| 1. |
|
|
| 2. |
|
|
| 3. |
- Thomas, HS, et al.
(author)
-
- 2019
-
swepub:Mat__t
|
|
| 4. |
- Andersson, C, et al.
(author)
-
Research highlights from the 2017 ERS International Congress: airway diseases in focus
- 2018
-
In: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 4:1
-
Journal article (peer-reviewed)abstract
- For another year, high-quality research studies from around the world transformed the annual ERS International Congress into a vivid platform to discuss trending research topics, to produce new research questions and to further push the boundaries of respiratory medicine and science. This article reviews only some of the high-quality research studies on asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and chronic cough that were presented during the congress through the Airway Diseases Assembly (ERS Assembly 5) and places them into the context of current knowledge and research challenges.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Andersson, KM, et al.
(author)
-
GGTASE DEFICIENT MACROPHAGES ALTER INTEGRIN EXPRESSION ON LYMPHOCYTES AND FACILITATE DEVELOPMENT OF ARTHRITIS
- 2020
-
In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 205-206
-
Conference paper (other academic/artistic)abstract
- Geranylgeranyltransferase type I (GGTaseI) is the enzyme responsible for the prenylation/ lipidation of the RhoA family proteins, which keeps them attached to the cell membrane. We reported that GGTaseI-deficient (GLC) mice develop a spontaneous and age-dependent arthritis, reproducing the pathology of RA1. Targeting GGTaseI activates RhoA proteins.Objectives:To study which of the activated Rho proteins is responsible for development of arthritis, we deleted individual RhoA, Rac1 or Cdc42 genes in GLC mice. We study consequences of GGTaseI deficiency for lymphocyte function.Methods:Double deficient mice that lack Rac1 (GLC Rac1fl/fl), RhoA (GLC RhoAfl/fl) and Cdc42 (GLC Cdc42fl/fl) were developed by Cre-technology using the LysM-promotor, and were on a mixed genetic background (129Ola/Hsd-C57BL/6)2. Joints of the hind paws were assessed for signs of arthritis histologically and by micro CT at age of 16 weeks. Phenotype of spleen CD4 and CD8 T cells was analysis by flow cytometry. Proliferation and cytokine production was assessed in spleen cultures by ELISA. Gene expression profile was analyzed by RT-PCR.Results:Deletion of Rho proteins had divergent effect on development of arthritis in GLC mice. We observed a reduction of the arthritis index in GLC Rac1fl/fl (n=19, p=0.027) and GLC RhoAfl/fl (n=4, p=0.007) mice compared to GLC (n=16), while GLC Cdc42fl/fl (n=4) had no change in arthritis development. GLC RhoAfl/fl mice increased the bone mass compared to GLC (p=0.029).Flow cytometry analysis showed that RA-prone GLC and GLC Cdc42fl/fl mice had lower number of CD4 cells in spleen. CD4 cells of RA-prone GLC and GLC Cdc42 mice had significantly higher subsets of the regulatory FoxP3+ and FOXp3+CD25+ cells (p=0.016-0.029 and p=0.016-0.029 respectively) compared to control and GLC RhoAfl/fl mice. Additionally, RA-prone mice had higher expression of receptors to extracellular matrix proteins collagen (α2β2) and fibronectin (α5β1) compared to control mice (p=0.016 and p=0.011 resp) and to RA-protected mice (GLC Rac1fl/fl and GLC RhoAfl/fl, p=0.0004 and p=0.011, resp). In total, both the number of FoxP3+ CD4 cells and the expression of α5β1 receptors on CD4 cells correlated strongly with the synovitis score (r=0.72, p=0.0017 and r=0.59, p=0.012, respectively).GGTaseI gene lays under the control of HOX proteins essential for cell homing. Importantly, HOX regulate the expression of integrins. Studying the expression of HoxA genes in spleen, we found that RA prone GLC and GLC Cdc42 mice tended to have lower expression of HoxA2 and higher expression of HoxA9 compared to RA-protected GLC Rac1 and GLC RhoA and to control mice. The Hoxa9/Hoxa2 ratio was significantly higher in RA prone mice compared to RA-protected mice (p=0.0085) and control mice (p=0.019). This ratio correlated with α5β1 receptors (r=0.55, p=0.0084), FOXP3+ CD4 cells (r=0.50, p=0.017), and the arthritis index (r=0.50, p=0.033).Conclusion:Taken together this study shows that Rho proteins play divergent role in development of arthritis. Activation of Rac1 and RhoA by GGTaseI deletion changes the pattern of HOXA proteins and increases expression of integrin receptors, which facilitates leukocyte influx in the paw joints. Deletion of Rac1 and RhoA has RA-protective effect in GLC mice.References:[1]Khan, O.M., et al.J Clin Invest121, 628 (2011).[2]Akula, M.K., et al.Nat Commun10, 3975 (2019).Disclosure of Interests:None declared
|
|
| 10. |
- Babayev, Rafig, et al.
(author)
-
Computational characterization of hydrogen direct injection and nonpremixed combustion in a compression-ignition engine
- 2021
-
In: International Journal of Hydrogen Energy. - : Elsevier BV. - 0360-3199. ; 46:35, s. 18678-18696
-
Journal article (peer-reviewed)abstract
- With the revived interest in hydrogen (H ) as a direct combustion fuel for engine applications, a computational study is conducted to assess the characteristics of H direct-injection (DI) compression-ignition (CI) non-premixed combustion concept. Development of a CFD modeling using CONVERGE CFD solver focuses on hydrogen's unique characteristics by utilizing a suitable numerical method to reproduce the direct H injection phenomena. A grid sensitivity study is performed to ensure the fidelity of results with optimal cost, and the models are validated against constant-volume optical chamber and diesel engine experimental data. The present study aims to contribute to the future development of DICI H combustion engines, providing detailed characterization of the combustion cycle, and highlighting several distinct aspects of CI nonpremixed H versus diesel combustion. First, unlike the common description of diesel sprays, hydrogen jets do not exhibit significant flame lift-off and air entrainment near injector nozzle, and the fuel-air interface is drastically more stratified with no sign of premixing. It is also found that the DICI H combustion concept is governed first by a free turbulent jet mixing phase, then by an in-cylinder global mixing phase. The former is drastically more dominant with the DICI H engine compared to conventional diesel engines. The free-jet mixing is also found to be more effective that the global mixing, which indicates the need to completely rethink the optimization strategies for CI engines when using H as fuel. 2 2 2 2 2 2 2 2
|
|
