Although whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders,about half of the patients still do not receive a molecular diagnosis....Although whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders,about half of the patients still do not receive a molecular diagnosis.The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing(RNA-seq)in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence.RNA-seq data can be used to identify aberrantly spliced genes,detect allele-specific expression,and identify gene expression outliers.Amongst eight studies utilizing RNA-seq,a mean diagnostic uplift of 15%has been reported.Here,we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.展开更多
For patients with lung disease,dry powder inhalers(DPI)are profoundly beneficial.The current study introduces and develops a series of dry powder inhalers(DPIs).A capsule-based(size 0)active DPI was considered.The stu...For patients with lung disease,dry powder inhalers(DPI)are profoundly beneficial.The current study introduces and develops a series of dry powder inhalers(DPIs).A capsule-based(size 0)active DPI was considered.The study aims to investigate whether swirling flow and outlet capillary diameter(dc_out)affect the percentage of emitted doses(ED)released from the capsule.Spiral vanes were added to the capillary inlet to produce a swirling flow.Computational fluid dynamics(CFD)was applied to simulate the problem.The results were compared with previous in vitro and numerical studies to validate the results.Based on the derived results,the small swirl parameter(SP)enhances the secondary flow and recirculation zone.It increases the central jet flow,which increases the ED value by about 5–20%compared to no-swirl flow.However,as the airflow rate increases,the recirculation zone enlarges,vorticities become dominant,and asymmetrical flow patterns emerge.Consequently,ED%drops significantly(more than 50%).As d_(c_out)decreases,the vorticities around the outlet capillary become more potent,which is undesirable.Indeed,the emptying of the capsule does not happen ideally.The research provides a perspective on the device's design and DPI performance.展开更多
基金Bavarian State Ministry of Health and Care,Grant/Award Number:DMB-1805-0002。
文摘Although whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders,about half of the patients still do not receive a molecular diagnosis.The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing(RNA-seq)in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence.RNA-seq data can be used to identify aberrantly spliced genes,detect allele-specific expression,and identify gene expression outliers.Amongst eight studies utilizing RNA-seq,a mean diagnostic uplift of 15%has been reported.Here,we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.
基金This work was supported the National Natural Science Foundation of China(grant No.12172146).
文摘For patients with lung disease,dry powder inhalers(DPI)are profoundly beneficial.The current study introduces and develops a series of dry powder inhalers(DPIs).A capsule-based(size 0)active DPI was considered.The study aims to investigate whether swirling flow and outlet capillary diameter(dc_out)affect the percentage of emitted doses(ED)released from the capsule.Spiral vanes were added to the capillary inlet to produce a swirling flow.Computational fluid dynamics(CFD)was applied to simulate the problem.The results were compared with previous in vitro and numerical studies to validate the results.Based on the derived results,the small swirl parameter(SP)enhances the secondary flow and recirculation zone.It increases the central jet flow,which increases the ED value by about 5–20%compared to no-swirl flow.However,as the airflow rate increases,the recirculation zone enlarges,vorticities become dominant,and asymmetrical flow patterns emerge.Consequently,ED%drops significantly(more than 50%).As d_(c_out)decreases,the vorticities around the outlet capillary become more potent,which is undesirable.Indeed,the emptying of the capsule does not happen ideally.The research provides a perspective on the device's design and DPI performance.
