Tight reservoirs are typically developed by horizontal wells and multi-stage hydraulic fracturing.The conglomerate reservoir is one type of tight reservoirs,which is different from homogeneous rock,such as tight sands...Tight reservoirs are typically developed by horizontal wells and multi-stage hydraulic fracturing.The conglomerate reservoir is one type of tight reservoirs,which is different from homogeneous rock,such as tight sandstone.This is because that the existence of gravels makes conglomerate have strong hetero-geneity.Thus,it is difficult to grasp the fracture mechanism and the law of fracture propagation of conglomerate,which limits the efficient development of the conglomerate reservoir.In this paper,the fracture characteristics and factors influencing the fracturing of Mahu conglomerate were studied by uniaxial compression,acoustic emission monitoring and X-ray computed tomography(CT)scanning experiments.The results show that the fracture characteristics of conglomerates are influenced by the gravel content and cement.The conglomerate in the study area is mainly divided into carbonate cemented conglomerate and clay cemented conglomerate.The fracture complexity of carbonate cemented conglomerate first increases and then decreases with increasing gravel content.However,for clay cemented conglomerates,the fracture complexity increases over the gravel content.The crack development stress is a significant parameter in the crack assessment of conglomerates.This study is useful to understand the influence of meso-fabric characteristics of conglomerates on their fracturing and crack evolution and guides the design of hydraulic fracturing.展开更多
Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Ta...Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.展开更多
This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes,which has not been depicted by the known neurodegenerative disease....This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes,which has not been depicted by the known neurodegenerative disease.We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia,Parkinsonism,and cognitive function,as well as brain magnetic resonance imaging scans with seven sequences.We searched for co-segregations of abnormal repeat-expansion loci,pathogenic variants in known spinocerebellar ataxiarelated genes,and novel rare mutations via whole-genome sequencing and linkage analysis.A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay.This pedigree presented novel late-onset core characteristics including cerebellar ataxia,Parkinsonism,and pyramidal signs in all nine affected members.Brain magnetic resonance imaging showed cerebellar/pons atrophy,pontine-midline linear hyperintensity,decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus,and hypo-intensities of the cerebellar dentate nuclei,basal ganglia,mesencephalic red nuclei,and substantia nigra,all of which suggested neurodegeneration.Whole-genome sequencing identified a novel pathogenic heterozygous mutation(E795V)in the CARS gene,meanwhile,exhibited none of the known repeat-expansions or point mutations in pathogenic genes.Remarkably,this CARS mutation causes a 20%decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type.All family members carrying a heterozygous mutation CARS(E795V)had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia.These findings identify novel pathogenesis of Parkinsonismspinocerebellar ataxia and provide insights into its genetic architecture.展开更多
Background： Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variant...Background： Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKALI, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods： Twelve single nucleotide polymorphisms （rs7756992/rs10946398 in CDKAL1, rsl 111875 in HHEA; rs391300 in SRR, rs17584499 in PTPRD. rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5） were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results： Birthweight was inversely associated with CDKAL 1-rs 10946398 （β = -41 g [95% confidence interval [CI]： -80, 3], P= 0.034）, common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight （β = 36 g [95% CI： -72, -0.2], P = 0.048）. The risk allele in SRR showed a trend toward a reduction ofbirthweight （P =0.085）. Conclusions： This study identified the association between type 2 diabetes risk variants in CDKAL 1 and birthweight in Chinese Hart individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.展开更多
Objective:Wc conducted a population based case-control study to evaluate the effect of estrogen associated variables in Alzhcimer′s disease.Methods:A total of 2995 female residents aged 55 years or older was drawn-by...Objective:Wc conducted a population based case-control study to evaluate the effect of estrogen associated variables in Alzhcimer′s disease.Methods:A total of 2995 female residents aged 55 years or older was drawn-by means of stratified multistage cluster sampling in urban and rural areas of Beijing.Wc collected gynecological data of 2995 females.Cases were females Alzheimer′s disease ascertained by DSM-Ⅳcriteria and NINCDS-ADRDA critcria.Controls were female residents whose MMSE scores upper than 50 percentage.Odds Ratio were calculated from Logistic models.Results:By a Logistic stepwise multiple regression model,we found that the risk of dementia in women increased with increasing age(OR per year,1.21,95%CI,1.16-1.27).The risk decreased with increased duration with menstrual cycles(OR per year,0.8L,95%CI,0.68 to 0.97).The risk decreased with increased age of menopause(OR per year,0.97,95%CI,0.91 to 1.04).The risk decreased in women ever suffered from uterine,ovary,or breast tumor(OR,0.30,95%C1:0.04-2.28).Conclusion:The risk of AD decreased with increased duration of menstrual cycles and increased age of menopause and in wome ever suffered fiom uterine.ovary or breast tumor.These findings offers additional support for a protective influence of estrogen.展开更多
基金supported by the Natural Science Youth Project of University Scientific Research Plan in Xinjiang(XJEDU2021Y053)the Talent Introduction Research Project of China University of Petroleum Beijing at Karamay(XQSQ20200056)+1 种基金Development of Conglomerate Reservoir Laboratory in Xinjiang(2019D04008)the Strategic Cooperation Technology Projects of CNPC and CUPB(Grant No.ZLZX2020-01).
文摘Tight reservoirs are typically developed by horizontal wells and multi-stage hydraulic fracturing.The conglomerate reservoir is one type of tight reservoirs,which is different from homogeneous rock,such as tight sandstone.This is because that the existence of gravels makes conglomerate have strong hetero-geneity.Thus,it is difficult to grasp the fracture mechanism and the law of fracture propagation of conglomerate,which limits the efficient development of the conglomerate reservoir.In this paper,the fracture characteristics and factors influencing the fracturing of Mahu conglomerate were studied by uniaxial compression,acoustic emission monitoring and X-ray computed tomography(CT)scanning experiments.The results show that the fracture characteristics of conglomerates are influenced by the gravel content and cement.The conglomerate in the study area is mainly divided into carbonate cemented conglomerate and clay cemented conglomerate.The fracture complexity of carbonate cemented conglomerate first increases and then decreases with increasing gravel content.However,for clay cemented conglomerates,the fracture complexity increases over the gravel content.The crack development stress is a significant parameter in the crack assessment of conglomerates.This study is useful to understand the influence of meso-fabric characteristics of conglomerates on their fracturing and crack evolution and guides the design of hydraulic fracturing.
文摘Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.
基金supported by the NIH-NIA Research Project (R21AG036454)the National Key R&D Program of China (2016YFC0901500)+4 种基金CAMS Innovation Fund for Medical Sciences (2016-12M-1-004)the National Key R&D Program of China (2016YFC1305900)the National Natural Science Foundation of China (3203004)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB02030001)Shenzhen Municipal of Government of China (JCYJ20170412153248372 and JCYJ20180507183615145).
文摘This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes,which has not been depicted by the known neurodegenerative disease.We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia,Parkinsonism,and cognitive function,as well as brain magnetic resonance imaging scans with seven sequences.We searched for co-segregations of abnormal repeat-expansion loci,pathogenic variants in known spinocerebellar ataxiarelated genes,and novel rare mutations via whole-genome sequencing and linkage analysis.A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay.This pedigree presented novel late-onset core characteristics including cerebellar ataxia,Parkinsonism,and pyramidal signs in all nine affected members.Brain magnetic resonance imaging showed cerebellar/pons atrophy,pontine-midline linear hyperintensity,decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus,and hypo-intensities of the cerebellar dentate nuclei,basal ganglia,mesencephalic red nuclei,and substantia nigra,all of which suggested neurodegeneration.Whole-genome sequencing identified a novel pathogenic heterozygous mutation(E795V)in the CARS gene,meanwhile,exhibited none of the known repeat-expansions or point mutations in pathogenic genes.Remarkably,this CARS mutation causes a 20%decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type.All family members carrying a heterozygous mutation CARS(E795V)had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia.These findings identify novel pathogenesis of Parkinsonismspinocerebellar ataxia and provide insights into its genetic architecture.
基金Source of Support： This study was supported by grants from the Natural Sciences Foundation of Beijing （No. 5072042）, National Natural Science Foundation of China （No. 81170736）, National Key Program of Clinical Science. Conflict of Interest： None declared.
文摘Background： Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKALI, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods： Twelve single nucleotide polymorphisms （rs7756992/rs10946398 in CDKAL1, rsl 111875 in HHEA; rs391300 in SRR, rs17584499 in PTPRD. rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5） were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results： Birthweight was inversely associated with CDKAL 1-rs 10946398 （β = -41 g [95% confidence interval [CI]： -80, 3], P= 0.034）, common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight （β = 36 g [95% CI： -72, -0.2], P = 0.048）. The risk allele in SRR showed a trend toward a reduction ofbirthweight （P =0.085）. Conclusions： This study identified the association between type 2 diabetes risk variants in CDKAL 1 and birthweight in Chinese Hart individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.
文摘Objective:Wc conducted a population based case-control study to evaluate the effect of estrogen associated variables in Alzhcimer′s disease.Methods:A total of 2995 female residents aged 55 years or older was drawn-by means of stratified multistage cluster sampling in urban and rural areas of Beijing.Wc collected gynecological data of 2995 females.Cases were females Alzheimer′s disease ascertained by DSM-Ⅳcriteria and NINCDS-ADRDA critcria.Controls were female residents whose MMSE scores upper than 50 percentage.Odds Ratio were calculated from Logistic models.Results:By a Logistic stepwise multiple regression model,we found that the risk of dementia in women increased with increasing age(OR per year,1.21,95%CI,1.16-1.27).The risk decreased with increased duration with menstrual cycles(OR per year,0.8L,95%CI,0.68 to 0.97).The risk decreased with increased age of menopause(OR per year,0.97,95%CI,0.91 to 1.04).The risk decreased in women ever suffered from uterine,ovary,or breast tumor(OR,0.30,95%C1:0.04-2.28).Conclusion:The risk of AD decreased with increased duration of menstrual cycles and increased age of menopause and in wome ever suffered fiom uterine.ovary or breast tumor.These findings offers additional support for a protective influence of estrogen.
