Mechanisms responsible for resistance of sublines derived from leukemia cell lines to an antitumor agent 9-beta-D-arabinofuranosyl-2-fluoroadenine

An agent 9-beta-D-arabinofuranosyl-2-fluoroadenine (2-F-Ara-A) is a main metabolite of fludarabine, a fluorinated purine analogue with antitumor activity in lymphoproliferative malignancies. In this study, the mechanism responsible for the resistance of cancer cells to fludarabine was examined using the 2-F-Ara-A-resistant sublines JOK-1/F-Ara-A and L1210/F-Ara-A from a human hairy leukemic cell line (JOK-1) and a mouse leukemic cell line (L1210) respectively, which were established by continuous treatment of the parental cell lines with 2-F-AraA. JOK-1/F-Ara-A and L1210/F-Ara-A cells were more than 55 and 29 times more resistant to 2-F-Ara-A than were their parent cell lines, and showed a high cross-resistance to 1-beta-D-arabinofuranosylcytosine but not to doxorubicin or vincristine. These resistant sublines intracellularly accumulated almost the same amount of 2-F-Ara-A as did their parent cell lines. However, the amount of 2-F-Ara-ATP, a cytotoxic metabolite of 2-F-Ara-A, decreased by 2.6% (JOK-1/F-Ara-A C3), 6% (L1210/F-Ara-A C1) and 3.7% (L1210/F-Ara-A C7) relative to the levels in the parent cell lines. Enzymatically, these resistant cells hardly activated deoxycytidine (dCyd) and 2-F-Ara-A. In addition, the abilities to phosphorylate deoxyadenosine and deoxyguanosine were also decreased in the resistant cells in comparison with the parent cells. These findings suggest that the deficiency in activity of dCyd kinase may contribute to the resistance of 2-F-Ara-A.     

Some characteristics of a cellular receptor for virulent infectious bursal disease virus by using flow cytometry

A flow cytometric virus binding assay that directly visualizes the binding of infectious bursal disease virus (IBDV) to its target cells was established. The chicken B lymphoblastoid cell line, LSCC-BK3, which is permissive for IBDV infection, bound high levels of the virus. Another B lymphoblastoid cell line, LSCC-1104-B1, bound low levels of the virus, although it was nonpermissive. No virus binding was detected in nonpermissive T lymphoblastoid cell lines. In the binding assay to heterogeneous cell populations of chicken lymphocytes, IBDV (a highly virulent OKYM strain) bound to 94% cells in the lymphocytes prepared from the bursa of Fabricius, 37% cells in those prepared from the spleen, 3% cells in those prepared from the thymus, and 21% cells in those prepared from the blood. Most of the cells, which bound the virus, were surface immunoglobulin M (SIgM)-positive, but a small number of them were SIgM-negative. Additionally, the binding of IBDV to the LSCC-BK3 cells was affected by treatment of the cells with proteases and N-glycosylation inhibitors. These findings may indicate that the IBDV host range is mainly controlled by the presence of a virus receptor composed of N-glycosylated protein associated with the subtle differentiation stage of B-lymphocytes represented mostly by SIgM-bearing cells.     

Process and device characterization for a 30-GHz fT submicrometer double poly-Si bipolar technology using BF2-implanted base with rapid thermal process

Process and device parameters are characterized in detail for a 30-GHz f_T submicrometer double poly-Si bipolar technology using a BF₂-implanted base with a rapid thermal annealing (RTA) process. Temperature ramping during the emitter poly-Si film deposition process minimizes interfacial oxide film growth. An emitter RTA process at 1050°C for 30 s is required to achieve an acceptable emitter-base junction leakage current with an emitter resistance of 6.7×10^-7 Ω-cm², while achieving an emitter junction depth of 50 nm with a base width of 82 nm. The primary transistor parameters and the tradeoffs between cutoff frequency and collector-to-emitter breakdown voltage are characterized as functions of base implant dose, pedestal collector implant dose, link-base implant dose, and epitaxial-layer thickness. Transistor geometry dependences of device characteristics are also studied. Based on the characterization results for poly-Si resistors, boron-doped p-type poly-Si resistors show significantly better performance in temperature coefficient and linearity than arsenic-doped n-type poly-Si resistors     

Effects of computers on Japanese schools

In this paper I consider how the computer can or should be accepted in Japanese schools. The concept of teaching in Japan stresses learning from a long-term perspective. Whereas in the instructional technology, on which the CAI or the Tutoring System depends, step-by-step attainments in relatively short time are emphasized. The former is reluctant in using the computer, but both share the Platonic perspective which are goal-oriented. However, The Socratic teacher, who intends to activate students' innate disposition to be better, would find another way of teaching and use of the computer.     

Highly reliable a‐IGZO TFTs on a plastic substrate for flexible AMOLED displays

We have successfully reduced threshold voltage shifts of amorphous In–Ga–Zn–O thin‐film transistors (a‐IGZO TFTs) on transparent polyimide films against bias‐temperature stress below 100 mV, which is equivalent to those on glass substrates. This high reliability was achieved by dense IGZO thin films and annealing temperature below 300 °C. We have reduced bulk defects of IGZO thin films and interface defects between gate insulator and IGZO thin film by optimizing deposition conditions of IGZO thin films and annealing conditions. Furthermore, a 3.0‐in. flexible active‐matrix organic light‐emitting diode was demonstrated with the highly reliable a‐IGZO TFT backplane on polyimide film. The polyimide film coating process is compatible with mass‐production lines. We believe that flexible organic light‐emitting diode displays can be mass produced using a‐IGZO TFT backplane on polyimide films.     

Properties of Va metal-B films prepared by r.f.-sputtering

Ta_100-x B _x alloy films were prepared by r.f.-sputtering in the chemical composition range 45 x 77. Ta_100-x B _x (45 x 58) films consist of the amorphous phase, while the TaB₂ crystal phase was observed in Ta_100-x B _x (66 x 77) films. A remarkable preferred orientation with the (001) plane of TaB₂ parallel to the film surface was observed in Ta₃₄B₆₆. The d.c. electrical conductivity of Ta_100-x B _x (45 x 77) films decreases with increasing boron content in the range 6.7 × 10³ to 1.3 × 10^3–1 cm^–1. The micro-Vickers hardness of Ta_100-x B _x (45 x 77) films was in the range 2200 to 2600 kg mm^–2.     

Preparation of rod-shaped BaTiO3 powder

Rod-shaped BaTiO₃ powder particles have been prepared from rod-shaped TiO₂ ·nH₂O and BaCO₃ in molten chloride. The morphology of BaTiO₃ particles was studied referring to the effects of the chemical species of the starting titanium compound, amount of chloride, particle size of the titanium compound and reaction conditions, and the preparation condition of rod-shaped BaTiO₃ has been determined: i.e., large TiO₂ ·nH₂O particles were heated at 700°C in molten salt with an equal amount of BaTiO₃. This condition was effective in suppressing the formation of BaTiO₃ by a solution-precipitation process as well as the deformation of either TiO₂ ·nH₂O or BaTiO₃, which are responsible for the formation of equiaxed BaTiO₃ particles. The obtained rod-shaped BaTiO₃ particles had a cubic symmetry. Electron diffraction analysis showed that the following topotactic relation is retained; 0 1 0_{potassium tetratitanate} 0 1 0_{hydrated titania} 1 0 0_anatase 1 0 0_{barium titanate}     

Preparation of Co-N films by rf-sputtering

Co-N films in the wide compositional range can be prepared by reactive sputtering. Co-N sputtered films consist of one or two phases, such as CoN, Co₂N, Co₃N, Co₄N and -Co. Co₄N phase with a cubic unit cell is observed, and its lattice constant isa = 0.3586 nm. The preferred orientation is observed on the Co-N films, CoN (200) plane, Co₄N (1 1 1) plane and -Co (002) plane parallel to the film surface, respectively. Saturation magnetization _s of Co-N sputtered film decreases from 160 to 1.7 e.m.u. g^–1 with increasing content of N from 0 to 21.7 at%, and coercive force_I H _c is the range of 43 to 5000e at room temperature.     

Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.     

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.