of these fatty acids depending on the level of insulin resistance. Materials and Methods: This cross-sectional study utilized national health and nutrition survey data from 2014 to 2016. From the data, a relation of n-3 and n-6 fatty acid intakes to metabolic syndrome and Hemoglobin A1c (HbA1c)'s role in the relation was evaluated and analyzed for 4852 patients between 40 and 64 years old. Intake frequency of 112 nutrition and daily consumption amounts were identified, and intakes of n-3 and n-4 fatty acids were calculated from this data. Metabolic syndrome was determined for each participant using diagnostic standards for the Asian population published by the National Cholesterol Education Program. Results: Among the total 4852 subjects, 1583 (32.6%) had metabolic syndrome; 736 of 1875 (39.3%) males and 847 of 2977 (28.5%) females had the syndrome. In males, when their HbA1c was low (<5.4%), intakes of both n-3 and n-6 fatty acids were related to a 43−63% decreased prevalence of metabolic syndrome with significance, and a similar negative tendency was also observed in females. On the contrary, for both males and females, no statistically significant correlation was present when HbA1c was high. Conclusion: It was considered that consistent and regular dietary intakes of n-3 and n-6 fatty acids may contribute greatly to prevent or treat metabolic syndrome in healthy males with normal insulin sensitivity, but the effect of their dietary intakes was found to be limited in a group with strong insulin resistance. The conclusion of this study presents a valuable reference and knowledge to provide nutritional education to the general population.
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Resistência à Insulina , Síndrome Metabólica , Adulto , Estudos Transversais , Dieta , Ácidos Graxos , Ácidos Graxos Ômega-6 , Feminino , Hemoglobinas Glicadas , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Inquéritos NutricionaisRESUMO
Given the increased recognition of the importance of physiologically relevant microenvironments when designing in vitro assays, microphysiological systems (MPS) that mimic the critical function and structure of tissues and organs have gained considerable attention as alternatives to traditional experimental models. Accordingly, the field is growing rapidly, and some promising MPS are being tested for use in pharmaceutical development and toxicological testing. However, most MPS are complex and require additional infrastructure, which limits their successful translation. Here, we present a pumpless, modular MPS consisting of 1) a resistance module that controls flow rate and 2) a physiologically relevant, three-dimensional blood vessel module. Flow is provided by an attached reservoir tank that feeds fluid into the resistance channel via hydrostatic pressure. The flow rate is controlled by the height of the media in the tank and the resistance channel's dimensions. The flow from the resistance module is streamed into the blood vessel module using a liquid bridge. We utilize optical coherence tomography (OCT) to measure fluid velocity at regions of interest. The endothelial cells cultured in the MPS remain viable for up to 14 days and demonstrate the functional characteristics of the human blood vessels verified by tight junction expression and diffusion assay. Our results show that a modular MPS can simulate a functional endothelium in vitro while simplifying the operation of the MPS. The simplicity of the system allows for modifications to incorporate other microenvironmental components and to build other organ-modeling systems easily.
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Células Endoteliais , Dispositivos Lab-On-A-Chip , Humanos , PerfusãoRESUMO
Glaucoma is an optic neuropathy in which the degeneration of retinal ganglion cells (RGCs) results in irreversible vison loss. Therefore, neuroprotection of RGCs from glaucomatous afflictions is crucial for glaucoma treatment. In this study, we aimed to investigate the beneficial effects of statins in the protection of RGCs using a rat model. Glaucomatous injury was induced in rats by chronic ocular hypertension (OHT) achieved after performing a circumlimbal suture. The rats were given either statins such as simvastatin and atorvastatin or a solvent weekly for 6 weeks. Retina sections underwent hematoxylin and eosin, Brn3a, or cleaved casepase-3 staining to evaluate RGC survival. In addition, modulation of glial activation was assessed. While the retinas without statin treatment exhibited increased RGC death due to chronic OHT, statins promoted the survival of RGCs and reduced apoptosis. Statins also suppressed chronic OHT-mediated glial activation in the retina. Our results demonstrate that statins exert neuroprotective effects in rat retinas exposed to chronic OHT, which may support the prospect of statins being a glaucoma treatment.
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Glaucoma/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão Ocular/tratamento farmacológico , Degeneração Retiniana/tratamento farmacológico , Animais , Modelos Animais de Doenças , Glaucoma/genética , Glaucoma/patologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Neuroproteção/genética , Fármacos Neuroprotetores/farmacologia , Hipertensão Ocular/genética , Hipertensão Ocular/patologia , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia , Doenças do Nervo Óptico/tratamento farmacológico , Doenças do Nervo Óptico/genética , Doenças do Nervo Óptico/patologia , Ratos , Retina/efeitos dos fármacos , Retina/patologia , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Fator de Transcrição Brn-3A/química , Fator de Transcrição Brn-3A/isolamento & purificaçãoRESUMO
The hypothalamic regulation of appetite governs whole-body energy balance. Satiety is regulated by endocrine factors including leptin, and impaired leptin signaling is associated with obesity. Despite the anorectic effect of leptin through the regulation of the hypothalamic feeding circuit, a distinct downstream mediator of leptin signaling in neuron remains unclear. Angiopoietin-like growth factor (AGF) is a peripheral activator of energy expenditure and antagonizes obesity. However, the regulation of AGF expression in brain and localization to mediate anorectic signaling is unknown. Here, we demonstrated that AGF is expressed in proopiomelanocortin (POMC)-expressing neurons located in the arcuate nucleus (ARC) of the hypothalamus. Unlike other brain regions, hypothalamic AGF expression is stimulated by leptin-induced signal transducers and activators of transcription 3 (STAT3) phosphorylation. In addition, leptin treatment to hypothalamic N1 cells significantly enhanced the promoter activity of AGF. This induction was abolished by the pretreatment of ruxolitinib, a leptin signaling inhibitor. These results indicate that hypothalamic AGF expression is induced by leptin and colocalized to POMC neurons.
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Proteínas Semelhantes a Angiopoietina/genética , Proteínas Semelhantes a Angiopoietina/metabolismo , Hipotálamo/metabolismo , Leptina/metabolismo , Transdução de Sinais , Proteína 6 Semelhante a Angiopoietina , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Encéfalo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Fosforilação , Pró-Opiomelanocortina/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
OBJECTIVES: The purpose of this study was to characterize the impact of cutaneous lupus erythematosus (CLE) in adults and identify the clinical and non-clinical factors associated with quality of life (QoL), using the Revised Wilson and Cleary Model. METHODS: 101 patients diagnosed with CLE were included in this cross-sectional study. QoL was measured with the Cutaneous Lupus Erythematosus Quality of Life (CLEQoL) scale and disease activity and damage with the Cutaneous Lupus Activity and Severity Index (CLASI). Patient demographics, clinical, and disease characteristics were also collected. Descriptive statistics were calculated, and multiple regression was employed to determine significant (p < 0.05) predictors of overall QoL. Data were analyzed using SPSS v24. RESULTS: The overall regression QoL model was significantly different from zero, (F = 24.96; df = 14, 76; p = <0.001). Disease activity (ß = 0.13), pain (ß = 0.13), fatigue (ß = 0.24), body image (ß = 0.62), and side effects (ß = -0.13) were significant predictors of overall QoL while controlling for other predictor variables. Patients who experienced higher levels of disease activity, fatigue severity, pain levels, and greater degree of body dissatisfaction had significantly poorer QoL. Fewer side effects experienced from CLE medications were significantly associated with higher QoL. CONCLUSIONS: Study findings support the considerable burden associated with CLE. Several modifiable variables such as pain, fatigue, body image, and disease activity were associated with QoL. Therefore, interventions that incorporate these variables may reduce negative impacts on QoL life and improve health outcomes in CLE patients. Furthermore, given the chronic and recurring nature of the condition, strategies focused on improving QoL are needed for this vulnerable population.
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Indicadores Básicos de Saúde , Lúpus Eritematoso Cutâneo/psicologia , Modelos Teóricos , Qualidade de Vida , Adulto , Imagem Corporal/psicologia , Estudos Transversais , Fadiga/fisiopatologia , Feminino , Nível de Saúde , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Dor/fisiopatologia , Índice de Gravidade de DoençaRESUMO
In this paper, an actuator fault estimation technique is proposed for quadcopters under uncertainties. In previous studies, matching conditions were required for the observer design, but they were found to be complex for solving linear matrix inequalities (LMIs). To overcome these limitations, in this study, an improved intermediate estimator algorithm was applied to the quadcopter model, which can be used to estimate actuator faults and system states. The system stability was validated using Lyapunov theory. It was shown that system errors are uniformly ultimately bounded. To increase the accuracy of the proposed fault estimation algorithm, a magnitude order balance method was applied. Experiments were verified with four scenarios to show the effectiveness of the proposed algorithm. Two first scenarios were compared to show the effectiveness of the magnitude order balance method. The remaining scenarios were described to test the reliability of the presented method in the presence of multiple actuator faults. Different from previous studies on observer-based fault estimation, this proposal not only can estimate the fault magnitude of the roll, pitch, yaw, and thrust channel, but also can estimate the loss of control effectiveness of each actuator under uncertainties.
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Switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, one of the adenosine triphosphate (ATP)-dependent chromatin remodeler complexes. The unique role of SMARCB1 has been reported in various cellular contexts. Here, we focused on the general role of the ubiquitous expression of SMARCB1 in a normal cell state. We selected ARPE19 (human primary retinal pigment epithelium) and IMR90 (from human fetal lung fibroblasts) cell lines as they have completely different contexts. Furthermore, although these cell lines have been immortalized, they are relatively close to normal human cells. The loss of SMARCB1 in ARPE19 and IMR90 cells reduced cell cycle progression via the upregulation of P21. Transcriptome analysis followed by SMARCB1 knockdown in both cell lines revealed that SMARCB1 was not only involved in cell maintenance but also conferred immunomodulation. Of note, SMARCB1 bound to interleukin (IL) 6 promoter in a steady state and dissociated in an active immune response state, suggesting that SMARCB1 was a direct repressor of IL6, which was further confirmed via loss- and gain-of-function studies. Taken together, we demonstrated that SMARCB1 is a critical gatekeeper molecule of the cell cycle and immune response.
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Regulação da Expressão Gênica , Epitélio Pigmentado da Retina/metabolismo , Proteína SMARCB1/fisiologia , Trifosfato de Adenosina/metabolismo , Ciclo Celular , Linhagem Celular , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Humanos , Imunidade , Interleucina-6/metabolismo , TranscriptomaRESUMO
OBJECTIVE: Combination of two stressors on alteration of mineral footprints in animals needs due attention to meet maximum production and welfare, particularly in grazing sheep. This study tested whether ewes (Ovis aries) exposed to water deprivation and thermal-humidity stressors had altered mineral footprints in their wool, serum, urine, and feces. METHODS: Nine ewes (age = 3 years; mean body weight = 41±3.5 kg) were divided among a control group with free access to water, and treatment groups with water deprivation lasting either 2 h (2hWD) or 3 h (3hWD) after feeding. Using a 3×3 Latin square design, animals were assigned to treatment groups for three sampling periods of 21 days each (n = 9). Blood was collected by jugular venipuncture. Wool was collected at the end of periods 2 and 3. Metabolic crates designed with metal grated floors were used for urine and feces collection. We measured sodium (Na), magnesium (Mg), phosphorus (P), chloride (Cl), calcium (Ca), manganese (Mn), copper (Cu), iron (Fe), and zinc (Zn). RESULTS: The wool mineral levels did not differ between the treatment groups, although K was marginally lower (p = 0.10) in the 2hWD group. The serum and urine mineral levels did not differ between the treatments (p>0.05). Fecal K was significantly lower in the 2hWD group than in the other groups (p≤0.05). CONCLUSION: In conclusion, water deprivation and thermal-humidity exposure altered the excretion of K, but not of other minerals, in the wool, urine, feces, or serum of ewes. Thus, no additional mineral supplementation is needed for water deprived ewes during thermalhumidity exposure.
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PURPOSE: We investigated the performance of 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil to detect prostate cancer with a whole mount histopathology reference. MATERIALS AND METHODS: This retrospective HIPAA (Health Insurance Portability and Accountability Act) compliant, institutional review board approved, case-control study included patients who underwent 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil from July 2009 to December 2016 prior to prostatectomy. The tumor detection rate was calculated for total and index lesions. Lesion magnetic resonance imaging and histopathology features were compared between the 2 groups. Using SPSS®, version 24 p <0.05 was considered significant. RESULTS: A total of 871 whole mount histopathology lesions in 429 patients with a mean ± SD age of 61.8 ± 7 years were included in analysis. The subcohorts with and without an endorectal coil comprised 260 and 169 patients with a total of 529 and 342 lesions, respectively. The overall tumor detection rates in all patients, and in the endorectal coil and nonendorectal coil subcohorts were 49.6% (432 of 871 patients), 50.5% (267 of 529) and 48.2% (165 of 342), respectively. The index tumor detection rates overall, and in the endorectal coil and nonendorectal coil subcohorts were 77.6% (333 of 429 patients), 78.5% (204 of 260) and 76.3% (129 of 169), respectively. In the endorectal coil and nonendorectal coil subcohorts we detected 35.9% (66 of 184) and 48.4% (76 of 157) of anterior lesions (p = 0.019), 58% (200 of 345) and 48.1% (89 of 185) of posterior lesions (p = 0.025), 37.3% (41 of 110) and 54.4% (62 of 114) of transition zone lesions (p = 0.010), and 53.7% (225 of 419) and 45.2% (103 of 228) of peripheral lesions (p = 0.033), respectively. After adjusting for clinical and pathological factors the endorectal coil group only showed higher detection of peripheral and posterior prostate cancer. CONCLUSIONS: We found that 3 Tesla multiparametric magnetic resonance imaging with and without an endorectal coil had similar detection of overall and index prostate cancer. However, the endorectal coil subcohort had significantly higher detection of posterior and peripheral prostate cancer, and lower detection of anterior and transition zone prostate cancer.
Assuntos
Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: Improve 19F magnetic resonance imaging uniformity of perfluorocarbon (PFC)-labeled cells by using a secondary inductive resonator tuned to 287 MHz to enhance the induced radio frequency (RF) magnetic field (B1) at 7.05 T. MATERIALS AND METHODS: Following Faraday's induction law, the sign of induced B1 made by the secondary resonator can be changed depending on the tuning of the resonator. A secondary resonator located on the opposite side of the phantom of the 19F surface coil can be shown to enhance or subtract the induced B1 field, depending upon its tuning. RESULTS: The numerical simulation results of rotating transmit B1 magnitude (|B 1 + |) and corresponding experimental 19F images were compared without and with the secondary resonator. With the secondary resonator tuned to 287 MHz, improvements of |B 1 + | and 19F image uniformity were demonstrated. The use of the secondary resonator improved our ability to visualize transplanted cell location non-invasively over a period of 6 weeks. CONCLUSION: The secondary resonator tuned to enhance the induced B1 results in improved image uniformity in a pre-clinical application, enabling cell tracking of PFC-labeled cells with the secondary resonator.
Assuntos
Rastreamento de Células/métodos , Imagem por Ressonância Magnética de Flúor-19 , Flúor/química , Campos Magnéticos , Transplante de Células-Tronco , Animais , Desenho de Equipamento , Fluorocarbonos , Camundongos , Modelos Teóricos , Imagens de Fantasmas , Ondas de Rádio , Razão Sinal-RuídoRESUMO
In this paper, fault detection and fault-tolerant control strategies are proposed to handle the issues of both actuator faults and disturbances in a hexacopter. A dynamic model of a hexacopter is first derived to develop a model-based fault detection system. Secondly, the altitude control based on a sliding mode and disturbance observer is presented to tackle the disturbance issue. Then, a nonlinear Thau observer is applied to estimate the states of a hexacopter and to generate the residuals. Using a fault detection unit, the motor failure is isolated to address the one or two actuator faults. Finally, experimental results are tested on a DJI F550 hexacopter platform and Pixhawk2 flight controller to verify the effectiveness of the proposed approach. Unlike previous studies, this work can integrate fault detection and fault-tolerant control design as a single unit. Moreover, the developed fault detection and fault-tolerant control method can handle up to two actuator failures in presence of disturbances.