AIM In order to study the association betweenthe null genotypes of GSTM1 and GSTT1 and thegenetic susceptibility to hepatocellularcarcinoma(HCC).METHODS The genotypes of GSTM1 and GSTT1of 63 cases of HCC and 88 contro...AIM In order to study the association betweenthe null genotypes of GSTM1 and GSTT1 and thegenetic susceptibility to hepatocellularcarcinoma(HCC).METHODS The genotypes of GSTM1 and GSTT1of 63 cases of HCC and 88 controls were detectedwith the multiple PCR technique.RESULTS The frequency of GSTM1 nullgenotype was 57.1% among the cases,and42.0% among the controls,the difference beingstatistically significant(χ~2=3.35,P=0.067),but χ~2 value approaching the significance level.The odds ratio was 1.84(95% Cl= 0.91-3.37).The frequency of GSTT1 non-null genotype was87.3% among the cases and 52.5% among thecontrols,the difference being statisticallysignificant(χ~2=11.42,P=0.0007274).The oddsratio was 4.13(95% Cl=1.64-10.70).According to the cross analysis,the GSTT1 non-null genotype was more closely associated withHCC than GSTM1 null genotype,and these twofactors play an approximate additive interactionin the occurrence of HCC.CONCLUSION The persons with GSTM1 nullgenotype and GSTT1 non-null genotype have theincreased risk to HCC.展开更多
Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasio...Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasionally,chronic liver disease.We report an incidental finding of a novel null AAT allele,Q0Milano,consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene,in an Italian child with persistently increased liver enzymes,a mild decrease in circulating AAT levels and without any pulmonary disease.Q0Milano variant results in an unfunctional protein lacking of AAT active site,as the resultant protein is truncated near PiS locus involved in AAT protein stability.展开更多
Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, ...Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, especially in ethnically well-defined groups but not in Tabuk. This study investigated the variability in the distribution of the null phenotypes of GSTM1 and GSTT1 in the population of Tabuk (northwestern part of Saudi Arabia). Method: This study was conducted on 200 subjects of Tabuk—northwestern part of Saudi Arabia among which 100 were chronic smokers and 100 were nonsmokers. The subjects were reporting to hospital for routine checkup. All were without past history of any chronic disease and no significant abnormality. GST genotyping was done by multiplex PCR-based methods. The smoker and control groups were compared using a chi-square test with P GSTM1 deletion homozygosity of 14% and 1% was reported among non smokers and smokers, respectively whereas GSTT1 deletion homozygosity of 28% and 6% was reported among non smokers and smokers, respectively. Our results indicate that there are major differences in allelic distribution of GSTM1 and GSTT1 genes between the two groups investigated. Combined analysis of both genes revealed that 15% of smokers and non smokers harbor the deleted genotype of GSTM1 and 34% of smokers and non smokers harbor the deleted genotype of GSTT1 with significant differences. Conclusion: This study enables selecting subgroups among the general population who are more susceptible to DNA damage and will help genetic studies on the association of GST polymorphisms with disease risks and drug effects in Arab population. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.展开更多
In this paper, we show that new modified double cosine trigonometric sums introduced in [1] are inappropriate, the class of double sequences Jintroduced there is unusable for such sums and consequently the results obt...In this paper, we show that new modified double cosine trigonometric sums introduced in [1] are inappropriate, the class of double sequences Jintroduced there is unusable for such sums and consequently the results obtained in it are completely incorrect. We here introduce appropriate modified double cosine trigonometric sums making the class Jusable considering a particular double cosine trigonometric series.展开更多
The original description of a novel severe bleeding disorder as"Hereditary Pseudohemophilia"by Erik von Willebrand can currently be labelled as von Willebrand disease(VWD)type 3.VWD type 3 is autosomal reces...The original description of a novel severe bleeding disorder as"Hereditary Pseudohemophilia"by Erik von Willebrand can currently be labelled as von Willebrand disease(VWD)type 3.VWD type 3 is autosomal recessive caused by homozygous or double heterozygous null mutations in the von Willebrand factor(VWF)gene and typically characterized by prolonged bleeding time and APTT,FⅧ:C levels below 2%,undetectable VWF:Ag,VWF:RCo and VWF:CB and absence of ristocetin induced platelet aggregation(RIPA).Autosomal recessive von Willebrand disease type 3 VWD with virtual complete VWF deficiency are homozygous or compound heterozygous for two null alleles(gene deletions,stop codons,frame shift mutations,splice site mutations,and absence of m RNA).Reports on severerecessive VWD compound heterozygous for a null allele and a missense mutation and homozygous or double heterozygous for missense mutations are associated with very low but measurable FⅧand VWF:Ag and should be reclassified as severe recessive type 1 VWD.Homozygous missense or compound missense/null mutations related to recessive severe type 1 VWD have been indentified in the VWF prosequence D1 and D2domains,the D4,B1-3,C1-2 domains,and only a very few in the dimmerization site(D3 domain).The detection of even tiny amounts of VWF:Ag after desmopressin acetate(DDAVP)or in hidden sites like platelets allows the differentiation between patients with VWD type 3 and homozygous or double heterozygous recessive severe type 1.Carriers of a null allele related to VWD type 3 or a missense mutation related with severe recessive type 1 VWD may present with mild VWD with low penetrance of bleeding in particular when associated with blood group O.Heterozygous obligatory carriers(OC)of a null mutation or a missense mutation related to recessive VWD type 3 or severe type 1both present with asymptomatic or mild VWD type 1 in particular when associated with blood group O.The response to DDAVP of OC of either a nonsense or a missense mutation appears to be abnormal and diagnostic with a 3-times higher response of FⅧ:C as compared to VWF:Ag.In contrast,the responses to DDAVP of FⅧ:C and VWF:Ag are equally good in individuals with low VWF levels related to blood group O and a normal VWF gene and protein(pseudo-VWD).These observations are completely in line with and extend the original observations of von Willebrand in a large family with VWD type 3 and asymptomatic or mild true type1 VWD in OC.展开更多
为改善拖曳线列阵声呐的尾向探测能力,降低拖船噪声对半波长间距阵尾向探测性能的制约,本文关注四分之一波长间距阵对连续波信号和带限噪声的响应。研究表明,四分之一波长间距阵具有非对称的端向指向性,与半波长间距阵相比有约20 d B的...为改善拖曳线列阵声呐的尾向探测能力,降低拖船噪声对半波长间距阵尾向探测性能的制约,本文关注四分之一波长间距阵对连续波信号和带限噪声的响应。研究表明,四分之一波长间距阵具有非对称的端向指向性,与半波长间距阵相比有约20 d B的空间抑制能力,能有效抑制拖船辐射噪声干扰。本文还提出用零陷权组合传感器构成四分之一波长间距阵,理论上其抗拖船噪声干扰的效果比四分之一波长间距阵更好。展开更多
Measles virus (MV) is a negative strand RNA virus of the family Paramyxoviridae, and the attenuated Edmonston-B strain can be engineered by the reverse genetics system. Here we constructed the recombinant Edmonston st...Measles virus (MV) is a negative strand RNA virus of the family Paramyxoviridae, and the attenuated Edmonston-B strain can be engineered by the reverse genetics system. Here we constructed the recombinant Edmonston strain of measles virus (MV-Ed) that expressed hepatitis C virus (HCV) envelope proteins (rMV-E1E2). The rMV-E1E2 successfully expressed HCV E1 and E2 proteins. To evaluate its immunogenicity, NOD/Scid/Jak3null mice that were engrafted with human peripheral blood mononuclear cells (huPBMC-NOJ) were infected with this rMV-E1E2. Although human lymphocytes could be isolated from the spleens of mock-infected mice during the 2-weeks-long experiment, the proportion of mice that were infected with MV or rMV-E1E2 was decreased in a viral dose-dependent manner. Over 103 PFU of virus infection decreased the human PBL to less than 5%. Significant decrease of B cell population in human PBL from rMV-E1E2 infected NOD-SCID mice and decrease of T cell population in those from MV infected mice were observed. Human antibody production in these mice was also examined. Thus, the results in this study may contribute for future improvement of recombinant vaccine using measles virus vector.展开更多
Autoreactive CD8^(+)T cells,which play an indispensable role inβcell destruction,represent an emerging target for the prevention of type 1 diabetes(T1D).Altered peptide ligands(APLs)can efficiently induce antigen-spe...Autoreactive CD8^(+)T cells,which play an indispensable role inβcell destruction,represent an emerging target for the prevention of type 1 diabetes(T1D).Altered peptide ligands(APLs)can efficiently induce antigen-specific T cells anergy,apoptosis or shifts in the immune response.Here,we found that HLA-A*0201-restricted CD8^(+)T cell responses against a primaryβ-cell autoantigen insulin epitope InsB15–14 were present in both NOD.β2m null.HHD NOD mice and T1D patients.We generated several APL candidates for InsB15–14 by residue substitution at the p6 position.Only H6F exhibited an inhibitory effect on mInsB1_(5–14)-specific CD8^(+)T cell responses in vitro.H6F treatment significantly reduced the T1D incidence,which was accompanied by diminished autoreactive CD8^(+)T cell responses to mInsB15-14,inhibited infiltration of CD8^(+)and CD4^(+)T cells in the pancreas and reduced pro-inflammatory cytokine production in pancreatic and splenic T cells in NOD.β2m^(null).HHD mice.Mechanistically,H6F treatment significantly augmented a tiny portion of CD8^(+)CD25^(+)Foxp3^(+)T cells in the spleen and especially in the pancreas.This subset exhibited typical Treg phenotypes and required peptide-specific restimulation to exert immunosuppressive activity.Therefore,this APL H6F may be a promising candidate with potential clinical application value for antigen-specific prevention of T1D.展开更多
The Faddeev model is a fundamental model in relativistic quantum field theory used to model elementary particles. The Faddeev model can be regarded as a system of non-linear wave equations with both quasi-linear and s...The Faddeev model is a fundamental model in relativistic quantum field theory used to model elementary particles. The Faddeev model can be regarded as a system of non-linear wave equations with both quasi-linear and semi-linear non-linearities, which is particularly challenging in two space dimensions. A key feature of the system is that there exist undifferentiated wave components in the non-linearities, which somehow causes extra difficulties. Nevertheless, the Cauchy problem in two space dimenions was tackled by Lei-Lin-Zhou(2011) with small, regular, and compactly supported initial data, using Klainerman’s vector field method enhanced by a novel angular-radial anisotropic technique.In the present paper, the authors revisit the Faddeev model and remove the compactness assumptions on the initial data by Lei-Lin-Zhou(2011). The proof relies on an improved L2norm estimate of the wave components in Theorem 3.1 and a decomposition technique for non-linearities of divergence form.展开更多
基金the National Natural Science Foundation of China,No.39470628the Scientific Foundation of Ministry of Health,China,No.96-1-189
文摘AIM In order to study the association betweenthe null genotypes of GSTM1 and GSTT1 and thegenetic susceptibility to hepatocellularcarcinoma(HCC).METHODS The genotypes of GSTM1 and GSTT1of 63 cases of HCC and 88 controls were detectedwith the multiple PCR technique.RESULTS The frequency of GSTM1 nullgenotype was 57.1% among the cases,and42.0% among the controls,the difference beingstatistically significant(χ~2=3.35,P=0.067),but χ~2 value approaching the significance level.The odds ratio was 1.84(95% Cl= 0.91-3.37).The frequency of GSTT1 non-null genotype was87.3% among the cases and 52.5% among thecontrols,the difference being statisticallysignificant(χ~2=11.42,P=0.0007274).The oddsratio was 4.13(95% Cl=1.64-10.70).According to the cross analysis,the GSTT1 non-null genotype was more closely associated withHCC than GSTM1 null genotype,and these twofactors play an approximate additive interactionin the occurrence of HCC.CONCLUSION The persons with GSTM1 nullgenotype and GSTT1 non-null genotype have theincreased risk to HCC.
基金Supported by The Borsa M.Coppo AISF,Italian Association for the Study of the Liver to Rametta R
文摘Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by reduced serum levels of alpha1-antitrypsin(AAT)due to mutations in the SERPINA1 gene causing early onset pulmonary emphysema and,occasionally,chronic liver disease.We report an incidental finding of a novel null AAT allele,Q0Milano,consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene,in an Italian child with persistently increased liver enzymes,a mild decrease in circulating AAT levels and without any pulmonary disease.Q0Milano variant results in an unfunctional protein lacking of AAT active site,as the resultant protein is truncated near PiS locus involved in AAT protein stability.
文摘Background: The variability in the distribution of the null phenotypes of GSTM1 and GSTT1, due to total or partial gene deletion resulting in the lack of the active enzyme, has been reported in different populations, especially in ethnically well-defined groups but not in Tabuk. This study investigated the variability in the distribution of the null phenotypes of GSTM1 and GSTT1 in the population of Tabuk (northwestern part of Saudi Arabia). Method: This study was conducted on 200 subjects of Tabuk—northwestern part of Saudi Arabia among which 100 were chronic smokers and 100 were nonsmokers. The subjects were reporting to hospital for routine checkup. All were without past history of any chronic disease and no significant abnormality. GST genotyping was done by multiplex PCR-based methods. The smoker and control groups were compared using a chi-square test with P GSTM1 deletion homozygosity of 14% and 1% was reported among non smokers and smokers, respectively whereas GSTT1 deletion homozygosity of 28% and 6% was reported among non smokers and smokers, respectively. Our results indicate that there are major differences in allelic distribution of GSTM1 and GSTT1 genes between the two groups investigated. Combined analysis of both genes revealed that 15% of smokers and non smokers harbor the deleted genotype of GSTM1 and 34% of smokers and non smokers harbor the deleted genotype of GSTT1 with significant differences. Conclusion: This study enables selecting subgroups among the general population who are more susceptible to DNA damage and will help genetic studies on the association of GST polymorphisms with disease risks and drug effects in Arab population. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.
文摘In this paper, we show that new modified double cosine trigonometric sums introduced in [1] are inappropriate, the class of double sequences Jintroduced there is unusable for such sums and consequently the results obtained in it are completely incorrect. We here introduce appropriate modified double cosine trigonometric sums making the class Jusable considering a particular double cosine trigonometric series.
文摘The original description of a novel severe bleeding disorder as"Hereditary Pseudohemophilia"by Erik von Willebrand can currently be labelled as von Willebrand disease(VWD)type 3.VWD type 3 is autosomal recessive caused by homozygous or double heterozygous null mutations in the von Willebrand factor(VWF)gene and typically characterized by prolonged bleeding time and APTT,FⅧ:C levels below 2%,undetectable VWF:Ag,VWF:RCo and VWF:CB and absence of ristocetin induced platelet aggregation(RIPA).Autosomal recessive von Willebrand disease type 3 VWD with virtual complete VWF deficiency are homozygous or compound heterozygous for two null alleles(gene deletions,stop codons,frame shift mutations,splice site mutations,and absence of m RNA).Reports on severerecessive VWD compound heterozygous for a null allele and a missense mutation and homozygous or double heterozygous for missense mutations are associated with very low but measurable FⅧand VWF:Ag and should be reclassified as severe recessive type 1 VWD.Homozygous missense or compound missense/null mutations related to recessive severe type 1 VWD have been indentified in the VWF prosequence D1 and D2domains,the D4,B1-3,C1-2 domains,and only a very few in the dimmerization site(D3 domain).The detection of even tiny amounts of VWF:Ag after desmopressin acetate(DDAVP)or in hidden sites like platelets allows the differentiation between patients with VWD type 3 and homozygous or double heterozygous recessive severe type 1.Carriers of a null allele related to VWD type 3 or a missense mutation related with severe recessive type 1 VWD may present with mild VWD with low penetrance of bleeding in particular when associated with blood group O.Heterozygous obligatory carriers(OC)of a null mutation or a missense mutation related to recessive VWD type 3 or severe type 1both present with asymptomatic or mild VWD type 1 in particular when associated with blood group O.The response to DDAVP of OC of either a nonsense or a missense mutation appears to be abnormal and diagnostic with a 3-times higher response of FⅧ:C as compared to VWF:Ag.In contrast,the responses to DDAVP of FⅧ:C and VWF:Ag are equally good in individuals with low VWF levels related to blood group O and a normal VWF gene and protein(pseudo-VWD).These observations are completely in line with and extend the original observations of von Willebrand in a large family with VWD type 3 and asymptomatic or mild true type1 VWD in OC.
文摘为改善拖曳线列阵声呐的尾向探测能力,降低拖船噪声对半波长间距阵尾向探测性能的制约,本文关注四分之一波长间距阵对连续波信号和带限噪声的响应。研究表明,四分之一波长间距阵具有非对称的端向指向性,与半波长间距阵相比有约20 d B的空间抑制能力,能有效抑制拖船辐射噪声干扰。本文还提出用零陷权组合传感器构成四分之一波长间距阵,理论上其抗拖船噪声干扰的效果比四分之一波长间距阵更好。
文摘Measles virus (MV) is a negative strand RNA virus of the family Paramyxoviridae, and the attenuated Edmonston-B strain can be engineered by the reverse genetics system. Here we constructed the recombinant Edmonston strain of measles virus (MV-Ed) that expressed hepatitis C virus (HCV) envelope proteins (rMV-E1E2). The rMV-E1E2 successfully expressed HCV E1 and E2 proteins. To evaluate its immunogenicity, NOD/Scid/Jak3null mice that were engrafted with human peripheral blood mononuclear cells (huPBMC-NOJ) were infected with this rMV-E1E2. Although human lymphocytes could be isolated from the spleens of mock-infected mice during the 2-weeks-long experiment, the proportion of mice that were infected with MV or rMV-E1E2 was decreased in a viral dose-dependent manner. Over 103 PFU of virus infection decreased the human PBL to less than 5%. Significant decrease of B cell population in human PBL from rMV-E1E2 infected NOD-SCID mice and decrease of T cell population in those from MV infected mice were observed. Human antibody production in these mice was also examined. Thus, the results in this study may contribute for future improvement of recombinant vaccine using measles virus vector.
基金supported by the National Natural Science Foundation of China(No.31570931 and No.31771002)the National Key Project for Research&Development of China(Grant no.2016YFA0502204).
文摘Autoreactive CD8^(+)T cells,which play an indispensable role inβcell destruction,represent an emerging target for the prevention of type 1 diabetes(T1D).Altered peptide ligands(APLs)can efficiently induce antigen-specific T cells anergy,apoptosis or shifts in the immune response.Here,we found that HLA-A*0201-restricted CD8^(+)T cell responses against a primaryβ-cell autoantigen insulin epitope InsB15–14 were present in both NOD.β2m null.HHD NOD mice and T1D patients.We generated several APL candidates for InsB15–14 by residue substitution at the p6 position.Only H6F exhibited an inhibitory effect on mInsB1_(5–14)-specific CD8^(+)T cell responses in vitro.H6F treatment significantly reduced the T1D incidence,which was accompanied by diminished autoreactive CD8^(+)T cell responses to mInsB15-14,inhibited infiltration of CD8^(+)and CD4^(+)T cells in the pancreas and reduced pro-inflammatory cytokine production in pancreatic and splenic T cells in NOD.β2m^(null).HHD mice.Mechanistically,H6F treatment significantly augmented a tiny portion of CD8^(+)CD25^(+)Foxp3^(+)T cells in the spleen and especially in the pancreas.This subset exhibited typical Treg phenotypes and required peptide-specific restimulation to exert immunosuppressive activity.Therefore,this APL H6F may be a promising candidate with potential clinical application value for antigen-specific prevention of T1D.
基金supported by the National Natural Science Foundation of China(No.11725102)the China Postdoctoral Science Foundation(No.2021M690702)+1 种基金the National Support Program for Young Top-Notch TalentsShanghai Science and Technology Program(Nos.21JC1400600,19JC1420101)。
文摘The Faddeev model is a fundamental model in relativistic quantum field theory used to model elementary particles. The Faddeev model can be regarded as a system of non-linear wave equations with both quasi-linear and semi-linear non-linearities, which is particularly challenging in two space dimensions. A key feature of the system is that there exist undifferentiated wave components in the non-linearities, which somehow causes extra difficulties. Nevertheless, the Cauchy problem in two space dimenions was tackled by Lei-Lin-Zhou(2011) with small, regular, and compactly supported initial data, using Klainerman’s vector field method enhanced by a novel angular-radial anisotropic technique.In the present paper, the authors revisit the Faddeev model and remove the compactness assumptions on the initial data by Lei-Lin-Zhou(2011). The proof relies on an improved L2norm estimate of the wave components in Theorem 3.1 and a decomposition technique for non-linearities of divergence form.
