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1.
Nat Commun ; 14(1): 1631, 2023 03 24.
Article in English | MEDLINE | ID: mdl-36959217

ABSTRACT

Acid sphingomyelinase (ASM) has been implicated in neurodegenerative disease pathology, including Alzheimer's disease (AD). However, the specific role of plasma ASM in promoting these pathologies is poorly understood. Herein, we explore plasma ASM as a circulating factor that accelerates neuropathological features in AD by exposing young APP/PS1 mice to the blood of mice overexpressing ASM, through parabiotic surgery. Elevated plasma ASM was found to enhance several neuropathological features in the young APP/PS1 mice by mediating the differentiation of blood-derived, pathogenic Th17 cells. Antibody-based immunotherapy targeting plasma ASM showed efficient inhibition of ASM activity in the blood of APP/PS1 mice and, interestingly, led to prophylactic effects on neuropathological features by suppressing pathogenic Th17 cells. Our data reveals insights into the potential pathogenic mechanisms underlying AD and highlights ASM-targeting immunotherapy as a potential strategy for further investigation.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Mice , Animals , Alzheimer Disease/genetics , Alzheimer Disease/therapy , Alzheimer Disease/pathology , Amyloid beta-Peptides , Mice, Transgenic , Sphingomyelin Phosphodiesterase/genetics , Disease Models, Animal , Immunotherapy , Amyloid beta-Protein Precursor
2.
J Nanosci Nanotechnol ; 19(10): 6437-6443, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31026974

ABSTRACT

The effects of Cu opening size on the mechanical properties of epoxy-contained Sn-58Bi solder joints were investigated by a low-speed shear test. Eight sample types were fabricated with various Cu opening sizes and solder pastes. The Cu opening sizes of the component and substrate were 200 µm or 380 µm, respectively, and the component formed a Sn-3.0Ag-0.5Cu (SAC305) solder bump which was placed on the Sn-58Bi solder paste or epoxy Sn-58Bi solder paste printed on the substrate and then reflowed. The microstructures of the solder joints were observed using scanning electron microscopy (SEM), and the chemical compositions were analyzed by energy-dispersive X-ray spectroscopy (EDS) and electron probe X-ray micro-analyzer (EPMA). Epoxy was formed around the solder joints after the reflow process, improving the bonding strength of the epoxy-contained solder joints. Specifically, the bonding strength of the epoxy Sn-58Bi solder joints increased about 2.9 times in the 200 µm (opening size of component)/380 µm (opening size of substrate) sample. When the opening size of the component and substrate differed, a fracture occurred at the smaller opening size. On the other hand, a fracture occurred at the substrate side for the SAC305 (solder paste of component)/Sn-58Bi (solder paste of substrate) solder joints, while a fracture occurred at the interface between SAC305 and Sn-58Bi at the SAC305/epoxy Sn-58Bi solder joints for samples with the same opening size between the component and substrate.

3.
J Nanosci Nanotechnol ; 18(9): 6162-6166, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29677761

ABSTRACT

The ball-grid array (BGA) is widely used to reduce component size and it had advantages such as high I/O pins and fine pitch. Typical Sn-Ag-Cu (SAC) solder alloys are used for formation of BGA because SAC solder has excellent characteristics among lead-free solders. However, the electronic components assembled by SAC solder were easily damaged by heat during manufacture process because SAC solder had high melting point of 220 °C. To prevent these thermal damages, SAC305 BGA component assembled by Sn-58Bi solder paste has been studied because Sn-58Bi solder had low melting point of 139 °C. In generally, Sn-58Bi solder was improved by additional elements or polymer such as epoxy because Sn-58Bi had a brittle property. However, the epoxy Sn-58Bi solder did not guaranteed high environmental reliability such as high-temperature high-humidity (HTHH) test. Thus, we evaluated the shear strength of solder joints assembled by SAC305 BGA components with Sn-58Bi solder paste and epoxy Sn-58Bi solder paste. The shear strength of solder joints was evaluated by die shear test after HTHH test at the 85 °C/85% RH conditions. The Cu6Sn5 intermetallic-compound (IMC) at the interface of solder joints was observed by scanning electron microscope (SEM). The IMC thickness of Sn-58Bi solder joints was smaller than that of epoxy Sn-58Bi solder. The shear strength was improved up to 20% by epoxy addition. The shear strength of epoxy Sn-58Bi solder joints dramatically decreased after HTHH test for 100 h.

4.
J Nanosci Nanotechnol ; 18(9): 6316-6320, 2018 09 01.
Article in English | MEDLINE | ID: mdl-29677789

ABSTRACT

Microstructures and mechanical property of Sn-3.0Ag-0.5Cu (SAC305) and epoxy Sn-3.0Ag-0.5Cu (epoxy SAC) solder joints were investigated with various surface finishes; organic solderability preservative (OSP), electroless nickel immersion gold (ENIG) and electroless nickel electroless palladium immersion gold (ENEPIG). Bending property of solder joints was evaluated by 3-point bend test method. Microstructure and chemical composition of solder joints was characterized by scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX), respectively. Epoxy did not effect on intermetallic compound (IMC) morphology. Scalloped shaped Cu6Sn5 IMC was observed at OSP surface finish. Chunky-like shaped and needle-like shaped (Ni,Cu)6Sn5 IMC were observed at the solder/ENIG joint and solder/ENEPIG joint, respectively. The bending cycles of SAC305/OSP joint, SAC305/ENIG joints and SAC305/ENEPIG joints were 720, 440 and 481 cycle numbers. The bending cycles of epoxy SAC and three types surface finished solder joints were over 1000 bending cycles. Under OSP surface finish, bending cycles of epoxy SAC solder was approximately 1.5 times higher than those of SAC305 solder joint. Bending cycles of epoxy SAC solder was over twice times higher than those of SAC305 solder with ENIG and ENEPIG surface finishes. The bending property of epoxy solder joint was enhanced due to epoxy fillet held the solder joint.

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