Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to th...Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(TF)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. Functional genomic analysis indicated PU.1 and MITF orchestrated a TF network essential for OC differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.展开更多
照明于我们而言至关重要。美国能源信息署(US Energy Information Administration)的一项估测证实了这一点:我们用于家居照明的耗电量(1290亿千瓦,占总耗电量的9%)相当于用来洗涤和烘干衣物、使用电脑,以及做饭时的耗电量之和。然而,这...照明于我们而言至关重要。美国能源信息署(US Energy Information Administration)的一项估测证实了这一点:我们用于家居照明的耗电量(1290亿千瓦,占总耗电量的9%)相当于用来洗涤和烘干衣物、使用电脑,以及做饭时的耗电量之和。然而,这些能源中的大部分都被浪费了。众所周知,白炽灯泡的能效非常低,只有大约5%的输出可以转换为光能,其余则转换为热能。而发光二极管(LED)展开更多
Ambient ozone(O3)was first identified as a key harmful air pollutant in the study of photochemical smog during the 1950s in Los Angeles.Subsequent studies uncovered that surface O3 was not emitted directly,but formed ...Ambient ozone(O3)was first identified as a key harmful air pollutant in the study of photochemical smog during the 1950s in Los Angeles.Subsequent studies uncovered that surface O3 was not emitted directly,but formed from the reactions of nitrogen oxides(NO_(x))and volatile organic compounds(VOCs)in sunlight.Quantifying the relationship between O3 and its two main precursors,NOx and VOCs,is considered to be the cornerstone for enabling successful mitigation of O3.In the past,a central area for the study and practice of O3 pollution control was Los Angeles and the surrounding area.The ambient O3 concentrations in the area were successfully and continuously reduced from 400 ppb(1 ppb=109 m^(3)/m^(3))to ca.120 ppb due to the joint mitigation of VOC and NOx emissions from 1960 to 2010[1].Nevertheless,O3 pollution still represents one of the most pervasive and stubborn environmental problems in megacities worldwide,with many populous centres regularly breaching WHO 8-hour Interim Targets-1 levels(160 lg/m^(3)),not to mention the updated air quality guideline value of 100 lg/m^(3).The difficulty of O3 pollution control is due to a number of factors,including its non-linear relationship with NOx[2],the difficulty of anthropogenic VOC control[3]and the contributions of biogenic VOCs.展开更多
Aim:Autologous fat grafting has gained acceptance as a technique to improve aesthetic outcomes in breast reconstruction.The purpose of this study was to share our clinical experience using autologous fat injection to ...Aim:Autologous fat grafting has gained acceptance as a technique to improve aesthetic outcomes in breast reconstruction.The purpose of this study was to share our clinical experience using autologous fat injection to correct contour deformities during breast reconstruction.Methods:A single surgeon,prospectively maintained database of patients who underwent autologous fat injection during breast reconstruction from January 2008 to November 2013 at McGill University Health Center was reviewed.Patient characteristics,breast history,type of breast reconstruction,volume of fat injected,and complications were analyzed.Results:One hundred and twenty-four patients benefited from autologous fat injection from January 2008 to November 2013,for a total of 187 treated breasts.The patients were on average 49.3 years old(±8.9 years).Fat was harvested from the medial thighs(20.5%),flanks(39.1%),medial thighs and flanks(2.9%),trochanters(13.3%),medial knees(2.7%),and abdomen(21.9%).An average of 49.25 mL of fat was injected into each reconstructed breast.A total of 187 breasts in 124 patients were lipo-infiltrated during the second stage of breast reconstruction.Thirteen breasts(in 12 separate patients)were injected several years after having undergone lumpectomy and radiotherapy.Of the 187 treated breasts,118 were reconstructed with expanders to implants,45 with deep inferior epigastric perforator flaps,9 with latissimus dorsi flaps with implants,4 with transverse rectus abdominis myocutaneous flaps,and 13 had previously undergone lumpectomy and radiotherapy.Six complications were noted in the entire series,for a rate of 3.2%.All were in previously radiated breasts.Average follow-up time was 12 months(range:2-36 months).Conclusion:Fat injection continues to grow in popularity as an adjunct to breast reconstruction.Our experience demonstrates a low complication rate as compared to most surgical interventions of the breast and further supports its safety in breast reconstruction.However,caution should be used when treating previously radiated breasts.展开更多
Hong Kong’s first architect-turned barrister Dr James Lee gives a concise review of how China's Mainland courts approach the enforcement of the arbitral awards published in Hong Kong Special Administrative Region...Hong Kong’s first architect-turned barrister Dr James Lee gives a concise review of how China's Mainland courts approach the enforcement of the arbitral awards published in Hong Kong Special Administrative Region.Particular attention is drawn to the development trend after promulgation of ' The Arrangement'.展开更多
基金supported by NIH-NIAMS Grant 2R01AR044719-15A (M.C.O. and S.M.S.)NIH-NIAMS Grant K08AR062590 (J.F.C.)
文摘Genome-wide association studies(GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast-and osteoclast(OC)-specific functions. Specifically, in OCs, a PU.1-dependent transcription factor(TF)network was revealed. Deletion of PU.1 in OCs in mice resulted in severe osteopetrosis. Functional genomic analysis indicated PU.1 and MITF orchestrated a TF network essential for OC differentiation. Several of these TFs were regulated by cooperative binding of PU.1 with BRD4 to form superenhancers. Further, PU.1 is essential for conformational changes in the superenhancer region of Nfatc1. In summary, our study demonstrates that combining GWASs with genome-wide binding studies and model organisms could decipher lineage-specific pathways contributing to complex disease states.
文摘照明于我们而言至关重要。美国能源信息署(US Energy Information Administration)的一项估测证实了这一点:我们用于家居照明的耗电量(1290亿千瓦,占总耗电量的9%)相当于用来洗涤和烘干衣物、使用电脑,以及做饭时的耗电量之和。然而,这些能源中的大部分都被浪费了。众所周知,白炽灯泡的能效非常低,只有大约5%的输出可以转换为光能,其余则转换为热能。而发光二极管(LED)
基金supported by the Natural Science Foundation of Beijing Municipality(JQ19031)the National Natural Science Foundation of China(22221004,91844301,and 91544225).
文摘Ambient ozone(O3)was first identified as a key harmful air pollutant in the study of photochemical smog during the 1950s in Los Angeles.Subsequent studies uncovered that surface O3 was not emitted directly,but formed from the reactions of nitrogen oxides(NO_(x))and volatile organic compounds(VOCs)in sunlight.Quantifying the relationship between O3 and its two main precursors,NOx and VOCs,is considered to be the cornerstone for enabling successful mitigation of O3.In the past,a central area for the study and practice of O3 pollution control was Los Angeles and the surrounding area.The ambient O3 concentrations in the area were successfully and continuously reduced from 400 ppb(1 ppb=109 m^(3)/m^(3))to ca.120 ppb due to the joint mitigation of VOC and NOx emissions from 1960 to 2010[1].Nevertheless,O3 pollution still represents one of the most pervasive and stubborn environmental problems in megacities worldwide,with many populous centres regularly breaching WHO 8-hour Interim Targets-1 levels(160 lg/m^(3)),not to mention the updated air quality guideline value of 100 lg/m^(3).The difficulty of O3 pollution control is due to a number of factors,including its non-linear relationship with NOx[2],the difficulty of anthropogenic VOC control[3]and the contributions of biogenic VOCs.
文摘Aim:Autologous fat grafting has gained acceptance as a technique to improve aesthetic outcomes in breast reconstruction.The purpose of this study was to share our clinical experience using autologous fat injection to correct contour deformities during breast reconstruction.Methods:A single surgeon,prospectively maintained database of patients who underwent autologous fat injection during breast reconstruction from January 2008 to November 2013 at McGill University Health Center was reviewed.Patient characteristics,breast history,type of breast reconstruction,volume of fat injected,and complications were analyzed.Results:One hundred and twenty-four patients benefited from autologous fat injection from January 2008 to November 2013,for a total of 187 treated breasts.The patients were on average 49.3 years old(±8.9 years).Fat was harvested from the medial thighs(20.5%),flanks(39.1%),medial thighs and flanks(2.9%),trochanters(13.3%),medial knees(2.7%),and abdomen(21.9%).An average of 49.25 mL of fat was injected into each reconstructed breast.A total of 187 breasts in 124 patients were lipo-infiltrated during the second stage of breast reconstruction.Thirteen breasts(in 12 separate patients)were injected several years after having undergone lumpectomy and radiotherapy.Of the 187 treated breasts,118 were reconstructed with expanders to implants,45 with deep inferior epigastric perforator flaps,9 with latissimus dorsi flaps with implants,4 with transverse rectus abdominis myocutaneous flaps,and 13 had previously undergone lumpectomy and radiotherapy.Six complications were noted in the entire series,for a rate of 3.2%.All were in previously radiated breasts.Average follow-up time was 12 months(range:2-36 months).Conclusion:Fat injection continues to grow in popularity as an adjunct to breast reconstruction.Our experience demonstrates a low complication rate as compared to most surgical interventions of the breast and further supports its safety in breast reconstruction.However,caution should be used when treating previously radiated breasts.
文摘Hong Kong’s first architect-turned barrister Dr James Lee gives a concise review of how China's Mainland courts approach the enforcement of the arbitral awards published in Hong Kong Special Administrative Region.Particular attention is drawn to the development trend after promulgation of ' The Arrangement'.
