Virtual screening can be a helpful approach to propose treatments for COVID-19 by developing inhibitors for blocking the attachment of the virus to human cells. This study uses molecular docking, recovery time and dyn...Virtual screening can be a helpful approach to propose treatments for COVID-19 by developing inhibitors for blocking the attachment of the virus to human cells. This study uses molecular docking, recovery time and dynamics to analyze if potential inhibitors of main protease (M<sup>pro</sup>) of SARS-CoV-2 can interfere in the attachment of nanobodies, specifically Nb20, in the receptor binding domain (RBD) of SARS-CoV-2. The potential inhibitors are four compounds previously identified in a fluorescence resonance energy transfer (FRET)-based enzymatic assay for the SARS-CoV-2 M<sup>pro</sup>: Boceprevir, Calpain Inhibitor II, Calpain Inhibitor XII, and GC376. The findings reveal that Boceprevir has the higher affinity with the RBD/Nb20 complex, followed by Calpain Inhibitor XII, GC376 and Calpain Inhibitor II. The recovery time indicates that the RBD/Nb20 complex needs a relatively short time to return to what it was before the presence of the ligands. For the RMSD the Boceprevir and Calpain Inhibitor II have the shortest interaction times, while Calpain Inhibitor XII shows slightly more interaction, but with significant pose fluctuations. On the other hand, GC376 remains stably bound for a longer duration compared to the other compounds, suggesting that they can potentially interfere with the neutralization process of Nb20.展开更多
BACKGROUND Pulmonary embolism(PE)is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis(DVT).However,clinical and biochemical factors that are related to the stability...BACKGROUND Pulmonary embolism(PE)is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis(DVT).However,clinical and biochemical factors that are related to the stability of DVT are not fully understood.AIM To evaluate the relationships between plasma antigen levels of factor XII(FXII:Ag)and factor XI(FXI:Ag)with the stability of DVT.METHODS Patients with DVT and no PE,DVT and PE,and controls with no DVT or PE that matched for age,gender,and comorbidities were included in this study.FXII:Ag and FXI:Ag in peripheral venous blood were measured using enzyme-linked immunosorbent assays.RESULTS Using the 95th percentile of FXI:Ag in patients with DVT and PE as the cut-off,a higher FXI:Ag was associated with a higher risk of unstable DVT(odds ratio:3.15,95%confidence interval:1.18-8.43,P=0.019).Stratified analyses showed consistent results in patients≤60 years(P=0.020),but not in those>60 years(P=0.346).CONCLUSION Higher plasma FXI:Ag might be a marker for unstable DVT,which might be associated with PE in these patients.展开更多
This paper deals with Bayesian inference and prediction problems of the Burr type XII distribution based on progressive first failure censored data. We consider the Bayesian inference under a squared error loss functi...This paper deals with Bayesian inference and prediction problems of the Burr type XII distribution based on progressive first failure censored data. We consider the Bayesian inference under a squared error loss function. We propose to apply Gibbs sampling procedure to draw Markov Chain Monte Carlo (MCMC) samples, and they have in turn, been used to compute the Bayes estimates with the help of importance sampling technique. We have performed a simulation study in order to compare the proposed Bayes estimators with the maximum likelihood estimators. We further consider two sample Bayes prediction to predicting future order statistics and upper record values from Burr type XII distribution based on progressive first failure censored data. The predictive densities are obtained and used to determine prediction intervals for unobserved order statistics and upper record values. A real life data set is used to illustrate the results derived.展开更多
Five triterpenoid saponins were isolated from the Chinese traditional medicine Eclipta prostrata L.. On the basis of their chemical properties and spectral data, they were identified as eclalbasaponins II(1), I(2), II...Five triterpenoid saponins were isolated from the Chinese traditional medicine Eclipta prostrata L.. On the basis of their chemical properties and spectral data, they were identified as eclalbasaponins II(1), I(2), III(3), 3-O-[b-D-glucopyranosyl(12)-b-D-glucopyranosyl]-16a-ethoxy-olean-12-ene-28-oic acid-28-O-b-D-glu-copyranoside(4) and 3-O-[(2-O-sulfuryl-b-D-glucopyranosyl)(12)-b-D-glucopyranosyl]-echinocystic acid-28-O-b-D-glucopyranoside(5). Compounds 4 and 5 are new compounds and named eclalbasaponins XI and XII, respectively. Compounds 1 and 5 induced morphological deformation of Pyricularia oryzae mycelia.展开更多
Background: Factor XII (Hageman Factor) is the initiating factor for the Intrinsic Pathway of Coagulation. Very low levels of Factor XII have been associated with increased levels of activated Partial Thromboplastin T...Background: Factor XII (Hageman Factor) is the initiating factor for the Intrinsic Pathway of Coagulation. Very low levels of Factor XII have been associated with increased levels of activated Partial Thromboplastin Time (aPTT). Association of Factor XII deficiency is more with thromboembolic disorders rather than bleeding tendencies. Aim: To learn more about the relationship of factor XII (Hageman Factor) deficiency and high levels of activated Partial Thromboplastin Time. Case Presentation: The Patient was admitted with complains of recurrent headaches and loin pain. Patient was incidentally found to have prolonged activated Partial Thromboplastin Time. This led to investigations which ultimately provided the evidence of severely low levels of Hageman Factor. Conclusion: Hageman Factor deficiency causes prolonged activated Partial Thromboplastin Time. However, most of the patients are asymptomatic for many years despite Hageman Factor deficiency.展开更多
Bayesian predictive probability density function is obtained when the underlying pop-ulation distribution is exponentiated and subjective prior is used. The corresponding predictive survival function is then obtained ...Bayesian predictive probability density function is obtained when the underlying pop-ulation distribution is exponentiated and subjective prior is used. The corresponding predictive survival function is then obtained and used in constructing 100(1 – ?)% predictive interval, using one- and two- sample schemes when the size of the future sample is fixed and random. In the random case, the size of the future sample is assumed to follow the truncated Poisson distribution with parameter λ. Special attention is paid to the exponentiated Burr type XII population, from which the data are drawn. Two illustrative examples are given, one of which uses simulated data and the other uses data that represent the breaking strength of 64 single carbon fibers of length 10, found in Lawless [40].展开更多
In this paper, we recall for physicists how it is possible using the principle of maximization of the Boltzmann-Shannon entropy to derive the Burr-Singh-Maddala (BurrXII) double power law probability distribution func...In this paper, we recall for physicists how it is possible using the principle of maximization of the Boltzmann-Shannon entropy to derive the Burr-Singh-Maddala (BurrXII) double power law probability distribution function and its approximations (Pareto, loglogistic.) and extension (GB2…) first used in econometrics. This is possible using a deformation of the power function, as this has been done in complex systems for the exponential function. We give to that distribution a deep stochastic interpretation using the theory of Weron et al. Applied to thermodynamics, the entropy nonextensivity can be accounted for by assuming that the asymptotic exponents are scale dependent. Therefore functions which describe phenomena presenting power-law asymptotic behaviour can be obtained without introducing exotic forms of the entropy.展开更多
Factor XII (Hageman factor) is an important protease that plays a major role in the initiation of the intrinsic pathway of blood coagulation and fibrinolysis and kinin formation. It is still unclear whether factor XII...Factor XII (Hageman factor) is an important protease that plays a major role in the initiation of the intrinsic pathway of blood coagulation and fibrinolysis and kinin formation. It is still unclear whether factor XII deficiency causes any disorders during pregnancy. Because the main clinical feature in patients with factor XII deficiency is thrombosis rather than bleeding, low dose aspirin would be expected to prevent first trimester miscarriage and a decrease in factor XII level itself was found to be an independent risk factor in recurrent miscarriage. The woman in a 31-year-old patient, with personal and family antecedents without interest and preceding obstetrics of two spontaneous abortions in the first quarter of the pregnancy without apparent cause. In the study of infertility practiced emphasizes a partition of not more than one centimetre of length in the uterine found by hysteroscopy exploration and in the study of hipercoagulability a light deficiency of the factor XII. Himself guideline processing with low dose of aspirin (125 mgr/day) and preconception folic acid (5 mgr/day), remains expectant mother and in the week 12 of her third pregnancy itself guideline antitrombotic prophylaxis with heparin of low molecular weight by subcutaneous way. The pregnancy reaches the week 39 without incidents of interest and the expectant mother give birth of spontaneous form to health boy. Repeated abortions may be associated with reduced level of factor XII activity of unknown origin and low-dose aspirin may prevent miscarriage caused for decreased factor XII levels in patients with a history of recurrent first trimester miscarriage.展开更多
Maximum likelihood and Bayes estimators of the parameters, survival function (SF) and hazard rate function (HRF) are obtained for the three-parameter exponentiated Burr type XII distribution when sample is available f...Maximum likelihood and Bayes estimators of the parameters, survival function (SF) and hazard rate function (HRF) are obtained for the three-parameter exponentiated Burr type XII distribution when sample is available from type II censored scheme. Bayes estimators have been developed using the standard Bayes and MCMC methods under square error and LINEX loss functions, using informative type of priors for the parameters. Simulation comparison of various estimation methods is made when n = 20, 40, 60 and censored data. The Bayes estimates are found to be, generally, better than the maximum likelihood estimates against the proposed prior, in the sense of having smaller mean square errors. This is found to be true whether the data are complete or censored. Estimates improve by increasing sample size. Analysis is also carried out for real life data.展开更多
Intrinsic or acquired resistance to chemotherapy is a major hurdle in the treatment of cancer.One of the key mechanisms of resistance is the overexpression of the drug efflux transporter P-glycoprotein(Pgp).Pgp overex...Intrinsic or acquired resistance to chemotherapy is a major hurdle in the treatment of cancer.One of the key mechanisms of resistance is the overexpression of the drug efflux transporter P-glycoprotein(Pgp).Pgp overexpression renders a large number of mechanistically unrelated chemotherapies ineffective.Targeting Pgp inhibition directly to overcome drug resistance,although conceptually and mechanistically attractive,has not translated to the clinic,in part because Pgp also has a critical protective function in many healthy tissues.It was recently discovered that carbonic anhydrase XII(CA XII),an enzyme associated with pH regulation in cancer,is co-expressed and co-located with Pgp in drug resistant cancer cells.CA XII is also upregulated by hypoxia,which is another microenvironmental factor that contributes to drug resistance.Here,we review findings that demonstrate modulation of CA XII may offer a promising new approach towards overcoming the longstanding hurdle of drug resistance and therapy failure against solid cancers.This review covers the use of CA XII inhibitors,both small molecule and antibody,in combination with chemotherapeutics that are substrates for Pgp.This combination therapy approach restores the efficacy of chemotherapy in resistant cells and offers a potential new therapeutic window to re-examine the targeting of Pgp as a safe,effective,and novel anticancer strategy.展开更多
Hereditary angioedema(HAE)is an uncommon genetic disorder characterized by recurrent episodes of edema involving subcutaneous tissue and submucosa.The pathogenesis of HAE reflects an intricate coordinated regulation o...Hereditary angioedema(HAE)is an uncommon genetic disorder characterized by recurrent episodes of edema involving subcutaneous tissue and submucosa.The pathogenesis of HAE reflects an intricate coordinated regulation of components of complement,kinin and hemostatic pathway.Till date,mutations in 4 different genes have been identified to cause HAE which includes serine protease inhibitor G1(SERPING1),factor XII(F12),plasminogen(PLG)and angiopoietin 1(ANGPT 1).These mutations lead to increased bradykinin 2 receptor mediated signalling via increased production of bradykinin except mutations in ANGPT1 gene that disturbs the cytoskeletal assembly of vascular endothelial cells.In this review we aim to summarize the recent advances in the pathogenesis and genetics of HAE.We also provide an overview of possible future prospects in the identification of new genetic defects in HAE.展开更多
2,3,4,6-Tetra-O-acetyl-α-D-galactopyranosyl bromide reacted with carboxylic acids in the presence of CaH_2 and Ag_2CO_3 and small amount of I_2 to give good yields of l-O-acyl-β-D- galactopyranose tetraaeetates.β-A...2,3,4,6-Tetra-O-acetyl-α-D-galactopyranosyl bromide reacted with carboxylic acids in the presence of CaH_2 and Ag_2CO_3 and small amount of I_2 to give good yields of l-O-acyl-β-D- galactopyranose tetraaeetates.β-Anomers of glycosyl esters were obtained by this improved Koenigs-Knorr method.展开更多
文摘Virtual screening can be a helpful approach to propose treatments for COVID-19 by developing inhibitors for blocking the attachment of the virus to human cells. This study uses molecular docking, recovery time and dynamics to analyze if potential inhibitors of main protease (M<sup>pro</sup>) of SARS-CoV-2 can interfere in the attachment of nanobodies, specifically Nb20, in the receptor binding domain (RBD) of SARS-CoV-2. The potential inhibitors are four compounds previously identified in a fluorescence resonance energy transfer (FRET)-based enzymatic assay for the SARS-CoV-2 M<sup>pro</sup>: Boceprevir, Calpain Inhibitor II, Calpain Inhibitor XII, and GC376. The findings reveal that Boceprevir has the higher affinity with the RBD/Nb20 complex, followed by Calpain Inhibitor XII, GC376 and Calpain Inhibitor II. The recovery time indicates that the RBD/Nb20 complex needs a relatively short time to return to what it was before the presence of the ligands. For the RMSD the Boceprevir and Calpain Inhibitor II have the shortest interaction times, while Calpain Inhibitor XII shows slightly more interaction, but with significant pose fluctuations. On the other hand, GC376 remains stably bound for a longer duration compared to the other compounds, suggesting that they can potentially interfere with the neutralization process of Nb20.
基金Supported by the Fund for Key Research and Development Program Project of Shannxi ProvinceNo. 2017SF-254
文摘BACKGROUND Pulmonary embolism(PE)is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis(DVT).However,clinical and biochemical factors that are related to the stability of DVT are not fully understood.AIM To evaluate the relationships between plasma antigen levels of factor XII(FXII:Ag)and factor XI(FXI:Ag)with the stability of DVT.METHODS Patients with DVT and no PE,DVT and PE,and controls with no DVT or PE that matched for age,gender,and comorbidities were included in this study.FXII:Ag and FXI:Ag in peripheral venous blood were measured using enzyme-linked immunosorbent assays.RESULTS Using the 95th percentile of FXI:Ag in patients with DVT and PE as the cut-off,a higher FXI:Ag was associated with a higher risk of unstable DVT(odds ratio:3.15,95%confidence interval:1.18-8.43,P=0.019).Stratified analyses showed consistent results in patients≤60 years(P=0.020),but not in those>60 years(P=0.346).CONCLUSION Higher plasma FXI:Ag might be a marker for unstable DVT,which might be associated with PE in these patients.
文摘This paper deals with Bayesian inference and prediction problems of the Burr type XII distribution based on progressive first failure censored data. We consider the Bayesian inference under a squared error loss function. We propose to apply Gibbs sampling procedure to draw Markov Chain Monte Carlo (MCMC) samples, and they have in turn, been used to compute the Bayes estimates with the help of importance sampling technique. We have performed a simulation study in order to compare the proposed Bayes estimators with the maximum likelihood estimators. We further consider two sample Bayes prediction to predicting future order statistics and upper record values from Burr type XII distribution based on progressive first failure censored data. The predictive densities are obtained and used to determine prediction intervals for unobserved order statistics and upper record values. A real life data set is used to illustrate the results derived.
文摘Five triterpenoid saponins were isolated from the Chinese traditional medicine Eclipta prostrata L.. On the basis of their chemical properties and spectral data, they were identified as eclalbasaponins II(1), I(2), III(3), 3-O-[b-D-glucopyranosyl(12)-b-D-glucopyranosyl]-16a-ethoxy-olean-12-ene-28-oic acid-28-O-b-D-glu-copyranoside(4) and 3-O-[(2-O-sulfuryl-b-D-glucopyranosyl)(12)-b-D-glucopyranosyl]-echinocystic acid-28-O-b-D-glucopyranoside(5). Compounds 4 and 5 are new compounds and named eclalbasaponins XI and XII, respectively. Compounds 1 and 5 induced morphological deformation of Pyricularia oryzae mycelia.
文摘Background: Factor XII (Hageman Factor) is the initiating factor for the Intrinsic Pathway of Coagulation. Very low levels of Factor XII have been associated with increased levels of activated Partial Thromboplastin Time (aPTT). Association of Factor XII deficiency is more with thromboembolic disorders rather than bleeding tendencies. Aim: To learn more about the relationship of factor XII (Hageman Factor) deficiency and high levels of activated Partial Thromboplastin Time. Case Presentation: The Patient was admitted with complains of recurrent headaches and loin pain. Patient was incidentally found to have prolonged activated Partial Thromboplastin Time. This led to investigations which ultimately provided the evidence of severely low levels of Hageman Factor. Conclusion: Hageman Factor deficiency causes prolonged activated Partial Thromboplastin Time. However, most of the patients are asymptomatic for many years despite Hageman Factor deficiency.
文摘Bayesian predictive probability density function is obtained when the underlying pop-ulation distribution is exponentiated and subjective prior is used. The corresponding predictive survival function is then obtained and used in constructing 100(1 – ?)% predictive interval, using one- and two- sample schemes when the size of the future sample is fixed and random. In the random case, the size of the future sample is assumed to follow the truncated Poisson distribution with parameter λ. Special attention is paid to the exponentiated Burr type XII population, from which the data are drawn. Two illustrative examples are given, one of which uses simulated data and the other uses data that represent the breaking strength of 64 single carbon fibers of length 10, found in Lawless [40].
文摘In this paper, we recall for physicists how it is possible using the principle of maximization of the Boltzmann-Shannon entropy to derive the Burr-Singh-Maddala (BurrXII) double power law probability distribution function and its approximations (Pareto, loglogistic.) and extension (GB2…) first used in econometrics. This is possible using a deformation of the power function, as this has been done in complex systems for the exponential function. We give to that distribution a deep stochastic interpretation using the theory of Weron et al. Applied to thermodynamics, the entropy nonextensivity can be accounted for by assuming that the asymptotic exponents are scale dependent. Therefore functions which describe phenomena presenting power-law asymptotic behaviour can be obtained without introducing exotic forms of the entropy.
文摘Factor XII (Hageman factor) is an important protease that plays a major role in the initiation of the intrinsic pathway of blood coagulation and fibrinolysis and kinin formation. It is still unclear whether factor XII deficiency causes any disorders during pregnancy. Because the main clinical feature in patients with factor XII deficiency is thrombosis rather than bleeding, low dose aspirin would be expected to prevent first trimester miscarriage and a decrease in factor XII level itself was found to be an independent risk factor in recurrent miscarriage. The woman in a 31-year-old patient, with personal and family antecedents without interest and preceding obstetrics of two spontaneous abortions in the first quarter of the pregnancy without apparent cause. In the study of infertility practiced emphasizes a partition of not more than one centimetre of length in the uterine found by hysteroscopy exploration and in the study of hipercoagulability a light deficiency of the factor XII. Himself guideline processing with low dose of aspirin (125 mgr/day) and preconception folic acid (5 mgr/day), remains expectant mother and in the week 12 of her third pregnancy itself guideline antitrombotic prophylaxis with heparin of low molecular weight by subcutaneous way. The pregnancy reaches the week 39 without incidents of interest and the expectant mother give birth of spontaneous form to health boy. Repeated abortions may be associated with reduced level of factor XII activity of unknown origin and low-dose aspirin may prevent miscarriage caused for decreased factor XII levels in patients with a history of recurrent first trimester miscarriage.
文摘Maximum likelihood and Bayes estimators of the parameters, survival function (SF) and hazard rate function (HRF) are obtained for the three-parameter exponentiated Burr type XII distribution when sample is available from type II censored scheme. Bayes estimators have been developed using the standard Bayes and MCMC methods under square error and LINEX loss functions, using informative type of priors for the parameters. Simulation comparison of various estimation methods is made when n = 20, 40, 60 and censored data. The Bayes estimates are found to be, generally, better than the maximum likelihood estimates against the proposed prior, in the sense of having smaller mean square errors. This is found to be true whether the data are complete or censored. Estimates improve by increasing sample size. Analysis is also carried out for real life data.
文摘Intrinsic or acquired resistance to chemotherapy is a major hurdle in the treatment of cancer.One of the key mechanisms of resistance is the overexpression of the drug efflux transporter P-glycoprotein(Pgp).Pgp overexpression renders a large number of mechanistically unrelated chemotherapies ineffective.Targeting Pgp inhibition directly to overcome drug resistance,although conceptually and mechanistically attractive,has not translated to the clinic,in part because Pgp also has a critical protective function in many healthy tissues.It was recently discovered that carbonic anhydrase XII(CA XII),an enzyme associated with pH regulation in cancer,is co-expressed and co-located with Pgp in drug resistant cancer cells.CA XII is also upregulated by hypoxia,which is another microenvironmental factor that contributes to drug resistance.Here,we review findings that demonstrate modulation of CA XII may offer a promising new approach towards overcoming the longstanding hurdle of drug resistance and therapy failure against solid cancers.This review covers the use of CA XII inhibitors,both small molecule and antibody,in combination with chemotherapeutics that are substrates for Pgp.This combination therapy approach restores the efficacy of chemotherapy in resistant cells and offers a potential new therapeutic window to re-examine the targeting of Pgp as a safe,effective,and novel anticancer strategy.
文摘Hereditary angioedema(HAE)is an uncommon genetic disorder characterized by recurrent episodes of edema involving subcutaneous tissue and submucosa.The pathogenesis of HAE reflects an intricate coordinated regulation of components of complement,kinin and hemostatic pathway.Till date,mutations in 4 different genes have been identified to cause HAE which includes serine protease inhibitor G1(SERPING1),factor XII(F12),plasminogen(PLG)and angiopoietin 1(ANGPT 1).These mutations lead to increased bradykinin 2 receptor mediated signalling via increased production of bradykinin except mutations in ANGPT1 gene that disturbs the cytoskeletal assembly of vascular endothelial cells.In this review we aim to summarize the recent advances in the pathogenesis and genetics of HAE.We also provide an overview of possible future prospects in the identification of new genetic defects in HAE.
文摘2,3,4,6-Tetra-O-acetyl-α-D-galactopyranosyl bromide reacted with carboxylic acids in the presence of CaH_2 and Ag_2CO_3 and small amount of I_2 to give good yields of l-O-acyl-β-D- galactopyranose tetraaeetates.β-Anomers of glycosyl esters were obtained by this improved Koenigs-Knorr method.
