The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Zhong-qiu Zhou - One of the best experts on this subject based on the ideXlab platform.
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Macrophage MSR1 promotes BMSC osteogenic differentiatIon and M2-like polarizatIon by activating PI3K/AKT/GSK3β/β-catenin pathway.
Theranostics, 2020Co-Authors: Shujie Zhao, Fanqi Kong, Jian Jie, Hao Liu, Ya-qing Yang, Bin Jiang, Dong-dong Wang, Zhong-qiu ZhouAbstract:Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socIoeconomic implicatIons. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiatIon through the osteogenic pathway during fracture healing has attracted much attentIon. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossificatIon (Io) in vivo. The potential functIons and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed Io in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3β/β-catenin signaling increased ability to promote osteogenic differentiatIon of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3β/β-catenin pathway in the co-culture system that facilitated M2-like polarizatIon by enhancing mitochondrial oxidative phosphorylatIon. ConclusIon: Our findings revealed a prevIously unrecognized functIon of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.
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macrophage msr1 promotes bmsc osteogenic differentiatIon and m2 like polarizatIon by activating pi3k akt gsk3β β catenin pathway
Theranostics, 2020Co-Authors: Shujie Zhao, Fanqi Kong, Jian Jie, Hao Liu, Ya-qing Yang, Bin Jiang, Dong-dong Wang, Zhong-qiu Zhou, Pengyu Tang, Jian ChenAbstract:Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socIoeconomic implicatIons. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiatIon through the osteogenic pathway during fracture healing has attracted much attentIon. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossificatIon (Io) in vivo. The potential functIons and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed Io in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3β/β-catenin signaling increased ability to promote osteogenic differentiatIon of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3β/β-catenin pathway in the co-culture system that facilitated M2-like polarizatIon by enhancing mitochondrial oxidative phosphorylatIon. ConclusIon: Our findings revealed a prevIously unrecognized functIon of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.
Jay Lofstead - One of the best experts on this subject based on the ideXlab platform.
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SC - Insights for exascale Io APIs from building a petascale Io API
Proceedings of the International Conference on High Performance Computing Networking Storage and Analysis, 2013Co-Authors: Jay Lofstead, Robert RossAbstract:Near the dawn of the petascale era, Io libraries had reached a stability in their functIon and data layout with only incremental changes being incorporated. The shift in technology, particularly the scale of parallel file systems and the number of compute processes, prompted revisiting best practices for optimal Io performance. Among other efforts like PLFS, the project that led to ADIoS, the ADaptable Io System, was motivated by both the shift in technology and the historical requirement, for optimal Io performance, to change how simulatIons performed Io depending on the platform. To solve both issues, the ADIoS team, along with consultatIon with other leading Io experts, sought to build a new Io platform based on the assumptIons inherent in the petascale hardware platforms. This paper helps inform the design of future Io platforms with a discussIon of lessons learned as part of the process of designing and building ADIoS.
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adaptable metadata rich Io methods for portable high performance Io
International Parallel and Distributed Processing Symposium, 2009Co-Authors: Jay Lofstead, Fang Zheng, Scott Klasky, Karsten SchwanAbstract:Since Io performance on HPC machines strongly depends on machine characteristics and configuratIon, it is important to carefully tune Io libraries and make good use of appropriate library APIs. For instance, on current petascale machines, independent Io tends to outperform collective Io, in part due to bottlenecks at the metadata server. The problem is exacerbated by scaling issues, since each Io library scales differently on each machine, and typically, operates efficiently to different levels of scaling on different machines. With scientific codes being run on a variety of HPC resources, efficient code executIon requires us to address three important issues: (1) end users should be able to select the most efficient Io methods for their codes, with minimal effort in terms of code updates or alteratIons; (2) such performance-driven choices should not prevent data from being stored in the desired file formats, since those are crucial for later data analysis; and (3) it is important to have efficient ways of identifying and selecting certain data for analysis, to help end users cope with the flood of data produced by high end codes. This paper employs ADIoS, the ADaptable Io System, as an Io API to address (1)–(3) above. Concerning (1), ADIoS makes it possible to independently select the Io methods being used by each grouping of data in an applicatIon, so that end users can use those Io methods that exhibit best performance based on both Io patterns and the underlying hardware. In this paper, we also use this facility of ADIoS to experimentally evaluate on petascale machines alternative methods for high performance Io. Specific examples studied include methods that use strong file consistency vs. delayed parallel data consistency, as that provided by MPI-Io or POSIX Io. Concerning (2), to avoid linking Io methods to specific file formats and attain high Io performance, ADIoS introduces an efficient intermediate file format, termed BP, which can be converted, at small cost, to the standard file formats used by analysis tools, such as NetCDF and HDF-5. Concerning (3), associated with BP are efficient methods for data characterizatIon, which compute attributes that can be used to identify data sets without having to inspect or analyze the entire data contents of large files.
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IPDPS - Adaptable, metadata rich Io methods for portable high performance Io
2009 IEEE International Symposium on Parallel & Distributed Processing, 2009Co-Authors: Jay Lofstead, Fang Zheng, Scott Klasky, Karsten SchwanAbstract:Since Io performance on HPC machines strongly depends on machine characteristics and configuratIon, it is important to carefully tune Io libraries and make good use of appropriate library APIs. For instance, on current petascale machines, independent Io tends to outperform collective Io, in part due to bottlenecks at the metadata server. The problem is exacerbated by scaling issues, since each Io library scales differently on each machine, and typically, operates efficiently to different levels of scaling on different machines. With scientific codes being run on a variety of HPC resources, efficient code executIon requires us to address three important issues: (1) end users should be able to select the most efficient Io methods for their codes, with minimal effort in terms of code updates or alteratIons; (2) such performance-driven choices should not prevent data from being stored in the desired file formats, since those are crucial for later data analysis; and (3) it is important to have efficient ways of identifying and selecting certain data for analysis, to help end users cope with the flood of data produced by high end codes. This paper employs ADIoS, the ADaptable Io System, as an Io API to address (1)–(3) above. Concerning (1), ADIoS makes it possible to independently select the Io methods being used by each grouping of data in an applicatIon, so that end users can use those Io methods that exhibit best performance based on both Io patterns and the underlying hardware. In this paper, we also use this facility of ADIoS to experimentally evaluate on petascale machines alternative methods for high performance Io. Specific examples studied include methods that use strong file consistency vs. delayed parallel data consistency, as that provided by MPI-Io or POSIX Io. Concerning (2), to avoid linking Io methods to specific file formats and attain high Io performance, ADIoS introduces an efficient intermediate file format, termed BP, which can be converted, at small cost, to the standard file formats used by analysis tools, such as NetCDF and HDF-5. Concerning (3), associated with BP are efficient methods for data characterizatIon, which compute attributes that can be used to identify data sets without having to inspect or analyze the entire data contents of large files.
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flexible Io and integratIon for scientific codes through the adaptable Io system adIos
Challenges of Large Applications in Distributed Environments, 2008Co-Authors: Jay Lofstead, Scott Klasky, Karsten Schwan, Norbert Podhorszki, Chen JinAbstract:Scientific codes are all subject to variatIon in performance depending on the runtime platform and/or configuratIon, the output writing API employed, and the file system for output. Since changing the Io routines to match the optimal or desired configuratIon for a given system can be costly in terms of human time and machine resources, the Adaptable Io System provides an API nearly as simple as POSIX Io that also provides developers with the flexibility of selectIon the optimal Io routines for a given platform, without recompilatIon. As a side effect, we also gain the ability to transparently integrate more tightly with workflow systems like Kepler and Pegasus and visualizatIon systems like Visit with no runtime impact. We achieve this through our library of highly tuned Io routines and other transport methods selected and configured in an XML file read only at startup. ADIoS-based Io has demonstrated high levels of performance and scalability. For example, we have achieved 20 GB/sec write performance using GTC on the Jaguar Cray XT4 system at Oak Ridge NatIonal Labs (about 50\% of peak performance). We can change GTC output among MPI-Io synchronous, MPI-Io collective, POSIX Io, no Io (for baseline testing), asynchronous Io using the Georgia Tech DataTap system, and Visit directly for in situ visualizatIon with no changes to the source code. We designed this initial versIon of ADIoS based on the data requirements of 7 major scientific codes (GTC, Chimera, GTS, XGC1, XGC0, FLASH, and S3D) and have successfully adapted all of them to use ADIoS for all of their Io needs.
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Adaptive Io System (ADIoS)
2008Co-Authors: Chen Jin, Jay Lofstead, Scott Klasky, Karsten Schwan, Stephen W Hodson, Hasan Abbasi, Wei-keng Liao, Manish Parashar, Ciprian DocanAbstract:ADIoS is a state of the art componentizatIon of the Io system that has demonstrated impressive Io performance results on the Cray XT system at ORNL. ADIoS separates the selectIon and implementatIon of any particular Io routines from the scientific code offering unprecedented flexibility in the choices for processing and storing data. The API was modelled on F90 Io routines emphasizing simplicity and clarity using external metadata for richness. The metadata is described in a stand-along XML file that is parsed once on code startup and determines what Io routines and parameters are used by the client code for each grouping of data elements generated by the code. By employing this API, a simple change to an entry in the XML file changes the codes to use either synchronous MPI-Io, collective MPI-Io, parallel HDF5, pnetcdf, NULL (no output), or asynchronous transports such as the Rutgers DART implementatIon and the Georgia Tech DataTap method. Simply by restarting the code, the new Io routines selected in the XML file will be employed. Furthermore, we have been defining additIonal metadata tags to support in-situ visualizatIon solely through changes in the XML metadata file. The power of this technique is demonstrated on the GTC, GTC_S, XGC1, S3D, Chimera, and Flash codes. We show that when these codes run on a large number of processors, they can sustain high I/O bandwidth when they write out their restart and analysis files.
Masahiko Hibi - One of the best experts on this subject based on the ideXlab platform.
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Gsx2 is required for specificatIon of neurons in the inferIor olivary nuclei from Ptf1a-expressing neural progenitors in zebrafish.
Development (Cambridge England), 2020Co-Authors: Tsubasa Itoh, Marina Sakagami, Kazuhide Asakawa, Koichi Kawakami, Takashi Shimizu, Miki Takeuchi, Kenta Sumiyama, Masahiko HibiAbstract:Neurons in the inferIor olivary nuclei (Io neurons) send climbing fibers to Purkinje cells to elicit functIons of the cerebellum. Io neurons and Purkinje cells are derived from neural progenitors expressing the proneural gene ptf1a In this study, we found that the homeobox gene gsx2 was co-expressed with ptf1a in Io progenitors in zebrafish. Both gsx2 and ptf1a zebrafish mutants showed a strong reductIon or loss of Io neurons. The expressIon of ptf1a was not affected in gsx2 mutants, and vice versa. In Io progenitors, the ptf1a mutatIon increased apoptosis whereas the gsx2 mutatIon did not, suggesting that ptf1a and gsx2 are regulated independently of each other and have distinct roles. The fibroblast growth factors (Fgf) 3 and 8a, and retinoic acid signals negatively and positively, respectively, regulated gsx2 expressIon and thereby the development of Io neurons. mafba and Hox genes are at least partly involved in the Fgf- and retinoic acid-dependent regulatIon of Io neuronal development. Our results indicate that gsx2 mediates the rostro-caudal positIonal signals to specify the identity of Io neurons from ptf1a-expressing neural progenitors.
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Gsx2 is involved in specificatIon of neurons in the inferIor olivary nuclei from Ptf1a-expressing neuronal progenitors in zebrafish
2020Co-Authors: Tsubasa Itoh, Takeuchi Miki, Marina Sakagami, Kazuhide Asakawa, Koichi Kawakami, Takashi Shimizu, Masahiko HibiAbstract:Neurons in the inferIor olivary nuclei (Io neurons) send climbing fibers to Purkinje cells to elicit functIons of the cerebellum. Io neurons and Purkinje cells are derived from neural progenitors expressing the proneural gene ptf1a. In this study, we found that the homeobox gene gsx2 was co-expressed with ptf1a in Io progenitors in zebrafish. Both gsx2 and ptf1a zebrafish mutants showed a strong reductIon or loss of Io neurons. The expressIon of ptf1a was not affected in gsx2 mutants and vice versa. In Io progenitors, the ptf1a mutatIon increased apoptosis whereas the gsx2 mutatIon did not, suggesting that ptf1a and gsx2 are independently regulated and have distinct roles. The fibroblast growth factors (Fgf) 3/8a and retinoic acid signals negatively and positively, respectively, regulated gsx2 expressIon and thereby the development of Io neurons. mafba and hox genes are at least partly involved in the Fgf- and retinoic acid-dependent regulatIon of Io neuronal development. Our results indicate that gsx2 mediates the rostro-caudal positIonal signals to specify the identity of Io neurons from ptf1a-expressing neural progenitors.
Shujie Zhao - One of the best experts on this subject based on the ideXlab platform.
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Macrophage MSR1 promotes BMSC osteogenic differentiatIon and M2-like polarizatIon by activating PI3K/AKT/GSK3β/β-catenin pathway.
Theranostics, 2020Co-Authors: Shujie Zhao, Fanqi Kong, Jian Jie, Hao Liu, Ya-qing Yang, Bin Jiang, Dong-dong Wang, Zhong-qiu ZhouAbstract:Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socIoeconomic implicatIons. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiatIon through the osteogenic pathway during fracture healing has attracted much attentIon. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossificatIon (Io) in vivo. The potential functIons and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed Io in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3β/β-catenin signaling increased ability to promote osteogenic differentiatIon of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3β/β-catenin pathway in the co-culture system that facilitated M2-like polarizatIon by enhancing mitochondrial oxidative phosphorylatIon. ConclusIon: Our findings revealed a prevIously unrecognized functIon of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.
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macrophage msr1 promotes bmsc osteogenic differentiatIon and m2 like polarizatIon by activating pi3k akt gsk3β β catenin pathway
Theranostics, 2020Co-Authors: Shujie Zhao, Fanqi Kong, Jian Jie, Hao Liu, Ya-qing Yang, Bin Jiang, Dong-dong Wang, Zhong-qiu Zhou, Pengyu Tang, Jian ChenAbstract:Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socIoeconomic implicatIons. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiatIon through the osteogenic pathway during fracture healing has attracted much attentIon. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossificatIon (Io) in vivo. The potential functIons and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed Io in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3β/β-catenin signaling increased ability to promote osteogenic differentiatIon of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3β/β-catenin pathway in the co-culture system that facilitated M2-like polarizatIon by enhancing mitochondrial oxidative phosphorylatIon. ConclusIon: Our findings revealed a prevIously unrecognized functIon of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.
Jian Chen - One of the best experts on this subject based on the ideXlab platform.
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macrophage msr1 promotes bmsc osteogenic differentiatIon and m2 like polarizatIon by activating pi3k akt gsk3β β catenin pathway
Theranostics, 2020Co-Authors: Shujie Zhao, Fanqi Kong, Jian Jie, Hao Liu, Ya-qing Yang, Bin Jiang, Dong-dong Wang, Zhong-qiu Zhou, Pengyu Tang, Jian ChenAbstract:Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socIoeconomic implicatIons. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiatIon through the osteogenic pathway during fracture healing has attracted much attentIon. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossificatIon (Io) in vivo. The potential functIons and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed Io in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3β/β-catenin signaling increased ability to promote osteogenic differentiatIon of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3β/β-catenin pathway in the co-culture system that facilitated M2-like polarizatIon by enhancing mitochondrial oxidative phosphorylatIon. ConclusIon: Our findings revealed a prevIously unrecognized functIon of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.
