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Funabashi, Japan

Nishino T.,Nissan Chemical Industries | Wang C.,Chiba University | Wang C.,Japan Science and Technology Agency | Mochizuki-Kashio M.,Chiba University | And 6 more authors.
PLoS ONE | Year: 2011

Background: Human cord blood (hCB) is the main source of hematopoietic stem and progenitor cells (HSCs/PCs) for transplantation. Efforts to overcome relative shortages of HSCs/PCs have led to technologies to expand HSCs/PCs ex vivo. However, methods suitable for clinical practice have yet to be fully established. Methodology/Principal Findings: In this study, we screened biologically active natural products for activity to promote expansion of hCB HSCs/PCs ex vivo, and identified Garcinol, a plant-derived histone acetyltransferase (HAT) inhibitor, as a novel stimulator of hCB HSC/PC expansion. During a 7-day culture of CD34 +CD38 - HSCs supplemented with stem cell factor and thrombopoietin, Garcinol increased numbers of CD34 +CD38 - HSCs/PCs more than 4.5-fold and Isogarcinol, a derivative of Garcinol, 7.4-fold. Furthermore, during a 7-day culture of CD34 + HSCs/PCs, Garcinol expanded the number of SCID-repopulating cells (SRCs) 2.5-fold. We also demonstrated that the capacity of Garcinol and its derivatives to expand HSCs/PCs was closely correlated with their inhibitory effect on HAT. The Garcinol derivatives which expanded HSCs/PCs inhibited the HAT activity and acetylation of histones, while inactive derivatives did not. Conclusions/Significance: Our findings identify Garcinol as the first natural product acting on HSCs/PCs and suggest the inhibition of HAT to be an alternative approach for manipulating HSCs/PCs. © 2011 Nishino et al.

Nimura M.,Waseda University | Mizuno J.,Waseda University | Shigetou A.,Japan National Institute of Materials Science | Sakuma K.,IBM | And 3 more authors.
IEEE Transactions on Components, Packaging and Manufacturing Technology | Year: 2013

This paper describes a hybrid Au-underfill resin bonding method with lock-and-key structure for 3-D integration. In 3-D large scale integration (LSI), the gap between stacked chips becomes narrower because the bump dimension and pitch are smaller than those encountered in 2-D LSI. Therefore, the filling of gaps less than 10 $\mu{\rm m}$ using capillary forces often becomes insufficient because of the surface condition. To address this challenge, we study a hybrid bonding method in which the metal-metal and resin-resin bonding are carried out simultaneously with a chip resin applied previously only around the bump. To realize hybrid bonding on the entire chip, we fabricate indent and protrusion structures, which are called lock-and-key structures. The key structure is fabricated by a process that can remove the resin on the bumps by ${\rm O}2 plasma irradiation. The lock structure is fabricated by conventional photolithography and dry etching. By means of hybrid bonding with the lock-and-key structure, we have achieved the Au bump bonding and the filling of 4-$\mu{\rm m}$ gaps between the stacked chips, concurrently. The cross-sectional transmission electron microscopy image of the bonded sample demonstrated that no significant gap exists at both the Au-Au and resin-resin interfaces. In addition, the shear strength of the sample bonded with resin is 10 times higher than that without the resin. The electrical continuity of the Au bump connections after hybrid bonding has also been determined. © 2011-2012 IEEE.

Ohyama M.,Waseda University | Nimura M.,Waseda University | Mizuno J.,Waseda University | Shoji S.,Waseda University | And 3 more authors.
Proceedings - Electronic Components and Technology Conference | Year: 2015

This paper describes hybrid bonding technology of Cu/Sn microbumps and adhesive with silica filler for three-dimensional (3D) interconnection of single-micron pitch. We fabricated bonding structure composed of 8-μm pitch Cu/Sn bumps and uncured adhesive with by using combination process of resin-chemical mechanical polishing (CMP) and O2/CHF3 plasma etching. Adhesive with silica filler is conventionally used for reduction of mechanical stress around microbumps by lowering CTE of underfill. With the bonding structure, the Cu/Sn microbumps and the adhesive were simultaneously bonded in N2 atmospheric pressure after surface treatment of Ar/H2 plasma irradiation. Results of scanning electron microscope (SEM) and scanning ion microscope (SIM) analyses show that Sn of microbumps was properly wetted on Cu film without resin and silica filler trapping. The adhesive was also bonded on Cu film in 6-μm gap between chips. The shear strength was 17.85 MPa. Therefore, proposed method is highly effective for hybrid bonding of single-micron pitch aimed at future ultra-high density 3D interconnection. © 2015 IEEE.

Sasaki T.,Nagaoka University of Technology | Shoho T.,Nissan Chemical Industries | Goto K.,Nissan Chemical Industries | Sakamoto M.,Nagaoka University of Technology | And 3 more authors.
Applied Physics A: Materials Science and Processing | Year: 2016

We investigated the photoalignment properties of a liquid crystalline composite. The composite consisted of a low molecular weight nematic liquid crystal (LC) and a photoreactive liquid crystalline polymer containing 4-(4-methoxycinnamoyloxy)biphenyl side groups. Homogeneously aligned LC composite cells were fabricated using rubbed substrates and were then exposed to a linearly polarized (LP) ultraviolet (UV) laser beam. The alignment states of the LC composites were characterized using a LP visible laser beam. The LC composite in the cell was realigned by LP UV exposure and subsequent annealing. The direction of the realignment could be controlled by the polarization direction of the LP UV beam. The relationship between the realignment direction and the rubbing strength of the substrates was also investigated. A large realignment was induced in the LC composite cell when the azimuthal anchoring strength of the rubbed substrates was relatively weak. © 2016, Springer-Verlag Berlin Heidelberg.

Nimura M.,Waseda University | Mizuno J.,Waseda University | Shoji S.,Waseda University | Sakuma K.,IBM | And 3 more authors.
IEEE Transactions on Components, Packaging and Manufacturing Technology | Year: 2014

In this paper, we describe a hybrid bonding technology of Au microbump and adhesive using a planar adhesive structure for 3-D large-scale integration (LSI). Hybrid bonding means that both the microbump electrode and adhesive are simultaneously bonded. In 3-D LSI, the gaps between bonded chips are <10 μm because the pitch of the microbumps is decreased. Conventionally, adhesive resin is injected into the gaps by means of capillary force. However, the filling of the gaps is insufficient due to surface conditions. To address this challenge, we evaluated hybrid bonding with a planar adhesive structure fabricated by chemical-mechanical polishing. The bonding results showed that connection between the Au bumps and adhesive filling in the 6-?m gap between bonded Si chips was achieved without readily visible void in the range of 6 mm × 6 mm. All 900 bumps were also electrically connected. The shear strength of the bonded sample was 13 MPa. Therefore, we determined that the proposed hybrid bonding technology is highly effective for 3-D LSI with fine-pitch microbumps. © 2011-2012 IEEE.

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