Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blaza...Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blazars of the Roma-BZCAT catalog. Using two machine learning methods, namely a combination of PCA with k-means clustering and Kohonen's self-organizing maps(SOMs), we have constructed an independent classification of the blazars(five classes) and compared the classes with the known Roma-BZCAT classification(FSRQs, BL Lacs, galaxy-dominated BL Lacs, and blazars of an uncertain type) as well as with the high synchrotron peaked(HSP) blazars from the 3HSP catalog and blazars from the TeVCat catalog. The obtained groups demonstrate concordance with the BL Lac/FSRQ classification along with a continuous character of the change in the properties. The group of HSP blazars stands out against the overall distribution. We examine the characteristics of the five groups and demonstrate distinctions in their spectral energy distribution shapes. The effectiveness of the clustering technique for objective analysis of multiparametric arrays of experimental data is demonstrated.展开更多
AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIV)-infected patients.METHODS Single nucle...AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIV)-infected patients.METHODS Single nucleotide polymorphisms(SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus(HCV) coinfection. A total of 158 patients were included, 57 of whom were HCVcoinfected. All patients drank < 50 g ethanol/day. Diverse SNPs(MMP-1-1607 1G/2G, MMP-8-799C/T, MMP-9-1562 C/T, MMP-13-77A/G, TNF-α-308 G/A,CCR5-?32), and serum levels of MMPs(2, 3, 8, 9 and 10) and TIMPs(1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis(F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kP a.RESULTS A total of 34 patients(21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2(P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values(P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements(P = 0.01). Multivariate analyses showed that high levels of MMP-2(OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2(OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender(OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2.CONCLUSION Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIVinfected patients with/without HCV coinfection.展开更多
The crystal structural data of TACE, MMP-1, MMP-2, MMP-3 and MMP-9 were obtained from PDB database, and then their catalytic domains' properties including conformation, molecular surface hydrophobicity and electrosta...The crystal structural data of TACE, MMP-1, MMP-2, MMP-3 and MMP-9 were obtained from PDB database, and then their catalytic domains' properties including conformation, molecular surface hydrophobicity and electrostatic potential were analyzed and compared by using Insight II molecular modeling software. It was found that the conformation and molecular surface hydrophobicity of catalytic domains of TACE and MMPs were not obviously different, but the molecular surface electrostatic potential of catalytic domain of TACE' and MMPs had obvious differences. The findings are helpful in the Rational Drug Design of TACE selective inhibitor.展开更多
Signals of touch,pressure,pain,temperature,position,and vibration are transmitted from the peripheral nervous system(PNS)to the dorsal horn of the segmental spinal cord via pseudounipolar dorsal root ganglia(DRG)n...Signals of touch,pressure,pain,temperature,position,and vibration are transmitted from the peripheral nervous system(PNS)to the dorsal horn of the segmental spinal cord via pseudounipolar dorsal root ganglia(DRG)neurons.Sensory information gathering relies on functional integrity of DRG neurons and can be interrupted by PNS injury due to trauma,disease or exposure to drugs, toxins or viral pathogens. Despite the high regenerative capacity of DRG neurons, sensory recovery after PNS injury is often incomplete and severe neuropathic pain may last for years. Although numerous mechanisms of PNS injury have been established, neuropathic pain is refractory to therapy, contributing to the physical and emotional suffering of patients and the enormous economic burden to society.展开更多
文摘Based on the collected multiwavelength data, namely in the radio(NVSS, FIRST, RATAN-600), IR(WISE),optical(Pan-STARRS), UV(GALEX), and X-ray(ROSAT, Swift-XRT) ranges, we have performed a cluster analysis for the blazars of the Roma-BZCAT catalog. Using two machine learning methods, namely a combination of PCA with k-means clustering and Kohonen's self-organizing maps(SOMs), we have constructed an independent classification of the blazars(five classes) and compared the classes with the known Roma-BZCAT classification(FSRQs, BL Lacs, galaxy-dominated BL Lacs, and blazars of an uncertain type) as well as with the high synchrotron peaked(HSP) blazars from the 3HSP catalog and blazars from the TeVCat catalog. The obtained groups demonstrate concordance with the BL Lac/FSRQ classification along with a continuous character of the change in the properties. The group of HSP blazars stands out against the overall distribution. We examine the characteristics of the five groups and demonstrate distinctions in their spectral energy distribution shapes. The effectiveness of the clustering technique for objective analysis of multiparametric arrays of experimental data is demonstrated.
基金Supported by the Oviedo University research grants,Nos.UNIOV-12-MA-03 and SV-PA-13-ECOEMP-57
文摘AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIV)-infected patients.METHODS Single nucleotide polymorphisms(SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus(HCV) coinfection. A total of 158 patients were included, 57 of whom were HCVcoinfected. All patients drank < 50 g ethanol/day. Diverse SNPs(MMP-1-1607 1G/2G, MMP-8-799C/T, MMP-9-1562 C/T, MMP-13-77A/G, TNF-α-308 G/A,CCR5-?32), and serum levels of MMPs(2, 3, 8, 9 and 10) and TIMPs(1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis(F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kP a.RESULTS A total of 34 patients(21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2(P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values(P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements(P = 0.01). Multivariate analyses showed that high levels of MMP-2(OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2(OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender(OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2.CONCLUSION Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIVinfected patients with/without HCV coinfection.
基金This work was supported by a grant from the National Nature Science Foundation of China (Grants No.31371309).
文摘The crystal structural data of TACE, MMP-1, MMP-2, MMP-3 and MMP-9 were obtained from PDB database, and then their catalytic domains' properties including conformation, molecular surface hydrophobicity and electrostatic potential were analyzed and compared by using Insight II molecular modeling software. It was found that the conformation and molecular surface hydrophobicity of catalytic domains of TACE and MMPs were not obviously different, but the molecular surface electrostatic potential of catalytic domain of TACE' and MMPs had obvious differences. The findings are helpful in the Rational Drug Design of TACE selective inhibitor.
基金Department of Veteran’s Affairs Merit Review Award 5I01BX000638(to VIS)National Institutes of Health R01DE022757(to VIS and AYS)supported this study
文摘Signals of touch,pressure,pain,temperature,position,and vibration are transmitted from the peripheral nervous system(PNS)to the dorsal horn of the segmental spinal cord via pseudounipolar dorsal root ganglia(DRG)neurons.Sensory information gathering relies on functional integrity of DRG neurons and can be interrupted by PNS injury due to trauma,disease or exposure to drugs, toxins or viral pathogens. Despite the high regenerative capacity of DRG neurons, sensory recovery after PNS injury is often incomplete and severe neuropathic pain may last for years. Although numerous mechanisms of PNS injury have been established, neuropathic pain is refractory to therapy, contributing to the physical and emotional suffering of patients and the enormous economic burden to society.