The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithel...The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a conse-quence.In IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast differentiation.Together,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.展开更多
Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an...Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully explained.Within human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties.This review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.展开更多
An initial prediction of the particulate mode of flow in pneumatic conveying systems is beneficial as this knowledge can provide clearer direction to the pneumatic conveying design process. There are three general cat...An initial prediction of the particulate mode of flow in pneumatic conveying systems is beneficial as this knowledge can provide clearer direction to the pneumatic conveying design process. There are three general categories of modes of flow, two dense flows： fluidised dense phase and plug flow, and dilute phase oniy. Detailed in this paper is a review of the commonly used and available techniques for predicting mode of flow. Two types of predictive charts were defined： basic particle parameter based （e.g. particle size and density） and air-particle parameter based （e.g. permeability and de-aeration）. The basic particle techniques were found to have strong and weak areas of predictive ability, on the basis of a comparison with data from materials with known mode of flow capability. It was found that there was only slight improvement in predictive ability when the particle density was replaced by loose-poured bulk density in the basic parameter techniques. The air-particle-parameter-based techniques also showed well-defined regions for mode of flow prediction though the data set used was smaller than that for the basic techniques. Also, it was found to be difficult to utilise de-aeration values from different researchers and subsequently, an air-particle-based technique was developed which does not require any de-aeration parameter in its assessment.展开更多
Current models for pressure drop prediction of slug flow pneumatic conveying in a horizontal pipeline system assume some type of steady state conditions for prediction, which limits their capability for increased pred...Current models for pressure drop prediction of slug flow pneumatic conveying in a horizontal pipeline system assume some type of steady state conditions for prediction, which limits their capability for increased predictive accuracy relative to experimental data. This is partly because of the nature of slug flow pneumatic conveying system, which, as a dynamic system, never becomes stable. By utilising conservation of mass （airflow）, a dynamic pressure analysis model is proposed on the basis of the derivative of the upstream pressure behaviour. The rate of air permeation through slug, one of the important factors in the conservation model, is expressed as a function of a slug permeability factor. Other factors such as slug velocity, slug length and the fraction of stationary layer were also considered. Several test materials were conveyed in single-slug tests to verify the proposed pressure drop model, showing good agreement between the model and experimental results.展开更多
Current modelling techniques for the prediction of conveying line pressure drop in low velocity dense phase pneumatic conveying are largely based on steady state analyses. Work in this area has been on-going for many ...Current modelling techniques for the prediction of conveying line pressure drop in low velocity dense phase pneumatic conveying are largely based on steady state analyses. Work in this area has been on-going for many years with only marginal improvements in the accuracy of prediction being achieved. Experimental and theoretical investigations undertaken by the authors suggest that the flow mechanisms involved in dense phase conveying are dominated by transient effects rather than those of steady state and are possibly the principal reasons for the limited improvement in accuracy. This paper reports on investigations on the pressure fluctuation behaviour in dense phase pneumatic conveying of powders. The pressure behaviour of the gas flow in the top section of the pipeline was found to exhibit pulsatile oscillations. In particular, the pulse velocity showed variation in magnitude while the frequency of the oscillations rarely exceeded 5 Hz. A wavelet analysis using the Daubechie 4 wavelet found that the amplitude of the oscillations increased along the pipeline. Furthermore, there was significant variation in gas pulse amplitude for different types of particulate material.展开更多
Understanding of the dynamic particulate flow structures within a dense gas-fly ash pneumatic conveyor must be improved in order to better aid its design guidance.The complex pulsatile movement of the gas-fly ash mixt...Understanding of the dynamic particulate flow structures within a dense gas-fly ash pneumatic conveyor must be improved in order to better aid its design guidance.The complex pulsatile movement of the gas-fly ash mixture dominates the flow performance within the pipeline,and historically,non-invasive measurement devices such as the electrical capacitance tomography（ECT） were often used to sufficiently capture the flow dynamics.However,inadequate studies have been conducted on the pulsatile flow phenomenon,which directly relate to the gas-fly ash two-phase flow performance.This paper aims to investigate the pulsatile flows using an ECT device.Initially,pulsatile flow patterns under various experimental conditions were obtained through ECT.Pulses within a flow were then characterised into pulse growth and decay segments,which represent the superficial fluidisation and deaeration processes during conveying.Subsequently,structural and statistical analyses were performed on the pulse growth and decay segments.Results suggested that the increasing air mass flow rate led to the decrease of the superficial fluidisation/deaeration magnitude,however,the increase of the superficial fluidisation/deaeration durations.Also,the air mass flow rate was indicated as the dominant factor in determining the pulsing statistical parameters.This research provides fundamental insights for further modelling the dense fly ash pneumatic flows.展开更多
基金supported by the UK Medical Research Council(MR/S025480/1)the UK Academy of Medical Sciences/the Wellcome Trust Springboard Award(SBF002/1038)+2 种基金AAIR Charity.ZX and LY were supported by China Scholarship Council.YZ was supported by an Institute for Life Sciences PhD Studentship.JD was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK(FC001070)the UK Medical Research Council(FC001070)the Wellcome Trust(FC001070).
文摘The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a conse-quence.In IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast differentiation.Together,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.
基金supported by the UK Medical Research Council(MR/S025480/1)the UK Academy of Medical Sciences/the Well-come Trust Springboard Award[SBF002\1038]LY and ZX were sup-ported by the China Scholarship Council.
文摘Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully explained.Within human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties.This review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.
文摘An initial prediction of the particulate mode of flow in pneumatic conveying systems is beneficial as this knowledge can provide clearer direction to the pneumatic conveying design process. There are three general categories of modes of flow, two dense flows： fluidised dense phase and plug flow, and dilute phase oniy. Detailed in this paper is a review of the commonly used and available techniques for predicting mode of flow. Two types of predictive charts were defined： basic particle parameter based （e.g. particle size and density） and air-particle parameter based （e.g. permeability and de-aeration）. The basic particle techniques were found to have strong and weak areas of predictive ability, on the basis of a comparison with data from materials with known mode of flow capability. It was found that there was only slight improvement in predictive ability when the particle density was replaced by loose-poured bulk density in the basic parameter techniques. The air-particle-parameter-based techniques also showed well-defined regions for mode of flow prediction though the data set used was smaller than that for the basic techniques. Also, it was found to be difficult to utilise de-aeration values from different researchers and subsequently, an air-particle-based technique was developed which does not require any de-aeration parameter in its assessment.
文摘Current models for pressure drop prediction of slug flow pneumatic conveying in a horizontal pipeline system assume some type of steady state conditions for prediction, which limits their capability for increased predictive accuracy relative to experimental data. This is partly because of the nature of slug flow pneumatic conveying system, which, as a dynamic system, never becomes stable. By utilising conservation of mass （airflow）, a dynamic pressure analysis model is proposed on the basis of the derivative of the upstream pressure behaviour. The rate of air permeation through slug, one of the important factors in the conservation model, is expressed as a function of a slug permeability factor. Other factors such as slug velocity, slug length and the fraction of stationary layer were also considered. Several test materials were conveyed in single-slug tests to verify the proposed pressure drop model, showing good agreement between the model and experimental results.
文摘Current modelling techniques for the prediction of conveying line pressure drop in low velocity dense phase pneumatic conveying are largely based on steady state analyses. Work in this area has been on-going for many years with only marginal improvements in the accuracy of prediction being achieved. Experimental and theoretical investigations undertaken by the authors suggest that the flow mechanisms involved in dense phase conveying are dominated by transient effects rather than those of steady state and are possibly the principal reasons for the limited improvement in accuracy. This paper reports on investigations on the pressure fluctuation behaviour in dense phase pneumatic conveying of powders. The pressure behaviour of the gas flow in the top section of the pipeline was found to exhibit pulsatile oscillations. In particular, the pulse velocity showed variation in magnitude while the frequency of the oscillations rarely exceeded 5 Hz. A wavelet analysis using the Daubechie 4 wavelet found that the amplitude of the oscillations increased along the pipeline. Furthermore, there was significant variation in gas pulse amplitude for different types of particulate material.
文摘Understanding of the dynamic particulate flow structures within a dense gas-fly ash pneumatic conveyor must be improved in order to better aid its design guidance.The complex pulsatile movement of the gas-fly ash mixture dominates the flow performance within the pipeline,and historically,non-invasive measurement devices such as the electrical capacitance tomography（ECT） were often used to sufficiently capture the flow dynamics.However,inadequate studies have been conducted on the pulsatile flow phenomenon,which directly relate to the gas-fly ash two-phase flow performance.This paper aims to investigate the pulsatile flows using an ECT device.Initially,pulsatile flow patterns under various experimental conditions were obtained through ECT.Pulses within a flow were then characterised into pulse growth and decay segments,which represent the superficial fluidisation and deaeration processes during conveying.Subsequently,structural and statistical analyses were performed on the pulse growth and decay segments.Results suggested that the increasing air mass flow rate led to the decrease of the superficial fluidisation/deaeration magnitude,however,the increase of the superficial fluidisation/deaeration durations.Also,the air mass flow rate was indicated as the dominant factor in determining the pulsing statistical parameters.This research provides fundamental insights for further modelling the dense fly ash pneumatic flows.
