Present status of J-PARC MUSE Shimomura, K; Koda, A; Pant, A D ...
Journal of physics. Conference series,
03/2023, Letnik:
2462, Številka:
1
Journal Article
Recenzirano
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Abstract
At J-PARC MUSE, since the
µ
SR2017 conference and up to FY2022, there have been several new developments at the facility, including the completion of a new experimental area S2 at the ...surface muon beamline S-line and the first muon beam extraction to the H1 area in the H-line, mainly to carry out high-statistics fundamental physics experiments. Several new studies are also underway, such as applying negative muon non-destructive elemental analysis to the analysis of samples returned from the asteroid Ryugu in the D2 area of the D-line. This paper reports on the latest status of MUSE.
The binding of advanced glycation end products (AGE) to the receptor for AGE (RAGE) is known to deteriorate various cell functions and is implicated in the pathogenesis of diabetic vascular ...complications. Here we show that AGE, tumor necrosis factor-α (TNF-α), and 17β-estradiol (E2) up-regulated RAGE mRNA and protein levels in human microvascular endothelial cells and ECV304 cells, with the mRNA stability being essentially invariant. Transient transfection experiments with human RAGE promoter-luciferase chimeras revealed that the region from nucleotide number −751 to −629 and the region from −239 to −89 in the RAGE 5′-flanking sequence exhibited the AGE/TNF-α and E2 responsiveness, respectively. Site-directed mutation of an nuclear factor-κB (NF-κB) site at −671 or of Sp-1 sites at −189 and −172 residing in those regions resulted in an abrogation of the AGE/TNF-α- or E2-mediated transcriptional activation. Electrophoretic mobility shift assays revealed that ECV304 cell nuclear extracts contained factors which retarded the NF-κB and Sp-1 elements, and that the DNA-protein complexes were supershifted by anti-p65/p50 NF-κB and anti-Sp-1/estrogen receptor α antibodies, respectively. These results suggest that AGE, TNF-α, and E2 can activate the RAGE gene through NF-κB and Sp-1, causing enhanced AGE-RAGE interactions, which would lead to an exacerbation of diabetic microvasculopathy.
Poly(ADP-ribose) glycohydrolase (PARG) is the primary enzyme responsible for the degradation of poly(ADP-ribose). PARG dysfunction sensitizes cells to alkylating agents and induces cell death; ...however, the details of this effect have not been fully elucidated. Here, we investigated the mechanism by which PARG deficiency leads to cell death in different cell types using methylmethanesulfonate (MMS), an alkylating agent, and Parg(-/-) mouse ES cells and human cancer cell lines. Parg(-/-) mouse ES cells showed increased levels of γ-H2AX, a marker of DNA double strand breaks (DSBs), accumulation of poly(ADP-ribose), p53 network activation, and S-phase arrest. Early apoptosis was enhanced in Parg(-/-) mouse ES cells. Parg(-/-) ES cells predominantly underwent caspase-dependent apoptosis. PARG was then knocked down in a p53-defective cell line, MIAPaCa2 cells, a human pancreatic cancer cell line. MIAPaCa2 cells were sensitized to MMS by PARG knockdown. Enhanced necrotic cell death was induced in MIAPaCa2 cells after augmenting γ-H2AX levels and S-phase arrest. Taken together, these data suggest that DSB repair defect causing S-phase arrest, but p53 status was not important for sensitization to alkylation DNA damage by PARG dysfunction, whereas the cell death pathway is dependent on the cell type. This study demonstrates that functional inhibition of PARG may be useful for sensitizing at least particular cancer cells to alkylating agents.
The hydrothermal vapour treatment method was used to prepare ceramic biomaterials. Hydroxyapatite (Ca10(PO4)6(OH)2; HA) ceramics prepared by sintering with a random crystal surface have already been ...used as bone-repair materials which can directly bond to natural bone. If HA materials could have a tailored specific crystal surface, they should offer the advantages of adsorptive activity and osteoconductivity in comparison with sintered HA. Porous HA sheets of about 50 micron to 1 mm in thickness and porous HA granules of about 50 micron to 1 mm in size with a tailored crystal surface were prepared by the hydrothermal vapour exposure method at temperatures below 200 C. Porous sheets and porous granules of HA with a controlled crystal surface should be suitable for cultured bone scaffolds, bone graft materials and drug delivery system. 18 refs.
Several thrombogenic abnormalities are associated with diabetes. To investigate the underlying molecular mechanisms, we examined the effects of advanced glycation endproducts (AGE), non-enzymatically ...glycated protein derivatives, on the production of prostacyclin (PGI2), an anti-thrombogenic prostanoid, and of plasminogen activator inhibitor-1 (PAI-1), a fast-acting serine protease inhibitor of fibrinolysis, in human microvascular endothelial cells (EC). Firstly, AGE-bovine serum albumin (BSA) but not non-glycated BSA, was found to considerably decrease the production of PGI2 to about two-thirds of the control value. Secondly, quantitative reverse transcription-polymerase chain reaction showed that AGE-BSA increased the EC levels of mRNA coding for PAI-1, this being associated with a concomitant increase in the immunoreactive PAI-1 contents and the anti-fibrinolytic activity. Thirdly, the effects of AGE on PGI2 and PAI-1 syntheses in EC were found to be mediated by a receptor for AGE (RAGE) because antisense DNA against RAGE mRNA could reverse the AGE effects. Further, it was found that AGE decreased the intracellular cyclic AMP concentrations in EC and that cyclic AMP agonists such as dibutyryl cyclic AMP, forskolin and PGI2 analogue reduced the AGE-stimulated PAI-1 production, suggesting the involvement of cyclic AMP in the AGE-signalling pathway. The results thus suggest that AGE have the ability to cause platelet aggregation and fibrin stabilization, resulting in a predisposition to thrombogenesis and thereby contributing to the development and progression of diabetic vascular complications.
Differential scanning calorimetry (DSC) measurements were performed for water confined within mesoporous silica substrates of TMPS-4 and TMPS-4M (TMPS-4 modified with 3-aminopropyltriethoxysilane) ...with highly ordered cylindrical channels. The pore diameter of TMPS-4M estimated by the DSC measurements corresponds to the results obtained by nitrogen adsorption measurements.
Metal–insulator type nano-granular soft magnetic thin films have been note-worthily developed as a new soft magnetic material for electric devices that demand further miniaturization and higher ...frequency operation. The formation of nano-granular structure is strongly related to the magnitude of heat formation (Δ
H) of intergranule materials. Forming a larger Δ
H allows a clearer granular structure to be obtained. The HRTEM observation reveals that neighboring granules in NGSM films contact at the considerable points, and the soft magnetism is explainable in terms of random anisotropy model for nano-crystalline materials. Addition of Pd in Co–O-based NGSM films enhances the compositional range of soft magnetic film and their
H
k
up to 400
Oe. A large
H
k
in NGSM films means that the films exhibit an excellent
μ–f response.
The muon science facility (MUSE), along with the neutron, hadron, and neutrino facilities, is one of the experimental areas of the J-PARC project. The MUSE facility is located in the Materials and ...Life Science Facility (MLF), which is a building integrated to include both neutron and muon science programs. Since the autumn of 2008, users operation is effective and making use of the pulsed muon beam particularly at the D-Line. Unfortunately, MUSE suffered severe damages from the earthquake on March 11, 2011, the so-called "Higashi-Nippon Dai-Shinsai". We managed to have a stable operation of the superconducting solenoid magnet with use of the on-line refrigerator on December, 2012, although we had to overcome a lot of difficulties against components not working properly. But we had to stop again the whole operations on May 2013, because of the radioactive materials leakage accident at the Hadron Hall Experimental Facility. Finally we restarted the users' runs on February 2014.
Three crystalline phases, two metastable and one most-stable phase, were found in 2,5-dichlorothiophene by differential scanning calorimetry (DSC). The relaxation processes from one metastable ...crystalline phase to another and from this metastable phase to the stable phase were investigated by tracing the enthalpy change for a long time under constant temperature using DSC. The Avrami index
n, in the Avrami equation, was found to be approximately 2 for both relaxation processes.
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