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1.
Nanotechnology ; 30(39): 394003, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242472

RESUMO

The evolution of surface cleanliness and the electronic properties-Dirac voltage(V Dirac), hysteresis and mobility (µ) of a graphene field-effect transistor (GFET)-were monitored by measuring lateral force microscopy and drain current (I D) as a function of gate voltage (V G), after mechanically cleaning the surface, scan-by-scan, with contact-mode atomic force microscopy. Both the surface cleanliness and the electronic properties evolved, showing a sudden improvement and then saturation for a mobility of around 2200 cm2 V-1 s-1. We found that the mobility suppression of the as-fabricated GFET deviated from a randomly distributed impurities model, which predicted a greater mobility than obtained from the measured V Dirac. Therefore, the substrate impurities are excluded from the origins of the extraordinary suppression of the mobility, and the possible origin will be discussed.

2.
JACC Cardiovasc Imaging ; 12(11 Pt 1): 2196-2206, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30772219

RESUMO

OBJECTIVES: This study aimed to investigate clinical and coronary computed tomographic angiography (CTA) characteristics of lesions that progressed to chronic total occlusion (CTO). BACKGROUND: CTO is one of the most common reasons for referral to coronary artery bypass surgery. Prediction and adequate early management for future CTO lesions may be beneficial. METHODS: The study evaluated patients with at least 1 vessel with a diameter stenosis of ≥70% on invasive coronary angiography (ICA) who underwent previous coronary CTA >12 months before ICA, from 2006 to 2015. The study compared the baseline clinical and coronary CTA characteristics of the patients with future CTO lesions with those of the patients with future non-CTO lesions (patient-level analysis) and compared coronary CTA findings between the future CTO lesion with the most stenotic non-CTO lesion in each CTO patient (lesion-level analysis). RESULTS: Among the 216 patients, 32 (14.8%) had a CTO lesion on ICA. In patient-level analysis, no significant differences in clinical characteristics were found, whereas the coronary CTA culprit lesions of the CTO group had a smaller minimal lumen diameter (MLD) with more adverse plaque characteristics. In lesion-level analysis, future CTO lesions had a smaller MLD, a smaller reference segment diameter (RD), and longer lesion length. These lesions were more likely to be noncalcified plaques with a noneccentric cross-sectional distribution, and had a higher remodeling index, lower mean plaque attenuation (MPA), and more napkin-ring signs. In multivariate analysis and receiver-operating characteristic curve analysis, MLD of <2.0 mm, RD of <3.2 mm, and MPA of <50 Hounsfield units were independent predictors of future CTO lesions. The risk of CTO development in lesions with triple risk factors was 14-fold higher than that of the lesions with no risk factors. CONCLUSIONS: Lesions that progressed to CTO had more severe baseline coronary CTA features than non-CTO lesions. A small MLD, small RD, and low MPA were independent predictors of progression to CTO.

3.
Nat Commun ; 10(1): 987, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30804336

RESUMO

The original version of this Article contained an error in the spelling of the author Matthew Holwill, which was incorrectly given as Mathew Holwill. This has now been corrected in both the PDF and HTML versions of the Article.

4.
Nat Commun ; 10(1): 230, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30651554

RESUMO

Despite a rich choice of two-dimensional materials, which exists these days, heterostructures, both vertical (van der Waals) and in-plane, offer an unprecedented control over the properties and functionalities of the resulted structures. Thus, planar heterostructures allow p-n junctions between different two-dimensional semiconductors and graphene nanoribbons with well-defined edges; and vertical heterostructures resulted in the observation of superconductivity in purely carbon-based systems and realisation of vertical tunnelling transistors. Here we demonstrate simultaneous use of in-plane and van der Waals heterostructures to build vertical single electron tunnelling transistors. We grow graphene quantum dots inside the matrix of hexagonal boron nitride, which allows a dramatic reduction of the number of localised states along the perimeter of the quantum dots. The use of hexagonal boron nitride tunnel barriers as contacts to the graphene quantum dots make our transistors reproducible and not dependent on the localised states, opening even larger flexibility when designing future devices.

5.
J Am Heart Assoc ; 7(6)2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29535141

RESUMO

BACKGROUND: Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P<0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P=0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P=0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P=0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P=0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF. CONCLUSIONS: In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Nefropatias/fisiopatologia , Rim/fisiopatologia , Admissão do Paciente , Volume Sistólico , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Creatinina/sangue , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Nefropatias/diagnóstico , Nefropatias/mortalidade , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros , República da Coreia/epidemiologia , Medição de Risco , Fatores de Risco , Fatores de Tempo
6.
Cardiovasc Diabetol ; 17(1): 10, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29325562

RESUMO

BACKGROUND: Statins are widely used for lipid lowering in patients with coronary artery disease (CAD), but increasing evidence indicates an association between statin use and new-onset of diabetes mellitus (NODM). Epicardial adipose tissue (EAT) refers to the visceral fat surrounding the heart, which is associated with metabolic diseases. We sought to determine the association between EAT thickness and NODM in CAD patients treated with high-intensity statins. METHODS: We conducted a retrospective medical record review of CAD patients treated with high-intensity statins for at least 6 months after percutaneous coronary intervention performed between January 2009 and June 2013 at Seoul National University Bundang Hospital. EAT thickness was measured by echocardiography using standardized methods. RESULTS: A total of 321 patients were enrolled, who received high-intensity statins for a mean of 952 days; atorvastatin 40 mg in 204 patients (63.6%), atorvastatin 80 mg in 57 patients (17.8%), and rosuvastatin 20 mg in 60 patients (18.7%). During the follow-up period of 3.9 ± 1.7 years, NODM occurred in 40 patients (12.5%). On Cox proportional-hazard regression analysis, EAT thickness at systole [for each 1 mm: hazard ratio (HR) 1.580; 95% confidence interval (CI) 1.346-1.854; P < 0.001] and prediabetes at baseline (HR 4.321; 95% CI 1.998-9.349; P < 0.001) were the only independent predictors of NODM. Using binary cutoff values derived from the receiver operating characteristic curve analysis, EAT thickness at systole larger than 5.0 mm had an HR of 3.402 (95% CI 1.751-6.611, P < 0.001), sensitivity of 52.5%, and specificity of 80.8% for predicting NODM. Also, patients with EAT thickness ≥ 5 mm and prediabetes at baseline had a 12.0-times higher risk of developing NODM compared to the risk noted in patients with EAT thickness < 5 mm and normal glucose tolerance at baseline. CONCLUSION: Epicardial adipose tissue thickness at systole is a consistent independent predictor of NODM in patients with CAD treated with high-intensity statins. Such predictors may help physicians plan adequate surveillance for early detection of NODM.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Atorvastatina/efeitos adversos , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus/induzido quimicamente , Ecocardiografia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pericárdio/diagnóstico por imagem , Rosuvastatina Cálcica/efeitos adversos , Idoso , Atorvastatina/administração & dosagem , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Rosuvastatina Cálcica/administração & dosagem , Seul , Fatores de Tempo , Resultado do Tratamento
7.
Int J Cardiol ; 248: 239-245, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28821416

RESUMO

BACKGROUND: Hyponatremia is a well-known risk factor for worse outcomes in heart failure (HF) patients. The impact of hyponatremia according to the ejection fraction (EF) is unclear. We evaluated the prognostic value of hyponatremia according to HF type. METHODS AND RESULTS: The Korea Acute Heart Failure (KorAHF) registry consecutively enrolled 5625 patients. Hyponatremia was defined as serum sodium level<135mmol/L at hospital admission. HF with preserved and reduced ejection fraction were defined as an LVEF ≥50% and LVEF ≤40%, respectively. Among 5103 patients with available EF, 2088 (60%) had HFrEF, and 1284 (25%) had HFpEF. There was no difference in serum sodium level between the groups (HFrEF: 137.4±4.7mmol/L vs. HFpEF: 137.5±5.0mmol/L, P=0.710). Hyponatremic patients had higher in-hospital mortality or urgent heart transplantation in all (11.3% vs. 4.5%, P<0.001), in HFrEF (13.1% vs. 4.9%, P<0.001), and in HFpEF (6.0% vs. 1.9%, P<0.001). After adjustment for significant covariates, hyponatremia was associated with 1.5 fold increased risk for 1-year post-discharge death in the HFrEF group (HR, 1.52; 95% CI, 1.24-1.86), but not in the HFpEF group (HR, 1.16; 95% CI, 0.84-1.61). During admission, the sodium status changed in 22% of the patients and the discharge sodium status had greater prognostic value. CONCLUSIONS: Hyponatremia is independent of HF type. Hyponatremia is a significant risk factor for adverse in-hospital outcomes; however its long-term prognostic value is only limited to patients with HFrEF, but not for those with HFpEF.


Assuntos
Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Hiponatremia/diagnóstico , Hiponatremia/epidemiologia , Sistema de Registros , Volume Sistólico/fisiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Hiponatremia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Tempo
8.
J Forensic Sci ; 62(3): 796-799, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27990633

RESUMO

This study presented a Ferris wheel accident case. A Ferris wheel is composed of many parts, and the outmost ring of it is assembled using a lock pin. This accident occurred because the lock pin caught the door of a gondola and the gondola overturned. Five of the seven passengers in the gondola fell to the ground, along with the gondola's viewing window. The investigation revealed that the gondola became stuck when its door was caught by a lock pin at the Ferris wheel's three o'clock position. The contact between the door and the lock pin was due to a structural problem: There was not enough space allotted between the door and the lock pin. Therefore, if a passenger pushed on the gondola's door, the potential existed for contact between the door and the lock pin.

9.
Chem Commun (Camb) ; 52(62): 9636-9, 2016 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-27384472

RESUMO

Dual-functional photocatalysis for H2 evolution with the simultaneous mineralization of 4-chlorophenol was achieved under de-aerated conditions using a Cr2O3/Rh/SrTiO3 photocatalyst which has Rh nanoparticles covered with a thin Cr2O3 barrier layer to selectively control and maximize the dual-functional photocatalytic activity.

10.
Sci Rep ; 6: 19733, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-26792630

RESUMO

The emergence of metallic conduction in layered dichalcogenide semiconductor materials by chemical doping is one of key issues for two-dimensional (2D) materials engineering. At present, doping methods for layered dichalcogenide materials have been limited to an ion intercalation between layer units or electrostatic carrier doping by electrical bias owing to the absence of appropriate substitutional dopant for increasing the carrier concentration. Here, we report the occurrence of metallic conduction in the layered dichalcogenide of SnSe2 by the direct Se-site doping with Cl as a shallow electron donor. The total carrier concentration up to ~10(20) cm(-3) is achieved by Cl substitutional doping, resulting in the improved conductivity value of ~170 S · cm(-1) from ~1.7 S · cm(-1) for non-doped SnSe2. When the carrier concentration exceeds ~10(19) cm(-3), the conduction mechanism is changed from hopping to degenerate conduction, exhibiting metal-insulator transition behavior. Detailed band structure calculation reveals that the hybridized s-p orbital from Sn 5s and Se 4p states is responsible for the degenerate metallic conduction in electron-doped SnSe2.

11.
Eur Arch Otorhinolaryngol ; 273(6): 1607-13, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26050221

RESUMO

Globus symptoms are not uncommon after an uncomplicated thyroidectomy. However, their associated factors and etiology have not been investigated. We investigated the etiology and factors related to globus symptoms after thyroidectomy. The medical records of 289 patients who underwent thyroidectomy and completed a voice analysis, psychiatric screening, and voice-related questionnaires before and 1 month after the surgery were reviewed. Patients were excluded if they had globus symptoms before surgery or scored high on the psychiatric questionnaire. The selected patients were divided into two groups according to development of globus symptoms after surgery. Clinicopathological parameters and results of the voice analysis and voice-related questionnaires were compared between the two groups. A total of 157 patients were enrolled, and more than half (80/155, 51 %) showed development of globus symptoms 1 month after thyroidectomy. Female patients [hazard ratio (HR), 2.605; P = 0.010], patients who had central lymph node metastasis (HR, 3.533; P = 0.001), and patients who underwent central neck dissection (HR, 3.652; P = 0.014) had a higher probability of developing globus symptoms. Patients who developed globus symptoms scored higher on the voice-related questionnaire, and had a greater decrease in speaking fundamental frequency (P < 0.001). Globus symptoms developed after 1 month in more than half of patients who underwent thyroidectomy. Female sex and central lymph node metastasis and dissection increased the possibility of developing the symptoms.


Assuntos
Corpos Estranhos , Complicações Pós-Operatórias , Transtornos das Sensações/etiologia , Fatores Sexuais , Tireoidectomia/efeitos adversos , Adulto , Idoso , Dissecação , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Inquéritos e Questionários , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Distúrbios da Voz/etiologia , Adulto Jovem
12.
Laryngoscope ; 126(2): 357-66, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26404562

RESUMO

OBJECTIVES/HYPOTHESIS: Gabapentin and pregabalin are useful for treating neuropathic pain because of their antiallodynic and antihyperalgesic properties, which may be beneficial in managing acute postoperative pain. The goal of this meta-analysis was to perform a systematic review of the literature on the effect of gabapentinoids on postoperative pain following tonsillectomy, and its adverse effects in patients. DATA SOURCES: MEDLINE, SCOPUS, and Cochrane database. METHODS: Two authors independently searched the databases from their inception of article collection to May 2015. Included in the analysis were studies that compared preoperative gabapentinoid administration (gabapentinoids groups) with a placebo or pain control agent (control group) during a 24-hour postoperative period, the outcomes of interest being postoperative pain intensity; rescue analgesic consumption; or adverse effects such as sedation, nausea and vomiting, dizziness, and headache. RESULTS: The pain score reported by the physician during the first 8 hours, as well as the need for analgesics during 24 hours postoperatively, were significantly decreased in the gabapentinoids group versus the control group. Additionally, there was no significant difference between gabapentinoids and control groups for adverse effect during 24 hours postoperatively. In the subgroup analyses (gabapentin and pregabalin) regarding pain-related measurements, two subgroups showed the similar effect on reducing the postoperative pain severity. CONCLUSION: Preoperative administration of gabapentinoids could provide pain relief without side effects in patients undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of gabapentinoids according to the high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted in order to confirm the results of this study. LEVEL OF EVIDENCE: NA.


Assuntos
Aminas/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Pregabalina/uso terapêutico , Tonsilectomia/efeitos adversos , Ácido gama-Aminobutírico/uso terapêutico , Analgésicos/uso terapêutico , Gabapentina , Humanos , Medição da Dor , Dor Pós-Operatória/diagnóstico
13.
Nat Struct Mol Biol ; 22(2): 124-31, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25580578

RESUMO

Kinases perform phosphoryl-transfer reactions in milliseconds; without enzymes, these reactions would take about 8,000 years under physiological conditions. Despite extensive studies, a comprehensive understanding of kinase energy landscapes, including both chemical and conformational steps, is lacking. Here we scrutinize the microscopic steps in the catalytic cycle of adenylate kinase, through a combination of NMR measurements during catalysis, pre-steady-state kinetics, molecular-dynamics simulations and crystallography of active complexes. We find that the Mg(2+) cofactor activates two distinct molecular events: phosphoryl transfer (>10(5)-fold) and lid opening (10(3)-fold). In contrast, mutation of an essential active site arginine decelerates phosphoryl transfer 10(3)-fold without substantially affecting lid opening. Our results highlight the importance of the entire energy landscape in catalysis and suggest that adenylate kinases have evolved to activate key processes simultaneously by precise placement of a single, charged and very abundant cofactor in a preorganized active site.


Assuntos
Adenilato Quinase/química , Adenilato Quinase/metabolismo , Sítios de Ligação , Catálise , Domínio Catalítico , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos Moleculares
14.
J Transl Med ; 12: 283, 2014 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-25297058

RESUMO

BACKGROUND: The Y-75 (Ginsan) acidic polysaccharide from Korean Panax ginseng has been shown to function as an immunomodulatory molecule. However, the efficacy of Y-75 has not been evaluated in clinical trial. METHODS: We verified Y-75 (6 g/day) for safety and immune efficacy in 72 healthy volunteers aged 50-75 years using a randomized, placebo-controlled, parallel, double-blind study. The activities of natural killer (NK) cells and peripheral blood phagocytes, as well as serum levels of monocyte-derived mediators, were assessed before and after administration for 8 and 14 weeks. This trial is registered at ClinicalTrials.gov (NCT02161198). RESULTS: Y-75 significantly enhanced NK cell cytotoxic activity by 35.2% and 40.2% from baseline after administration for 8 and 14 weeks, respectively. The phagocytic activity of peripheral blood cells was also significantly increased by 25.2% and 39.4% and serum level of TNF-α by 38.2% and 44.5% after treatment for 8 and 14 weeks, respectively. Differences in the efficacy of variables compared to the placebo group were also significant. Administration of Y-75 was well tolerated without treatment-related adverse events or alteration of complete blood cell count or blood chemistry over the entire study period. CONCLUSION: Y-75 was shown to be a safe and potentially effective natural alternative for enhancing immune function.


Assuntos
Panax/química , Polissacarídeos/efeitos adversos , Polissacarídeos/farmacologia , Idoso , Citotoxicidade Imunológica/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/efeitos dos fármacos , Placebos , Polissacarídeos/administração & dosagem , Resultado do Tratamento
15.
PLoS One ; 9(8): e105799, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25165816

RESUMO

BACKGROUND AND PURPOSE: The time of hospital arrival may have an effect on prognosis of various vascular diseases. We examined whether off-hour admission would affect the 3-month functional outcome in acute ischemic stroke patients admitted to tertiary hospitals. METHODS: We analyzed the 'off-hour effect' in consecutive patients with acute ischemic stroke using multi-center prospective stroke registry. Work-hour admission was defined as when the patient arrived at the emergency department between 8 AM and 6 PM from Monday to Friday and between 8 AM and 1 PM on Saturday. Off-hour admission was defined as the rest of the work-hours and statutory holidays. Multivariable logistic regression was used to analyze the association between off-hour admission and 3-month unfavorable functional outcome defined as modified Rankin Scale (mRS) 3-6. Multivariable model included age, sex, risk factors, prehospital delay time, intravenous thrombolysis, stroke subtypes and severity as covariates. RESULTS: A total of 7075 patients with acute ischemic stroke were included in this analysis: mean age, 67.5 (±13.0) years; male, 58.6%. In multivariable analysis, off-hour admission was not associated with unfavorable functional outcome (OR, 0.89; 95% CI, 0.72-1.09) and mortality (OR, 1.09; 95% CI, 0.77-1.54) at 3 months. Moreover, off-hour admission did not affect a statistically significant shift of 3-month mRS distributions (OR, 0.90; 95% CI, 0.78-1.05). CONCLUSIONS: 'Off-hour' admission is not associated with an unfavorable 3-month functional outcome in acute ischemic stroke patients admitted to tertiary hospitals in Korea. This finding indicates that the off-hour effects could be overcome with well-organized stroke management strategies.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Hospitalização , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros , Terapia Trombolítica , Fatores de Tempo , Resultado do Tratamento
16.
Elife ; 3: e02667, 2014 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-24867643

RESUMO

We elucidate the molecular mechanisms of two distinct activation strategies (autophosphorylation and TPX2-mediated activation) in human Aurora A kinase. Classic allosteric activation is in play where either activation loop phosphorylation or TPX2 binding to a conserved hydrophobic groove shifts the equilibrium far towards the active conformation. We resolve the controversy about the mechanism of autophosphorylation by demonstrating intermolecular autophosphorylation in a long-lived dimer by combining X-ray crystallography with functional assays. We then address the allosteric activation by TPX2 through activity assays and the crystal structure of a domain-swapped dimer of dephosphorylated Aurora A and TPX2(1-25). While autophosphorylation is the key regulatory mechanism in the centrosomes in the early stages of mitosis, allosteric activation by TPX2 of dephosphorylated Aurora A could be at play in the spindle microtubules. The mechanistic insights into autophosphorylation and allosteric activation by TPX2 binding proposed here, may have implications for understanding regulation of other protein kinases.DOI: http://dx.doi.org/10.7554/eLife.02667.001.


Assuntos
Aurora Quinase A/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Regulação Alostérica , Aurora Quinase A/química , Biocatálise , Proteínas de Ciclo Celular/química , Cristalografia por Raios X , Humanos , Cinética , Proteínas Associadas aos Microtúbulos/química , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Proteínas Nucleares/química , Fosforilação , Fosfotreonina/metabolismo , Ligação Proteica , Conformação Proteica , Multimerização Proteica , Estabilidade Proteica , Estrutura Terciária de Proteína , Soluções , Especificidade por Substrato
17.
Ergonomics ; 57(7): 1102-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24758176

RESUMO

UNLABELLED: The aim of the study was to evaluate the difference in legibility between e-books and paper books by using an eye tracker. Eight male and eight female subjects free of eye disease participated in the experiment. The experiment was conducted using a 2 × 3 within-subject design. The book type (e-book, paper book) and font size (8 pt, 10 pt, 12 pt) were independent variables, and fixation duration time, saccade length, blink rate and subjective discomfort were dependent variables. In the results, all dependent variables showed that reading paper books provided a better experience than reading e-books did. These results indicate that the legibility of e-books needs further improvement, considering fixation duration time, saccade movement, eye fatigue, device and so on. PRACTITIONER SUMMARY: This study evaluated the legibility difference between e-books and paper books from the viewpoint of readability, eye fatigue and subjective discomfort by using an eye tracker. The results showed that paper books provided a better experience than e-books. This indicates that the readability of e-books needs further improvement in relation to paper books.


Assuntos
Livros , Leitura , Adulto , Equipamentos e Provisões Elétricas , Medições dos Movimentos Oculares/instrumentação , Movimentos Oculares/fisiologia , Feminino , Humanos , Masculino , Adulto Jovem
18.
Acta Crystallogr D Biol Crystallogr ; 70(Pt 1): 2-10, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24419373

RESUMO

The TNF receptor-associated factor (TRAF) proteins are structurally similar scaffold proteins that mediate between members of the TNF receptor (TNFR) family and downstream effector molecules such as kinases in the immune signalling pathway. Seven TRAFs have been identified, including TRAF4, which is a unique member that participates in many ontogenic processes, including nerve-system development. TRAFs commonly contain the TRAF domain, which mediates interaction with target receptors and effectors. As a first step towards elucidating the molecular mechanisms of the TRAF4-mediated signalling pathway, the first crystal structure of the human TRAF4 TRAF domain with a coiled-coil domain is reported at 2.3 Šresolution.


Assuntos
Fator 4 Associado a Receptor de TNF/química , Sequência de Aminoácidos , Sequência Conservada , Cristalografia por Raios X , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Alinhamento de Sequência , Transdução de Sinais
19.
J Nanosci Nanotechnol ; 14(11): 8879-83, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25958621

RESUMO

A series of X-Mg3(VO4)2-MgO-ZrO2 nano-catalysts with different vanadium content (X = 3.3, 5.3, 7.0, 10.2, and 13.4) were prepared by a single-step citric acid-derived sol-gel method for use in the oxidative dehydrogenation of n-butane to n-butene and 1,3-butadiene. The effect of vanadium content of X-Mg3(VO4)2-MgO-ZrO2 nano-catalysts on their physicochemical properties and catalytic activities in the oxidative dehydrogenation of n-butane was investigated. Successful formation of X-Mg3(VO4)2-MgO-ZrO2 nano-catalysts was confirmed by XRD, Raman spectroscopy, and ICP-AES analyses. The catalytic performance of X-Mg3(VO4)2-MgO-ZrO2 nano-catalysts strongly depended on vanadium content. All the X-Mg3(VO4)2-MgO-ZrO2 nano-catalysts showed a stable catalytic performance without catalyst deactivation during the reaction. Among the catalysts tested, 7.0-Mg3(VO4)2-MgO-ZrO2 nano-catalyst showed the best catalytic performance in terms of yield for total dehydrogenation products (TDP, n-butene and 1,3-butadiene). TPRO (temperature-programmed reoxidation) experiments were carried out to measure the oxygen capacity of the catalyst. Experimental results revealed that oxygen capacity of the catalyst was closely related to the catalytic performance. Yield for TDP increased with increasing oxygen capacity of the catalyst.

20.
J Nanosci Nanotechnol ; 13(12): 8110-5, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24266201

RESUMO

Magnesia-zirconia (MgO-ZrO2) support was prepared by a sol-gel method, and magnesium vanadate nano-catalysts supported on magnesia-zirconia (X-Mg3(VO4)2/MgO-ZrO2) were then prepared by a wet impregnation method with a variation of vanadium content (X = 6.6, 9.9, 12.8, 15.2, and 19.1 wt%). X-Mg3(VO4)2/MgO-ZrO2 nano-catalysts were applied to the oxidative dehydrogenation of n-butane to n-butene and 1,3-butadiene. The formation of X-Mg3(VO4)2/MgO-ZrO2 nano-catalysts was well confirmed by XRD, XPS, and ICP-AES analyses. 15.2-Mg3(VO4)2/MgO-ZrO2 and 19.1-Mg3(VO4)2/MgO-ZrO2 catalysts experienced a catalyst deactivation, while the other Mg3(VO4)2/MgO-ZrO2 catalysts showed a stable catalytic performance during the whole reaction time. The effect of oxygen property of X-Mg3(VO4)2/MgO-ZrO2 nano-catalysts on the catalytic performance in the oxidative dehydrogenation of n-butane was investigated. Experimental results revealed that oxygen capacity of the catalyst was closely related to the catalytic performance, while oxygen mobility of the catalyst played an important role in the catalyst stability. Among the catalysts tested, 12.8-Mg3(VO4)2/MgO-ZrO2 catalyst showed the best catalytic performance in terms of yield for TDP (total dehydrogenation products).


Assuntos
Butanos/química , Hidrogênio/química , Magnésio/química , Nanoestruturas , Vanadatos/química , Zircônio/química , Catálise , Oxirredução
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