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1.
Cardiology ; 145(7): 456-466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101865

RESUMO

OBJECTIVE: We aimed to study the effect of cariporide (CP) on protecting the saphenous vein and the role of acetaldehyde dehydrogenase 2 (ALDH2) in coronary artery bypass grafting (CABG). BACKGROUND: The saphenous vein is the main graft material used in CABG. Recent studies suggested that CP is effective in protecting against various cardiovascular diseases. METHODS: Segments of a surgically removed saphenous vein were used to examine the vascular response to CP. The ALDH2 genotype and expression of related proteins were assessed by Western blotting and immunohistochemistry. RESULTS: Among the conditions tested, the University of Wisconsin solution with CP (4°C, 5 min) treatment showed the best protective effect on the saphenous vein. The incidence of major adverse cardiac events was higher in the ALDH2-GA (heterozygous mutant) genotype population after CABG. CONCLUSION: CP plays a role in reducing the production of reactive oxygen species and apoptosis by ALDH2-mediated mitochondrial function improvement. The ALDH2 mutant genotype might be one of the risk factors for coronary atherosclerotic heart disease.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Doença da Artéria Coronariana/genética , Guanidinas/uso terapêutico , Veia Safena/efeitos dos fármacos , Veia Safena/patologia , Sulfonas/uso terapêutico , Adenosina , Adulto , Aldeído-Desidrogenase Mitocondrial/sangue , Alopurinol , Apoptose/efeitos dos fármacos , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Feminino , Genótipo , Glutationa , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos , Rafinose , Espécies Reativas de Oxigênio/sangue , Veia Safena/transplante
2.
Sensors (Basel) ; 18(4)2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29690629

RESUMO

Computer-generated graphics (CGs) are images generated by computer software. The rapid development of computer graphics technologies has made it easier to generate photorealistic computer graphics, and these graphics are quite difficult to distinguish from natural images (NIs) with the naked eye. In this paper, we propose a method based on sensor pattern noise (SPN) and deep learning to distinguish CGs from NIs. Before being fed into our convolutional neural network (CNN)-based model, these images—CGs and NIs—are clipped into image patches. Furthermore, three high-pass filters (HPFs) are used to remove low-frequency signals, which represent the image content. These filters are also used to reveal the residual signal as well as SPN introduced by the digital camera device. Different from the traditional methods of distinguishing CGs from NIs, the proposed method utilizes a five-layer CNN to classify the input image patches. Based on the classification results of the image patches, we deploy a majority vote scheme to obtain the classification results for the full-size images. The experiments have demonstrated that (1) the proposed method with three HPFs can achieve better results than that with only one HPF or no HPF and that (2) the proposed method with three HPFs achieves 100% accuracy, although the NIs undergo a JPEG compression with a quality factor of 75.

3.
Int Heart J ; 59(6): 1211-1218, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30305585

RESUMO

The enormous majority of previous reports focused on evaluating the safety and efficacy of sequential saphenous vein (SV) coronary bypass grafting; however, no reports to date have revealed concern regarding the impacts of the number of distal anastomoses of sequential SV grafting on graft patency after coronary artery bypass grafting (CABG). This single-center retrospective study aimed to evaluate the impacts of three versus two distal anastomoses per single SV conduit on SV graft patency after off-pump CABG, and to determine the independent risk factors for sequential SV graft failure.From January 2011 to December 2014, 1320 eligible patients were assigned to either a triple group (three distal anastomoses of sequential SV grafting, n = 758) or a double group (two distal anastomoses of sequential SV grafting, n = 562). The primary endpoint was over a 2-year follow-up SV graft failure after off-pump CABG.The triple and double group received a similar total patency rate of sequential SV conduits (86.5% versus 87.1%, P = 0.757). The number of distal anastomoses of sequential SV grafting (three versus two) was not a predictive factor for the follow-up graft failure of sequential SV conduits (HR = 0.91, 95% CI: 0.66-2.29, P = 0.137). Moreover, the two groups received a similar follow-up survival freedom from repeat revascularization (χ2 = 1.881, log-rank P = 0.170).Three versus two distal anastomoses per single SV conduit received a similar SV graft patency. The number of distal anastomoses of sequential SV grafting was not an independent risk factor for graft failure.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Veia Safena/transplante , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco
4.
Int Heart J ; 59(1): 35-42, 2018 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-29279526

RESUMO

This study aimed to evaluate the feasibility and the mid-term efficacy of an in situ skeletonized right internal mammary artery (IMA) bypass grafting to a left anterior descending artery (LAD), and to determine risk factors for IMA graft failure in a single-center study.From January 2012 to December 2015, 189 patients (173 males, 50.6 ± 6.0 years old) undergoing first isolated coronary artery bypass grafting surgery with the in situ skeletonized right IMA grafting to the LAD were included in this study. Baseline characteristics, peroperative data, and follow-up outcomes were investigated and analyzed.The length of the in situ skeletonized right IMA grafts was 18.6 ± 1.2 cm (17.0-22.0 cm). Intraoperative graft flow of the in situ skeletonized right IMA grafting to LAD was 42 ± 9 mL/minute (18-72 mL/minute) associated with measured pulsatility index of 0.8-4.3. In-hospital mortality was 0.5%. Postoperative morbidity included acute myocardial infarction (0.5%), stroke (0.5%), and deep sternal wound infections (1.1%). The mid-term survival was 97.2% and the incidence of repeat revascularization was 0.6%. The patency rate of the in situ skeletonized right IMA grafting to the LAD was 97.1% by computed tomography angiography examination during the follow-up period of 23.2 ± 9.7 months. Additionally, logistic regression analysis showed that intraoperative graft flow had an independent influence on the risk of the mid-term right IMA graft failure.The strategy of the in situ skeletonized right IMA grafting to the LAD is feasible and effective. Intraoperative graft flow was an independent risk factor for the mid-term right IMA graft failure.


Assuntos
Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Circulação Coronária , Vasos Coronários/cirurgia , Artéria Torácica Interna/transplante , Grau de Desobstrução Vascular , Adulto , Idoso , China/epidemiologia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Artéria Torácica Interna/diagnóstico por imagem , Artéria Torácica Interna/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
Int Heart J ; 59(4): 727-735, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-29794393

RESUMO

Sequential grafting may be an effective way to maximize the benefits of the left internal mammary artery (LIMA) conduit. Despite increasing clinical application, the strategy of sequential LIMA grafting has not been proven its superiority. This single-center retrospective study aimed to evaluate the in-hospital and mid-term outcomes of sequential grafting of in situ skeletonized LIMA to the left coronary system.According to the use of sequential or separate LIMA grafting, 1505 eligible patients were assigned to a sequential group (n = 230) and a control group (n = 1275). According to sequential LIMA graft configurations, patients with sequential LIMA grafting were divided into a DOM subgroup (n = 113) and a DLAD subgroup (n = 117). The clinical outcomes and LIMA graft patency were investigated and compared.Sequential LIMA grafting compared with separate LIMA grafting was not an independent predictor either of in-hospital adverse events or follow-up survival free from repeat revascularization during the follow-up period of 32.4 ± 8.5 months. Sequential LIMA grafting had similar LIMA graft patency with separate LIMA grafting (99.5% of 1st sequential sites and 97.7% of 2nd sites versus 98.2% of LIMA-LAD grafts) at 32.3 ± 8.5 months after coronary artery bypass grafting (CABG) surgery. Additionally, the two subgroups received similar mid-term clinical outcomes and graft patency of LIMA segments.Sequential grafting of in situ skeletonized LIMA to the left coronary system resulted in excellent clinical outcomes and graft patency. The two sequential LIMA graft configurations received similar clinical outcomes and graft patency.


Assuntos
Doença da Artéria Coronariana/cirurgia , Vasos Coronários , Oclusão de Enxerto Vascular , Anastomose de Artéria Torácica Interna-Coronária , Artéria Torácica Interna/cirurgia , Enxerto Vascular , Idoso , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Feminino , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/etiologia , Humanos , Anastomose de Artéria Torácica Interna-Coronária/efeitos adversos , Anastomose de Artéria Torácica Interna-Coronária/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Enxerto Vascular/efeitos adversos , Enxerto Vascular/métodos , Grau de Desobstrução Vascular
6.
Circ J ; 82(1): 102-109, 2017 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-28794353

RESUMO

BACKGROUND: To evaluate in-hospital and mid-term outcomes of sequential vs. separate grafting of in situ skeletonized left internal mammary artery (LIMA) to the left coronary system in a single-center, propensity-matched study.Methods and Results:After propensity score-matching, 120 pairs of patients undergoing first scheduled isolated coronary artery bypass grafting (CABG) with in situ skeletonized LIMA grafting to the left anterior descending artery (LAD) territory were entered into a sequential group (sequential grafting of LIMA to the diagonal artery and then to the LAD) or a control group (separate grafting of LIMA to the LAD). The in-hospital and follow-up clinical outcomes and follow-up LIMA graft patency were compared. Both propensity score-matched groups had similar in-hospital and follow-up clinical outcomes. Sequential LIMA grafting was not found to be an independent predictor of adverse events. During a follow-up period of 27.0±7.3 months, 99.1% patency for the diagonal site and 98.3% for the LAD site were determined by coronary computed tomographic angiography after sequential LIMA grafting, both of which were similar with graft patency of separate grafting of in situ skeletonized LIMA to the LAD. CONCLUSIONS: Revascularization of the left coronary system using a skeletonized LIMA resulted in excellent in-hospital and mid-term clinical outcomes and graft patency using sequential grafting.


Assuntos
Ponte de Artéria Coronária/métodos , Vasos Coronários/cirurgia , Artéria Torácica Interna/cirurgia , Revascularização Miocárdica/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Resultado do Tratamento , Grau de Desobstrução Vascular
7.
Bioorg Med Chem Lett ; 25(5): 1030-5, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25666818

RESUMO

The design and synthesis of two closely related series of prostacyclin receptor agonist compounds that showed excellent human IP receptor potency and efficacy is described. Compounds from this series showed in vivo activity after SC dosing in the monocrotaline model of PAH in rat.


Assuntos
Descoberta de Drogas , Hipertensão Pulmonar/tratamento farmacológico , Receptores de Prostaglandina/agonistas , Animais , Humanos , Hipertensão Pulmonar/induzido quimicamente , Monocrotalina , Agregação Plaquetária/efeitos dos fármacos , Ratos , Receptores de Prostaglandina/metabolismo
8.
Cardiology ; 131(2): 109-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25895517

RESUMO

BACKGROUND: An intra-aortic balloon pump (IABP) is the most commonly used circulatory assist device in cardiac surgery. We hypothesized that prophylactic application of an IABP improves early clinical outcome of high-risk patients undergoing scheduled off-pump coronary artery bypass grafting (OPCABG). METHODS: From January 2010 to December 2013, hemodynamically stable, high-risk patients undergoing scheduled OPCABG with preincision use of an IABP were recruited to the IABP group. Using the propensity score-matching method, every patient in the IABP group was matched with another patient (the control group) with a similar propensity score who received an IABP on an as-needed basis during or after OPCABG. Surgical mortality and major morbidity rates were compared between groups. RESULTS: A total of 116 patient pairs were included in this study. In patients in the IABP group, postoperative low cardiac output and respiratory as well as renal failure were less frequent, intensive care unit stay was shorter, and surgical mortality was lower compared to patients in the control group. In multivariate logistic regression, timing of IABP implantation, as an independent risk factor, was associated with postoperative low cardiac output (OR=2.02, 95% CI 1.28-5.76), respiratory failure (OR=1.86, 95% CI 1.19-4.27), renal failure (OR=2.96, 95% CI 1.51-6.63) and surgical mortality (OR=2.45, 95% CI 1.42-6.07). CONCLUSIONS: Prophylactic application of an IABP improves postoperative cardiac performance, reduces respiratory and renal complications, and consequently lowers surgical mortality in high-risk patients undergoing scheduled OPCABG.


Assuntos
Angina Instável/cirurgia , Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Doença das Coronárias/cirurgia , Balão Intra-Aórtico/métodos , Angina Instável/mortalidade , Estudos de Casos e Controles , Ponte de Artéria Coronária sem Circulação Extracorpórea/mortalidade , Doença das Coronárias/mortalidade , Feminino , Humanos , Balão Intra-Aórtico/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Troponina I/metabolismo
9.
Int Heart J ; 56(2): 144-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25740396

RESUMO

Low cardiac output syndrome (LCOS) is one of the most important complications following coronary artery bypass grafting (CABG) and results in higher morbidity and mortality. However, few reports have focused on the predictors of LCOS following CABG. This study aimed to evaluate the predictors of LCOS following isolated CABG through the review of 1524 consecutive well-documented patients in a single center, retrospective trial.The relevant preoperative and intraoperative data of patients with complete information from medical records undergoing isolated CABG from January 2010 to December 2013 in our center were investigated and retrospectively analyzed. LCOS was considered when the following criteria were met: signs of impairment of body perfusion and need for inotropic support with vasoactive drugs or mechanical circulatory support with an intra-aortic balloon pump to maintain systolic blood pressure greater than 90 mmHg.LCOS developed in 205 patients following CABG, accounting for 13.5% of the total population. The in-hospital mortality in the LCOS group was significantly higher than that in the non-LCOS group (25.4% versus 1.8%, P < 0.0001). In addition to the length of ICU stay and postoperative hospital stay, LCOS was correlated with negative cerebral, respiratory and renal outcomes. Through univariate analysis and then logistic regression analysis, the predictors of LCOS following CABG included older age (age > 65 years) (OR = 1.85, 95%CI 1.27-3.76), impaired left ventricular function (OR = 2.05, 95%CI 1.53-4.54), on-pump CABG (OR = 2.16, 95%CI 1.53-4.86), emergent CPB (OR = 9.15, 95%CI 3.84-16.49), and incomplete revascularization (OR = 2.62, 95%CI 1.79-5.15).LCOS following isolated CABG caused higher mortality, higher rates of morbidity, and longer ICU and postoperative hospital stays. Older age, impaired left ventricular function, on-pump CABG, emergent CPB, and incomplete revascularization were identified as 5 predictors of LCOS following isolated CABG surgery.


Assuntos
Baixo Débito Cardíaco/etiologia , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Fatores Etários , Idoso , Baixo Débito Cardíaco/diagnóstico , Baixo Débito Cardíaco/terapia , Ponte Cardiopulmonar , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Balão Intra-Aórtico , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Função Ventricular Esquerda
10.
ScientificWorldJournal ; 2014: 802347, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24672376

RESUMO

A robust H.264/AVC video watermarking scheme for copyright protection with self-adaptive drift compensation is proposed. In our scheme, motion vector residuals of macroblocks with the smallest partition size are selected to hide copyright information in order to hold visual impact and distortion drift to a minimum. Drift compensation is also implemented to reduce the influence of watermark to the most extent. Besides, discrete cosine transform (DCT) with energy compact property is applied to the motion vector residual group, which can ensure robustness against intentional attacks. According to the experimental results, this scheme gains excellent imperceptibility and low bit-rate increase. Malicious attacks with different quantization parameters (QPs) or motion estimation algorithms can be resisted efficiently, with 80% accuracy on average after lossy compression.


Assuntos
Gravação em Vídeo
11.
J Genet Psychol ; : 1-16, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373089

RESUMO

Strategies for favoring close others, such as friends and in-group members, benefit individuals and society. Although younger and older children apply these sharing strategies, how they integrate these relationships remain understudied. Friendship and group membership sometimes conflict (e.g. a friend from another, even a rival group), driving the question of how children behave in such situations. To address this question, this preregistered study recruited 121 4-6-year-olds and 94 9-12-year-olds from a middle-class community in China. A 2 (friend vs. stranger) by 2 (in vs. out-group) between-subjects design was applied per age group. Participants were asked to share seven objects with a recipient, who was either a stranger, or a previously nominated friend and from an in- or out-group (manipulated in the Minimal Group Paradigm). The results showed that children in both age groups shared more with friends than with strangers. However, only 4-6-year-olds shared more resources with in-group members than with out-group ones. Moreover, 4-6-year-olds did not distinguish between an out-group friend and an in-group stranger, while 9-12-year-olds shared more with an out-group friend relative to an ingroup stranger, indicating that friendship outweighs minimal group membership only among 9-12-year-olds. Furthermore, there was an interaction between age and minimal group membership, implying a decrease in the minimal group effect between 4-6-year-olds and 9-12-year-olds. Accordingly, the implications of friendship and minimal group effects, and their relative influence on sharing during childhood are discussed.

12.
Nat Commun ; 15(1): 2197, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467628

RESUMO

The superconductivity in systems containing dispersionless (flat) bands is seemingly paradoxical, as traditional Bardeen-Cooper-Schrieffer theory requires an infinite enhancement of the carrier masses. However, the combination of flat and steep (dispersive) bands within the multiple band scenario might boost superconducting responses, potentially explaining high-temperature superconductivity in cuprates and metal hydrides. Here, we report on the magnetic penetration depths, the upper critical field, and the specific heat measurements, together with the first-principles calculations for the Mo5Si3-xPx superconducting family. The band structure features a flat band that gradually approaches the Fermi level as a function of phosphorus doping x, reaching the Fermi level at x ≃ 1.3. This leads to an abrupt change in nearly all superconducting quantities. The superfluid density data placed on the 'Uemura plot' results in two separated branches, thus indicating that the emergence of a flat band enhances correlations between conducting electrons.

13.
J Phys Condens Matter ; 35(21)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36913736

RESUMO

We report the discovery and detailed investigation of superconductivity in Mo4Ga20As. Mo4Ga20As crystallizes in a space group ofI4/m(No. 87), with the lattice parametersa= 12.86352 Å andc= 5.30031 Å. The resistivity, magnetization, and specific heat data reveal Mo4Ga20As to be a type-II superconductor withTc= 5.6 K. The upper and lower critical fields are estimated to be 2.78 T and 22.0 mT, respectively. In addition, electron-phonon coupling in Mo4Ga20As is possibly stronger than the BCS weak-coupling limit. First-principles calculations suggest the Fermi level being dominated by the Mo-4dand Ga-4porbitals.

14.
IEEE Trans Cybern ; 52(10): 10814-10826, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33878009

RESUMO

As one of the most important topics in image forensics, resampling detection has developed rapidly in recent years. However, the robustness to JPEG compression is still challenging for most classical spectrum-based methods, since JPEG compression severely degrades the image contents and introduces block artifacts in the boundary of the compression grid. In this article, we propose a method to estimate the upscaling factors on double JPEG compressed images in the presence of image upscaling between the two compressions. We first analyze the spectrum of scaled images and give an overall formulation of how the scaling factors along with the parameters of JPEG compression and image contents influence the appearance of tampering artifacts. The expected positions of five kinds of characteristic peaks are analytically derived. Then, we analyze the features of double JPEG compressed images in the block discrete cosine transform (BDCT) domain and present an inverse scaling strategy for the upscaling factor estimation with a detailed proof. Finally, a fusion method is proposed that through frequency-domain analysis, a candidate set of upscaling factors is given, and through analysis in the BDCT domain, the optimal estimation from all candidates is determined. The experimental results demonstrate that the proposed method outperforms other state-of-the-art methods.

15.
Dev Cell ; 5(6): 877-89, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14667410

RESUMO

Hearts of mice lacking Isl1, a LIM homeodomain transcription factor, are completely missing the outflow tract, right ventricle, and much of the atria. isl1 expression and lineage tracing of isl1-expressing progenitors demonstrate that Isl1 is a marker for a distinct population of undifferentiated cardiac progenitors that give rise to the cardiac segments missing in isl1 mutants. Isl1 function is required for these progenitors to contribute to the heart. In isl1 mutants, isl1-expressing progenitors are progressively reduced in number, and FGF and BMP growth factors are downregulated. Our studies define two sets of cardiogenic precursors, one of which expresses and requires Isl1 and the other of which does not. Our results have implications for the development of specific cardiac lineages, left-right asymmetry, cardiac evolution, and isolation of cardiac progenitor cells.


Assuntos
Cardiopatias Congênitas/genética , Coração/embriologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Miocárdio/citologia , Proteínas do Tecido Nervoso , Células-Tronco/fisiologia , Animais , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Linhagem da Célula/fisiologia , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Endoderma/citologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Homozigoto , Proteínas com Homeodomínio LIM , Mesoderma/citologia , Camundongos , Camundongos Knockout , Faringe/citologia , Faringe/embriologia , Gravidez , Fatores de Transcrição
16.
J Pharmacol Exp Ther ; 331(1): 96-103, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19628629

RESUMO

We have evaluated the receptor pharmacology, antiplatelet activity, and vascular pharmacology of APD791 [3-methoxy-N-(3-(1-methyl-1H-pyrazol-5-yl)-4-(2-morpholinoethoxy)phenyl)benzamide] a novel 5-hydroxytryptamine 2A (5-HT(2A)) receptor antagonist. APD791 displayed high-affinity binding to membranes (K(i) = 4.9 nM) and functional inverse agonism of inositol phosphate accumulation (IC(50) = 5.2 nM) in human embryonic kidney cells stably expressing the human 5-HT(2A) receptor. In competition binding assays, APD791 was greater than 2000-fold selective for the 5-HT(2A) receptor versus 5-HT(2C) and 5-HT(2B) receptors, and was inactive when tested against a wide panel of other G-protein-coupled receptors. APD791 inhibited 5-HT-mediated amplification of ADP-stimulated human and dog platelet aggregation (IC(50) = 8.7 and 23.1 nM, respectively). Similar potency was observed for inhibition of 5-HT-stimulated DNA synthesis in rabbit aortic smooth muscle cells (IC(50) = 13 nM) and 5-HT-mediated vasoconstriction in rabbit aortic rings. Oral administration of APD791 to dogs resulted in acute (1-h) and subchronic (10-day) inhibition of 5-HT-mediated amplification of collagen-stimulated platelet aggregation in whole blood. Two active metabolites, APD791-M1 and APD791-M2, were generated upon incubation of APD791 with human liver microsomes and were also indentified in dogs after oral administration of APD791. The affinity and selectivity profiles of both metabolites were similar to APD791. These results demonstrate that APD791 is an orally available, high-affinity 5-HT(2A) receptor antagonist with potent activity on platelets and vascular smooth muscle.


Assuntos
Benzamidas/química , Benzamidas/farmacologia , Plaquetas/efeitos dos fármacos , Morfolinas/química , Morfolinas/farmacologia , Músculo Liso Vascular/fisiologia , Ativação Plaquetária/fisiologia , Pirazóis/química , Pirazóis/farmacologia , Receptor 5-HT2A de Serotonina/fisiologia , Antagonistas do Receptor 5-HT2 de Serotonina , Antagonistas da Serotonina/farmacologia , Administração Oral , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Benzamidas/farmacocinética , Plaquetas/fisiologia , Linhagem Celular , Estudos Cross-Over , Cães , Relação Dose-Resposta a Droga , Feminino , Haplorrinos , Humanos , Masculino , Morfolinas/farmacocinética , Músculo Liso Vascular/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Pirazóis/farmacocinética , Coelhos , Ratos , Receptor 5-HT2A de Serotonina/sangue , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/sangue , Antagonistas da Serotonina/farmacocinética , Especificidade da Espécie
17.
Math Biosci Eng ; 16(6): 6907-6922, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31698595

RESUMO

Recently, fully convolutional network (FCN) has been successfully used to locate spliced regions in synthesized images. However, all the existing FCN-based algorithms use real-valued FCN to process each channel separately. As a consequence, they fail to capture the inherent correlation between color channels and the integrity of three channels. So, in this paper, quaternion fully convolutional network (QFCN) is proposed to generalize FCN to quaternion domain by replacing real-valued conventional blocks in FCN with quaternion conventional blocks. In addition, a new color image splicing localization algorithm is proposed by combining QFCNs and superpixel (SP)-enhanced pairwise conditional random field (CRF). QFCNs consider three different versions (QFCN32, QFCN16, and QFCN8) with different up-sampling layers. The SP-enhanced pairwise CRF is used to refine the results of QFCNs. Experimental results on three publicly available datasets demonstrate that the proposed algorithm outperforms the existing algorithms including some conventional algorithms and some deep learning-based algorithms.

18.
Eur J Pharmacol ; 586(1-3): 234-43, 2008 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-18358471

RESUMO

We have evaluated the anti-platelet and vascular pharmacology of AR246686, a novel 5-hydroxytryptamine2A (5-HT2A) receptor antagonist. AR246686 displayed high affinity binding to membranes of HEK cells stably expressing recombinant human and rat 5-HT2A receptors (Ki=0.2 nM and 0.4 nM, respectively). Functional antagonism (IC50=1.9 nM) with AR246686 was determined by inhibition of ligand-independent inositol phosphate accumulation in the 5-HT2A stable cell line. We observed 8.7-fold and 1360-fold higher affinity of AR246686 for the 5-HT2A receptor vs. 5-HT2C and 5-HT2B receptors, respectively. AR246686 inhibited 5-HT-induced amplification of ADP-stimulated human platelet aggregation (IC50=21 nM). Similar potency was observed for inhibition of 5-HT stimulated DNA synthesis in rat aortic smooth muscle cells (IC(50)=10 nM) and 5-HT-mediated contraction in rat aortic rings. Effects of AR246686 on arterial thrombosis and bleeding time were studied in a rat model of femoral artery occlusion. Oral dosing of AR246686 to rats resulted in prolongation of time to occlusion at 1 mg/kg, whereas increased bleeding time was observed at a dose of 20 mg/kg. In contrast, both bleeding time and time to occlusion were increased at the same dose (10 mg/kg) of clopidogrel. These results demonstrate that AR246686 is a high affinity 5-HT2A receptor antagonist with potent activity on platelets and vascular smooth muscle. Further, oral administration results in anti-thrombotic effects at doses that are free of significant effects on traumatic bleeding time.


Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Fibrinolíticos/farmacologia , Compostos de Fenilureia/farmacologia , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/farmacologia , Anfetaminas/metabolismo , Animais , Aorta Torácica/efeitos dos fármacos , Tempo de Sangramento , Plaquetas/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , DNA/biossíntese , DNA/genética , Fibrinolíticos/farmacocinética , Humanos , Fosfatos de Inositol/metabolismo , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/química , Serotonina/metabolismo , Vasoconstrição/efeitos dos fármacos
19.
Artigo em Inglês | MEDLINE | ID: mdl-29994181

RESUMO

During the past twenty years, there has been a great interest in the study of spread spectrum (SS) watermarking. However, it is still a challenging task to design a secure and robust SS watermarking method. In this paper, we first define a family of secure SS watermarking methods, named as spherical watermarking (SW). The watermarked correlation of SW is defined to be uniformly distributed on a spherical surface, and this makes SW be key-secure against the watermarked-only attack. Then, we propose an implementation of SW, called transportation SW (TSW), which is designed to decrease embedding distortion in a recursive manner using the transportation theory, meanwhile keeping the security of SW. Moreover, we present a theoretical analysis of the embedding distortion and robustness of the proposed method. Finally, extensive experiments are conducted on simulated signals and real images. The experimental results show that TSW is more robust than existing secure SS watermarking methods.

20.
IEEE Trans Cybern ; 48(8): 2307-2320, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28841562

RESUMO

Security analysis is a very important issue for digital watermarking. Several years ago, according to Kerckhoffs' principle, the famous four security levels, namely insecurity, key security, subspace security, and stego-security, were defined for spread-spectrum (SS) embedding schemes in the framework of watermarked-only attack. However, up to now there has been little application of the definition of these security levels to the theoretical analysis of the security of SS embedding schemes, due to the difficulty of the theoretical analysis. In this paper, based on the security definition, we present a theoretical analysis to evaluate the security levels of five typical SS embedding schemes, which are the classical SS, the improved SS (ISS), the circular extension of ISS, the nonrobust and robust natural watermarking, respectively. The theoretical analysis of these typical SS schemes are successfully performed by taking advantage of the convolution of probability distributions to derive the probabilistic models of watermarked signals. Moreover, simulations are conducted to illustrate and validate our theoretical analysis. We believe that the theoretical and practical analysis presented in this paper can bridge the gap between the definition of the four security levels and its application to the theoretical analysis of SS embedding schemes.

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