The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform

Philip A Marsden - One of the best experts on this subject based on the ideXlab platform.

  • mesenchymal stromal stem cells modulate response to experimental sepsis induced lung injury via regulation of mir 27a 5p in recipient mice
    Thorax, 2020
    Co-Authors: Nadim Younes, Louis Zhou, Hajera Amatullah, Shirley H J Mei, Raquel Herrero, Jose A Lorente, Duncan J Stewart, Philip A Marsden
    Abstract:

    Introduction Mesenchymal stromal cell (MSC) therapy mitigates lung injury and improves survival in murine models of sepsis. Precise mechanisms of therapeutic benefit remain poorly understood. Objectives To identify host-derived regulatory elements that may contribute to the therapeutic effects of MSCs, we profiled the microRNAome (miRNAome) and transcriptome of lungs from mice randomised to experimental polymicrobial sepsis-induced lung injury treated with either placebo or MSCs. Methods and results A total of 11 997 genes and 357 microRNAs (miRNAs) expressed in lungs were used to generate a Statistical Estimate of association between miRNAs and their putative mRNA targets; 1395 miRNA:mRNA significant association pairs were found to be differentially expressed (false discovery rate ≤0.05). MSC administration resulted in the downregulation of miR-27a-5p and upregulation of its putative target gene VAV3 (adjusted p=1.272E-161) in septic lungs. In human pulmonary microvascular endothelial cells, miR-27a-5p expression levels were increased while VAV3 was decreased following lipopolysaccharide (LPS) or tumour necrosis factor (TNF) stimulation. Transfection of miR-27a-5p mimic or inhibitor resulted in increased or decreased VAV3 message, respectively. Luciferase reporter assay demonstrated specific binding of miR-27a-5p to the 3'UTR of VAV3. miR27a-5p inhibition mitigated TNF-induced (1) delayed wound closure, increased (2) adhesion and (3) transendothelial migration but did not alter permeability. In vivo, cell infiltration was attenuated by intratracheal coinstillation of the miR-27a-5p inhibitor, but this did not protect against endotoxin-induced oedema formation. Conclusions Our data support involvement of miR-27a-5p and VAV3 in cellular adhesion and infiltration during acute lung injury and a potential role for miR-27a-based therapeutics for acute respiratory distress syndrome.

Hajera Amatullah - One of the best experts on this subject based on the ideXlab platform.

  • mesenchymal stromal stem cells modulate response to experimental sepsis induced lung injury via regulation of mir 27a 5p in recipient mice
    Thorax, 2020
    Co-Authors: Nadim Younes, Louis Zhou, Hajera Amatullah, Shirley H J Mei, Raquel Herrero, Jose A Lorente, Duncan J Stewart, Philip A Marsden
    Abstract:

    Introduction Mesenchymal stromal cell (MSC) therapy mitigates lung injury and improves survival in murine models of sepsis. Precise mechanisms of therapeutic benefit remain poorly understood. Objectives To identify host-derived regulatory elements that may contribute to the therapeutic effects of MSCs, we profiled the microRNAome (miRNAome) and transcriptome of lungs from mice randomised to experimental polymicrobial sepsis-induced lung injury treated with either placebo or MSCs. Methods and results A total of 11 997 genes and 357 microRNAs (miRNAs) expressed in lungs were used to generate a Statistical Estimate of association between miRNAs and their putative mRNA targets; 1395 miRNA:mRNA significant association pairs were found to be differentially expressed (false discovery rate ≤0.05). MSC administration resulted in the downregulation of miR-27a-5p and upregulation of its putative target gene VAV3 (adjusted p=1.272E-161) in septic lungs. In human pulmonary microvascular endothelial cells, miR-27a-5p expression levels were increased while VAV3 was decreased following lipopolysaccharide (LPS) or tumour necrosis factor (TNF) stimulation. Transfection of miR-27a-5p mimic or inhibitor resulted in increased or decreased VAV3 message, respectively. Luciferase reporter assay demonstrated specific binding of miR-27a-5p to the 3'UTR of VAV3. miR27a-5p inhibition mitigated TNF-induced (1) delayed wound closure, increased (2) adhesion and (3) transendothelial migration but did not alter permeability. In vivo, cell infiltration was attenuated by intratracheal coinstillation of the miR-27a-5p inhibitor, but this did not protect against endotoxin-induced oedema formation. Conclusions Our data support involvement of miR-27a-5p and VAV3 in cellular adhesion and infiltration during acute lung injury and a potential role for miR-27a-based therapeutics for acute respiratory distress syndrome.

Louis Zhou - One of the best experts on this subject based on the ideXlab platform.

  • mesenchymal stromal stem cells modulate response to experimental sepsis induced lung injury via regulation of mir 27a 5p in recipient mice
    Thorax, 2020
    Co-Authors: Nadim Younes, Louis Zhou, Hajera Amatullah, Shirley H J Mei, Raquel Herrero, Jose A Lorente, Duncan J Stewart, Philip A Marsden
    Abstract:

    Introduction Mesenchymal stromal cell (MSC) therapy mitigates lung injury and improves survival in murine models of sepsis. Precise mechanisms of therapeutic benefit remain poorly understood. Objectives To identify host-derived regulatory elements that may contribute to the therapeutic effects of MSCs, we profiled the microRNAome (miRNAome) and transcriptome of lungs from mice randomised to experimental polymicrobial sepsis-induced lung injury treated with either placebo or MSCs. Methods and results A total of 11 997 genes and 357 microRNAs (miRNAs) expressed in lungs were used to generate a Statistical Estimate of association between miRNAs and their putative mRNA targets; 1395 miRNA:mRNA significant association pairs were found to be differentially expressed (false discovery rate ≤0.05). MSC administration resulted in the downregulation of miR-27a-5p and upregulation of its putative target gene VAV3 (adjusted p=1.272E-161) in septic lungs. In human pulmonary microvascular endothelial cells, miR-27a-5p expression levels were increased while VAV3 was decreased following lipopolysaccharide (LPS) or tumour necrosis factor (TNF) stimulation. Transfection of miR-27a-5p mimic or inhibitor resulted in increased or decreased VAV3 message, respectively. Luciferase reporter assay demonstrated specific binding of miR-27a-5p to the 3'UTR of VAV3. miR27a-5p inhibition mitigated TNF-induced (1) delayed wound closure, increased (2) adhesion and (3) transendothelial migration but did not alter permeability. In vivo, cell infiltration was attenuated by intratracheal coinstillation of the miR-27a-5p inhibitor, but this did not protect against endotoxin-induced oedema formation. Conclusions Our data support involvement of miR-27a-5p and VAV3 in cellular adhesion and infiltration during acute lung injury and a potential role for miR-27a-based therapeutics for acute respiratory distress syndrome.

Nadim Younes - One of the best experts on this subject based on the ideXlab platform.

  • mesenchymal stromal stem cells modulate response to experimental sepsis induced lung injury via regulation of mir 27a 5p in recipient mice
    Thorax, 2020
    Co-Authors: Nadim Younes, Louis Zhou, Hajera Amatullah, Shirley H J Mei, Raquel Herrero, Jose A Lorente, Duncan J Stewart, Philip A Marsden
    Abstract:

    Introduction Mesenchymal stromal cell (MSC) therapy mitigates lung injury and improves survival in murine models of sepsis. Precise mechanisms of therapeutic benefit remain poorly understood. Objectives To identify host-derived regulatory elements that may contribute to the therapeutic effects of MSCs, we profiled the microRNAome (miRNAome) and transcriptome of lungs from mice randomised to experimental polymicrobial sepsis-induced lung injury treated with either placebo or MSCs. Methods and results A total of 11 997 genes and 357 microRNAs (miRNAs) expressed in lungs were used to generate a Statistical Estimate of association between miRNAs and their putative mRNA targets; 1395 miRNA:mRNA significant association pairs were found to be differentially expressed (false discovery rate ≤0.05). MSC administration resulted in the downregulation of miR-27a-5p and upregulation of its putative target gene VAV3 (adjusted p=1.272E-161) in septic lungs. In human pulmonary microvascular endothelial cells, miR-27a-5p expression levels were increased while VAV3 was decreased following lipopolysaccharide (LPS) or tumour necrosis factor (TNF) stimulation. Transfection of miR-27a-5p mimic or inhibitor resulted in increased or decreased VAV3 message, respectively. Luciferase reporter assay demonstrated specific binding of miR-27a-5p to the 3'UTR of VAV3. miR27a-5p inhibition mitigated TNF-induced (1) delayed wound closure, increased (2) adhesion and (3) transendothelial migration but did not alter permeability. In vivo, cell infiltration was attenuated by intratracheal coinstillation of the miR-27a-5p inhibitor, but this did not protect against endotoxin-induced oedema formation. Conclusions Our data support involvement of miR-27a-5p and VAV3 in cellular adhesion and infiltration during acute lung injury and a potential role for miR-27a-based therapeutics for acute respiratory distress syndrome.

Olivier L. Gilbert - One of the best experts on this subject based on the ideXlab platform.

  • Representation of geometric variations using matrix transforms for Statistical tolerance analysis in assemblies
    Research in Engineering Design, 1994
    Co-Authors: Daniel E. Whitney, Olivier L. Gilbert, Marek Jastrzębski
    Abstract:

    The goal of this article is to develop a tolerance representation for assemblies compatible with tolerance analysis based on a closed-form algorithm used in robotic applications. A methodology is described that represents standard Y14.5M-1982 tolerances using homogeneous 4×4 matrix transforms. Transforms represent both the nominal relations between parts and the variations caused by geometric deviations allowed by the tolerances. The analysis calculates a Statistical Estimate of the location of the N th part in an assembly starting from the first part or a fixture. Except for form tolerances , most types of tolerance specifications are compatible with the proposed representation. This approach is well suited to integration with CAD systems and feature-based design. Since assembly apparatus errors can be calculated using the same methodology, one can predict the relative position and angle errors between two parts about to be mated. This permits useful evaluation of assembly equipment errors, comparison of different product tolerance assignments, and calculations of assembly process capability.

  • representation of geometric variations using matrix transforms for Statistical tolerance analysis in assemblies
    International Conference on Robotics and Automation, 1993
    Co-Authors: D Whitney, Olivier L. Gilbert
    Abstract:

    The authors report on efforts to develop a tolerance representation for assemblies compatible with tolerance analysis based on a closed form algorithm used in robotic applications. A methodology to represent standard Y14.5M-1982 tolerances using homogeneous matrix transforms is described. Transforms represent both the nominal relations between parts and the variations caused by geometric deviations allowed by the tolerances. The analysis calculates a Statistical Estimate of the location of the Nth part in an assembly starting from the first part or a fixture. Except for form tolerances, most types of tolerance specifications are compatible with the proposed representation. This approach is well suited for integration with CAD systems and feature-based design. >