In this study, we propose to use the principal component analysis (PCA) and regression model to incorporate linkage disequilibrium (LD) in genomic association data analysis. To accommodate LD in genomic data and r...In this study, we propose to use the principal component analysis (PCA) and regression model to incorporate linkage disequilibrium (LD) in genomic association data analysis. To accommodate LD in genomic data and reduce multiple testing, we suggest performing PCA and extracting the PCA score to capture the variation of genomic data, after which regression analysis is used to assess the association of the disease with the principal component score. An empirical analysis result shows that both genotype-based correlation matrix and haplotype-based LD matrix can produce similar results for PCA. Principal component score seems to be more powerful in detecting genetic association because the principal component score is quantitatively measured and may be able to capture the effect of multiple loci.展开更多
Specific-locus mutations induced in the ad-3region of two-component heterokaryons ofNeurospora have been compared by means ofMutational Spectra.Genetic characterization ofad-3 mutations has revealed that there are maj...Specific-locus mutations induced in the ad-3region of two-component heterokaryons ofNeurospora have been compared by means ofMutational Spectra.Genetic characterization ofad-3 mutations has revealed that there are majorclasses:gene/point mutations,multilocus deletionmutations and unknowns (mutants that grow toorapidly alone on minimal medium to be classified).展开更多
Objective:The accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs.However,there is no widely adopted biopsy guideline up to date.Our study aimed to de...Objective:The accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs.However,there is no widely adopted biopsy guideline up to date.Our study aimed to determine whether multi-quadrants biopsy improves the yield of cervical lesions.Methods:Eleven population-based cervical cancer screening studies were conducted in China.Cytology,highrisk human papillomavirus(hrHPV)testing and visual inspection were performed for primary screening.Females positive on one or more tests were referred for colposcopy and biopsy.The proportion of detected cervical intraepithelial neoplasia(CIN)2+and yields by quadrant lesion-targeted biopsy or 4-quadrant random biopsy were compared.Results:Among 4,923 females included,1,606 had quadrant lesion-targeted biopsy,and 3,317 had 4-quadrant random biopsy.The cumulative CIN2+yield increased from 0.10 for only one quadrant-targeted biopsy to 0.21,0.34,and 0.58 for at most two,three and four quadrants targeted biopsies.Among hrHPV positive females with high-grade squamous intraepithelial lesion(HSIL)+cytology,the cumulative CIN2+yield of a second targeted biopsy in another quadrant was significantly increased(P<0.05).Among hrHPV-negative females,the yield of 4-quadrant random biopsies was 0.005,and the yield by lesion-targeted biopsies was 0.017.For hrHPV positive females who had 4-quadrant random biopsy,the additional CIN2+yield for HSIL+,low-grade squamous intraepithelial lesion(LSIL)cytology,or abnormal visual inspection via acetic acid and Lugol’s iodine(VIA/VILI)were 0.46,0.11,0.14.Conclusions:A 4-quadrant random biopsy is recommended only for hrHPV positive females with HSIL cytology,and is acceptable if hrHPV positive with LSIL cytology or with abnormal VIA/VILI.Our findings add evidences for an objective and practical biopsy standard to guide colposcopy in cervical cancer screening programs in low-and middle-income countries.展开更多
The measurement of specific-locus mutations in various eukaryotic organismshas been used as a mechanism to estimate the genetic consequences of humanexposure to environmental mutagens.Specific-iocus assays are usually...The measurement of specific-locus mutations in various eukaryotic organismshas been used as a mechanism to estimate the genetic consequences of humanexposure to environmental mutagens.Specific-iocus assays are usually confined tosingle genes and measure various types of genetic damage ranging from single base-pair substitutions to multilocus deletions.Not all such assays measure the samerange of genetic damage.Thus.different specific-locus assays may provide differentdata,both quantitative and qualitative.as a result of exposure to the sameenvironmental mutagen.The specific-locus assay in the ad-3 region of Neurosporacrassa measures genetic damage at 2 closely linked loci as well as other loci in thegenome.As a result.this assay permits a comprehensive evaluation of the types ofgenetic damage produced by different environmental mutagens.In this paper.thespectrum of genetic damage that can be detected in Neurospora is reviewed andcompared with other eukaryotic systems.展开更多
The continuous rise in heat dissipation of integrated circuits necessitates advanced thermal solutions to ensure system reliability and efficiency. Thermoelectric coolers are among the most promising techniques for de...The continuous rise in heat dissipation of integrated circuits necessitates advanced thermal solutions to ensure system reliability and efficiency. Thermoelectric coolers are among the most promising techniques for dealing with localized on-chip hot spots. This study focuses on establishing a holistic optimization methodol- ogy for such thermoelectric coolers, in which a thermo- electric element's thickness and the electrical current are optimized to minimize source temperature with respect to ambient, when the thermal and electrical parasitic effects are considered. It is found that when element thickness and electrical current are optimized for a given system architecture, a "heat flux vs. temperature difference" Pareto frontier curve is obtained, indicating that there is an optimum thickness and a corresponding optimum current that maximize the achievable temperature reduc- tion while removing a particular heat flux. This methodol- ogy also provides the possible system level AT's that can be achieved for a range of heat fluxes, defining the upper limits of thermoelectric cooling for that architecture. In this study, use was made of an extensive analytical model, which was verified using commercially available finite element analysis software. Through the optimization process, 3 pairs of master curves were generated, which were then used to compose the Pareto frontier for any given system architecture. Finally, a case study wasperformed to provide an in-depth demonstration of the optimization procedure for an example application.展开更多
文摘In this study, we propose to use the principal component analysis (PCA) and regression model to incorporate linkage disequilibrium (LD) in genomic association data analysis. To accommodate LD in genomic data and reduce multiple testing, we suggest performing PCA and extracting the PCA score to capture the variation of genomic data, after which regression analysis is used to assess the association of the disease with the principal component score. An empirical analysis result shows that both genotype-based correlation matrix and haplotype-based LD matrix can produce similar results for PCA. Principal component score seems to be more powerful in detecting genetic association because the principal component score is quantitatively measured and may be able to capture the effect of multiple loci.
文摘Specific-locus mutations induced in the ad-3region of two-component heterokaryons ofNeurospora have been compared by means ofMutational Spectra.Genetic characterization ofad-3 mutations has revealed that there are majorclasses:gene/point mutations,multilocus deletionmutations and unknowns (mutants that grow toorapidly alone on minimal medium to be classified).
基金the Chinese Academy of Medical Sciences Initiative for Innovative Medicine(No.2016-I2M-1-019)the National Natural Science Foundation of China(No.81322040)。
文摘Objective:The accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs.However,there is no widely adopted biopsy guideline up to date.Our study aimed to determine whether multi-quadrants biopsy improves the yield of cervical lesions.Methods:Eleven population-based cervical cancer screening studies were conducted in China.Cytology,highrisk human papillomavirus(hrHPV)testing and visual inspection were performed for primary screening.Females positive on one or more tests were referred for colposcopy and biopsy.The proportion of detected cervical intraepithelial neoplasia(CIN)2+and yields by quadrant lesion-targeted biopsy or 4-quadrant random biopsy were compared.Results:Among 4,923 females included,1,606 had quadrant lesion-targeted biopsy,and 3,317 had 4-quadrant random biopsy.The cumulative CIN2+yield increased from 0.10 for only one quadrant-targeted biopsy to 0.21,0.34,and 0.58 for at most two,three and four quadrants targeted biopsies.Among hrHPV positive females with high-grade squamous intraepithelial lesion(HSIL)+cytology,the cumulative CIN2+yield of a second targeted biopsy in another quadrant was significantly increased(P<0.05).Among hrHPV-negative females,the yield of 4-quadrant random biopsies was 0.005,and the yield by lesion-targeted biopsies was 0.017.For hrHPV positive females who had 4-quadrant random biopsy,the additional CIN2+yield for HSIL+,low-grade squamous intraepithelial lesion(LSIL)cytology,or abnormal visual inspection via acetic acid and Lugol’s iodine(VIA/VILI)were 0.46,0.11,0.14.Conclusions:A 4-quadrant random biopsy is recommended only for hrHPV positive females with HSIL cytology,and is acceptable if hrHPV positive with LSIL cytology or with abnormal VIA/VILI.Our findings add evidences for an objective and practical biopsy standard to guide colposcopy in cervical cancer screening programs in low-and middle-income countries.
文摘The measurement of specific-locus mutations in various eukaryotic organismshas been used as a mechanism to estimate the genetic consequences of humanexposure to environmental mutagens.Specific-iocus assays are usually confined tosingle genes and measure various types of genetic damage ranging from single base-pair substitutions to multilocus deletions.Not all such assays measure the samerange of genetic damage.Thus.different specific-locus assays may provide differentdata,both quantitative and qualitative.as a result of exposure to the sameenvironmental mutagen.The specific-locus assay in the ad-3 region of Neurosporacrassa measures genetic damage at 2 closely linked loci as well as other loci in thegenome.As a result.this assay permits a comprehensive evaluation of the types ofgenetic damage produced by different environmental mutagens.In this paper.thespectrum of genetic damage that can be detected in Neurospora is reviewed andcompared with other eukaryotic systems.
文摘The continuous rise in heat dissipation of integrated circuits necessitates advanced thermal solutions to ensure system reliability and efficiency. Thermoelectric coolers are among the most promising techniques for dealing with localized on-chip hot spots. This study focuses on establishing a holistic optimization methodol- ogy for such thermoelectric coolers, in which a thermo- electric element's thickness and the electrical current are optimized to minimize source temperature with respect to ambient, when the thermal and electrical parasitic effects are considered. It is found that when element thickness and electrical current are optimized for a given system architecture, a "heat flux vs. temperature difference" Pareto frontier curve is obtained, indicating that there is an optimum thickness and a corresponding optimum current that maximize the achievable temperature reduc- tion while removing a particular heat flux. This methodol- ogy also provides the possible system level AT's that can be achieved for a range of heat fluxes, defining the upper limits of thermoelectric cooling for that architecture. In this study, use was made of an extensive analytical model, which was verified using commercially available finite element analysis software. Through the optimization process, 3 pairs of master curves were generated, which were then used to compose the Pareto frontier for any given system architecture. Finally, a case study wasperformed to provide an in-depth demonstration of the optimization procedure for an example application.